Comparison of extended colectomy and limited resection in patients with Lynch syndrome.
Natarajan, Nagendra; Watson, Patrice; Silva-Lopez, Edibaldo; Lynch, Henry T
2010-01-01
The purpose of the study was to determine the advantages and disadvantages of prophylactic/extended colectomy (subtotal colectomy) in patients with Lynch syndrome who manifest colorectal cancer. A retrospective cohort using Creighton University's hereditary cancer database was used to identify cases and controls. Cases are patients who underwent subtotal colectomy, either with no colorectal cancer diagnosis (prophylactic) or at diagnosis of first colorectal cancer; controls for these 2 types of cases were, respectively, patients who underwent no colon surgery or those having limited resection at time of diagnosis of first colorectal cancer. The Kaplan-Meier and proportional hazard regression models from the Statistical Analysis Software program was used to calculate the difference in survival, time to subsequent colorectal cancer, and subsequent abdominal surgery between cases and controls. The event-free survival of our study did not reach 50%, so we used the event-free survival at 5 years as our parameter to compare the 2 groups. The event-free survival for subsequent colorectal cancer, subsequent abdominal surgery, and death was 94%, 84%, and 93%, respectively, for cases and 74%, 63%, and 88%, respectively, for controls. Times to subsequent colorectal cancer and subsequent abdominal surgery were significantly shorter in the control group (P < .006 and P < .04, respectively). No significant difference was identified with respect to survival time between the cases and controls. Even though no survival benefit was identified between the cases and controls the increased incidence of metachronous colorectal cancer and increased abdominal surgeries among controls warrant the recommendation of subtotal colectomy in patients with Lynch syndrome.
Huhn, Stefanie; da Silva Filho, Miguel I; Sanmuganantham, Tharmila; Pichulik, Tica; Catalano, Calogerina; Pardini, Barbara; Naccarati, Alessio; Polakova-Vymetálkova, Veronika; Jiraskova, Katerina; Vodickova, Ludmila; Vodicka, Pavel; Löffler, Markus W; Courth, Lioba; Wehkamp, Jan; Din, Farhat V N; Timofeeva, Maria; Farrington, Susan M; Jansen, Lina; Hemminki, Kari; Chang-Claude, Jenny; Brenner, Hermann; Hoffmeister, Michael; Dunlop, Malcolm G; Weber, Alexander N R; Försti, Asta
2018-01-01
Nod-like receptors (NLRs) are important innate pattern recognition receptors and regulators of inflammation or play a role during development. We systematically analysed 41 non-synonymous single nucleotide polymorphisms (SNPs) in 21 NLR genes in a Czech discovery cohort of sporadic colorectal cancer (CRC) (1237 cases, 787 controls) for their association with CRC risk and survival. Five SNPs were found to be associated with CRC risk and eight with survival at 5% significance level. In a replication analysis using data of two large genome-wide association studies (GWASs) from Germany (DACHS: 1798 cases and 1810 controls) and Scotland (2210 cases and 9350 controls) the associations found in the Czech discovery set were not confirmed. However, expression analysis in human gut-related tissues and immune cells revealed that the NLRs associated with CRC risk or survival in the discovery set were expressed in primary human colon or rectum cells, CRC tissue and/or cell lines, providing preliminary evidence for a potential involvement of NLRs in general in CRC development and/or progression. Most interesting was the finding that the enigmatic development-related NLRP5 (also known as MATER) was not expressed in normal colon tissue but in colon cancer tissue and cell lines. Future studies may show whether regulatory variants instead of coding variants might affect the expression of NLRs and contribute to CRC risk and survival.
Williams, Paul; Pendyala, Lakshmana; Superko, Robert
2011-03-24
Case-control studies typically exclude fatal endpoints from the case set, which we hypothesize will substantially underestimate risk if survival is genotype-dependent. The loss of fatal cases is particularly nontrivial for studies of coronary heart disease (CHD) because of significantly reduced survival (34% one-year fatality following a coronary attack). A case in point is the KIF6 Trp719Arg polymorphism (rs20455). Whereas six prospective studies have shown that carriers of the KIF6 Trp719Arg risk allele have 20% to 50% greater CHD risk than non-carriers, several cross-sectional case-control studies failed to show that carrier status is related to CHD. Computer simulations were therefore employed to assess the impact of the loss of fatal events on gene associations in cross-sectional case-control studies, using KIF6 Trp719Arg as an example. Ten replicates of 1,000,000 observations each were generated reflecting Canadian demographics. Cardiovascular disease (CVD) risks were assigned by the Framingham equation and events distributed among KIF6 Trp719Arg genotypes according to published prospective studies. Logistic regression analysis was used to estimate odds ratios between KIF6 genotypes. Results were examined for 33%, 41.5%, and 50% fatality rates for incident CVD.In the absence of any difference in percent fatalities between genotypes, the odds ratios (carriers vs. noncarriers) were unaffected by survival bias, otherwise the odds ratios were increasingly attenuated as the disparity between fatality rates increased between genotypes. Additional simulations demonstrated that statin usage, shown in four clinical trials to substantially reduce the excess CHD risk in the KIF6 719Arg variant, should also attenuate the KIF6 719Arg odds ratio in case-control studies. These computer simulations show that exclusions of prior CHD fatalities attenuate odds ratios of case-control studies in proportion to the difference in the percent fatalities between genotypes. Disproportionate CHD survival for KIF6 Trip719Arg carriers is suggested by their 50% greater risk for recurrent myocardial infarction. This, and the attenuation of KIF6 719Arg carrier risk with statin use, may explain the genotype's weak association with CHD in cross-sectional case-control studies. The results may be relevant to the underestimation of risk in cross-sectional case-control studies of other genetic CHD-risk factors affecting survival.
Xia, Yan; Wang, Dawei; Zhang, Nan; Wang, Zhihao; Pang, Li
2018-02-01
To investigate the prognostic value of plasma serotonin levels in colorectal cancer (CRC). Preoperative plasma serotonin levels of 150 healthy control (HC) cases, 150 benign colorectal polyp (BCP) cases, and 176 CRC cases were determined using radioimmunoassay assay. Serotonin levels were compared between HC, BCP, and CRC cases, and those in CRC patients were related to 5-year outcome. Plasma serotonin levels were markedly higher in CRC patients than in either HCs or BCP cases. An elevated serotonin level was significantly associated with advanced tumor node metastasis. Receiver operating characteristic curve analysis showed that the level of serotonin had a high predictive value for disease recurrence and mortality. Multivariate analysis revealed that high serotonin level was significantly associated with poor recurrence-free survival and overall survival. Our results suggest that a high peri-operative plasma serotonin level is useful as a prognostic biomarker for CRC recurrence and poor survival. © 2017 Wiley Periodicals, Inc.
Survivorship analysis of Cotrel-Dubousset instrumentation in idiopathic scoliosis.
Bago, J; Ramirez, M; Pellise, F; Villanueva, C
2003-08-01
This study presents a survivorship analysis of Cotrel-Dubousset instrumentation in the surgical treatment of idiopathic scoliosis. Between 1987 and 1995, a total of 133 patients with idiopathic scoliosis received posterior spine fusion and instrumentation with the CD system at our center. The patients' mean age at surgery was 16.5 years (range 11-43 years). The magnitude of the thoracic scoliosis averaged 62.7 degrees (range 40 degrees -125 degrees ) and that of the lumbar curve was 58.8 degrees (range 40 degrees -100 degrees ). On average, 12.2 segments were fused (range 8-17) and, excluding the rods, 14.1 implants were set for each patient (range 10-21). Survivorship analysis was carried out using the Kaplan-Meier method. Implant removal was considered the terminal event, or "death". The effect of several variables on survival rate was determined with the Cox regression method. The patients remained in the study for 56.7 months (range 2-120 months). One-hundred and ten patients were withdrawn ("censored"): 90 "alive" (did not require repeat surgery and attended follow-up control in 1997) and 20 "lost" (did not attend control in 1997). Twenty-three patients attained the terminal event of implant removal for a variety of reasons: acute infection (three cases), late infection (ten cases), implant failure requiring revision (six cases) and local pain (four cases). The survival rate was 95.5% at 3 months, 94.7% at 6 months, 93.9% at 1 year, 91.5% at 2 years, 82.2% at 5 years and 76.5% at 10 years. The magnitude of the curves, total number of implants and number of fused segments did not correlate with survival probability. A positive correlation was found between survival rate and correction loss between surgery and last control. A survival rate of 76.5% at 10 years is unexpectedly low. Current data suggest that the incapacity to maintain correction after initial surgery plays a major roll in the long-term evolution of Cotrel-Dubousset instrumentation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Belkacemi, Yazid; University of Lille II, Lille; Bousquet, Guilhem
Purpose: To better identify prognostic factors for local control and survival, as well as the role of different therapeutic options, for phyllodes tumors, a rare fibroepithelial neoplasm of the breast. Methods and Materials: Data from 443 women treated between 1971 and 2003 were collected from the Rare Cancer Network. The median age was 40 years (range, 12-87 years). Tumors were benign in 284 cases (64%), borderline in 80 cases (18%), and malignant in 79 cases (18%). Surgery consisted of breast-conserving surgery (BCS) in 377 cases (85%) and total mastectomy (TM) in 66 cases (15%). Thirty-nine patients (9%) received adjuvant radiotherapymore » (RT). Results: After a median follow-up of 106 months, local recurrence (LR) and distant metastases rates were 19% and 3.4%, respectively. In the malignant and borderline group (n = 159), RT significantly decreased LR (p = 0.02), and TM had better results than BCS (p = 0.0019). Multivariate analysis revealed benign histology, negative margins, and no residual disease (no RD) after initial treatment and RT delivery as independent favorable prognostic factors for local control; benign histology and low number of mitosis for disease-free survival; and pathologic tumor size = 3 cm and no tumor necrosis for overall survival. In the malignant and borderline subgroup multivariate analysis TM was the only favorable independent prognostic factor for disease-free survival. Conclusions: This study showed that phyllodes tumor patients with no RD after treatment have better local control. Benign tumors have a good prognosis after surgery alone. In borderline and malignant tumors, TM had better results than BCS. Thus, in these forms adjuvant RT should be considered according to histologic criteria.« less
Garner, Alan A; Barker, Claire L; Weatherall, Andrew D
2015-11-06
Drowning patients may benefit from the advanced airway management capabilities that can be provided by physician staffed helicopter emergency medical services. The aim of this study is to describe paediatric drowning patients treated by such a service examining tasking systems, initial physiology at the incident scene, survival and neurological outcome. Retrospective analysis of paediatric drowning victims over a 5- year period. Case identification system, patient age, site of drowning, presence or absence of cardiac output, first Glasgow Coma Scale (GCS) score and interventions were collected from prehospital notes, and survival and neurological outcomes from hospital and rehabilitation notes. The P-HEMS direct case identification system operating in parallel with a central control system identified all severe drowning cases but 3 of 7 cases (43%) were missed when the central control system operated in isolation. All severe drowning cases (22) identified for P-HEMS response were intubated and transported directly to a paediatric specialist centre. Intubation required adjuvant anaesthesia in 10 (45%) cases. All children with GCS greater than eight on arrival of the P-HEMS survived neurologically intact. Seven of eight children with a GCS between four and seven survived without neurological impairment and all children with a GCS greater than three survived. Four of twelve asystolic children survived including one child who at 18 months post drowning is neurologically normal. All children who survived had return of spontaneous circulation prior to arrival in the emergency department. P-HEMS played a significant role in the management of severe paediatric drowning in this case series. Requirement for P-HEMS only interventions were high and all identified cases were transferred directly to a paediatric specialist centre. Discontinuation of the P-HEMS direct case identication system that operated during the majority of the study period resulted in deterioration in system performance with some paediatric drowning cases subsequently not identified for P-HEMS response being transported to adult hospitals.
Bayesian survival analysis in clinical trials: What methods are used in practice?
Brard, Caroline; Le Teuff, Gwénaël; Le Deley, Marie-Cécile; Hampson, Lisa V
2017-02-01
Background Bayesian statistics are an appealing alternative to the traditional frequentist approach to designing, analysing, and reporting of clinical trials, especially in rare diseases. Time-to-event endpoints are widely used in many medical fields. There are additional complexities to designing Bayesian survival trials which arise from the need to specify a model for the survival distribution. The objective of this article was to critically review the use and reporting of Bayesian methods in survival trials. Methods A systematic review of clinical trials using Bayesian survival analyses was performed through PubMed and Web of Science databases. This was complemented by a full text search of the online repositories of pre-selected journals. Cost-effectiveness, dose-finding studies, meta-analyses, and methodological papers using clinical trials were excluded. Results In total, 28 articles met the inclusion criteria, 25 were original reports of clinical trials and 3 were re-analyses of a clinical trial. Most trials were in oncology (n = 25), were randomised controlled (n = 21) phase III trials (n = 13), and half considered a rare disease (n = 13). Bayesian approaches were used for monitoring in 14 trials and for the final analysis only in 14 trials. In the latter case, Bayesian survival analyses were used for the primary analysis in four cases, for the secondary analysis in seven cases, and for the trial re-analysis in three cases. Overall, 12 articles reported fitting Bayesian regression models (semi-parametric, n = 3; parametric, n = 9). Prior distributions were often incompletely reported: 20 articles did not define the prior distribution used for the parameter of interest. Over half of the trials used only non-informative priors for monitoring and the final analysis (n = 12) when it was specified. Indeed, no articles fitting Bayesian regression models placed informative priors on the parameter of interest. The prior for the treatment effect was based on historical data in only four trials. Decision rules were pre-defined in eight cases when trials used Bayesian monitoring, and in only one case when trials adopted a Bayesian approach to the final analysis. Conclusion Few trials implemented a Bayesian survival analysis and few incorporated external data into priors. There is scope to improve the quality of reporting of Bayesian methods in survival trials. Extension of the Consolidated Standards of Reporting Trials statement for reporting Bayesian clinical trials is recommended.
Weisenburger, Dennis D; Savage, Kerry J; Harris, Nancy Lee; Gascoyne, Randy D; Jaffe, Elaine S; MacLennan, Kenneth A; Rüdiger, Thomas; Pileri, Stefano; Nakamura, Shigeo; Nathwani, Bharat; Campo, Elias; Berger, Francoise; Coiffier, Bertrand; Kim, Won-Seog; Holte, Harald; Federico, Massimo; Au, Wing Y; Tobinai, Kensei; Armitage, James O; Vose, Julie M
2011-03-24
The International Peripheral T-cell Lymphoma Project is a collaborative effort to better understand peripheral T-cell lymphoma (PTCL). A total of 22 institutions submitted clinical and pathologic material on 1314 cases. One objective was to analyze the clinical and pathologic features of 340 cases of PTCL, not otherwise specified. The median age of the patients was 60 years, and the majority (69%) presented with advanced stage disease. Most patients (87%) presented with nodal disease, but extranodal disease was present in 62%. The 5-year overall survival was 32%, and the 5-year failure-free survival was only 20%. The majority of patients (80%) were treated with combination chemotherapy that included an anthracycline, but there was no survival advantage. The International Prognostic Index (IPI) was predictive of both overall survival and failure-free survival (P < .001). Multivariate analysis of clinical and pathologic prognostic factors, respectively, when controlling for the IPI, identified bulky disease (≥ 10 cm), thrombocytopenia (< 150 × 10(9)/L), and a high number of transformed tumor cells (> 70%) as adverse predictors of survival, but only the latter was significant in final analysis. Thus, the IPI and a single pathologic feature could be used to stratify patients with PTCL-not otherwise specified for novel and risk-adapted therapies.
Pandith, Arshad A; Qasim, Iqbal; Zahoor, Wani; Shah, Parveen; Bhat, Abdul R
2018-01-10
ACE I/D and MTHFR C677T gene polymorphisms can be seen as candidate genes for glioma on the basis of their biological functions and their involvement in different cancers. The aim of this study was to analyze potential association and overall survival between MTHFR C677T and ACE I/D polymorphism in glioma patients in our population. We tested genotype distribution of 112 glioma patients against 141 cancer-free controls from the same region. Kaplan-Meier survival analysis was performed to evaluate overall survival of patients for both genes. No significant differences were found among MTHFR C677T wild type C and variant genotypes CT/TT with glioma patients. In ACE, the distribution of variant ID and DD was found to be significantly higher in glioma cases as compared to controls (p<0.0001). ACE DD genotypes were highly presented in glioma cases 26.8% versus 10.6% in controls (p<0.0001) and conferred 5-fold risk for predisposition in glioma cases. Per copy D allele frequency was found higher in cases than in controls (0.54 versus 0.25: p<0.0001). Interestingly we found a significant overall survival (with log rank p<0.01) in patients who presented with ACE DD genotypes had the least estimated overall survival of 13.4months in comparison to 21. 7 and 17.6months for ACE II and I/D genotypes respectively. We conclude ACE I/D polymorphism plays a vital role in predisposition of higher risk for glioma. We also suggest that ACE DD genotypes may act as an important predictive biomarker for overall survival of glioma patients. Copyright © 2017. Published by Elsevier B.V.
Gorfine, Malka; Bordo, Nadia; Hsu, Li
2017-01-01
Summary Consider a popular case–control family study where individuals with a disease under study (case probands) and individuals who do not have the disease (control probands) are randomly sampled from a well-defined population. Possibly right-censored age at onset and disease status are observed for both probands and their relatives. For example, case probands are men diagnosed with prostate cancer, control probands are men free of prostate cancer, and the prostate cancer history of the fathers of the probands is also collected. Inherited genetic susceptibility, shared environment, and common behavior lead to correlation among the outcomes within a family. In this article, a novel nonparametric estimator of the marginal survival function is provided. The estimator is defined in the presence of intra-cluster dependence, and is based on consistent smoothed kernel estimators of conditional survival functions. By simulation, it is shown that the proposed estimator performs very well in terms of bias. The utility of the estimator is illustrated by the analysis of case–control family data of early onset prostate cancer. To our knowledge, this is the first article that provides a fully nonparametric marginal survival estimator based on case–control clustered age-at-onset data. PMID:27436674
The Impact Of Palifermin Use On Hematopoietic Cell Transplant Outcomes In Children
Saber, Wael; Zhang, Mei-Jie; Steinert, Patricia; Chen, Min; Horowitz, Mary M
2016-01-01
Purpose Clinical trials evaluating palifermin have enrolled few pediatric patients precluding safety analyses in large groups of children. We compared hematopoietic cell transplant (HCT) outcomes among pediatric patients from a large database who did or did not receive palifermin as a preventive treatment for oral mucositis. Patients and Methods Pediatric patients and controls, matched for HCT and donor type, disease, disease status and age, were selected from the Center for International Blood and Marrow Transplant Research (CIBMTR) database and a 1:3 matched cohort analysis was performed. Stratified Cox proportional hazards models were built and propensity score adjustments were used to compare overall and disease-free survival outcomes between palifermin-treated and untreated patients. Results Three controls were identified for 90% of palifermin recipients. The remaining cases were matched with two (8%) or one (2%) controls, for a total of 210 palifermin-treated patients matched with 606 controls. Median follow-up was 31 months in cases and 36 months in controls. 57% of patients underwent allogeneic HCT, mostly for acute leukemia, and 43% underwent autologous HCT, mostly for solid tumors. In univariate analyses, two-year survival and disease-free survival rates after allogeneic HCT (58% vs 66%, P = .109; 49% vs 60%, P = .060) and after autologous HCT (73% vs 77%, P = .474; 60% vs 64%, P = .637) were similar between palifermin-treated patients and matched controls. In multivariate analysis, palifermin treatment did not significantly increase the risk of mortality (relative risk [RR] 1.20, 95% CI 0.87–1.66) or relapse (RR 1.12, 95% CI 0.78–1.62) compared with matched controls. No significant differences in rates of acute or chronic graft-vs-host disease (GVHD) were observed between palifermin-treated patients and matched controls. Conclusion Among the pediatric patients undergoing HCT, overall survival, disease-free survival, neutrophil recovery, and GVHD rates were similar between palifermin-treated patients and matched controls. PMID:27090960
Walline, Heather M; Carey, Thomas E; Goudsmit, Christine M; Bellile, Emily L; D'Souza, Gypsyamber; Peterson, Lisa A; McHugh, Jonathan B; Pai, Sara I; Lee, J Jack; Shin, Dong M; Ferris, Robert L
2017-02-01
In this study, high-risk HPV (hrHPV) incidence, prognostic biomarkers, and outcome were assessed in HIV-positive (case) and HIV-negative (control) patients with head and neck squamous cell cancer (HNSCC). HIV-positive cases were matched to controls by tumor site, sex, and age at cancer diagnosis. A tissue microarray (TMA) was constructed and DNA isolated from tumor tissue. MultiPlex-PCR MassArray, L1-PCR, and in situ hybridization were used to assess hrHPV. TMA sections were stained for p16ink4a, TP53, RB, CCND1, EGFR, and scored for intensity and proportion of positive tumor cells. The HNSCC cohort included 41 HIV-positive cases and 41 HIV-negative controls. Tumors from 11 of 40 (28%) cases, and 10 of 41 (24%) controls contained hrHPV. p16 expression, indicative of E7 oncogene activity, was present in 10 of 11 HPV-positive cases and 7 of 10 HPV-positive controls. Low p16 and high TP53 expression in some HPV-positive tumors suggested HPV-independent tumorigenesis. Survival did not differ in cases and controls. RB expression was significantly associated with poor survival (P = 0.01). High TP53 expression exhibited a trend for poorer survival (P = 0.12), but among cases, association with poor survival reached statistical significance (P = 0.04). The proportion of HPV-positive tumors was similar, but the heterogeneity of HPV types was higher in the HIV-positive cases than in HIV-negative controls. High RB expression predicted poor survival, and high TP53 expression was associated with poorer survival in the HIV-positive cases but not HIV-negative controls. HIV infection did not increase risk of death from HNSCC, and HPV-positive tumors continued to be associated with a significantly improved survival, independent of HIV status. Mol Cancer Res; 15(2); 179-88. ©2016 AACR. ©2016 American Association for Cancer Research.
Yu, James B; Wilson, Lynn D; Dasgupta, Tina; Castrucci, William A; Weidhaas, Joanne B
2008-07-01
The role of postmastectomy radiotherapy (PMRT) for lymph node-negative locally advanced breast carcinoma (T3N0M0) after modified radical mastectomy (MRM) with regard to improvement in survival remains an area of controversy. The 1973-2004 National Cancer Institute (NCI) Surveillance, Epidemiology, and End Results (SEER) database was examined for patients with T3N0M0 ductal, lobular, or mixed ductal and lobular carcinoma of the breast who underwent MRM, treated from 1988-2003. Patients who were men, who had positive lymph nodes, who survived < or =6 months, for whom breast cancer was not the first malignancy, who had nonbeam radiation, intraoperative or preoperative radiation were excluded. The average treatment effect of PMRT on mortality was estimated with a propensity score case-matched analysis. In all, 1777 patients were identified; 568 (32%) patients received PMRT. Median tumor size was 6.3 cm. The median number of lymph nodes examined was 14 (range, 1-49). Propensity score matched case-control analysis showed no improvement in overall survival with the delivery of PMRT in this group. Older patients, patients with ER- disease (compared with ER+), and patients with high-grade tumors (compared with well differentiated) had increased mortality. The use of PMRT for T3N0M0 breast carcinoma after MRM is not associated with an increase in overall survival. It was not possible to analyze local control in this study given the limitations of the SEER database. The impact of potential improvement in local control as it relates to overall survival should be the subject of further investigation. (Copyright) 2008 American Cancer Society.
Hayashi, Takahito; Ago, Kazutoshi; Nakamae, Takuma; Higo, Eri; Ogata, Mamoru
2016-06-01
Interleukin (IL)-8 has been suggested to be a positive regulator of myelination in the central nervous system, in addition to its principal role as a chemokine for neutrophils. Immunostaining for beta-amyloid precursor protein (AβPP) is an effective tool for detecting traumatic axonal injury, although AβPP immunoreactivity can also indicate axonal injury due to hypoxic causes. In this study, we examined IL-8 and AβPP immunoreactivity in sections of corpus callosum obtained from deceased patients with blunt head injury and from equivalent control tissue. AβPP immunoreactivity was detected in injured axons, such as axonal bulbs and varicose axons, in 24 of 44 head injury cases. These AβPP immunoreactive cases had survived for more than 3h. The AβPP immunostaining pattern can be classified into two types: traumatic (Pattern 1) and non-traumatic (Pattern 2) axonal injuries, which we described previously [Hayashi et al. Int. J. Legal Med. 129 (2015) 1085-1090]. Three of 44 control cases also showed AβPP immunoreactive injured axons as Pattern 2. In contrast, IL-8 immunoreactivity was detected in 7 AβPP immunoreactive and in 2 non-AβPP immunoreactive head injury cases, but was not detected in any of the 44 control cases, including the 3 AβPP immunoreactive control cases. The IL-8 immunoreactive cases had survived from 3 to 24 days, whereas those cases who survived less than 3 days (n=29) and who survived 90 days (n=1) were not IL-8 immunoreactive. Moreover, IL-8 was detected as Pattern 1 axons only. In addition, double immunofluorescence analysis showed that IL-8 is expressed by oligodendrocytes surrounding injured axons. In conclusion, our results suggest that immunohistochemical detection of IL-8 may be useful as a complementary diagnostic marker of traumatic axonal injury. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Population-based analysis of survival for hypoplastic left heart syndrome.
Hirsch, Jennifer C; Copeland, Glenn; Donohue, Janet E; Kirby, Russell S; Grigorescu, Violanda; Gurney, James G
2011-07-01
To analyze survival patterns among infants with hypoplastic left heart syndrome (HLHS) in the State of Michigan. Cases of HLHS prevalent at live birth were identified and confirmed within the Michigan Birth Defects Registry from 1992 to 2005 (n=406). Characteristics of infants with HLHS were compared with a 10:1 random control sample. Compared with 4060 control subjects, the 406 cases of HLHS were more frequently male (62.6% vs 51.4%), born prematurely (<37 weeks gestation; 15.3% vs 8.7%), and born at low birth weight (LBW) (<2.5 kg; 16.0% vs 6.6%). HLHS 1-year survival rate improved over the study period (P=.041). Chromosomal abnormalities, LBW, premature birth, and living in a high poverty neighborhood were significantly associated with death. Controlling for neighborhood poverty, term infants versus preterm with HLHS or LBW were 3.2 times (95% CI: 1.9-5.3; P<.001) more likely to survive at least 1 year. Controlling for age and weight, infants from low-poverty versus high-poverty areas were 1.8 times (95% CI: 1.1-2.8; P=.015) more likely to survive at least 1 year. Among infants with HLHS in Michigan, those who were premature, LBW, had chromosomal abnormalities, or lived in a high-poverty area were at increased risk for early death. Copyright © 2011 Mosby, Inc. All rights reserved.
Chen, Hongliang; Wu, Kejin; Wang, Maoli; Wang, Fuwen; Zhang, Mingdi; Zhang, Peng
2017-12-01
There are controversies in the comparison of overall survival between invasive micropapillary carcinoma of the breast (IMPC) and invasive ductal carcinoma (IDC). The objective of this study was to compare the long-term survival outcome between non-metastatic IMPC and IDC. The Surveillance, Epidemiology, and End Results database was searched to identify women with non-metastatic IMPC and IDC diagnosed between 2001 and 2013. Comparisons of patient and tumor characteristics were performed using Pearson's chi-square. The propensity score matching method was applied with each IMPC matched to one IDC. Breast cancer-specific survival (BCSS) and overall survival (OS) were estimated using the Kaplan-Meier product limit method and compared across groups using the log-rank statistic. Multivariate analysis was performed through Cox models. IMPC was presented with aggressive clinical presentations such as larger tumor, more positive lymph nodes, and more advanced stage compared with IDC. A higher rate of estrogen receptor (ER)/progesterone receptor (PR) positivity was also observed in IMPC. With a median follow-up of 64 months, IMPC had a better BCSS (P = 0.031) and OS (P = 0.012) compared with IDC. In a case-control analysis IMPC was still an independent favorable prognostic factor for BCSS (HR = 0.410, P < 0.001, 95% CI: 0.293-0.572) and OS (HR = 0.497, P < 0.001, 95% CI: 0.387-0.637). In subgroup analysis, IMPC always showed a better survival outcome compared with IDC except in AJCC stage I and histologic grade I disease. IMPC has a better long-term survival outcome compared with IDC in spite of its highly aggressive clinical presentation. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Home visit program improves technique survival in peritoneal dialysis.
Martino, Francesca; Adıbelli, Z; Mason, G; Nayak, A; Ariyanon, W; Rettore, E; Crepaldi, Carlo; Rodighiero, Mariapia; Ronco, Claudio
2014-01-01
Peritoneal dialysis (PD) is a home therapy, and technique survival is related to the adherence to PD prescription at home. The presence of a home visit program could improve PD outcomes. We evaluated its effects on clinical outcome during 1 year of follow-up. This was a case-control study. The case group included all 96 patients who performed PD in our center on January 1, 2013, and who attended a home visit program; the control group included all 92 patients who performed PD on January 1, 2008. The home visit program consisted of several additional visits to reinforce patients' confidence in PD management in their own environment. Outcomes were defined as technique failure, peritonitis episode, and hospitalization. Clinical and dialysis features were evaluated for each patient. The case group was significantly older (p = 0.048), with a lower grade of autonomy (p = 0.033), but a better hemoglobin level (p = 0.02) than the control group. During the observational period, we had 11 episodes of technique failure. We found a significant reduction in the rate of technique failure in the case group (p = 0.004). Furthermore, survival analysis showed a significant extension of PD treatment in the patients supported by the home visit program (52 vs. 48.8 weeks, p = 0.018). We did not find any difference between the two groups in terms of peritonitis and hospitalization rate; however, trends toward a reduction of Gram-positive peritonitis rates as well as prevalence and duration of hospitalization related to PD problems were identified in the case group. The retrospective nature of the analysis was a limitation of this study. The home visit program improves the survival of PD patients and could reduce the rate of Gram-positive peritonitis and hospitalization. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=365168.
Bala, Lakshmi; Mehrotra, Mayank; Mohindra, Samir; Saxena, Rajan; Khetrapal, Chunni Lal
2013-02-01
Fulminant hepatic failure is associated with liver metabolic derangements which could have fatal consequences. The aim of the present study is to identify serum markers for early prediction of the outcome. Proton nuclear magnetic resonance spectroscopic studies of serum of fulminant hepatic failure patients due to viral hepatitis with grade II/III of encephalopathy (twenty-four: ten prospective and fourteen retrospective) and twenty-five controls were undertaken. Of the twenty-four patients, fifteen survived with medical management alone while nine had fatal outcome. The results demonstrated significantly elevated indices of amino acids (alanine, lysine, glutamine, histidine, tyrosine, phenylalanine and 1,2-propanediol) in fatal cases compared to survivors and controls. Principal component analysis showed clear separation of fatal and surviving cases. Liver function parameters were significantly deranged in patients but they failed to provide early significant differences between surviving and fatal cases. Compared to model for end-stage liver disease scores, principal component analysis appear to be better as an early prognostic indicator. Biochemical mapping of pathways suggested interruptions in amino acid metabolism and urea cycle. Proton nuclear magnetic resonance studies of serum have the potential of rapidly identifying patients with irreversible fulminant hepatic failure requiring liver transplantation as life saving option. Copyright © 2012 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.
2012-01-01
Introduction Merkel cell carcinoma (MCC) is a rare tumour of skin. This study is a retrospective audit of patients with MCC from St Vincent’s and Mater Hospital, Sydney, Australia. The aim of this study was to investigate the influence of radiotherapy (RT) on the local and regional control of MCC lesions and survival of patients with MCC. Method The data bases in anatomical pathology, RT and surgery. We searched for patients having a diagnosis of MCC between 1996 and 2007. Patient, tumour and treatment characteristics were collected and analysed. Univariate survival analysis of categorical variables was conducted with the Kaplan-Meier method together with the Log-Rank test for statistical significance. Continuous variables were assessed using the Cox regression method. Multivariate analysis was performed for significant univariate results. Results Sixty seven patients were found. Sixty two who were stage I-III and were treated with radical intent were analysed. 68% were male. The median age was 74 years. Forty-two cases (68%) were stage I or II, and 20 cases (32%) were stage III. For the subset of 42 stage I and II patients, those that had RT to their primary site had a 2-year local recurrence free survival of 89% compared with 36% for patients not receiving RT (p<0.001). The cumulative 2-year regional recurrence free survival for patients having adjuvant regional RT was 84% compared with 43% for patients not receiving this treatment (p<0.001). Immune status at initial surgery was a significant predictor for OS and MCCSS. In a multivariate analysis combining macroscopic size (mm) and immune status at initial surgery, only immune status remained a significant predictor of overall survival (HR=2.096, 95% CI: 1.002-4.385, p=0.049). Conclusions RT is associated with significant improvement in local and regional control in Merkel cell carcinoma. Immunosuppression is an important factor in overall survival. PMID:23075308
Role of survivor bias in pancreatic cancer case-control studies.
Hu, Zhen-Huan; Connett, John E; Yuan, Jian-Min; Anderson, Kristin E
2016-01-01
The purpose of this study was to evaluate the impact of survivor bias on pancreatic cancer case-control studies. The authors constructed five case-loss scenarios based on the Iowa Women's Health Study cohort to reflect how case recruitment in population-based studies varies by case survival time. Risk factors for disease incidence included smoking, body mass index (BMI), waist circumference, diabetes, and alcohol consumption. Odds ratios (ORs) were estimated by conditional logistic regression and quantitatively compared by the interactions between risk factors and 3-month survival time. Additionally, Kaplan-Meier estimates for overall survival were compared within the subset cohort of pancreatic cancer cases. BMI and waist circumference showed a significant inverse relationship with survival time. Decreasing trends in ORs for BMI and waist circumference were observed with increasing case survival time. The interaction between BMI and survival time based on a cutpoint of 3 months was significant (P < .01) as was the interaction between waist circumference and survival time (P < .01). The findings suggested that case losses could result in survivor bias causing underestimated odds ratios for both BMI and waist circumference, whereas other risk factors were not significantly affected by case losses. Copyright © 2016 Elsevier Inc. All rights reserved.
Golan, Talia; Sella, Tal; O'Reilly, Eileen M; Katz, Matthew H G; Epelbaum, Ron; Kelsen, David P; Borgida, Ayelet; Maynard, Hannah; Kindler, Hedy; Friedmen, Eitan; Javle, Milind; Gallinger, Steven
2017-03-14
BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. A larger multi-centre, case-control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ 2 - and Fisher's exact test, and median DFS/OS using Kaplan-Meier method and log-rank testing. Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34-78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly treated controls (n=7) (39.1 vs 12.4 months, P=0.255). In this retrospective analysis, the prognosis of surgically resectable BRCA-associated PDAC is no different than that of sporadic PDAC from the same institution. The role of platinum-based adjuvant therapy in this setting requires prospective investigation.
The Impact of Palifermin Use on Hematopoietic Cell Transplant Outcomes in Children.
Saber, Wael; Zhang, Mei-Jie; Steinert, Patricia; Chen, Min; Horowitz, Mary M
2016-08-01
Clinical trials evaluating palifermin have enrolled few pediatric patients, precluding safety analyses in large groups of children. We compared hematopoietic cell transplantation (HCT) outcomes among pediatric patients who did or did not receive palifermin as a preventive treatment for oral mucositis. Pediatric patients and controls, matched for HCT and donor type, disease, disease status, and age, were selected from the Center for International Blood and Marrow Transplant Research database and a 1:3 matched cohort analysis was performed. Stratified Cox proportional hazards models were built and propensity score adjustments were used to compare overall and disease-free survival outcomes between palifermin-treated and untreated patients. Three controls were identified for 90% of palifermin recipients. The remaining cases were matched with 2 (8%) controls or 1 (2%) control, for a total of 210 palifermin-treated patients matched with 606 controls. Median follow-up was 31 months in cases and 36 months in controls. Fifty-seven percent of patients underwent allogeneic HCT, mostly for acute leukemia, and 43% underwent autologous HCT, mostly for solid tumors. In univariate analyses, 2-year survival and disease-free survival rates after allogeneic HCT (58% versus 66%, P = .109; 49% versus 60%, P = .06) and after autologous HCT (73% versus 77%, P = .474; 60% versus 64%, P = .637) were similar between palifermin-treated patients and matched controls. In multivariate analysis, palifermin treatment did not significantly increase the risk of mortality (relative risk [RR], 1.20; 95% confidence interval [CI], .87 to 1.66) or of relapse (RR, 1.12; 95% CI, .78 to 1.62) compared with matched controls. No significant differences in rates of acute or chronic graft-versus-host disease (GVHD) were observed between palifermin-treated patients and matched controls. Among pediatric patients undergoing HCT, overall survival, disease-free survival, neutrophil recovery, and GVHD rates were similar between palifermin-treated patients and matched controls. Copyright © 2016 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.
pN0(i+) Breast Cancer: Treatment Patterns, Locoregional Recurrence, and Survival Outcomes
DOE Office of Scientific and Technical Information (OSTI.GOV)
Karam, Irene; Breast Cancer Outcomes Unit, British Columbia Cancer Agency, Vancouver, BC; Lesperance, Maria F.
Purpose: To examine treatment patterns, recurrence, and survival outcomes in patients with pN0(i+) breast cancer. Methods and Materials: Subjects were 5999 women with AJCC (6th edition) pT1-3, pN0-N1a, M0 breast cancer diagnosed between 2003 and 2006. Of these, 4342 (72%) had pN0, 96 (2%) had pN0(i+), 349 (6%) had pNmic (micrometastases >0.2 mm to ≤2 mm), and 1212 (20%) had pN1a (1-3 positive macroscopic nodes) disease. Treatment characteristics and 5-year Kaplan-Meier local recurrence, regional recurrence (RR), locoregional recurrence (LRR), and overall survival were compared between nodal subgroups. Multivariable analysis was performed using Cox regression modeling. A 1:3 case-match analysis examinedmore » outcomes in pN0(i+) cases compared with pN0 controls matched for similar tumor and treatment characteristics. Results: Median follow-up was 4.8 years. Adjuvant systemic therapy use increased with nodal stage: 81%, 92%, 95%, and 94% in pN0, pN0(i+), pNmic, and pN1a disease, respectively (P<.001). Nodal radiation therapy (RT) use also increased with nodal stage: 1.7% in pN0, 27% in pN0(i+), 33% in pNmic, and 63% in pN1a cohorts (P<.001). Five-year Kaplan-Meier outcomes in pN0 versus pN0(i+) cases were as follows: local recurrence 1.7% versus 3.7% (P=.20), RR 0.5% versus 2.2% (P=.02), and LRR 2.1% versus 5.8% (P=.02). There were no RR events in 26 patients with pN0(i+) disease who received nodal RT and 2 RR events in 70 patients who did not receive nodal RT. On multivariable analysis, pN0(i+) was not associated with worse locoregional control or survival. On case-match analysis, LRR and overall survival were similar between pN0(i+) and matched pN0 counterparts. Conclusions: Nodal involvement with isolated tumor cells is not a significant prognostic factor for LRR or survival in this study's multivariable and case-match analyses. These data do not support the routine use of nodal RT in the setting of pN0(i+) disease. Prospective studies are needed to define optimal locoregional management for women with pN0(i+) breast cancer.« less
Kojicic, Marija; Reriani, Martin K.; Fernández Pérez, Evans R.; Thakur, Lokendra; Kashyap, Rahul; Van Buskirk, Camille M.; Gajic, Ognjen
2010-01-01
Background: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) commonly complicate transfusion in critically ill patients. Prior outcome studies of TACO and TRALI have focused on short-term morbidity and mortality, but the long-term survival and quality of life (QOL) of these patients remain unknown. Methods: In a nested case-control study, we compared survival and QOL between critically ill medical patients who developed pulmonary edema after transfusion (TRALI or TACO) and medical critically ill transfused controls, matched by age, gender, and admission diagnostic group. QOL in survivors was assessed with a 36-item short form health survey 1 year after initial hospitalization. Results: Hospital, 1-year, and 2-year mortality among the 74 TRALI cases and 74 matched controls were 43.2% vs 24.3% (P = .020), 63.8% vs 46.4% (P = .037) and 74.3% vs 54.3% (P = .031), whereas among the 51 TACO cases and 51 matched controls these values were 7.8% vs 11.8% (P = .727), 38.0% vs 28.0% (P = .371), and 44.9% vs 38.8% (P = .512). When adjusted for age and baseline severity of illness in a Cox proportional hazard analysis, the development of TRALI remained associated with decreased survival (hazard ratio 1.86; 95% CI, 1.19-2.93; P = .006). Both TRALI (P = .006, P = .03) and TACO (P = .03, P = .049) were associated with prolonged ICU and hospital lengths of stay. Conclusions: In critically ill medical patients, development of TRALI, but not TACO, is independently associated with decreased long-term survival. PMID:19837827
Montgomery, Ann L; Fadel, Shaza; Kumar, Rajesh; Bondy, Sue; Moineddin, Rahim; Jha, Prabhat
2014-01-01
Research in areas of low skilled attendant coverage found that maternal mortality is paradoxically higher in women who seek obstetric care. We estimated the effect of health-facility admission on maternal survival, and how this effect varies with skilled attendant coverage across India. Using unmatched population-based case-control analysis of national datasets, we compared the effect of health-facility admission at any time (antenatal, intrapartum, postpartum) on maternal deaths (cases) to women reporting pregnancies (controls). Probability of maternal death decreased with increasing skilled attendant coverage, among both women who were and were not admitted to a health-facility, however, the risk of death among women who were admitted was higher (at 50% coverage, OR = 2.32, 95% confidence interval 1.85-2.92) than among those women who were not; while at higher levels of coverage, the effect of health-facility admission was attenuated. In a secondary analysis, the probability of maternal death decreased with increasing coverage among both women admitted for delivery or delivered at home but there was no effect of admission for delivery on mortality risk (50% coverage, OR = 1.0, 0.80-1.25), suggesting that poor quality of obstetric care may have attenuated the benefits of facility-based care. Subpopulation analysis of obstetric hemorrhage cases and report of 'excessive bleeding' in controls showed that the probability of maternal death decreased with increasing skilled attendant coverage; but the effect of health-facility admission was attenuated (at 50% coverage, OR = 1.47, 0.95-1.79), suggesting that some of the effect in the main model can be explained by women arriving at facility with complications underway. Finally, highest risk associated with health-facility admission was clustered in women with education ≤ 8 years. The effect of health-facility admission did vary by skilled attendant coverage, and this effect appears to be driven partially by reverse causality; however, inequitable access to and possibly poor quality of healthcare for primary and emergency services appears to play a role in maternal survival as well.
Golan, Talia; Sella, Tal; O'Reilly, Eileen M; Katz, Matthew H G; Epelbaum, Ron; Kelsen, David P; Borgida, Ayelet; Maynard, Hannah; Kindler, Hedy; Friedmen, Eitan; Javle, Milind; Gallinger, Steven
2017-01-01
Background: BRCA1/BRCA2 germ line (GL) mutation carriers with pancreatic adenocarcinoma (PDAC) may have distinct outcomes. We recently described an apparent more favourable prognosis of surgically resected BRCA-associated PDAC patients in a single-arm, uncontrolled, retrospective study. However, the prognostic impact of GL BRCA1/2 mutations in surgically resected PDAC has not been compared with a matched control population. Methods: A larger multi-centre, case–control retrospective analysis was performed. Cases were patients with surgically resected, BRCA1/2-associated PDAC from 2004 to 2013. Controls included surgically resected PDAC cases treated during the same time period that were either BRCA non-carriers, or had no family history of breast, ovarian or pancreatic cancers. Cases and controls were matched by: age at diagnosis (within ±5-year period) and institution. Demographics, clinical history, overall survival (OS) and disease-free survival (DFS) were abstracted from patient records. Statistical comparisons were assessed using χ2- and Fisher's exact test, and median DFS/OS using Kaplan–Meier method and log-rank testing. Results: Twenty-five patients with BRCA1-(n=4) or BRCA2 (N=21)-associated resectable PDAC were identified. Mean age was 55.7 years (range, 34–78 years), 48% (n=12) were females and 76% (n=19) were Jewish. Cases were compared (1 : 2) with 49 resectable PDAC controls, and were balanced for age, ethnicity and other relevant clinical and pathological features. BRCA-associated PDAC patients received neoadjuvant, or adjuvant platinum-based treatment more frequently than controls (7 out of 8 vs 6 out of 14) and (7 out of 21 vs 3 out of 44), respectively. No significant difference in median OS (37.06 vs 38.77 months, P=0.838) and in DFS (14.3 vs 12.0 months, P=0.303) could be demonstrated between cases and controls. A trend to increased DFS was observed among BRCA-positive cases treated with neoadjuvant/adjuvant platinum-containing regimens (n=10) compared with similarly treated controls (n=7) (39.1 vs 12.4 months, P=0.255). Conclusions: In this retrospective analysis, the prognosis of surgically resectable BRCA-associated PDAC is no different than that of sporadic PDAC from the same institution. The role of platinum-based adjuvant therapy in this setting requires prospective investigation. PMID:28183138
Biagi, Federico; Marchese, Alessandra; Ferretti, Francesca; Ciccocioppo, Rachele; Schiepatti, Annalisa; Volta, Umberto; Caio, Giacomo; Ciacci, Carolina; Zingone, Fabiana; D'Odorico, Anna; Carroccio, Antonio; Ambrosiano, Giuseppe; Mansueto, Pasquale; Gasbarrini, Antonio; Piscaglia, Anna Chiara; Andrealli, Alida; Astegiano, Marco; Segato, Sergio; Neri, Matteo; Meggio, Alberto; de Pretis, Giovanni; De Vitis, Italo; Gobbi, Paolo; Corazza, Gino Roberto
2014-08-07
Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history.
Atighechi, Saeid; Meybodian, Mojtaba; Dadgarnia, Mohammad Hossein; Baradaranfar, Mohammad Hossein; Behniafard, Nasim
2016-05-01
The human papilloma virus (HPV) can play a role in the development of head and neck squamous cell carcinoma (SCC). Our aim was to assess the prevalence of HPV DNA in SCC of the larynx. The impact of HPV infection on patient survival was also evaluated. This case-control study was performed in 44 patients with SCC of the larynx (case group), while the control group comprised samples obtained from cadavers with no previous history of malignancy. A preliminary pathologic evaluation was performed on all samples in the control group (36 samples) to ensure the absence of dysplasia or malignancy. Polymerase chain reaction (PCR) was used to detect HPV DNA. After completing the treatment protocol, patients were followed to assess the impact of HPV infection on overall survival (OS). PCR evaluation in the case group showed that HPV DNA was successfully isolated from 11 (25%) samples, while only two (5.6%) HPV DNA-positive were obtained from cadavers. According to these results, a significant difference was obtained in the prevalence of HPV DNA and laryngeal SCC between cases and controls (P=0.031). No statistically significant difference was observed in the OS of patients with or without HPV infection in the case group (P=0.235). Based on these results, we suggest that the prevalence of HPV infection is higher in laryngeal SCC subjects compared with healthy individuals. Although a longer OS was seen in HPV-positive patients, survival analysis did not show a significant difference in the comparison of HPV-positive and negative findings in SCC patients.
Possible role for interleukins as biomarkers for mortality and recurrence in oral cancer.
Arduino, Paolo G; Menegatti, Elisa; Cappello, Nazario; Martina, Eugenio; Gardino, Nicolò; Tanteri, Carlotta; Cavallo, Franco; Scully, Crispian; Broccoletti, Roberto
2015-05-26
Salivary and serum levels of interleukin-6 (IL-6) and interleukin-8 (IL-8) have previously been studied in oral cancer with conflicting results. We designed a controlled study to assess the correlation between pretreatment salivary and serum levels of IL-6 and IL-8, and all-cause survival and cancer recurrence in oral cancer patients. Fifty-two oral cancer patients and 52 healthy control cases were selected. In univariate analysis, salivary IL-6 and IL-8 seemed to be more expressed in cases (p<0.001 and p = 0.010, respectively). Multivariate analysis showed that higher pretreatment saliva IL-6 levels were significantly associated with better survival (hazard ratio [HR] = 8.62; 95% confidence interval [95% CI], 1.21-62.50; p = 0.031). To date, this is the largest prospective controlled study that has analyzed the pretreatment salivary and serum levels of IL-6 and IL-8 in oral cancer patients, suggesting salivary IL-6 as a possible prognostic biomarker. But further validation in a larger sample is still necessary.
Elaimy, Ameer L.; Thumma, Sudheer R.; Lamm, Andrew F.; Mackay, Alexander R.; Lamoreaux, Wayne T.; Fairbanks, Robert K.; Demakas, John J.; Cooke, Barton S.; Lee, Christopher M.
2012-01-01
Brain metastases are the most common cancerous neoplasm in the brain. The treatment of these lesions is challenging and often includes a multimodality management approach with whole-brain radiation therapy, stereotactic radiosurgery, and neurosurgery options. Although advances in biomedical imaging technologies and the treatment of extracranial cancer have led to the overall increase in the survival of brain metastases patients, the finding that select patients survive several years remains puzzling. For this reason, we present the case of a 70-year-old patient who was diagnosed with multiple brain metastases from small-cell lung cancer five years ago and is currently alive following treatment with chemotherapy for the primary cancer and whole-brain radiation therapy and Gamma Knife radiosurgery on four separate occasions for the neurological cancer. Since the diagnosis of brain metastases five years ago, the patient's primary cancer has remained controlled. Furthermore, multiple repeat GKRS procedures provided this patient with high levels of local tumor control, which in combination with a stable primary cancer led to an extended period of survival and a highly functional life. Further analysis and clinical research will be valuable in assessing the durability of multiple GKRS for brain metastases patients who experience long-term survival. PMID:23091748
Honjo, Osami; Atlin, Cori R; Mertens, Luc; Al-Radi, Osman O; Redington, Andrew N; Caldarone, Christopher A; Van Arsdell, Glen S
2011-08-01
This study was to determine whether atrioventricular valve repair modifies natural history of single-ventricle patients with atrioventricular valve insufficiency and to identify factors predicting survival and reintervention. Fifty-seven (13.5%) of 422 single-ventricle patients underwent atrioventricular valve repair. Valve morphology, regurgitation mechanism, and ventricular morphology and function were analyzed for effect on survival, transplant, and reintervention with multivariate logistic and Cox regression models. Comparative analysis used case-matched controls. Atrioventricular valve was tricuspid in 67% and common in 28%. Ventricular morphology was right in 83%. Regurgitation mechanisms were prolapse (n = 24, 46%), dysplasia (n = 18, 35%), annular dilatation (n = 8, 15%), and restriction or cleft (n = 2, 4%). Postrepair insufficiency was none or trivial in 14 (26%), mild in 33 (61%), and moderate in 7 (13%). Survival in repair group was lower than in matched controls (78.9% vs 92.7% at 1 year, 68.7% vs 90.6% at 3 years, P = .015). Patients with successful repair and normal ventricular function had equivalent survival to matched controls (P = .36). Independent predictors for death or transplant included increased indexed annular size (P = .05), increased cardiopulmonary bypass time (P = .04), and decreased postrepair ventricular function (P = .01). Ventricular dilation was a time-related factor for all events, including failed repair. Survival was lower in single-ventricle patients operated on for atrioventricular valve insufficiency than in case-matched controls. Patients with little postoperative residual regurgitation and preserved ventricular function had equivalent survival to controls. Lower grade ventricular function and ventricular dilation correlated with death and repair failure, suggesting that timing of intervention may affect outcome. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.
2014-01-01
Background Coeliac disease is a common enteropathy characterized by an increased mortality mainly due to its complications. The natural history of complicated coeliac disease is characterised by two different types of course: patients with a new diagnosis of coeliac disease that do not improve despite a strict gluten-free diet (type A cases) and previously diagnosed coeliac patients that initially improved on a gluten-free diet but then relapsed despite a strict diet (type B cases). Our aim was to study the prognosis and survival of A and B cases. Methods Clinical and laboratory data from coeliac patients who later developed complications (A and B cases) and sex- and age-matched coeliac patients who normally responded to a gluten-free diet (controls) were collected among 11 Italian centres. Results 87 cases and 136 controls were enrolled. Complications tended to occur rapidly after the diagnosis of coeliac disease and cumulative survival dropped in the first months after diagnosis of complicated coeliac disease. Thirty-seven cases died (30/59 in group A, 7/28 in group B). Type B cases presented an increased survival rate compared to A cases. Conclusions Complicated coeliac disease is an extremely serious condition with a high mortality and a short survival. Survival depends on the type of natural history. PMID:25103857
Manor, Yifat; Chaushu, Gavriel; Lorean, Adi; Mijiritzky, Eithan
2015-01-01
To evaluate the survival rate of dental implants replacing failed implants in grafted maxillary sinuses using the lateral approach vs nongrafted posterior maxillae. A retrospective analysis was conducted to study the survival of secondary dental implants inserted in the posterior maxilla in previously failed implant sites between the years 2000 and 2010. The study group consisted of patients who had also undergone maxillary sinus augmentation, and the control group consisted of patients in whom implants in the posterior maxilla had failed. Clinical and demographic data were analyzed using a structured form. Seventy-five patients with a total of 75 replaced implants were included in the study. The study group comprised 40 patients and the control group, 35 patients. None of the replaced implants in the study group failed, resulting in an overall survival of 100%; three replaced implants in the control group failed (92% survival). The main reason for the primary implant removal was lack of osseointegration (35 [87.5%] of 40 study group implants and 23 [65.7%] of 35 control group implants [P = .027]). The difference between the groups with regard to the timing of primary implant failure was statistically significant. The study group had more early failures of the primary implant than did the control group (77% vs 62%; P = .038). Dental implants replaced in the posterior maxilla had a high survival rate. A higher rate of survival was found in augmented maxillary sinus sites. Within the limits of the present study, it can be concluded that previous implant failures in the grafted maxillary sinus should not discourage practitioners from a second attempt.
Freeman, Randall J; Li, Yuanzhang; Niebuhr, David W
2011-05-01
The estimated incidence of idiopathic venous thromboembolism (IVTE) cases in the United States ranges from 24,000 to 282,000/year. This analysis explores the incidence and prevalence of IVTE in the military and if cases experience increased attrition. The Defense Medical Surveillance System was searched for incident IVTE cases from 1998 through 2007. Enlisted cases were each matched to 3 controls. Kaplan-Meier survival analysis and Cox proportional hazard modeling were performed. We matched 463 cases to 1,389 controls. Outpatient IVTE rates have increased markedly from 1998 through 2007. Cases of all-cause attrition risk (0.56 [95% CI = 0.44, 0.72]) and rates were significantly less than controls (p < 0.0001), and cases of medical attrition risk (1.64 [95% CI = 1.13, 2.37]) and rates were significantly higher (p < 0.01). Increasing rates with lower attrition suggests increasing case prevalence. Health care providers must maintain a high index of suspicion for venous thromboembolism to minimize adverse sequelae affecting health, unit readiness, and medical costs.
Evaluating disease management program effectiveness: an introduction to survival analysis.
Linden, Ariel; Adams, John L; Roberts, Nancy
2004-01-01
Currently, the most widely used method in the disease management industry for evaluating program effectiveness is the "total population approach." This model is a pretest-posttest design, with the most basic limitation being that without a control group, there may be sources of bias and/or competing extraneous confounding factors that offer plausible rationale explaining the change from baseline. Survival analysis allows for the inclusion of data from censored cases, those subjects who either "survived" the program without experiencing the event (e.g., achievement of target clinical levels, hospitalization) or left the program prematurely, due to disenrollement from the health plan or program, or were lost to follow-up. Additionally, independent variables may be included in the model to help explain the variability in the outcome measure. In order to maximize the potential of this statistical method, validity of the model and research design must be assured. This paper reviews survival analysis as an alternative, and more appropriate, approach to evaluating DM program effectiveness than the current total population approach.
Out-of-hospital cardiac arrest survival in international airports.
Masterson, Siobhán; McNally, Bryan; Cullinan, John; Vellano, Kimberly; Escutnaire, Joséphine; Fitzpatrick, David; Perkins, Gavin D; Koster, Rudolph W; Nakajima, Yuko; Pemberton, Katherine; Quinn, Martin; Smith, Karen; Jónsson, Bergþór Steinn; Strömsöe, Anneli; Tandan, Meera; Vellinga, Akke
2018-03-14
The highest achievable survival rate following out-of-hospital cardiac arrest is unknown. Data from airports serving international destinations (international airports) provide the opportunity to evaluate the success of pre-hospital resuscitation in a relatively controlled but real-life environment. This retrospective cohort study included all cases of out-of-hospital cardiac arrest at international airports with resuscitation attempted between January 1st, 2013 and December 31st, 2015. Crude incidence, patient, event characteristics and survival to hospital discharge/survival to 30 days (survival) were calculated. Mixed effect logistic regression analyses were performed to identify predictors of survival. Variability in survival between airports/countries was quantified using the median odds ratio. There were 800 cases identified, with an average of 40 per airport. Incidence was 0.024/100,000 passengers per year. Percentage survival for all patients was 32%, and 58% for patients with an initial shockable heart rhythm. In adjusted analyses, initial shockable heart rhythm was the strongest predictor of survival (odds ratio, 36.7; 95% confidence interval [CI], 15.5-87.0). In the bystander-witnessed subgroup, delivery of a defibrillation shock by a bystander was a strong predictor of survival (odds ratio 4.8; 95% CI, 3.0-7.8). Grouping of cases was significant at country level and survival varied between countries. In international airports, 32% of patients survived an out-of-hospital cardiac arrest, substantially more than in the general population. Our analysis suggested similarity between airports within countries, but differences between countries. Systematic data collection and reporting are essential to ensure international airports continually maximise activities to increase survival. Copyright © 2018 Elsevier B.V. All rights reserved.
Atighechi, Saeid; Meybodian, Mojtaba; Dadgarnia, Mohammad Hossein; Baradaranfar, Mohammad Hossein; Behniafard, Nasim
2016-01-01
Introduction: The human papilloma virus (HPV) can play a role in the development of head and neck squamous cell carcinoma (SCC). Our aim was to assess the prevalence of HPV DNA in SCC of the larynx. The impact of HPV infection on patient survival was also evaluated. Materials and Methods: This case-control study was performed in 44 patients with SCC of the larynx (case group), while the control group comprised samples obtained from cadavers with no previous history of malignancy. A preliminary pathologic evaluation was performed on all samples in the control group (36 samples) to ensure the absence of dysplasia or malignancy. Polymerase chain reaction (PCR) was used to detect HPV DNA. After completing the treatment protocol, patients were followed to assess the impact of HPV infection on overall survival (OS). Results: PCR evaluation in the case group showed that HPV DNA was successfully isolated from 11 (25%) samples, while only two (5.6%) HPV DNA-positive were obtained from cadavers. According to these results, a significant difference was obtained in the prevalence of HPV DNA and laryngeal SCC between cases and controls (P=0.031). No statistically significant difference was observed in the OS of patients with or without HPV infection in the case group (P=0.235). Conclusion: Based on these results, we suggest that the prevalence of HPV infection is higher in laryngeal SCC subjects compared with healthy individuals. Although a longer OS was seen in HPV-positive patients, survival analysis did not show a significant difference in the comparison of HPV-positive and negative findings in SCC patients. PMID:27429948
[Method to calculate the additional hospital stay in patients with cross infection].
Angeles-Garay, Ulises; Velázquez-Chávez, Yesenia; Molinar-Ramos, Fernando; Anaya-Flores, Verónica E; Uribe-Márquez, Samuel E
2009-01-01
To calculate additional hospital stay due to specific cross infection. Cases and controls study; matched by age +/- 2 years, sex, specialty in which were taken care, diagnosis, surgical procedure and hospitalization stay, between July 2005-June 2006. t test, chi(2) to calculate death risk, Kaplan-Meier analysis to calculate survival, Hosmer-Lemeshow test to know the contribution of cross infection for additional hospital stay due to cross infection (AHSDCI). We identified 851 patients with 1347 cross infection in 16 528 discharges. We could match 677. The cases stayed 25.42 days and the controls 13.29 (p < 0.01). The death risk for the cases was 5.8 (CI 95 % = 3.7-8.6, p < 0.01), four weeks survival 55.3 % for cases and 79.2 % for the controls. The AHSDCI for pneumonia was 10.39 days, urinary-tract-infection 6.28, bacteremia 8.92, vascular-catheter-related infection 3.31, surgical site infections 7.42, and skin and soft-tissue-infection 3.31 (p < 0.05). We used a multivariate model fitted to patient's gravity and complexity to extract the proportion days of AHSDCI of each cross infection.
Evaluation of margins in head and neck squamous cell carcinoma from the surgeon's perspective.
Baumeister, Philipp; Baumüller, Konstantin; Harréus, Ulrich; Reiter, Maximilian; Welz, Christian
2018-05-01
The surgeon's evaluation of resection status based on frozen section analysis during operation and pathological examination of resected specimens often differ. For this study, we recapitulated the surgeon's perspective during an operation, accordingly classified the evaluation of margins by the surgeon, and analyzed its impact on the outcome compared with the pathological results. This was a retrospective analysis. As data sources, paper-based and digital patient files, as well as the Munich Cancer Registry database were used. Three hundred ninety-six cases were included in this analysis. Only the evaluation of margins by the surgeon influenced local control, and the pathological results influenced disease-free survival (DFS). Surprisingly, margins of >5 mm of normal tissue to cancer growth led to local control and overall survival (OS) significantly worse than 1 to 5-mm resections. The evaluation of margins by the surgeon is of significant importance for local control and OS. It is largely based on frozen section analysis, which, therefore, should be used whenever possible. © 2018 Wiley Periodicals, Inc.
Kelner, Natalie; Vartanian, José Guilherme; Pinto, Clóvis Antônio Lopes; Coutinho-Camillo, Cláudia Malheiros; Kowalski, Luiz Paulo
2014-09-01
The aim of this study was to evaluate the results of elective neck dissection compared with observation (control group) in selected cases of early carcinoma of the oral tongue and floor of the mouth. It was a retrospective analysis of 222 patients who had the tumour resected (161 also had elective neck dissection). Occult lymph node metastases were detected in 33/161 (21%), and neck recurrences were diagnosed in 10 of the 61 patients in the control group (16%). Occult lymph node metastases reduced the 5-year disease-specific survival from 90% to 65% (p=0.001) and it was 96% among the controls. The 5-year disease-specific survival was 85% in the group treated by neck dissection and 96% in the observation group (p=0.09). Rigorous follow-up of selected low risk patients is associated with high rates of salvage, and overall survival was similar to the observed survival in patients treated by elective neck dissection. Observation is a reasonable option in the treatment of selected patients. Copyright © 2014 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.
Johansson, Mattias; Fanidi, Anouar; Muller, David C.; Bassett, Julie K.; Midttun, Øivind; Vollset, Stein Emil; Travis, Ruth C.; Palli, Domenico; Mattiello, Amalia; Sieri, Sabina; Trichopoulou, Antonia; Lagiou, Pagona; Trichopoulos, Dimitrios; Ljungberg, Börje; Hallmans, Göran; Weiderpass, Elisabete; Skeie, Guri; González, Carlos A.; Dorronsoro, Miren; Peeters, Petra H.; Bueno-de-Mesquita, H. B(as).; Ros, Martine M.; Boutron Ruault, Marie-Christine; Fagherazzi, Guy; Clavel, Françoise; Sánchez, María-José; Gurrea, Aurelio Barricarte; Navarro, Carmen; Quiros, J. Ramon; Overvad, Kim; Tjønneland, Anne; Aleksandrova, Krassimira; Vineis, Paolo; Gunter, Marc J.; Kaaks, Rudolf; Giles, Graham; Relton, Caroline; Riboli, Elio; Boeing, Heiner; Ueland, Per Magne; Severi, Gianluca; Brennan, Paul
2014-01-01
Background The etiology of renal cell carcinoma (RCC) is only partially understood, but a metabolic component appears likely. We investigated biomarkers of one-carbon metabolism and RCC onset and survival. Methods The European Prospective Investigation into Cancer and Nutrition (EPIC) recruited 385747 participants with blood samples between 1992 and 2000, and this analysis included 556 RCC case-control pairs. A subsequent replication study included 144 case-control pairs nested within the Melbourne Collaborative Cohort Study (MCCS). Plasma concentrations of vitamin B2, vitamin B6, folate, vitamin B12, methionine and homocysteine were measured in prediagnostic samples and evaluated with respect to RCC risk using conditional and unconditional logistic regression models, and to all-cause mortality in RCC cases using Cox regression models. All statistical tests were two-sided. Results EPIC participants with higher plasma concentrations of vitamin B6 had lower risk of RCC, the odds ratio comparing the 4th and 1st quartiles (OR4vs1) being 0.40 95% confidence interval [CI] = 0.28 to 0.57, P trend < .001. We found similar results after adjusting for potential confounders (adjusted P trend < .001). In survival analysis, the hazard ratio for all-cause mortality in RCC cases when comparing the 4th and 1st quartiles (HR4vs1) of vitamin B6 was 0.57 (95% CI = 0.37 to 0.87, P trend < .001). Subsequent replication of these associations within the MCCS yielded very similar results for both RCC risk (OR4vs1 = 0.47, 95% CI = 0.23 to 0.99, P trend = .07) and all-cause mortality (HR4vs1 = 0.56, 95% CI = 0.27 to 1.17, P trend = .02). No association was evident for the other measured biomarkers. Conclusion Study participants with higher circulating concentrations of vitamin B6 had lower risk of RCC and improved survival following diagnosis in two independent cohorts. PMID:25376861
Kuo, Phoebe; Sosa, Julie A; Burtness, Barbara A; Husain, Zain A; Mehra, Saral; Roman, Sanziana A; Yarbrough, Wendell G; Judson, Benjamin L
2016-06-15
The current study was performed to characterize trends and survival outcomes for chemotherapy in the definitive and adjuvant treatment of hypopharyngeal cancer in the United States. A total of 16,248 adult patients diagnosed with primary hypopharyngeal cancer without distant metastases between 1998 and 2011 were identified in the National Cancer Data Base. The association between treatment modality and overall survival was analyzed using Kaplan-Meier survival curves and 5-year survival rates. A multivariate Cox regression analysis was performed on a subset of 3357 cases to determine the treatment modalities that predict improved survival when controlling for demographic and clinical factors. There was a significant increase in the use of chemotherapy with radiotherapy both as definitive treatment (P<.001) and as adjuvant chemoradiotherapy with surgery (P=.001). This was accompanied by a decrease in total laryngectomy/pharyngectomy rates (P<.001). Chemoradiotherapy was associated with improved 5-year survival compared with radiotherapy alone in the definitive setting (31.8% vs 25.2%; log rank P<.001). Similarly, in multivariateanalysis, definitive radiotherapy was found to be associated with compromised survival compared with definitive chemoradiotherapy (hazard ratio, 1.51; P<.001). Survival analysis revealed that overall 5-year survival rates were higher for chemoradiotherapy compared with radiotherapy alone in the definitive setting, but were comparable between surgery with chemoradiotherapy and surgery with radiotherapy. Cancer 2016;122:1853-60. © 2016 American Cancer Society. © 2016 American Cancer Society.
Blanchard, Pierre; Belkhir, Farid; Temam, Stéphane; El Khoury, Clément; De Felice, Francesca; Casiraghi, Odile; Patrikidou, Anna; Mirghani, Haitham; Levy, Antonin; Even, Caroline; Gorphe, Philippe; Nguyen, France; Janot, François; Tao, Yungan
2017-03-01
There is controversy regarding prognosis and treatment of young patients with oral cavity cancer compared to their older counterparts. We conducted a retrospective case-matched analysis of all adult patients younger than 40 years and treated at our institution for a squamous cell carcinoma of the oral cavity. Only non-metastatic adult patients (age >18) with oral tongue cancer were eventually included and matched 1:1 with patients over 40 years of age, at least 20 years older than the cases, with same T and N category and treatment period. Sixty-three patients younger than 40 had an oral cavity squamous cell cancer out of which 57 had an oral tongue primary during the period 1999-2012, and 50 could be matched with an older control. No difference could be seen between younger and older patients with regard to overall, cancer-specific, or progression-free survival. The patterns of failure were similar, although in young patients, almost all failures occurred during the first 2 years following treatment. Although overall survival shows a trend toward lower survival in older patients, cancer-specific survival and analysis of pattern failure suggest that disease prognosis is similar between young and older adults with oral tongue cancer. Further work is needed to identify the younger patients with poorer prognosis who overwhelmingly fail during the first year after treatment and could benefit from treatment intensification. Until then, young adults ought to be treated using standard guidelines.
Ruano, R; Rodo, C; Peiro, J L; Shamshirsaz, A A; Haeri, S; Nomura, M L; Salustiano, E M A; de Andrade, K K; Sangi-Haghpeykar, H; Carreras, E; Belfort, M A
2013-10-01
To document perinatal outcomes following use of the 'Solomon technique' in the selective photocoagulation of placental anastomoses for severe twin-twin transfusion syndrome (TTTS). Between January 2010 and July 2012, data were collected from 102 consecutive monochorionic twin pregnancies complicated by severe TTTS that underwent fetoscopic laser ablation at four different centers. We compared outcomes between subjects that underwent selective laser coagulation using the Solomon technique (cases) and those that underwent selective laser coagulation without this procedure (controls). Of the 102 pregnancies examined, 26 (25.5%) underwent the Solomon technique and 76 (74.5%) did not. Of the 204 fetuses, 139 (68.1%) survived up to 30 days of age. At least one twin survived in 82 (80.4%) pregnancies and both twins survived in 57 (55.9%) pregnancies. When compared with the control group, the Solomon-technique group had a significantly higher survival rate for both twins (84.6 vs 46.1%; P < 0.01) and a higher overall neonatal survival rate (45/52 (86.5%) vs 94/152 (61.8%); P < 0.01). Use of the Solomon technique remained independently associated with dual twin survival (adjusted odds ratio (aOR), 11.35 (95% CI, 3.11-53.14); P = 0.0007) and overall neonatal survival rate (aOR, 4.65 (95% CI, 1.59-13.62); P = 0.005) on multivariable analysis. There were no cases of recurrent TTTS or twin anemia-polycythemia sequence (TAPS) in the Solomon-technique group. Use of the Solomon technique following selective laser coagulation of placental anastomoses appears to improve twin survival and may reduce the risk of recurrent TTTS and TAPS. Our data support the idea of performing a randomized controlled trial to evaluate the effectiveness of the Solomon technique. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.
Zhang, Y W; Chen, L; Bai, Y; Zheng, X
2011-09-01
Published data on the long-term survival results of patients with localized esophageal carcinoma receiving late course accelerated hyper-fractionated radiotherapy (LCAF RT) versus conventional fractionated radiotherapy (CF RT) are inconclusive. In order to derive a more precise estimation of the both treatment-regimes, a meta-analysis based on systematic review of published articles was performed. A meta-analysis was performed using trials identified through Pubmed and Chinese national knowledge infrastructure. Results in 5-year survival and 5-year local control were collected from randomized trials comparing LCAF RT with CF RT. Review Manager (The Cochrane Collaboration, Oxford, England) and Stata software (Stata Corporation, College Station, TX, USA) were used for data management. A total of 11 trials were involved in this analysis with 572 cases and 567 controls. Our results showed that LCAF RT, compared with CF RT, significantly improved the 5-year survival (odds ratio [OR]= 2.93, 95% confidence interval [CI]: 2.15-4.00, P < 0.00001) and 5-year local control (OR = 3.96, 95% CI: 2.91-5.38, P < 0.00001). LCAF RT was more therapeutically beneficial than CF RT in the localized esophageal carcinoma. © 2011 Copyright the Authors. Journal compilation © 2011, Wiley Periodicals, Inc. and the International Society for Diseases of the Esophagus.
Head and neck adenoid cystic carcinoma: A prospective multicenter REFCOR study of 95 cases.
Meyers, M; Granger, B; Herman, P; Janot, F; Garrel, R; Fakhry, N; Poissonnet, G; Baujat, B
2016-02-01
To describe the clinical, histological and therapeutic characteristics of a prospective multicenter series of 95 head and neck adenoid cystic carcinoma patients, and to determine any prognostic factors for disease-free survival. Ninety-five patients with adenoid cystic carcinoma were included in the Réseau d'Expertise Français Des Cancers ORL Rares (REFCOR, French Rare Head and Neck Cancer Expert Network) database between 2009 and 2012. The primary site was the salivary glands in 39 cases, sinus cavities (including hard palate) in 36 cases, pharynx-larynx-trachea in 14 cases, and lips and oral cavity in 4 cases. The tumor was stage I in 15% of cases, stage II in 23%, stage III in 26% and stage IV in 36%. Nine patients had cervical lymph node involvement and 5 had metastases at diagnosis. Fifty-six percent of patients were managed by surgery with postoperative radiation therapy. During follow-up, 3 patients died, 9 developed metastases and 12 showed recurrence or local progression. Mean follow-up was 18 months. On univariate analysis, disease-free survival correlated with T stage (P=0.05), N stage (P=0.003), resection margins (P=0.04), lymph node involvement on histology (P=0.01), and absence of chemotherapy (P=0.03). On multivariate analysis, disease-free survival correlated with T stage (P=0.01), N stage (P=0.09) and surgery (P=0.005). The essential issue in adenoid cystic carcinoma is long-term control. The present results confirm that the reference attitude is radical surgical resection for optimal local control. Adjuvant radiation therapy did not emerge as a prognostic factor. This study also provides a starting-point for translational studies in pathology and genetics. Copyright © 2015 Elsevier Masson SAS. All rights reserved.
Chronic kidney disease in dogs in UK veterinary practices: prevalence, risk factors, and survival.
O'Neill, D G; Elliott, J; Church, D B; McGreevy, P D; Thomson, P C; Brodbelt, D C
2013-01-01
The prevalence for chronic kidney disease (CKD) in dogs varies widely (0.05-3.74%). Identified risk factors include advancing age, specific breeds, small body size, and periodontal disease. To estimate the prevalence and identify risk factors associated with CKD diagnosis and survival in dogs. Purebred dogs were hypothesized to have higher CKD risk and poorer survival characteristics than crossbred dogs. A merged clinical database of 107,214 dogs attending 89 UK veterinary practices over a 2-year period (January 2010-December 2011). A longitudinal study design estimated the apparent prevalence (AP) whereas the true prevalence (TP) was estimated using Bayesian analysis. A nested case-control study design evaluated risk factors. Survival analysis used the Kaplan-Meier survival curve method and multivariable Cox proportional hazards regression modeling. The CKD AP was 0.21% (95% CI: 0.19-0.24%) and TP was 0.37% (95% posterior credibility interval 0.02-1.44%). Significant risk factors included increasing age, being insured, and certain breeds (Cocker Spaniel, Cavalier King Charles Spaniel). Cardiac disease was a significant comorbid disorder. Significant clinical signs included halitosis, weight loss, polyuria/polydipsia, urinary incontinence, vomiting, decreased appetite, lethargy, and diarrhea. The median survival time from diagnosis was 226 days (95% CI 112-326 days). International Renal Interest Society stage and blood urea nitrogen concentration at diagnosis were significantly associated with hazard of death due to CKD. Chronic kidney disease compromises dog welfare. Increased awareness of CKD risk factors and association of blood biochemistry results with survival time should facilitate diagnosis and optimize case management to improve animal survival and welfare. Copyright © 2013 by the American College of Veterinary Internal Medicine.
Min Lee, Charles Kyung; Li, Shufeng; Tran, Duy Cong; Zhu, Gefei Alex; Kim, Jinah; Kwong, Bernice Y; Chang, Anne Lynn S
2018-05-29
Cutaneous adverse events are common with Programmed Death (PD)-1/ PD-Ligand (L)1 inhibitors. However, the nature of the specific cutaneous adverse event of dermatitis has not been investigated across various PD-1/PD-L1 inhibitors. Oncologic outcomes potentially associated with dermatitis are not well characterized. (s): To assess the nature of dermatitis after PD-1/PD-L1 inhibitor exposure and oncologic outcomes associated with dermatitis. Retrospective, matched, case-control study conducted at a single academic center. The most common histologic patterns were lichenoid dermatitis (50%) and spongiotic dermatitis (40%). Overall tumor response rate was 65.0% for cases and 17.0% for controls (p=0.0007), odds ratio: 7.3 (95% CI 2.3-23.1). Progression Free Survival (PFS) and Overall Survival (OS) times were significantly longer for cases than controls by Kaplan-Meier analysis (p<0.0001 and 0.0203, respectively). Retrospective design and relatively small sample size precluded matching on all cancer types. Lichenoid and spongiotic dermatitis associated with PD-1/PD-L1 inhibitors could be a sign of robust immune response and improved oncologic outcomes. The predictive value of PD-1/PD-L1 related dermatitis on cancer outcomes awaits investigation through prospective multicenter studies for specific cancer types. Copyright © 2018. Published by Elsevier Inc.
Ishida, Tsunehiro; Kasumi, Fujio; Sakamoto, Goi; Makita, Masujiro; Tominaga, Takeshi; Simozuma, Kohjiro; Enomoto, Kohji; Fujiwara, Kiyoshi; Nanasawa, Takeshi; Fukutomi, Takashi; Hirota, Teruyuki; Fukuda, Mamoru; Miura, Shigeto; Koyama, Hiroki; Inaji, Hideo; Sonoo, Hiroshi
1992-01-01
Clinicopathologic characteristics and prognosis of breast cancer patients associated with pregnancy and lactation were clarified by means of a case‐control study of matched non‐pregnant and non‐lactating patients with breast cancer. From 18 institutions in Japan, a total of 192 subjects with breast cancer diagnosed during pregnancy (72 cases) and lactation (120 cases) were collected between 1970 and 1988, accounting for 0.76% of all breast cancer patients. The duration of symptoms was longer and tumor size was larger in the study subjects. Although the disease‐free interval was longer than that in the control patients, the survival time was shorter. There was no characteristic difference in histologic type. Vascular invasion and lymph node metastasis were found more frequently in the subjects. The positive rates of estrogen receptor and progesterone receptor were lower in the subjects. The 5‐ and 10‐year survival rates of the study patients were 65% and 55%, respectively, and these survivals were significantly lower than those of the control (P < 0.001). The survival rates were poorer in the subjects, in accordance with stage and lymph node metastasis. The results suggest that most of the patients with breast cancer diagnosed during pregnancy and lactation are in a more advanced stage because of a delay in detection and diagnosis, and hence have unfavorable prognosis. Therefore, it is important to diagnose and treat early for improvement of prognosis in patients with breast cancer during pregnancy and lactation. PMID:1483929
Loan, James J M; Mankahla, Ncedile; Meintjes, Graeme; Fieggen, A Graham
2017-10-16
Hydrocephalus is a recognised complication of human immunodeficiency virus (HIV)-related opportunistic infections. Symptomatic raised cerebrospinal fluid pressure can be treated with ventriculoperitoneal shunt insertion (VPS). In HIV-infected patients however, there is a concern that VPS might be associated with unacceptably high rates of mortality. We aim to systematically review and appraise published literature to determine reported outcomes and identify predictors of outcome following VPS in relevant subgroups of HIV-infected adults. The following electronic databases will be searched: The Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (PubMed), EMBASE, CINAHL (EBSCOhost), LILACS (BIREME), Research Registry ( www.researchregistry.com ), the metaRegister of Controlled Trials (mRCT) ( www.controlled-trials.com ), ClinicalTrials.gov ( www.clinicaltrials.gov ) and OpenSIGLE database. Any randomised studies, cohort studies, case-control studies, interrupted time series or sequential case series reporting survival following VPS in HIV-infected individuals will be included. If high-quality homogenous studies exist, meta-analysis will be conducted to determine 1-, 6- and 12-month mortality with comparison made between underlying aetiologies of hydrocephalus. This study will generate a comprehensive review of VPS in HIV-infected patients for publication. The primary outcome of meta-analysis is 12-month survival. If only low-quality, heterogeneous studies are available, this study will demonstrate this deficiency and will be of value in justifying and aiding the design of future studies. PROSPERO CRD42016052239.
Archer, D C; Pinchbeck, G L; Proudman, C J
2011-08-01
Epiploic foramen entrapment (EFE) has been associated with reduced post operative survival compared to other types of colic but specific factors associated with reduced long-term survival of these cases have not been evaluated in a large number of horses using survival analysis. To describe post operative survival of EFE cases and to identify factors associated with long-term survival. A prospective, multicentre, international study was conducted using clinical data and long-term follow-up information for 126 horses diagnosed with EFE during exploratory laparotomy at 15 clinics in the UK, Ireland and USA. Descriptive data were generated and survival analysis performed to identify factors associated with reduced post operative survival. For the EFE cohort that recovered following anaesthesia, survival to hospital discharge was 78.5%. Survival to 1 and 2 years post operatively was 50.6 and 34.3%, respectively. The median survival time of EFE cases undergoing surgery was 397 days. Increased packed cell volume (PCV) and increased length of small intestine (SI) resected were significantly associated with increased likelihood of mortality when multivariable analysis of pre- and intraoperative variables were analysed. When all pre-, intra- and post operative variables were analysed separately, only horses that developed post operative ileus (POI) were shown to be at increased likelihood of mortality. Increased PCV, increased length of SI resected and POI are all associated with increased likelihood of mortality of EFE cases. This emphasises the importance of early diagnosis and treatment and the need for improved strategies in the management of POI in order to reduce post operative mortality in these cases. The present study provides evidence-based information to clinicians and owners of horses undergoing surgery for EFE about long-term survival. These results are applicable to university and large private clinics over a wide geographical area. © 2011 EVJ Ltd.
The HLA-matching effect in different cohorts of kidney transplant recipients: 10 years later.
Sasaki, Nori; Idica, Adam
2010-01-01
Almost all the HLA-matching effects found by the 2000 analysis were confirmed by this study. The only HLA-matching effect found in the 2000 analysis that disappeared were those of "small matching effect" found in sub-populations of type I diabetes (PRA < 10%, donor age 20-35). The 2000 analysis found a lack of HLA matching effect in non-African American kidney transplant patients with type I diabetes between 1987 and 2000. The 2000 analysis found that a patients' ethnic group was a factor in graft survival; African American patients were found to have a significantly lower 10-year graft survival in the 5 or 6 mismatched group (27%) compared to Caucasian patients (40%). In addition, Asian patients (42%) had higher graft survival compared to that of Caucasian patients. In this study, we observe a similar pattern with death-censored graft analysis for all ethnic groups with 10-year graft survivals at 72.9% for Asians, 69.5% for Caucasians, and 49.3% for African Americans. There was an overall lack of HLA-matching effect on patient survival in the 2000 analysis. In our current analysis, the patient survivals remained virtually the same despite moderate increase in graft survival over the same period of time. The HLA-C locus mismatch was found to have additive effect to the 10-year graft survival trends observed in A and B mismatch cases. HLA-DQ mismatch on the other hand, showed limited HLA-matching effect and did not show the same additive effect as C. There are various possible issues in the DQ mismatch analysis, from the consistency of DQ typing results, lack of diversity in the DQ antigen, to the possibility of DQ mismatch having little effect on the graft survival. Utilizing kidney transplant cases performed from 1995 through 2000, the 2000 analysis projected 10-year survivals of 64% and 47% for the 0 ABDR mismatch and 5 or 6 ABDR mismatched cases respectively; the 2000 projection only missed actual death-censored survivals by 9% lower for the 0 mismatch and 17% lower for the 5 or 6 mismatch cases. Utilizing the transplant cases of 2005 through 2009, we projected their 10-year graft survivals for year 2020. The 10-year graft survival for 0 ABDR mismatched patients is expected to be over 85% and nearly 70% for 5 or 6 ABDR mismatched patients. The general upward trend of graft survival we have observed in the last 10 years has been dependent upon the development of novel transplant protocols and use of novel immunomodulatory reagents. This trend is likely to continue given the promise of new drugs and personalized healthcare. The decreasing range of the differences in the 10-year graft survival between best matched and worst matched HLA groups is also likely to continue. One interesting trend that is clearly evident is the increasing difference between the best and worst HLA-matching in terms of the associated graft half-life. The positive HLA-matching effect on long-term graft survival is clearly evident and should be taken into consideration for all kidney transplants.
Chen, I-Chun; Lee, Ming-Huei; Lin, Hsuan-Hung; Wu, Shang-Liang; Chang, Kun-Min; Lin, Hsiu-Ying
2017-05-01
Interstitial cystitis/bladder pain syndrome (IC/BPS) has several well-known comorbid psychiatric manifestations, including insomnia, anxiety, and depression. We hypothesized that somatoform disorder, which is a psychosomatic disease, can be used as a sensitive psychiatric phenotype of IC/BPS. We investigated whether somatoform disorder increases the risk of IC/BPS.A nested case-control study and a retrospective cohort study were followed up over a 12-year period (2002-2013) in the Taiwan Health Insurance Reimbursement Database. In the nested case-control study, 1612 patients with IC/BPS were matched in a 1:2 ratio to 3224 controls based on propensity scores. The odds ratio for somatoform disorder was calculated using conditional logistic regression analysis. In the retrospective cohort study, 1436 patients with somatoform disorder were matched in a 1:2 ratio to 2872 patients with nonsomatoform disorder based on propensity scores. Cox regression analysis was used to estimate the hazard ratio associated with the development of IC/BPS in patients with somatoform disorder, and the cumulative survival probability was tested using the Kaplan-Meier analysis.We found that the odds ratio for somatoform disorder was 2.46 (95% confidence interval [CI], 1.05-5.76). Although the average time until IC/BPS development in the control subjects was 11.5 ± 1.3 years, this interval was shorter in patients with somatoform disorder (6.3 ± 3.6 years). The hazard ratio for developing IC/BPS was 2.50 (95% CI 1.23-5.58); the adjusted hazard ratio was 2.26 (95% CI 1.002-5.007). The patients and controls also differed significantly in their cumulative survival probability for IC/BPS (log rank P < .05).Evidence from the nested case-control study and retrospective cohort study consistently indicated that somatoform disorder increases the risk for IC/BPS. Our study suggests that somatoform disorder can be used as a sensitive psychiatric phenotype to predict IC/BPS. Any past history of somatoform disorder should be documented while examining patients with IC/BPS.
Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome.
Lahrouchi, Najim; Raju, Hariharan; Lodder, Elisabeth M; Papatheodorou, Efstathios; Ware, James S; Papadakis, Michael; Tadros, Rafik; Cole, Della; Skinner, Jonathan R; Crawford, Jackie; Love, Donald R; Pua, Chee J; Soh, Bee Y; Bhalshankar, Jaydutt D; Govind, Risha; Tfelt-Hansen, Jacob; Winkel, Bo G; van der Werf, Christian; Wijeyeratne, Yanushi D; Mellor, Greg; Till, Jan; Cohen, Marta C; Tome-Esteban, Maria; Sharma, Sanjay; Wilde, Arthur A M; Cook, Stuart A; Bezzina, Connie R; Sheppard, Mary N; Behr, Elijah R
2017-05-02
Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and comprehensive clinical evaluation of surviving relatives. We evaluated 302 expertly validated SADS cases with suitable DNA (median age: 24 years; 65% males) who underwent next-generation sequencing using an extended panel of 77 primary electrical disorder and cardiomyopathy genes. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. The yield of combined molecular autopsy and clinical evaluation in 82 surviving families was evaluated. A gene-level rare variant association analysis was conducted in SADS cases versus controls. A clinically actionable pathogenic or likely pathogenic variant was identified in 40 of 302 cases (13%). The main etiologies established were catecholaminergic polymorphic ventricular tachycardia and long QT syndrome (17 [6%] and 11 [4%], respectively). Gene-based rare variants association analysis showed enrichment of rare predicted deleterious variants in RYR2 (p = 5 × 10 -5 ). Combining molecular autopsy with clinical evaluation in surviving families increased diagnostic yield from 26% to 39%. Molecular autopsy for electrical disorder and cardiomyopathy genes, using ACMG guidelines for variant classification, identified a modest but realistic yield in SADS. Our data highlighted the predominant role of catecholaminergic polymorphic ventricular tachycardia and long QT syndrome, especially the RYR2 gene, as well as the minimal yield from other genes. Furthermore, we showed the enhanced utility of combined clinical and genetic evaluation. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.
Brown, Allen W; Leibson, Cynthia L; Mandrekar, Jay; Ransom, Jeanine E; Malec, James F
2014-01-01
To examine the contribution of co-occurring nonhead injuries to hazard of death after traumatic brain injury (TBI). A random sample of Olmsted County, Minnesota, residents with confirmed TBI from 1987 through 1999 was identified. Each case was assigned an age- and sex-matched, non-TBI "regular control" from the population. For "special cases" with accompanying nonhead injuries, 2 matched "special controls" with nonhead injuries of similar severity were assigned. Vital status was followed from baseline (ie, injury date for cases, comparable dates for controls) through 2008. Cases were compared first with regular controls and second with regular or special controls, depending on case type. In total, 1257 cases were identified (including 221 special cases). For both cases versus regular controls and cases versus regular or special controls, the hazard ratio was increased from baseline to 6 months (10.82 [2.86-40.89] and 7.13 [3.10-16.39], respectively) and from baseline through study end (2.92 [1.74-4.91] and 1.48 [1.09-2.02], respectively). Among 6-month survivors, the hazard ratio was increased for cases versus regular controls (1.43 [1.06-2.15]) but not for cases versus regular or special controls (1.05 [0.80-1.38]). Among 6-month survivors, accounting for nonhead injuries resulted in a nonsignificant effect of TBI on long-term mortality.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Smid, Ernst J.; Stoter, T. Rianne; Bloemena, Elisabeth
2006-08-01
Purpose: The aim of this study was to investigate the prognostic significance of epidermal growth factor (EGFr) expression in oral cavity squamous cell carcinoma (OCSCC) treated with curative surgery and postoperative radiotherapy. Methods and Materials: This retrospective study included 165 OCSCC patients. The expression of EGFr was assessed on paraffin-embedded tissue of the primary tumor by immunohistochemistry using a monoclonal antibody directed against EGFr. Intensity of the EGFr expression was scored by two authors blinded for the clinical outcome. Results: In the univariate analysis, locoregional control at 3 years (LRC) in the EGFr-negative cases was 69% compared with 77% inmore » the EGFr-positive cases (p 0.22). In the multivariate analysis for local control, a significant interaction was found between EGFr and overall treatment time of radiation (OTT). After stratification for EGFr expression, the OTT was of no importance in the EGFr-negative cases, whereas a significant difference in LRC was found in the EGFr-positive cases, in which the LRC after 3 years was 69% and 94% in case of an OTT of 0-42 days and >42 days, respectively (p = 0.009; hazard ratio = 3.42; 95% confidence interval, 1.28-8.96). No significant association was found between EGFr expression and overall survival. Conclusions: In the present study, no association was found between EGFr expression and outcome regarding locoregional control and overall survival. However, the results of the present study suggest that patients with squamous cell carcinoma of the oral cavity with high EGFr expression benefit more from a reduction of the overall treatment time of postoperative radiation than those with low EGFr expression.« less
Plantinga, N L; de Smet, A M G A; Oostdijk, E A N; de Jonge, E; Camus, C; Krueger, W A; Bergmans, D; Reitsma, J B; Bonten, M J M
2018-05-01
Selective digestive decontamination (SDD) and selective oropharyngeal decontamination (SOD) improved intensive care unit (ICU), hospital and 28-day survival in ICUs with low levels of antibiotic resistance. Yet it is unclear whether the effect differs between medical and surgical ICU patients. In an individual patient data meta-analysis, we systematically searched PubMed and included all randomized controlled studies published since 2000. We performed a two-stage meta-analysis with separate logistic regression models per study and per outcome (hospital survival and ICU survival) and subsequent pooling of main and interaction effects. Six studies, all performed in countries with low levels of antibiotic resistance, yielded 16 528 hospital admissions and 17 884 ICU admissions for complete case analysis. Compared to standard care or placebo, the pooled adjusted odds ratios for hospital mortality was 0.82 (95% confidence interval (CI) 0.72-0.93) for SDD and 0.84 (95% CI 0.73-0.97) for SOD. Compared to SOD, the adjusted odds ratio for hospital mortality was 0.90 (95% CI 0.82-0.97) for SDD. The effects on hospital mortality were not modified by type of ICU admission (p values for interaction terms were 0.66 for SDD and control, 0.87 for SOD and control and 0.47 for SDD and SOD). Similar results were found for ICU mortality. In ICUs with low levels of antibiotic resistance, the effectiveness of SDD and SOD was not modified by type of ICU admission. SDD and SOD improved hospital and ICU survival compared to standard care in both patient populations, with SDD being more effective than SOD. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.
HSP90, HSPA8, HIF-1 alpha and HSP70-2 polymorphisms in breast cancer: a case-control study.
Zagouri, Flora; Sergentanis, Theodoros N; Gazouli, Maria; Tsigginou, Alexandra; Dimitrakakis, Constantine; Papaspyrou, Irene; Eleutherakis-Papaiakovou, Evaggelos; Chrysikos, Dimosthenis; Theodoropoulos, George; Zografos, George C; Antsaklis, Aris; Dimopoulos, Athanassios-Meletios; Papadimitriou, Christos A
2012-12-01
This case control study aims to investigate the role of HSP90 Gln488His (C > G), HSP70-2 P1/P2, HIF-1 alpha C1772T and HSPA8 intronic 1541-1542delGT polymorphisms as potential risk factors and/or prognostic markers for breast cancer. 113 consecutive incident cases of histologically confirmed ductal breast cancer and 124 healthy cases were recruited. The above mentioned polymorphisms were genotyped; multivariate logistic regression was performed. HSP90 GG (His/His) genotype was associated with elevated breast cancer risk. Similarly, the allele dose-response model pointed to increase in breast cancer risk per G allele. HSP70-2 P1/P2, HSPA8 intronic 1541-1542delGT and HIF-1 alpha polymorphisms were not associated with breast cancer risk, as evidenced by the dose-response allele models. The positive association between HSP90 G allele and breast cancer risk seemed to pertain to both premenopausal and postmenopausal women. With respect to survival analysis, none of the aforementioned polymorphisms was associated with either disease-free survival or overall survival. HSP90α Gln488His polymorphism seems to be a risk factor for breast cancer. On the other hand, our study did not point to excess risk conferred by HSPA8 1541-1542delGT, Hsp70-2 P1/P2 and HIF-1α C1772T.
Gross, Arnd; Ziepert, Marita; Scholz, Markus
2012-01-01
Analysis of clinical studies often necessitates multiple graphical representations of the results. Many professional software packages are available for this purpose. Most packages are either only commercially available or hard to use especially if one aims to generate or customize a huge number of similar graphical outputs. We developed a new, freely available software tool called KMWin (Kaplan-Meier for Windows) facilitating Kaplan-Meier survival time analysis. KMWin is based on the statistical software environment R and provides an easy to use graphical interface. Survival time data can be supplied as SPSS (sav), SAS export (xpt) or text file (dat), which is also a common export format of other applications such as Excel. Figures can directly be exported in any graphical file format supported by R. On the basis of a working example, we demonstrate how to use KMWin and present its main functions. We show how to control the interface, customize the graphical output, and analyse survival time data. A number of comparisons are performed between KMWin and SPSS regarding graphical output, statistical output, data management and development. Although the general functionality of SPSS is larger, KMWin comprises a number of features useful for survival time analysis in clinical trials and other applications. These are for example number of cases and number of cases under risk within the figure or provision of a queue system for repetitive analyses of updated data sets. Moreover, major adjustments of graphical settings can be performed easily on a single window. We conclude that our tool is well suited and convenient for repetitive analyses of survival time data. It can be used by non-statisticians and provides often used functions as well as functions which are not supplied by standard software packages. The software is routinely applied in several clinical study groups.
Gross, Arnd; Ziepert, Marita; Scholz, Markus
2012-01-01
Background Analysis of clinical studies often necessitates multiple graphical representations of the results. Many professional software packages are available for this purpose. Most packages are either only commercially available or hard to use especially if one aims to generate or customize a huge number of similar graphical outputs. We developed a new, freely available software tool called KMWin (Kaplan-Meier for Windows) facilitating Kaplan-Meier survival time analysis. KMWin is based on the statistical software environment R and provides an easy to use graphical interface. Survival time data can be supplied as SPSS (sav), SAS export (xpt) or text file (dat), which is also a common export format of other applications such as Excel. Figures can directly be exported in any graphical file format supported by R. Results On the basis of a working example, we demonstrate how to use KMWin and present its main functions. We show how to control the interface, customize the graphical output, and analyse survival time data. A number of comparisons are performed between KMWin and SPSS regarding graphical output, statistical output, data management and development. Although the general functionality of SPSS is larger, KMWin comprises a number of features useful for survival time analysis in clinical trials and other applications. These are for example number of cases and number of cases under risk within the figure or provision of a queue system for repetitive analyses of updated data sets. Moreover, major adjustments of graphical settings can be performed easily on a single window. Conclusions We conclude that our tool is well suited and convenient for repetitive analyses of survival time data. It can be used by non-statisticians and provides often used functions as well as functions which are not supplied by standard software packages. The software is routinely applied in several clinical study groups. PMID:22723912
Zhao, Ming; Wang, Jian-peng; Wu, Pei-hong; Zhang, Fu-jun; Huang, Zi-lin; Li, Wang; Zhang, Liang; Pan, Chang-chuan; Li, Chuan-xing; Jiang, Yong
2010-11-09
To evaluate the clinical efficacy and survival rate of transarterial chemoembolization (TACE) alone or plus radiofrequency ablation (RFA) in patients with intermediate or advanced stage primary hepatocellular carcinoma (HCC). In this retrospective study, 467 cases received RFA or TACE plus RFA. Among them, 167 cases with strict clinical procedure (TACE alone or plus RFA) and complete follow-up data were included. Eighty-seven cases received TACE and 80 cases had TACE plus RFA between January 2000 and December 2006. Hierarchical analyses were performed using log-rank tests and survival curve was estimated by Kaplan-Meier method. A total of 167 patients received TACE alone or plus RFA for a follow-up period of 1 to 89 months. In the TACE alone group, the time-to-progression (TTP) was an average of 3.6 months. The median survival was 13 months, one-year survival rate 52.9%, three-year survival rate 11.5% and five-year survival rate 4.6%. In the TACE plus RFA group, the TTP time was an average of 10.8 months. The median survival time was 30 months, one-year survival rate 85.0%, three-year survival rate 45.0% and five-year survival rate 11.3%. In the TACE alone group, the median survival of intermediate stage HCC was 14 months, one-year survival rate 62.2%, three-year survival rate 13.3% and five-year survival rate 4.4%; In the TACE plus RFA group, the median survival of intermediate stage HCC was 14 months, one-year survival rate 90.1%, three-year survival rate 52.9% and five-year survival rate 13.7%. All differences of two groups has statistical significance (P < 0.05). In intermediate stage HCC, the median survival of TACE alone group was 14 months, one-year survival rate 62.2%, three-year survival rate 13.3%, five-year survival rate 4.4% versus 32 months, 90.1%, 52.9%, 13.7% in the TACE plus RFA group respectively. For the advanced stage HCC, the median survival time was 12 months, one-year survival rate 35%, three-year survival rate 7.1% and five-year survival rate 0 in the TACE alone group versus 28 months, 62.1%, 24.1% and 6.9% in the TACE plus RFA group (P = 0.00). There was significantly statistic difference between both groups in intermediate and advanced staging HCC. Among them, 60/485 (12.4%) patients required a therapy of post-TACE hepatic dysfunctions versus 13/168 (7.7%) in the TACE plus RFA group (P = 0.004, ANOVA method). The regimen of TACE plus RFA has the advantages of tumor control, liver function protection and survival extending in the treatment of HCC than TACE alone in intermediate or advanced stage HCC.
Pinkston, Christina M; Baumgartner, Richard N; Connor, Avonne E; Boone, Stephanie D; Baumgartner, Kathy B
2015-12-01
We investigated the association of physical activity with survival for 601 Hispanic women and 682 non-Hispanic white women who participated in the population-based breast cancer case-control New Mexico Women's Health Study. We identified 240 deaths among cases diagnosed with a first primary invasive breast cancer between 1992 and 1994, and 88 deaths among controls. Follow-up extended through 2012 for cases and 2008 for controls. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. Higher levels of total physical activity were inversely associated with all-cause mortality among Hispanic cases (Quartile (Q)4: HR = 0.55, 95% CI 0.31-0.99). A non-significant trend was observed for recreational activity in Hispanic cases also (Q4: HR = 0.50, 95% CI 0.23-1.09, p for trend = 0.08). No significant associations were noted for non-Hispanic white cases or for controls. The results suggest that increasing physical activity may be protective against mortality in Hispanic women with breast cancer, despite reporting lower levels of recreational activity than non-Hispanic white women or Hispanic controls. Public health programs in Hispanic communities should promote physical activity in women as a means of decreasing breast cancer risk and improving survival.
Schurr, Paulus; Lentz, Edda; Block, Suzette; Kaifi, Jussuf; Kleinhans, Helge; Cataldegirmen, Guellue; Kutup, Asad; Schneider, Claus; Strate, Tim; Yekebas, Emre; Izbicki, Jakob
2008-07-01
To date, the survival benefit of redo surgery in locally recurrent rectal adenocarcinoma remains unclear. In an institutional study, operations for recurrence were retrospectively analyzed. Survival was calculated using the Kaplan-Meier plot and Cox regression analysis. A total of 72 patients with local recurrence were explored or resected. In 38 patients, there was synchronous distant organ recurrence. Forty-five of 72 were re-resected and in 37 of 45 cases, R0 situations were achieved. In 11 of 38 metastasized patients, both local and distant organ recurrence were successfully removed. For obtaining tumor control, resections of inner genitals, bladder, and sacral bone were necessary in 10, 4, and 11 patients, respectively. Survival was better for patients re-resected with a median overall survival of 54.9 months, as compared with 31.1 months among non-resected patients (p = 0.0047, log-rank test). Subgroup analysis revealed that a benefit of re-resection was observed to a lesser extent in synchronous local and in distant disease. Cox analysis showed that initial Dukes stage and complete resections of local recurrences were independently determining prognosis (relative risk 1.762 and 0.689, p = 0.008 and p = 0.002, respectively). Radical surgery for local recurrence can improve survival if complete tumor clearance is achieved, and concomitant distant tumor load should not principally preclude re-resection.
[Clinical analysis of prenatal diagnosis and intervention for primary pleural effusion of 13 cases].
Wang, X Q; Li, W J; Yan, R L; Xiang, J W; Liu, M Y
2018-02-25
Objective: To optimize the clinical managements of primary fetal hydrothorax (PFHT) fetus by comparing the perinatal survival rate of different prenatal treatments. Methods: Totally 13 fetuses diagnosed with PFHT from July 2009 to December 2015 in the First Affiliated Hospital of Jinan University were collected and received prenatal expectant treatment, thoracocentesis (TC), and thoraco-amniotic shunting (TAS), respectively. The perinatal survival rate was compared among the three treatments. Results: Among 13 fetuses of PFHT, pleural effusion was absorbed or remained stable in 2(2/13) cases, and progressed in 11(11/13) cases. Six cases received expectant treatment (2 cases had termination of pregnancy due to progressing effusion, 2 cases had term delivery, and 2 cases had intrauterine death); the perinatal survival rate was 2/6. Six cases received TC (2 cases had term delivery, 2 cases had preterm delivery, and 2 cases had termination of pregnancy due to progressing effusion), the perinatal survival rate was 4/6. One case received TC+TAS (term delivery), the perinatal survival rate was 1/1. The overall perinatal survival rate of prenatal intrauterine intervention was 5/7. Conclusions: The clinical process of PFHT is changeable, and the pleural effusion will progress with gestational age. Intrauterine interventions could improve the perinatal survival rate.
Palaghita, Andreea; Jost, Daniel; Despreaux, Thomas; Bougouin, Wulfran; Beganton, Frankie; Loeb, Thomas; Tourtier, Jean Pierre; Descatha, Alexis
2016-08-01
The aim of this study was to describe the characteristics of out-of-hospital cardiac arrest (OHCA) in different workplaces, their management, and the survival rate. A post hoc analysis included all the OHCA cases that occurred at the workplace and were listed in the Fire Brigade of Paris database registry (2010 to 2014). Utstein-style variables, survival, and types of workplace were analyzed. The study included 298 OHCA cases, mostly young (44% between 18 and 50 years), male (86%), and nontraumatic (86%). Differences in the survival chain were found to be related to the types of work location: bystander cardiopulmonary resuscitation was performed in 0% to 55% of cases, and workplace-automated external defibrillators were used in 0% to 20% of cases. Long-term survival without major incapacity was 0% to 23%. The characteristics of OHCA differ as a function of the type of workplace.
Hashmi, Ahmed; Guckenberger, Matthias; Kersh, Ron; Gerszten, Peter C; Mantel, Frederick; Grills, Inga S; Flickinger, John C; Shin, John H; Fahim, Daniel K; Winey, Brian; Oh, Kevin; John Cho, B C; Létourneau, Daniel; Sheehan, Jason; Sahgal, Arjun
2016-11-01
OBJECTIVE This study is a multi-institutional pooled analysis specific to imaging-based local control of spinal metastases in patients previously treated with conventional external beam radiation therapy (cEBRT) and then treated with re-irradiation stereotactic body radiotherapy (SBRT) to the spine as salvage therapy, the largest such study to date. METHODS The authors reviewed cases involving 215 patients with 247 spinal target volumes treated at 7 institutions. Overall survival was calculated on a patient basis, while local control was calculated based on the spinal target volume treated, both using the Kaplan-Meier method. Local control was defined as imaging-based progression within the SBRT target volume. Equivalent dose in 2-Gy fractions (EQD2) was calculated for the cEBRT and SBRT course using an α/β of 10 for tumor and 2 for both spinal cord and cauda equina. RESULTS The median total dose/number of fractions of the initial cEBRT was 30 Gy/10. The median SBRT total dose and number of fractions were 18 Gy and 1, respectively. Sixty percent of spinal target volumes were treated with single-fraction SBRT (median, 16.6 Gy and EQD2/10 = 36.8 Gy), and 40% with multiple-fraction SBRT (median 24 Gy in 3 fractions, EQD2/10 = 36 Gy). The median time interval from cEBRT to re-irradiation SBRT was 13.5 months, and the median duration of patient follow-up was 8.1 months. Kaplan-Meier estimates of 6- and 12-month overall survival rates were 64% and 48%, respectively; 13% of patients suffered a local failure, and the 6- and 12-month local control rates were 93% and 83%, respectively. Multivariate analysis identified Karnofsky Performance Status (KPS) < 70 as a significant prognostic factor for worse overall survival, and single-fraction SBRT as a significant predictive factor for better local control. There were no cases of radiation myelopathy, and the vertebral compression fracture rate was 4.5%. CONCLUSIONS Re-irradiation spine SBRT is effective in yielding imaging-based local control with a clinically acceptable safety profile. A randomized trial would be required to determine the optimal fractionation.
Predictors of survival in mucosal melanoma of the head and neck.
Jethanamest, Daniel; Vila, Peter M; Sikora, Andrew G; Morris, Luc G T
2011-10-01
The head and neck is the most common site of mucosal melanoma, a cancer with poor prognosis. In contrast to cutaneous melanoma, mucosal melanoma of the head and neck (MMHN) is uncommon, with limited data regarding outcomes and prognostic factors drawn from small, single-institution case series. In order to identify factors predictive of survival, we analyzed MMHN outcomes in a large US cohort. MMHN cases (n = 815) diagnosed in the USA between 1973 and 2007 were analyzed in the Surveillance, Epidemiology, and End Results registry, and cause of death was individually determined in 778 (95.5%) cases. Kaplan-Meier survival analysis and Cox proportional hazards regression were used to analyze prognostic variables. Disease-specific survival status was determined in 778 (95.5%) cases. The 5- and 10-year rates of overall survival (OS) were 25.2 and 12.2%; disease-specific survival (DSS), 32.4 and 19.3%. On multivariable analysis, anatomic primary site was an independent predictor of OS and DSS, with tumors in the nasal cavity and oral cavity associated with survival superior to tumors in the nasopharynx and paranasal sinuses. Age > 70 years, tumor size, nodal status, and distant metastasis status were additional independent predictors of poorer survival. In this large cohort of patients with MMHN, we have identified several novel factors robustly predictive of overall and melanoma-specific survival.
Expression of E-cadherin in canine anal sac gland carcinoma and its association with survival.
Polton, G A; Brearley, M J; Green, L M; Scase, T J
2007-12-01
The objective of this study was to determine whether an association could be demonstrated between survival and the expression of the adhesion molecule E-cadherin by the neoplastic cells in a group of dogs with anal sac gland carcinomas (ASGCs). Archived formalin-fixed, paraffin wax-embedded primary tumour specimens were obtained for 36 cases of canine ASGC with known clinical management and survival data. Immunohistochemical methods were used to evaluate E-cadherin expression by the neoplastic cells and data were evaluated for an association between E-cadherin expression and survival. On univariate analysis, the median survival time for cases with tumours expressing E-cadherin in more than 75% of cells was significantly greater than that for cases with tumours expressing E-cadherin in fewer than 75% of cells (1168 versus 448 days, P = 0.0246). Both E-cadherin expression and presence or absence of distant metastases were significantly associated with survival on multivariate analysis. This study demonstrates that expression of E-cadherin at the cytoplasmic membrane in canine ASGCs is variable and potentially predictive of survival.
Garcia-Closas, Montserrat; Davis, Sean; Meltzer, Paul; Lissowska, Jolanta; Horne, Hisani N.; Sherman, Mark E.; Lee, Maxwell
2015-01-01
Identification of prognostic gene expression signatures may enable improved decisions about management of breast cancer. To identify a prognostic signature for breast cancer, we performed DNA methylation profiling and identified methylation markers that were associated with expression of ER, PR, HER2, CK5/6 and EGFR proteins. Methylation markers that were correlated with corresponding mRNA expression levels were identified using 208 invasive tumors from a population-based case-control study conducted in Poland. Using this approach, we defined the Methylation Expression Index (MEI) signature that was based on a weighted sum of mRNA levels of 57 genes. Classification of cases as low or high MEI scores were related to survival using Cox regression models. In the Polish study, women with ER-positive low MEI cancers had reduced survival at a median of 5.20 years of follow-up, HR=2.85 95%CI=1.25-6.47. Low MEI was also related to decreased survival in four independent datasets totaling over 2500 ER-positive breast cancers. These results suggest that integrated analysis of tumor expression markers, DNA methylation, and mRNA data can be an important approach for identifying breast cancer prognostic signatures. Prospective assessment of MEI along with other prognostic signatures should be evaluated in future studies. PMID:25773928
Statin use and breast cancer survival and risk: a systematic review and meta-analysis.
Wu, Qi-Jun; Tu, Chao; Li, Yuan-Yuan; Zhu, Jingjing; Qian, Ke-Qing; Li, Wen-Jing; Wu, Lang
2015-12-15
The purpose of this study is to determine the associations between statin use and breast cancer survival and risk by performing a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science up to August 2015 for identifying relevant prospective or case-control studies, or randomized clinical trials. Five prospective studies involving 60,911 patients reported the association between statin use and breast cancer mortality. Eleven prospective studies, 12 case-control studies and 9 randomized clinical trials involving 83,919 patients reported the association between statin use and breast cancer risk. After pooling estimates from all available studies, there was a significantly negative association between pre-diagnosis statin use and breast cancer mortality (for overall survival (OS): hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.54-0.84; for disease specific survival (DSS): HR = 0.72, 95% CI 0.53-0.99). There was also a significant inverse association between post-diagnosis statin use and breast cancer DSS (HR = 0.65, 95% CI 0.43-0.98), although the association with breast cancer OS did not reach statistical significance (HR = 0.71, 95% CI 0.48-1.07). Additionally, there was a non-linear relationship for the duration of post-diagnosis statin use with breast cancer specific mortality. On the other hand, with regards to the relationship between statin use and breast cancer risk, no significant association was detected. Our analyses suggest that although statin use may not influence breast cancer risk, the use of statin may be associated with decrease mortality of breast cancer patients. Further large-scale studies are warranted to validate our findings.
Crespo-Solis, Erick; Espinosa-Bautista, Karla; Alvarado-Ibarra, Martha; Rozen-Fuller, Etta; Pérez-Rocha, Fernando; Nava-Gómez, Chantal; Ortiz-Zepeda, Maricela; Álvarez-Vera, José Luis; Ramos-Peñafiel, Christian Omar; Meillón-García, Luis Antonio; Rodríguez-Rodríguez, Sergio; Pomerantz-Okon, Alan; Turrubiates-Hernández, Francisco Javier; Demichelis-Gómez, Roberta
2018-06-01
Acute lymphoblastic leukemia (ALL) is a hematologic malignancy characterized by the clonal expansion of hematopoietic lymphoid progenitors. With new target therapies, the survival of adults with ALL has improved in the past few decades. Unfortunately, there are no large ALL patient series in many Latin American countries. Data from the Acute Leukemia Workgroup that includes five Mexico City referral centers were used. Survival was estimated for adult patients with ALL during 2009-2015. In total, 559 adults with ALL were included. The median age was 28 years; 67% were classified into the adolescent and young adult group. Cytogenetic information was available in 54.5% of cases. Of the 305 analyzed cases, most had a normal caryotype (70.5%) and Philadelphia-positive was present in 16.7%. The most commonly used treatment regimen was hyper-CVAD. In approximately 20% of cases, there was considerable delay in the administration of chemotherapy. Primarily refractory cases accounted for 13.1% of patients. At the time of analysis, 26.7% of cases had survived. The 3-year overall survival was 22.1%. The main cause of death was disease progression in 228 (55.6%). Clinical and public health strategies are needed to improve diagnosis, treatment and survivorship care for adult with ALL. This multicentric report represents the largest series in Mexico of adult ALL patients in which a survival analysis and risk identification were obtained. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Gregori, Dario; Rosato, Rosalba; Zecchin, Massimo; Di Lenarda, Andrea
2005-01-01
This paper discusses the use of bivariate survival curves estimators within the competing risk framework. Competing risks models are used for the analysis of medical data with more than one cause of death. The case of dilated cardiomiopathy is explored. Bivariate survival curves plot the conjoint mortality processes. The different graphic representation of bivariate survival analysis is the major contribute of this methodology to the competing risks analysis.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Zain, Zakiyah, E-mail: zac@uum.edu.my; Ahmad, Yuhaniz, E-mail: yuhaniz@uum.edu.my; Azwan, Zairul, E-mail: zairulazwan@gmail.com, E-mail: farhanaraduan@gmail.com, E-mail: drisagap@yahoo.com
Colorectal cancer is the third and the second most common cancer worldwide in men and women respectively, and the second in Malaysia for both genders. Surgery, chemotherapy and radiotherapy are among the options available for treatment of patients with colorectal cancer. In clinical trials, the main purpose is often to compare efficacy between experimental and control treatments. Treatment comparisons often involve several responses or endpoints, and this situation complicates the analysis. In the case of colorectal cancer, sets of responses concerned with survival times include: times from tumor removal until the first, the second and the third tumor recurrences, andmore » time to death. For a patient, the time to recurrence is correlated to the overall survival. In this study, global score test methodology is used in combining the univariate score statistics for comparing treatments with respect to each survival endpoint into a single statistic. The data of tumor recurrence and overall survival of colorectal cancer patients are taken from a Malaysian hospital. The results are found to be similar to those computed using the established Wei, Lin and Weissfeld method. Key factors such as ethnic, gender, age and stage at diagnose are also reported.« less
NASA Astrophysics Data System (ADS)
Zain, Zakiyah; Aziz, Nazrina; Ahmad, Yuhaniz; Azwan, Zairul; Raduan, Farhana; Sagap, Ismail
2014-12-01
Colorectal cancer is the third and the second most common cancer worldwide in men and women respectively, and the second in Malaysia for both genders. Surgery, chemotherapy and radiotherapy are among the options available for treatment of patients with colorectal cancer. In clinical trials, the main purpose is often to compare efficacy between experimental and control treatments. Treatment comparisons often involve several responses or endpoints, and this situation complicates the analysis. In the case of colorectal cancer, sets of responses concerned with survival times include: times from tumor removal until the first, the second and the third tumor recurrences, and time to death. For a patient, the time to recurrence is correlated to the overall survival. In this study, global score test methodology is used in combining the univariate score statistics for comparing treatments with respect to each survival endpoint into a single statistic. The data of tumor recurrence and overall survival of colorectal cancer patients are taken from a Malaysian hospital. The results are found to be similar to those computed using the established Wei, Lin and Weissfeld method. Key factors such as ethnic, gender, age and stage at diagnose are also reported.
Primary Spinal Cord Melanoma: A Case Report and a Systemic Review of Overall Survival.
Zhang, Mingzhe; Liu, Raynald; Xiang, Yi; Mao, Jianhui; Li, Guangjie; Ma, Ronghua; Sun, Zhaosheng
2018-06-01
The incidence of primary spinal cord melanoma (PSCM) is rare. Several case series and case reports have been published in the literature. However, the predictive factors of PSCM survival and management options are not discussed in detail. We present a case of PSCM; total resection was achieved and chemotherapy was given postoperatively. A comprehensive search was performed on PubMed's electronic database using the words "primary spinal cord melanoma." Survival rates with various gender, location, treatment, and metastasis condition were collected from the published articles and analyzed. Fifty nine cases were eligible for the survival analysis; 54% were male and 46% were female. Patient sex did not influence overall survival. The most common location was the thorax. Patient sex and tumor location did not influence overall survival. The major presenting symptoms were weakness and paresthesia of the extremities. Metastasis or dissemination was noted in 45.16% of 31 patients. In the Kaplan-Meier survival analysis, patients who had metastasis had the worst prognosis. Extent of resection was not related to mortality. Patients who received surgery and surgery with adjuvant therapy had a better median survival than did those who had adjuvant therapy alone. Prognosis was worst in those patients who underwent only adjuvant therapy without surgery (5 months). Surgery is the first treatment of choice in treating PSCM. The goal of tumor resection is to reduce symptoms. Adjuvant therapy after surgery had a beneficial effect on limiting the metastasis. Copyright © 2018 Elsevier Inc. All rights reserved.
Dong, Xing; Zhang, Kevin; Ren, Yuan; Wilson, Reda; O'Neil, Mary Elizabeth
2016-01-01
Studying population-based cancer survival by leveraging the high-quality cancer incidence data collected by the Centers for Disease Control and Prevention's National Program of Cancer Registries (NPCR) can offer valuable insight into the cancer burden and impact in the United States. We describe the development and validation of a SASmacro tool that calculates population-based cancer site-specific relative survival estimates comparable to those obtained through SEER*Stat. The NPCR relative survival analysis SAS tool (NPCR SAS tool) was developed based on the relative survival method and SAS macros developed by Paul Dickman. NPCR cancer incidence data from 25 states submitted in November 2012 were used, specifically cases diagnosed from 2003 to 2010 with follow-up through 2010. Decennial and annual complete life tables published by the National Center for Health Statistics (NCHS) for 2000 through 2009 were used. To assess comparability between the 2 tools, 5-year relative survival rates were calculated for 25 cancer sites by sex, race, and age group using the NPCR SAS tool and the National Cancer Institute's SEER*Stat 8.1.5 software. A module to create data files for SEER*Stat was also developed for the NPCR SAS tool. Comparison of the results produced by both SAS and SEER*Stat showed comparable and reliable relative survival estimates for NPCR data. For a majority of the sites, the net differences between the NPCR SAS tool and SEER*Stat-produced relative survival estimates ranged from -0.1% to 0.1%. The estimated standard errors were highly comparable between the 2 tools as well. The NPCR SAS tool will allow researchers to accurately estimate cancer 5-year relative survival estimates that are comparable to those produced by SEER*Stat for NPCR data. Comparison of output from the NPCR SAS tool and SEER*Stat provided additional quality control capabilities for evaluating data prior to producing NPCR relative survival estimates.
Cost-effectiveness of rehabilitation after an acute coronary event: a randomised controlled trial.
Briffa, Tom G; Eckermann, Simon D; Griffiths, Alison D; Harris, Phillip J; Heath, M Rose; Freedman, Saul B; Donaldson, Lana T; Briffa, N Kathryn; Keech, Anthony C
2005-11-07
To estimate the incremental effects on cost and quality of life of cardiac rehabilitation after an acute coronary syndrome. Open randomised controlled trial with 1 year's follow-up. Analysis was on an intention-to-treat basis. Two tertiary hospitals in Sydney. 18 sessions of comprehensive exercise-based outpatient cardiac rehabilitation or conventional care as provided by the treating doctor. 113 patients aged 41-75 years who were self-caring and literate in English. Patients with uncompensated heart failure, uncontrolled arrhythmias, severe and symptomatic aortic stenosis or physical impairment were excluded. Costs (hospitalisations, medication use, outpatient visits, investigations, and personal expenses); and measures of quality of life. Incremental cost per quality-adjusted life year (QALY) saved at 1 year (this estimate combines within-study utility effects with reported 1-year risk of survival and treatment effects of rehabilitation on mortality). Sensitivity analyses around a base case estimate included alternative assumptions of no treatment effect on survival, 3 years of treatment effect on survival and variations in utility. The estimated incremental cost per QALY saved for rehabilitation relative to standard care was 42,535 US dollars when modelling included the reported treatment effect on survival. This increased to 70,580 US dollars per QALY saved if treatment effect on survival was not included. The results were sensitive to variations in utility and ranged from 19,685 US dollars per QALY saved to rehabilitation not being cost-effective. The effects on quality of life tend to reinforce treatment advantages on survival for patients having postdischarge rehabilitation after an acute coronary syndrome. The estimated base case incremental cost per QALY saved is consistent with those historically accepted by decision making authorities such as the Pharmaceutical Benefits Advisory Committee.
Survival analysis for customer satisfaction: A case study
NASA Astrophysics Data System (ADS)
Hadiyat, M. A.; Wahyudi, R. D.; Sari, Y.
2017-11-01
Most customer satisfaction surveys are conducted periodically to track their dynamics. One of the goals of this survey was to evaluate the service design by recognizing the trend of satisfaction score. Many researchers recommended in redesigning the service when the satisfaction scores were decreasing, so that the service life cycle could be predicted qualitatively. However, these scores were usually set in Likert scale and had quantitative properties. Thus, they should also be analyzed in quantitative model so that the predicted service life cycle would be done by applying the survival analysis. This paper discussed a starting point for customer satisfaction survival analysis with a case study in healthcare service.
Reliability of dietary information from surrogate respondents.
Hislop, T G; Coldman, A J; Zheng, Y Y; Ng, V T; Labo, T
1992-01-01
A self-administered food frequency questionnaire was included as part of a case-control study of breast cancer in 1980-82. In 1986-87, a second food frequency questionnaire was sent to surviving cases and husbands of deceased cases; 30 spouses (86% response rate) and 263 surviving cases (88% response rate) returned questionnaires. The dietary questions concerned consumption of specific food items by the case before diagnosis of breast cancer. Missing values were less common in the second questionnaire; there was no significant difference in missing values between surviving cases and spouses of deceased cases. Kappa statistics comparing responses in the first and second questionnaires were significantly lower for spouses of deceased cases than for surviving cases. Reported level of confidence by the husbands regarding knowledge about their wives' eating habits did not influence the kappa statistics or the frequencies of missing values. The lack of good agreement has important implications for the use of proxy interviews from husbands in retrospective dietary studies.
Research Waste: How Are Dental Survival Articles Indexed and Reported?
Layton, Danielle M; Clarke, Michael
2016-01-01
Research waste occurs when research is ignored, cannot be found, cannot be used, or is unintentionally repeated. This article aims to investigate how dental survival analyses were indexed and reported, and to discuss whether errors in indexing and writing articles are affecting identification and use of survival articles, contributing to research waste. Articles reporting survival of dental prostheses in humans (also known as time-to-event) were identified by searching 50 dental journals that had the highest Impact Factor in 2008. These journals were hand searched twice (Kappa 0.92), and the articles were assessed by two independent reviewers (Kappa 0.86) to identify dental survival articles ("case" articles, n = 95), likely false positives (active controls, n = 91), and all other true negative articles (passive controls, n = 6,769). This means that the study used a case:control method. Once identified, the different groups of articles were assessed and compared. Allocation of medical subject headings (MeSH) by MEDLINE indexers that related to survival was sought, use of words by authors in the abstract and title that related to survival was identified, and use of words and figures by authors that related to survival in the articles themselves was also sought. Differences were assessed with chi-square and Fisher's Exact statistics. Reporting quality was also assessed. The results were reviewed to discuss their potential impact on research waste. Allocation of survival-related MeSH index terms across the three article groups was inconsistent and inaccurate. Statistical MeSH had not been allocated to 30% of the dental survival "case" articles and had been incorrectly allocated to 15% of active controls. Additionally, information reported by authors in titles and abstracts varied, with only two-thirds of survival "case" articles mentioning survival "statistics" in the abstract. In the articles themselves, time-to-event statistical methods, survival curves, and life tables were poorly reported or constructed. Overall, the low quality of indexing by indexers and reporting by authors means that these articles will not be readily identifiable through electronic searches, and, even if they are found, the poor reporting quality makes it unnecessarily difficult for readers to understand and use them. There are substantial problems with the reporting of time-to-event analyses in the dental literature. These problems will adversely impact how these articles can be found and used, thereby contributing to research waste. Changes are needed in the way that authors report these studies and the way indexers classify them.
Gaertner, Katharina; Müllner, Michael; Friehs, Helmut; Schuster, Ernst; Marosi, Christine; Muchitsch, Ilse; Frass, Michael; Kaye, Alan David
2014-04-01
Current literature suggests a positive influence of additive classical homeopathy on global health and well-being in cancer patients. Besides encouraging case reports, there is little if any research on long-term survival of patients who obtain homeopathic care during cancer treatment. Data from cancer patients who had undergone homeopathic treatment complementary to conventional anti-cancer treatment at the Outpatient Unit for Homeopathy in Malignant Diseases, Medical University Vienna, Department of Medicine I, Vienna, Austria, were collected, described and a retrospective subgroup-analysis with regard to survival time was performed. Patient inclusion criteria were at least three homeopathic consultations, fatal prognosis of disease, quantitative and qualitative description of patient characteristics, and survival time. In four years, a total of 538 patients were recorded to have visited the Outpatient Unit Homeopathy in Malignant Diseases, Medical University Vienna, Department of Medicine I, Vienna, Austria. 62.8% of them were women, and nearly 20% had breast cancer. From the 53.7% (n=287) who had undergone at least three homeopathic consultations within four years, 18.7% (n=54) fulfilled inclusion criteria for survival analysis. The surveyed neoplasms were glioblastoma, lung, cholangiocellular and pancreatic carcinomas, metastasized sarcoma, and renal cell carcinoma. Median overall survival was compared to expert expectations of survival outcomes by specific cancer type and was prolonged across observed cancer entities (p<0.001). Extended survival time in this sample of cancer patients with fatal prognosis but additive homeopathic treatment is interesting. However, findings are based on a small sample, and with only limited data available about patient and treatment characteristics. The relationship between homeopathic treatment and survival time requires prospective investigation in larger samples possibly using matched-pair control analysis or randomized trials. Copyright © 2014 Elsevier Ltd. All rights reserved.
Improved Survival in Male Melanoma Patients in the Era of Sentinel Node Biopsy.
Koskivuo, I; Vihinen, P; Mäki, M; Talve, L; Vahlberg, T; Suominen, E
2017-03-01
Sentinel node biopsy is a standard method for nodal staging in patients with clinically localized cutaneous melanoma, but the survival advantage of sentinel node biopsy remains unsolved. The aim of this case-control study was to investigate the survival benefit of sentinel node biopsy. A total of 305 prospective melanoma patients undergoing sentinel node biopsy were compared with 616 retrospective control patients with clinically localized melanoma whom have not undergone sentinel node biopsy. Survival differences were calculated with the median follow-up time of 71 months in sentinel node biopsy patients and 74 months in control patients. Analyses were calculated overall and separately in males and females. Overall, there were no differences in relapse-free survival or cancer-specific survival between sentinel node biopsy patients and control patients. Male sentinel node biopsy patients had significantly higher relapse-free survival ( P = 0.021) and cancer-specific survival ( P = 0.024) than control patients. In females, no differences were found. Cancer-specific survival rates at 5 years were 87.8% in sentinel node biopsy patients and 85.2% in controls overall with 88.3% in male sentinel node biopsy patients and 80.6% in male controls and 87.3% in female sentinel node biopsy patients and 89.8% in female controls. Sentinel node biopsy did not improve survival in melanoma patients overall. While females had no differences in survival, males had significantly improved relapse-free survival and cancer-specific survival following sentinel node biopsy.
Effects of environmental factors on child survival in Bangladesh: a case control study.
Hoque, B A; Chakraborty, J; Chowdhury, J T; Chowdhury, U K; Ali, M; el Arifeen, S; Sack, R B
1999-03-01
The need for further studies on relationships between deaths and environmental variables has been reported in the literature. This case-control study was, therefore, carried out to find out the associations between several social and environmental variables and deaths of children due to infectious diseases such as those leading to diarrhoea, acute respiratory infection, measles and other diseases. Six hundred and twenty-five deaths (cases) and an equal number of matched living children (controls) aged 1-59 months, were studied in rural Matlab. An analysis of crude and adjusted odds ratio showed differential associations. Sources of drinking water, amount of stored water, conditions of latrines, number of persons sleeping with the child and the type of cooking site were statistically significantly associated with deaths due to infectious diseases after controlling for breast feeding, immunization, and the family size. Significant associations were also observed between: (i) the sources of drinking water and deaths due to ARI, and (ii) conditions of latrines and deaths due to diarrhoeal diseases, after controlling for the confounding variables. Several other environmental factors also showed associations with these various death groups, but they were not statistically significant. The size of the samples in death groups (small) and the prevalence of more or less homogeneous environmental health conditions probably diminished the magnitude of the effects. The results of the study reconfirm the importance of environmental health intervention in child survival, irrespective of breast-feeding, immunization, and selected social variables.
Lee, Yi-Chan; Lee, Ta-Jen; Tsang, Ngan-Ming; Huang, Yenlin; Hsu, Cheng-Lung; Hsin, Li-Jen; Lee, Yi-Hsuan; Chang, Kai-Ping
2018-02-05
Sinonasal adenoid cystic carcinoma is a rare malignancy of the head and neck. Cavernous sinus invasion from sinonasal adenoid cystic carcinoma and its related management have rarely been investigated. This study evaluated the relationship between treatment outcome and cavernous sinus involvement in addition to other parameters. A retrospective case series study was conducted at a tertiary referral center. The medical records of 47 patients diagnosed with primary sinonasal adenoid cystic carcinoma between 1984 and 2015 were retrospectively reviewed. The survival impact of the primary treatment modalities and the anatomic sites of tumor involvement were analyzed. Cavernous sinus invasion was observed in 8 patients (17%), of whom 7 had ACC tumors originating from the maxillary sinus. The results of univariate analysis revealed that tumor stage, primary surgery, and the absence of skull-base and infratemporal fossa invasion were associated with better overall survival (P = 0.033, P = 0.012, P = 0.011, and P = 0.040, respectively) and better disease-free survival (P = 0.019, P = 0.001, P = 0.017, and P = 0.029, respectively). Multivariate analysis identified primary surgery as the only independent prognostic factor for disease-free survival (P = 0.026). Cavernous sinus invasion by sinonasal adenoid cystic carcinoma was not associated with worse overall survival or disease-free survival (P = 0.200 and P = 0.198, respectively). Because maxillary adenoid cystic carcinoma is associated with a higher rate of cavernous sinus invasion, such cases warrant caution during preoperative planning. Primary surgery as the initial therapy provides better locoregional control and survival for patients with sinonasal adenoid cystic carcinoma. Cavernous sinus invasion did not significantly impact survival; thus, it should not be regarded as a contraindication for curative treatment.
He, Shizhi; Li, Pingdong; Zhong, Qi; Hou, Lizhen; Yu, Zhenkun; Huang, Zhigang; Chen, Xuejun; Fang, Jugao; Chen, Xiaohong
This study was to investigate clinicopathologic characteristics and prognostic factors in adenoid cystic carcinoma of head and neck minor salivary glands. We conducted a retrospective review of 130 patients with adenoid cystic carcinoma of head and neck minor salivary glands that were evaluated between 2000 and 2013 in Beijng Tongren Hospital. Five-year overall survival and disease-free survival rates were 80.8% and 55.6%. Local recurrence rate was 40%, regional recurrence 3.8%, and distant metastasis was 28.5%. On univariate analysis, solid histological subtype, perineural invasion, positive surgical margins and advanced stages were found to be poor prognostic indicators. On multivariate analysis, solid histological subtype and positive surgical margins were significant prognostic factors of worse overall survival. Solid histological subtype and positive surgical margins were the most important predictors of poor outcome in adenoid cystic carcinoma of minor salivary glands. Surgery with postoperative radiation were recommended treatment and offered durable local control. Copyright © 2016 Elsevier Inc. All rights reserved.
DeSimone, Daniel C.; Baddour, Larry M.; Lahr, Brian D.; Chung, Heath H.; Wilson, Walter R.; Steckelberg, James M.
2013-01-01
Background Most patients with infective endocarditis (IE) manifest fever. Comparison of endocarditis patients with and without fever, and whether the lack of fever in IE is a marker for poorer outcomes, such as demonstrated in other severe infectious diseases, have not been defined. Methods and Results Cases from the Mayo Clinic, Rochester, Minnesota, Division of Infectious Diseases IE registry, a single-center database that contains all cases of IE treated at our center. Diagnosis date between 1970 and 2006, which met the modified Duke criteria for definite endocarditis, without fever was included. There were 240 euthermic endocarditis cases included in this analysis, with 282 febrile controls selected by frequency matching on gender and decade of diagnosis. Euthermic patients had a median age of 63.6 years (±16.1) as compared to 59.0 years (±16.4) in the febrile control group (p=0.001). Median (IQR) symptom duration prior to diagnosis was 4.0 (1.0, 12.0) weeks in the euthermic group compared to 3.0 (1.0, 8.0) weeks in the febrile controls (p= 0.006). From unadjusted analyses, survival rates were 87% in euthermic cases versus 83% in febrile controls across 28-day follow-up (p=0.164), and 72% in euthermic group cases versus 69% in febrile controls across 1-year follow-up (p=0.345). Also unadjusted, the 1-year cumulative incidence rate of valve surgery was higher in euthermic cases versus febrile controls (50% vs. 39%, p= 0.004). Conclusions Patients with euthermic endocarditis are older, and lack of fever was associated with longer symptom duration and delayed diagnosis prior to IE diagnosis. Despite a higher unadjusted rate of valve surgery in euthermic patients, the result was not significant when adjusting for baseline confounders. Differences in survival rates at both 28-days and 365-days were not statistically significant between the two groups. PMID:24244630
Bunn, T L; Slavova, S; Struttmann, T W; Browning, S R
2005-09-01
A retrospective population-based case-control study was conducted to determine whether driver sleepiness/fatigue and inattention/distraction increase the likelihood that a commercial motor vehicle collision (CVC) will be fatal. Cases were identified as CVC drivers who died (fatal) and controls were drivers who survived (nonfatal) an injury collision using the Kentucky Collision Report Analysis for Safer Highways (CRASH) electronic database from 1998-2002. Cases and controls were matched on unit type and roadway type. Conditional logistic regression was performed. Driver sleepiness/fatigue, distraction/inattention, age of 51 years of age and older, and nonuse of safety belts increase the odds that a CVC will be fatal. Primary safety belt law enactment and enforcement for all states, commercial vehicle driver education addressing fatigue and distraction and other approaches including decreased hours-of-service, rest breaks and policy changes, etc. may decrease the probability that a CVC will be fatal.
Yang, Xiao-Bing; Wu, Wan-Yin; Long, Shun-Qin; Deng, Hong; Pan, Zong-Qi
2014-12-01
Some patients with non-small-cell lung cancer (NSCLC) respond well to the EGFR tyrosine kinase inhibitor gefitinib. Chinese herbal medicine (CHM) was effective in improving the quality of life and prolonging overall survival in patient with NSCLC. We aim to determine whether gefitinib plus CHM could prolong the progression-free survival (PFS) or median survival time (MST) in patients with NSCLC than gefitinib alone. We retrospectively analyzed 159 non-small-cell lung cancer patients with the method of retrospective case-control study, matching factors included gender, age categories (30-39,40-49,50-59,60-69,70-79), pathological stage (IIIB or IV), smoking status (never: <100 lifetime cigarettes, or ever: ≥100 lifetime cigarettes), pathology, and performance status. Among the 159 patients, 100 patients treated with gefitinib (250mg/day orally) plus CHM ("Fuzheng Kang'ai" decoction, a Chinese herbal medicine, 250ml/bid/day orally), 59 patients treated with gefitinib (250mg/day orally) only. PFS and MST were analyzed for the whole population. 58 pairs were matched successfully. 1 patient (treated with gefitinib) with the age of 27 years failed to be matched. Progression-free survival was significantly longer in patients treated with gefitinib plus CHM than with gefitinib: median PFS was 13.1 months (95% CI 6.50-19.70) with gefitinib plus CHM versus 11.43 months (95% CI 7.95-14.91) with gefitinib (log-rank P=0.013). Median overall survival was longer with gefitinib plus CHM than with gefitinib: median MST was 22.83 months (95% CI 17.51-28.16) with gefitinib plus CHM versus 18.7 months (95% CI 16.83-20.57) with gefitinib (log-rank P=0.049). The most common adverse event was rash, the incidence in the gefitinib plus CHM group was 41.38% while in the gefitinib group was 24.14% (P=0.048). This case-control analysis suggested that treatment with gefitinib plus CHM prolonged PFS and MST compared with gefitinib in patients with NSCLC, and it is worthy of further study. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.
George, Rebecca; Smith, Annette; Schleis, Stephanie; Brawner, William; Almond, Gregory; Kent, Michael; Wypij, Jackie; Borrego, Juan; Moore, Antony; Keyerleber, Michele; Kraiza, Sarah
2016-05-01
Tumors of the nasal cavity comprise approximately 1% of all neoplasms in dogs. Canine intranasal lymphoma is rare and reports evaluating the outcome of treatment are lacking. The goal of this observational, descriptive, multi-institutional study was to evaluate the overall median survival times (MSTs) in a group of dogs with intranasal lymphoma that were treated with irradiation and/or chemotherapy. Dogs meeting these inclusion criteria were retrospectively recruited from medical archives at multiple institutions. Eighteen cases of intermediate to high grade intranasal lymphoma and six cases of low-grade intranasal lymphoma were identified. The date of diagnosis, method of diagnosis, treatment received (radiation and/or chemotherapy protocols), and date of death were recorded. Kaplan-Meier survival analysis was performed on the intermediate to high grade group to calculate overall MST. Log-rank tests were performed to compare effects of treatment with radiation therapy ± chemotherapy and chemotherapy alone. Kaplan-Meier survival analysis was performed separately on the low-grade group. The overall MST was 375 days for the intermediate to high grade group. Cases treated with radiation ± chemotherapy had an MST of 455 days (n = 12) and those treated with chemotherapy alone (n = 6) had an MST of 157 days in the intermediate to high grade group. The MST was 823 days for the low-grade group. Results support the use of radiation therapy for treatment of canine intranasal lymphoma, however a randomized, controlled, clinical trial would be needed for more definitive recommendations. The role of adjunctive chemotherapy also may require further investigation. © 2016 American College of Veterinary Radiology.
Lou, Jianlin; Wang, Shengye; Wang, Kejing; Chen, Chao; Zhao, Jianqiang; Guo, Liang
2015-10-01
To investigate the treatment strategies of squamous cell carcinoma of cervical lymph nodes from an unknown primary site (SCCUP) and the value of neck dissection (ND). The study included 133 patients referred to the Zhejiang Cancer Hospital from 2001 to 2012, with 109 males and 24 females. Distribution of patients by N status was as follows: N1 - 14 cases; N2a - 21 cases; N2b - 78 cases; N2c - 7 cases; and N3 - 13 cases. 104 patients underwent surgeries of ND while 29 patients underwent nonsurgical treatment. Among 104 patients, 24 underwent classic radical ND, 16 modified ND, 53 selective ND, and 11 extended ND. The selection of surgical strategy was determined by the extent and location of disease. According to the range of ND, 50 patients underwent ND for Levels I-V, 46 for Levels II-V, 4 for Levels I-III, 3 for Levels II-VI, and 1 for Levels I-VI. The data were analyzed with SPSS version 16.0. The differences between groups were calculated by χ2 tests. The actual overall survival (OS) rates were calculated by the Kaplan-Meier method. Different factors affecting the OS were determined by the log-rank test on univariate analysis. Cox regression was used to evaluate the multivariate analysis. The 5-year OS rate of the whole cohort was 67.1%; and the median survival time was 70.0 months. The 5-year OS of ND group and of the non-ND group were 71.3% and 53.2%, respectively (P = 0.061). Cox analysis indicated that N stage (P = 0.000), bilateral neck metastasis (P = 0.001), extracapsular spread (ES) (P = 0.016), and ND (P = 0.028) were independent prognostic factors for the OS of SCCUP. 25 patients (18.8%) had neck recurrence or residue. The locoregional failure rate of ND group and of the non-ND group were 13.5% and 37.9%, respectively (P = 0.003). Logistic regression analysis indicated that higher N stage was the main risk factor for locoregional failure (P = 0.015). N stage, bilateral neck metastasis, ES, and ND were the main factors for the survival rate of SCCUP. N3 stage was the independent risk factor for locoregional failure. ND could significantly increase the locoregional control and may benefit the survival rate.
Lee, Mei-Ling Ting; Whitmore, G A; Laden, Francine; Hart, Jaime E; Garshick, Eric
2009-01-01
A case-control study of lung cancer mortality in U.S. railroad workers in jobs with and without diesel exhaust exposure is reanalyzed using a new threshold regression methodology. The study included 1256 workers who died of lung cancer and 2385 controls who died primarily of circulatory system diseases. Diesel exhaust exposure was assessed using railroad job history from the US Railroad Retirement Board and an industrial hygiene survey. Smoking habits were available from next-of-kin and potential asbestos exposure was assessed by job history review. The new analysis reassesses lung cancer mortality and examines circulatory system disease mortality. Jobs with regular exposure to diesel exhaust had a survival pattern characterized by an initial delay in mortality, followed by a rapid deterioration of health prior to death. The pattern is seen in subjects dying of lung cancer, circulatory system diseases, and other causes. The unique pattern is illustrated using a new type of Kaplan-Meier survival plot in which the time scale represents a measure of disease progression rather than calendar time. The disease progression scale accounts for a healthy-worker effect when describing the effects of cumulative exposures on mortality.
Pruksakorn, Dumnoensun; Phanphaisarn, Areerak; Arpornchayanon, Olarn; Uttamo, Nantawat; Leerapun, Taninnit; Settakorn, Jongkolnee
2015-12-01
Osteosarcoma is a common and aggressive primary malignant bone tumor occurring in children and adolescents. It is one of the most aggressive human cancers and the most common cause of cancer-associated limb loss. As treatment in Thailand has produced a lower survival rate than in developed countries; therefore, this study identified survival rate and the poor prognostic factors of osteosarcoma in Northern Thailand. The retrospective cases of osteosarcoma, diagnosis between 1 January 1996 and 31 December 2013, were evaluated. Five and ten year overall survival rates were analyzed using time-to-event analysis. Potential prognostic factors were identified by multivariate regression analysis. There were 208 newly diagnosed osteosarcomas during that period, and 144 cases met the criteria for analysis. The majority of the osteosarcoma cases (78.5%) were aged 0-24 years. The overall 5- and 10-year survival rates were 37.9% and 33.6%, respectively. Presence of metastasis at initial examination, delayed and against treatment co-operation, and axial skeletal location were identified as independent prognostic factors for survival, with hazard ratios of 4.3, 2.5 and 3.8, and 3.1, respectively. This osteosarcoma cohort had a relatively poor overall survival rate. The prognostic factors identified would play a critical role in modifying survival rates of osteosarcoma patients; as rapid disease recognition, a better treatment counselling, as well as improving of chemotherapeutic regimens were found to be important in improving the overall survival rate in Thailand. Copyright © 2015 Elsevier Ltd. All rights reserved.
Fan, Cong; Zhang, Juan; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao
2018-05-04
RAD50 is a highly conserved DNA double-strand break (DSB) repair gene. However, the associations between RAD50 germline mutations and the survival and risk of breast cancer have not been fully elucidated. Here, we aimed to investigate the clinical impact of RAD50 germline mutations in a large cohort of unselected breast cancer patients. In this study, RAD50 germline mutations were determined using next-generation sequencing in 7657 consecutive unselected breast cancer patients without BRCA1/2 mutations. We also screened for RAD50 recurrent mutations (L719fs, K994fs, and H1269fs) in 5000 healthy controls using Sanger sequencing. We found that 26 out of 7657 (0.34%) patients had RAD50 pathogenic mutations, and 16 patients carried one of the three recurrent mutations (L719fs, n=6 cases; K994fs, n=5 cases; and H1269fs, n=5 cases); the recurrent mutation rate was 0.21%. The frequency of the three recurrent mutations in the 5000 healthy controls was 0.18% (9/5000). These mutations did not confer an increased risk of breast cancer in the studied patients [odds ratios (OR), 1.16; 95% confidence interval (CI), 0.51-2.63; P = 0.72]. Nevertheless, multivariate analysis revealed that RAD50 pathogenic mutations were an independent unfavourable predictor of recurrence-free survival (RFS) [adjusted hazard ratio (HR) 2.66; 95% CI, 1.18-5.98; P=0.018] and disease-specific survival (DSS) (adjusted HR 4.36; 95% CI, 1.58-12.03; P=0.004) in the entire study cohort. Our study suggested that RAD50 germline mutations are not associated with an increased risk of breast cancer, but patients with RAD50 germline mutations have unfavourable survival compared with patients without these mutations. This article is protected by copyright. All rights reserved. © 2018 UICC.
Diao, Mengyuan; Huang, Fenglou; Guan, Jun; Zhang, Zhe; Xiao, Yan; Shan, Yi; Lin, Zhaofen; Ding, Liangcai
2013-08-01
Therapeutic hypothermia has been recommended for the treatment of cardiac arrest patients who remain comatose after the return of spontaneous circulation. However, the optimal time to initiate therapeutic hypothermia remains unclear. The objective of the present study is to assess the effectiveness and safety of prehospital therapeutic hypothermia after cardiac arrest. Databases such as MEDLINE, Embase, and Cochrane Library were searched from their establishment date to May of 2012 to retrieve randomized control trials on prehospital therapeutic hypothermia after cardiac arrest. Thereafter, the studies retrieved were screened based on predefined inclusion and exclusion criteria. Data were extracted and the quality of the included studies was evaluated. A meta-analysis was performed by using the Cochrane Collaboration Review Manager 5.1.6 software. Five studies involving 633 cases were included, among which 314 cases were assigned to the treatment group and the other 319 cases to the control group. The meta-analysis indicated that prehospital therapeutic hypothermia after cardiac arrest produced significant differences in temperature on hospital admission compared with in-hospital therapeutic hypothermia or normothermia (patient data; mean difference=-0.95; 95% confidence interval -1.15 to -0.75; I(2)=0%). However, no significant differences were observed in the survival to the hospital discharge, favorable neurological outcome at hospital discharge, and rearrest. The risk of bias was low; however, the quality of the evidence was very low. This review demonstrates that prehospital therapeutic hypothermia after cardiac arrest can decrease temperature on hospital admission. On the other hand, regarding the survival to hospital discharge, favorable neurological outcome at hospital discharge, and rearrest, our meta-analysis and review produces non-significant results. Using the Grading of Recommendations, Assessment, Development and Evaluation methodology, we conclude that the quality of evidence is very low. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Smyrnioudis, Mary E; O'Rourke, Dorcas P; Rosenbaum, Matthew D; Brewer, Kori L; Meggs, William J
2014-09-01
Pressure immobilization bandages delay mortality for 8 hours after coral snake envenomation, but long-term efficacy has not been established. The objective of this study is to determine the long-term efficacy of pressure immobilization bandages after coral snake envenomation in the absence of antivenom therapy. A randomized, observational pilot study was conducted. Ten pigs (17.3-25.6 kg) were sedated, intubated for 5 hours, and injected subcutaneously with 10 mg of lyophilized Micrurus fulvius venom resuspended in water. Pigs were randomly assigned to a control group (no treatment) or a treatment group (compression bandage and splint) approximately 1 minute after envenomation. Bandage pressure was not controlled. Pigs were monitored daily for 21 days for signs of respiratory depression, decreased oxygen saturations, and paralysis. In case of respiratory depression, pigs were humanely euthanized and time to death recorded. Statistical analysis was performed with Fisher exact test, Mann-Whitney U test, and Kaplan-Meier survival curve as appropriate. Median survival time of control animals was 307 minutes compared with 1172 minutes in treated animals (P = .10). Sixty percent of pigs in the treatment group survived to 24 hours vs 0% of control pigs (P = .08). Two of the treatment pigs survived to the end point of 21 days but showed necrosis of the distal lower extremity. Long-term survival after coral snake envenomation is possible in the absence of antivenom with the use of pressure immobilization bandages. The applied pressure of the bandage is critical to allowing survival without necrosis. Future studies should be designed to accurately monitor the pressures applied. Copyright © 2014 Elsevier Inc. All rights reserved.
Peter, Raphael Simon; Rosenbohm, Angela; Dupuis, Luc; Brehme, Torben; Kassubek, Jan; Rothenbacher, Dietrich; Nagel, Gabriele; Ludolph, Albert Christian
2017-10-01
Weight loss appears as a strong predictor of survival of patients with amyotrophic lateral sclerosis, yet no data are currently available to describe the life course history of pre-diagnostic body mass index (BMI) in these patients. 393 ALS cases (mean age: 65.8 years, 57.3% men) and 791 controls matched by age and sex from a population-based case-control study of the ALS Registry Swabia were analyzed. Differences of BMI change in cases and controls over time were modeled using a multilevel additive model. In addition, survival in ALS cases by BMI change was modeled using an accelerated failure time model adjusted for prognostic factors. In ALS cases, BMI was consistently higher than in controls in the 20-70 years before the interview. Conditional logistic regression revealed an odds ratio of 1.05 (95% confidence interval (CI) 1.00-1.11, p = 0.041) per 1 kg/m 2 higher BMI 35-45 years before interview. However, a sharp decrease was evident in the BMI of ALS cases about 10 years before disease onset. Moreover, weight loss was strongly associated with shorter survival in ALS patients. Illustrating this, patients with stable weight showed a median survival time of 22.1 (95%-CI 19.2-25.0) months, as compared to 13.4 (95%-CI 10.5-16.3) months for patients with weight loss of 2.5 kg/m 2 over the last 3 months before the interview. Thus, alterations in body weight are present in ALS patients already decades before clinical manifestation of ALS, while weight loss precedes motor symptoms of several years and is associated with poor prognosis.
Shrock, D; Palmer, R F; Taylor, B
1999-05-01
Psychosocial factors have been linked to the development and progression of cancer and shown to be relevant in cancer care. However, the evidence that psychosocial interventions affect cancer survival is less conclusive. Few methodologically sound studies have addressed this issue. To investigate the effects of a 6-week psychosocial intervention on survival among patients with stage I breast and prostate cancer. Matched case-control. 3 rural hospitals or cancer centers in central Pennsylvania. 21 breast and 29 prostate stage I cancer patients (treatment group) matched with 74 breast and 65 prostate stage I cancer patients from the same hospitals who did not receive the intervention (control group). Six 2-hour health psychology classes conducted by a licensed staff psychologist. Survival time was compared between the 2 groups and with national norms. The intervention group lived significantly longer than did matched controls. At 4- to 7-year follow-up (median = 4.2 years), none of the breast cancer patients in the intervention group died, whereas 12% of those in the control group died. Twice as many matched-control prostate cancer patients died compared with those in the intervention group (28% vs 14%). Control group survival was similar to national norms. These results are consistent with prior clinical trials and suggest that short-term psychosocial interventions that encourage the expression of emotions, provide social support, and teach coping skills can influence survival among cancer patients. However, self-selection bias cannot be ruled out as an alternative explanation for the results. These interventions merit further consideration and research.
Zhu, Xiaonian; Liu, Wei; Qiu, Xiaoqiang; Wang, Zhigang; Tan, Chao; Bei, Chunhua; Qin, Linyuan; Ren, Yuan; Tan, Shengkui
2017-10-03
Hepatocellular carcinoma (HCC) is a malignant cancer causing deleterious health effect worldwide, especially in China. So far clinical cure rate and long-term survival rate of HCC remains low. Most HCC patients after cancer resection have recurrence or metastasis within 5 years. This study aims to explore the genetic association of mutL homolog 1 ( MLH1 ) polymorphisms with HCC risk and prognosis. Four candidate MLH1 polymorphisms, rs1800734, rs10849, rs3774343 and rs1540354 were studied from a hospital-based case-control study including 1,036 cases (HCC patients) and 1,036 controls (non-HCC patients) in Guangxi, China. All these SNPs interacted with environmental risk factors, such as HBV infection, alcohol intake and smoking in the pathogenesis of HCC. However, only rs1800734 had significant difference between cases and controls. Compared to the AA genotype, patients with AG, GG and AG/GG genotype of rs1800734 had an increased risk of HCC [ORs (95% CI) = 1.217 (1.074∼1.536), 1.745 (1.301∼2.591) and 1.291 (1.126∼1.687)] and a decreased survival time [co-dominant, HR (95% CI) = 1.553 (1.257∼1.920); dominant, HR (95% CI) = 2.207 (1.572∼3.100)]. Furthermore, we found that tumor number, tumor staging, metastasis and rs1800734 were associated with the overall survival of HCC patients by multivariate COX regression analysis. No significant difference was found between the other three MLH1 polymorphisms with HCC risk and prognosis. Our study suggests MLH1 SNP, rs1800734 as a new predictor for poor prognosis of HCC patients.
Reproductive Steroid Hormones and Recurrence-Free Survival in Women with a History of Breast Cancer
Rock, Cheryl L.; Flatt, Shirley W.; Laughlin, Gail A.; Gold, Ellen B.; Thomson, Cynthia A.; Natarajan, Loki; Jones, Lovell A.; Caan, Bette J.; Stefanick, Marcia L.; Hajek, Richard A.; Al-Delaimy, Wael K.; Stanczyk, Frank Z.; Pierce, John P.
2008-01-01
Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01−1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03−1.53), and free estradiol (HR, 1.31; 95% CI, 1.03−1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer. PMID:18323413
Sinha, Parul; Hackman, Trevor; Nussenbaum, Brian; Wu, Ningying; Lewis, James S.; Haughey, Bruce H.
2014-01-01
Background Modest survival rates are published for treatment of oral squamous cell carcinoma (OSCC) using conventional approaches. Few cohort studies are available for transoral resection of OSCC. Methods Analysis for recurrence, survival, and prognosis of patients with OSCC treated with transoral laser microsurgery (TLM) ± neck dissection was obtained from a prospective database. Results Ninety-five patients (71 patients had stages T1–T2 and 24 had stages T3–T4 disease) with minimum follow-up of 24 months met criteria and demonstrated negative margins in 95%. Five-year local control (LC) and disease-specific survival (DSS) were 78% and 76%, respectively. Surgical salvage achieved an absolute final locoregional control of 92%. Immune compromise and final margins were prognostic for LC, whereas T classification, N classification, TNM stage, comorbidity, and perineural invasion were also significant for DSS. Conclusion We document a large series of patients with OSCC treated with TLM, incorporating T1 to T4 primaries. A significant proportion of stage III/IV cases demonstrates feasibility of TLM in higher stages, with final margin positivity of 5%, LC greater than 90%, and comparable survival outcomes. PMID:23729304
Rama, Ranganathan; Shanta, Viswanathan
2008-01-01
Abstract Objective To measure the bias in absolute cancer survival estimates in the absence of active follow-up of cancer patients in developing countries. Methods Included in the study were all incident cases of the 10 most common cancers and corresponding subtypes plus all tobacco-related cancers not ranked among the top 10 that were registered in the population-based cancer registry in Chennai, India, during 1990–1999 and followed through 2001. Registered incident cases were first matched with those in the all-cause mortality database from the vital statistics division of the Corporation of Chennai. Unmatched incident cancer cases were then actively followed up to determine their survival status. Absolute survival was estimated by using an actuarial method and applying different assumptions regarding the survival status (alive/dead) of cases under passive and active follow-up. Findings Before active follow-up, matches between cases ranged from 20% to 66%, depending on the site of the primary tumour. Active follow-up of unmatched incident cases revealed that 15% to 43% had died by the end of the follow-up period, while the survival status of 4% to 38% remained unknown. Before active follow-up of cancer patients, 5-year absolute survival was estimated to be between 22% and 47% higher, than when conventional actuarial assumption methods were applied to cases that were lost to follow-up. The smallest survival estimates were obtained when cases lost to follow-up were excluded from the analysis. Conclusion Under the conditions that prevail in India and other developing countries, active follow-up of cancer patients yields the most reliable estimates of cancer survival rates. Passive case follow-up alone or applying standard methods to estimate survival is likely to result in an upward bias. PMID:18670662
Fanidi, Anouar; Muller, David C.; Midttun, Øivind; Ueland, Per Magne; Vollset, Stein Emil; Relton, Caroline; Vineis, Paolo; Weiderpass, Elisabete; Skeie, Guri; Brustad, Magritt; Palli, Domenico; Tumino, Rosario; Grioni, Sara; Sacerdote, Carlotta; Bueno-de-Mesquita, H. B(as).; Peeters, Petra H.; Boutron-Ruault, Marie-Christine; Kvaskoff, Marina; Cadeau, Claire; Huerta, José María; Sánchez, Maria-José; Agudo, Antonio; Lasheras, Cristina; Quirós, J. Ramón; Chamosa, Saioa; Riboli, Elio; Travis, Ruth C.; Ward, Heather; Murphy, Neil; Khaw, Kay-Tee; Trichopoulou, Antonia; Lagiou, Pagona; Papatesta, Eleni-Maria; Boeing, Heiner; Kuehn, Tilman; Katzke, Verena; Steffen, Annika; Johansson, Anders; Brennan, Paul; Johansson, Mattias
2016-01-01
Experimental and epidemiological data suggest that vitamin D play a role in pathogenesis and progression of cancer, but prospective data on head and neck cancer (HNC) and oesophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants with blood samples between 1992 and 2000. This analysis includes 497 case-control pairs of the head and neck and oesophagus, as well as 443 additional controls. Circulating 25(OH)D3 were measured in pre-diagnostic samples and evaluated in relation to HNC and oesophagus cancer risk and post-diagnosis all-cause mortality. After controlling for risk factors, a doubling of 25(OH)D3 was associated with 30% lower odds of HNC (OR 0.70, 95% confidence interval [95% CI] 0.56–0.88, Ptrend = 0.001). Subsequent analyses by anatomical sub-site indicated clear inverse associations with risk of larynx and hypopharynx cancer combined (OR 0.55, 95CI% 0.39–0.78) and oral cavity cancer (OR 0.60, 95CI% 0.42–0.87). Low 25(OH)D3 concentrations were also associated with higher risk of death from any cause among HNC cases. No clear association was seen with risk or survival for oesophageal cancer. Study participants with elevated circulating concentrations of 25(OH)D3 had decreased risk of HNC, as well as improved survival following diagnosis. PMID:27812016
Fanidi, Anouar; Muller, David C; Midttun, Øivind; Ueland, Per Magne; Vollset, Stein Emil; Relton, Caroline; Vineis, Paolo; Weiderpass, Elisabete; Skeie, Guri; Brustad, Magritt; Palli, Domenico; Tumino, Rosario; Grioni, Sara; Sacerdote, Carlotta; Bueno-de-Mesquita, H B As; Peeters, Petra H; Boutron-Ruault, Marie-Christine; Kvaskoff, Marina; Cadeau, Claire; Huerta, José María; Sánchez, Maria-José; Agudo, Antonio; Lasheras, Cristina; Quirós, J Ramón; Chamosa, Saioa; Riboli, Elio; Travis, Ruth C; Ward, Heather; Murphy, Neil; Khaw, Kay-Tee; Trichopoulou, Antonia; Lagiou, Pagona; Papatesta, Eleni-Maria; Boeing, Heiner; Kuehn, Tilman; Katzke, Verena; Steffen, Annika; Johansson, Anders; Brennan, Paul; Johansson, Mattias
2016-11-04
Experimental and epidemiological data suggest that vitamin D play a role in pathogenesis and progression of cancer, but prospective data on head and neck cancer (HNC) and oesophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants with blood samples between 1992 and 2000. This analysis includes 497 case-control pairs of the head and neck and oesophagus, as well as 443 additional controls. Circulating 25(OH)D 3 were measured in pre-diagnostic samples and evaluated in relation to HNC and oesophagus cancer risk and post-diagnosis all-cause mortality. After controlling for risk factors, a doubling of 25(OH)D 3 was associated with 30% lower odds of HNC (OR 0.70, 95% confidence interval [95% CI] 0.56-0.88, P trend = 0.001). Subsequent analyses by anatomical sub-site indicated clear inverse associations with risk of larynx and hypopharynx cancer combined (OR 0.55, 95CI% 0.39-0.78) and oral cavity cancer (OR 0.60, 95CI% 0.42-0.87). Low 25(OH)D 3 concentrations were also associated with higher risk of death from any cause among HNC cases. No clear association was seen with risk or survival for oesophageal cancer. Study participants with elevated circulating concentrations of 25(OH)D 3 had decreased risk of HNC, as well as improved survival following diagnosis.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Antoni, Delphine, E-mail: Dantoni@strasbourg.unicancer.fr; Clavier, Jean-Baptiste; Pop, Marius
2013-07-15
Purpose: To retrospectively evaluate the prognostic factors and survival of a series of 777 patients with brain metastases (BM) from a single institution. Methods and Materials: Patients were treated with surgery followed by whole-brain radiation therapy (WBRT) or with WBRT alone in 16.3% and 83.7% of the cases, respectively. The patients were RPA (recursive partitioning analysis) class I, II, and III in 11.2%, 69.6%, and 18.4% of the cases, respectively; RPA class II-a, II-b, and II-c in 8.3%, 24.8%, and 66.9% of the cases, respectively; and with GPA (graded prognostic assessment) scores of 0-1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0 in 35%,more » 27.5%, 18.2%, and 8.6% of the cases, respectively. Results: The median overall survival (OS) times according to RPA class I, II, and III were 20.1, 5.1, and 1.3 months, respectively (P<.0001); according to RPA class II-a, II-b, II-c: 9.1, 8.9, and 4.0 months, respectively (P<.0001); and according to GPA score 0-1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0: 2.5, 4.4, 9.0, and 19.1 months, respectively (P<.0001). By multivariate analysis, the favorable independent prognostic factors for survival were as follows: for gastrointestinal tumor, a high Karnofsky performance status (KPS) (P=.0003) and an absence of extracranial metastases (ECM) (P=.003); for kidney cancer, few BM (P=.002); for melanoma, few BM (P=.01), an absence of ECM (P=.002), and few ECM (P=.0002); for lung cancer, age (P=.007), a high KPS (P<.0001), an absence of ECM (P<.0001), few ECM and BM (P<.0001 and P=.0006, respectively), and control of the primary tumor (P=.004); and for breast cancer, age (P=.001), a high KPS (P=.007), control of the primary tumor (P=.05), and few ECM and BM (P=.01 and P=.0002, respectively). The triple-negative subtype was a significant unfavorable factor (P=.007). Conclusion: Prognostic factors varied by pathology. Our analysis confirms the strength of prognostic factors used to determine the GPA score, including the genetic subtype for breast cancer.« less
Miles, Fayth L.; Chang, Shen-Chih; Morgenstern, Hal; Tashkin, Donald; Rao, Jian-Yu; Cozen, Wendy; Mack, Thomas; Lu, Qing-Yi; Zhang, Zuo-Feng
2016-01-01
The effect of red and processed meats on cancer survival is unclear. We sought to examine the role of total and processed red meat consumption on all-cause mortality among patients with cancers of the upper aerodigestive tract (UADT) and lung, in order to test our hypothesis that red or processed meat was associated with overall mortality in these patients. Using data from a population-based case-control study conducted in Los Angeles County, we conducted a case-only analysis to examine the association of red or processed meat consumption on mortality after 12 years of follow-up, using a diet history questionnaire. Cox regression was used to estimate adjusted hazards ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders. Of 601 UADT cancer cases and 611 lung cancer cases, there were 248 and 406 deaths, respectively, yielding crude mortality rates of 0.07 and 0.12 deaths per year. Comparing the highest with lowest quartile of red meat consumption, the adjusted HR was 1.64 (95% CI: 1.04, 2.57) among UADT cancer cases; for red or processed meat the adjusted HR was 1.76 (95% CI: 1.10, 2.82). A dose-response trend was observed. A weaker association was observed with red meat consumption and overall mortality among lung cancer cases. In conclusion, this case-only analysis demonstrated that increased consumption of red or processed meats was associated with mortality among UADT cancer cases, and weakly associated with mortality among lung cancer cases. PMID:27188908
Miles, Fayth L; Chang, Shen-Chih; Morgenstern, Hal; Tashkin, Donald; Rao, Jian-Yu; Cozen, Wendy; Mack, Thomas; Lu, Qing-Yi; Zhang, Zuo-Feng
2016-06-01
The effect of red and processed meats on cancer survival is unclear. We sought to examine the role of total and processed red meat consumption on all-cause mortality among patients with cancers of the upper aerodigestive tract (UADT) and lung, in order to test our hypothesis that red or processed meat was associated with overall mortality in these patients. Using data from a population-based case-control study conducted in Los Angeles County, we conducted a case-only analysis to examine the association of red or processed meat consumption on mortality after 12 years of follow-up, using a diet history questionnaire. Cox regression was used to estimate adjusted hazard ratios (HRs) with 95% confidence intervals (CIs), adjusting for potential confounders. Of 601 UADT cancer cases and 611 lung cancer cases, there were 248 and 406 deaths, respectively, yielding crude mortality rates of 0.07 and 0.12 deaths per year. Comparing the highest with lowest quartile of red meat consumption, the adjusted HR was 1.64 (95% CI, 1.04-2.57) among UADT cancer cases; for red or processed meat, the adjusted HR was 1.76 (95% CI, 1.10-2.82). A dose-response trend was observed. A weaker association was observed with red meat consumption and overall mortality among lung cancer cases. In conclusion, this case-only analysis demonstrated that increased consumption of red or processed meats was associated with mortality among UADT cancer cases and WAS weakly associated with mortality among lung cancer cases. Copyright © 2016 Elsevier Inc. All rights reserved.
Case-control studies in neurosurgery.
Nesvick, Cody L; Thompson, Clinton J; Boop, Frederick A; Klimo, Paul
2014-08-01
Observational studies, such as cohort and case-control studies, are valuable instruments in evidence-based medicine. Case-control studies, in particular, are becoming increasingly popular in the neurosurgical literature due to their low cost and relative ease of execution; however, no one has yet systematically assessed these types of studies for quality in methodology and reporting. The authors performed a literature search using PubMed/MEDLINE to identify all studies that explicitly identified themselves as "case-control" and were published in the JNS Publishing Group journals (Journal of Neurosurgery, Journal of Neurosurgery: Pediatrics, Journal of Neurosurgery: Spine, and Neurosurgical Focus) or Neurosurgery. Each paper was evaluated for 22 descriptive variables and then categorized as having either met or missed the basic definition of a case-control study. All studies that evaluated risk factors for a well-defined outcome were considered true case-control studies. The authors sought to identify key features or phrases that were or were not predictive of a true case-control study. Those papers that satisfied the definition were further evaluated using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. The search detected 67 papers that met the inclusion criteria, of which 32 (48%) represented true case-control studies. The frequency of true case-control studies has not changed with time. Use of odds ratios (ORs) and logistic regression (LR) analysis were strong positive predictors of true case-control studies (for odds ratios, OR 15.33 and 95% CI 4.52-51.97; for logistic regression analysis, OR 8.77 and 95% CI 2.69-28.56). Conversely, negative predictors included focus on a procedure/intervention (OR 0.35, 95% CI 0.13-0.998) and use of the word "outcome" in the Results section (OR 0.23, 95% CI 0.082-0.65). After exclusion of nested case-control studies, the negative correlation between focus on a procedure/intervention and true case-control studies was strengthened (OR 0.053, 95% CI 0.0064-0.44). There was a trend toward a negative association between the use of survival analysis or Kaplan-Meier curves and true case-control studies (OR 0.13, 95% CI 0.015-1.12). True case-control studies were no more likely than their counterparts to use a potential study design "expert" (OR 1.50, 95% CI 0.57-3.95). The overall average STROBE score was 72% (range 50-86%). Examples of reporting deficiencies were reporting of bias (28%), missing data (55%), and funding (44%). The results of this analysis show that the majority of studies in the neurosurgical literature that identify themselves as "case-control" studies are, in fact, labeled incorrectly. Positive and negative predictors were identified. The authors provide several recommendations that may reverse the incorrect and inappropriate use of the term "case-control" and improve the quality of design and reporting of true case-control studies in neurosurgery.
[Application of damage control concept in severe limbs fractures combining with multiple trauma].
Bayin, Er-gu-le; Jin, Hong-bing; Li, Ming
2015-09-01
To discuss the application and clinical effect of damage control concept in the treatment of severe limbs fractures combining with multiple trauma. From July 2009 to July 2012, 30 patients with severe limbs fractures combining with multiple trauma were treated with the damage control concept, included 20 males and 10 females with an average age of (34.03 ± 12.81) years old ranging from 20 to 60 years old; the ISS averaged (35.00 ± 12.81) points (ranged from 26 to 54 points). And the control group also contained 30 patients with severe limbs fractures combining with multiple trauma treated by the traditional operation from June 2006 to June 2009, there were 23 males and 7 females with an average age of (34.23 ± 11.04) years old ranging from 18 to 65 years old. The ISS averaged (35.56 ± 11.04) points (ranged from 26 to 51 points). The age, gender, ISS, Gustilo classification, operation time, intraoperative blood loss, blood transfusion,postoperative complications and mortality rate were observed and compared. In the damage control concept group,there were 28 cases surviving and 2 cases (6.7%) death; 6 cases of postoperative complication included 2 cases of adult respiratory distress syndrome, 1 case of multiple organ failure, 1 case of disseminated intravascular coagulation and 2 cases of wound infection. In the control group, there were 22 cases surviving and 8 cases death(26.7%); 13 cases of postoperative complication included 4 cases of adult respiratory distress syndrome,2 cases of multiple organ failure, 2 cases of disseminated intravascular coagulation and 3 cases of wound infection. There were no statistically significant differences between two groups in age, gender, ISS, Gustilo classfication and complication (P > 0.05), however there were statistically significant differences in mortality rate, operation time, blodd loss, blodd transfusion between two groups (P < 0.05). Damage control concept is used to treat severe limbs fractures combining with multiple trauma which has the rapid and effective therapy, can improve survival rate and reduce complication.
Clinical outcomes of gastrointestinal stromal tumor in southern Thailand
Pornsuksiri, Kittima; Chewatanakornkul, Siripong; Kanngurn, Samornmas; Maneechay, Wanwisa; Chaiyapan, Walawee; Sangkhathat, Surasak
2012-01-01
AIM: To review a single institutional experience in clinical management of gastrointestinal stromal tumors (GIST) and analyze for factors determining treatment outcome. METHODS: Clinicopathological data of patients with a diagnosis of GIST who were treated at our institute during November 2004 to September 2009 were retrospectively reviewed. RESULTS: Ninety-nine cases were included in the analysis. Primary tumor sites were at the stomach in and small bowel in 44% and 33%, respectively. Thirty-one cases already had metastasis at presentation and the most common metastatic site was the liver. Sixty-four cases (65%) were in the high-risk category. Surgical treatment was performed in 77 cases (78%), 3 of whom received upfront targeted therapy. Complete resection was achieved in 56 cases (73% of operative cases) and of whom 27 developed local recurrence or distant metastasis at a median duration of 2 years. Imatinib was given as a primary therapy in unresectable cases (25 cases) and as an adjuvant in cases with residual tumor (21 cases). Targeted therapy gave partial response in 7 cases (15%), stable disease in 27 cases (57%) and progressive disease in 13 cases (28%). Four-year overall survival was 74% (95% CI: 61%-83%). Univariate survival analysis found that low-risk tumor, gastric site, complete resection and response to imatinib were associated with better survival. CONCLUSION: The overall outcomes of GIST can be predicted by risk-categorization. Surgery alone may not be a curative treatment for GIST. Response to targeted therapy is a crucial survival determinant in these patients. PMID:23444235
Desai, A; Wu, H; Sun, L; Sesterhenn, I A; Mostofi, F K; McLeod, D; Amling, C; Kusuda, L; Lance, R; Herring, J; Foley, J; Baldwin, D; Bishoff, J T; Soderdahl, D; Moul, J W
2002-01-01
The objectives of this work were to evaluate the efficacy of controlled close step-sectioned and whole-mounted radical prostatectomy specimen processing in prediction of clinical outcome as compared to the traditional processing techniques. Two-hundred and forty nine radical prostatectomy (RP) specimens were whole-mounted and close step-sectioned at caliper-measured 2.2-2.3 mm intervals. A group of 682 radical prostatectomy specimens were partially sampled as control. The RPs were performed during 1993-1999 with a mean follow-up of 29.3 months, pretreatment PSA of 0.1-40, and biopsy Gleason sums of 5-8. Disease-free survival based on biochemical or clinical recurrence and secondary intervention were computed using a Kaplan-Meier analysis. There were no significant differences in age at diagnosis, age at surgery, PSA at diagnosis, or biopsy Gleason between the two groups (P<0.05). Compared with the non-close step-sectioned group, the close step-sectioned group showed higher detection rates of extra-prostatic extension (215 (34.1%) vs, 128 (55.4%), P<0.01), and seminal vesicle invasion (50 (7.6%) vs 35 (14.7%), P<0.01). The close step-sectioned group correlated with greater 3-y disease-free survival in organ-confined (P<0.01) and specimen-confined (P<0.01) cases, over the non-uniform group. The close step-sectioned group showed significantly higher disease-free survival for cases with seminal vesicle invasion (P=0.046). No significant difference in disease-free survival was found for the positive margin group (P=0.39) between the close step-sectioned and non-uniform groups. The close step-sectioned technique correlates with increased disease-free survival rates for organ and specimen confined cases, possibly due to higher detection rates of extra-prostatic extension and seminal vesicle invasion. Close step-sectioning provides better assurance of organ-confined disease, resulting in enhanced prediction of outcome by pathological (TNM) stage.
Long-term chemotherapy with lomustine of intracranial meningioma occurring in a miniature schnauzer.
Jung, Dong-In; Kim, Ha-Jung; Park, Chul; Kim, Ju-Won; Kang, Byeong-Teck; Lim, Chae-Young; Park, Eun-Hee; Sur, Jung-Hyang; Seo, Min-Ho; Hahm, Dae-Hyun; Park, Hee-Myung
2006-04-01
A 14-year-old male miniature schnauzer was referred to us because it was circling to the right. A mass in the diencephalon was noted on brain magnetic resonance images. The dura was thickened with marked linear enhancement after contrast administration. Based on diagnostic image analysis, this lesion strongly suggested meningioma. The patient's symptoms were well controlled by a combination therapy of prednisolone and lomustine (CCNU), and survived for thirteen months after diagnosis. This case was diagnosed as a meningioma based on histopathological findings. This report describes the clinical findings, imaging characteristics, and pathologic features of a diencephalic and mesencephalic meningioma and long-term survival after lomustine and prednisolone therapy.
Kim, Joo Yeong; Shin, Sang Do; Ro, Young Sun; Song, Kyoung Jun; Lee, Eui Jung; Park, Chang Bae; Hwang, Seung Sik
2013-08-01
This study aimed to determine whether active post-resuscitation care (APRC) was associated with improved out-of-hospital cardiac arrest (OHCA) outcomes on a nationwide level. We used a national OHCA cohort database consisting of hospital and ambulance data. We included all survivors of OHCA, excluding patients with non-cardiac etiology, younger than 15 years, and with unknown outcomes, from (2008 to 2010). The APRC was defined when the OHCA patients received mild therapeutic hypothermia (MTH) or active cardiac care (ACC), such as intravenous thrombolysis, percutaneous coronary intervention, coronary artery bypass surgery, and pacemaker/implantable cardioverter defibrillator insertion, as well as routine intensive care; patients receiving conservative post-resuscitation care (CPRC) served as the other group. The primary and secondary outcomes were survival to discharge and a good neurological outcome (cerebral performance category [CPC] 1-2), respectively. We extracted propensity-matched samples to control for selection bias. A multivariable logistic regression analysis was used to compare the APRC and CPRC groups adjusting for potential risks to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). Of total 64,155 patients, 4557 survived to admission and were included in the final analysis. Out of these patients, 1599 (35.1%) cases survived to discharge, and 499 (11.0%) cases were discharged with good neurological recoveries. Overall, 695 cases (15.3%) received any APRC, including MTH (n=377, 8.3%) and ACC (370, 8.1%). The outcomes was better in the APRC group than in the CPRC group for survival to discharge (58.7% vs. 30.8%, p<0.001) and good neurological outcome (27.2% vs. 8.0%, p<0.001), respectively. In the total cohort, the adjusted ORs of the APRC group compared to those the CPRC group were 2.15 (95% CI 1.78-2.59) for survival to discharge and 2.54 (95% CI 1.98-3.27) for a good neurological outcome. In the propensity score-matched cohort, the adjusted ORs for survival to discharge and good neurological outcome of APRC were significantly favorable. Active post-resuscitation care resulted in significantly improved outcomes in adult OHCA patients with a presumed cardiac etiology in a nationwide, retrospective, observational study. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
Long survival in a 69,XXX triploid infant in Greece.
Iliopoulos, Dimitrios; Vassiliou, Georgia; Sekerli, Eleni; Sidiropoulou, Vasiliki; Tsiga, Alexandra; Dimopoulou, Despina; Voyiatzis, Nikolaos
2005-12-30
The live birth of a triploidy infant is a very rare event and death usually occurs within the first hours of life. Triploid cases with a survival of more than two months are infrequent. We report on an infant with a 69,XXX chromosome constitution who survived 164 days. Chromosomal analysis demonstrated a 69,XXX karyotype with no evidence of mosaicism. This is the longest survival reported for this condition to date in Greece and the fourth longest worldwide. The infant was admitted to our clinic several times due to respiratory problems, and supplementary oxygen was required. The improved survival of our case was possibly due to better management of respiratory illness and prematurity, and these are essential factors that physicians should consider carefully with such rare cases.
38 CFR 3.701 - Elections of pension or compensation.
Code of Federal Regulations, 2010 CFR
2010-07-01
... rights of all dependents in that case. An election by a surviving spouse controls the claims of all children including children over 18 and children not in the custody of the surviving spouse. The election of improved pension by a surviving spouse, however, shall not prejudice the rights of any child...
DOE Office of Scientific and Technical Information (OSTI.GOV)
Stessin, Alexander M.; Weill Medical College of Cornell University, New York, NY; Meyer, Joshua E.
2008-11-15
Purpose: Cancer of the exocrine pancreas is the fifth leading cause of cancer death in the United States. Neoadjuvant chemoradiation has been investigated in several trials as a strategy for downstaging locally advanced disease to resectability. The aim of the present study is to examine the effect of neoadjuvant radiation therapy (RT) vs. other treatments on long-term survival for patients with resectable pancreatic cancer in a large population-based sample group. Methods and Materials: The Surveillance, Epidemiology, and End Results (SEER) registry database (1994-2003) was queried for cases of surgically resected pancreatic cancer. Retrospective analysis was performed. The endpoint of themore » study was overall survival. Results: Using Kaplan-Meier analysis we found that the median overall survival of patients receiving neoadjuvant RT was 23 months vs. 12 months with no RT and 17 months with adjuvant RT. Using Cox regression and controlling for independent covariates (age, sex, stage, grade, and year of diagnosis), we found that neoadjuvant RT results in significantly higher rates of survival than other treatments (hazard ratio [HR], 0.55; 95% confidence interval, 0.38-0.79; p = 0.001). Specifically comparing adjuvant with neoadjuvant RT, we found a significantly lower HR for death in patients receiving neoadjuvant RT rather than adjuvant RT (HR, 0.63; 95% confidence interval, 0.45-0.90; p = 0.03). Conclusions: This analysis of SEER data showed a survival benefit for the use of neoadjuvant RT over surgery alone or surgery with adjuvant RT in treating pancreatic cancer. Therapeutic strategies that use neoadjuvant RT should be further explored for patients with resectable pancreatic cancer.« less
Postoperative venous thromboembolism predicts survival in cancer patients.
Auer, Rebecca Ann C; Scheer, Adena Sarah; McSparron, Jakob I; Schulman, Allison R; Tuorto, Scott; Doucette, Steve; Gonsalves, Jamie; Fong, Yuman
2012-05-01
To determine whether a postoperative venous thromboembolism (VTE) is associated with a worse prognosis and/or a more advanced cancer stage and to evaluate the association between a postoperative VTE and cancer-specific survival when known prognostic factors, such as age, stage, cancer type, and type of surgery, are controlled. It is unknown whether oncology patients who develop a venous thromboembolism after a complete curative resection are at the same survival disadvantage as oncology patients with a spontaneous VTE. A retrospective case control study was conducted at Memorial Sloan-Kettering Cancer Center. Years of study: January 1, 2000, to December 31, 2005. Median follow-up: 24.9 months (Interquartile range 13.0, 43.0). All cancer patients who underwent abdominal, pelvic, thoracic, or soft tissue procedures and those who developed a VTE within 30 days of the procedure were identified from a prospective morbidity and mortality database. Overall survival (OS) was calculated for the entire cohort. In the matched cohort, OS and disease-specific survival (DSS) were calculated for stages 0 to 3 and stages 0 to 2. A total of 23,541 cancer patients underwent an invasive procedure and 474 (2%) had a postoperative VTE. VTE patients had a significantly worse 5-year OS compared to no-VTE patients (43.8% vs 61.2%; P < 0.0001); 205 VTE patients (stages 0-3) were matched to 2050 controls by age, sex, cancer type, stage, and surgical procedure. In this matched analysis, VTE patients continued to demonstrate a significantly worse prognosis with an inferior 5-year OS (54.7% vs 66.3%; P < 0.0001) and DSS (67.8% vs 79.5%; P = 0.0007) as compared to controls. The survival difference persisted in early stage disease (stage 0-2), with 5-year DSS of 82.9% versus 87.3% (P = 0.01). Postoperative VTE in oncology patients with limited disease and a complete surgical resection is associated with an inferior cancer survival. A postoperative VTE remains a poor prognostic factor, even when controlling for age, stage, cancer type, and surgical procedure further supporting an independent link between hypercoagulability and cancer survival.
Vannucchi, Alessandro M; Kantarjian, Hagop M; Kiladjian, Jean-Jacques; Gotlib, Jason; Cervantes, Francisco; Mesa, Ruben A; Sarlis, Nicholas J; Peng, Wei; Sandor, Victor; Gopalakrishna, Prashanth; Hmissi, Abdel; Stalbovskaya, Viktoriya; Gupta, Vikas; Harrison, Claire; Verstovsek, Srdan
2015-09-01
Ruxolitinib, a potent Janus kinase 1/2 inhibitor, resulted in rapid and durable improvements in splenomegaly and disease-related symptoms in the 2 phase III COMFORT studies. In addition, ruxolitinib was associated with prolonged survival compared with placebo (COMFORT-I) and best available therapy (COMFORT-II). We present a pooled analysis of overall survival in the COMFORT studies using an intent-to-treat analysis and an analysis correcting for crossover in the control arms. Overall, 301 patients received ruxolitinib (COMFORT-I, n=155; COMFORT-II, n=146) and 227 patients received placebo (n=154) or best available therapy (n=73). After a median three years of follow up, intent-to-treat analysis showed that patients who received ruxolitinib had prolonged survival compared with patients who received placebo or best available therapy [hazard ratio=0.65; 95% confidence interval (95%CI): 0.46-0.90; P=0.01]; the crossover-corrected hazard ratio was 0.29 (95%CI: 0.13-0.63). Both patients with intermediate-2- or high-risk disease showed prolonged survival, and patients with high-risk disease in the ruxolitinib group had survival similar to that of patients with intermediate-2-risk disease in the control group. The Kaplan-Meier estimate of overall survival at week 144 was 78% in the ruxolitinib arm, 61% in the intent-to-treat control arm, and 31% in the crossover-adjusted control arm. While larger spleen size at baseline was prognostic for shortened survival, reductions in spleen size with ruxolitinib treatment correlated with longer survival. These findings are consistent with previous reports and support that ruxolitinib offers a survival benefit for patients with myelofibrosis compared with conventional therapies. (clinicaltrials.gov identifiers: COMFORT-I, NCT00952289; COMFORT-II, NCT00934544). Copyright© Ferrata Storti Foundation.
Ablation effects of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells.
Chen, Kaiyun; Zhu, Shuguang; Xiang, Guoan; Duan, Xiaopeng; He, Jiwen; Chen, Guihua
2016-05-01
To have in-depth analysis of clinical ablation effect of noninvasive radiofrequency field-induced hyperthermia on liver cancer cells, this paper collected liver cancer patients' treatment information from 10 hospitals during January 2010 and December 2011, from which 1050 cases of patients were randomly selected as study object of observation group who underwent noninvasive radiofrequency field-induced hyperthermia treatment; in addition, 500 cases of liver cancer patients were randomly selected as study object of control group who underwent clinical surgical treatment. After treatment was completed, three years of return visit were done, survival rates of the two groups of patients after 1 year, 2 years, and 3 years were compared, and clinical effects of radiofrequency ablation of liver cancer were evaluated. Zoom results show that the two groups are similar in terms of survival rate, and the difference is without statistical significance. 125 patients in observation group had varying degrees of adverse reactions, while 253 patients in control group had adverse reactions. There was difference between groups P < 0.05, with significant statistical significance. It can be concluded that radiofrequency ablation of liver cancer is more secure. Therefore, the results of this study fully demonstrate that liver cancer treatment with noninvasive radiofrequency field-induced hyperthermia is with safety effect and satisfactory survival rate, thus with relatively high clinical value in clinical practice.
Piecewise exponential survival times and analysis of case-cohort data.
Li, Yan; Gail, Mitchell H; Preston, Dale L; Graubard, Barry I; Lubin, Jay H
2012-06-15
Case-cohort designs select a random sample of a cohort to be used as control with cases arising from the follow-up of the cohort. Analyses of case-cohort studies with time-varying exposures that use Cox partial likelihood methods can be computer intensive. We propose a piecewise-exponential approach where Poisson regression model parameters are estimated from a pseudolikelihood and the corresponding variances are derived by applying Taylor linearization methods that are used in survey research. The proposed approach is evaluated using Monte Carlo simulations. An illustration is provided using data from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of male smokers in Finland, where a case-cohort study of serum glucose level and pancreatic cancer was analyzed. Copyright © 2012 John Wiley & Sons, Ltd.
Konerman, Monica A; Price, Jennifer C; Campbell, Catherine Y; Eluri, Swathi; Gurakar, Ahmet; Hamilton, James; Li, Zhiping
2016-07-05
BACKGROUND Cardiopulmonary (CP) outcomes remain a leading cause of morbidity and mortality following liver transplantation (LT). The optimal CP risk stratification of LT candidates remains unclear. The aim of this study was to evaluate the association of pre-LT transthoracic echocardiogram (TTE) findings and 6-month post-LT outcomes. MATERIAL AND METHODS This retrospective review analyzed adults who underwent LT, comparing those who died within 6 months of LT (cases; n=38) with age- and sex-matched patients who survived >6 months (controls; n=38). Cases were categorized by cause of death (COD) defined as either a primary CP process (n=20) or a non-CP process (n=18). Data were analyzed using logistic regression and survival analysis was performed using Kaplan-Meier curves. RESULTS There was a higher odds of death within 6 months of LT with ≥ mild mitral regurgitation (OR 3.44, p=0.03) or an incomplete assessment of right ventricular systolic function (RVSF) (OR 24, p=0.004). On subgroup analysis, these findings only persisted in patients with a CP COD. Patients with CP COD were older (61 vs. 54.5, p=0.04), had longer intervals between TTE and LT (122 vs. 29 days, p=0.05), less complete assessments of RVSF (p=0.009), and lower RV fractional area change (p=0.04) compared to patients with non-CP COD. CONCLUSIONS Multiple TTE parameters were associated with patients who died within 6 months of LT, and in particular patients with a CP COD. Our findings suggest that pre-LT TTEs can convey useful CP risk stratification information and emphasizes the importance of adequately assessing these parameters prior to LT.
Sapkota, Yadav; Vivo, Immaculata De; Steinthorsdottir, Valgerdur; Fassbender, Amelie; Bowdler, Lisa; Buring, Julie E; Edwards, Todd L; Jones, Sarah; O, Dorien; Peterse, Daniëlle; Rexrode, Kathryn M; Ridker, Paul M; Schork, Andrew J; Thorleifsson, Gudmar; Wallace, Leanne M; Kraft, Peter; Morris, Andrew P; Nyholt, Dale R; Edwards, Digna R Velez; Nyegaard, Mette; D'Hooghe, Thomas; Chasman, Daniel I; Stefansson, Kari; Missmer, Stacey A; Montgomery, Grant W
2017-09-12
Genome-wide association (GWA) studies have identified 19 independent common risk loci for endometriosis. Most of the GWA variants are non-coding and the genes responsible for the association signals have not been identified. Herein, we aimed to assess the potential role of protein-modifying variants in endometriosis using exome-array genotyping in 7164 cases and 21005 controls, and a replication set of 1840 cases and 129016 controls of European ancestry. Results in the discovery sample identified significant evidence for association with coding variants in single-variant (rs1801232-CUBN) and gene-level (CIITA and PARP4) meta-analyses, but these did not survive replication. In the combined analysis, there was genome-wide significant evidence for rs13394619 (P = 2.3 × 10 -9 ) in GREB1 at 2p25.1 - a locus previously identified in a GWA meta-analysis of European and Japanese samples. Despite sufficient power, our results did not identify any protein-modifying variants (MAF > 0.01) with moderate or large effect sizes in endometriosis, although these variants may exist in non-European populations or in high-risk families. The results suggest continued discovery efforts should focus on genotyping large numbers of surgically-confirmed endometriosis cases and controls, and/or sequencing high-risk families to identify novel rare variants to provide greater insights into the molecular pathogenesis of the disease.
The effect of first chromosome long arm duplication on survival of endometrial carcinoma.
Sever, Erman; Doğer, Emek; Çakıroğlu, Yiğit; Sünnetçi, Deniz; Çine, Naci; Savlı, Hakan; Yücesoy, İzzet
2014-12-01
The aim of this study is to investigate the effect of first chromosome long arm duplication (dup(1q)) in cases with endometrial carcinoma detected with array based comperative genomic hybridization (aCGH) on survival from the cancer. A total of 53 patients with the diagnosis of endometrial carcinom due to endometrial biopsy and who have been operated for this reason have been allocated in the study. Frozen section biopsy and staging surgery have been performed for all the cases. Samples obtained from the tumoral mass have been investigated for chromosomal aberrations with aCGH method. Kaplan-Meier and Cox-regression analysis have been performed for survival analysis. Among 53 cases with endometrial carcinomas, dup(1q) was diagnosed in 14 (26.4%) of the cases. For the patient group that has been followed-up for 24 months (3-33 months), dup(1q) (p=.01), optimal cytoreduction (p<.001), lymph node positivity (p=.006), tumor stage >1 (p=.006) and presence of high risk tumor were the factors that were associated with survival. Cox-regression analysis has revealed that optimal cytoreduction was the most important prognostic factor (p=.02). Presence of 1q duplication can be used as a prognostic factor in the preoperative period.
The effect of first chromosome long arm duplication on survival of endometrial carcinoma
Sever, Erman; Doğer, Emek; Çakıroğlu, Yiğit; Sünnetçi, Deniz; Çine, Naci; Savlı, Hakan; Yücesoy, İzzet
2014-01-01
Objective: The aim of this study is to investigate the effect of first chromosome long arm duplication (dup(1q)) in cases with endometrial carcinoma detected with array based comperative genomic hybridization (aCGH) on survival from the cancer. Materials and Methods: A total of 53 patients with the diagnosis of endometrial carcinom due to endometrial biopsy and who have been operated for this reason have been allocated in the study. Frozen section biopsy and staging surgery have been performed for all the cases. Samples obtained from the tumoral mass have been investigated for chromosomal aberrations with aCGH method. Kaplan-Meier and Cox-regression analysis have been performed for survival analysis. Results: Among 53 cases with endometrial carcinomas, dup(1q) was diagnosed in 14 (26.4%) of the cases. For the patient group that has been followed-up for 24 months (3-33 months), dup(1q) (p=.01), optimal cytoreduction (p<.001), lymph node positivity (p=.006), tumor stage >1 (p=.006) and presence of high risk tumor were the factors that were associated with survival. Cox-regression analysis has revealed that optimal cytoreduction was the most important prognostic factor (p=.02). Conclusion: Presence of 1q duplication can be used as a prognostic factor in the preoperative period. PMID:28913021
Castet, Jean-Francois; Saleh, Joseph H.
2013-01-01
This article develops a novel approach and algorithmic tools for the modeling and survivability analysis of networks with heterogeneous nodes, and examines their application to space-based networks. Space-based networks (SBNs) allow the sharing of spacecraft on-orbit resources, such as data storage, processing, and downlink. Each spacecraft in the network can have different subsystem composition and functionality, thus resulting in node heterogeneity. Most traditional survivability analyses of networks assume node homogeneity and as a result, are not suited for the analysis of SBNs. This work proposes that heterogeneous networks can be modeled as interdependent multi-layer networks, which enables their survivability analysis. The multi-layer aspect captures the breakdown of the network according to common functionalities across the different nodes, and it allows the emergence of homogeneous sub-networks, while the interdependency aspect constrains the network to capture the physical characteristics of each node. Definitions of primitives of failure propagation are devised. Formal characterization of interdependent multi-layer networks, as well as algorithmic tools for the analysis of failure propagation across the network are developed and illustrated with space applications. The SBN applications considered consist of several networked spacecraft that can tap into each other's Command and Data Handling subsystem, in case of failure of its own, including the Telemetry, Tracking and Command, the Control Processor, and the Data Handling sub-subsystems. Various design insights are derived and discussed, and the capability to perform trade-space analysis with the proposed approach for various network characteristics is indicated. The select results here shown quantify the incremental survivability gains (with respect to a particular class of threats) of the SBN over the traditional monolith spacecraft. Failure of the connectivity between nodes is also examined, and the results highlight the importance of the reliability of the wireless links between spacecraft (nodes) to enable any survivability improvements for space-based networks. PMID:23599835
Castet, Jean-Francois; Saleh, Joseph H
2013-01-01
This article develops a novel approach and algorithmic tools for the modeling and survivability analysis of networks with heterogeneous nodes, and examines their application to space-based networks. Space-based networks (SBNs) allow the sharing of spacecraft on-orbit resources, such as data storage, processing, and downlink. Each spacecraft in the network can have different subsystem composition and functionality, thus resulting in node heterogeneity. Most traditional survivability analyses of networks assume node homogeneity and as a result, are not suited for the analysis of SBNs. This work proposes that heterogeneous networks can be modeled as interdependent multi-layer networks, which enables their survivability analysis. The multi-layer aspect captures the breakdown of the network according to common functionalities across the different nodes, and it allows the emergence of homogeneous sub-networks, while the interdependency aspect constrains the network to capture the physical characteristics of each node. Definitions of primitives of failure propagation are devised. Formal characterization of interdependent multi-layer networks, as well as algorithmic tools for the analysis of failure propagation across the network are developed and illustrated with space applications. The SBN applications considered consist of several networked spacecraft that can tap into each other's Command and Data Handling subsystem, in case of failure of its own, including the Telemetry, Tracking and Command, the Control Processor, and the Data Handling sub-subsystems. Various design insights are derived and discussed, and the capability to perform trade-space analysis with the proposed approach for various network characteristics is indicated. The select results here shown quantify the incremental survivability gains (with respect to a particular class of threats) of the SBN over the traditional monolith spacecraft. Failure of the connectivity between nodes is also examined, and the results highlight the importance of the reliability of the wireless links between spacecraft (nodes) to enable any survivability improvements for space-based networks.
Cai, Xiaopeng; Liu, Xu; Yu, Haitao; Li, Jiguang; Zheng, Xinyu
2012-01-01
Breast cancer has a high incidence worldwide, while Chinese patients have some special characteristics compared to Western patients. A meta-analysis was carried out to determine the effectiveness of breast-conserving therapy (BCT) or mastectomy therapy (MT) for early-stage breast cancers in Chinese women. A fully recursive literature search was conducted in the Chinese Biomedical Literature Database. Case-control trials were considered for inclusion. Analyses were carried out using the Review Manager software (RevMan, version 5.0). The meta-analysis showed that the 3-year or 5-year overall survival, the locoregional recurrence rate, and the metastasis rate were not statistically different between the BCT group and the MT group, but the complication recurrence rate increased in the MT group. Subgroup analysis indicated that no significant differences were observed in the affected limb swelling recurrence rate between the BCT group and the MT group. BCT was the better choice than MT for Chinese women with early-stage breast cancer. Copyright © 2012 S. Karger AG, Basel.
[ANALYSIS OF IMPLANT-RELATED COMPLICATIONS AFTER HINGE KNEE REPLACEMENT FOR TUMORS AROUND THE KNEE].
Li, Dong; Ma, Huanzhi; Zhang, Wei; Sun, Chengliang; Lu, Xiaoyong; Gao, Yutong; Zhou, Dongsheng
2015-08-01
To investigate the reasons and managements of implant-related complications after hinge knee replacement for tumors around the knee. A retrospective analysis was made on the clinical data of 96 patients undergoing hinge knee replacement between January 2000 and December 2012. There were 64 males and 32 females with the mean age of 31.0 years (range, 15-72 years). The most common tumor type was osteosarcoma (72 cases), and the second was giant cell tumor (15 cases). The tumor located at the distal femurs in 52 cases and at the proximal tibias in 44 cases. Fifteen hinge and 81 rotating hinge prostheses were used. The recurrence, metastasis, and survival were recorded. The implant-related complications were observed. The median follow-up time was 43.5 months (range, 10-156 months). Complications were observed in 21 patients (25 implant-related complications); 13 complications located at the femur and 12 complications at the tibia. The complications included aseptic loosening (8 cases), deep infection (7 cases), prosthetic breakage (4 cases), peri-prosthetic fracture (2 cases), and dislocation (4 cases). Most deep infection occurred within 12 months after operation (6/7), and most aseptic loosening after 40 months of operation (6/8). The rate of limb salvage was 90.6% (87/96) and the amputation rate was 9.4% (9/96). The overall survival rate of the prosthesis was 76.7% (5-year) and 47.2% (10-year). The 5-year survival rate was 82.9% for femoral prosthesis and 71.0% for tibial prosthesis, showing no significant difference (P = 0.954). Hinge knee prosthesis still has a high rate of complications. Deep infection is main reason to decrease short-term prosthetic survival rate, and aseptic loosening shortens the long-short prosthetic survival time.
van Rein, Nienke; Cannegieter, Suzanne C; Rosendaal, Frits R; Reitsma, Pieter H; Lijfering, Willem M
2014-02-01
Selection bias in case-control studies occurs when control selection is inappropriate. However, selection bias due to improper case sampling is less well recognized. We describe how to recognize survivor bias (i.e., selection on exposed cases) and illustrate this with an example study. A case-control study was used to analyze the effect of statins on major bleedings during treatment with vitamin K antagonists. A total of 110 patients who experienced such bleedings were included 18-1,018 days after the bleeding complication and matched to 220 controls. A protective association of major bleeding for exposure to statins (odds ratio [OR]: 0.56; 95% confidence interval: 0.29-1.08) was found, which did not become stronger after adjustment for confounding factors. These observations lead us to suspect survivor bias. To identify this bias, results were stratified on time between bleeding event and inclusion, and repeated for a negative control (an exposure not related to survival): blood group non-O. The ORs for exposure to statins increased gradually to 1.37 with shorter time between outcome and inclusion, whereas ORs for the negative control remained constant, confirming our hypothesis. We recommend the presented method to check for overoptimistic results, that is, survivor bias in case-control studies. Copyright © 2014 Elsevier Inc. All rights reserved.
Brenner, Hermann; Jansen, Lina
2015-12-01
The proportion of cases registered by death certificates only (DCO) is a widely used indicator for potential bias in cancer survival studies. Period analysis is increasingly used to derive up-to-date cancer survival estimates. We aimed to assess whether reported DCO proportions should be restricted to the specific recent calendar period ("restricted period") or refer to all diagnosis years of included patients ("full period"). We assessed correlations of bias in period survival estimates resulting from DCO cases with DCO proportions in the restricted and full period, respectively. We used cancer registry data to simulate bias and DCO proportions resulting from various patterns of underreporting of deceased cases. We show results for six common cancers with very different prognosis and five different age groups. In all scenarios, the expected bias was highly correlated with expected DCO proportions in both periods, but correlations were consistently higher with DCO proportions in the restricted period. In period analyses of cancer survival, DCO proportions for the restricted period of specific interest are a better indicator of potential bias due to underreporting of deceased cases than DCO proportions for all years of diagnosis of included patients. Copyright © 2015 Elsevier Inc. All rights reserved.
Nayak, Seema; Bhatt, M L B; Goel, Madhu Mati; Gupta, Seema; Mahdi, Abbas Ali; Mishra, Anupam; Mehrotra, Divya
2018-01-01
Radioresistance is one of the main determinants of treatment outcome in oral squamous cell carcinoma (OSCC), but its prediction is difficult. Several authors aimed to establish radioresistant OSCC cell lines to identify genes with altered expression in response to radioresistance. The development of OSCC is a multistep carcinogenic process that includes activation of several oncogenes and inactivation of tumour suppressor genes. TGM-3 is a tumour suppressor gene and contributes to carcinogenesis process. The aim of this study was to estimate serum and tissue expression of TGM-3 and its correlation with clinico-pathological factors and overall survival in patients of OSCC undergoing chemo-radiotherapy. Tissue expression was observed in formalin fixed tissue biopsies of 96 cases of OSCC and 32 healthy controls were subjected to immunohistochemistry (IHC) by using antibody against TGM-3 and serum level was estimated by ELISA method. mRNA expression was determined by using Real-Time PCR. Patients were followed for 2 year for chemo radiotherapy response. In OSCC, 76.70% cases and in controls 90.62% were positive for TGM-3 IHC expression. TGM-3 expression was cytoplasmic and nuclear staining expressed in keratinized layer, stratum granulosum and stratum spinosum in controls and tumour cells. Mean serum TGM-3 in pre chemo-radiotherapy OSCC cases were 1304.83±573.55, post chemo-radiotherapy samples were 1530.64±669.33 and controls were 1869.16±1377.36, but difference was significant in pre chemo-radiotherapy samples as compared to controls (p<0.018). This finding was also confirmed by real- time PCR analysis in which down regulation (-7.92 fold change) of TGM-3 in OSCC as compared to controls. TGM-3 expression was significantly associated with response to chemo-radiotherapy treatment (p<0.007) and overall survival (p<0.015). Patents having higher level of TGM-3 expression have good response to chemo-radiotherapy and also have better overall survival. TGM-3 may serve as a candidate biomarker for responsiveness to chemo-radiotherapy treatment in OSCC patients.
Davidson, B; Goldberg, I; Gotlieb, W H; Lerner-Geva, L; Ben-Baruch, G; Kopolovic, J
1998-07-01
Seventy-five squamous cell carcinomas of the uterine cervix and 10 controls were stained for Ulex Europaeus lectin 1 (UEA-1) and anti-CD31, and the results were analyzed with respect to patient age, clinical stage, tumor grade, and survival during a follow-up period of 1 to 13 years. The patients' mean age at the time of diagnosis was 47.8 years (range, 27 to 83). Seventeen patients died of disease, 2 had disease recurrence, and 51 patients remained free of disease; 5 patients were lost to follow-up. Twenty-eight cases (37.3%) showed focal membranous staining for UEA-1 and 9 cases (12%) showed a diffuse pattern; 38 cases (50.7%) were UEA-1 negative. Poor survival was related to diffuse membranous UEA-1 immunoreactivity (p = 0.02), age (p = 0.014), grade (p = 0.02), and stage (p = 0.0002). CD31-positive neoplastic cells displayed a cytoplasmic pattern. Fifteen cases (20%) had diffuse staining and another 15 (20%) stained focally; 45 cases (60%) were CD31-negative. The adjacent nonneoplastic epithelium and all 10 controls were uniformly negative for CD31. Variable staining of the endocervical epithelium and weak or negative staining of ectocervical epithelium for UEA-1 were observed. However, the epithelium in all controls was negative for UEA-1. Poor survival was related to both focal and diffuse staining for CD31 (p = 0.01 and p = 0.03, respectively). Staining by both UEA-1 and anti-CD31 retained its correlation with survival after exclusion of stage la tumors.
Devos, Jennifer M; Gaber, Ahmed Osama; Teeter, Larry D; Graviss, Edward A; Patel, Samir J; Land, Geoffrey A; Moore, Linda W; Knight, Richard J
2014-03-15
Renal transplant recipients with de novo DSA (dDSA) experience higher rates of rejection and worse graft survival than dDSA-free recipients. This study presents a single-center review of dDSA monitoring in a large, multi-ethnic cohort of renal transplant recipients. The authors performed a nested case-control study of adult kidney and kidney-pancreas recipients from July 2007 through July 2011. Cases were defined as dDSA-positive whereas controls were all DSA-negative transplant recipients. DSA were determined at 1, 3, 6, 9, and 12 months posttransplant, and every 6 months thereafter. Of 503 recipients in the analysis, 24% developed a dDSA, of whom 73% had dDSA against DQ antigen. Median time to dDSA was 6.1 months (range 0.2-44.6 months). After multivariate analysis, African American race, kidney-pancreas recipient, and increasing numbers of human leukocyte antigen mismatches were independent risk factors for dDSA. Recipients with dDSA were more likely to suffer an acute rejection (AR) (35% vs. 10%, P<0.001), an antibody-mediated AR (16% vs. 0.3%, P<0.001), an AR ascribed to noncompliance (8% vs. 2%, P=0.001), and a recurrent AR (6% vs. 1%, P=0.002) than dDSA-negative recipients. At a median follow-up of 31 months, the death-censored actuarial graft survival of dDSA recipients was worse than the DSA-free cohort (P=0.002). Yet, for AR-free recipients, there was no difference in graft survival between cohorts (P=0.66). Development of dDSA was associated with an increased incidence of graft loss, yet the detrimental effect of dDSA was limited in the intermediate term to recipients with AR.
Booster seat laws and child fatalities: a case-control study.
Farmer, P; Howard, A; Rothman, L; Macpherson, A
2009-10-01
A case-control study examined, primarily, the association between booster seat laws and fatalities among children in frontal collisions and, secondarily, the association between booster seat laws and reported restraint use, and restraint use and child fatalities. Children who died in a crash in the US were cases, and children who survived a fatal crash were controls. Subjects were child passengers (4-8 years old) in the Fatality Analysis Reporting System Database, 1995-2005. In states with a booster seat law, children were less likely to die than in states without a law (OR 0.80; 95% CI 0.66 to 0.98). They were also more likely to be restrained (adjusted OR 1.59; 95% CI 1.21 to 2.09) and were more likely to be correctly restrained (adjusted OR 4.44; 95% CI 3.18 to 6.20). It is concluded that booster seat laws are associated with a decrease in child deaths and an increase in correct restraint use among children involved in a fatal crash in the USA.
2012-01-01
Background We explore the benefits of applying a new proportional hazard model to analyze survival of breast cancer patients. As a parametric model, the hypertabastic survival model offers a closer fit to experimental data than Cox regression, and furthermore provides explicit survival and hazard functions which can be used as additional tools in the survival analysis. In addition, one of our main concerns is utilization of multiple gene expression variables. Our analysis treats the important issue of interaction of different gene signatures in the survival analysis. Methods The hypertabastic proportional hazards model was applied in survival analysis of breast cancer patients. This model was compared, using statistical measures of goodness of fit, with models based on the semi-parametric Cox proportional hazards model and the parametric log-logistic and Weibull models. The explicit functions for hazard and survival were then used to analyze the dynamic behavior of hazard and survival functions. Results The hypertabastic model provided the best fit among all the models considered. Use of multiple gene expression variables also provided a considerable improvement in the goodness of fit of the model, as compared to use of only one. By utilizing the explicit survival and hazard functions provided by the model, we were able to determine the magnitude of the maximum rate of increase in hazard, and the maximum rate of decrease in survival, as well as the times when these occurred. We explore the influence of each gene expression variable on these extrema. Furthermore, in the cases of continuous gene expression variables, represented by a measure of correlation, we were able to investigate the dynamics with respect to changes in gene expression. Conclusions We observed that use of three different gene signatures in the model provided a greater combined effect and allowed us to assess the relative importance of each in determination of outcome in this data set. These results point to the potential to combine gene signatures to a greater effect in cases where each gene signature represents some distinct aspect of the cancer biology. Furthermore we conclude that the hypertabastic survival models can be an effective survival analysis tool for breast cancer patients. PMID:23241496
Effect of tumor location on survival in urinary bladder adenocarcinoma: A population-based analysis.
Dutta, Rahul; Abdelhalim, Ahmed; Martin, Jeremy W; Vernez, Simone L; Faltas, Bishoy; Lotan, Yair; Youssef, Ramy F
2016-12-01
To investigate the prognostic significance of tumor location on survival outcomes in patients with urinary bladder adenocarcinoma (BAC). We retrospectively analyzed cases of BAC with known tumor location from the Surveillance, Epidemiology, and End Results database from 1973 to 2012. Data regarding patient demographics, tumor characteristics, and oncological and survival outcomes were collected. Patients were subgrouped according to tumor location into urachal/dome (dome and urachus [UD]), lateral wall (anterior, posterior, and lateral bladder walls [LW]), and base (trigone, ureteral orifices, and bladder neck [BL]). A total of 1,361 cases of BAC with known tumor location were identified. More UD tumors were low grade (grade I and II; 51%) than LW (33%) and BL (43%) tumors (P<0.0001). UD lesions were the most likely to have metastatic spread (23% vs. 17% for LW and 15% for BL) (P<0.0001). The 5-year overall survival (OS) and disease-specific survival (DSS) rates were 37.3% and 49.0%, respectively, for all BAC. Furthermore, the 5-year OS rates were 42.3%, 35.9%, and 28.4% for UD, LW, and BL lesions, respectively (P<0.0001), whereas the 5-year DSS rates were 50.2%, 51.7%, and 42.1% for UD, LW, and BL lesions, respectively (P = 0.0097). Multivariate Cox regression analysis controlling for tumor stage and grade demonstrated that both tumors of the LW (hazards ratio [HR] = 1.52 for OS and 1.30 for DSS) and BL (HR = 1.71 for OS and 1.57 for DSS) conferred a worse prognosis relative to those of the UD (P< 0.05). Tumor location of BAC is an independent prognostic factor for disease outcome. Our results suggest that the urachal and dome locations are associated with relatively favorable survival and oncological outcomes, whereas basal location confers poorer outcomes. Copyright © 2016 Elsevier Inc. All rights reserved.
Yang, Wei; Yan, Kun; Wu, Gong-Xiong; Wu, Wei; Fu, Ying; Lee, Jung-Chieh; Zhang, Zhong-Yi; Wang, Song; Chen, Min-Hua
2015-01-01
AIM: To investigate the treatment strategies and long-term outcomes of radiofrequency ablation (RFA) of hepatocellular carcinoma (HCC) in difficult locations and to compare the results with non-difficult HCC. METHODS: From 2004 to 2012, a total of 470 HCC patients underwent ultrasound-guided percutaneous RFA. Among these HCC patients, 382 with tumors located ≤ 5 mm from a major vessel/bile duct (n = 87), from peripheral important structures (n = 232) or from the liver capsule (n = 63) were regarded as difficult cases. There were 331 male patients and 51 female patients, with an average age of 55.3 ± 10.1 years old. A total of 235 and 147 patients had Child-Pugh class A and class B liver function, respectively. The average tumor size was 3.4 ± 1.2 cm. Individual treatment strategies were developed to treat these difficult cases. During the same period, 88 HCC patients with tumors that were not in difficult locations served as the control group. In the control group, 74 patients were male, and 14 patients were female, with an average age of 57.4 ± 11.8 years old. Of these, 62 patients and 26 patients had Child-Pugh class A and class B liver function, respectively. Regular follow-up after RFA was performed to assess treatment efficacy. Survival results were generated from Kaplan-Meier estimates, and multivariate analysis was performed using the Cox regression model. RESULTS: Early tumor necrosis rate in the difficult group was similar to that in the control group (97.6% vs 94.3%, P = 0.080). The complication rate in the difficult group was significantly higher than that in the control group (4.9% vs 0.8%, P = 0.041). The follow-up period ranged from 6 to 116 mo, with an average of 28 ± 22.4 mo. Local progression rate in the difficult group was significantly higher than that in the control group (12.7% vs 7.1%, P = 0.046). However, the 1-, 3-, 5-, and 7-year overall survival rates in the difficult group were not significantly different from those in the control group (84.3%, 54.4%, 41.2%, and 29.9% vs 92.5%, 60.3%, 43.2%, and 32.8%, respectively, P = 0.371). Additionally, a multivariate analysis revealed that tumor location was not a significant risk factor for survival. CONCLUSION: There was no significant difference in long-term overall survival between the two groups even though the local progression rate was higher in the difficult group. PMID:25663774
2014-01-01
Background and importance Recurrent malignant gliomas (RMGs) are very difficult to control, and no standard treatments have been established for them. We performed boron neutron capture therapy (BNCT) for patients with RMG. BNCT enables high-dose particle radiation to be applied selectively to tumor cells. However, RMG cases generally receive nearly 60 Gy X-ray irradiation prior to re-irradiation by BNCT. Therefore, even with tumor-selective particle radiation BNCT, radiation necrosis in the brain and symptomatic pseudoprogression may develop. In four of our recent patients with RMG after BNCT, we applied the anti-VEGF antibody bevacizumab to treat two pathological entities. This approach appeared to prolong survival. Here we present the case reports of these four consecutive patients with RMG and discuss the novel use of bevacizumab in this context. Clinical presentation Four patients with RMGs were treated with BNCT at our institutes. Upon the referral for BNCT, they were assessed as belonging to the recursive partitioning analysis (RPA) class 3 (n = 3 patients) or RPA class 4 (n = 1 patient) (the RPA classification for RMG was advocated by Carson et al. in 2007). The estimated median survival times for RPA classes 3 and 4 were 3.8 and 10.8 months, respectively, after some treatment at the recurrence. We applied BNCT for these four patients and administered bevacizumab when the lesions were considered radiation necrosis or symptomatic pseudoprogression. The class 3 patients survived after the BNCT for 14, 16.5 and > 23 months, and the class 4 patient survived > 26 months, with favorable improvements in clinical symptoms. Conclusion BNCT with the addition of bevacizumab for radiation necrosis or symptomatic pseudoprogression improved the clinical symptoms and prolonged the survival in RMG patients. PMID:24387301
Sieber, Monique; Dreßler, Jan; Franke, Heike; Pohlers, Dirk; Ondruschka, Benjamin
2018-04-01
Traumatic brain injury (TBI) is a very common entity that leads to numerous fatalities all over the world. Therefore, forensic pathologists are in desperate need of supplemental methodological tools for the diagnosis of TBI in everyday practice besides the standard autopsy. The present study determined post-mortem neuron specific enolase (NSE) and S100 calcium-binding protein B (S100B) levels as biological markers of an underlying TBI in autopsy cases. Paired serum and CSF samples of 92 fatalities were collected throughout routine autopsies. Afterwards, the marker levels were assessed using commercially available immunoassays (ECLIA, Roche Diagnostics). For statistical analysis, we compared the TBI cases to three control groups (sudden natural death by acute myocardial infarction, traumatic death without impact on the head, cerebral hypoxia). Moreover, the TBI cases were subdivided according to their survival time of the trauma. Brain specimens have been collected and stained immunohistochemically against the aforementioned proteins to illustrate their typical cellular staining patterns with an underlying TBI compared to non-TBI fatalities. CSF NSE and S100B levels were elevated after TBI compared to all control groups (p < 0.001). Although this finding can already be investigated among the TBI cases dying immediately subsequent to the trauma, the marker levels in CSF increase with longer survival times until a peak level within the first three days after trauma. There is a strong correlation between both marker levels in CSF (r = 0.67). The presence or absence of cerebral tissue contusion following the initial trauma does not seem to affect the CSF levels of both proteins (p > 0.05). Post-mortem serum levels of both proteins were not elevated in TBI cases compared to controls (p > 0.05). Former elaborated cut-off values in CSF were confirmed and were only exceeded when a TBI survival time of at least 30 min was reached. The present results report that post-mortem NSE and S100B CSF levels are significantly elevated subsequent to a fatal TBI. Copyright © 2018 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
Arakawa, Reiko; Arakawa, Masayuki; Kaneko, Kaori; Otsuki, Noriko; Aoki, Ryoko; Saito, Kayoko
2016-08-01
Spinal muscular atrophy is a neurodegenerative disorder caused by the deficient expression of survival motor neuron protein in motor neurons. A major goal of disease-modifying therapy is to increase survival motor neuron expression. Changes in survival motor neuron protein expression can be monitored via peripheral blood cells in patients; therefore we tested the sensitivity and utility of imaging flow cytometry for this purpose. After the immortalization of peripheral blood lymphocytes from a human healthy control subject and two patients with spinal muscular atrophy type 1 with two and three copies of SMN2 gene, respectively, we used imaging flow cytometry analysis to identify significant differences in survival motor neuron expression. A bright detail intensity analysis was used to investigate differences in the cellular localization of survival motor neuron protein. Survival motor neuron expression was significantly decreased in cells derived from patients with spinal muscular atrophy relative to those derived from a healthy control subject. Moreover, survival motor neuron expression correlated with the clinical severity of spinal muscular atrophy according to SMN2 copy number. The cellular accumulation of survival motor neuron protein was also significantly decreased in cells derived from patients with spinal muscular atrophy relative to those derived from a healthy control subject. The benefits of imaging flow cytometry for peripheral blood analysis include its capacities for analyzing heterogeneous cell populations; visualizing cell morphology; and evaluating the accumulation, localization, and expression of a target protein. Imaging flow cytometry analysis should be implemented in future studies to optimize its application as a tool for spinal muscular atrophy clinical trials. Copyright © 2016 Elsevier Inc. All rights reserved.
Ji, Yan; Vogel, Rachel Isaksson; Lou, Emil
2016-01-01
Background Pituitary carcinomas (PC) and atypical pituitary adenomas (APA) are rare variants of pituitary tumors for which no evidence-based treatment currently exists. We sought to determine whether temozolomide represents an effective chemotherapeutic option for patients with PC and APA. Methods A systematic review was performed using all published cases of PC and APA treated with temozolomide, and for which information on treatment regimen, clinical response, and survival could be identified. The primary goal of this analysis was to describe overall survival and progression-free survival among PC and APA patients after temozolomide treatment. Secondary goals included assessment of response rate and biomarkers of response. Results We identified 57 cases and obtained follow-up data on 54 patients (31 APA and 23 PC) for analysis. Estimates of 5-year progression-free survival and overall survival were 21.9% and 57.4% for patients with APA and 36.1% and 56.2% for patients with PC. Among those who responded to temozolomide, overall survival was marginally statistically significantly greater for patients on long-term temozolomide therapy compared with those who were not (5-year overall survival 91.7% vs 54.1%, P = .08); Progression-free survival results were similar but not statistically significant. The objective response rate was 48.4% for patients with APA and 65.2% for patients with PC. Stable disease occurred in 29% of APA and 17.4% of PC patients. Neither histology nor expression of Ki-67 correlated with response; however, negative O6-methylguanine-DNA methyltransferase staining was strongly related to response to temozolomide in patients with APA (P < .001). Conclusions Temozolomide is an effective treatment of both PC and APA, and long-term treatment can be considered for particularly aggressive cases. PMID:27551432
Risk factors for measles death: Kyegegwa District, western Uganda, February-September, 2015.
Mafigiri, Richardson; Nsubuga, Fred; Ario, Alex Riolexus
2017-07-03
On 18 August 2015, Kyegegwa District reported eight deaths during a measles outbreak to the Uganda Ministry of Health (MoH). We investigated this death cluster to verify the cause, identify risk factors, and inform public health interventions. We defined a probable measles case as onset of fever and generalised rash in a Kyegegwa District resident from 1 February - 15 September 2015, plus ≥1 of the following: coryza, conjunctivitis, and cough. A confirmed measles case was a probable case with measles-specific IgM positivity. A measles death was a death of a probable or confirmed case-person. We conducted an active case-finding to identify measles patients who survived or died. In a case-control study, we compared risk factors between 16 measles patients who died (cases) and 48 who survived (controls), matched by age (±4 years) and village of residence. We identified 94 probable measles cases, 10 (11%) were confirmed by positive measles-specific IgM. Of the 64 probable measles patients aged <5 years, 16 died (case-fatality rate = 25%). In the case-control study, no history of vaccination against measles was found in 94% (15/16) among the case-persons (i.e., measles patients who died) and 54% (26/48) among the controls (i.e., measles patients who survived) (OR M-H = 12; 95% CI = 1.6-104), while 56% (9/16) of case-persons and 67% (17/48) of controls (OR M-H = 2.3; 95% CI =0.74-7.4) did not receive vitamin A supplementation during illness. 63% (10/16) among the case-persons and 6.3% (3/48) of the controls (OR M-H = 33; 95% CI = 6.8-159) were not treated for measles illness at a health facility (a proxy for more appropriate treatment), while 38% (6/16) of the case-persons and 25% (12/48) of the controls (OR M-H = 2.5; 95% CI = 0.67-9.1) were malnourished. Lack of vaccination and no treatment in a health facility increased the risk for measles deaths. The one-dose measles vaccination currently in the national vaccination schedule had a protective effect against measles death. We recommended enhancing measles vaccination and adherence to measles treatment guidelines.
Ward-Peterson, Melissa; Acuña, Juan M.; Alkhalifah, Mohammed K.; Nasiri, Abdulrahman M.; Al-Akeel, Elharith S.; Alkhaldi, Talal M.; Dawari, Sakhr A.; Aldaham, Sami A.
2016-01-01
Abstract Melanoma is a treatable and preventable skin cancer. It is responsible for 75% of deaths among all skin cancers. Previous studies have found that race/ethnicity may play a role in survival among melanoma patients. However, there are no studies that cover 30 years and take race into account for the U.S. population. This study is a secondary analysis of the National Cancer Institute's Surveillance, Epidemiology, and End Result (SEER) Program. Adults with primary cutaneous melanoma from 1982 to 2011 were included; the final sample size was 185,219. The outcome was survival; both cause-specific and all-cause mortality were examined. The main exposure was race/ethnicity. Kaplan–Meier survival analysis was used to estimate overall survival. Cox proportional hazards regression was used to estimate unadjusted and adjusted hazard ratios (HRs). A P-value less than 0.05 was considered statistically significant. More than 50% of patients in all races/ethnicities were diagnosed at the in situ or localized stage. Non-Hispanic White patients were more frequently diagnosed at the in situ stage. Overall, more men were diagnosed than women. The majority of cases among all races were men. Non-Hispanic Black females represented the smallest percentage of melanoma cases among all races. The smallest number of diagnoses across all races/ethnicities was made from 1982 to 1991. Median follow-up was 81 months and no collinearity was observed in the adjusted models. When examining cause-specific mortality and controlling for site and stage at diagnosis, gender, age and decade of diagnosis, the HR for non-Hispanic Black patients was lower than that for non-Hispanic White patients (HR 0.7; 95% confidence interval (CI): 0.6–0.8). However, when examining all-cause mortality, this difference disappeared (HR 1.1; 95% CI: 1.0–1.2). Stage at diagnosis impacted HR; patients diagnosed with distant metastases had significantly worse survival. When taking cause-specific mortality into consideration and after controlling for stage and site at diagnosis, gender, and age and decade of diagnosis, non-Hispanic Black patients had a lower HR compared to non-Hispanic White patients. However, this difference disappeared when examining all-cause mortality. Further research is needed to explore this finding and to determine what factors may be associated with late-stage melanoma diagnosis. PMID:27124020
Huang, Hui; Zhai, Zhifang; Shen, Zhu; Lin, Hui
2016-01-01
Purpose The present study determined the clinical characteristics and prognostic factors in patients with malignant melanoma based on a series of 82 cases from January 2009 to December 2014 in Southwest Hospital and a meta-analysis (including 12 articles) involving 958 patients in China. Materials and methods The database elements included basic demographic data and prognosticators which were extracted from medical records. Statistical analyses of survival, and multivariate analyses of factors associated with survival were performed using the Kaplan—Meier method, and the Cox proportional hazard model, respectively. Literatures were identified through systematic searches in PubMed, Embase, the Cochrane Library, China National Knowledge Infrastructure (CNKI) and Weipu database (VIP) database for the period from inception to December 2015. The meta-analysis was conducted using R 3.1.1 meta-analysis software Results In this series of 82 cases, the median age of the patients was 57.50 years. Melanoma was located in the foot in 79% of patients. Sixty-one patients (74.4%) were classified as stage II-III. Thirty-two patients (39.0%) had acral malignant melanoma, and 31 patients (37.8%) had nodular malignant melanoma. The clinical characteristics of melanoma were similar to those in areas outside southwest China (from results of the meta-analysis). The median survival time was 29.50 months. The 1-year, 3-year, and 5-year survival rates were 84.1%, 39.0% and 10.9%, respectively. COX regression following multi-factor analysis showed that ulcer, tumor boundary and lymph node metastasis were associated with prognosis. Conclusions The clinical characteristics of melanoma in Chinese were different from those in Caucasians. Ulcer, tumor margins, and lymph node metastasis were significantly associated with prognosis. Immune therapy may prolong the median survival time of patients with acral melanoma, nodular melanoma, or stage I-III disease, although these differences were not statistically significant. PMID:27861496
Yan, Shunchao; Li, Kai; Jiao, Xin; Zou, Huawei
2015-01-01
Background Ovarian function suppression (OFS) significantly downregulates the concentration of plasma estrogens. However, it is unclear whether it offers any survival benefits if combined with adjuvant tamoxifen treatment in premenopausal women. This meta-analysis was designed to assess data from previous studies involving adjuvant tamoxifen treatment plus OFS in premenopausal breast cancer. Methods Electronic literature databases (PubMed, Embase, the Web of Science, and the Cochrane Library) were searched for relevant randomized controlled trials published prior to February 1, 2015. Only randomized controlled trials that compared tamoxifen alone with tamoxifen plus OFS for premenopausal women with breast cancer were selected. The evaluated endpoints were disease-free survival and overall survival. Results Four randomized controlled trials comprising 6,279 patients (OFS combination, n=3,133; tamoxifen alone, n=3,146) were included in the meta-analysis. There was no significant improvement in disease-free survival or overall survival with addition of OFS in either the whole population or the hormone receptor-positive subgroup. The risk of distant recurrence was not reduced with the addition of OFS in the whole population. A subgroup analysis showed that addition of OFS significantly improved overall survival in patients who were administered chemotherapy. Conclusion Based on the available studies, concurrent administration of OFS and adjuvant tamoxifen treatment for premenopausal women with breast cancer has no effect on prolonging disease-free survival and overall survival, excluding patients who were administered chemotherapy. It should not be widely recommended, except perhaps for women who were hormone-receptor positive and who were also administered adjuvant chemotherapy. PMID:26109867
Toenail selenium, genetic variation in selenoenzymes and risk and outcome in glioma.
Peeri, Noah C; Creed, Jordan H; Anic, Gabriella M; Thompson, Reid C; Olson, Jeffrey J; LaRocca, Renato V; Chowdhary, Sajeel A; Brockman, John D; Gerke, Travis A; Nabors, L Burton; Egan, Kathleen M
2018-05-16
Selenium is an essential trace element obtained through diet that plays a critical role in DNA synthesis and protection from oxidative damage. Selenium intake and polymorphisms in selenoproteins have been linked to the risk of certain cancers though data for glioma are sparse. In a case-control study of glioma, we examined the associations of selenium in toenails and genetic variants in the selenoenzyme pathway with the risk of glioma and patient survival. A total of 423 genetic variants in 29 candidate genes in the selenoenzyme pathway were studied in 1547 glioma cases and 1014 healthy controls. Genetic associations were also examined in the UK Biobank cohort comprised of 313,868 persons with 322 incident glioma cases. Toenail selenium was measured in a subcohort of 300 glioma cases and 300 age-matched controls from the case-control study. None of the 423 variants studied were consistently associated with glioma risk in the case-control and cohort studies. Moreover, toenail selenium in the case-control study had no significant association with glioma risk (p trend = 0.70) or patient survival among 254 patients with high grade tumors (p trend = 0.70). The present study offers no support for the hypothesis that selenium plays a role in the onset of glioma or patient outcome. Copyright © 2018 Elsevier Ltd. All rights reserved.
Wang, Xin-Hua; Long, Zi-Wen
2017-06-20
This case-control study aims to investigate the correlations of EGF G1380A, bFGF C754G and VEGF T460C polymorphisms with the susceptibility and prognosis of malignant melanoma. A total of 153 patients with multiple primary melanomas were collected as the case group and another 170 healthy individuals were selected as the control group. ELISA and PCR-RFLP were performed to test the serum level of VEGF and to analyze the genotype as well as allele frequencies of VEGF T460C, EGF G1380A, and bFGF C754G, respectively. The patients were assigned into complete remission (CR), partial remission (PR) and non-remission groups after treatment. HE and CD34 staining were conducted in tissue samples of CR and PR patients. Event-free survival (EFS) and overall survival (OS) were measured. AA genotype of EGF G1380A and GG genotype of bFGF C754G had higher frequency distribution in the case group than the control group. Patients with AA genotype of EGF G1380 and GG genotype of bFGF C754G had an elevated VEGF level in comparison to other genotypes. Patients with GA+GG genotypes of EGF G1380A and CG+CC genotypes of bFGF C754G had higher EFS and OS than those with AA genotype and those with GG genotype, respectively. According to the haplotype analysis, the case group had a notably higher frequency of TAG and CAG along with while lower frequency of TGG and CGC compared with the control group. Logistic regression analysis revealed that the polymorphisms of EGF G1380A and bFGF C754G as well as the haploid TAG increased the susceptibility of malignant melanoma. The results indicated that EGF G1380A and bFGF C754G gene polymorphisms were associated with the susceptibility and prognosis of malignant melanoma, and that the polymorphisms of EGF G1380A and bFGF C754G as well as the haploid TAG increased the susceptibility of malignant melanoma. Copyright © 2017 Elsevier B.V. All rights reserved.
Kim, Daniel Seung; Kim, Jerry H; Burt, Amber A; Crosslin, David R; Burnham, Nancy; Kim, Cecilia E; McDonald-McGinn, Donna M; Zackai, Elaine H; Nicolson, Susan C; Spray, Thomas L; Stanaway, Ian B; Nickerson, Deborah A; Heagerty, Patrick J; Hakonarson, Hakon; Gaynor, J William; Jarvik, Gail P
2016-04-01
Copy number variants (CNVs) are duplications or deletions of genomic regions. Large CNVs are potentially pathogenic and are overrepresented in children with congenital heart disease (CHD). We sought to determine the frequency of large CNVs in children with isolated CHD, and to evaluate the relationship of these potentially pathogenic CNVs with transplant-free survival. These cases are derived from a prospective cohort of patients with nonsyndromic CHD (n = 422) identified before first surgery. Healthy pediatric controls (n = 500) were obtained from the electronic Medical Records and Genetic Epidemiology Network, and CNV frequency was contrasted for CHD cases and controls. CNVs were determined algorithmically; subsequently screened for >95% overlap between 2 methods, size (>300 kb), quality score, overlap with a gene, and novelty (absent from databases of known, benign CNVs); and separately validated by quantitative polymerase chain reaction. Survival likelihoods for cases were calculated using Cox proportional hazards modeling to evaluate the joint effect of CNV burden and known confounders on transplant-free survival. Children with nonsyndromic CHD had a higher burden of potentially pathogenic CNVs compared with pediatric controls (12.1% vs 5.0%; P = .00016). Presence of a CNV was associated with significantly decreased transplant-free survival after surgery (hazard ratio, 3.42; 95% confidence interval, 1.66-7.09; P = .00090) with confounder adjustment. We confirm that children with isolated CHD have a greater burden of rare/large CNVs. We report a novel finding that these CNVs are associated with an adjusted 2.55-fold increased risk of death or transplant. These data suggest that CNV burden is an important modifier of survival after surgery for CHD. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Minatel, Emilio; Trovo, Marco, E-mail: marcotrovo33@hotmail.com; Bearz, Alessandra
Purpose: To prospectively assess the survival, patterns of failure, and prognostic factors in a large cohort of patients with malignant pleural mesothelioma who had undergone a novel trimodal therapeutic approach, including lung-sparing surgery, chemotherapy, and subsequent treatment with high doses of intensity modulated radiation therapy (IMRT) to the whole hemithorax. Methods and Materials: The analysis was conducted on the data from 69 patients. Of the 69 patients, 35 underwent extended pleurectomy/decortication (P/D), with resection of the entire pleura, along with portions of the pericardium and diaphragm and 34, partial pleurectomy, defined as partial removal of parietal or visceral pleura formore » diagnostic purposes, leaving gross tumor behind in all cases. All patients received cisplatin/pemetrexed chemotherapy. Postoperative IMRT was delivered to the entire hemithorax, excluding the intact lung. The IMRT dose was 50 Gy in 25 fractions. Any fluorodeoxyglucose-avid areas or regions of particular concern for residual disease were given a simultaneous boost to 60 Gy. Results: The median follow-up duration was 19 months. No difference was seen in overall survival and locoregional control between the extended P/D group and the partial pleurectomy group. The 2-year overall survival was 65% and 58% in the extended P/D and partial pleurectomy groups, respectively (P=.94). Locoregional control at 2 years was 65% and 64% in the extended P/D and partial pleurectomy groups, respectively (P=.75). The predominant pattern of failure was distant: 19 patients (27.5%) developed distant metastases as the first site of relapse. Gross residual disease after surgery was significantly associated with overall survival (hazard ratio 3.45). One fatal pneumonitis was reported; 14 cases (20%) of grade 2 to 3 pneumonitis were documented. Conclusions: Radical IMRT after lung-sparing surgery and chemotherapy for malignant pleural mesothelioma leads to promising survival results and acceptable toxicity rates. The similarity of survival between patients treated with extended P/D or partial pleurectomy observed in our study is intriguing.« less
Gram-Negative Bacterial Wound Infections
2014-05-01
shows an effect with increasing concentration, however survival analysis does not show a significant difference between treatment groups and controls ...with 3 dead larvae in the 25 mM group compared to a single dead larva in the control group (Fig. 7). Probit analysis estimates the lethal...statistically differ- ent from that of the control group . The levels (CFU/g) of bacteria in lung tissue correlated with the survival curves. The median
Duffy, Sonia A; Ronis, David L; McLean, Scott; Fowler, Karen E; Gruber, Stephen B; Wolf, Gregory T; Terrell, Jeffrey E
2009-04-20
Our prior work has shown that the health behaviors of head and neck cancer patients are interrelated and are associated with quality of life; however, other than smoking, the relationship between health behaviors and survival is unclear. A prospective cohort study was conducted to determine the relationship between five pretreatment health behaviors (smoking, alcohol, diet, physical activity, and sleep) and all-cause survival among 504 head and neck cancer patients. Smoking status was the strongest predictor of survival, with both current smokers (hazard ratio [HR] = 2.4; 95% CI, 1.3 to 4.4) and former smokers (HR = 2.0; 95% CI, 1.2 to 3.5) showing significant associations with poor survival. Problem drinking was associated with survival in the univariate analysis (HR = 1.4; 95% CI, 1.0 to 2.0) but lost significance when controlling for other factors. Low fruit intake was negatively associated with survival in the univariate analysis only (HR = 1.6; 95% CI, 1.1 to 2.1), whereas vegetable intake was not significant in either univariate or multivariate analyses. Although physical activity was associated with survival in the univariate analysis (HR = 0.95; 95% CI, 0.93 to 0.97), it was not significant in the multivariate model. Sleep was not significantly associated with survival in either univariate or multivariate analysis. Control variables that were also independently associated with survival in the multivariate analysis were age, education, tumor site, cancer stage, and surgical treatment. Variation in selected pretreatment health behaviors (eg, smoking, fruit intake, and physical activity) in this population is associated with variation in survival.
Survival in patients with metachronous second primary lung cancer.
Ha, Duc; Choi, Humberto; Chevalier, Cory; Zell, Katrina; Wang, Xiao-Feng; Mazzone, Peter J
2015-01-01
Four to 10% of patients with non-small cell lung cancer subsequently develop a metachronous second primary lung cancer. The decision to perform surveillance or screening imaging for patients with potentially cured lung cancer must take into account the outcomes expected when detecting metachronous second primaries. To assess potential survival differences between patients with metachronous second primary lung cancer compared to matched patients with first primary lung cancer. We retrospectively reviewed patients diagnosed with lung cancer at the Cleveland Clinic (2006-2010). Metachronous second primary lung cancer was defined as lung cancer diagnosed after a 4-year, disease-free interval from the first lung cancer, or if there were two different histologic subtypes diagnosed at different times. Patients with first primary lung cancer diagnosed in the same time period served as control subjects. Propensity score matching was performed using age, sex, smoking history, histologic subtype, and collaborative stage, with a 1:3 case-control ratio. Survival analyses were performed by Cox proportional hazards modeling and Kaplan-Meier estimates. Forty-four patients met criteria for having a metachronous second primary lung cancer. There were no statistically significant differences between case subjects and control subjects in prognostic variables. The median survival time and 2-year overall survival rate for the metachronous second primary group, compared with control subjects, were as follows: 11.8 versus 18.4 months (P = 0.18) and 31.0 versus 40.9% (P = 0.28). The survival difference was largest in those with stage I metachronous second primaries (median survival time, 26.8 vs. 60.4 mo, P = 0.09; 2-year overall survival, 56.3 vs. 71.2%, P = 0.28). Patients with stage I metachronous second primary lung cancer may have worse survival than those who present with a first primary lung cancer. This could influence the benefit-risk balance of screening the high-risk cohort with a previously treated lung cancer.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Hayeon, E-mail: kimh2@upmc.edu; Gill, Beant; Beriwal, Sushil
Purpose: To conduct a cost-effectiveness analysis to determine whether stereotactic body radiation therapy (SBRT) is a cost-effective therapy compared with radiofrequency ablation (RFA) for patients with unresectable colorectal cancer (CRC) liver metastases. Methods and Materials: A cost-effectiveness analysis was conducted using a Markov model and 1-month cycle over a lifetime horizon. Transition probabilities, quality of life utilities, and costs associated with SBRT and RFA were captured in the model on the basis of a comprehensive literature review and Medicare reimbursements in 2014. Strategies were compared using the incremental cost-effectiveness ratio, with effectiveness measured in quality-adjusted life years (QALYs). To account formore » model uncertainty, 1-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay threshold of $100,000 per QALY gained. Results: In base case analysis, treatment costs for 3 fractions of SBRT and 1 RFA procedure were $13,000 and $4397, respectively. Median survival was assumed the same for both strategies (25 months). The SBRT costs $8202 more than RFA while gaining 0.05 QALYs, resulting in an incremental cost-effectiveness ratio of $164,660 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of median survival from both treatments. Stereotactic body radiation therapy was economically reasonable if better survival was presumed (>1 month gain) or if used for large tumors (>4 cm). Conclusions: If equal survival is assumed, SBRT is not cost-effective compared with RFA for inoperable colorectal liver metastases. However, if better local control leads to small survival gains with SBRT, this strategy becomes cost-effective. Ideally, these results should be confirmed with prospective comparative data.« less
Breast-cancer adjuvant therapy with zoledronic acid.
Coleman, Robert E; Marshall, Helen; Cameron, David; Dodwell, David; Burkinshaw, Roger; Keane, Maccon; Gil, Miguel; Houston, Stephen J; Grieve, Robert J; Barrett-Lee, Peter J; Ritchie, Diana; Pugh, Julia; Gaunt, Claire; Rea, Una; Peterson, Jennifer; Davies, Claire; Hiley, Victoria; Gregory, Walter; Bell, Richard
2011-10-13
Data suggest that the adjuvant use of bisphosphonates reduces rates of recurrence and death in patients with early-stage breast cancer. We conducted a study to determine whether treatment with zoledronic acid, in addition to standard adjuvant therapy, would improve disease outcomes in such patients. In this open-label phase 3 study, we randomly assigned 3360 patients to receive standard adjuvant systemic therapy either with or without zoledronic acid. The zoledronic acid was administered every 3 to 4 weeks for 6 doses and then every 3 to 6 months to complete 5 years of treatment. The primary end point of the study was disease-free survival. A second interim analysis revealed that a prespecified boundary for lack of benefit had been crossed. At a median follow-up of 59 months, there was no significant between-group difference in the primary end point, with a rate of disease-free survival of 77% in each group (adjusted hazard ratio in the zoledronic acid group, 0.98; 95% confidence interval [CI], 0.85 to 1.13; P=0.79). Disease recurrence or death occurred in 377 patients in the zoledronic acid group and 375 of those in the control group. The numbers of deaths--243 in the zoledronic acid group and 276 in the control group--were also similar, resulting in rates of overall survival of 85.4% in the zoledronic acid group and 83.1% in the control group (adjusted hazard ratio, 0.85; 95% CI, 0.72 to 1.01; P=0.07). In the zoledronic acid group, there were 17 confirmed cases of osteonecrosis of the jaw (cumulative incidence, 1.1%; 95% CI, 0.6 to 1.7; P<0.001) and 9 suspected cases; there were no cases in the control group. Rates of other adverse effects were similar in the two study groups. These findings do not support the routine use of zoledronic acid in the adjuvant management of breast cancer. (Funded by Novartis Pharmaceuticals and the National Cancer Research Network; AZURE Current Controlled Trials number, ISRCTN79831382.).
Tomasello, Gianluca; Petrelli, Fausto; Ghidini, Michele; Russo, Alessandro; Passalacqua, Rodolfo; Barni, Sandro
2017-07-13
The combination of fluorouracil, oxaliplatin, and irinotecan plus bevacizumab (FOLFOXIRI-Bev) is an established and effective first-line chemotherapy regimen for metastatic colorectal cancer. However, resection rates of metastases and overall survival with this schedule have never been systematically evaluated in published studies including, but not limited to, the TRIBE (TRIplet plus BEvacizumab) trial. To assess the clinical efficacy of FOLFOXIRI-Bev, including outcomes and rates of surgical conversions. A systematic review was conducted in October 2016 in concordance with the PRISMA guidelines of PubMed, the Cochrane Central Register of Controlled Trials, SCOPUS, Web of Science, Google Scholar, CINAHL, Ovid, and EMBASE using the terms FOLFOXIRI and bevacizumab and (colorectal cancer). Clinical trials, retrospective case series, and prospective case series that used FOLFOXIRI-Bev for the treatment of initially unresectable metastatic colorectal cancer in humans were included. Individual case reports and retrospective case series with fewer than 10 patients were excluded. Data were extracted independently by 2 reviewers on a predesigned, standardized form. Ultimately, data were aggregated to obtain the pooled effect size of efficacy, according to the random-effects model and weighted for the number of patients included in each trial. Median overall survival and progression-free survival, overall response rates, and rates of R0 surgical conversions and overall surgical conversions. Eleven FOLFOXIRI-Bev studies published between 2010 and 2016 met the inclusion criteria and were pooled for analysis. The studies included 889 patients, with 877 patients clinically evaluable for overall response rates. The objective response rate to FOLFOXIRI-Bev was 69% (95% CI, 65%-72%; I2 = 25%). The rate of overall surgical conversions was 39.1% (95% CI, 26.9%-52.8%), and the rate of R0 surgical conversions was 28.1% (95% CI, 18.1%-40.8%). Median pooled overall survival was 30.2 months (95% CI, 26.5-33.7 months) in 6 trials with data available, and progression-free survival was 12.4 months (95% CI, 10.0-14.3 months) in 9 trials with data available. In meta-regression analysis, variables significantly associated with conversion surgery were disease limited to the liver and a higher median number of cycles (close to 12). For patients with surgically unresectable metastatic colorectal cancer, FOLFOXIRI-Bev is associated with a significant overall response rate. Such an effective regimen leads to a probability of surgical conversion of distant metastases approaching 40%, with more than one-fourth of patients having an R0 resection.
Chen, J H; Lee, C H; Chang, C M; Yin, W Y
2016-04-01
In kidney transplantation, obesity is associated with poorer graft survival and patient survival. Bariatric surgery may provide benefit for these patients, not only by inducing weight loss, but also via reduction of diabetes. We report a case of morbid obesity, poorly controlled new-onset diabetes mellitus, and gout after kidney transplantation that was treated with laparoscopic sleeve gastrectomy 3 years after kidney transplantation. After 1 year of follow-up, 76% excessive body weight loss was attained. No complications were noted. The operation also provided total remission of diabetes and gout as well as good graft survival. Based on our experience, laparoscopic sleeve gastrectomy may be a feasible treatment for obese patients after renal transplantation to help resolve obesity and control new-onset diabetes. However, the timing of operation and the long-term potential for graft and patient survivals with this operation require further study. Copyright © 2016 Elsevier Inc. All rights reserved.
Salcido, David D; Schmicker, Robert H; Buick, Jason E; Cheskes, Sheldon; Grunau, Brian; Kudenchuk, Peter; Leroux, Brian; Zellner, Stephanie; Zive, Dana; Aufderheide, Tom P; Koller, Allison C; Herren, Heather; Nuttall, Jack; Sundermann, Matthew L; Menegazzi, James J
2017-06-01
Previous work has demonstrated that when out-of-hospital cardiac arrest (OHCA) patients achieve return of spontaneous circulation (ROSC), but subsequently have another cardiac arrest prior to hospital arrival (rearrest), the probability of survival to hospital discharge is significantly decreased. Additionally, few modifiable factors for rearrest are known. We sought to examine the association between rearrest and compression-to-ventilation ratio during cardiopulmonary resuscitation (CPR) and to confirm the association between rearrest and outcomes. Rearrest incidence would be similar between cases treated with 30:2 or continuous chest compression (CCC) CPR, but inversely related to survival and good neurological outcome. We conducted a secondary analysis of a large randomized-controlled trial of CCC versus 30:2 CPR for the treatment of OHCA between 2011 and 2015 among 8 sites of the Resuscitation OUTCOMES: Consortium (ROC). Patients were randomized through an emergency medical services (EMS) agency-level cluster randomization design to receive either 30:2 or CCC CPR. Case data were derived from prehospital patient care reports, digital defibrillator files, and hospital records. The primary analysis was an as-treated comparison of the proportion of patients with a rearrest for patients who received 30:2 versus those who received CCC. In addition, we assessed the association between rearrest and both survival to hospital discharge and favorable neurological outcome (Modified Rankin Score≤3) in patients with and without ROSC upon ED arrival using multivariable logistic regression adjusting for age, sex, initial rhythm and measures of CPR quality. There were 14,109 analyzable cases that were determined to have definitively received either CCC or 30:2 CPR. Of these, 4713 had prehospital ROSC and 2040 (43.2%) had at least one rearrest. Incidence of rearrest was not significantly different between patients receiving CCC and 30:2 (44.1% vs 41.8%; adjusted OR: 1.01; 95% CI: 0.88, 1.16). Rearrest was significantly associated with lower survival (23.3% vs 36.9%; adjusted OR: 0.46; 95%CI: 0.36-0.51) and worse neurological outcome (19.4% vs 30.2%; adjusted OR: 0.46; 95%CI: 0.38, 0.55). Rearrest occurrence was not significantly different between patients receiving CCC and 30:2, and was inversely associated with survival to hospital discharge and MRS. Copyright © 2017 Elsevier B.V. All rights reserved.
Diwakar, Lavanya; Morris, Rachel K; Barton, Pelham; Middleton, Lee J; Kilby, Mark D; Roberts, Tracy E
2013-01-01
To determine the cost-effectiveness of in-utero percutaneous Vesico Amniotic Shunt (VAS) in the management of fetal lower urinary tract obstruction (LUTO). Model based economic analysis using data from the randomised controlled arm of the PLUTO (percutaneous vesico-amniotic shunting for lower urinary tract obstruction) trial. Fetal medicine departments in United Kingdom, Ireland and Netherlands. Pregnant women with a male, singleton fetus with LUTO. Costs and outcomes were prospectively collected in the trial; three separate base case analyses were performed using the intention to treat (ITT), per protocol and uniform prior methods. Deterministic and probabilistic sensitivity analyses were performed to explore data uncertainty. Survival at 28 days, 1 year and disease free survival at 1 year. VAS was more expensive but appeared to result in higher rates of survival compared with conservative management in patients with LUTO. Using ITT analysis the incremental cost effectiveness ratios based on outcomes of survival at 28 days, 1 year, or 1 morbidity-free year on the VAS arm were £ 15,506, £ 15,545, and £ 43,932, respectively. VAS is a more expensive option compared to the conservative approach in the management of individuals with LUTO. Data from the RCT suggest that VAS improves neonatal survival but does not result in significant improvements in morbidity. Our analysis concludes that VAS is not likely to be cost effective in the management of these patients given the NICE (National Institute of Health and Clinical Excellence) cost threshold of £ 20,000 per QALY.
Tuygun, Can; Kankaya, Duygu; Imamoglu, Abdurrahim; Sertcelik, Ayse; Zengin, Kursad; Oktay, Murat; Sertcelik, Nurettin
2011-01-01
To investigate the expression of sex-specific hormone receptors in normal bladder urothelium and urothelial carcinomas (UCs) of the bladder, and to analyze clinicopathological features and survival outcomes according to receptor expression. We evaluated the clinical data and tumor specimens of 139 patients with bladder cancer (BC). In addition, 72 samples of normal urothelium were included. Immunohistochemistry was performed using streptavidin-biotin peroxidase method, a monoclonal androgen receptor (AR), and an estrogen receptor-β (ERβ) antibody on paraffin-embedded tissue sections. Expression levels of each receptor were assessed by evaluating 500 tumor cells for each case and the percentage of positively-stained nuclei was recorded. None of the 58 male control cases showed any AR and ERβ expression. Five (35, 71%) of the 14 female control cases expressed ERβ. Of the 139 patients with UCs, 71 (51, 07%) expressed AR (62 male vs. 9 female; P = 0.413) and 44 (31, 65%) (39 male vs. 5 female; P = 0.402) showed ERβ expression (P < 0.001). No significant relationship was found between ERβ expression levels and tumor grades, and stages (P = 0.441; P = 0.247). AR expression was significantly lower in T2-tumors (21%) than in Ta-tumors (60%) and T1-tumors (60%) (P < 0.001). It was significantly higher in low-grade papillary UCs (64%) compared with high-grade papillary UCs (44%) and infiltrative high-grade UCs (17%) (P = 0.039; P < 0.001). Data of 79 patients with noninvasive BC were eligible to present, with a median 29 months follow-up. AR expression level did not influence recurrence-free survival (RFS) and progression-free survival (PFS) (P = 0.095; P = 0.110). No significant association was found between ERβ expression level and RFS (P = 0.293). PFS in patients with lower ERβ-expressing tumors was significantly better than that in patients with higher ERβ-expressing tumors (P = 0.035). Multivariate analysis confirmed this significant influence on PFS (P = 0.025). Although ERβ expression had no impact on histopathological tumor characteristics, decrease in its expression may be associated with better PFS rates in patients with noninvasive BC. Conversely, loss of AR expression was associated with higher grade UCs and invasive UCs, but had no prognostic effect on survival. Finally, sex-specific hormone receptors alone cannot be responsible for gender differences in BC rates because they were expressed in similar rates in both sexes. Copyright © 2011 Elsevier Inc. All rights reserved.
Cancer survival among children of Turkish descent in Germany 1980–2005: a registry-based analysis
Spix, Claudia; Spallek, Jacob; Kaatsch, Peter; Razum, Oliver; Zeeb, Hajo
2008-01-01
Background Little is known about the effect of migrant status on childhood cancer survival. We studied cancer survival among children of Turkish descent in the German Cancer Childhood Registry, one of the largest childhood cancer registries worldwide. Methods We identified children of Turkish descent among cancer cases using a name-based approach. We compared 5-year survival probabilities of Turkish and other children in three time periods of diagnosis (1980–87, 1988–95, 1996–2005) using the Kaplan-Meier method and log-rank tests. Results The 5-year survival probability for all cancers among 1774 cases of Turkish descent (4.76% of all 37.259 cases) was 76.9% compared to 77.6% in the comparison group (all other cases; p = 0.15). We found no age- or sex-specific survival differences (p-values between p = 0.18 and p = 0.90). For the period 1980–87, the 5-year survival probability among Turkish children with lymphoid leukaemia was significantly lower (62% versus 75.8%; p < 0.0001), this remains unexplained. For more recently diagnosed leukaemias, we saw no survival differences for Turkish and non-Turkish children. Conclusion Our results suggest that nowadays Turkish migrant status has no bearing on the outcome of childhood cancer therapies in Germany. The inclusion of currently more than 95% of all childhood cancer cases in standardised treatment protocols is likely to contribute to this finding. PMID:19040749
[HIV/AIDS related mortality in southern Shanxi province and its risk factors].
Ning, Shaoping; Xue, Zidong; Wei, Jun; Mu, Shengcai; Xu, Yajuan; Jia, Shaoxian; Qiu, Chao; Xu, Jianqing
2015-03-01
To explore factors influencing mortality rate of HIV/AIDS and to improve the effectiveness of antiretroviral therapy (ART). By means of retrospective cohort study and the AIDS control information system, HIV/AIDS case reports and antiviral treatment information of 4 cities in southern Shanxi province up to end of December 2012 were selected, to calculate the mortality rate and treatment coverage based on further data collected, along with analysis using the Cox proportional hazards survival regression. 4 040 cases confirmed of HIV/AIDS were included in this study. The average age was (36.0 ± 12.9) years, with 65.3% being male, 56.5% being married, 73.5% having junior high school education or lower, 58.4% being peasants, 54.3% with sexually transmitted infection (40.1% were heterosexual, 14.2% were homosexual), and 38.9% were infected via blood transmission (20.2% were former plasma donors, 16.2% blood transfusion or products recipients, 2.4% were injection drug users). Overall mortality decreased from 40.2 per 100 person/year in 2004 to 6.3 per 100 person/year in 2012, with treatment coverage concomitantly increasing from almost 14.8% to 63.4%. Cox proportional hazards survival regression was used on 4 040 qualified cases, demonstrating the top mortality risk factor was without antiretroviral therapy (RR = 14.9, 95% CI: 12.7-17.4). Cox proportional hazards survival regression was made on 1 938 cases of antiviral treatment, demonstrating that the mortality risk of underweight or obese before treatment was higher than those of normal and overweight cases (RR = 2.7, 95% CI: 1.6-4.5), and the mortality of those having a CD4(+) T-lymphocyte count ≤ 50 cells per µl before treatment was more than 50 cases (RR = 2.6, 95% CI: 1.5-4.5); Cox proportional hazards survival regression was made on 2 102 cases of untreated cases, demonstrating the mortality risk of those initially diagnosed as AIDS was higher than those initially diagnosed as HIV (RR = 3.4, 95% CI: 2.9-4.0). The ART could successfully make lower HIV/AIDS mortality rate, indicating effective ART can further decrease mortality.
Zhang, Xueyan; Wang, Huimin; Jin, Bo; Dong, Qianggang; Huang, Jinsu; Han, Baohui
2013-04-01
In recent years, cases of lung adenocarcinoma morbidity have consistently grown. OCT4 is the key gene that controls the automatic renewal of stem cells, and regulates the proliferation and differentiation of cancer stem cells. The aim of this study is to detect OCT4 expression in lung adenocarcinoma tissues, and to evaluate its relevance in the metastasis, chemotherapeutic effect, and prognosis in lung adenocarcinoma patients. Immunofluorescence method was employed to detect OCT4 expression in lung adenocarcinoma tissues. The relationship between OCT4 expression and clinical pathological indicators is examined through chi-square test. Moreover, the survival rate is calculated through the Kaplan-Meier survivorship curve. Finally, the relevance between the indicators and patient survival is estimated using Cox analysis. Among the 126 tissue samples of lung adenocarcinoma, 91 showed OCT4 positive cells. OCT4 expression is closely related to metastasis and chemoresistance in lung adenocarcinoma patients, and negatively corresponds to the patients' disease-free survival and survival periods. OCT4 expression is related to metastasis and chemoresistance in lung adenocarcinoma patients, and thus indicates poor prognosis.
Dhir, Mashaal; Jones, Heather L; Shuai, Yongli; Clifford, Amber K; Perkins, Samantha; Steve, Jennifer; Hogg, Melissa E; Choudry, M Haroon A; Pingpank, James F; Holtzman, Matthew P; Zeh, Herbert J; Bahary, Nathan; Bartlett, David L; Zureikat, Amer H
2017-01-01
In the era of effective modern systemic chemotherapy (CT), the role of hepatic arterial infusion of fluoxuridine (HAI-FUDR) in the treatment of isolated unresectable colorectal liver metastasis (IU-CRCLM) remains controversial. This study aimed to compare the overall survival (OS) of HAI-FUDR in combination with modern systemic CT versus modern systemic CT alone in patients with IU-CRCLM. This was a case-control study of IU-CRCLM patients who underwent HAI + modern systemic CT or modern systemic CT alone. Modern systemic CT was defined as the use of multidrug regimens containing oxaliplatin and/or irinotecan ± biologics. Overall, 86 patients met the inclusion criteria (n = 40 for the HAI + CT group, and n = 46 for the CT-alone group). Both groups were similar in demographics, primary and stage IV tumor characteristics, and treatment-related variables (carcinoembryonic antigen, use of biologic agents, total number of lines of systemic CT administered) (all p > 0.05). Additionally, both groups were comparable with respect to liver tumor burden [median number of lesions (13.5 vs. 15), percentage of liver tumor replacement (37.5 vs. 40 %), and size of largest lesion] (all p > 0.05). Median OS in the HAI + CT group was 32.8 months compared with 15.3 months in the CT-alone group (p < 0.0001). Multivariate analysis revealed HAI + CT (hazard ratio 0.4, 95 % confidence interval 0.21-0.72; p = 0.003), Eastern Cooperative Oncology Group status, and receipt of increasing number of lines of systemic CT to be independent predictors of survival. In this case-control study of patients with IU-CRCLM, HAI in combination with CT was associated with improved OS when compared with modern systemic CT alone.
Zhang, Xianxiang; Shao, Shihong; Gao, Yuan; Zhang, Maoshen; Lu, Yun
2016-03-01
To investigate the relationship between extranodal tumor deposits and prognosis in patients with colorectal cancer. The literatures on extranodal tumor deposits and postoperative survival rate in patients with colorectal cancer published at home and abroad from 1990 to 2014 were retrieved in 15 English literature databases such as MEDLINE/PubMed, Web of Science, Directory of Open Access Journals(DOAJ), SpringerLink and Chinese literature databases such as Chinese Biomedical Literature Database CD-ROM, China National Knowledge Infrastructure (CNKI) Database with the internet platform of Yonsei University Library. After screening for inclusion, data extraction and quality assessment, meta-analysis was conducted by the Review Manager 5.3 software. There were 10 studies meeting the inclusion criteria for meta-analysis. The total sample size of the studies was 4 068 cases with ENTD(+) 727 cases, while ENTD(-) 3 341 cases. Meta analysis showed that 5-year overall survival rate and 5-year relapse-free survival rate were significantly lower in ENTD(+) group than those in ENTD(-) group (OR 0.27, 0.23; 95% CI:0.18 to 0.43, 0.16 to 0.34 respectively, both P=0.000); the 5-year overall survival rates were both significantly lower in ENTD(+) group as compared to ENTD(-) group for patients with N0 and N(+) colorectal cancer (both P<0.05). Extranodal tumor deposits is a poor prognostic factor of patients with colorectal cancer.
Jiang, Jingmei; Liu, Boqi; Nasca, Philip C; Han, Wei; Zou, Xiaonong; Zeng, Xianjia; Tian, Xiaobing; Wu, Yanping; Zhao, Ping; Li, Junyao
2009-10-28
To assess the validation of a novel control selection design by comparing the consistency between the new design and a routine design in a large case-control study that was incorporated into a nationwide mortality survey in China. A nationwide mortality study was conducted during 1989-1991. Surviving spouses or other relatives of all adults who died during 1986-1988 provided detailed information about their own as well as the deceased person's smoking history. In this study, 130,079 males who died of various smoking-related cancers at age 35 or over were taken as cases, while 103,248 male surviving spouses (same age range with cases) of women who died during the same period and 49,331 males who died from causes other than those related to smoking were used as control group 1 and control group 2, respectively. Consistency in the results when comparing cases with each of the control groups was assessed. Consistency in the results was observed in the analyses using different control groups although cancer deaths varied with region and age. Equivalence could be ascertained using a 15% criterion in most cancer deaths which had high death rates in urban areas, but they were uncertain for most cancers in rural areas irrespective of whether the hypothesis testing showed significant differences or not. Sex-matched living spouse control design as an alternative control selection for a case-control study is valid and feasible, and the basic principles of the equivalence study are also supported by epidemiological survey data.
Yin, W J; Zhu, X; Yang, H Y; Sun, W Y; Wu, M J
2018-01-08
Objective: To investigate the impact of clinicopathological features, gene rearrangements and protein expression of bcl-6, bcl-2, C-MYC and chemotherapy regime on the prognosis of patients with primary central nervous system diffuse large B-cell lymphoma (PCNS-DLBCL). Methods: Thirty-three cases of PCNS-DLBCL diagnosed from January 2006 to December 2016 at Zhejiang Cancer Hospital were collected. The expression of CD10, bcl-6, bcl-2, MUM1 and MYC were detected by immunohistochemical staining (IHC). The presence of EB virus was detected by in situ hybridization(EBER). Copy number variation (ICN) and translocation status of bcl-6, bcl-2 and C-MYC genes were detected by fluorescence in situ hybridization (FISH). The relationship between the above indexes and the prognosis was analyzed by univariate, bivariate survival analysis and multiple Cox hazard regression analysis. Results: The study included 33 patients of PCNS-DLBCL, without evidence of primary or secondary immunodeficient disease. Male to female ratio was 1.36∶1.00, and the average age was 56 years. Twenty cases had single lesion while 13 had multiple lesions. Deep brain involvement was seen in 12 cases. All patients underwent partial or total tumor resection. Five patients received whole brain post-surgery radiotherapy, nine patients received high-dose methotrexate (HD-MTX) based chemotherapy, and 12 patients received whole-brain radiotherapy combined with HD-MTX based chemotherapy. Severn patients received no further treatment and rituximab was used in 8 patients. According to the Hans model, 27 cases were classified as non-GCB subtypes (81.8%). Bcl-2 was positive in 25 cases (75.8%, 25/33) and highly expressed in 8 (24.2%). MYC was positive in 12 cases (36.4%) and double expression of bcl-2 and MYC was seen in 6 cases. EBER positive rate was 10.0%(3/30), all of which had multiple lesions. Two bcl-6 gene translocations and 3 amplifications were found in 28 patients. Two translocations, 3 ICN or with both bcl-2 gene translocation and ICN were found in 30 patients. Four ICNs of C-MYC gene were found in 28 patients. Elevated protein in cerebrospinal fluid (CSF) was found in 13 patients. LDH increased in 10 cases. Follow-up period was 2-90 months with the average survival time of (23.0±3.7) months and two-year survival rate of 39.0%. Univariate survival analysis showed that overexpression of bcl-2 protein (≥70%) and MYC protein (≥40%), bcl-2 gene abnormality (including copy number increase and translocation), C-MYC gene copy number increased were adverse factors for survival. C-MYC/ bcl-2 gene double hit was seen in 2 cases. Bivariate survival analysis found that of bcl-2/MYC protein double expression and bcl-2 and C-MYC genes double aberration were significantly associated with adverse outcomes. Cox multivariate risk regression analysis found that gender, cerebrospinal fluid protein increasing, and ICN of C-MYC gene were independent poor prognostic factors. DH-MTX based comprehensive chemotherapy was associated with better prognosis. Conclusions: Double hit at genomic level (copy number variations and gene rearrangements) and double protein expression of bcl-2 and C-MYC in PCNS-DLBCL are significantly associated with an adverse outcome. DH-MTX based comprehensive treatment may prolong the patient survival.
Thathia, Shabnam H.; Ferguson, Stuart; Gautrey, Hannah E.; van Otterdijk, Sanne D.; Hili, Michela; Rand, Vikki; Moorman, Anthony V.; Meyer, Stefan; Brown, Robert; Strathdee, Gordon
2012-01-01
Background Altered regulation of many transcription factors has been shown to be important in the development of leukemia. TWIST2 modulates the activity of a number of important transcription factors and is known to be a regulator of hematopoietic differentiation. Here, we investigated the significance of epigenetic regulation of TWIST2 in the control of cell growth and survival and in response to cytotoxic agents in acute lymphoblastic leukemia. Design and Methods TWIST2 promoter methylation status was assessed quantitatively, by combined bisulfite and restriction analysis (COBRA) and pyrosequencing assays, in multiple types of leukemia and TWIST2 expression was determined by quantitative reverse transcriptase polymerase chain reaction analysis. The functional role of TWIST2 in cell proliferation, survival and response to chemotherapy was assessed in transient and stable expression systems. Results We found that TWIST2 was inactivated in more than 50% of cases of childhood and adult acute lymphoblastic leukemia through promoter hypermethylation and that this epigenetic regulation was especially prevalent in RUNX1-ETV6-driven cases. Re-expression of TWIST2 in cell lines resulted in a dramatic reduction in cell growth and induction of apoptosis in the Reh cell line. Furthermore, re-expression of TWIST2 resulted in increased sensitivity to the chemotherapeutic agents etoposide, daunorubicin and dexamethasone and TWIST2 hypermethylation was almost invariably found in relapsed adult acute lymphoblastic leukemia (91% of samples hypermethylated). Conclusions This study suggests a dual role for epigenetic inactivation of TWIST2 in acute lymphoblastic leukemia, initially through altering cell growth and survival properties and subsequently by increasing resistance to chemotherapy. PMID:22058208
Lee, Jeeyun; Au, Wing-Yan; Park, Min Jae; Suzumiya, Junji; Nakamura, Shigeo; Kameoka, Jun-Ichi; Sakai, Chikara; Oshimi, Kazuo; Kwong, Yok-Lam; Liang, Raymond; Yiu, Harry; Wong, Kam-Hung; Cheng, Hoi-Ching; Ryoo, Baek-Yeol; Suh, Cheolwon; Ko, Young Hyeh; Kim, Kihyun; Lee, Jae-Won; Kim, Won Seog; Suzuki, Ritsuro
2008-12-01
Extranodal natural killer (NK)/T cell lymphoma, nasal type, is a recently recognized distinct entity and the most common type of non-B cell extranodal lymphoma in Asia. This retrospective analysis studied the potential survival benefits of hematopoeitic stem cell transplantation (HSCT) compared with a historical control group. A total of 47 patients from 3 previously published series of HSCT were matched according to NK/T cell lymphoma International Prognostic Index (NKIPI) risk groups and disease status at transplantation with 107 patients from a historical control group for analysis. After a median follow-up of 116.5 months, the median survival time was not determined for the HSCT group, but it was 43.5 months for the control group (95% confidence interval [CI] = 6.7 to 80.3 months; P = .127, log-rank test). In patients who were in complete remission (CR) at the time of HSCT or at surveillance after remission, disease-specific survival rates were significantly higher in the HSCT group compared with the control group (disease-specific 5-year survival rate, 87.3% for HSCT vs 67.8% for non-HSCT; P = .027). In contrast, in subgroup analysis on non-CR patients at the time of HSCT or non-HSCT treatment, disease-specific survival rates were not significantly prolonged in the HSCT group compared with the control group (1-year survival rate, 66.7% for HSCT vs 28.6% for non-HSCT; P = .141). The impact of HSCT on the survival of all patients was significantly retained at the multivariate level with a 2.1-fold (95% CI =1.2- to 3.7-fold) reduced risk of death (P = .006). HSCT seems to confer a survival benefit in patients who attained CR on postremission consolidation therapy. These findings suggest that, in particular, patients in CR with high NKIPI risk scores at diagnosis should receive full consideration for HSCT.
Cao, Zipei; Wei, Lijuan; Zhu, Weizhi; Yao, Xuping
2018-03-01
Reduction of cyclin-dependent kinase inhibitor 2A (CDKN2A) (p16 and p14) expression through DNA methylation has been reported in prostate cancer (PCa). This meta-analysis was conducted to assess the difference of p16 and p14 methylation between PCa and different histological types of nonmalignant controls and the correlation of p16 or p14 methylation with clinicopathological features of PCa. According to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement criteria, articles were searched in PubMed, Embase, EBSCO, Wanfang, and CNKI databases. The strength of correlation was calculated by the pooled odds ratios (ORs) and their corresponding 95% confidence intervals (95% CIs). Trial sequential analysis (TSA) was used to estimate the required population information for significant results. A total of 20 studies published from 1997 to 2017 were identified in this meta-analysis, including 1140 PCa patients and 530 cases without cancer. Only p16 methylation in PCa was significantly higher than in benign prostatic lesions (OR = 4.72, P = .011), but had a similar level in PCa and adjacent tissues or high-grade prostatic intraepithelial neoplasias (HGPIN). TSA revealed that this analysis on p16 methylation is a false positive result in cancer versus benign prostatic lesions (the estimated required information size of 5116 participants). p16 methylation was not correlated with PCa in the urine and blood. Besides, p16 methylation was not linked to clinical stage, prostate-specific antigen (PSA) level, and Gleason score (GS) of patients with PCa. p14 methylation was not correlated with PCa in tissue and urine samples. No correlation was observed between p14 methylation and clinical stage or GS. CDKN2A mutation and copy number alteration were not associated with prognosis of PCa in overall survival and disease-free survival. CDKN2A expression was not correlated with the prognosis of PCa in overall survival (492 cases) (P > .1), while CDKN2A expression was significantly associated with a poor disease-free survival (P < .01). CDKN2A methylation may not be significantly associated with the development, progression of PCa. Although CDKN2A expression had an unfavorable prognosis in disease-free survival. More studies are needed to confirm our results.
Djordjevic, V; Bukurov, B; Arsovic, N; Dimitrijevic, M; Jesic, S; Nesic, V; Petrovic, Z
2016-12-01
To evaluate the efficacy of bilateral selective neck dissection of levels II-IV in elective and therapeutic management of the neck as a part of primary surgical treatment of patients with supraglottic laryngeal cancer and clinically negative cervical findings (N0). Institutional, observational, case-control study with historic control of patients who underwent primary supraglottic tumour surgery, and a prospective cohort of patient, who underwent, besides the operation of primary tumour, bilateral selective neck dissection (level II-IV). University, tertiary level hospital, national referral centre. The study included 193 patients with supraglottic cancer and without palpable or ultrasound positive cervical findings who were surgically treated from 1988 to 2005. Besides the operation of primary tumour, all patients in the study group underwent bilateral selective neck dissection (level II-IV). Patients in the control group (N = 51) underwent primary tumour operation only and were followed up regularly. In cases with postoperative regional recurrences, the radical neck dissection was performed. All patients with histopathological confirmation of occult metastases were administered radiotherapy treatment (60 Gy) in the postoperative period. Five-year overall survival rate. Occult cervical metastases were found in 18% of patients. They were present in level II in 77.5%, in level III in 20% of cases and in one patient in level IV (2.5%); the extracapsular spread was observed in 20% of cases. Postoperative regional metastases were found in 4.15% of cases in the study group, and in 11.8% in the control group, which proved to be significantly higher. The five-year overall survival rate showed no significant difference between the study group and the control group. The incidence of postoperative regional recurrences could be reduced by performing bilateral selective neck dissection simultaneously with primary tumour operation, but with no influence on the survival rate. © 2015 John Wiley & Sons Ltd.
Duffy, Sonia A.; Ronis, David L.; McLean, Scott; Fowler, Karen E.; Gruber, Stephen B.; Wolf, Gregory T.; Terrell, Jeffrey E.
2009-01-01
Purpose Our prior work has shown that the health behaviors of head and neck cancer patients are interrelated and are associated with quality of life; however, other than smoking, the relationship between health behaviors and survival is unclear. Patients and Methods A prospective cohort study was conducted to determine the relationship between five pretreatment health behaviors (smoking, alcohol, diet, physical activity, and sleep) and all-cause survival among 504 head and neck cancer patients. Results Smoking status was the strongest predictor of survival, with both current smokers (hazard ratio [HR] = 2.4; 95% CI, 1.3 to 4.4) and former smokers (HR = 2.0; 95% CI, 1.2 to 3.5) showing significant associations with poor survival. Problem drinking was associated with survival in the univariate analysis (HR = 1.4; 95% CI, 1.0 to 2.0) but lost significance when controlling for other factors. Low fruit intake was negatively associated with survival in the univariate analysis only (HR = 1.6; 95% CI, 1.1 to 2.1), whereas vegetable intake was not significant in either univariate or multivariate analyses. Although physical activity was associated with survival in the univariate analysis (HR = 0.95; 95% CI, 0.93 to 0.97), it was not significant in the multivariate model. Sleep was not significantly associated with survival in either univariate or multivariate analysis. Control variables that were also independently associated with survival in the multivariate analysis were age, education, tumor site, cancer stage, and surgical treatment. Conclusion Variation in selected pretreatment health behaviors (eg, smoking, fruit intake, and physical activity) in this population is associated with variation in survival. PMID:19289626
Riches, M L; Trifilio, S; Chen, M; Ahn, K W; Langston, A; Lazarus, H M; Marks, D I; Martino, R; Maziarz, R T; Papanicolou, G A; Wingard, J R; Young, J-A H; Bennett, C L
2016-02-01
Risk factors for non-Aspergillus mold infection (NAMI) and the impact on transplant outcome are poorly assessed in the current era of antifungal agents. Outcomes of 124 patients receiving allogeneic hematopoietic cell transplantation (HCT) diagnosed with either mucormycosis (n=72) or fusariosis (n=52) between days 0 and 365 after HCT are described and compared with a control cohort (n=11 856). Patients with NAMI had more advanced disease (mucormycois: 25%, fusariosis: 23% and controls: 18%; P=0.004) and were more likely to have a Karnofsky performance status (KPS) <90% at HCT (mucormycosis: 42%, fusariosis: 38% and controls: 28%; P=0.048). The 1-year survival after HCT was 22% (15-29%) for cases and was significantly inferior compared with controls (65% (64-65%); P<0.001). Survival from infection was similarly dismal regardless of mucormycosis: 15% (8-25%) and fusariosis: 21% (11-33%). In multivariable analysis, NAMI was associated with a sixfold higher risk of death (P<0.0001) regardless of the site or timing of infection. Risk factors for mucormycosis include preceding acute GvHD, prior Aspergillus infection and older age. For fusariosis, increased risks including receipt of cord blood, prior CMV infection and transplant before May 2002. In conclusion, NAMI occurs infrequently, is associated with high mortality and appears with similar frequency in the current antifungal era.
Lung cancer in renal transplant recipients: A case-control study.
Rousseau-Gazaniol, Claire; Fraboulet, Séverine; Couderc, Louis-Jean; Kreis, Henri; Borie, Raphaël; Tricot, Leila; Anglicheau, Dany; Martinez, Frank; Doubre, Hélène; Bonnette, Pierre; Mellot, François; Massiani, Marie-Ange; Pelle, Gaëlle; Sage, Edouard; Moisson, Patricia; Delahousse, Michel; Zemoura, Leila; Chapelier, Alain; Hamid, Abdul Monem; Puyo, Philippe; Longchampt, Elisabeth; Legendre, Christophe; Friard, Sylvie; Catherinot, Emilie
2017-09-01
Solid organ transplant patients are at heightened risk of several cancers compared to the general population. Secondary to a higher number of procedures and better survival after transplantation, cancer is a rising health concern in this situation. Limited data exist for lung cancer (LC) after renal transplantation. We report here the most important series of renal transplant recipients with lung cancer. Retrospective study of all cases of LC diagnosed in three French Renal Transplant Units from 2003 to 2012. A control group consisted of non-transplant patients with LC matched with the cases for age (<30; 30-50; 50-65; >65 years), gender and diagnosis date. We recruited two controls for each case. Thirty patients (median age 60 years; range 29-85; male/female ratio 80/20%) with LC were analysed. LC incidence was 1.89/1000 person-years over the period 2008-2012. All patients were former or active smokers (median 30 pack-years). Transplanted patients had significantly more comorbidities, mainly cardiovascular disease. The median interval of time from kidney transplantation (KT) to diagnosis of LC was 7 years (range 0.5-47 years). LC was incidentally diagnosed in 40%. Most patients (70%) had advanced LC (stage III or IV) disease. Stage of LC at diagnosis was similar in cases and controls. Surgery and chemotherapy were proposed to the same proportion of patients. In cases, mortality was cancer related in 87% and median survival time after diagnosis was 24 months. Survival was not significantly different between the 2 groups. Despite frequent medical and radiological examinations, diagnosis of LC is usually made at an advanced stage and the overall prognosis remains poor. Copyright © 2017 Elsevier B.V. All rights reserved.
Logue, Mark W.; Smith, Alicia K.; Baldwin, Clinton; Wolf, Erika J.; Guffanti, Guia; Ratanatharathorn, Andrew; Stone, Annjanette; Schichman, Steven A.; Humphries, Donald; Binder, Elisabeth B.; Arloth, Janine; Menke, Andreas; Uddin, Monica; Wildman, Derek; Galea, Sandro; Aiello, Allison E.; Koenen, Karestan C.; Miller, Mark W.
2015-01-01
We examined the association between posttraumatic stress disorder (PTSD) and gene expression using whole blood samples from a cohort of trauma-exposed white non-Hispanic male veterans (115 cases and 28 controls). 10,264 probes of genes and gene transcripts were analyzed. We found 41 that were differentially expressed in PTSD cases versus controls (multiple-testing corrected p<0.05). The most significant was DSCAM, a neurological gene expressed widely in the developing brain and in the amygdala and hippocampus of the adult brain. We then examined the 41 differentially expressed genes in a meta-analysis using two replication cohorts and found significant associations with PTSD for 7 of the 41 (p<0.05), one of which (ATP6AP1L) survived multiple-testing correction. There was also broad evidence of overlap across the discovery and replication samples for the entire set of genes implicated in the discovery data based on the direction of effect and an enrichment of p<0.05 significant probes beyond what would be expected under the null. Finally, we found that the set of differentially expressed genes from the discovery sample was enriched for genes responsive to glucocorticoid signaling with most showing reduced expression in PTSD cases compared to controls. PMID:25867994
Praestegaard, Camilla; Jensen, Allan; Jensen, Signe M; Nielsen, Thor S S; Webb, Penelope M; Nagle, Christina M; DeFazio, Anna; Høgdall, Estrid; Rossing, Mary Anne; Doherty, Jennifer A; Wicklund, Kristine G; Goodman, Marc T; Modugno, Francesmary; Moysich, Kirsten; Ness, Roberta B; Edwards, Robert; Matsuo, Keitaro; Hosono, Satoyo; Goode, Ellen L; Winham, Stacey J; Fridley, Brooke L; Cramer, Daniel W; Terry, Kathryn L; Schildkraut, Joellen M; Berchuck, Andrew; Bandera, Elisa V; Paddock, Lisa E; Massuger, Leon F; Wentzensen, Nicolas; Pharoah, Paul; Song, Honglin; Whittemore, Alice; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A; Ramus, Susan J; Gentry-Maharaj, Alexandra; Wu, Anna H; Pearce, Celeste L; Pike, Malcolm; Lee, Alice W; Sutphen, Rebecca; Chang-Claude, Jenny; Risch, Harvey A; Kjaer, Susanne K
2017-06-01
Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer. We obtained data from 19 case-control studies in the Ovarian Cancer Association Consortium (OCAC), including 9,114 women diagnosed with ovarian cancer. Cox regression models were used to estimate adjusted study-specific hazard ratios (HRs), which were combined into pooled hazard ratios (pHR) with corresponding 95% confidence intervals (CIs) under random effects models. Overall, 5,149 (57%) women died during a median follow-up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08-1.28) and former smokers (pHR = 1.10, 95% CI: 1.02-1.18) had worse survival compared with never smoking women. In histotype-stratified analyses, associations were observed for mucinous (current smoking: pHR = 1.91, 95% CI: 1.01-3.65) and serous histotypes (current smoking: pHR = 1.11, 95% CI: 1.00-1.23; former smoking: pHR = 1.12, 95% CI: 1.04-1.20). Further, our results suggested that current smoking has a greater impact on survival among women with localized than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis. © 2017 UICC.
Præstegaard, Camilla; Jensen, Allan; Jensen, Signe M.; Nielsen, Thor S. S.; Webb, Penelope M.; Nagle, Christina M.; DeFazio, Anna; Høgdall, Estrid; Rossing, Mary Anne; Doherty, Jennifer A.; Wicklund, Kristine G.; Goodman, Marc T.; Modugno, Francesmary; Moysich, Kirsten; Ness, Roberta B.; Edwards, Robert; Matsuo, Keitaro; Hosono, Satoyo; Goode, Ellen L.; Winham, Stacey J; Fridley, Brooke L.; Cramer, Daniel W.; Terry, Kathryn L.; Schildkraut, Joellen M.; Berchuck, Andrew; Bandera, Elisa V.; Paddock, Lisa E.; Massuger, Leon F.; Wentzensen, Nicolas; Pharoah, Paul; Song, Honglin; Whittemore, Alice; McGuire, Valerie; Sieh, Weiva; Rothstein, Joseph; Anton-Culver, Hoda; Ziogas, Argyrios; Menon, Usha; Gayther, Simon A.; Ramus, Susan J.; Gentry-Maharaj, Alexandra; Wu, Anna H.; Pearce, Celeste L.; Pike, Malcolm; Lee, Alice W.; Sutphen, Rebecca; Chang-Claude, Jenny; Risch, Harvey A.; Kjaer, Susanne K.
2017-01-01
Cigarette smoking is associated with an increased risk of developing mucinous ovarian tumors but whether it is associated with ovarian cancer survival overall or for the different histotypes is unestablished. Furthermore, it is unknown whether the association between cigarette smoking and survival differs according to strata of ovarian cancer stage at diagnosis. In a large pooled analysis, we evaluated the association between various measures of cigarette smoking and survival among women with epithelial ovarian cancer. We obtained data from 19 case-control studies in the Ovarian Cancer Association Consortium (OCAC), including 9,114 women diagnosed with ovarian cancer. Cox regression models were used to estimate adjusted study-specific hazard ratios (HRs), which were combined into pooled hazard ratios (pHR) with corresponding 95% confidence intervals (CIs) under random effects models. Overall, 5,149 (57%) women died during a median follow-up period of 7.0 years. Among women diagnosed with ovarian cancer, both current (pHR = 1.17, 95% CI: 1.08–1.28) and former smokers (pHR = 1.10, 95% CI: 1.02–1.18) had worse survival compared with never smoking women. In histotype-stratified analyses, associations were observed for mucinous (current smoking: pHR = 1.91, 95% CI: 1.01–3.65) and serous histotypes (current smoking: pHR = 1.11, 95% CI: 1.00–1.23; former smoking: pHR = 1.12, 95% CI: 1.04–1.20). Further, our results suggested that current smoking has a greater impact on survival among women with localized than disseminated disease. The identification of cigarette smoking as a modifiable factor associated with survival has potential clinical importance as a focus area to improve ovarian cancer prognosis. PMID:28063166
Shankar, Ganesh M; Clarke, Michelle J; Ailon, Tamir; Rhines, Laurence D; Patel, Shreyaskumar R; Sahgal, Arjun; Laufer, Ilya; Chou, Dean; Bilsky, Mark H; Sciubba, Daniel M; Fehlings, Michael G; Fisher, Charles G; Gokaslan, Ziya L; Shin, John H
2017-07-01
OBJECTIVE Primary osteosarcoma of the spine is a rare osseous neoplasm. While previously reported retrospective studies have demonstrated that overall patient survival is impacted mostly by en bloc resection and chemotherapy, the continued management of residual disease remains to be elucidated. This systematic review was designed to address the role of revision surgery and multimodal adjuvant therapy in cases in which en bloc excision is not initially achieved. METHODS A systematic literature search spanning the years 1966 to 2015 was performed on PubMed, Medline, EMBASE, and Web of Science to identify reports describing outcomes of patients who underwent biopsy alone, neurological decompression, or intralesional resection for osteosarcoma of the spine. Studies were reviewed qualitatively, and the clinical course of individual patients was aggregated for quantitative meta-analysis. RESULTS A total of 16 studies were identified for inclusion in the systematic review, of which 8 case reports were summarized qualitatively. These studies strongly support the role of chemotherapy for overall survival and moderately support adjuvant radiation therapy for local control. The meta-analysis revealed a statistically significant benefit in overall survival for performing revision tumor debulking (p = 0.01) and also for chemotherapy at relapse (p < 0.01). Adjuvant radiation therapy was associated with longer survival, although this did not reach statistical significance (p = 0.06). CONCLUSIONS While the initial therapeutic goal in the management of osteosarcoma of the spine is neoadjuvant chemotherapy followed by en bloc marginal resection, this objective is not always achievable given anatomical constraints and other limitations at the time of initial clinical presentation. This systematic review supports the continued aggressive use of revision surgery and multimodal adjuvant therapy when possible to improve outcomes in patients who initially undergo subtotal debulking of osteosarcoma. A limitation of this systematic review is that lesions amenable to subsequent resection or tumors inherently more sensitive to adjuvants would exaggerate a therapeutic effect of these interventions when studied in a retrospective fashion.
Survival of two post systems--five-year results of a randomized clinical trial.
Schmitter, Marc; Hamadi, Khaled; Rammelsberg, Peter
2011-01-01
To assess the survival rate of two different post systems after 5 years of service with a prospective randomized controlled trial. One hundred patients in need of a post were studied. Half of the patients received long glass fiber-reinforced posts, while the other half received long metal screw posts. The posts were assigned randomly. After at least 5 years (mean, 61.37 months), follow-ups were established. When a complication occurred prior to this recall, the type and time of the complication was documented. Statistical analysis was performed using the log-rank test and Kaplan-Meier analysis. Additionally, a Cox regression was performed to analyze risk factors. The survival rate of fiber-reinforced posts was 71.8%. In the metal screw post group, the survival rate was significantly lower, 50.0% (log-rank test, P = .026). Metal posts resulted more often in more unfavorable complications (eg, root fractures); consequently, more teeth (n = 17) had to be extracted. The Cox regression identified the following risk factors: position of the tooth (anterior vs posterior teeth), degree of coronal tooth destruction, and the post system (fiber-reinforced post vs metal screw post). Fiber-reinforced restorations loosened in several patients; in some of these cases (n = 6), patients did not notice this, leading to the extraction of teeth. Long metal screw posts should be used with great care in endodontically treated teeth. Besides the selection of the post system, other factors influence the survival of the restoration.
Landi, Maria Teresa; Consonni, Dario; Rotunno, Melissa; Bergen, Andrew W; Goldstein, Alisa M; Lubin, Jay H; Goldin, Lynn; Alavanja, Michael; Morgan, Glen; Subar, Amy F; Linnoila, Ilona; Previdi, Fabrizio; Corno, Massimo; Rubagotti, Maurizia; Marinelli, Barbara; Albetti, Benedetta; Colombi, Antonio; Tucker, Margaret; Wacholder, Sholom; Pesatori, Angela C; Caporaso, Neil E; Bertazzi, Pier Alberto
2008-06-06
Lung cancer is the leading cause of cancer mortality worldwide. Tobacco smoking is its primary cause, and yet the precise molecular alterations induced by smoking in lung tissue that lead to lung cancer and impact survival have remained obscure. A new framework of research is needed to address the challenges offered by this complex disease. We designed a large population-based case-control study that combines a traditional molecular epidemiology design with a more integrative approach to investigate the dynamic process that begins with smoking initiation, proceeds through dependency/smoking persistence, continues with lung cancer development and ends with progression to disseminated disease or response to therapy and survival. The study allows the integration of data from multiple sources in the same subjects (risk factors, germline variation, genomic alterations in tumors, and clinical endpoints) to tackle the disease etiology from different angles. Before beginning the study, we conducted a phone survey and pilot investigations to identify the best approach to ensure an acceptable participation in the study from cases and controls. Between 2002 and 2005, we enrolled 2101 incident primary lung cancer cases and 2120 population controls, with 86.6% and 72.4% participation rate, respectively, from a catchment area including 216 municipalities in the Lombardy region of Italy. Lung cancer cases were enrolled in 13 hospitals and population controls were randomly sampled from the area to match the cases by age, gender and residence. Detailed epidemiological information and biospecimens were collected from each participant, and clinical data and tissue specimens from the cases. Collection of follow-up data on treatment and survival is ongoing. EAGLE is a new population-based case-control study that explores the full spectrum of lung cancer etiology, from smoking addiction to lung cancer outcome, through examination of epidemiological, molecular, and clinical data. We have provided a detailed description of the study design, field activities, management, and opportunities for research following this integrative approach, which allows a sharper and more comprehensive vision of the complex nature of this disease. The study is poised to accelerate the emergence of new preventive and therapeutic strategies with potentially enormous impact on public health.
Nava-Sánchez, A; Munguía-Steyer, R; Córdoba-Aguilar, A
2014-08-01
Hormones are key regulators of resource allocation among functions and thus play an important role in resource-based trade-offs. The juvenile hormone (JH) is an insect hormone that mediates resource allocation between immunity and life history components. Here, we have tested whether this is the case using the house cricket. We investigated whether increased levels of JH (using methoprene, a JH analog) enable an enhanced survival and fecundity (via egg number) at the cost of reduced hemocyte number (a trait that is associated with immune response in insects) in the house cricket, Acheta domesticus L. We had three groups of adult crickets of both sexes: experimental (methoprene and acetone), positive control (methoprene), and negative control (no manipulation). Prior to and after experimental treatments, we counted the number of hemocytes (for the case of both sexes) and recorded the number of eggs laid and survival of females after the manipulation. There was no difference in hemocyte number, egg number, and survival. These results do not support a JH-mediated trade-off among immune ability, survival, and fecundity. We provide arguments to explain the lack of JH-mediated trade-offs in the house cricket.
Tang, Z H; Geng, Z M; Chen, C; Si, S B; Cai, Z Q; Song, T Q; Gong, P; Jiang, L; Qiu, Y H; He, Y; Zhai, W L; Li, S P; Zhang, Y C; Yang, Y
2018-05-01
Objective: To investigate the clinical value of Bayesian network in predicting survival of patients with advanced gallbladder cancer(GBC)who underwent curative intent surgery. Methods: The clinical data of patients with advanced GBC who underwent curative intent surgery in 9 institutions from January 2010 to December 2015 were analyzed retrospectively.A median survival time model based on a tree augmented naïve Bayes algorithm was established by Bayesia Lab software.The survival time, number of metastatic lymph nodes(NMLN), T stage, pathological grade, margin, jaundice, liver invasion, age, sex and tumor morphology were included in this model.Confusion matrix, the receiver operating characteristic curve and area under the curve were used to evaluate the accuracy of the model.A priori statistical analysis of these 10 variables and a posterior analysis(survival time as the target variable, the remaining factors as the attribute variables)was performed.The importance rankings of each variable was calculated with the polymorphic Birnbaum importance calculation based on the posterior analysis results.The survival probability forecast table was constructed based on the top 4 prognosis factors. The survival curve was drawn by the Kaplan-Meier method, and differences in survival curves were compared using the Log-rank test. Results: A total of 316 patients were enrolled, including 109 males and 207 females.The ratio of male to female was 1.0∶1.9, the age was (62.0±10.8)years.There was 298 cases(94.3%) R0 resection and 18 cases(5.7%) R1 resection.T staging: 287 cases(90.8%) T3 and 29 cases(9.2%) T4.The median survival time(MST) was 23.77 months, and the 1, 3, 5-year survival rates were 67.4%, 40.8%, 32.0%, respectively.For the Bayesian model, the number of correctly predicted cases was 121(≤23.77 months) and 115(>23.77 months) respectively, leading to a 74.86% accuracy of this model.The prior probability of survival time was 0.503 2(≤23.77 months) and 0.496 8(>23.77 months), the importance ranking showed that NMLN(0.366 6), margin(0.350 1), T stage(0.319 2) and pathological grade(0.258 9) were the top 4 prognosis factors influencing the postoperative MST.These four factors were taken as observation variables to get the probability of patients in different survival periods.Basing on these results, a survival prediction score system including NMLN, margin, T stage and pathological grade was designed, the median survival time(month) of 4-9 points were 66.8, 42.4, 26.0, 9.0, 7.5 and 2.3, respectively, there was a statistically significant difference in the different points( P <0.01). Conclusions: The survival prediction model of GBC based on Bayesian network has high accuracy.NMLN, margin, T staging and pathological grade are the top 4 risk factors affecting the survival of patients with advanced GBC who underwent curative resection.The survival prediction score system based on these four factors could be used to predict the survival and to guide the decision making of patients with advanced GBC.
Beaty, Lynne E; Salice, Christopher J
2013-10-01
Invasive species are costly and difficult to control. In order to gain a mechanistic understanding of potential control measures, individual-based models uniquely parameterized to reflect the salient life-history characteristics of invasive species are useful. Using invasive Australian Rhinella marina as a case study, we constructed a cohort- and individual-based population simulation that incorporates growth and body size of terrestrial stages. We used this allometric approach to examine the efficacy of nontraditional control methods (i.e., tadpole alarm chemicals and native meat ants) that may have indirect effects on population dynamics mediated by effects on body size. We compared population estimates resulting from these control methods with traditional hand removal. We also conducted a sensitivity analysis to investigate the effect that model parameters, specifically those associated with growth and body size, had on adult population estimates. Incremental increases in hand removal of adults and juveniles caused nonlinear decreases in adult population estimates, suggesting less return with increased investment in hand-removal efforts. Applying tadpole alarm chemicals or meat ants decreased adult population estimates on the same level as removing 15-25% of adults and juveniles by hand. The combined application of tadpole alarm chemicals and meat ants resulted in approximately 80% decrease in adult abundance, the largest of any applied control method. In further support of the nontraditional control methods, which greatly affected the metamorph stage, our model was most sensitive to changes in metamorph survival, juvenile survival, metamorph growth rate, and adult survival. Our results highlight the use and insights that can be gained from individual-based models that incorporate growth and body size and the potential success that nontraditional control methods could have in controlling established, invasive Rhinella marina populations.
Lozneanu, Ludmila; Avădănei, Roxana; Cîmpean, Anca Maria; Giuşcă, Simona Eliza; Amălinei, Cornelia; Căruntu, Irina-Draga
2015-01-01
To prove the presence of EG-VEGF in tumor ovary and to analyze its involvement in the ovarian carcinogenesis, as promoter of angiogenesis, in relationship with the clinicopathological prognostic factors and survival. The study group comprises tumor tissue specimens from 50 cases of surgically treated ovarian cancer that were immunohistochemically investigated. A scoring system based on the percentage of positive cells and the intensity of staining was applied for the semiquantitative assessment of EG-VEGF, as negative or positive. Statistics involved χ2 test, and Kaplan-Meier and log-rank test. EG-VEGF was positive in 35 cases (70%) and negative in 15 cases (30%). Our data confirmed the predominance of EG-VEGF positivity in the serous subiype as compared to endometrioid and clear cell subtypes, and its absence in mucinous subtype. Moreover, we demonstrated that EG-VEGF is overexpressed mainly in high-grade ovarian carcinomas (type II) than in low-grade ones. Significant differences were registered between the EG-VEGF positive or negative expression and tumor stage and histological subtypes, respectively. Survival analysis showed no differences in patient's survival and EG-VEGF positive and negative cases. The analysis of EG-VEGF expression in ovarian tumors points out the relationship between the enhanced potential for tumor angiogenesis and the tumor aggressivity.
Hsu, Po-Kuei; Chen, Hui-Shan; Wang, Bing-Yen; Wu, Shiao-Chi; Liu, Chao-Yu; Shih, Chih-Hsun; Liu, Chia-Chuan
2015-01-28
To study the "hospital type-outcome" and "volume-outcome" relationships in patients with esophageal cancer who receive non-surgical treatments. A total of 6106 patients with esophageal cancer diagnosed between 2008 and 2011 were identified from a national population-based cancer registry in Taiwan. The hospital types were defined as medical center and non-medical center. The threshold for high-volume hospitals was based on a median volume of 225 cases between 2008 and 2011 (annual volume, >56 cases) or an upper quartile (>75%) volume of 377 cases (annual volume>94 cases). Cox regression analyses were used to determine the effects of hospital type and volume outcome on patient survival. A total of 3955 non-surgically treated patients were included in the survival analysis. In the unadjusted analysis, the significant prognostic factors included cT, cN, cM stage, hospital type and hospital volume (annual volume, >94 vs ≤94). The 1- and 3-year overall survival rates in the non-medical centers (36.2% and 13.2%, respectively) were significantly higher than those in the medical centers (33.5% and 11.3%, respectively; P=0.027). The 1- and 3-year overall survival rates in hospitals with an annual volume of ≤94 (35.3% and 12.6%, respectively) were significantly higher than those with an annual volume of >94 (31.1% and 9.4%, respectively; P=0.001). However, in the multivariate analysis, the hospital type was not statistically significant. Only cT, cN, and cM stages and hospital volume (annual volume>94 vs ≤94) were independent prognostic factors. Whether the treatment occurs in medical centers is not a significant prognostic factor. High-volume hospitals were not associated with better survival rates compared with low-volume hospitals.
Hong, Ye; Wu, Lu-Peng; Ye, Feng; Zhou, Yan-Ming
2015-12-01
High incidence of intrahepatic recurrence is a major surgical limitation following hepatectomy of hepatocellular carcinoma (HCC). This study was intended to investigate the effects of adjuvant intrahepatic injection of iodine-131-lipiodol on disease recurrence and survival in patients with HCC who underwent resection. A computerized literature search was performed to identify relevant articles. Data synthesis was performed using Review Manager 5.0 software, and results are presented as odds ratio (OR) with 95 % confidence intervals. Two randomized controlled trials and three case-control studies with a total of 334 participants were analyzed. Iodine-131-lipiodol treatment achieved significantly lower rates of intrahepatic recurrence (OR = 0.48, 95 % confidence interval (95 % CI) = 0.30-0.74; P = 0.001) and early recurrence (<2 year) (OR = 0.45, 95 % CI = 0.23-0.89; P = 0.02). Likewise, iodine-131-lipiodol treatment improved both the 5-year disease-free survival and overall survival significantly (OR = 1.85, 95 % CI = 1.13-3.03; P = 0.01; OR = 2.00, 95 % CI = 0.99-4.04; P = 0.05, respectively). Adjuvant intrahepatic injection of iodine-131-lipiodol resulted in a preventive effect on recurrence and improved survival after resection of HCC. Further larger, multi-centred, randomized prospective trial is warranted.
Integrating Spirituality into a Group Psychotherapy Program for Women Surviving from Breast Cancer
Fallah, R; Golzari, M; Dastani, M; Akbari, ME
2011-01-01
Background In spite of a significant relation between spirituality and hope, happiness and life satisfaction, the effectiveness of spiritual interventions in the mentioned mental strengths has been less dealt with. The present study is conducted in order to determine the effectiveness of spiritual group intervention on the increase of hope, life satisfaction and happiness in women surviving from breast cancer. Methods Sixty women surviving from Breast Cancer were voluntarily assigned in to case and control groups, and were assessed before and after Islamic perspective spiritual intervention by spiritual experience, hope, happiness and life satisfaction questionnaires. Statistical analysis of data was performed using descriptive and inferential statistics through covariance. Results The spiritual intervention resulted in significant increase of hope, happiness and life satisfaction (P < 0.05). Conclusion Spiritual intervention appears to be a potentially beneficial intervention for increasing mental strengths among those suffering from breast cancer. Therefore, it seems necessary to consider it as an important element incomprehensive treatment, plans, and in palliative and supportive care. PMID:26328054
Re-analysis of survival data of cancer patients utilizing additive homeopathy.
Gleiss, Andreas; Frass, Michael; Gaertner, Katharina
2016-08-01
In this short communication we present a re-analysis of homeopathic patient data in comparison to control patient data from the same Outpatient´s Unit "Homeopathy in malignant diseases" of the Medical University of Vienna. In this analysis we took account of a probable immortal time bias. For patients suffering from advanced stages of cancer and surviving the first 6 or 12 months after diagnosis, respectively, the results show that utilizing homeopathy gives a statistically significant (p<0.001) advantage over control patients regarding survival time. In conclusion, bearing in mind all limitations, the results of this retrospective study suggest that patients with advanced stages of cancer might benefit from additional homeopathic treatment until a survival time of up to 12 months after diagnosis. Copyright © 2016 Elsevier Ltd. All rights reserved.
How Are Investment Returns Affected By Competition Control and Southern Oak Seedling Survival?
Donald L. Grebner; Andrew W. Ezell; Deborah A. Gaddis; Steven H. Bullard
2004-01-01
Increasing numbers of landowners are establishing hardwood plantations to satisfy their management objectives. Despite a dearth of research on competition control and its effects on initial hardwood plantation survival and investment returns, this study examines alternative competition control regimes for southern oak establishment. The analysis includes estimates of...
Breil, Bernhard; Semjonow, Axel; Müller-Tidow, Carsten; Fritz, Fleur; Dugas, Martin
2011-02-16
Survival or outcome information is important for clinical routine as well as for clinical research and should be collected completely, timely and precisely. This information is relevant for multiple usages including quality control, clinical trials, observational studies and epidemiological registries. However, the local hospital information system (HIS) does not support this documentation and therefore this data has to generated by paper based or spreadsheet methods which can result in redundantly documented data. Therefore we investigated, whether integrating the follow-up documentation of different departments in the HIS and reusing it for survival analysis can enable the physician to obtain survival curves in a timely manner and to avoid redundant documentation. We analysed the current follow-up process of oncological patients in two departments (urology, haematology) with respect to different documentation forms. We developed a concept for comprehensive survival documentation based on a generic data model and implemented a follow-up form within the HIS of the University Hospital Muenster which is suitable for a secondary use of these data. We designed a query to extract the relevant data from the HIS and implemented Kaplan-Meier plots based on these data. To re-use this data sufficient data quality is needed. We measured completeness of forms with respect to all tumour cases in the clinic and completeness of documented items per form as incomplete information can bias results of the survival analysis. Based on the form analysis we discovered differences and concordances between both departments. We identified 52 attributes from which 13 were common (e.g. procedures and diagnosis dates) and were used for the generic data model. The electronic follow-up form was integrated in the clinical workflow. Survival data was also retrospectively entered in order to perform survival and quality analyses on a comprehensive data set. Physicians are now able to generate timely Kaplan-Meier plots on current data. We analysed 1029 follow-up forms of 965 patients with survival information between 1992 and 2010. Completeness of forms was 60.2%, completeness of items ranges between 94.3% and 98.5%. Median overall survival time was 16.4 years; median event-free survival time was 7.7 years. It is feasible to integrate survival information into routine HIS documentation such that Kaplan-Meier plots can be generated directly and in a timely manner.
Phase 3 Trial of 177Lu-Dotatate for Midgut Neuroendocrine Tumors.
Strosberg, Jonathan; El-Haddad, Ghassan; Wolin, Edward; Hendifar, Andrew; Yao, James; Chasen, Beth; Mittra, Erik; Kunz, Pamela L; Kulke, Matthew H; Jacene, Heather; Bushnell, David; O'Dorisio, Thomas M; Baum, Richard P; Kulkarni, Harshad R; Caplin, Martyn; Lebtahi, Rachida; Hobday, Timothy; Delpassand, Ebrahim; Van Cutsem, Eric; Benson, Al; Srirajaskanthan, Rajaventhan; Pavel, Marianne; Mora, Jaime; Berlin, Jordan; Grande, Enrique; Reed, Nicholas; Seregni, Ettore; Öberg, Kjell; Lopera Sierra, Maribel; Santoro, Paola; Thevenet, Thomas; Erion, Jack L; Ruszniewski, Philippe; Kwekkeboom, Dik; Krenning, Eric
2017-01-12
Patients with advanced midgut neuroendocrine tumors who have had disease progression during first-line somatostatin analogue therapy have limited therapeutic options. This randomized, controlled trial evaluated the efficacy and safety of lutetium-177 ( 177 Lu)-Dotatate in patients with advanced, progressive, somatostatin-receptor-positive midgut neuroendocrine tumors. We randomly assigned 229 patients who had well-differentiated, metastatic midgut neuroendocrine tumors to receive either 177 Lu-Dotatate (116 patients) at a dose of 7.4 GBq every 8 weeks (four intravenous infusions, plus best supportive care including octreotide long-acting repeatable [LAR] administered intramuscularly at a dose of 30 mg) ( 177 Lu-Dotatate group) or octreotide LAR alone (113 patients) administered intramuscularly at a dose of 60 mg every 4 weeks (control group). The primary end point was progression-free survival. Secondary end points included the objective response rate, overall survival, safety, and the side-effect profile. The final analysis of overall survival will be conducted in the future as specified in the protocol; a prespecified interim analysis of overall survival was conducted and is reported here. At the data-cutoff date for the primary analysis, the estimated rate of progression-free survival at month 20 was 65.2% (95% confidence interval [CI], 50.0 to 76.8) in the 177 Lu-Dotatate group and 10.8% (95% CI, 3.5 to 23.0) in the control group. The response rate was 18% in the 177 Lu-Dotatate group versus 3% in the control group (P<0.001). In the planned interim analysis of overall survival, 14 deaths occurred in the 177 Lu-Dotatate group and 26 in the control group (P=0.004). Grade 3 or 4 neutropenia, thrombocytopenia, and lymphopenia occurred in 1%, 2%, and 9%, respectively, of patients in the 177 Lu-Dotatate group as compared with no patients in the control group, with no evidence of renal toxic effects during the observed time frame. Treatment with 177 Lu-Dotatate resulted in markedly longer progression-free survival and a significantly higher response rate than high-dose octreotide LAR among patients with advanced midgut neuroendocrine tumors. Preliminary evidence of an overall survival benefit was seen in an interim analysis; confirmation will be required in the planned final analysis. Clinically significant myelosuppression occurred in less than 10% of patients in the 177 Lu-Dotatate group. (Funded by Advanced Accelerator Applications; NETTER-1 ClinicalTrials.gov number, NCT01578239 ; EudraCT number 2011-005049-11 .).
A Nation-Wide Cancer Registry-Based Study of Adenosquamous Carcinoma in Taiwan
Lan, Yuan-Tzu; Huang, Kuo-Hung; Liu, Chien-An; Tai, Ling-Chen; Chen, Ming-Huang; Chao, Yee; Li, Anna Fen-Yau; Chiou, Shih-Hwa; Shyr, Yi-Ming; Wu, Chew-Wun; Fang, Wen-Liang
2015-01-01
Background Adenosqamous carcinoma (ASC) is a rare disease involving various organs, yet there are no large-scale population-based comparative studies on ASC among different organs. Methods The incidence and overall survival of ASC among various organs in cases diagnosed in Taiwan from January 1, 2003 to December 31, 2010 were calculated and compared using data from the Taiwan Cancer Registry (TCR). The various organs were classified and divided into three different systems: the female reproductive, respiratory, and alimentary systems. Survival analysis were also compared among 30,850 patients diagnosed as ASC, adenocarcinoma (AC) or squamous cell carcinoma (SCC) in organs with frequent ASC. Results During the study period, a total of 576 ASC cases were diagnosed in Taiwan. The most common primary system was respiratory (73.8%), followed by alimentary (16.2%) and female reproductive (10%). The overall survival were significantly higher for cases involving the female reproductive system, followed by the respiratory and alimentary systems (P = 0.016). The median overall survival were worse in males than females for cases involving the respiratory system (22.4 vs. 31.8 months, P = 0.044). Multivariate analysis showed that age≧65, more advanced T and N categories were independent unfavorable prognostic factors of overall survival in ASC. ASC histology is an independent unfavorable prognostic factor compared with AC and SCC. Conclusions ASC at an old age and more advanced T and N categories were found to be associated with a poor prognosis. PMID:26445240
Rosenbohm, Angela; Nagel, Gabriele; Peter, Raphael S; Brehme, Torben; Koenig, Wolfgang; Dupuis, Luc; Rothenbacher, Dietrich; Ludolph, Albert C
2018-05-01
Knowledge about the metabolic states of patients with amyotrophic lateral sclerosis (ALS) may provide a therapeutic approach. To investigate the association between the onset and prognosis of ALS and serum retinol-binding protein 4 (RBP4) concentration as a biomarker for insulin resistance and vitamin A metabolism. Case-control design for risk factors of ALS; cohort design for prognostic factors within ALS cases. Between October 1, 2010, and June 30, 2014, a population-based case-control study with randomly selected controls was established based on the ALS Registry Swabia in southern Germany, with a target population of 8.4 million inhabitants. Response rates were 64.8% among the cases and 18.7% among the controls. The dates of analysis were April 2016 to May 2017. Serum samples were measured for RBP4. Information on covariates was assessed by an interview-based standardized questionnaire. Main outcomes and measures were adjusted odds ratios for risk of ALS associated with serum RBP4 concentration, as well as time to death associated with RBP4 concentration at baseline in ALS cases only. Conditional logistic regression was applied to calculate multivariable odds ratios for risk of ALS. Survival models were used in cases only to appraise their prognostic value. Data from 289 patients with ALS (mean [SD] age, 65.7 [10.5] years; 172 [59.5%] male) and 504 controls (mean [SD] age, 66.3 [9.8] years; 299 [59.3%] male) were included in the case-control study. Compared with controls, ALS cases were characterized by lower body mass index, less educational attainment, smoking, light occupational work intensity, and self-reported diabetes. The median serum RBP4 concentration was lower in ALS cases than in controls (54.0 vs 59.5 mg/L). In the multivariable model, increasing RBP4 concentration was associated with reduced odds for ALS (top vs bottom quartile odds ratio, 0.36; 95% CI, 0.22-0.59; P for trend <.001), which persisted after further adjustment for renal function and for leptin and adiponectin. Among 279 ALS cases during a median follow-up of 14.5 months, 104 died (mean [SD] age, 68.9 [10.3] years; 56 [53.9%] male). In this ALS cohort, an inverse association was found between serum RBP4 concentration as a continuous measure and survival. RBP4 was inversely related to risk for and prognosis of ALS, suggesting that vitamin A metabolism or impaired insulin signaling could be involved. Further research, including a prospective design and other biological markers, is necessary to clarify the role of insulin resistance in the pathogenesis of ALS.
Golwala, Zainab Mohammedi; Shah, Hardik; Gupta, Neeraj; Sreenivas, V; Puliyel, Jacob M
2016-06-01
Thrombocytopenia has been shown to predict mortality. We hypothesize that platelet indices may be more useful prognostic indicators. Our study subjects were children one month to 14 years old admitted to our hospital. To determine whether platelet count, plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) and their ratios can predict mortality in hospitalised children. Children who died during hospital stay were the cases. Controls were age matched children admitted contemporaneously. The first blood sample after admission was used for analysis. Receiver operating characteristic (ROC) curve was used to identify the best threshold for measured variables and the ratios studied. Multiple regression analysis was done to identify independent predictors of mortality. Forty cases and forty controls were studied. Platelet count, PCT and the ratios of MPV/Platelet count, MPV/PCT, PDW/Platelet count, PDW/PCT and MPV × PDW/Platelet count × PCT were significantly different among children who survived compared to those who died. On multiple regression analysis the ratio of MPV/PCT, PDW/Platelet count and MPV/Platelet count were risk factors for mortality with an odds ratio of 4.31(95% CI, 1.69-10.99), 3.86 (95% CI, 1.53-9.75), 3.45 (95% CI, 1.38-8.64) respectively. In 67% of the patients who died MPV/PCT ratio was above 41.8 and PDW/Platelet count was above 3.86. In 65% of patients who died MPV/Platelet count was above 3.45. The MPV/PCT, PDW/Platelet count and MPV/Platelet count, in the first sample after admission in this case control study were predictors of mortality and could predict 65% to 67% of deaths accurately.
Bühnemann, Claudia; Li, Simon; Yu, Haiyue; Branford White, Harriet; Schäfer, Karl L; Llombart-Bosch, Antonio; Machado, Isidro; Picci, Piero; Hogendoorn, Pancras C W; Athanasou, Nicholas A; Noble, J Alison; Hassan, A Bassim
2014-01-01
Driven by genomic somatic variation, tumour tissues are typically heterogeneous, yet unbiased quantitative methods are rarely used to analyse heterogeneity at the protein level. Motivated by this problem, we developed automated image segmentation of images of multiple biomarkers in Ewing sarcoma to generate distributions of biomarkers between and within tumour cells. We further integrate high dimensional data with patient clinical outcomes utilising random survival forest (RSF) machine learning. Using material from cohorts of genetically diagnosed Ewing sarcoma with EWSR1 chromosomal translocations, confocal images of tissue microarrays were segmented with level sets and watershed algorithms. Each cell nucleus and cytoplasm were identified in relation to DAPI and CD99, respectively, and protein biomarkers (e.g. Ki67, pS6, Foxo3a, EGR1, MAPK) localised relative to nuclear and cytoplasmic regions of each cell in order to generate image feature distributions. The image distribution features were analysed with RSF in relation to known overall patient survival from three separate cohorts (185 informative cases). Variation in pre-analytical processing resulted in elimination of a high number of non-informative images that had poor DAPI localisation or biomarker preservation (67 cases, 36%). The distribution of image features for biomarkers in the remaining high quality material (118 cases, 104 features per case) were analysed by RSF with feature selection, and performance assessed using internal cross-validation, rather than a separate validation cohort. A prognostic classifier for Ewing sarcoma with low cross-validation error rates (0.36) was comprised of multiple features, including the Ki67 proliferative marker and a sub-population of cells with low cytoplasmic/nuclear ratio of CD99. Through elimination of bias, the evaluation of high-dimensionality biomarker distribution within cell populations of a tumour using random forest analysis in quality controlled tumour material could be achieved. Such an automated and integrated methodology has potential application in the identification of prognostic classifiers based on tumour cell heterogeneity.
Messali, Andrew; Hay, Joel W.; Villacorta, Reginald
2013-01-01
Background The objective of this work was to determine the cost-effectiveness of temozolomide compared with that of radiotherapy alone in the adjuvant treatment of newly diagnosed glioblastoma. Temozolomide is the only chemotherapeutic agent to have demonstrated a significant survival benefit in a randomized clinical trial. Our analysis builds on earlier work by incorporating caregiver time costs and generic temozolomide availability. It is also the first analysis applicable to the US context. Methods A systematic literature review was conducted to collect relevant data. Transition probabilities were calculated from randomized controlled trial data comparing temozolomide plus radiotherapy with radiotherapy alone. Direct costs were calculated from charges reported by the Mayo Clinic. Utilities were obtained from a previous cost-utility analysis. Using these data, a Markov model with a 1-month cycle length and 5-year time horizon was constructed. Results The addition of brand Temodar and generic temozolomide to the standard radiotherapy regimen was associated with base-case incremental cost-effectiveness ratios of $102 364 and $8875, respectively, per quality-adjusted life-year. The model was most sensitive to the progression-free survival associated with the use of only radiotherapy. Conclusions Both the brand and generic base-case estimates are cost-effective under a willingness-to-pay threshold of $150 000 per quality-adjusted life-year. All 1-way sensitivity analyses produced incremental cost-effectiveness ratios below this threshold. We conclude that both the brand Temodar and generic temozolomide are cost-effective treatments for newly diagnosed glioblastoma within the US context. However, assuming that the generic product produces equivalent quality of life and survival benefits, it would be significantly more cost-effective than the brand option. PMID:23935155
Comparison of ORSAT and SCARAB Reentry Analysis Tools for a Generic Satellite Test Case
NASA Technical Reports Server (NTRS)
Kelley, Robert L.; Hill, Nicole M.; Rochelle, W. C.; Johnson, Nicholas L.; Lips, T.
2010-01-01
Reentry analysis is essential to understanding the consequences of the full life cycle of a spacecraft. Since reentry is a key factor in spacecraft development, NASA and ESA have separately developed tools to assess the survivability of objects during reentry. Criteria such as debris casualty area and impact energy are particularly important to understanding the risks posed to people on Earth. Therefore, NASA and ESA have undertaken a series of comparison studies of their respective reentry codes for verification and improvements in accuracy. The NASA Object Reentry Survival Analysis Tool (ORSAT) and the ESA Spacecraft Atmospheric Reentry and Aerothermal Breakup (SCARAB) reentry analysis tools serve as standard codes for reentry survivability assessment of satellites. These programs predict whether an object will demise during reentry and calculate the debris casualty area of objects determined to survive, establishing the reentry risk posed to the Earth's population by surviving debris. A series of test cases have been studied for comparison and the most recent uses "Testsat," a conceptual satellite composed of generic parts, defined to use numerous simple shapes and various materials for a better comparison of the predictions of these two codes. This study is an improvement on the others in this series because of increased consistency in modeling techniques and variables. The overall comparison demonstrated that the two codes arrive at similar results. Either most objects modeled resulted in close agreement between the two codes, or if the difference was significant, the variance could be explained as a case of semantics in the model definitions. This paper presents the main results of ORSAT and SCARAB for the Testsat case and discusses the sources of any discovered differences. Discussion of the results of previous comparisons is made for a summary of differences between the codes and lessons learned from this series of tests.
HIV-associated lung cancer: survival in an unselected cohort.
Hoffmann, Christian; Kohrs, Fabienne; Sabranski, Michael; Wolf, Eva; Jaeger, Hans; Wyen, Christoph; Siehl, Jan; Baumgarten, Axel; Hensel, Manfred; Jessen, Arne; Schaaf, Bernhard; Vogel, Martin; Bogner, Johannes; Horst, Heinz-August; Stephan, Christoph
2013-10-01
Lung cancer is one of the most common non-AIDS-defining malignancies in HIV-infected patients. However, data on clinical outcome and prognostic factors are scarce. This was a national German multicentre, retrospective cohort analysis of all cases of lung cancer seen in HIV-infected individuals from 2000 through 2010. Survival was analyzed with respect to the use of antiretroviral therapy (ART), specific lung cancer therapies, and other potential prognostic factors. A total of 72 patients (mean age 55.5 y, CD4 T-cells 383/μl) were evaluated in this analysis. At time of lung cancer diagnosis, 86% were on ART. Of these, 79% had undetectable HIV-1 RNA (< 50 copies/ml) for a mean duration of 4.0 y. All but 1 patient were current or former heavy smokers (mean 42 package y). The median estimated overall survival was 1.08 y, with a 2-y overall survival of 24%. The prognosis did not improve during the observation time. A limited lung cancer stage of I-IIIA was associated with better overall survival when compared with the advanced stages IIIb/IV (p = 0.0003). Other factors predictive of improved overall survival were better performance status, CD4 T-cells > 200/μl, and a non-intravenous drug use transmission risk for HIV. Currently, most cases of lung cancer occur in the setting of limited immune deficiency and a long-lasting viral suppression. As in HIV-negative cases, the clinical stage of lung cancer is highly predictive of survival, and long-term overall survival can only be achieved at the limited stages. The still high mortality underscores the importance of smoking cessation strategies in HIV-infected patients.
Proton Pump Inhibitor use as a risk factor for Enterobacteriaceal infection: a case-control study.
Cunningham, Richard; Jones, Lewis; Enki, Doyo Gragn; Tischhauser, Robert
2018-06-01
Gastric acid suppressants increase the risk of gastroenteritis by allowing ingested pathogens to survive passage through the stomach. It is not known whether the same mechanism affects transmission of Enterobacteriacae. We carried out a case-control study to answer this question. To determine whether use of Proton Pump Inhibitors (PPIs) increases the risk of infection with Enterobacteriacae in hospital patients. Retrospective case-control study in a teaching hospital in South West England. Cases were 126 patients infected with extended-spectrum beta-lactamase producing Enterobacteriacae (ESBL) between April 2014 and March 2015. Use of PPIs, H2 receptor antagonists or antacids at the time of admission or in the preceding six months was compared with 126 demographically matched controls infected with non-ESBL producing Enterobacteriacae and 126 uninfected controls, matched by primary diagnosis. 66 of 126 ESBL cases, 62 of 126 non-ESBL controls and 34 of 126 uninfected controls were prescribed PPIs on or within 6 months of admission. Multivariable logistic regression analysis gave an Odds Ratio (95% confidence interval) of 3.37 (1.84 - 6.18) for PPI exposure versus uninfected controls and 1.15 (0.68 - 1.95) for ESBL infection versus non-ESBL infection. H2RA and antacids were not significantly associated with infection. PPI exposure within the previous 6 months is significantly associated with infection with both ESBL and non-ESBL producing bacteria. Reducing inappropriate use of PPIs may be a novel way of reducing transmission, which might reduce antibiotic use and help control antimicrobial resistance. Copyright © 2018. Published by Elsevier Ltd.
Sinonasal fibrosarcoma: analysis of the Surveillance, Epidemiology, and End Results database.
Patel, Tapan D; Carniol, Eric T; Vázquez, Alejandro; Baredes, Soly; Liu, James K; Eloy, Jean Anderson
2016-02-01
Primary fibrosarcoma of the sinonasal region is an infrequently occurring malignant neoplasm. Fibrosarcomas are most commonly found in the extremities, with only 1% of fibrosarcomas reported in the head and neck region. This study analyzes the demographic, clinicopathologic, and survival characteristics of sinonasal fibrosarcoma (SNFS). The Surveillance, Epidemiology, and End Results (SEER) database (1973 to 2012) was queried for SNFS cases. Data were analyzed with respect to various demographic and clinicopathologic factors. Survival was analyzed using the Kaplan-Meier model. Fifty-one cases of fibrosarcoma were identified in the sinonasal region. The mean age at diagnosis was 54.5 years and the mean survival was 119.7 months. There was no gender predilection with a male-to-female ratio of 1.04:1. The maxillary sinus was the most common site of involvement (54.9%), followed by the nasal cavity (23.5%). Five-year survival analysis revealed an overall survival rate of 71.7%, disease-specific survival rate of 77.8%, and relative survival (RS) rate of 78.8%. Disease-specific survival was better among those treated with surgery (with [76.2%] or without [87.5%] adjuvant radiotherapy) than those treated with primary radiotherapy alone (33.3%) (p = 0.0069). SNFS is a rare entity. This study represents the largest series of SNFS to date. The mainstay of treatment for this tumor is surgical resection with or without radiotherapy. © 2015 ARS-AAOA, LLC.
Zheng, Zhuojun; Zhu, Yuandong; Li, Xiaodong; Hu, Wenwei; Jiang, Jingting
2017-01-01
Objective This study investigated the impact of marital status on cancer-caused specific mortality among acute myeloid leukemia (AML) patients in the United States. Methods We used the Surveillance, Epidemiology and End Results program to identify 50,825 patients who had their clinical and follow-up information available and were diagnosed for AML between the years 1988 and 2015. The univariate and multivariable Cox regression models were used to analyze the patient data, and to minimize the group differences due to covariates between groups, a 1:1 propensity score matching was used in subsequent subgroup analysis. Results Our study demonstrated that married patients were less likely to die due to AML after adjusting for demographic and clinicopathological variables, than patients with variable unmarried status. Further analysis indicated that widowed, divorced and never married status correlated with poor cancer-cause specific survival than being married in almost all subgroups after being adjusted for the aforementioned variables (P<0.05). However, the difference between married and separated was not apparent. Moreover, similar survival analysis results were also observed in the 1:1 matched subgroups of marital status, but they displayed varied prognostic factors between them. The association of survival benefit with marriage in AML was consistent with the published survival benefit of conventional therapeutic approaches. Conclusion Overall, our study concluded that unmarried AML patients were at greater risk of cancer-specific mortality than married, and thus indicated that physicians should focus on health care strategies that target social support, in order to reduce the cancer-specific mortality in unmarried patients. PMID:28977979
Diwakar, Lavanya; Morris, Rachel K.; Barton, Pelham; Middleton, Lee J.; Kilby, Mark D.; Roberts, Tracy E.
2013-01-01
Objective To determine the cost-effectiveness of in-utero percutaneous Vesico Amniotic Shunt (VAS) in the management of fetal lower urinary tract obstruction (LUTO) Design Model based economic analysis using data from the randomised controlled arm of the PLUTO (percutaneous vesico-amniotic shunting for lower urinary tract obstruction) trial. Setting Fetal medicine departments in United Kingdom, Ireland and Netherlands. Population or Sample Pregnant women with a male, singleton fetus with LUTO. Methods Costs and outcomes were prospectively collected in the trial; three separate base case analyses were performed using the intention to treat (ITT), per protocol and uniform prior methods. Deterministic and probabilistic sensitivity analyses were performed to explore data uncertainty. Main Outcome Measures Survival at 28 days, 1 year and disease free survival at 1 year. Results VAS was more expensive but appeared to result in higher rates of survival compared with conservative management in patients with LUTO. Using ITT analysis the incremental cost effectiveness ratios based on outcomes of survival at 28 days, 1 year, or 1 morbidity-free year on the VAS arm were £15,506, £15,545, and £43,932, respectively. Conclusions VAS is a more expensive option compared to the conservative approach in the management of individuals with LUTO. Data from the RCT suggest that VAS improves neonatal survival but does not result in significant improvements in morbidity. Our analysis concludes that VAS is not likely to be cost effective in the management of these patients given the NICE (National Institute of Health and Clinical Excellence) cost threshold of £20,000 per QALY. PMID:24376546
Cui, Peiyuan; Pang, Qing; Wang, Yong; Qian, Zhen; Hu, Xiaosi; Wang, Wei; Li, Zongkuang; Zhou, Lei; Man, Zhongran; Yang, Song; Jin, Hao; Liu, Huichun
2018-06-01
We mainly aimed to preliminarily explore the prognostic values of nutrition-based prognostic scores in patients with advanced hilar cholangiocarcinoma (HCCA).We retrospectively analyzed 73 cases of HCCA, who underwent percutaneous transhepatic biliary stenting (PTBS) combined with I seed intracavitary irradiation from November 2012 to April 2017 in our department. The postoperative changes of total bilirubin (TBIL), direct bilirubin (DBIL), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and albumin (ALB) were observed. The preoperative clinical data were collected to calculate the nutrition-based scores, including controlling nutritional status (CONUT), C-reactive protein/albumin ratio (CAR), and prognostic nutritional index (PNI). Kaplan-Meier curve and Cox regression model were used for overall survival (OS) analyses.The serum levels of TBIL, DBIL, ALT, AST, and ALP significantly reduced, and ALB significantly increased at 1 month and 3 months postoperatively. The median survival time of the cohort was 12 months and the 1-year survival rate was 53.1%. Univariate analysis revealed that the statistically significant factors related to OS were CA19-9, TBIL, ALB, CONUT, and PNI. Multivariate analysis further identified CA19-9, CONUT, and PNI as independent prognostic factors.Nutrition-based prognostic scores, CONUT and PNI in particular, can be used as predictors of survival in unresectable HCCA.
Genome-wide Analyses Identify KIF5A as a Novel ALS Gene.
Nicolas, Aude; Kenna, Kevin P; Renton, Alan E; Ticozzi, Nicola; Faghri, Faraz; Chia, Ruth; Dominov, Janice A; Kenna, Brendan J; Nalls, Mike A; Keagle, Pamela; Rivera, Alberto M; van Rheenen, Wouter; Murphy, Natalie A; van Vugt, Joke J F A; Geiger, Joshua T; Van der Spek, Rick A; Pliner, Hannah A; Shankaracharya; Smith, Bradley N; Marangi, Giuseppe; Topp, Simon D; Abramzon, Yevgeniya; Gkazi, Athina Soragia; Eicher, John D; Kenna, Aoife; Mora, Gabriele; Calvo, Andrea; Mazzini, Letizia; Riva, Nilo; Mandrioli, Jessica; Caponnetto, Claudia; Battistini, Stefania; Volanti, Paolo; La Bella, Vincenzo; Conforti, Francesca L; Borghero, Giuseppe; Messina, Sonia; Simone, Isabella L; Trojsi, Francesca; Salvi, Fabrizio; Logullo, Francesco O; D'Alfonso, Sandra; Corrado, Lucia; Capasso, Margherita; Ferrucci, Luigi; Moreno, Cristiane de Araujo Martins; Kamalakaran, Sitharthan; Goldstein, David B; Gitler, Aaron D; Harris, Tim; Myers, Richard M; Phatnani, Hemali; Musunuri, Rajeeva Lochan; Evani, Uday Shankar; Abhyankar, Avinash; Zody, Michael C; Kaye, Julia; Finkbeiner, Steven; Wyman, Stacia K; LeNail, Alex; Lima, Leandro; Fraenkel, Ernest; Svendsen, Clive N; Thompson, Leslie M; Van Eyk, Jennifer E; Berry, James D; Miller, Timothy M; Kolb, Stephen J; Cudkowicz, Merit; Baxi, Emily; Benatar, Michael; Taylor, J Paul; Rampersaud, Evadnie; Wu, Gang; Wuu, Joanne; Lauria, Giuseppe; Verde, Federico; Fogh, Isabella; Tiloca, Cinzia; Comi, Giacomo P; Sorarù, Gianni; Cereda, Cristina; Corcia, Philippe; Laaksovirta, Hannu; Myllykangas, Liisa; Jansson, Lilja; Valori, Miko; Ealing, John; Hamdalla, Hisham; Rollinson, Sara; Pickering-Brown, Stuart; Orrell, Richard W; Sidle, Katie C; Malaspina, Andrea; Hardy, John; Singleton, Andrew B; Johnson, Janel O; Arepalli, Sampath; Sapp, Peter C; McKenna-Yasek, Diane; Polak, Meraida; Asress, Seneshaw; Al-Sarraj, Safa; King, Andrew; Troakes, Claire; Vance, Caroline; de Belleroche, Jacqueline; Baas, Frank; Ten Asbroek, Anneloor L M A; Muñoz-Blanco, José Luis; Hernandez, Dena G; Ding, Jinhui; Gibbs, J Raphael; Scholz, Sonja W; Floeter, Mary Kay; Campbell, Roy H; Landi, Francesco; Bowser, Robert; Pulst, Stefan M; Ravits, John M; MacGowan, Daniel J L; Kirby, Janine; Pioro, Erik P; Pamphlett, Roger; Broach, James; Gerhard, Glenn; Dunckley, Travis L; Brady, Christopher B; Kowall, Neil W; Troncoso, Juan C; Le Ber, Isabelle; Mouzat, Kevin; Lumbroso, Serge; Heiman-Patterson, Terry D; Kamel, Freya; Van Den Bosch, Ludo; Baloh, Robert H; Strom, Tim M; Meitinger, Thomas; Shatunov, Aleksey; Van Eijk, Kristel R; de Carvalho, Mamede; Kooyman, Maarten; Middelkoop, Bas; Moisse, Matthieu; McLaughlin, Russell L; Van Es, Michael A; Weber, Markus; Boylan, Kevin B; Van Blitterswijk, Marka; Rademakers, Rosa; Morrison, Karen E; Basak, A Nazli; Mora, Jesús S; Drory, Vivian E; Shaw, Pamela J; Turner, Martin R; Talbot, Kevin; Hardiman, Orla; Williams, Kelly L; Fifita, Jennifer A; Nicholson, Garth A; Blair, Ian P; Rouleau, Guy A; Esteban-Pérez, Jesús; García-Redondo, Alberto; Al-Chalabi, Ammar; Rogaeva, Ekaterina; Zinman, Lorne; Ostrow, Lyle W; Maragakis, Nicholas J; Rothstein, Jeffrey D; Simmons, Zachary; Cooper-Knock, Johnathan; Brice, Alexis; Goutman, Stephen A; Feldman, Eva L; Gibson, Summer B; Taroni, Franco; Ratti, Antonia; Gellera, Cinzia; Van Damme, Philip; Robberecht, Wim; Fratta, Pietro; Sabatelli, Mario; Lunetta, Christian; Ludolph, Albert C; Andersen, Peter M; Weishaupt, Jochen H; Camu, William; Trojanowski, John Q; Van Deerlin, Vivianna M; Brown, Robert H; van den Berg, Leonard H; Veldink, Jan H; Harms, Matthew B; Glass, Jonathan D; Stone, David J; Tienari, Pentti; Silani, Vincenzo; Chiò, Adriano; Shaw, Christopher E; Traynor, Bryan J; Landers, John E
2018-03-21
To identify novel genes associated with ALS, we undertook two lines of investigation. We carried out a genome-wide association study comparing 20,806 ALS cases and 59,804 controls. Independently, we performed a rare variant burden analysis comparing 1,138 index familial ALS cases and 19,494 controls. Through both approaches, we identified kinesin family member 5A (KIF5A) as a novel gene associated with ALS. Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia (SPG10) and Charcot-Marie-Tooth type 2 (CMT2). In contrast, ALS-associated mutations are primarily located at the C-terminal cargo-binding tail domain and patients harboring loss-of-function mutations displayed an extended survival relative to typical ALS cases. Taken together, these results broaden the phenotype spectrum resulting from mutations in KIF5A and strengthen the role of cytoskeletal defects in the pathogenesis of ALS. Copyright © 2018 Elsevier Inc. All rights reserved.
Fernández-Miranda, María de la Calle; Cruceyra Bertriu, Mireia; Rodríuez-González, Roberto; Magdaleno-Dans, Fernando; Omeñaca Teres, Félix; González González, Antonio
2012-04-01
happens in the womb when the death of one of the twins, it is necessary to consider the factors that influence the perinatal outcome of surviving fetus. To review the outcome of twin pregnancies complicated by single fetal intrauterine death and how it can increase morbidity to its co-twin and its mother. A retrospective analysis of the fifty one twin pregnancies complicated by single fetal intrauterine death in the second or third trimester in our centre from December 1999 to December 2010. Of the total amount of 1996 twin pregnancies attended in our centre, 51 were complicated by single fetal intrauterine death (2.5%). In 68.7% of the cases we found several maternal complications, such as 12.2% of preeclampsia and 12% of coagulopathies. As for the dead foetus, there was a 47% of malformations, a 19.6% of intrauterine fetal growth restriction and there was a 9.8% of cases complicated by twin-twin transfusion syndrome. In the group of the surviving co-twin, 9.8% developed intrauterine growth restriction, 9.8% oligohydramnios and 9.8% Doppler alterations. There was a high risk of prematurity with 43.1% of the births under 34 weeks and 13.7% under 30 weeks of pregnancy. The percentage of caesarean was 64.7%. There was 3 cases of co-twin died intra-uterus, and one more died postpartum. A 10% of the newborns had some kind of neurological disability. It seems that surviving co-twin prognosis is mainly compromised by prematurity and its consequences. There should be more prospective research to inform decision-making and evaluate and control the potential maternal and fetal risks.
Martínez-Camblor, Pablo; Larrañaga, Nerea; Sarasqueta, Cristina; Mitxelena, María José; Basterretxea, Mikel
2009-01-01
To analyze time of disease-free survival and relative survival in women diagnosed with breast cancer in the province of Gipuzkoa within the context of competing risks by assessing differences between the direct use of the Kaplan-Meier estimator and the multiple decrement method on the one hand, and relative survival on the other. All registered breast cancer cases in Gipuzkoa in 1995 and 1996 with stages other than stage IV were included. An 8-year follow-up for recurrence and a 10-year follow-up for survival were performed. Time of disease-free survival was studied by the multiple decrement model. Observed survival and survival corrected by the expected mortality in the population (relative survival) were also studied. Estimation of the probability of recurrence at 8 years with the multiple decrement method was 8.8% lower than that obtained with the Kaplan-Meier method. The difference between the observed and relative survival rates at 10 years was 10.8%. Both results show how, in this case, the Kaplan-Meier estimator overestimates both the probability of recurrence and that of mortality from the disease. Two issues are often overlooked when performing survival analyses: firstly, because of the lack of independence between survival time and censoring time, the results obtained by the Kaplan-Meier estimator are uninterpretable; secondly, it is an incontrovertible fact that one way or another, everyone causes failures. In this approach, survival analyses must take into account the probability of failure in the general population of reference. The results obtained in this study show that superficial use of the Kaplan Meier estimator overestimates both the probability of recurrence and that of mortality caused by the disease.
Asayama, Yoshiki; Nishie, Akihiro; Ishigami, Kousei; Ushijima, Yasuhiro; Takayama, Yukihisa; Okamoto, Daisuke; Fujita, Nobuhiro; Ohtsuka, Takao; Yoshizumi, Tomoharu; Aishima, Shinichi; Oda, Yoshinao; Honda, Hiroshi
2017-06-01
To determine whether washout characteristics of dynamic contrast-enhanced computed tomography (CT) could predict survival in patients with extrahepatic cholangiocarcinoma (EHC). This study collected 46 resected cases. All cases were examined by dynamic contrast study on multidetector-row CT. Region-of-interest measurements were obtained at the non-enhanced, portal venous phase and delayed phase in the tumour and were used to calculate the washout ratio as follows: [(attenuation value at portal venous phase CT - attenuation value at delayed enhanced CT)/(attenuation value at portal venous phase CT - attenuation value at unenhanced CT)] × 100. On the basis of the median washout ratio, we classified the cases into two groups, a high-washout group and low-washout group. Associations between overall survival and various factors including washout rates were analysed. The median washout ratio was 29.4 %. Univariate analysis revealed that a lower washout ratio, venous invasion, lymphatic permeation and lymph node metastasis were associated with shorter survival. Multivariate analysis identified the lower washout ratio as an independent prognostic factor (hazard ratio, 3.768; p value, 0.027). The washout ratio obtained from the contrast-enhanced CT may be a useful imaging biomarker for the prediction of survival of patients with EHC. • Dynamic contrast study can evaluate the aggressiveness of extrahepatic cholangiocarcinoma. • A lower washout ratio was an independent prognostic factor for overall survival. • CT can predict survival and inform decisions on surgical options or chemotherapy.
Associated injuries, management, and outcomes of blunt abdominal aortic injury.
de Mestral, Charles; Dueck, Andrew D; Gomez, David; Haas, Barbara; Nathens, Avery B
2012-09-01
Blunt abdominal aortic injury (BAAI) is very rare, and current literature is limited to case series of single-center experience. Through an analysis of the National Trauma Data Bank, the largest aggregation of United States trauma registry data, our aim was to characterize the associated injury pattern, contemporary management, and in-hospital outcomes of patients with BAAI. We used a nested case-control design. The overall cohort consisted of adult patients (age ≥ 16 years) severely injured (Injury Severity Score ≥ 16) after blunt trauma who were treated at a level 1 or 2 trauma center in years 2007 to 2009. Cases were patients with BAAI and were frequency-matched by age group and mechanism to randomly selected controls at a one-to-five ratio. Multivariable matched analysis (conditional logistic regression) was used to derive adjusted measures of association between BAAI and adjacent arterial, intra-abdominal, and bony injuries. We identified 436 patients with BAAI from 180 centers. The mean Injury Severity Score was 35 ± 14, and most patients were injured in motor vehicle crashes (84%). Multivariable analysis showed injury to the thoracic aorta, renal and iliac artery, small bowel, colon, liver, pancreas, and kidney, as well as lumbar spine fractures were independently associated with BAAI. A total of 394 patients (90%) were managed nonoperatively, and 42 (10%) underwent repair. Of these 42 patients, 29 (69%) underwent endovascular repair, with 11 patients undergoing open aortic repair and two extra-anatomic bypasses. Median time from admission to repair was 1 day (interquartile range, 1-2 days). Overall mortality was 29%. A total of 271 (69%) patients managed nonoperatively survived to hospital discharge. The index of suspicion for BAAI should be raised in severely injured patients by the presence of injuries to the lumbar spine, bowel, retroperitoneal organs, and adjacent major arteries. Although endovascular repair is the most common intervention, most patients are managed nonoperatively and survive to hospital discharge. Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.
Sjölund, Katarina; Andersson, Anna; Nilsson, Erik; Nilsson, Ola; Ahlman, Håkan
2010-01-01
Background Gastrointestinal stromal tumors (GISTs) express the receptor tyrosine kinase KIT. Most GISTs have mutations in the KIT or PDGFRA gene, causing activation of tyrosine kinase. Imatinib, a tyrosine kinase inhibitor (TKI), is the first-line palliative treatment for advanced GISTs. Sunitinib was introduced for patients with mutations not responsive to imatinib. The aim was to compare the survival of patients with high-risk resected GISTs treated with TKI prior to surgery with historical controls and to determine if organ-preserving surgery was facilitated. Methods Ten high-risk GIST-patients had downsizing/adjuvant TKI treatment: nine with imatinib and one with sunitinib. The patients were matched with historical controls (n = 89) treated with surgery alone, from our population-based series (n = 259). Mutational analysis of KIT and PDGFRA was performed in all cases. The progression-free survival was calculated. Results The primary tumors decreased in mean diameter from 20.4 cm to 10.5 cm on downsizing imatinib. Four patients with R0 resection and a period of adjuvant imatinib had no recurrences versus 67% in the historical control group. Four patients with residual liver metastases have stable disease on continuous imatinib treatment after surgery. One patient has undergone reoperation with liver resection. The downsizing treatment led to organ-preserving surgery in nine patients and improved preoperative nutritional status in one patient. Conclusions Downsizing TKI is recommended for patients with bulky tumors with invasion of adjacent organs. Sunitinib can be used for patients in case of imatinib resistance (e.g., wild-type GISTs), underlining the importance of mutational analysis for optimal surgical planning. PMID:20512492
Plasma Mesothelin as a Novel Diagnostic and Prognostic Biomarker in Colorectal Cancer
Li, Shuwei; Xie, Lisheng; He, Lei; Fan, Zhimin; Xu, Junhua; Xu, Kaili; Zhu, Lingjun; Ma, Gaoxiang; Du, Mulong; Chu, Haiyan; Zhang, Zhengdong; Ni, Min; Wang, Meilin
2017-01-01
Objective Mesothelin is a cell surface protein and overexpressed in many cancers. However, the potential value of mesothelin as plasma biomarker in colorectal cancer has not been explored. The purpose of this study was to identify whether plasma mesothelin is a suitable diagnostic and prognostic biomarker for colorectal cancer. Methods We performed a two-stage case-control study to evaluate plasma mesothelin levels in colorectal cancer using enzyme-linked immunosorbent assay (ELISA). Preoperative and postoperative plasma were collected to examine the level changes influenced by surgery. Receiver operating characteristic (ROC) curves were applied to identify the diagnostic value of plasma mesothelin. We also conducted univariate Kaplan-Meier survival analysis and Cox regression analysis of patients with survival information. Results We found that the plasma mesothelin levels in colorectal cancer patients were significantly higher than that in the controls (P < 0.001) with an AUC value of 0.690 (95% CI = 0.625 to 0.752). Individuals with lower mesothelin level had a longer survival time (adjusted HR = 4.43, 95% CI = 1.93-10.15, P < 0.001). Furthermore, Patients had slightly decreased mesothelin levels in postoperative plasma than preoperative plasma, although the alteration was not statistically significant (P = 0.052). Conclusion Our findings highlight the correlative relationship between plasma mesothelin levels and the presence and progression of colorectal cancer. Plasma mesothelin may be a potential diagnostic and, or prognostic biomarker for colorectal cancer. PMID:28638449
Ventura-Ríos, Lucio; Bañuelos-Ramírez, David; Hernández-Quiroz, María del Carmen; Robles-San Román, Manuel; Irazoque-Palazuelos, Fedra; Goycochea-Robles, María Victoria
2012-01-01
This work reports patient treatment survival and adverse events related to Biologic Therapy (BT), identified by a multicenter ambispective registry of 2047 rheumatic patients undergoing BT and including a control group of Rheumatoid Arthritis (RA) patients not using BT. The most common diagnoses were: RA 79.09%, Ankylosing Spondilytis 7.96%, Psoriatic Arthritis 4.40%, Systemic Lupus Erythematosus 3.37%, Juvenile Idiopathic Arthritis 1.17%. A secondary analysis included 1514 cases from the total sample and was performed calculating an incidence rate of any adverse events of 178 × 1000/BT patients per year vs 1009 × 1000/control group patients per year with a 1.6 RR (95% CI 1.4-1.9). For serious adverse events the RR was: 15.4 (95% CI 3.7-63.0, P<.0001). Global BT survival was 80% at 12 months, 61% at 24 months, 52% at 36 months and 45% at 48 months and SMR: 0.23 (95% CI 0.0-49.0) for BT vs 0.00 (95% CI 0.0-0.2) for the control group. In conclusion, BT was associated to a higher infection risk and adverse events, compared to other patients. Mortality using BT was not higher than expected for general population with same gender and age. Copyright © 2011 Elsevier España, S.L. All rights reserved.
ATXN2 trinucleotide repeat length correlates with risk of ALS.
Sproviero, William; Shatunov, Aleksey; Stahl, Daniel; Shoai, Maryam; van Rheenen, Wouter; Jones, Ashley R; Al-Sarraj, Safa; Andersen, Peter M; Bonini, Nancy M; Conforti, Francesca L; Van Damme, Philip; Daoud, Hussein; Del Mar Amador, Maria; Fogh, Isabella; Forzan, Monica; Gaastra, Ben; Gellera, Cinzia; Gitler, Aaron D; Hardy, John; Fratta, Pietro; La Bella, Vincenzo; Le Ber, Isabelle; Van Langenhove, Tim; Lattante, Serena; Lee, Yi-Chung; Malaspina, Andrea; Meininger, Vincent; Millecamps, Stéphanie; Orrell, Richard; Rademakers, Rosa; Robberecht, Wim; Rouleau, Guy; Ross, Owen A; Salachas, Francois; Sidle, Katie; Smith, Bradley N; Soong, Bing-Wen; Sorarù, Gianni; Stevanin, Giovanni; Kabashi, Edor; Troakes, Claire; van Broeckhoven, Christine; Veldink, Jan H; van den Berg, Leonard H; Shaw, Christopher E; Powell, John F; Al-Chalabi, Ammar
2017-03-01
We investigated a CAG trinucleotide repeat expansion in the ATXN2 gene in amyotrophic lateral sclerosis (ALS). Two new case-control studies, a British dataset of 1474 ALS cases and 567 controls, and a Dutch dataset of 1328 ALS cases and 691 controls were analyzed. In addition, to increase power, we systematically searched PubMed for case-control studies published after 1 August 2010 that investigated the association between ATXN2 intermediate repeats and ALS. We conducted a meta-analysis of the new and existing studies for the relative risks of ATXN2 intermediate repeat alleles of between 24 and 34 CAG trinucleotide repeats and ALS. There was an overall increased risk of ALS for those carrying intermediate sized trinucleotide repeat alleles (odds ratio 3.06 [95% confidence interval 2.37-3.94]; p = 6 × 10 -18 ), with an exponential relationship between repeat length and ALS risk for alleles of 29-32 repeats (R 2 = 0.91, p = 0.0002). No relationship was seen for repeat length and age of onset or survival. In contrast to trinucleotide repeat diseases, intermediate ATXN2 trinucleotide repeat expansion in ALS does not predict age of onset but does predict disease risk. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.
A comparative study of mixture cure models with covariate
NASA Astrophysics Data System (ADS)
Leng, Oh Yit; Khalid, Zarina Mohd
2017-05-01
In survival analysis, the survival time is assumed to follow a non-negative distribution, such as the exponential, Weibull, and log-normal distributions. In some cases, the survival time is influenced by some observed factors. The absence of these observed factors may cause an inaccurate estimation in the survival function. Therefore, a survival model which incorporates the influences of observed factors is more appropriate to be used in such cases. These observed factors are included in the survival model as covariates. Besides that, there are cases where a group of individuals who are cured, that is, not experiencing the event of interest. Ignoring the cure fraction may lead to overestimate in estimating the survival function. Thus, a mixture cure model is more suitable to be employed in modelling survival data with the presence of a cure fraction. In this study, three mixture cure survival models are used to analyse survival data with a covariate and a cure fraction. The first model includes covariate in the parameterization of the susceptible individuals survival function, the second model allows the cure fraction to depend on covariate, and the third model incorporates covariate in both cure fraction and survival function of susceptible individuals. This study aims to compare the performance of these models via a simulation approach. Therefore, in this study, survival data with varying sample sizes and cure fractions are simulated and the survival time is assumed to follow the Weibull distribution. The simulated data are then modelled using the three mixture cure survival models. The results show that the three mixture cure models are more appropriate to be used in modelling survival data with the presence of cure fraction and an observed factor.
Yu, Zhen-Gang; Wang, Bing-Zhe; Cheng, Zhao-Zhong
2017-09-01
Accumulated data over the years have suggested that hypoxia inducible factor-1 alpha (HIF-1α) and its downstream vascular endothelial growth factor (VEGF) gene may be linked with chronic obstructive pulmonary disease (COPD). This study aims to investigate the association of HIF-1α and VEGF genetic polymorphisms and their correlated risks with COPD. COPD patients (case group) and healthy individuals (control group) were recruited. DNA was extracted to detect HIF-1α and VEGF genetic polymorphisms. Basal lung volume and forced expiratory capacity in 1st second (FEV1)/forced vital capacity (FVC) and FEV 1 /predicted value (pred)% were calculated. Genotype and allele distributions in HIF-1α and VEGF genes were analyzed. Kaplan-Meier curves and logistic regression model were used for analysis of survival and COPD risk factors. Haplotypes for HIF-1α rs11549465 and rs11549467 were analyzed. FEV 1 /FVC and FEV1/pred% in the case group were lower than the control group. Frequencies of HIF-1α rs11549465 CT + TT genotype and T allele, and rs11549467 GA + AA genotype and A allele were higher in the case group than the control group. Patients with rs11549465 CT + TT had higher COPD risk than those with the CC genotype. Patients with rs11549467 GA + AA showed higher COPD risk and lower FEV 1 /FVC and FEV 1 /pred% than those with the GG genotype. Patients with HIF-1α TA haplotype showed higher COPD risk than those with the CG haplotype. Survival rate of patients with HIF-1α rs11549467 GG genotype was higher than those with the GA + AA genotype. HIF-1α rs11549467 polymorphism may be associated with COPD risk. Copyright © 2017. Published by Elsevier Taiwan.
Larsen, Fin Stolze; Schmidt, Lars Ebbe; Bernsmeier, Christine; Rasmussen, Allan; Isoniemi, Helena; Patel, Vishal C; Triantafyllou, Evangelos; Bernal, William; Auzinger, Georg; Shawcross, Debbie; Eefsen, Martin; Bjerring, Peter Nissen; Clemmesen, Jens Otto; Hockerstedt, Krister; Frederiksen, Hans-Jørgen; Hansen, Bent Adel; Antoniades, Charalambos G; Wendon, Julia
2016-01-01
Acute liver failure (ALF) often results in cardiovascular instability, renal failure, brain oedema and death either due to irreversible shock, cerebral herniation or development of multiple organ failure. High-volume plasma exchange (HVP), defined as exchange of 8-12 or 15% of ideal body weight with fresh frozen plasma in case series improves systemic, cerebral and splanchnic parameters. In this prospective, randomised, controlled, multicentre trial we randomly assigned 182 patients with ALF to receive either standard medical therapy (SMT; 90 patients) or SMT plus HVP for three days (92 patients). The baseline characteristics of the groups were similar. The primary endpoint was liver transplantation-free survival during hospital stay. Secondary-endpoints included survival after liver transplantation with or without HVP with intention-to-treat analysis. A proof-of-principle study evaluating the effect of HVP on the immune cell function was also undertaken. For the entire patient population, overall hospital survival was 58.7% for patients treated with HVP vs. 47.8% for the control group (hazard ratio (HR), with stratification for liver transplantation: 0.56; 95% confidence interval (CI), 0.36-0.86; p=0.0083). HVP prior to transplantation did not improve survival compared with patients who received SMT alone (CI 0.37 to 3.98; p=0.75). The incidence of severe adverse events was similar in the two groups. Systemic inflammatory response syndrome (SIRS) and sequential organ failure assessment (SOFA) scores fell in the treated group compared to control group, over the study period (p<0.001). Treatment with HVP improves outcome in patients with ALF by increasing liver transplant-free survival. This is attributable to attenuation of innate immune activation and amelioration of multi-organ dysfunction. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.
Yu, Zong-Yang; Liu, Zhi-Zhen; Ouyang, Xue-Nong; Du, Jian; Dai, Xi-Hu; Chen, Xi; Zhao, Zhong-Quan; Wang, Wen-Wu; Li, Jie
2012-02-01
To examine the effect of a Chinese medicinal herbal formula (Feitai Capsule, ) on the quality of life (QOL) and progression-free survival (PFS) of patients with unresectable non-small cell lung cancer (NSCLC). Sixty-two patients were randomly divided into the treatment group (31 cases) and the control group (31 cases). For the treatment group, 4 capsules (1.2 g/capsule) of Feitai Capsule were administered 3 times a day after meals for 3 weeks; then no drug was administered for 1 week. This schedule was continued for at least 3 more cycles (12 weeks totally). If there were no obvious toxic reactions, the treatment was extended. The patients were evaluated at least once every 8 weeks until progressive disease (PD). For the control group, the regular follow-up and evaluation were performed at least once every 8 weeks until PD. Clinical symptoms, objective response, physical constitution and energy, QOL, and PFS were evaluated regularly. Analysis of variance (ANOVA), a non-parametric test, and analysis of covariance were used to compare clinical features, amelioration of clinical symptoms, physical constitution and energy, and QOL. Kaplan-Meier analysis was used to compare the two-group PFS. Sixty patients finished the final evaluation, with 30 patients in each group. Baseline characters between groups were not significantly different (P>0.05). The control group had a 36.7% improvement in clinical symptoms, while the treatment group had a 73.3% improvement. This difference was statistically significant (Z= -2.632, P=0.008). The control group had a 26.7% improvement in the Karnofsky performance status (KPS), while the treatment group had a 53.4% improvement. This was also significantly different (Z=-2.182, P=0.029). A comparative analysis indicated a positive correlation (r=0.917, P<0.001). Compared with the control group, QOL in the treatment group was significantly improved, except in the social/family condition and doctor-patient relationship indicators. The PFS of the treatment group and control group were 6.23 months and 4.67 months, respectively (P=0.048). Feitai Capsule, a Chinese medicinal herbal treatment could improve the QOL and extend the PFS of the unresectable NSCLC patients.
Expression and clinical significance of survivin in ovarian cancer: A meta-analysis.
He, Xiaoyan; Yang, Kehu; Wang, Hailin; Chen, Xiaohong; Wu, Huifang; Yao, Liang; Ma, Shouye
2018-01-01
To assess the clinicopathological significance of survivin in ovarian carcinoma through this meta-analysis. PubMed, EMBASE, Web of Science, and The Cochrane Library databases were searched for relevant studies published through September, 2017. Included studies reported the case-control study of surviving expression with ovarian cancer and its clinicopathological characteristics. The quality assessment was performed according to the Newcastle-Ottawa Scale (NOS) for quality assessment of case-control studies. Statistical analysis was performed with the software Stata 12.0. Twelve eligible studies with a total of 1097 patients were included in this meta-analysis. Survivin overexpression was closely related to FIGO stage (I-II vs. III-IV) of ovarian carcinoma (odds ratio [OR] = 0.26,95% confidence interval [CI]:0.16,0.42),P<0.00001),tumor grade (G1-G2 vs. G3) (OR = 0.29,95%CI(0.17, 0.51),P <0.0001), but was not significantly associated with lymphatic metastasis (OR = 1.53, 95%CI(0.77, 3.03, P = 0.23),ascites (OR = 0.89,95%CI(0.39,2.05),P = 0.79). Our meta-analysis shows that survivin is strongly associated with FIGO stage and tumor grade of ovarian carcinoma. Maybe survivin is a novel clinicopathological marker of ovarian carcinoma.
Ali, Alaa M.G.; Schmidt, Marjanka K.; Bolla, Manjeet K.; Wang, Qin; Gago-Dominguez, M.; Castelao, J. Esteban; Carracedo, Angel; Garzón, Victor Muñoz; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Chang-Claude, Jenny; Vrieling, Alina; Rudolph, Anja; Seibold, Petra; Nevanlinna, Heli; Muranen, Taru A.; Aaltonen, Kirsimari; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Horio, Akiyo; John, Esther M.; Sherman, Mark; Lissowska, Jolanta; Figueroa, Jonine; Garcia-Closas, Montserrat; Anton-Culver, Hoda; Shah, Mitul; Hopper, John L.; Trichopoulou, Antonia; Bueno-de-Mesquita, Bas; Krogh, Vittorio; Weiderpass, Elisabete; Andersson, Anne; Clavel-Chapelon, Françoise; Dossus, Laure; Fagherazzi, Guy; Peeters, Petra H.; Olsen, Anja; Wishart, Gordon C.; Easton, Douglas F.; Borgquist, Signe; Overvad, Kim; Barricarte, Aurelio; González, Carlos A.; Sánchez, María-José; Amiano, Pilar; Riboli, Elio; Key, Tim; Pharoah, Paul D.
2015-01-01
Background Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts. Methods A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for “moderate drinkers” versus nondrinkers. An analysis of individual participant data using Cox regression was carried out using data from 11 case cohorts. Results We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate post-diagnosis alcohol consumption was not associated with overall survival [HR, 0.95; 95% confidence interval (CI), 0.85–1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80; 95% CI, 0.73–0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ER-positive disease, there was little evidence that pre- or postdiagnosis alcohol consumption is associated with breast cancer–specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer–specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease. Conclusion There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer–specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer–specific mortality in ER-negative disease. Impact Considering the totality of the evidence, moderate postdiagnosis alcohol consumption is unlikely to have a major adverse effect on the survival of women with breast cancer. PMID:24636975
van Ginderdeuren, R; van Limbergen, E; Spileers, W
2005-10-01
To analyse local tumour control, radiation related complications, visual acuity, enucleation rate, and survival after brachytherapy of small to medium sized choroidal melanoma (CM) with a high dose rate (HDR) strontium-90 (Sr-90) applicator. From 1983 until 2000, 98 eyes with CM were treated with Sr-90 brachytherapy. The main outcome measures were actuarial rates of the patients' survival, ocular conservation rate, tumour regression, complication rates, and preservation of visual acuity. End point rates were estimated using Kaplan-Meier analysis. The median follow up time was 6.7 years (0.5-18.8 years). Actuarial melanoma free patient survival rate was 85% (SE 4.8%) after 18 years. Actuarial rate of ocular conservation and complete tumour regression was 90% (SE 3.8%) after 15 years. In 93% local tumour control was achieved, 88% showed a stable scar. Recurrence of the tumour on the border caused enucleation of six eyes (7%). In three cases (4%) retinal detachment was the end point. No cases of optic atrophy or of sight impairing retinopathy outside the treated area were found. Actuarial rate of preservation of visual acuity of 1/10 was 65% at 5 years and 45% at 15 years of follow up (SE 5.9% and 8.8%). Sr-90 brachytherapy is as effective as iodine or ruthenium brachytherapy for small to medium sized CM but causes fewer complications. The preservation of vision is better than with all other described radioisotopes. HDR Sr-90 brachytherapy can therefore safely be recommended for small to medium sized CM.
van Ginderdeuren, R; van Limbergen, E; Spileers, W
2005-01-01
Aim: To analyse local tumour control, radiation related complications, visual acuity, enucleation rate, and survival after brachytherapy of small to medium sized choroidal melanoma (CM) with a high dose rate (HDR) strontium-90 (Sr-90) applicator. Methods: From 1983 until 2000, 98 eyes with CM were treated with Sr-90 brachytherapy. The main outcome measures were actuarial rates of the patients’ survival, ocular conservation rate, tumour regression, complication rates, and preservation of visual acuity. End point rates were estimated using Kaplan-Meier analysis. Results: The median follow up time was 6.7 years (0.5–18.8 years). Actuarial melanoma free patient survival rate was 85% (SE 4.8%) after 18 years. Actuarial rate of ocular conservation and complete tumour regression was 90% (SE 3.8%) after 15 years. In 93% local tumour control was achieved, 88% showed a stable scar. Recurrence of the tumour on the border caused enucleation of six eyes (7%). In three cases (4%) retinal detachment was the end point. No cases of optic atrophy or of sight impairing retinopathy outside the treated area were found. Actuarial rate of preservation of visual acuity of 1/10 was 65% at 5 years and 45% at 15 years of follow up (SE 5.9% and 8.8%). Conclusions: Sr-90 brachytherapy is as effective as iodine or ruthenium brachytherapy for small to medium sized CM but causes fewer complications. The preservation of vision is better than with all other described radioisotopes. HDR Sr-90 brachytherapy can therefore safely be recommended for small to medium sized CM. PMID:16170122
Incidence and Survival in Breast Cancer Patients and Stressful Life Events.
Fallah, Raheleh; Akbari, Mohammad Esmaeil; Azargashb, Eznollah; Khayamzadeh, E
2016-01-01
Due to increasing incidence of breast cancer, recognition of risk factors has become increasingly important. Over the past few decades, among risk factors of this disease, stressful life events have attracted particular attention, but their relationship with breast cancer incidence and survival remains a mystery. This study aimed to examine the relationship between severe stressful life events and incidence and survival of women with breast cancer. In this case-control study, using a structured telephone interview with 355 women with breast cancer and also with 516 women with benign breast diseases who were matched in demographic characteristics, necessary information about the experience of major stressful events in the years before the diagnosis were collected. Data were analyzed using statistical methods of χ2, t, and Kaplan-Meier with a significance level of <0.05. Generally, in the case and control groups, there were no significant association between experience of stressful life events and incidence of breast cancer. Regarding associations between each of the events and incidence of breast cancer only "severe interpersonal problems with spouse" was significant. In the breast cancer group, even after controlling confounding variables, there was no significant association between major stressful events and disease-free survival, or overall 5-and 10-year survival. In this study, only "severe interpersonal problems with spouse" was confirmed as a risk factor. This result can be useful in developing preventive policies. More research regarding the interactive effects of psycho-social factors in the incidence and survival of breast cancer with stressful life events is recommended.
Scialò, Carlo; Novi, Giovanni; Bandettini di Poggio, Monica; Canosa, Antonio; Sormani, Maria Pia; Mandich, Paola; Origone, Paola; Truffelli, Romina; Mancardi, Giovanni Luigi; Caponnetto, Claudia
Our objectives were: (1) to assess amyotrophic lateral sclerosis (ALS) incidence and its trend over time in Liguria, an Italian north-western region, performing an analysis of data prospectively collected from 1 January 2009 to 31 December 2014; (2) to determine the mean and median survival in the 2009-2014 Ligurian ALS incident cases; and (3) to evaluate the presence of disease prognostic factors. The Liguria Register for ALS (LIGALS) is an ongoing, multicentre prospective register enrolling all ALS incident cases in Liguria. Cases were identified using several concurrent sources. ALS diagnosis was based on El Escorial revised criteria (EEC-R). Two hundred and ninety-eight patients were enrolled in this study. The mean annual crude incidence rate in the 2009-2014 period was 3.11/100,000 population (95% CI 2.77-3.49); the point prevalence at 31 December 2014 was 7.85/100,000 (95% CI 6.54-9.36) population. Survival analysis demonstrated a median survival from symptom onset of 37.0 months (95% CI 32.0-42.0). In conclusion, ALS crude incidence in Liguria is higher compared to other Italian regions. Clinical and epidemiological data are comparable with those of the Italian ALS population. Survival analysis showed that higher age at onset, bulbar onset, definite EEC-R diagnostic category and a shorter diagnostic delay are related with worse outcomes.
Yu, Doris S F; Lee, Diana T F; Stewart, Simon; Thompson, David R; Choi, Kai-Chow; Yu, Cheuk-Man
2015-08-01
To determine the effect of nurse-implemented transitional care (TC) on readmission and mortality rates in Chinese individuals with chronic heart failure (CHF) in Hong Kong. Single-center randomized controlled trial of TC versus usual care (UC). University-affiliated hospital in Hong Kong. Hospitalized Chinese individuals with CHF (N = 178; aged 78.6 ± 6.9, 45% male). The TC group received a predischarge visit, two home visits, and then regular telephone calls over 9 months to provide self-care education and support, optimized health surveillance, and facilitation in use of community services. Primary endpoints were event-free survival, all-cause hospital readmission, and mortality during the 9-month follow-up. Secondary endpoints were length of hospital stay, self-care, and health-related quality of life (HRQL). Data were analyzed using survival analysis and generalized estimating equations, following an intention-to-treat principle. Survival analysis indicated no significant differences in event-free survival, hospital readmission, or mortality between the TC and UC groups, although the TC group had a lower hospital readmission rate at 6 weeks (8.1% vs 16.3%, P = .048) and lower mortality at 9 months (4.1% vs 13.8%, P = .03). The TC group also had a shorter hospital stay (P = .006) and significantly better self-care and HRQL. Because of attrition, sensitivity analyses were conducted to examine whether the intention-to-treat assumption affected the results. Per-protocol population analyses (hazard ratio (HR) = 0.40, 95% confidence interval (CI) = 0.17-0.93) and worst-case-scenario analysis (HR = 0.44, 95% CI = 0.25-0.77) suggested a lower mortality risk in the TC group. The translation of individual-centered nurse-implemented TC to the Chinese culture and healthcare context of Hong Kong appears beneficial. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.
Talikowska, Milena; Tohira, Hideo; Finn, Judith
2015-11-01
To conduct a systematic review and meta-analysis to determine whether cardiopulmonary resuscitation (CPR) quality, as indicated by parameters such as chest compression depth, compression rate and compression fraction, is associated with patient survival from cardiac arrest. Five databases were searched (MEDLINE, Embase, CINAHL, Scopus and Cochrane) as well as the grey literature (MedNar). To satisfy inclusion criteria, studies had to document human cases of in- or out-of hospital cardiac arrest where CPR quality had been recorded using an automated device and linked to patient survival. Where indicated (I(2)<75%), meta-analysis was undertaken to examine the relationship between individual CPR quality parameters and either survival to hospital discharge (STHD) or return of spontaneous circulation (ROSC). Database searching yielded 8,842 unique citations, resulting in the inclusion of 22 relevant articles. Thirteen were included in the meta-analysis. Chest compression depth was significantly associated with STHD (mean difference (MD) between survivors and non-survivors 2.59 mm, 95% CI: 0.71, 4.47); and with ROSC (MD 0.99 mm, 95% CI: 0.04, 1.93). Within the range of approximately 100-120 compressions per minute (cpm), compression rate was significantly associated with STHD; survivors demonstrated a lower mean compression rate than non-survivors (MD -1.17 cpm, 95% CI: -2.21, -0.14). Compression fraction could not be examined by meta-analysis due to high heterogeneity, however a higher fraction appeared to be associated with survival in cases with a shockable initial rhythm. Chest compression depth and rate were associated with survival outcomes. More studies with consistent reporting of data are required for other quality parameters. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Samlowski, Wolfram E; Majer, Martin; Boucher, Kenneth M; Shrieve, Annabelle F; Dechet, Christopher; Jensen, Randy L; Shrieve, Dennis C
2008-11-01
Brain metastases are a frequent complication in patients with metastatic clear cell renal cancer. Survival after whole-brain radiotherapy (WBRT) is disappointing. A retrospective analysis of multimodality treatment was performed in patients who had received linear accelerator (LINAC)-based stereotactic radiosurgery (SRS). Thirty-two patients underwent SRS-based treatment for 71 metastatic foci between 2000 and 2006. All patients had a Karnofsky performance status >or=70 and all 32 patients had extracranial metastatic disease (Radiation Therapy Oncology Group recursive partitioning analysis [RPA] Class 2). Survival was calculated from the time of diagnosis of brain metastases. The minimum potential follow-up was 1 year after SRS. Univariate and multivariate analysis of potential prognostic factors affecting survival was performed. Twenty-six patients required only 1 SRS treatment (84%) to achieve central nervous system (CNS) control, whereas 5 patients received 2 to 3 treatments (16%). The median survival of renal cancer patients from the diagnosis of brain metastases was 10.1 months (95% confidence interval, 6.4-14.8 months). One-year and 3-year survival rates were 43% and 16%, respectively. The addition of surgery or WBRT did not appear to prolong survival. Immunotherapy after control of brain metastases with SRS appeared to result in significantly improved survival. Survival was also found to be strongly influenced by prognostic stratification of metastatic disease using Motzer or modified risk criteria. The results of the current study demonstrated that SRS-based treatment of patients with up to 5 brain metastases from clear cell renal cancer is feasible and results in excellent CNS control. Survival beyond 3 years from the time of diagnosis of brain metastases was achievable in 16% of patients and was associated with the use of systemic immunotherapy with interleukin-2 and interferon but not antiangiogenic agents.
Du, Xianglin L; Lin, Charles C; Johnson, Norman J; Altekruse, Sean
2011-07-15
This is the first study to use the linked National Longitudinal Mortality Study and Surveillance, Epidemiology, and End Results (SEER) data to determine the effects of individual-level socioeconomic factors (health insurance, education, income, and poverty status) on racial disparities in receiving treatment and in survival. This study included 13,234 cases diagnosed with the 8 most common types of cancer (female breast, colorectal, prostate, lung and bronchus, uterine cervix, ovarian, melanoma, and urinary bladder) at age ≥ 25 years, identified from the National Longitudinal Mortality Study-SEER data during 1973 to 2003. Kaplan-Meier methods and Cox regression models were used for survival analysis. Three-year all-cause observed survival for cases diagnosed with local-stage cancers of the 8 leading tumors combined was ≥ 82% regardless of race/ethnicity. More favorable survival was associated with higher socioeconomic status. Compared with whites, blacks were less likely to receive first-course cancer-directed surgery, perhaps reflecting a less favorable stage distribution at diagnosis. Hazard ratio (HR) for cancer-specific mortality was significantly higher among blacks compared with whites (HR, 1.2; 95% confidence interval [CI], 1.1-1.3) after adjusting for age, sex, and tumor stage, but not after further controlling for socioeconomic factors and treatment (HR, 1.0; 95% CI, 0.9-1.1). HRs for all-cause mortality among patients with breast cancer and for cancer-specific mortality in patients with prostate cancer were significantly higher for blacks compared with whites after adjusting for socioeconomic factors, treatment, and patient and tumor characteristics. Favorable survival was associated with higher socioeconomic status. Racial disparities in survival persisted after adjusting for individual-level socioeconomic factors and treatment for patients with breast and prostate cancer. Copyright © 2011 American Cancer Society.
Laryngeal cancer in the United States: changes in demographics, patterns of care, and survival.
Hoffman, Henry T; Porter, Kimberly; Karnell, Lucy H; Cooper, Jay S; Weber, Randall S; Langer, Corey J; Ang, Kie-Kian; Gay, Greer; Stewart, Andrew; Robinson, Robert A
2006-09-01
Survival has decreased among patients with laryngeal cancer during the past 2 decades in the United States. During this same period, there has been an increase in the nonsurgical treatment of laryngeal cancer. The objectives of this study were to identify trends in the demographics, management, and outcome of laryngeal cancer in the United States and to analyze factors contributing to the decreased survival. The authors conducted a retrospective, longitudinal study of laryngeal cancer cases. Review of the National Cancer Data Base (NCDB) revealed 158,426 cases of laryngeal squamous cell carcinoma (excluding verrucous carcinoma) diagnosed between the years 1985 and 2001. Analysis of these case records addressed demographics, management, and survival for cases grouped according to stage, site, and specific TNM classifications. This review of data from the NCDB analysis confirms the previously identified trend toward decreasing survival among patients with laryngeal cancer from the mid-1980s to mid-1990s. Patterns of initial management across this same period indicated an increase in the use of chemoradiation with a decrease in the use of surgery despite an increase in the use of endoscopic resection. The most notable decline in the 5-year relative survival between the 1985 to 1990 period and the 1994 to 1996 period occurred among advanced-stage glottic cancer, early-stage supraglottic cancers, and supraglottic cancers classified as T3N0M0. Initial treatment of T3N0M0 laryngeal cancer (all sites) in the 1994 to 1996 period resulted in poor 5-year relative survival for those receiving either chemoradiation (59.2%) or irradiation alone (42.7%) when compared with that of patients after surgery with irradiation (65.2%) and surgery alone (63.3%). In contrast, identical 5-year relative survival (65.6%) rates were observed during this same period for the subset of T3N0M0 glottic cancers initially treated with either chemoradiation or surgery with irradiation. The decreased survival recorded for patients with laryngeal cancer in the mid-1990s may be related to changes in patterns of management. Future studies are warranted to further evaluate these associations.
Han, Sheng; Huang, Yanming; Wang, Zixun; Li, Zhonghua; Qin, Xiaofei; Wu, Anhua
2014-11-01
Allergy and immunoglobulin E levels are inversely associated with glioma risk. Previous studies have focused on respiratory and food allergies, and little information is available regarding drug allergies. This study evaluated the rate of positive penicillin skin tests (PenSTs) and blood eosinophil counts in a large population of patients with glioma compared with nontumor controls to provide evidence for the relationship between drug allergies and glioma risk. A retrospective case-control study was conducted in patients diagnosed with glioma (n = 913) between January 2004 and June 2013. The study patients were matched with nontumor controls (n = 1091) for age, sex, and date of admission to the hospital. Preoperative results of the PenST and eosinophil counts were obtained, and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using conditional logistic regression models, while a Kaplan-Meier analysis was used to assess overall survival. The percentage of positive PenSTs was higher among patients with glioma than in control subjects. The age-, sex-, and admission date-adjusted OR for positive versus negative PenSTs was 2.392 (95% CI 1.891-3.026). Eosinophil counts were also higher in glioma cases than in controls: the OR for eosinophil > 0.06 × 10(9)/L versus ≤ 0.06 × 10(9)/L was 1.923 (95% CI 1.608-2.301). There was no association between positive PenST/eosinophil counts and glioma grade or patient survival (n = 105). In contrast to previously reported relationships between allergy and glioma, in the present study a significantly higher rate of positive PenSTs and higher eosinophil counts were found in patients with glioma than in nontumor controls. These results suggest a complex relationship between allergies and glioma development.
Fagerholm, Rainer; Schmidt, Marjanka K; Khan, Sofia; Rafiq, Sajjad; Tapper, William; Aittomäki, Kristiina; Greco, Dario; Heikkinen, Tuomas; Muranen, Taru A; Fasching, Peter A; Janni, Wolfgang; Weinshilboum, Richard; Loehberg, Christian R; Hopper, John L; Southey, Melissa C; Keeman, Renske; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Chenevix-Trench, Georgia; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Seibold, Petra; Couch, Fergus J; Olson, Janet E; Andrulis, Irene L; Knight, Julia A; García-Closas, Montserrat; Figueroa, Jonine; Hooning, Maartje J; Jager, Agnes; Shah, Mitul; Perkins, Barbara J; Luben, Robert; Hamann, Ute; Kabisch, Maria; Czene, Kamila; Hall, Per; Easton, Douglas F; Pharoah, Paul D P; Liu, Jianjun; Eccles, Diana; Blomqvist, Carl; Nevanlinna, Heli
2015-04-10
We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.
Di Cello, Annalisa; Rania, Erika; Zuccalà, Valeria; Venturella, Roberta; Mocciaro, Rita; Zullo, Fulvio; Morelli, Michele
2015-11-01
To evaluate the misdiagnosis between endometrial biopsy and definitive surgical pathology and to assess whether the failure in recognizing preoperatively high-risk endometrial carcinoma (EC) can impact oncological outcomes. A retrospective study was conducted to evaluate patients with EC diagnosed by preoperative endometrial biopsy who subsequently underwent surgical staging between 2006 and 2013 at our institution. In patients with a surgical diagnosis of high-risk EC, histotype and grade change between the endometrial biopsy and surgical specimen (discordance diagnosis) were evaluated and correlated to survival outcomes. Cox's regression model for multivariable analysis was used to evaluate the effect of several variables (age, stage, discordance in diagnosis, co-morbidities, frozen section, extensive surgical staging and adjuvant chemotherapy) on the survival rate. Data from 447 patients were reviewed. Among 109 women with surgical diagnosis of high-risk EC, 35 (32.1%) were preoperatively misdiagnosed. Of these 35 women, 24 (68.6%) cases were upgraded to grade 3, and 11 (3.4%) were upgraded to serous or clear cell type in the definitive specimen. The 5-year overall survival (OS; 70.2 vs. 86.8%; p=0.029), disease-specific survival (DSS; 72.5 vs. 88.2%; p=0.039) and recurrence free survival (RFS; 62.6 vs. 82.5%; p=0.024) were significantly lower in the high-risk EC patients who were preoperatively undiagnosed in the endometrial biopsy compared with patients with an appropriate preoperative histological diagnosis. Controlling for age, stage, co-morbidities, frozen section, extensive surgical staging and adjuvant chemotherapy, multivariable analysis revealed that discordance in diagnosis was associated with poorer survival outcomes. Failure to recognize preoperatively high-risk ECs is associated with worse outcomes. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.
Chan, Paul S; Krein, Sarah L; Tang, Fengming; Iwashyna, Theodore J; Harrod, Molly; Kennedy, Mary; Lehrich, Jessica; Kronick, Steven; Nallamothu, Brahmajee K
2016-05-01
Although survival of patients with in-hospital cardiac arrest varies markedly among hospitals, specific resuscitation practices that distinguish sites with higher cardiac arrest survival rates remain unknown. To identify resuscitation practices associated with higher rates of in-hospital cardiac arrest survival. Nationwide survey of resuscitation practices at hospitals participating in the Get With the Guidelines-Resuscitation registry and with 20 or more adult in-hospital cardiac arrest cases from January 1, 2012, through December 31, 2013. Data analysis was performed from June 10 to December 22, 2015. Risk-standardized survival rates for cardiac arrest were calculated at each hospital and were then used to categorize hospitals into quintiles of performance. The association between resuscitation practices and quintiles of survival was evaluated using hierarchical proportional odds logistic regression models. Overall, 150 (78.1%) of 192 eligible hospitals completed the study survey, and 131 facilities with 20 or more adult in-hospital cardiac arrest cases comprised the final study cohort. Risk-standardized survival rates after in-hospital cardiac arrest varied substantially (median, 23.7%; range, 9.2%-37.5%). Several resuscitation practices were associated with survival on bivariate analysis, although only 3 were significant after multivariable adjustment: monitoring for interruptions in chest compressions (adjusted odds ratio [OR] for being in a higher survival quintile category, 2.71; 95% CI, 1.24-5.93; P = .01), reviewing cardiac arrest cases monthly (adjusted OR for being in a higher survival quintile category, 8.55; 95% CI, 1.79-40.00) or quarterly (OR, 6.85; 95% CI, 1.49-31.30; P = .03), and adequate resuscitation training (adjusted OR, 3.23; 95% CI, 1.21-8.33; P = .02). Using survey information from acute care hospitals participating in a national quality improvement registry, we identified 3 resuscitation strategies associated with higher hospital rates of survival for patients with in-hospital cardiac arrest. These strategies can form the foundation for best practices for resuscitation care at hospitals given the high incidence and variation in survival for in-hospital cardiac arrest.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gong, Y; Yu, J; Yeung, V
Purpose: Artificial neural networks (ANN) can be used to discover complex relations within datasets to help with medical decision making. This study aimed to develop an ANN method to predict two-year overall survival of patients with peri-ampullary cancer (PAC) following resection. Methods: Data were collected from 334 patients with PAC following resection treated in our institutional pancreatic tumor registry between 2006 and 2012. The dataset contains 14 variables including age, gender, T-stage, tumor differentiation, positive-lymph-node ratio, positive resection margins, chemotherapy, radiation therapy, and tumor histology.After censoring for two-year survival analysis, 309 patients were left, of which 44 patients (∼15%) weremore » randomly selected to form testing set. The remaining 265 cases were randomly divided into training set (211 cases, ∼80% of 265) and validation set (54 cases, ∼20% of 265) for 20 times to build 20 ANN models. Each ANN has one hidden layer with 5 units. The 20 ANN models were ranked according to their concordance index (c-index) of prediction on validation sets. To further improve prediction, the top 10% of ANN models were selected, and their outputs averaged for prediction on testing set. Results: By random division, 44 cases in testing set and the remaining 265 cases have approximately equal two-year survival rates, 36.4% and 35.5% respectively. The 20 ANN models, which were trained and validated on the 265 cases, yielded mean c-indexes as 0.59 and 0.63 on validation sets and the testing set, respectively. C-index was 0.72 when the two best ANN models (top 10%) were used in prediction on testing set. The c-index of Cox regression analysis was 0.63. Conclusion: ANN improved survival prediction for patients with PAC. More patient data and further analysis of additional factors may be needed for a more robust model, which will help guide physicians in providing optimal post-operative care. This project was supported by PA CURE Grant.« less
Kawano, Shingo; Komai, Yoshinobu; Ishioka, Junichiro; Sakai, Yasuyuki; Fuse, Nozomu; Ito, Masaaki; Kihara, Kazunori; Saito, Norio
2016-10-01
The aim of this study was to determine risk factors for survival after retrograde placement of ureteral stents and develop a prognostic model for advanced gastrointestinal tract (GIT: esophagus, stomach, colon and rectum) cancer patients. We examined the clinical records of 122 patients who underwent retrograde placement of a ureteral stent against malignant extrinsic ureteral obstruction. A prediction model for survival after stenting was developed. We compared its clinical usefulness with our previous model based on the results from nephrostomy cases by decision curve analysis. Median follow-up period was 201 days (8-1490) and 97 deaths occurred. The 1-year survival rate in this cohort was 29%. Based on multivariate analysis, primary site of colon origin, absence of retroperitoneal lymph node metastasis and serum albumin >3g/dL were significantly associated with a prolonged survival time. To develop a prognostic model, we divided the patients into 3 risk groups of favorable: 0-1 factors (N.=53), intermediate: 2 risk factors (N.=54), and poor: 3 risk factors (N.=15). There were significant differences in the survival profiles of these 3 risk groups (P<0.0001). Decision curve analyses revealed that the current model has a superior net benefit than our previous model for most of the examined probabilities. We have developed a novel prognostic model for GIT cancer patients who were treated with retrograde placement of a ureteral stent. The current model should help urologists and medical oncologists to predict survival in cases of malignant extrinsic ureteral obstruction.
SARTZ, L.; De JONG, B.; HJERTQVIST, M.; PLYM-FORSHELL, L.; ALSTERLUND, R.; LÖFDAHL, S.; OSTERMAN, B.; STÅHL, A.; ERIKSSON, E.; HANSSON, H.-B.; KARPMAN, D.
2008-01-01
SUMMARY A large outbreak of enterohaemorrhagic Escherichia coli (EHEC) infections occurred in southern Sweden during autumn 2002. A matched case-control study was performed and indicated an association between consumption of fermented sausage and EHEC infection (odds ratio 5·4, P<0·002). Pulsed-field gel electrophoresis analysis identified a strain of E. coli O157:H7 in clinical faecal isolates, which was identical to a strain isolated from sausage samples obtained from households of infected individuals. A combination of microbiological and epidemiological results established a link between sausage consumption and the outbreak in 30 out of a total of 39 investigated cases. Contaminated beef was suspected to be the source of infection. Delayed start of fermentation, lack of heat-treatment and a short curing period in cold temperature were identified as the main factors enabling EHEC survival. EHEC can survive throughout the entire production process of fermented sausage if curing conditions are inadequate. PMID:17445322
Dawson, J; Jameson-Shortall, E; Emerton, M; Flynn, J; Smith, P; Gundle, R; Murray, D
2000-09-01
We reviewed 598 cemented Charnley and Hi-nek total hip arthroplasties at 7 years. Data were obtained from general practitioners, hospital medical notes, microfilm, and patient questionnaires. Outcome measures were revision rates, survival analysis, 12-item Oxford Hip Score, and satisfaction ratings. There were 471 Charnley (79%) and 127 Hi-nek (21%) total hip arthroplasties; 139 deaths (23%) occurred, and 5 (<1%) were lost to follow-up. Characteristics of the Charnley and Hi-nek patient groups were similar, with more information missing for Charnley cases. Revision rates were Charnley, 37 (8%), and Hi-nek, 6 (5%) (not significant). Survival analysis revealed no difference between the 2 groups (P = .23). The patients' median Oxford Hip Score was low/good (19), slightly worse for the Hi-nek group (not significant). Taking all evidence together, neither implant was outperforming the other at 7 years.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Fallai, Carlo, E-mail: carlo.fallai@istitutotumori.mi.i; Perrone, Federica; Licitra, Lisa
Purpose: To study the prognostic value of the TP53 mutation and human papilloma virus (HPV) status in oropharyngeal squamous cell carcinoma (OPSCC). Methods and materials: The TP53 mutation and HPV status were analyzed in 78 cases of locoregionally advanced OPSCC. The possible correlation of these factors with locoregiownal control, relapse-free survival, disease-specific survival, and overall survival (OS) was also investigated. Results: Of these 78 cases, 22 had disruptive and 22 had non-disruptive (silent) TP53 mutations; the remaining 34 cases had wild-type (WT) TP53. HPV 16 DNA was found in 9 cases (11%), but all HPV-positive (HPV+) cases carried a functionalmore » p53 protein, except for 1 case that had a silent mutation. HPV+ patients fared better than HPV-negative (HPV-) patients in terms of all survival parameters, with highly statistically significant differences between the groups. Specifically, no distant metastases were observed in the HPV+ patients, whereas they occurred in 17% of the HPV- patients. However, no difference was observed between the WT TP53 and mutation group, even when this was analyzed in terms of disruptive and non-disruptive mutations. Regardless, treatment with chemotherapy nearly doubled the 5-year OS rates, both in the mutation (42% vs. 22%) and WT (30 vs. 16%) group, but only the mutation group showed improvement in all survival parameters. In addition, the second tumor-free 5-year survival rate was 72% in HPV- cases, but no second tumors were observed in HPV+ and WT p53 cases. Conclusions: Patients with HPV+ OPSCC have an excellent prognosis after radiochemotherapy, but cisplatin-based chemotherapy may not confer a satisfactory outcome, especially in WT cases, thereby justifying the additional or alternative use of taxanes and epidermal growth factor receptors inhibitors. Uncommon distant metastases and second tumors in the HPV+ group may be cause for clinicians to review the follow-up policies in these patients.« less
Muruet, Walter; Rudd, Anthony; Wolfe, Charles D A; Douiri, Abdel
2018-03-01
Intravenous thrombolysis with alteplase is one of the few approved treatments for acute ischemic stroke; nevertheless, little is known about its long-term effects on survival and recovery because clinical trials follow-up times are limited. Patients registered between January 2005 and December 2015, to the population-based South London Stroke Register of first-ever strokes. Propensity score was used to match thrombolyzed and control cases to a 1:2 ratio by demographical and clinical covariates. The primary outcome was survival up to 10 years using Kaplan-Meier estimates, Cox proportional hazards, and restricted mean survival time. Secondary outcomes included stroke recurrence and functional status (Barthel Index and Frenchay Activities Index scores) at 5 years. From 2052 ischemic strokes, 246 treated patients were matched to 492 controls. Median follow-up time 5.45 years (interquartile range, 4.56). Survival was higher in the treatment group (median, 5.72 years) compared with control group (4.98 years, stratified log-rank test <0.001). The number needed to treat to prevent 1 death at 5 years was 12 and 20 at 10 years. After Cox regression analysis, thrombolysis reduced risk of mortality by 37% (hazard ratio, 0.63; 95% confidence interval [CI], 0.48-0.82) at 10 years; however, after introducing a multiplicative interaction term into the model, mortality risk reduction was 42% (hazard ratio, 0.58; 95% CI, 0.40-0.82) at 10 years for those arriving within 3 hours to the hospital. On average, in a 10-year period, treated patients lived 1 year longer than controls. At 5 years, thrombolysis was associated with independence (Barthel Index≥90; odds ratio, 3.76; 95% CI, 1.22-13.34) and increased odds of a higher Frenchay Activities Index (proportional odds ratio, 2.37; 95% CI, 1.16-4.91). There was no difference in stroke recurrence. Thrombolysis with intravenous alteplase is associated with improved long-term survival and functional status after ischemic stroke. © 2018 The Authors.
Khurmi, Manpreet Singh; Sayinzoga, Felix; Berhe, Atakilt; Bucyana, Tatien; Mwali, Assumpta Kayinamura; Manzi, Emmanuel; Muthu, Maharajan
2017-01-01
The Newborn Survival Case study in Rwanda provides an analysis of the newborn health and survival situation in the country. It reviews evidence-based interventions and coverage levels already implemented in the country; identifies key issues and bottlenecks in service delivery and uptake of services by community/beneficiaries, and provides key recommendations aimed at faster reduction in newborn mortality rate. This study utilized mixed method research including qualitative and quantitative analyses of various maternal and newborn health programs implemented in the country. This included interviewing key stakeholders at each level, field visits and also interviewing beneficiaries for assessment of uptake of services. Monitoring systems such as Health Management Information Systems (HMIS), maternal and newborn death audits were reviewed and data analyzed to aid these analyses. Policies, protocols, various guidelines and tools for monitoring are already in place however, implementation of these remains a challenge e.g. infection control practices to reduce deaths due to sepsis. Although existing staff are quite knowledgeable and are highly motivated, however, shortage of health personnel especially doctors in an issue. New facilities are being operationalized e.g. at Gisenyi, however, the existing facilities needs expansion. It is essential to implement high impact evidence based interventions but coverage levels need to be significantly high in order to achieve higher reduction in newborn mortality rate. Equity approach should be considered in planning so that the services are better implemented and the poor and needy can get the benefits of public health programs.
Zhou, Jing; Zhao, Rongce; Wen, Feng; Zhang, Pengfei; Wu, Yifan; Tang, Ruilei; Chen, Hongdou; Zhang, Jian; Li, Qiu
2016-06-02
Fluorouracil, leucovorin, irinotecan, oxaliplatin (FOLFIRINOX) and gemcitabine plus nab-paclitaxel (GEM-N) have shown a significant survival benefit for the treatment of metastatic pancreatic cancer. The objective of this study was to assess the cost-effectiveness of FOLFIRINOX versus GEM-N for treating metastatic pancreatic cancer based on the PRODIGE and MPACT trials. A decision model was performed to compare FOLFIRINOX with GEM-N. Primary base case data were identified from PRODIGE and MPACT trials. Costs were estimated and incremental cost-effectiveness ratio (ICER) was calculated at West China Hospital, Sichuan University, China. Survival benefits were reported in quality-adjusted life-years (QALY). Finally, sensitive analysis was performed by varying potentially modifiable parameters in the model. The base-case analysis showed that FOLFIRINOX cost $37,203.75 and yielded a survival of 0.67 QALY, and GEM-N cost $32,080.59 and yielded a survival of 0.51 QALY in the entire treatment. Thus, the ICER of FOLFIRINOX versus GEM-N was $32,019.75 per QALY gained. The GEM-N regimen was more cost-effective compared with the FOLFIRINOX regimen for the treatment of metastatic pancreatic cancer from a Chinese perspective.
Increased flexibility for modeling telemetry and nest-survival data using the multistate framework
Devineau, Olivier; Kendall, William L.; Doherty, Paul F.; Shenk, Tanya M.; White, Gary C.; Lukacs, Paul M.; Burnham, Kenneth P.
2014-01-01
Although telemetry is one of the most common tools used in the study of wildlife, advances in the analysis of telemetry data have lagged compared to progress in the development of telemetry devices. We demonstrate how standard known-fate telemetry and related nest-survival data analysis models are special cases of the more general multistate framework. We present a short theoretical development, and 2 case examples regarding the American black duck and the mallard. We also present a more complex lynx data analysis. Although not necessary in all situations, the multistate framework provides additional flexibility to analyze telemetry data, which may help analysts and biologists better deal with the vagaries of real-world data collection.
Zorzon, M; Antonutti, L; Masè, G; Biasutti, E; Vitrani, B; Cazzato, G
1995-09-01
The purpose of the present study was to make an attempt to ascertain the etiology of transient global amnesia (TGA), which is still disputed more than 30 years after the first description of this clinical entity. In a case-control study, we compared the prevalence of vascular risk factors in 64 TGA patients with 64 first-ever transient ischemic attack (TIA) control subjects and 108 normal community-based control subjects matched for age and sex. We prospectively studied the vascular events and mortality rates of the TGA cases and of the TIA control subjects. Then we compared the outcome of the two groups using actuarial analysis based on survival curves. We did not find evidence of an increased risk of TGA associated with any vascular risk factor. In contrast to TIA control subjects, no TGA patient suffered stroke, myocardial infarction, or TIA during the follow-up period. Migraine was more common in TGA patients than in both normal and TIA control subjects. In three patients (4.5%), the TGA was eventually considered to be of epileptic origin. The results of our case-control and longitudinal studies point to the conclusion that TGA and TIA do not share the same etiology. Since half of our patients had a precipitating event in their history, it is reasonable to hypothesize that spreading depression may play a role in TGA. The significant positive association between migraine and TGA may support this hypothesis. Epilepsy may mimic TGA in a minority of cases.
A breath test for malignant mesothelioma using an electronic nose.
Chapman, Eleanor A; Thomas, Paul S; Stone, Emily; Lewis, Craig; Yates, Deborah H
2012-08-01
Malignant mesothelioma (MM) is a rare tumour which is difficult to diagnose in its early stages. Earlier detection of MM could potentially improve survival. Exhaled breath sampling of volatile organic compounds (VOCs) using a carbon polymer array (CPA) electronic nose recognises specific breath profiles characteristic of different diseases, and can distinguish between patients with lung cancer and controls. With MM, the potential confounding effect of other asbestos-related diseases (ARDs) needs to be considered. We hypothesised that as CPA electronic nose would distinguish patients with MM, patients with benign ARDs, and controls with high sensitivity and specificity. 20 MM, 18 ARD and 42 control subjects participated in a cross-sectional, case-control study. Breath samples were analysed using the Cyranose 320 (Smiths Detection, Pasadena, CA, USA), using canonical discriminant analysis and principal component reduction. 10 MM subjects created the training set. Smell prints from 10 new MM patients were distinguished from control subjects with an accuracy of 95%. Patients with MM, ARDs and control subjects were correctly identified in 88% of cases. Exhaled breath VOC profiling can accurately distinguish between patients with MM, ARDs and controls using a CPA electronic nose. This could eventually translate into a screening tool for high-risk populations.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Marelli, Laura; Stigliano, Rosa; Triantos, Christos
2007-02-15
Background. Chemoembolization (TACE) improves survival in cirrhotic patients with hepatocellular carcinoma (HCC). The optimal schedule, or whether embolization (TAE) alone gives the same survival advantage, is not known. Purpose. To evaluate whether specific patient characteristics and/or radiological transarterial techniques result in better outcomes. Method. A PubMed search was carried out for cohort and randomized trials (n = 175) testing transarterial therapies; meta-analysis was performed where appropriate. Results. Anticancer drugs were used as sole agent in 75% of cases (double 15% and triple 6%): doxorubicin (36%), cisplatin (31%), epirubicin (12%), mitoxantrone (8%), mitomycin (8%), and SMANCS (5%). Embolizing agents used were:more » gelatin sponge particles (71%), polyvinyl alcohol (PVA) particles (8%), degradable starch microspheres (DSM) (4%), and embospheres (4%). Sessions per patient were 2.5 {+-} 1.5 (interval: 2 months). Objective response was 40 {+-} 20%; survival rates at 1, 2, 3, and 5 years were: 62 {+-} 20%, 42 {+-} 17%, 30 {+-} 15%, and 19 {+-} 16%, respectively, and survival time was 18 {+-} 9.5 months. The post-TACE complications were: acute liver failure, 7.5% (range 0-49%); acute renal failure, 1.8% (0-13%); encephalopathy, 1.8% (0-16%); ascites, 8.3% (0-52%); upper gastrointestinal bleeding; 3% (0-22%); and hepatic or splenic abscess, 1.3% (0-2.5%). Treatment-related mortality was 2.4% (0-9.5%), mainly due to acute liver failure. Our meta-analysis of nine randomized controlled trials (RCTs) confirmed that TACE improves survival; but a meta-analysis of TACE versus TAE alone (3 RCTs, 412 patients) demonstrated no survival difference. Conclusions. No chemotherapeutic agent appears better than any other. There is no evidence for benefit with lipiodol. Gelatin sponge is the most used embolic agent, but PVA particles may be better. TAE appears as effective as TACE. New strategies to reduce the risk of post-TACE complications are required.« less
Prognostic value of preoperative serum CA 242 in Esophageal squamous cell carcinoma cases.
Feng, Ji-Feng; Huang, Ying; Chen, Qi-Xun
2013-01-01
Carbohydrate antigen (CA) 242 is inversely related to prognosis in many cancers. However, few data regarding CA 242 in esophageal cancer (EC) are available. The aim of this study was to determine the prognostic value of CA 242 and propose an optimum cut-off point in predicting survival difference in patients with esophageal squamous cell carcinoma (ESCC). A retrospective analysis was conducted of 192 cases. A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimum cuf- off point. Univariate and multivariate analyses were performed to evaluate prognostic parameters for survival. The positive rate for CA 242 was 7.3% (14/192). The ROC curve for survival prediction gave an optimum cut-off of 2.15 (U/ml). Patients with CA 242 ≤ 2.15 U/ml had significantly better 5-year survival than patients with CA 242 >2.15 U/ml (45.4% versus 22.6%; P=0.003). Multivariate analysis showed that differentiation (P=0.033), CA 242 (P=0.017), T grade (P=0.004) and N staging (P<0.001) were independent prognostic factors. Preoperative CA 242 is a predictive factor for long-term survival in ESCC, especially in nodal-negative patients. We conclude that 2.15 U/ml may be the optimum cuf-off point for CA 242 in predicting survival in ESCC.
Survival analysis of biliary tract cancer cases in Turkey.
Akca, Zeki; Mutlu, Hasan; Erden, Abdulsamet; Buyukcelik, Abdullah; Cihan, Yasemin Benderli; Goksu, Sema Sezgin; Aslan, Tuncay; Sezer, Emel Yaman; Inal, Ali
2014-01-01
Because of the relative rarity of biliary tract cancers (BTCs), defining long term survival results is difficult. In the present study, we aimed to evaluate the survival of a series of cases in Turkey. A totally of 47 patients with billiary tract cancer from Mersin Goverment Hospital, Acibadem Kayseri Hospital and Kayseri Training and Research Hospital were analyzed retrospectively using hospital records between 2006-2012. The median overall survival was 19.3±3.9 months for all patients. The median disease free and overall survivals were 24.3±5.3 and 44.1±12.9 months in patients in which radical surgery was performed , but in those with with inoperable disease they were only 5.3±1.5 and 10.7±3.2 months, respectively. BTCs have a poor prognosis. Surgery with a microscopic negative margin is still the only curative treatment.
Heritable DNA methylation marks associated with susceptibility to breast cancer.
Joo, Jihoon E; Dowty, James G; Milne, Roger L; Wong, Ee Ming; Dugué, Pierre-Antoine; English, Dallas; Hopper, John L; Goldgar, David E; Giles, Graham G; Southey, Melissa C
2018-02-28
Mendelian-like inheritance of germline DNA methylation in cancer susceptibility genes has been previously reported. We aimed to scan the genome for heritable methylation marks associated with breast cancer susceptibility by studying 25 Australian multiple-case breast cancer families. Here we report genome-wide DNA methylation measured in 210 peripheral blood DNA samples provided by family members using the Infinium HumanMethylation450. We develop and apply a new statistical method to identify heritable methylation marks based on complex segregation analysis. We estimate carrier probabilities for the 1000 most heritable methylation marks based on family structure, and we use Cox proportional hazards survival analysis to identify 24 methylation marks with corresponding carrier probabilities significantly associated with breast cancer. We replicate an association with breast cancer risk for four of the 24 marks using an independent nested case-control study. Here, we report a novel approach for identifying heritable DNA methylation marks associated with breast cancer risk.
Andersen, N S; Jensen, M K; de Nully Brown, P; Geisler, C H
2002-02-01
This study presents the first large clinical analysis of 105 unselected mantle cell lymphoma (MCL) patients diagnosed from 1992 to 2000 in a well-defined Danish population. The annual incidences were 0.7/100000 for men and 0.2/100000 for women, with no significant change during the study period. Of 97 evaluable cases, 43% achieved a complete response (CR) after initial therapy. The median disease-free (DFS) and overall survival (OS) rates were 15 and 30 months, respectively. In multivariate analysis, splenomegaly (P=0.002), anaemia (P=0.0001) and age (P=0.002), but not the international prognostic index (IPI) and the Ann Arbor staging system, had an independent impact on survival. Moreover, in a sub-analysis of 45 younger MCL patients (<65 years), a trend towards an OS plateau of 58% was observed in cases without splenomegaly and anaemia (n=29). Thus, in contrast to previously suggested prognostic factors, these variables may prove useful for clinical decisions in a significant subset of MCL patients.
Fassan, Matteo; Indraccolo, Stefano; Calabrese, Fiorella; Favaretto, Adolfo; Bonanno, Laura; Polo, Valentina; Zago, Giulia; Lunardi, Francesca; Attili, Ilaria; Pavan, Alberto; Rugge, Massimo; Guarneri, Valentina; Conte, PierFranco; Pasello, Giulia
2017-01-01
Introduction Tyrosine-kinase inhibitors (TKIs) represent the best treatment for advanced non-small cell lung cancer (NSCLC) with common exon 19 deletion or exon 21 epidermal growth factor receptor mutation (EGFRm). This is an observational study investigating epidemiology, clinical features and treatment outcome of NSCLC cases harbouring rare/complex EGFRm. Results Among 764 non-squamous NSCLC cases with known EGFRm status, 26(3.4%) harboured rare/complex EGFRm. Patients receiving first-line TKIs (N = 17) achieved median Progression Free Survival (PFS) and Overall Survival (OS) of 53 (IC 95%, 2–105) and 84 (CI 95%, 27–141) weeks respectively, without significant covariate impact. Response Rate and Disease Control Rate (DCR) were 47% and 65%, respectively. Uncommon exon 19 mutations achieved longer OS and PFS and higher DCR compared with exon 18 and 20 mutations. No additional gene mutation was discovered by MassARRAY analysis. TKIs were globally well tolerated. Materials and methods A retrospective review of advanced non-squamous NSCLC harbouring rare/complex EGFRm referred to our Center between 2010 and 2015 was performed. Additional molecular pathways disregulation was explored in selected cases, through MassARRAY analysis. Conclusions Peculiar clinical features and lower TKIs sensitivity of uncommon/complex compared with common EGFRm were shown. Exon 19 EGFRm achieved the best TKIs treatment outcome, while the optimal treatment of exon 18 and 20 mutations should be further clarified. PMID:28427238
NASA Astrophysics Data System (ADS)
Astuti Thamrin, Sri; Taufik, Irfan
2018-03-01
Dengue haemorrhagic fever (DHF) is an infectious disease caused by dengue virus. The increasing number of people with DHF disease correlates with the neighbourhood, for example sub-districts, and the characteristics of the sub-districts are formed from individuals who are domiciled in the sub-districts. Data containing individuals and sub-districts is a hierarchical data structure, called multilevel analysis. Frequently encountered response variable of the data is the time until an event occurs. Multilevel and spatial models are being increasingly used to obtain substantive information on area-level inequalities in DHF survival. Using a case study approach, we report on the implications of using multilevel with spatial survival models to study geographical inequalities in all cause survival.
Common germline polymorphisms associated with breast cancer-specific survival.
Pirie, Ailith; Guo, Qi; Kraft, Peter; Canisius, Sander; Eccles, Diana M; Rahman, Nazneen; Nevanlinna, Heli; Chen, Constance; Khan, Sofia; Tyrer, Jonathan; Bolla, Manjeet K; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Lush, Michael; Dunning, Alison M; Shah, Mitul; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Lambrechts, Dieter; Weltens, Caroline; Leunen, Karin; van Ongeval, Chantal; Nordestgaard, Børge G; Nielsen, Sune F; Flyger, Henrik; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Blomqvist, Carl; Aittomäki, Kristiina; Fagerholm, Rainer; Muranen, Taru A; Olsen, Janet E; Hallberg, Emily; Vachon, Celine; Knight, Julia A; Glendon, Gord; Mulligan, Anna Marie; Broeks, Annegien; Cornelissen, Sten; Haiman, Christopher A; Henderson, Brian E; Schumacher, Frederick; Le Marchand, Loic; Hopper, John L; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C; Cross, Simon S; Reed, Malcolm Wr; Giles, Graham G; Milne, Roger L; McLean, Catriona; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Hooning, Maartje J; Hollestelle, Antoinette; Martens, John Wm; van den Ouweland, Ans Mw; Marme, Federick; Schneeweiss, Andreas; Yang, Rongxi; Burwinkel, Barbara; Figueroa, Jonine; Chanock, Stephen J; Lissowska, Jolanta; Sawyer, Elinor J; Tomlinson, Ian; Kerin, Michael J; Miller, Nicola; Brenner, Hermann; Butterbach, Katja; Holleczek, Bernd; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M; Li, Jingmei; Brand, Judith S; Humphreys, Keith; Devilee, Peter; Tollenaar, Robert Aem; Seynaeve, Caroline; Radice, Paolo; Peterlongo, Paolo; Manoukian, Siranoush; Ficarazzi, Filomena; Beckmann, Matthias W; Hein, Alexander; Ekici, Arif B; Balleine, Rosemary; Phillips, Kelly-Anne; Benitez, Javier; Zamora, M Pilar; Perez, Jose Ignacio Arias; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Gronwald, Jacek; Durda, Katarzyna; Hamann, Ute; Kabisch, Maria; Ulmer, Hans Ulrich; Rüdiger, Thomas; Margolin, Sara; Kristensen, Vessela; Nord, Siljie; Evans, D Gareth; Abraham, Jean; Earl, Helena; Poole, Christopher J; Hiller, Louise; Dunn, Janet A; Bowden, Sarah; Yang, Rose; Campa, Daniele; Diver, W Ryan; Gapstur, Susan M; Gaudet, Mia M; Hankinson, Susan; Hoover, Robert N; Hüsing, Anika; Kaaks, Rudolf; Machiela, Mitchell J; Willett, Walter; Barrdahl, Myrto; Canzian, Federico; Chin, Suet-Feung; Caldas, Carlos; Hunter, David J; Lindstrom, Sara; Garcia-Closas, Montserrat; Couch, Fergus J; Chenevix-Trench, Georgia; Mannermaa, Arto; Andrulis, Irene L; Hall, Per; Chang-Claude, Jenny; Easton, Douglas F; Bojesen, Stig E; Cox, Angela; Fasching, Peter A; Pharoah, Paul Dp; Schmidt, Marjanka K
2015-04-22
Previous studies have identified common germline variants nominally associated with breast cancer survival. These associations have not been widely replicated in further studies. The purpose of this study was to evaluate the association of previously reported SNPs with breast cancer-specific survival using data from a pooled analysis of eight breast cancer survival genome-wide association studies (GWAS) from the Breast Cancer Association Consortium. A literature review was conducted of all previously published associations between common germline variants and three survival outcomes: breast cancer-specific survival, overall survival and disease-free survival. All associations that reached the nominal significance level of P value <0.05 were included. Single nucleotide polymorphisms that had been previously reported as nominally associated with at least one survival outcome were evaluated in the pooled analysis of over 37,000 breast cancer cases for association with breast cancer-specific survival. Previous associations were evaluated using a one-sided test based on the reported direction of effect. Fifty-six variants from 45 previous publications were evaluated in the meta-analysis. Fifty-four of these were evaluated in the full set of 37,954 breast cancer cases with 2,900 events and the two additional variants were evaluated in a reduced sample size of 30,000 samples in order to ensure independence from the previously published studies. Five variants reached nominal significance (P <0.05) in the pooled GWAS data compared to 2.8 expected under the null hypothesis. Seven additional variants were associated (P <0.05) with ER-positive disease. Although no variants reached genome-wide significance (P <5 x 10(-8)), these results suggest that there is some evidence of association between candidate common germline variants and breast cancer prognosis. Larger studies from multinational collaborations are necessary to increase the power to detect associations, between common variants and prognosis, at more stringent significance levels.
A Framework for RFID Survivability Requirement Analysis and Specification
NASA Astrophysics Data System (ADS)
Zuo, Yanjun; Pimple, Malvika; Lande, Suhas
Many industries are becoming dependent on Radio Frequency Identification (RFID) technology for inventory management and asset tracking. The data collected about tagged objects though RFID is used in various high level business operations. The RFID system should hence be highly available, reliable, and dependable and secure. In addition, this system should be able to resist attacks and perform recovery in case of security incidents. Together these requirements give rise to the notion of a survivable RFID system. The main goal of this paper is to analyze and specify the requirements for an RFID system to become survivable. These requirements, if utilized, can assist the system in resisting against devastating attacks and recovering quickly from damages. This paper proposes the techniques and approaches for RFID survivability requirements analysis and specification. From the perspective of system acquisition and engineering, survivability requirement is the important first step in survivability specification, compliance formulation, and proof verification.
Respiratory cancer population-based survival in Mumbai, India.
Yeole, Balkrishna B
2005-01-01
Survival experience of patients with cancer of the larynx (ICD-32) or lung (ICD-34) registered by the Mumbai (Bombay) population based cancer registry, India, during the years 1992-94 was determined. The vital statistics of the patients were established by matching with death certificates from the Mumbai Municipal death register and by active methods such as telephone enquiry, reply-paid postal enquiry, house visits and scrutiny of case records. Of the 1905 (675 larynx and 1230 lung) eligible cases for analysis, 1480 were dead (450 larynx and 1030 lung) and 425 were alive (225 larynx and 200 lung). The overall 5-year observed and relative survival rates for laryngeal cancers were 29.1% and 36.4%, and for lung cancers were 12.5% and 15.9% respectively. On multivariate analysis, age, treatment and clinical extent of disease emerged as independent predictors of survival with both cancers. People aged 55 years and above had a relative risk of four or more for laryngeal cancer and 2.3 times and more for lung cancer death as compared to those aged less than 35 years. Early detection and prompt treatment should improve overall survival from lung as well as laryngeal cancer.
Ma, X-M; Sun, X; Yang, G-W; Yu, M-W; Zhang, G-L; Yu, J; Zhang, Y; Wang, X-M
2017-10-01
The platelet-to-lymphocyte ratio (PLR) is a predictive clinical biomarker for different cancers. However, the results of several studies investigating the association between the PLR and the prognosis of ovarian cancer have been inconclusive. Therefore, there is a need to conduct a meta-analysis to estimate the prognostic value of the PLR in ovarian cancer. We searched the EMBASE, Medline, PubMed, and Web of Science databases to identify clinical studies that had evaluated the association between the PLR and ovarian cancer prognosis. Outcomes evaluated included overall survival (OS) and progression-free survival (PFS). We also analyzed PLR differences between malignant ovarian masses and the controls. Twelve relevant studies that comprised 2340 patients were selected for the meta-analysis. The results revealed that elevated PLR was significantly associated with poor OS (hazard ratio (HR) 1.63, 95% confidence interval (CI) 1.05-2.56, p < 0.01) and PFS (HR 1.61, 95% CI 1.03-2.51, p < 0.01). The PLRs in malignant cases were higher than in controls (mean difference = 63.57, 95% CI 39.47-87.66, p < 0.00001). An elevated PLR is associated with poor prognosis in patients with ovarian cancer. The PLR could be employed as a prognostic marker in patients with ovarian cancer.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kim, Hayeon, E-mail: kimh2@upmc.edu; Rajagopalan, Malolan S.; Beriwal, Sushil
Purpose: Stereotactic body radiation therapy (SBRT) has been proposed for the palliation of painful vertebral bone metastases because higher radiation doses may result in superior and more durable pain control. A phase III clinical trial (Radiation Therapy Oncology Group 0631) comparing single fraction SBRT with single fraction external beam radiation therapy (EBRT) in palliative treatment of painful vertebral bone metastases is now ongoing. We performed a cost-effectiveness analysis to compare these strategies. Methods and Materials: A Markov model, using a 1-month cycle over a lifetime horizon, was developed to compare the cost-effectiveness of SBRT (16 or 18 Gy in 1 fraction)more » with that of 8 Gy in 1 fraction of EBRT. Transition probabilities, quality of life utilities, and costs associated with SBRT and EBRT were captured in the model. Costs were based on Medicare reimbursement in 2014. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and effectiveness was measured in quality-adjusted life years (QALYs). To account for uncertainty, 1-way, 2-way and probabilistic sensitivity analyses were performed. Strategies were evaluated with a willingness-to-pay (WTP) threshold of $100,000 per QALY gained. Results: Base case pain relief after the treatment was assumed as 20% higher in SBRT. Base case treatment costs for SBRT and EBRT were $9000 and $1087, respectively. In the base case analysis, SBRT resulted in an ICER of $124,552 per QALY gained. In 1-way sensitivity analyses, results were most sensitive to variation of the utility of unrelieved pain; the utility of relieved pain after initial treatment and median survival were also sensitive to variation. If median survival is ≥11 months, SBRT cost <$100,000 per QALY gained. Conclusion: SBRT for palliation of vertebral bone metastases is not cost-effective compared with EBRT at a $100,000 per QALY gained WTP threshold. However, if median survival is ≥11 months, SBRT costs ≤$100,000 per QALY gained, suggesting that selective SBRT use in patients with longer expected survival may be the most cost-effective approach.« less
Inflammation and white matter degeneration persist for years after a single traumatic brain injury.
Johnson, Victoria E; Stewart, Janice E; Begbie, Finn D; Trojanowski, John Q; Smith, Douglas H; Stewart, William
2013-01-01
A single traumatic brain injury is associated with an increased risk of dementia and, in a proportion of patients surviving a year or more from injury, the development of hallmark Alzheimer's disease-like pathologies. However, the pathological processes linking traumatic brain injury and neurodegenerative disease remain poorly understood. Growing evidence supports a role for neuroinflammation in the development of Alzheimer's disease. In contrast, little is known about the neuroinflammatory response to brain injury and, in particular, its temporal dynamics and any potential role in neurodegeneration. Cases of traumatic brain injury with survivals ranging from 10 h to 47 years post injury (n = 52) and age-matched, uninjured control subjects (n = 44) were selected from the Glasgow Traumatic Brain Injury archive. From these, sections of the corpus callosum and adjacent parasaggital cortex were examined for microglial density and morphology, and for indices of white matter pathology and integrity. With survival of ≥3 months from injury, cases with traumatic brain injury frequently displayed extensive, densely packed, reactive microglia (CR3/43- and/or CD68-immunoreactive), a pathology not seen in control subjects or acutely injured cases. Of particular note, these reactive microglia were present in 28% of cases with survival of >1 year and up to 18 years post-trauma. In cases displaying this inflammatory pathology, evidence of ongoing white matter degradation could also be observed. Moreover, there was a 25% reduction in the corpus callosum thickness with survival >1 year post-injury. These data present striking evidence of persistent inflammation and ongoing white matter degeneration for many years after just a single traumatic brain injury in humans. Future studies to determine whether inflammation occurs in response to or, conversely, promotes white matter degeneration will be important. These findings may provide parallels for studying neurodegenerative disease, with traumatic brain injury patients serving as a model for longitudinal investigations, in particular with a view to identifying potential therapeutic interventions.
Catovsky, D; Richards, S; Matutes, E; Oscier, D; Dyer, M J S; Bezares, R F; Pettitt, A R; Hamblin, T; Milligan, D W; Child, J A; Hamilton, M S; Dearden, C E; Smith, A G; Bosanquet, A G; Davis, Z; Brito-Babapulle, V; Else, M; Wade, R; Hillmen, P
2007-07-21
Previous studies of patients with chronic lymphocytic leukaemia reported high response rates to fludarabine combined with cyclophosphamide. We aimed to establish whether this treatment combination provided greater survival benefit than did chlorambucil or fludarabine. 777 patients with chronic lymphocytic leukaemia requiring treatment were randomly assigned to fludarabine (n=194) or fludarabine plus cyclophosphamide (196) for six courses, or chlorambucil (387) for 12 courses. The primary endpoint was overall survival, with secondary endpoints of response rates, progression-free survival, toxic effects, and quality of life. Analysis was by intention to treat. This study is registered as an International Standard Randomised Controlled Trial, number NCT 58585610. There was no significant difference in overall survival between patients given fludarabine plus cyclophosphamide, fludarabine, or chlorambucil. Complete and overall response rates were better with fludarabine plus cyclophosphamide than with fludarabine (complete response rate 38%vs 15%, respectively; overall response rate 94%vs 80%, respectively; p<0.0001 for both comparisons), which were in turn better than with chlorambucil (complete response rate 7%, overall response rate 72%; p=0.006 and 0.04, respectively). Progression-free survival at 5 years was significantly better with fludarabine plus cyclophosphamide (36%) than with fludarabine (10%) or chlorambucil (10%; p<0.00005). Fludarabine plus cyclophosphamide was the best combination for all ages, including patients older than 70 years, and in prognostic groups defined by immunoglobulin heavy chain gene (V(H)) mutation status and cytogenetics, which were tested in 533 and 579 cases, respectively. Patients had more neutropenia and days in hospital with fludarabine plus cyclophosphamide, or fludarabine, than with chlorambucil. There was less haemolytic anaemia with fludarabine plus cyclophosphamide (5%) than with fludarabine (11%) or chlorambucil (12%). Quality of life was better for responders, but preliminary analyses showed no significant difference between treatments. A meta-analysis of these data and those of two published phase III trials showed a consistent benefit for the fludarabine plus cyclophosphamide regimen in terms of progression-free survival. Fludarabine plus cyclophosphamide should now become the standard treatment for chronic lymphocytic leukaemia and the basis for new protocols that incorporate monoclonal antibodies.
Graham, Frances F; Harte, David Jg
2017-05-12
To investigate a possible link between liquefaction dust exposure and the noticeable increase in legionellosis cases in response to major earthquakes in 2010 and 2011 that resulted in widespread soil disturbance (liquefaction) in parts of Christchurch, New Zealand. We culture tested liquefaction-affected soil for Legionella spp. in the six months following the first earthquake in 2010. Thirty silt samples were collected randomly from locations within Christchurch's metropolitan area that were affected by liquefaction. The samples were tested to determine the presence of Legionella using qualitative and quantitative methods. Liquefaction-affected soil samples from three sites were further subjected to particle size distribution analysis and determination of major oxides. A controlled field study was established using six silt samples and one control (commercial compost), seeded with a wild-type strain of Legionella bozemanae serogroup (sg) 1 and persistence monitored over a 60-day period by culturing for the presence of Legionella. Dry matter determinations were undertaken so that total Legionella could be calculated on a dry weight basis. Legionella bacteria were undetectable after day one in the silt samples. However, L. bozemanae sg1 was detected in the control sample for the entire study period. This study showed that the liquefaction-affected soil could not contribute directly to the observed increase in legionellosis cases after the earthquakes due to its inability to support growth and survival of the Legionella bacteria.
An inherited NBN mutation is associated with poor prognosis prostate cancer
Cybulski, C; Wokołorczyk, D; Kluźniak, W; Jakubowska, A; Górski, B; Gronwald, J; Huzarski, T; Kashyap, A; Byrski, T; Dębniak, T; Gołąb, A; Gliniewicz, B; Sikorski, A; Świtała, J; Borkowski, T; Borkowski, A; Antczak, A; Wojnar, Ł; Przybyła, J; Sosnowski, M; Małkiewicz, B; Zdrojowy, R; Sikorska-Radek, P; Matych, J; Wilkosz, J; Różański, W; Kiś, J; Bar, K; Bryniarski, P; Paradysz, A; Jersak, K; Niemirowicz, J; Słupski, P; Jarzemski, P; Skrzypczyk, M; Dobruch, J; Domagała, P; Narod, S A; Lubiński, J
2013-01-01
Background: To establish the contribution of eight founder alleles in three DNA damage repair genes (BRCA1, CHEK2 and NBS1) to prostate cancer in Poland, and to measure the impact of these variants on survival among patients. Methods: Three thousand seven hundred fifty men with prostate cancer and 3956 cancer-free controls were genotyped for three founder alleles in BRCA1 (5382insC, 4153delA, C61G), four alleles in CHEK2 (1100delC, IVS2+1G>A, del5395, I157T), and one allele in NBS1 (657del5). Results: The NBS1 mutation was detected in 53 of 3750 unselected cases compared with 23 of 3956 (0.6%) controls (odds ratio (OR)=2.5; P=0.0003). A CHEK2 mutation was seen in 383 (10.2%) unselected cases and in 228 (5.8%) controls (OR=1.9; P<0.0001). Mutation of BRCA1 (three mutations combined) was not associated with the risk of prostate cancer (OR=0.9; P=0.8). In a subgroup analysis, the 4153delA mutation was associated with early-onset (age ⩽60 years) prostate cancer (OR=20.3, P=0.004). The mean follow-up was 54 months. Mortality was significantly worse for carriers of a NBS1 mutation than for non-carriers (HR=1.85; P=0.008). The 5-year survival for men with an NBS1 mutation was 49%, compared with 72% for mutation-negative cases. Conclusion: A mutation in NBS1 predisposes to aggressive prostate cancer. These data are relevant to the prospect of adapting personalised medicine to prostate cancer prevention and treatment. PMID:23149842
Estimation of the cure rate in Iranian breast cancer patients.
Rahimzadeh, Mitra; Baghestani, Ahmad Reza; Gohari, Mahmood Reza; Pourhoseingholi, Mohamad Amin
2014-01-01
Although the Cox's proportional hazard model is the popular approach for survival analysis to investigate significant risk factors of cancer patient survival, it is not appropriate in the case of log-term disease free survival. Recently, cure rate models have been introduced to distinguish between clinical determinants of cure and variables associated with the time to event of interest. The aim of this study was to use a cure rate model to determine the clinical associated factors for cure rates of patients with breast cancer (BC). This prospective cohort study covered 305 patients with BC, admitted at Shahid Faiazbakhsh Hospital, Tehran, during 2006 to 2008 and followed until April 2012. Cases of patient death were confirmed by telephone contact. For data analysis, a non-mixed cure rate model with Poisson distribution and negative binomial distribution were employed. All analyses were carried out using a developed Macro in WinBugs. Deviance information criteria (DIC) were employed to find the best model. The overall 1-year, 3-year and 5-year relative survival rates were 97%, 89% and 74%. Metastasis and stage of BC were the significant factors, but age was significant only in negative binomial model. The DIC also showed that the negative binomial model had a better fit. This study indicated that, metastasis and stage of BC were identified as the clinical criteria for cure rates. There are limited studies on BC survival which employed these cure rate models to identify the clinical factors associated with cure. These models are better than Cox, in the case of long-term survival.
Chen, Zhiqiang; Pu, Liyong; Gao, Wen; Zhang, Long; Han, Guoyong; Zhu, Qin; Li, Xiangcheng; Wu, Jindao; Wang, Xuehao
2017-04-25
Although the prognostic value of marital status has been implicated in many cancers, its prognostic impact on cholangiocarcinoma has not yet been determined. The aim of this study was to examine the association between marital status and cholangiocarcinoma survival. We included 8,776 extrahepatic cholangiocarcinoma cases and 1,352 intrahepatic cholangiocarcinoma cases between 1973 and 2013 from the Surveillance, Epidemiology, and End Results database. We found widowed patients were more likely to be female, aged more than 70, and from low income areas. Multivariate analysis indicated that marital status was an independent prognostic factor for extrahepatic cholangiocarcinoma patients. Subgroup analysis suggested the widowed status independently predicted poor survival at regional stage and in older patients with intrahepatic cholangiocarcinoma. To conclude, marital status is a valuable prognostic factor in cholangiocarcinoma, and widowed patients are at greater risk of death than others.
Markovina, Stephanie; Youssef, Fady; Roy, Amit; Aggarwal, Sonya; Khwaja, Shariq; DeWees, Todd; Tan, Benjamin; Hunt, Steven; Myerson, Robert J; Chang, Daniel T; Parikh, Parag J; Olsen, Jeffrey R
2017-10-01
To compare treatment and toxicity outcomes between a phase 2 institutional trial of near total neoadjuvant therapy (nTNT) for locally advanced rectal cancer and a similar historical control cohort treated at Washington University in St. Louis with the current US standard of care, defined as neoadjuvant chemoradiotherapy (NCRT), total mesorectal excision (TME), and adjuvant FOLFOX chemotherapy; to expand the comparison to an additional institution, patients treated with similar NCRT at Stanford University were included. Sixty-nine patients with cT3-4N0-2M0 rectal adenocarcinoma enrolled on the Washington University in St. Louis phase 2 study of nTNT were included for analysis. Patients treated at the same institution with conventional NCRT and adjuvant FOLFOX were matched for exact cTNM stage. Forty-one patients treated with NCRT at Stanford University were included in a second analysis. Kaplan-Meier analysis with log-rank test was used to compare local control, distant metastasis-free survival, disease-free survival, and overall survival. Median follow-up was 49 and 54 months for nTNT and NCRT, respectively. Pathologic complete response and T-downstaging rates were 28% versus 16% (P=.21) and 75% versus 41% (P<.001) in the nTNT and NCRT cohorts, respectively. Three-year disease-free survival (85% vs 68%, P=.032) was significantly better in the nTNT group. Actuarial 3-year local control (92% vs 96%, P=.36) and overall survival (96% vs 88%, P=.67) were similar. The Stanford cohort had significantly lower clinical stage. After controlling for clinical stage, age, tumor location, institution, and number of chemotherapy cycles, nTNT treatment remained significantly associated with lower risk of recurrence (P=.006). Patients treated with nTNT had higher T-downstaging and superior distant metastasis-free survival and disease-free survival compared with conventional NCRT when matched for tumor location and exact cTNM stage. Near total neoadjuvant therapy remained a significant multivariate predictor for improved outcome when including patients treated with NCRT at another institution. Published by Elsevier Inc.
Bădulescu, Fl; Bădulescu, Adriana; Crişan, Anda; Popescu, Florina Carmen
2013-01-01
A prospective study made by authors was initiated in 2000 in order to analyze differences in terms of response rate, overall survival and progression free survival for patients with advanced head and neck carcinoma treated with radiotherapy vs. radiochemotherapy, respectively and to analyze the role of modern molecular biomarkers in the prognosis of these patients (p53, EGFR and Ki67). It was detected one significant difference appeared between the two groups for response rate (p<0.0001) and median overall survival [18.8 months in Group A and 17.2 months in Group B, with a hazard ratio for survival of 0.88 (95% CI, 0.75-1.12, p<0.0001]. Progression free survival was not significant different between these two groups [6.9 months for Group A and 7.2 months for Group B, p=0.3179]. Multivariate analysis by sex, age, TNM stage, site of disease, revealed TNM stage and site of disease as clinical phenotypes with predictive value. Also, the molecular biomarkers p53, EGFR and Ki67 have a prognostic significance in head and neck cancer in addition to the established clinical prognostic factors such as the stage, site of the tumor and the type of treatment. Because of material reasons, we decided to carry out the immunohistochemical marking in the group of patients who were radiochemotherapy-treated and the results of multivariate analysis reached statistical significance threshold in terms of response rate to treatment, overall survival and disease-free interval. Furthermore, immunohistochemical examination was not performed for patients with rhinopharyngeal carcinoma with marked radiochemosensibility and reduced tumor aggressiveness reflected in significantly better therapeutic outcomes by treatment response rate, overall survival and disease free interval. In the present study of the 93 cases that underwent immunohistochemical staining for EGFR, the majority (66 cases) showed a positive reaction for this marker, in 36 cases are highly immunohistochemical staining, and in 30 cases were weakly positive. In addition, cell proliferation was intense in 26 cases in which Ki67 index was greater than 45%, p53 protein expression was positive in 18 cases, but the majority (22) of cases showed a positive reaction for this marker; index was greater than 55%, and in the most (22) cases p53 protein was not expressed. Radio/chemoradiotherapy regimen associated with molecular anti-EGFR target therapy is standard therapy in advanced squamous head and neck carcinoma.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Duprez, Frederic, E-mail: frederic.duprez@ugent.be; Madani, Indira; Morbee, Lieve
2012-05-01
Purpose: To report late ocular (primary endpoint) and other toxicity, disease control, and survival (secondary endpoints) after intensity-modulated radiotherapy (IMRT) for sinonasal tumors. Methods and Materials: Between 1998 and 2009, 130 patients with nonmetastatic sinonasal tumors were treated with IMRT at Ghent University Hospital. Prescription doses were 70 Gy (n = 117) and 60-66 Gy (n = 13) at 2 Gy per fraction over 6-7 weeks. Most patients had adenocarcinoma (n = 82) and squamous cell carcinoma (n = 23). One hundred and one (101) patients were treated postoperatively. Of 17 patients with recurrent tumors, 9 were reirradiated. T-stages weremore » T1-2 (n = 39), T3 (n = 21), T4a (n = 38), and T4b (n = 22). Esthesioneuroblastoma was staged as Kadish A, B, and C in 1, 3, and 6 cases, respectively. Results: Median follow-up was 52, range 15-121 months. There was no radiation-induced blindness in 86 patients available for late toxicity assessment ({>=}6 month follow-up). We observed late Grade 3 tearing in 10 patients, which reduced to Grade 1-2 in 5 patients and Grade 3 visual impairment because of radiation-induced ipsilateral retinopathy and neovascular glaucoma in 1 patient. There was no severe dry eye syndrome. The worst grade of late ocular toxicity was Grade 3 (n = 11), Grade 2 (n = 31), Grade 1 (n = 33), and Grade 0 (n = 11). Brain necrosis and osteoradionecrosis occurred in 6 and 1 patients, respectively. Actuarial 5-year local control and overall survival were 59% and 52%, respectively. On multivariate analysis local control was negatively affected by cribriform plate and brain invasion (p = 0.044 and 0.029, respectively) and absence of surgery (p = 0.009); overall survival was negatively affected by cribriform plate and orbit invasion (p = 0.04 and <0.001, respectively) and absence of surgery (p = 0.001). Conclusions: IMRT for sinonasal tumors allowed delivering high doses to targets at minimized ocular toxicity, while maintaining disease control and survival. Avoidance of severe dry eye syndrome and radiation-induced blindness suggests IMRT as a standard treatment for sinonasal tumors.« less
A protein and mRNA expression-based classification of gastric cancer.
Setia, Namrata; Agoston, Agoston T; Han, Hye S; Mullen, John T; Duda, Dan G; Clark, Jeffrey W; Deshpande, Vikram; Mino-Kenudson, Mari; Srivastava, Amitabh; Lennerz, Jochen K; Hong, Theodore S; Kwak, Eunice L; Lauwers, Gregory Y
2016-07-01
The overall survival of gastric carcinoma patients remains poor despite improved control over known risk factors and surveillance. This highlights the need for new classifications, driven towards identification of potential therapeutic targets. Using sophisticated molecular technologies and analysis, three groups recently provided genetic and epigenetic molecular classifications of gastric cancer (The Cancer Genome Atlas, 'Singapore-Duke' study, and Asian Cancer Research Group). Suggested by these classifications, here, we examined the expression of 14 biomarkers in a cohort of 146 gastric adenocarcinomas and performed unsupervised hierarchical clustering analysis using less expensive and widely available immunohistochemistry and in situ hybridization. Ultimately, we identified five groups of gastric cancers based on Epstein-Barr virus (EBV) positivity, microsatellite instability, aberrant E-cadherin, and p53 expression; the remaining cases constituted a group characterized by normal p53 expression. In addition, the five categories correspond to the reported molecular subgroups by virtue of clinicopathologic features. Furthermore, evaluation between these clusters and survival using the Cox proportional hazards model showed a trend for superior survival in the EBV and microsatellite-instable related adenocarcinomas. In conclusion, we offer as a proposal a simplified algorithm that is able to reproduce the recently proposed molecular subgroups of gastric adenocarcinoma, using immunohistochemical and in situ hybridization techniques.
Wang, Yinqing; Cai, Ranze; Wang, Rui; Wang, Chunhua; Chen, Chunmei
2018-06-01
This is a retrospective study.The aim of this study was to illustrate the survival outcomes of patients with classic ependymoma (CE) and identify potential prognostic factors.CE is the most common category of spinal ependymomas, but few published studies have discussed predictors of the survival outcome.A Boolean search of the PubMed, Embase, and OVID databases was conducted by 2 investigators independently. The objects were intramedullary grade II ependymoma according to 2007 WHO classification. Univariate Kaplan-Meier analysis and Log-Rank tests were performed to identify variables associated with progression-free survival (PFS) or overall survival (OS). Multivariate Cox regression was performed to assess hazard ratios (HRs) with 95% confidence intervals (95% CIs). Statistical analysis was performed by SPSS version 23.0 (IBM Corp.) with statistical significance defined as P < .05.A total of 35 studies were identified, including 169 cases of CE. The mean follow-up time across cases was 64.2 ± 51.5 months. Univariate analysis showed that patients who had undergone total resection (TR) had better PFS and OS than those with subtotal resection (STR) and biopsy (P = .002, P = .004, respectively). Within either univariate or multivariate analysis (P = .000, P = .07, respectively), histological type was an independent prognostic factor for PFS of CE [papillary type: HR 0.002, 95% CI (0.000-0.073), P = .001, tanycytic type: HR 0.010, 95% CI (0.000-0.218), P = .003].It was the first integrative analysis of CE to elucidate the correlation between kinds of factors and prognostic outcomes. Definite histological type and safely TR were foundation of CE's management. 4.
Toyomaki, Haruya; Sekiguchi, Satoshi; Sasaki, Yosuke; Sueyoshi, Masuo; Makita, Kohei
2018-02-01
The objective of this study was to investigate factors that caused rapid spread during the early phase of the porcine epidemic diarrhea (PED) epidemic in Japan in 2013 and 2014. Anonymized datasets from all pig farms were provided by Kagoshima (709 farms) and Miyazaki Prefectures (506 farms). Semi-parametric survival analysis was conducted using the first 180 days from the first case on December 3, 2013 in Kagoshima Prefecture. To compare the hazard between different farm management types, univariable survival analysis was conducted. As farm sizes varied among different farm types, bivariable survival analysis was conducted for farm size categories and farm density per km 2 for each management type. A case-control study using a postal questionnaire survey was conducted in September 2014, and risk factor analysis was performed using generalized linear models with binomial errors. The hazard was significantly higher in farrow-to-finish farms than fattening farms [hazard ratio (HR) = 1.6, p < 0.01], but was not significantly different between reproduction and fattening farms (HR = 1.3, p = 0.16). In separate bivariable survival analyses for each farm type, large- and middle-scale farms had higher hazard than small-scale farms in fattening (HR = 5.8 and 2.6, respectively, both p < 0.01) and reproduction farms (HR = 4.0 and 3.6, respectively, both p < 0.01). In farrow-to-finish farms, large-scale farms had higher hazard than small-scale farms (HR = 2.8, p < 0.01), and higher farm density per km 2 was also a risk factor (HR = 7.6, p < 0.01). In the case-control study, questionnaires were returned from 78 PED virus-infected and 91 non-infected farms. The overall response rate was 34%. Risk factors of the final model were occurrence of porcine reproductive and respiratory syndrome in the past 5 years [odds ratio (OR) = 1.97, 95% confidence interval (CI): 0.97-4.00, p = 0.054], use of a common compost station (OR = 2.51, 95%CI: 1.08-5.83, p = 0.03), and use of a pig excrement disposal service (OR = 2.64, 95%CI: 1.05-6.63, p = 0.04). High hazard in farrow-to-finish farms suggested transmission from slaughterhouses to susceptible suckling piglets. Hazard associated with large-scale farms and high density might be due to frequent vehicle entrance and transmission by roads. Improvement of farm hygiene management and avoidance of risky practices associated with contact with pig excrement were keys in preventing invasion of PED virus to a farm. Copyright © 2017 Elsevier B.V. All rights reserved.
Rades, Dirk; Lohynska, Radka; Veninga, Theo; Stalpers, Lukas J A; Schild, Steven E
2007-12-01
The majority of breast cancer patients with brain metastases receive whole-brain radiotherapy (WBRT) and have a survival of only a few months. A short WBRT regimen would be preferable if it provides survival that is similar to that achieved with longer programs. This retrospective study compared survival and local control within the brain resulting from short-course WBRT with longer programs in 207 breast cancer patients. Sixty-nine patients treated with 5 fractions of 4 grays (Gy) each given within 5 days were compared with 138 patients treated with 10 fractions of 3 Gy each given over 2 weeks or 20 fractions of 2 Gy each given over 4 weeks. Six additional potential prognostic factors were investigated: age, Karnofsky performance score (KPS), number of brain metastases, the presence of extracranial metastases, interval from tumor diagnosis to WBRT, and recursive partitioning analysis (RPA) class. On univariate analysis, the WBRT regimen was not found to be associated with survival (P=.254) or local control (P=.397). Improved survival was associated with a KPS>70 (P<.001), single brain metastasis (P=.023), the absence of extracranial metastases (P<.001), and lower RPA class (P<.001). On multivariate analysis, which was performed without RPA class because this is a confounding variable, KPS (relative risk [RR] of 4.00; P<.001) and the presence of extracranial metastases (RR of 1.54; P=.024) maintained statistical significance. On univariate analysis, local control was associated with KPS (P<.001) and RPA class (P<.001). On multivariate analysis, local control was found to be associated with a KPS>70 (RR of 5.75; P<.001). Short-course WBRT with 5 fractions of 4 Gy each resulted in survival and local control that were similar to longer programs in breast cancer patients with brain metastases. The dose of 5 fractions of 4 Gy each appears preferable for the majority of these patients because it is less time consuming and more convenient. Copyright (c) 2007 American Cancer Society.
Alarcón, Graciela S; McGwin, Gerald; Bertoli, Ana M; Fessler, Barri J; Calvo-Alén, Jaime; Bastian, Holly M; Vilá, Luis M; Reveille, John D
2007-09-01
In patients with systemic lupus erythematosus (SLE), hydroxychloroquine prevents disease flares and damage accrual and facilitates the response to mycophenolate mofetil in those with renal involvement. A study was undertaken to determine whether hydroxychloroquine also exerts a protective effect on survival. Patients with SLE from the multiethnic LUMINA (LUpus in MInorities: NAture vs nurture) cohort were studied. A case-control study was performed within the context of this cohort in which deceased patients (cases) were matched for disease duration (within 6 months) with alive patients (controls) in a proportion of 3:1. Survival was the outcome of interest. Propensity scores were derived by logistic regression to adjust for confounding by indication as patients with SLE with milder disease manifestations are more likely to be prescribed hydroxychloroquine. A conditional logistic regression model was used to estimate the risk of death and hydroxychloroquine use with and without the propensity score as the adjustment variable. There were 608 patients, of whom 61 had died (cases). Hydroxychloroquine had a protective effect on survival (OR 0.128 (95% CI 0.054 to 0.301 for hydroxychloroquine alone and OR 0.319 (95% CI 0.118 to 0.864) after adding the propensity score). As expected, the propensity score itself was also protective. Hydroxychloroquine, which overall is well tolerated by patients with SLE, has a protective effect on survival which is evident even after taking into consideration the factors associated with treatment decisions. This information is of importance to all clinicians involved in the care of patients with SLE.
Results of Liver Transplantation With Donors Older than 75 Years: A Case-Control Study.
León Díaz, F J; Fernández Aguilar, J L; Sánchez Pérez, B; Montiel Casado, C; Aranda Narváez, J M; Pérez Daga, J A; Suárez Muñoz, M Á; Santoyo Santoyo, J
2016-09-01
The inclusion of elderly donors can increase the pool of organs available for transplantation. The objective of this study was to compare clinical outcomes and survival rates of patients who received livers from donors aged ≥75 years versus younger donors. We considered all liver transplantations performed in our unit from January 2006 to January 2015. Thirty-two patients received a liver from a cadaveric donor aged ≥75 years (study group), and their outcomes were compared with those of patients who received a liver from a younger donor (control group) immediately before and after each transplantation in the study group. This is a descriptive, retrospective, case-control study carried out to analyze the characteristics of donors and recipients as well as the clinical course and survival of recipients of older and younger donors. Statistically significant differences were observed according to donors' age (53.3 ± 13.6 vs 79 ± 3.4 years; P < .001). In total, 6.2% of the recipients of a liver from a donor aged <75 years required retransplantation versus 15.6% of recipients of donors ≥75 years. Patient survivals at 1, 3, and 5 years, respectively, were 89%, 78.6%, and 74.5% for recipients of donors <75 years versus 83.4%, 79.4%, and 59.6% for the study group. Livers from older donors can be safely used for transplantation with acceptable survival rates. However, survival rates are lower for recipients of livers from older donors compared with younger donors, and survival only increased with retransplantation. Copyright © 2016 Elsevier Inc. All rights reserved.
Matsuo, Koji; Machida, Hiroko; Shoupe, Donna; Melamed, Alexander; Muderspach, Laila I; Roman, Lynda D; Wright, Jason D
2016-10-01
To characterize contributing factors for ovarian conservation during surgical treatment for endometrial cancer and to examine the association of ovarian conservation on survival of young women with early-stage, low-grade tumors. This was a population-based study using the Surveillance, Epidemiology, and End Results program to identify surgically treated stage I type I (grade 1-2 endometrioid histology) endometrial cancer cases diagnosed between 1983 and 2012 (N=86,005). Multivariable models were used to identify independent factors for ovarian conservation. Survival outcomes and cause of death were examined for women aged younger than 50 with stage I type I endometrial cancer who underwent ovarian conservation (1,242 among 12,860 women [9.7%]). On multivariable analysis, age younger than 50 years, grade 1 endometrioid histology, and tumor size 2.0 cm or less were noted to be independent factors for ovarian conservation (all, P<.001). For 9,110 women aged younger than 50 years with stage I grade 1 tumors, cause-specific survival was similar between ovarian conservation and oophorectomy cases (20-year rates 98.9% compared with 97.7%, P=.31), whereas overall survival was significantly higher in ovarian conservation cases than oophorectomy cases (88.8% compared with 82.0%, P=.011). On multivariable analysis, ovarian conservation remained an independent prognostic factor for improved overall survival (adjusted hazard ratio 0.73, 95% confidence interval [CI] 0.54-0.98, P=.036) and was independently associated with a lower cumulative risk of death resulting from cardiovascular disease compared with oophorectomy (20-year rates, 2.3% compared with 3.7%, adjusted hazard ratio 0.40, 95% CI 0.17-0.91, P=.029). Contrary, cause-specific survival (20-year rates 94.6% compared with 96.1%, P=.68) and overall survival (81.0% compared with 80.6%, P=.91) were similar between ovarian conservation and oophorectomy among 3,750 women aged younger than 50 years with stage I grade 2 tumors. Ovarian conservation is performed in less than 10% of young women with stage I type I endometrial cancer. Ovarian conservation is associated with decreased mortality in young women with stage I grade 1 tumors.
Gaudy-Marqueste, C; Dussouil, A S; Carron, R; Troin, L; Malissen, N; Loundou, A; Monestier, S; Mallet, S; Richard, M A; Régis, J M; Grob, J J
2017-10-01
Targeted therapy (TT) and immunotherapies (ITs) have dramatically improved survival in metastatic melanoma (MM). However, their efficacy on brain metastasis (BM) remains limited and poorly documented. Retrospective cohort of consecutive MM patients (pts) with BMs, all systematically upfront treated by Gamma-Knife (GK) at first BM and retreated in case of new BMs, from 2010 to 2015 at the time when ipilimumab BRAF ± MEK inhibitors and anti-PD1 were introduced in practice. Survival after 1st GK (OS GK1 ) according to prognostic factors and treatment. Among 179 consecutive pts treated by GK, 109 received IT and/or TT after the 1st GK. Median OS GK1 was 10.95 months and 1- and 2-year survival rates were 49.5% and 27.4%, respectively, versus a median overall survival (OS) of 2.29 months (p < .001) in those who did not receive IT or TT. In pts who initially had a single BM, median OS and 1- and 2-year survival rates were 14.46 months, 66.7% and 43.4%, respectively; in pts with 2-3 BMs: 8.85 months, 46.4% and 31%, respectively; in pts with >3 BMs: 7.25 months, 37.2% and 11.9%, respectively. Multivariate analysis for OS GK1 confirmed that IT and TT were significantly and highly protective. Best OS GK1 was observed in BRAF-wild-type pts receiving anti-PD1 or in BRAF-mutated pts receiving BRAF-inhibitors and anti-PD1 (12.26 and 14.82 months, respectively). In real-life MM pts with BMs, a strategy aiming at controlling BM with GK together with TT and/or TT seems to achieve unprecedented survival rates. Copyright © 2017 Elsevier Ltd. All rights reserved.
Romano, Francesco Jacopo; Guadagno, Elia; Solari, Domenico; Borrelli, Giorgio; Pignatiello, Sara; Cappabianca, Paolo; Del Basso De Caro, Marialaura
2018-06-01
Glioblastoma is one of the most malignant cancers, with a distinguishing dismal prognosis: surgery followed by chemo- and radiotherapy represents the current standard of care, and chemo- and radioresistance underlie disease recurrence and short overall survival of patients suffering from this malignancy. ATM is a kinase activated by autophosphorylation upon DNA doublestrand breaks arising from errors during replication, byproducts of metabolism, chemotherapy or ionizing radiations; TP53 is one of the most popular tumor suppressor, with a preeminent role in DNA damage response and repair. To study the effects of the immunohistochemical expression of p-ATM and p53 in glioblastoma patients, 21 cases were retrospectively examined. In normal brain tissue, p-ATM was expressed only in neurons; conversely, in tumors cells, the protein showed a variable cytoplasmic expression (score: +,++,+++), with being completely undetectable in three cases. Statistical analysis revealed that high p-ATM score (++/+++) strongly correlated to shorter survival (P = 0.022). No difference in overall survival was registered between p53 normally expressed (NE) and overexpressed (OE) glioblastoma patients (P = 0.669). Survival analysis performed on the results from combined assessment of the two proteins showed that patients with NE p53 /low pATM score had longer overall survival than the NE p53/ high pATM score counterpart. Cox-regression analysis confirmed this finding (HR = 0.025; CI 95% = 0.002-0.284; P = 0.003). Our study outlined the immunohistochemical expression of p-ATM/p53 in glioblastomas and provided data on their possible prognostic/predictive of response role. A "non-oncogene addiction" to ATM for NEp53 glioblastoma could be postulated, strengthening the rationale for development of ATM inhibiting drugs. © 2018 Wiley Periodicals, Inc.
Li, Ziyu; Wang, Yinkui; Shan, Fei; Ying, Xiangji; Wu, Zhouqiao; Xue, Kan; Miao, Rulin; Zhang, Yan; Ji, Jiafu
2018-05-10
This study aims to evaluate the new ypTNM staging system in Chinese gastric cancer patients. We conducted retrospective survival and regression analyses using a database of gastric cancer patients who underwent neoadjuvant chemotherapy at the Peking University Cancer Hospital and Institute from January 2007 to January 2015. A total of 473 patients were included in the study with 28 pathological complete response (pCR) cases, 3 ypT0N1 cases, 65 stage I cases, 126 stage II cases, and 251 stage III cases. The pCR cases had similar survival to stage I patients (p > 0.05). The 3-year disease-free survival (DFS) and 5-year overall survival (OS) rates of stage I, II and III patients were significantly different (3-year DFS: 89.0, 75.5, and 39.6%, p < 0.001; 5-year OS: 89.6, 65.5, and 36.5%, p = 0.001). Both ypT and ypN are independent predictors of patient survival, while further log-rank tests showed that the ypN stage is of better prognostic value than ypT. Subgrouping analysis revealed that stage III patients of ypT4b and ypN3 had worse survival compared to the rest of stage III cases (p < 0.001). The c-index values of the ypTNM stage and modified ypTNM stage (stage III divided into IIIa and IIIb) were 0.657 and 0.708, respectively (p < 0.001). Our data showed significant differences in survival among gastric cancer patients at different ypTNM stages, indicating its prognostic value in the Chinese population. Further detailed analyses may facilitate the subgrouping of each stage to allow for a more accurate evaluation of disease prognosis in gastric cancer patients.
Prognostic Value of RUNX1 Mutations in AML: A Meta-Analysis
Jalili, Mahdi; Yaghmaie, Marjan; Ahmadvand, Mohammad; Alimoghaddam, Kamran; Mousavi, Seyed Asadollah; Vaezi, Mohammad; Ghavamzadeh, Ardeshir
2018-02-26
The RUNX1 (AML1) gene is a relatively infrequent mutational target in cases of acute myeloid leukemia (AML). Previous work indicated that RUNX1 mutations can have pathological and prognostic implications. To evaluate prognostic value, we conducted a meta-analysis of 4 previous published works with data for survival according to RUNX1 mutation status. Pooled hazard ratios for overall survival and disease-free survival were 1.55 (95% confidence interval (CI) = 1.11–2.15; p-value = 0.01) and 1.76 (95% CI = 1.24–2.52; p-value = 0.002), respectively, for cases positive for RUNX1 mutations. This evidence supports clinical implications of RUNX1 mutations in the development and progression of AML cases and points to the possibility of a distinct category within the newer WHO classification. Though it must be kept in mind that the present work was based on data extracted from observational studies, the findings suggest that the RUNX1 status can contribute to risk-stratification and decision-making in management of AML. Creative Commons Attribution License
Chopra, A S; Wong, N; Ziegler, C P; Morrison, L J
2016-04-01
Physiologic monitoring of resuscitative efforts during cardiac arrest is gaining in importance, as it provides a real-time window into the cellular physiology of patients. The aim of this review is to assess the quality of evidence surrounding the use of physiologic monitoring to guide cardiopulmonary resuscitation (CPR), and to examine whether the evidence demonstrates an improvement in patient outcome when comparing hemodynamic-directed CPR versus standard CPR. Studies were obtained through a search of the PubMed, Embase and Cochrane databases. Peer-reviewed randomized trials, case-control studies, systematic reviews, and cohort studies that titrated CPR to physiologic measures, compared results to standard CPR, and examined patient outcome were included. Six studies met inclusion criteria, with all studies conducted in animal populations. Four studies examined the effects of hemodynamic-directed CPR on survival, with 35/37 (94.6%) animals surviving in the hemodynamic-directed CPR groups and 12/35 (34.3%) surviving in the control groups (p<0.001). Two studies examined the effects of hemodynamic-directed CPR on ROSC, with 22/30 (73.3%) achieving ROSC in the hemodynamic-directed CPR group and 19/30 (63.3%) achieving ROSC in the control group (p=0.344). These results suggest a trend in survival from hemodynamic-directed CPR over standard CPR, however the small sample size and lack of human data make these results of limited value. Future human studies examining hemodynamic-directed CPR versus current CPR standards are needed to enhance our understanding of how to effectively use physiologic measures to improve resuscitation efforts and ultimately incorporate concrete targets into international resuscitation guidelines. Crown Copyright © 2016. Published by Elsevier Ireland Ltd. All rights reserved.
Cordier, A-G; Jani, J C; Cannie, M M; Rodó, C; Fabietti, I; Persico, N; Saada, J; Carreras, E; Senat, M-V; Benachi, A
2015-08-01
To investigate the value of fetal stomach position in predicting postnatal outcome in left-sided congenital diaphragmatic hernia (CDH) with and without fetoscopic endoluminal tracheal occlusion (FETO). This was a retrospective review of CDH cases that were expectantly managed or treated with FETO, assessed from May 2008 to October 2013, in which we graded, on a scale of 1-4, stomach position on the four-chamber view of the heart with respect to thoracic structures. Logistic regression analysis was used to investigate the effect of management center (Paris, Brussels, Barcelona, Milan), stomach grading, observed-to-expected lung area-to-head circumference ratio (O/E-LHR), gestational age at delivery, birth weight in expectantly managed CDH, gestational ages at FETO and at removal and period of tracheal occlusion, on postnatal survival in CDH cases treated with FETO. We identified 67 expectantly managed CDH cases and 47 CDH cases that were treated with FETO. In expectantly managed CDH, stomach position and O/E-LHR predicted postnatal survival independently. In CDH treated with FETO, stomach position and gestational age at delivery predicted postnatal survival independently. In left-sided CDH with or without FETO, stomach position is predictive of postnatal survival. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.
Doherty, Sarah M; Jackman, Louise M; Kirwan, John F; Dunne, Deirdre; O'Connor, Kieran G; Rouse, John M
2016-12-01
The incidence of melanoma is rising worldwide. Current Irish guidelines from the National Cancer Control Programme state suspicious pigmented lesions should not be removed in primary care. There are conflicting guidelines and research advising who should remove possible melanomas. To determine whether initial diagnostic excision biopsy of cutaneous malignant melanoma in primary versus secondary care leads to poorer survival. Analysis of data comprising 7116 cases of cutaneous malignant melanoma from the National Cancer Registry Ireland between January 2002 and December 2011. Single predictor variables were examined by the chi-square or Mann-Whitney U test. The effects of single predictor variables on survival were examined by Cox proportionate hazards modelling and a multivariate Cox model of survival based on excision in a non-hospital setting versus hospital setting was derived with adjusted and unadjusted hazard ratios. Over a 10-year period 8.5% of melanomas in Ireland were removed in a non-hospital setting. When comparing melanoma death between the hospital and non-hospital groups, the adjusted hazard ratio was 1.56 (95%CI: 1.08-2.26); (P = .02), indicating a non-inferior outcome for the melanoma cases initially treated in the non-hospital group, after adjustment for significant covariates. This study suggests that initial excision biopsy carried out in general practice does not lead to a poorer outcome. [Box: see text].
Mycological studies housed in the Apollo 16 microbial ecology evaluation device
NASA Technical Reports Server (NTRS)
Volz, P. A.
1973-01-01
Survival, death, and phenotype count have yielded variation in the number of fungi recovered from the controls and the flight exposed cuvettes during preliminary analysis of postflight first phase data. Also the preliminary analysis was indicative that fungi exposed to specific space flight conditions demonstrated variable survival rates and phenotype counts. Specific space flight conditions included full light space exposure for Chaetomium globosum, exposure at 300- and 254-nanometer wavelengths for Rhodotorula rubra, full light and 280-nanometer wavelength exposure for Trichophyton terrestre, and 254-nanometer wavelength exposure for Saccharomyces cerevisiae. In general, phenotype counts for flight cuvettes and survival rates for control cuvettes were higher compared with the remaining cuvettes.
Genetic polymorphisms in the vitamin D pathway in relation to lung cancer risk and survival
Kong, Jinyu; Xu, Fangxiu; Qu, Jinli; Wang, Yu; Gao, Ming; Yu, Herbert; Qian, Biyun
2015-01-01
Studies have suggested that vitamin D may have protective effects against cancer development or tumor progression. To search for additional evidence, we investigated the role of genetic polymorphisms involved in the vitamin D pathway in non-small cell lung cancer (NSCLC). We evaluated common genetic polymorphisms associated with the vitamin D pathway in relation to NSCLC in a case-control study of 603 newly diagnosed NSCLC patients and 661 matched healthy controls. Seven single nucleotide polymorphisms (SNPs) were genotyped, the expression of CYP27B1 and CYP24A1 were measured in 153 tumor samples and their associations with genotypes and patient survival were also analyzed. In the case-control comparison, we found SNP rs3782130 (CYP27B1), rs7041 (GC), rs6068816 and rs4809957 (CYP24A1) associated with NSCLC risk. The risk of NSCLC was increased with the number of risk alleles. CYP27B1 and CYP24A1 expression were significantly different between tumor and normal tissues in NSCLC. High CYP27B1 expression was associated with better overall survival, and the expression was different by the rs3782130 genotype. The study suggests that some genetic polymorphisms involved in the vitamin D pathway may associate with NSCLC risk, and one of the polymorphisms (rs3782130) may affect gene expression and patient survival. PMID:25544771
Trivia, Ana Letícia; de Carvalho Pinto, Carlos José
2018-01-19
Forensic entomotoxicology investigates the effects of chemical substances in the development of scavenger insects and the reflection on estimating the minimum postmortem interval (PMI). To evaluate the impact of the chemotherapeutic drugs cyclophosphamide (CF) and methotrexate (MTX) on the postembryonic development of Chrysomya megacephala, controlled experiments were performed by rearing the larvae on spiked minced beef with different concentrations of these drugs. The results indicated that CF significantly decreased their developmental rate up to 28 h but had no significant effect on larval and adult sizes, survival rate, and sex ratio, whereas MTX decreased larval and adult sizes, survival rate, and there was a deviation in the expected sex ratio toward females in MTX-exposed larvae but had no significant impact on developmental rate. These negative interference factors should be considered in cases of suspected death of people that have undergone chemotherapy. © 2018 American Academy of Forensic Sciences.
Nusinersen versus Sham Control in Infantile-Onset Spinal Muscular Atrophy.
Finkel, Richard S; Mercuri, Eugenio; Darras, Basil T; Connolly, Anne M; Kuntz, Nancy L; Kirschner, Janbernd; Chiriboga, Claudia A; Saito, Kayoko; Servais, Laurent; Tizzano, Eduardo; Topaloglu, Haluk; Tulinius, Már; Montes, Jacqueline; Glanzman, Allan M; Bishop, Kathie; Zhong, Z John; Gheuens, Sarah; Bennett, C Frank; Schneider, Eugene; Farwell, Wildon; De Vivo, Darryl C
2017-11-02
Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein. We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included overall survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis. In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41%] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P=0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P=0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups. Among infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug. (Funded by Biogen and Ionis Pharmaceuticals; ENDEAR ClinicalTrials.gov number, NCT02193074 .).
A clinical study of 407 cases of nasopharyngeal carcinoma in Hong Kong
DOE Office of Scientific and Technical Information (OSTI.GOV)
Teo, P.; Tsao, S.Y.; Shiu, W.
Four hundred and seven cases of nasopharyngeal carcinoma were analyzed retrospectively; 403/407 were evaluable for recurrence and survival. Parapharyngeal boost significantly decreased local recurrences in parapharyngeal diseases without base of skull involvement (T2p), but not with base of skull involvement (T3p). Enhanced local control of T2p with boost was significant without neoadjuvant chemotherapy. Tumors localized within the nasopharynx (T1) and tumors with nasal involvement (T2n) suffering from local persistences after external radiation therapy were treated with an intracavitary afterloading method. They had survival and recurrence rates comparable to complete responders to external radiation therapy. Patients with bulky cervical nodes (maximalmore » diameter greater than or equal to 4 cm, N1-N3), treated with neoadjuvant chemotherapy with cis-diamminedichloroplatinum II and 5-fluorouracil, had a regional failure rate, distant metastasis rate, actuarial survival rate, and disease-free survival rate comparable to those with smaller nodes treated with external radiation therapy alone. A simple modification of the Ho's classification by regrouping the T-stages into 'early T-stages' and 'advanced T-stages' and by combining the N1 and the N2 has greatly increased the power of the system in predicting local recurrence and distant metastasis, respectively. There was an overall improvement of the actuarial survival rate and disease-free survival rate over the historical control, and its significance is discussed.« less
Carbon Ion Radiation Therapy for Unresectable Sacral Chordoma: An Analysis of 188 Cases
DOE Office of Scientific and Technical Information (OSTI.GOV)
Imai, Reiko, E-mail: r_imai@nirs.go.jp; Kamada, Tadashi; Araki, Nobuhito
2016-05-01
Purpose: To evaluate the results of carbon ion radiation therapy administered to 188 patients with unresectable primary sacral chordomas. Patients and Methods: One hundred eighty-eight patients were treated with carbon ion radiation therapy at a single institute between 1996 and 2013 and retrospectively analyzed. The median age was 66 years. The highest proximal invasion reached past S2 level in 137 patients. The median clinical target volume was 345 cm{sup 3}. One hundred six patients received 67.2 gray equivalents (GyE)/16 fractions (fr), 74 patients received 70.4 GyE/16 fr, 7 patients received 73.6 GyE/16 fr, and 1 patient received 64.0 GyE/16 fr. Results: The median follow-upmore » period was 62 months (range, 6.8-147.5 months). Seventy percent of patients were followed for 5 years or until death. The 5-year local control, overall survival, and disease-free survival rates were 77.2%, 81.1%, and 50.3%, respectively. Forty-one patients had a local recurrence. Sex, tumor volume, level of proximal invasion, and irradiated dose were unrelated to local control. There was grade 3 toxicity of the peripheral nerves in 6 patients and grade 4 toxicity of the skin in 2 patients. Ambulation remained in 97% of patients. Conclusions: Carbon ion radiation therapy was safe and effective for unresectable chordoma and provided good local control and survival while preserving ambulation.« less
Sabin, Lora L; Knapp, Anna B; MacLeod, William B; Phiri-Mazala, Grace; Kasimba, Joshua; Hamer, Davidson H; Gill, Christopher J
2012-01-01
The Lufwanyama Neonatal Survival Project ("LUNESP") was a cluster randomized, controlled trial that showed that training traditional birth attendants (TBAs) to perform interventions targeting birth asphyxia, hypothermia, and neonatal sepsis reduced all-cause neonatal mortality by 45%. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness, and factors that might improve cost-effectiveness. We calculated LUNESP's financial and economic costs and the economic cost of implementation for a forecasted ten-year program (2011-2020). In each case, we calculated the incremental cost per death avoided and disability-adjusted life years (DALYs) averted in real 2011 US dollars. The forecasted 10-year program analysis included a base case as well as 'conservative' and 'optimistic' scenarios. Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. The estimated financial and economic costs of LUNESP were $118,574 and $127,756, respectively, or $49,469 and $53,550 per year. Fixed costs accounted for nearly 90% of total costs. For the 10-year program, discounted total and annual program costs were $256,455 and $26,834 respectively; for the base case, optimistic, and conservative scenarios, the estimated cost per death avoided was $1,866, $591, and $3,024, and cost per DALY averted was $74, $24, and $120, respectively. Outcomes were robust to variations in local costs, but sensitive to variations in intervention effect size, number of births attended by TBAs, and the extent of foreign consultants' participation. Based on established guidelines, the strategy of using trained TBAs to reduce neonatal mortality was 'highly cost effective'. We strongly recommend consideration of this approach for other remote rural populations with limited access to health care.
Sabin, Lora L.; Knapp, Anna B.; MacLeod, William B.; Phiri-Mazala, Grace; Kasimba, Joshua; Hamer, Davidson H.; Gill, Christopher J.
2012-01-01
Background The Lufwanyama Neonatal Survival Project (“LUNESP”) was a cluster randomized, controlled trial that showed that training traditional birth attendants (TBAs) to perform interventions targeting birth asphyxia, hypothermia, and neonatal sepsis reduced all-cause neonatal mortality by 45%. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness, and factors that might improve cost-effectiveness. Methods and Findings We calculated LUNESP's financial and economic costs and the economic cost of implementation for a forecasted ten-year program (2011–2020). In each case, we calculated the incremental cost per death avoided and disability-adjusted life years (DALYs) averted in real 2011 US dollars. The forecasted 10-year program analysis included a base case as well as ‘conservative’ and ‘optimistic’ scenarios. Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. The estimated financial and economic costs of LUNESP were $118,574 and $127,756, respectively, or $49,469 and $53,550 per year. Fixed costs accounted for nearly 90% of total costs. For the 10-year program, discounted total and annual program costs were $256,455 and $26,834 respectively; for the base case, optimistic, and conservative scenarios, the estimated cost per death avoided was $1,866, $591, and $3,024, and cost per DALY averted was $74, $24, and $120, respectively. Outcomes were robust to variations in local costs, but sensitive to variations in intervention effect size, number of births attended by TBAs, and the extent of foreign consultants' participation. Conclusions Based on established guidelines, the strategy of using trained TBAs to reduce neonatal mortality was ‘highly cost effective’. We strongly recommend consideration of this approach for other remote rural populations with limited access to health care. PMID:22545117
Toma, Claudio; Hervás, Amaia; Balmaña, Noemí; Salgado, Marta; Maristany, Marta; Vilella, Elisabet; Aguilera, Francisco; Orejuela, Carmen; Cuscó, Ivon; Gallastegui, Fátima; Pérez-Jurado, Luis Alberto; Caballero-Andaluz, Rafaela; Diego-Otero, Yolanda de; Guzmán-Alvarez, Guadalupe; Ramos-Quiroga, Josep Antoni; Ribasés, Marta; Bayés, Mònica; Cormand, Bru
2013-09-01
Neurotransmitter systems and neurotrophic factors can be considered strong candidates for autism spectrum disorder (ASD). The serotoninergic and dopaminergic systems are involved in neurotransmission, brain maturation and cortical organization, while neurotrophic factors (NTFs) participate in neurodevelopment, neuronal survival and synapses formation. We aimed to test the contribution of these candidate pathways to autism through a case-control association study of genes selected both for their role in central nervous system functions and for pathophysiological evidences. The study sample consisted of 326 unrelated autistic patients and 350 gender-matched controls from Spain. We genotyped 369 tagSNPs to perform a case-control association study of 37 candidate genes. A significant association was obtained between the DDC gene and autism in the single-marker analysis (rs6592961, P = 0.00047). Haplotype-based analysis pinpointed a four-marker combination in this gene associated with the disorder (rs2329340C-rs2044859T-rs6592961A-rs11761683T, P = 4.988e-05). No significant results were obtained for the remaining genes after applying multiple testing corrections. However, the rs167771 marker in DRD3, associated with ASD in a previous study, displayed a nominal association in our analysis (P = 0.023). Our data suggest that common allelic variants in the DDC gene may be involved in autism susceptibility.
Ascertaining serum levels of trace elements in melanoma patients using PIXE and HR-ICPMS
NASA Astrophysics Data System (ADS)
Bernardes, S.; Tabacniks, M. H.; Santos, I. D. A. O.; Oliveira, A. F.; Shie, J. N.; Sarkis, J. E. S.; Oliveira, T.
2014-01-01
Melanoma is a serious and deadly form of skin cancer. However, patients' chances of survival and recovery are considerably increased when it is diagnosed and treated in its early stages. In this study, trace element concentrations in serum samples from patients with melanoma were measured using PIXE (Proton Induced X-ray Emission) and HR-ICPMS (High-Resolution Inductively Coupled Plasma Mass Spectrometry), with the purpose of correlating these concentrations with the disease. Blood samples from 30 melanoma patients and 116 healthy donors were collected at São Paulo Hospital (protocol CEP 1036/08 UNIFESP). Relevant clinical information on the patients has also been included in the statistical analysis. Analysis of the control group showed different P and Mg concentrations in individuals above and below 40 years of age. P, S, Ca, Cu and Zn concentrations in healthy individuals differed according to gender, highlighting the necessity to include age and gender variables in the case-control analysis. There were also differences in K, S, Ca and Se concentrations between the control and melanoma groups.
Kulik, Ulf; Lehner, Frank; Klempnauer, Jürgen; Borlak, Jürgen
2017-08-01
The shortage of liver donations demands the use of suboptimal grafts with steatosis being a frequent finding. Although ≤30% macrovesicular steatosis is considered to be safe the risk for primary non-function (PNF) and outcome after re-transplantation (re-OLT) is unknown. Among 1205 orthotopic liver transplantations performed at our institution the frequency, survival and reason of re-OLT were evaluated. PNF (group A) cases and those with initial transplant function but subsequent need for re-OLT (group B) were analysed. Histopathology and clinical judgement determined the cause of PNF and included an assessment of hepatic steatosis. Additionally, survival of fatty liver allografts (group C) not requiring re-OLT was considered in Kaplan-Meier and multivariate regression analysis. A total of 77 high urgency re-OLTs were identified and included 39 PNF cases. Nearly 70% of PNF cases were due to primary fatty liver allografts. The 3-month in-hospital mortality for PNF cases after re-OLT was 46% and the mean survival after re-OLT was 0.5 years as compared to 5.2 and 5.1 years for group B, C, respectively, (P<.008). In multivariate Cox regression analysis only hepatic steatosis was associated with an inferior survival (HR 4.272, P=.002). The MELD score, donor BMI, age, cold ischaemic time, ICU stay, serum sodium and transaminases did not influence overall survival. Our study highlights fatty liver allografts to be a major cause for PNF with excessive mortality after re-transplantation. The findings demand the development of new methods to predict risk for PNF of fatty liver allografts. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.
Fritz, Peter; Dippon, Jürgen; Müller, Simon; Goletz, Sven; Trautmann, Christian; Pappas, Xenophon; Ott, German; Brauch, Hiltrud; Schwab, Matthias; Winter, Stefan; Mürdter, Thomas; Brinkmann, Friedhelm; Faisst, Simone; Rössle, Susanne; Gerteis, Andreas; Friedel, Godehard
2018-03-01
In this retrospective study, we compared breast cancer patients treated with and without mistletoe lectin I (ML-I) in addition to standard breast cancer treatment in order to determine a possible effect of this complementary treatment. This study included 18,528 patients with invasive breast cancer. Data on additional ML-I treatments were reported for 164 patients. We developed a "similar case" method with a distance measure retrieved from the beta variable in Cox regression to compare these patients, after stage adjustment, with their non-ML-1 treated counterparts in order to answer three hypotheses concerning overall survival, recurrence free survival and life quality. Raw data analysis of an additional ML-I treatment yielded a worse outcome (p=0.02) for patients with ML treatment, possibly due to a bias inherent in the ML-I-treated patients. Using the "similar case" method (a case-based reasoning approach) we could not confirm this harm for patients using ML-I. Analysis of life quality data did not demonstrate reliable differences between patients treated with ML-I treatment and those without proven ML-I treatment. Based on a "similar case" model we did not observe any differences in the overall survival (OS), recurrence-free survival (RFS), and quality of life data between breast cancer patients with standard treatment and those who in addition to standard treatment received ML-I treatment. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
Samstein, Robert M; Carvajal, Richard D; Postow, Michael A; Callahan, Margaret K; Shoushtari, Alexander N; Patel, Snehal G; Lee, Nancy Y; Barker, Christopher A
2016-09-01
Sinonasal mucosal melanoma is a rare neoplasm with a poor prognosis. Retrospective analysis was conducted on 78 patients with localized sinonasal mucosal melanoma treated at Memorial Sloan Kettering Cancer Center (MSKCC from 1998-2013). Demographic, tumor, imaging, and treatment factors were recorded and survival and disease-control outcomes were analyzed. Median overall survival (OS) and disease-specific survival (DSS) were 32 and 50 months, respectively. Median locoregional recurrence-free survival (LRFS) and distant recurrence-free survival (DRFS) were 43 and 12 months, respectively. Multivariate analysis demonstrated greater OS in nasal cavity tumors and earlier T classification. Radiotherapy (RT) was associated with significantly greater LRFS (5-years; 35% vs 59%; p = .01), but no difference in OS. Post-RT positron emission tomography (PET) response was associated with greater OS. Distant metastasis is the predominant mode of recurrence in sinonasal mucosal melanoma, but local recurrence remains common. RT is associated with improved local control, but no survival benefit. The prognostic value of post-RT PET imaging warrants further investigation. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1310-1317, 2016. © 2016 Wiley Periodicals, Inc.
A Case Study of a Combat Aircraft’s Single Hit Vulnerability
1986-09-01
Survivability Life Cycle 21 3.2 Interfaces of the FMECA Process 27 3.3 Example FMEA Format 29 3.4 Example DMEA Matrix 33 3.5 Example Disablement Diagram 34...Typical Hi-Hi/Hi-Hi Mission 58 5.5 A-20 Conceptual Tactics 60 7.1 A-20 Fuel System 73 7.2 A-20 Hydraulics System 75 7.3 A-20 Flight Controls System 77 7.4...effect severity. The FMECA procedure is performed in two steps, (1) a Fail- ure Mode and Effects Analysis ( FMEA ) and (2) a Damage Mode and Effects
Ippolito, Matthew M; Kamavu, Luc K; Kabuya, Jean-Bertin; Tente, Catherine; Chileshe, Edward; Wapachole, McBerth; Thuma, Philip E; Muleba, Mbanga; Chaponda, Mike; Mulenga, Modest; Moss, William J; For The Southern And Central Africa International Centers Of Excellence For Malaria Research
2018-04-23
Malaria remains a public health crisis in areas where it has resisted control efforts. In Nchelenge District, a high- transmission area in northern Zambia, malaria accounts for more than one-third of pediatric hospitalizations and nearly one-half of hospital deaths in children. To identify risk factors for death due to malaria, we conducted a retrospective, time-matched case-control study of 126 children hospitalized with malaria who died (cases) and 126 children who survived (controls). There were no differences in age, gender, hemoglobin concentration, or prevalence of severe anemia between cases and controls. Children who died were more likely to come from villages located at greater distances from the hospital than children who survived (median 13.5 versus 3.2 km). Each additional kilometer of distance from the hospital increased the odds of death by 4% (odds ratio 1.04, 95% confidence interval 1.01-1.07, P < 0.01). Extent of anemia and admission during periods when blood was unavailable for transfusion were associated with early death ( P ≤ 0.03). Delays in initiation of treatment of severe malaria contribute to the increased odds of death in children referred from more distant health centers, and might be mitigated by transportation improvements, capacity at rural health posts to administer treatment before transfer, hospital triage systems that minimize time to treatment, and reliable blood product stores at referral hospitals.
Ulnar osteosarcoma in dogs: 30 cases (1992-2008).
Sivacolundhu, Ramesh K; Runge, Jeffrey J; Donovan, Taryn A; Barber, Lisa G; Saba, Corey F; Clifford, Craig A; de Lorimier, Louis-Philippe; Atwater, Stephen W; DiBernardi, Lisa; Freeman, Kim P; Bergman, Philip J
2013-07-01
To examine the biological behavior of ulnar osteosarcoma and evaluate predictors of survival time in dogs. Retrospective case series. 30 dogs with primary ulnar osteosarcoma. Medical records were reviewed. Variables recorded and examined to identify predictors of survival time were signalment, tumor location in the ulna, tumor length, serum alkaline phosphatase activity, surgery type, completeness of excision, tumor stage, tumor grade, histologic subtype, development of metastases, and use of chemotherapy. 30 cases were identified from 9 institutions. Eleven dogs were treated with partial ulnar ostectomy and 14 with amputation; in 5 dogs, a resection was not performed. Twenty-two dogs received chemotherapy. Median disease-free interval and survival time were 437 and 463 days, respectively. Negative prognostic factors for survival time determined via univariate analyses were histologic subtype and development of lung metastases. Telangiectatic or telangiectatic-mixed subtype (n = 5) was the only negative prognostic factor identified via multivariate analysis (median survival time, 208 days). Dogs with telangiectatic subtype were 6.99 times as likely to die of the disease. The prognosis for ulnar osteosarcoma in this population was no worse and may have been better than the prognosis for dogs with osteosarcoma involving other appendicular sites. Partial ulnar ostectomy was associated with a low complication rate and good to excellent function and did not compromise survival time. Telangiectatic or telangiectatic-mixed histologic subtype was a negative prognostic factor for survival time. The efficacy of chemotherapy requires further evaluation.
PROgnosticating COeliac patieNts SUrvivaL: the PROCONSUL score.
Biagi, Federico; Schiepatti, Annalisa; Malamut, Georgia; Marchese, Alessandra; Cellier, Christophe; Bakker, Sjoerd F; Mulder, Chris J J; Volta, Umberto; Zingone, Fabiana; Ciacci, Carolina; D'Odorico, Anna; Andrealli, Alida; Astegiano, Marco; Klersy, Catherine; Corazza, Gino R
2014-01-01
It has been shown that mortality rates of coeliac patients correlate with age at diagnosis of coeliac disease, diagnostic delay for coeliac disease, pattern of clinical presentation and HLA typing. Our aim was to create a tool that identifies coeliac patients at higher risk of developing complications. To identify predictors of complications in patients with coeliac disease, we organised an observational multicenter case-control study based on a retrospective collection of clinical data. Clinical data from 116 cases (patients with complicated coeliac disease) and 181 controls (coeliac patients without any complications) were collected from seven European centres. For each case, one or two controls, matched to cases according to the year of assessment, gender and age, were selected. Diagnostic delay, pattern of clinical presentation, HLA typing and age at diagnosis were used as predictors. Differences between cases and controls were detected for diagnostic delay and classical presentation. Conditional logistic models based on these statistically different predictors allowed the development of a score system. Tertiles analysis showed a relationship between score and risk of developing complications. A score that shows the risk of a newly diagnosed coeliac patient developing complications was devised for the first time. This will make it possible to set up the follow-up of coeliac patients with great benefits not only for their health but also for management of economic resources. We think that our results are very encouraging and represent the first attempt to build a prognostic score for coeliac patients.
PROgnosticating COeliac patieNts SUrvivaL: The PROCONSUL Score
Biagi, Federico; Schiepatti, Annalisa; Malamut, Georgia; Marchese, Alessandra; Cellier, Christophe; Bakker, Sjoerd F.; Mulder, Chris J. J.; Volta, Umberto; Zingone, Fabiana; Ciacci, Carolina; D’Odorico, Anna; Andrealli, Alida; Astegiano, Marco; Klersy, Catherine; Corazza, Gino R.
2014-01-01
Introduction It has been shown that mortality rates of coeliac patients correlate with age at diagnosis of coeliac disease, diagnostic delay for coeliac disease, pattern of clinical presentation and HLA typing. Our aim was to create a tool that identifies coeliac patients at higher risk of developing complications. Methods To identify predictors of complications in patients with coeliac disease, we organised an observational multicenter case-control study based on a retrospective collection of clinical data. Clinical data from 116 cases (patients with complicated coeliac disease) and 181 controls (coeliac patients without any complications) were collected from seven European centres. For each case, one or two controls, matched to cases according to the year of assessment, gender and age, were selected. Diagnostic delay, pattern of clinical presentation, HLA typing and age at diagnosis were used as predictors. Results Differences between cases and controls were detected for diagnostic delay and classical presentation. Conditional logistic models based on these statistically different predictors allowed the development of a score system. Tertiles analysis showed a relationship between score and risk of developing complications. Discussion A score that shows the risk of a newly diagnosed coeliac patient developing complications was devised for the first time. This will make it possible to set up the follow-up of coeliac patients with great benefits not only for their health but also for management of economic resources. Conclusions We think that our results are very encouraging and represent the first attempt to build a prognostic score for coeliac patients. PMID:24392112
Twelves, C. J.; Thomson, C. S.; Gould, A.; Dewar, J. A.
1998-01-01
We have investigated factors influencing the survival of women with early breast cancer in Scotland. In a retrospective study, clinical, treatment and 'service' factors, e.g. surgical case load, deprivation and geographical area (health board of first treatment) were recorded from hospital records. A total of 2148 women with invasive breast cancer diagnosed in 1987 were identified from the Scottish Cancer Registry, of whom 1619 without metastases at diagnosis underwent surgery as part of their primary treatment. In a multivariate analysis, clinical factors (age, clinical stage, pathological tumour size, node status and oestrogen receptor status) all influenced survival. After allowing for these clinical factors, surgical case load and deprivation did not have statistically significant effects on survival. By contrast, health board did affect survival. This was explained in part by the selection of patients for surgery. There appeared, however, to be a residual effect that may be related to differences in the use of adjuvant systemic treatment among the different health boards. We conclude that, in Scotland, geographical variation in both surgical and non-surgical treatment has a greater effect on variability in survival for women with breast cancer than surgical case load and deprivation. PMID:9744492
Rosendahl, Mikkel; Mosgaard, Berit Jul; Høgdall, Claus
2016-10-01
To determine if survival in stage I ovarian cancer is influenced by cyst emptying, lymph node resection and chemotherapy. A survival analysis of 607 patients with ovarian cancer in stage IA, IA with cyst emptying (IAempty) and IC1 was performed. There was no difference in five-year survival between IA (87%) and IC1 (87%) (p=0.899), between IA and IAempty (86%) (p=0.500) nor between IA+IAempty (87%) and IC1 without IAempty (84%) (p=0.527). Five-year survival rate (5YSR) was significantly higher after lymph node resection in stage IA (94% vs. 85%; p=0.01) and IA+IC1 (93% vs. 85%; p=0.004). In multivariate analysis, lymph node resection improved prognosis significantly for all sub-stages, whereas stage and chemotherapy did not affect survival. In stage IA ovarian cancer, controlled cyst emptying without spill does not worsen prognosis. Lymph node resection is associated with improved survival in stage IA and IC1. Chemotherapy should only be offered where randomized controlled studies have shown a benefit. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
Pre-treatment plasma proteomic markers associated with survival in oesophageal cancer
Kelly, P; Paulin, F; Lamont, D; Baker, L; Clearly, S; Exon, D; Thompson, A
2012-01-01
Background: The incidence of oesophageal adenocarcinoma is increasing worldwide but survival remains poor. Neoadjuvant chemotherapy can improve survival, but prognostic and predictive biomarkers are required. This study built upon preclinical approaches to identify prognostic plasma proteomic markers in oesophageal cancer. Methods: Plasma samples collected before and during the treatment of oesophageal cancer and non-cancer controls were analysed by surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectroscopy (MS). Protein peaks were identified by MS in tryptic digests of purified fractions. Associations between peak intensities obtained in the spectra and clinical endpoints (survival, disease-free survival) were tested by univariate (Fisher's exact test) and multivariate analysis (binary logistic regression). Results: Plasma protein peaks were identified that differed significantly (P<0.05, ANOVA) between the oesophageal cancer and control groups at baseline. Three peaks, confirmed as apolipoprotein A-I, serum amyloid A and transthyretin, in baseline (pre-treatment) samples were associated by univariate and multivariate analysis with disease-free survival and overall survival. Conclusion: Plasma proteins can be detected prior to treatment for oesophageal cancer that are associated with outcome and merit testing as prognostic and predictive markers of response to guide chemotherapy in oesophageal cancer. PMID:22294182
Pre-treatment plasma proteomic markers associated with survival in oesophageal cancer.
Kelly, P; Paulin, F; Lamont, D; Baker, L; Clearly, S; Exon, D; Thompson, A
2012-02-28
The incidence of oesophageal adenocarcinoma is increasing worldwide but survival remains poor. Neoadjuvant chemotherapy can improve survival, but prognostic and predictive biomarkers are required. This study built upon preclinical approaches to identify prognostic plasma proteomic markers in oesophageal cancer. Plasma samples collected before and during the treatment of oesophageal cancer and non-cancer controls were analysed by surface-enhanced laser desorption/ionisation time-of-flight (SELDI-TOF) mass spectroscopy (MS). Protein peaks were identified by MS in tryptic digests of purified fractions. Associations between peak intensities obtained in the spectra and clinical endpoints (survival, disease-free survival) were tested by univariate (Fisher's exact test) and multivariate analysis (binary logistic regression). Plasma protein peaks were identified that differed significantly (P<0.05, ANOVA) between the oesophageal cancer and control groups at baseline. Three peaks, confirmed as apolipoprotein A-I, serum amyloid A and transthyretin, in baseline (pre-treatment) samples were associated by univariate and multivariate analysis with disease-free survival and overall survival. Plasma proteins can be detected prior to treatment for oesophageal cancer that are associated with outcome and merit testing as prognostic and predictive markers of response to guide chemotherapy in oesophageal cancer.
Long-term TNF-alpha blockade in patients with amyloid A amyloidosis complicating rheumatic diseases.
Fernández-Nebro, Antonio; Olivé, Alejandro; Castro, María Carmen; Varela, Angela Herranz; Riera, Elena; Irigoyen, Maria V; García de Yébenes, María Jesús; García-Vicuña, Rosario
2010-05-01
To evaluate the effectiveness and safety of anti-tumor necrosis factor therapy in patients with amyloid A amyloidosis. Multicenter, controlled, dynamic prospective cohort study of 36 patients with amyloid A amyloidosis (94% kidney involvement) treated with anti-tumor necrosis factor agents (drug exposure of 102.97 patient-years). As an external control group, 35 propensity score-matched non-amyloid patients were chosen from the Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología registry. The end points were kidney response and progression, anti-tumor necrosis factor continuation rate, patient survival, and adverse events. At the end of follow-up, a kidney response was observed in 12 of 22 patients (54.5%) and a kidney progression was observed in 6 of 36 patients (17%). The kidney amyloidosis remained stable in 16 of 36 patients (44%). The level of acute phase reactants diminished but did not reach the normal level. The continuation rates of anti-tumor necrosis factor drugs among patients with amyloid A amyloidosis after 1, 2, 3, and 4 or more years were 80%, 80%, 61%, and 52%, respectively, comparable to controls. The 5-year cumulative survival of amyloid A amyloidosis cases was 90.6%, and the 10-year survival was 78.5%. In a multivariate Cox regression analysis, the duration of amyloidosis and the level of proteinuria at the onset of anti-tumor necrosis factor treatment were independent predictors of treatment failure, whereas the level of proteinuria was the only factor that predicts mortality. Most adverse events were similar in both groups, although the number of infections was 3 times higher in amyloid A amyloidosis cases. Anti-tumor necrosis factor drugs are effective in treating amyloid A amyloidosis, although they might increase the risk of infection. Copyright 2010 Elsevier Inc. All rights reserved.
Clinical Significance of SASH1 Expression in Glioma.
Yang, Liu; Zhang, Haitao; Yao, Qi; Yan, Yingying; Wu, Ronghua; Liu, Mei
2015-01-01
SAM and SH3 domain containing 1 (SASH1) is a recently discovered tumor suppressor gene. The role of SASH1 in glioma has not yet been described. We investigated SASH1 expression in glioma cases to determine its clinical significance on glioma pathogenesis and prognosis. We produced tissue microarrays using 121 patient-derived glioma samples and 30 patient-derived nontumor cerebral samples. Immunohistochemistry and Western blotting were used to evaluate SASH1 expression. We used Fisher's exact tests to determine relationships between SASH1 expression and clinicopathological characteristics; Cox regression analysis to evaluate the independency of different SASH1 expression; Kaplan-Meier analysis to determine any correlation of SASH1 expression with survival rate. SASH1 expression was closely correlated with the WHO glioma grade. Of the 121 cases, 66.9% with low SASH1 expression were mostly grade III-IV cases, whereas 33.1% with high SASH1 expression were mostly grades I-II. Kaplan-Meier analysis revealed a significant positive correlation between SASH1 expression and postoperative survival. SASH1 was widely expressed in normal and low-grade glioma tissues. SASH1 expression strongly correlated with glioma grades, showing higher expression at a lower grade, which decreased significantly as grade increased. Furthermore, SASH1 expression was positively correlated with better postoperative survival in patients with glioma.
Early mortality and morbidity after total hip arthroplasty in patients with femoral neck fracture
Hailer, Nils P; Garland, Anne; Rogmark, Cecilia; Garellick, Göran; Kärrholm, Johan
2016-01-01
Background and purpose — Early postoperative mortality is relatively high after total hip arthroplasty (THA) that has been performed due to femoral neck fracture. However, this has rarely been investigated after adjustment for medical comorbidity and comparison with the mortality in an age-matched population. We therefore assessed early mortality in hip fracture patients treated with a THA, in the setting of a nationwide matched cohort study. Patients and methods — 24,699 patients who underwent THA due to a femoral neck fracture between 1992 and 2012 were matched with 118,518 controls. Kaplan-Meier survival analysis was used to calculate cumulative unadjusted survival, and Cox regression models were fitted to compute hazard ratios (HRs) and 95% confidence intervals (CIs), with adjustment for age, sex, comorbidity, and socioeconomic background. Results — 90-day survival was 96.3% (95% CI: 96.0–96.5) for THA cases and 98.7% (95% CI: 98.6–98.8) for control individuals, giving an adjusted HR of 2.2 (95% CI: 2.0–2.4) for THA cases compared to control individuals. Comorbidity burden increased in THA cases over time, but the adjusted risk of death within 90 days did not differ statistically significantly between the time periods investigated (1992–1998, 1999–2005, and 2006–2012). A Charlson comorbidity index of 3 or more, an American Society of Anesthesiologists (ASA) grade of 3 and above, male sex, an age of 80 years and above, an income below the first quartile, and a lower level of education were all associated with an increased risk of 90-day mortality. Interpretation — The adjusted early mortality in femoral neck fracture patients who underwent THA was about double that in a matched control population. Patients with femoral neck fracture but with no substantial comorbidity and an age of less than 80 years appear to have a low risk of early death. Patients older than 80 years and those with a Charlson comorbidity index of more than 2 have a high risk of early death, and such patients would perhaps benefit from treatment strategies other than THA, but this should be investigated further. PMID:27649030
DOE Office of Scientific and Technical Information (OSTI.GOV)
Nelson, John W.; Ghafoori, A. Paiman; Willett, Christopher G.
Purpose: Extrahepatic cholangiocarcinoma is a rare malignancy. Despite radical resection, survival remains poor, with high rates of local and distant failure. To clarify the role of radiotherapy with chemotherapy, we performed a retrospective analysis of resected patients who had undergone chemoradiotherapy. Methods and Materials: A total of 45 patients (13 with proximal and 32 with distal disease) underwent resection plus radiotherapy (median dose, 50.4 Gy). All but 1 patient received concurrent fluoropyrimidine-based chemotherapy. The median follow-up was 30 months for all patients and 40 months for survivors. Results: Of the 45 patients, 33 underwent adjuvant radiotherapy, and 12 were treatedmore » neoadjuvantly. The 5-year actuarial overall survival, disease-free survival, metastasis-free survival, and locoregional control rates were 33%, 37%, 42%, and 78%, respectively. The median survival was 34 months. No patient died perioperatively. Patient age {<=}60 years and perineural involvement adversely affected survival on univariate analysis. Patients undergoing R0 resection had a significantly improved rate of local control but no survival advantage. Despite having more advanced disease at presentation, patients treated neoadjuvantly had a longer survival (5-year survival 53% vs. 23%, p = 0.16) and similar rates of Grade 2-3 surgical morbidity (16% vs. 33%, p = 0.24) compared with those treated in the postoperative setting. Conclusion: These study results suggest a possible local control benefit from chemoradiotherapy combined with surgery in patients with advanced, resected biliary cancer. Furthermore, our results suggest that a treatment strategy that includes preoperative chemoradiotherapy might result in improved tumor resectability with similar surgical morbidity compared with patients treated postoperatively, as well as potentially improved survival outcomes. Distant failure remains a significant failure pattern, suggesting the need for more effective systemic therapy.« less
Bilski, M; Surdyka, D; Paśnik, I; Bilska, M; Cisek, P; Korona, P; Szumiło, J; Grzybowska-Szatkowska, L
2018-01-01
Spleen sarcoma is one of the most rare soft tissue malignancies. The annual incidence is 0.14-0.25/1,000,000 and the average age of diagnosis is 50 to 73 years. The incidence of this cancer has been increasing. Treatment of choice is surgical splenectomy, which rarely gives good results due to the aggressive course of the disease as well as the high potential for metastasis. Overall survival in primary spleen sarcomas as described by various authors is between 4 and 14 months. 80% of patients after spleen rupture do not survive 6 months. We report the case of a 42-year-old male diagnosed with spleen angiosarcoma. The patient underwent surgery in an emergency mode because of rapid rupture of the organ. Due to positive surgical margins, he underwent adjuvant radiochemotherapy followed by chemotherapy. Overall survival time was relatively long (23 months). The international guidelines provide information based on limited data. The role of postoperative radiotherapy in angiosarcomas remains controversial. Postoperative radiotherapy may increase local disease control, especially after nonradical operation, but this does not translate into improvement in overall survival time of these patients. The case shows that adjuvant radiotherapy as part of cancer treatment strategy may prolong the overall survival.
Sinonasal adenoid cystic carcinoma: a population-based analysis of 694 cases.
Unsal, Aykut A; Chung, Sei Y; Zhou, Albert H; Baredes, Soly; Eloy, Jean Anderson
2017-03-01
Currently, limited literature exists about sinonasal adenoid cystic carcinoma (SNACC). In this study, we analyze the demographics, survival, and treatment efficacy of this rare entity. Our study was a retrospective population-based analysis of SNACC in the Surveillance, Epidemiology, and End Results (SEER) database assessing the 40-year time-frame of 1973 to 2013. Six hundred ninety-four SNACC patients were identified; 53.2% were female and 46.8% were male. Caucasians were most commonly affected (77.1%). SNACC most often arose from the maxillary sinuses, followed by the nasal cavity. The majority of SNACC cases presented as stage IV disease. Nodal and distant metastases were present in 3.6% and 7.1% of all cases, respectively. Overall 5-, 10-, and 20-year disease-specific survival (DSS) rates were 66.5%, 41.1%, and 17.6%, respectively. The presence of distant metastasis dropped the 5-year DSS rate from 64.5% to 20.0%. Cases treated with combined surgery and adjuvant radiotherapy had a slightly improved 5-year DSS rate compared with surgery alone (73.5% vs 72.5%). Surgery alone resulted in higher 10- and 20-year DSS rates (54.2% and 36.8%, respectively) when compared with combined therapy (44.2% and 15.5%), radiotherapy alone (10.8% and 0%), and no surgery or radiotherapy (9.3% and 0%). This study represents the largest cohort of SNACC patients to date. Factors that confer a survival benefit in SNACC include M0 disease, and presentation primarily in the nasal cavity. Overall low rates of nodal metastasis may not warrant the use of elective neck dissections, unless there is clinical suspicion. Modalities of therapy that include surgery greatly improve survival. Adjuvant radiotherapy appears to slightly improve 5-year disease-free survival but does not impact long-term survival. © 2016 ARS-AAOA, LLC.
A meta-analysis of bevacizumab combined with chemotherapy in the treatment of ovarian cancer.
Wang, T S; Lei, W; Cui, W; Wen, P; Guo, H F; Ding, S G; Yang, Y P; Xu, Y Q; Lv, S W; Zhu, Y L
2014-03-01
Angiogenesis plays an important role in the biology of ovarian cancer. The clinical efficacy and side effects of bevacizumab, the vascular endothelial growth factor inhibitor, on survival and toxicity in women with this ovarian cancer, was not conclusive. We performed this systematic review and meta-analysis in order to clarify the efficacy of bevacizumab combined with chemotherapy in the treatment of ovarian cancer. We searched the electronic database of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials and CNKI for clinical controlled trials of comparing bevacizumab combined with chemotherapy and chemotherapy alone in the treatment of ovarian cancer. The primary outcomes of eligible studies included median progression-free survival (PFS), overall survival (OS), and toxicities such as enterobrosis, hypertension, albuminuria, congestive heart failure (CHF), neutrophils, thrombosis, and bleeding. The Hazard ratio (HR) and relative risk were used for the meta-analysis and were expressed with 95% confidence intervals (CIs). All the statistical analyses were carried out by Stata 11.0 software (http://www.stata.com; Stata Corporation, College Station, TX, USA). We included 5 studies with 1798 cases in the bevacizumab combined with the chemotherapy group and 1810 subjects in the chemotherapy alone group. The pooled results showed that bevacizumab + chemotherapy compared with chemotherapy alone can significant prolong the median PFS (HR, 0.64; 95% CI, 0.46-0.82; P < 0.05) but not the OS (HR, 0.84; 95% CI, 0.59-10.9; P > 0.05); the toxicity analysis showed that the enterobrosis, hypertension, albuminuria, neutrophils, thrombosis, and bleeding were significantly increased in the bevacizumab + chemotherapy group compared with chemotherapy alone (Pall < 0.05). But the CHF risk between the two groups was not statistical different (P > 0.05). Bevacizumab combined with chemotherapy prolonged the median PFS in patients with ovarian cancer but also increase the risk of developing enterobrosis, hypertension, albuminuria, neutrophils, thrombosis, and bleeding.
Post-Landing Orion Crew Survival in Warm Ocean Areas: A Case Study in Iterative Environmental Design
NASA Technical Reports Server (NTRS)
Rains, George E.; Bue, Grant C.; Pantermuehl, Jerry
2008-01-01
The Orion crew module (CM) is being designed to perform survivable land and water landings. There are many issues associated with post-landing crew survival. In general, the most challenging of the realistic Orion landing scenarios from an environmental control standpoint is the off-nominal water landing. Available power and other consumables will be very limited after landing, and it may not be possible to provide full environmental control within the crew cabin for very long after splashdown. Given the bulk and thermal insulation characteristics of the crew-worn pressure suits, landing in a warm tropical ocean area would pose a risk to crew survival from elevated core body temperatures, if for some reason the crewmembers were not able to remove their suits and/or exit the vehicle. This paper summarizes the analyses performed and conclusions reached regarding post-landing crew survival following a water landing, from the standpoint of the crew s core body temperatures.
[Prognostic significance of MYCN amplification in children neuroblastic tumors].
Niu, Huilin; Xu, Tao; Wang, Fenghua; Chen, Zhengrong; Gao, Qiu; Yi, Peng; Xia, Jianqing
2015-02-01
To summarize the clinicopathologic features of neuroblastic tumors (NT), and to explore the prognostic significance of MYCN amplification in NT. The clinicopathologic data of 267 NT were reviewed. MYCN gene amplification was detected by fluorescence in situ hybridization (FISH) in 119 cases and the relationship with pathological characteristics and prognostic significance were analyzed. The study included 267 cases of children NT from patients aged from 1 day to 13 years (median 27 months). The male to female ratio was 1.43. There were 38 cases (14.2%), 43 cases (16.1%), 71 cases (26.6%), and 115 cases (43.1%) of INSS stages I, II, III and IV respectively.Favorable histology group had 157 cases (59.9%); unfavorable histology group had 110 cases (40.1%).Of the 119 NT cases with MYCN FISH performed, 18 cases (15.1%) showed amplification and the signal ratio of MYCN to CEP2 was 4.08-43.29. One hundred and one cases of non-amplified MYCN included MYCN gain in 79 cases (66.3%) and MYCN negative in 22 cases (18.5%). MYCN expression showed significant difference (P = 0.000) between ages, gender, NT type and MKI, but not INPC and clinical stage (P > 0.05).Of the 18 cases with MYCN amplification, 3 were undifferentiated, and 15 poorly differentiated; 17 had high MKI and one moderate MKI. All 18 cases were in unfavorable histology group; the overall survival rate was 3/18, with an average survival time of (17.9 ± 2.4) months.Of the 101 MYCN non-amplification cases, the overall survival rate was 68.3% (69/101), with an average survival time of (29.8 ± 1.3) months. Survival analysis showed the cases with MYCN amplification had worse prognosis (P < 0.05). NT were commonly diagnosed in early ages and easily to metastasize. Most of cases with favorable histology. The cases of MYCN amplification showed unfavorable histology, and the majority cases with high MKI; The patients with MYCN gene amplification had poor prognosis.
2016-01-01
Glioblastoma (GBM) can be classified into molecular subgroups, on the basis of biomarker expression. Here, we classified our cohort of 163 adult GBMs into molecular subgroups according to the expression of proteins encoded by genes of alpha thalassemia/mental retardation syndrome X-linked (ATRX), isocitrate dehydrogenase (IDH) and TP53. We focused on the survival rate of molecular subgroups, depending on each and various combination of these biomarkers. ATRX, IDH1 and p53 protein expression were evaluated immunohistochemically and Kaplan-Meier analysis were carried out in each group. A total of 15.3% of enrolled GBMs demonstrated loss of ATRX expression (ATRX-), 10.4% expressed an aberrant IDH1 R132H protein (IDH1+), and 48.4% exhibited p53 overexpression (p53+). Survival differences were statistically significant when single protein expression or different combinations of expression of these proteins were analyzed. In conclusion, in the case of single protein expression, the patients with each IDH1+, or ATRX-, or p53- GBMs showed better survival than patients with counterparts protein expressed GBMs. In the case of double protein pairs, the patients with ATRX-/p53-, ATRX-/IDH1+, and IDH1+/p53- GBMs revealed better survival than the patients with GBMs with the remained pairs. In the case of triple protein combinations, the patients with ATRX-/p53-/IDH+ showed statistically significant survival gain than the patients with remained combination of proteins-expression status. Therefore, these three biomarkers, individually and as a combination, can stratify GBMs into prognostically relevant subgroups and have strong prognostic values in adult GBMs. PMID:27478330
Clinical lung transplantation from uncontrolled non-heart-beating donors revisited.
Gomez-de-Antonio, David; Campo-Cañaveral, Jose Luis; Crowley, Silvana; Valdivia, Daniel; Cordoba, Mar; Moradiellos, Javier; Naranjo, Jose Manual; Ussetti, Piedad; Varela, Andrés
2012-04-01
The aim of our study is to review and update the long-term results from our previously published series of lung transplantation in uncontrolled non-heart-beating donors (NHBDs). A prospective collection of data was undertaken from all lung transplants performed among uncontrolled NHBDs between 2002 and December 2009. The statistical analysis was performed using SPSS software and survival was estimated using the Kaplan-Meier method. Twenty-nine lung transplants were performed. Mean total ischemic times for the first and second lung were 575 minutes (SD 115.6) and 701 minutes (SD 111.3), respectively. Primary graft dysfunction (PGD) G1, G2 and G3 occurred in 5 cases (17%), 5 cases (17%) and 11 cases (38%), respectively. Overall hospital mortality rate was 17% (5 patients). Statistical analysis revealed a statistically significant association of mortality with ischemic times and with PGD. In terms of overall survival, 3-month, 1-year, 2-year and 5-year survival rates were 78%, 68%, 57% and 51%, respectively, and the conditional survival rates in those who survived the first 3 months were 86%, 72% and 65%, respectively. The cumulative incidence of bronchiolitis obliterans syndrome (BOS) was 11%, 35% and 45% at 1, 3 and 5 years, respectively. Lung transplantation from uncontrolled non-heart-beating donors shows acceptable results for both mid- and long-term survival and BOS; however, the higher rates of PGD and its impact on early mortality must make us more demanding with respect to the acceptance criteria and methods of evaluation used with these donors. Copyright © 2012 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.
Palliative sedation in end-of-life care and survival: a systematic review.
Maltoni, Marco; Scarpi, Emanuela; Rosati, Marta; Derni, Stefania; Fabbri, Laura; Martini, Francesca; Amadori, Dino; Nanni, Oriana
2012-04-20
Palliative sedation is a clinical procedure aimed at relieving refractory symptoms in patients with advanced cancer. It has been suggested that sedative drugs may shorten life, but few studies exist comparing the survival of sedated and nonsedated patients. We present a systematic review of literature on the clinical practice of palliative sedation to assess the effect, if any, on survival. A systematic review of literature published between January 1980 and December 2010 was performed using MEDLINE and EMBASE databases. Search terms included palliative sedation, terminal sedation, refractory symptoms, cancer, neoplasm, palliative care, terminally ill, end-of-life care, and survival. A manual search of the bibliographies of electronically identified articles was also performed. Eleven published articles were identified describing 1,807 consecutive patients in 10 retrospective or prospective nonrandomized studies, 621 (34.4%) of whom were sedated. One case-control study was excluded from prevalence analysis. The most frequent reason for sedation was delirium in the terminal stages of illness (median, 57.1%; range, 13.8% to 91.3%). Benzodiazepines were the most common drug category prescribed. Comparing survival of sedated and nonsedated patients, the sedation approach was not shown to be associated with worse survival. Even if there is no direct evidence from randomized clinical trials, palliative sedation, when appropriately indicated and correctly used to relieve unbearable suffering, does not seem to have any detrimental effect on survival of patients with terminal cancer. In this setting, palliative sedation is a medical intervention that must be considered as part of a continuum of palliative care.
Yuan, Meiqin; Wang, Zeng; Hu, Guinv; Yang, Yunshan; Lv, Wangxia; Lu, Fangxiao; Zhong, Haijun
2016-01-01
Peritoneal metastasis (PM) is a poor prognostic factor in patients with gastric cancer. The aim of this study was to evaluate the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) in patients with advanced gastric cancer with PM by retrospective analysis. A total of 54 gastric cancer patients with positive ascitic fluid cytology were included in this study: 23 patients were treated with systemic chemotherapy combined with HIPEC (HIPEC+ group) and 31 received systemic chemotherapy alone (HIPEC- group). The patients were divided into 4 categories according to the changes of ascites, namely disappear, decrease, stable and increase. The disappear + decrease rate in the HIPEC+ group was 82.60%, which was statistically significantly superior to that of the HIPEC- group (54.80%). The disappear + decrease + stable rate was 95.70% in the HIPEC+ group and 74.20% in the HIPEC- group, but the difference was not statistically significant. In 33 patients with complete survival data, including 12 from the HIPEC+ and 21 from the HIPEC- group, the median progression-free survival was 164 and 129 days, respectively, and the median overall survival (OS) was 494 and 223 days, respectively. In patients with ascites disappear/decrease/stable, the OS appeared to be better compared with that in patients with ascites increase, but the difference was not statistically significant. Further analysis revealed that patients with controlled disease (complete response + partial response + stable disease) may have a better OS compared with patients with progressive disease, with a statistically significant difference. The toxicities were well tolerated in both groups. Therefore, HIPEC was found to improve survival in advanced gastric cancer patients with PM, but the difference was not statistically significant, which may be attributed to the small number of cases. Further studies with larger samples are required to confirm our data. PMID:27446587
How can survival processing improve memory encoding?
Luo, Meng; Geng, Haiyan
2013-11-01
We investigated the psychological mechanism of survival processing advantage from the perspective of false memory in two experiments. Using a DRM paradigm in combination with analysis based on signal detection theory, we were able to separately examine participants' utilization of verbatim representation and gist representation. Specifically, in Experiment 1, participants rated semantically related words in a survival scenario for a survival condition but rated pleasantness of words in the same DRM lists for a non-survival control condition. The results showed that participants demonstrated more gist processing in the survival condition than in the pleasantness condition; however, the degree of item-specific processing in the two encoding conditions did not significantly differ. In Experiment 2, the control task was changed to a category rating task, in which participants were asked to make category ratings of words in the category lists. We found that the survival condition involved more item-specific processing than did the category condition, but we found no significant difference between the two encoding conditions at the level of gist processing. Overall, our study demonstrates that survival processing can simultaneously promote gist and item-specific representations. When the control tasks only promoted either item-specific representation or gist representation, memory advantages of survival processing occurred.
Faraz, Shahdabul; Pannullo, Susan; Rosenblum, Marc; Smith, Andrew; Wernicke, A. Gabriella
2016-01-01
Glioblastoma is not only the most common primary brain tumor, but also the most aggressive. Currently, the most effective treatment of surgery, chemotherapy and radiation therapy allows for a modest median survival of 15 months. Here, we report a case of a 57-year-old male with histologically confirmed glioblastoma with unfavorable prognostic characteristics (poor performance status and persistent neurological symptoms after surgery), whose expected 5-year survival is 0%. Further genetic analysis offered a mixed prognostic picture with positive methylation of 0-6-methylguinine-DNA (deoxyribonucleic acid) methyltransferase (MGMT; favorable prognosis) and wild-type isocitrate dehydrogenase 1 (IDH-1; unfavorable prognosis). Remarkably, the patient showed a progression-free survival of 5.5 years and a total survival of 6.5 years. In the context of recently published literature, the authors hypothesize that the patient’s use of the antipsychotic medication risperidone may have had a potential antitumor effect. Risperidone antagonizes the dopamine-2 receptor and the serotonin-7 receptor, both of which have been individually implicated in the growth and progression of glioblastoma. To the authors’ knowledge, this is the first clinical case in the literature to explore this association. PMID:27800031
Nie, Z Q; Ou, Y Q; Zhuang, J; Qu, Y J; Mai, J Z; Chen, J M; Liu, X Q
2016-05-01
Conditional logistic regression analysis and unconditional logistic regression analysis are commonly used in case control study, but Cox proportional hazard model is often used in survival data analysis. Most literature only refer to main effect model, however, generalized linear model differs from general linear model, and the interaction was composed of multiplicative interaction and additive interaction. The former is only statistical significant, but the latter has biological significance. In this paper, macros was written by using SAS 9.4 and the contrast ratio, attributable proportion due to interaction and synergy index were calculated while calculating the items of logistic and Cox regression interactions, and the confidence intervals of Wald, delta and profile likelihood were used to evaluate additive interaction for the reference in big data analysis in clinical epidemiology and in analysis of genetic multiplicative and additive interactions.
Chong, Dawn Q; Banbury, Barbara L; Phipps, Amanda I; Hua, Xinwei; Kocarnik, Jonathan; Peters, Ulrike; Berndt, Sonja I; Huang, Wen-Yi; Potter, John D; Slattery, Martha L; White, Emily; Campbell, Peter T; Harrison, Tabitha; Newcomb, Polly A; Chan, Andrew T
2018-05-01
A family history of colorectal cancer (CRC) in first-degree relatives (FDRs) increases the risk of CRC. However, the influence of family history on survival among CRC patients remains unclear. We conducted a pooled analysis of survival in 5010 incident CRC cases. Cox proportional hazards models were used to estimate the association of family history with overall survival (OS) and CRC-specific survival (CSS). We also assessed the impact of the number of affected FDRs and age at CRC diagnosis in the affected FDRs on survival. Among CRC cases, 819 (16%) patients reported a family history of CRC. There were 1580 total deaths over a median follow-up of 4.6 years, of which 1046 (66%) deaths were due to CRC. Having a family history of CRC was not associated with OS [hazard ratio (HR), 1.03; 95% confidence interval (CI), 0.89-1.19] or CSS (HR, 1.13; 95% CI, 0.95-1.36)]. There were no associations between the number of affected relatives or age at CRC diagnosis of the affected relative with survival (all P trend > 0.05). However, a family history of CRC did confer worse CSS in patients diagnosed with distal colon cancer (HR, 1.45, 95% CI, 1.03-2.04). A family history of CRC was generally not associated with survival after CRC diagnosis. However, having a family history of CRC was associated with worse CRC prognosis in individuals with distal colon cancer, suggesting a possible genetic predisposition with distinct pathogenic mechanism that may lead to worse survival in this group. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Patel, Samir; Portelance, Lorraine; Gilbert, Lucy
2007-08-01
Purpose: To retrospectively assess prognostic factors and patterns of recurrence in patients with pathologic Stage III endometrial cancer. Methods and Materials: Between 1989 and 2003, 107 patients with pathologic International Federation of Gynecology and Obstetrics Stage III endometrial adenocarcinoma confined to the pelvis were treated at our institution. Adjuvant radiotherapy (RT) was delivered to 68 patients (64%). The influence of multiple patient- and treatment-related factors on pelvic and distant control and overall survival (OS) was evaluated. Results: Median follow-up for patients at risk was 41 months. Five-year actuarial OS was significantly improved in patients treated with adjuvant RT (68%) comparedmore » with those with resection alone (50%; p = 0.029). Age, histology, grade, uterine serosal invasion, adnexal involvement, number of extrauterine sites, and treatment with adjuvant RT predicted for improved survival in univariate analysis. Multivariate analysis revealed that grade, uterine serosal invasion, and treatment with adjuvant RT were independent predictors of survival. Five-year actuarial pelvic control was improved significantly with the delivery of adjuvant RT (74% vs. 49%; p = 0.011). Depth of myometrial invasion and treatment with adjuvant RT were independent predictors of pelvic control in multivariate analysis. Conclusions: Multiple prognostic factors predicting for the outcome of pathologic Stage III endometrial cancer patients were identified in this analysis. In particular, delivery of adjuvant RT seems to be a significant independent predictor for improved survival and pelvic control, suggesting that pelvic RT should be routinely considered in the management of these patients.« less
Studer, A; Poulin, R
2014-05-01
The potential of species for evolutionary adaptation in the context of global climate change has recently come under scrutiny. Estimates of phenotypic variation in biological traits may prove valuable for identifying species, or groups of species, with greater or lower potential for evolutionary adaptation, as this variation, when heritable, represents the basis for natural selection. Assuming that measures of trait variability reflect the evolutionary potential of these traits, we conducted an analysis across trematode species to determine the potential of these parasites as a group to adapt to increasing temperatures. Firstly, we assessed how the mean number of infective stages (cercariae) emerging from infected snail hosts as well as the survival and infectivity of cercariae are related to temperature. Secondly and importantly in the context of evolutionary potential, we assessed how coefficients of variation for these traits are related to temperature, in both cases controlling for other factors such as habitat, acclimatisation, latitude and type of target host. With increasing temperature, an optimum curve was found for mean output and mean infectivity, and a linear decrease for survival of cercariae. For coefficients of variation, temperature was only an important predictor in the case of cercarial output, where results indicated that there is, however, no evidence for limited trait variation at the higher temperature range. No directional trend was found for either variation of survival or infectivity. These results, characterising general patterns among trematodes, suggest that all three traits considered may have potential to change through adaptive evolution. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.
Pasquali, Sandro; Yim, Guang; Vohra, Ravinder S; Mocellin, Simone; Nyanhongo, Donald; Marriott, Paul; Geh, Ju Ian; Griffiths, Ewen A
2017-03-01
This network meta-analysis compared overall survival after neoadjuvant or adjuvant chemotherapy (CT), radiotherapy (RT), or combinations of both (chemoradiotherapy, CRT) or surgery alone to identify the most effective approach. The optimal treatment for resectable esophageal cancer is unknown. A search for randomized controlled trials reporting on neoadjuvant and adjuvant therapies was conducted. Using a network meta-analysis, treatments were ranked based on their effectiveness for improving survival. In 33 eligible randomized controlled trials, 6072 patients were randomized to receive either surgery alone (N = 2459) or neoadjuvant CT (N = 1332), RT (N = 58), and CRT (N = 1196) followed by surgery or surgery followed by adjuvant CT (N = 542), RT (N = 383), and CRT (N = 102). Twenty-one comparisons were generated. Neoadjuvant CRT followed by surgery compared with surgery alone was the only treatment to significantly improve survival [hazard ratio (HR) = 0.77, 95% confidence interval (CI): 0.68-0.87]. When trials were grouped considering neoadjuvant and adjuvant therapies and surgery alone, neoadjuvant therapies combined with surgery compared with surgery alone showed a survival advantage (HR = 0.83, 95% CI 0.76-0.90), whereas surgery along with adjuvant therapies showed no significant survival advantage (HR = 0.87, 95% CI 0.67-1.14). A subgroup analysis of neoadjuvant therapies showed a superior effectiveness of neoadjuvant CRT and surgery compared with surgery alone (HR = 0.77, 95% CI 0.68-0.87). This network meta-analysis showed neoadjuvant CRT followed by surgery to be the most effective strategy in improving survival of resectable esophageal cancer. Resources should be focused on developing the most effective neoadjuvant CRT regimens for both adenocarcinomas and squamous cell carcinomas of the esophagus.
Miller, Benjamin J; Gao, Yubo; Duchman, Kyle R
2017-09-01
There is continuing debate regarding the ideal modality for local control of the primary tumor for patients with Ewing's sarcoma. The primary aim of this study is to investigate the impact of the method of local control on overall survival in patients with Ewing's sarcoma. The National Cancer Data Base was used to identify patients <40 years of age with high-grade Ewing's sarcoma of bone. A Kaplan-Meier survival analysis was performed at 2, 5, and 10 years. Factors with a level of significance of P < 0.1 at the 5-year time point were included in a multivariate Cox proportional hazards model. Diminished 5-year survival was noted for patients with metastatic disease, local control with radiation alone, age ≥18 years, tumor size >8 cm, and male sex while controlling for tumor site. Surgery alone was consistently the method of local control that resulted in the highest overall survival. Surgery alone resulted in the best overall survival for patients with Ewing's sarcoma of bone. The results of this investigation provide support to the approach of surgical resection with negative margins when possible. © 2017 Wiley Periodicals, Inc.
Wang, Huanbin; Yao, Han; Li, Chushu; Liang, Lunxi; Zhang, Yao; Shi, Hubing; Zhou, Chongzhi; Chen, Yingxuan; Fang, Jing-Yuan; Xu, Jie
2017-01-01
Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46.3 vs 69.1 mo; p = 0.0004). The association remained significant in multivariate COX regression analysis (hazard ratio = 2.778, 95% confidence interval [CI] = 1.668-4.627; p < 0.0001). In the validation CRC data set, significant association between PD-L2 overexpression and poor survival was supported by the univariate analysis (27.1 vs. 88.9 mo; p = 0.0002) and multivariate model (hazard ratio = 7.09, 95%CI 1.78-28.16; p = 0.005). Western Blot revealed strong induction of PD-L2 expression by interferon-γ (IFNγ) in CRC cells, and the mRNA levels of both genes were significantly correlated in CRC tissue samples. Suppression of glycosylation with tunicamycin caused a shift in molecular weight and significant decrease in the expression of PD-L2 protein. In conclusion, PD-L2 overexpression in CRC cells, under the regulation by IFNγ and glycosylation, associates with poor survival of patients with colorectal cancer. These findings highlight PD-L2 as a promising therapeutic target in CRC and suggest potential routes to control PD-L2 expression in CRC cells.
Wang, Huanbin; Yao, Han; Li, Chushu; Liang, Lunxi; Zhang, Yao; Shi, Hubing; Zhou, Chongzhi; Chen, Yingxuan; Fang, Jing-Yuan
2017-01-01
ABSTRACT Colorectal cancer (CRC) is the second leading cause of cancer death worldwide, and immune checkpoint blockade therapy provides an opportunity for improving the outcome of CRC patients. Recent studies suggest that programmed death ligand-1 (PD-L1) is only expressed in 12% of CRCs. Here, we demonstrate that PD-L2 is expressed in approximately 40% CRCs, and its expression independently associates with poor survival of CRC patients. By detection of PD-L2 expression by immunofluorescence in 124 CRC cases with 10-y survival data, we found significant association between PD-L2 overexpression in cancer cells and worse overall survival (46.3 vs 69.1 mo; p = 0.0004). The association remained significant in multivariate COX regression analysis (hazard ratio = 2.778, 95% confidence interval [CI] = 1.668–4.627; p < 0.0001). In the validation CRC data set, significant association between PD-L2 overexpression and poor survival was supported by the univariate analysis (27.1 vs. 88.9 mo; p = 0.0002) and multivariate model (hazard ratio = 7.09, 95%CI 1.78–28.16; p = 0.005). Western Blot revealed strong induction of PD-L2 expression by interferon-γ (IFNγ) in CRC cells, and the mRNA levels of both genes were significantly correlated in CRC tissue samples. Suppression of glycosylation with tunicamycin caused a shift in molecular weight and significant decrease in the expression of PD-L2 protein. In conclusion, PD-L2 overexpression in CRC cells, under the regulation by IFNγ and glycosylation, associates with poor survival of patients with colorectal cancer. These findings highlight PD-L2 as a promising therapeutic target in CRC and suggest potential routes to control PD-L2 expression in CRC cells. PMID:28811964
El Jellas, Khadija; Hoem, Dag; Hagen, Kristin G; Kalvenes, May Britt; Aziz, Sura; Steine, Solrun J; Immervoll, Heike; Johansson, Stefan; Molven, Anders
2017-07-01
Both serology-based and genetic studies have reported an association between pancreatic cancer risk and ABO blood groups. We have investigated this relationship in a cohort of pancreatic cancer patients from Western Norway (n = 237) and two control materials (healthy blood donors, n = 379; unselected hospitalized patients, n = 6149). When comparing patient and blood donor ABO allele frequencies, we found only the A 1 allele to be associated with significantly higher risk for pancreatic ductal adenocarcinoma (PDAC) (23.8% vs. 17.9%; OR = 1.43, P = 0.018). Analyzing phenotypes, blood group A was more frequent among PDAC cases than blood donors (50.8% vs. 40.6%; OR = 1.51, P = 0.021), an enrichment fully explained by the A 1 subgroup. Blood group O frequency was lower in cases than in blood donors (33.8% vs. 42.7%; OR = 0.69, P = 0.039). This lower frequency was confirmed when cases were compared to hospitalized patients (33.8% vs. 42.9%; OR = 0.68, P = 0.012). Results for blood group B varied according to which control cohort was used for comparison. When patients were classified according to surgical treatment, the enrichment of blood group A was most prominent among unresected cases (54.0%), who also had the lowest prevalence of O (28.7%). There was a statistically significant better survival (P = 0.04) for blood group O cases than non-O cases among unresected but not among resected patients. Secretor status did not show an association with PDAC or survival. Our study demonstrates that pancreatic cancer risk is influenced by ABO status, in particular blood groups O and A 1 , and that this association may reflect also in tumor resectability and survival. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
Lai, Chung-Yu; Lin, Fu-Huang; Chu, Hsin; Ku, Chih-Hung; Tsai, Shih-Hung; Chung, Chi-Hsiang; Chien, Wu-Chien; Wu, Chun-Hsien; Chu, Chi-Ming; Chang, Chi-Wen
2018-01-01
The chain of survival has been shown to improve the chances of survival for victims of cardiac arrest. Post-cardiac arrest care has been demonstrated to significantly impact the survival of out-of-hospital cardiac arrest (OHCA). How post-cardiac arrest care influences the survival of OHCA patients has been a main concern in recent years. The objective of this study was to assess the survival outcome of hospitalized OHCA patients and determine the factors associated with improved survival in terms of survival to discharge. We conducted a retrospective observational study by analyzing records from the National Health Insurance Research Database of Taiwan from 2007 to 2013. We collected cases with an International Classification of Disease Clinical Modification, 9th revision primary diagnosis codes of 427.41 (ventricular fibrillation, VF) or 427.5 (cardiac arrest) and excluded patients less than 18 years old, as well as cases with an unknown outcome or a combination of traumatic comorbidities. We then calculated the proportion of survival to discharge among hospitalized OHCA patients. Factors associated with the dependent variable were examined by logistic regression. Statistical analysis was conducted using SPSS 22 (IBM, Armonk, NY). Of the 11,000 cases, 2,499 patients (22.7%) survived to hospital discharge. The mean age of subjects who survived to hospital discharge and those who did not was 66.7±16.7 and 71.7±15.2 years, respectively. After adjusting for covariates, neurological failure, cardiac comorbidities, hospital level, intensive care unit beds, transfer to another hospital, and length of hospital stay were independent predictors of improved survival. Cardiac rhythm on admission was a strong factor associated with survival to discharge (VF vs. non-VF: adjusted odds ratio: 3.51; 95% confidence interval: 3.06-4.01). In conclusion, cardiac comorbidities, hospital volume, cardiac rhythm on admission, transfer to another hospital and length of hospital stay had a significant positive association with survival to discharge in hospitalized OHCA patients in Taiwan.
Yadav, Siddhartha; Yadav, Dhiraj; Zakalik, Dana
2017-07-01
Squamous cell carcinoma of breast accounts for less than 0.1% of all breast cancers. The purpose of this study is to describe the epidemiology and survival of this rare malignancy. Data were extracted from the National Cancer Institute's Surveillance, Epidemiology and End Results Registry to identify women diagnosed with squamous cell carcinoma of breast between 1998 and 2013. SEER*Stat 8.3.1 was used to calculate age-adjusted incidence, age-wise distribution, and annual percentage change in incidence. Kaplan-Meier curves were plotted for survival analysis. Univariate and multivariate Cox proportional hazard regression model was used to determine predictors of survival. A total of 445 cases of squamous cell carcinoma of breast were diagnosed during the study period. The median age of diagnosis was 67 years. The overall age-adjusted incidence between 1998 and 2013 was 0.62 per 1,000,000 per year, and the incidence has been on a decline. Approximately half of the tumors were poorly differentiated. Stage II was the most common stage at presentation. Majority of the cases were negative for expression of estrogen and progesterone receptor. One-third of the cases underwent breast conservation surgery while more than half of the cases underwent mastectomy (unilateral or bilateral). Approximately one-third of cases received radiation treatment. The 1-year and 5-year cause-specific survival was 81.6 and 63.5%, respectively. Excluding patient with metastasis or unknown stage at presentation, in multivariate Cox proportional hazard model, older age at diagnosis and higher tumor stage (T3 or T4) or nodal stage at presentation were significant predictors of poor survival. Our study describes the unique characteristics of squamous cell carcinoma of breast and demonstrates that it is an aggressive tumor with a poor survival. Older age and higher tumor or nodal stages at presentation were independent predictors of poor survival for loco-regional stages.
Cheskes, Sheldon; Schmicker, Robert H; Rea, Tom; Morrison, Laurie J; Grunau, Brian; Drennan, Ian R; Leroux, Brian; Vaillancourt, Christian; Schmidt, Terri A; Koller, Allison C; Kudenchuk, Peter; Aufderheide, Tom P; Herren, Heather; Flickinger, Katharyn H; Charleston, Mark; Straight, Ron; Christenson, Jim
2017-07-01
Measures of chest compression fraction (CCF), compression rate, compression depth and pre-shock pause have all been independently associated with improved outcomes from out-of-hospital (OHCA) cardiac arrest. However, it is unknown whether compliance with American Heart Association (AHA) guidelines incorporating all the aforementioned metrics, is associated with improved survival from OHCA. We performed a secondary analysis of prospectively collected data from the Resuscitation Outcomes Consortium Epistry-Cardiac Arrest database. As per the 2015 American Heart Association (AHA) guidelines, guideline compliant cardiopulmonary resuscitation (CPR) was defined as CCF >0.8, chest compression rate 100-120/minute, chest compression depth 50-60mm, and pre-shock pause <10s. Multivariable logistic regression models controlling for Utstein variables were used to assess the relationship between global guideline compliance and survival to hospital discharge and neurologically intact survival with MRS ≤3. Due to potential confounding between CPR quality metrics and cases that achieved early ROSC, we performed an a priori subgroup analysis restricted to patients who obtained ROSC after ≥10min of EMS resuscitation. After allowing for study exclusions, 19,568 defibrillator records were collected over a 4-year period ending in June 2015. For all reported models, the reference standard included all cases who did not meet all CPR quality benchmarks. For the primary model (CCF, rate, depth), there was no significant difference in survival for resuscitations that met all CPR quality benchmarks (guideline compliant) compared to the reference standard (OR 1.26; 95% CI: 0.80, 1.97). When the dataset was restricted to patients obtaining ROSC after ≥10min of EMS resuscitation (n=4,158), survival was significantly higher for those resuscitations that were guideline compliant (OR 2.17; 95% CI: 1.11, 4.27) compared to the reference standard. Similar findings were obtained for neurologically intact survival with MRS ≤3 (OR 3.03; 95% CI: 1.12, 8.20). In this observational study, compliance with AHA guidelines for CPR quality was not associated with improved outcomes from OHCA. Conversely, when restricting the cohort to those with late ROSC, compliance with guidelines was associated with improved clinical outcomes. Strategies to improve overall guideline compliance may have a significant impact on outcomes from OHCA. Copyright © 2017 Elsevier B.V. All rights reserved.
Fazeli, Bahare; Ravari, Hassan; Assadi, Reza
2012-08-01
The aim of this study was first to describe the natural history of Buerger's disease (BD) and then to discuss a clinical approach to this disease based on multivariate analysis. One hundred eight patients who corresponded with Shionoya's criteria were selected from 2000 to 2007 for this study. Major amputation was considered the ultimate adverse event. Survival analyses were performed by Kaplan-Meier curves. Independent variables including gender, duration of smoking, number of cigarettes smoked per day, minor amputation events and type of treatments, were determined by multivariate Cox regression analysis. The recorded data demonstrated that BD may present in four forms, including relapsing-remitting (75%), secondary progressive (4.6%), primary progressive (14.2%) and benign BD (6.2%). Most of the amputations occurred due to relapses within the six years after diagnosis of BD. In multivariate analysis, duration of smoking of more than 20 years had a significant relationship with further major amputation among patients with BD. Smoking cessation programs with experienced psychotherapists are strongly recommended for those areas in which Buerger's disease is common. Patients who have smoked for more than 20 years should be encouraged to quit smoking, but should also be recommended for more advanced treatment for limb salvage.
Reilly, J T; Snowden, J A; Spearing, R L; Fitzgerald, P M; Jones, N; Watmore, A; Potter, A
1997-07-01
The prognostic significance of cytogenetic abnormalities was determined in 106 patients with well-characterized idiopathic myelofibrosis who were successfully karyotyped at diagnosis. 35% of the cases exhibited a clonal abnormality (37/106), whereas 65% (69/106) had a normal karyotype. Three characteristic defects, namely del(13q) (nine cases), del(20q) (eight cases) and partial trisomy 1q (seven cases), were present in 64.8% (24/37) of patients with clonal abnormalities. Kaplan-Meier plots and log rank analysis demonstrated an abnormal karyotype to be an adverse prognostic variable (P<0.001). Of the eight additional clinical and haematological parameters recorded at diagnosis, age (P<0.01), anaemia (haemoglobin < or = 10 g/dl: P<0.001), platelet (< or = 100 x 10(9)/l, P<0.0001) and leucocyte count (> 10.3 x 10(9)/l; P=0.06) were also associated with a shorter survival. In contrast, sex, spleen and liver size, and percentage blast cells were not found to be significant. Multivariate analysis, using Cox's regression, revealed karyotype, haemoglobin concentration, platelet and leucocyte counts to retain their unfavourable prognostic significance. A simple and useful schema for predicting survival in idiopathic myelofibrosis has been produced by combining age, haemoglobin concentration and karyotype with median survival times varying from 180 months (good-risk group) to 16 months (poor-risk group).
Chen, Li-Sheng; Yen, Amy Ming-Fang; Duffy, Stephen W; Tabar, Laszlo; Lin, Wen-Chou; Chen, Hsiu-Hsi
2010-10-01
Population-based routine service screening has gained popularity following an era of randomized controlled trials. The evaluation of these service screening programs is subject to study design, data availability, and the precise data analysis for adjusting bias. We developed a computer-aided system that allows the evaluation of population-based service screening to unify these aspects and facilitate and guide the program assessor to efficiently perform an evaluation. This system underpins two experimental designs: the posttest-only non-equivalent design and the one-group pretest-posttest design and demonstrates the type of data required at both the population and individual levels. Three major analyses were developed that included a cumulative mortality analysis, survival analysis with lead-time adjustment, and self-selection bias adjustment. We used SAS AF software to develop a graphic interface system with a pull-down menu style. We demonstrate the application of this system with data obtained from a Swedish population-based service screen and a population-based randomized controlled trial for the screening of breast, colorectal, and prostate cancer, and one service screening program for cervical cancer with Pap smears. The system provided automated descriptive results based on the various sources of available data and cumulative mortality curves corresponding to the study designs. The comparison of cumulative survival between clinically and screen-detected cases without a lead-time adjustment are also demonstrated. The intention-to-treat and noncompliance analysis with self-selection bias adjustments are also shown to assess the effectiveness of the population-based service screening program. Model validation was composed of a comparison between our adjusted self-selection bias estimates and the empirical results on effectiveness reported in the literature. We demonstrate a computer-aided system allowing the evaluation of population-based service screening programs with an adjustment for self-selection and lead-time bias. This is achieved by providing a tutorial guide from the study design to the data analysis, with bias adjustment. Copyright © 2010 Elsevier Inc. All rights reserved.
Association of choline and betaine levels with cancer incidence and survival: A meta-analysis.
Youn, Jiyoung; Cho, Eunyoung; Lee, Jung Eun
2018-03-22
Evidences suggest possible link between betaine and choline, methyl group donors, and cancer progression. We examined the association between choline and betaine levels and cancer incidence and survival in a meta-analysis of observational studies. We identified observational studies examining the association between choline and/or betaine levels from diet or blood and cancer incidence and survival by searching the PubMed and Web of Science databases for studies published up to Jan, 2018. After applying the selection criteria, 28 observational studies (9 case-control, 1 cross-sectional, and 18 cohort studies) were included. Relative risks (RRs) and 95% confidence intervals (CIs) were extracted, and combined RRs were calculated using random-effects models. Choline levels were not associated with cancer incidence in a meta-analysis of cohort studies. Betaine levels reduced the risk of cancer incidence in a meta-analysis of cohort studies; combined relative risks (RRs) (95% CIs) comparing the top with the bottom categories were 0.93 (0.87-0.99). When we analyzed separately according to exposure assessment method, combined RRs (95% CIs) comparing the top with the bottom categories of betaine levels were 0.87 (95% CI: 0.78-0.95) for dietary betaine and 0.88 (95% CI: 0.77-0.99) for blood levels of betaine. There were no significant associations with cancer survivorship of choline or betaine levels. We concluded that high betaine levels were associated with lower risk of the cancer incidence, especially for colorectal cancer. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Cardiopulmonary resuscitation quality: Widespread variation in data intervals used for analysis.
Talikowska, Milena; Tohira, Hideo; Bailey, Paul; Finn, Judith
2016-05-01
There is a growing body of evidence for the relationship between CPR quality and survival in cardiac arrest patients. We sought to describe the characteristics of the analysis intervals used across studies. Relevant papers were selected as described in our recent systematic review. From these papers we collected information about (1) the time interval used for analysis; (2) the event that marked the beginning of the analysis interval; and (3) the minimum amount of CPR quality data required for a case to be included in the analysed cohort. We then compared this data across papers. Twenty-one studies reported on the association between CPR quality and cardiac arrest patient survival. In two thirds of studies data from the start of the resuscitation episode was analysed, in particular the first 5min. Commencement of the analysis interval was marked by various events including ECG pad placement and first chest compression. Nine studies specified a minimum amount of data that had to have been collected for the individual case to be included in the analysis; most commonly 1min of data. The use of shorter intervals allowed for inclusion of more cases as it included cases that did not have a complete dataset. To facilitate comparisons across studies, a standardised definition of the data analysis interval should be developed; one that maximises the amount of cases available without compromising the data's representability of the resuscitation effort. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Mou, Hong-Yuan; Nie, Hong-Ming; Hu, Xiao-Yu
2017-04-28
To verify the value of Gutuo Jiejiu decoction in improving the survival of patients with severe alcoholic hepatitis (SAH). We performed a retrospective cohort study in consecutive patients diagnosed with SAH at the Teaching Hospital of Chengdu University of Traditional Chinese Medicine and Shuguang Hospital, Shanghai University of Traditional Chinese Medicine. The traditional Chinese medicine formula Gutuo Jiejiu decoction was employed as an exposure factor. Patients from the Teaching Hospital of Chengdu University of Traditional Chinese Medicine who had been treated with Gutuo Jiejiu decoction + prednisone were assigned to an observation group, and patients from Shuguang Hospital, Shanghai University of Traditional Chinese Medicine who had been treated with prednisone alone were selected as a control group. A retrospective analysis was performed by comparing age, alcohol intake, and clinical parameters of liver injury before and after treatment. Additionally, the 3- and 12-mo survival rates and the occurrence of complications were analyzed. One hundred and twenty-eight eligible patients were selected from 175 cases with SAH, of which 68 were assigned to the observation group and the other 60 to the control group. No significant difference was found in the patients' baseline characteristics ( P > 0.05). However, significant improvements of 90-d survival rate [56/68 (82.4%) vs 27/60 (45.0%), P = 0.0000] and 365-d survival rate [48/68 (70.6%) vs 13/60 (21.7%), P = 00000] were observed in the observation group after treatment. After the first 3 mo of treatment, more improvements in the clinical parameters and scoring systems related to liver injury occurred in the observation group than in the control group ( P < 0.05). After treatment for 12 mo, the differences in the clinical parameters and scoring systems related to liver injury between the two groups were more significant ( P < 0.05). No significant differences in complications and adverse effects were found between the two groups. Gutuo Jiejiu decoction could improve the survival rates and clinical parameters of liver injury in patients with SAH, and may represent a new option for treating SAH.
Du, Jun-dong; Liu, Rong; Jiao, Hua-bo; Xiang, De-dong; Yin, Hui-nan; Li, Zhen-cai; Li, Tao; Zhu, Zi-man; Li, Zhan-liang
2011-05-01
To explore the effects of percutaneous transhepatic radiofrequency ablation (PRFA) combined with tumor edge of percutaneous absolute ethanol injection (PEI) on liver cancer adjacent to major blood vessels. Seventy five patients with liver cancer adjacent to major blood vessels were randomly divided into two groups: PRFA+PEI therapy group (38 cases) and PRFA control group (37 cases). Tumor necrosis rate, AFP levels, local recurrence rate, median for survival time and cum survival were used as the evaluation index to evaluate the efficacies of the two methods. Tumor necrosis rates of the therapy group and the control group were 84.2% and 54.1% (P < 0.01), respectively; AFP levels of therapy group and control group at 1, 3, 6 and 12 months after treatment were (105.0 ± 35.5) μg/L, (28.4 ± 4.3) μg/L, (58.6 ± 6.7) μg/L, (89.5 ± 12.5) μg/L and (137.2 ± 34.6) μg/L, (84.2 ± 18.4) μg/L, (106.6 ± 20.3) μg/L, (173.7 ± 32.0) μg/L, respectively. The rates of therapy group was significantly lower than of control group. Local recurrence rates of the therapy group and control group were 2.6%, 7.9%, 13.2% and 31.6% vs 10.8%, 21.6% , 40.5% and 62.1% (P < 0.05) at 3, 6, 12 and 24 months after treatment, respectively. Median for survival time of the therapy group and control group were 28.0 ± 2.8 months and 19.0 ± 3.6 months, respectively. Cum survival of the therapy group and control group were 84.2%, 78.9%, 60.5% and 31.6% vs 78.4%, 67.6%, 37.8% and 8.1% (P < 0.05) at 6, 12, 24 and 36 months after treatment, respectively. PEI as a supplementary treatment of PRFA can effectively improve the treatment of liver cancer adjacent to major blood vessels and significantly reduce the local recurrence rate and improve long-term survival rates.
MYC and Human Telomerase Gene (TERC) Copy Number Gain in Early-stage Non–small Cell Lung Cancer
Flacco, Antonella; Ludovini, Vienna; Bianconi, Fortunato; Ragusa, Mark; Bellezza, Guido; Tofanetti, Francesca R.; Pistola, Lorenza; Siggillino, Annamaria; Vannucci, Jacopo; Cagini, Lucio; Sidoni, Angelo; Puma, Francesco; Varella-Garcia, Marileila; Crinò, Lucio
2015-01-01
Objectives We investigated the frequency of MYC and TERC increased gene copy number (GCN) in early-stage non–small cell lung cancer (NSCLC) and evaluated the correlation of these genomic imbalances with clinicopathologic parameters and outcome. Materials and Methods Tumor tissues were obtained from 113 resected NSCLCs. MYC and TERC GCNs were tested by fluorescence in situ hybridization (FISH) according to the University of Colorado Cancer Center (UCCC) criteria and based on the receiver operating characteristic (ROC) classification. Results When UCCC criteria were applied, 41 (36%) cases for MYC and 41 (36%) cases for TERC were considered FISH-positive. MYC and TERC concurrent FISH-positive was observed in 12 cases (11%): 2 (17%) cases with gene amplification and 10 (83%) with high polysomy. By using the ROC analysis, high MYC (mean ≥2.83 copies/cell) and TERC (mean ≥2.65 copies/cell) GCNs were observed in 60 (53.1%) cases and 58 (51.3%) cases, respectively. High TERC GCN was associated with squamous cell carcinoma (SCC) histology (P = 0.001). In univariate analysis, increased MYC GCN was associated with shorter overall survival (P = 0.032 [UCCC criteria] or P = 0.02 [ROC classification]), whereas high TERC GCN showed no association. In multivariate analysis including stage and age, high MYC GCN remained significantly associated with worse overall survival using both the UCCC criteria (P = 0.02) and the ROC classification (P = 0.008). Conclusions Our results confirm MYC as frequently amplified in early-stage NSCLC and increased MYC GCN as a strong predictor of worse survival. Increased TERC GCN does not have prognostic impact but has strong association with squamous histology. PMID:25806711
Structuring Formal Control Systems Specifications for Reuse: Surviving Hardware Changes
NASA Technical Reports Server (NTRS)
Thompson, Jeffrey M.; Heimdahl, Mats P. E.; Erickson, Debra M.
2000-01-01
Formal capture and analysis of the required behavior of control systems have many advantages. For instance, it encourages rigorous requirements analysis, the required behavior is unambiguously defined, and we can assure that various safety properties are satisfied. Formal modeling is, however, a costly and time consuming process and if one could reuse the formal models over a family of products, significant cost savings would be realized. In an ongoing project we are investigating how to structure state-based models to achieve a high level of reusability within product families. In this paper we discuss a high-level structure of requirements models that achieves reusability of the desired control behavior across varying hardware platforms in a product family. The structuring approach is demonstrated through a case study in the mobile robotics domain where the desired robot behavior is reused on two diverse platforms-one commercial mobile platform and one build in-house. We use our language RSML (-e) to capture the control behavior for reuse and our tool NIMBUS to demonstrate how the formal specification can be validated and used as a prototype on the two platforms.
Jakab, Zsuzsanna; Juhasz, Attila; Nagy, Csilla; Schuler, Dezso; Garami, Miklos
2017-09-01
The Hungarian Childhood Cancer Registry, a population-based national registry of the Hungarian Paediatric Haemato-Oncology Network founded in 1971, monitors the incidence and mortality of childhood cancer. Our aims were to carry out a longitudinal study to investigate the trends and spatial inequalities of incidence and survival of leukaemia, and the association between survival and deprivation in Hungary. All cases of childhood leukaemia and myelodysplasia were analysed (3157 cases, 1971-2015, age: 0-14 years). Time trends and the annual percentage change in direct standardized incidence and mortality were assessed. Survival and association with deprivation were assessed using the Kaplan-Meier method and Cox regression. Incidence rates of leukaemia (23.5-56.0/million) increased with an average annual percent change (AAPC) of 1%, determined by an increase in the incidence of acute lymphoblastic leukaemia (14.6-39.2/million, AAPC: 1.25%). Kaplan-Meier analysis showed a significant improvement in overall survival over the study period. Starting from 25% of cases surviving 5 years in the 70s; the overall 5-year survival reached 80% by 2010. Survival differences were observed with sex, leukaemia type and age at diagnosis. A reverse association was found in the survival probability of leukaemia by degree of deprivation. The Cox proportional hazards model verified a significant reverse association with deprivation [hazard ratio=1.08 (1.04-1.12)]. This is the first nationwide study to confirm the prognostic role of deprivation on the basis of a large cohort of patients with childhood leukaemia during a 45-year period. To maintain further improvement in treatment results, it is important to detect inequalities. Our results showed that deprivation may also be important in the survival of leukaemia.
Charrier, J A; Steen, C L; Borrero, E
2017-01-01
A diagnosis of severe sepsis or septic shock has been shown to significantly increase mortality rate independent of other factors. Research has revealed all cause hospital case fatality rates have declined yet the percentage of severe sepsis cases continues to increase and age-adjusted mortality rates from severe sepsis and septic shock has significantly increased during the same time period. Patients with severe sepsis demonstrate ongoing mortality rate increases for up to 2 years following hospitalization when compared to aged matched controls of nonseptic patients. International guidelines with mortality benefit for the management of severe sepsis and septic shock have been illustrated in the latest surviving sepsis campaign. The objective of this study was to increase the percentage of patients admitted to the hospital with a diagnosis of severe sepsis or septic shock who met guidelines based on surviving sepsis campaign. A retrospective chart review was conducted for patients admitted to UHC from January 2016 to present to identify cases with a diagnosis of severe sepsis or septic shock, and whether they met guidelines set forth by surviving sepsis campaign both before and after an intervention program which included interviews with providers failing to meet protocol, educational sessions on guidelines to meet protocol, resident led quality improvement workshops to address barriers to meeting protocol, and development of an EMR power plan to assist providers on meeting protocol. 139 cases with a diagnosis, or meeting criteria for, severe sepsis or septic shock were identified during the period of 1/1/2016-9/30/2016 with an average of 43 percent of total cases which met guidelines. Trend analysis revealed increased compliance following resident lead intervention program with 31 percent and 49 percent before and after intervention, respectively. ICU data is currently being analyzed for meeting guidelines and have not been included in current data. The most common reason for failing guidelines was failure to obtain or repeat lactic acid on time (46 percent ); and failure to give timely antibiotics (22 percent );. The percentage of patients admitted to the hospital with a diagnosis of severe sepsis or septic shock at UHC meeting guidelines set forth by surviving sepsis campaign has improved following resident lead intervention program. Intervention strategies to further improve compliance with guidelines with a goal >60 percent are currently being analyzed.
Wang, Yan-Gang; Wang, Peng; Wang, Bin; Fu, Zheng-Ju; Zhao, Wen-Juan; Yan, Sheng-Li
2014-01-01
Previous studies suggested that diabetes mellitus was associated with cancer risk and prognosis, but studies investigating the relationship between diabetes mellitus and survival in patients with hepatocellular carcinoma (HCC) reported inconsistent findings. To derive a more precise estimate of the prognostic role of diabetes mellitus in HCC, we systematically reviewed published studies and carried out a meta-analysis. Eligible articles were identified in electronic databases from their inception through September 16, 2013. To evaluate the correlation between diabetes mellitus and prognosis in HCC, the pooled hazard ratios (HR) and their 95% confidence intervals (95% CI) for poorer overall and disease-free survivals were calculated by standard meta-analysis techniques with fixed-effects or random-effects models. 21 studies with a total of 9,767 HCC patients stratifying overall survival and/or disease-free survival in HCC patients by diabetes mellitus status were eligible for meta-analysis. 20 studies with a total of 9,727 HCC cases investigated the overall survival, and 10 studies with a total of 2,412 HCC patients investigated the disease-free survival. The pooled HRs for overall survival and disease-free survival were 1.46 (95% CI, 1.29 to 1.66; P<0.001) and 1.57 (95% CI, 1.21 to 2.05; P = 0.001), respectively. The adjusted HRs for overall survival and disease-free survival were 1.55 (95% CI, 1.27 to 1.91; P<0.001) and 2.15 (95% CI, 1.75 to 2.63; P<0.001), respectively. In addition, for patients receiving hepatic resection, diabetes mellitus was associated with both poorer overall survival and poorer disease-free survival, and for patients receiving non-surgical treatment or patients receiving radiofrequency ablation, diabetes mellitus was associated with poorer overall survival. There was no evidence for publication bias. Diabetes mellitus is independently associated with both poorer overall survival and poorer disease-free survival in HCC patients.
Zhang, L L; Cao, F F; Wang, Y; Meng, F L; Zhang, Y; Zhong, D S; Zhou, Q H
2015-05-01
The application of newer signaling pathway-targeted agents has become an important addition to chemotherapy in the treatment of advanced non-small cell lung cancer (NSCLC). In this study, we evaluated the efficacy and toxicities of PKC inhibitors combined with chemotherapy versus chemotherapy alone for patients with advanced NSCLC systematically. Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook 5.1.0. The outcome measures were tumor response rate, disease control rate, progression-free survival (PFS), overall survival (OS), and adverse effects. Five randomized controlled trials, comprising totally 1,005 patients, were included in this study. Meta-analysis showed significantly decreased response rate (RR 0.79; 95 % CI 0.64-0.99) and disease control rate (RR 0.90; 95 % CI 0.82-0.99) in PKC inhibitors-chemotherapy groups versus chemotherapy groups. There was no significant difference between the two treatment groups regarding progression-free survival (PFS, HR 1.05; 95 % CI 0.91-1.22) and overall survival (OS, HR 1.00; 95 % CI 0.86-1.16). The risk of grade 3/4 neutropenia, leucopenia, and thrombosis/embolism increased significantly in PKC inhibitors combination groups as compared with chemotherapy alone groups. The use of PKC inhibitors in addition to chemotherapy was not a valid alternative for patients with advanced NSCLC.
Gotti, Daria; Raffetti, Elena; Albini, Laura; Sighinolfi, Laura; Maggiolo, Franco; Di Filippo, Elisa; Ladisa, Nicoletta; Angarano, Gioacchino; Lapadula, Giuseppe; Pan, Angelo; Esposti, Anna Degli; Fabbiani, Massimiliano; Focà, Emanuele; Scalzini, Alfredo; Donato, Francesco; Quiros-Roldan, Eugenia
2014-01-01
We studied survival and associated risk factors in an Italian nationwide cohort of HIV-infected individuals after an AIDS-defining cancer (ADC) or non-AIDS-defining cancer (NADC) diagnosis in the modern cART era. Multi-center, retrospective, observational study of HIV patients included in the MASTER Italian Cohort with a cancer diagnosis from January 1998 to September 2012. Malignancies were divided into ADC or NADC on the basis of the Centre for Disease Control-1993 classification. Recurrence of cancer and metastases were excluded. Survivals were estimated according to the Kaplan-Meier method and compared according to the log-rank test. Statistically significant variables at univariate analysis were entered in a multivariate Cox regression model. Eight hundred and sixty-six cancer diagnoses were recorded among 13,388 subjects in the MASTER Database after 1998: 435 (51%) were ADCs and 431 (49%) were NADCs. Survival was more favorable after an ADC diagnosis than a NADC diagnosis (10-year survival: 62.7%±2.9% vs. 46%±4.2%; p = 0.017). Non-Hodgkin lymphoma had lower survival rates than patients with Kaposi sarcoma or cervical cancer (10-year survival: 48.2%±4.3% vs. 72.8%±4.0% vs. 78.5%±9.9%; p<0.001). Regarding NADCs, breast cancer showed better survival (10-year survival: 65.1%±14%) than lung cancer (1-year survival: 28%±8.7%), liver cancer (5-year survival: 31.9%±6.4%) or Hodgkin lymphoma (10-year survival: 24.8%±11.2%). Lower CD4+ count and intravenous drug use were significantly associated with decreased survival after ADCs or NADCs diagnosis. Exposure to cART was found to be associated with prolonged survival only in the case of ADCs. cART has improved survival in patients with an ADC diagnosis, whereas the prognosis after a diagnosis of NADCs is poor. Low CD4+ counts and intravenous drug use are risk factors for survival following a diagnosis of ADCs and Hodgkin lymphoma in the NADC group.
Gotti, Daria; Raffetti, Elena; Albini, Laura; Sighinolfi, Laura; Maggiolo, Franco; Di Filippo, Elisa; Ladisa, Nicoletta; Angarano, Gioacchino; Lapadula, Giuseppe; Pan, Angelo; Esposti, Anna Degli; Fabbiani, Massimiliano; Focà, Emanuele; Scalzini, Alfredo; Donato, Francesco; Quiros-Roldan, Eugenia
2014-01-01
Objectives We studied survival and associated risk factors in an Italian nationwide cohort of HIV-infected individuals after an AIDS-defining cancer (ADC) or non-AIDS-defining cancer (NADC) diagnosis in the modern cART era. Methods Multi-center, retrospective, observational study of HIV patients included in the MASTER Italian Cohort with a cancer diagnosis from January 1998 to September 2012. Malignancies were divided into ADC or NADC on the basis of the Centre for Disease Control-1993 classification. Recurrence of cancer and metastases were excluded. Survivals were estimated according to the Kaplan-Meier method and compared according to the log-rank test. Statistically significant variables at univariate analysis were entered in a multivariate Cox regression model. Results Eight hundred and sixty-six cancer diagnoses were recorded among 13,388 subjects in the MASTER Database after 1998: 435 (51%) were ADCs and 431 (49%) were NADCs. Survival was more favorable after an ADC diagnosis than a NADC diagnosis (10-year survival: 62.7%±2.9% vs. 46%±4.2%; p = 0.017). Non-Hodgkin lymphoma had lower survival rates than patients with Kaposi sarcoma or cervical cancer (10-year survival: 48.2%±4.3% vs. 72.8%±4.0% vs. 78.5%±9.9%; p<0.001). Regarding NADCs, breast cancer showed better survival (10-year survival: 65.1%±14%) than lung cancer (1-year survival: 28%±8.7%), liver cancer (5-year survival: 31.9%±6.4%) or Hodgkin lymphoma (10-year survival: 24.8%±11.2%). Lower CD4+ count and intravenous drug use were significantly associated with decreased survival after ADCs or NADCs diagnosis. Exposure to cART was found to be associated with prolonged survival only in the case of ADCs. Conclusions cART has improved survival in patients with an ADC diagnosis, whereas the prognosis after a diagnosis of NADCs is poor. Low CD4+ counts and intravenous drug use are risk factors for survival following a diagnosis of ADCs and Hodgkin lymphoma in the NADC group. PMID:24760049
Marital status independently predicts testis cancer survival--an analysis of the SEER database.
Abern, Michael R; Dude, Annie M; Coogan, Christopher L
2012-01-01
Previous reports have shown that married men with malignancies have improved 10-year survival over unmarried men. We sought to investigate the effect of marital status on 10-year survival in a U.S. population-based cohort of men with testis cancer. We examined 30,789 cases of testis cancer reported to the Surveillance, Epidemiology, and End Results (SEER 17) database between 1973 and 2005. All staging were converted to the 1997 AJCC TNM system. Patients less than 18 years of age at time of diagnosis were excluded. A subgroup analysis of patients with stages I or II non-seminomatous germ cell tumors (NSGCT) was performed. Univariate analysis using t-tests and χ(2) tests compared characteristics of patients separated by marital status. Multivariate analysis was performed using a Cox proportional hazard model to generate Kaplan-Meier survival curves, with all-cause and cancer-specific mortality as the primary endpoints. 20,245 cases met the inclusion criteria. Married men were more likely to be older (38.9 vs. 31.4 years), Caucasian (94.4% vs. 92.1%), stage I (73.1% vs. 61.4%), and have seminoma as the tumor histology (57.3% vs. 43.4%). On multivariate analysis, married status (HR 0.58, P < 0.001) and Caucasian race (HR 0.66, P < 0.001) independently predicted improved overall survival, while increased age (HR 1.05, P < 0.001), increased stage (HR 1.53-6.59, P < 0.001), and lymphoid (HR 4.05, P < 0.001), or NSGCT (HR 1.89, P < 0.001) histology independently predicted death. Similarly, on multivariate analysis, married status (HR 0.60, P < 0.001) and Caucasian race (HR 0.57, P < 0.001) independently predicted improved testis cancer-specific survival, while increased age (HR 1.03, P < 0.001), increased stage (HR 2.51-15.67, P < 0.001), and NSGCT (HR 2.54, P < 0.001) histology independently predicted testis cancer-specific death. A subgroup analysis of men with stages I or II NSGCT revealed similar predictors of all-cause survival as the overall cohort, with retroperitoneal lymph node dissection (RPLND) as an additional independent predictor of overall survival (HR 0.59, P = 0.001), despite equal rates of the treatment between married and unmarried men (44.8% vs. 43.4%, P = 0.33). Marital status is an independent predictor of improved overall and cancer-specific survival in men with testis cancer. In men with stages I or II NSGCT, RPLND is an additional predictor of improved overall survival. Marital status does not appear to influence whether men undergo RPLND. Copyright © 2012 Elsevier Inc. All rights reserved.
Herold, Christian; Ueberreiter, Klaus; Busche, Marc N; Vogt, Peter M
2013-04-01
Autologous fat transplantation has gained great recognition in aesthetic and reconstructive surgery. Two main aspects are of predominant importance for progress control after autologous fat transplantation to the breast: quantitative information about the rate of fat survival in terms of effective volume persistence and qualitative information about the breast tissue to exclude potential complications of autologous fat transplantation. There are several tools available for use in evaluating the rate of volume survival. They are extensively compared in this review. The anthropometric method, thermoplastic casts, and Archimedes' principle of water displacement are not up to date anymore because of major drawbacks, first and foremost being reduced reproducibility and exactness. They have been replaced by more exact and reproducible tools such as MRI volumetry or 3D body surface scans. For qualitative and quantitative progress control, MRI volumetry offers all the necessary information: evaluation of fat survival and diagnostically valuable imaging to exclude possible complications of autologous fat transplantation. For frequent follow-up, e.g., monthly volume analysis, repeated MRI exams would not be good for the patient and are not cost effective. In these cases, 3D surface imaging is a good tool and especially helpful in a private practice setting where fast data acquisition is needed. This tool also offers the possibility of simulating the results of autologous fat transplantation. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Yaeger, Rona; Cowell, Elizabeth; Chou, Joanne F; Gewirtz, Alexandra N; Borsu, Laetitia; Vakiani, Efsevia; Solit, David B; Rosen, Neal; Capanu, Marinela; Ladanyi, Marc; Kemeny, Nancy
2015-04-15
RAS and PIK3CA mutations in metastatic colorectal cancer (mCRC) have been associated with worse survival. We sought to evaluate the impact of RAS and PIK3CA mutations on cumulative incidence of metastasis to potentially curable sites of liver and lung and other sites such as bone and brain. We performed a computerized search of the electronic medical record of our institution for mCRC cases genotyped for RAS or PIK3CA mutations from 2008 to 2012. Cases were reviewed for patient characteristics, survival, and site-specific metastasis. Among the 918 patients identified, 477 cases were RAS wild type, and 441 cases had a RAS mutation (394 at KRAS exon 2, 29 at KRAS exon 3 or 4, and 18 in NRAS). RAS mutation was significantly associated with shorter median overall survival (OS) and on multivariate analysis independently predicted worse OS (HR, 1.6; P < .01). RAS mutant mCRC exhibited a significantly higher cumulative incidence of lung, bone, and brain metastasis and on multivariate analysis was an independent predictor of involvement of these sites (HR, 1.5, 1.6, and 3.7, respectively). PIK3CA mutations occurred in 10% of the 786 cases genotyped, did not predict for worse survival, and did not exhibit a site-specific pattern of metastatic spread. The metastatic potential of CRC varies with the presence of RAS mutation. RAS mutation is associated with worse OS and increased incidence of lung, bone, and brain metastasis. An understanding of this site-specific pattern of spread may help to inform physicians' assessment of symptoms in patients with mCRC. © 2014 American Cancer Society.
Akyurek, Nalan; Uner, Aysegul; Benekli, Mustafa; Barista, Ibrahim
2012-09-01
Diffuse large B-cell lymphomas (DLBCLs) are a biologically heterogeneous group in which various gene alterations have been reported. The aim of this study was to investigate the frequency and prognostic impact of BCL2, BCL6, and MYC rearrangements in cyclophosphamide, doxorubicin, vincristine, and prednisone plus rituximab (R-CHOP)-treated DLBCL cases. Tissue microarrays were constructed from 239 cases of DLBCL, and the expressions of CD10, BCL6, MUM1/IRF4, and BCL2 were evaluated by immunohistochemistry. MYC, BCL2, and BCL6 rearrangements were investigated by interphase fluorescence in situ hybridization on tissue microarrays. Survival analysis was constructed from 145 R-CHOP-treated patients. MYC, BCL2, and BCL6 rearrangements were detected in 14 (6%), 36 (15%), and 69 (29%) of 239 DLBCL patients. Double or triple rearrangements were detected in 7 (3%) of 239 DLBCL cases. Of these, 4 had BCL2 and MYC, 2 had BCL6 and MYC, and 1 had BCL2, BCL6, and MYC rearrangements. The prognosis of these cases was extremely poor, with a median survival of 9 months. MYC rearrangement was associated with significantly worse overall survival (P = .01), especially for the cases with GC phenotype (P = .009). BCL6 rearrangement also predicted significantly shorter overall survival (P = .04), especially for the non-GC phenotype (P = .03). BCL2 rearrangement had no prognostic impact on outcome. International Prognostic Index (P = .004) and MYC rearrangement (P = .009) were independent poor prognostic factors. Analysis of MYC gene rearrangement along with BCL2 and BCL6 is critical in identifying high-risk patients with poor prognosis. Copyright © 2011 American Cancer Society.
Utilization of advanced-age donors in renal transplantation.
Olaverri, J G; Mora Christian, J; Elorrieta, P; Esnaola, K; Rodríguez, P; Marrón, I; Uriarte, I; Landa, M J; Zarraga, S; Gainza, F J; Aranzabal, J; Zabala, J A; Pertusa, C
2011-11-01
The shortage of organ availability in recent years has made it necessary to use grafts from advanced-aged donors to maintain the rate of renal transplantation in our country. The objective of this study was to evaluate the graft function and patient survival using kidneys from deceased donors of over 65 year of age. From 2005 until 2010, we compared the outcomes of patients who received grafts from donors over 65 years old vs less than 65 years. We observed no significant difference in sex, time on dialysis, or cold ischemia time between the groups. As expected the recipient age was significantly different. For the analysis of survival, we used the Tablecloth-Haenzel test and the Kaplan-Meier survival estimator. Actuarial survivals at 3 years after transplantation showed 84.8% among patients transplanted with kidneys from donors over 65 years old versus 97.5% in the control group. The graft survival was 78.8% among expanded criteria versus 86.85% in the control group. When we analyzed graft survival using an "exitus-censured" analysis, we obtained graft survivals of 89.1% in the expanded criteria kidney group versus 88.6% among the controls. We concluded that the use of kidney from donors over 65 years of age allows us to increase the rate of renal transplantation to about 15 to 20 per million population, with good graft and patient survivals provided that the protocol for expanded criteria organs ensured proper macroscopic and microscopic evaluation of the organ for transplantation. Copyright © 2011. Published by Elsevier Inc.
Dey, D; Kenu, E; Isenberg, D A
2013-08-01
We determined whether any individual cancers are increased or decreased in a cohort of 595 patients with systemic lupus erythematosus (SLE) followed for up to 32 years at the University College London Hospitals Lupus Clinic, looking for any associated clinical or serological factors and the prognosis after cancer diagnosis. We undertook a careful retrospective review of the medical records and identified all individuals diagnosed with cancer. For controls, we selected three other patients in the cohort who had not developed cancer, carefully matched for age, sex, ethnicity and disease duration, to determine if any obvious differences emerged in a nested case-control design. Thirty-three patients developed cancer after being diagnosed with SLE. There was a statistically insignificant small increase in overall cancer risk, standardized incidence ratios (SIRs) 1.05 (95% CI 0.52-1.58) and increased SIRs for cervical, prostate, anal and pancreatic cancers and reduction in breast cancer SIRs. Haematological and musculoskeletal manifestations, anticardiolipin and antithyroid globulin antibodies were found to be positively associated with cancer risk in multivariate analysis. There was no drug, dose or duration was associated with cancer risk. There was a reduction in survival with a cancer fatality rate of 84.2% (p < 0.0001). We found a very small but statistically insignificant increased cancer risk with reduction in survival. Whereas some cancers appear to be more common in SLE, notably prostate and cervical cancer, others, particularly breast cancer, are less frequent. Multiple clinical and serological factors are involved in the increased risk of malignancy in SLE. No drug dose or duration effect was identified.
Anthelmintic activity of Spigelia anthelmia extract against gastrointestinal nematodes of sheep.
Ademola, I O; Fagbemi, B O; Idowu, S O
2007-06-01
In vitro (larval development assay) and in vivo studies were conducted to determine possible direct anthelmintic effect of ethanolic and aqueous extracts of Spigelia anthelmia towards different ovine gastrointestinal nematodes. The effect of extracts on development and survival of infective larvae stage (L(3)) was assessed. Best-fit LC(50) values were computed by global model of non-linear regression curve fitting (95% confidence interval). Therapeutic efficacy of the ethanolic extracts administered orally at a dose rate of 125, 250, and 500 mg/kg, relative to a non-medicated control group of sheep harbouring naturally acquired infection of gastrointestinal nematodes, was evaluated in vivo.The presence of S. anthelmia extracts in the cultures decreased the survival of L(3) larvae. The LC(50) of aqueous extract (0.714 mg/ml) differ significantly from the LC(50) of the ethanolic extract (0.628 mg/ml) against the strongyles (p < 0.05, paired t-test). Faecal egg counts on day 12 after treatment showed that the extract is effective, relative to control (one-way analysis of variance [ANOVA], Dunnett's multiple comparison test) at 500 mg/kg against Strongyloides spp. (p < 0.01), 250 mg/kg against Oesophagostomum spp., Trichuris spp. (p < 0.05), and 125 mg/kg against Haemonchus spp. and Trichostrongylus spp. (p < 0.01). The effect of the doses is significant in all cases, the day after treatment is also extremely significant in most cases, whereas interaction between dose and day after treatment is significant (two-way ANOVA). S. anthelmia extract could, therefore, find application in the control of helminth in livestock, by the ethnoveterinary medicine approach.
Outcomes in Treatment for Intradural Spinal Cord Ependymomas
DOE Office of Scientific and Technical Information (OSTI.GOV)
Volpp, P. Brian; Han, Khanh; Kagan, A. Robert
2007-11-15
Purpose: Spinal cord ependymomas are rare tumors, accounting for <2% of all primary central nervous system tumors. This study assessed the treatment outcomes for patients diagnosed with spinal cord ependymomas within the Southern California Kaiser Permanente system. Methods and Materials: We studied 23 patients treated with surgery with or without external beam radiotherapy (EBRT). The local and distant control rates and overall survival rates were determined. Results: The overall local control, overall recurrence, and 9-year overall survival rate was 96%, 17.4%, and 63.9%, respectively. Conclusions: The results of our study indicate that en bloc gross total resection should be themore » initial treatment, with radiotherapy reserved primarily for postoperative cases with unfavorable characteristics such as residual tumor, anaplastic histologic features, or piecemeal resection. Excellent local control and overall survival rates can be achieved using modern microsurgical techniques, with or without local radiotherapy.« less
Matsumura, Y; Matsumoto, J; Idoguchi, K; Kondo, H; Ishida, T; Kon, Y; Tomita, K; Ishida, K; Hirose, T; Umakoshi, K; Funabiki, T
2017-08-22
Resuscitative endovascular balloon occlusion of the aorta (REBOA) is now a feasible and less invasive resuscitation procedure. This study aimed to compare the clinical course of trauma and non-trauma patients undergoing REBOA. Patient demographics, etiology, bleeding sites, hemodynamic response, length of critical care, and cause of death were recorded. Characteristics and outcomes were compared between non-trauma and trauma patients. Kaplan-Meier survival analysis was then conducted. Between August 2011 and December 2015, 142 (36 non-trauma; 106 trauma) cases were analyzed. Non-traumatic etiologies included gastrointestinal bleeding, obstetrics and gynecology-derived events, visceral aneurysm, abdominal aortic aneurysm, and post-abdominal surgery. The abdomen was a common bleeding site (69%), followed by the pelvis or extra-pelvic retroperitoneum. None of the non-trauma patients had multiple bleeding sites, whereas 45% of trauma patients did (P < 0.001). No non-trauma patients required resuscitative thoracotomy compared with 28% of the trauma patients (P < 0.001). Non-trauma patients presented a lower 24-h mortality than trauma patients (19 vs. 51%, P = 0.001). The non-trauma cases demonstrated a gradual but prolonged increased mortality, whereas survival in trauma cases rapidly declined (P = 0.009) with similar hospital mortality (68 vs. 64%). Non-trauma patients who survived for 24 h had 0 ventilator-free days and 0 ICU-free days vs. a median of 19 and 12, respectively, for trauma patients (P = 0.33 and 0.39, respectively). Non-hemorrhagic death was more common in non-trauma vs. trauma patients (83 vs. 33%, P < 0.001). Non-traumatic hemorrhagic shock often resulted from a single bleeding site, and resulted in better 24-h survival than traumatic hemorrhage among Japanese patients who underwent REBOA. However, hospital mortality increased steadily in non-trauma patients affected by non-hemorrhagic causes after a longer period of critical care.
Kelly, Paul J; Lin, Yijie Brittany; Yu, Alvin Y C; Ropper, Alexander E; Nguyen, Paul L; Marcus, Karen J; Hacker, Fred L; Weiss, Stephanie E
2011-09-01
To review the safety and efficacy of linear accelerator-based stereotactic radiosurgery (SRS) for brainstem metastases. We reviewed all patients with brain metastases treated with SRS at DF/BWCC from 2001 to 2009 to identify patients who had SRS to a single brainstem metastasis. Overall survival and freedom-from-local failure rates were calculated from the date of SRS using the Kaplan-Meier method. Prognostic factors were evaluated using the log-rank test and Cox proportional hazards model. A total of 24 consecutive patients with brainstem metastases had SRS. At the time of SRS, 21/24 had metastatic lesions elsewhere within the brain. 23/24 had undergone prior WBRT. Primary diagnoses included eight NSCLC, eight breast cancer, three melanoma, three renal cell carcinoma and two others. Median dose was 13 Gy (range, 8-16). One patient had fractionated SRS 5 Gy ×5. Median target volume was 0.2 cc (range, 0.02-2.39). The median age was 57 years (range, 42-92). Follow-up information was available in 22/24 cases. At the time of analysis, 18/22 patients (82%) had died. The median overall survival time was 5.3 months (range, 0.8-21.1 months). The only prognostic factor that trended toward statistical significance for overall survival was the absence of synchronous brain metastasis at the time of SRS; 1-year overall survival was 31% with versus 67% without synchronous brain metastasis (log rank P = 0.11). Non-significant factors included primary tumor histology and status of extracranial disease (progressing vs. stable/absent). Local failure occurred in 4/22 cases (18%). Actuarial freedom from local failure for all cases was 78.6% at 1 year. RTOG grade 3 toxicities were recorded in two patients (ataxia, confusion). Linac-based SRS for small volume brainstem metastases using a median dose of 13 Gy is associated with acceptable local control and low morbidity.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Dorth, Jennifer A., E-mail: jennifer.dorth@duke.edu; Prosnitz, Leonard R.; Broadwater, Gloria
2012-11-01
Purpose: While consolidation radiation therapy (i.e., RT administered after chemotherapy) is routine treatment for patients with early-stage diffuse large B-cell lymphoma (DLBCL), the role of consolidation RT in stage III-IV DLBCL is controversial. Methods and Materials: Cases of patients with stage III-IV DLBCL treated from 1991 to 2009 at Duke University, who achieved a complete response to chemotherapy were reviewed. Clinical outcomes were calculated using the Kaplan-Meier method and were compared between patients who did and did not receive RT, using the log-rank test. A multivariate analysis was performed using Cox proportional hazards model. Results: Seventy-nine patients were identified. Chemotherapymore » (median, 6 cycles) consisted of anti-CD20 antibody rituximab combined with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; 65%); cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP; 22%); or other (13%). Post-chemotherapy imaging consisted of positron emission tomography (PET)/computed tomography (CT) (73%); gallium with CT (14%); or CT only (13%). Consolidation RT (median, 25 Gy) was given to involved sites of disease in 38 (48%) patients. Receipt of consolidation RT was associated with improved in-field control (92% vs. 69%, respectively, p = 0.028) and event-free survival (85% vs. 65%, respectively, p = 0.014) but no difference in overall survival (85% vs. 78%, respectively, p = 0.15) when compared to patients who did not receive consolidation RT. On multivariate analysis, no RT was predictive of increased risk of in-field failure (hazard ratio [HR], 8.01, p = 0.014) and worse event-free survival (HR, 4.3, p = 0.014). Conclusions: Patients with stage III-IV DLBCL who achieve negative post-chemotherapy imaging have improved in-field control and event-free survival with low-dose consolidation RT.« less
Using the entire history in the analysis of nested case cohort samples.
Rivera, C L; Lumley, T
2016-08-15
Countermatching designs can provide more efficient estimates than simple matching or case-cohort designs in certain situations such as when good surrogate variables for an exposure of interest are available. We extend pseudolikelihood estimation for the Cox model under countermatching designs to models where time-varying covariates are considered. We also implement pseudolikelihood with calibrated weights to improve efficiency in nested case-control designs in the presence of time-varying variables. A simulation study is carried out, which considers four different scenarios including a binary time-dependent variable, a continuous time-dependent variable, and the case including interactions in each. Simulation results show that pseudolikelihood with calibrated weights under countermatching offers large gains in efficiency if compared to case-cohort. Pseudolikelihood with calibrated weights yielded more efficient estimators than pseudolikelihood estimators. Additionally, estimators were more efficient under countermatching than under case-cohort for the situations considered. The methods are illustrated using the Colorado Plateau uranium miners cohort. Furthermore, we present a general method to generate survival times with time-varying covariates. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.
NASA Technical Reports Server (NTRS)
Pereira, Jeremy J.; Lauer, Michael S.; Bashir, Mohammad; Afridi, Imran; Blackstone, Eugene H.; Stewart, William J.; McCarthy, Patrick M.; Thomas, James D.; Asher, Craig R.
2002-01-01
OBJECTIVE: We sought to assess whether aortic valve replacement (AVR) among patients with severe aortic stenosis (AS), severe left ventricular (LV) dysfunction and a low transvalvular gradient (TVG) is associated with improved survival. BACKGROUND: The optimal management of patients with severe AS with severe LV dysfunction and a low TVG remains controversial. METHODS: Between 1990 and 1998, we evaluated 68 patients who underwent AVR at our institution (AVR group) and 89 patients who did not undergo AVR (control group), with an aortic valve area < or = 0.75 cm(2), LV ejection fraction < or = 35% and mean gradient < or = 30 mm Hg. Using propensity analysis, survival was compared between a cohort of 39 patients in the AVR group and 56 patients in the control group. RESULTS: Despite well-matched baseline characteristics among propensity-matched patients, the one- and four-year survival rates were markedly improved in patients in the AVR group (82% and 78%), as compared with patients in the control group (41% and 15%; p < 0.0001). By multivariable analysis, the main predictor of improved survival was AVR (adjusted risk ratio 0.19, 95% confidence interval 0.09 to 0.39; p < 0.0001). The only other predictors of mortality were age and the serum creatinine level. CONCLUSIONS: Among select patients with severe AS, severe LV dysfunction and a low TVG, AVR was associated with significantly improved survival.
[Adenoid cystic carcinoma of the head and neck: a review of 30 cases].
Raux-Rakotomalala, F; Houliat, Th; Martel, J; Stoll, D; Bébéar, J P; Darrouzet, V
2003-01-01
To evaluate treatment results and identify prognostics factors which determine local and regional treatment failure and crude survival in adenoid cystic tumours (ACT) in the head and neck. A retrospective study (1984 to 2001) of 30 cases of adenoid cystic tumour. The mean age was 56.9 years, with a sex ratio female to male of 2:1. Tumours of all sites were encountered, most (26.7%) being in the nose and sinuses and major salivary glands (26.6%). Tumours at the T4 stage were found in 14 cases, mainly situated in the nose and sinuses (50%). No patient had cervical lymphadenopathy, while two patients (6.7%) had bony metastases at the time of diagnosis. Two patients (6.7%) were treated by surgery alone, for T1 and T2 tumours; four patients (13%) had radiotherapy alone, and 24 patients (80%) had surgery with post-operative radiotherapy with a mean dose of 60.3 Grays (56-65 Grays). Local recurrence occurred in 30.8% (nine cases) after a mean interval of 43 months (1 to 10 years). Treatment of these recurrences was by revision surgery in six cases, leading to local control in one case, but in a patient with pulmonary metastases. No cases of lymph node recurrence were observed. 30% of patients developed metastases; these were pulmonary in 44% and bony in 33.3%. Mean follow-up was five years. Crude survival at 3 years was 91%, at 5 years 86%, and at 10 years 50%. The percentage tumour-free survival was 70% at 3 years, and 57% at 5 years. 22 patients (73.3%) are still alive, 17 of them recurrence-free. Analysis of the prognostic factors has shown tumour to be more aggressive in the nose and sinuses when they presented at an advanced stage (T4); recurrence was more common when excision was incomplete, or if there was peri-neural spread. Tumours of "massive" histological type carried a poorer prognosis than those of cribrigorm type (60% death compared with 10%). The development of metastases is independent of local recurrence. Metastases to bone appear to be more rapidly aggressive than pulmonary metastases, which may remain asymptomatic for some time. Combined radiotherapy and surgery have allowed improved local control of ACT, but the therapeutic challenge remains the multiply recurrent ACT, or those with symptomatic metastases, and this despite new research techniques (neutral therapy, immuno-histochemistry, molecular biology). ACT are rare tumours, whose prognosis remains poor.
Prognostic Factors for Outcomes of In-Flight Sudden Cardiac Arrest on Commercial Airlines.
Alves, Paulo M; DeJohn, Charles A; Ricaurte, Eduard M; Mills, William D
In-flight cardiac arrest (IFCA) is a relatively rare but challenging event. Outcomes and prognostic factors are not entirely understood for victims of IFCAs in commercial aviation. This was a retrospective cohort study of airline passengers who experienced IFCA. Demographic and operational variables were studied to identify association in a multivariate logistic regression model with the outcome of survival-to-hospital. In-flight medical emergencies were processed by a ground-based medical center. Subsequent comparisons were made between reported shockable-rhythm (RSR) and reported non-shockable-rhythm (RNSR) groups. Logistic regression was also used to identify predictors for shock advised and flight diversions using a case control study design. Significant predictors for survival-to-hospital were RSR and remaining flight time to destination. The percentage of RSR cases was 24.6%. The survival to hospital admission was 22.7% (22/97) for passengers in RSR compared with 2.4% (7/297) in the RNSR group. The adjusted odds ratio for survival-to-hospital for the RSR group compared to the RNSR group was 13.6 (5.5-33.5). The model showed odds for survival to hospital decreased with longer scheduled remaining flight duration with adjusted OR = 0.701 (0.535-0.920) per hour increase. No correlation between diversions and survival for RSR cases was found. Survival-to-hospital from IFCAs is best when an RSR is present. The percentage of RSR cases was lower than in other out-of-hospital cardiac arrest (OHCA) settings, which suggests delayed discovery. Flight diversions did not significantly affect resuscitation outcome. We emphasize good quality cardio-pulmonary resuscitation (CPR) and early defibrillation as key factors for IFCA survival. Alves PM, DeJohn CA, Ricaurte EM, Mills WD. Prognostic factors for outcomes of in-flight sudden cardiac arrest on commercial airlines. Aerosp Med Hum Perform. 2016; 87(10):862-868.
Association of Ulex europaeus agglutinin I binding with invasion in endometrial carcinoma.
Ambros, R A; Kurman, R J
1993-10-01
Ulex europaeus agglutinin I (UEA-I), a lectin which specifically binds L-fucose, has been shown to extensively bind endometrial carcinoma cells but not benign endometrial glands. Patterns of UEA-I binding were examined in five cases of uteri containing proliferative endometrium, five cases of endometrial hyperplasia, and 54 cases of endometrioid (typical) carcinoma of the endometrium and correlated with the histologic features of the tumor and its behavior. Whereas proliferative endometrium showed luminal staining only, diffuse cytoplasmic staining was frequently seen in hyperplasia and carcinoma. Carcinomas with a high percentage of tumor cells staining with UEA-I tended to be high-grade with a greater tendency to deep myometrial and vascular invasion than tumors with little or no staining. By univariate survival analysis, the extent of UEA-I binding was found to correlate with patient survival. By multivariate analysis, however, survival correlated most closely with the presence of deep myometrial and vascular invasion, and UEA-I binding was not found to be an independent prognostic indicator. This study suggests that increased fucosylation of proteins in endometrioid cancer cells may play a role in myometrial and vascular invasion.
Jurczyszyn, Artur; Nahi, Hareth; Avivi, Irit; Gozzetti, Alessandro; Niesvizky, Ruben; Yadlapati, Sujitha; Jayabalan, David S; Robak, Paweł; Pika, Tomas; Andersen, Kristian T; Rasche, Leo; Mądry, Krzysztof; Woszczyk, Dariusz; Raźny, Małgorzata; Usnarska-Zubkiewicz, Lidia; Knopińska-Posłuszny, Wanda; Wojciechowska, Małgorzata; Guzicka-Kazimierczak, Renata; Joks, Monika; Grosicki, Sebastian; Ciepłuch, Hanna; Rymko, Marcin; Vesole, David H; Castillo, Jorge J
2016-12-01
We compared the outcomes of multiple myeloma (MM) patients aged 21-40 and 41-60 years in the novel agent era. This case-control study included 1089 patients between 2000 and 2015. Cases and controls were matched for sex, International Staging System (ISS) stage and institution. There were 173 patients in the younger group and 916 patients in the older group. Younger patients presented with a higher incidence of lytic lesions (82% vs. 72%; P = 0·04) and high-risk cytogenetic abnormalities (83% vs. 68%; P = 0·007), but lower rate of elevated lactate dehydrogenase (21% vs. 44%; P < 0·001). Five- and 10-year overall survival (OS) in younger versus older patients was 83% vs. 67% and 56% vs. 39%, respectively (P < 0·001). Similar results were seen when studying the subset of 780 patients who underwent autologous transplantation. Younger patients with ISS stage 1 had a better OS than older patients (P < 0·001). There was no survival difference between younger and older patients with ISS stage 2 or 3. Younger MM patients, aged 21-40 years, treated in the era of novel agents have a better OS than their counterparts aged 41-60 years, but the survival advantage observed in younger patients was lost in more advanced stages of MM. © 2016 John Wiley & Sons Ltd.
Reddy, Sreekanth P; Britto, Ramona; Vinnakota, Katyayni; Aparna, Hebbar; Sreepathi, Hari Kishore; Thota, Balaram; Kumari, Arpana; Shilpa, B M; Vrinda, M; Umesh, Srikantha; Samuel, Cini; Shetty, Mitesh; Tandon, Ashwani; Pandey, Paritosh; Hegde, Sridevi; Hegde, A S; Balasubramaniam, Anandh; Chandramouli, B A; Santosh, Vani; Kondaiah, Paturu; Somasundaram, Kumaravel; Rao, M R Satyanarayana
2008-05-15
Current methods of classification of astrocytoma based on histopathologic methods are often subjective and less accurate. Although patients with glioblastoma have grave prognosis, significant variability in patient outcome is observed. Therefore, the aim of this study was to identify glioblastoma diagnostic and prognostic markers through microarray analysis. We carried out transcriptome analysis of 25 diffusely infiltrating astrocytoma samples [WHO grade II--diffuse astrocytoma, grade III--anaplastic astrocytoma, and grade IV--glioblastoma (GBM)] using cDNA microarrays containing 18,981 genes. Several of the markers identified were also validated by real-time reverse transcription quantitative PCR and immunohistochemical analysis on an independent set of tumor samples (n = 100). Survival analysis was carried out for two markers on another independent set of retrospective cases (n = 51). We identified several differentially regulated grade-specific genes. Independent validation by real-time reverse transcription quantitative PCR analysis found growth arrest and DNA-damage-inducible alpha (GADD45alpha) and follistatin-like 1 (FSTL1) to be up-regulated in most GBMs (both primary and secondary), whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 were up-regulated in the majority of primary GBM. Further, identification of the grade-specific expression of GADD45alpha and FSTL1 by immunohistochemical staining reinforced our findings. Analysis of retrospective GBM cases with known survival data revealed that cytoplasmic overexpression of GADD45alpha conferred better survival while the coexpression of FSTL1 with p53 was associated with poor survival. Our study reveals that GADD45alpha and FSTLI are GBM-specific whereas superoxide dismutase 2 and adipocyte enhancer binding protein 1 are primary GBM-specific diagnostic markers. Whereas GADD45alpha overexpression confers a favorable prognosis, FSTL1 overexpression is a hallmark of poor prognosis in GBM patients.
Singh, Babu; Qureshi, Muhammad M; Truong, Minh Tam; Sahni, Debjani
2018-02-03
The optimal surgical approach (wide local excision (WLE) vs. Mohs micrographic surgery (MOHS)) for treating Merkel cell carcinoma (MCC) is yet to be determined. To compare survival outcomes in patients with early stage MCC treated with MOHS versus WLE. A retrospective review of all cases in the National Cancer Data Base (NCDB) of MCC of clinical Stage I-II MCC treated with WLE or MOHS was performed. 1,795 cases of Stage I-II MCC were identified who underwent WLE (N=1,685) or MOHS (N=110). There was no difference in residual tumor on surgical margins between the two treatment groups (p=0.588). On multivariate analysis, there was no difference in overall survival between the treatment modalities (adjusted HR 1.02; 95% CI 0.72-1.45, p=0.897). There was no difference in overall survival between the two groups on propensity score matched analysis. Disease specific survival was not reported as this data in not available in the NCDB. MOHS appears to be as effective as WLE in treating early stage MCC. Copyright © 2018. Published by Elsevier Inc.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bush, David A., E-mail: dbush@llu.edu; Smith, Jason C.; Slater, Jerry D.
2016-05-01
Purpose: To describe results of a planned interim analysis of a prospective, randomized clinical trial developed to compare treatment outcomes among patients with newly diagnosed hepatocellular carcinoma (HCC). Methods and Materials: Eligible subjects had either clinical or pathologic diagnosis of HCC and met either Milan or San Francisco transplant criteria. Patients were randomly assigned to transarterial chemoembolization (TACE) or to proton beam radiation therapy. Patients randomized to TACE received at least 1 TACE with additional TACE for persistent disease. Proton beam radiation therapy was delivered to all areas of gross disease to a total dose of 70.2 Gy in 15 daily fractionsmore » over 3 weeks. The primary endpoint was progression-free survival, with secondary endpoints of overall survival, local tumor control, and treatment-related toxicities as represented by posttreatment days of hospitalization. Results: At the time of this analysis 69 subjects were available for analysis. Of these, 36 were randomized to TACE and 33 to proton. Total days of hospitalization within 30 days of TACE/proton was 166 and 24 days, respectively (P<.001). Ten TACE and 12 proton patients underwent liver transplantation after treatment. Viable tumor identified in the explanted livers after TACE/proton averaged 2.4 and 0.9 cm, respectively. Pathologic complete response after TACE/proton was 10%/25% (P=.38). The 2-year overall survival for all patients was 59%, with no difference between treatment groups. Median survival time was 30 months (95% confidence interval 20.7-39.3 months). There was a trend toward improved 2-year local tumor control (88% vs 45%, P=.06) and progression-free survival (48% vs 31%, P=.06) favoring the proton beam treatment group. Conclusions: This interim analysis indicates similar overall survival rates for proton beam radiation therapy and TACE. There is a trend toward improved local tumor control and progression-free survival with proton beam. There are significantly fewer hospitalization days after proton treatment, which may indicate reduced toxicity with proton beam therapy.« less
Rassnick, Kenneth M; Goldkamp, Carrie E; Erb, Hollis N; Scrivani, Peter V; Njaa, Bradley L; Gieger, Tracy L; Turek, Michelle M; McNiel, Elizabeth A; Proulx, David R; Chun, Ruthanne; Mauldin, Glenna E; Phillips, Brenda S; Kristal, Orna
2006-08-01
To evaluate factors associated with survival in dogs with nasal carcinomas that did not receive treatment or received only palliative treatment. Retrospective case series. 139 dogs with histologically confirmed nasal carcinomas. Medical records, computed tomography images, and biopsy specimens of nasal carcinomas were reviewed. Only dogs that were not treated with radiation, surgery, chemotherapy, or immunotherapy and that survived > or = 7 days from the date of diagnosis were included. The Kaplan-Meier method was used to estimate survival time. Factors potentially associated with survival were compared by use of log-rank and Wilcoxon rank sum tests. Multivariable survival analysis was performed by use of the Cox proportional hazards regression model. Overall median survival time was 95 days (95% confidence interval [CI], 73 to 113 days; range, 7 to 1,114 days). In dogs with epistaxis, the hazard of dying was 2.3 times that of dogs that did not have epistaxis. Median survival time of 107 dogs with epistaxis was 88 days (95% CI, 65 to 106 days) and that of 32 dogs without epistaxis was 224 days (95% CI, 54 to 467 days). The prognosis of dogs with untreated nasal carcinomas is poor. Treatment strategies to improve outcome should be pursued.
Diéras, Véronique; Miles, David; Verma, Sunil; Pegram, Mark; Welslau, Manfred; Baselga, José; Krop, Ian E; Blackwell, Kim; Hoersch, Silke; Xu, Jin; Green, Marjorie; Gianni, Luca
2017-06-01
The antibody-drug conjugate trastuzumab emtansine is indicated for the treatment of patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane. Approval of this drug was based on progression-free survival and interim overall survival data from the phase 3 EMILIA study. In this report, we present a descriptive analysis of the final overall survival data from that trial. EMILIA was a randomised, international, open-label, phase 3 study of men and women aged 18 years or older with HER2-positive unresectable, locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane. Enrolled patients were randomly assigned (1:1) via a hierarchical, dynamic randomisation scheme and an interactive voice response system to trastuzumab emtansine (3·6 mg/kg intravenously every 3 weeks) or control (capecitabine 1000 mg/m 2 self-administered orally twice daily on days 1-14 on each 21-day cycle, plus lapatinib 1250 mg orally once daily on days 1-21). Randomisation was stratified by world region (USA vs western Europe vs or other), number of previous chemotherapy regimens for unresectable, locally advanced, or metastatic disease (0 or 1 vs >1), and disease involvement (visceral vs non-visceral). The coprimary efficacy endpoints were progression-free survival (per independent review committee assessment) and overall survival. Efficacy was analysed in the intention-to-treat population; safety was analysed in all patients who received at least one dose of study treatment, with patients analysed according to the treatment actually received. On May 30, 2012, the study protocol was amended to allow crossover from control to trastuzumab emtansine after the second interim overall survival analysis crossed the prespecified overall survival efficacy boundary. This study is registered with ClinicalTrials.gov, number NCT00829166. Between Feb 23, 2009, and Oct 13, 2011, 991 eligible patients were enrolled and randomly assigned to either trastuzumab emtansine (n=495) or capecitabine and lapatinib (control; n=496). In this final descriptive analysis, median overall survival was longer with trastuzumab emtansine than with control (29·9 months [95% CI 26·3-34·1] vs 25·9 months [95% CI 22·7-28·3]; hazard ratio 0·75 [95% CI 0·64-0·88]). 136 (27%) of 496 patients crossed over from control to trastuzumab emtansine after the second interim overall survival analysis (median follow-up duration 24·1 months [IQR 19·5-26·1]). Of those patients originally randomly assigned to trastuzumab emtansine, 254 (51%) of 495 received capecitabine and 241 [49%] of 495 received lapatinib (separately or in combination) after study drug discontinuation. In the safety population (488 patients treated with capecitabine plus lapatinib, 490 patients treated with trastuzumab emtansine), fewer grade 3 or worse adverse events occurred with trastuzumab emtansine (233 [48%] of 490) than with capecitabine plus lapatinib control treatment (291 [60%] of 488). In the control group, the most frequently reported grade 3 or worse adverse events were diarrhoea (103 [21%] of 488 patients) followed by palmar-plantar erythrodysaesthesia syndrome (87 [18%]), and vomiting (24 [5%]). The safety profile of trastuzumab emtansine was similar to that reported previously; the most frequently reported grade 3 or worse adverse events in the trastuzumab emtansine group were thrombocytopenia (70 [14%] of 490), increased aspartate aminotransferase levels (22 [5%]), and anaemia (19 [4%]). Nine patients died from adverse events; five of these deaths were judged to be related to treatment (two in the control group [coronary artery disease and multiorgan failure] and three in the trastuzumab emtansine group [metabolic encephalopathy, neutropenic sepsis, and acute myeloid leukaemia]). This descriptive analysis of final overall survival in the EMILIA trial shows that trastuzumab emtansine improved overall survival in patients with previously treated HER2-positive metastatic breast cancer even in the presence of crossover treatment. The safety profile was similar to that reported in previous analyses, reaffirming trastuzumab emtansine as an efficacious and tolerable treatment in this patient population. F Hoffmann-La Roche/Genentech. Copyright © 2017 Elsevier Ltd. All rights reserved.
Jiang, Jingmei; Liu, Boqi; Sitas, Freddy; Zeng, Xianjia; Chen, Junshi; Han, Wei; Zou, Xiaonong; Wu, Yanping; Zhao, Ping; Li, Junyao
2010-05-01
We assessed the effect of smoking on death from chronic obstructive pulmonary disease (COPD) in China by employing a large population-based, case-spouse control study design using data from a nationwide survey of mortality. During 1989-1991, a nationwide retrospective survey of mortality was conducted in China. For approximately 1,000,000 adults dying from all causes during 1986-1988, their surviving spouses or other informants provided detailed information about their own as well as the deceased person's smoking history. For this study, 183,393 individuals who died of COPD at age > or = 40 years were taken as cases, while 272,984 sex-matched surviving spouses of subjects who died from any cause were taken as controls. COPD death rates for smokers were more than twice as high as those of non-smokers, with a dose-response risk pattern, despite the fact that COPD death rates varied widely by region and age. Tobacco accounted for 41.4% of COPD deaths in men, but only 13.5% of those in women, who had a lower rate of smoking. A case-spouse control study, as an alternative design, is valid and feasible in utilizing information from population-based, retrospective mortality survey data for an analytical epidemiological study of disease etiology. Copyright 2010 Formosan Medical Association & Elsevier. Published by Elsevier B.V. All rights reserved.
Jia, Xu; Shanmugam, Chandrakumar; Paluri, Ravi K; Jhala, Nirag C; Behring, Michael P; Katkoori, Venkat R; Sugandha, Shajan P; Bae, Sejong; Samuel, Temesgen; Manne, Upender
2017-03-21
Although loss of heterozygosity (LOH) at chromosome location 18q21 and decreased expression of SMAD4 in invasive colorectal cancers (CRCs) correlate with poor patient survival, the prognostic value of LOH at 18q21 and sub-cellular localization of SMAD4 have not been evaluated in relation to tumor stage. Genomic DNA samples from 209 formalin-fixed, paraffin-embedded sporadic CRC tissues and their matching controls were analyzed for 18q21 LOH, and corresponding tissue sections were evaluated by immunohistochemistry for expression of SMAD4 and assessed for its sub-cellular localization (nuclear vs. cytoplasmic). In addition, 53 frozen CRCs and their matching control tissues were analyzed for their mutational status and mRNA expression of SMAD4. The phenotypic expression pattern and LOH status were evaluated for correlation with patient survival by the use of Kaplan-Meier and Cox regression models. LOH of 18q21 was detected in 61% of the informative cases. In 8% of the cases, missense point mutations were detected in Smad4. In CRCs, relative to controls, there was increased SMAD4 staining in the cytoplasm (74%) and decreased staining in the nuclei (37%). LOH of 18q21 and high cytoplasmic localization of SMAD4 were associated with shortened overall survival of Stage II patients, whereas low nuclear expression of SMAD4 was associated with worse survival, but only for patients with Stage III CRCs. LOH of 18q21 and high cytoplasmic localization of SMAD4 in Stage II CRCs and low nuclear SMAD4 in Stage III CRCs are predictors of shortened patient survival.
Jia, Xu; Shanmugam, Chandrakumar; Paluri, Ravi K.; Jhala, Nirag C.; Behring, Michael P.; Katkoori, Venkat R.; Sugandha, Shajan P.; Bae, Sejong; Samuel, Temesgen; Manne, Upender
2017-01-01
Background Although loss of heterozygosity (LOH) at chromosome location 18q21 and decreased expression of SMAD4 in invasive colorectal cancers (CRCs) correlate with poor patient survival, the prognostic value of LOH at 18q21 and sub-cellular localization of SMAD4 have not been evaluated in relation to tumor stage. Methods Genomic DNA samples from 209 formalin-fixed, paraffin-embedded sporadic CRC tissues and their matching controls were analyzed for 18q21 LOH, and corresponding tissue sections were evaluated by immunohistochemistry for expression of SMAD4 and assessed for its sub-cellular localization (nuclear vs. cytoplasmic). In addition, 53 frozen CRCs and their matching control tissues were analyzed for their mutational status and mRNA expression of SMAD4. The phenotypic expression pattern and LOH status were evaluated for correlation with patient survival by the use of Kaplan-Meier and Cox regression models. Results LOH of 18q21 was detected in 61% of the informative cases. In 8% of the cases, missense point mutations were detected in Smad4. In CRCs, relative to controls, there was increased SMAD4 staining in the cytoplasm (74%) and decreased staining in the nuclei (37%). LOH of 18q21 and high cytoplasmic localization of SMAD4 were associated with shortened overall survival of Stage II patients, whereas low nuclear expression of SMAD4 was associated with worse survival, but only for patients with Stage III CRCs. Conclusions LOH of 18q21 and high cytoplasmic localization of SMAD4 in Stage II CRCs and low nuclear SMAD4 in Stage III CRCs are predictors of shortened patient survival. PMID:28423626
DOE Office of Scientific and Technical Information (OSTI.GOV)
Valery, Charles A., E-mail: charles.valery@psl.aphp.f; Boskos, Christos; Boisserie, Gilbert
Purpose: Treatment of cerebral metastases located inside the brainstem remains a challenge, as the brainstem is considered to be a neurological organ at risk, whatever the treatment strategy. We report a retrospective study of 30 consecutive patients treated in our institution between 2005 and 2007 with micromultileaf linear accelerator (LINAC) -radiosurgery for brainstem metastases, with reduced doses compared to those usually reported in the literature. Methods and Materials: Mean follow-up was 311 days (range, 41-1351). Median age was 57 years (range, 37-82), Mean Karnofsky Index (KI) was 80. Primary tumor site was lung (n = 13), breast (n = 4),more » kidney (n = 4), skin (melanoma; n = 3), and others (n = 6). Primary tumor was controlled in 17 cases; extracranial metastases were controlled in 12 cases. Mean number of metastases was 1.46 (one to three); median volume was 2.82 cc (0.06-18). Dose was delivered by a micromultileaf collimator 6-MV LINAC . Results: Dose administered at the 70% isodose was 13.4 Gy (range, 8.2-15). Median survival was 10 months. Local control rates at 3, 6, and 12 months were 100%, 100%, and 79% respectively. Median neurological control duration was 5 months. Neurological control rates at 3, 6, and 12 months were 73%, 42%, and 25%, respectively. No parameter was found to significantly correlate with survival, local, or cerebral control. No patients had severe side effects (Grade III-IV), according to the Radiation Therapy Oncology Group (RTOG) scale. Conclusion: Lower doses than previously reported can achieve the same local control and survival rates in brain metastases, with minimal side effects.« less
Marcos-Gragera, R; Galceran, J; Martos, C; de Munain, A L; Vicente-Raneda, M; Navarro, C; Quirós-Garcia, J R; Sánchez, M-J; Ardanaz, E; Ramos, M; Mateos, A; Salmerón, D; Felipe, S; Peris-Bonet, R
2017-03-01
We have analysed incidence and survival trends of children and adolescents with leukaemia registered in Spanish population-based cancer registries during the period 1983-2007. Childhood and adolescent leukaemia cases were drawn from the 11 Spanish population-based cancer registries. For survival, registries with data for the period 1991-2005 and follow-up until 31-12-2010 were included. Overall incidence trends were evaluated using joinpoint analysis. Observed survival rates were estimated using Kaplan-Meier, and trends were tested using the log-rank test. Based on 2606 cases (2274 children and 332 adolescents), the overall age-adjusted incidence rate (ASRw) of leukaemia was 47.9 cases per million child-years in children and 23.8 in adolescents. The ASRw of leukaemia increased with an annual percentage change of 9.6 % (95 % CI: 2.2-17.6) until 1990 followed by a stabilisation of rates. In adolescents, incidence did not increase. Five-year survival increased from 66 % in 1991-1995 to 76 % in 2001-2005. By age, survival was dramatically lower in infants (0) and adolescents (15-19) than in the other age groups and no improvement was observed. In both children and adolescents, differences in 5-year survival rates among major subgroups of leukaemias were significant. The increasing incidence trends observed in childhood leukaemias during the study period were confined to the beginning of the period. Remarkable improvements in survival have been observed in Spanish children with leukaemias. However, this improvement was not observed in infants and adolescents.
Number of negative lymph nodes as a prognostic factor in esophageal squamous cell carcinoma.
Ma, Mingquan; Tang, Peng; Jiang, Hongjing; Gong, Lei; Duan, Xiaofeng; Shang, Xiaobin; Yu, Zhentao
2017-10-01
The aim of this study is to investigate the number of negative lymph nodes (NLNs) as a prognostic factor for survival in patients with resected esophageal squamous cell carcinoma. A total of 381 esophageal squamous cell carcinoma patients who had underwent surgical resection as the primary treatment was enrolled into this retrospective study. The impact of number of NLNs on patient's overall survival was assessed and compared with the factors among the current tumor-nodes-metastasis (TNM) staging system. The number of NLNs was closely related to the overall survival, and the 5-year survival rate was 45.4% for number of NLNs of >20 (142 cases) and 26.4% for NLNs ≤ 20 (239 cases) (P = 0.001). In multivariate survival analysis, the number of NLNs remained an independent prognostic factor (P = 0.002) as did the other current TNM factors. For subgroup analysis, the predictive value of number of NLNs was significant in patients with T3 or T4 disease (P = 0.001) and patients with N1 and N2-3 disease (P = 0.025, 0.043), but not in patients with T1 or T2 disease or patients with N0 disease. The number of NLNs, which represents the extent of lymphadenectomy for esophageal squamous cell carcinoma, could impact the overall survival of patients with resected esophageal squamous cell carcinoma, especially among those with nodal-positive disease and advanced T-stage tumor. © 2016 John Wiley & Sons Australia, Ltd.
Listeria: A foodborne pathogen that knows how to survive.
Gandhi, Megha; Chikindas, Michael L
2007-01-01
The foodborne pathogen Listeria is the causative agent of listeriosis, a severe disease with high hospitalization and case fatality rates. Listeria monocytogenes can survive and grow over a wide range of environmental conditions such as refrigeration temperatures, low pH and high salt concentration. This allows the pathogen to overcome food preservation and safety barriers, and pose a potential risk to human health. This review focuses on the key issues such as survival of the pathogen in adverse environments, and the important adaptation and survival mechanisms such as biofilm formation, quorum sensing and antimicrobial resistance. Studies on the development of technologies to prevent and control L. monocytogenes contamination in foods and food processing facilities are also discussed.
Wang, Xiao-Yun; Zhao, Yu-Liang
2010-12-21
To observe the clinical efficacy and adverse effects of taxol plus carboplatin (TP) or gemcitabine plus carboplatin (GP) in patients with advanced non-small-cell lung carcinoma. A total of 86 patients with advanced non-small-cell lung carcinoma with a histologically confirmed diagnosis at our department were treated with at least two cycles of drug therapy according to the WHO standard. There were 43 cases in TP group and 43 cases in GP group. TP group: taxol 150 mg/m(2), d1, carboplatin 300 mg/m(2) in d1; GP group: gemcitabine 1000 mg/m(2), 30 min, d1, 8, carboplatin 300 mg/m(2) in d1, 3 weeks a cycle. The efficacy and side effects were analyzed after two cycles of chemotherapy. When TP and GP groups were compared, the effective rate was 44.2% vs 39.5%; disease control rate (CR + PR + SD): 81.4% vs 74.4%; median time to progress (TTP): 4.6 vs 4.5 months; medium survivals: 8.6 vs 8.8 months; 1-year survival rates: 17.2% vs 18.1%; 2-year survival rates: 8% vs 10%. The statistic analysis showed that the two groups had no significant difference. The main cytotoxicities of GP and TP groups were predominantly thrombocytopenia and leucopenia respectively. The two groups had no significant statistical difference. The incidences of allergen, alopecia and peripheral neurotoxicity were higher in the TP group. The two groups had statistical difference. Tolerance was excellent in both groups. The therapeutic effect and tolerance are excellent for advanced non-small cell lung carcinoma. The efficacy and survival rate of two groups show no statistical difference.
Mesli, Smain Nabil; Regagba, Derbali; Tidjane, Anisse; Benkalfat, Mokhtar; Abi-Ayad, Chakib
2016-01-01
The aim of our study was to analyze histoprognostic factors in patients with non-metastatic rectal cancer operated at the division of surgery "A" in Tlemcen, west Algeria, over a period of six years. Retrospective study of 58 patients with rectal adenocarcinoma. Evaluation criterion was survival. Parameters studied were sex, age, tumor stage, tumor recurrence. The average age was 58 years, 52% of men and 48% of women, with sex-ratio (1,08). Tumor seat was: middle rectum 41.37%, lower rectum 34.48% and upper rectum 24.13%. Concerning TNM clinical staging, patients were classified as stage I (17.65%), stage II (18.61%), stage III (53.44%) and stage IV (7.84%). Median overall survival was 40 months ±2,937 months. Survival based on tumor staging: stage III and IV had a lower 3 years survival rate (19%) versus stage I, II which had a survival rate of 75% (P = 0.000) (95%). Patients with tumor recurrences had a lower 3 years survival rate compared to those who had no tumoral recurrences (30.85% vs 64.30% P = 0.043). In this series, univariate analysis of prognostic factors affecting survival allowed to retain only three factors influencing survival: tumor size, stage and tumor recurrences. In multivariate analysis using Cox's model only one factor was retained: tumor recurrence.
Dzhenkov, Deyan L; Kitanova, Martina; Donev, Ivan S; Ghenev, Peter
2017-01-01
Background Glioblastoma multiforme (GBM) is a class IV astrocytic tumor, the most malignant of the four groups of World Health Organization (WHO) tumors with astrocytic differentiation. Aim The aim of this study was to establish whether a correlation exists between the Ki-67 index of tumors with astrocytic differentiation, WHO grade, and patient survival. Materials and methods A retrospective non-clinical approach to patient selection was chosen for the aim of the study. A total of 47 patients diagnosed and treated for CNS tumors with astrocytic differentiation in the St. Marina University Hospital, Varna, Bulgaria, from September 2012 to July 2016 were retrospectively included into the study cohort. The cases were tested for their immunohistochemistry (IHC) reaction with Ki-67 after their original Hematoxylin and Eosin and IHC slides were reviewed by a single author and blind coded. The Ki-67 positivity index of the nuclei was estimated after digitalization of the slides and calculated by the ImmunoRatio automated counting tool. The individual Ki-67 index and patient survival of each case were statistically compared. Results The histopathological groups, after the blind Ki-67 index automated calculation was carried out, revealed no WHO grade I, two WHO grade II samples, four WHO grade III samples and 41 WHO grade IV cases, and these were included in the analysis. The two samples of WHO grade II astrocytic tumors had a mean Ki-67 index of 25%; however, they comprised tumors with an individual index of 43% and 7%, both individual values with a highly unlikely index for this group. The four samples of WHO grade III had a mean Ki-67 index of 4%, standard deviation ±2.16 (p>0.05), with the lowest index being 1% and the highest one being 6%. Both WHO grade II and III did not include enough samples to allow for a proper statistical analysis of patient survival. The 41 GBM cases had a mean Ki-67 index of 17.34%, standard deviation ±10.79 (p>0.05). Statistical analysis of the Ki-67 index divided dichotomously into two groups and patient survival revealed that cases with a high Ki-67 index had no significant difference in survival when compared to those with low expression. Conclusions Based on the reported results, the mean Ki-67 percentage of positive nuclei in GBM tumor samples cannot be used to estimate the survival of patients. However, Ki-67 remains a valuable IHC pathological tool. PMID:28845375
Transients control in Raman fiber amplifiers
NASA Astrophysics Data System (ADS)
Freitas, Marcio; Givigi, Sidney N., Jr.; Klein, Jackson; Calmon, Luiz C.; de Almeida, Ailson R.
2004-11-01
Raman fiber amplifiers (RFA) are being used in optical transmission communication systems in the recent years due to their advantages in comparison to erbium-doped fiber amplifiers (EDFA). Recently the analysis of RFAs dynamic response and transients control has become important in order to predict the system response to add/drop of channels or cable cuts in optical systems, and avoid impairments caused by the power transients. Fast signal power transients in the surviving channels are caused by the cross-gain saturation effect in RFA and the slope of the gain saturation characteristics determines the steady-state surviving channel power excursion. We are presenting the modeling and analysis of power transients and its control using a pump control method for a single and multi-pump scheme.
Haslem, Derrick S.; Chakravarty, Ingo; Fulde, Gail; Gilbert, Heather; Tudor, Brian P.; Lin, Karen; Ford, James M.; Nadauld, Lincoln D.
2018-01-01
The impact of precision oncology on guiding treatment decisions of late-stage cancer patients was previously studied in a retrospective analysis. However, the overall survival and costs were not previously evaluated. We report the overall survival and healthcare costs associated with precision oncology in these patients with advanced cancer. Building on a matched cohort study of 44 patients with metastatic cancer who received all of their care within a single institution, we evaluated the overall survival and healthcare costs for each patient. We analyzed the outcomes of 22 patients who received genomic testing and targeted therapy (precision oncology) between July 1, 2013 and January 31, 2015, and compared to 22 historically controlled patients (control) who received standard chemotherapy (N = 17) or best supportive care (N = 5). The median overall survival was 51.7 weeks for the targeted treatment group and 25.8 weeks for the control group (P = 0.008) when matching on age, gender, histological diagnosis and previous treatment lines. Average costs over the entire period were $2,720 per week for the targeted treatment group and $3,453 per week for the control group, (P = 0.036). A separate analysis of 1,814 patients with late-stage cancer diagnoses found that those who received a targeted cancer treatment (N = 93) had 6.9% lower costs in the last 3 months of life compared with those who did not. These findings suggest that precision oncology may improve overall survival for refractory cancer patients while lowering average per-week healthcare costs, resource utilization and end-of-life costs. PMID:29552312
Anterolateral minithoracotomy versus median sternotomy for mitral valve disease: a meta-analysis.
Ding, Chao; Jiang, Da-ming; Tao, Kai-yu; Duan, Qun-jun; Li, Jie; Kong, Min-jian; Shen, Zhong-hua; Dong, Ai-qiang
2014-06-01
Mitral valve disease tends to be treated with anterolateral minithoracotomy (ALMT) rather than median sternotomy (MS), as ALMT uses progressively smaller incisions to promote better cosmetic outcomes. This meta-analysis quantifies the effects of ALMT on surgical parameters and post-operative outcomes compared with MS. One randomized controlled study and four case-control studies, published in English from January 1996 to January 2013, were identified and evaluated. ALMT showed a significantly longer cardiopulmonary bypass time (P=0.001) and aortic cross-clamp time (P=0.05) compared with MS. However, the benefits of ALMT were evident as demonstrated by a shorter length of hospital stay (P<0.00001). According to operative complications, the onset of new arrhythmias following ALMT decreased significantly as compared with MS (P=0.05); however, the incidence of peri-operative mortality (P=0.62), re-operation for bleeding (P=0.37), neurologic events (P=0.77), myocardial infarction (P=0.84), gastrointestinal complications (P=0.89), and renal insufficiency (P=0.67) were similar to these of MS. Long-term follow-up data were also examined, and revealed equivalent survival and freedom from mitral valve events. Current clinical data suggest that ALMT is a safe and effective alternative to the conventional approach and is associated with better short-term outcomes and a trend towards longer survival.
Anterolateral minithoracotomy versus median sternotomy for mitral valve disease: a meta-analysis
Ding, Chao; Jiang, Da-ming; Tao, Kai-yu; Duan, Qun-jun; Li, Jie; Kong, Min-jian; Shen, Zhong-hua; Dong, Ai-qiang
2014-01-01
Objective: Mitral valve disease tends to be treated with anterolateral minithoracotomy (ALMT) rather than median sternotomy (MS), as ALMT uses progressively smaller incisions to promote better cosmetic outcomes. This meta-analysis quantifies the effects of ALMT on surgical parameters and post-operative outcomes compared with MS. Methods: One randomized controlled study and four case-control studies, published in English from January 1996 to January 2013, were identified and evaluated. Results: ALMT showed a significantly longer cardiopulmonary bypass time (P=0.001) and aortic cross-clamp time (P=0.05) compared with MS. However, the benefits of ALMT were evident as demonstrated by a shorter length of hospital stay (P<0.00001). According to operative complications, the onset of new arrhythmias following ALMT decreased significantly as compared with MS (P=0.05); however, the incidence of peri-operative mortality (P=0.62), re-operation for bleeding (P=0.37), neurologic events (P=0.77), myocardial infarction (P=0.84), gastrointestinal complications (P=0.89), and renal insufficiency (P=0.67) were similar to these of MS. Long-term follow-up data were also examined, and revealed equivalent survival and freedom from mitral valve events. Conclusions: Current clinical data suggest that ALMT is a safe and effective alternative to the conventional approach and is associated with better short-term outcomes and a trend towards longer survival. PMID:24903989
Al-Mamgani, A; van Rooij, P H; Woutersen, D P; Mehilal, R; Tans, L; Monserez, D; Baatenburg de Jong, R J
2013-08-01
To evaluate the outcomes of patients with early stage glottic cancer (GC) treated with radiotherapy (RT). The current study report on a retrospective analysis of oncologic outcome of 1050 patients with T1-2N0 glottic cancer treated with radiotherapy. Prospective assessment of quality of life (QoL) and voice handicap index (VHI) was performed in all patients treated from 2006 onwards (n = 233). Local control (LC), regional control (RC), disease-free survival (DFS), overall survival (OS), quality of life and voice handicap index. After a median follow-up of 90 months (range 3-309), the actuarial rates of local control, regional control, disease-free survival and overall survival were 85%, 99%, 84% and 81% at 5 years and 82%, 98%, 80% and 61% at 10 years, respectively. On multivariate analysis, T2 tumours, smoking after radiotherapy and conventional radiation scheme correlated significantly with poor local control. Patients who continued smoking after radiotherapy had also significantly lower overall survival rates (OR 4.3, P < 0.001). Hypothyroidism was reported in 18% of patients. Slight and temporary deterioration of quality of life scores was reported. Patient-reported xerostomia and dysphagia at 48 months were -7.1 and -6.5, compared with baseline, respectively. Voice handicap index improved significantly from 37 at baseline to 18 at 48 months. Patients with T2b and those who continued smoking had significantly worse voice handicap index. In the current study, excellent outcome with good quality of life and voice handicap index scores were reported. T2 tumours, in particular T2b, and continuing smoking after radiotherapy correlated significantly with poor local control and worse voice handicap index. © 2013 John Wiley & Sons Ltd.
The balanced survivor average causal effect.
Greene, Tom; Joffe, Marshall; Hu, Bo; Li, Liang; Boucher, Ken
2013-05-07
Statistical analysis of longitudinal outcomes is often complicated by the absence of observable values in patients who die prior to their scheduled measurement. In such cases, the longitudinal data are said to be "truncated by death" to emphasize that the longitudinal measurements are not simply missing, but are undefined after death. Recently, the truncation by death problem has been investigated using the framework of principal stratification to define the target estimand as the survivor average causal effect (SACE), which in the context of a two-group randomized clinical trial is the mean difference in the longitudinal outcome between the treatment and control groups for the principal stratum of always-survivors. The SACE is not identified without untestable assumptions. These assumptions have often been formulated in terms of a monotonicity constraint requiring that the treatment does not reduce survival in any patient, in conjunction with assumed values for mean differences in the longitudinal outcome between certain principal strata. In this paper, we introduce an alternative estimand, the balanced-SACE, which is defined as the average causal effect on the longitudinal outcome in a particular subset of the always-survivors that is balanced with respect to the potential survival times under the treatment and control. We propose a simple estimator of the balanced-SACE that compares the longitudinal outcomes between equivalent fractions of the longest surviving patients between the treatment and control groups and does not require a monotonicity assumption. We provide expressions for the large sample bias of the estimator, along with sensitivity analyses and strategies to minimize this bias. We consider statistical inference under a bootstrap resampling procedure.
Germline PARP4 mutations in patients with primary thyroid and breast cancers.
Ikeda, Yuji; Kiyotani, Kazuma; Yew, Poh Yin; Kato, Taigo; Tamura, Kenji; Yap, Kai Lee; Nielsen, Sarah M; Mester, Jessica L; Eng, Charis; Nakamura, Yusuke; Grogan, Raymon H
2016-03-01
Germline mutations in the PTEN gene, which cause Cowden syndrome, are known to be one of the genetic factors for primary thyroid and breast cancers; however, PTEN mutations are found in only a small subset of research participants with non-syndrome breast and thyroid cancers. In this study, we aimed to identify germline variants that may be related to genetic risk of primary thyroid and breast cancers. Genomic DNAs extracted from peripheral blood of 14 PTEN WT female research participants with primary thyroid and breast cancers were analyzed by whole-exome sequencing. Gene-based case-control association analysis using the information of 406 Europeans obtained from the 1000 Genomes Project database identified 34 genes possibly associated with the phenotype with P < 1.0 × 10(-3). Among them, rare variants in the PARP4 gene were detected at significant high frequency (odds ratio = 5.2; P = 1.0 × 10(-5)). The variants, G496V and T1170I, were found in six of the 14 study participants (43%) while their frequencies were only 0.5% in controls. Functional analysis using HCC1143 cell line showed that knockdown of PARP4 with siRNA significantly enhanced the cell proliferation, compared with the cells transfected with siControl (P = 0.02). Kaplan-Meier analysis using Gene Expression Omnibus (GEO), European Genome-phenome Archive (EGA) and The Cancer Genome Atlas (TCGA) datasets showed poor relapse-free survival (P < 0.001, Hazard ratio 1.27) and overall survival (P = 0.006, Hazard ratio 1.41) in a PARP4 low-expression group, suggesting that PARP4 may function as a tumor suppressor. In conclusion, we identified PARP4 as a possible susceptibility gene of primary thyroid and breast cancer. © 2016 Society for Endocrinology.
Germline PARP4 mutations in patients with primary thyroid and breast cancers
Ikeda, Yuji; Kiyotani, Kazuma; Yew, Poh Yin; Kato, Taigo; Tamura, Kenji; Yap, Kai-Lee; Nielsen, Sarah M.; Mester, Jessica L; Eng, Charis; Nakamura, Yusuke; Grogan, Raymon H.
2016-01-01
Germline mutations in the PTEN gene, which cause Cowden syndrome (CS), are known to be one of the genetic factors for primary thyroid and breast cancers, however, PTEN mutations are found in only a small subset of research participants with non-syndrome breast and thyroid cancers. In this study, we aimed to identify germline variants that may be related to genetic risk of primary thyroid and breast cancers. Genomic DNAs extracted from peripheral blood of 14 PTEN-wild-type female research participants with primary thyroid and breast cancers were analyzed by whole-exome sequencing. Gene-based case control association analysis using the information of 406 Europeans obtained from the 1000 Genomes Project database identified 34 genes possibly associated with the phenotype with P<1.0×10−3. Among them, rare variants in the PARP4 gene were detected at significant high frequency (odds ratio = 5.2, P = 1.0×10−5). The variants, G496V and T1170I, were found in 6 of the 14 study participants (43%) while their frequencies were only 0.5% in controls. Functional analysis using HCC1143 cell line showed that knockdown of PARP4 with siRNA significantly enhanced the cell proliferation, compared with the cells transfected with siControl (P = 0.02). Kaplan-Meier analysis using GEO, EGA and TCGA datasets showed poor progression-free survival (P = 0.006, Hazard ratio 0.71) and overall survival (P < 0.0001, Hazard ratio 0.79) in a PARP4 low-expression group, suggesting that PARP4 may function as a tumor suppression. In conclusion, we identified PARP4 as a possible susceptibility gene of primary thyroid and breast cancer. PMID:26699384
Heart retransplantation: a 23-year single-center clinical experience.
Schnetzler, B; Pavie, A; Dorent, R; Camproux, A C; Leger, P; Delcourt, A; Gandjbakhch, I
1998-04-01
The main causes of allograft failure after cardiac transplantation are primary graft dysfunction, intractable acute rejection, and coronary graft disease. Despite the important progress in the last several years in graft preservation, surgical techniques, immunosuppression, and treatment of coronary graft disease, retransplantation in selected cases is the only way to achieve long-term recipient survival. We compare here in a case-control study 24 retransplantations with 47 first transplants in patients matched for date of transplantation. Between 1973 and 1996, 1,063 patients underwent cardiac transplantation in our institution. In this cohort, 22 patients had a total of 24 retransplantations (2 second-time retransplantations). The causes of retransplantations were primary graft failure (n=4), acute rejection (n=7), coronary graft disease (n=11), and miscellaneous (n=2). Survival at 1 and 5 years of patients with retransplantations is 45.5% and 31.2%, and survival of control patients is 59.4% and 38.8% (p=0.07). An interval between first transplantation and retransplantation shorter (n=11) or longer (n=13) than 1 year is associated with a 1-year survival of 27.3% and 61.5% and a 4-year survival of 27.3% and 46%, respectively (not significant). Intervals shorter than 1 year between first transplantation and retransplantation were exclusively secondary to primary graft failure or intractable acute rejection. In the face of lack of donor grafts, these and other data indicate that retransplantation should be considered cautiously, especially when the interval between the first transplantation and retransplantation is short.
Friemel, Juliane; Foraita, Ronja; Günther, Kathrin; Heibeck, Mathias; Günther, Frauke; Pflueger, Maren; Pohlabeln, Hermann; Behrens, Thomas; Bullerdiek, Jörn; Nimzyk, Rolf; Ahrens, Wolfgang
2016-03-11
The survival time of patients with head and neck squamous cell carcinoma (HNSCC) is related to health behavior, such as tobacco smoking and alcohol consumption. Poor oral health (OH), dental care (DC) and the frequent use of mouthwash have been shown to represent independent risk factors for head and neck cancerogenesis, but their impact on the survival of HNSCC patients has not been systematically investigated. Two hundred seventy-six incident HNSCC cases recruited for the ARCAGE study were followed through a period of 6-10 years. Interview-based information on wearing of dentures, gum bleeding, teeth brushing, use of floss and dentist visits were grouped into weighted composite scores, i.e. oral health (OH) and dental care (DH). Use of mouthwash was assessed as frequency per day. Also obtained were other types of health behavior, such as smoking, alcohol drinking and diet, appreciated as both confounding and study variables. Endpoints were progression-free survival, overall survival and tumor-specific survival. Prognostic values were estimated using Kaplan-Meier analysis and Cox proportional hazards regression models. A good dental care score, summarizing annual dental visits, daily teeth cleaning and use of floss was associated with longer overall survival time (p = .001). The results of the Cox regression models similarly suggested a higher risk of tumor progression and shortened overall survival in patients with poor dental care, but the results lost their statistical significance after other types of health behavior had been controlled for. Frequent use of mouthwash (≥ 2 times/day) significantly increased the risk of tumor-specific death (HR = 2.26; CI = 1.19-4.32). Alcohol consumption and tobacco smoking were dose-dependently associated with tumor progression and shorter overall survival. Frequent mouthwash use of ≥ 2 times/day seems to elevate the risk of tumor-specific death in HNSCC patients. Good dental care scores are associated with longer overall survival.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Magome, T; Haga, A; Igaki, H
Purpose: Although many outcome prediction models based on dose-volume information have been proposed, it is well known that the prognosis may be affected also by multiple clinical factors. The purpose of this study is to predict the survival time after radiotherapy for high-grade glioma patients based on features including clinical and dose-volume histogram (DVH) information. Methods: A total of 35 patients with high-grade glioma (oligodendroglioma: 2, anaplastic astrocytoma: 3, glioblastoma: 30) were selected in this study. All patients were treated with prescribed dose of 30–80 Gy after surgical resection or biopsy from 2006 to 2013 at The University of Tokyomore » Hospital. All cases were randomly separated into training dataset (30 cases) and test dataset (5 cases). The survival time after radiotherapy was predicted based on a multiple linear regression analysis and artificial neural network (ANN) by using 204 candidate features. The candidate features included the 12 clinical features (tumor location, extent of surgical resection, treatment duration of radiotherapy, etc.), and the 192 DVH features (maximum dose, minimum dose, D95, V60, etc.). The effective features for the prediction were selected according to a step-wise method by using 30 training cases. The prediction accuracy was evaluated by a coefficient of determination (R{sup 2}) between the predicted and actual survival time for the training and test dataset. Results: In the multiple regression analysis, the value of R{sup 2} between the predicted and actual survival time was 0.460 for the training dataset and 0.375 for the test dataset. On the other hand, in the ANN analysis, the value of R{sup 2} was 0.806 for the training dataset and 0.811 for the test dataset. Conclusion: Although a large number of patients would be needed for more accurate and robust prediction, our preliminary Result showed the potential to predict the outcome in the patients with high-grade glioma. This work was partly supported by the JSPS Core-to-Core Program(No. 23003) and Grant-in-aid from the JSPS Fellows.« less
Risk factors for concurrent bacteremia in adult patients with dengue.
Thein, Tun-Linn; Ng, Ee-Ling; Yeang, Ming S; Leo, Yee-Sin; Lye, David C
2017-06-01
Bacteremia in dengue may occur with common exposure to pathogens in association with severe organ impairment or severe dengue, which may result in death. Cohort studies identifying risk factors for concurrent bacteremia among patients with dengue are rare. We conducted a retrospective case-control study of adult patients with dengue who were admitted to the Department of Infectious Diseases at Tan Tock Seng Hospital, Singapore from 2004 to 2008. For each case of dengue with concurrent bacteremia (within the first 72 hours of admission), we selected four controls without bacteremia, who were matched on year of infection and dengue confirmation method. Conditional logistic regression was performed to identify risk factors for concurrent bacteremia. Among 9,553 patients with dengue, 29 (0.3%) had bacteremia. Eighteen of these patients (62.1%) had concurrent bacteremia. The predominant bacteria were Staphylococcus aureus, one of which was a methicillin-resistant strain. Dengue shock syndrome occurred more frequently and hospital stay was longer among cases than among controls. Three cases did not survive, whereas none of the controls died. In multivariate analysis, being critically ill at hospital presentation was independently associated with 15 times the likelihood of a patient with dengue having concurrent bacteremia. Concurrent bacteremia in adult patients with dengue is uncommon but presents atypically and results in more deaths and longer hospital stay. Given the associated mortality, collection of blood cultures and empiric antibiotic therapy may be considered in patients who are critically ill. Copyright © 2015. Published by Elsevier B.V.
Helgadottir, Hildur; Tuominen, Rainer; Olsson, Håkan; Hansson, Johan; Höiom, Veronica
2017-11-01
Worse outcomes have been noted in patients with multiple primary melanomas (MPMs) than in patients with single primary melanomas. We investigated how family history of melanoma and germline CDKN2A mutation status of MPM patients affects risks of developing subsequent melanomas and other cancers and survival outcomes. Comprehensive data on cancer diagnoses and deaths of MPM patients, their first-degree relatives, and matched controls were obtained through Swedish national health care and population registries. Familial MPM cases with germline CDKN2A mutations were youngest at the diagnosis of their second melanoma (median age 42 years) and had among the MPM cohorts the highest relative risks (RR) compared to controls of developing >2 melanomas (RR 238.4, 95% CI 74.8-759.9). CDKN2A mutated MPM cases and their first-degree relatives were the only cohorts with increased risks of nonskin cancers compared to controls (RR 3.6, 95% CI 1.9-147.1 and RR 3.2, 95% CI 1.9-5.6, respectively). In addition, CDKN2A mutated MPM cases had worse survival compared with both cases with familial (HR 3.0, 95% CI 1.3-8.1) and sporadic wild-type MPM (HR 2.63, 95% CI 1.3-5.4). Our study examined outcomes in subgroups of MPM patients, which affected the sample size of the study groups. This study demonstrates that CDKN2A mutation status and family history of melanoma significantly affects outcomes of MPM patients. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Happold, Caroline; Gorlia, Thierry; Chinot, Olivier; Gilbert, Mark R.; Nabors, L. Burt; Wick, Wolfgang; Pugh, Stephanie L.; Hegi, Monika; Cloughesy, Timothy; Roth, Patrick; Reardon, David A.; Perry, James R.; Mehta, Minesh P.; Stupp, Roger
2016-01-01
Purpose Symptomatic epilepsy is a common complication of glioblastoma and requires pharmacotherapy. Several uncontrolled retrospective case series and a post hoc analysis of the registration trial for temozolomide indicated an association between valproic acid (VPA) use and improved survival outcomes in patients with newly diagnosed glioblastoma. Patients and Methods To confirm the hypothesis suggested above, a combined analysis of survival association of antiepileptic drug use at the start of chemoradiotherapy with temozolomide was performed in the pooled patient cohort (n = 1,869) of four contemporary randomized clinical trials in newly diagnosed glioblastoma: AVAGlio (Avastin in Glioblastoma; NCT00943826), CENTRIC (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Methylated Gene Promoter Status; NCT00689221), CORE (Cilengitide, Temozolomide, and Radiation Therapy in Treating Patients With Newly Diagnosed Glioblastoma and Unmethylated Gene Promoter Status; NCT00813943), and Radiation Therapy Oncology Group 0825 (NCT00884741). Progression-free survival (PFS) and overall survival (OS) were compared between: (1) any VPA use and no VPA use at baseline or (2) VPA use both at start of and still after chemoradiotherapy. Results of Cox regression models stratified by trial and adjusted for baseline prognostic factors were analyzed. The same analyses were performed with levetiracetam (LEV). Results VPA use at start of chemoradiotherapy was not associated with improved PFS or OS compared with all other patients pooled (PFS: hazard ratio [HR], 0.91; 95% CI, 0.77 to 1.07; P = .241; OS: HR, 0.96; 95% CI, 0.80 to 1.15; P = .633). Furthermore, PFS and OS of patients taking VPA both at start of and still after chemoradiotherapy were not different from those without antiepileptic drug use at both time points (PFS: HR, 0.92; 95% CI, 0.74 to 1.15; P = .467; OS: HR, 1.10; 95% CI, 0.86 to 1.40; P = .440). Similarly, no association with improved outcomes was observed for LEV use. Conclusion The results of this analysis do not justify the use of VPA or LEV for reasons other than seizure control in patients with newly diagnosed glioblastoma outside clinical trials. PMID:26786929
Clinical Significance of SASH1 Expression in Glioma
Yang, Liu; Zhang, Haitao; Yao, Qi; Yan, Yingying; Wu, Ronghua; Liu, Mei
2015-01-01
Objective. SAM and SH3 domain containing 1 (SASH1) is a recently discovered tumor suppressor gene. The role of SASH1 in glioma has not yet been described. We investigated SASH1 expression in glioma cases to determine its clinical significance on glioma pathogenesis and prognosis. Methods. We produced tissue microarrays using 121 patient-derived glioma samples and 30 patient-derived nontumor cerebral samples. Immunohistochemistry and Western blotting were used to evaluate SASH1 expression. We used Fisher's exact tests to determine relationships between SASH1 expression and clinicopathological characteristics; Cox regression analysis to evaluate the independency of different SASH1 expression; Kaplan-Meier analysis to determine any correlation of SASH1 expression with survival rate. Results. SASH1 expression was closely correlated with the WHO glioma grade. Of the 121 cases, 66.9% with low SASH1 expression were mostly grade III-IV cases, whereas 33.1% with high SASH1 expression were mostly grades I-II. Kaplan-Meier analysis revealed a significant positive correlation between SASH1 expression and postoperative survival. Conclusions. SASH1 was widely expressed in normal and low-grade glioma tissues. SASH1 expression strongly correlated with glioma grades, showing higher expression at a lower grade, which decreased significantly as grade increased. Furthermore, SASH1 expression was positively correlated with better postoperative survival in patients with glioma. PMID:26424902
Incidence and survival of stomach cancer in a high-risk population of Chile
Heise, Katy; Bertran, Enriqueta; Andia, Marcelo E; Ferreccio, Catterina
2009-01-01
AIM: To study the incidence and survival rate of stomach cancer (SC) and its associated factors in a high risk population in Chile. METHODS: The population-based cancer registry of Valdivia, included in the International Agency for Research on Cancer system, covers 356 396 residents of Valdivia Province, Southern Chile. We studied all SC cases entered in this Registry during 1998-2002 (529 cases). Population data came from the Chilean census (2002). Standardized incidence rates per 100 000 inhabitants (SIR) using the world population, cumulative risk of developing cancer before age 75, and rate ratios by sex, age, ethnicity and social factors were estimated. Relative survival (Ederer II method) and age-standardized estimates (Brenner method) were calculated. Specific survival rates (Kaplan-Meier) were measured at 3 and 5 years and survival curves were analyzed with the Logrank and Breslow tests. Survival was studied in relation to demographics, clinical presentation, laboratory results and medical management of the cases. Those variables significantly associated with survival were later included in a Cox multivariate model. RESULTS: Between 1998 and 2002, 529 primary gastric cancers occurred in Valdivia (crude incidence rate 29.2 per 100 000 inhabitants). Most cases were male (69.0%), residents of urban areas (57.5%) and Hispanic (83.2%), with a low education level (84.5% < 8 school years). SC SIR was higher in men than women (40.8 and 14.8 respectively, P < 0.001), risk factors were low education RR 4.4 (95% CI: 2.9-6.8) and 1.6, (95% CI: 1.1-2.1) for women and men respectively and Mapuche ethnicity only significant for women (RR 2.2, 95% CI: 1.2-3.7). Of all cases, 76.4% were histologically confirmed, 11.5% had a death certificate only (DCO), 56.1% were TNM stage IV; 445 cases (84.1%) were eligible for survival analysis, all completed five years follow-up; 42 remained alive, 392 died of SC and 11 died from other causes. Specific 5-year survival, excluding cases with DCO, was 10.6% (95% CI: 7.7-13.5); 5-year relative survival rate was 12.3% (95% CI: 9.1-16.1), men 10.9% (95% CI: 7.4-15.2) and women 16.1% (95% CI: 9.5-24.5). Five-year specific survival was higher for patients aged < 55 years (17.3%), with intestinal type of cancer (14.6%), without metastasis (22.2%), tumor size < 4 cm (60.0%), without lymphatic invasion (77.1%), only involvement of the mucous membrane (100%). Statistically significant independent prognostic factors were: TNM staging, diffuse type, metastasis, supraclavicular adenopathy, palpable tumor, and hepatitis or ascites. CONCLUSION: Social determinants are the main risk factors for SC, but not for survival. An advanced clinical stage at consultation is the main cause of poor SC survival. PMID:19370783
Mehta, Shreya; de Reuver, Philip R.; Gill, Preetjote; Andrici, Juliana; D’Urso, Lisa; Mittal, Anubhav; Pavlakis, Nick; Clarke, Stephen; Samra, Jaswinder S.; Gill, Anthony J.
2015-01-01
Abstract Somatostatin receptors (SSTR) are commonly expressed by neuroendocrine tumors. Expression of SSTR-2a and SSTR-5 may impact symptomatic management; however, the impact on survival is unclear. The aim of this study is to correlate SSTR-2a and SSTR-5 expression in pancreatic neuroendocrine tumors (PNETs) with survival. This study is designed to determine the prognostic significance of somatostatin receptors SSTR-2a and SSTR-5 in PNETs. This retrospective cohort study included cases of resected PNETs between 1992 and 2014. Clinical data, histopathology, expression of SSTR and Ki-67 by immunohistochemistry, and long-term survival were analyzed. A total of 99 cases were included in this study. The mean age was 57.8 years (18–87 years) and median tumor size was 25 mm (range 8–160 mm). SSTR-2a and SSTR-5 expression was scored as negative (n = 19, 19.2%; n = 75, 75.8%, respectively) and positive (n = 80, 80.1%; n = 24, 24.2%). The median follow-up was 49 months. SSTR-2a expression was associated with improved overall survival, with cumulative survival rates at 1, 3, and 5 years being 97.5%, 91.5%, and 82.9%, respectively. Univariate analysis demonstrated better survival in SSTR-2a positive patients (log rank P = 0.04). SSTR-5 expression was not associated with survival outcomes (log rank P = 0.94). Multivariate analysis showed that positive SSTR-2a expression is a stronger prognostic indicator for overall survival [Hazard Ratio (HR): 0.2, 95% Confidence interval (CI): 0.1–0.8] compared to high Ki-67 (HR: 0.8, 95% CI: 0.1–5.7). Expression of SSTR-2a is an independent positive prognostic factor for survival in PNETs. PMID:26447992
Park, Young-Jin; Cho, Sung-Am
2010-06-01
To evaluate the survival rate of implants placed in the maxillary tuberosity region using the fixed prosthesis in partially edentulous cases. Of implant-treated patients who visited Kyung Pook National University Hospital, 7 partially edentulous patients (2 male and 5 female; mean age, 52.3 years; range, approximately 43 to 65) were selected according to the following criteria: 1) less than 3-mm thickness alveolar bone reaming at the first molar area and 2) 1 to 2 fixture premolars, with the additional implant at the maxillary tuberosity region. For the control group, patients who had nontuberosity areas were selected. After 1 to 7 years, marginal bone level, fixture mobility, and radiolucency of tuberosity fixtures of the fixed prostheses were evaluated by digital panorama (Starpacs, Infinitt, Seoul, Korea). None of the fixtures of the tuberosity-installed implants for 1 to 7 years failed. The marginal bone level around the implants of the maxillary tuberosity 1 to 6 years (average 3.4 years) after the final prostheses was approximately 0.6 to 1.3 mm, with an average of 0.94 mm. The fixture installation at the maxillary tuberosity using the unilateral partially edentulous implant-fixed prosthesis would be a clinically acceptable treatment module. 2010 American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.
Does chemotherapy improve survival in high-risk stage I and II Merkel cell carcinoma of the skin?
DOE Office of Scientific and Technical Information (OSTI.GOV)
Poulsen, Michael G.; Rischin, Danny; Porter, Ian
2006-01-01
Purpose: The effectiveness of synchronous carboplatin, etoposide, and radiation therapy in improving survival was evaluated by comparison of a matched set of historic control subjects with patients treated in a prospective Phase II study that used synchronous chemotherapy and radiation and adjuvant chemotherapy. Patients and Methods: Patients were included in the analysis if they had disease localized to the primary site and nodes, and they were required to have at least one of the following high-risk features: recurrence after initial therapy, involved nodes, primary size greater than 1 cm, or gross residual disease after surgery. All patients who received chemotherapymore » were treated in a standardized fashion as part of a Phase II study (Trans-Tasman Radiation Oncology Group TROG 96:07) from 1997 to 2001. Radiation was delivered to the primary site and nodes to a dose of 50 Gy in 25 fractions over 5 weeks, and synchronous carboplatin (AUC 4.5) and etoposide, 80 mg/m{sup 2} i.v. on Days 1 to 3, were given in Weeks 1, 4, 7, and 10. The historic group represents a single institution's experience from 1988 to 1996 and was treated with surgery and radiation alone, and patients were included if they fulfilled the eligibility criteria of TROG 96:07. Patients with occult cutaneous disease were not included for the purpose of this analysis. Because of imbalances in the prognostic variables between the two treatment groups, comparisons were made by application of Cox's proportional hazard modeling. Overall survival, disease-specific survival, locoregional control, and distant control were used as endpoints for the study. Results: Of the 102 patients who had high-risk Stage I and II disease, 40 were treated with chemotherapy (TROG 96:07) and 62 were treated without chemotherapy (historic control subjects). When Cox's proportional hazards modeling was applied, the only significant factors for overall survival were recurrent disease, age, and the presence of residual disease. For disease-specific survival, recurrent disease was the only significant factor. Primary site on the lower limb had an adverse effect on locoregional control. For distant control, the only significant factor was residual disease. Conclusions: The multivariate analysis suggests chemotherapy has no effect on survival, but because of the wide confidence limits, a chemotherapy effect cannot be excluded. A study of this size is inadequately powered to detect small improvements in survival, and a larger randomized study remains the only way to truly confirm whether chemotherapy improves the results in high-risk MCC.« less
Carr, Brian I; Buch, Shama C; Kondragunta, Venkateswarlu; Pancoska, Petr; Branch, Robert A
2008-08-01
A total of 967 patients with unresectable and untransplantable, biopsy-proven hepatocellular carcinoma (HCC) were prospectively evaluated at baseline and followed up till death. Survival was the end-point for all analyses. We found in our overall analysis, that male gender, ascites, cirrhosis, portal vein thrombosis (PVT), elevated alpha-fetoprotein (AFP) or bilirubin or alkaline phosphatases were each statistically significant adverse prognostic factors. Patients with normal AFP survived longer than those with elevated AFP, in the presence of PVT, large or bilobar tumors or cirrhosis. We used a bivariate analysis to separate patient subgroups based on poor liver function and aggressive tumor characteristics. In subgroup analysis based on these subsets, there was clear discrimination in survival between subsets; in addition both cirrhosis and presence of PVT were significant, independent but modest risk factors. The results of this large dataset show that amongst nonsurgical HCC patients, there are clear subsets with longer survival than other subsets. This data also supports the concept of heterogeneity of HCC.
Chen, Wei-Jen; Ho, Chi-Kung; Shyu, Shi-Sen; Chen, Cheng-Chung; Lin, Guei-Ging; Chou, Li-Shiu; Fang, Yun-Ju; Yeh, Pin-Yang; Chung, Tieh-Chi; Chou, Frank Huang-Chih
2013-07-17
Suicide attempts constitute a serious clinical problem and have important implications for healthcare resources. The aim of the present study was to evaluate the effectiveness of case management using crisis postcards over a 6-month follow-up period. A randomised controlled trial was conducted in Kaohsiung, Taiwan. Prevention of further suicide attempts was compared between two groups with and without the postcard intervention. The intervention group consisted of 373 participants (139 males, 234 females; age: 39.8 ± 14.0 yrs.). The control group consisted of 388 participants (113 males, 275 females; age: 40.0 ± 16.0 yrs.). A survival analysis was used to test the effectiveness of the crisis postcard intervention for the prevention of suicide reattempts. Per-protocol and intention-to-treat analyses were conducted. The intention-to-treat analysis indicated that the crisis postcard had no effect (hazard ratio = 0.84; 95% CI = 0.56 - 1.29), whereas the per-protocol analysis showed a strong benefit for the crisis postcard (hazard ratio = 0.39; 95% CI = 0.21 - 0.72). Although the results of the present study indicated that the postcard intervention did not reduce subsequent suicide behaviour, our study provides an alteration to the postcard intervention. Further studies need to be conducted to clarify whether this type of intervention can reduce subsequent suicidal behaviour, with a particular focus on reducing the rate of loss to follow-up.
Hamady, Zaed Z R; Lodge, J Peter A; Welsh, Fenella K; Toogood, Giles J; White, Alan; John, Timothy; Rees, Myrddin
2014-03-01
To investigate the influence of clear surgical resection margin width on disease recurrence rate after intentionally curative resection of colorectal liver metastases. There is consensus that a histological positive resection margin is a predictor of disease recurrence after resection of colorectal liver metastases. The dispute, however, over the width of cancer-free resection margin required is ongoing. Analysis of observational prospectively collected data for 2715 patients who underwent primary resection of colorectal liver metastases from 2 major hepatobiliary units in the United Kingdom. Histological cancer-free resection margin was classified as positive (if cancer cells present at less than 1 mm from the resection margin) or negative (if the distance between the cancer and the margin is 1 mm or more). The negative margin was further classified according to the distance from the tumor in millimeters. Predictors of disease-free survival were analyzed in univariate and multivariate analyses. A case-match analysis by a propensity score method was undertaken to reduce bias. A 1-mm cancer-free resection margin was sufficient to achieve 33% 5-year overall disease-free survival. Extra margin width did not add disease-free survival advantage (P > 0.05). After the propensity case-match analysis, there is no statistical difference in disease-free survival between patients with negative narrow and wider margin clearance [hazard ratio (HR) 1.0; 95% (confidence interval) CI: 0.9-1.2; P = 0.579 at 5-mm cutoff and HR 1.1; 95% CI: 0.96-1.3; P = 0.149 at 10-mm cutoff]. Patients with extrahepatic disease and positive lymph node primary tumor did not have disease-free survival advantage despite surgical margin clearance (9 months for <1-mm vs 12 months for ≥1-mm margin clearance; P = 0.062). One-mm cancer-free resection margin achieved in patients with colorectal liver metastases should now be considered the standard of care.
Flaherty, Keith T; Hennig, Michael; Lee, Sandra J; Ascierto, Paolo A; Dummer, Reinhard; Eggermont, Alexander M M; Hauschild, Axel; Kefford, Richard; Kirkwood, John M; Long, Georgina V; Lorigan, Paul; Mackensen, Andreas; McArthur, Grant; O'Day, Steven; Patel, Poulam M; Robert, Caroline; Schadendorf, Dirk
2015-01-01
Summary Background Recent phase 3 trials have shown an overall survival benefit in metastatic melanoma. We aimed to assess whether progression-free survival (PFS) could be regarded as a reliable surrogate for overall survival through a meta-analysis of randomised trials. Methods We systematically reviewed randomised trials comparing treatment regimens in metastatic melanoma that included dacarbazine as the control arm, and which reported both PFS and overall survival with a standard hazard ratio (HR). We correlated HRs for overall survival and PFS, weighted by sample size or by precision of the HR estimate, assuming fixed and random effects. We did sensitivity analyses according to presence of crossover, trial size, and dacarbazine dose. Findings After screening 1649 reports and meeting abstracts published before Sept 8, 2013, we identified 12 eligible randomised trials that enrolled 4416 patients with metastatic melanoma. Irrespective of weighting strategy, we noted a strong correlation between the treatment effects for PFS and overall survival, which seemed independent of treatment type. Pearson correlation coefficients were 0.71 (95% CI 0.29–0.90) with a random-effects assumption, 0.85 (0.59–0.95) with a fixed-effects assumption, and 0.89 (0.68–0.97) with sample-size weighting. For nine trials without crossover, the correlation coefficient was 0.96 (0.81–0.99), which decreased to 0.93 (0.74–0.98) when two additional trials with less than 50% crossover were included. Inclusion of mature follow-up data after at least 50% crossover (in vemurafenib and dabrafenib phase 3 trials) weakened the PFS to overall survival correlation (0.55, 0.03–0.84). Inclusion of trials with no or little crossover with the random-effects assumption yielded a conservative statement of the PFS to overall survival correlation of 0.85 (0.51–0.96). Interpretation PFS can be regarded as a robust surrogate for overall survival in dacarbazine-controlled randomised trials of metastatic melanoma; we postulate that this association will hold as treatment standards evolve and are adopted as the control arm in future trials. Funding None. PMID:24485879
Gawron, Andrew J; Fought, Angela J; Lissowska, Jolanta; Ye, Weimin; Zhang, Xiao; Chow, Wong-Ho; Beane Freeman, Laura E; Hou, Lifang
2011-03-01
To examine if genetic variations in chemokine receptor and ligand genes are associated with gastric cancer risk and survival. The study included 298 cases and 417 controls from a population-based study of gastric cancer conducted in Warsaw, Poland in 1994-1996. We investigated seven single nucleotide polymorphisms in a chemokine ligand (CXCL12) and chemokine receptor (CCR2, CCR5, CX3CR1) genes and one frameshift deletion (CCR5) in blood leukocyte DNA in relation to gastric cancer risk and survival. Genotyping was conducted at the NCI Core Genotyping Facility. Odds ratios and 95% confidence intervals were computed using univariate and multivariate logistic regression models. Survival analysis was performed using Cox proportional hazards models. Gastric cancer risk was not associated with single chemokine polymorphisms. A CCR5 haplotype that contained the common alleles of IVS1+151 G>T (rs2734648), IVS2+80 C>T (rs1800024) and minor allele of IVS1+246 A>G (rs1799987) was associated with a borderline significantly increased risk (OR = 1.5, 95% CI: 1.0?2.2). For gastric cancer cases, there was a greater risk of death for carriers of the minor alleles of CCR2 Ex2+241 G>A (rs1799864) (HR = 1.5, 95% CI: 1.1-2.1) and CCR5 IVS2+80 C>T (rs1800024) (HR = 1.5, 95% CI: 1.1-2.1). Carriers of the CCR5 minor allele of IVS1+151 G>T (rs2734648) had a decreased risk of death compared to homozygote carriers of the common allele (HR = 0.8, 95% CI: 0.6-1.0). Our findings do not support an association between gastric cancer risk and single chemokine genetic variation. The observed associations between cancer risk and a CCR5 haplotype and between survival and polymorphisms in CCR2 and CCR5 need replication in future studies.
Sylvester, Peter T.; Evans, John A.; Zipfel, Gregory J.; Chole, Richard A.; Uppaluri, Ravindra; Haughey, Bruce H.; Getz, Anne E.; Silverstein, Julie; Rich, Keith M.; Kim, Albert H.; Dacey, Ralph G.
2014-01-01
Purpose The clinical benefit of combined intraoperative magnetic resonance imaging (iMRI) and endoscopy for transsphenoidal pituitary adenoma resection has not been completely characterized. This study assessed the impact of microscopy, endoscopy, and/or iMRI on progression-free survival, extent of resection status (gross-, near-, and subtotal resection), and operative complications. Methods Retrospective analyses were performed on 446 transsphenoidal pituitary adenoma surgeries at a single institution between 1998 and 2012. Multivariate analyses were used to control for baseline characteristics, differences during extent of resection status, and progression-free survival analysis. Results Additional surgery was performed after iMRI in 56/156 cases (35.9 %), which led to increased extent of resection status in 15/156 cases (9.6 %). Multivariate ordinal logistic regression revealed no increase in extent of resection status following iMRI or endoscopy alone; however, combining these modalities increased extent of resection status (odds ratio 2.05, 95 % CI 1.21–3.46) compared to conventional transsphenoidal microsurgery. Multivariate Cox regression revealed that reduced extent of resection status shortened progression-free survival for near- versus gross-total resection [hazard ratio (HR) 2.87, 95 % CI 1.24–6.65] and sub- versus near-total resection (HR 2.10; 95 % CI 1.00–4.40). Complication comparisons between microscopy, endoscopy, and iMRI revealed increased perioperative deaths for endoscopy versus microscopy (4/209 and 0/237, respectively), but this difference was non-significant considering multiple post hoc comparisons (Fisher exact, p = 0.24). Conclusions Combined use of endoscopy and iMRI increased pituitary adenoma extent of resection status compared to conventional transsphenoidal microsurgery, and increased extent of resection status was associated with longer progression-free survival. Treatment modality combination did not significantly impact complication rate. PMID:24599833
Balan, Shabeesh; Yamada, Kazuo; Iwayama, Yoshimi; Hashimoto, Takanori; Toyota, Tomoko; Shimamoto, Chie; Maekawa, Motoko; Takagai, Shu; Wakuda, Tomoyasu; Kameno, Yosuke; Kurita, Daisuke; Yamada, Kohei; Kikuchi, Mitsuru; Hashimoto, Tasuku; Kanahara, Nobuhisa; Yoshikawa, Takeo
2017-07-01
Involvement of the gamma-aminobutyric acid (GABA)-ergic system in schizophrenia pathogenesis through disrupted neurodevelopment has been highlighted in numerous studies. However, the function of common genetic variants of this system in determining schizophrenia risk is unknown. We therefore tested the association of 375 tagged SNPs in genes derived from the GABAergic system, such as GABA A receptor subunit genes, and GABA related genes (glutamate decarboxylase genes, GABAergic-marker gene, genes involved in GABA receptor trafficking and scaffolding) in Japanese schizophrenia case-control samples (n=2926; 1415 cases and 1511 controls). We observed nominal association of SNPs in nine GABA A receptor subunit genes and the GPHN gene with schizophrenia, although none survived correction for study-wide multiple testing. Two SNPs located in the GABRA1 gene, rs4263535 (P allele =0.002; uncorrected) and rs1157122 (P allele =0.006; uncorrected) showed top hits, followed by rs723432 (P allele =0.007; uncorrected) in the GPHN gene. All three were significantly associated with schizophrenia and survived gene-wide multiple testing. Haplotypes containing associated variants in GABRA1 but not GPHN were significantly associated with schizophrenia. To conclude, we provided substantiating genetic evidence for the involvement of the GABAergic system in schizophrenia susceptibility. These results warrant further investigations to replicate the association of GABRA1 and GPHN with schizophrenia and to discern the precise mechanisms of disease pathophysiology. Copyright © 2017 Elsevier B.V. All rights reserved.
Epidemiology of aplastic anemia: a prospective multicenter study.
Montané, Eva; Ibáñez, Luisa; Vidal, Xavier; Ballarín, Elena; Puig, Ramon; García, Nuria; Laporte, Joan-Ramon
2008-04-01
Aplastic anemia is a rare and severe disease. Its incidence varies considerably worldwide. We aimed at describing the epidemiology of this disease, including the incidence, mortality and survival trends, in a well-defined population. Since 1980, a case-control surveillance study of aplastic anemia has been carried out by a cooperative group, in the metropolitan area of Barcelona. Inclusion is dependent on the patient having at least two of the following features: white blood cell count < or = 3.5 x 10(9)/L, platelet count < or = 50 x 10(9)/L, hemoglobin <10 g/L or hematocrit of <30%; when only one of these last two criteria is fulfilled, a reticulocyte count of < or = 30 x 10(9)/L is also required. The bone marrow biopsy has to be compatible with the diagnosis of aplastic anemia. Between 1980 and 2003, a total of 235 cases of aplastic anemia were identified. The overall incidence was 2.34 per million inhabitants per year and the incidence increased with age. Most of the cases were classified as severe or very severe aplastic anemia. Survival rates at 3 months, and at 2 and 15 years after the diagnosis were 73%, 57%, and 51%, respectively. Advanced age and more severe disease at the time of diagnosis were associated with a lower survival rate. There was a trend to a better 2-year survival rate among patients treated with bone marrow transplantation. Forty-nine cases (20.8%) were exposed to drugs reported to be associated with aplastic anemia, and 21 (8.9%) to toxic agents. The incidence of aplastic anemia in Barcelona is low but the case fatality rate is high. Advanced age and severe disease at the time of diagnosis were associated with decreased survival.
Risk of failure of primary hip arthroscopy—a population-based study
Degen, Ryan M.; Pan, Ting J.; Chang, Brenda; Mehta, Nabil; Chamberlin, Peter D.; Ranawat, Anil S.; Nawabi, Danyal H.; Kelly, Bryan T.
2017-01-01
Abstract The aims of this study are (i) to report on the rates of subsequent surgery following hip arthroscopy and (ii) to identify prognostic variables associated with revision surgery, survival rates and complication rates. The Statewide Planning and Research Cooperative System database, a census of hospital admissions and ambulatory surgery in New York State, was used to identify cases of primary hip arthroscopy. Demographic information and rates of subsequent revision hip arthroscopy or arthroplasty were collected. The risks were modeled with use of age, sex, procedure and surgeon volume as risk factors. Survival analyses were also performed, and 30-day complication was recorded. We identified 8267 procedures in 7836 patients from 1998 to 2012. Revision surgery occurred in 1087 cases (13.2%) at a mean of 1.7 ± 1.6 (mean ± SD) years. Revision arthroscopy accounted for 311 cases (3.8%), and arthroplasty for 796 (9.7%) cases. Survival analysis showed a 2-year survival rate of 88.1%, 5-year of 80.7% and 10-year of 74.9%. Regression analysis revealed that age >50 years [hazard ratio (HR) 2.09; confidence interval (CI) 1.82–2.39, P < 0.01] and a diagnosis of osteoarthritis (HR 2.72; CI 2.21–3.34, P < 0.01) were associated with increased risk of re-operation. Labral repair was associated with a lower risk of re-operation (HR 0.71; CI 0.54–0.93, P = 0.01). Finally, higher surgeon volume (>164 cases/year) resulted in a lower risk of re-operation versus lower volume (<102 cases/year) (HR 0.42; CI 0.32–0.54, P < 0.01). The 30-day complication rate was 0.2%. Older age and pre-existing osteoarthritis increased the likelihood of re-operation following hip arthroscopy, whereas performing a labral repair and having the procedure performed by a higher-volume surgeon lowered the risk of re-operation. PMID:28948033
Khan, Mohemmed N; Konuthula, Neeraja; Parasher, Arjun; Genden, Eric M; Miles, Brett A; Govindaraj, Satish; Iloreta, Alfred M
2017-02-01
Sinonasal undifferentiated carcinoma (SNUC) is a rare, aggressive malignancy of unknown etiology with a poor overall prognosis. Its relative rarity has made it difficult to determine the impact of different treatment modalities on survival. Retrospective study of cases in the National Cancer Data Base (NCDB). NCDB cases that were diagnosed as having SNUC between January 1, 2004, and December 31, 2013 were included in the analysis. Outcomes of patients treated with surgery followed adjuvant chemoradiotherapy were compared with definitive chemoradiotherapy. A 5-year survival rate of 42.2% was observed in the 460 patients in the analysis. American Joint Committee on Cancer (AJCC) clinical staging data were available for 304 patients. Of these patients, 60.2% had advanced tumors (AJCC stage 3 or 4). Surgery followed by adjuvant chemoradiotherapy was associated with better survival than definitive chemoradiotherapy (55.8% vs 42.6%, p = 0.007) in the study population. However, in late-stage tumors, there was no difference in survival between the 2 treatment groups (p = 0.22). For late-stage tumors, the time to initiation of adjuvant therapy was 49.2 ± 5.1 days for the surgery plus adjuvant therapy group as compared with 25.9 ± 2.6 days in the definitive chemoradiotherapy group (p < 0.0001), yet this did not appear to affect outcomes. No differences in age, gender, race, Charlson-Deyo score, facility type (academic vs nonacademic), or radiation dose were found between the 2 treatment groups (p > 0.05). Margin status played a critical role in the success of surgical resection, as no patients with positive margin status receiving adjuvant therapy survived to 5 years. Surgery may play a role in a multimodality approach to treatment of late-stage SNUC if the tumor is amenable to surgical resection and negative margins can be reliably obtained. However, in cases where there may be difficulty obtaining negative margins, or this is considered unlikely preoperatively, surgical resection does not appear to provide any additional survival benefit. © 2016 ARS-AAOA, LLC.
Sejima, Takehiro; Morizane, Shuichi; Hinata, Nobuyuki; Yao, Akihisa; Isoyama, Tadahiro; Saito, Motoaki; Takenaka, Atsushi
2012-01-01
To investigate Fas, Fas ligand (FasL) and Bcl-2 expression, which are considered to be important apoptotic regulatory factors in renal cell carcinomas (RCCs). mRNA quantification and immunohistochemistry allowed for the determination of the expression of these three factors in surgically resected tumors from 82 patients with RCC. The correlation of protein and gene expression with more than 10 years of survival data following nephrectomy (along with clinical and pathologic parameters) was analyzed using uni- and multivariate statistical models. A significantly poorer outcome was observed in patients with tumors expressing high levels of Fas mRNA in the multivariate analysis (p = 0.0002). In addition, patient survival was significantly worse in FasL mRNA-positive tumor cases when compared with FasL mRNA-negative cases (p = 0.0345). Ten cases relapsed more than 5 years after nephrectomy. Among them, the tumors of 8 cases (80%) did not express FasL mRNA. Analysis of Bcl-2 did not show statistical significance of Bcl-2 expression as a prognostic indicator. The data suggest that pronounced Fas expression is a surrogate biomarker of active cancer cell proliferation. Given the FasL tumor counterattack theory, FasL overexpression in RCC may be one of the host immune deficiencies, consequently leading to poor prognosis. Copyright © 2012 S. Karger AG, Basel.
Clinical Inquiry: Is megestrol acetate safe and effective for malnourished nursing home residents?
Wen, Frances K; Millar, James; Oberst-Walsh, Linda; Nashelsky, Joan
2018-02-01
No. Megestrol acetate (MA) is neither safe nor effective for stimulating appetite in malnourished nursing home residents. It increases the risk of deep vein thrombosis (strength of recommendation [SOR]: C, 2 retrospective chart reviews), but isn't associated with other new or worsening events or disorders (SOR: B, single randomized controlled trial [RCT]). Over a 25-week period, MA wasn't associated with increased mortality (SOR: B, single RCT). After 44 months, however, MA-treated patients showed decreased median survival (SOR: B, single case-control study). Consistent, meaningful weight gain was not observed with MA treatment (SOR: B, single case-control study, single RCT, 2 retrospective chart reviews, single prospective case-series).
A probabilistic technique for the assessment of complex dynamic system resilience
NASA Astrophysics Data System (ADS)
Balchanos, Michael Gregory
In the presence of operational uncertainty, one of the greatest challenges in systems engineering is to ensure system effectiveness, mission capability and survivability for large scale, complex system architectures. Historic events such as the 2003 Northeastern Blackout, and the 2005 Hurricane Katrina, have underlined the great importance of system safety, and survivability. With safety management currently applied on a reactive basis to emerging incidents and risk challenges, there is a paradigm shift from passive, reactive and diagnosis-based approaches to the development of architectures that will autonomously manage safety and survivability through active, proactive and prognosis-based engineering solutions. The shift aims to bring safety considerations early in the engineering design process, in order to reduce retrofitting and additional safety certification costs, increase flexibility in risk management, and essentially make safety be "built-in" the design. As a possible enabling research direction, resilience engineering is an emerging discipline, pertinent to safety management, which offers alternative insights on the design of more safe and survivable system architectures. Conceptually, resilience engineering brings new perspectives on the understanding of system safety, accidents, failures, performance degradations and risk. A resilient system can "absorb" the impact of change due to unexpected disturbances, while it "adapts" to change, in order to maintain the system's physical integrity and capability to carry on with its mission. The leading hypothesis advocates that if a complex dynamic system is more resilient, then it would be more survivable, thus more effective, despite the unexpected disturbances that could affect its normal operating conditions. For investigating the impact of more resilient systems on survivability and safety, a framework for theoretical resilience estimations has been formulated. It constitutes the basis for quantitative techniques for total system resilience evaluation, based on scenario-based, dynamic system simulations. Physics-based Modeling and Simulation (M&S) is applied for dynamical system behavior analysis, which includes system performance, health monitoring, damage propagation and overall mission capability. For the development of the assessment framework and testing of a resilience assessment technique, a small-scale canonical problem has been formulated, involving a computational model of a degradable and reconfigurable spring-mass-damper SDOF system, in a multiple main and redundant spring configuration. A rule-based feedback controller is responsible for system performance recovery, through the application of different reconfiguration strategies and strategic activation of the necessary main or redundant springs. Uncertainty effects on system operation are introduced through disturbance factors, such as external forces with varying magnitude, input frequency, event duration and occurrence time. Such factors are the basis for scenario formulation, in support of a Monte Carlo simulation analysis. Case studies with varying levels of damping and different reconfiguration strategies, involve the investigation of operational uncertainty effects on system performance, mission capability, and system survivability. These studies furthermore explore uncertainty effects on resilience functions that describe the system's capacities on "restoring" mission capability, on "absorbing" the effects of changing conditions, and on "adapting" to the occurring change. The proposed resilience assessment technique or the Topological Investigation for Resilient and Effective Systems, through Increased Architecture Survivability (TIRESIAS) is then applied and demonstrated for a naval system application, in the form of a reduced scale, reconfigurable cooling network of a naval combatant. Uncertainty effects are modeled through combinations of different number of network fluid leaks. The TIRESIAS approach on the system baseline (32-control valve configuration) has allowed for the investigation of leak effects on survival times, mission capability degradations, as well as the resilience function capacities. As part of the technique demonstration, case studies were conducted for different architecture configurations, which have been generated for different total number of control valves and valve locations on the topology.
Graft survival of diabetic versus nondiabetic donor tissue after initial keratoplasty.
Vislisel, Jesse M; Liaboe, Chase A; Wagoner, Michael D; Goins, Kenneth M; Sutphin, John E; Schmidt, Gregory A; Zimmerman, M Bridget; Greiner, Mark A
2015-04-01
To compare corneal graft survival using tissue from diabetic and nondiabetic donors in patients undergoing initial Descemet stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty (PKP). A retrospective chart review of pseudophakic eyes that underwent DSAEK or PKP was performed. The primary outcome measure was graft failure. Cox proportional hazard regression and Kaplan-Meier survival analyses were used to compare diabetic versus nondiabetic donor tissue for all keratoplasty cases. A total of 183 eyes (136 DSAEK, 47 PKP) were included in the statistical analysis. Among 24 procedures performed using diabetic donor tissue, there were 4 cases (16.7%) of graft failure (3 DSAEK, 1 PKP), and among 159 procedures performed using nondiabetic donor tissue, there were 18 cases (11.3%) of graft failure (12 DSAEK, 6 PKP). Cox proportional hazard ratio of graft failure for all cases comparing diabetic with nondiabetic donor tissue was 1.69, but this difference was not statistically significant (95% confidence interval, 0.56-5.06; P = 0.348). There were no significant differences in Kaplan-Meier curves comparing diabetic with nondiabetic donor tissue for all cases (P = 0.380). Statistical analysis of graft failure by donor diabetes status within each procedure type was not possible because of the small number of graft failure events involving diabetic tissue. We found similar rates of graft failure in all keratoplasty cases when comparing tissue from diabetic and nondiabetic donors, but further investigation is needed to determine whether diabetic donor tissue results in different graft failure rates after DSAEK compared with PKP.
Secondary Intracranial Tumors Following Radiotherapy for Pituitary Adenomas: A Systematic Review
Yamanaka, Ryuya; Sato, Toshiteru; Hayano, Azusa; Takashima, Yasuo
2017-01-01
Pituitary adenomas are often treated with radiotherapy for the management of tumor progression or recurrence. Despite the improvement in cure rates, patients treated by radiotherapy are at risk of development of secondary malignancies. We conducted a comprehensive literature review of the secondary intracranial tumors that occurred following radiotherapy to pituitary adenomas to obtain clinicopathological characteristics. The analysis included 48 neuroepithelial tumors, 37 meningiomas, and 52 sarcomas which were published between 1959–2017, although data is missing regarding overall survival and type of irradiation in a significant proportion of the reports. The average onset age for the pituitary adenoma was 37.2 ± 14.4 years and the average latency period before the diagnosis of the secondary tumor was 15.2 ± 8.7 years. Radiotherapy was administered in pituitary adenomas at an average dose of 52.0 ± 19.5 Gy. The distribution of pituitary adenomas according to their function was prolactinoma in 10 (7.2%) cases, acromegaly in 37 (27.0%) cases, Cushing disease in 4 (2.9%) cases, PRL+GH in 1 (0.7%) case, non-functioning adenoma in 57 (41.6%) cases. Irradiation technique delivered was lateral opposing field in 23 (16.7%) cases, 3 or 4 field technique in 27 (19.6%) cases, rotation technique in 10 (7.2%) cases, radio surgery in 6 (4.3%) cases. Most of the glioma or sarcoma had been generated after lateral opposing field or 3/4 field technique. Fibrosarcomas were predominant before 1979 (p < 0.0001). The median overall survival time for all neuroepithelial tumors was 11 months (95% confidence intervals (CI), 3–14). Patients with gliomas treated with radiotherapy exhibited a non-significant positive trend with longer overall survival. The median overall survival time for sarcoma cases was 6 months (95% CI, 1.5–9). The median survival time in patients with radiation and/or chemotherapy for sarcomas exhibited a non-significant positive trend with longer overall survival. In patients treated with radiotherapy for pituitary adenomas, the risk of secondary tumor incidence warrants a longer follow up period. Moreover, radiation and/or chemotherapy should be considered in cases of secondary glioma or sarcoma following radiotherapy to the pituitary adenomas. PMID:28786923
Improvement in initial survival of spinal injuries: a 10-year audit.
Tan, H B; Sloan, J P; Barlow, I F
2005-08-01
A 10-year retrospective study of all spinal injuries presenting to the Leeds Teaching Hospitals between 1991 and 2001. The hospitals provide secondary care to a population of 750,000 and tertiary care to a population of 2-3 million. In total 1119 spinal injuries were studied. The overall survival rate was 89%. The commonest age group for presentation was 25-29 years with a secondary peak in the seventh decade, a mean overall of 43 years. 66% of injuries occurred in males. The commonest cause was a fall from a height (44%), with road traffic accidents (RTA) causing 43%. Pedestrians were most at risk within the road traffic group, making up 63% of cases. Isolated cervical spine injuries made up 37% of all cases. Cervical fractures were most associated with neurological injury (50%). Immediate survival has increased over the decade from 83% in 1991 to 93% in 2001. The probability of survival was significant at P = 0.006 and actual survival at P = 0.012 (Pearson correlation). The causal analysis has not been carried out but it is thought likely that improved quality of care is responsible.
Clinical Characteristics of Patients With Renal Cell Carcinoma and Metastasis to the Thyroid Gland.
Jackson, Gregory; Fino, Nora; Bitting, Rhonda L
2017-01-01
Renal cell carcinoma (RCC) is the most common malignancy to metastasize to the thyroid gland. The aims of this study are as follows: (1) to analyze the clinical characteristics of patients with thyroid involvement of RCC and (2) in patients with RCC thyroid metastasis, to determine whether RCC metastasis to glandular organs only portends a better prognosis compared with other patterns of RCC metastasis. Patients from Wake Forest Baptist Medical Center (WFBMC) diagnosed with thyroid metastasis from RCC were identified and medical records retrospectively examined. A systematic review of the literature for cases of RCC involving the thyroid gland was also performed. The clinical characteristics of the institutional cohort and the cases from the literature review were compared. Descriptive statistical analysis was performed, and overall survival (OS) was summarized using Kaplan-Meier methods. The median OS for the WFBMC cohort was 56.4 months. In the literature review cohort, OS of patients with RCC thyroid metastasis was 213.6 months, and there was no statistically significant survival difference based on the site of metastasis. Median survival after thyroid metastasis from RCC for the WFBMC and literature cohort was 21.6 and 45.6 months, respectively. Metastatic RCC should be included in the differential of a new thyroid mass. Treatment directed at the thyroid metastasis results in prolonged survival in some cases. Further analysis into the genomic differences and mechanisms of thyroid metastasis is warranted.
Fatal corrosive attack: a study of 13 cases from central Delhi, India.
Behera, C; Rani, A; Pradhan, M; Dikshit, P C
2014-06-01
The present study is a retrospective analysis of 13 cases of deaths, which resulted from throwing of corrosives over the body. The cases were autopsied at the Department of Forensic Medicine, Maulana Azad Medical College & Associated Hospitals, Delhi, India, during a period of 13 years from July 1998 to June 2011. The cases represented approximately 0.1% of all autopsy cases during the same period. Data were analyzed with regard to the age, sex, place of occurrence, pattern of injury, survival period, and cause of death. Of these cases, 8 (61.54%) were male, and 5 (38.46%) were female. The most common age group of the victim was 21 to 30 years (46.15%). Six of the victims were attacked on the road side. Face and thorax were involved in all cases (100%). The average total body surface area of burn was 56.69%.The mean survival period was 28.2 days. In 53.85% of cases, the cause of death was septicemia.
Local control of osteogenic sarcoma by radiation and chemotherapy
DOE Office of Scientific and Technical Information (OSTI.GOV)
Caceres, E.; Zaharia, M.; Valdivia, S.
Sixteen patients with osteogenic sarcoma of limbs were treated with high dose methotrexate followed by leucovorin rescue, adriamycin and radiotherapy to the primary tumor. A post-treatment surgical biopsy was performed in 15 of the 16 patients. In 12 of 15 patients (80%), the follow-up biopsy was negative for active tumor. Complications of treatment were myelosuppression (16 cases), moist desquamation (13 cases), soft tissue necrosis (2 cases) local infection (2 cases), fibrosis (9 cases) and bone fracture (4 cases). The mean survival time in this group of patients was 712 days.
Look, Xinqi; Li, Huihua; Ng, Mingwei; Lim, Eric Tien Siang; Pothiawala, Sohil; Tan, Kenneth Boon Kiat; Sewa, Duu Wen; Shahidah, Nur; Pek, Pin Pin; Ong, Marcus Eng Hock
2018-01-01
Targeted temperature management post-cardiac arrest is currently implemented using various methods, broadly categorized as internal and external. This study aimed to evaluate survival-to-hospital discharge and neurological outcomes (Glasgow-Pittsburgh Score) of post-cardiac arrest patients undergoing internal cooling verses external cooling. A randomized controlled trial of post-resuscitation cardiac arrest patients was conducted from October 2008-September 2014. Patients were randomized to either internal or external cooling methods. Historical controls were selected matched by age and gender. Analysis using SPSS version 21.0 presented descriptive statistics and frequencies while univariate logistic regression was done using R 3.1.3. 23 patients were randomized to internal cooling and 22 patients to external cooling and 42 matched controls were selected. No significant difference was seen between internal and external cooling in terms of survival, neurological outcomes and complications. However in the internal cooling arm, there was lower risk of developing overcooling (p=0.01) and rebound hyperthermia (p=0.02). Compared to normothermia, internal cooling had higher survival (OR=3.36, 95% CI=(1.130, 10.412), and lower risk of developing cardiac arrhythmias (OR=0.18, 95% CI=(0.04, 0.63)). Subgroup analysis showed those with cardiac cause of arrest (OR=4.29, 95% CI=(1.26, 15.80)) and sustained ROSC (OR=5.50, 95% CI=(1.64, 20.39)) had better survival with internal cooling compared to normothermia. Cooling curves showed tighter temperature control for internal compared to external cooling. Internal cooling showed tighter temperature control compared to external cooling. Internal cooling can potentially provide better survival-to-hospital discharge outcomes and reduce cardiac arrhythmia complications in carefully selected patients as compared to normothermia. Copyright © 2017. Published by Elsevier Inc.
Faro, Albert; Shepherd, Ross; Huddleston, Charles B; Lowell, Jeffrey; Gandhi, Sanjiv; Nadler, Michelle; Sweet, Stuart C
2007-06-15
Simultaneous liver-lung transplantation is an infrequent but technically feasible procedure in patients with end-stage lung disease and advanced liver disease. We characterize the outcomes of pediatric patients who underwent this procedure at our institution. We performed a retrospective, case-control study and reviewed the medical records of all patients referred to our transplant program from its inception. Seven patients were listed for simultaneous liver-lung transplant. The five patients who survived to transplant were matched to 13 controls who underwent isolated bilateral sequential lung transplant for underlying diagnosis, age at time of transplant, gender, and era of transplant. Outcome measures included patient and graft survival, occurrence of bronchiolitis obliterans (BO), and episodes of rejection. Of the five study patients who underwent liver-lung transplant, one died of multiorgan failure 11 days after transplant compared with 9 of 13 controls who died. The median survival for the study patients was 89 months (range, 0-112 months) compared with the controls, who had a median survival of 34 months (range, 0-118 months). The remaining four patients had bronchiolitis obliterans syndrome scores of 0 compared with 5 of 13 control patients (P=0.02). The rate of acute rejection per 100 patient days was 0.012 for the study patients compared with 0.11 for the controls (P=0.025). Simultaneous liver-lung transplantation is a technically feasible procedure with excellent long-term outcomes. The surviving study subjects remain free from bronchiolitis obliterans syndrome. These results suggest that the transplanted liver may bestow immunologic privilege to the lung allograft.
Ercolani, G; Dazzi, A; Giovinazzo, F; Ruzzenente, A; Bassi, C; Guglielmi, A; Scarpa, A; D'Errico, A; Pinna, A D
2015-09-01
Few papers deal with pathologic characteristics and outcome of the 3 different cholangiocarcinomas based on location (intrahepatic, peri-hilar, distal). There is little evidence regarding similarity and differences. From two tertiary referral Italian Centers (in Bologna and Verona), 479 patients with cholangiocarcinoma were evaluated between 1980 and 2011. Several pathologic characteristics and their impact on survival were analyzed among resected patients for cholangiocarcinomas depending on the site of origin. Tumour location was intrahepatic in 172 cases (36%), peri-hilar in 243 (51) and distal in 64(13%). Curative resection was performed in 339 (70%) patients. Intrahepatic cholangiocarcinoma showed higher probability to achieve R0 resection (81%), but was more frequently associated with presence of microvascular invasion (71%). Distal cholangiocarcinoma presented less R0 resections (58%), higher lymphnode involvement (60%) and lower microvascular invasion (49%). Hilar cholangiocarcinoma had intermediate characteristics (R0: 65% of cases). Median follow up was 30.2 ± 38 months; the 5 years overall survival was 31% in the resected population. Overall survival curves were similar among the three groups. At univariate analysis surgical margins, lymphnode status, perineural invasion, T category, TNM stage, microvascular invasion, tumour grading had significant impact on survival. At multivariate analysis, only microvascular invasion was significantly related to long term results (HR = 1,7; 95% CI = 1,0-2,5)". Micro-vascular invasion has the strongest impact on survival in all three types of cholangiocarcinoma. In case of comparable pathologic characteristics and stage, the three tumors show similar outcome; depending on location, it shows a different tendency to invade bordering structures which affect the outcome. Copyright © 2015 Elsevier Ltd. All rights reserved.
Mocellin, Simone; Pasquali, Sandro; Rossi, Carlo Riccardo; Nitti, Donato
2011-07-01
The proportion of positive among examined lymph nodes (lymph node ratio [LNR]) has been recently proposed as an useful and easy-to-calculate prognostic factor for patients with cutaneous melanoma. However, its independence from the standard prognostic system TNM has not been formally proven in a large series of patients. Patients with histologically proven cutaneous melanoma were identified from the Surveillance Epidemiology End Results database. Disease-specific survival was the clinical outcome of interest. The prognostic ability of conventional factors and LNR was assessed by multivariable survival analysis using the Cox regression model. Eligible patients (n = 8,177) were diagnosed with melanoma between 1998 and 2006. Among lymph node-positive cases (n = 3,872), most LNR values ranged from 1% to 10% (n = 2,187). In the whole series (≥5 lymph nodes examined) LNR significantly contributed to the Cox model independently of the TNM effect on survival (hazard ratio, 1.28; 95% confidence interval, 1.23-1.32; P < .0001). On subgroup analysis, the significant and independent prognostic value of LNR was confirmed both in patients with ≥10 lymph nodes examined (n = 4,381) and in those with TNM stage III disease (n = 3,658). In all cases, LNR increased the prognostic accuracy of the survival model. In this large series of patients, the LNR independently predicted disease-specific survival, improving the prognostic accuracy of the TNM system. Accordingly, the LNR should be taken into account for the stratification of patients' risk, both in clinical and research settings. Copyright © 2011 Mosby, Inc. All rights reserved.
Hwang, Jae Ha; Kim, Dong Wan; Kim, Kwang Seog; Lee, Sam Yong
2018-06-01
Thrombosis is the most common complication of thrombocytosis, which can be particularly damaging to reattached digits. We present a guideline about digital replantation when thrombocytosis is expected. We report a case of an 18-year-old man who sustained a traumatic amputation of two fingers and splenic rupture in a traffic accident. He underwent digital replantation the day after splenectomy when life-threatening conditions had been managed. The platelet count increased to over 1,300,000/mm and post-splenectomy reactive thrombocytosis was diagnosed. Hydroxyurea and anagrelide were administered to control the platelet count after consultation with a hematologist. The reattached fingers survived without any complication. In patients with digital amputation, replantation can be attempted, even when thrombocytosis is expected, when requested by the patient. Furthermore, the platelet count should be actively controlled with medication to improve the survival rate of the reattached finger.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Sorbe, Bengt, E-mail: bengt.sorbe@orebroll.se; Horvath, Gyoergy; Andersson, Hakan
Purpose: To evaluate the value of adjuvant external beam pelvic radiotherapy as adjunct to vaginal brachytherapy (VBT) in medium-risk endometrial carcinoma, with regard to locoregional tumor control, recurrences, survival, and toxicity. Methods and Materials: Consecutive series of 527 evaluable patients were included in this randomized trial. Median follow-up for patients alive was 62 months. The primary study endpoints were locoregional recurrences and overall survival. Secondary endpoints were recurrence-free survival, recurrence-free interval, cancer-specific survival, and toxicity. Results: Five-year locoregional relapse rates were 1.5% after external beam radiotherapy (EBRT) plus VBT and 5% after vaginal irradiation alone (p = 0.013), and 5-yearmore » overall survival rates were 89% and 90%, respectively (p = 0.548). Endometrial cancer-related death rates were 3.8% after EBRT plus VBT and 6.8% after VBT (p = 0.118). Pelvic recurrences (exclusively vaginal recurrence) were reduced by 93% by the addition of EBRT to VBT. Deep myometrial infiltration was a significant prognostic factor in this medium-risk group of endometrioid carcinomas but not International Federation of Gynecology and Obstetrics grade or DNA ploidy. Combined radiotherapy was well tolerated, with serious (Grade 3) late side effects of less than 2%. However, there was a significant difference in favor of VBT alone. Conclusions: Despite a significant locoregional control benefit with combined radiotherapy, no survival improvement was recorded, but increased late toxicity was noted in the intestine, bladder, and vagina. Combined RT should probably be reserved for high-risk cases with two or more high-risk factors. VBT alone should be the adjuvant treatment option for purely medium-risk cases.« less
Genome-Wide Methylation Analyses in Glioblastoma Multiforme
Lai, Rose K.; Chen, Yanwen; Guan, Xiaowei; Nousome, Darryl; Sharma, Charu; Canoll, Peter; Bruce, Jeffrey; Sloan, Andrew E.; Cortes, Etty; Vonsattel, Jean-Paul; Su, Tao; Delgado-Cruzata, Lissette; Gurvich, Irina; Santella, Regina M.; Ostrom, Quinn; Lee, Annette; Gregersen, Peter; Barnholtz-Sloan, Jill
2014-01-01
Few studies had investigated genome-wide methylation in glioblastoma multiforme (GBM). Our goals were to study differential methylation across the genome in gene promoters using an array-based method, as well as repetitive elements using surrogate global methylation markers. The discovery sample set for this study consisted of 54 GBM from Columbia University and Case Western Reserve University, and 24 brain controls from the New York Brain Bank. We assembled a validation dataset using methylation data of 162 TCGA GBM and 140 brain controls from dbGAP. HumanMethylation27 Analysis Bead-Chips (Illumina) were used to interrogate 26,486 informative CpG sites in both the discovery and validation datasets. Global methylation levels were assessed by analysis of L1 retrotransposon (LINE1), 5 methyl-deoxycytidine (5m-dC) and 5 hydroxylmethyl-deoxycytidine (5hm-dC) in the discovery dataset. We validated a total of 1548 CpG sites (1307 genes) that were differentially methylated in GBM compared to controls. There were more than twice as many hypomethylated genes as hypermethylated ones. Both the discovery and validation datasets found 5 tumor methylation classes. Pathway analyses showed that the top ten pathways in hypomethylated genes were all related to functions of innate and acquired immunities. Among hypermethylated pathways, transcriptional regulatory network in embryonic stem cells was the most significant. In the study of global methylation markers, 5m-dC level was the best discriminant among methylation classes, whereas in survival analyses, high level of LINE1 methylation was an independent, favorable prognostic factor in the discovery dataset. Based on a pathway approach, hypermethylation in genes that control stem cell differentiation were significant, poor prognostic factors of overall survival in both the discovery and validation datasets. Approaches that targeted these methylated genes may be a future therapeutic goal. PMID:24586730
Yarlagadda, Bharat B; Meier, Josh C; Lin, Derrick T; Emerick, Kevin S; Deschler, Daniel G
2017-01-01
Adenoid cystic carcinoma of the minor salivary glands can be challenging and marked by high rates of local recurrence despite appropriate surgical resection. Management of this pathology in the base of the tongue is particularly difficult given the poor functional outcomes traditionally associated with an aggressive surgical approach. This article presents a case series of patients who underwent up-front surgical resection followed by free tissue transfer reconstruction. A retrospective analysis was performed of patients with adenoid cystic carcinoma of the base of the tongue who underwent composite resection and reconstruction with a radial forearm free flap. Three patients met inclusion criteria and underwent analysis. All patients achieved locoregional control after at least 4 years of surveillance. In addition, all patients were decannulated and were swallowing without the need for gastrostomy tube feeding. This series demonstrates that for select patients with adenoid cystic carcinoma of the base of the tongue, excellent locoregional control can be achieved with acceptable functional outcomes and prolonged survival when appropriate reconstructive measures are employed.
Le Guyader-Peyrou, Sandra; Orazio, Sébastien; Dejardin, Olivier; Maynadié, Marc; Troussard, Xavier; Monnereau, Alain
2017-03-01
The survival of patients with diffuse large B-cell lymphoma has increased during the last decade as a result of addition of anti-CD20 to anthracycline-based chemotherapy. Although the trend is encouraging, there are persistent differences in survival within and between the USA and European countries suggesting that non-biological factors play a role. Our aim was to investigate the influence of such factors on relative survival of patients with diffuse large B-cell lymphoma. We conducted a retrospective, multicenter, registry-based study in France on 1165 incident cases of diffuse large B-cell lymphoma between 2002 and 2008. Relative survival analyses were performed and missing data were controlled with the multiple imputation method. In a multivariate analysis, adjusted for age, sex and International Prognostic Index, we confirmed that time period was associated with a better 5-year relative survival. The registry area, the medical specialty of the care department (onco-hematology versus other), the time to travel to the nearest teaching hospital, the place of treatment (teaching versus not-teaching hospital -borderline significance), a comorbidity burden and marital status were independently associated with the 5-year relative survival. Adjusted for first-course treatment, inclusion in a clinical trial and treatment discussion in a multidisciplinary meeting were strongly associated with a better survival outcome. In contrast, socio-economic status (determined using the European Deprivation Index) was not associated with outcome. Despite therapeutic advances, various non-biological factors affected the relative survival of patients with diffuse large B-cell lymphoma. The notion of lymphoma-specific expertise seems to be essential to achieve optimal care management and reopens the debate regarding centralization of these patients' care in hematology/oncology departments. Copyright© Ferrata Storti Foundation.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Kang, Chung-Jan; Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Lin, Chien-Yu
2011-11-15
Purpose: The objective of this retrospective study was twofold: (1) to investigate prognostic factors for clinical outcomes in patients with poorly differentiated oral cavity squamous cell carcinoma and (2) to identify specific prognostic subgroups that may help to guide treatment decisions. Methods and Materials: We examined 102 patients with poorly differentiated oral cavity squamous cell carcinoma. All patients were followed for at least 24 months after surgery or until death. The 5-year rates of local control, neck control, distant metastasis, disease-free, disease-specific, and overall survival served as main outcome measures. Results: The 5-year rates were as follows: local control (79%),more » neck control (64%), distant metastases (27%), disease-free survival (48%), disease-specific survival (52%), and overall survival (42%). Multivariable analysis showed that the number of pathologically positive nodes ({>=}4 vs. {<=}3) was a significant predictor of neck control, distant metastasis, and disease-free, disease-specific, and overall survival rates. In addition, the presence of tumor depth of {>=}11 mm (vs. <11 mm) was a significant predictor of distant metastasis, disease-specific survival, and overall survival rates. The combination of the two predictors (26.5%, 27/102) was independently associated with poorer neck control (p = 0.0319), distant metastasis (p < 0.0001), and disease-free (p < 0.0001), disease-specific (p < 0.0001), and overall survival (p < 0.0001) rates. Conclusions: In patients with poorly differentiated oral cavity squamous cell carcinoma, the presence of at least 4 pathologically positive lymph nodes and of a pathological tumor depth {>=}11 mm identifies a subset of subjects with poor clinical outcomes. Patients carrying both risk factors are suitable candidates for the development of novel therapeutic approaches.« less
Tumor characteristics and survival outcomes of women with tamoxifen-related uterine carcinosarcoma.
Matsuo, Koji; Ross, Malcolm S; Bush, Stephen H; Yunokawa, Mayu; Blake, Erin A; Takano, Tadao; Ueda, Yutaka; Baba, Tsukasa; Satoh, Shinya; Shida, Masako; Ikeda, Yuji; Adachi, Sosuke; Yokoyama, Takuhei; Takekuma, Munetaka; Takeuchi, Satoshi; Nishimura, Masato; Iwasaki, Keita; Yanai, Shiori; Klobocista, Merieme M; Johnson, Marian S; Machida, Hiroko; Hasegawa, Kosei; Miyake, Takahito M; Nagano, Tadayoshi; Pejovic, Tanja; Shahzad, Mian Mk; Im, Dwight D; Omatsu, Kohei; Ueland, Frederick R; Kelley, Joseph L; Roman, Lynda D
2017-02-01
To examine tumor characteristics and survival outcome of women with uterine carcinosarcoma who had a history of tamoxifen use. This is a multicenter retrospective study examining stage I-IV uterine carcinosarcoma cases based on history of tamoxifen use. Patient demographics, tumor characteristics, treatment pattern, and survival outcomes were compared between tamoxifen users and non-users. Sixty-six cases of tamoxifen-related uterine carcinosarcoma were compared to 1009 cases with no history of tamoxifen use. Tamoxifen users were more likely to be older (mean age, 69 versus 64, P<0.001) and had a past history of malignancy (100% versus 12.7%, P<0.001). Tamoxifen-related uterine carcinosarcoma was significantly associated with a higher proportion of stage IA disease (48.4% versus 29.9%) and a lower risk of stage IVB disease (7.8% versus 16.0%) compared to tamoxifen-unrelated carcinosarcoma (P=0.034). Deep myometrial tumor invasion was less common in uterine carcinosarcoma related to tamoxifen use (28.3% versus 48.8%, P=0.002). On univariate analysis, tamoxifen use was not associated with progression-free survival (5-year rates 44.5% versus 46.8%, P=0.48) and disease-specific survival (64.0% versus 59.1%, P=0.39). After adjusting for age, past history of malignancy, stage, residual disease status at surgery, and postoperative treatment patterns, tamoxifen use was not associated with progression-free survival (adjusted-hazard ratio 0.86, 95% confidence interval 0.50 to 1.50, P=0.60) and disease-specific survival (adjusted-hazard ratio 0.68, 95% confidence interval 0.36 to 1.29, P=0.24). Our study suggests that tamoxifen-related uterine carcinosarcoma may have favorable tumor characteristics but have comparable stage-specific survival outcomes compared to tamoxifen-unrelated uterine carcinosarcoma. Copyright © 2016 Elsevier Inc. All rights reserved.
López-Ortiz, M I; Pérez, C M; Suárez, E; Ríos-Dávila, R
1999-12-01
The EcoEléctrica Mangrove Planting Project, a five-year voluntary effort, has the purpose of testing a recently developed mangrove planting technique at the EcoEléctrica site in Peñuelas, Puerto Rico. The goal of the project is to provide empirical validation to promote or improve the technique to be used in recovering mangrove ecosystems in Puerto Rico and United States. The research presented herein analyzed the information collected on the first two years of the project. The proportions of remaining casings and seeds per study zone were compared using the chi-square distribution. Zone 1 had the least pipes lost while Zone 4 had the most (p < 0.05). Forty-three percent of the seeds in Zone 1 remained in the casing, while 26% remained in Zone 2 (p = 0.03). Median growth rates of seeds per study zone showed that Zone 1 had the highest median growth rates. Survival analysis described the survival experience of the seeds, and differences in survival probabilities were compared with the log-rank test. Zone 1 seeds had a better survival experience compared to Zones 2, 3 and 4 (p < 0.0001). Survival probabilities for being free of spots were over 60% during the whole study period. No significant differences were observed in the survival experience with the use-or-no use of casing extensions (p = 0.40), and the use-or-no use of nursed seeds (p = 0.26). Differences in survival probabilities might be attributed to variations in wave energy, depth or substrate conditions. This hypothesis will be evaluated in the second phase of the study.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Gielda, Benjamin T., E-mail: Benjamin_gielda@rush.edu; Mehta, Par; Khan, Atif
Background: Preoperative concurrent chemoradiotherapy (CRT) is an accepted treatment for potentially resectable, locally advanced, non-small-cell lung cancer (NSCLC). We reviewed a decade of single institution experience with preoperative split-course CRT followed by surgical resection to evaluate survival and identify factors that may be helpful in predicting outcome. Methods and Materials: All patients treated with preoperative split-course CRT and resection at Rush University Medical Center (RUMC) between January 1999 and December 2008 were retrospectively analyzed. Endpoints included overall survival (OS), progression-free survival (PFS), local-regional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS). Patient and treatment related variables were assessed for correlationmore » with outcomes. Results: A total of 54 patients were analyzed, 76% Stage IIIA, 18% Stage IIIB, and 6% oligometastatic. The pathologic complete response (pCR) rate was 31.5%, and the absence of nodal metastases (pN0) was 64.8%. Median OS and 3-year actuarial survival were 44.6 months and 50%, respectively. Univariate analysis revealed initial stage (p < 0.01) and percent weight change during CRT (p < 0.01) significantly correlated with PFS/OS. On multivariate analysis initial stage (HR, 2.4; 95% CI, 1.18-4.90; p = 0.02) and percent weight change (HR, 0.79; 95% CI, 0.67-0.93; p < 0.01) maintained significance with respect to OS. There were no cases of Grade 3+ esophagitis, and there was a single case of Grade 3 febrile neutropenia. Conclusions: The strong correlation between weight change during CRT and OS/PFS suggests that this clinical parameter may be useful as a complementary source of predictive information in addition to accepted factors such as pathological response.« less
Rituximab for the treatment of relapsed/refractory chronic lymphocytic leukaemia.
Dretzke, J; Barton, P; Kaambwa, B; Connock, M; Uthman, O; Bayliss, S; Meads, C
2010-10-01
This paper presents a summary of the evidence review group (ERG) report on the clinical effectiveness and cost-effectiveness of rituximab with chemotherapy compared to chemotherapy only for the treatment of relapsed/refractory chronic lymphocytic leukaemia (CLL) based on the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. Evidence was available in the form of one open-label, ongoing, unpublished randomised controlled trial (RCT), REACH (Rituximab in the Study of Relapsed Chronic Lymphocytic Leukemia), conducted by the manufacturer, which compared rituximab with a fludarabine and cyclophosphamide combination (R-FC) to fludarabine and cyclophosphamide (FC) only. REACH was scheduled to run for 8 years; however, the data provided were immature, with a median observation time at the time of data analysis of 2.1 years. REACH provided evidence of prolonged progression free survival with R-FC compared to FC (10 months, investigators' data), but no evidence of an overall survival benefit with R-FC. Patients refractory to fludarabine and with prior rituximab exposure were excluded from REACH and no controlled studies were identified by the ERG for these patient groups. The ERG had concerns about the structure of the economic model submitted by the manufacturer, which did not allow improvement in quality of life from treatment while in a progressed state. The manufacturer's model further assumed a divergence in cumulative deaths between the R-FC and FC treatment arms from the outset, which did not accord with observed data from REACH. When the survival advantage was removed, the manufacturer's base-case incremental cost-effectiveness ratio (ICER) changed from 15,593 pounds to between 40,000 pounds and 42,000 pounds per quality-adjusted life-year (QALY). With no survival advantage, the ICER became sensitive to changes in utility. There was no good empirical evidence on the utility of CLL patients in different states. Allowing for the possibility of a survival advantage with rituximab (although not supported by current evidence), the ERG performed further modelling, which found that rituximab would be cost-effective at 20,000 pounds/QALY (30,000 pounds/QALY) if a reduction in survival advantage relative to the manufacturer's base case of 40% (80%) was assumed. The guidance issued by NICE in July 2010 as a result of the STA recommends rituximab with FC for people with relapsed or refractory chronic lymphocytic leukaemia, except when the condition is refractory to fludarabine or where there has been previous treatment with rituximab.
Gong, Jun; Wu, Daniel; Chuang, Jeremy; Tuli, Richard; Simard, John; Hendifar, Andrew
2017-11-01
This review highlights the evidence supporting symptom control and quality-of-life (QOL) measures as predictors of survival in treatment-refractory metastatic colorectal cancer (mCRC) and describes a composite symptom control and QOL end point recently reported in a Phase III trial that may serve as a more reasonable end point of efficacy in this population. A literature search was conducted using MEDLINE to identify clinical studies (including case series and observational, retrospective, and prospective studies) that reported the predictive value of QOL measures for survival in mCRC. The search was limited by the following key words: quality of life, survival, and colorectal cancer. We then performed a second search limited to studies of randomized and Phase III design in mCRC to identify studies that used QOL assessments as their primary end points. A manual search was also performed to include additional studies of potential relevance. There is increasing evidence to support that symptom control and QOL measures are predictors of survival in treatment-refractory mCRC and can serve as an alternative but equally as important end point to survival in this population. A recent large, randomized Phase III trial using a composite primary end point of lean body mass, pain, anorexia, and fatigue reported the feasibility in evaluating benefit in mCRC beyond conventional clinical trial end points. Future studies in treatment-refractory mCRC may be better served by evaluating improvement in symptom control and QOL, which may otherwise serve as the best predictor of survival in last-line treatment settings. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.
Who is most affected by prenatal alcohol exposure: Boys or girls?
May, Philip A; Tabachnick, Barbara; Hasken, Julie M; Marais, Anna-Susan; de Vries, Marlene M; Barnard, Ronel; Joubert, Belinda; Cloete, Marise; Botha, Isobel; Kalberg, Wendy O; Buckley, David; Burroughs, Zachary R; Bezuidenhout, Heidre; Robinson, Luther K; Manning, Melanie A; Adnams, Colleen M; Seedat, Soraya; Parry, Charles D H; Hoyme, H Eugene
2017-08-01
To examine outcomes among boys and girls that are associated with prenatal alcohol exposure. Boys and girls with fetal alcohol spectrum disorders (FASD) and randomly-selected controls were compared on a variety of physical and neurobehavioral traits. Sex ratios indicated that heavy maternal binge drinking may have significantly diminished viability to birth and survival of boys postpartum more than girls by age seven. Case control comparisons of a variety of physical and neurobehavioral traits at age seven indicate that both sexes were affected similarly for a majority of variables. However, alcohol-exposed girls had significantly more dysmorphology overall than boys and performed significantly worse on non-verbal IQ tests than males. A three-step sequential regression analysis, controlling for multiple covariates, further indicated that dysmorphology among girls was significantly more associated with five maternal drinking variables and three distal maternal risk factors. However, the overall model, which included five associated neurobehavioral measures at step three, was not significant (p=0.09, two-tailed test). A separate sequential logistic regression analysis of predictors of a FASD diagnosis, however, indicated significantly more negative outcomes overall for girls than boys (Nagelkerke R 2 =0.42 for boys and 0.54 for girls, z=-2.9, p=0.004). Boys and girls had mostly similar outcomes when prenatal alcohol exposure was linked to poor physical and neurocognitive development. Nevertheless, sex ratios implicate lower viability and survival of males by first grade, and girls have more dysmorphology and neurocognitive impairment than boys resulting in a higher probability of a FASD diagnosis. Copyright © 2017 Elsevier B.V. All rights reserved.
Lewis, James S; Scantlebury, Juliette B; Luo, Jingqin; Thorstad, Wade L
2012-07-01
Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all surgically resected cases (149) were reviewed. Anaplasia was defined as any × 40 field with ≥ 3 tumor nuclei with diameters ≥ 5 lymphocyte nuclei (~25 μm), and multinucleation was defined as any × 40 field with ≥ 3 tumor cells with multiple nuclei. p16 was positive in 128 cases (85.9%), 64 cases (43.0%) showed anaplasia, and 71 (47.7%) showed multinucleation. Anaplasia and multinucleation were highly related (P<0.001), and both also correlated with histologic type (P<0.001 and P=0.01, respectively), p16 status (P=0.09 and 0.03, respectively), and partially with nodal extracapsular extension. There was no correlation with any of the other variables. In univariate analysis, cases showing anaplasia or multinucleation had worse overall, disease-specific, and disease-free survival (P<0.006 for all). Higher T-stage, keratinizing histologic type, extracapsular extension, and smoking also all correlated with worse survival. In multivariate analysis, anaplasia and multinucleation both predicted worse disease-specific survival (hazard ratio 9.9, P=0.04; and hazard ratio 11.9, P=0.02, respectively) independent of the other variables. In summary, among surgically resectable oropharyngeal SCC (including among just the p16-positive cohort), tumor cell anaplasia and multinucleation independently correlated with disease recurrence and poorer survival.
Lewis, James S.; Scantlebury, Juliette B.; Luo, Jingqin; Thorstad, Wade L.
2013-01-01
Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all surgically resected cases (149) were reviewed. Anaplasia was defined as any ×40 field with ≥ 3 tumor nuclei with diameters ≥ 5 lymphocyte nuclei (~25 μm), and multinucleation was defined as any ×40 field with ≥ 3 tumor cells with multiple nuclei. p16 was positive in 128 cases (85.9%), 64 cases (43.0%) showed anaplasia, and 71 (47.7%) showed multinucleation. Anaplasia and multinucleation were highly related (P < 0.001), and both also correlated with histologic type (P < 0.001 and P = 0.01, respectively), p16 status (P = 0.09 and 0.03, respectively), and partially with nodal extracapsular extension. There was no correlation with any of the other variables. In univariate analysis, cases showing anaplasia or multinucleation had worse overall, disease-specific, and disease-free survival (P < 0.006 for all). Higher T-stage, keratinizing histologic type, extracapsular extension, and smoking also all correlated with worse survival. In multivariate analysis, anaplasia and multinucleation both predicted worse disease-specific survival (hazard ratio 9.9, P = 0.04; and hazard ratio 11.9, P = 0.02, respectively) independent of the other variables. In summary, among surgically resectable oropharyngeal SCC (including among just the p16-positive cohort), tumor cell anaplasia and multinucleation independently correlated with disease recurrence and poorer survival. PMID:22743286
Fridman, Masha; Barnes, Vanessa; Whyman, Andrew; Currell, Alex; Bernard, Stephen; Walker, Tony; Smith, Karen L
2007-11-01
This study describes the epidemiology of sudden cardiac arrest patients in Victoria, Australia, as captured via the Victorian Ambulance Cardiac Arrest Register (VACAR). We used the VACAR data to construct a new model of out-of-hospital cardiac arrest (OHCA), which was specified in accordance with observed trends. All cases of cardiac arrest in Victoria that were attended by Victorian ambulance services during the period of 2002-2005. Overall survival to hospital discharge was 3.8% among 18,827 cases of OHCA. Survival was 15.7% among 1726 bystander witnessed, adult cardiac arrests of presumed cardiac aetiology, presenting in ventricular fibrillation or ventricular tachycardia (VF/VT), where resuscitation was attempted. In multivariate logistic regression analysis, bystander CPR, cardiac arrest (CA) location, response time, age and sex were predictors of VF/VT, which, in turn, was a strong predictor of survival. The same factors that affected VF/VT made an additional contribution to survival. However, for bystander CPR, CA location and response time this additional contribution was limited to VF/VT patients only. There was no detectable association between survival and age younger than 60 years or response time over 15min. The new model accounts for relationships among predictors of survival. These relationships indicate that interventions such as reduced response times and bystander CPR act in multiple ways to improve survival.
Qiu, Kun-Yin; Liao, Xiong-Yu; Huang, Ke; Li, Yang; Weng, Wen-Jun; Xu, Hong-Gui; Fang, Jian-Pei; Wu, Ruo-Hao; Zhou, Dun-Hua
2018-04-01
To investigate the efficacy and safety of NOPHO-AML 2004 chemotherapy regimen for treatment of children with acute myelocytic leukemia(non-M3). Thirty-three patients aged 1-13 with acute myelocytic leukemia (non-M3) were diagnosed from January 2013 to June 2017. FAB typing showed that 1 case in M0, 4 cases in M1, 12 cases in M2, 5 cases in M4, 8 cases in M5, 1 case in M6, and 2 cases in M7; Risk stratification showed that: 19 cases in standard risk, and 14 cases in high risk. All patients were treated with NOPHO-AML 2004 chemotherapy regimen. SPSS 22.0 software was used, the Kaplan-Meier survival analysis method and Cox regression model were used for statistical analysis. In the first course of treatment (AIET), among 33 child patients there were 27 cases with complete remission, and 5 cases with non-remission, thus the remission rate was 81.8%. Out of the 5 child patients without remission, 4 cases reached to the complete remission after the second course (AM), and 1 case did not remission, thus the total remission rate was 96.9%.9 cases (27.3%) underwent bone marrow recurrence and the median recurrence time was 30 months after complete continuous remission. Univariate analysis showed that age and erythrocyte transfusion frequency were significant factors to affect the early treatment response; the multiple Cox regression analysis showed that: age >7, MRD positive, erythrocyte transfusion >4 times and poor response to early treatment were independent risk factors for recurrence; Allogeneic hematopoietic stem cell transplantation(HSCT) in 8 high-risk children received enhanced chemotherapy had better efficacy as compared with the chemotherapy alone. The 3-year event-free survival rate was 59.9%, and 3-year overall survival rate was 69.2%. 33 children patients experienced varying degrees of infection and myelosuppression, or drug-related gastrointestinal reactions and allergic reactions, patients were tolerable to these side reactions after active symptomatic treatment. NOPHO-AML 2004 chemotherapy regimen has high response rate and good tolerance, early treatment response is an important factor influencing prognosis. Age and repeated red blood cell infusions are the important factors influencing the prognosis, which promote bone marrow recurrence in AML children. For the children suffered from clinical high-risk AML, the NOPHO-AML 2004 chemotherapy regimen combined with HSCT can improve the prognosis of patients.
Hernández Guerrero, Angélica; Sánchez del Monte, Julio; Sobrino Cossío, Sergio; Alonso Lárraga, Octavio; Delgado de la Cruz, Lourdes; Frías Mendívil, M Mauricio; Frías Mendívil, C Mauricio
2006-01-01
To determine the factors prognostics of early mortality in the malignant billary estenosis after the endoscopic derivation. The surgical, percutaneous or endoscopic derivation is the alternative of palliative treatment in the biliary obstruction unresectable. The factors prognostic the early mortality after surgical derivation are: hemoglobin < 10 g/dL, serum bilirubin > 10 mg/dL and serum albumin < 2.5 g/dL; for the percutaneous derivation they are the sanguineous urea more of 4.3 mmol/L and hemoglobin < 10.9 g/dL; whereas in the single endoscopic derivation type 3 of Bismuth and the infectious complications after the endoscopic colangiography and the absence of the clinical success were factors prognoses of early mortality. Descriptive and retrospective analysis of 97 cases with malignant biliary obstruction. The factors were evaluated prognoses of early mortality. Univariated and bivaried analysis and of survival by the method of Kaplan-Meier was made curved. 97 cases were included that presented/displayed unresectable disease and had a biochemical control subsequent to the drainage. They were 58 women and 39 men. More frequent symptoms: ictericia, pain and prurito. 61 cases of distal obstruction and 36 with proximal obstruction. Twenty deaths (25.9%) happened within the 30 later days to the treatment. The bilirubin > 14 mg/dL and the proximal location were like predicting of early mortality. The obstruction biliary more frequent is located in choledocho distal and is of pancreatic origin. The main factors associated to early mortality are: the bilirubin > of 14 mg/dL and the proximal location reason why is important the suitable selection of patient candidates to endoscopic derivation. The survival is better in the distal obstruction.
Savina, Marion; Gourgou, Sophie; Italiano, Antoine; Dinart, Derek; Rondeau, Virginie; Penel, Nicolas; Mathoulin-Pelissier, Simone; Bellera, Carine
2018-03-01
In cancer randomized controlled trials (RCT), alternative endpoints are increasingly being used in place of overall survival (OS) to reduce sample size, duration and cost of trials. It is necessary to ensure that these endpoints are valid surrogates for OS. Our aim was to identify meta-analyses that evaluated surrogate endpoints for OS and assess the strength of evidence for each meta-analysis (MA). We performed a systematic review to identify MA of cancer RCTs assessing surrogate endpoints for OS. We evaluated the strength of the association between the endpoints based on (i) the German Institute of Quality and Efficiency in Health Care guidelines and (ii) the Biomarker-Surrogate Evaluation Schema. Fifty-three publications reported on 164 MA, with heterogeneous statistical methods Disease-free survival (DFS) and progression-free survival (PFS) showed good surrogacy properties for OS in colorectal, lung and head and neck cancers. DFS was highly correlated to OS in gastric cancer. The statistical methodology used to evaluate surrogate endpoints requires consistency in order to facilitate the accurate interpretation of the results. Despite the limited number of clinical settings with validated surrogate endpoints for OS, there is evidence of good surrogacy for DFS and PFS in tumor types that account for a large proportion of cancer cases. Copyright © 2017 Elsevier B.V. All rights reserved.
Moreso, Francesc; Alonso, Angel; Gentil, Miguel A; González-Molina, Miguel; Capdevila, Lluis; Marcén, Roberto; Pascual, Julio; Serón, Daniel
2010-09-01
Epidemiological studies have failed to show an improvement in graft survival beyond 1 year after kidney transplantation possibly because of an increased number of expanded donors and older recipients. Thus, we performed a case-control study matching patients transplanted in different eras by donor and recipient characteristics. We considered renal transplant recipients included in the database of the Spanish Chronic Allograft Dysfunction Study Group in 1990, 1994, 1998 and 2002 (n = 4842). We matched patients from these cohorts considering the following variables: donor and recipient age, cause of donor death, hepatitis C virus, panel reactive antibodies and re-transplantation. We identified a total of 896 patients distributed in four cohorts of 224 matched patients. Between 1990 and 2002, the use of cyclosporin decreased (96%, 94%, 80% and 23% respectively, P = 0.001), while the use of tacrolimus increased (0%, 1%, 15% and 63% respectively, P = 0.001) and the prevalence of acute rejection decreased (46%, 37.9%, 20.6% and 15.8% respectively, P < 0.001). One-year serum creatinine was 1.63 +/- 0.66, 1.64 +/- 0.70, 1.44 +/- 0.52 and 1.38 +/- 0.75 respectively, P = 0.001. Graft survival beyond the first year between 1990 and 2002 significantly improved while patient survival did not. Transplant outcome has improved between 1990 and 2002 when donors and recipients of similar characteristics are compared.
Epidemiology of gynecologic cancers in China
2018-01-01
Cancer has become a major disease burden across the globe. It was estimated that 4.29 million new incident cases and 2.81 million death cases of cancer would occur in 2015 in China, with the age-standardized incidence rate (ASIR) of 201.1 per 100,000 and age-standardized mortality rate (ASMR) of 126.9 per 100,000, respectively. For females, 2 of the top 10 most common types of cancer would be gynecologic cancers, with breast cancer being the most prevalent (268.6 thousand new incident cases) and cervical cancer being the 7th most common cancer (98.9 thousand new incident cases). The incidence and mortality of gynecologic cancers have been constantly increasing in China over last 2 decades, which become a major health concern for women. Survival rates of gynecologic cancers are generally not satisfactory and decrease along with advancing stage, though national data on survival are still not available. It is of great importance to overview on the epidemiology of gynecologic cancers, which may provide scientific clues for strategy-making of prevention and control, and eventually lowering the incidence and mortality rate as well as improving the survival rate in the future. PMID:29185265
Orlow, Irene; Reiner, Anne S; Thomas, Nancy E; Roy, Pampa; Kanetsky, Peter A; Luo, Li; Paine, Susan; Armstrong, Bruce K; Kricker, Anne; Marrett, Loraine D; Rosso, Stefano; Zanetti, Roberto; Gruber, Stephen B; Anton-Culver, Hoda; Gallagher, Richard P; Dwyer, Terence; Busam, Klaus; Begg, Colin B; Berwick, Marianne
2016-01-01
Factors known to affect melanoma survival include age at presentation, sex and tumor characteristics. Polymorphisms also appear to modulate survival following diagnosis. Result from other studies suggest that vitamin D receptor (VDR) polymorphisms (SNPs) impact survival in patients with glioma, renal cell carcinoma, lung, breast, prostate and other cancers; however, a comprehensive study of VDR polymorphisms and melanoma-specific survival is lacking. We aimed to investigate whether VDR genetic variation influences survival in patients with cutaneous melanoma. The analysis involved 3566 incident single and multiple primary melanoma cases enrolled in the international population-based Genes, Environment, and Melanoma Study. Melanoma-specific survival outcomes were calculated for each of 38 VDR SNPs using a competing risk analysis after adjustment for covariates. There were 254 (7.1%) deaths due to melanoma during the median 7.6 years follow-up period. VDR SNPs rs7299460, rs3782905, rs2239182, rs12370156, rs2238140, rs7305032, rs1544410 (BsmI) and rs731236 (TaqI) each had a statistically significant (trend P values < 0.05) association with melanoma-specific survival in multivariate analysis. One functional SNP (rs2239182) remained significant after adjustment for multiple testing using the Monte Carlo method. None of the SNPs associated with survival were significantly associated with Breslow thickness, ulceration or mitosis. These results suggest that the VDR gene may influence survival from melanoma, although the mechanism by which VDR exerts its effect does not seem driven by tumor aggressiveness. Further investigations are needed to confirm our results and to understand the relationship between VDR and survival in the combined context of tumor and host characteristics. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.
Orlow, Irene; Reiner, Anne S.; Thomas, Nancy E.; Roy, Pampa; Kanetsky, Peter A.; Luo, Li; Paine, Susan; Armstrong, Bruce K.; Kricker, Anne; Marrett, Loraine D.; Rosso, Stefano; Zanetti, Roberto; Gruber, Stephen B.; Anton-Culver, Hoda; Gallagher, Richard P.; Dwyer, Terence; Busam, Klaus; Begg, Colin B.; Berwick, Marianne
2016-01-01
Factors known to affect melanoma survival include age at presentation, sex and tumor characteristics. Polymorphisms also appear to modulate survival following diagnosis. Result from other studies suggest that vitamin D receptor (VDR) polymorphisms (SNPs) impact survival in patients with glioma, renal cell carcinoma, lung, breast, prostate and other cancers; however, a comprehensive study of VDR polymorphisms and melanoma-specific survival is lacking. We aimed to investigate whether VDR genetic variation influences survival in patients with cutaneous melanoma. The analysis involved 3566 incident single and multiple primary melanoma cases enrolled in the international population-based Genes, Environment, and Melanoma Study. Melanoma-specific survival outcomes were calculated for each of 38 VDR SNPs using a competing risk analysis after adjustment for covariates. There were 254 (7.1%) deaths due to melanoma during the median 7.6 years follow-up period. VDR SNPs rs7299460, rs3782905, rs2239182, rs12370156, rs2238140, rs7305032, rs1544410 (BsmI) and rs731236 (TaqI) each had a statistically significant (trend P values < 0.05) association with melanoma-specific survival in multivariate analysis. One functional SNP (rs2239182) remained significant after adjustment for multiple testing using the Monte Carlo method. None of the SNPs associated with survival were significantly associated with Breslow thickness, ulceration or mitosis. These results suggest that the VDR gene may influence survival from melanoma, although the mechanism by which VDR exerts its effect does not seem driven by tumor aggressiveness. Further investigations are needed to confirm our results and to understand the relationship between VDR and survival in the combined context of tumor and host characteristics. PMID:26521212
Stereotactic radiosurgery for multiple brain metastases
NASA Astrophysics Data System (ADS)
Lee, Anna; (Josh Yamada, Yoshiya
2017-01-01
Whole brain radiation therapy has been the traditional treatment of choice for patients with multiple brain metastases. Although stereotactic radiosurgery is widely accepted for the management to up to 4 brain metastases, its use is still controversial in cases of 5 or more brain metastases. Randomized trials have suggested that stereotactic radiosurgery alone is appropriate in up to 4 metastases without concomitant whole brain radiation. Level 1 evidence also suggests that withholding whole brain radiation may also reduce the impact of radiation on neurocognitive function and also may even offer a survival advantage. A recent analysis of a large multicentre prospective database has suggested that there are no differences in outcomes such as the likelihood of new metastasis or leptomeningeal disease in cases of 2-10 brain metastases, nor in overall survival. Hence in the era of prolonged survival with stage IV cancer, stereotactic radiosurgery is a reasonable alternative to whole brain radiation in order to minimize the impact of treatment upon quality of life without sacrificing overall survival.
Palta, Manisha; Patel, Pretesh; Broadwater, Gloria; Willett, Christopher; Pepek, Joseph; Tyler, Douglas; Zafar, S Yousuf; Uronis, Hope; Hurwitz, Herbert; White, Rebekah; Czito, Brian
2012-05-01
Ampullary carcinoma is a rare malignancy. Despite radical resection, survival rates remain low with high rates of local failure. We performed a single-institution outcomes analysis to define the role of concurrent chemoradiotherapy (CRT) in addition to surgery. A retrospective analysis was performed of all patients undergoing potentially curative pancreaticoduodenectomy for adenocarcinoma of the ampulla of Vater at Duke University Hospitals between 1976 and 2009. Time-to-event analysis was performed comparing all patients who underwent surgery alone to the cohort of patients receiving CRT in addition to surgery. Local control (LC), disease-free survival (DFS), overall survival (OS), and metastases-free survival (MFS) were estimated using the Kaplan-Meier method. A total of 137 patients with ampullary carcinoma underwent Whipple procedure. Of these, 61 patients undergoing resection received adjuvant (n = 43) or neoadjuvant (n = 18) CRT. Patients receiving chemoradiotherapy were more likely to have poorly differentiated tumors (P = .03). Of 18 patients receiving neoadjuvant therapy, 67% were downstaged on final pathology with 28% achieving pathologic complete response (pCR). With a median follow-up of 8.8 years, 3-year local control was improved in patients receiving CRT (88% vs 55%, P = .001) with trend toward 3-year DFS (66% vs 48%, P = .09) and OS (62% vs 46%, P = .074) benefit in patients receiving CRT. Long-term survival rates are low and local failure rates high following radical resection alone. Given patterns of relapse with surgery alone and local control benefit in patients receiving CRT, the use of chemoradiotherapy in selected patients should be considered.
DOE Office of Scientific and Technical Information (OSTI.GOV)
Bishop, Andrew J.; Greenfield, Brad; Mahajan, Anita
2014-10-01
Purpose: We compared proton beam therapy (PBT) with intensity modulated radiation therapy (IMRT) for pediatric craniopharyngioma in terms of disease control, cyst dynamics, and toxicity. Methods and Materials: We reviewed records from 52 children treated with PBT (n=21) or IMRT (n=31) at 2 institutions from 1996-2012. Endpoints were overall survival (OS), disease control, cyst dynamics, and toxicity. Results: At 59.6 months' median follow-up (PBT 33 mo vs IMRT 106 mo; P<.001), the 3-year outcomes were 96% for OS, 95% for nodular failure-free survival and 76% for cystic failure-free survival. Neither OS nor disease control differed between treatment groups (OS P=.742;more » nodular failure-free survival P=.546; cystic failure-free survival P=.994). During therapy, 40% of patients had cyst growth (20% requiring intervention); immediately after therapy, 17 patients (33%) had cyst growth (transient in 14), more commonly in the IMRT group (42% vs 19% PBT; P=.082); and 27% experienced late cyst growth (32% IMRT, 19% PBT; P=.353), with intervention required in 40%. Toxicity did not differ between groups. On multivariate analysis, cyst growth was related to visual and hypothalamic toxicity (P=.009 and .04, respectively). Patients given radiation as salvage therapy (for recurrence) rather than adjuvant therapy had higher rates of visual and endocrine (P=.017 and .024, respectively) dysfunction. Conclusions: Survival and disease-control outcomes were equivalent for PBT and IMRT. Cyst growth is common, unpredictable, and should be followed during and after therapy, because it contributes to late toxicity. Delaying radiation therapy until recurrence may result in worse visual and endocrine function.« less
Harrabi, Semi B; Adeberg, Sebastian; Welzel, Thomas; Rieken, Stefan; Habermehl, Daniel; Debus, Jürgen; Combs, Stephanie E
2014-09-16
There are already numerous reports about high local control rates in patients with craniopharyngioma but there are only few studies with follow up times of more than 10 years. This study is an analysis of long term control, tumor response and side effects after fractionated stereotactic radiotherapy (FSRT) for patients with craniopharyngioma. 55 patients who were treated with FSRT for craniopharyngioma were analyzed. Median age was 37 years (range 6-70 years), among them eight children < 18 years. Radiotherapy (RT) was indicated for progressive disease after neurosurgical resection or postoperatively after repeated resection or partial resection. A median dose of 52.2 Gy (50 - 57.6 Gy) was applied with typical dose per fraction of 1.8 Gy five times per week. The regular follow up examinations comprised in addition to contrast enhanced MRI scans thorough physical examinations and clinical evaluation. During median follow up of 128 months (2 - 276 months) local control rate was 95.3% after 5 years, 92.1% after 10 years and 88.1% after 20 years. Overall survival after 10 years was 83.3% and after 20 years 67.8% whereby none of the deaths were directly attributed to craniopharyngioma. Overall treatment was tolerated well with almost no severe acute or chronic side effects. One patient developed complete anosmia, another one's initially impaired vision deteriorated further. In 83.6% of the cases with radiological follow up a regression of irradiated tumor residues was monitored, in 7 cases complete response was achieved. 44 patients presented themselves initially with endocrinologic dysfunction none of them showed signs of further deterioration during follow up. No secondary malignancies were observed. Long term results for patients with craniopharyngioma after stereotactic radiotherapy are with respect to low treatment related side effects as well as to local control and overall survival excellent.
Kenu, E; Isenberg, DA
2013-01-01
Objectives We determined whether any individual cancers are increased or decreased in a cohort of 595 patients with systemic lupus erythematosus (SLE) followed for up to 32 years at the University College London Hospitals Lupus Clinic, looking for any associated clinical or serological factors and the prognosis after cancer diagnosis. Methods We undertook a careful retrospective review of the medical records and identified all individuals diagnosed with cancer. For controls, we selected three other patients in the cohort who had not developed cancer, carefully matched for age, sex, ethnicity and disease duration, to determine if any obvious differences emerged in a nested case-control design. Results Thirty-three patients developed cancer after being diagnosed with SLE. There was a statistically insignificant small increase in overall cancer risk, standardized incidence ratios (SIRs) 1.05 (95% CI 0.52–1.58) and increased SIRs for cervical, prostate, anal and pancreatic cancers and reduction in breast cancer SIRs. Haematological and musculoskeletal manifestations, anticardiolipin and antithyroid globulin antibodies were found to be positively associated with cancer risk in multivariate analysis. There was no drug, dose or duration was associated with cancer risk. There was a reduction in survival with a cancer fatality rate of 84.2% (p < 0.0001). Conclusion We found a very small but statistically insignificant increased cancer risk with reduction in survival. Whereas some cancers appear to be more common in SLE, notably prostate and cervical cancer, others, particularly breast cancer, are less frequent. Multiple clinical and serological factors are involved in the increased risk of malignancy in SLE. No drug dose or duration effect was identified. PMID:23857987
A case-control study of non-AIDS-defining cancers in a prospective cohort of HIV-infected patients.
Rodríguez Arrondo, Francisco; von Wichmann, Miguel Ángel; Camino, Xabier; Goenaga, Miguel Ángel; Ibarguren, Maialen; Azcune, Harkaitz; Bustinduy, María Jesús; Ferrero, Oscar; Muñoz, Josefa; Ibarra, Sofía; Aguirrebengoa, Koldo; Goicoetxea, Josune; Bereciartua, Elena; Montejo, Miguel; García, M Asunción; Martínez, Eduardo; Portu, Joseba; Metola, Luis; Silvariño, Rafael; Sarasqueta, Cristina; Arrizabalaga, Julio; Iribarren, Jose Antonio
2018-04-23
We present a case-control study of non-AIDS-defining cancers (NADCs) in a cohort of HIV-infected patients where we value the incidence, survival and prognostic factors of mortality. All NADCs diagnosis conducted from 2007 to 2011 in 7 hospitals were collected prospectively, with a subsequent follow up until December 2013. A control group of 221 HIV patients without a diagnosis of cancer was randomly selected. Two hundred and twenty-one NADCs were diagnosed in an initial cohort of 7,067 HIV-infected patients. The most common were: hepatocellular carcinoma 20.5%, lung 18.7%, head and neck 11.9% and anal 10.5%. The incidence rate of NADCs development was 7.84/1,000 people-year. In addition to aging and smoking, time on ART (OR 1.11; 95% CI 1.05-1.17) and PI use (OR 1.72; 95% CI 1.0-2.96) increased the risk of developing a NADC. During follow-up 53.42% died, with a median survival time of 199.5 days. In the analysis of the prognostic factors of mortality the low values of CD4 at tumour diagnosis (OR 0.99; 95% CI 0.99-1.0; P=.033), and the previous diagnosis of AIDS (OR 2.06; 95% CI 1.08-3.92) were associated with higher mortality. Predictors of NADCs in our cohort were age, smoking, CD4 lymphocytes and time on ART. Mortality is high, with NADC risk factors being low CD4 count and previous diagnosis of AIDS. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.
Lopez, Jose Luis; Cabrera, Patricia; Ordoñez, Rafael; Marquez, Catalina; Ramirez, Gema Lucia; Praena-Fernandez, Juan Manuel; Ortiz, Maria Jose
2011-01-01
Background Radiotherapy (RT) plays an important role in the multidisciplinary management of Ewing's Sarcoma (ES), especially in unresectable cases. Aim Assessment of efficacy of RT in terms of local control in pediatric patients with primary ES of bone. Materials and methods Thirty-six patients younger than 17 years old with ES treated with combined RT and chemotherapy with (N = 14) or without (N = 22) prior surgery from 1981 to 2008 were retrospectively reviewed. Since 1995, they were all treated according to the Spanish Society of Pediatric Oncology protocol (55.5% cases). Those patients received vincristine, ifosfamide, doxorubicin and etoposide. The TNM classification was as follows: 17 T1, 18 T2 and 1 T3; 36 N0; 29 M0, 5 M1a and 2 M1b. Analysis was stratified by treatment: definitive RT or pre/postoperative RT. Results The 36 patients (21 male; 15 female) had a median age of 10 years (range 2–17 years). Median follow-up of living patients was 105 months. The 2-year local control (LC) rate for all patients was 88%. Five-year LC rates for patients treated with definitive and pre/postoperative RT were 91% and 86%, respectively. Two-year overall survival and disease-free survival rates for all patients were 68% and 66%, respectively. Low phosphatase alkaline levels and local and distant recurrences were significantly predictive of worse prognosis (P = 0.021, P = 0.011, P = 0.007, respectively). Conclusion Radiotherapy with and without surgery is a highly effective local treatment option in the multidisciplinary management of ES in pediatric patients. PMID:24376965
[Prognostic significance of mean amplitude of glycemic excursion in patients with severe burn].
Zang, Z D; Yan, Z; Hui, J J; Yan, J; Chen, H Y
2016-01-01
To retrospectively analyze the prognostic significance of mean amplitude of glycemic excursion (MAGE) in patients with severe burn. A study involving 76 patients with severe burn admitted into Department of Burns of the Third People's Hospital of Wuxi City from January 2011 to August 2014, conforming to the inclusion criteria was conducted. Data of their demography, injury, and treatment were collected. Blood glucose level of patients was measured during the first 72 h after admission, and MAGE was calculated. (1) The patients were divided into survival group (n=46) and death group (n=30) according to the outcome within post injury day (PID) 90. The MAGE level of patients was compared between two groups. (2) The patients were divided into 3 groups by tertiles of MAGE within 72 h after admission, with 26 cases in low tertile group (MAGE<3.3 mmol/L), 27 cases in middle tertile group (with MAGE from 3.3 to 5.5 mmol/L), 23 cases in high tertile group (MAGE>5.5 mmol/L). The surviving curve was drawn using the Kaplan-Meier method to compare survival rates and surviving time of patients among the 3 groups within PID 90. Data were processed with t test, one-way analysis of variance, LSD test, chi-square test, and Fisher's exact test. The surviving curve was analyzed by the Log-rank test. Correlation was analyzed between demography, acute physiology and chronic health evaluation Ⅱ score, injury, treatment, sepsis, length of ICU stay, MAGE and death of patients using the univariate and multivariate Cox regression analysis. Receiver operating characteristic (ROC) curve of MAGE was drawn to predict death for 76 patients. Within 72 h after admission, the MAGE of patients in death group was (6.0±1.4) mmol/L, which was significantly higher than that in survival group [(3.5±1.2) mmol/L, t=9.219, P=0.004]. The survival rates of patients in low tertile, middle tertile, and high tertile groups within PID 90 were respectively 88.5% (23/26), 59.3% (16/27), and 30.4% (7/23), with significant differences among 3 groups (χ(2)=18.073, P<0.001). The surviving time of patients in low tertile group [(83±21) d] was significantly longer than that of middle tertile group [(63±34) d, P<0.05]. The surviving time of patients was longer in low tertile and middle tertile groups than in high tertile group [(46±37) d, with P values below 0.05]. Total burn area, sepsis, blood purification, and MAGE were independent risk factors of death (with hazard ratio respectively 4.324, 1.591, 1.886, 2.047; 95% confidence interval respectively 2.978-6.119, 1.005-1.657, 1.614-2.408, 1.852-3.161; P<0.05 or P<0.01). The area under the ROC curve of MAGE for predicting death for 76 patients was 0.870 (with 95% confidence interval 0.786-0.966, P<0.001), and 4.7 mmol/L was chosen as the optimal threshold value, with sensitivity of 86.7% and specificity of 89.1%. The increase of MAGE in patients with severe burn is significantly associated with poor prognosis; controlling the glucose level fluctuation guided by measuring MAGE may be helpful in reducing mortality of patients.
Ward, Michael P; Schuermann, James A; Highfield, Linda D; Murray, Kristy O
2006-12-20
Equine West Nile virus (WNV) encephalomyelitis cases - based on clinical signs and ELISA serology test results - reported to Texas disease control authorities during 2002 were analyzed to provide insights into the epidemiology of the disease within a previously disease-free population. The epidemic occurred between June 27 and December 17 (peaking in early October) and 1,698 cases were reported. Three distinct epidemic phases were identified, occurring mostly in southeast, northwest and then central Texas. Significant (P<0.05) disease clusters were identified in northwest and northern Texas. Most (91.1%) cases had no recent travel history, and most (68.9%) cases had not been vaccinated within the previous 12 months. One-third of cases did not survive, 71.2% of which were euthanatized. The most commonly reported presenting signs included ataxia (69%), abnormal gait (52%), muscle fasciculations (49%), depression (32%) and recumbency (28%). Vaccination status, ataxia, falling down, recumbency and lip droop best explained the risk of not surviving WNV disease. Results suggest that the peak risk period for encephalomyelitis caused by WNV may vary substantially among regions within Texas. Recumbent horses have a poor prognosis for survival. Vaccines, even if not administered sufficiently in advance of WNV infection within a district, may reduce the risk of death by at least 44%.
Chen, M; Jiang, G L; Fu, X L; Wang, L J; Qian, H; Chen, G Y; Zhao, S; Liu, T F
2000-04-01
A retrospective study was carried out to evaluate the impact of overall treatment time (OTT) on the results of radiation therapy for non-small cell lung cancer (NSCLC). From Jan. 1990 to Dec. 1996, 256 patients with stages I-IIIb NSCLC entered this analysis. All patients received definitive radiotherapy. Biologically effective dose (BED) was used to standardize the irradiation effects. The correlation between OTT and local progression-free survival was analyzed by linear-regression and Cox proportional hazard models. The prognostic variables for survival and distant metastasis were also briefly studied. OTT had been shortened in 64 patients because of an accelerated hyperfractioned irradiation, while OTT was prolonged i n 114 patients due to interruptions of irradiation courses. The main ca uses of interruption were machine breakdown or delayed preparations of c errobend block for boost fields (55%), holidays (11%) and treatment toxi city and side effects (34%). Patients tre ated with prolonged OTT (> 45 days) had significant poorer local progression-free survival than whom with OTT of =45 days, 1, 3 and 5 year actuarial local progression-free survivals being 49, 17 and 15% for the former, and 74, 35 and 25% for the latter, respectively (P<0.001). BED-T that contained the factor of OTT correlated directly to local controls, which implied that BED-T represented radiobiological effects accurately, in other words, OTT had played a role in determining the radiobiological effects. Linear-regression on 103 cases treated with BED of 80-85 Gy(10) showed that 3 year local progression-free survival decreased by 9% per week with prolongation of OTT, or vice versa it increased by 9% per week with shortening OTT in an OTT range of 30-76 days. Cox multivariate analyses confirmed that OTT was an independent prognostic factor for local controls. OTT may have played an important role in determining local controls in radiotherapy for NSCLC. One should always keep in mind to make the OTT as short as possible, provided the patients can tolerate it, and to reduce irradiation interruptions for whatever reasons to a minimum.
Abstract: This case study application provides discussion on a selected application of advanced concepts, included in the End of Asset Life Reinvestment decision-making process tool, using Milwaukee Metropolitan Sewer District (MMSD) pump and motor data sets. The tool provides s...
Breast Cancer and the Environment on Long Island Follow-up Study
A follow-up study on women with breast cancer who participated in the parent population-based case-control study of Long Island women to determine whether environmental and other lifestyle factors influence breast cancer survival.
Domingo-Domènech, Eva; Benavente, Yolanda; González-Barca, Eva; Montalban, Carlos; Gumà, Josep; Bosch, Ramón; Wang, Sophia S; Lan, Qing; Whitby, Denise; Fernández de Sevilla, Alberto; Rothman, Nathaniel; de Sanjosé, Sílvia
2007-11-01
Single-nucleotide polymorphisms (SNP) in interleukin-10 (IL-10) genes can influence immune responses, which may affect the outcome of patients with lymphoid neoplasms. The aim of this study was to explore the association between polymorphisms of IL-10-(1082A>G) and IL-10-(3575T>A) with the overall survival in patients with lymphoid neoplasms. We analyzed two IL-10 SNP (-1082 and -3575) in 472 consecutive cases with lymphoid neoplasms. Genotypes were tested for association with overall survival and classical prognostic factors by multivariate analysis. Haplotype analysis was carried out using the haplostats package implemented in R software. The implications for survival of patients with lymphoma were evaluated using multivariate analysis. Lymphoma patients with the IL-10-(3575T>A) genotype had a better overall survival (p= 0.002), as did the subgroup with non-Hodgkin's lymphoma (NHL) (p=0.05). Patients with the IL10(-1082GG) genotype had a better median overall survival (p=0.05). When both genotypes were included in a multivariate analysis, IL-10(-3575AA) genotype was the only independent prognostic factor for survival (HR=0.20, 95%CI 0.05-0.92). Patients with the IL-10(-1082) and (-3575) G-A/G-A diplotype had a longer overall survival (p=0.003) and this combination appeared to be an independent prognostic factor for survival (HR:0.26; 95%CI 0.08-0.83). The IL-10(-3575A/A) genotype was identified as a marker of favorable survival. Because the IL-10(-1082) and (-3575) G-A/G-A diplotype was also identified as an indicator of longer survival, we cannot exclude the potential additive role of the IL-10(-1082GG) genotype. These results need to be replicated in larger series and examined in different NHL subtypes.
[Expression and clinical significance of 5hmC in bladder urothelial carcinoma].
Li, Jie; Xu, Yuqiao; Zhang, Zhiwen; Zhang, Ming; Zhang, Zhekai; Zhang, Feng; Li, Qing
2016-02-01
To investigate the expression of 5-hydroxymethylcytosine (5hmC) in bladder urothelial carcinoma (UC) and its clinical significance. The expression of 5hmC in 21 cases of UC tissues and pericarcinous urinary tract epithelium was detected by immunohistochemical staining. Then the expression of 5hmC in the surgical resection of UC tissues in 92 cases was also surveyed. Non parametric U Mann-Whitney test was used to analyze the correlation between 5hmC expression and clinical data. Single factor survival analysis was performed by Kaplan-Meier test. The expression of 5hmC in normal urinary tract epithelium and UC tissues was significantly different, but there was no significant difference in the expression of 5hmC between low and high grades of UC tissues as well as between different TNM grades. Kaplan-Meier single factor survival analysis showed that there was no significant correlation between the 5hmC expression level and the survival rate or the recurrence-free survival of UC patients. The expression level of 5hmC in UC tissues is significantly lower than that in pericarcinous urinary tract epithelium. There is no correlation between the 5hmC expression and the progression, prognosis and recurrence of UC.
Intestinal diffuse large B-cell lymphoma: an evaluation of different staging systems.
Hwang, Hee Sang; Yoon, Dok Hyun; Suh, Cheolwon; Park, Chan-Sik; Huh, Jooryung
2014-01-01
The gastrointestinal tract is the most common primary extranodal site for diffuse large B-cell lymphoma (DLBCL). However, there is no consensus on the most appropriate staging system for intestinal DLBCL. We evaluated the utility of the modified Ann Arbor system, the Lugano system, and the Paris staging system (a modification of the Tumor, Node, Metastases [TNM] staging for epithelial tumors) in 66 cases of resected intestinal DLBCL. The cases were treated with surgery, plus either cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) chemotherapy alone (n=26) or with the addition of rituximab immunotherapy (n=40). Median follow-up time was 40.4 months (range, 2.1-171.6 months). Fifty-six patients (84.8%) achieved complete remission. The overall 5-yr survival rate was 86.4% (57/66). Of the stage categories defined for each staging system, only the T stage of the Paris classification showed prognostic significance for overall survival by univariate analysis. However, none of the stage parameters was significantly correlated with patient survival on multivariate analysis. In conclusion, the results suggest that the T stage of the Paris classification system may be a prognostic indicator in intestinal DLBCL. The results also imply that in surgically resected intestinal DLBCL, the addition of rituximab to the CHOP regimen does not confer significant survival advantage.
Austin, Peter C; Fine, Jason P
2017-04-15
In studies with survival or time-to-event outcomes, a competing risk is an event whose occurrence precludes the occurrence of the primary event of interest. Specialized statistical methods must be used to analyze survival data in the presence of competing risks. We conducted a review of randomized controlled trials with survival outcomes that were published in high-impact general medical journals. Of 40 studies that we identified, 31 (77.5%) were potentially susceptible to competing risks. However, in the majority of these studies, the potential presence of competing risks was not accounted for in the statistical analyses that were described. Of the 31 studies potentially susceptible to competing risks, 24 (77.4%) reported the results of a Kaplan-Meier survival analysis, while only five (16.1%) reported using cumulative incidence functions to estimate the incidence of the outcome over time in the presence of competing risks. The former approach will tend to result in an overestimate of the incidence of the outcome over time, while the latter approach will result in unbiased estimation of the incidence of the primary outcome over time. We provide recommendations on the analysis and reporting of randomized controlled trials with survival outcomes in the presence of competing risks. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.
Fine, Jason P.
2017-01-01
In studies with survival or time‐to‐event outcomes, a competing risk is an event whose occurrence precludes the occurrence of the primary event of interest. Specialized statistical methods must be used to analyze survival data in the presence of competing risks. We conducted a review of randomized controlled trials with survival outcomes that were published in high‐impact general medical journals. Of 40 studies that we identified, 31 (77.5%) were potentially susceptible to competing risks. However, in the majority of these studies, the potential presence of competing risks was not accounted for in the statistical analyses that were described. Of the 31 studies potentially susceptible to competing risks, 24 (77.4%) reported the results of a Kaplan–Meier survival analysis, while only five (16.1%) reported using cumulative incidence functions to estimate the incidence of the outcome over time in the presence of competing risks. The former approach will tend to result in an overestimate of the incidence of the outcome over time, while the latter approach will result in unbiased estimation of the incidence of the primary outcome over time. We provide recommendations on the analysis and reporting of randomized controlled trials with survival outcomes in the presence of competing risks. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID:28102550
Moore, Antony S; Rassnick, Kenneth M; Frimberger, Angela E
2017-09-01
OBJECTIVE To determine histologic and clinical factors associated with survival time in dogs with stage II splenic hemangiosarcoma treated by splenectomy and a chemotherapy protocol in which an anthracycline was alternated with lomustine. DESIGN Retrospective case series. ANIMALS 30 dogs with stage II splenic hemangiosarcoma. PROCEDURES Medical records of 3 facilities were reviewed to identify dogs treated for stage II splenic hemangiosarcoma between June 2011 and October 2014. Information collected included signalment, disease staging data, whether anemia was present, date of splenectomy, chemotherapy protocol, adverse effects, and date of death or last follow-up. Histologic slides were reviewed and scored by pathologists. Associations between variables of interest and survival data were evaluated statistically. RESULTS Median survival time for all dogs was 158 days (range, 55 to 560 days), and the 1-year survival rate was 16%. On multivariate analysis, only the histologically determined mitotic score was significantly associated with survival time. The median survival time of 292 days for dogs with a mitotic score of 0 (< 11 mitoses/10 hpf; n = 9) was significantly longer than that for dogs with higher scores (indicating higher mitotic rates); the 1-year survival rate for these dogs was 42%. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that future studies should take histologic factors, particularly mitotic rate, as well as tumor stage into account when assessing treatment effects on survival time of dogs with splenic hemangiosarcoma.
Kim, Jun Won; Kim, Tae Hyung; Kim, Jie-Hyun; Lee, Ik Jae
2018-01-01
AIM To evaluate toxicity and treatment outcome of high-dose radiotherapy (RT) for cervical esophageal cancer (CEC). METHODS We reviewed a total of 62 consecutive patients who received definitive RT for stage I to III cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local (occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed. RESULTS Grade 1, 2, and 3 esophagitis occurred in 19 (30.6%), 39 (62.9%), and 4 patients (6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients (25.8%) developed post-RT stenosis, of which 7 cases (43.8%) were malignant. Four patients (6.5%) developed tracheoesophageal fistula (TEF), of which 3 (75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4 (P = 0.001), complete circumference involvement (P < 0.0001), stenosis at diagnosis (P = 0.024), and endoscopic complete response (P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis (P = 0.003). A higher dose (≥ 60 Gy) was not associated with occurrence of post-RT stenosis or TEF. With a median follow-up of 24.3 (range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival (OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement (P = 0.023), stenosis at diagnosis (P < 0.0001), and occurrence of post-RT stenosis or TEF (P < 0.001) in univariate analysis, while stenosis at diagnosis (P = 0.004) and occurrence of post-RT stenosis or TEF (P = 0.023) were significant in multivariate analysis. CONCLUSION Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up. PMID:29467556
Kim, Jun Won; Kim, Tae Hyung; Kim, Jie-Hyun; Lee, Ik Jae
2018-02-21
To evaluate toxicity and treatment outcome of high-dose radiotherapy (RT) for cervical esophageal cancer (CEC). We reviewed a total of 62 consecutive patients who received definitive RT for stage I to III cervical esophageal cancer between 2001 and 2015. Patients who received < 45 Gy, treated for lesions below sternal notch, treated with palliative aim, treated with subsequent surgical resection, or diagnosed with synchronous hypopharyngeal cancer were excluded. Treatment failures were divided into local (occurring within the RT field), outfield-esophageal, and regional [occurring in regional lymph node(s)] failures. Factors predictive of esophageal stenosis requiring endoscopic dilation were analyzed. Grade 1, 2, and 3 esophagitis occurred in 19 (30.6%), 39 (62.9%), and 4 patients (6.5%), respectively, without grade ≥ 4 toxicities. Sixteen patients (25.8%) developed post-RT stenosis, of which 7 cases (43.8%) were malignant. Four patients (6.5%) developed tracheoesophageal fistula (TEF), of which 3 (75%) cases were malignant. Factors significantly correlated with post-RT stenosis were stage T3/4 ( P = 0.001), complete circumference involvement ( P < 0.0001), stenosis at diagnosis ( P = 0.024), and endoscopic complete response ( P = 0.017) in univariate analysis, while complete circumference involvement was significant in multivariate analysis ( P = 0.003). A higher dose (≥ 60 Gy) was not associated with occurrence of post-RT stenosis or TEF. With a median follow-up of 24.3 (range, 3.4-152) mo, the 2 y local control, outfield esophageal control, progression-free survival, and overall survival (OS) rates were 78.9%, 90.2%, 49.6%, and 57.3%, respectively. Factors significantly correlated with OS were complete circumference involvement ( P = 0.023), stenosis at diagnosis ( P < 0.0001), and occurrence of post-RT stenosis or TEF ( P < 0.001) in univariate analysis, while stenosis at diagnosis ( P = 0.004) and occurrence of post-RT stenosis or TEF ( P = 0.023) were significant in multivariate analysis. Chemoradiation for CEC was well tolerated, and a higher dose was not associated with stenosis. Patients with complete circumferential involvement require close follow-up.
Pérez-Beteta, Julián; Luque, Belén; Arregui, Elena; Calvo, Manuel; Borrás, José M; López, Carlos; Martino, Juan; Velasquez, Carlos; Asenjo, Beatriz; Benavides, Manuel; Herruzo, Ismael; Martínez-González, Alicia; Pérez-Romasanta, Luis; Arana, Estanislao; Pérez-García, Víctor M
2016-01-01
Objective: The main objective of this retrospective work was the study of three-dimensional (3D) heterogeneity measures of post-contrast pre-operative MR images acquired with T1 weighted sequences of patients with glioblastoma (GBM) as predictors of clinical outcome. Methods: 79 patients from 3 hospitals were included in the study. 16 3D textural heterogeneity measures were computed including run-length matrix (RLM) features (regional heterogeneity) and co-occurrence matrix (CM) features (local heterogeneity). The significance of the results was studied using Kaplan–Meier curves and Cox proportional hazards analysis. Correlation between the variables of the study was assessed using the Spearman's correlation coefficient. Results: Kaplan–Meyer survival analysis showed that 4 of the 11 RLM features and 4 of the 5 CM features considered were robust predictors of survival. The median survival differences in the most significant cases were of over 6 months. Conclusion: Heterogeneity measures computed on the post-contrast pre-operative T1 weighted MR images of patients with GBM are predictors of survival. Advances in knowledge: Texture analysis to assess tumour heterogeneity has been widely studied. However, most works develop a two-dimensional analysis, focusing only on one MRI slice to state tumour heterogeneity. The study of fully 3D heterogeneity textural features as predictors of clinical outcome is more robust and is not dependent on the selected slice of the tumour. PMID:27319577
Molina, David; Pérez-Beteta, Julián; Luque, Belén; Arregui, Elena; Calvo, Manuel; Borrás, José M; López, Carlos; Martino, Juan; Velasquez, Carlos; Asenjo, Beatriz; Benavides, Manuel; Herruzo, Ismael; Martínez-González, Alicia; Pérez-Romasanta, Luis; Arana, Estanislao; Pérez-García, Víctor M
2016-07-04
The main objective of this retrospective work was the study of three-dimensional (3D) heterogeneity measures of post-contrast pre-operative MR images acquired with T 1 weighted sequences of patients with glioblastoma (GBM) as predictors of clinical outcome. 79 patients from 3 hospitals were included in the study. 16 3D textural heterogeneity measures were computed including run-length matrix (RLM) features (regional heterogeneity) and co-occurrence matrix (CM) features (local heterogeneity). The significance of the results was studied using Kaplan-Meier curves and Cox proportional hazards analysis. Correlation between the variables of the study was assessed using the Spearman's correlation coefficient. Kaplan-Meyer survival analysis showed that 4 of the 11 RLM features and 4 of the 5 CM features considered were robust predictors of survival. The median survival differences in the most significant cases were of over 6 months. Heterogeneity measures computed on the post-contrast pre-operative T 1 weighted MR images of patients with GBM are predictors of survival. Texture analysis to assess tumour heterogeneity has been widely studied. However, most works develop a two-dimensional analysis, focusing only on one MRI slice to state tumour heterogeneity. The study of fully 3D heterogeneity textural features as predictors of clinical outcome is more robust and is not dependent on the selected slice of the tumour.
Li, Bin-bin; Xie, Xiao-Yan; Jia, Sheng-Nan
2015-02-01
Recurrent adenoid cystic carcinoma (rAdCC) can be challenging to be treated with brachytherapy, although brachytherapy is safe and effective in treating head and neck cancers. Patients of adenoid cystic carcinoma (AdCC), who underwent resection and iodine 125 ((125)I) radioactive seed implantation, were recruited for this study. Clinical data, surgical details of resection and seed implantation, histologic characteristics, and prognosis were studied. There were 16 rAdCC cases among 140 cases of AdCC treated with brachytherapy and resection. The mean follow-up duration for the recurrent cases was 61 months. The 3-year local control rate of rAdCC was 51.6%, and the overall disease-specific survival rate was 49.4%. Eight patients showed distant metastasis (50%, 8/16). The histologic grades of 10 rAdCCs were upgraded (62.5%, 10/16).Two cases displayed sarcomatous transformation after brachytherapy (1.4%, 2/140). Although the overall local control rate and survival rate were relatively favorable, some rAdCCs with an aggressive phenotype appeared to respond poorly to (125)I seed implantation. Preventive adjuvant chemotherapy should be prescribed for these rAdCCs. Copyright © 2014 Elsevier Inc. All rights reserved.
Salmen, Marcus; Ewy, Gordon A; Sasson, Comilla
2012-01-01
To determine whether the use of cardiocerebral resuscitation (CCR) or AHA/ERC 2005 Resuscitation Guidelines improved patient outcomes from out-of-hospital cardiac arrest (OHCA) compared to older guidelines. Systematic review and meta-analysis. MEDLINE, EMBASE, Web of Science and the Cochrane Library databases. We also hand-searched study references and consulted experts. Design: randomised controlled trials and observational studies. OHCA patients, age >17 years. 'Control' protocol versus 'Study' protocol. 'Control' protocol defined as AHA/ERC 2000 Guidelines for cardiopulmonary resuscitation (CPR). 'Study' protocol defined as AHA/ERC 2005 Guidelines for CPR, or a CCR protocol. Survival to hospital discharge. High-quality or medium-quality studies, as measured by the Newcastle Ottawa Scale using predefined categories. Twelve observational studies met inclusion criteria. All the three studies using CCR demonstrated significantly improved survival compared to use of AHA 2000 Guidelines, as did five of the nine studies using AHA/ERC 2005 Guidelines. Pooled data demonstrate that use of a CCR protocol has an unadjusted OR of 2.26 (95% CI 1.64 to 3.12) for survival to hospital discharge among all cardiac arrest patients. Among witnessed ventricular fibrillation/ventricular tachycardia (VF/VT) patients, CCR increased survival by an OR of 2.98 (95% CI 1.92 to 4.62). Studies using AHA/ERC 2005 Guidelines showed an overall trend towards increased survival, but significant heterogeneity existed among these studies. We demonstrate an association with improved survival from OHCA when CCR protocols or AHA/ERC 2005 Guidelines are compared to use of older guidelines. In the subgroup of patients with witnessed VF/VT, there was a threefold increase in OHCA survival when CCR was used. CCR appears to be a promising resuscitation protocol for Emergency Medical Services providers in increasing survival from OHCA. Future research will need to be conducted to directly compare AHA/ERC 2010 Guidelines with the CCR approach.
What affects local community hospitals' survival in turbulent times?
Chiang, Hung-Che; Wang, Shiow-Ing
2015-06-01
Hospital closures became a prevalent phenomenon in Taiwan after the implementation of a national health insurance program. A wide range of causes contributes to the viability of hospitals, but little is known about the situation under universal coverage health systems. The purpose of present study is to recognize the factors that may contribute to hospital survival under the universal coverage health system. This is a retrospective case-control study. Local community hospitals that contracted with the Bureau of National Health Insurance in 1998 and remained open during the period 1998-2011 are the designated cases. Controls are local community hospitals that closed during the same period. Using longitudinal representative health claim data, 209 local community hospitals that closed during 1998-2011 were compared with 165 that remained open. Variables related to institutional characteristics, degree of competition, characteristics of patients and financial performance were analyzed by logistic regression models. Hospitals' survival was positively related to specialty hospital, the number of respiratory care beds, the physician to population ratio, the number of clinics in the same region, a highly competitive market and the occupancy rate of elderly patients in the hospital. Teaching hospitals, investor-owned hospitals, the provision of obstetrics services or home care, and the number of medical centers or other local community hospitals may jeopardize the chance of survival. Factors-enhanced local hospitals to survive under the universal coverage health system have been identified. Hospital managers could manipulate these findings and adapt strategies for subsistence. © The Author 2015. Published by Oxford University Press in association with the International Society for Quality in Health Care; all rights reserved.
The effect of time until surgical intervention on survival in dogs with secondary septic peritonitis
Bush, Maxwell; Carno, Margaret A.; St. Germaine, Lindsay; Hoffmann, Daniel E.
2016-01-01
This retrospective study examined the effect of time to intervention on outcome in cases of dogs with secondary septic peritonitis, and also searched for other potential prognostic factors. The medical records of 55 dogs were reviewed. No association was found between outcome and the time from hospital admission to surgical source control. However, several other factors were found to influence survival, including: age, needing vasopressors, lactate, pre-operative packed cell volume, serum alkaline phosphatase, serum total bilirubin, and post-operative serum albumin. These values were then used to create accurate pre- and post-operative survival prediction models. PMID:27928174
[Sinonasal carcinoma and exposure to wood and leather dust: analysis of 36 cases].
Bracci, M; Mariotti, L; Staffolani, S; Strafella, E; Carlucci, C; Pasquini, E; Tarchini, P; Re, M; Santarelli, L
2012-01-01
In order to define the best strategies of prevention and diagnosis of sinonasal cancer, the aim of our study was the investigation of the etiological and prognostic factors related to 36 cases. The enrolled cases were composed mostly of men working in the footwear industry, with a mean age of 63.7 years and mean exposure of 34.6 years. The period between the start of exposure and the appearance of the neoplasm was of 44.6 years, the time between the onset of symptoms and diagnosis was of 10.8 months. Our results suggest that a diagnosis within 6 months after the onset of symptoms is associated with a lower tumor stage, a better survival and to a lower rate of recurrence. Nasal obstruction (58.3%) and epistaxis (52.7%) are the main initial symptoms. In order to obtain an early diagnosis, in addition to periodic clinical controls, a proper information of workers is required.
Zhang, W; Qi, X M; Chen, A X; Zhang, P; Cao, X C; Xiao, C H
2017-05-23
Objective: In this study, we evaluated the effect of supraclavicular lymph node dissection in breast cancer patients who presented with ipsilateral supraclavicular lymph node metastasis (ISLM) without distant metastasis. Methods: A total of 90 patients with synchronous ISLM without distant metastasis between 2000 and 2009 were retrospectively analyzed. Patients were retrospectively divided into two groups, namely supraclavicular lymph node dissection group(34 patients) and non-dissection group(56 patients), according to whether they underwentsupraclavicular lymph node dissection or not.The Kaplan-Meier method was applied to analyze the locoregional relapse free survival (LRFS) and overall survival(OS). Results: Median follow-upwas 85 months(range, 6 to 11 months). Local recurrence in 32 cases, 47 cases of distant metastasis, of which 25 patients were accompanied by both locoregional relapse and distant metastasis. Of the 32 patients with locoregional relapse, 11 patients were in the lymph node dissection group and 21 patients in the control group. Of the 47 patients with distant metastases, 17 were treated with lymph node dissection, 30 in the control group. Thirty-two patients died in the whole group and 16 patients underwentlymph node dissection and 16 patients didn't. There was no significant difference between the rate of 5-year LRFS and 5-year OS ( P =0.359, P =0.246). For patients of ER negative, the 5-year loco-regional relapse free survival rates were 63.7% and 43.3% in supraclavicular lymph node dissection group and control group, respectively. The 5-year overall survival rates were 52.1% and 52.3%, respectively, and there were no statistically significant differences ( P =0.118, P =0.951). For patients of PR negative, the 5-yearloco-regional relapse free rates were 59.8% and 46.2%, respectively, and the 5-year overall survival rates were 50.6% and 43.2%, respectively, and there was no significant difference between the two groups ( P =0.317, P =0.973). The 5-year recurrence-free survival rates of human epidermal growth factor receptor 2 (HER2)-positive patients were 61.2% and 48.0%( P =0.634), respectively, and the 5-year overall survival rates were 37.2% and 65.4%( P =0.032). Forty-seven patients suffered distant metastases and the 5-year metastases free survival rates were 37.3% and 38.5% in supraclavicular lymph node dissection group and control group, respectively. Conclusion: Supraclavicular lymph node dissection maybe an effective approach to improve the loco-regional control for the patients with ISLM, especially for ER negative and PR negative subtypes, but it might has adverseeffects for the patients with negative HER2 status.
dos Santos Silva, I; Mangtani, P; De Stavola, B L; Bell, J; Quinn, M; Mayer, D
2003-08-04
Ethnic differences in breast cancer survival have been observed in the USA but have not been examined in Britain. We aimed to investigate such differences between South Asian (i.e. those with family roots in the Indian subcontinent) and non-South Asian (essentially British-native) women in England. Primary breast cancer cases incident in 1986 -1993 and resident in South East England were ascertained through the Thames Cancer and Registry and followed up to the end of 1997. Cases of South Asian ethnicity were identified on the basis of their names by using a previously validated computer algorithm. A total of 1037 South Asian and 50 201 non-South Asian breast cancer cases were included in the analysis; 30% of the South Asian (n=312) and 44% (n=22 201) of the non-South Asian cases died during follow-up. South Asian cases had a higher relative survival than non-South Asians throughout the follow-up period. The 10-year relative survival rates were 72.6% (95% confidence interval: 69.0, 75.9%) and 65.2% (64.5, 65.8%) for South Asians and non-South Asians, respectively. The excess mortality rates experienced by South Asians were 82% (72, 94%) of those experienced by non-South Asians (P=0.004). The magnitude of this effect was slightly reduced with adjustment for differences in age at diagnosis, but was strengthened with further adjustment for differences in stage at presentation and socioeconomic deprivation (excess mortality rates in South Asians relative to non-South Asians=72% (63, 82%), P&<0.001). These findings indicate that the higher survival from breast cancer in the first 10 years after diagnosis among South Asian was not due to differences in age at diagnosis, socioeconomic deprivation or disease stage at presentation.
Feng, Xu; Fang, Xue; Xia, Lingzi; Ren, Yangwu; Li, Xuelian; Quan, Xiaowei; Zhou, Baosen
2017-01-01
PPP1R13L and CD3EAP were confirmed to play important roles in transcription and apoptosis. SNPs in PPP1R13L and CD3EAP may be associated with lung cancer risk and survival. This study investigated the association of PPP1R13L rs1005165 and CD3EAP rs967591 with non-small cell lung cancer (NSCLC) risk and survival in Chinese non-smoking females. 442 NSCLC cases and 480 cancer-free controls were conducted in the case-control study, and 283 cases were in cohort study. Genotype was determined by Taqman real-time PCR. The statistical analyses were performed by SPSS 22.0 software. We found that rs1005165 and rs967591 were significantly associated with NSCLC risk in Chinese non-smoking females. For rs1005165, compared with homozygous wild CC genotype, carriers of CT or TT genotype had lower risk of NSCLC (adjusted ORs were 0.675 and 0.713, 95% CI were 0.461-0.988 and 0.525-0.968, respectively), adjusted OR for dominant model was 0.702, 95% CI was 0.526-0.937. For rs967591, AA genotype (adjusted OR = 0.721, 95% CI = 0.532-0.978) and at least one A allele (GA+AA) (adjusted OR = 0.716, 95% CI = 0.536-0.956) were significantly correlated with lower risk of NSCLC, compared with GG genotype. But we didn’t find correlation between the two SNPs and survival time in Chinese non-smoking NSCLC females. In general, we found PPP1R13L rs1005165 and CD3EAP rs967591 might be associated with lower NSCLC risk in Chinese non-smoking females, but no significant relationship was found with NSCLC survival. PMID:29108262
Shen, Sipeng; Shi, Qianwen; Bai, Jianling; Li, Jin; Qin, Shukui; Yu, Hao; Chen, Feng
2017-01-01
Apatinib is reported to significantly improve the overall survival (OS) of patients with advanced gastric cancer who have previously failed second-line chemotherapy. However, it is not well understood whether apatinib acts by improving progression or by prolonging post-progression survival. Here, based on phase III clinical trial data, the mediating effect of apatinib on patient overall survival was systematically quantified, through progression-free survival (PFS), post-progression survival (PPS), and the disease control rate (DCR). PFS was the primary mediator of the association between apatinib treatment and OS, with an indirect-effect mean survival time ratio of 1.63 (95%CI 1.35-1.97), which mediated 93.5% of the treatment effect. The DCR was also a significant mediator among secondary efficacy endpoints, and had an indirect-effect mean survival time ratio of 1.47 (95%CI 1.20-1.79, 50.9% mediated). Both primary and other targets of the DCR had similar results. The results indicated that apatinib treatment prolongs progression-free survival rather than post-progression survival, and in turn, leads to improved overall survival. Additionally, our study highlights the value of mediation analysis in clinical trials in providing additional information to build upon traditional primary analysis. PMID:27793017
Huang, Lihong; Wei, Yongyue; Shen, Sipeng; Shi, Qianwen; Bai, Jianling; Li, Jin; Qin, Shukui; Yu, Hao; Chen, Feng
2017-04-25
Apatinib is reported to significantly improve the overall survival (OS) of patients with advanced gastric cancer who have previously failed second-line chemotherapy. However, it is not well understood whether apatinib acts by improving progression or by prolonging post-progression survival. Here, based on phase III clinical trial data, the mediating effect of apatinib on patient overall survival was systematically quantified, through progression-free survival (PFS), post-progression survival (PPS), and the disease control rate (DCR). PFS was the primary mediator of the association between apatinib treatment and OS, with an indirect-effect mean survival time ratio of 1.63 (95%CI 1.35-1.97), which mediated 93.5% of the treatment effect. The DCR was also a significant mediator among secondary efficacy endpoints, and had an indirect-effect mean survival time ratio of 1.47 (95%CI 1.20-1.79, 50.9% mediated). Both primary and other targets of the DCR had similar results. The results indicated that apatinib treatment prolongs progression-free survival rather than post-progression survival, and in turn, leads to improved overall survival. Additionally, our study highlights the value of mediation analysis in clinical trials in providing additional information to build upon traditional primary analysis.
Hearing Loss in Children With Asymptomatic Congenital Cytomegalovirus Infection
Chung, Winnie; Flores, Marily; Blum, Peggy; Caviness, A. Chantal; Bialek, Stephanie R.; Grosse, Scott D.; Miller, Jerry A.; Demmler-Harrison, Gail
2017-01-01
OBJECTIVES: To assess the prevalence, characteristics, and risk of sensorineural hearing loss (SNHL) in children with congenital cytomegalovirus infection identified through hospital-based newborn screening who were asymptomatic at birth compared with uninfected children. METHODS: We included 92 case-patients and 51 controls assessed by using auditory brainstem response and behavioral audiometry. We used Kaplan–Meier survival analysis to estimate the prevalence of SNHL, defined as ≥25 dB hearing level at any frequency and Cox proportional hazards regression analyses to compare SNHL risk between groups. RESULTS: At age 18 years, SNHL prevalence was 25% (95% confidence interval [CI]: 17%–36%) among case-patients and 8% (95% CI: 3%–22%) in controls (hazard ratio [HR]: 4.0; 95% CI: 1.2–14.5; P = .02). Among children without SNHL by age 5 years, the risk of delayed-onset SNHL was not significantly greater for case-patients than for controls (HR: 1.6; 95% CI: 0.4–6.1; P = .5). Among case-patients, the risk of delayed-onset SNHL was significantly greater among those with unilateral congenital/early-onset hearing loss than those without (HR: 6.9; 95% CI: 2.5–19.1; P < .01). The prevalence of severe to profound bilateral SNHL among case-patients was 2% (95% CI: 1%–9%). CONCLUSIONS: Delayed-onset and progression of SNHL among children with asymptomatic congenital cytomegalovirus infection continued to occur throughout adolescence. However, the risk of developing SNHL after age 5 years among case-patients was not different than in uninfected children. Overall, 2% of case-patients developed SNHL that was severe enough for them to be candidates for cochlear implantation. PMID:28209771
E-cadherin genetic variants predict survival outcome in breast cancer patients.
Memni, Hager; Macherki, Yosra; Klayech, Zahra; Ben-Haj-Ayed, Ahlem; Farhat, Karim; Remadi, Yassmine; Gabbouj, Sallouha; Mahfoudh, Wijden; Bouzid, Nadia; Bouaouina, Noureddine; Chouchane, Lotfi; Zakhama, Abdelfattah; Hassen, Elham
2016-11-16
E-cadherin is a major component of adherens junctions that regulates cell shape and maintains tissue integrity. A complete loss or any decrease in cell surface expression of E-cadherin will interfere with the cell-to-cell junctions' strength and leads to cell detachment and escape from the primary tumor site. In this prospective study, three functional single nucleotide polymorphisms (-347G/GA, rs5030625; -160C/A, rs16260; +54C/T, rs1801026), were found to modulate E-cadherin expression. 577 DNA samples from breast cancer (BC) cases were genotyped by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). We detected no significant correlations between each polymorphism and the clinical parameters of the patients whereas the GACC haplotype was significantly associated with low SBR grading. Overall survival analysis showed that both -347G/G and +54C/C wild (wt) genotypes had a significantly worse effect compared to the other genotypes (non-wt). Moreover, carrying simultaneously both the -347 and +54 wt genotypes confers a significantly higher risk of death. However, with metastatic recurrence, the death-rate was null in patients carrying the non-wt genotypes, and attained 37% in those carrying the wt genotype. A multivariate analysis showed that these two polymorphisms are independent prognostic factors for overall survival in BC patients. Our results support the fact that E-cadherin genetic variants control disease severity and progression and could be a marker of disease outcome. These findings could be useful in selecting patients that should be monitored differently.
Niitsu, Hiroaki; Hinoi, Takao; Kawaguchi, Yasuo; Ohdan, Hideki; Hasegawa, Hirotoshi; Suzuka, Ichio; Fukunaga, Yosuke; Yamaguchi, Takashi; Endo, Shungo; Tagami, Soichi; Idani, Hitoshi; Ichihara, Takao; Watanabe, Kazuteru; Watanabe, Masahiko
2016-01-01
It remains controversial whether open or laparoscopic surgery should be indicated for elderly patients with colorectal cancer and a poor performance status. In those patients aged 80 years or older with Eastern Cooperative Oncology Group performance status score of 2 or greater who received elective surgery for stage 0 to stage III colorectal adenocarcinoma and had no concomitant malignancies and who were enrolled in a multicenter case-control study entitled "Retrospective study of laparoscopic colorectal surgery for elderly patients" that was conducted in Japan between 2003 and 2007, background characteristics and short-term and long-term outcomes for open surgery and laparoscopic surgery were compared. Of the 398 patients included, 295 underwent open surgery and 103 underwent laparoscopic surgery. There were no significant differences in the baseline characteristics between open surgery and laparoscopic surgery patients, except for previous abdominal surgery and TNM stage. The median operation duration was shorter with open surgery (open surgery, 153 min; laparoscopic surgery, 202 min; P < 0.001), and less blood loss occurred with laparoscopic surgery (median open surgery, 109 g; median laparoscopic surgery, 30 g; P < 0.001). An operation duration of 180 min or more (odds ratio, 1.97; 95 % confidence interval, 1.17-3.37; P = 0.011) and selection of laparoscopic surgery (odds ratio, 0.41; 95 % confidence interval, 0.22-0.75; P = 0.003) were statistically significant in the multivariate analysis for postoperative morbidity. Moreover, laparoscopic surgery did not result in an inferior overall survival rate compared with open surgery (log-rank test P = 0.289, 0.278, 0.346, 0.199, for all-stage, stage 0-I, stage II, and stage III disease, respectively). Laparoscopic surgery in elderly colorectal cancer patients with a poor performance status is safe and not inferior to open surgery in terms of overall survival.
Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.
Stewart, A Keith; Rajkumar, S Vincent; Dimopoulos, Meletios A; Masszi, Tamás; Špička, Ivan; Oriol, Albert; Hájek, Roman; Rosiñol, Laura; Siegel, David S; Mihaylov, Georgi G; Goranova-Marinova, Vesselina; Rajnics, Péter; Suvorov, Aleksandr; Niesvizky, Ruben; Jakubowiak, Andrzej J; San-Miguel, Jesus F; Ludwig, Heinz; Wang, Michael; Maisnar, Vladimír; Minarik, Jiri; Bensinger, William I; Mateos, Maria-Victoria; Ben-Yehuda, Dina; Kukreti, Vishal; Zojwalla, Naseem; Tonda, Margaret E; Yang, Xinqun; Xing, Biao; Moreau, Philippe; Palumbo, Antonio
2015-01-08
Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. We randomly assigned 792 patients with relapsed multiple myeloma to carfilzomib with lenalidomide and dexamethasone (carfilzomib group) or lenalidomide and dexamethasone alone (control group). The primary end point was progression-free survival. Progression-free survival was significantly improved with carfilzomib (median, 26.3 months, vs. 17.6 months in the control group; hazard ratio for progression or death, 0.69; 95% confidence interval [CI], 0.57 to 0.83; P=0.0001). The median overall survival was not reached in either group at the interim analysis. The Kaplan-Meier 24-month overall survival rates were 73.3% and 65.0% in the carfilzomib and control groups, respectively (hazard ratio for death, 0.79; 95% CI, 0.63 to 0.99; P=0.04). The rates of overall response (partial response or better) were 87.1% and 66.7% in the carfilzomib and control groups, respectively (P<0.001; 31.8% and 9.3% of patients in the respective groups had a complete response or better; 14.1% and 4.3% had a stringent complete response). Adverse events of grade 3 or higher were reported in 83.7% and 80.7% of patients in the carfilzomib and control groups, respectively; 15.3% and 17.7% of patients discontinued treatment owing to adverse events. Patients in the carfilzomib group reported superior health-related quality of life. In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile. (Funded by Onyx Pharmaceuticals; ClinicalTrials.gov number, NCT01080391.).
Adjuvant mitotane treatment for adrenocortical carcinoma.
Terzolo, Massimo; Angeli, Alberto; Fassnacht, Martin; Daffara, Fulvia; Tauchmanova, Libuse; Conton, Pier Antonio; Rossetto, Ruth; Buci, Lisa; Sperone, Paola; Grossrubatscher, Erika; Reimondo, Giuseppe; Bollito, Enrico; Papotti, Mauro; Saeger, Wolfgang; Hahner, Stefanie; Koschker, Ann-Cathrin; Arvat, Emanuela; Ambrosi, Bruno; Loli, Paola; Lombardi, Gaetano; Mannelli, Massimo; Bruzzi, Paolo; Mantero, Franco; Allolio, Bruno; Dogliotti, Luigi; Berruti, Alfredo
2007-06-07
Adrenocortical carcinoma is a rare neoplasm characterized by a high risk of recurrence after radical resection. Whether the use of mitotane is beneficial as an adjuvant treatment has been controversial. Our aim was to evaluate the efficacy of adjuvant mitotane in prolonging recurrence-free survival. We performed a retrospective analysis involving 177 patients with adrenocortical cancer who had undergone radical surgery at 8 centers in Italy and 47 centers in Germany between 1985 and 2005. Adjuvant mitotane was administered to 47 Italian patients after radical surgery (mitotane group), whereas 55 Italian patients and 75 German patients (control groups 1 and 2, respectively) did not receive adjuvant treatment after surgery. Baseline features in the mitotane group and the control group from Italy were similar; the German patients were significantly older (P=0.03) and had more stage I or II adrenocortical carcinomas (P=0.02) than did patients in the mitotane group. Recurrence-free survival was significantly prolonged in the mitotane group, as compared with the two control groups (median recurrence-free survival, 42 months, as compared with 10 months in control group 1 and 25 months in control group 2). Hazard ratios for recurrence were 2.91 (95% confidence interval [CI], 1.77 to 4.78; P<0.001) and 1.97 (95% CI, 1.21 to 3.20; P=0.005), respectively. Multivariate analysis indicated that mitotane treatment had a significant advantage for recurrence-free survival. Adverse events associated with mitotane were mainly of grade 1 or 2, but temporary dose reduction was needed in 13% of patients. Adjuvant mitotane may prolong recurrence-free survival in patients with radically resected adrenocortical carcinoma. Copyright 2007 Massachusetts Medical Society.
Ayerra, Arrate Querejeta; Mena, Estefanía Palacios; Fabregas, Joan Pera; Miguelez, Cristina Gutiérrez; Guedea, Ferran
2010-03-01
Lip cancer can be treated by surgery, external radiotherapy, and/or brachytherapy (BT). In recent years, BT has become increasingly favored for this type of cancer. The aim of the present study was to analyze local control and survival of patients treated at our institution between July 1989 and June 2008. We performed a retrospective study of 121 patients (109 males and 12 females) who underwent lip cancer brachytherapy from July 1989 to June 2008. Median age was 67 years and median follow-up was 31.8 months (range 20-188 months). Out of 121 patients, 100 (82.6%) were treated with low dose rate (LDR) BT while the remaining 21 patients (17.4%) received high dose rate (HDR) BT. The most common cell type was squamous cell carcinoma (115 cases; 95%) and most tumors were located on the lower lip (107 patients; 88.4%). Most cases were either stage T1 (62 patients; 51.2%), or T2 (44 cases; 36.4%). After 15 years of follow-up, overall survival was 89.5%, cause-specific survival 97.8%, and disease-free survival 86.6%. Local, regional, and distant control at 15 years were 90%, 92%, and 98.8%, respectively. Grade 3 mucosal toxicity was observed in 23% of patients treated with LDR compared to 33% of HDR patients, and grade 4 mucosal toxicity in 9% versus 0% in the HDR group. Our findings confirm that brachytherapy is an effective treatment for lip cancer. The results from our series are in line with those published elsewhere. Based on our limited data, HDR appears to be equally as good as LDR, although this needs to be confirmed by further studies.
Quality of life in children and adolescents surviving cancer.
Bradley Eilertsen, Mary-Elizabeth; Jozefiak, Thomas; Rannestad, Toril; Indredavik, Marit S; Vik, Torstein
2012-04-01
To explore subjective and proxy reported QoL (Quality of Life) in children and adolescents surviving cancer three years after diagnosis compared with healthy controls. Case-control study including 50 children and adolescents diagnosed with cancer between January 1, 1993 and January 1, 2003 and treated at the Paediatric Department of St. Olav's University Hospital in Trondheim, Norway. Data were collected using The Inventory of Life Quality in Children and Adolescents (ILC) and the KINDL QoL questionnaires (parent and self-reports), as well as by collecting data for any somatic late effects and psychological problems from the medical records of children surviving cancer. Adolescents surviving cancer as a group assessed their QoL as similar to that of their peers. However, adolescents surviving brain tumours or those with late effects reported lower QoL and an increased number of QoL domains perceived as problematic, even many years after diagnosis and treatment. Parents generally report a poorer QoL for their children surviving cancer and a greater number of QoL domains experienced as problematic compared with parent controls. To improve the child's total functioning and well-being we conclude that when planning long-term follow-up care, rehabilitation of children and adolescents with cancer, especially for survivors with brain tumours, and with late effects should particularly take into account their subjectively perceived and proxy reported QoL, in addition to their psychological problems and psychosocial functioning. Copyright © 2011 Elsevier Ltd. All rights reserved.
PTEN IDENTIFIED AS IMPORTANT RISK FACTOR OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE
Hosgood, H Dean; Menashe, Idan; He, Xingzhou; Chanock, Stephen; Lan, Qing
2009-01-01
Common genetic variation may play an important role in altering chronic obstructive pulmonary disease (COPD) risk. In Xuanwei, China, the COPD rate is more than twice the Chinese national average, and COPD is strongly associated with in-home coal use. To identify genetic variation that may be associated with COPD in a population with substantial in-home coal smoke exposures, we evaluated 1,261 single nucleotide polymorphisms (SNPs) in 380 candidate genes potentially relevant for cancer and other human diseases in a population-based case-control study in Xuanwei (53 cases; 107 controls). PTEN was the most significantly associated gene with COPD in a minP analysis using 20,000 permutations (P = 0.00005). SNP-based analyses found that homozygote variant carriers of PTEN rs701848 (ORTT = 0.12, 95%CI = 0.03 - 0.47) had a significant decreased risk of COPD. PTEN, or phosphatase and tensin homolog, is an important regulator of cell cycle progression and cellular survival via the AKT signaling pathway. Our exploratory analysis suggests that genetic variation in PTEN may be an important risk factor of COPD in Xuanwei. However, due to the small sample size, additional studies are needed to evaluate these associations within Xuanwei and other populations with coal smoke exposures. PMID:19625176
Rosenberg, Aaron S.; Ruthazer, Robin; Paulus, Jessica K.; Kent, David M.; Evens, Andrew M.; Klein, Andreas K.
2016-01-01
Background Multiple myeloma/plasmacytoma-like post-transplant lymphoproliferative disorder (PTLD-MM) is a rare complication of solid organ transplant. Case series have shown variable outcomes and survival data in the modern era are lacking. Methods A cohort of 212 PTLD-MM patients was identified in the Scientific Registry of Transplant Recipients between 1999-2011. Overall survival (OS) was estimated using the Kaplan-Meier method and the effects of treatment and patient characteristics on OS evaluated with Cox proportional hazards models. OS in 185 PTLD-MM patients was compared with 4048 matched controls with multiple myeloma (SEER-MM) derived from SEER. Results Men comprised 71% of patients; extramedullary disease was noted in 58%. Novel therapeutic agents were used in 19% of patients (more commonly 2007-2011 versus 1999-2006 (P=0.01)), reduced immunosuppression in 55%, and chemotherapy in 32%. Median OS was 2.4 years, and improved in the later time period (aHR 0.64, P=0.05). Advanced age, creatinine>2, Caucasian race and use of OKT3 were associated with inferior OS in multivariable analysis. OS of PTLD-MM is significantly inferior to SEER-MM patients (aHR 1.6, p<0.001). Improvements in OS over time differed between PTLD-MM and SEER-MM. Median OS of patients diagnosed 2000-2005 was shorter for PTLD-MM than SEER-MM patients (18 vs 47 months P<0.001). There was no difference among those diagnosed 2006-2010 (44 mo vs median not reached P=0.5) (interaction P=0.08). Conclusions Age at diagnosis, elevated creatinine, Caucasian race and OKT3 were associated with inferior survival in patients with PTLD-MM. Survival of PTLD-MM is inferior to SEER-MM, though significant improvements in survival have been documented. PMID:27771291
Use of mobile and cordless phones and survival of patients with glioma.
Hardell, Lennart; Carlberg, Michael
2013-01-01
We analysed the survival of patients after glioma diagnosis in relation to the use of wireless phones. All cases diagnosed between 1997 and 2003 with a malignant brain tumour (n = 1,251) in our case-control studies were included and followed from the date of diagnosis to the date of death or until May 30, 2012. For glioma, the use of wireless phones (mobile and cordless phones) gave a hazard ratio (HR) = 1.1 (95% confidence interval, CI = 0.9-1.2), with > 10-year latency HR = 1.2 (95% CI = 1.002-1.5, p trend = 0.02). For astrocytoma grade I-II (low-grade), the results were, HR = 0.5 (95% CI = 0.3-0.9) and for astrocytoma grade IV (glioblastoma), HR = 1.1 (95% CI = 0.95-1.4), with > 10 year latency HR = 1.3 (95% CI = 1.03-1.7). In the highest tertile (> 426 h) of cumulative use, HR = 1.2 (95% CI = 0.95-1.5) was found for glioblastoma. The results were similar for mobile and cordless phones. Decreased survival of glioma cases with long-term and high cumulative use of wireless phones was found. A survival disadvantage for astrocytoma grade IV, but a survival benefit for astrocytoma grade I-II was observed which could be due to exposure-related tumour symptoms leading to earlier diagnosis and surgery in that patient group. Copyright © 2012 S. Karger AG, Basel.
Parent-Child Communication and Marijuana Initiation: Evidence Using Discrete-Time Survival Analysis
Nonnemaker, James M.; Silber-Ashley, Olivia; Farrelly, Matthew C.; Dench, Daniel
2012-01-01
This study supplements existing literature on the relationship between parent-child communication and adolescent drug use by exploring whether parental and/or adolescent recall of specific drug-related conversations differentially impact youth's likelihood of initiating marijuana use. Using discrete-time survival analysis, we estimated the hazard of marijuana initiation using a logit model to obtain an estimate of the relative risk of initiation. Our results suggest that parent-child communication about drug use is either not protective (no effect) or—in the case of youth reports of communication—potentially harmful (leading to increased likelihood of marijuana initiation). PMID:22958867
Elmer, Jonathan; Scutella, Michael; Pullalarevu, Raghevesh; Wang, Bo; Vaghasia, Nishit; Trzeciak, Stephen; Rosario-Rivera, Bedda L.; Guyette, Francis X.; Rittenberger, Jon C.; Dezfulian, Cameron
2014-01-01
Purpose Previous observational studies have inconsistently associated early hyperoxia with worse outcomes after cardiac arrest and have methodological limitations. We tested this association using a high-resolution database controlling for multiple disease-specific markers of severity of illness and care processes. Methods This was a retrospective analysis of a single-center, prospective registry of consecutive cardiac arrest patients. We included patients who survived and were mechanically ventilated ≥24h after arrest. Our main exposure was arterial oxygen tension (PaO2), which we categorized hourly for 24 hours as severe hyperoxia (>300mmHg), moderate or probable hyperoxia (101-299mmHg), normoxia (60-100mmHg) or hypoxia (<60mmHg). We controlled for Utstein-style covariates, markers of disease severity and markers of care responsiveness. We performed unadjusted and multiple logistic regression to test the association between oxygen exposure and survival to discharge, and used ordered logistic regression to test the association of oxygen exposure with neurological outcome and Sequential Organ Failure Assessment (SOFA) score at 24h. Results Of 184 patients, 36% were exposed to severe hyperoxia and overall mortality was 54%. Severe hyperoxia, but not moderate or probable hyperoxia, was associated with decreased survival in both unadjusted and adjusted analysis (adjusted odds ratio (OR) for survival 0.83 per hour exposure, P=0.04). Moderate or probable hyperoxia was not associated with survival but was associated with improved SOFA score 24h (OR 0.92, P<0.01). Conclusion Severe hyperoxia was independently associated with decreased survival to hospital discharge. Moderate or probable hyperoxia was not associated with decreased survival and was associated with improved organ function at 24h. PMID:25472570
Lattanzi, Michael; Han, Joseph; Moran, Una; Utter, Kierstin; Tchack, Jeremy; Sabado, Rachel Lubong; Berman, Russell; Shapiro, Richard; Huang, Hsin-Hui; Osman, Iman; Bhardwaj, Nina; Pavlick, Anna C
2018-05-18
Cancer-testis antigen NY-ESO-1 is a highly immunogenic melanoma antigen which has been incorporated into adjuvant vaccine clinical trials. Three such early-phase trials were conducted at our center among patients with high-risk resected melanoma. We herein report on the pooled long-term survival outcomes of these patients in comparison to historical controls. All melanoma patients treated at NYU Langone Health under any of three prospective adjuvant NY-ESO-1 vaccine trials were retrospectively pooled into a single cohort. All such patients with stage III melanoma were subsequently compared to historical control patients identified via a prospective institutional database with protocol-driven follow-up. Survival times were calculated using the Kaplan-Meier method, and Cox proportional hazard models were employed to identify significant prognostic factors and control for confounding variables. A total of 91 patients were treated with an NY-ESO-1 vaccine for the treatment of high-risk resected melanoma. Of this group, 67 patients were stage III and were selected for comparative analysis with 123 historical control patients with resected stage III melanoma who received no adjuvant therapy. Among the pooled vaccine cohort (median follow-up 61 months), the estimated median recurrence-free survival was 45 months, while the median overall survival was not yet reached. In the control cohort of 123 patients (median follow-up 30 months), the estimated median recurrence-free and overall survival were 22 and 58 months, respectively. Within the retrospective stage III cohort, NY-ESO-1 vaccine was associated with decreased risk of recurrence (HR = 0.56, p < 0.01) and death (HR = 0.51, p = 0.01). Upon controlling for sub-stage, the adjuvant NY-ESO-1 clinical trial cohort continued to exhibit decreased risk of recurrence (HR = 0.45, p < 0.01) and death (HR = 0.40, p < 0.01). In this small retrospective cohort of resected stage III melanoma patients, adjuvant NY-ESO-1 vaccine immunotherapy was associated with longer recurrence-free and overall survival relative to historical controls. These data support the continued investigation of adjuvant NY-ESO-1 based immunotherapy regimens in melanoma.
Taghaddosinejad, Fakhreddin; Farzaneh, Esmaeil; Ghazanfari-Nasrabad, Mahdi; Eizadi-Mood, Nastaran; Hajihosseini, Morteza; Mehrpour, Omid
2016-01-01
Aluminum phosphide (AlP) is a very effective indoor and outdoor pesticide. We investigated the effects of N-acetyl cysteine (NAC) on the survival time, hemodynamics, and cardiac biochemical parameters at various time intervals in some cases of AlP poisoning. This research was a case-control study to evaluate 63 AlP poisoned patients during 2010-2012. Patients with cardiovascular complications of AlP to be treated with intravenous NAC plus conventional treatment were considered as the case group and compared with patients who did not receive NAC. NAC infusion was administered to the case group at 300 mg/kg for 20 h. The data gathered included age, sex, heart rate, Systolic blood pressure (SBP), creatine phosphokinase (CPK), creatine kinase MB (CK-MB), and ECG at the admission time and 12, 18, and 24 h after admission. Analysis of repeated measures was performed to check the variability of parameters over time. The mean ages in the case and control groups were 26.65 ± 1.06 (19-37 years) and 28.39 ± 1.11 (18-37 years), respectively (P = 0.266). Most of the patients were female (56.5%). CK-MB means were significantly different between the two groups, but no differences between the other variables were observed. Also, CK-MB, CPK, heart rate, and systolic blood pressure means became significantly different over time (0, 12, 18, and 24 h) in both groups (P < 0.001). NAC prevented sharp heart rate fluctuations in AlP patients in the case group. Regarding the outcomes, 17 patients died (10 patients in the control and 7 patients in the case groups). No side-effects of NAC were observed. Our patients could be managed by the positive role of NAC as the biochemical index of cardiotoxicity was found to elevate in both the case and control groups. Therefore, for the management protocol optimization, NAC evaluation should be done in further cases.
Zhang, Xu-Chao; Cao, Xu; Sun, Chun; Xie, Zhi; Guo, Jian-Jun; Yang, Jin-Ji; Yang, Xue-Ning; Dai, Hang-Jun; Li, Su-Chun; Xu, Xin-Ran; Zuo, Yun-Xia; Chen, Meng; Koeppen, Hartmut; He, Jing; Kiermaier, Astrid; Shames, David; Cheng, Gang; Wu, Yi-Long
2018-03-01
The goal of this study is to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese non-small cell lung cancer (NSCLC) patients to inform the clinical development of anti-PD1/PD-L1 agents in this population. We used phosphatase and tensin homolog (PTEN) expression through IHC as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were then analyzed with a clinically validated PD-L1 IHC assay. The results were correlated with baseline characteristics and clinical outcomes. PTEN IHC showed that 108 TMA samples and 105 whole-section samples qualified for PD-L1 IHC. With a clinically relevant cutoff, 41.7% of the TMA samples were PD-L1 positive. PD-L1 level was much lower in EGFR-mutant patients and seemed to be a favorable prognostic factor for both overall survival (OS) and recurrence-free survival (RFS). These findings were confirmed in the whole-section samples except that their survival data were not mature enough for correlation analysis. In summary, PD-L1 expression was detected in approximately 40% of PTEN-qualified Chinese NSCLC samples, negatively correlated with EGFR mutation and seemed to be a favorable prognostic factor for both OS and RFS. Notably, the different results from PTEN-qualified and PTEN-disqualified samples underscore the importance of tissue quality control prior to biomarker testing.
Schimmer, Barbara; Nygard, Karin; Eriksen, Hanne-Merete; Lassen, Jørgen; Lindstedt, Bjørn-Arne; Brandal, Lin T; Kapperud, Georg; Aavitsland, Preben
2008-01-01
Background On 20–21 February 2006, six cases of diarrhoea-associated haemolytic uraemic syndrome (HUS) were reported by paediatricians to the Norwegian Institute of Public Health. We initiated an investigation to identify the etiologic agent and determine the source of the outbreak in order to implement control measures. Methods A case was defined as a child with diarrhoea-associated HUS or any person with an infection with the outbreak strain of E. coli O103 (defined by the multi-locus variable number tandem repeats analysis (MLVA) profile) both with illness onset after January 1st 2006 in Norway. After initial hypotheses-generating interviews, we performed a case-control study with the first fifteen cases and three controls for each case matched by age, sex and municipality. Suspected food items were sampled, and any E. coli O103 strains were typed by MLVA. Results Between 20 February and 6 April 2006, 17 cases were identified, of which 10 children developed HUS, including one fatal case. After pilot interviews, a matched case-control study was performed indicating an association between a traditional cured sausage (odds ratio 19.4 (95% CI: 2.4–156)) and STEC infection. E. coli O103:H25 identical to the outbreak strain defined by MLVA profile was found in the product and traced back to contaminated mutton. Conclusion We report an outbreak caused by a rare STEC variant (O103:H25, stx2-positive). More than half of the diagnosed patients developed HUS, indicating that the causative organism is particularly virulent. Small ruminants continue to be important reservoirs for human-pathogen STEC. Improved slaughtering hygiene and good manufacturing practices for cured sausage products are needed to minimise the possibility of STEC surviving through the entire sausage production process. PMID:18387178
Rhee, Deok-Joo; Kong, Doo-Sik; Kim, Won Seog; Park, Kwon-Byong; Lee, Jung-Il; Suh, Yeon-Lim; Song, Sang Young; Kim, Sung Tae; Lim, Do-Hoon; Park, Kwan; Kim, Jong Hyun; Nam, Do-Hyun
2009-11-01
The aim of this study was to assess the efficacy of adjuvant TMZ chemotherapy for newly diagnosed GBM patients who were treated with surgery followed by radiotherapy alone. Between January 2003 and April 2005, 59 consecutive GBM patients underwent radiation therapy after surgical resection and subsequently received TMZ chemotherapy. For the comparative analysis, we selected 60 clinically matched GBM patients who underwent radiotherapy followed by nitrosourea-based chemotherapy (NUBC), at the same institution between June 1995 and April 2005. The study cohort was divided into two groups, those with adjuvant TMZ treatment and with NUBC. 59 patients with adjuvant TMZ treatment were assigned to the treatment group and 60 patients with NUBC to the control group. The median overall survival for the treatment group was 18.2 months (95% CI, 11.7-24.7 months), compared with the survival of 14.5 months (95% CI, 11.2-17.7 months) for the control group (p=0.019). The progression-free survival for the treatment group was 5.6 months (95% CI, 4.4-6.7 months), while the control group showed progression-free survival of 3.3 months (95% CT, 3.2-6.0 months) (p=0.030). Uni- and multivariate analysis revealed that extent of surgical resection, age > or =55 years and postoperative KPS were significantly associated with survival. Adjuvant TMZ chemotherapy provided a clinically relevant benefit of survival, as compared with NUBC. Thus, we suggest that adjuvant TMZ chemotherapy may be effective even for patients who did not receive concomitant chemoradiotherapy for GBM.
Correia, Francisco; Gouveia, Sónia; Felino, António Campos; Costa, Ana Lemos; Almeida, Ricardo Faria
To evaluate the differences between the survival rates of implants placed in patients with no history of periodontal disease (NP) and in patients with a history of chronic periodontal disease (CP). A retrospective cohort study was conducted in which all consenting patients treated with dental implants in a private clinic in Oporto, Portugal, from November 2, 2002 through February 11, 2011 were included. All patients were treated consecutively by the same experimental operator. This study aimed to analyze how the primary outcomes (presence of disease, time of placement, and time of loading) and the secondary outcomes (severity-generalized periodontitis, brand, implant length, prosthesis type, prosthesis metal-ceramic extension) influence the survival rate of dental implants. The survival analysis was performed through the Kaplan-Meier method, and the equality of survival distributions for all groups was tested with the log-rank test with a significance level of .05 for all comparisons. The sample consisted of 202 patients (47% NP and 53% CP) and 689 implants (31% NP and 69% CP). The survival rate in the NP and CP groups showed no statistically significant differences (95.8% versus 93.1%; P ≥ .05). Implants were lost before loading in 54.9% of the cases. The majority of the implants were lost in the first year and stabilized after the second year. Survival rates in the NP and CP patients showed no statistically significant differences when comparing the following factors: subclassification of the disease, implant brands, implant length (short/standard), type of prosthesis, extension of the prosthesis metal-ceramic, and time of placement and loading (P ≥ .05). This work disclosed no statistically significant differences in terms of survival rates when compared with the control group. Placing implants in patients with a history of periodontal disease appears to be viable and safe.
Kundu, Madan G; Acharyya, Suddhasatta
2017-02-01
PFS is often used as a surrogate endpoint for OS in metastatic breast cancer studies. We have evaluated the association of treatment effect on PFS with significant HR OS (and how this association is affected by other factors) in published prospective metastatic breast cancer studies. A systematic literature search in PubMed identified prospective metastatic breast cancer studies. Treatment effects on PFS were determined using hazard ratio (HR PFS ), increase in median PFS (ΔMED PFS ) and % increase in median PFS (%ΔMED PFS ). Diagnostic accuracy of PFS measures (HR PFS , ΔMED PFS and %ΔMED PFS ) in predicting significant HR OS was assessed using receiver operating characteristic (ROC) curves and classification tree approach (CART). Seventy-four cases (i.e., treatment to control comparisons) from 65 individual publications were identified for the analyses. Of these, 16 cases reported significant treatment effect on HR OS at 5% level of significance. Median number of deaths reported in these cases were 153. Area under the ROC curve (AUC) for diagnostic measures as HR PFS , ΔMED PFS and %ΔMED PFS were 0.69, 0.70 and 0.75, respectively. Classification tree results identified %ΔMED PFS and number of deaths as diagnostic measure for significant HR OS . Only 7.9% (3/39) cases with ΔMED PFS shorter than 48.27% reported significant HR OS . There were 7 cases with ΔMED PFS of 48.27% or more and number of deaths reported as 227 or more - of these 5 cases reported significant HR OS . %ΔMED PFS was found to be a better diagnostic measure for predicting significant HR OS . Our analysis results also suggest that consideration of total number of deaths may further improve its diagnostic performance. Based on our study results, the studies with 50% improvement in median PFS are more likely to produce significant HR OS if the total number of OS events at the time of analysis is 227 or more. Copyright © 2016 Elsevier Inc. All rights reserved.
Neoadjuvant treatments for locally advanced, resectable esophageal cancer: A network meta-analysis.
Chan, Kelvin K W; Saluja, Ronak; Delos Santos, Keemo; Lien, Kelly; Shah, Keya; Cramarossa, Gemma; Zhu, Xiaofu; Wong, Rebecca K S
2018-02-14
The relative survival benefits and postoperative mortality among the different types of neoadjuvant treatments (such as chemotherapy only, radiotherapy only or chemoradiotherapy) for esophageal cancer patients are not well established. To evaluate the relative efficacy and safety of neoadjuvant therapies in resectable esophageal cancer, a Bayesian network meta-analysis was performed. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were searched for publications up to May 2016. ASCO and ASTRO annual meeting abstracts were also searched up to the 2015 conferences. Randomized controlled trials that compared at least two of the following treatments for resectable esophageal cancer were included: surgery alone, surgery preceded by neoadjuvant chemotherapy, neoadjuvant radiotherapy or neoadjuvant chemoradiotherapy. The primary outcome assessed from the trials was overall survival. Thirty-one randomized controlled trials involving 5496 patients were included in the quantitative analysis. The network meta-analysis showed that neoadjuvant chemoradiotherapy improved overall survival when compared to all other treatments including surgery alone (HR 0.75, 95% CR 0.67-0.85), neoadjuvant chemotherapy (HR 0.83. 95% CR 0.70-0.96) and neoadjuvant radiotherapy (HR 0.82, 95% CR 0.67-0.99). However, the risk of postoperative mortality increased when comparing neoadjuvant chemoradiotherapy to either surgery alone (RR 1.46, 95% CR 1.00-2.14) or to neoadjuvant chemotherapy (RR 1.58, 95% CR 1.00-2.49). In conclusion, neoadjuvant chemoradiotherapy improves overall survival but may also increase the risk of postoperative mortality in patients locally advanced resectable esophageal carcinoma. © 2018 UICC.
Bibby, Anna C; De Fonseka, Duneesha; Morley, Anna J; Keenan, Emma; Addeo, Alfredo; Smith, Sarah; Edey, Anthony J; Maskell, Nick A
2017-12-08
Mesothelioma is an aggressive thoracic tumour with a poor prognosis. The only treatment that extends survival is chemotherapy. However, in the UK, up to 50% of patients who are suitable for chemotherapy choose not to receive it, opting for active symptom control instead. The aim of this prospective, single-centre observational study was to describe the characteristics of patients who chose active symptom control over chemotherapy and explore their reasons for doing so. Two hundred consecutive patients with mesothelioma from one UK centre were included. Eligibility for chemotherapy and choice of first-line treatment were recorded prospectively. Patient characteristics and outcomes were compared using descriptive statistics, regression analysis and survival analysis. Reasons for choosing active symptom control over chemotherapy were extracted, retrospectively. People who chose active symptom control were older, more likely to be female and had worse performance statuses than patients who received front-line chemotherapy. Concern over side effects, the modest survival benefit and previous adverse experiences with chemotherapy were reported as reasons for the decision. Median survival was 13.9 months in the chemotherapy group compared with 6.7 months in the active symptom control group. This is the first study to describe the characteristics of patients with mesothelioma who chose active symptom control over chemotherapy, in the front-line setting. Important differences were seen between this group and patients who received chemotherapy, although confounding is likely to have affected some outcomes. Future research could use qualitative methods to explore patients' reasons for choosing active symptom control, and to further elucidate the decision-making process.
Outcomes for patients with congenital hepatoblastoma.
Trobaugh-Lotrario, Angela D; Chaiyachati, Barbara H; Meyers, Rebecka L; Häberle, Beate; Tomlinson, Gail E; Katzenstein, Howard M; Malogolowkin, Marcio H; von Schweinitz, Dietrich; Krailo, Mark; Feusner, James H
2013-11-01
Congenital hepatoblastoma, diagnosed in the first month of life, has been reported to have a poor prognosis; however, a comprehensive evaluation of this entity is lacking. We retrospectively reviewed two patients from the senior authors' personal series and 25 cases identified in the databases of several multicenter group studies (INT-0098, P9645, 881, P9346, HB 89, HB94, and HB 99). We compared this series with cases of congenital hepatoblastoma previously published in the literature. The 3-year survival in our case series was 86% (18/21) with a follow-up of 44-230 months (median 85.5 months). Presentation and treatment were not substantially different from hepatoblastoma cohorts unselected for age. Survival was comparable to the reported disease free survival for a similar cohort of hepatoblastoma patients unselected for age between 1986 and 2002 (82.5%) [von Schweinitz et al., Eur J Cancer 1997; 33:1243-1249]. The 2-year survival of cases reported in the literature was 0% (0/9) and 42% (10/24) for patients reported before and after 1990, respectively. Congenital hepatoblastoma does not appear to confer a worse prognosis. The improved survival of our current series of patients, collected from the past 20 years of German and American multicenter trials and personal series, suggests that the outcome of hepatoblastoma at this young age is much better than has been historically reported. More rigorous analysis should be conducted in future multicenter trials. It is possible that congenital hepatoblastoma should be treated like all other patients with hepatoblastoma provided that the child is stable enough to proceed with surgery and chemotherapy. Copyright © 2013 Wiley Periodicals, Inc.
Gallart, X; Gomez, J C; Fernández-Valencia, J A; Combalía, A; Bori, G; García, S; Rios, J; Riba, J
2014-01-01
To evaluate the short-term results of an ultra high molecular weight polyethylene retentive cup in patients at high risk of dislocation, either primary or revision surgery. Retrospective review of 38 cases in order to determine the rate of survival and failure analysis of a constrained cemented cup, with a mean follow-up of 27 months. We studied demographic data, complications, especially re-dislocations of the prosthesis and, also the likely causes of system failure analyzed. In 21.05% (8 cases) were primary surgery and 78.95% were revision surgery (30 cases). The overall survival rate by Kaplan-Meier method was 70.7 months. During follow-up 3 patients died due to causes unrelated to surgery and 2 infections occurred. 12 hips had at least two previous surgeries done. It wasn't any case of aseptic loosening. Four patients presented dislocation, all with a 22 mm head (P=.008). Our statistical analysis didn't found relationship between the abduction cup angle and implant failure (P=.22). The ultra high molecular weight polyethylene retentive cup evaluated in this series has provided satisfactory short-term results in hip arthroplasty patients at high risk of dislocation. Copyright © 2014 SECOT. Published by Elsevier Espana. All rights reserved.
Choi, Junjeong; Park, Sung-Hye; Khang, Shin Kwang; Suh, Yeon-Lim; Kim, Sang Pyo; Lee, Youn Soo; Kwon, Hyun Seok; Kang, Seok-Gu; Kim, Se Hoon
2016-12-01
Hemangiopericytoma (HPC) in the central nervous system (CNS) is a rare disease with distinctive biological/clinical characteristics compared with meningioma. Cases of HPCs of the CNS were collected, and clinicopathological records were retrospectively reviewed and analyzed. Immunohistochemistry (IHC) for proliferative markers (Ki-67, PHH3) and STAT6 were performed. A total of 140 cases were collected, with mean follow-up of 77 months (median 58.8 months; range 0.53-540.5 months). 1-, 5-, 10-, and 20-year survival rates were 99.1, 94.0, 74.4, and 61.9 %, respectively. Thirty-nine patients (27.9 %) had recurrent disease. Mean and median times to recurrence were 62.9 and 47.3 months with 1-, 5-, 10-, and 20-year recurrence-free survival rates of 98.3, 78.3, 50.1, and 11.0 %, respectively. Thirteen patients (9.3 %) developed extracranial metastases. No adjuvant radiation therapy, higher histologic grades, failure of gross-total resection, and cases with gamma-knife surgery (GKS) were factors associated with shorter disease-free survival (log-rank test, p = 0.02, 0.00, 0.02, 0.00), among which high histologic grade and cases with GKS were significant in multivariable analysis. Strong nuclear STAT6 expression was noted in HPCs in 62 cases of HPCs (60/62, 96.8 %), whereas diffuse weak positivity was demonstrated in all meningioma cases. The survival rate in patients with HPC of the CNS is comparable to that of previously reported series. Recurrence remains a critical clinical issue of the disease. Identification of NAB2-STAT6 fusion transcript with surrogate IHC marker is a valuable diagnostic tool in the differential diagnosis of the disease.
Photodynamic therapy for pancreatic and biliary tract carcinoma
NASA Astrophysics Data System (ADS)
Pereira, Stephen P.
2009-02-01
Patients with non-resectable pancreatic and biliary tract cancer (cholangiocarcinoma and gallbladder cancer) have a dismal outlook with conventional palliative therapies, with a median survival of 3-9 months and a 5 year survival of less than 3%. Surgery is the only curative treatment but is appropriate in less than 20% of cases, and even then is associated with a 5-year survival of less than 30%. Although most applications of photodynamic therapy (PDT) in gastroenterology have been on lesions of the luminal gut, there is increasing experimental and clinical evidence for its efficacy in cancers of the pancreas and biliary tract. Our group has carried out the only clinical study of PDT in pancreatic carcinoma reported to date, and showed that PDT is feasible for local debulking of pancreatic cancer. PDT has also been used with palliative intent in patients with unresectable cholangiocarcinoma, with patients treated with stenting plus PDT reporting improvements in cholestasis, quality of life and survival compared with historical or randomized controls treated with stenting alone. Further controlled studies are needed to establish the influence of PDT and chemotherapy on the survival and quality of life of patients with pancreatic and biliary tract carcinoma.
Powell, Steven; Chan, Tze Yuan; Bhat, Rammohan; Lam, Kimberly; Narlawar, Ranjeet S; Cullen, Nicola; Littler, Peter
2010-08-01
Tunneled hemodialysis catheters become essential in dialysis access when there is no possibility of using a functioning arteriovenous fistula. Collateral or occluded veins visible on ultrasound are used for puncture and passage of catheters into the central venous system. Chronically occluded veins are crossed with guidewires to allow dilatation and subsequent passage of hemodialysis catheters. We performed a retrospective analysis of patient demographics, comorbidities, procedural complications, functional survival, performance, and history of previous vascular access. The study group was compared with two control groups in which dialysis catheters were inserted either by radiologists in the interventional suite or by clinicians on the wards. Nineteen patients from the study group were compared with same number of patients in both control groups. The mean age of the study group was higher compared with the control groups. There was no significant difference in mean functional survival, infection rates, dialysis pump speeds in the first 2 weeks, and procedural complications between the study group and the controls. The study group had a significantly higher number of previous vascular access interventions, longer dialysis careers, and more comorbidities. Tunneled dialysis catheter placement by way of collateral or occluded veins appears safe and effective. These techniques give the operator further options when faced with patients possessing challenging vascular access. Indeed, there may be a case for preferential use of these veins to keep patent central veins in reserve.
Abstract:This case study application provides discussion on a selected application of advanced concepts, included in the End of Asset Life Reinvestment decision-making process tool, using a utility practitioner’s data set. The tool provides step-by-step process guidance to the as...
Niitsu, Hiroaki; Hinoi, Takao; Shimomura, Manabu; Egi, Hiroyuki; Hattori, Minoru; Ishizaki, Yasuyo; Adachi, Tomohiro; Saito, Yasufumi; Miguchi, Masashi; Sawada, Hiroyuki; Kochi, Masatoshi; Mukai, Shoichiro; Ohdan, Hideki
2015-04-24
In stage IV colorectal cancer (CRC) with unresectable metastases, whether or not resection of the primary tumor should be indicated remains controversial. We aim to determine the impact of primary tumor resection on the survival of stage IV CRC patients with unresectable metastases. We retrospectively investigated 103 CRC patients with stage IV colorectal cancer with metastases, treated at Hiroshima University Hospital between 2007 and 2013. Of these, those who had resectable primary tumor but unresectable metastases and received any chemotherapy were included in the study. We analyzed the overall survival (OS) and short-term outcomes between the patients who received up-front systemic chemotherapy (USC group) and those who received primary tumor resection followed by chemotherapy (PTR group). Of the 57 included patients, 15 underwent USC and 42 PTR. The median survival times were 13.4 and 23.9 months in the USC and PTR groups, respectively (P = 0.093), but multivariate analysis for the overall survival showed no significant difference between the two groups (hazard ratio, 1.30; 95% confidence interval (CI), 0.60 to 2.73, P = 0.495). In the USC group, the disease control rate of primary tumor was observed in 12 patients (80.0%), but emergency laparotomy was required for 1 patient. Morbidity in the PTR group was observed in 18 cases (42.9%). The overall survival did not differ significantly between the USC and PTR groups. USC may help avoid unnecessary resection and consequently the high morbidity rate associated with primary tumor resection for stage IV CRC with unresectable metastases.
Chocron, Richard; Bougouin, Wulfran; Beganton, Frankie; Juvin, Philippe; Loeb, Thomas; Adnet, Frédéric; Lecarpentier, Eric; Lamhaut, Lionel; Jost, Daniel; Marijon, Eloi; Cariou, Alain; Jouven, Xavier; Dumas, Florence
2017-09-01
As post-cardiac arrest care may influence patients' outcome, characteristics of receiving hospitals should be integrated in the evaluation of survival. We aimed at assessing the influence of care level center on patients' survival at hospital discharge using a regional registry of out-of-hospital cardiac arrest patients (OHCA). We retrospectively analysed a Utstein and in-hospital data prospectively collected for all non-traumatic OHCA patients, in whom a successful return of spontaneous circulation (ROSC) had been obtained, from a large metropolitan area (Great Paris). Receiving hospitals were categorized in 3 groups as follows: A centers (High-case volume with cath-lab 24/7), B centers (Intermediate-case volume with cath-lab partly available) and C centers (Low-case volume and no cath-lab) We compared patients' characteristics and outcome in the 3 groups and performed a multivariate logistic regression using survival to discharge as primary endpoint. Between May 2011 and December 2013, 1476 patients were admitted in 48 hospitals (group A: n=917; group B: n=428; group C: n=91). Overall survival rate at discharge was 433/1436 (30%). Patients' baseline characteristics significantly differed, as hospitals from group A received younger patients with a higher rate of shockable cardiac rhythms (p<0.001). Unadjusted survival rate differed significantly among the 3 groups of hospitals (respectively 34%, 25% and 15.4% for A-C, p<0.01). In multivariate analysis, the category of receiving hospital was no longer associated with survival, even in the subgroup of witnessed arrest and shockable patients. In this population-based study, characteristics of receiving hospitals are not associated with survival rate at discharge. This might be partially explained by the prehospital triage organization used in France. Copyright © 2017. Published by Elsevier B.V.
A case-control study of boat-related injuries and fatalities in Washington State.
Stempski, Sarah; Schiff, Melissa; Bennett, Elizabeth; Quan, Linda
2014-08-01
To identify risk factors associated with boat-related injuries and deaths. We performed a case-control study using the Washington Boat Accident Investigation Report Database for 2003-2010. Cases were fatally injured boat occupants, and controls were non-fatally injured boat occupants involved in a boating incident. We evaluated the association between victim, boat and incident factors and risk of death using Poisson regression to estimate RRs and 95% CIs. Of 968 injured boaters, 26% died. Fatalities were 2.6 times more likely to not be wearing a personal flotation device (PFD) and 2.2 times more likely to not have any safety features on their boat compared with those who survived. Boating fatalities were more likely to be in a non-motorised boat, to have alcohol involved in the incident, to be in an incident that involved capsizing, sinking, flooding or swamping, and to involve a person leaving the boat voluntarily, being ejected or falling than those who survived. Increasing PFD use, safety features on the boat and alcohol non-use are key strategies and non-motorised boaters are key target populations to prevent boating deaths. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Li, Nan; Petrick, Jessica L; Steck, Susan E; Bradshaw, Patrick T; McClain, Kathleen M; Niehoff, Nicole M; Engel, Lawrence S; Shaheen, Nicholas J; Risch, Harvey A; Vaughan, Thomas L; Wu, Anna H; Gammon, Marilie D
2017-12-01
During the past 40 years, esophageal/gastric cardia adenocarcinoma (EA/GCA) incidence increased in Westernized countries, but survival remained low. A parallel increase in sugar intake, which may facilitate carcinogenesis by promoting hyperglycaemia, led us to examine sugar/carbohydrate intake in association with EA/GCA incidence and survival. We pooled 500 EA cases, 529 GCA cases and 2027 controls from two US population-based case-control studies with cases followed for vital status. Dietary intake, assessed by study-specific food frequency questionnaires, was harmonized and pooled to estimate 12 measures of sugar/carbohydrate intake. Multivariable-adjusted odds ratios (ORs) and hazard ratios [95% confidence intervals (CIs)] were calculated using multinomial logistic regression and Cox proportional hazards regression, respectively. EA incidence was increased by 51-58% in association with sucrose (ORQ5vs.Q1 = 1.51, 95% CI = 1.01-2.27), sweetened desserts/beverages (ORQ5vs.Q1 = 1.55, 95% CI = 1.06-2.27) and the dietary glycaemic index (ORQ5vs.Q1 = 1.58, 95% CI = 1.13-2.21). Body mass index (BMI) and gastro-esophageal reflux disease (GERD) modified these associations (Pmultiplicative-interaction ≤ 0.05). For associations with sucrose and sweetened desserts/beverages, respectively, the OR was elevated for BMI < 25 (ORQ4-5vs.Q1-3 = 1.79, 95% CI = 1.26-2.56 and ORQ4-5vs.Q1-3 = 1.45, 95% CI = 1.03-2.06), but not BMI ≥ 25 (ORQ4-5vs.Q1-3 = 1.05, 95% CI = 0.76-1.44 and ORQ4-5vs.Q1-3 = 0.85, 95% CI = 0.62-1.16). The EA-glycaemic index association was elevated for BMI ≥ 25 (ORQ4-5vs.Q1-3 = 1.38, 95% CI = 1.03-1.85), but not BMI < 25 (ORQ4-5vs.Q1-3 = 0.88, 95% CI = 0.62-1.24). The sucrose-EA association OR for GERD < weekly was 1.58 (95% CI = 1.16-2.14), but for GERD ≥ weekly was 1.01 (95% CI = 0.70-1.47). Sugar/carbohydrate measures were not associated with GCA incidence or EA/GCA survival. If confirmed, limiting intake of sucrose (e.g. table sugar), sweetened desserts/beverages, and foods that contribute to a high glycaemic index, may be plausible EA risk reduction strategies. Published by Oxford University Press on behalf of the International Epidemiological Association 2017. This work is written by US Government employees and is in the public domain in the United States.
Nakamura, Noboru; Vaidya, Anil; Levi, David M.; Kato, Tomoaki; Nery, Jose R.; Madariaga, Juan R.; Molina, Enrique; Ruiz, Phillip; Gyamfi, Anthony; Tzakis, Andreas G.
2006-01-01
Background. Orthotopic liver transplantation (OLT) in adult patients has traditionally been performed using conventional caval reconstruction technique (CV) with veno-venous bypass. Recently, the piggyback technique (PB) without veno-venous bypass has begun to be widely used. The aim of this study was to assess the effect of routine use of PB on OLTs in adult patients. Patients and methods. A retrospective analysis was undertaken of 1067 orthotopic cadaveric whole liver transplantations in adult patients treated between June 1994 and July 2001. PB was used as the routine procedure. Patient demographics, factors including cold ischemia time (CIT), warm ischemia time (WIT), operative time, transfusions, blood loss, and postoperative results were assessed. The effects of clinical factors on graft survival were assessed by univariate and multivariate analyses.In all, 918 transplantations (86%) were performed with PB. Blood transfusion, WIT, and usage of veno-venous bypass were less with PB. Seventy-five (8.3%) cases with PB had refractory ascites following OLT (p=NS). Five venous outflow stenosis cases (0.54%) with PB were noted (p=NS). The liver and renal function during the postoperative periods was similar. Overall 1-, 3-, and 5-year patient survival rates were 85%, 78%, and 72% with PB. Univariate analysis showed that cava reconstruction method, CIT, WIT, amount of transfusion, length of hospital stay, donor age, and tumor presence were significant factors influencing graft survival. Multivariate analysis further reinforced the fact that CIT, donor age, amount of transfusion, and hospital stay were prognostic factors for graft survival. Conclusions. PB can be performed safely in the majority of adult OLTs. Results of OLT with PB are as same as for CV. Liver function, renal function, morbidity, mortality, and patient and graft survival are similar to CV. However, amount of transfusion, WIT, and use of veno-venous bypass are less with PB. PMID:18333273