Sample records for advanced clinical staging

  1. Systematic genomic identification of colorectal cancer genes delineating advanced from early clinical stage and metastasis

    PubMed Central

    2013-01-01

    Background Colorectal cancer is the third leading cause of cancer deaths in the United States. The initial assessment of colorectal cancer involves clinical staging that takes into account the extent of primary tumor invasion, determining the number of lymph nodes with metastatic cancer and the identification of metastatic sites in other organs. Advanced clinical stage indicates metastatic cancer, either in regional lymph nodes or in distant organs. While the genomic and genetic basis of colorectal cancer has been elucidated to some degree, less is known about the identity of specific cancer genes that are associated with advanced clinical stage and metastasis. Methods We compiled multiple genomic data types (mutations, copy number alterations, gene expression and methylation status) as well as clinical meta-data from The Cancer Genome Atlas (TCGA). We used an elastic-net regularized regression method on the combined genomic data to identify genetic aberrations and their associated cancer genes that are indicators of clinical stage. We ranked candidate genes by their regression coefficient and level of support from multiple assay modalities. Results A fit of the elastic-net regularized regression to 197 samples and integrated analysis of four genomic platforms identified the set of top gene predictors of advanced clinical stage, including: WRN, SYK, DDX5 and ADRA2C. These genetic features were identified robustly in bootstrap resampling analysis. Conclusions We conducted an analysis integrating multiple genomic features including mutations, copy number alterations, gene expression and methylation. This integrated approach in which one considers all of these genomic features performs better than any individual genomic assay. We identified multiple genes that robustly delineate advanced clinical stage, suggesting their possible role in colorectal cancer metastatic progression. PMID:24308539

  2. Development and validation of a clinically applicable score to classify cachexia stages in advanced cancer patients

    PubMed Central

    Zhou, Ting; Wang, Bangyan; Liu, Huiquan; Yang, Kaixiang; Thapa, Sudip; Zhang, Haowen; Li, Lu

    2018-01-01

    Abstract Background Cachexia is a multifactorial syndrome that is highly prevalent in advanced cancer patients and leads to progressive functional impairments. The classification of cachexia stages is essential for diagnosing and treating cachexia. However, there is a lack of simple tools with good discrimination for classifying cachexia stages. Therefore, our study aimed to develop a clinically applicable cachexia staging score (CSS) and validate its discrimination of clinical outcomes for different cachexia stages. Methods Advanced cancer patients were enrolled in our study. A CSS comprising the following five components was developed: weight loss, a simple questionnaire of sarcopenia (SARC‐F), Eastern Cooperative Oncology Group, appetite loss, and abnormal biochemistry. According to the CSS, patients were classified into non‐cachexia, pre‐cachexia, cachexia, and refractory cachexia stages, and clinical outcomes were compared among the four groups. Results Of the 297 participating patients, data from 259 patients were ultimately included. Based on the CSS, patients were classified into non‐cachexia (n = 69), pre‐cachexia (n = 68), cachexia (n = 103), and refractory cachexia (n = 19) stages. Patients with more severe cachexia stages had lower skeletal muscle indexes (P = 0.002 and P = 0.004 in male and female patients, respectively), higher prevalence of sarcopenia (P = 0.017 and P = 0.027 in male and female patients, respectively), more severe symptom burden (P < 0.001), poorer quality of life (P < 0.001 for all subscales except social well‐being), and shorter survival times (P < 0.001). Conclusions The CSS is a simple and clinically applicable tool with excellent discrimination for classifying cachexia stages. This score is extremely useful for the clinical treatment and prognosis of cachexia and for designing clinical trials. PMID:29372594

  3. Clinical and Cost Implications of Universal Versus Locally Advanced-Stage and Advanced-Stage-Only Molecular Testing for Epidermal Growth Factor Receptor Mutations and Anaplastic Lymphoma Kinase Rearrangements in Non-Small Cell Lung Carcinoma: A Tertiary Academic Institution Experience.

    PubMed

    Sauter, Jennifer L; Butnor, Kelly J

    2016-04-01

    Although epidermal growth factor receptor (EGFR)- and anaplastic lymphoma kinase (ALK)-directed therapies are not approved for patients with early-stage non-small cell lung carcinoma (NSCLC), many institutions perform EGFR and ALK testing for all patients with NSCLC at the time of initial diagnosis. Current consensus guidelines recommend EGFR testing and suggest ALK testing at the time of initial diagnosis for patients with advanced disease. To examine the cost and clinical impact of EGFR and ALK testing of patients with early-stage NSCLC. Records from all patients with a diagnosis of NSCLC made on a nonresection specimen at our institution during a single calendar year (2012) were reviewed, and a cost analysis was performed. Of 133 total patients, 47 (35%) had early-stage (stage I or II) disease and 86 (65%) had locally advanced (stage III) or advanced (stage IV) disease at presentation. Eight of 47 patients with early-stage disease (17%) had progression/recurrence during 18 to 30 months of follow-up, 6 of 8 (75%) of whom had pathologic confirmation of progression/recurrence. The estimated additional cost of EGFR and ALK testing for all newly diagnosed patients with NSCLC at our institution is $75,200 per year, compared to testing only patients with locally advanced and advanced-stage disease. The cost of universal molecular testing of NSCLC is substantial. EGFR and ALK testing of patients with early-stage disease appears to have negligible clinical impact, as most patients do not have disease recurrence/progression. Those whose disease recurs/progresses typically undergo rebiopsy. Our findings do not support the practice of universal EGFR and ALK testing in NSCLC at the time of initial diagnosis.

  4. Staging laparoscopy improves treatment decision-making for advanced gastric cancer.

    PubMed

    Hu, Yan-Feng; Deng, Zhen-Wei; Liu, Hao; Mou, Ting-Yu; Chen, Tao; Lu, Xin; Wang, Da; Yu, Jiang; Li, Guo-Xin

    2016-02-07

    To evaluate the clinical value of staging laparoscopy in treatment decision-making for advanced gastric cancer (GC). Clinical data of 582 patients with advanced GC were retrospectively analyzed. All patients underwent staging laparoscopy. The strength of agreement between computed tomography (CT) stage, endoscopic ultrasound (EUS) stage, laparoscopic stage, and final stage were determined by weighted Kappa statistic (Kw). The number of patients with treatment decision-changes was counted. A χ(2) test was used to analyze the correlation between peritoneal metastasis or positive cytology and clinical characteristics. Among the 582 patients, the distributions of pathological T classifications were T2/3 (153, 26.3%), T4a (262, 45.0%), and T4b (167, 28.7%). Treatment plans for 211 (36.3%) patients were changed after staging laparoscopy was performed. Two (10.5%) of 19 patients in M1 regained the opportunity for potential radical resection by staging laparoscopy. Unnecessary laparotomy was avoided in 71 (12.2%) patients. The strength of agreement between preoperative T stage and final T stage was in almost perfect agreement (Kw = 0.838; 95% confidence interval (CI): 0.803-0.872; P < 0.05) for staging laparoscopy; compared with CT and EUS, which was in fair agreement. The strength of agreement between preoperative M stage and final M stage was in almost perfect agreement (Kw = 0.990; 95% CI: 0.977-1.000; P < 0.05) for staging laparoscopy; compared with CT, which was in slight agreement. Multivariate analysis revealed that tumor size (≥ 40 mm), depth of tumor invasion (T4b), and Borrmann type (III or IV) were significantly correlated with either peritoneal metastasis or positive cytology. The best performance in diagnosing P-positive was obtained when two or three risk factors existed. Staging laparoscopy can improve treatment decision-making for advanced GC and decrease unnecessary exploratory laparotomy.

  5. MRI helps depict clinically undetectable risk factors in advanced stage retinoblastomas.

    PubMed

    Galluzzi, Paolo; Hadjistilianou, Theodora; Cerase, Alfonso; Toti, Paolo; Leonini, Sara; Bracco, Sandra; de Francesco, Sonia; Galimberti, Daniela; Balducci, Donatella; Piu, Pietro; Monti, Lucia; Bellini, Matteo; Caini, Mauro; Rossi, Alessandro

    2015-02-01

    This study compared high-resolution MRI with histology in advanced stage retinoblastomas in which ophthalmoscopy and ultrasonography did not give an exhaustive depiction of the tumour and/or its extension. MRI of orbits and head in 28 retinoblastoma patients (28 eyes) treated with primary enucleation were evaluated. Iris neoangiogenesis, infiltrations of optic nerve, choroid, anterior segment and sclera suspected at MR and histology were compared. Abnormal anterior segment enhancement (AASE) was also correlated with histologically proven infiltrations. Brain images were also evaluated. Significant values were obtained for: prelaminar optic nerve (ON) sensitivity (0.88), positive predictive value (PPV) (0.75) and negative predictive value (NPV) (0.71); post-laminar ON sensitivity (0.50), specificity (0.83), PPV (0.50) and NPV (0.83); overall choroid sensitivity (0.82), and massive choroid NPV (0.69); scleral specificity (1), and NPV (1). AASE correlated with iris neoangiogenesis in 14 out of 19 eyes, and showed significant values for: overall ON PPV (0.65), prelaminar ON sensitivity (0.65), and PPV (0.61), post-laminar ON NPV (0.64); overall choroid sensitivity (0.77), PPV (0.59) and NPV (0.73); scleral NPV (0.83); anterior segment sensitivity (1), and NPV (1). Odds ratios (OR) and accuracy were significant in scleral and prelaminar optic nerve infiltration. Brain examination was unremarkable in all cases. High-resolution MRI may add important findings to clinical evaluation of advanced stage retinoblastomas. © The Author(s) 2015 Reprints and permissions:]br]sagepub.co.uk/journalsPermissions.nav.

  6. EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

    PubMed

    Pi, Can; Xu, Chong-Rui; Zhang, Ming-Feng; Peng, Xiao-Xiao; Wei, Xue-Wu; Gao, Xing; Yan, Hong-Hong; Zhou, Qing

    2018-05-02

    EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear. We retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA-IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition. A total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early-stage and 949 to the advanced-stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced-stage group (P < 0.001). The total EGFR mutation rate in the early-stage group was similar to that in the advanced-stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early-stage and advanced-stage groups. Early-stage and advanced-stage groups exhibited the same EGFR mutation frequencies and types. © 2018 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

  7. [Clinical Advanced in Early-stage ALK-positive Non-small Cell Lung Cancer Patients].

    PubMed

    Gao, Qiongqiong; Jiang, Xiangli; Huang, Chun

    2017-02-20

    Lung cancer is the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with the majority of the cases diagnosed at the advanced stage. Molecular targeted therapy is becoming the focus attention for advanced NSCLC. Echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene (EML4-ALK) is among the most common molecular targets of NSCLC; its specific small-molecule tyrosine kinase inhibitors (TKIs) are approved for use in advanced NSCLC cases of ALK-positive. However, the influence of EML4-ALK fusion gene on the outcome of early-stage NSCLC cases and the necessity of application of TKIs for early-stage ALK-positive NSCLC patients are still uncertain. In this paper, we summarized the progression of testing methods for ALK-positive NSCLC patients as well as clinicopathological implication, outcome, and necessity of application of TKIs for early-stage ALK-positive NSCLC patients.

  8. Advanced Hepatocellular Carcinoma: Which Staging Systems Best Predict Prognosis?

    PubMed Central

    Huitzil-Melendez, Fidel-David; Capanu, Marinela; O'Reilly, Eileen M.; Duffy, Austin; Gansukh, Bolorsukh; Saltz, Leonard L.; Abou-Alfa, Ghassan K.

    2010-01-01

    Purpose The purpose of cancer staging systems is to accurately predict patient prognosis. The outcome of advanced hepatocellular carcinoma (HCC) depends on both the cancer stage and the extent of liver dysfunction. Many staging systems that include both aspects have been developed. It remains unknown, however, which of these systems is optimal for predicting patient survival. Patients and Methods Patients with advanced HCC treated over a 5-year period at Memorial Sloan-Kettering Cancer Center were identified from an electronic medical record database. Patients with sufficient data for utilization in all staging systems were included. TNM sixth edition, Okuda, Barcelona Clinic Liver Cancer (BCLC), Cancer of the Liver Italian Program (CLIP), Chinese University Prognostic Index (CUPI), Japan Integrated Staging (JIS), and Groupe d'Etude et de Traitement du Carcinome Hepatocellulaire (GETCH) systems were ranked on the basis of their accuracy at predicting survival by using concordance index (c-index). Other independent prognostic variables were also identified. Results Overall, 187 eligible patients were identified and were staged by using the seven staging systems. CLIP, CUPI, and GETCH were the three top-ranking staging systems. BCLC and TNM sixth edition lacked any meaningful prognostic discrimination. Performance status, AST, abdominal pain, and esophageal varices improved the discriminatory ability of CLIP. Conclusion In our selected patient population, CLIP, CUPI, and GETCH were the most informative staging systems in predicting survival in patients with advanced HCC. Prospective validation is required to determine if they can be accurately used to stratify patients in clinical trials and to direct the appropriate need for systemic therapy versus best supportive care. BCLC and TNM sixth edition were not helpful in predicting survival outcome, and their use is not supported by our data. PMID:20458042

  9. Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers

    PubMed Central

    Blakely, Collin M.; Watkins, Thomas B.K.; Wu, Wei; Gini, Beatrice; Chabon, Jacob J.; McCoach, Caroline E.; McGranahan, Nicholas; Wilson, Gareth A.; Birkbak, Nicolai J.; Olivas, Victor R.; Rotow, Julia; Maynard, Ashley; Wang, Victoria; Gubens, Matthew A.; Banks, Kimberly C.; Lanman, Richard B.; Caulin, Aleah F.; John, John St.; Cordero, Anibal R.; Giannikopoulos, Petros; Simmons, Andrew D.; Mack, Philip C.; Gandara, David R.; Husain, Hatim; Doebele, Robert C.; Riess, Jonathan W.; Diehn, Maximilian; Swanton, Charles; Bivona, Trever G.

    2017-01-01

    A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant protein product (e.g. EGFR inhibitor treatment in EGFR-mutant lung cancers). However, genetically-driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1122 EGFR-mutant lung cancer cell-free DNA samples and whole exome analysis of seven longitudinally collected tumor samples from an EGFR-mutant lung cancer patient, we identify critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers. We define new pathways limiting EGFR inhibitor response, including WNT/β-catenin and cell cycle gene (e.g. CDK4, CDK6) alterations. Tumor genomic complexity increases with EGFR inhibitor treatment and co-occurring alterations in CTNNB1, and PIK3CA exhibit non-redundant functions that cooperatively promote tumor metastasis or limit EGFR inhibitor response. This study challenges the prevailing single-gene driver oncogene view and links clinical outcomes to co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancer patients. PMID:29106415

  10. Worldwide Esophageal Cancer Collaboration: clinical staging data.

    PubMed

    Rice, T W; Apperson-Hansen, C; DiPaola, L M; Semple, M E; Lerut, T E M R; Orringer, M B; Chen, L-Q; Hofstetter, W L; Smithers, B M; Rusch, V W; Wijnhoven, B P L; Chen, K N; Davies, A R; D'Journo, X B; Kesler, K A; Luketich, J D; Ferguson, M K; Räsänen, J V; van Hillegersberg, R; Fang, W; Durand, L; Allum, W H; Cecconello, I; Cerfolio, R J; Pera, M; Griffin, S M; Burger, R; Liu, J-F; Allen, M S; Law, S; Watson, T J; Darling, G E; Scott, W J; Duranceau, A; Denlinger, C E; Schipper, P H; Ishwaran, H; Blackstone, E H

    2016-10-01

    To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data-simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival-for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5-25 mg/kg 2 , 47%), little weight loss (2.4 ± 7.8 kg), 0-1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cN0 (44%), cM0 (95%), and cG2-G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cN0 versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection. © 2016 International Society for Diseases of the Esophagus.

  11. Worldwide Esophageal Cancer Collaboration: clinical staging data

    PubMed Central

    Rice, T. W.; Apperson-Hansen, C.; DiPaola, L. M.; Semple, M. E.; Lerut, T. E. M. R.; Orringer, M. B.; Chen, L.-Q.; Hofstetter, W. L.; Smithers, B. M.; Rusch, V. W.; Wijnhoven, B. P. L.; Chen, K. N.; Davies, A. R.; D’Journo, X. B.; Kesler, K. A.; Luketich, J. D.; Ferguson, M. K.; Räsänen, J. V.; van Hillegersberg, R.; Fang, W.; Durand, L.; Allum, W. H.; Cecconello, I.; Cerfolio, R. J.; Pera, M.; Griffin, S. M.; Burger, R.; Liu, J.-F; Allen, M. S.; Law, S.; Watson, T. J.; Darling, G. E.; Scott, W. J.; Duranceau, A.; Denlinger, C. E.; Schipper, P. H.; Ishwaran, H.; Blackstone, E. H.

    2017-01-01

    SUMMARY To address uncertainty of whether clinical stage groupings (cTNM) for esophageal cancer share prognostic implications with pathologic groupings after esophagectomy alone (pTNM), we report data—simple descriptions of patient characteristics, cancer categories, and non-risk-adjusted survival—for clinically staged patients from the Worldwide Esophageal Cancer Collaboration (WECC). Thirty-three institutions from six continents submitted data using variables with standard definitions: demographics, comorbidities, clinical cancer categories, and all-cause mortality from first management decision. Of 22,123 clinically staged patients, 8,156 had squamous cell carcinoma, 13,814 adenocarcinoma, 116 adenosquamous carcinoma, and 37 undifferentiated carcinoma. Patients were older (62 years) men (80%) with normal body mass index (18.5–25 mg/kg2, 47%), little weight loss (2.4 ± 7.8 kg), 0–1 ECOG performance status (67%), and history of smoking (67%). Cancers were cT1 (12%), cT2 (22%), cT3 (56%), cNO (44%), cMO (95%), and cG2–G3 (89%); most involved the distal esophagus (73%). Non-risk-adjusted survival for squamous cell carcinoma was not distinctive for early cT or cN; for adenocarcinoma, it was distinctive for early versus advanced cT and for cNO versus cN+. Patients with early cancers had worse survival and those with advanced cancers better survival than expected from equivalent pathologic categories based on prior WECC pathologic data. Thus, clinical and pathologic categories do not share prognostic implications. This makes clinically based treatment decisions difficult and pre-treatment prognostication inaccurate. These data will be the basis for the 8th edition cancer staging manuals following risk adjustment for patient characteristics, cancer categories, and treatment characteristics and should direct 9th edition data collection. PMID:27731549

  12. Pilot study of psilocybin treatment for anxiety in patients with advanced-stage cancer.

    PubMed

    Grob, Charles S; Danforth, Alicia L; Chopra, Gurpreet S; Hagerty, Marycie; McKay, Charles R; Halberstadt, Adam L; Greer, George R

    2011-01-01

    Researchers conducted extensive investigations of hallucinogens in the 1950s and 1960s. By the early 1970s, however, political and cultural pressures forced the cessation of all projects. This investigation reexamines a potentially promising clinical application of hallucinogens in the treatment of anxiety reactive to advanced-stage cancer. To explore the safety and efficacy of psilocybin in patients with advanced-stage cancer and reactive anxiety. A double-blind, placebo-controlled study of patients with advanced-stage cancer and anxiety, with subjects acting as their own control, using a moderate dose (0.2 mg/kg) of psilocybin. A clinical research unit within a large public sector academic medical center. Twelve adults with advanced-stage cancer and anxiety. In addition to monitoring safety and subjective experience before and during experimental treatment sessions, follow-up data including results from the Beck Depression Inventory, Profile of Mood States, and State-Trait Anxiety Inventory were collected unblinded for 6 months after treatment. Safe physiological and psychological responses were documented during treatment sessions. There were no clinically significant adverse events with psilocybin. The State-Trait Anxiety Inventory trait anxiety subscale demonstrated a significant reduction in anxiety at 1 and 3 months after treatment. The Beck Depression Inventory revealed an improvement of mood that reached significance at 6 months; the Profile of Mood States identified mood improvement after treatment with psilocybin that approached but did not reach significance. This study established the feasibility and safety of administering moderate doses of psilocybin to patients with advanced-stage cancer and anxiety. Some of the data revealed a positive trend toward improved mood and anxiety. These results support the need for more research in this long-neglected field. clinicaltrials.gov Identifier: NCT00302744.

  13. Clinical staging of Fibrodysplasia Ossificans Progressiva (FOP).

    PubMed

    Pignolo, Robert J; Kaplan, Frederick S

    2018-04-01

    Fibrodyplasia ossificans progressiva (FOP) is an ultra-rare genetic condition of heterotopic ossification (HO) that results in progressive loss of joint function, ultimately rendering movement impossible. Death is most commonly the result of thoracic insufficiency syndrome, or complications related to recurrent respiratory infections. There are no current treatments for FOP, but early and emerging clinical trials offer hope for this devastating disease. With the recent reporting of a comprehensive global natural history study, scales to assess joint dysfunction, and a more accurate prediction of joint survival, it is now possible to construct a conceptual framework for the clinical staging of FOP. Based on assessment of FOP features in seven areas, it is possible to assign five clinical stages. FOP features include flare-up activity, body regions affected, thoracic insufficiency, other complications, activities of daily living (ADLs), ambulatory status, and the cumulative joint involvement scale (CAJIS) score. Assessments of these features assign an individual with FOP to early/mild, moderate, severe, profound, or late-stage disease. These criteria seek to be flexible enough to be used by clinicians without reliance on advanced imaging or specialized testing, as well as by investigators involved in research or clinical trial studies who would have these tools available. These staging measures for FOP assess the influence of HO and accelerated joint dysfunction (due to congenital abnormalities) on the ability to perform common functional activities, and thus a delay or lack of progression from one stage to the next represents the ultimate test of efficacy for drug trials. This framework will serve both as a prediction tool for FOP progression as well as a critical opportunity to substantiate therapeutic interventions. The staging system proposed here will permit an accurate assessment of severity to appropriately develop or revise clinical plans of care, define

  14. [Advanced Parkinson's disease: clinical characteristics and treatment (part 1)].

    PubMed

    Kulisevsky, J; Luquin, M R; Arbelo, J M; Burguera, J A; Carrillo, F; Castro, A; Chacón, J; García-Ruiz, P J; Lezcano, E; Mir, P; Martinez-Castrillo, J C; Martínez-Torres, I; Puente, V; Sesar, A; Valldeoriola-Serra, F; Yañez, R

    2013-10-01

    A large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced Parkinson's disease. To define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease. This consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL). Severe motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  15. Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals.

    PubMed

    Rice, Thomas W; Ishwaran, Hemant; Blackstone, Eugene H; Hofstetter, Wayne L; Kelsen, David P; Apperson-Hansen, Carolyn

    2016-11-01

    We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was "pinched," with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. © 2016 International Society for Diseases of the Esophagus.

  16. Recommendations for clinical staging (cTNM) of cancer of the esophagus and esophagogastric junction for the 8th edition AJCC/UICC staging manuals

    PubMed Central

    Rice, Thomas W.; Ishwaran, Hemant; Blackstone, Eugene H.; Hofstetter, Wayne L.; Kelsen, David P.; Apperson-Hansen, Carolyn

    2017-01-01

    SUMMARY We report analytic and consensus processes that produced recommendations for clinical stage groups (cTNM) of esophageal and esophagogastric junction cancer for the AJCC/UICC cancer staging manuals, 8th edition. The Worldwide Esophageal Cancer Collaboration (WECC) provided data on 22,123 clinically staged patients with epithelial esophageal cancers. Risk-adjusted survival for each patient was developed using random survival forest analysis from which (1) data-driven clinical stage groups were identified wherein survival decreased monotonically and was distinctive between and homogeneous within groups and (2) data-driven anatomic clinical stage groups based only on cTNM. The AJCC Upper GI Task Force, by smoothing, simplifying, expanding, and assessing clinical applicability, produced (3) consensus clinical stage groups. Compared with pTNM, cTNM survival was “pinched,” with poorer survival for early cStage groups and better survival for advanced ones. Histologic grade was distinctive for data-driven grouping of cT2N0M0 squamous cell carcinoma (SCC) and cT1-2N0M0 adenocarcinoma, but consensus removed it. Grouping was different by histopathologic cell type. For SCC, cN0-1 was distinctive for cT3 but not cT1-2, and consensus removed cT4 subclassification and added subgroups 0, IVA, and IVB. For adenocarcinoma, N0-1 was distinctive for cT1-2 but not cT3-4a, cStage II subgrouping was necessary (T1N1M0 [IIA] and T2N0M0 [IIB]), advanced cancers cT3-4aN0-1M0 plus cT2N1M0 comprised cStage III, and consensus added subgroups 0, IVA, and IVB. Treatment decisions require accurate cStage, which differs from pStage. Understaging and overstaging are problematic, and additional factors, such as grade, may facilitate treatment decisions and prognostication until clinical staging techniques are uniformly applied and improved. PMID:27905171

  17. Nomogram for suboptimal cytoreduction at primary surgery for advanced stage ovarian cancer.

    PubMed

    Gerestein, Cornelis G; Eijkemans, Marinus J; Bakker, Jeanette; Elgersma, Otto E; van der Burg, Maria E L; Kooi, Geertruida S; Burger, Curt W

    2011-11-01

    Maximal cytoreduction to minimal residual tumor is the most important determinant of prognosis in patients with advanced stage epithelial ovarian cancer (EOC). Preoperative prediction of suboptimal cytoreduction, defined as residual tumor >1 cm, could guide treatment decisions and improve counseling. The objective of this study was to identify predictive computed tomographic (CT) scan and clinical parameters for suboptimal cytoreduction at primary cytoreductive surgery for advanced stage EOC and to generate a nomogram with the identified parameters, which would be easy to use in daily clinical practice. Between October 2005 and December 2008, all patients with primary surgery for suspected advanced stage EOC at six participating teaching hospitals in the South Western part of the Netherlands entered the study protocol. To investigate independent predictors of suboptimal cytoreduction, a Cox proportional hazard model with backward stepwise elimination was utilized. One hundred and fifteen patients with FIGO stage III/IV EOC entered the study protocol. Optimal cytoreduction was achieved in 52 (45%) patients. A suboptimal cytoreduction was predicted by preoperative blood platelet count (p=0.1990; odds ratio (OR)=1.002), diffuse peritoneal thickening (DPT) (p=0.0074; OR=3.021), and presence of ascites on at least two thirds of CT scan slices (p=0.0385; OR=2.294) with a for-optimism corrected c-statistic of 0.67. Suboptimal cytoreduction was predicted by preoperative platelet count, DPT and presence of ascites. The generated nomogram can, after external validation, be used to estimate surgical outcome and to identify those patients, who might benefit from alternative treatment approaches.

  18. The advanced-stage therapy group.

    PubMed

    Berman, A; Weinberg, H

    1998-10-01

    Many authors describe a stage of maturity in the development of groups, but each highlights a different dimension. This article describes the characteristics of the advanced stage and the main axes along which it develops (internalization and containment, symbolization, self and self-other development, differentiation and individuation). It also offers a conceptual explanation for these developments and attempts to identify the conditions necessary for the emergence of this stage of maturity. An understanding of this stage and the conditions required for its development can be used by the group leader as a compass to help him or her navigate the group toward this objective.

  19. Novel clinical staging for patients with end-stage gastrointestinal carcinoma.

    PubMed

    Yasuda, Naokuni; Nakashima, Osamu; Ohnaka, Toru; Kamisaka, Koji; Tsunoda, Akira; Kusano, Mitsuo

    2006-01-01

    We created a new clinical staging system for end-stage gastrointestinal (GI) carcinoma to clarify the therapeutic goals for these patients. Data were obtained from a retrospective review of medical charts. Based on daily clinical observation of 144 patients with end-stage GI carcinoma, we classified the terminal stages as A, B, C, and D. The mean durations of terminal stages A, B, C, and D were 19, 16.6, 6.6, and 1.8 days, respectively, in patients with end-stage gastric cancer and 28.5, 9.1, 5.4, and 1.9 days, respectively, in patients with colorectal cancer. Moreover, 88.0% of patients with gastric carcinoma and 82.6% of patients with colorectal carcinoma passed through terminal stages A, B, C, and D sequentially. The patients in terminal stage B experienced temporary relief of symptoms, but those in terminal stage C did not (P < 0.05). These terminal stages can easily be judged by clinical observation and may be an effective new tool with which to manage patients with end-stage GI carcinoma and their families.

  20. Effect of hydronephrosis on survival in advanced stage cervical cancer.

    PubMed

    Goklu, Mehmet Rıfat; Seckin, Kerem Doga; Togrul, Cihan; Goklu, Yasemin; Tahaoglu, Ali Emre; Oz, Murat; Ertas, Ibrahim Egemen

    2015-01-01

    Hydronephrosis is frequently encountered in advanced stage cervical cancers, and may be associated with mortality. In the present study, we aimed to demonstrate the effect of hydronephrosis on survival in patients with inoperable advanced stage cervical cancer. The study data were acquired by retrospective analysis of the patient records belonging to 165 women with FIGO (International Federation of Gynecology and Obstetrics) stage-IIIB or more advanced cervical cancer, which were not surgical candidates. Parameters including patient age, pathological diagnosis, disease stage, pelvic sidewall extension, presence of hydronephrosis and administration of chemoradiation were analyzed. Further, the effects of these variables on survival were assessed. P values less than 0.05 were considered statistically significant. The distribution of the study patients according to disease stage was as follows: 131 (79.4%) had stage-IIIB, 18 (10.9%) had stage-IVB and 16 (% 9.7) patients had stage-IVA disease. Hydronephrosis was not evident in 91 (55.2%) of these patients, whereas 41 (24.8%) had unilateral and 33 (20%) patients had bilateral hydronephrosis. When compared to mean survival in patients who did not have hydronephrosis, survival was significantly shortened in patients who had bilateral and unilateral hydronephrosis (p<0.05). There was no significant survival difference between patients with unilateral and bilateral hydronephrosis (p>0.05). Although patient age, pathological type, pelvic involvement, and chemotherapy treatment rates were similar (p>0.05), radiotherapy requirement rate and disease stage were significantly different among the study groups (p<0.05). Hydronephrosis was found to be a significant predictor of poor survival in patients with advanced stage cervical cancer, irrespective of unilateral or bilateral involvement.While waiting for future studies with larger sample sizes, we believe that the FIGO stages in advanced cervical cancer could further be

  1. Bioinformatics Analysis Reveals Distinct Molecular Characteristics of Hepatitis B-Related Hepatocellular Carcinomas from Very Early to Advanced Barcelona Clinic Liver Cancer Stages.

    PubMed

    Kong, Fan-Yun; Wei, Xiao; Zhou, Kai; Hu, Wei; Kou, Yan-Bo; You, Hong-Juan; Liu, Xiao-Mei; Zheng, Kui-Yang; Tang, Ren-Xian

    2016-01-01

    Hepatocellular carcinoma (HCC)is the fifth most common malignancy associated with high mortality. One of the risk factors for HCC is chronic hepatitis B virus (HBV) infection. The treatment strategy for the disease is dependent on the stage of HCC, and the Barcelona clinic liver cancer (BCLC) staging system is used in most HCC cases. However, the molecular characteristics of HBV-related HCC in different BCLC stages are still unknown. Using GSE14520 microarray data from HBV-related HCC cases with BCLC stages from 0 (very early stage) to C (advanced stage) in the gene expression omnibus (GEO) database, differentially expressed genes (DEGs), including common DEGs and unique DEGs in different BCLC stages, were identified. These DEGs were located on different chromosomes. The molecular functions and biology pathways of DEGs were identified by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and the interactome networks of DEGs were constructed using the NetVenn online tool. The results revealed that both common DEGs and stage-specific DEGs were associated with various molecular functions and were involved in special biological pathways. In addition, several hub genes were found in the interactome networks of DEGs. The identified DEGs and hub genes promote our understanding of the molecular mechanisms underlying the development of HBV-related HCC through the different BCLC stages, and might be used as staging biomarkers or molecular targets for the treatment of HCC with HBV infection.

  2. 8th edition AJCC/UICC staging of cancers of the esophagus and esophagogastric junction: application to clinical practice.

    PubMed

    Rice, Thomas W; Patil, Deepa T; Blackstone, Eugene H

    2017-03-01

    The 8th edition of the American Joint Committee on Cancer (AJCC) staging of epithelial cancers of the esophagus and esophagogastric junction (EGJ) presents separate classifications for clinical (cTNM), pathologic (pTNM), and postneoadjuvant (ypTNM) stage groups. Histopathologic cell type markedly affects survival of clinically and pathologically staged patients, requiring separate groupings for each cell type, but ypTNM groupings are identical for both cell types. Clinical categories, typically obtained by imaging with minimal histologic information, are limited by resolution of each method. Strengths and shortcomings of clinical staging methods should be recognized. Complementary cytology or histopathology findings may augment imaging and aid initial treatment decision-making. However, prognostication using clinical stage groups remains coarse and inaccurate compared with pTNM. Pathologic staging is losing its relevance for advanced-stage cancer as neoadjuvant therapy replaces esophagectomy alone. However, it remains relevant for early-stage cancers and as a staging and survival reference point. Although pathologic stage could facilitate decision-making, its use to direct postoperative adjuvant therapy awaits more effective treatment. Prognostication using pathologic stage groups is the most refined of all classifications. Postneoadjuvant staging (ypTNM) is introduced by the AJCC but not adopted by the Union for International Cancer Control (UICC). Drivers of this addition include absence of equivalent pathologic (pTNM) categories for categories peculiar to the postneoadjuvant state (ypT0N0-3M0 and ypTisN0-3M0), dissimilar stage group compositions, and markedly different survival profiles. Thus, prognostication is specific for patients undergoing neoadjuvant therapy. The role of ypTNM classification in additional treatment decision-making is currently limited. Precision cancer care advances are necessary for this information to be clinically useful.

  3. Treatment with DAV for advanced-stage hemangiosarcoma in dogs.

    PubMed

    Dervisis, Nikolaos G; Dominguez, Pedro A; Newman, Rebecca G; Cadile, Casey D; Kitchell, Barbara E

    2011-01-01

    Hemangiosarcoma (HSA) is an aggressive disease that is fairly common in the dog. The authors evaluated a doxorubicin, dacarbazine, and vincristine (DAV) combination protocol in dogs with nonresectable stage II and stage III HSA. Twenty-four dogs were enrolled in this prospective, phase 2 study. Doxorubicin and dacarbazine were administered on day 1 while vincristine was administered on days 8 and 15. The protocol was repeated every 21 days for a maximum of six cycles or until disease progression. Toxicity and efficacy were assessed by clinical and laboratory evaluation and by questionnaires completed by the owners. Of the 24 included dogs, 19 were evaluable for response. The response rate (including five complete responses and four partial responses) was 47.4%. Median time to tumor progression was 101 days and median overall survival was 125 days. Significant toxicities were noted, including 41 high-grade hematologic and 12 high-grade gastrointestinal toxic events. Five dogs discontinued treatment due to chemotherapy-related toxicities, but no treatment-related deaths occurred. Multivariate analysis identified patient age (relative risk [RR], 2.3, P=0.049) to be negatively associated with time to progression whereas dacarbazine dose reductions (RR, 0.06, P=0.031) were positively associated with time to progression. Dacarbazine dose reduction was the sole factor positively associated with overall survival (RR, 0.28, P=0.015). In conclusion, the DAV combination appears to offer clinical responses and may prolong survival in dogs with advanced-stage HSA.

  4. Health system delay and its effect on clinical stage of breast cancer: Multicenter study.

    PubMed

    Unger-Saldaña, Karla; Miranda, Alfonso; Zarco-Espinosa, Gelasio; Mainero-Ratchelous, Fernando; Bargalló-Rocha, Enrique; Miguel Lázaro-León, Jesús

    2015-07-01

    The objective of this study was to determine the correlation between health system delay and clinical disease stage in patients with breast cancer. This was a cross-sectional study of 886 patients who were referred to 4 of the largest public cancer hospitals in Mexico City for the evaluation of a probable breast cancer. Data on time intervals, sociodemographic factors, and clinical stage at diagnosis were retrieved. A logistic regression model was used to estimate the average marginal effects of delay on the probability of being diagnosed with advanced breast cancer (stages III and IV). The median time between problem identification and the beginning of treatment was 7 months. The subinterval with the largest delay was that between the first medical consultation and diagnosis (median, 4 months). Only 15% of the patients who had cancer were diagnosed with stage 0 and I disease, and 48% were diagnosed with stage III and IV disease. Multivariate analyses confirmed independent correlations for the means of problem identification, patient delay, health system delay, and age with a higher probability that patients would begin cancer treatment in an advanced stage. In the sample studied, the majority of patients with breast cancer began treatment after a delay. Both patient delays and provider delays were associated with advanced disease. Research aimed at identifying specific access barriers to medical services is much needed to guide the design of tailored health policies that go beyond the promotion of breast care awareness and screening participation to include improvements in health services that facilitate access to timely diagnosis and treatment. © 2015 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

  5. SPIRIT advance care planning intervention in early stage dementias: An NIH stage I behavioral intervention development trial.

    PubMed

    Song, Mi-Kyung; Ward, Sandra E; Hepburn, Kenneth; Paul, Sudeshna; Shah, Raj C; Morhardt, Darby J

    2018-06-02

    People in the early stages of Alzheimer's disease and related dementias (ADRD) are encouraged to engage in advance care planning (ACP) while they are still competent to appoint a surrogate decision maker and meaningfully participate in ACP discussions with the surrogate. In this NIH Stage I behavioral intervention development trial, we will adapt and test an efficacious ACP intervention, SPIRIT (Sharing Patient's Illness Representation to Increase Trust), with people with mild dementia and their surrogates to promote open, honest discussions while such discussions about end-of-life care are possible. We will first adapt SPIRIT (in person) to target people with mild dementia and their surrogates through a process of modification-pretesting-refinement using stakeholders (persons with mild dementia, family caregivers, and clinicians) and experts, including adapting the delivery mode to interactive web-based videoconference format (SPIRIT-remote). Then in a 3-group RCT with 120 patient-surrogate dyads, we will evaluate the feasibility and acceptability of SPIRIT in-person and SPIRIT remote, and preliminary efficacy of SPIRIT compared to usual care on preparedness outcomes for end-of-life decision making (dyad congruence on goals of care, patient decisional conflict, and surrogate decision-making confidence) shortly after the intervention. This Stage I research of SPIRIT will generate valuable insights regarding how to improve ACP for people with mild dementia who will progress to an advanced stage of the disease in the foreseeable future. ClinicalTrials.gov NCT03311711, Registered 10/12/2017. Copyright © 2018. Published by Elsevier Inc.

  6. BH3-only protein Bim predicts advanced stage of cutaneous melanoma.

    PubMed

    Gambichler, T; Rooms, I; Scholl, L; Stockfleth, E; Stücker, M; Sand, M

    2016-11-01

    Bim having strong pro-apoptotic effects belongs to the BH3-only proteins of the Bcl-2 protein family and contributes to survival pathways in cancer cells. We aimed to investigate Bim protein expression in cutaneous melanoma (CM). Bim protein expression was assessed by immunohistochemistry in primary and metastatic melanomas and correlated with clinical and histopathological features. The Bim immunoreactivity score of the primary melanomas investigated (4.6 ± 1.5) was significantly (P < 0.0001) higher than that observed in metastases (2.8 ± 1.1). Low Bim expression was significantly associated with primary nodular melanoma type (P = 0.005). Moreover, Bim expression was significantly inversely correlated with tumour thickness (r = -0.36; P = 0.0035), advanced stage of disease (stage III and IV; r = -0.60; P < 0.0001), disease relapse (r = -0.18; P = 0.034) and disease-related death (r = -0.19; P = 0.026). Advanced stage of disease was independently predicted by low Bim expression (P = 0.0010, odds ratio: 0.22, 95% CI: 0.10-0.56) on multivariate analysis; however, Bim was not shown to be an independent predictor for disease relapse (P = 0.40) and disease-related death (P = 0.77). Our data demonstrate that Bim protein expression is significantly inversely correlated with melanoma features that are associated with worse prognosis. We have shown that Bim protein expression in CM is an independent predictor for advanced disease confirming that this pro-apoptotic BH3-only protein might be a potent biomarker and promising therapeutic target. © 2016 European Academy of Dermatology and Venereology.

  7. Management of advanced pancreatic cancer in daily clinical practice.

    PubMed

    Giuliani, Jacopo; Piacentini, Paolo; Bonetti, Andrea

    2016-01-01

    The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.

  8. To evaluate disparity between clinical and pathological tumor-node-metastasis staging in oral cavity squamous cell carcinoma patients and its impact on overall survival: An institutional study.

    PubMed

    Gupta, Karan; Panda, Naresh K; Bakshi, Jaimanti; Das, Ashim

    2015-01-01

    Accurate clinical staging is important for patient counseling, treatment planning, prognostication, and rational design of clinical trials. In head and neck squamous cell carcinoma, discrepancy between clinical and pathological staging has been reported. To evaluate any disparity between clinical and pathological tumor-node-metastasis (TNM) staging in oral cavity squamous cell carcinoma (OCSCC) patients and any impact of the same on survival. Retrospective chart review from year 2007 to 2013, at a tertiary care center. All survival analyses were performed using SPSS for Windows version 15 (Chicago, IL, USA). Disease-free survival curves were generated using Kaplan-Meier algorithm. One hundred and twenty-seven patients with OCSCC were analyzed. Seventy-nine (62.2%) were males and 48 (37.8%) females with a mean age at presentation 43.6 years (29-79 years). The highest congruence between clinical and pathological T-staging seen for clinical stage T1 and T4 at 76.9% and 73.4% with pathological T-stage. Similarly, the highest congruence between clinical and pathological N-stage seen for clinical N0 and N3 at 86.4% and 91.7% with pathological N-stage. Of clinically early stage patients, 67.5% remained early stage, and 32.5% were upstaged to advanced stage following pathological analysis. Of the clinically advanced stage patients, 75% remained advanced, and 25% were pathologically downstaged. This staging discrepancy did not significantly alter the survival. Some disparity exists in clinical and pathological TNM staging of OCSCC, which could affect treatment planning and survival of patients. Hence, more unified and even system of staging for the disease is required for proper decision-making.

  9. Tumor angiogenesis in advanced stage ovarian carcinoma.

    PubMed

    Hollingsworth, H C; Kohn, E C; Steinberg, S M; Rothenberg, M L; Merino, M J

    1995-07-01

    Tumor angiogenesis has been found to have prognostic significance in many tumor types for predicting an increased risk of metastasis. We assessed tumor vascularity in 43 cases of advanced stage (International Federation of Gynecologists and Obstetricians stages III and IV) ovarian cancer by using the highly specific endothelial cell marker CD34. Microvessel counts and stage were associated with disease-free survival and with overall survival by Kaplan-Meier analysis. The plots show that higher stage, higher average vessel count at 200x (200x avg) and 400x (400x avg) magnification and highest vessel count at 400x (400x high) magnification confer a worse prognosis for disease-free survival. Average vessel count of less than 16 (400x avg, P2 = 0.01) and less than 45 (200x avg, P2 = 0.026) suggested a better survival. Similarly, a high vessel count of less than 20 (400x high, P2 = 0.019) conferred a better survival as well. The plots suggest that higher stage, higher average vessel count at 200x and 400x, and highest vessel count at 200x and 400x show a trend to worse overall survival as well. With the Cox proportional hazards model, stage was the best predictor of overall survival, however, the average microvessel count at 400x was found to be the best predictor of disease-free survival. These results suggest that analysis of neovascularization in advanced stage ovarian cancer may be a useful prognostic factor.

  10. Subcortical volumetric differences between clinical stages of young people with affective and psychotic disorders.

    PubMed

    Eggins, Peta S; Hatton, Sean N; Hermens, Daniel F; Hickie, Ian B; Lagopoulos, Jim

    2018-01-30

    The aim of this study was to investigate differences in subcortical and hippocampal volumes between healthy controls, young people at an early stage of affective and psychotic disorders and those in more advanced stages, to identify markers associated with functional outcomes and illness severity. Young people presenting to youth mental health services with admixtures of depressive, manic and psychotic symptoms (n = 141), and healthy counterparts (n = 49), aged 18-25 were recruited. Participants underwent magnetic resonance imaging, clinical assessments and were rated as to their current clinical stage. Eighty-four patients were classified at the attenuated syndrome stage (Stage 1b) and 57 were classified as having discrete and persistent disorders (Stage 2+). Automated segmentation was performed using NeuroQuant® to determine volumes of subcortical and hippocampus structures which were compared between groups and correlated with clinical and functional outcomes. Compared to healthy controls, Stage 2+ patients showed significantly reduced right amygdala volumes. Whereas Stage 1b patients showed significantly reduced left caudate volumes compared to healthy controls. Smaller left caudate volume correlated with greater psychological distress and impaired functioning. This study shows a clinical application for an automated program to identify and track subcortical changes evident in young people with emerging psychopathology. Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.

  11. Expression signatures of early-stage and advanced medaka melanomas.

    PubMed

    Klotz, Barbara; Kneitz, Susanne; Regensburger, Martina; Hahn, Lena; Dannemann, Michael; Kelso, Janet; Nickel, Birgit; Lu, Yuan; Boswell, William; Postlethwait, John; Warren, Wesley; Kunz, Manfred; Walter, Ronald B; Schartl, Manfred

    2018-06-01

    Melanoma is one of the most aggressive tumors with a very low survival rate once metastasized. The incidence of newly detected cases increases every year suggesting the necessity of development and application of innovative treatment strategies. Human melanoma develops from melanocytes localized in the epidermis of the skin to malignant tumors because of deregulated effectors influencing several molecular pathways. Despite many advances in describing the molecular changes accompanying melanoma formation, many critical and clinically relevant molecular features of the transformed pigment cells and the underlying mechanisms are largely unknown. To contribute to a better understanding of the molecular processes of melanoma formation, we use a transgenic medaka melanoma model that is well suited for the investigation of melanoma tumor development because fish and human melanocytes are both localized in the epidermis. The purpose of our study was to gain insights into melanoma development from the first steps of tumor formation up to melanoma progression and to identify gene expression patterns that will be useful for monitoring treatment effects in drug screening approaches. Comparing transcriptomes from juvenile fish at the tumor initiating stage with nevi and advanced melanoma of adults, we identified stage specific expression signatures and pathways that are characteristic for the development of medaka melanoma, and are also found in human malignancies. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Pretreatment tables predicting pathologic stage of locally advanced prostate cancer.

    PubMed

    Joniau, Steven; Spahn, Martin; Briganti, Alberto; Gandaglia, Giorgio; Tombal, Bertrand; Tosco, Lorenzo; Marchioro, Giansilvio; Hsu, Chao-Yu; Walz, Jochen; Kneitz, Burkhard; Bader, Pia; Frohneberg, Detlef; Tizzani, Alessandro; Graefen, Markus; van Cangh, Paul; Karnes, R Jeffrey; Montorsi, Francesco; van Poppel, Hein; Gontero, Paolo

    2015-02-01

    Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. Retropubic RP and pelvic lymphadenectomy. Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

  13. "EXHALE": exercise as a strategy for rehabilitation in advanced stage lung cancer patients: a randomized clinical trial comparing the effects of 12 weeks supervised exercise intervention versus usual care for advanced stage lung cancer patients.

    PubMed

    Quist, Morten; Langer, Seppo W; Rørth, Mikael; Christensen, Karl Bang; Adamsen, Lis

    2013-10-14

    Lung cancer is the leading cause of cancer death in North America and Western Europe. Patients with lung cancer in general have reduced physical capacity, functional capacity, poor quality of life and increased levels of anxiety and depression. Intervention studies indicate that physical training can address these issues. However, there is a lack of decisive evidence regarding the effect of physical exercise in patients with advanced lung cancer. The aim of this study is to evaluate the effects of a twelve weeks, twice weekly program consisting of: supervised, structured training in a group of advanced lung cancer patients (cardiovascular and strength training, relaxation). A randomized controlled trial will test the effects of the exercise intervention in 216 patients with advanced lung cancer (non-small cell lung cancer (NSCLC) stage IIIb-IV and small cell lung cancer (SCLC) extensive disease (ED)). Primary outcome is maximal oxygen uptake (VO₂peak). Secondary outcomes are muscle strength (1RM), functional capacity (6MWD), lung capacity (Fev1) and patient reported outcome (including anxiety, depression (HADS) and quality of life (HRQOL)). The present randomized controlled study will provide data on the effectiveness of a supervised exercise intervention in patients receiving systemic therapy for advanced lung cancer. It is hoped that the intervention can improve physical capacity and functional level, during rehabilitation of cancer patients with complex symptom burden and help them to maintain independent function for as long as possible. http://ClinicalTrials.gov, NCT01881906.

  14. Liquid biopsy: A potential and promising diagnostic tool for advanced stage non-small cell lung cancer patients.

    PubMed

    Doval, D C; Deshpande, R; Dhabhar, B; Babu, K G; Prabhash, K; Chopra, R; Sripada, P V; Deshmukh, C; Suryavanshi, M

    2017-12-01

    More than 50% of non-small cell lung cancer (NSCLC) cases harbor an actionable mutation, and molecular testing at different intervals can help in personalized and targeted treatment. Core tissue biopsy and needle biopsy done at the time of diagnosis/disease progression are interventional, time-consuming and can affect the patients adversely. Noninterventional biomarker testing by liquid biopsy promises to revolutionize advanced stage cancer screening. The present report was formulated based on an expert panel meeting of renowned oncologists who gave their opinions for minimally invasive liquid biopsy to detect targetable molecular biomarkers in advanced NSCLC cases. An exhaustive literature search was done to support their recommendations. Clinical utility of minimally invasive liquid biopsy, for detection of molecular biomarkers in advanced stage NSCLC patients, was broadly discussed by the key opinion leaders.

  15. Retinopathy of prematurity: mutations in the Norrie disease gene and the risk of progression to advanced stages.

    PubMed

    Haider, M Z; Devarajan, L V; Al-Essa, M; Srivastva, B S; Kumar, H; Azad, R; Rashwan, N

    2001-04-01

    Retinopathy of prematurity (ROP) is a retinal vascular disease that occurs in infants with short gestational age and low birth weight and may lead to retinal detachment and blindness. Missense mutations in the Norrie disease (ND) gene have been associated with the risk of progression to advanced stages in cases of ROP from the US and also in clinically similar ND and familial exudative vitreoretinopathy. We have screened two ND gene mutations, namely A105T and Val60Glu, by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and allele-specific PCR methods, respectively, in 210 Kuwaiti premature newborns to replicate these findings in a different ethnic group. In the Kuwaiti premature newborn cohort, 115 of 210 babies had no eye problems and served as controls, while 95 were cases of ROP. In 71 of 95 ROP cases, the disease regressed spontaneously on or before stage 3, while in 24 of 95 ROP cases the disease progressed to advanced stages 4 and 5. In case of missense mutation (A105T), the AA genotype was detected in 96% of controls compared with 87% of ROP cases (NS); similarly no significant difference was found between spontaneously regressed ROP cases and those who progressed to advanced stages. For the Val60Glu mutation, no significant association was detected between the genotype and progression of ROP to advanced stages. Unlike data from the US, our findings from a Kuwaiti cohort of ROP cases and controls suggest a lack of association between the two ND gene mutations (A105T and Val60Glu) and ROP and the risk of progression of the disease to advanced stages.

  16. Rewards and advancements for clinical pharmacists.

    PubMed

    Goodwin, S Diane; Kane-Gill, Sandra L; Ng, Tien M H; Melroy, Joel T; Hess, Mary M; Tallian, Kimberly; Trujillo, Toby C; Vermeulen, Lee C

    2010-01-01

    The American College of Clinical Pharmacy charged the Clinical Practice Affairs Committee to review and update the College's 1995 White Paper, "Rewards and Advancements for Clinical Pharmacy Practitioners." Because of the limited data on the present state of rewards and advancements for clinical pharmacists, an online survey of "front-line" clinical pharmacists and pharmacy managers was conducted (1126 total respondents, 14% response rate). The resulting White Paper discusses motivators and existing systems of rewards and advancements for clinical pharmacists, as well as perceived barriers to implementation of these systems. Clinical pharmacists reported work-life balance, a challenging position, and opportunities for professional advancement as the most important factors for career success. At the time of the survey, financial rewards appeared not to be a major motivator for clinical pharmacists. Managers underestimated the importance that clinical pharmacists place on work-life balance and favorable work schedules. Although almost two thirds of the clinical pharmacists surveyed had not developed a professional development plan, 84% indicated an interest in career planning. Both clinical pharmacists and managers rated the lack of a clear reward and advancement structure as the most important barrier to effective systems of rewards and advancements. Pharmacy managers and administrators are encouraged to develop effective systems of rewards and advancements for clinical pharmacists that positively impact patient care and the institution's mission; these systems will benefit the clinical pharmacist, the health care institution, and the patient.

  17. Health-related quality-of-life outcomes: a reflexology trial with patients with advanced-stage breast cancer.

    PubMed

    Wyatt, Gwen; Sikorskii, Alla; Rahbar, Mohammad Hossein; Victorson, David; You, Mei

    2012-11-01

    To evaluate the safety and efficacy of reflexology, a complementary therapy that applies pressure to specific areas of the feet. Longitudinal, randomized clinical trial. Thirteen community-based medical oncology clinics across the midwestern United States. A convenience sample of 385 predominantly Caucasian women with advanced-stage breast cancer receiving chemotherapy and/or hormonal therapy. Following the baseline interview, women were randomized into three primary groups: reflexology (n = 95), lay foot manipulation (LFM) (n = 95), or conventional care (n = 96). Two preliminary reflexology (n = 51) and LFM (n = 48) test groups were used to establish the protocols. Participants were interviewed again postintervention at study weeks 5 and 11. Breast cancer-specific health-related quality of life (HRQOL), physical functioning, and symptoms. No adverse events were reported. A longitudinal comparison revealed significant improvements in physical functioning for the reflexology group compared to the control group (p = 0.04). Severity of dyspnea was reduced in the reflexology group compared to the control group (p < 0.01) and the LFM group (p = 0.02). No differences were found on breast cancer-specific HRQOL, depressive symptomatology, state anxiety, pain, and nausea. Reflexology may be added to existing evidence-based supportive care to improve HRQOL for patients with advanced-stage breast cancer during chemotherapy and/or hormonal therapy. Reflexology can be recommended for safety and usefulness in relieving dyspnea and enhancing functional status among women with advanced-stage breast cancer.

  18. [Prognostic factors of advanced stage non-small-cell lung cancer].

    PubMed

    Kwas, H; Guermazi, E; Khattab, A; Hrizi, C; Zendah, I; Ghédira, H

    2017-09-01

    Primary lung cancer is the leading cause of cancer death in men in the world. Although the introduction of new drugs, new therapeutic strategies and despite therapeutic advances, the prognosis is relatively improved during the last years. To evaluate the prognosis of patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) and to identify prognostic factors at these stages. A retrospective study, including 140 cases of locally advanced or metastatic NSCLC diagnosed in our department between 2003 and 2013. The average age was 61±10 years (35 to 90 years). Sex ratio was 18. The delays management were 80±25 days for presentation, 45±20 days for the diagnostic, while the treatment delay was 8±2.33 days. The cancer was at stage IIIA in 14%, IIIB in 27% and IV in 59%. Six months and one-year survival was between 50 and 74% and between 9 and 25%, respectively. Better survival was observed in patients with NSCLC on stage III, having better performance status, having comorbid conditions, with prolonged delays management, a short therapeutic delay and patients who received specific antitumor treatment. The prognostic factors in locally advanced and metastatic NSCLC in our patients were: stage of cancer, performance status, comorbid conditions, delay of management and specific antitumoral treatment. These factors should be considered in the management of patients with advanced NSCLC. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  19. Clinical Practice of Adjuvant Chemotherapy in Patients with Early-Stage Epithelial Ovarian Cancer.

    PubMed

    Frielink, Lindy M J; Pijlman, Brenda M; Ezendam, Nicole P M; Pijnenborg, Johanna M A

    2016-01-01

    Adjuvant platinum-based chemotherapy improves survival in women with early-stage epithelial ovarian cancer (EOC). Yet, there is a wide variety in clinical practice. All patients diagnosed with FIGO I and IIa EOC (2006-2010) in the south of the Netherlands were analyzed. The percentage of patients that received adjuvant chemotherapy was determined as well as the comprehensiveness of staging and outcome. Forty percent (54/135) of the patients with early-stage EOC received adjuvant chemotherapy. Treatment with adjuvant chemotherapy was associated with FIGO stage, clear-cell histology and nonoptimal staging. Optimal staging was achieved in 50%, and nonoptimal staging was associated with advanced age, comorbidity and treatment in a non-referral hospital. Overall, there was no difference in outcome between patients with and without adjuvant chemotherapy. Yet, in grade 3 tumors, adjuvant chemotherapy seems beneficial. Selective treatment of patients with early-stage EOC might reduce adjuvant chemotherapy without compromising outcome. © 2016 S. Karger AG, Basel.

  20. Sub-classification of Advanced-Stage Hepatocellular Carcinoma: A Cohort Study Including 612 Patients Treated with Sorafenib.

    PubMed

    Yoo, Jeong-Ju; Chung, Goh Eun; Lee, Jeong-Hoon; Nam, Joon Yeul; Chang, Young; Lee, Jeong Min; Lee, Dong Ho; Kim, Hwi Young; Cho, Eun Ju; Yu, Su Jong; Kim, Yoon Jun; Yoon, Jung-Hwan

    2018-04-01

    Advanced hepatocellular carcinoma (HCC) is associated with various clinical conditions including major vessel invasion, metastasis, and poor performance status. The aim of this study was to establish a prognostic scoring system and to propose a sub-classification of the Barcelona-Clinic Liver Cancer (BCLC) stage C. This retrospective study included consecutive patientswho received sorafenib for BCLC stage C HCC at a single tertiary hospital in Korea. A Cox proportional hazard model was used to develop a scoring system, and internal validationwas performed by a 5-fold cross-validation. The performance of the model in predicting risk was assessed by the area under the curve and the Hosmer-Lemeshow test. A total of 612 BCLC stage C HCC patients were sub- classified into strata depending on their performance status. Five independent prognostic factors (Child-Pugh score, α-fetoprotein, tumor type, extrahepatic metastasis, and portal vein invasion) were identified and used in the prognostic scoring system. This scoring system showed good discrimination (area under the receiver operating characteristic curve, 0.734 to 0.818) and calibration functions (both p < 0.05 by the Hosmer-Lemeshow test at 1 month and 12 months, respectively). The differences in survival among the different risk groups classified by the total score were significant (p < 0.001 by the log-rank test in both the Eastern Cooperative Oncology Group 0 and 1 strata). The heterogeneity of patientswith BCLC stage C HCC requires sub-classification of advanced HCC. A prognostic scoring system with five independent factors is useful in predicting the survival of patients with BCLC stage C HCC.

  1. [Staging gastritis with the OLGA system: prevalence of advanced stages of gastric atrophy in Mexican patients].

    PubMed

    Ramírez-Mendoza, P; Ruiz-Castillo, S A; Maroun-Marun, C; Trujillo-Benavides, O; Baltazar-Montúfar, P; Méndez del Monte, R; Angeles-Garay, U

    2011-01-01

    Gastric adenocarcinoma of intestinal type is preceded by inflammation, which produces mucosal atrophy and intestinal metaplasia, progressing eventually to dysplasia and invasive cancer. Recently an international group, the Operative Link on Gastritis Assessment (OLGA) proponed a staging system for gastric biopsies. To recognize the distribution of advanced stages of gastric mucosal atrophy in Mexican patients with dyspepsia according to the OLGA system. We apply the OLGA system for cancer risk (Stages 0 to IV) to 322 gastric biopsies from consecutive patients with dyspepsia. Using the Sydney protocol, we recorded the presence of atrophy, dysplasia and the relationship with ulcer disease. We report the stage of atrophy for each region and the Helicobacter pylori infection status. We documented 72 (22.4%) cases with atrophy, 50 of them (69.4%) were metaplastic-type. Overall, nine biopsies (2.78%) were stage III (all of them with metaplastic-type atrophy) and there was not stage IV cases. We did not find high-grade dysplasia or intramucosal carcinoma. In 8 of subjects with stage III, we observed low-grade dysplasia. We documented gastric ulcer in 5 patients with stage II, 60% of them with associated low-grade dysplasia. Five patients with duodenal ulcer were found in stages 0 and I. We found low prevalence of advanced stages of mucosal gastric atrophy among patients with dyspepsia. However we recognized 9 patients with stage III according to OLGA system worthy of follow-up because the high risk for developing gastric cancer.

  2. Health-Related Quality-of-Life Outcomes: A Reflexology Trial With Patients With Advanced-Stage Breast Cancer

    PubMed Central

    Wyatt, Gwen; Sikorskii, Alla; Rahbar, Mohammad Hossein; Victorson, David; You, Mei

    2013-01-01

    Purpose/Objectives To evaluate the safety and efficacy of reflexology, a complementary therapy that applies pressure to specific areas of the feet. Design Longitudinal, randomized clinical trial. Setting Thirteen community-based medical oncology clinics across the midwestern United States. Sample A convenience sample of 385 predominantly Caucasian women with advanced-stage breast cancer receiving chemotherapy and/or hormonal therapy. Methods Following the baseline interview, women were randomized into three primary groups: reflexology (n = 95), lay foot manipulation (LFM) (n = 95), or conventional care (n = 96). Two preliminary reflexology (n = 51) and LFM (n = 48) test groups were used to establish the protocols. Participants were interviewed again postintervention at study weeks 5 and 11. Main Research Variables Breast cancer–specific health-related quality of life (HRQOL), physical functioning, and symptoms. Findings No adverse events were reported. A longitudinal comparison revealed significant improvements in physical functioning for the reflexology group compared to the control group (p = 0.04). Severity of dyspnea was reduced in the reflexology group compared to the control group (p < 0.01) and the LFM group (p = 0.02). No differences were found on breast cancer–specific HRQOL, depressive symptomatology, state anxiety, pain, and nausea. Conclusions Reflexology may be added to existing evidence-based supportive care to improve HRQOL for patients with advanced-stage breast cancer during chemotherapy and/or hormonal therapy. Implications for Nursing Reflexology can be recommended for safety and usefulness in relieving dyspnea and enhancing functional status among women with advanced-stage breast cancer. PMID:23107851

  3. Use of routinely available clinical, nutritional, and functional criteria to classify cachexia in advanced cancer patients.

    PubMed

    Vigano, Antonio A L; Morais, José A; Ciutto, Lorella; Rosenthall, Leonard; di Tomasso, Jonathan; Khan, Sarah; Olders, Henry; Borod, Manuel; Kilgour, Robert D

    2017-10-01

    Cachexia is a highly prevalent syndrome in cancer and chronic diseases. However, due to the heterogeneous features of cancer cachexia, its identification and classification challenge clinical practitioners. To determine the clinical relevance of a cancer cachexia classification system in advanced cancer patients. Beginning with the four-stage classification system proposed for cachexia [non-cachexia (NCa), pre-cachexia (PCa), cachexia (Ca) and refractory cachexia (RCa)], we assigned patients to these cachexia stages according to five classification criteria available in clinical practice: 1) biochemistry (high C-reactive protein or leukocytes, or hypoalbuminemia, or anemia), 2) food intake (normal/decreased), weight loss: 3) moderate (≤5%) or 4) significant (>5%/past six months) and 5) performance status (Eastern Cooperative Oncology Group Performance Status ≥ 3). We then determined if symptom severity, body composition changes, functional levels, hospitalizations and survival rates varied significantly across cachexia stages. Two-hundred and ninety-seven advanced cancer patients with primary gastrointestinal and lung tumors were included. Patients were classified into Ca (36%), PCa and RCa (21%, respectively) and NCa (15%). Significant (p < 0.05) differences were observed among cachexia stages for most of the outcome measures (symptoms, body composition, handgrip strength, emergency room visits and length of hospital stays) according to cachexia severity. Survival also differed between cachexia stages (except between PCa and Ca). Five clinical criteria can be used to stage cancer cachexia patients and predict important clinical, nutritional and functional outcomes. The lack of statistical difference between PCa and Ca in almost all clinical outcomes examined suggests either that the PCa group includes patients already affected by early cachexia or that more precise criteria are needed to differentiate PCa from Ca patients. More studies are required to

  4. Racial disparities in advanced stage colorectal cancer survival

    PubMed Central

    Wallace, Kristin; Hill, Elizabeth G.; Lewin, David N.; Williamson, Grace; Oppenheimer, Stephanie; Ford, Marvella E.; Wargovich, Michael J.; Berger, Franklin G.; Bolick, Susan W.; Thomas, Melanie B.; Alberg, Anthony J.

    2013-01-01

    Purpose African Americans (AA) have a higher incidence and lower survival from colorectal cancer (CRC) compared to European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry (SCCCR) is used to investigate the relationship between race and age on advanced stage CRC survival. Methods The study population was comprised of 3865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2673 (69%) EA and 1192 (31%) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95% confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards (CPH) regression models to generate Hazard Ratios (HR) and 95% CI. Results We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (< 50 years), AA race was associated with a 1.34 (95% CI 1.06-1.71) higher risk of death compared to EA. Among older patients, we observed a modest increase risk of death among AA men compared to EA (HR 1.16 (95% CI 1.01-1.32) but no difference by race among women (HR 0.94 (95% CI 0.82-1.08)). Moreover, we observed that the disparity in survival has worsened over the past 15 years. Conclusions Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those < 50 years old. PMID:23296454

  5. Implications of inaccurate clinical nodal staging in pancreatic adenocarcinoma.

    PubMed

    Swords, Douglas S; Firpo, Matthew A; Johnson, Kirsten M; Boucher, Kenneth M; Scaife, Courtney L; Mulvihill, Sean J

    2017-07-01

    Many patients with stage I-II pancreatic adenocarcinoma do not undergo resection. We hypothesized that (1) clinical staging underestimates nodal involvement, causing stage IIB to have a greater percent of resected patients and (2) this stage-shift causes discrepancies in observed survival. The Surveillance, Epidemiology, and End Results (SEER) research database was used to evaluate cause-specific survival in patients with pancreatic adenocarcinoma from 2004-2012. Survival was compared using the log-rank test. Single-center data on 105 patients who underwent resection of pancreatic adenocarcinoma without neoadjuvant treatment were used to compare clinical and pathologic nodal staging. In SEER data, medium-term survival in stage IIB was superior to IB and IIA, with median cause-specific survival of 14, 9, and 11 months, respectively (P < .001). Seventy-two percent of stage IIB patients underwent resection vs 28% in IB and 36% in IIA (P < .001). In our institutional data, 12.4% of patients had clinical evidence of nodal involvement vs 69.5% by pathologic staging (P < .001). Among clinical stage IA-IIA patients, 71.6% had nodal involvement by pathologic staging. Both SEER and institutional data support substantial underestimation of nodal involvement by clinical staging. This finding has implications in decisions regarding neoadjuvant therapy and analysis of outcomes in the absence of pathologic staging. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Clinical stages in patients with primary and subsequent cancers based on the czech cancer registry 1976-2005.

    PubMed

    Geryk, Edvard; Stampach, Radim; Dítě, Petr; Kozel, Jiří; Horváth, Teodor; Kubíček, Petr

    2013-01-01

    Of 1,486,984 new cancers registered in the Czech Cancer Registry in 1976-2005, 290,312 (19.5%) were multiple malignant neoplasms (MMNs), of which there were 65,292 primary and 89,796 subsequent cases in men and 59,970 primary and 75,254 subsequent cases in women. The duplicities were higher in women, and the triplicities and others (3-6 MMNs) were higher in men. The most frequent diagnoses were the primary cancers of skin, gastrointestinal and urinary tract, male genital organs, respiratory tract in men, and cancers of skin, breast, female genital organs, and gastrointestinal tract in women. The analysis of the early and advanced clinical stages shows that the number of subsequent advanced stages increased after primary advanced stages. Their time-age-space distributions visualized maps of MMNs in 14 Czech regions. These results support the improvement of algorithms of dispensary care for the early detection of the subsequent neoplasms.

  7. Clinical diagnosis and staging of cholangiocarcinoma

    PubMed Central

    Blechacz, Boris; Komuta, Mina; Roskams, Tania; Gores, Gregory J.

    2012-01-01

    Cholangiocarcinoma is the most frequent biliary malignancy. It is difficult to diagnose owing to its anatomic location, growth patterns and lack of definite diagnostic criteria. Currently, cholangiocarcinoma is classified into the following types according to its anatomic location along the biliary tree: intrahepatic, perihilar or distal extrahepatic cholangiocarcinoma. These cholangiocarcinoma types differ in their biological behavior and management. The appropriate stratification of patients with regard to the anatomic location and stage of cholangiocarcinoma is a key determinate in their management. Staging systems can guide this stratification and provide prognostic information. In addition, staging systems are essential in order to compare and contrast the outcomes of different therapeutic approaches. A number of staging systems exist for cholangiocarcinoma—several early ones have been updated, and new ones are being developed. We discuss the emerging diagnostic criteria as well as the different staging systems for cholangiocarcinoma, and provide a critical appraisal regarding these advances in biliary tract malignancies. PMID:21808282

  8. Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages.

    PubMed

    Al Obeed, Omar A; Alkhayal, Khayal A; Al Sheikh, Abdulmalik; Zubaidi, Ahmad M; Vaali-Mohammed, Mansoor-Ali; Boushey, Robin; Mckerrow, James H; Abdulla, Maha-Hamadien

    2014-12-28

    To detect the expression of tumor necrosis factor-α (TNF-α) in colorectal cancer (CRC) cells among Saudi patients, and correlate its expression with clinical stages of cancer. Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital. Patient demographic information, including age and gender, tumor sites, and histological type of CRC, was recorded. To measure TNF-α mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed, paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse transcription polymerase chain reaction were performed. Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-α by immunohistochemistry. The relative expression of TNF-α mRNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue. High TNF-α gene expression was associated with Stage III and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty-three percent of patients (25/30) showed strong TNF-α positive staining, while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30) were negative. We showed the presence of elevated TNF-α gene expression in cancer cells, which strongly correlated with advanced stages of tumor. High levels of TNF-α expression could be an independent diagnostic indicator of colorectal cancer, and targeting TNF-α might be a promising prognostic tool by assessment of the clinical stages of CRC.

  9. Increased expression of tumor necrosis factor-α is associated with advanced colorectal cancer stages

    PubMed Central

    Al Obeed, Omar A; Alkhayal, Khayal A; Al Sheikh, Abdulmalik; Zubaidi, Ahmad M; Vaali-Mohammed, Mansoor-Ali; Boushey, Robin; Mckerrow, James H; Abdulla, Maha-Hamadien

    2014-01-01

    AIM: To detect the expression of tumor necrosis factor-α (TNF-α) in colorectal cancer (CRC) cells among Saudi patients, and correlate its expression with clinical stages of cancer. METHODS: Archival tissue specimens were collected from 30 patients with CRC who had undergone surgical intervention at King Khalid University Hospital. Patient demographic information, including age and gender, tumor sites, and histological type of CRC, was recorded. To measure TNF-α mRNA expression in CRC, total RNA was extracted from tumor formalin-fixed, paraffin-embedded, and adjacent normal tissues. Reverse transcription and reverse transcription polymerase chain reaction were performed. Colorectal tissue microarrays were constructed to investigate the protein expression of TNF-α by immunohistochemistry. RESULTS: The relative expression of TNF-α mRNA in colorectal cancer was significantly higher than that seen in adjacent normal colorectal tissue. High TNF-α gene expression was associated with Stage III and IV neoplasms when compared with earlier tumor stages (P = 0.004). Eighty-three percent of patients (25/30) showed strong TNF-α positive staining, while only 10% (n = 3/30) of patients showed weak staining, and 7% (n = 2/30) were negative. We showed the presence of elevated TNF-α gene expression in cancer cells, which strongly correlated with advanced stages of tumor. CONCLUSION: High levels of TNF-α expression could be an independent diagnostic indicator of colorectal cancer, and targeting TNF-α might be a promising prognostic tool by assessment of the clinical stages of CRC. PMID:25561807

  10. Racial disparities in advanced-stage colorectal cancer survival.

    PubMed

    Wallace, Kristin; Hill, Elizabeth G; Lewin, David N; Williamson, Grace; Oppenheimer, Stephanie; Ford, Marvella E; Wargovich, Michael J; Berger, Franklin G; Bolick, Susan W; Thomas, Melanie B; Alberg, Anthony J

    2013-03-01

    African-Americans (AA) have a higher incidence of and lower survival from colorectal cancer (CRC) compared with European Americans (EA). In the present study, statewide, population-based data from South Carolina Central Cancer Registry are used to investigate the relationship between race and age on advanced-stage CRC survival. The study population was comprised of 3,865 advanced pathologically documented colon and rectal adenocarcinoma cases diagnosed between 01 January 1996 and 31 December 2006: 2,673 (69 %) EA and 1,192 (31 %) AA. Kaplan-Meier methods were used to generate median survival time and corresponding 95 % confidence intervals (CI) by race, age, and gender. Factors associated with survival were evaluated by fitting Cox proportional hazards regression models to generate hazard ratios (HR) and 95 % CI. We observed a significant interaction between race and age on CRC survival (p = 0.04). Among younger patients (<50 years), AA race was associated with a 1.34 times (95 % CI 1.06-1.71) higher risk of death compared with EA. Among older patients, we observed a modest increase in risk of death among AA men compared with EA [HR 1.16 (95 % CI 1.01-1.32)] but no difference by race between women [HR 0.94 (95 % CI 0.82-1.08)]. Moreover, we observed that the disparity in survival has worsened over the past 15 years. Future studies that integrate clinical, molecular, and treatment-related data are needed for advancing understanding of the racial disparity in CRC survival, especially for those <50 years old.

  11. Perioperative BRAF inhibitors in locally advanced stage III melanoma.

    PubMed

    Zippel, Douglas; Markel, Gal; Shapira-Frommer, Roni; Ben-Betzalel, Guy; Goitein, David; Ben-Ami, Eytan; Nissan, Aviram; Schachter, Jacob; Schneebaum, Schlomo

    2017-12-01

    Stage III malignant melanoma is a heterogeneous disease where those cases deemed marginally resectable or irresecatble are frequently incurable by surgery alone. Targeted therapy takes advantage of the high incidence of BRAF mutations in melanomas, most notably the V600E mutation. These agents have rarely been used in a neoadjuvant setting prior to surgery. Thirteen consecutive patients with confirmed BRAF V600E regionally advanced melanoma deemed marginally resectable or irrresectable, were treated with BRAF inhibiting agents, prior to undergoing surgery. The primary outcome measures were a successful resection and pathological response. Disease-free survival was a secondary outcome measure. Overall, 12/13 patients showed a marked clinical responsiveness to medical treatment, enabling a macroscopically successful resection in all cases. Four patients had a complete pathological response with no viable tumor evident in the resected specimens and eight patients showed evidence of minimally residual tumor with extensive tumoral necrosis and fibrosis. One patient progressed and died before surgery. At a median follow up of 20 months, 10 patients remain free of disease. Perioperative treatment with BRAF inhibiting agents in BRAFV600E mutated Stage III melanoma patients facilitates surgical resection and affords satisfactory disease free survival. © 2017 Wiley Periodicals, Inc.

  12. Developing an advanced practice nurse-led liver clinic.

    PubMed

    McAfee, Jean L

    2012-01-01

    End-stage liver disease (ESLD) is a leading cause of digestive disease deaths in the United States and continues to increase exponentially every year. Best practice does not currently recognize or utilize a clinic practice model for ESLD management. Advanced practice registered nurses (APRNs) can impact ESLD disease management by implementing an outpatient clinic care model to focus on treatment compliance, patient education, improvement of patient outcomes, and reduction in hospital admission rates for ESLD patients. A review of 15 research articles was completed to determine the impact APRNs can make on chronic care of ESLD patients. Results from the review support APRN analysis, assessment, diagnosis, treatment, intervention, and evaluation of ESLD patients. The literature reviewed also demonstrates that ESLD patients have improved symptom management when maintained in an outpatient setting, allowing for decreased hospital and insurance expenditures. Following evaluation of the evidence, it was concluded that an APRN-led ESLD clinic merits further study.

  13. Rectosigmoidian Involvement in Advanced-stage Ovarian Cancer - Intraoperative Decisions.

    PubMed

    Bacalbasa, Nicolae; Balescu, Irina; Dima, Simona

    2017-01-01

    Ovarian cancer remains one of the most commonly encountered malignancies affecting women worldwide, that is unfortunately commonly diagnosed in advanced stages of the disease. In these stages, the tumoral process usually involves the surrounding viscera throughout contiguity or induces the apparition of distant metastases via peritoneal, lymphatic or hematogenous spread, multiple resections being needed in order to achieve a good control of the disease. In the present study, we present a case series of 12 patients in whom various surgical procedures on the rectosigmoidian loop were performed in order to achieve debulking surgery to no residual disease. Digestive tract resections consisted of rectosigmoidian resection with left colostomy in three cases, low rectosigmoidian resections with anastomosis in eight cases and a stripping procedure of the peritoneal layer in one case. Due to the close proximity of the digestive and gynecological tract, advanced-stage ovarian tumors frequently involve the rectosigmoidian loop, imposing association of digestive tract surgical procedures. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  14. Racial/Ethnic, socioeconomic, and geographic disparities of cervical cancer advanced-stage diagnosis in Texas.

    PubMed

    Zhan, F Benjamin; Lin, Yan

    2014-01-01

    Advanced-stage diagnosis is among the primary causes of mortality among cervical cancer patients. With the wide use of Pap smear screening, cervical cancer advanced-stage diagnosis rates have decreased. However, disparities of advanced-stage diagnosis persist among different population groups. A challenging task in cervical cancer disparity reduction is to identify where underserved population groups are. Based on cervical cancer incidence data between 1995 and 2008, this study investigated advanced-stage cervical cancer disparities in Texas from three social domains: Race/ethnicity, socioeconomic status (SES), and geographic location. Effects of individual and contextual factors, including age, tumor grade, race/ethnicity, as well as contextual SES, spatial access to health care, sociocultural factors, percentage of African Americans, and insurance expenditures, on these disparities were examined using multilevel logistic regressions. Significant variations by race/ethnicity and SES were found in cervical cancer advanced-stage diagnosis. We also found a decline in racial/ethnic disparities of advanced cervical cancer diagnosis rate from 1995 to 2008. However, the progress was slower among African Americans than Hispanics. Geographic disparities could be explained by age, race/ethnicity, SES, and the percentage of African Americans in a census tract. Our findings have important implications for developing effective cervical cancer screening and control programs. We identified the location of underserved populations who need the most assistance with cervical cancer screening. Cervical cancer intervention programs should target Hispanics and African Americans, as well as individuals from communities with lower SES in geographic areas where higher advanced-stage diagnosis rates were identified in this study. Copyright © 2014 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

  15. [Clinical analysis of 25 patients with aggressive peripheral T-cell lymphoma in advanced stage treated with autologous stem cell transplantation].

    PubMed

    Zou, Dehui; Huang, Wenyang; Liu, Hong; Fu, Mingwei; Li, Zengjun; Sui, Weiwei; Qi, Junyuan; Zhao, Yaozhong; Ru, Kun; Han, Mingzhe; Qiu, Lugui

    2015-06-01

    To investigate the outcomes of autologous stem cell transplantation (ASCT) for patients with aggressive peripheral T-cell lymphoma (PTCLs) in advanced stage. The clinical data of 25 patients in complete remission (CR) with aggressive PTCLs received ASCT from May 1997 to June 2013 were retrospectively analyzed. ① Of the 25 cases, 16 were unspecified PTCL (PTCL-U), 4 with angioimmunoblastic T cell lymphoma (AITL), 3 with anaplastic large cell lymphoma (ALCL) and 2 with hepatosplenic T cell lymphoma (HSTL), with a median age of 30(12-54) years old. Ratio of male to female is 16∶9. The distribution of stages was 8 cases with stage Ⅲ and 17 patients with stage Ⅳ. Nine patients presented with bone marrow involvement. Before ASCT, 18 patients were in CR1 and 7 patients were in CR2. ②Two patients with HSTL in stage ⅣB and IPI score 4/5 in CR1 relapsed and died within 12 months after ASCT. At a median follow-up of 38 (range 14-110) months, the estimated 3-year probability of PFS and OS for the other 23 patients was (63.1 ± 10.5)% and (71.8 ± 9.9)%, respectively. The patients in first CR had a better survival than the patients in second CR. The 3-year probability of PFS were (74.9 ± 11.0)% vs (33.3 ± 19.2)% (P=0.092) and OS were (80.2 ± 10.4)% vs (50.0 ± 20.4)% (P=0.043), respectively. The 3-year probability of PFS and OS were (40.0 ± 17.4)% and (53.3 ± 17.3)% in bone marrow involvement patients and the corresponding figure were (77.9 ± 11.3)% and (84.4 ± 10.2)% in non- bone marrow involvement patients. ASCT could improve the survival of aggressive PTCLs. Non CR1 status and bone marrow involvement had negative influence on OS in patients with aggressive PTCLs treated by ASCT. The prognosis was very poor in patients with HSTL and satisfactory regimens should be investigated.

  16. Rectosigmoidian Involvement in Advanced-stage Ovarian Cancer – Intraoperative Decisions

    PubMed Central

    BACALBASA, NICOLAE; BALESCU, IRINA; DIMA, SIMONA

    2017-01-01

    Background/Aim: Ovarian cancer remains one of the most commonly encountered malignancies affecting women worldwide, that is unfortunately commonly diagnosed in advanced stages of the disease. In these stages, the tumoral process usually involves the surrounding viscera throughout contiguity or induces the apparition of distant metastases via peritoneal, lymphatic or hematogenous spread, multiple resections being needed in order to achieve a good control of the disease. Patients and Methods: In the present study, we present a case series of 12 patients in whom various surgical procedures on the rectosigmoidian loop were performed in order to achieve debulking surgery to no residual disease. Results: Digestive tract resections consisted of rectosigmoidian resection with left colostomy in three cases, low rectosigmoidian resections with anastomosis in eight cases and a stripping procedure of the peritoneal layer in one case. Conclusion: Due to the close proximity of the digestive and gynecological tract, advanced-stage ovarian tumors frequently involve the rectosigmoidian loop, imposing association of digestive tract surgical procedures. PMID:28882968

  17. Prognostic impact of perineural invasion and lymphovascular invasion in advanced stage oral squamous cell carcinoma.

    PubMed

    Jardim, J F; Francisco, A L N; Gondak, R; Damascena, A; Kowalski, L P

    2015-01-01

    Perineural invasion (PNI) and lymphovascular invasion (LVI) have been associated with the risk of local recurrences and lymph node metastasis. The aim of this study was to evaluate the prognostic impact of PNI and LVI in patients with advanced stage squamous cell carcinoma of the tongue and floor of the mouth. One hundred and forty-two patients without previous treatment were selected. These patients underwent radical surgery with neck dissection and adjuvant treatment. Clinicopathological data were retrieved from the medical charts, including histopathology and surgery reports. Univariate analysis was performed to assess the impact of studied variables on survival. Overall survival was negatively influenced by six tumour-related factors: increasing T stage (P = 0.003), more than two clinically positive nodes (P = 0.002), extracapsular spread of lymph node metastasis (P < 0.001), tumour thickness (P = 0.04), PNI (P < 0.001), and LVI (P = 0.012). Disease-free survival was influenced by PNI (P = 0.04), extracapsular spread of lymph node metastasis (P = 0.008), and N stage (P = 0.006). Multivariate analysis showed PNI to be an independent predictor for overall survival (P = 0.01) and disease-free survival (P = 0.03). Thus the presence of PNI in oral carcinoma surgical specimens has a significant impact on survival outcomes in patients with advanced stage tumours submitted to radical surgery and adjuvant radiotherapy/radiochemotherapy. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  18. Clinical Phenotype Predicts Early Staged Bilateral Deep Brain Stimulation in Parkinson’s Disease

    PubMed Central

    Sung, Victor W.; Watts, Ray L.; Schrandt, Christian J.; Guthrie, Stephanie; Wang, Deli; Amara, Amy W.; Guthrie, Barton L.; Walker, Harrison C.

    2014-01-01

    Object While many centers place bilateral DBS systems simultaneously, unilateral STN DBS followed by a staged contralateral procedure has emerged as a treatment option for many patients. However little is known about whether the preoperative phenotype predicts when staged placement of a DBS electrode in the opposite subthalamic nucleus will be required. We aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second subthalamic deep brain stimulation (DBS) electrode in patients who undergo unilateral subthalamic DBS for Parkinson's disease (PD). Methods Eighty-two consecutive patients with advanced PD underwent unilateral subthalamic DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression determined preoperative characteristics that predicted staged placement of a second electrode in the opposite subthalamic nucleus. Preoperative measurements included aspects of the Unified Parkinson Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. Results At 2 years follow-up, 28 of the 82 patients (34%) had undergone staged placement of a contralateral electrode while the remainder chose to continue with unilateral stimulation. Statistically significant improvements in UPDRS total and part 3 scores were retained at the end of the 2 year follow-up period in both subsets of patients. Multivariate logistic regression showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (odds ratio 13.4; 95% confidence interval 2.8, 64.9), high tremor subscore (OR 7.2; CI 1.5, 35.0), and low body weight (OR 5.5; CI 1.4, 22.3). Conclusions This single center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral subthalamic DBS. These data may aid in the management of patients with advanced PD who undergo subthalamic DBS. PMID

  19. Clinical staging: its importance in therapeutic decisions and clinical trials.

    PubMed

    Denis, L J

    1992-02-01

    International collaboration has resulted in a revised and unified 1987 formulation for the TNM classification in solid tumors. The simplification and eliminations of most variables caused difficulties for the clinical use of the system in some tumors such as bladder cancer. The approval of the proposed adaptation covering the tumor mass, subdividing the T4 category and adapting the stage grouping, resolves these difficulties. Published reports demonstrate support for the TNM system as a clinical base for treatment decisions and prognosis. The TNMG stage and grade are important basic prognostic factors, but other prognostic factors, especially biologic tumor activity, are under clinical investigation. The TNM classification is the initial evaluation after histologic confirmation of cancer to guide treatment and prognosis. The quality of the evaluation is enhanced by precise communication on the employed methodology.

  20. Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model.

    PubMed

    Scarisbrick, Julia J; Prince, H Miles; Vermeer, Maarten H; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L; Rodríguez-Peralto, Jose L; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T; Duvic, Madeleine; Whittaker, Sean J; Kim, Youn H

    2015-11-10

    Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and identifies markers with independent prognostic value

  1. Breast cancer in Kurdish women of northern Iraq: incidence, clinical stage, and case control analysis of parity and family risk.

    PubMed

    Majid, Runnak A; Mohammed, Hazha A; Saeed, Heshu M; Safar, Banaz M; Rashid, Rekawt M; Hughson, Michael D

    2009-12-11

    Breast cancer in the Middle-East occurs in relatively young women and frequently presents as advanced disease. A protective effect of multiparity is not apparent, and high familial risk is reported in some countries. This study investigates breast cancer rates and clinical stage related to age in the Kurdish region of Iraq and evaluates risk associated with parity and family history. Findings are compared with nearby countries and the West. Sulaimaniyah Directorate of Health records identified 539 women diagnosed with breast cancer during 2006-2008. Clinical survey forms were completed on 296 patients and on 254 age-matched controls. Age specific incidence rates were calculated from Directorate of Health population estimates. Average patient age was 47.4 +/- 11 years and 59.5% were pre-menopausal. Diagnosis was at clinical stage 1 for 4.1%, stage 2 for 43.5%, stage 3 for 26.0%, and stage 4 for 8.1% of patients. For 18.2%, stage was unknown. Annual breast cancer incidence rates per 100,000 women peaked at 168.9 at age 55 to 59 and declined to 57.3 at 60 and above. Patients had an average of 5.0 +/- 3.3 children compared to 5.4 +/- 3.5 for controls, P = 0.16. A first degree family member had breast cancer among 11.1% of patients and 2.1% of controls (P < 0.001) with > 50% of these patients and controls being > or =50 years old. No statistically significant relationship was found between tumor stage and age, P = 0.59. In Kurdish Iraq, breast cancer is predominantly a disease of pre-menopausal women having multiple pregnancies. For younger patients, breast cancer incidence was similar to the West and possibly higher than many Middle-Eastern countries, but unlike the West, the estimated rates declined markedly in the elderly. The familial breast cancer risk for both older and younger women was within the general population risk of Western countries. Clinical stages were advanced and indicated delays in diagnosis that were unrelated to patient age.

  2. Advanced practice nurses' scope of practice: a qualitative study of advanced clinical competencies.

    PubMed

    Nieminen, Anna-Lena; Mannevaara, Bodil; Fagerström, Lisbeth

    2011-12-01

    To describe and explore Advanced Practice Nurses' clinical competencies and how these are expressed in clinical practice. Discussion concerning advanced clinical practice has been ongoing in the USA since the 1960s and in the UK since the late 1980s. Approximately 24 countries, excluding the USA, have implemented the role of Advance Practice Nurse (APN). In the Nordic countries, especially Sweden and Finland, APNs have been introduced in some organizations but their competency domains have not yet been clearly defined. The study's theoretical framework emanates from Aristotle's three-dimensional view of knowledge that is epistêmê, technê, and phronesis. Between October 2005 and January 2006, focus group interviews of Clinical Nurse Specialists who provide expert functions in pediatric, internal medicine, and surgical units (n = 26) and APN students (n = 8) were conducted. The data material was analyzed using inductive content analysis. Grouped into five main themes, the study results indicate that APNs possess advanced level clinical competencies in: (A) assessment of patients' caring needs and nursing care activities, (B) the caring relationship, (C) multi-professional teamwork, (D) development of competence and nursing care, and (E) leadership in a learning and caring culture. Clinical competencies consist of advanced skills, which typify an expanding role that offers new possibilities for holistic patient care practice. APNs' scope of practice is characterized by responsibility and competence in making autonomous judgments based on expanded clinical competence. On an advanced level, clinical competence consists not merely of advanced skills for assessing and meeting the needs of patients but also the creation of safe and trustful relationships with patients and collaboration with colleagues. APNs can realize advanced skills in their actions through their manner of knowing, doing, and being. © 2011 The Authors. Scandinavian Journal of Caring Sciences © 2011

  3. Post-operative radiation therapy for advanced-stage oropharyngeal cancer.

    PubMed

    Hansen, Eric; Panwala, Kathryn; Holland, John

    2002-11-01

    Between 1985 and 1999, 43 patients with locally-advanced, resectable oropharyngeal cancer were treated with combined surgery and post-operative radiation therapy (RT) at Oregon Health and Science University. Five patients (12 per cent) had Stage III disease and 38 patients (88 per cent) had Stage IV disease. All patients had gross total resections of the primary tumour. Thirty-seven patients had neck dissections for regional disease. RT consisted of a mean tumour-bed dose of 63.0 Gy delivered in 1.8-2.0 Gy fractions over a mean of 49 days. At three- and five-years, the actuarial local control was 96 per cent and the actuarial local/regional control was 80 per cent. The three- and five-year actuarial rates of distant metastases were 41 per cent and 46 per cent, respectively. The actuarial overall survival at three- and five-years was 41 per cent and 34 per cent, respectively. The actuarial rates of progression-free survival were 49 per cent at three-years and 45 per cent at five years. Combined surgery and post-operative RT for advanced-stage oropharyngeal cancer results in excellent local/regional control. This particular group of patients experienced a high-rate of developing distant metastases.

  4. MicroRNA‑133b inhibits connective tissue growth factor in colorectal cancer and correlates with the clinical stage of the disease.

    PubMed

    Guo, Yihang; Li, Xiaorong; Lin, Changwei; Zhang, Yi; Hu, Gui; Zhou, Jianyu; Du, Juan; Gao, Kai; Gan, Yi; Deng, Hao

    2015-04-01

    Accumulating evidence indicates that dysregulation of microRNA‑133b (miR‑133b) is an important step in the development of certain types of human cancer and contributes to tumorigenesis. Altered expression of miR‑133b has been reported in colon carcinoma, but its association with clinical stage in colorectal cancer (CRC) has remained elusive. Connective tissue growth factor (CTGF), a potentially promising candidate gene for interaction with miR‑133b, was screened using microarray analysis. The expression of miR‑133b and CTGF was evaluated using reverse transcription‑quantitative polymerase chain reaction and western blot analysis. The regulatory effects of miR‑133b on CTGF were evaluated using a dual‑luciferase reporter assay. CTGF was identified as a functional target of miR‑133b. The results demonstrated low expression of miR‑133b in CRC specimens with poor cell differentiation (P=0.011), lymph node metastasis (P=0.037) and advanced clinical stages (stage III or IV vs. I or II; P=0.036). Furthermore, there was a significant association between a high level of expression of CTGF mRNA and an advanced clinical stage (stage III or IV vs. I or II; P=0.015) and lymph node metastasis (P=0.034). CTGF expression was negatively regulated by miR‑133b in the human colorectum, suggesting that miR‑133b and CTGF may be candidate therapeutic targets in colorectal cancer.

  5. Multimodal endocavitary ultrasound versus MRI and clinical findings in pre- and post-treatment advanced cervical cancer. Preliminary report.

    PubMed

    Csutak, Csaba; Badea, Radu; Bolboaca, Sorana D; Ordeanu, Claudia; Nagy, Viorica M; Fekete, Zsolt; Chiorean, Liliana; Dudea, Sorin M

    2016-03-01

    The aim of this study was to evaluate the use of pre and post-therapy transrectal and transvaginal ultrasonography (TRUS, TVUS) with contrast enhancement and strain elastography compared with clinical examination and magnetic resonance imaging (MRI) in the assessment of advanced stage cervical cancer. This was a prospective study, carried out over a period of nine months on subjects with advanced-stage cervical cancer (stage >/= IIB). All included patients were examined clinically and underwent abdomino-pelvic contrast enhanced MRI and multimodal US examinations (TRUS with strain elastography and contrast enhanced TVUS) at the time of diagnosis and after radiochemotherapy. Tumor size and staging at TRUS and TVUS was compared with the same data obtained by clinical examination and MRI. Pathology was the golden standard. Eight patients accomplished the inclusion criteria. In five cases the tumor stage was identical on clinical and MRI examinations. In all cases parametrial infiltration was diagnosed by all pre-treatment examinations. No significant differences were observed in tumor size between clinical, US and MRI exams either at baseline or post-therapy, in native or post-contrast examinations. The size of the tumor evaluated pre-treatment proved to be significantly smaller post-contrast in both US and MRI examinations compared with the native images. Post-therapy, no significant differences were observed on US measured tumor dimensions when comparing native with post-contrast images. Oppositely, significant smaller dimensions were observed on post-contrast MRI compared with native scans. TRUS is accurate in the estimation of pre-therapy cervical cancer dimension. The post therapy tumor evaluation is better performed with MRI. The use of intravenous contrast agents on both examinations did not improved the accuracy of tumor evaluation pre or post-therapy.

  6. Fertility-sparing surgery in advanced stage malignant ovarian germ cell tumor: a case report.

    PubMed

    Ghalleb, Montassar; Bouzaiene, Hatem; Slim, Skander; Hadiji, Achraf; Hechiche, Monia; Ben Hassouna, Jamel; Rahal, Khaled

    2017-12-17

    Malignant ovarian germ cell tumor is a rare type of disease, which generally has a good prognosis due to the high chemosensitivity of this type of tumor. Fertility preservation is an important issue because malignant ovarian germ cell tumor commonly affects young women. Although conservation is the standard for early stage, it becomes more debatable as the disease progresses to more advanced stages. Report the case of a patient with an International Federation of Gynecology and Obstetrics Stage IIIc malignant ovarian germ cell tumor, who had conservative surgery and chemotherapy with a good fertility outcome. A 23-year-old North African woman with a left malignant ovarian germ cell tumor stage IIIc was treated by left adnexectomy and omentectomy followed by chemotherapy. A 15-year follow-up showed no signs of relapse, and she completed three full-term natural pregnancies. Malignant ovarian germ cell tumor is a rare ovarian tumor with a good prognosis. It is usually associated with a good fertility outcome in early stages. However, due to the rarity of the disease in advanced stages, the fertility outcome for this group of patients is not clear. This lack of data surrounding advanced stages points to the need for a meta-analysis of all published cases.

  7. Evaluation of Therapeutics for Advanced-Stage Heart Failure and Other Severely-Debilitating or Life-Threatening Diseases.

    PubMed

    Prescott, J S; Andrews, P A; Baker, R W; Bogdanffy, M S; Fields, F O; Keller, D A; Lapadula, D M; Mahoney, N M; Paul, D E; Platz, S J; Reese, D M; Stoch, S A; DeGeorge, J J

    2017-08-01

    Severely-debilitating or life-threatening (SDLT) diseases include conditions in which life expectancy is short or quality of life is greatly diminished despite available therapies. As such, the medical context for SDLT diseases is comparable to advanced cancer and the benefit vs. risk assessment and development of SDLT disease therapeutics should be similar to that of advanced cancer therapeutics. A streamlined development approach would allow patients with SDLT conditions earlier access to therapeutics and increase the speed of progression through development. In addition, this will likely increase the SDLT disease therapeutic pipeline, directly benefiting patients and reducing the economic and societal burden of SDLT conditions. Using advanced-stage heart failure (HF) as an example that illustrates the concepts applicable to other SDLT indications, this article proposes a streamlined development paradigm for SDLT disease therapeutics and recommends development of aligned global regulatory guidance. © 2017 American Society for Clinical Pharmacology and Therapeutics.

  8. Histogram analysis of apparent diffusion coefficient maps for assessing thymic epithelial tumours: correlation with world health organization classification and clinical staging.

    PubMed

    Kong, Ling-Yan; Zhang, Wei; Zhou, Yue; Xu, Hai; Shi, Hai-Bin; Feng, Qing; Xu, Xiao-Quan; Yu, Tong-Fu

    2018-04-01

    To investigate the value of apparent diffusion coefficients (ADCs) histogram analysis for assessing World Health Organization (WHO) pathological classification and Masaoka clinical stages of thymic epithelial tumours. 37 patients with histologically confirmed thymic epithelial tumours were enrolled. ADC measurements were performed using hot-spot ROI (ADC HS-ROI ) and histogram-based approach. ADC histogram parameters included mean ADC (ADC mean ), median ADC (ADC median ), 10 and 90 percentile of ADC (ADC 10 and ADC 90 ), kurtosis and skewness. One-way ANOVA, independent-sample t-test, and receiver operating characteristic were used for statistical analyses. There were significant differences in ADC mean , ADC median , ADC 10 , ADC 90 and ADC HS-ROI among low-risk thymoma (type A, AB, B1; n = 14), high-risk thymoma (type B2, B3; n = 9) and thymic carcinoma (type C, n = 14) groups (all p-values <0.05), while no significant difference in skewness (p = 0.181) and kurtosis (p = 0.088). ADC 10 showed best differentiating ability (cut-off value, ≤0.689 × 10 -3 mm 2 s -1 ; AUC, 0.957; sensitivity, 95.65%; specificity, 92.86%) for discriminating low-risk thymoma from high-risk thymoma and thymic carcinoma. Advanced Masaoka stages (Stage III and IV; n = 24) tumours showed significant lower ADC parameters and higher kurtosis than early Masaoka stage (Stage I and II; n = 13) tumours (all p-values <0.05), while no significant difference on skewness (p = 0.063). ADC 10 showed best differentiating ability (cut-off value, ≤0.689 × 10 -3 mm 2 s -1 ; AUC, 0.913; sensitivity, 91.30%; specificity, 85.71%) for discriminating advanced and early Masaoka stage epithelial tumours. ADC histogram analysis may assist in assessing the WHO pathological classification and Masaoka clinical stages of thymic epithelial tumours. Advances in knowledge: 1. ADC histogram analysis could help to assess WHO pathological classification of thymic epithelial tumours. 2. ADC histogram analysis could

  9. Advanced Low-Noise Research Fan Stage Design

    NASA Technical Reports Server (NTRS)

    Neubert, Robert; Bock, Larry; Malmborg, Eric; Owen-Peer, William

    1997-01-01

    This report describes the design of the Advanced Low-Noise Research Fan stage. The fan is a variable pitch design, which is designed at the cruise pitch condition. Relative to the cruise setting, the blade is closed at takeoff and opened for reverse thrust operation. The fan stage is a split flow design with fan exit guide vanes (FEGVs) and core stators. The fan stage design is combined with a nacelle and engine core duct to form a powered fan/nacelle subscale model. This model is intended for use in combined aerodynamic, acoustic, and structural testing in a wind tunnel. The fan has an outer diameter of 22 in. and a hub-to-tip of 0.426 in., which allows the use of existing NASA fan and cowl force balance and rig drive systems. The design parameters were selected to permit valid acoustic and aerodynamic comparisons with the Pratt & Whitney (P&W) 17- and 22-in. rigs previously tested under NASA contract. The fan stage design is described in detail. The results of the design axisymmetric and Navier-Stokes aerodynamic analysis are presented at the critical design conditions. The structural analysis of the fan rotor and attachment is included. The blade and attachment are predicted to have adequate low-cycle fatigue life and an acceptable operating range without resonant stress or flutter. The stage was acoustically designed with airfoil counts in the FEGV and core stator to minimize noise. A fan/FEGV tone analysis developed separately under NASA contract was used to determine the optimum airfoil counts. The fan stage was matched to the existing nacelle, designed under the previous P&W low-noise contract, to form a fan/nacelle model for wind tunnel testing. It is an axisymmetric nacelle for convenience in testing and analysis. Previous testing confirmed that the nacelle performed as required at various aircraft operating conditions.

  10. The newly proposed clinical and post-neoadjuvant treatment staging classifications for gastric adenocarcinoma for the American Joint Committee on Cancer (AJCC) staging.

    PubMed

    In, Haejin; Ravetch, Ethan; Langdon-Embry, Marisa; Palis, Bryan; Ajani, Jaffer A; Hofstetter, Wayne L; Kelsen, David P; Sano, Takeshi

    2018-01-01

    New stage grouping classifications for clinical (cStage) and post-neoadjuvant treatment (ypStage) stage for gastric adenocarcinoma have been proposed for the eighth edition of the AJCC manual. This article summarizes the analysis for these stages. Gastric adenocarcinoma patients diagnosed in 2004-2009 were identified from the National Cancer Database (NCDB). The cStage cohort included both surgical and nonsurgical cases, and the ypStage cohort included only patients who had chemotherapy or radiation therapy before surgery. Survival differences between the stage groups were determined by the log-rank test and prognostic accuracy was assessed by concordance index. Analysis was performed using SAS 9.4 (SAS, Cary, NC, USA). Five strata for cStage and four strata for ypStage were developed. The 5-year survival rates for cStages were 56.77%, 47.39%, 33.1%, 25.9%, and 5.0% for stages I, IIa, IIb, III, and IV, respectively, and the rates for ypStage were 74.2%, 46.3%, 19.2%, and 11.6% for stages I, II, III, and IV, respectively. The log-rank test showed that survival differences were well stratified and stage groupings were ordered and distinct (p < 0.0001). The proposed cStage and ypStage classification was sensitive and specific and had high prognostic accuracy (cStage: c index = 0.81, 95% CI, 0.79-0.83; ypStage: c index = 0.80, 95% CI, 0.73-0.87). The proposed eighth edition establishes two new staging schemata that provide essential prognostic data for patients before treatment and for patients who have undergone surgery following neoadjuvant therapy. These additions are a significant advance to the AJCC staging manual and will provide critical guidance to clinicians in making informed decisions throughout the treatment course.

  11. Breast cancer in kurdish women of northern Iraq: incidence, clinical stage, and case control analysis of parity and family risk

    PubMed Central

    2009-01-01

    Background Breast cancer in the Middle-East occurs in relatively young women and frequently presents as advanced disease. A protective effect of multiparity is not apparent, and high familial risk is reported in some countries. This study investigates breast cancer rates and clinical stage related to age in the Kurdish region of Iraq and evaluates risk associated with parity and family history. Findings are compared with nearby countries and the West. Methods Sulaimaniyah Directorate of Health records identified 539 women diagnosed with breast cancer during 2006-2008. Clinical survey forms were completed on 296 patients and on 254 age-matched controls. Age specific incidence rates were calculated from Directorate of Health population estimates. Results Average patient age was 47.4 ± 11 years and 59.5% were pre-menopausal. Diagnosis was at clinical stage 1 for 4.1%, stage 2 for 43.5%, stage 3 for 26.0%, and stage 4 for 8.1% of patients. For 18.2%, stage was unknown. Annual breast cancer incidence rates per 100,000 women peaked at 168.9 at age 55 to 59 and declined to 57.3 at 60 and above. Patients had an average of 5.0 ± 3.3 children compared to 5.4 ± 3.5 for controls, P = 0.16. A first degree family member had breast cancer among 11.1% of patients and 2.1% of controls (P < 0.001) with > 50% of these patients and controls being ≥50 years old. No statistically significant relationship was found between tumor stage and age, P = 0.59. Conclusions In Kurdish Iraq, breast cancer is predominantly a disease of pre-menopausal women having multiple pregnancies. For younger patients, breast cancer incidence was similar to the West and possibly higher than many Middle-Eastern countries, but unlike the West, the estimated rates declined markedly in the elderly. The familial breast cancer risk for both older and younger women was within the general population risk of Western countries. Clinical stages were advanced and indicated delays in diagnosis that were unrelated to

  12. From orphan drugs to adopted therapies: Advancing C3-targeted intervention to the clinical stage

    PubMed Central

    Mastellos, Dimitrios C.; Reis, Edimara S.; Yancopoulou, Despina; Hajishengallis, George; Ricklin, Daniel; Lambris, John D.

    2016-01-01

    Complement dysregulation is increasingly recognized as an important pathogenic driver in a number of clinical disorders. Complement-triggered pathways intertwine with key inflammatory and tissue destructive processes that can either increase the risk of disease or exacerbate pathology in acute or chronic conditions. The launch of the first complement-targeted drugs in the clinic has undeniably stirred the field of complement therapeutic design, providing new insights into complement's contribution to disease pathogenesis and also helping to leverage a more personalized, comprehensive approach to patient management. In this regard, a rapidly expanding toolbox of complement therapeutics is being developed to address unmet clinical needs in several immune-mediated and inflammatory diseases. Elegant approaches employing both surface-directed and fluid-phase inhibitors have exploited diverse components of the complement cascade as putative points of therapeutic intervention. Targeting C3, the central hub of the system, has proven to be a promising strategy for developing biologics as well as small-molecule inhibitors with clinical potential. Complement modulation at the level of C3 has recently shown promise in preclinical primate models, opening up new avenues for therapeutic intervention in both acute and chronic indications fueled by uncontrolled C3 turnover. This review highlights recent developments in the field of complement therapeutics, focusing on C3-directed inhibitors and alternative pathway (AP) regulator-based approaches. Translational perspectives and considerations are discussed, particularly with regard to the structure-guided drug optimization and clinical advancement of a new generation of C3-targeted peptidic inhibitors. PMID:27353192

  13. Barriers to Advance Care Planning in End-Stage Renal Disease: Who is to Blame, and What Can be Done?

    PubMed

    Kelley, Alan Taylor; Turner, Jeffrey; Doolittle, Benjamin

    2018-07-01

    Patients with end-stage renal disease experience significant mortality and morbidity, including cognitive decline. Advance care planning has been emphasized as a responsibility and priority of physicians caring for patients with chronic kidney disease in order to align with patient values before decision-making capacity is lost and to avoid suffering. This emphasis has proven ineffective, as illustrated in the case of a patient treated in our hospital. Is this ineffectiveness a consequence of failure in the courtroom or the clinic? Through our own experience we affirm what has been written before: that legal precedent favors intensive treatment in virtually all cases without 'clear and convincing evidence' of a patient's previously declared wishes to the contrary. Equally clear is that more than 20 years of support in the clinical literature suggesting advance care planning early in the course of disease can address challenges in the legal system for those lacking capacity. However, many physicians fail to recognize the need for advance care planning in a timely manner and lack the necessary training to provide it. The need for more training and new tools to recognize opportunities for advance care planning in daily practice remains unmet.

  14. Defining end-stage renal disease in clinical trials: a framework for adjudication.

    PubMed

    Agarwal, Rajiv

    2016-06-01

    Unlike definition of stroke and myocardial infarction, there is no uniformly agreed upon definition to adjudicate end-stage renal disease (ESRD). ESRD remains the most unambiguous and clinically relevant end point for clinical trialists, regulators, payers and patients with chronic kidney disease. The prescription of dialysis to patients with advanced chronic kidney disease is subjective and great variations exist among physicians and countries. Given the difficulties in diagnosing ESRD, the presence of estimated GFR <15 mL/min/1.7 3m(2) itself has been suggested as an end point. However, this definition is still a surrogate since many patients may live years without being symptomatic or needing dialysis. The purpose of this report is to describe a framework to define when the kidney function ends and when ESRD can be adjudicated. Discussed in this report are (i) the importance of diagnosing symptomatic uremia or advanced asymptomatic uremia thus establishing the need for dialysis; (ii) establishing the chronicity of dialysis so as to distinguish it from acute dialysis; (iii) establishing ESRD when dialysis is unavailable, refused or considered futile and (iv) the adjudication process. Several challenges and ambiguities that emerge in clinical trials and their possible solutions are provided. The criteria proposed herein may help to standardize the definition of ESRD and reduce the variability in adjudicating the most important renal end point in clinical trials of chronic kidney disease. Published by Oxford University Press on behalf of ERA-EDTA 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  15. First Brazilian Consensus of Advanced Prostate Cancer: Recommendations for Clinical Practice.

    PubMed

    Sasse, Andre Deeke; Wiermann, Evanius Garcia; Herchenhorn, Daniel; Bastos, Diogo Assed; Schutz, Fabio A; Maluf, Fernando Cotait; Coura, George; Morbeck, Igor Alexandre Protzner; Cerci, Juliano J; Smaletz, Oren; Lima, Volney Soares; Adamy, Ari; Campos, Franz Santos de; Carvalhal, Gustavo Franco; Cezar, Leandro Casemiro; Dall'Oglio, Marcos Francisco; Sadi, Marcus Vinicius; Reis, Rodolfo Borges Dos; Nogueira, Lucas

    2017-01-01

    Prostate cancer still represents a major cause of morbidity, and still about 20% of men with the disease are diagnosed or will progress to the advanced stage without the possibility of curative treatment. Despite the recent advances in scientific and technological knowledge and the availability of new therapies, there is still considerable heterogeneity in the therapeutic approaches for metastatic prostate cancer. This article presents a summary of the I Brazilian Consensus on Advanced Prostate Cancer, conducted by the Brazilian Society of Urology and Brazilian Society of Clinical Oncology. Experts were selected by the medical societies involved. Forty issues regarding controversial issues in advanced disease were previously elaborated. The panel met for consensus, with a threshold established for 2/3 of the participants. The treatment of advanced prostate cancer is complex, due to the existence of a large number of therapies, with different response profiles and toxicities. The panel addressed recommendations on preferred choice of therapies, indicators that would justify their change, and indicated some strategies for better sequencing of treatment in order to maximize the potential for disease control with the available therapeutic arsenal. The lack of consensus on some topics clearly indicates the absence of strong evidence for some decisions. Copyright® by the International Brazilian Journal of Urology.

  16. Classification of hepatocellular carcinoma stages from free-text clinical and radiology reports

    PubMed Central

    Yim, Wen-wai; Kwan, Sharon W; Johnson, Guy; Yetisgen, Meliha

    2017-01-01

    Cancer stage information is important for clinical research. However, they are not always explicitly noted in electronic medical records. In this paper, we present our work on automatic classification of hepatocellular carcinoma (HCC) stages from free-text clinical and radiology notes. To accomplish this, we defined 11 stage parameters used in the three HCC staging systems, American Joint Committee on Cancer (AJCC), Barcelona Clinic Liver Cancer (BCLC), and Cancer of the Liver Italian Program (CLIP). After aggregating stage parameters to the patient-level, the final stage classifications were achieved using an expert-created decision logic. Each stage parameter relevant for staging was extracted using several classification methods, e.g. sentence classification and automatic information structuring, to identify and normalize text as cancer stage parameter values. Stage parameter extraction for the test set performed at 0.81 F1. Cancer stage prediction for AJCC, BCLC, and CLIP stage classifications were 0.55, 0.50, and 0.43 F1.

  17. Clinical stage, therapy, and prognosis in canine anal sac gland carcinoma.

    PubMed

    Polton, Gerry A; Brearley, Malcolm J

    2007-01-01

    Reports of canine anal sac gland carcinoma (ASGC) describe varied clinical presentations and management and differing responses to therapy. A unifying approach to clinical stage determination and management of this disease has yet to be presented. An ordinal clinical staging scheme for canine ASGC can be devised on the basis of responses to therapy for a retrospective cohort of affected dogs. 130 dogs with naturally occurring ASGC. A simplified clinical stage system and a management algorithm for canine ASGC were derived from retrospective evaluation of a cohort of 80 dogs; applicability of both was then prospectively evaluated in a cohort of 50 dogs. Retrospective evaluation revealed 4 statistically significant negative prognostic indicators for survival: lack of therapy, presence of distant metastases, presence of lymph node metastases, and primary tumor size. Lymph node extirpation was a statistically significant positive prognostic indicator by bivariate analysis. In both retrospective and prospective analyses, the modified clinical stage scheme revealed a significant association with survival time. The clinical staging scheme permits differentiation between groups in terms of prognosis and, therefore, decisions on therapy. This will facilitate application of appropriate therapy and enhanced communication and collaboration in further investigations of ASGC.

  18. Guidelines on Chemotherapy in Advanced Stage Gynecological Malignancies: An Evaluation of 224 Professional Societies and Organizations

    PubMed Central

    Polyzos, Nikolaos P.; Mauri, Davide; Ioannidis, John P. A.

    2011-01-01

    Background Clinical practice guidelines are important for guiding practice, but it is unclear if they are commensurate with the available evidence. Methods We examined guidelines produced by cancer and gynecological societies and organizations and evaluated their coverage of and stance towards chemotherapy for advanced stage disease among 4 gynecological malignancies (breast, ovarian, cervical, endometrial cancer) where the evidence for the use of chemotherapy is very different (substantial and conclusive for breast and ovarian cancer, limited and suggesting no major benefit for cervical and endometrial cancer). Eligible societies and organizations were identified through systematic internet searches (last update June 2009). Pertinent websites were scrutinized for presence of clinical practice guidelines, and relative guidelines were analyzed. Results Among 224 identified eligible societies and organizations, 69 (31%) provided any sort of guidelines, while recommendations for chemotherapy on advanced stage gynecological malignancies were available in 20 of them. Only 14 had developed their own guideline, and only 5 had developed guidelines for all 4 malignancies. Use of levels of evidence and grades of recommendations, and aspects of the production, implementation, and timeliness of the guidelines did not differ significantly across malignancies. Guidelines on breast and ovarian cancer utilized significantly more randomized trials and meta-analyses. Guidelines differed across malignancies on their coverage of disease-free survival (p = 0.033), response rates (p = 0.024), symptoms relief (p = 0.005), quality of life (p = 0.001) and toxicity (p = 0.039), with breast and ovarian cancer guidelines typically covering more frequently these outcomes. All guidelines explicitly or implicitly endorsed the use of chemotherapy. Conclusions Clinical practice guidelines are provided by the minority of professional societies and organizations. Available

  19. Reduced Empathy Scores in Patients with Parkinson's Disease: A Non-Motor Symptom Associated with Advanced Disease Stages.

    PubMed

    Schmidt, Nele; Paschen, Laura; Deuschl, Günther; Witt, Karsten

    2017-01-01

    Empathy describes the ability to infer and share emotional experiences of other people and is a central component of normal social functioning. Impaired empathy might be a non-motor symptom in Parkinson's disease (PD). To examine empathic abilities and their relationship to clinical and cognitive functioning in PD patients. Empathy was measured in 75 non-demented PD patients and 34 age-matched healthy controls using a German version of the Interpersonal Reactivity Index. Moreover, we collected demographic and clinical data and conducted a comprehensive neuropsychological test battery. PD patients had a significant lower global empathy score than healthy controls. Furthermore, we found significant group differences for the cognitive empathy scales but not for the scales which are sensitive for affective empathy components. The empathy decrease was significantly higher in advanced Hoehn & Yahr stages. There were only sporadic significant correlations between empathy scores and cognitive variables. PD patients show a stage dependent empathy score decrease which is driven mainly by cognitive aspects of empathy. However, emotional empathy aspects are not reduced.

  20. The prediction of progression-free and overall survival in women with an advanced stage of epithelial ovarian carcinoma.

    PubMed

    Gerestein, C G; Eijkemans, M J C; de Jong, D; van der Burg, M E L; Dykgraaf, R H M; Kooi, G S; Baalbergen, A; Burger, C W; Ansink, A C

    2009-02-01

    Prognosis in women with ovarian cancer mainly depends on International Federation of Gynecology and Obstetrics stage and the ability to perform optimal cytoreductive surgery. Since ovarian cancer has a heterogeneous presentation and clinical course, predicting progression-free survival (PFS) and overall survival (OS) in the individual patient is difficult. The objective of this study was to determine predictors of PFS and OS in women with advanced stage epithelial ovarian cancer (EOC) after primary cytoreductive surgery and first-line platinum-based chemotherapy. Retrospective observational study. Two teaching hospitals and one university hospital in the south-western part of the Netherlands. Women with advanced stage EOC. All women who underwent primary cytoreductive surgery for advanced stage EOC followed by first-line platinum-based chemotherapy between January 1998 and October 2004 were identified. To investigate independent predictors of PFS and OS, a Cox' proportional hazard model was used. Nomograms were generated with the identified predictive parameters. The primary outcome measure was OS and the secondary outcome measures were response and PFS. A total of 118 women entered the study protocol. Median PFS and OS were 15 and 44 months, respectively. Preoperative platelet count (P = 0.007), and residual disease <1 cm (P = 0.004) predicted PFS with a optimism corrected c-statistic of 0.63. Predictive parameters for OS were preoperative haemoglobin serum concentration (P = 0.012), preoperative platelet counts (P = 0.031) and residual disease <1 cm (P = 0.028) with a optimism corrected c-statistic of 0.67. PFS could be predicted by postoperative residual disease and preoperative platelet counts, whereas residual disease, preoperative platelet counts and preoperative haemoglobin serum concentration were predictive for OS. The proposed nomograms need to be externally validated.

  1. TDP-43 stage, mixed pathologies, and clinical Alzheimer's-type dementia.

    PubMed

    James, Bryan D; Wilson, Robert S; Boyle, Patricia A; Trojanowski, John Q; Bennett, David A; Schneider, Julie A

    2016-11-01

    Hyperphosphorylated transactive response DNA-binding protein 43 (TDP-43, encoded by TARDBP ) proteinopathy has recently been described in ageing and in association with cognitive impairment, especially in the context of Alzheimer's disease pathology. To explore the role of mixed Alzheimer's disease and TDP-43 pathologies in clinical Alzheimer's-type dementia, we performed a comprehensive investigation of TDP-43, mixed pathologies, and clinical Alzheimer's-type dementia in a large cohort of community-dwelling older subjects. We tested the hypotheses that TDP-43 with Alzheimer's disease pathology is a common mixed pathology; is related to increased likelihood of expressing clinical Alzheimer's-type dementia; and that TDP-43 pathologic stage is an important determinant of clinical Alzheimer's-type dementia. Data came from 946 older adults with ( n = 398) and without dementia ( n = 548) from the Rush Memory and Aging Project and Religious Orders Study. TDP-43 proteinopathy (cytoplasmic inclusions) was present in 496 (52%) subjects, and the pattern of deposition was classified as stage 0 (none; 48%), stage 1 (amygdala; 18%), stage 2 (extension to hippocampus/entorhinal; 21%), or stage 3 (extension to neocortex; 14%). TDP-43 pathology combined with a pathologic diagnosis of Alzheimer's disease was a common mixed pathology (37% of all participants), and the proportion of subjects with clinical Alzheimer's-type dementia formerly labelled 'pure pathologic diagnosis of Alzheimer's disease' was halved when TDP-43 was considered. In logistic regression models adjusted for age, sex, and education, TDP-43 pathology was associated with clinical Alzheimer's-type dementia (odds ratio = 1.51, 95% confidence interval = 1.11, 2.05) independent of pathological Alzheimer's disease (odds ratio = 4.30, 95% confidence interval = 3.08, 6.01) or other pathologies (infarcts, arteriolosclerosis, Lewy bodies, and hippocampal sclerosis). Mixed Alzheimer's disease and TDP-43 pathologies were

  2. Airway reconstruction: review of an approach to the advanced-stage laryngotracheal stenosis.

    PubMed

    Bitar, Mohamad Ahmad; Al Barazi, Randa; Barakeh, Rana

    The management of laryngotracheal stenosis is complex and is influenced by multiple factors that can affect the ultimate outcome. Advanced lesions represent a special challenge to the treating surgeon to find the best remedying technique. To review the efficacy of our surgical reconstructive approach in managing advanced-stage laryngotracheal stenosis treated at a tertiary medical center. A retrospective review of all patients that underwent open laryngotracheal repair/reconstruction by the senior author between 2002 and 2014. Patients with mild/moderate stenosis (e.g. stage 1 or 2), or those who had an open reconstructive procedure prior to referral, were excluded. Patients who had only endoscopic treatment (e.g. laser, balloon dilatation) and were not subjected to an open reconstructive procedure at our institution, were not included in this study. Variables studied included patient demographics, clinical presentation, etiology of the laryngotracheal pathology, the location of stenosis, the stage of stenosis, the type of corrective or reconstructive procedure performed with the type of graft used (where applicable), the type and duration of stent used, the post-reconstruction complications, and the duration of follow-up. Outcome measures included decannulation rate, total number of reconstructive surgeries needed to achieve decannulation, and the number of post-operative endoscopies needed to reach a safe patent airway. Twenty five patients were included, aged 0.5 months to 45 years (mean 13.5 years, median 15 years) with 16 males and 9 females. Seventeen patients (68%) were younger than 18 years. Most patients presented with stridor, failure of decannulation, or respiratory distress. Majority had acquired etiology for their stenosis with only 24% having a congenital pathology. Thirty-two reconstructive procedures were performed resulting in decannulating 24 patients (96%), with 15/17 (88%) pediatric patients and 5/8 (62.5%) adult patients requiring only a single

  3. Determining the satisfaction levels of the family members of patients with advanced-stage cancer.

    PubMed

    Ozcelik, Hanife; Cakmak, Deniz Ezgi; Fadiloglu, Cicek; Yildirim, Yasemin; Uslu, Ruchan

    2015-06-01

    The objective of our study was to determine the satisfaction levels of family members of patients with advanced-stage cancer. This descriptive study was conducted in the palliative care and medical oncology clinics of a university hospital in the province of Izmir between April of 2011 and January of 2012. The study sample consisted of a total of 145 family members, who were selected from among the family members of patients with advanced-stage cancer receiving palliative treatment. The study data were obtained using the Patient Description Form and Family Satisfaction Scale during face-to-face interviews with patients. Some 67% of patients were female and 33% male, 70% were married, 35% were high school graduates, and 34.5% were housewives. The average total family satisfaction score was 76.87 ± 1.14, and the average scores for the component variables were as follows: information giving 74.37 ± 1.28, availability of care 78.40 ± 1.17, physical care 78.99 ± 1.09, and psychosocial care 74.52 ± 1.30. We found a relationship between the level of satisfaction of family members and (1) gender, (2) occupation, (3) presence of someone supporting the care, and (4) possession of sufficient information about the patient (p < 0.05). Satisfaction levels of participants were determined to be high. We found that family member satisfaction levels were affected by gender and occupation, the existence of someone supporting the care, and possession of sufficient information about the patient.

  4. Nomogram for 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer.

    PubMed

    Nieuwenhuyzen-de Boer, G M; Gerestein, C G; Eijkemans, M J C; Burger, C W; Kooi, G S

    2016-01-01

    Extensive surgical procedures to achieve maximal cytoreduction in patients with advanced stage epithelial ovarian cancer (EOC) are inevitably associated with postoperative morbidity and mortality. This study aimed to identify preoperative predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC and to develop a nomogram for individual risk assessment. Patients in The Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007. All peri- and postoperative complications within 30 days after surgery were registered and classified. To investigate predictors of 30-day morbidity, a Cox proportional hazard model with backward stepwise elimination was utilized. The identified predictors were entered into a nomogram. The main outcome was to identify parameters that predict operative risk. 293 patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. Thirty-day morbidity was seen in 99 (34%) patients. Morbidity could be predicted by age (p = 0.033; OR 1.024), preoperative hemoglobin (p = 0.194; OR 0.843), and WHO performance status (p = 0.015; OR 1.821) with a optimism-corrected c-statistic of 0.62. Determinants co-morbidity status, serum CA125 level, platelet count, and presence of ascites were comparable in both groups. Thirty-day morbidity after primary cytoreductive surgery for advanced stage EOC could be predicted by age, hemoglobin, and WHO performance status. The generated nomogram could be valuable for predicting operative risk in the individual patient.

  5. Challenges of advanced hepatocellular carcinoma

    PubMed Central

    Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

    2016-01-01

    Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

  6. Treatment of localized-stage follicular lymphoma.

    PubMed

    Sorigue, Marc; Tuset, Victòria; Sancho, Juan-Manuel

    2018-05-12

    Follicular lymphoma (FL) is the most common indolent lymphoma and it most frequently presents in an advanced-stage. Therapeutic considerations for advanced-stage are different from those of localized-stage FL, in which radiotherapy (RT) is generally recommended. However, the available evidence suffers from shortcomings that are relatively specific to this clinical entity due to its rarity and long survival with all available treatment modalities, including that most of the existing evidence originated at a time when diagnostic classifications, staging procedures and radiotherapeutic standards were different from those available today and when anti-CD20 monoclonal antibodies were not available. Available treatment modalities include observation, systemic therapy only, RT only and RT in combination with systemic therapy. We review the evidence available with each of them and the data from present day clinical practice studies as well as briefly discuss what diagnostic and therapeutic developments may take place in the next few years. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Staging in bipolar disorder: from theoretical framework to clinical utility.

    PubMed

    Berk, Michael; Post, Robert; Ratheesh, Aswin; Gliddon, Emma; Singh, Ajeet; Vieta, Eduard; Carvalho, Andre F; Ashton, Melanie M; Berk, Lesley; Cotton, Susan M; McGorry, Patrick D; Fernandes, Brisa S; Yatham, Lakshmi N; Dodd, Seetal

    2017-10-01

    Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at-risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end-stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures. These include progressive biochemical, neuroimaging and cognitive changes, and potentially stage-specific differences in response to pharmacological and psychosocial treatments. Mechanistically, staging models imply the presence of an active disease process that, if not remediated, can lead to neuroprogression, a more malignant disease course and functional deterioration. Biological elements thought to be operative in bipolar disorder include a genetic diathesis, physical and psychic trauma, epigenetic changes, altered neurogenesis and apoptosis, mitochondrial dysfunction, inflammation, and oxidative stress. Many available agents, such as lithium, have effects on these targets. Staging models also suggest the utility of stage-specific treatment approaches that may not only target symptom reduction, but also impede illness neuroprogression. These treatment approaches range from prevention for at-risk individuals, to early intervention strategies for prodromal and newly diagnosed individuals, complex combination therapy for rapidly recurrent illness, and palliative-type approaches for those at chronic, late stages of illness. There is hope that prompt initiation of potentially disease modifying therapies may preclude or attenuate the cognitive and structural changes seen in the later stages of bipolar disorder. The aims of this paper are to: a

  8. Variation in advanced stage at diagnosis of lung and female breast cancer in an English region 2006-2009.

    PubMed

    Lyratzopoulos, G; Abel, G A; Barbiere, J M; Brown, C H; Rous, B A; Greenberg, D C

    2012-03-13

    Understanding variation in stage at diagnosis can inform interventions to improve the timeliness of diagnosis for patients with different cancers and characteristics. We analysed population-based data on 17,836 and 13,286 East of England residents diagnosed with (female) breast and lung cancer during 2006-2009, with stage information on 16,460 (92%) and 10,435 (79%) patients, respectively. Odds ratios (ORs) of advanced stage at diagnosis adjusted for patient and tumour characteristics were derived using logistic regression. We present adjusted ORs of diagnosis in stages III/IV compared with diagnosis in stages I/II. For breast cancer, the frequency of advanced stage at diagnosis increased stepwise among old women (ORs: 1.21, 1.46, 1.68 and 1.78 for women aged 70-74, 75-79, 80-84 and ≥85, respectively, compared with those aged 65-69 , P<0.001). In contrast, for lung cancer advanced stage at diagnosis was less frequent in old patients (ORs: 0.82, 0.74, 0.73 and 0.66, P<0.001). Advanced stage at diagnosis was more frequent in more deprived women with breast cancer (OR: 1.23 for most compared with least deprived, P=0.002), and in men with lung cancer (OR: 1.14, P=0.011). The observed patterns were robust to sensitivity analyses approaches for handling missing stage data under different assumptions. Interventions to help improve the timeliness of diagnosis of different cancers should be targeted at specific age groups.

  9. Six-minute walk test and heart rate variability: lack of association in advanced stages of heart failure.

    PubMed

    Woo, M A; Moser, D K; Stevenson, L W; Stevenson, W G

    1997-09-01

    The 6-minute walk and heart rate variability have been used to assess mortality risk in patients with heart failure, but their relationship to each other and their usefulness for predicting mortality at 1 year are unknown. To assess the relationships between the 6-minute walk test, heart rate variability, and 1-year mortality. A sample of 113 patients in advanced stages of heart failure (New York Heart Association Functional Class III-IV, left ventricular ejection < 0.25) were studied. All 6-minute walks took place in an enclosed, level, measured corridor and were supervised by the same nurse. Heart rate variability was measured by using (1) a standard-deviation method and (2) Poincaré plots. Data on RR intervals obtained by using 24-hour Holter monitoring were analyzed. Survival was determined at 1 year after the Holter recording. The results showed no significant associations between the results of the 6-minute walk and the two measures of heart rate variability. The results of the walk were related to 1-year mortality but not to the risk of sudden death. Both measures of heart rate variability had significant associations with 1-year mortality and with sudden death. However, only heart rate variability measured by using Poincaré plots was a predictor of total mortality and risk of sudden death, independent of left ventricular ejection fraction, serum levels of sodium, results of the 6-minute walk test, and the standard-deviation measure of heart rate variability. Results of the 6-minute walk have poor association with mortality and the two measures of heart rate variability in patients with advanced-stage heart failure and a low ejection fraction. Further studies are needed to determine the optimal clinical usefulness of the 6-minute walk and heart rate variability in patients with advanced-stage heart failure.

  10. Cutaneous Lymphoma International Consortium Study of Outcome in Advanced Stages of Mycosis Fungoides and Sézary Syndrome: Effect of Specific Prognostic Markers on Survival and Development of a Prognostic Model

    PubMed Central

    Scarisbrick, Julia J.; Prince, H. Miles; Vermeer, Maarten H.; Quaglino, Pietro; Horwitz, Steven; Porcu, Pierluigi; Stadler, Rudolf; Wood, Gary S.; Beylot-Barry, Marie; Pham-Ledard, Anne; Foss, Francine; Girardi, Michael; Bagot, Martine; Michel, Laurence; Battistella, Maxime; Guitart, Joan; Kuzel, Timothy M.; Martinez-Escala, Maria Estela; Estrach, Teresa; Papadavid, Evangelia; Antoniou, Christina; Rigopoulos, Dimitis; Nikolaou, Vassilki; Sugaya, Makoto; Miyagaki, Tomomitsu; Gniadecki, Robert; Sanches, José Antonio; Cury-Martins, Jade; Miyashiro, Denis; Servitje, Octavio; Muniesa, Cristina; Berti, Emilio; Onida, Francesco; Corti, Laura; Hodak, Emilia; Amitay-Laish, Iris; Ortiz-Romero, Pablo L.; Rodríguez-Peralto, Jose L.; Knobler, Robert; Porkert, Stefanie; Bauer, Wolfgang; Pimpinelli, Nicola; Grandi, Vieri; Cowan, Richard; Rook, Alain; Kim, Ellen; Pileri, Alessandro; Patrizi, Annalisa; Pujol, Ramon M.; Wong, Henry; Tyler, Kelly; Stranzenbach, Rene; Querfeld, Christiane; Fava, Paolo; Maule, Milena; Willemze, Rein; Evison, Felicity; Morris, Stephen; Twigger, Robert; Talpur, Rakhshandra; Kim, Jinah; Ognibene, Grant; Li, Shufeng; Tavallaee, Mahkam; Hoppe, Richard T.; Duvic, Madeleine; Whittaker, Sean J.; Kim, Youn H.

    2015-01-01

    Purpose Advanced-stage mycosis fungoides (MF; stage IIB to IV) and Sézary syndrome (SS) are aggressive lymphomas with a median survival of 1 to 5 years. Clinical management is stage based; however, there is wide range of outcome within stages. Published prognostic studies in MF/SS have been single-center trials. Because of the rarity of MF/SS, only a large collaboration would power a study to identify independent prognostic markers. Patients and Methods Literature review identified the following 10 candidate markers: stage, age, sex, cutaneous histologic features of folliculotropism, CD30 positivity, proliferation index, large-cell transformation, WBC/lymphocyte count, serum lactate dehydrogenase, and identical T-cell clone in blood and skin. Data were collected at specialist centers on patients diagnosed with advanced-stage MF/SS from 2007. Each parameter recorded at diagnosis was tested against overall survival (OS). Results Staging data on 1,275 patients with advanced MF/SS from 29 international sites were included for survival analysis. The median OS was 63 months, with 2- and 5-year survival rates of 77% and 52%, respectively. The median OS for patients with stage IIB disease was 68 months, but patients diagnosed with stage III disease had slightly improved survival compared with patients with stage IIB, although patients diagnosed with stage IV disease had significantly worse survival (48 months for stage IVA and 33 months for stage IVB). Of the 10 variables tested, four (stage IV, age > 60 years, large-cell transformation, and increased lactate dehydrogenase) were independent prognostic markers for a worse survival. Combining these four factors in a prognostic index model identified the following three risk groups across stages with significantly different 5-year survival rates: low risk (68%), intermediate risk (44%), and high risk (28%). Conclusion To our knowledge, this study includes the largest cohort of patients with advanced-stage MF/SS and

  11. A modified varying-stage adaptive phase II/III clinical trial design.

    PubMed

    Dong, Gaohong; Vandemeulebroecke, Marc

    2016-07-01

    Conventionally, adaptive phase II/III clinical trials are carried out with a strict two-stage design. Recently, a varying-stage adaptive phase II/III clinical trial design has been developed. In this design, following the first stage, an intermediate stage can be adaptively added to obtain more data, so that a more informative decision can be made. Therefore, the number of further investigational stages is determined based upon data accumulated to the interim analysis. This design considers two plausible study endpoints, with one of them initially designated as the primary endpoint. Based on interim results, another endpoint can be switched as the primary endpoint. However, in many therapeutic areas, the primary study endpoint is well established. Therefore, we modify this design to consider one study endpoint only so that it may be more readily applicable in real clinical trial designs. Our simulations show that, the same as the original design, this modified design controls the Type I error rate, and the design parameters such as the threshold probability for the two-stage setting and the alpha allocation ratio in the two-stage setting versus the three-stage setting have a great impact on the design characteristics. However, this modified design requires a larger sample size for the initial stage, and the probability of futility becomes much higher when the threshold probability for the two-stage setting gets smaller. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Evolution and clinical impact of co-occurring genetic alterations in advanced-stage EGFR-mutant lung cancers. | Office of Cancer Genomics

    Cancer.gov

    A widespread approach to modern cancer therapy is to identify a single oncogenic driver gene and target its mutant-protein product (for example, EGFR-inhibitor treatment in EGFR-mutant lung cancers). However, genetically driven resistance to targeted therapy limits patient survival. Through genomic analysis of 1,122 EGFR-mutant lung cancer cell-free DNA samples and whole-exome analysis of seven longitudinally collected tumor samples from a patient with EGFR-mutant lung cancer, we identified critical co-occurring oncogenic events present in most advanced-stage EGFR-mutant lung cancers.

  13. Brief cognitive assessment of Alzheimer's disease in advanced stages: Proposal for a Brazilian version of the Short Battery for Severe Impairment (SIB-8).

    PubMed

    Wajman, José Roberto; Bertolucci, Paulo Henrique Ferreira

    2013-01-01

    The measurement of cognitive abilities of patients with severe dementia can serve a wide range of methodological and clinical needs. To validate a proposed severe impairment battery SIB-8 for a Brazilian population sample as part of the neuropsychological assessment of patients with Alzheimer's disease (AD) in advanced stages. After a systematic process of translation and back-translation, the SIB-8 was applied to 95 patients with AD at different stages; moderate, moderately severe and severe according to FAST subdivisions (5, 6 and 7), with scores on the Mini-Mental State Examination (MMSE) of between 5 and 15 and followed by the Division of Behavioral Neurology and the Center for Aging Brain of the Federal University of São Paulo - UNIFESP. Inferential data revealed that the SIB-8 instrument behaved differently at each stage of the disease with a statistical value of sensitivity p<0.001, gradually reflecting the expected course of the dementia, inherent with the decline of cognitive functions. Findings indicated that the SIB-8 is a useful tool for the evaluation and prospective comparison of AD patients in advanced stages, retaining its original characteristics in our population.

  14. Body weight, hemoglobin, and absolute neutrophil count in patients with advanced-stage epithelial ovarian cancer who received chemotherapy: A single-center study

    NASA Astrophysics Data System (ADS)

    Gunawan, Y.; Winarto, H.

    2017-08-01

    The side effects of chemotherapy, a treatment modality of ovarian cancer, can disrupt overall treatment. To date, the clinical and laboratory profiles of ovarian cancer patients during chemotherapy have not been investigated. This study aimed to elucidate the clinical and laboratory profiles of patients with advanced-stage epithelial ovarian cancer who received chemotherapy in Dr. Cipto Mangunkusumo Hospital, including body mass index (BMI), hemoglobin (Hb), and absolute neutrophil count (ANC). To generate these clinical and laboratory profiles, we collected secondary data from the medical records of advanced-stage epithelial ovarian cancer patients who received six cycles of carboplatin and paclitaxel chemotherapy. We enrolled 23 patients with advanced-stage epithelial ovarian cancer patients who received six cycles of chemotherapy. Mean patient BMI before and after chemotherapy was 22.86 kg/m2 and 21.78 kg/m2, respectively. Hb levels before chemotherapy were 8-13 g/dl, with Hb < 10 g/dl in one patient (4.35%) and Hb ≥ 10 g/dl in 22 patients (95.65%). Mean ANC was 5845.6 ± 3325.0. An average of 24.65% of patients experienced anemia after each cycle of chemotherapy. Mean ANC before chemotherapy was 3.5582 ± 3.3250. An average of 26.81% of patients had ANC <1500 after each cycle of chemotherapy; no patients had ANC <1500 before chemotherapy initiation. After six cycles of chemotherapy, three patients (13.04%) had mild neutropenia, four patients (17.39%) had moderate neutropenia, and one patient (4.35%) had severe neutropenia. Of the 22 patients with Hb ≥ 10 g/dl before chemotherapy, 16 (72.72%) experienced a decrease in ANC during chemotherapy. Of the 20 patients (60.87%) with normal BMI or higher, 14 experienced a decrease in ANC during chemotherapy. The mean patient body weight decreased after six cycles of chemotherapy. Hb and ANC were persistently decreased in approximately a quarter of the 23 subjects. The decrease in ANC was not influenced by initial Hb

  15. Predictors of Locally Advanced Disease at Presentation and Clinical Outcomes Among Cervical Cancer Patients Admitted at a Tertiary Hospital in Botswana.

    PubMed

    Nassali, Mercy Nkuba; Tadele, Melese; Nkuba, Robert Michael; Modimowame, Jamieson; Enyeribe, Iwuh; Katse, Edwin

    2018-05-23

    The aim of this study was to determine predictors of locally advanced disease at presentation and clinical outcomes among cervical cancer patients in Botswana to inform interventional strategies. Retrospective review of 149 medical records of new cervical cancer patients was conducted between August 2016 and February 2017 at the Princess Marina Hospital. Data collected included sociodemographics, presenting symptoms, stage of disease, comorbidities, interventions, and clinical outcomes. STATA 12 was used for data analysis. Frequencies were used to describe patient demographics and clinical variables. Bivariate and multivariate binary logistic regression analyses were used to determine association between stage of disease at presentation and patient characteristics. P ≤ 0.05 was considered significant. Mean age was 49.5 years. Nine (89.2%) in 10 patients had locally advanced cervical cancer (stage IB1-IVB). Two thirds (65.1%) were human immunodeficiency virus positive. Previous cervical cancer screening was low at 38.3%. Common symptoms were abnormal vaginal bleeding, low abdominal pain, and malodorous vaginal discharge reported among 75.8%, 66.4%, and 39.6% of cases, respectively. Overall, 32 (21.5%) were declared cured, 52 (34.9%) improved, and 11 (7.4%) opted for home-based care. Hospital deaths were 41 (27.5%). Major causes of death were renal failure (48.7%) and severe anemia (39%). Thirteen (8.7%) were lost to follow-up. Being unmarried (odds ratio [OR], 3.9), lack of cervical cancer screening (OR, 6.68), presentation with vaginal bleeding (OR, 7.69), and low abdominal pain (OR, 4.69) were associated with advanced disease at presentation. Lack of cervical cancer screening, vaginal bleeding, low abdominal pain, and unmarried status were associated with advanced disease at presentation. We recommend scale-up of cervical cancer screening and its integration into routine human immunodeficiency virus care. Capacity building in gynecologic oncology and palliative

  16. Staging in bipolar disorder: from theoretical framework to clinical utility

    PubMed Central

    Berk, Michael; Post, Robert; Ratheesh, Aswin; Gliddon, Emma; Singh, Ajeet; Vieta, Eduard; Carvalho, Andre F.; Ashton, Melanie M.; Berk, Lesley; Cotton, Susan M.; McGorry, Patrick D.; Fernandes, Brisa S.; Yatham, Lakshmi N.; Dodd, Seetal

    2017-01-01

    Illness staging is widely utilized in several medical disciplines to help predict course or prognosis, and optimize treatment. Staging models in psychiatry in general, and bipolar disorder in particular, depend on the premise that psychopathology moves along a predictable path: an at‐risk or latency stage, a prodrome progressing to a first clinical threshold episode, and one or more recurrences with the potential to revert or progress to late or end‐stage manifestations. The utility and validity of a staging model for bipolar disorder depend on its linking to clinical outcome, treatment response and neurobiological measures. These include progressive biochemical, neuroimaging and cognitive changes, and potentially stage‐specific differences in response to pharmacological and psychosocial treatments. Mechanistically, staging models imply the presence of an active disease process that, if not remediated, can lead to neuroprogression, a more malignant disease course and functional deterioration. Biological elements thought to be operative in bipolar disorder include a genetic diathesis, physical and psychic trauma, epigenetic changes, altered neurogenesis and apoptosis, mitochondrial dysfunction, inflammation, and oxidative stress. Many available agents, such as lithium, have effects on these targets. Staging models also suggest the utility of stage‐specific treatment approaches that may not only target symptom reduction, but also impede illness neuroprogression. These treatment approaches range from prevention for at‐risk individuals, to early intervention strategies for prodromal and newly diagnosed individuals, complex combination therapy for rapidly recurrent illness, and palliative‐type approaches for those at chronic, late stages of illness. There is hope that prompt initiation of potentially disease modifying therapies may preclude or attenuate the cognitive and structural changes seen in the later stages of bipolar disorder. The aims of this paper

  17. Clinical effectiveness of multimodality treatment on advanced pediatric hepatoblastoma.

    PubMed

    Zhang, Y; Zhang, W-L; Huang, D-S; Hong, L; Wang, Y-Z; Zhu, X; Hu, H-M; Zhang, P-W; Yi, Y; Han, T

    2014-01-01

    To investigate the effect of multimodality treatment of advanced paediatric hepatoblastoma and the factors affecting the prognosis. 35 childhood patients were treated with multimodality treatments consisting of chemotherapy, surgery, interventional therapy, and autologous peripheral blood stem cell transplantation. Patients were followed up every month. 33 patients completed the follow-up, of which 17 were in complete remission, 5 were in partial remission, 1 case got worse, and 10 died. The remission rate was 66.7% (22/33), and the overall survival rate was 69.7% (23/33). 1 patient with advanced hepatoblastoma got high-dose chemotherapy combined with autologous peripheral blood stem cell transplantation (APBSCT) treatment, and a primary lesion by 18 x 15 x 9 cm reduced to 10 x 8 x 4 cm. Remote metastases significantly alleviated, and partial remission reached six months. The overall survival was 9 months after transplantation. Patients with the mixed phenotype of hepatoblastoma had a worse prognosis than with the epithelial phenotype (p < 0.001), and patients in stage IV had a lower survival rate than in stage III (p < 0.001). Multimodality treatment can effectively improve remission rate and prolong the survival of children with the advanced hepatoblastoma. In addition, alpha-fetoprotein (AFP), hepatoblastoma pathological classification and staging are of great use in prediction of prognosis.

  18. Physical activity in patients with advanced-stage cancer: a systematic review of the literature.

    PubMed

    Albrecht, Tara A; Taylor, Ann Gill

    2012-06-01

    The importance of physical activity for chronic disease prevention and management has become generally well accepted. The number of research interventions and publications examining the benefits of physical activity for patients with cancer has been rising steadily. However, much of that research has focused on the impact of physical activity either prior to or early in the cancer diagnosis, treatment, and survivorship process. Research focusing on the effects of physical activity, specifically for patients with advanced-stage cancer and poorer prognostic outcomes, has been addressed only recently. The purpose of this article is to examine the state of the science for physical activity in the advanced-stage disease subset of the cancer population. Exercise in a variety of intensities and forms, including yoga, walking, biking, and swimming, has many health benefits for people, including those diagnosed with cancer. Research has shown that, for people with cancer (including advanced-stage cancer), exercise can decrease anxiety, stress, and depression while improving levels of pain, fatigue, shortness of breath, constipation, and insomnia. People diagnosed with cancer should discuss with their oncologist safe, easy ways they can incorporate exercise into their daily lives.

  19. Pair-wise comparison analysis of differential expression of mRNAs in early and advanced stage primary colorectal adenocarcinomas

    PubMed Central

    Lau, Tze Pheng; Roslani, April Camilla; Lian, Lay Hoong; Chai, Hwa Chia; Lee, Ping Chin; Hilmi, Ida; Goh, Khean Lee; Chua, Kek Heng

    2014-01-01

    Objectives To characterise the mRNA expression patterns of early and advanced stage colorectal adenocarcinomas of Malaysian patients. Design Comparative expression analysis. Setting and participants We performed a combination of annealing control primer (ACP)-based PCR and reverse transcription-quantitative real-time PCR for the identification of differentially expressed genes (DEGs) associated with early and advanced stage primary colorectal tumours. We recruited four paired samples from patients with colorectal cancer (CRC) of Dukes’ A and B for the preliminary differential expression study, and a total of 27 paired samples, ranging from CRC stages I to IV, for subsequent confirmatory test. The tumouric samples were obtained from the patients with CRC undergoing curative surgical resection without preoperative chemoradiotherapy. The recruited patients with CRC were newly diagnosed with CRC, and were not associated with any hereditary syndromes, previously diagnosed cancer or positive family history of CRC. The paired non-cancerous tissue specimens were excised from macroscopically normal colonic mucosa distally located from the colorectal tumours. Primary and secondary outcome measures The differential mRNA expression patterns of early and advanced stage colorectal adenocarcinomas compared with macroscopically normal colonic mucosa were characterised by ACP-based PCR and reverse transcription-quantitative real-time PCR. Results The RPL35, RPS23 and TIMP1 genes were found to be overexpressed in both early and advanced stage colorectal adenocarcinomas (p<0.05). However, the ARPC2 gene was significantly underexpressed in early colorectal adenocarcinomas, while the advanced stage primary colorectal tumours exhibited an additional overexpression of the C6orf173 gene (p<0.05). Conclusions We characterised two distinctive gene expression patterns to aid in the stratification of primary colorectal neoplasms among Malaysian patients with CRC. Further work can be done to

  20. Major clinical research advances in gynecologic cancer in 2014.

    PubMed

    Suh, Dong Hoon; Lee, Kyung Hun; Kim, Kidong; Kang, Sokbom; Kim, Jae Weon

    2015-04-01

    In 2014, 9 topics were selected as major advances in clinical research for gynecologic oncology: 2 each in cervical and corpus cancer, 4 in ovarian cancer, and 1 in breast cancer. For cervical cancer, several therapeutic agents showed viable antitumor clinical response in recurrent and metastatic disease: bevacizumab, cediranib, and immunotherapies including human papillomavirus (HPV)-tumor infiltrating lymphocytes and Z-100. The HPV test received FDA approval as the primary screening tool of cervical cancer in women aged 25 and older, based on the results of the ATHENA trial, which suggested that the HPV test was a more sensitive and efficient strategy for cervical cancer screening than methods based solely on cytology. For corpus cancers, results of a phase III Gynecologic Oncology Group (GOG) 249 study of early-stage endometrial cancer with high-intermediate risk factors are followed by the controversial topic of uterine power morcellation in minimally invasive gynecologic surgery. Promising results of phase II studies regarding the effectiveness of olaparib in various ovarian cancer settings are summarized. After a brief review of results from a phase III study on pazopanib maintenance therapy in advanced ovarian cancer, 2 outstanding 2014 ASCO presentations cover the topic of using molecular subtypes in predicting response to bevacizumab. A review of the use of opportunistic bilateral salpingectomy as an ovarian cancer preventive strategy in the general population is presented. Two remarkable studies that discussed the effectiveness of adjuvant ovarian suppression in premenopausal early breast cancer have been selected as the last topics covered in this review.

  1. TDP-43 stage, mixed pathologies, and clinical Alzheimer’s-type dementia

    PubMed Central

    James, Bryan D.; Wilson, Robert S.; Boyle, Patricia A.; Trojanowski, John Q.; Bennett, David A.; Schneider, Julie A.

    2016-01-01

    Hyperphosphorylated transactive response DNA-binding protein 43 (TDP-43, encoded by TARDBP) proteinopathy has recently been described in ageing and in association with cognitive impairment, especially in the context of Alzheimer’s disease pathology. To explore the role of mixed Alzheimer’s disease and TDP-43 pathologies in clinical Alzheimer’s-type dementia, we performed a comprehensive investigation of TDP-43, mixed pathologies, and clinical Alzheimer’s-type dementia in a large cohort of community-dwelling older subjects. We tested the hypotheses that TDP-43 with Alzheimer’s disease pathology is a common mixed pathology; is related to increased likelihood of expressing clinical Alzheimer’s-type dementia; and that TDP-43 pathologic stage is an important determinant of clinical Alzheimer’s-type dementia. Data came from 946 older adults with (n = 398) and without dementia (n = 548) from the Rush Memory and Aging Project and Religious Orders Study. TDP-43 proteinopathy (cytoplasmic inclusions) was present in 496 (52%) subjects, and the pattern of deposition was classified as stage 0 (none; 48%), stage 1 (amygdala; 18%), stage 2 (extension to hippocampus/entorhinal; 21%), or stage 3 (extension to neocortex; 14%). TDP-43 pathology combined with a pathologic diagnosis of Alzheimer’s disease was a common mixed pathology (37% of all participants), and the proportion of subjects with clinical Alzheimer’s-type dementia formerly labelled ‘pure pathologic diagnosis of Alzheimer’s disease’ was halved when TDP-43 was considered. In logistic regression models adjusted for age, sex, and education, TDP-43 pathology was associated with clinical Alzheimer’s-type dementia (odds ratio = 1.51, 95% confidence interval = 1.11, 2.05) independent of pathological Alzheimer’s disease (odds ratio = 4.30, 95% confidence interval = 3.08, 6.01) or other pathologies (infarcts, arteriolosclerosis, Lewy bodies, and hippocampal sclerosis). Mixed Alzheimer’s disease and

  2. [Comparative analysis of TACE alone or plus RFA in the treatment of 167 cases of intermediate and advanced staged primary hepatocellular carcinoma].

    PubMed

    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

  3. A Model to Predict the Use of Surgical Resection for Advanced-Stage Non-Small Cell Lung Cancer Patients.

    PubMed

    David, Elizabeth A; Andersen, Stina W; Beckett, Laurel A; Melnikow, Joy; Kelly, Karen; Cooke, David T; Brown, Lisa M; Canter, Robert J

    2017-11-01

    For advanced-stage non-small cell lung cancer, chemotherapy and chemoradiotherapy are the primary treatments. Although surgical intervention in these patients is associated with improved survival, the effect of selection bias is poorly defined. Our objective was to characterize selection bias and identify potential surgical candidates by constructing a Surgical Selection Score (SSS). Patients with clinical stage IIIA, IIIB, or IV non-small cell lung cancer were identified in the National Cancer Data Base from 1998 to 2012. Logistic regression was used to develop the SSS based on clinical characteristics. Estimated area under the receiver operating characteristic curve was used to assess discrimination performance of the SSS. Kaplan-Meier analysis was used to compare patients with similar SSSs. We identified 300,572 patients with stage IIIA, IIIB, or IV non-small cell lung cancer without missing data; 6% (18,701) underwent surgical intervention. The surgical cohort was 57% stage IIIA (n = 10,650), 19% stage IIIB (n = 3,483), and 24% stage IV (n = 4,568). The areas under the receiver operating characteristic curve from the best-fit logistic regression model in the training and validation sets were not significantly different, at 0.83 (95% confidence interval, 0.82 to 0.83) and 0.83 (95% confidence interval, 0.82 to 0.83). The range of SSS is 43 to 1,141. As expected, SSS was a good predictor of survival. Within each quartile of SSS, patients in the surgical group had significantly longer survival than nonsurgical patients (p < 0.001). A prediction model for selection of patients for surgical intervention was created. Once validated and prospectively tested, this model may be used to identify patients who may benefit from surgical intervention. Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  4. Two-stage, low noise advanced technology fan. 5: Acoustic final report

    NASA Technical Reports Server (NTRS)

    Sofrin, T. G.; Riloff, N., Jr.

    1975-01-01

    The NASA Q2S(quiet two-stage) fan is a 0.836m (32.9 in.) diameter model of the STF 433 engine fan, selected in a 1972 study for an Advanced Technology Transport (ATT) airplane. Noise-control features include: low tip speed, moderate stage pressure rise, large blade-vane spacings, no inlet guide vanes, and optimum blade and vane numbers. Tests were run on the baseline Q2S fan with standard inlet and discharge ducts. Further tests were made of a translating centerbody sonic inlet device and treated discharge ducts. Results were scaled to JT8D and JT3D engine fan size for comparison with current two-stage fans, and were also scaled to STF 433 fan size to compare calculated ATT flyover noise with FAR 36 limits. Baseline Q2S results scaled to JT8D and JT3D engine fan sizes showed substantial noise reductions. Calculated unsuppressed baseline ATT flyovers averaged about 2.5 EPNdB below FAR 36 limits. Using measured sonic inlet results, scaled baseline Q2S fan results, and calculated attenuations for a 1975 technology duct liner, projected flyover noise calculations for the ATT averaged about FAR 36 limits minus 10 EPNdB. Advances in suppression technology required to meet the 1985 goal of FAR 36 limits minus 20 EPNdB are discussed.

  5. Reconsidering Clinical Staging Model: A Case of Genetic High Risk for Schizophrenia.

    PubMed

    Lee, Tae Young; Kim, Minah; Kim, Sung Nyun; Kwon, Jun Soo

    2017-01-01

    The clinical staging model is considered a useful and practical method not only in dealing with the early stage of psychosis overcoming the debate about diagnostic boundaries but also in emerging mood disorder. However, its one limitation is that it cannot discriminate the heterogeneity of individuals at clinical high risk for psychosis, but lumps them all together. Even a healthy offspring of schizophrenia can eventually show clinical symptoms and progress to schizophrenia under the influence of genetic vulnerability and environmental stress even after the peak age of onset of schizophrenia. Therefore, individuals with genetic liability of schizophrenia may require a more intensive intervention than recommended by the staging model based on current clinical status.

  6. Electrochemotherapy efficacy evaluation for treatment of locally advanced stage III cutaneous squamous cell carcinoma: a 22-cases retrospective analysis.

    PubMed

    Di Monta, Gianluca; Caracò, Corrado; Simeone, Ester; Grimaldi, Antonio Maria; Marone, Ugo; Di Marzo, Massimiliano; Vanella, Vito; Festino, Lucia; Palla, Marco; Mori, Stefano; Mozzillo, Nicola; Ascierto, Paolo Antonio

    2017-04-26

    Extensive squamous cell carcinoma has few therapeutic options. In such cases, electrochemotherapy involving electroporation combined with antineoplastic drug appears to be a new potential option and may be considered as an alternative treatment. The aim of this retrospective single-center study was to evaluate electrochemotherapy efficacy in treatment of locally advanced stage III squamous cell carcinoma, in which surgical procedures would have entailed wide tissue sacrifice. Clinical features, treatment response, and adverse effects were evaluated in 22 patients treated with electrochemotherapy with intravenous injection of bleomycin for extensive stage III cutaneous squamous cell carcinoma. Treatment of cutaneous lesions were performed according to the European Standard Operating Procedures of Electrochemotherapy. Overall response to electrochemotherapy treatment was observed in 18 (81.8%) patients. Clinical response with necrosis of tumor mass was observed from the first session and lasted for all follow up period that ranged between 5 and 48 months with a median of 34 months. Overall the treatment was well tolerated with a very low complication rate. Electrochemotherapy represents a safe and effective therapeutic approach, associated with a good tolerability.

  7. Expression of protease-activated receptor-2 (PAR-2) is related to advanced clinical stage and adverse prognosis in ovarian clear cell carcinoma.

    PubMed

    Aman, Murasaki; Ohishi, Yoshihiro; Imamura, Hiroko; Shinozaki, Tomoko; Yasutake, Nobuko; Kato, Kiyoko; Oda, Yoshinao

    2017-06-01

    Recent studies demonstrated that protease-activated receptor-2 (PAR-2) correlates with tumor progression in various tissues. On the other hand, oxidative stress arising from endometriosis has been considered a cause of carcinogenesis in ovarian clear cell carcinoma (OCCC). We previously demonstrated that oxidative stress up-regulates PAR-2 expression, and we conducted the present study to investigate the PAR-2 expression and its relation to clinicopathological factors and oxidative stress in OCCC. We performed an immunohistochemical evaluation in 95 cases of OCCC. For the evaluation of oxidative stress markers, 31 cases of ovarian endometrioid carcinoma (OEC) were also examined. No significant differences in the expression of cyclooxygenase-2 and inducible nitric oxide synthase were observed between OCCC and OEC. Sixty-two percent of the OCCC cases showed high 8-hydroxydeoxyguanosine expression, whereas all of the OEC cases showed almost negative immunoreactivities. The presence of endometriosis did not affect the expression of these oxidative stress markers or prognosis. High PAR-2 expression was observed in 20% (14/71) of the early International Federation of Gynecology and Obstetrics (FIGO) stage cases and 58% (14/24) of the advanced FIGO stage cases. High PAR-2 expression was significantly correlated with advanced FIGO stage and shorter overall survival. We found no correlations between PAR-2 expression and oxidative stress in OCCC. Our results suggest that PAR-2 plays an important role in the progression of OCCC. The expression of 8-hydroxydeoxyguanosine is a characteristic finding of OCCC, indicating that the injury of DNA by oxidative stress may be involved in the carcinogenesis of OCCC. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Variability in CKD stage in outpatients followed in two large renal clinics.

    PubMed

    Sikaneta, Tabo; Abdolell, Mohamed; Taskapan, Hulya; Roscoe, Janet; Fung, Jason; Nagai, Gordon; Ting, Robert H; Ng, Paul; Wu, George; Oreopoulos, Dimitrios; Tam, Paul Y

    2012-10-01

    Chronic kidney disease (CKD) is staged by glomerular filtration rate (GFR). CKD stages sometimes vary between routine office visits, and it is unknown if this impacts renal and patient survival separately from a cross-sectional CKD stage value. We quantified and categorized CKD stage variability in a large group of outpatients and correlated this with clinical and demographic features and with renal and patient survival. All estimated GFRs were staged in the first observation period. CKD stages were then categorized as static, improving, worsening, or fluctuating. Logistic regression analysis was performed to identify clinical variables associated with CKD stage variability. Death and dialysis progression rates were then collected and analyzed using Cox proportional regression. During a 1.1-year observation period, 1,262 patients (mean age 71.25 years) had a mean 5 eGFR's. CKD stages were static in 60.4%, worsened in 14.4%, improved in 7.4%, and fluctuated in 17.2% of patients. Secondary analysis revealed heavy proteinuria and East Asian ethnicity to be negatively, and diabetes mellitus and previous acute kidney injury to be positively associated with improving CKD stages. Cox proportional regression of 902 patients analyzed 2.3 years later revealed a negative association with improving CKD stage and subsequent need for dialysis. CKD stage changed in 40% of 1,262 elderly patients when determined 5 times in just over 1 year. Improving CKD stage was the only variability pattern significantly associated with any of the clinical outcomes when assessed 2.3 years later, being unlikely to be linked with subsequent need for dialysis.

  9. Assessment of capabilities in persons with advanced stage of dementia: Validation of The Montessori Assessment System (MAS).

    PubMed

    Erkes, Jérôme; Camp, Cameron J; Raffard, Stéphane; Gély-Nargeot And, Marie-Christine; Bayard, Sophie

    2017-01-01

    This study evaluated the validity and reliability of the Montessori Assessment System. The Montessori Assessment System assesses preserved abilities in persons with moderate to severe dementia. In this respect, this instrument provides crucial information for the development of effective person-centered care plans. A total of 196 persons with a diagnosis of dementia in the moderate to severe stages of dementia were recruited in 10 long-term care facilities in France. All participants completed the Montessori Assessment System, the Clinical Dementia Rating Scale and/or the Mini Mental State Examination and the Severe Impairment Battery-short form. The internal consistency and temporal stability of the Montessori Assessment System were high. Additionally, good construct and divergent validity were demonstrated. Factor analysis showed a one-factor structure. The Montessori Assessment System demonstrated satisfactory psychometric properties while being a useful instrument to assess capabilities in persons with advanced stages of dementia and hence to develop person-centered plans of care.

  10. The experience of living with advanced-stage cancer: a thematic synthesis of the literature.

    PubMed

    García-Rueda, N; Carvajal Valcárcel, A; Saracíbar-Razquin, M; Arantzamendi Solabarrieta, M

    2016-07-01

    The aim of the study was to understand the experience of people living with advanced-stage cancer through literature. The search included The Cochrane Library, PubMed, PsycInfo, CINAHL and Cuiden. Thirteen studies were included. A qualitative meta-synthesis was conducted. One thread emerged from the thematic synthesis: the desire to live as normally as possible, despite being aware of the proximity of death. Three themes also emerged: "a process that is unique" with its four sub-themes; "support network" and "health context," each of them having two sub-themes. This study concludes that living with advanced-stage cancer is a unique and complex process which has both positive and negative aspects. The review provides a comprehensive view of the experience, which considers the importance of the support network and the health context in which the person lives. In this study, "normalcy" is the adjustment to the new reality and living as closely as possible to the way one lived before the disease, while developing a new relationship with being finite and death. A better understanding of the experience of living with advanced-stage cancer will help health professionals to identify the needs of the patients in order to plan individual, high-quality care. © 2016 John Wiley & Sons Ltd.

  11. Prevalence of ADHD symptoms across clinical stages of major depressive disorder.

    PubMed

    Bron, Tannetje I; Bijlenga, Denise; Verduijn, Judith; Penninx, Brenda W J H; Beekman, Aartjan T F; Kooij, J J Sandra

    2016-06-01

    Depression and ADHD often co-occur in clinical samples. Depression severity may be linked to ADHD symptomatology. We therefore assessed ADHD symptoms across clinical stages of major depressive disorder (MDD). We used 4-year follow-up data of the Netherlands Study of Depression and Anxiety (September 2008 until April 2011), including healthy controls, groups with remitted and current MDD (N=2053; age range 21-69 years; 66.8% females). Probable ADHD was defined as having current ADHD symptoms on the Conners Adult ADHD Rating Scale and a positive score on childhood or early-adolescent ADHD indicators. We examined ADHD symptom rates across (i) those with and without lifetime MDD, (ii) clinical characteristics of MDD including severity, course and outcomes, (iii) clinical stages of MDD. (i) The prevalence of ADHD symptoms was 0.4% in healthy controls, 5.7% in remitted MDD and 22.1% in current MDD (OR=4.5; 95% CI 3.1-6.5). (ii) ADHD symptom rates and odds were significantly increased among those with more severe depression (29.4%; OR=6.8; 95% CI 2.9-16.1), chronic depression (21.8%; OR=3.8; 95% CI 2.5-5.7), earlier age of onset of depressive symptoms (9.9%; OR=1.5; 95% CI 1.0-2.3), and comorbid anxiety disorders (29.0%; OR=3.4; 95% CI 2.0-5.7). (iii) ADHD symptom rates increased across clinical stages of MDD, up to 22.5% in chronic MDD. We used self-reports on ADHD symptoms. Also, clinical staging models have not yet been validated for mental disorders. ADHD symptoms are very common among MDD patients, especially among those in recurrent and chronic stages of MDD. Considering ADHD may be an important step forward in improving the treatment of depression. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. SEOM clinical guidelines in early-stage breast cancer 2015.

    PubMed

    Garcia-Saenz, J A; Bermejo, B; Estevez, L G; Palomo, A G; Gonzalez-Farre, X; Margeli, M; Pernas, S; Servitja, S; Rodriguez, C A; Ciruelos, E

    2015-12-01

    Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.

  13. Combined treatment of advanced stages of recurrent skin cancer of the head.

    PubMed

    Pompucci, Angelo; Rea, Giancarla; Farallo, Eugenio; Salgarello, Marzia; Campanella, Antonino; Fernandez, Eduardo

    2004-04-01

    The authors investigated whether skull base resection and primary free-flap reconstruction in a single-stage surgery is oncologically effective for treating advanced stages of recurrent skin cancer (RSC) of the head. Eighteen consecutive patients were surgically treated. Twelve of them underwent an anterolateral skull base resection, which was performed using a pterional craniotomy combined with an orbitozygomatic osteotomy. Six patients underwent a posterolateral skull base resection, which was performed using an asterional craniotomy combined with a retrolabyrinthine petrosectomy. The wide postoperative defects were covered with muscular or myocutaneous free flaps. The main factor influencing survival was the extent of the resection: patients with no or minimal residual disease showed a statistically significant longer survival time than those with consistent residual disease. Basal cell carcinoma had a better prognosis than squamous cell carcinoma. A trend toward improved survival was observed in patients classified as T4M0 with negative lymph nodes (N0), but this trend was not statistically significant. Adjuvant radiotherapy significantly influenced both survival time and the rate of local recurrence. The surgical morbidity rate was 27.8%; there were two transient cerebrospinal fluid leaks and three seventh cranial nerve injuries. Late complications included radionecrosis in one patient and skin erosion requiring a second surgery in another patient. No deaths occurred during a 30-day postoperative period. Advances in skull base surgery and free-flap reconstruction allowed the authors to treat patients with advanced-stage RSC of the head in a rather satisfactory manner. Only when it is impossible to achieve no or minimal residual disease should aggressive treatment be considered.

  14. Update on Merkel Cell Carcinoma: Epidemiology, Etiopathogenesis, Clinical Features, Diagnosis, and Staging.

    PubMed

    Llombart, B; Requena, C; Cruz, J

    2017-03-01

    Merkel cell carcinoma (MCC) is a rare, highly aggressive tumor, and local or regional disease recurrence is common, as is metastasis. MCC usually develops in sun-exposed skin in patients of advanced age. Its incidence has risen 4-fold in recent decades as the population has aged and immunohistochemical techniques have led to more diagnoses. The pathogenesis of MCC remains unclear but UV radiation, immunosuppression, and the presence of Merkel cell polyomavirus in the tumor genome seem to play key roles. This review seeks to update our understanding of the epidemiology, etiology, pathogenesis, and clinical features of MCC. We also review histologic and immunohistochemical features required for diagnosis. MCC staging is discussed, given its great importance in establishing a prognosis for these patients. Copyright © 2016 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Impact of paranasal sinus invasion on advanced nasopharyngeal carcinoma treated with intensity-modulated radiation therapy: the validity of advanced T stage of AJCC/UICC eighth edition staging system.

    PubMed

    Wang, Ying; Zhao, Jie; Zhao, Yajie; Yang, Zhen; Lei, Mingjun; Li, Zhanzhan; Wei, Rui; Chen, Dengming; He, Yuxiang; Shen, Liangfang

    2018-05-01

    The aim of this study was to clarify the prognostic role of paranasal sinus invasion in advanced NPC patients. Data of patients (n = 295) with advanced NPC (T3/T4N0-3 M0) treated with intensity-modulated radiation therapy were retrospectively analyzed. Staging was according to the AJCC/UICC eighth edition staging system. Overall survival (OS), local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-free survival (DFS) were calculated, and differences were compared between patients with and without paranasal sinus invasion. Multivariate analysis was used to identify the independent predictors of different survival parameters. Paranasal sinus invasion was present in 126 of 295 (42.7%) patients. Sphenoid, ethmoid, maxillary, and frontal sinus involvements were present in 123 of 295 (41.7%), 95 of 295 (32.2%), 45 of 295 (15.3%), and 0 of 295 (0%), respectively. All survival parameters were significantly better in patients without paranasal sinus invasion. When paranasal sinus invasion was reclassified as T4 instead of T3, all survival rates, other than LRFS (P = 0.156), were significantly better in the new T3 patients, and differences in all survival parameters remained nonsignificant between T3 with paranasal sinus invasion and T4 without paranasal sinus invasion patients (all P > 0.05). In multivariate analysis, paranasal sinus invasion was found to be an independent negative prognostic factor for OS, DFS, and DMFS (P = 0.016, P = 0.004, and P = 0.006, respectively), but not for LRFS (P = 0.068). Paranasal sinus invasion has prognostic value in advanced NPC. It may be reasonable to classify paranasal sinus invasion as T4 stage. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  16. A Novel Therapeutic Modality for Advanced Stage Prostate Cancer Treatment

    DTIC Science & Technology

    2017-10-01

    Unlimited The views, opinions and/or findings contained in this report are those of the author(s) and should not be construed as an official Department of...PrCa are non-selective and provide only limited response rate Thus, novel treatment modalities are needed to treat advanced stage PrCa. In this...of ORM on MTA1 protein. Considering effective therapeutic index of ORM, we are also making more potent analogues of ORM. These findings suggest that

  17. [Clinical patterns and stages of multiple organ failure in the elderly].

    PubMed

    Wang, S

    1990-05-01

    Multiple organ failure in the elderly (MOFE) is a new clinical syndrome different from multiple organ failure (MOF) caused by trauma occurring most often in young and mid-aged persons. The authors retrospectively analysed 158 cases of MOFE hospitalized in the past 12 years and commented on its definition, diagnostic criteria, clinical patterns and stages. The suggested definition of MOFE is the sequential 2 or more organs failure within a short period in the elderly patients (greater than or equal to 60 years old) with multiple organ chronic diseases in the presence of aging of organs and age-related malfunction. The most common precipitating factors are pulmonary infections and acute attack of chronic cardiac, cerebral and renal diseases. The interval between failures of various organs is mostly less than 10 days and seldom longer than 1 month. MOFE has 3 different patterns: rapid pattern with single phase; delayed pattern with two phases and recurrent pattern with multiple phase. In the last pattern the patients suffer from multiple attacks of multiple organ failure. It is only seen in MOFE, but not in MOF. The presentation of this particular pattern is related to the following facts: (1). A few organs or only the heart and lungs are involved. (2) Kidney, brain and hemopoietic system etc. usually with poor prognosis are not involved. (3) The age of patients are relatively younger. (4) More resuscitation experiences have been accumulated and better resuscitation measures are available. The clinical course of MOFE can be divided into 3 stages: prefailure stage (stage I), failure compensations stage (stage II) and decompensation stage (stage III).(ABSTRACT TRUNCATED AT 250 WORDS)

  18. Advanced stage nodular lymphocyte predominant Hodgkin lymphoma in children and adolescents: clinical characteristics and treatment outcome - a report from the SFCE & CCLG groups.

    PubMed

    Shankar, Ananth G; Roques, Gaelle; Kirkwood, Amy A; Lambilliotte, Anne; Freund, Katja; Leblanc, Thierry; Hayward, Janis; Abbou, Samuel; Ramsay, Alan D; Schmitt, Claudine; Gorde-Grosjean, Stephanie; Pacquement, Hélène; Haouy, Stephanie; Boudjemaa, Sabah; Aladjidi, Nathalie; Hall, Georgina W; Landman-Parker, Judith

    2017-04-01

    Advanced stage nodular lymphocyte predominant Hodgkin lymphoma (nLPHL) is extremely rare in children and as a consequence, optimal treatment for this group of patients has not been established. Here we retrospectively evaluated the treatments and treatment outcomes of 41 of our patients from the UK and France with advanced stage nLPHL. Most patients received chemotherapy, some with the addition of the anti CD20 antibody rituximab or radiotherapy. Chemotherapy regimens were diverse and followed either classical Hodgkin lymphoma or B non-Hodgkin lymphoma protocols. All 41 patients achieved a complete remission with first line treatment and 40 patients are alive and well in remission. Eight patients subsequently relapsed and 1 patient died of secondary cancer (9 progression-free survival events). The median time to progression for those who progressed was 21 months (5·9-73·8). The median time since last diagnosis is 87·3 months (8·44-179·20). Thirty-six (90%), 30 (75%) and 27 (68%) patients have been in remission for more than 12, 24 and 36 months, respectively. Overall, the use of rituximab combined with multi-agent chemotherapy as first line treatment seems to be a reasonable therapeutic option. © 2017 John Wiley & Sons Ltd.

  19. Is uniportal thoracoscopic surgery a feasible approach for advanced stages of non-small cell lung cancer?

    PubMed Central

    Fieira, Eva; Delgado, Maria; Mendez, Lucía; Fernandez, Ricardo; de la Torre, Mercedes

    2014-01-01

    Objectives Conventional video-assisted thoracoscopic (VATS) lobectomy for advanced lung cancer is a feasible and safe surgery in experienced centers. The aim of this study is to assess the feasibility of uniportal VATS approach in the treatment of advanced non-small cell lung cancer (NSCLC) and compare the perioperative outcomes and survival with those in early-stage tumors operated through the uniportal approach. Methods From June 2010 to December 2012, we performed 163 uniportal VATS major pulmonary resections. Only NSCLC cases were included in this study (130 cases). Patients were divided into two groups: (A) early stage and (B) advanced cases (>5 cm, T3 or T4, or tumors requiring neoadjuvant treatment). A descriptive and retrospective study was performed, comparing perioperative outcomes and survival obtained in both groups. A survival analysis was performed with Kaplan-Meier curves and the log-rank test was used to compare survival between patients with early and advanced stages. Results A total of 130 cases were included in the study: 87 (A) vs. 43 (B) patients (conversion rate 1.1 vs. 6.5%, P=0.119). Mean global age was 64.9 years and 73.8% were men. The patient demographic data was similar in both groups. Upper lobectomies (A, 52 vs. B, 21 patients) and anatomic segmentectomies (A, 4 vs. B, 0) were more frequent in group A while pneumonectomy was more frequent in B (A, 1 vs. B, 6 patients). Surgical time was longer (144.9±41.3 vs. 183.2±48.9, P<0.001), and median number of lymph nodes (14 vs. 16, P=0.004) were statistically higher in advanced cases. Median number of nodal stations (5 vs. 5, P=0.165), days of chest tube (2 vs. 2, P=0.098), HOS (3 vs. 3, P=0.072), and rate of complications (17.2% vs. 14%, P=0.075) were similar in both groups. One patient died on the 58th postoperative day. The 30-month survival rate was 90% for the early stage group and 74% for advanced cases Conclusions Uniportal VATS lobectomy for advanced cases of NSCLC is a safe and

  20. Clinical radiobiology of stage T2-T3 bladder cancer.

    PubMed

    Majewski, Wojciech; Maciejewski, Boguslaw; Majewski, Stanislaw; Suwinski, Rafal; Miszczyk, Leszek; Tarnawski, Rafal

    2004-09-01

    To evaluate the relationship between total radiation dose and overall treatment time (OTT) with the treatment outcome, with adjustment for selected clinical factors, in patients with Stage T2-T3 bladder cancer treated with curative radiotherapy (RT). The analysis was based on 480 patients with Stage T2-T3 bladder cancer who were treated at the Center of Oncology in Gliwice between 1975 and 1995. The mean total radiation dose was 65.5 Gy, and the mean OTT was 51 days. In 261 patients (54%), planned and unplanned gaps occurred during RT. Four fractionation schedules were used: (1) conventional fractionation (once daily, 1.8-2.5 Gy/fraction); (2) protracted fractionation (pelvic RT, once daily, 1.6-1.7 Gy/fraction, boost RT, once daily, 2.0 Gy/fraction); (3) accelerated hyperfractionated boost (pelvic RT, once daily, 2.0 Gy/fraction; boost RT, twice daily, 1.3-1.4 Gy/fraction); and (4) accelerated hyperfractionation (pelvic and boost RT, twice daily, 1.2-1.5 Gy/fraction). In all fractionation schedules, the total radiation dose was similar (average 65.5 Gy), but the OTT was different (mean 53 days for conventional fractionation, 62 days for protracted fractionation, 45 days for accelerated hyperfractionated boost, and 41 days for accelerated hyperfractionation). A Cox proportional hazard model and maximum likelihood logistic model were used to evaluate the relationship between the treatment-related parameters (total radiation dose, dose per fraction, and OTT) and clinical factors (clinical T stage, hemoglobin level and bladder capacity before RT) and treatment outcome. With a median follow-up of 76 months, the actuarial 5-year local control rate was 47%, and the overall survival rate was 40%. The logistic analysis, which included the total dose, OTT, and T stage, revealed that all of these factors were significantly related to tumor control probability (p = 0.021 for total radiation dose, p = 0.038 for OTT, and p = 0.00068 for T stage). A multivariate Cox model, which

  1. International neuroblastoma staging system stage 1 neuroblastoma: a prospective study and literature review.

    PubMed

    Kushner, B H; Cheung, N K; LaQuaglia, M P; Ambros, P F; Ambros, I M; Bonilla, M A; Ladanyi, M; Gerald, W L

    1996-07-01

    To gain insight into the management of non-metastatic neuroblastoma by examining clinical and biologic features of International Neuroblastoma Staging System (INSS) stage 1 tumors. Patients were staged by both the INSS and the Evans staging system and were evaluated for biologic prognostic factors. Patients with INSS stage 1 received no cytotoxic therapy. The literature was reviewed for clinical and biologic data about INSS stage 1. We evaluated 10 consecutive patients (median age, 17.5 months) with INSS stage 1; all remain disease-free (median follow-up duration, > 5 years). Tumors were in the abdomen (n = 6), chest (n = 3), or pelvis (n = 1). Neuroblastoma involved margins of resection in six tumors. Poor-prognostic biologic findings included tumor-cell diploidy (n = 2) and unfavorable Shimada histopathology (n = 2). Two patients were to receive chemotherapy for, respectively, a tumor deemed unresectable and a tumor classified as Evans stage III; second opinions resulted in surgical management alone in each case. Published reports confirm that some INSS stage 1 patients (1) are at risk for overtreatment, and (2) have poor-prognostic biologic findings yet do well. Surgery alone suffices for INSS stage 1 neuroblastoma, even if biologic prognostic factors are unfavorable, microscopic disease remains after surgery, and tumor size is suggestive of "advanced-stage" status in other staging systems. Attempts to resect regionally confined neuroblastomas should take precedence over immediate use of cytotoxic therapy; otherwise, some patients may receive chemotherapy or radiotherapy unnecessarily.

  2. The relationship between apoptosis and the expression of proliferating cell nuclear antigen and the clinical stages in gastric carcinoma.

    PubMed

    Tao, K; Chen, D; Tian, Y; Lu, X; Yang, X

    2000-01-01

    The relationship between the apoptosis and the expression of proliferating cell nuclear antigen (PCNA) and the clinical stages in gastric cancers was studied. By using terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) technique and PCNA immunohistochemical staining, the apoptosis and the expression of PCNA in tissue of gastric carcinoma were assayed in situ, the index of apoptosis (AI), index of PCNA (PI) and the rate of AI/PI were calculated. AI and PI in gastric cancer tissues were (6.5 +/- 3.7)% and (49.8 +/- 15.9)% respectively, and the rate of AI/PI was 0.13 +/- 0.05, which were obviously different from those of normal gastric mucosa in paragastric cancer (P < 0.01). With the advanced TNM stages of gastric carcinoma, the AI was decreased, PI was increased and the rate of AI/PI decreased in gastric carcinoma. There was significant difference in them between the gastric cancer tissues and normal gastric mucosa in pericarcinoma in TNM stage II to IV (P < 0.05). It was suggested that the decreased apoptotic cells and the increased proliferating cells were obviously related to the tumor genesis and tumor progression in gastric carcinoma. The AI, PI and the rate of AI/PI would become the prognostic factors in advanced gastric carcinoma.

  3. Advanced two-stage compressor program design of inlet stage

    NASA Technical Reports Server (NTRS)

    Bryce, C. A.; Paine, C. J.; Mccutcheon, A. R. S.; Tu, R. K.; Perrone, G. L.

    1973-01-01

    The aerodynamic design of an inlet stage for a two-stage, 10/1 pressure ratio, 2 lb/sec flow rate compressor is discussed. Initially a performance comparison was conducted for an axial, mixed flow and centrifugal second stage. A modified mixed flow configuration with tandem rotors and tandem stators was selected for the inlet stage. The term conical flow compressor was coined to describe a particular type of mixed flow compressor configuration which utilizes axial flow type blading and an increase in radius to increase the work input potential. Design details of the conical flow compressor are described.

  4. Regulation of Clinical Trials with Advanced Therapy Medicinal Products in Germany.

    PubMed

    Renner, Matthias; Anliker, Brigitte; Sanzenbacher, Ralf; Schuele, Silke

    2015-01-01

    In the European Union, clinical trials for Advanced Therapy Medicinal Products are regulated at the national level, in contrast to the situation for a Marketing Authorisation Application, in which a centralised procedure is foreseen for these medicinal products. Although based on a common understanding regarding the regulatory requirement to be fulfilled before conduct of a clinical trial with an Advanced Therapy Investigational Medicinal Product, the procedures and partly the scientific requirements for approval of a clinical trial application differ between the European Union Member States. This chapter will thus give an overview about the path to be followed for a clinical trial application and the subsequent approval process for an Advanced Therapy Investigational Medicinal Product in Germany and will describe the role of the stakeholders that are involved. In addition, important aspects of manufacturing, quality control and non-clinical testing of Advanced Therapy Medicinal Products in the clinical development phase are discussed. Finally, current and future approaches for harmonisation of clinical trial authorisation between European Union Member States are summarised.

  5. Experiences of family of patient with newly diagnosed advanced terminal stage hepatocellular cancer.

    PubMed

    Shih, Whei-Mei Jean; Hsiao, Ping-Ju; Chen, Min-Li; Lin, Mei-Hsiang

    2013-01-01

    Hepatocellular carcinoma (HCC) is the most common primary liver cancer and the third leading cause of cancer-related death worldwide due to its generally poor prognosis. Caregiver burden for liver cancer cases is higher than with other cancer and needs especial attention. To explore the experiences of families of patients with newly diagnosed advanced terminal stage hepatocellular cancer by interview. Nine participants were recruited in this study. Content analysis of the interviews revealed four themes: blaming oneself, disrupting the pace of life, searching all possible regimens, and not letting go. This study provides new insight into the needs and support of family members especially when they are facing loved ones with newly diagnosed advanced terminal stage HCC. These results will inform future supportive care service development and intervention research aimed at providing assistance in reducing unmet supportive care needs and psychological distress of these family members.

  6. Clinical trials and late-stage drug development for Alzheimer’s disease: an appraisal from 1984 to 2014

    PubMed Central

    Schneider, Lon S.; Mangialasche, Francesca; Andreasen, Niels; Feldman, Howard; Giacobini, Ezio; Jones, Roy; Mantua, Valentina; Mecocci, Patrizia; Pani, Luca; Winblad, Bengt; Kivipelto, Miia

    2014-01-01

    The modern era of drug development for Alzheimer’s disease began with the proposal of the cholinergic hypothesis of memory impairment and the 1984 research criteria for Alzheimer’s disease. Since then, despite the evaluation of numerous potential treatments in clinical trials, only four cholinesterase inhibitors and memantine have shown sufficient safety and efficacy to allow marketing approval at an international level. Although this is probably because the other drugs tested were ineffective, inadequate clinical development methods have also been blamed for the failures. Here we review the development of treatments for Alzheimer’s disease during the past 30 years, considering the drugs, potential targets, late-stage clinical trials, development methods, emerging use of biomarkers and evolution of regulatory considerations in order to summarize advances and anticipate future developments. We have considered late-stage Alzheimer’s disease drug development from 1984 to 2013, including individual clinical trials, systematic and qualitative reviews, meta-analyses, methods, commentaries, position papers and guidelines. We then review the evolution of drugs in late clinical development, methods, biomarkers and regulatory issues. Although a range of small molecules and biological products against many targets have been investigated in clinical trials, the predominant drug targets have been the cholinergic system and the amyloid cascade. Trial methods have evolved incrementally: inclusion criteria have largely remained focused on mild to moderate Alzheimer’s disease criteria, recently extending to early or prodromal Alzheimer disease or ‘mild cognitive impairment due to Alzheimer’s disease’, for drugs considered to be disease modifying. The duration of trials has remained at 6 to 12 months for drugs intended to improve symptoms; 18- to 24-month trials have been established for drugs expected to attenuate clinical course. Cognitive performance, activities

  7. Interim Positron Emission Tomography Response-Adapted Therapy in Advanced-Stage Hodgkin Lymphoma: Final Results of the Phase II Part of the HD0801 Study.

    PubMed

    Zinzani, Pier Luigi; Broccoli, Alessandro; Gioia, Daniela Maria; Castagnoli, Antonio; Ciccone, Giovannino; Evangelista, Andrea; Santoro, Armando; Ricardi, Umberto; Bonfichi, Maurizio; Brusamolino, Ercole; Rossi, Giuseppe; Anastasia, Antonella; Zaja, Francesco; Vitolo, Umberto; Pavone, Vincenzo; Pulsoni, Alessandro; Rigacci, Luigi; Gaidano, Gianluca; Stelitano, Caterina; Salvi, Flavia; Rusconi, Chiara; Tani, Monica; Freilone, Roberto; Pregno, Patrizia; Borsatti, Eugenio; Sacchetti, Gian Mauro; Argnani, Lisa; Levis, Alessandro

    2016-04-20

    The clinical impact of positron emission tomography (PET) evaluation performed early during first-line therapy in patients with advanced-stage Hodgkin lymphoma, in terms of providing a rationale to shift patients who respond poorly onto a more intensive regimen (PET response-adapted therapy), remains to be confirmed. The phase II part of the multicenter HD0801 study involved 519 patients with advanced-stage de novo Hodgkin lymphoma who received an initial treatment with doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) and who underwent an early ifosfamide-containing salvage treatment followed by stem-cell transplantation if they showed a positive PET evaluation after two cycles of chemotherapy (PET2). The primary end point was 2-year progression-free survival calculated for both PET2-negative patients (who completed a full six cycles of ABVD treatment) and PET2-positive patients. Overall survival was a secondary end point. In all, 103 of the 512 evaluable patients were PET2 positive. Among them, 81 received the scheduled salvage regimen with transplantation, 15 remained on ABVD (physician's decision, mostly because of minimally positive PET2), five received an alternative treatment, and two were excluded because of diagnostic error. On intention-to-treat analysis, the 2-year progression-free survival was 76% for PET2-positive patients (regardless of the salvage treatment they received) and 81% for PET2-negative patients. Patients with advanced-stage Hodgkin lymphoma for whom treatment was at high risk of failing appear to benefit from early treatment intensification with autologous transplantation, as indicated by the possibility of successful salvage treatment in more than 70% of PET2-positive patients through obtaining the same 2-year progression-free survival as the PET2-negative subgroup. © 2016 by American Society of Clinical Oncology.

  8. Value analysis of postoperative staging imaging for asymptomatic, early-stage breast cancer: implications of clinical variation on utility and cost.

    PubMed

    Pellet, Andrew C; Erten, Mujde Z; James, Ted A

    2016-06-01

    Routine staging imaging for early-stage breast cancer is not recommended. Despite this, there is clinical practice variation with imaging studies obtained for asymptomatic patients with a positive sentinel node (SN+). We characterize the utility, cost, and clinical implications of imaging studies obtained in asymptomatic SN+ patients. A retrospective review was performed of asymptomatic, clinically node-negative patients who were found to have a positive sentinel node after surgery. The type of imaging, subsequent tests/interventions, frequency of additional malignancy detected, and costs were recorded. From April 2009 to April 2013, a total of 50 of 113 (44%) asymptomatic patients underwent staging imaging for a positive sentinel node; 11 (22%) patients had at least 1 subsequent imaging study or diagnostic intervention. No instance of metastatic breast cancer was identified, with a total cost of imaging calculated at $116,905. Staging imaging for asymptomatic SN+ breast cancer demonstrates clinical variation. These tests were associated with low utility, increased costs, and frequent false positives leading to subsequent testing/intervention. Evidence-based standardization may help increase quality by decreasing unnecessary variation and cost. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Clinical significance of preoperative carcinoembryonic antigen level in patients with clinical stage IA non-small cell lung cancer.

    PubMed

    Maeda, Ryo; Suda, Takashi; Hachimaru, Ayumi; Tochii, Daisuke; Tochii, Sachiko; Takagi, Yasushi

    2017-01-01

    The objective of this study was to assess the preoperative serum carcinoembryonic antigen (CEA) level in patients with clinical stage IA non-small cell lung cancer (NSCLC) and to evaluate its clinical significance. Between January 2005 and December 2014, a total of 378 patients with clinical stage IA NSCLC underwent complete resection with systematic node dissection. The survival rate was estimated starting from the date of surgery to the date of either death or the last follow-up by the Kaplan-Meier method. Univariate analyses by log-rank tests were used to determine prognostic factors. Cox proportional hazards ratios were used to identify independent predictors of poor prognosis. Clinicopathological predictors of lymph node metastases were evaluated by logistic regression analyses. The 5-year survival rate of patients with an elevated preoperative serum CEA level was significantly lower than that of patients with a normal CEA level (75.5% vs. 87.7%; P=0.02). However, multivariate analysis did not show the preoperative serum CEA level to be an independent predictor of poor prognosis. Postoperative pathological factors, including lymphatic permeation, visceral pleural invasion, and lymph node metastases, tended to be positive in patients with an elevated preoperative serum CEA level. In addition, the CEA level was a statistically significant independent clinical predictor of lymph node metastases. The preoperative serum CEA level was not an independent predictor of poor prognosis in patients with pathological stage IA NSCLC but was an important clinical predictor of tumor invasiveness and lymph node metastases in patients with clinical stage IA NSCLC. Therefore, measurement of the preoperative serum CEA level should be considered even for patients with early-stage NSCLC.

  10. Para-aortic lymphadenectomy in advanced stage cervical cancer, a protocol for comparing safety, feasibility and diagnostic accuracy of surgical staging versus PET-CT; PALDISC trial.

    PubMed

    Tax, Casper; Abbink, Karin; Rovers, Maroeska M; Bekkers, Ruud L M; Zusterzeel, Petra L M

    2018-01-01

    Currently, a PET-CT is used to assess the need for extended field radiotherapy of para-aortic lymph nodes (PALN) in International Federation of Gynaecology and Obstetrics (FIGO) stage IB2, IIA2-IVA (locally advanced stage) cervical cancer. A small study established a sensitivity and specificity estimate for PALN metastases of 50% (95% CI; 7-93%) and 83% (95% CI; 52-98%), respectively. Surgical staging of PALN may lead to a higher diagnostic accuracy. However, surgical staging of para-aortic lymph nodes in locally advanced stage cervical cancer is not common practice. Therefore, a phase 2 randomised controlled trial is needed to assess its safety and feasibility. In addition to standard imaging (MRI or CT scan) with PET-CT, 30 adult women with FIGO stage IB2, IIA2-IVA cervical cancer will be randomised to receive either surgical staging or usual PET-CT staging. Administering extended field radiotherapy will be based on lymphadenectomy results for the intervention group and on the PET-CT results for the control group. Follow-up visits at 0, 3, 6, 9 and 12 months will assess health-related quality of life and progression-free survival.Primary safety and feasibility outcomes of surgical staging will be assessed by calculating means with 95% confidence intervals for duration of surgery, number of complications, blood loss, nodal yield after para-aortic lymphadenectomy and treatment delay due to surgical staging. Secondary patient-centred outcomes on quality of life and first year survival will be documented and compared between the two groups. Estimates of sensitivity, specificity and negative and positive predictive values of MRI, PET-CT and surgical staging will be presented with 95% CI.. All analysis will be performed according to the intention to treat principle. This study will assess safety and feasibility, expressed as the number and severity of complications, effect on quality of life and the treatment delay due to surgically staging para-aortic lymph nodes in

  11. Evaluation of the reliability of clinical staging of T2 N0 esophageal cancer: a review of the Society of Thoracic Surgeons database.

    PubMed

    Crabtree, Traves D; Kosinski, Andrzej S; Puri, Varun; Burfeind, William; Bharat, Ankit; Patterson, G Alexander; Hofstetter, Wayne; Meyers, Bryan F

    2013-08-01

    Clinical staging of esophageal cancer has improved with positron-emission tomography/computed tomography and endoscopic ultrasound imaging. Despite such progress, small single-center studies have questioned the reliability of clinical staging of T2 N0 esophageal cancer. This study broadly examines the adequacy of clinical staging of T2 N0 disease using The Society of Thoracic Surgeons database. We retrospectively studied 810 clinical stage T2 N0 patients from 2002 to 2011, with 58 excluded because of incomplete pathologic staging data. Clinical stage, pathologic stage, and preoperative characteristics were recorded. Logistic regression analysis was used to identify factors associated with upstaging at the time of surgical intervention. Among 752 clinical stage T2 N0 patients, 270 (35.9%) received induction therapy before the operation. Of 482 patients who went directly to surgical intervention, 132 (27.4%) were confirmed as pathologic T2 N0, 125 (25.9%) were downstaged (ie, T0-1 N0), and 225 (46.7%) were upstaged at the operation (T3-4 N0 or Tany N1-3). Exclusive tumor upstaging (ie, pathologic T3-4 N0) accounted for 41 patients (18.2%), whereas exclusive nodal upstaging (ie, pathological T1-2 N1-3) accounted for 100 (44.5%). Combined tumor and nodal upstaging (ie, pathological T3-4 N1-3) accounted for 84 patients (37.3%). Among patients who received induction therapy, 103 (38.1%) were upstaged vs 225 (46.7%) without induction therapy (p = 0.026). Comparing the induction therapy group and the primary surgical group, postoperative 30-day mortality (3.7% vs 3.7%, p > 0.99) and morbidity (46.3% vs 45%, p = 0.76) were similar. Despite advances in staging techniques, clinical staging of T2 N0 esophageal cancer remains unreliable. Recognizing T2 N0 as a threshold for induction therapy in esophageal cancer, many surgeons have opted to treat T2 N0 disease with induction therapy, even though one-quarter of these patients will be pathologic T1 N0. Although this study

  12. Recent technological advances in computed tomography and the clinical impact therein.

    PubMed

    Runge, Val M; Marquez, Herman; Andreisek, Gustav; Valavanis, Anton; Alkadhi, Hatem

    2015-02-01

    Current technological advances in CT, specifically those with a major impact on clinical imaging, are discussed. The intent was to provide for both medical physicists and practicing radiologists a summary of the clinical impact of each advance, offering guidance in terms of utility and day-to-day clinical implementation, with specific attention to radiation dose reduction.

  13. Evaluation of the 8th AJCC staging system for pathologically versus clinically staged pancreatic adenocarcinoma: A time to revisit a dogma?

    PubMed

    Abdel-Rahman, Omar

    2018-02-01

    The 8th edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic exocrine adenocarcinoma has been released. The current study seeks to assess the 7th and 8th editions among patients registered within the surveillance, epidemiology and end results (SEER) database. SEER database (2010-2013) has been accessed through SEER*Stat program and AJCC 8th edition stages were reconstructed utilizing the collaborative stage descriptions. Kaplan-Meier analysis of overall survival and pancreatic cancer-specific survival analyses (according to both 7th and 8th editions and according to whether pathological or clinical staging were conducted) has been performed. Multivariate analysis of factors affecting pancreatic cancer-specific survival was also conducted through a Cox proportional hazard model. A total of 18  948 patients with pancreatic adenocarcinoma were identified in the period from 2010-2013. Pancreatic cancer-specific survival among pathologically staged patients and according to the 8th edition showed significant differences for all pair wise comparisons among different stages (P < 0.0001) except for the comparison between stage IA and stage IB (P = 0.307) and the comparison between stage IB and stage IIA (P = 0.116). Moreover, P value for stage IA vs IIA was 0.014; while pancreatic cancer-specific survival according to the 7th edition among pathologically staged patients showed significant differences for all pair wise comparisons among different stages (P < 0.0001) except for the comparison between IA and IB (P = 0.072), the comparison between stage IIA and stage IIB (P = 0.065), the comparison between stage IIA and stage III (P = 0.059) and the comparison between IIB and III (P = 0.595). Among clinically staged patients (i.e. those who did not undergo initial radical surgery), the prognostic performance of both 7th and 8th stages for both overall survival and pancreatic cancer-specific survival was

  14. Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluations from the PITER network

    PubMed Central

    Gaeta, Giovanni Battista; Brunetto, Maurizia Rossana; Di Leo, Alfredo; Iannone, Andrea; Santantonio, Teresa Antonia; Giammario, Adele; Raimondo, Giovanni; Filomia, Roberto; Coppola, Carmine; Amoruso, Daniela Caterina; Blanc, Pierluigi; Del Pin, Barbara; Chemello, Liliana; Cavalletto, Luisa; Morisco, Filomena; Donnarumma, Laura; Rumi, Maria Grazia; Gasbarrini, Antonio; Siciliano, Massimo; Massari, Marco; Corsini, Romina; Coco, Barbara; Madonia, Salvatore; Cannizzaro, Marco; Zignego, Anna Linda; Monti, Monica; Russo, Francesco Paolo; Zanetto, Alberto; Persico, Marcello; Masarone, Mario; Villa, Erica; Bernabucci, Veronica; Taliani, Gloria; Biliotti, Elisa; Chessa, Luchino; Pasetto, Maria Cristina; Andreone, Pietro; Margotti, Marzia; Brancaccio, Giuseppina; Ieluzzi, Donatella; Borgia, Guglielmo; Zappulo, Emanuela; Calvaruso, Vincenza; Petta, Salvatore; Falzano, Loredana; Quaranta, Maria Giovanna; Weimer, Liliana Elena; Rosato, Stefano; Vella, Stefano; Giannini, Edoardo Giovanni

    2017-01-01

    Background Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure. Aim To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage. Methods Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers. Results Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count <120,000/mm3 and the sofosbuvir+ribavirin regimen were independent predictors of failure by logistic regression analysis. The failure rate was 7.6% for patients treated with regimens that are no longer recommended or considered suboptimal (sofosbuvir+ribavirin or simeprevir+sofosbuvir±ribavirin), whereas 1.4% for regimens containing sofosbuvir combined with daclatasvir or ledipasvir or other DAAs. Of the patients who failed to achieve SVR, 72 (51.8%) were retreated with a second DAA regimen, specifically 38 (52.7%) with sofosbuvir+daclatasvir, 27 (37.5%) with sofosbuvir+ledipasvir, and 7 (9.7%) with other DAAs ±ribavirin. Among these, 69 (96%) patients achieved SVR12 and 3 (4%) failed. During a median time of 6 months (range: 5–14 months) between failure and the second DAA therapy, the Child-Pugh class worsened in 12 (16.7%) patients: from A to B in 10 patients (19.6%) and from B to C in 2 patients (10.5%), whereas it did not change in the remaining 60 patients. Following the retreatment SVR12 (median time of 6 months; range: 3–12 months), the Child-Pugh class improved in 17 (23.6%) patients: from B to A in 14 (19.4%) patients, from C to A in 1 patient (1.4%) and from C to B in 2 (2.9%) patients; it remained unchanged in 53 patients (73.6%) and

  15. Incidence of DAA failure and the clinical impact of retreatment in real-life patients treated in the advanced stage of liver disease: Interim evaluations from the PITER network.

    PubMed

    Kondili, Loreta A; Gaeta, Giovanni Battista; Brunetto, Maurizia Rossana; Di Leo, Alfredo; Iannone, Andrea; Santantonio, Teresa Antonia; Giammario, Adele; Raimondo, Giovanni; Filomia, Roberto; Coppola, Carmine; Amoruso, Daniela Caterina; Blanc, Pierluigi; Del Pin, Barbara; Chemello, Liliana; Cavalletto, Luisa; Morisco, Filomena; Donnarumma, Laura; Rumi, Maria Grazia; Gasbarrini, Antonio; Siciliano, Massimo; Massari, Marco; Corsini, Romina; Coco, Barbara; Madonia, Salvatore; Cannizzaro, Marco; Zignego, Anna Linda; Monti, Monica; Russo, Francesco Paolo; Zanetto, Alberto; Persico, Marcello; Masarone, Mario; Villa, Erica; Bernabucci, Veronica; Taliani, Gloria; Biliotti, Elisa; Chessa, Luchino; Pasetto, Maria Cristina; Andreone, Pietro; Margotti, Marzia; Brancaccio, Giuseppina; Ieluzzi, Donatella; Borgia, Guglielmo; Zappulo, Emanuela; Calvaruso, Vincenza; Petta, Salvatore; Falzano, Loredana; Quaranta, Maria Giovanna; Weimer, Liliana Elena; Rosato, Stefano; Vella, Stefano; Giannini, Edoardo Giovanni

    2017-01-01

    Few data are available on the virological and clinical outcomes of advanced liver disease patients retreated after first-line DAA failure. To evaluate DAA failure incidence and the retreatment clinical impact in patients treated in the advanced liver disease stage. Data on HCV genotype, liver disease severity, and first and second line DAA regimens were prospectively collected in consecutive patients who reached the 12-week post-treatment and retreatment evaluations from January 2015 to December 2016 in 23 of the PITER network centers. Among 3,830 patients with advanced fibrosis (F3) or cirrhosis, 139 (3.6%) failed to achieve SVR. Genotype 3, bilirubin levels >1.5mg/dl, platelet count <120,000/mm3 and the sofosbuvir+ribavirin regimen were independent predictors of failure by logistic regression analysis. The failure rate was 7.6% for patients treated with regimens that are no longer recommended or considered suboptimal (sofosbuvir+ribavirin or simeprevir+sofosbuvir±ribavirin), whereas 1.4% for regimens containing sofosbuvir combined with daclatasvir or ledipasvir or other DAAs. Of the patients who failed to achieve SVR, 72 (51.8%) were retreated with a second DAA regimen, specifically 38 (52.7%) with sofosbuvir+daclatasvir, 27 (37.5%) with sofosbuvir+ledipasvir, and 7 (9.7%) with other DAAs ±ribavirin. Among these, 69 (96%) patients achieved SVR12 and 3 (4%) failed. During a median time of 6 months (range: 5-14 months) between failure and the second DAA therapy, the Child-Pugh class worsened in 12 (16.7%) patients: from A to B in 10 patients (19.6%) and from B to C in 2 patients (10.5%), whereas it did not change in the remaining 60 patients. Following the retreatment SVR12 (median time of 6 months; range: 3-12 months), the Child-Pugh class improved in 17 (23.6%) patients: from B to A in 14 (19.4%) patients, from C to A in 1 patient (1.4%) and from C to B in 2 (2.9%) patients; it remained unchanged in 53 patients (73.6%) and worsened in 2 (2.8%) patients. Of

  16. Clinical Characteristics and Prognosis of End-stage Hypertrophic Cardiomyopathy.

    PubMed

    Xiao, Yan; Yang, Kun-Qi; Yang, Yan-Kun; Liu, Ya-Xin; Tian, Tao; Song, Lei; Jiang, Xiong-Jing; Zhou, Xian-Liang

    2015-06-05

    End-stage hypertrophic cardiomyopathy (HCM) is complicated by substantial adverse events. However, few studies have focused on electrocardiographic features and their prognostic values in HCM. This study aimed to evaluate the clinical manifestations and prognostic value of electrocardiography in patients with end-stage HCM. End-stage HCM patients were enrolled from a total of 1844 consecutive HCM patients from April 2002 to November 2013 at Fuwai Hospital. Clinical data, including medical history, electrocardiography, and echocardiography, were analyzed. Cox hazards regression analysis was used to assess the risk factors for cardiovascular mortality. End-stage HCM was identified in 99 (5.4%) patients, averaged at 52 ± 16 years old at entry. Atrial fibrillation was observed in 53 patients and mural thrombus in 19 patients. During 3.9 ± 3.0 years of follow-up, embolic stroke, refractory heart failure, and death or transplantation were observed in 20, 39, and 51 patients, respectively. The incidence of annual mortality was 13.2%. Multivariate Cox hazards regression analysis identified New York Heart Association Class (NYHA) III/IV at entry (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.05-3.80; P = 0.036), left bundle branch block (LBBB) (HR: 2.80; 95% CI: 1.47-5.31; P = 0.002), and an abnormal Q wave (HR: 2.21; 95% CI: 1.16-4.23; P = 0.016) as independent predictors of cardiovascular death, in accordance with all-cause death and heart failure-related death. LBBB and an abnormal Q wave are risk factors of cardiovascular mortality in end-stage HCM and provide new evidence for early intervention. Susceptibility of end-stage HCM patients to mural thrombus and embolic events warrants further attention.

  17. Retrospective cohort study of the clinical performance of 1-stage dental implants.

    PubMed

    Carr, Alan B; Choi, Yong-Geun; Eckert, Steven E; Desjardins, Ronald P

    2003-01-01

    To evaluate long-term clinical performance of 1-stage dental implant prostheses at a single clinic, emphasizing clinical and demographic characteristics that affect implant survival. Dental records of all 308 patients (674 implants) treated with 1-stage implants at Mayo Clinic from October 1993 through May 2000 were reviewed from implant placement to last visit. Exposure and outcome variables affecting performance were collected separately to control bias in the data collection process. Additional confounding factors (age and sex) were adjusted with the stratified Cox proportional hazards model. Implant survival was determined by means of a Kaplan-Meier survival estimate. The log-rank test was used to determine the role of clinical and demographic variables in implant survival. The relative risk associated with the possible effect of clinical and demographic variables on implant survival was estimated with the Cox proportional hazards model. The implant survival rate (n = 654 implants) was 97% (mean +/- SD follow-up, 21.0 +/- 18.8 months; range, 1 to 78 months). Performance bias was limited because nearly all patients were treated by 1 prosthodontist. Two implants failed after loading (6 and 9 months). The incidence of complications was less than 4%. Among the implant failures, use of heterogeneous bone graft was associated with 4.8 times more failures than was use of autogenous bone graft (P = .04). After augmentation, delaying implant placement for 5 to 6 months resulted in 8.6 times more failures than the rate after earlier placement (P < .001). Retrospective review of the clinical performance of a 1-stage dental implant system yielded a 97% survival rate, with no failures noted after 13 months. Prosthetic complications were low, especially for fixed implant prostheses. Clinical performance of 1-stage dental implant prostheses between 1993 and 2000 demonstrated a high level of predictability.

  18. Clinical Presentation and Outcomes of Stage III or Stage IV Retinoblastoma in 80 Asian Indian Patients.

    PubMed

    Kaliki, Swathi; Patel, Anamika; Iram, Sadiya; Palkonda, Vijay Anand Reddy

    2017-05-01

    To describe the clinical features and outcomes of patients with stage III or IV retinoblastoma. This was a retrospective study of 80 patients. Based on the International Retinoblastoma Staging System (IRSS), the tumors (n = 81) belonged to stage IIIa (n = 38, 47%), IIIb (n = 1, 1%), IVa2 (n = 10, 12%), IVb1 (n = 14, 17%), and IVb3 (n = 18, 22%). Of 80 patients, 42 (53%) were compliant to treatment and 38 (47%) were non-compliant. All 38 patients who were non-compliant to treatment died of the disease at a mean duration of 13 months from diagnosis. Of the 42 patients compliant to treatment, 22 (52%) died before completion of treatment. Twenty patients with stage III disease (25%) could complete the multimodal treatment and 17 (71%) were alive and well at a median follow-up duration of 77 months. Compliant multimodality treatment is beneficial in patients with IRSS stage III disease. IRSS stage IV retinoblastoma has poor prognosis despite treatment. [J Pediatr Ophthalmol Strabismus. 2017;54(3):177-184.]. Copyright 2017, SLACK Incorporated.

  19. Evaluation of PET and laparoscopy in STagIng advanced gastric cancer: a multicenter prospective study (PLASTIC-study).

    PubMed

    Brenkman, H J F; Gertsen, E C; Vegt, E; van Hillegersberg, R; van Berge Henegouwen, M I; Gisbertz, S S; Luyer, M D P; Nieuwenhuijzen, G A P; van Lanschot, J J B; Lagarde, S M; de Steur, W O; Hartgrink, H H; Stoot, J H M B; Hulsewe, K W E; Spillenaar Bilgen, E J; van Det, M J; Kouwenhoven, E A; van der Peet, D L; Daams, F; van Sandick, J W; van Grieken, N C T; Heisterkamp, J; van Etten, B; Haveman, J W; Pierie, J P; Jonker, F; Thijssen, A Y; Belt, E J T; van Duijvendijk, P; Wassenaar, E; van Laarhoven, H W M; Wessels, F J; Haj Mohammad, N; van Stel, H F; Frederix, G W J; Siersema, P D; Ruurda, J P

    2018-04-20

    Initial staging of gastric cancer consists of computed tomography (CT) and gastroscopy. In locally advanced (cT3-4) gastric cancer, fluorodeoxyglucose positron emission tomography with CT (FDG-PET/CT or PET) and staging laparoscopy (SL) may have a role in staging, but evidence is scarce. The aim of this study is to evaluate the impact and cost-effectiveness of PET and SL in addition to initial staging in patients with locally advanced gastric cancer. This prospective observational cohort study will include all patients with a surgically resectable, advanced gastric adenocarcinoma (cT3-4b, N0-3, M0), that are scheduled for treatment with curative intent after initial staging with gastroscopy and CT. The modalities to be investigated in this study is the addition of PET and SL. The primary outcome of this study is the proportion of patients in whom the PET or SL lead to a change in treatment strategy. Secondary outcome parameters are: diagnostic performance, morbidity and mortality, quality of life, and cost-effectiveness of these additional diagnostic modalities. The study recently started in August 2017 with a duration of 36 months. At least 239 patients need to be included in this study to demonstrate that the diagnostic modalities are break-even. Based on the annual number of gastrectomies in the participating centers, it is estimated that approximately 543 patients are included in this study. In this study, it is hypothesized that performing PET and SL for locally advanced gastric adenocarcinomas results in a change of treatment strategy in 27% of patients and an annual cost-reduction in the Netherlands of €916.438 in this patient group by reducing futile treatment. The results of this study may be applicable to all countries with comparable treatment algorithms and health care systems. NCT03208621 . This trial was registered prospectively on June 30, 2017.

  20. The multisystem degeneration amyotrophic lateral sclerosis - neuropathological staging and clinical translation.

    PubMed

    Verde, Federico; Del Tredici, Kelly; Braak, Heiko; Ludolph, Albert

    2017-12-01

    Amyotrophic lateral sclerosis (ALS) is traditionally considered a disease affecting exclusively motor neurons. However, much evidence points towards additional involvement of brain systems other than the motor. As much as half of ALS patients display cognitive-behavioral disturbances. ALS shares with a considerable proportion of FTD cases the same neuropathological substrate, namely, inclusions of abnormally phosphorylated protein TDP-43 (pTDP-43). In analogy with pathological staging systems elaborated in the past decades for Alzheimer's disease (AD) and Parkinson's disease (PD), a model of staging of pTDP-43 pathology in sporadic ALS (sALS) has been recently proposed. According to it, 4 stages can be recognized, where pTDP-43 inclusions are found in the agranular motor cortex and α-motor neurons of the brain stem and spinal cord (stage 1), in prefrontal neocortex (middle frontal gyrus), reticular formation, and precerebellar nuclei (stage 2), in further areas of the prefrontal neocortex (gyrus rectus and orbitofrontal gyri), postcentrally located sensory cortex, and basal ganglia (stage 3), and in the anteromedial temporal lobe including the hippocampus (stage 4). Based on this staging effort, a corticofugal axonal model for spreading of pathology can be hypothesized, whereby pathology starts in the primary motor cortex and spreads from there via axonal projections to lower motor neurons and to subcortical structures. Recent neuroradiological evidence seems to support the proposed staging system. From the clinical standpoint, a proportion of ALS patients display extramotor deficits (namely cognitive-behavioural disturbances, impaired ocular movements, and extrapyramidal alterations), which seem to correspond to the pathological involvement of the relevant cerebral structures. This review describes neuropathological sALS staging and addresses clinical evidence corresponding to this staging, pointing towards the concept of ALS as a multisystem brain degeneration

  1. Patients with advanced hepatocellular carcinoma need a personalized management: A lesson from clinical practice.

    PubMed

    Giannini, Edoardo Giovanni; Bucci, Laura; Garuti, Francesca; Brunacci, Matteo; Lenzi, Barbara; Valente, Matteo; Caturelli, Eugenio; Cabibbo, Giuseppe; Piscaglia, Fabio; Virdone, Roberto; Felder, Martina; Ciccarese, Francesca; Foschi, Francesco Giuseppe; Sacco, Rodolfo; Svegliati Baroni, Gianluca; Farinati, Fabio; Rapaccini, Gian Lodovico; Olivani, Andrea; Gasbarrini, Antonio; Di Marco, Maria; Morisco, Filomena; Zoli, Marco; Masotto, Alberto; Borzio, Franco; Benvegnù, Luisa; Marra, Fabio; Colecchia, Antonio; Nardone, Gerardo; Bernardi, Mauro; Trevisani, Franco

    2018-05-01

    The Barcelona Clinic Liver Cancer (BCLC) advanced stage (BCLC C) of hepatocellular carcinoma (HCC) includes a heterogeneous population, where sorafenib alone is the recommended treatment. In this study, our aim was to assess treatment and overall survival (OS) of BCLC C patients subclassified according to clinical features (performance status [PS], macrovascular invasion [MVI], extrahepatic spread [EHS] or MVI + EHS) determining their allocation to this stage. From the Italian Liver Cancer database, we analyzed 835 consecutive BCLC C patients diagnosed between 2008 and 2014. Patients were subclassified as: PS1 alone (n = 385; 46.1%), PS2 alone (n = 146; 17.5%), MVI (n = 224; 26.8%), EHS (n = 51; 6.1%), and MVI + EHS (n = 29; 3.5%). MVI, EHS, and MVI + EHS patients had larger and multifocal/massive HCCs and higher alpha-fetoprotein (AFP) levels than PS1 and PS2 patients. Median OS significantly declined from PS1 (38.6 months) to PS2 (22.3 months), EHS (11.2 months), MVI (8.2 months), and MVI + EHS (3.1 months; P < 0.001). Among MVI patients, OS was longer in those with peripheral than with central (portal trunk) MVI (11.2 vs. 7.1 months; P = 0.005). The most frequent treatments were: curative approaches in PS1 (39.7%), supportive therapy in PS2 (41.8%), sorafenib in MVI (39.3%) and EHS (37.3%), and best supportive care in MVI + EHS patients (51.7%). Independent prognostic factors were: Model for End-stage Liver Disease score, Child-Pugh class, ascites, platelet count, albumin, tumor size, MVI, EHS, AFP levels, and treatment type. BCLC C stage does not identify patients homogeneous enough to be allocated to a single stage. PS1 alone is not sufficient to include a patient into this stage. The remaining patients should be subclassified according to PS and tumor features, and new patient-tailored therapeutic indications are needed. (Hepatology 2018;67:1784-1796). © 2017 by the American Association for the Study of Liver Diseases.

  2. A Bayesian-frequentist two-stage single-arm phase II clinical trial design.

    PubMed

    Dong, Gaohong; Shih, Weichung Joe; Moore, Dirk; Quan, Hui; Marcella, Stephen

    2012-08-30

    It is well-known that both frequentist and Bayesian clinical trial designs have their own advantages and disadvantages. To have better properties inherited from these two types of designs, we developed a Bayesian-frequentist two-stage single-arm phase II clinical trial design. This design allows both early acceptance and rejection of the null hypothesis ( H(0) ). The measures (for example probability of trial early termination, expected sample size, etc.) of the design properties under both frequentist and Bayesian settings are derived. Moreover, under the Bayesian setting, the upper and lower boundaries are determined with predictive probability of trial success outcome. Given a beta prior and a sample size for stage I, based on the marginal distribution of the responses at stage I, we derived Bayesian Type I and Type II error rates. By controlling both frequentist and Bayesian error rates, the Bayesian-frequentist two-stage design has special features compared with other two-stage designs. Copyright © 2012 John Wiley & Sons, Ltd.

  3. Validation of the Mayo Clinic Staging System in Determining Prognoses of Patients With Perihilar Cholangiocarcinoma.

    PubMed

    Coelen, Robert J S; Gaspersz, Marcia P; Labeur, Tim A; van Vugt, Jeroen L A; van Dieren, Susan; Willemssen, François E J A; Nio, Chung Y; IJzermans, Jan N M; Klümpen, Heinz-Josef; Groot Koerkamp, Bas; van Gulik, Thomas M

    2017-12-01

    Most systems for staging perihilar cholangiocarcinoma (PHC) have been developed for the minority of patients with resectable disease. The recently developed Mayo Clinic system for staging PHC requires only clinical and radiologic variables, but has not yet been validated. We performed a retrospective study to validate the Mayo Clinic staging system. We identified consecutive patients with suspected PHC who were evaluated and treated at 2 tertiary centers in The Netherlands, from January 2002 through December 2014. Baseline characteristics (performance status, carbohydrate antigen 19-9 level) used in the staging system were collected from medical records and imaging parameters (tumor size, suspected vascular involvement, and metastatic disease) were reassessed by 2 experienced abdominal radiologists. Overall survival was analyzed using the Kaplan-Meier method and comparison of staging groups was performed using the log-rank test and Cox proportional hazard regression analysis. Discriminative performance was quantified by the concordance index and compared with the radiologic TNM staging of the American Joint Committee on Cancer (7th ed). PHCs from 600 patients were staged according to the Mayo Clinic model (23 stage I, 80 stage II, 357 stage III, and 140 stage IV). The median overall survival time was 11.6 months. The median overall survival times for patients with stages I, II, III, and IV were 33.2 months, 19.7 months, 12.1 months, and 6.0 months, respectively; with hazard ratios of 1.0 (reference), 2.02 (95% confidence interval [CI], 1.14-3.58), 2.71 (95% CI, 1.59-4.64), and 4.00 (95% CI, 2.30-6.95), respectively (P < .001). The concordance index score was 0.59 for the entire cohort (95% CI, 0.56-0.61). The Mayo Clinic model performed slightly better than the radiologic American Joint Committee on Cancer TNM system. In a retrospective study of 600 patients with PHC, we validated the Mayo Clinic system for staging PHC. This 4-tier staging system may aid

  4. Long-Term Results of Concurrent Chemoradiotherapy for Advanced N2-3 Stage Nasopharyngeal Carcinoma

    PubMed Central

    Wang, Xue; Chen, Meng; Wu, Jing; Xu, Jian-Hua; Qian, Pu-Dong; Guo, Wen-Jie; Jiang, Xue-Song; Zhu, Huan-Feng; Gu, Jia-Jia; Wu, Jian-Feng; Zhang, Ye-wei; He, Xia

    2015-01-01

    Background N-stage is related to distant metastasis in nasopharyngeal carcinoma (NPC) patients. The purpose of this study was to evaluate the efficacy and toxicity of different nedaplatin-based chemotherapy regimens in advanced N2-3 stage NPC patients treated with intensity modulated radiation therapy (IMRT). Patients and Methods Between April 2005 and December 2009, a total of 128 patients with N2-3 advanced NPC were retrospectively analyzed. Patients were treated with IMRT concurrent with 2 cycles of chemotherapy consisting of either nedaplatin plus paclitaxel (NP group, n = 67) or nedaplatin plus fluorouracil and paclitaxel (NFP group, n = 61). Two to four cycles of adjuvant chemotherapy were then administered every 21 days following concurrent chemoradiotherapy. Results With a median follow-up of 60 months, the 5-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) for all patients were 81.4%, 71.5%, 87.8% and 82.0%, respectively. No significant difference in PFS (66.6% vs. 76.7%, P = 0.212) and LRRFS rates (89.0% vs. 86.3%, P = 0.664) was observed between the NP and NFP groups. The 5-year OS (75.4% vs. 88.5%, P = 0.046) and DMFS (75.1% vs. 89.0%, P = 0.042) rate were superior in the NFP group compared with the NP group. The NFP group had a higher incidence of grade 3–4 acute toxicities including bone marrow suppression (leukopenia: χ2 = 3.935, P = 0.047; anemia: χ2 = 9.760, P = 0.002; thrombocytopenia: χ2 = 8.821, P = 0.003), and both liver and renal dysfunction (χ2 = 5.206, P = 0.023) compared with the NP group. Late toxicities were moderate and no difference was observed between the two groups. Conclusion IMRT concurrent with nedaplatin-based chemotherapy is an advocated regimen for patients with advanced N2-3 stage NPC. Patients with advanced N2-3 stage may be better candidates for the NFP regimen although this regimen was associated with a high acute

  5. Experimental Results of the First Two Stages of an Advanced Transonic Core Compressor Under Isolated and Multi-Stage Conditions

    NASA Technical Reports Server (NTRS)

    Prahst, Patricia S.; Kulkarni, Sameer; Sohn, Ki H.

    2015-01-01

    NASA's Environmentally Responsible Aviation (ERA) Program calls for investigation of the technology barriers associated with improved fuel efficiency of large gas turbine engines. Under ERA the task for a High Pressure Ratio Core Technology program calls for a higher overall pressure ratio of 60 to 70. This mean that the HPC would have to almost double in pressure ratio and keep its high level of efficiency. The challenge is how to match the corrected mass flow rate of the front two supersonic high reaction and high corrected tip speed stages with a total pressure ratio of 3.5. NASA and GE teamed to address this challenge by using the initial geometry of an advanced GE compressor design to meet the requirements of the first 2 stages of the very high pressure ratio core compressor. The rig was configured to run as a 2 stage machine, with Strut and IGV, Rotor 1 and Stator 1 run as independent tests which were then followed by adding the second stage. The goal is to fully understand the stage performances under isolated and multi-stage conditions and fully understand any differences and provide a detailed aerodynamic data set for CFD validation. Full use was made of steady and unsteady measurement methods to isolate fluid dynamics loss source mechanisms due to interaction and endwalls. The paper will present the description of the compressor test article, its predicted performance and operability, and the experimental results for both the single stage and two stage configurations. We focus the detailed measurements on 97 and 100 of design speed at 3 vane setting angles.

  6. Exprimental Results of the First Two Stages of an Advanced Transonic Core Compressor Under Isolated and Multi-Stage Conditions.

    NASA Technical Reports Server (NTRS)

    Prahst, Patricia S.; Kulkarni, Sameer; Sohn, Ki H.

    2015-01-01

    NASA's Environmentally Responsible Aviation (ERA) Program calls for investigation of the technology barriers associated with improved fuel efficiency for large gas turbine engines. Under ERA, the highly loaded core compressor technology program attempts to realize the fuel burn reduction goal by increasing overall pressure ratio of the compressor to increase thermal efficiency of the engine. Study engines with overall pressure ratio of 60 to 70 are now being investigated. This means that the high pressure compressor would have to almost double in pressure ratio while keeping a high level of efficiency. NASA and GE teamed to address this challenge by testing the first two stages of an advanced GE compressor designed to meet the requirements of a very high pressure ratio core compressor. Previous test experience of a compressor which included these front two stages indicated a performance deficit relative to design intent. Therefore, the current rig was designed to run in 1-stage and 2-stage configurations in two separate tests to assess whether the bow shock of the second rotor interacting with the upstream stage contributed to the unpredicted performance deficit, or if the culprit was due to interaction of rotor 1 and stator 1. Thus, the goal was to fully understand the stage 1 performance under isolated and multi-stage conditions, and additionally to provide a detailed aerodynamic data set for CFD validation. Full use was made of steady and unsteady measurement methods to understand fluid dynamics loss source mechanisms due to rotor shock interaction and endwall losses. This paper will present the description of the compressor test article and its measured performance and operability, for both the single stage and two stage configurations. We focus the paper on measurements at 97% corrected speed with design intent vane setting angles.

  7. Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer.

    PubMed

    Strunk, H M; Henseler, J; Rauch, M; Mücke, M; Kukuk, G; Cuhls, H; Radbruch, L; Zhang, L; Schild, H H; Marinova, M

    2016-07-01

    Evaluation of ultrasound-guided high-intensity focused ultrasound (HIFU) used for the first time in Germany in patients with inoperable pancreatic cancer for reduction of tumor volume and relief of tumor-associated pain. 15 patients with locally advanced inoperable pancreatic cancer and tumor-related pain symptoms were treated by HIFU (n = 6 UICC stage III, n = 9 UICC stage IV). 13 patients underwent simultaneous standard chemotherapy. Ablation was performed using the JC HIFU system (Chongqing, China HAIFU Company) with an ultrasonic device for real-time imaging. Imaging follow-up (US, CT, MRI) and clinical assessment using validated questionnaires (NRS, BPI) was performed before and up to 15 months after HIFU. Despite biliary or duodenal stents (4/15) and encasement of visceral vessels (15/15), HIFU treatment was performed successfully in all patients. Treatment time and sonication time were 111 min and 1103 s, respectively. The applied total energy was 386 768 J. After HIFU ablation, contrast-enhanced imaging showed devascularization of treated tumor regions with a significant average volume reduction of 63.8 % after 3 months. Considerable pain relief was achieved in 12 patients after HIFU (complete or partial pain reduction in 6 patients). US-guided HIFU with a suitable acoustic pathway can be used for local tumor control and relief of tumor-associated pain in patients with locally advanced pancreatic cancer. • US-guided HIFU allows an additive treatment of unresectable pancreatic cancer.• HIFU can be used for tumor volume reduction.• Using HIFU, a significant reduction of cancer-related pain was achieved.• HIFU provides clinical benefit in patients with pancreatic cancer. Citation Format: • Strunk HM, Henseler J, Rauch M et al. Clinical Use of High-Intensity Focused Ultrasound (HIFU) for Tumor and Pain Reduction in Advanced Pancreatic Cancer. Fortschr Röntgenstr 2016; 188: 662 - 670. © Georg Thieme Verlag KG

  8. Test Review: Advanced Clinical Solutions for WAIS-IV and WMS-IV

    ERIC Educational Resources Information Center

    Chu, Yiting; Lai, Mark H. C.; Xu, Yining; Zhou, Yuanyuan

    2012-01-01

    The authors review the "Advanced Clinical Solutions for WAIS-IV and WMS-IV". The "Advanced Clinical Solutions (ACS) for the Wechsler Adult Intelligence Scale-Fourth Edition" (WAIS-IV; Wechsler, 2008) and the "Wechsler Memory Scale-Fourth Edition" (WMS-IV; Wechsler, 2009) was published by Pearson in 2009. It is a…

  9. Management of untreated advanced stage follicular lymphoma: Role of patient discernment.

    PubMed

    Umakanthan, Jayadev Manikkam; Lunning, Mathew A

    2018-03-01

    Follicular lymphoma is the most common indolent non-Hodgkin lymphoma. Advanced stage disease is common at diagnosis. The timing of treatment for follicular lymphoma is best approached by considering the combination of presence or absence of symptoms along with estimation of tumor burden. Upfront treatment strategies should take into initial presentation variables, pace of disease progression and goals of care after discussion with the patient. Treatment approaches remain diverse and patient discernment is paramount. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Histologic parameters predictive of disease outcome in women with advanced stage ovarian carcinoma treated with neoadjuvant chemotherapy.

    PubMed

    Samrao, Damanzoopinder; Wang, Dan; Ough, Faith; Lin, Yvonne G; Liu, Song; Menesses, Teodulo; Yessaian, Annie; Turner, Nicole; Pejovic, Tanja; Mhawech-Fauceglia, Paulette

    2012-12-01

    The use of neoadjuvant chemotherapy followed by tumor reduction surgery, also called interval debulking surgery (IDS), is considered an alternative therapeutic regimen for selected patients with advanced stage epithelial ovarian cancer (EOC). Although minimal residual disease has been proven to be a prognostic factor in traditional cytoreduction for advanced stage EOC, predictive factors after IDS still remain unexplored. The aim of this study was to determine the prognostic value of post-neoadjuvant histologic changes with clinical outcome. Three pathologists evaluated 67 cases for the following parameters: fibrosis, necrosis, residual tumor, and inflammation. The Cohen's kappa statistic was used to measure agreement among pathologists. Univariate and multivariate Cox proportional hazards models were used to determine the association between histologic parameters and recurrence-free survival (RFS) and overall survival (OS). There was substantial to almost perfect agreement among the three pathologists in all four histologic parameters (k ranged from 0.65 to 0.97). Fibrosis was associated with longer RFS (P = 0.0257) with a median of 20 months for tumors with fibrosis (3+) versus 12 months for tumors with fibrosis (1+, 2+) and longer OS (P = 0.0249) with a median of 51 months for tumors with fibrosis (3+) versus 32 months for tumors with fibrosis (1+, 2+). Our results revealed that patients with tumors exhibiting fibrosis (1+, 2+), as well as necrosis (0, 1+), had significant shorter RFS and OS (P = 0.059 and P = 0.0234, respectively). We suggest that the assessment of fibrosis and necrosis should be implemented in pathologic evaluation and prospectively validated in future studies.

  11. Skin denervation and its clinical significance in late-stage chronic kidney disease.

    PubMed

    Chao, Chi-Chao; Wu, Vin-Cent; Tan, Chun-Hsiang; Wang, Yi-Mei; Tseng, Ming-Tsung; Wu, Pei-Chen; Lin, Yea-Huey; Lin, Whei-Min; Wu, Kwan-Dun; Hsieh, Sung-Tsang

    2011-02-01

    To investigate the skin innervation and its clinical significance in late-stage chronic kidney disease (CKD). Case series. National Taiwan University Hospital, Taipei, Taiwan. Forty consecutive nondiabetic patients with late-stage CKD (14 female and 26 male; mean [SD] age, 60.7 [12.3] years), including 2 cases with stage 3 CKD, 6 with stage 4 CKD, and 32 with stage 5 CKD, ie, end-stage kidney disease. Clinical evaluation of neurological deficits, nerve conduction study, autonomic function tests, and a 3-mm-diameter skin biopsy specimen taken from the distal leg. Quantitation of epidermal innervation, parameters of nerve conduction study, R-R interval variability, and sympathetic skin response. Clinically, 21 patients (52.5%) were symptomatic with paresthesia over the limbs or autonomic symptoms. The intraepidermal nerve fiber (IENF) density was markedly reduced in patients with CKD compared with age- and sex-matched controls (mean [SD], 2.8 [2.0] vs 8.6 [2.8] fibers/mm; P < .001). Skin denervation was observed in 27 patients (67.5%). Fifteen patients (37.5%) had abnormalities on nerve conduction studies, and 29 patients (72.5%) had abnormal results on autonomic function tests. By analysis with multiple regression models, the IENF density was negatively correlated with the duration of renal disease (P = .02). Additionally, the R-R interval variability at rest was linearly correlated with the IENF density (P = .02) and the absence of sympathetic skin responses at the soles was associated with reduced IENF density (P = .03). Small-fiber sensory and autonomic neuropathies constitute the major form of neuropathy in late-stage CKD. Furthermore, skin denervation was associated with the duration of renal disease.

  12. Analysis of Stage and Clinical/Prognostic Factors for Lung Cancer from SEER Registries: AJCC Staging and Collaborative Stage Data Collection System

    PubMed Central

    Chen, Vivien W.; Ruiz, Bernardo A.; Hsieh, Mei-Chin; Wu, Xiao-Cheng; Ries, Lynn; Lewis, Denise R.

    2014-01-01

    Introduction The American Joint Committee on Cancer (AJCC) 7th edition introduced major changes in the staging of lung cancer, including Tumor (T), Node (N), Metastasis (M) (TNM) system and new stage/prognostic site-specific factors (SSFs), collected under the Collaborative Stage Version 2 (CSv2) Data Collection System. The intent was to improve the stage precision which could guide treatment options and ultimately lead to better survival. This report examines stage trends, the change in stage distributions from the AJCC 6th to the 7th edition, and findings of the prognostic SSFs for 2010 lung cancer cases. Methods Data were from the November 2012 submission of 18 Surveillance, Epidemiology, and End Results (SEER) Program population-based registries. A total of 344 797 cases of lung cancer, diagnosed in 2004–2010, were analyzed. Results The percentages of small tumors and early stage lung cancer cases increased from 2004 to 2010. The AJCC 7th edition, implemented for 2010 diagnosis year, subclassified tumor size and reclassified multiple tumor nodules, pleural effusions, and involvement of tumors in the contralateral lung, resulting in a slight decrease in stage IB and stage IIIB and a small increase in stage IIA and stage IV. Overall about 80% of cases remained the same stage group in AJCC 6th and 7th editions. About 21% of lung cancer patients had separate tumor nodules in the ipsilateral (same) lung, and 23% of the surgically resected patients had visceral pleural invasion, both adverse prognostic factors. Conclusion It is feasible for high quality population-based registries such as the SEER Program to collect more refined staging and prognostic SSFs that allows better categorization of lung cancer patients with different clinical outcomes and to assess their survival. PMID:25412390

  13. A Matched Cohort Study of Patients With End-Stage Heart Failure from Anthracycline-Induced Cardiomyopathy Requiring Advanced Cardiac Support.

    PubMed

    Thomas, Garry R; McDonald, Michael A; Day, Jennifer; Ross, Heather J; Delgado, Diego H; Billia, Filio; Butany, Jagdish W; Rao, Vivek; Amir, Eitan; Bedard, Philippe L; Thavendiranathan, Paaladinesh

    2016-11-15

    Anthracycline-induced cardiomyopathy (AIC) may progress to end-stage heart failure requiring mechanical circulatory support or orthotopic heart transplantation (OHT). Previous studies have described important clinical differences between AIC and nonischemic cardiomyopathy (NIC) cohorts requiring these advanced interventions. Therefore, we sought to extend this literature by comparing echocardiographic parameters, treatment strategies, and the prognosis between matched patients from these cohorts. This is a retrospective matched cohort study. All patients who received a ventricular assist device or OHT at a large Canadian center were reviewed (n = 421; 1988 to 2015) and subjects with clinical and pathologic evidence of AIC were included (n = 17, 4.0%). A comparison cohort with idiopathic NIC from the same database, matched 3:1 for age, gender, ethnicity, and year of heart failure onset was selected. The Mann-Whitney rank-sum and Fisher's exact tests were used for comparisons. Patients with AIC were predominantly women (70.6%) with heart failure diagnosed at age 40.2 ± 15.8 and 8.3 ± 8.9 years after anthracycline treatment. Compared with NIC, no differences were seen in co-morbidities, echocardiographic measures, the proportion of patients receiving a defibrillator, ventricular assist device, or OHT, the incidence of graft failure, and all-cause mortality. In contrast to other studies, AIC was not associated with a higher incidence of right ventricular dysfunction. A greater proportion of patients with AIC developed cancer (recurrence or new primary) post-OHT (21.4% vs 2.3%, p = 0.042). In conclusion, we demonstrate that when matched cohorts of patients with end-stage heart failure secondary to AIC and idiopathic NIC are compared, they are similar with respect to co-morbidities, degree of ventricular dysfunction, and advanced therapeutics used. The prognosis with OHT is also similar. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Behavioral variant frontotemporal dementia: advanced disease stages and death. A step to palliative care.

    PubMed

    Diehl-Schmid, J; Richard-Devantoy, S; Grimmer, T; Förstl, H; Jox, R

    2017-08-01

    The aim of the present study was to gain insight into the living and care situation in advanced behavioral variant frontotemporal dementia (bvFTD), to describe symptoms and findings in advanced bvFTD, and to evaluate somatic comorbidities and circumstances of death. Standardized interviews were conducted with family caregivers of 83 patients with bvFTD. Forty-four percent of the patients were already deceased at the time of the interview. At the time of the interview or death, respectively, 47% of the patients lived in a nursing home. The median time between symptom onset and nursing home admission was 5.0 ± 5.5 years. In moderate and severe dementia stages almost all patients suffered from severe disabilities including impairment of language, gait, swallowing, and of the ability to care for themselves. Sixteen percent of the patients had got enteral tube feeding. Comorbid somatic diseases were diagnosed in 46% of the patients. Twenty-three percent of the deceased patients had been admitted into a hospital before death. Cardiovascular disease and respiratory disease, mostly pneumonia, were the most frequent causes of death. Advanced bvFTD is characterized by severe cognitive impairment and physical disabilities. BvFTD leads to a premature death. Our findings stress the importance of strategies that maximize patient comfort in advanced disease stages and allow for a peaceful death. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  15. Determinants of stage at diagnosis of breast cancer in Nigerian women: sociodemographic, breast cancer awareness, health care access and clinical factors.

    PubMed

    Jedy-Agba, Elima; McCormack, Valerie; Olaomi, Oluwole; Badejo, Wunmi; Yilkudi, Monday; Yawe, Terna; Ezeome, Emmanuel; Salu, Iliya; Miner, Elijah; Anosike, Ikechukwu; Adebamowo, Sally N; Achusi, Benjamin; Dos-Santos-Silva, Isabel; Adebamowo, Clement

    2017-07-01

    Advanced stage at diagnosis is a common feature of breast cancer in Sub-Saharan Africa (SSA), contributing to poor survival rates. Understanding its determinants is key to preventing deaths from this cancer in SSA. Within the Nigerian Integrative Epidemiology of Breast Cancer Study, a multicentred case-control study on breast cancer, we studied factors affecting stage at diagnosis of cases, i.e. women diagnosed with histologically confirmed invasive breast cancer between January 2014 and July 2016 at six secondary and tertiary hospitals in Nigeria. Stage was assessed using clinical and imaging methods. Ordinal logistic regression was used to examine associations of sociodemographic, breast cancer awareness, health care access and clinical factors with odds of later stage (I, II, III or IV) at diagnosis. A total of 316 women were included, with a mean age (SD) of 45.4 (11.4) years. Of these, 94.9% had stage information: 5 (1.7%), 92 (30.7%), 157 (52.4%) and 46 (15.3%) were diagnosed at stages I, II, III and IV, respectively. In multivariate analyses, lower educational level (odds ratio (OR) 2.35, 95% confidence interval: 1.04, 5.29), not believing in a cure for breast cancer (1.81: 1.09, 3.01), and living in a rural area (2.18: 1.05, 4.51) were strongly associated with later stage, whilst age at diagnosis, tumour grade and oestrogen receptor status were not. Being Muslim (vs. Christian) was associated with lower odds of later stage disease (0.46: 0.22, 0.94). Our findings suggest that factors that are amenable to intervention concerning breast cancer awareness and health care access, rather than intrinsic tumour characteristics, are the strongest determinants of stage at diagnosis in Nigerian women.

  16. Prognostic value of miliary versus non-miliary sub-staging in advanced ovarian cancer.

    PubMed

    Eng, Kevin H; Morrell, Kayla; Starbuck, Kristen; Spring-Robinson, Chandra; Khan, Aalia; Cleason, Dana; Akman, Levent; Zsiros, Emese; Odunsi, Kunle; Szender, J Brian

    2017-07-01

    The presence of miliary disease during initial ovarian cancer debulking may reflect a distinct mode of peritoneal spread independent from size-based tumor staging and may explain variation in response to treatment and survival outcomes. To infer the prevalence, presentation and clinical implications of miliary disease we reviewed existing surgical records. Reports were available for 1008 primary debulking surgeries for ovarian, primary peritoneal or fallopian tube cancer between 2001 and 2015 (685 reports from 2005 to 2015). Clinical outcome data was available for 938 patients. We analyzed a high-stage sub-cohort for survival (N=436). Most records were evaluable for miliary disease (761/938); for these, the miliary phenotype was highly prevalent (249/761, 32.7%) and often accompanied by ascites (185/249, 74%). While optimal debulking rates were unaffected by miliary disease, total resection (R0) rates were poorer. Liver, stomach, spleen or bladder appeared to be sporadically involved while the omentum, mesentery, bowel, peritoneum and diaphragm were affected simultaneously (Spearman rho>0.5). Overall, miliary disease was associated with worse progression free survival, overall survival, and time from relapse to death independent of stage. Survival effects were particularly strong for Stage IV disease where median overall survival varied by over 30months (log-rank p=0.002). Miliary disease is an identifiable surgical phenotype reflecting a distinct clinical trajectory that adds prognostic information to standard disease burden-based staging. These findings should permit further retrospective investigation in a wider cohort and prompt the consideration of prospective structured operative reporting standards and treatment strategies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  17. Progress and prospects for blood-stage malaria vaccines.

    PubMed

    Miura, Kazutoyo

    2016-06-01

    There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015. However, no blood-stage vaccine has reached a phase III trial. The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines. In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed. Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part.

  18. Resting energy expenditure and body composition in bedridden institutionalized elderly women with advanced-stage pressure sores.

    PubMed

    Sergi, Giuseppe; Coin, Alessandra; Mulone, Silvana; Castegnaro, Eugenio; Giantin, Valter; Manzato, Enzo; Busetto, Luca; Inelmen, Emine Meral; Marin, Sara; Enzi, Giuliano

    2007-03-01

    Our study investigated nutritional status, body composition, and resting energy expenditure (REE) in elderly patients with advanced-stage pressure sores (PS), in addition to researching any hypermetabolic condition and its relationship with PS size. The study involved 52 institutionalized bedridden elderly women (aged 83.7 +/- 6.3 years), divided into two groups: 23 with advanced-stage (stage 3 and 4) PS and 29 without PS. Albumin, prealbumin, and retinol-binding protein were measured in all patients, and fat-free mass (FFM) and fat mass (FM) were obtained by dual-energy x-ray absorptiometry (DEXA). REE was measured by indirect calorimetry and predicted with the Harris-Benedict formula. PS area and volume were also measured. The elderly women with and without PS were comparable in age, FFM, and FM. Mean albumin, prealbumin, and retinol-binding protein values were lower in cases with PS. Unadjusted mean REE was significantly higher in patients with PS (1212.3 +/- 236.7 vs 1085.5 +/- 161.3 kcal/d; p <.05), even after adjusting for FFM or expressed per kilogram of body weight (25.8 +/- 6.7 vs 21.1 +/- 4.0 kcal/d/kg; p <.01). Hypermetabolism, i.e., a measured REE > 110% of the predicted REE, was seen in 74% of patients with PS and 38% of controls. The difference between measured and predicted REE (DeltaREE) correlated with PS volume (r = 0.58; p <.01), but not with area. Advanced-stage PS in elderly women are associated with a hypermetabolic state that is influenced by the volume of the PS.

  19. Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer.

    PubMed

    Park, Jin-Young; Heo, Eun Jin; Lee, Jeong-Won; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

    2016-03-01

    Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC.

  20. Outcomes of laparoscopic fertility-sparing surgery in clinically early-stage epithelial ovarian cancer

    PubMed Central

    Park, Jin-Young; Lee, Yoo-Young; Kim, Tae-Joong; Kim, Byoung-Gie; Bae, Duk-Soo

    2016-01-01

    Objective Fertility-sparing surgery (FSS) is becoming an important technique in the surgical management of young women with early-stage epithelial ovarian cancer (EOC). We retrospectively evaluated the outcome of laparoscopic FSS in presumed clinically early-stage EOC. Methods We retrospectively searched databases of patients who received laparoscopic FSS for EOC between January 1999 and December 2012 at Samsung Medical Center. Women aged ≤40 years were included. The perioperative, oncological, and obstetric outcomes of these patients were evaluated. Results A total of 18 patients was evaluated. The median age of the patients was 33.5 years (range, 14 to 40 years). The number of patients with clinically stage IA and IC was 6 (33.3%) and 12 (66.7%), respectively. There were 7 (38.9%), 5 (27.8%), 3 (16.7%), and 3 patients (16.7%) with mucinous, endometrioid, clear cell, and serous tumor types, respectively. Complete surgical staging to preserve the uterus and one ovary with adnexa was performed in 4 patients (22.2%). Two out of them were upstaged to The International Federation of Gynecology and Obstetrics stage IIIA1. During the median follow-up of 47.3 months (range, 11.5 to 195.3 months), there were no perioperative or long term surgical complications. Four women (22.2%) conceived after their respective ovarian cancer treatments. Three (16.7%) of them completed full-term delivery and one is expecting a baby. One patient had disease recurrence. No patient died of the disease. Conclusion FSS in young patients with presumed clinically early-stage EOC is a challenging and cautious procedure. Further studies are urgent to determine the safety and feasibility of laparoscopic FSS in young patients with presumed clinically early-stage EOC. PMID:26768783

  1. Personalizing Drug Selection Using Advanced Clinical Decision Support

    PubMed Central

    Pestian, John; Spencer, Malik; Matykiewicz, Pawel; Zhang, Kejian; Vinks, Alexander A.; Glauser, Tracy

    2009-01-01

    This article describes the process of developing an advanced pharmacogenetics clinical decision support at one of the United States’ leading pediatric academic medical centers. This system, called CHRISTINE, combines clinical and genetic data to identify the optimal drug therapy when treating patients with epilepsy or Attention Deficit Hyperactivity Disorder. In the discussion a description of clinical decision support systems is provided, along with an overview of neurocognitive computing and how it is applied in this setting. PMID:19898682

  2. Interferon after surgery for women with advanced (Stage II-IV) epithelial ovarian cancer.

    PubMed

    Lawal, Aramide O; Musekiwa, Alfred; Grobler, Liesl

    2013-06-06

    Epithelial ovarian cancer (EOC) is a life-threatening disease. Most often women become symptomatic only in the advanced stages of the disease, increasing the difficulty of treatment. Whilst the disease responds well to surgery and chemotherapy, the relapse rate is high. New treatments to prevent disease recurrence or progression, prolong survival, and increase the quality of life are needed. To assess the effectiveness and safety of interferon after surgery in the treatment of advanced (stage II-IV) EOC. The Cochrane Gynaecological Cancer Review Group Specialized Register, Cochrane Central Register of Controlled Trials (CENTRAL) Issue 1, 2012, MEDLINE and EMBASE were searched to January 2012. Handsearching of conference proceedings was also undertaken. Reference lists of reviews and included trials were screened and experts in the field were contacted for additional trials. Clinical trials registers were searched for ongoing trials. Randomised controlled trials (RCTs) involving participants with advanced EOC that compared post-operative chemotherapy alone with post-operative interferon therapy in combination with chemotherapy or post-operative chemotherapy followed by interferon or observation alone Two review authors (AL and AM) independently screened the search results for relevant trials and extracted pre-specified information from each included trial. Data were managed using Review Manager 5.1. Hazard ratios (HR) were calculated for time-to-event outcomes and risk ratios (RR) for dichotomous outcomes, with corresponding 95% confidence intervals (CI). Five trials, including 1476 participants, were included in the review. Two trials compared interferon with observation alone and three trials compared interferon plus chemotherapy with chemotherapy alone. A meta-analysis of two trials involving 370 participants found no significant difference in both overall survival (HR 1.14, 95% CI 0.84 to 1.55) and progression free survival (HR 0.99, 95% CI 0.79 to 1.24) between

  3. The Path to Advanced Practice Licensure for Clinical Nurse Specialists in Washington State.

    PubMed

    Schoonover, Heather

    The aim of this study was to provide a review of the history and process to obtaining advanced practice licensure for clinical nurse specialists in Washington State. Before 2016, Washington State licensed certified nurse practitioners, certified nurse midwives, and certified nurse anesthetists under the designation of an advanced registered nurse practitioner; however, the state did not recognize clinical nurse specialists as advanced practice nurses. The work to drive the rule change began in 2007. The Washington Affiliate of the National Association of Clinical Nurse Specialists used the Power Elite Theory to guide advocacy activities, building coalitions and support for the desired rule changes. On January 8, 2016, the Washington State Nursing Care Quality Assurance Commission voted to amend the state's advanced practice rules, including clinical nurse specialists in the designation of an advanced practice nurse. Since the rule revision, clinical nurse specialists in Washington State have been granted advanced registered nurse practitioner licenses. Driving changes in state regulatory rules requires diligent advocacy, partnership, and a deep understanding of the state's rule-making processes. To be successful in changing rules, clinical nurse specialists must build strong partnerships with key influencers and understand the steps in practice required to make the desired changes.

  4. CE: Original Research: Creating an Evidence-Based Progression for Clinical Advancement Programs.

    PubMed

    Burke, Kathleen G; Johnson, Tonya; Sites, Christine; Barnsteiner, Jane

    2017-05-01

    : Background: The Institute of Medicine (IOM) and the Quality and Safety Education for Nurses (QSEN) project have identified six nursing competencies and supported their integration into undergraduate and graduate nursing curricula nationwide. But integration of those competencies into clinical practice has been limited, and evidence for the progression of competency proficiency within clinical advancement programs is scant. Using an evidence-based approach and building on the competencies identified by the IOM and QSEN, a team of experts at an academic health system developed eight competency domains and 186 related knowledge, skills, and attitudes (KSAs) for professional nursing practice. The aim of our study was to validate the eight identified competencies and 186 related KSAs and determine their developmental progression within a clinical advancement program. Using the Delphi technique, nursing leadership validated the newly identified competency domains and KSAs as essential to practice. Clinical experts from 13 Magnet-designated hospitals with clinical advancement programs then participated in Delphi rounds aimed at reaching consensus on the developmental progression of the 186 KSAs through four levels of clinical advancement. Two Delphi rounds resulted in consensus by the expert participants. All eight competency domains were determined to be essential at all four levels of clinical practice. At the novice level of practice, the experts identified a greater number of KSAs in the domains of safety and patient- and family-centered care. At more advanced practice levels, the experts identified a greater number of KSAs in the domains of professionalism, teamwork, technology and informatics, and continuous quality improvement. Incorporating the eight competency domains and the 186 KSAs into a framework for clinical advancement programs will likely result in more clearly defined role expectations; enhance accountability; and elevate and promote nursing practice

  5. Prediction of 30-day morbidity after primary cytoreductive surgery for advanced stage ovarian cancer.

    PubMed

    Gerestein, C G; Nieuwenhuyzen-de Boer, G M; Eijkemans, M J; Kooi, G S; Burger, C W

    2010-01-01

    Treatment in advanced stage epithelial ovarian cancer (EOC) is based on primary cytoreductive surgery followed by platinum-based chemotherapy. Successful cytoreduction to minimal residual tumour burden is the most important determinant of prognosis. However, extensive surgical procedures to achieve maximal debulking are inevitably associated with postoperative morbidity and mortality. The objective of this study is to determine predictors of 30-day morbidity after primary cytoreductive surgery for advanced stage EOC. All patients in the South Western part of the Netherlands who underwent primary cytoreductive surgery for advanced stage EOC between January 2004 and December 2007 were identified from the Rotterdam Cancer Registry database. All peri- and postoperative complications within 30 days after surgery were registered and classified according to the definitions of the National Surgical Quality Improvement Programme (NSQIP). To investigate independent predictors of 30-day morbidity, a Cox proportional hazards model with backward stepwise elimination was utilised. The identified predictors were entered into a nomogram. Two hundred and ninety-three patients entered the study protocol. Optimal cytoreduction was achieved in 136 (46%) patients. 30-day morbidity was seen in 99 (34%) patients. Postoperative morbidity could be predicted by age (P=0.007; odds ratio [OR] 1.034), WHO performance status (P=0.046; OR 1.757), extent of surgery (P=0.1308; OR=2.101), and operative time (P=0.017; OR 1.007) with an optimism corrected c-statistic of 0.68. 30-day morbidity could be predicted by age, WHO performance status, operative time and extent of surgery. The generated nomogram could be valuable for predicting operative risk in the individual patient.

  6. Multidisciplinary management of very advanced stage III and IV melanoma: Proof-of-principle.

    PubMed

    Gutman, Haim; Ben-Ami, Eytan; Shapira-Frommer, Roni; Schachter, Jacob

    2012-08-01

    Patients with potentially resectable advanced stage III and IV melanoma are a selected subgroup that gain maximal advantage if treated in a melanoma center. Surgery combined with chemo/chemobiotherapy may yield durable remission and long-term palliation. Thirty-seven non-randomly selected patients underwent systemic therapy with the aim of consolidating treatment by surgery. Data were collected prospectively, and analyzed retrospectively. The median follow-up from diagnosis was 50 (3-307) months and 15 (1-156) months when calculated from the last intervention. Twenty-two males and 15 females, with a median age at diagnosis of 44 (20-71) years, with 13 trunk, 13 extremity, 3 head and neck and 8 unknown primary melanomas were included. There were 17 stage III and 20 stage IV patients with a median Breslow thickness of 3.7 (0.45-26) mm. Chemo/chemobiotherapy achieved 7 clinical complete responses (cCRs), 28 partial responses (PRs) and 2 instances of stable disease. Six of the 7 cCRs were operated on, securing pathological complete response in 5 and PR in one. Four of these five and the PR patient still have no evidence of disease (NED). Twenty-one of 30 PR patients were rendered NED by surgery; 14 of these 21 patients succumbed to melanoma, and one is alive with stable disease. Overall, 11 of 37 patients have not succumbed to melanoma, with a median of 72 (14-156) months survival following the last intervention. Of the eight patients with unknown primary melanomas, five have not succumbed to melanoma, with a median of 89 (30-156) months survival following the last intervention. Patients with marginally resectable stage III and IV melanoma have a significant 30% chance, according to this series, for durable remission if treated by a multidisciplinary team in a melanoma center using induction chemobiotherapy and surgery. Results are more favorable for patients with an unknown primary lesion. In view of the currently approved new effective treatments for melanoma, this

  7. HIV-infection has no prognostic impact on advanced-stage Hodgkin lymphoma.

    PubMed

    Sorigué, Marc; García, Olga; Tapia, Gustavo; Baptista, Maria-Joao; Moreno, Miriam; Mate, José-Luis; Sancho, Juan M; Feliu, Evarist; Ribera, Josep-Maria; Navarro, José-Tomás

    2017-06-19

    Classical Hodgkin lymphoma (cHL) is a non-AIDS-defining cancer with a good response to chemotherapy in the combined antiretroviral therapy (cART) era. The aim of the present study was to compare the characteristics, the response to treatment and the survival of advanced-stage cHL treated with adriamycin, bleomycin, vinblastine and dacarbazine (ABVD) between cART-treated HIV-positive and HIV-negative patients. We retrospectively analyzed advanced-stage cHL patients from a single institution, uniformly treated with ABVD. All HIV-positive patients received cART concomitantly with ABVD. A total of 69 patients were included in the study: 21 were HIV-positive and 48 were HIV-negative. HIV-positive patients had more aggressive features at cHL diagnosis, such as worse performance status, more frequent bone marrow involvement and mixed cellularity histologic subtype. There were no differences in complete response rate (89% in HIV-positive vs. 91% in HIV-negative), P = 1; disease-free survival (DFS) [10-year DFS probability (95% CI) 70% (41-99%) vs. 74% (57-91%)], P = 0.907 and overall survival (OS) [10-year OS probability (95% CI) 73% (52-94%) vs. 68% (51-85%)], P = 0.904. On multivariate analysis, HIV infection did not correlate with worse OS. Although HIV-positive patients with cHL had more aggressive baseline features in this series, there were no differences in response rate or survival between HIV-positive and HIV-negative patients.

  8. Textural features of pretreatment 18F-FDG PET/CT images: prognostic significance in patients with advanced T-stage oropharyngeal squamous cell carcinoma.

    PubMed

    Cheng, Nai-Ming; Fang, Yu-Hua Dean; Chang, Joseph Tung-Chieh; Huang, Chung-Guei; Tsan, Din-Li; Ng, Shu-Hang; Wang, Hung-Ming; Lin, Chien-Yu; Liao, Chun-Ta; Yen, Tzu-Chen

    2013-10-01

    Previous studies have shown that total lesion glycolysis (TLG) may serve as a prognostic indicator in oropharyngeal squamous cell carcinoma (OPSCC). We sought to investigate whether the textural features of pretreatment (18)F-FDG PET/CT images can provide any additional prognostic information over TLG and clinical staging in patients with advanced T-stage OPSCC. We retrospectively analyzed the pretreatment (18)F-FDG PET/CT images of 70 patients with advanced T-stage OPSCC who had completed concurrent chemoradiotherapy, bioradiotherapy, or radiotherapy with curative intent. All of the patients had data on human papillomavirus (HPV) infection and were followed up for at least 24 mo or until death. A standardized uptake value (SUV) of 2.5 was taken as a cutoff for tumor boundary. The textural features of pretreatment (18)F-FDG PET/CT images were extracted from histogram analysis (SUV variance and SUV entropy), normalized gray-level cooccurrence matrix (uniformity, entropy, dissimilarity, contrast, homogeneity, inverse different moment, and correlation), and neighborhood gray-tone difference matrix (coarseness, contrast, busyness, complexity, and strength). Receiver-operating-characteristic curves were used to identify the optimal cutoff values for the textural features and TLG. Thirteen patients were HPV-positive. Multivariate Cox regression analysis showed that age, tumor TLG, and uniformity were independently associated with progression-free survival (PFS) and disease-specific survival (DSS). TLG, uniformity, and HPV positivity were significantly associated with overall survival (OS). A prognostic scoring system based on TLG and uniformity was derived. Patients who presented with TLG > 121.9 g and uniformity ≤ 0.138 experienced significantly worse PFS, DSS, and OS rates than those without (P < 0.001, < 0.001, and 0.002, respectively). Patients with TLG > 121.9 g or uniformity ≤ 0.138 were further divided according to age, and different PFS and DSS were observed

  9. Risk factors for competing noncancer mortality after definitive treatment for advanced-stage head and neck cancer.

    PubMed

    Kim, Yong Han; Roh, Jong-Lyel; Kim, Sung-Bae; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon

    2018-05-27

    Patients with head and neck cancer (HNC) can die of index tumor progression and second tumor or noncancer causes. Here, we investigated the risk factors for competing noncancer mortality (NCM) in a prospective cohort of patients with advanced-stage HNC. A prospective observational study was conducted with 604 patients who underwent definitive treatment for advanced-stage HNC between 2010 and 2015. Main outcomes were NCM and cancer mortality (CM) defined as death from noncancer causes and HNC or second cancers, respectively. Cumulative incidence and cause-specific hazard functions were used to analyze the risk factors of NCM and CM. Age, smoking, Charlson comorbidity index (CCI), performance status, body mass index, rural residence, education and hemoglobin level at diagnosis, and chemotherapy were significantly associated with NCM (all P<0.05). Multivariate analyses showed that age, CCI, and hemoglobin were independent factors of NCM. Age (≥65 years), CCI (≥2), and hemoglobin (<11 g/dL) were related to 4.5-, 3.2-, and 2.7-fold increased adjusted risk of NCM, respectively. Old age, comorbidity, and hemoglobin at diagnosis were independent predictors of NCM. The risk factors could be used to predict noncancer death after definitive treatment for advanced-stage HNC. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  10. Anterior Urethral Advancement as a Single-Stage Technique for Repair of Anterior Hypospadias: Our Experience.

    PubMed

    Gite, Venkat A; Nikose, Jayant V; Bote, Sachin M; Patil, Saurabh R

    2017-07-02

    Many techniques have been described to correct anterior hypospadias with variable results. Anterior urethral advancement as one stage technique was first described by Ti Chang Shing in 1984. It was also used for the repair of strictures and urethrocutaneous fistulae involving distal urethra. We report our experience of using this technique with some modification for the repair of anterior hypospadias. In the period between 2013-2015, 20 cases with anterior hypospadias including 2 cases of glanular, 3 cases of coronal, 12 cases of subcoronal and 3 cases of distal penile hypospadias were treated with anterior urethral advancement technique. Patients' age groups ranged from 18 months to 10 years. Postoperatively, patients were passing urine from tip of neomeatus with satisfactory stream during follow up period of 6 months to 2 years. There were no major complications in any of our patients except in one patient who developed meatal stenosis which was treated by periodic dilatation. Three fold urethral mobilization was sufficient in all cases. Anterior urethral advancement technique is a single-stage procedure with good cosmetic results and least complications for anterior hypospadias repair in properly selected cases.

  11. Laparoscopic staging for apparent stage I epithelial ovarian cancer.

    PubMed

    Melamed, Alexander; Keating, Nancy L; Clemmer, Joel T; Bregar, Amy J; Wright, Jason D; Boruta, David M; Schorge, John O; Del Carmen, Marcela G; Rauh-Hain, J Alejandro

    2017-01-01

    Whereas advances in minimally invasive surgery have made laparoscopic staging technically feasible in stage I epithelial ovarian cancer, the practice remains controversial because of an absence of randomized trials and lack of high-quality observational studies demonstrating equivalent outcomes. This study seeks to evaluate the association of laparoscopic staging with survival among women with clinical stage I epithelial ovarian cancer. We used the National Cancer Data Base to identify all women who underwent surgical staging for clinical stage I epithelial ovarian cancer diagnosed from 2010 through 2012. The exposure of interest was planned surgical approach (laparoscopy vs laparotomy), and the primary outcome was overall survival. The primary analysis was based on an intention to treat: all women whose procedures were initiated laparoscopically were categorized as having had a planned laparoscopic procedure, regardless of subsequent conversion to laparotomy. We used propensity methods to match patients who underwent planned laparoscopic staging with similar patients who underwent planned laparotomy based on observed characteristics. We compared survival among the matched cohorts using the Kaplan-Meier method and Cox regression. We compared the extent of lymphadenectomy using the Wilcoxon rank-sum test. Among 4798 eligible patients, 1112 (23.2%) underwent procedures that were initiated laparoscopically, of which 190 (17%) were converted to laparotomy. Women who underwent planned laparoscopy were more frequently white, privately insured, from wealthier ZIP codes, received care in community cancer centers, and had smaller tumors that were more frequently of serous and less often of mucinous histology than those who underwent staging via planned laparotomy. After propensity score matching, time to death did not differ between patients undergoing planned laparoscopic vs open staging (hazard ratio, 0.77, 95% confidence interval, 0.54-1.09; P = .13). Planned

  12. At-risk studies and clinical antecedents of psychosis, bipolar disorder and depression: a scoping review in the context of clinical staging.

    PubMed

    Hartmann, Jessica A; Nelson, Barnaby; Ratheesh, Aswin; Treen, Devi; McGorry, Patrick D

    2018-06-04

    Identifying young people at risk of developing serious mental illness and identifying predictors of onset of illness has been a focus of psychiatric prediction research, particularly in the field of psychosis. Work in this area has facilitated the adoption of the clinical staging model of early clinical phenotypes, ranging from at-risk mental states to chronic and severe mental illness. It has been a topic of debate if these staging models should be conceptualised as disorder-specific or transdiagnostic. In order to inform this debate and facilitate cross-diagnostic discourse, the present scoping review provides a broad overview of the body of literature of (a) longitudinal at-risk approaches and (b) identified antecedents of (homotypic) illness progression across three major mental disorders [psychosis, bipolar disorder (BD) and depression], and places these in the context of clinical staging. Stage 0 at-risk conceptualisations (i.e. familial high-risk approaches) were identified in all three disorders. However, formalised stage 1b conceptualisations (i.e. ultra-high-risk approaches) were only present in psychosis and marginally in BD. The presence of non-specific and overlapping antecedents in the three disorders may support a general staging model, at least in the early stages of severe psychotic or mood disorders.

  13. Proof of Learning Outcome by the Advanced Clinical Competency Examination Trial after the Long-term Student's Practice in Pharmaceutical Education.

    PubMed

    Komori, Koji; Kataoka, Makoto; Kuramoto, Nobuyuki; Tsuji, Takumi; Nakatani, Takafumi; Yasuhara, Tomohisa; Mitamura, Shinobu; Hane, Yumiko; Ogita, Kiyokazu

    2016-01-01

    At Setsunan University, a debrief session (a poster session) is commonly performed by the students who have completed the long-term students' practice. Since the valuable changes in practical competency of the students cannot be evaluated through this session, we specified items that can help evaluate and methods that can help estimate the students' competency as clinical pharmacists. We subsequently carried out a trial called the "Advanced Clinical Competency Examination". We evaluated 103 students who had concluded the students' practice for the second period (Sep 1, 2014, to Nov 16, 2014): 70 students (called "All finish students") who had completed the practice in a hospital and pharmacy, and 33 students (called "Hospital finish students") who had finished the practice at a hospital only. The trial was executed in four stages. In the first stage, students drew pictures of something impressive they had learned during the practice. In the second stage, students were given patient cases and were asked, "What is this patient's problem?" and "How would you solve this problem?". In the third stage, the students discussed their answers in a group. In the fourth stage, each group made a poster presentation in separate rooms. By using a rubric, the teachers evaluated each student individually, the results of which showed that the "All finish students" could identify more problems than the "Hospital finish students".

  14. Prognostic relevance of biological subtype overrides that of TNM staging in breast cancer: discordance between stage and biology.

    PubMed

    Jung, Hyun Ae; Park, Yeon Hee; Kim, Moonjin; Kim, Sungmin; Chang, Won Jin; Choi, Moon Ki; Hong, Jung Yong; Kim, Seok Won; Kil, Won Ho; Lee, Jeong Eon; Nam, Seok Jin; Ahn, Jin Seok; Im, Young-Hyuck

    2015-02-01

    Recently, we faced difficult treatment decisions regarding appropriate adjuvant systemic treatment, especially for patients who show discordance between stage and tumor biology. The aim of this study was to compare the prognostic relevance of the TNM staging system with that of intrinsic subtype in breast cancer. We retrospectively identified women patients who received curative surgery for stage I-III breast cancer with available data on immunohistochemistry profiles including hormone receptor (HR) status, human epidermal growth factor receptor 2 (HER2) status, and Ki 67 staining at the Samsung Medical Center from January 2004 to September 2008. Primary outcomes were recurrence-free survival (RFS) and overall survival (OS). A total of 1145 patients were diagnosed with breast cancer and received curative surgery. Of these, 463 (40.4%) patients were stage I, and 682 (59.6%) were stage II or III. In addition, 701 (61.2%) patients were HR positive, 239 (20.9%) were HER2 positive, and 205 (20.9%) had triple-negative breast cancer. The 5-year RFS for the patients who were HR positive and HER2 negative with a low Ki 67 staining score (0-25%) was 99%. The 5-year RFS for patients who were HER2-positive or had triple-negative breast cancer were 89 and 83%, respectively (P value = <0.001). In multivariate analysis, advanced stage (II/III) and unfavorable biology (HER2 positive or triple negative) retained their statistical significance as predictors of decreased RFS and OS. Patients with advanced-stage disease (II or III) but favorable tumor biology (HR positive and HER2 negative and low Ki 67) had better clinical outcomes than those with stage I disease and unfavorable tumor biology in terms of RFS (99 versus 92%, P value = 0.011) and OS (99 versus 96%, P value = 0.03) at 5 years. The current results showed that intrinsic subtype has a greater prognostic impact in predicting clinical outcomes in subpopulations of patients with stage I-III breast cancer who show

  15. Clinical stage of oral cancer patients at the time of initial diagnosis.

    PubMed

    Shah, Irfan; Sefvan, Omer; Luqman, Uzair; Ibrahim, Waseem; Mehmood, Sana; Alamgir, Wajiha

    2010-01-01

    Squamous cell carcinoma is the most common oral cancer. Early diagnosis ensures better prognosis. Late diagnosis is however common around the world and contributes to the high morbidity and mortality related to oral cancer. The objective of this study was to determine the clinical stage of oral cancer patients at the time of diagnosis. This retrospective study was carried out on 334 oral cancer patients who presented to the outdoor departments of Armed Forces Institute of Dentistry, and Armed Forces Institute of Pathology, Rawalpindi from July 2008 to December 2009. The records that were reviewed included history and clinical examination findings. OPG and CT scans of the head and neck region, chest X-rays, abdominal ultrasounds and liver function tests. Size of the primary tumour, the size, number and laterality of the involved cervical lymph nodes and the presence/absence of distant metastases were documented and statistically analysed using SPSS-17. Out of the 334 patients, 203 (60.8%) were males and 131 (39.2%) females. The age range was from 21 to 88 years. Buccal mucosa was the most commonly involved site (32%). The primary tumour was 4 Cm or more in size, (T3/T4) 71.25% of the cases. Cervical lymph nodes were involved in 211 patients (63.2%) and distant metastases were present in 39 patients (11.7%). Overall, clinical stage IV was the most common (57.18%) followed by stage III (24.55%), stage II (13.77%) and stage I (4.49%). Oral cancers are diagnosed late (Stage III and IV) in Pakistan and need immediate public and professional attention.

  16. Predictors of Timely Access of Oncology Services and Advanced-Stage Cancer in an HIV-Endemic Setting

    PubMed Central

    Suneja, Gita; Tapela, Neo; Mapes, Abigail; Pusoentsi, Malebogo; Mmalane, Mompati; Hodgeman, Ryan; Boyer, Matthew; Musimar, Zola; Ramogola-Masire, Doreen; Grover, Surbhi; Nsingo-Bvochora, Memory; Kayembe, Mukendi; Efstathiou, Jason; Lockman, Shahin; Dryden-Peterson, Scott

    2016-01-01

    Background. Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access. Methods. Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed. Cox and logistic models were used to examine the effect of HIV and other predictors on time to oncology care and presentation with advanced cancer (stage III or IV). Results. Of the 1,146 patients analyzed, 584 (51%) had HIV and 615 (54%) had advanced cancer. The initial clinic visit occurred a mean of 144 days (median 29, interquartile range 0–185) after symptom onset, but subsequent mean time to oncology care was 406 days (median 160, interquartile range 59–653). HIV status was not significantly associated with time to oncology care (adjusted hazard ratio [aHR] 0.91, 95% confidence interval [CI] 0.79–1.06). However, patients who reported using traditional medicine/healers engaged in oncology care significantly faster (aHR 1.23, 95% CI 1.09–1.40) and those with advanced cancer entered care earlier (aHR 1.48, 95% CI 1.30–1.70). Factors significantly associated with advanced cancer included income <$50 per month (adjusted odds ratio [aOR] 1.35, 95% CI 1.05–1.75), male sex (aOR 1.45, 95% CI 1.12–1.87), and pain as the presenting symptom (aOR 1.39, 95% CI 1.03–1.88). Conclusion. Longitudinal HIV care did not reduce the substantial delay to cancer treatment. Research focused on reducing health system delay through coordination and navigation is needed. Implications for Practice: The majority (54%) of patients in this large cohort from Botswana presented with advanced-stage cancer despite universal access to free health care. Median time from first symptom to

  17. Predictors of Timely Access of Oncology Services and Advanced-Stage Cancer in an HIV-Endemic Setting.

    PubMed

    Brown, Carolyn A; Suneja, Gita; Tapela, Neo; Mapes, Abigail; Pusoentsi, Malebogo; Mmalane, Mompati; Hodgeman, Ryan; Boyer, Matthew; Musimar, Zola; Ramogola-Masire, Doreen; Grover, Surbhi; Nsingo-Bvochora, Memory; Kayembe, Mukendi; Efstathiou, Jason; Lockman, Shahin; Dryden-Peterson, Scott

    2016-06-01

    Three-quarters of cancer deaths occur in resource-limited countries, and delayed presentation contributes to poor outcome. In Botswana, where more than half of cancers arise in HIV-infected individuals, we sought to explore predictors of timely oncology care and evaluate the hypothesis that engagement in longitudinal HIV care improves access. Consenting patients presenting for oncology care from October 2010 to September 2014 were interviewed and their records were reviewed. Cox and logistic models were used to examine the effect of HIV and other predictors on time to oncology care and presentation with advanced cancer (stage III or IV). Of the 1,146 patients analyzed, 584 (51%) had HIV and 615 (54%) had advanced cancer. The initial clinic visit occurred a mean of 144 days (median 29, interquartile range 0-185) after symptom onset, but subsequent mean time to oncology care was 406 days (median 160, interquartile range 59-653). HIV status was not significantly associated with time to oncology care (adjusted hazard ratio [aHR] 0.91, 95% confidence interval [CI] 0.79-1.06). However, patients who reported using traditional medicine/healers engaged in oncology care significantly faster (aHR 1.23, 95% CI 1.09-1.40) and those with advanced cancer entered care earlier (aHR 1.48, 95% CI 1.30-1.70). Factors significantly associated with advanced cancer included income <$50 per month (adjusted odds ratio [aOR] 1.35, 95% CI 1.05-1.75), male sex (aOR 1.45, 95% CI 1.12-1.87), and pain as the presenting symptom (aOR 1.39, 95% CI 1.03-1.88). Longitudinal HIV care did not reduce the substantial delay to cancer treatment. Research focused on reducing health system delay through coordination and navigation is needed. The majority (54%) of patients in this large cohort from Botswana presented with advanced-stage cancer despite universal access to free health care. Median time from first symptom to specialized oncology care was 13 months. For HIV-infected patients (51% of total

  18. Personhood, patienthood, and clinical practice: reassessing advance directives.

    PubMed

    Rich, B A

    1998-09-01

    This article considers 2 major critiques of advance directives and offers a defense to each of them. The 1st critique is philosophical in nature and maintains that the moral authority of an advance directive is undercut by a failure of personal identity to survive the loss of decisional capacity. The response in this article is that this critique relies on a flawed and disfavored concept of persons and their persistence over time. The 2nd critique, pragmatic in nature, argues that advance directives cannot be authoritative because the requisite elements of an informed consent to or refusal of treatment are rarely present, and many such instruments are ambiguous. The author argues that if the creation of advance directives, as a form of advance care planning, is made an integral aspect of clinical practice, many more patients will elect to execute directives, and those directives will not be ambiguous.

  19. Preoperative tumour staging with multidisciplinary team assessment improves the outcome in locally advanced primary rectal cancer.

    PubMed

    Palmer, G; Martling, A; Cedermark, B; Holm, T

    2011-12-01

    Multidisciplinary team meetings have been introduced as a result of developments in preoperative radiological tumour staging and neoadjuvant treatment. Multidisciplinary team recommendations will influence treatment decisions but their effect on patient outcome is unknown. The aim of this study was to assess outcome in relation to preoperative local and distant staging, with or without multidisciplinary team assessment. A population-based registry of all patients with rectal cancer, treated in the Stockholm region from 1995 to 2004, identified 303 patients with locally advanced primary rectal cancer. The patients were classified into three groups: group 1, preoperative local and distant radiological tumour staging with discussion at a multidisciplinary team meeting; group 2, preoperative staging but no multidisciplinary team assessment; and group 3, no proper preoperative radiological staging. Neoadjuvant treatment was more prevalent in groups 1 and 2 than in group 3. The incidence of R0 resection differed significantly between the groups (52% in group 1, 43% in group 2 and 21% in group 3; P < 0.001). Local tumour control was achieved in 57%, 36%, and 19% of patients in groups 1, 2 and 3, respectively (P < 0.001). The estimated overall 5-year survival of patients was 30%, 28% and 12% in groups 1, 2 and 3, respectively. Preoperative radiological tumour staging in patients with locally advanced primary rectal cancer and discussion at a multidisciplinary team meeting increases the proportion of patients receiving neoadjuvant treatment and cancer-specific end-points. © 2011 The Authors. Colorectal Disease © 2011 The Association of Coloproctology of Great Britain and Ireland.

  20. Drivers of advanced stage at breast cancer diagnosis in the multicountry African breast cancer – disparities in outcomes (ABC‐DO) study

    PubMed Central

    Zietsman, Annelle; Galukande, Moses; Anele, Angelica; Adisa, Charles; Parham, Groesbeck; Pinder, Leeya; Cubasch, Herbert; Joffe, Maureen; Kidaaga, Frederick; Lukande, Robert; Offiah, Awa U.; Egejuru, Ralph O.; Shibemba, Aaron; Schuz, Joachim; Anderson, Benjamin O.; dos Santos Silva, Isabel; McCormack, Valerie

    2017-01-01

    Breast cancer (BC) survival rates in sub‐Saharan Africa (SSA) are low in part due to advanced stage at diagnosis. As one component of a study of the entire journey of SSA women with BC, we aimed to identify shared and setting‐specific drivers of advanced stage BC. Women newly diagnosed in the multicountry African Breast Cancer–Disparities in Outcomes (ABC‐DO) study completed a baseline interview and their stage information was extracted from medical records. Ordinal logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for advanced stage (I, II, III, IV) in relation to individual woman‐level, referral and biological factors. A total of 1795 women were included from Nigeria, Uganda, Zambia, and the multiracial populations of Namibia and South Africa, 1091 of whom (61%) were stage III/IV. Stage was lower in women with greater BC knowledge (OR 0.77 (95% CI: 0.70, 0.85) per point on a 6 point scale). More advanced stage was associated with being black (4.00 (2.79, 5.74)), having attended stage BC in SSA is largely attributed to modifiable factors and strategies to improve BC education and awareness in women and the health system should be intensified. PMID:29197068

  1. Progress and prospects for blood-stage malaria vaccines

    PubMed Central

    Miura, Kazutoyo

    2016-01-01

    ABSTRACT There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015. However, no blood-stage vaccine has reached a phase III trial. The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines. In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed. Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part. PMID:26760062

  2. [Advances of Molecular Diagnostic Techniques Application in Clinical Diagnosis.

    PubMed

    Ying, Bin-Wu

    2016-11-01

    Over the past 20 years,clinical molecular diagnostic technology has made rapid development,and became the most promising field in clinical laboratory medicine.In particular,with the development of genomics,clinical molecular diagnostic methods will reveal the nature of clinical diseases in a deeper level,thus guiding the clinical diagnosis and treatments.Many molecular diagnostic projects have been routinely applied in clinical works.This paper reviews the advances on application of clinical diagnostic techniques in infectious disease,tumor and genetic disorders,including nucleic acid amplification,biochip,next-generation sequencing,and automation molecular system,and so on.

  3. Advances in single- and multi-stage Stirling-type pulse tube cryocoolers for space applications in NLIP/SITP/CAS

    NASA Astrophysics Data System (ADS)

    Dang, Haizheng; Tan, Jun; Zha, Rui; Li, Jiaqi; Zhang, Lei; Zhao, Yibo; Gao, Zhiqian; Bao, Dingli; Li, Ning; Zhang, Tao; Zhao, Yongjiang; Zhao, Bangjian

    2017-12-01

    This paper presents a review of recent advances in single- and multi-stage Stirling-type pulse tube cryocoolers (SPTCs) for space applications developed at the National Laboratory for Infrared Physics, Shanghai Institute of Technical Physics, Chinese Academy of Sciences (NLIP/SITP/CAS). A variety of single-stage SPTCs operating at 25-150 K have been developed, including several mid-sized ones operating at 80-110 K. Significant progress has been achieved in coolers operating at 30-40 K which use common stainless steel meshes as regenerator matrices. Another important advance is the micro SPTCs with an overall mass of 300-800 g operating at high frequencies varying from 100 Hz to 400 Hz. The main purpose of developing two-stage SPTCs is to simultaneously acquire cooling capacities at both stages, obviating the need for auxiliary precooling in various applications. The three-stage SPTCs are developed mainly for applications at around 10 K, which are also used for precooling the J-T coolers to achieve further lower temperatures. The four-stage SPTCs are developed to directly achieve the liquid helium temperature for cooling space low-Tc superconducting devices and for the deep space exploration as well. Several typical development programs are described and an overview of the cooler performances is presented.

  4. Comprehensive genomic profiling of 295 cases of clinically advanced urothelial carcinoma of the urinary bladder reveals a high frequency of clinically relevant genomic alterations.

    PubMed

    Ross, Jeffrey S; Wang, Kai; Khaira, Depinder; Ali, Siraj M; Fisher, Huge A G; Mian, Badar; Nazeer, Tipu; Elvin, Julia A; Palma, Norma; Yelensky, Roman; Lipson, Doron; Miller, Vincent A; Stephens, Philip J; Subbiah, Vivek; Pal, Sumanta K

    2016-03-01

    In the current study, the authors present a comprehensive genomic profile (CGP)-based study of advanced urothelial carcinoma (UC) designed to detect clinically relevant genomic alterations (CRGAs). DNA was extracted from 40 µm of formalin-fixed, paraffin-embedded sections from 295 consecutive cases of recurrent/metastatic UC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 688X for all coding exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer, using process-matched normal control samples as a reference. CRGAs were defined as GAs linked to drugs on the market or currently under evaluation in mechanism-driven clinical trials. All 295 patients assessed were classified with high-grade (International Society of Urological Pathology classification) and advanced stage (stage III/IV American Joint Committee on Cancer) disease, and 294 of 295 patients (99.7%) had at least 1 GA on CGP with a mean of 6.4 GAs per UC (61% substitutions/insertions/deletions, 37% copy number alterations, and 2% fusions). Furthermore, 275 patients (93%) had at least 1 CRGA involving 75 individual genes with a mean of 2.6 CRGAs per UC. The most common CRGAs involved cyclin-dependent kinase inhibitor 2A (CDKN2A) (34%), fibroblast growth factor receptor 3 (FGFR3) (21%), phosphatidylinositol 3-kinase catalytic subunit alpha (PIK3CA) (20%), and ERBB2 (17%). FGFR3 GAs were diverse types and included 10% fusions. ERBB2 GAs were equally divided between amplifications and substitutions. ERBB2 substitutions were predominantly within the extracellular domain and were highly enriched in patients with micropapillary UC (38% of 32 cases vs 5% of 263 nonmicropapillary UC cases; P<.0001). Using a CGP assay capable of detecting all classes of GA simultaneously, an extraordinarily high frequency of CRGA was identified in a large series of patients with advanced UC. Cancer 2016;122:702-711. © 2015 American

  5. Vision 20/20: Automation and advanced computing in clinical radiation oncology

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moore, Kevin L., E-mail: kevinmoore@ucsd.edu; Moiseenko, Vitali; Kagadis, George C.

    This Vision 20/20 paper considers what computational advances are likely to be implemented in clinical radiation oncology in the coming years and how the adoption of these changes might alter the practice of radiotherapy. Four main areas of likely advancement are explored: cloud computing, aggregate data analyses, parallel computation, and automation. As these developments promise both new opportunities and new risks to clinicians and patients alike, the potential benefits are weighed against the hazards associated with each advance, with special considerations regarding patient safety under new computational platforms and methodologies. While the concerns of patient safety are legitimate, the authorsmore » contend that progress toward next-generation clinical informatics systems will bring about extremely valuable developments in quality improvement initiatives, clinical efficiency, outcomes analyses, data sharing, and adaptive radiotherapy.« less

  6. Vision 20/20: Automation and advanced computing in clinical radiation oncology

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Moore, Kevin L., E-mail: kevinmoore@ucsd.edu; Moiseenko, Vitali; Kagadis, George C.

    2014-01-15

    This Vision 20/20 paper considers what computational advances are likely to be implemented in clinical radiation oncology in the coming years and how the adoption of these changes might alter the practice of radiotherapy. Four main areas of likely advancement are explored: cloud computing, aggregate data analyses, parallel computation, and automation. As these developments promise both new opportunities and new risks to clinicians and patients alike, the potential benefits are weighed against the hazards associated with each advance, with special considerations regarding patient safety under new computational platforms and methodologies. While the concerns of patient safety are legitimate, the authorsmore » contend that progress toward next-generation clinical informatics systems will bring about extremely valuable developments in quality improvement initiatives, clinical efficiency, outcomes analyses, data sharing, and adaptive radiotherapy.« less

  7. Vision 20/20: Automation and advanced computing in clinical radiation oncology.

    PubMed

    Moore, Kevin L; Kagadis, George C; McNutt, Todd R; Moiseenko, Vitali; Mutic, Sasa

    2014-01-01

    This Vision 20/20 paper considers what computational advances are likely to be implemented in clinical radiation oncology in the coming years and how the adoption of these changes might alter the practice of radiotherapy. Four main areas of likely advancement are explored: cloud computing, aggregate data analyses, parallel computation, and automation. As these developments promise both new opportunities and new risks to clinicians and patients alike, the potential benefits are weighed against the hazards associated with each advance, with special considerations regarding patient safety under new computational platforms and methodologies. While the concerns of patient safety are legitimate, the authors contend that progress toward next-generation clinical informatics systems will bring about extremely valuable developments in quality improvement initiatives, clinical efficiency, outcomes analyses, data sharing, and adaptive radiotherapy.

  8. Challenges of assessing the clinical efficacy of asexual blood-stage Plasmodium falciparum malaria vaccines.

    PubMed

    Sheehy, Susanne H; Douglas, Alexander D; Draper, Simon J

    2013-09-01

    In the absence of any highly effective vaccine candidate against Plasmodium falciparum malaria, it remains imperative for the field to pursue all avenues that may lead to the successful development of such a formulation. The development of a subunit vaccine targeting the asexual blood-stage of Plasmodium falciparum malaria infection has proven particularly challenging with only limited success to date in clinical trials. However, only a fraction of potential blood-stage vaccine antigens have been evaluated as targets, and a number of new promising candidate antigen formulations and delivery platforms are approaching clinical development. It is therefore essential that reliable and sensitive methods of detecting, or ruling out, even modest efficacy of blood-stage vaccines in small clinical trials be established. In this article we evaluate the challenges facing blood-stage vaccine developers, assess the appropriateness and limitations of various in vivo approaches for efficacy assessment and suggest future directions for the field.

  9. Clinical cancer advances 2007: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

    PubMed

    Gralow, Julie; Ozols, Robert F; Bajorin, Dean F; Cheson, Bruce D; Sandler, Howard M; Winer, Eric P; Bonner, James; Demetri, George D; Curran, Walter; Ganz, Patricia A; Kramer, Barnett S; Kris, Mark G; Markman, Maurie; Mayer, Robert J; Raghavan, Derek; Ramsey, Scott; Reaman, Gregory H; Sawaya, Raymond; Schuchter, Lynn M; Sweetenham, John W; Vahdat, Linda T; Davidson, Nancy E; Schilsky, Richard L; Lichter, Allen S

    2008-01-10

    A MESSAGE FROM ASCO'S PRESIDENT: For the third year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO publishes this report to demonstrate the important progress being made on the front lines of clinical cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and organizations, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on the use of magnetic resonance imaging for breast cancer screening, the association between hormone replacement therapy and breast cancer incidence, the link between human papillomavirus and head and neck cancers, and the use of radiation therapy to prevent lung cancer from spreading. They also report on effective new targeted therapies for cancers that have been historically difficult to treat, such as liver cancer and kidney cancer, among many others. A total of 24 advances are featured in this year's report. These advances and many more over the past several years show that the nation's long-term investment in cancer research is paying off. But there are disturbing signs that progress could slow. We are now in the midst of the longest sustained period of flat government funding for cancer research in history. The budgets for the National Institutes of Health and the National Cancer Institute (NCI) have been unchanged for four years. When adjusted for inflation, cancer research funding has actually declined 12% since 2004. These budget constraints limit the NCI's ability to fund promising cancer research. In the past several years the number of grants that the NCI has been able to fund has significantly decreased; this year, in response to just the

  10. Validation of World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy and clinical predictors of low CD4 cell count in Uganda.

    PubMed

    Baveewo, Steven; Ssali, Francis; Karamagi, Charles; Kalyango, Joan N; Hahn, Judith A; Ekoru, Kenneth; Mugyenyi, Peter; Katabira, Elly

    2011-05-12

    The WHO clinical guidelines for HIV/AIDS are widely used in resource limited settings to represent the gold standard of CD4 counts for antiviral therapy initiation. The utility of the WHO-defined stage 1 and 2 clinical factors used in WHO HIV/AIDS clinical staging in predicting low CD4 cell count has not been established in Uganda. Although the WHO staging has shown low sensitivity for predicting CD4<200 cells/mm(3), it has not been evaluated at for CD4 cut-offs of <250 cells/mm(3) or <350 cells/mm(3). To validate the World Health Organisation HIV/AIDS clinical staging in predicting initiation of antiretroviral therapy in a low-resource setting and to determine the clinical predictors of low CD4 cell count in Uganda. Data was collected on 395 participants from the Joint Clinical Research Centre, of whom 242 (61.3%) were classified as in stages 1 and 2 and 262 (68%) were females. Participants had a mean age of 36.8 years (SD 8.5). We found a significant inverse correlation between the CD4 lymphocyte count and WHO clinical stages. The sensitivity the WHO clinical staging at CD4 cell count of 250 cells/mm(3) and 350 cells/mm(3) was 53.5% and 49.1% respectively. Angular cheilitis, papular pruritic eruptions and recurrent upper respiratory tract infections were found to be significant predictors of low CD4 cell count among participants in WHO stage 1 and 2. The WHO HIV/AIDS clinical staging guidelines have a low sensitivity and about half of the participants in stages 1 and 2 would be eligible for ART initiation if they had been tested for CD4 count. Angular cheilitis and papular pruritic eruptions and recurrent upper respiratory tract infections may be used, in addition to the WHO staging, to improve sensitivity in the interim, as access to CD4 machines increases in Uganda.

  11. Executive summary of the Stages of Reproductive Aging Workshop + 10: addressing the unfinished agenda of staging reproductive aging

    PubMed Central

    Harlow, Siobán D.; Gass, Margery; Hall, Janet E.; Lobo, Roger; Maki, Pauline; Rebar, Robert W.; Sherman, Sherry; Sluss, Patrick M.; de Villiers, Tobie J.

    2012-01-01

    Objective The aim of this article is to summarize the recommended updates to the 2001 Stages of Reproductive Aging Workshop (STRAW) criteria. The 2011 STRAW + 10 reviewed advances in understanding of the critical changes in hypothalamic-pituitary-ovarian function that occur before and after the final menstrual period. Methods Scientists from five countries and multiple disciplines evaluated data from cohort studies of midlife women and in the context of chronic illness and endocrine disorders on change in menstrual, endocrine, and ovarian markers of reproductive aging including antimüllerian hormone, inhibin-B, follicle-stimulating hormone, and antral follicle count. Modifications were adopted by consensus. Results STRAW + 10 simplified bleeding criteria for the early and late menopausal transition, recommended modifications to criteria for the late reproductive stage (Stage –3) and the early postmenopause stage (Stage +1), provided information on the duration of the late transition (Stage–1) and early postmenopause (Stage +1), and recommended application regardless of women's age, ethnicity, body size, or lifestyle characteristics. Conclusions STRAW + 10 provides a more comprehensive basis for assessing reproductive aging in research and clinical contexts. Application of the STRAW + 10 staging system should improve comparability of studies of midlife women and facilitate clinical decision making. Nonetheless, important knowledge gaps persist, and seven research priorities are identified. PMID:22343510

  12. Ares First Stage "Systemology" - Combining Advanced Systems Engineering and Planning Tools to Assure Mission Success

    NASA Technical Reports Server (NTRS)

    Seiler, James; Brasfield, Fred; Cannon, Scott

    2008-01-01

    Ares is an integral part of NASA s Constellation architecture that will provide crew and cargo access to the International Space Station as well as low earth orbit support for lunar missions. Ares replaces the Space Shuttle in the post 2010 time frame. Ares I is an in-line, two-stage rocket topped by the Orion Crew Exploration Vehicle, its service module, and a launch abort system. The Ares I first stage is a single, five-segment reusable solid rocket booster derived from the Space Shuttle Program's reusable solid rocket motor. The Ares second or upper stage is propelled by a J-2X main engine fueled with liquid oxygen and liquid hydrogen. This paper describes the advanced systems engineering and planning tools being utilized for the design, test, and qualification of the Ares I first stage element. Included are descriptions of the current first stage design, the milestone schedule requirements, and the marriage of systems engineering, detailed planning efforts, and roadmapping employed to achieve these goals.

  13. Clinical cancer advances 2006: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

    PubMed

    Ozols, Robert F; Herbst, Roy S; Colson, Yolonda L; Gralow, Julie; Bonner, James; Curran, Walter J; Eisenberg, Burton L; Ganz, Patricia A; Kramer, Barnett S; Kris, Mark G; Markman, Maurie; Mayer, Robert J; Raghavan, Derek; Reaman, Gregory H; Sawaya, Raymond; Schilsky, Richard L; Schuchter, Lynn M; Sweetenham, John W; Vahdat, Linda T; Winn, Rodger J

    2007-01-01

    A MESSAGE FROM ASCO's PRESIDENT For the second consecutive year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO developed this report to demonstrate the enormous progress being made on the front lines of cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and physicians, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on new targeted therapies that are improving survival and response rates in hard-to-treat cancers such as kidney cancer, HER-2-positive breast cancer, head and neck cancer, and chronic myelogenous leukemia; the FDA's approval of the world's first preventive vaccine for human papillomavirus (HPV), which has the potential to dramatically reduce the global burden of cervical cancer; and advances in the fast-growing field of personalized medicine, including a new lung cancer test that could help physicians better target treatments and predict prognosis. These advances are only part of the landscape. Survival rates are on the rise, the number of cancer deaths in the United States began declining for the first time since 1930, and new research is showing that the rates of certain common cancers, such as those of the breast and colon, have stabilized, and may have even begun to decline. However, cancer research still faces a number of major obstacles. At a time of extraordinary scientific potential, declining federal funding of cancer research threatens to stall or even reverse recent progress. Such funding cuts have already led to fewer clinical trials, fewer talented young physicians entering the field, and a growing bottleneck of basic science discoveries

  14. Functional Impairment of Myeloid Dendritic Cells during Advanced Stage of HIV-1 Infection: Role of Factors Regulating Cytokine Signaling.

    PubMed

    Sachdeva, Meenakshi; Sharma, Aman; Arora, Sunil K

    2015-01-01

    Severely immunocompromised state during advanced stage of HIV-1 infection has been linked to functionally defective antigen presentation by dendritic cells (DCs). The molecular mechanisms behind DC impairment are still obscure. We investigated changes in DC function and association of key regulators of cytokine signaling during different stages of HIV-1 infection and following antiretroviral therapy (ART). Phenotypic and functional characteristics of circulating myeloid DCs (mDCs) in 56 ART-naive patients (23 in early and 33 in advanced stage of disease), 36 on ART and 24 healthy controls were evaluated. Sixteen patients were studied longitudinally prior-to and 6 months after the start of ART. For functional studies, monocyte-derived DCs (Mo-DCs) were evaluated for endocytosis, allo-stimulation and cytokine secretion. The expression of suppressor of cytokine signaling (SOCS)-1 and other regulators of cytokine signaling was evaluated by real-time RT-PCR. The ability to respond to an antigenic stimulation was severely impaired in patients in advanced HIV-1 disease which showed partial recovery in the treated group. Mo-DCs from patients with advanced HIV-disease remained immature with low allo-stimulation and reduced cytokine secretion even after TLR-4 mediated stimulation ex-vivo. The cells had an increased expression of negative regulatory factors like SOCS-1, SOCS-3, SH2-containing phosphatase (SHP)-1 and a reduced expression of positive regulators like Janus kinase (JAK)2 and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)1. A functional recovery after siRNA mediated silencing of SOCS-1 in these mo-DCs confirms the role of negative regulatory factors in functional impairment of these cells. Functionally defective DCs in advanced stage of HIV-1 infection seems to be due to imbalanced state of negative and positive regulatory gene expression. Whether this is a cause or effect of increased viral replication at this stage of disease, needs

  15. An Effective Technique for Endoscopic Resection of Advanced Stage Angiofibroma

    PubMed Central

    Mohammadi Ardehali, Mojtaba; Samimi, Seyyed Hadi; Bakhshaee, Mehdi

    2014-01-01

    Introduction: In recent years, the surgical management of angiofibroma has been greatly influenced by the use of endoscopic techniques. However, large tumors that extend into difficult anatomic sites present major challenges for management by either endoscopy or an open-surgery approach which needs new technique for the complete en block resection. Materials and Methods: In a prospective observational study we developed an endoscopic transnasal technique for the resection of angiofibroma via pushing and pulling the mass with 1/100000 soaked adrenalin tampons. Thirty two patients were treated using this endoscopic technique over 7 years. The mean follow-up period was 36 months. The main outcomes measured were tumor staging, average blood loss, complications, length of hospitalization, and residual and/or recurrence rate of the tumor. Results: According to the Radkowski staging, 23,5, and 4 patients were at stage IIC, IIIA, and IIIB, respectively. Twenty five patients were operated on exclusively via transnasal endoscopy while 7 patients were managed using endoscopy-assisted open-surgery techniques. Mean blood loss in patients was 1261± 893 cc. The recurrence rate was 21.88% (7 cases) at two years following surgery. Mean hospitalization time was 3.56 ± 0.6 days. Conclusion: Using this effective technique, endoscopic removal of more highly advanced angiofibroma is possible. Better visualization, less intraoperative blood loss, lower rates of complication and recurrence, and shorter hospitalization time are some of the advantages. PMID:24505571

  16. Simultaneous diagnostic platform of genotyping EGFR, KRAS, and ALK in 510 Korean patients with non-small-cell lung cancer highlights significantly higher ALK rearrangement rate in advanced stage.

    PubMed

    Kim, Tae-Jung; Park, Chan Kwon; Yeo, Chang Dong; Park, Kihoon; Rhee, Chin Kook; Kim, Jusang; Kim, Seung Joon; Lee, Sang Haak; Lee, Kyo-Young; Yoon, Hyoung-Kyu

    2014-09-01

    Simultaneous genotyping has advantages in turnaround time and detecting the real mutational prevalence in unresectable non-small-cell lung cancer (NSCLC), a group not previously genetically characterized. We developed simultaneous panel of screening EGFR and KRAS mutations by direct sequencing or PNA clamping, and ALK rearrangement by fluorescent in situ hybridization (FISH) in multicenter manner. Of 510 NSCLC Korean patients, simultaneous genotyping identified mutations of EGFR (29.0%) and KRAS (8.6%) and rearrangement of ALK (9.2%). Seven patients had overlaps in mutations. Although several well-known associations between genotypes and clinical characteristics were identified, we found no relationship between ALK rearrangement and sex or smoking history. Unlike the other genotype mutations, ALK rearrangement was associated with advanced disease. Among the ALK-negative group, patients with 10-15% of ALK FISH split shared characteristics, such as younger age and advanced stage disease, more with the ALK-positive group (>15% ALK FISH split) than <10% ALK FISH split group. Simultaneous panel genotyping revealed more prevalent ALK rearrangements than reported in previous studies and their strong association with advanced stage irrespective of sex or smoking history. ALK rearrangement seems to be a marker for aggressive tumor biology and should be assessed in advanced disease. © 2014 Wiley Periodicals, Inc.

  17. Clinical benefit of antiangiogenic therapy in advanced and metastatic chondrosarcoma.

    PubMed

    Jones, Robin L; Katz, Daniela; Loggers, Elizabeth T; Davidson, Darin; Rodler, Eve T; Pollack, Seth M

    2017-08-29

    Chondrosarcoma is the most common bone sarcoma in adults. Conventional chondrosarcoma, the commonest histological subtype, is largely resistant to anthracycline-based chemotherapy. There have been anecdotal reports of durable clinical benefit with antiangiogenic agents in this disease. A retrospective search of patients treated at three sarcoma referral centers was performed to identify patients with advanced chondrosarcoma treated with antiangiogenic agents. The aim of this study was to evaluate the efficacy and safety of antiangiogenic agents in advanced chondrosarcoma. Ten patients were identified; seven with conventional, one each with clear cell, extraskeletal mesenchymal chondrosarcoma and extraskeletal myxoid chondrosarcoma. The median progression-free survival for patients with conventional and clear cell sarcoma was 22.6 months. Median overall survival has not been met. Antiangiogenic therapy was well tolerated in this series of patients. Our retrospective data suggest that antiangiogenic therapy can provide prolonged clinical benefit in advanced chondrosarcoma patients. Further prospective trials are required to precisely define the role of this class of agent in advanced chondrosarcoma.

  18. B-cell lymphoma 2 is associated with advanced tumor grade and clinical stage, and reduced overall survival in young Chinese patients with colorectal carcinoma.

    PubMed

    Wang, Jiasheng; He, Gan; Yang, Qiang; Bai, Lian; Jian, Bin; Li, Qugang; Li, Zhongfu

    2018-06-01

    The development of biomarkers that accurately and reliably detect colorectal cancer is a promising approach for colorectal cancer screening. Therefore, the objective of the present study was to evaluate the protein expression of α-methylacyl-CoA racemase (P504S/AMACR), tumor protein p53 (p53), B-cell lymphoma 2 (Bcl-2) and Ki-67/mindbomb E3 ubiquitin protein ligase 1 (MIB-1) in a population of Chinese patients with colorectal carcinoma. Colorectal tumors with matched normal tissue margins were collected from 148 surgical patients, and the demographic and clinical characteristics were collected. Immunohistochemical staining and western blot analysis of P504S/AMACR, p53, Bcl-2 and Ki-67/MIB-1 were conducted. Statistical analyses were used to compare protein expression in the colorectal tumors and matched normal tissue margins and to identify any associations between them and various clinicopathological parameters. Survival analyses were performed using the Kaplan-Meier method. In the present study, immunohistochemistry and western blot analysis revealed significantly higher expression of all four proteins in colorectal tumors compared with matched normal tissue margins (P<0.001). Spearman's rank correlation analysis revealed that Bcl-2 expression was negatively correlated with pathological grade and Tumor-Node-Metastasis (TNM) stage (-0.827 and -0.388, respectively; P<0.05). Bcl-2 expression was revealed to be a significant prognostic indicator of colorectal carcinoma [relative risk (95% CI), 0.703 (0.552-0.895); P<0.05]. The log-rank test revealed a significant association between low Bcl-2 expression and reduced overall survival (P=0.039), as well as a significant association between older age (>55 years) and reduced overall survival (P<0.001) in Chinese patients with colorectal carcinoma. In conclusion, low expression of Bcl-2 is significantly correlated with advanced pathological grade and TNM stage and is a prognostic indicator of reduced overall survival in

  19. NExT: Advancing Promising Cancer Therapies

    Cancer.gov

    The NCI Experimental Therapeutics (NExT) program works with researchers and top scientific experts to advance promising or novel cancer therapies from the earliest stages of research to clinical trials. Learn about recent successes from NExT in this Cancer Currents blog post.

  20. Integrating Bioethics into Clinical and Translational Science Research: A Roadmap

    PubMed Central

    Shapiro, Robyn S.; Layde, Peter M.

    2008-01-01

    Abstract Recent initiatives to improve human health emphasize the need to effectively and appropriately translate new knowledge gleaned from basic biomedical and behavioral research to clinical and community application. To maximize the beneficial impact of scientific advances in clinical practice and community health, and to guard against potential deleterious medical and societal consequences of such advances, incorporation of bioethics at each stage of clinical and translational science research is essential. At the earliest stage, bioethics input is critical to address issues such as whether to limit certain areas of scientific inquiry. Subsequently, bioethics input is important to assure not only that human subjects trials are conducted and reported responsibly, but also that results are incorporated into clinical and community practices in a way that promotes and protects bioethical principles. At the final stage of clinical and translational science research, bioethics helps to identify the need and approach for refining clinical practices when safety or other concerns arise. The framework we present depicts how bioethics interfaces with each stage of clinical and translational science research, and suggests an important research agenda for systematically and comprehensively assuring bioethics input into clinical and translational science initiatives. PMID:20443821

  1. [Impact of microdose clinical trials in the preclinical stage].

    PubMed

    Kim, Soonih

    2014-01-01

    A microdose clinical trial may be useful as a safe early-phase exploratory study using doses as low as 100 μg or less for determination of the disposition of a candidate compound in humans in a short period of time. This may increase confidence in candidate compounds, especially those for which it is difficult to predict disposition based on the results of in vitro or preclinical studies. In this study, we examined microdose trials performed in the preclinical stage for two first-in-class compounds with a new mechanism of action. These compounds showed species difference in first pass metabolism in the digestive tract and liver, causing uncertainty in prediction of disposition in humans. For this reason, first-in-human microdose clinical trials were performed. The results showed that the two compounds had effective blood concentrations after oral administration at a dose of 100 mg qd. Administration of an extremely small dose of one (14)C-labeled compound permitted identification of major metabolites. No toxic metabolites were detected. The preclinical toxic dose was determined based on prediction of blood exposure at the estimated maximum clinical dose. For the other candidate compound, the findings of the microdose trial indicated a high bioavailability after oral administration and low hepatic clearance after intravenous administration. These results suggested only a small risk of a change in disposition in patients with hepatic disorder. The data obtained for the two compounds suggest that microdose clinical trials can be useful for improving the process of candidate selection in the preclinical stage.

  2. Locally advanced breast cancer in Saudi Arabia: high frequency of stage III in a young population.

    PubMed

    Ezzat, A A; Ibrahim, E M; Raja, M A; Al-Sobhi, S; Rostom, A; Stuart, R K

    1999-07-01

    In the Kingdom of Saudi Arabia (KSA), breast cancer constitutes 18% of all cancers in Saudi women. Whilst locally advanced breast cancer disease is unusual in Western countries, it constitutes more than 40% of all non-metastatic breast cancer in KSA. The relative frequency of locally advanced disease among our breast cancer population and the lack of a uniform consensus in the literature about its optimal management have prompted this retrospective analysis of the medical records of patients with Stage III breast cancer patients seen at King Faisal Specialist Hospital and Research Center between 1981 and 1991. In all, 315 patients were identified. Their median age +/- SD was 46 +/- 11.6 years which is distinctly different from the 60-65 years median age in industrial Western nations. Most patients were younger than 50 years (64%) and premenopausal (62%). Patients were approximately equally divided between Stage IIIA and Stage III B. Patients received multimodality treatment, including surgery, adjuvant chemotherapy, tamoxifen, and adjuvant radiotherapy. Sixty-one patients were excluded from survival analysis as they were considered lost to follow-up. Of the remaining 254 patients, 73 (29%) were alive and disease free, and 18 patients (7%) were alive but with evidence of the disease. The remaining 163 (64%) had died from breast cancer or its related complications. Their median overall survival (OS) was 54 months, (95% CI, 27 to 121 months) and the median progression-free survival (PFS) was 28.8 months (95% CI, 14.2 to 113 months). Cox proportional hazard model identified Stage III B and the number of positive axillary lymph nodes as poor predictors of OS and PFS. Radiotherapy was the only adjuvant modality that affected survival favourably. The prognosis of patients with Stage III disease remains poor despite the use of a multimodality approach. The overall young age of our patients may have contributed to the poor outcome. Moreover, the adverse effect of Stage III

  3. Sarcopenia in Alcoholic Liver Disease: Clinical and Molecular Advances.

    PubMed

    Dasarathy, Jaividhya; McCullough, Arthur J; Dasarathy, Srinivasan

    2017-08-01

    Despite advances in treatment of alcohol use disorders that focus on increasing abstinence and reducing recidivism, alcoholic liver disease (ALD) is projected to be the major cause of cirrhosis and its complications. Malnutrition is recognized as the most frequent complication in ALD, and despite the high clinical significance, there are no effective therapies to reverse malnutrition in ALD. Malnutrition is a relatively imprecise term, and sarcopenia or skeletal muscle loss, the major component of malnutrition, is primarily responsible for the adverse clinical consequences in patients with liver disease. It is, therefore, critical to define the specific abnormality (sarcopenia) rather than malnutrition in ALD, so that therapies targeting sarcopenia can be developed. Skeletal muscle mass is maintained by a balance between protein synthesis and proteolysis. Both direct effects of ethanol (EtOH) and its metabolites on the skeletal muscle and the consequences of liver disease result in disturbed proteostasis (protein homeostasis) and consequent sarcopenia. Once cirrhosis develops in patients with ALD, abstinence is unlikely to be effective in completely reversing sarcopenia, as other contributors including hyperammonemia, hormonal, and cytokine abnormalities aggravate sarcopenia and maintain a state of anabolic resistance initiated by EtOH. Cirrhosis is also a state of accelerated starvation, with increased gluconeogenesis that requires amino acid diversion from signaling and substrate functions. Novel therapeutic options are being recognized that are likely to supplant the current "deficiency replacement" approach and instead focus on specific molecular perturbations, given the increasing availability of small molecules that can target specific signaling components. Myostatin antagonists, leucine supplementation, and mitochondrial protective agents are currently in various stages of evaluation in preclinical studies to prevent and reverse sarcopenia, in cirrhosis in

  4. Asian consensus workshop report: expert consensus guideline for the management of intermediate and advanced hepatocellular carcinoma in Asia.

    PubMed

    Han, Kwang-Hyub; Kudo, Masatochi; Ye, Sheng-Long; Choi, Jong Young; Poon, Roonni Tung-Ping; Seong, Jinsil; Park, Joong-Won; Ichida, Takafumi; Chung, Jin Wook; Chow, Pierce; Cheng, Ann-Lii

    2011-01-01

    Hepatocellular carcinoma (HCC) is a highly prevalent disease in many Asian countries, accounting for 80% of victims worldwide. Screening programs improve the detection of early HCC and have a positive impact on survival, but the majority of HCC patients in Asia still present with advanced stage disease. The treatment outcomes of HCC are affected by multiple variables, including liver function, performance status of the patient, and tumor stage. Therefore, it is not easy to apply a multidisciplinary therapeutic approach for optimal management. At present, limited numbers of HCC patients are eligible for curative therapies such as surgery or ablation in Asia. Therefore, most patients are eligible for only palliative treatments. For optimal management, the treatment choice is guided by staging systems and treatment guidelines. Numerous staging systems have been proposed and treatment guidelines vary by region. According to the Barcelona Clinic Liver Cancer (BCLC) guideline based on evidence from randomized clinical trials, only transarterial chemoembolization (TACE) is recommended for intermediate stage HCC and sorafenib for advanced stage HCC. However, treatment guidelines from Asian countries have adopted several other therapeutic modalities such as a surgical approach, hepatic arterial infusion chemotherapy, external radiation, and their combinations based on clinical experiences for intermediate and advanced stage HCC. Although TACE is the main therapeutic modality in the intermediate stage, overall therapeutic outcomes depend on the tumor size. In the advanced stage, the prognosis depends on the tumor status, e.g. major vessel invasion or extrahepatic spread. Thus, a new staging system representing prognoses suitable for Asian HCC patients and a corresponding optimal treatment algorithm should be further investigated using evidence-based data, which will finally bring about an Asian consensus for the management of intermediate and advanced stage HCC. Copyright

  5. The role of the clinical nurse specialist/neonatal nurse practitioner in a breastfeeding clinic: a model of advanced practice.

    PubMed

    Gibbins, S A; Green, P E; Scott, P A; MacDonell, J W

    2000-03-01

    A commitment to quality health care requires the development of innovative models of care. An example of such a model is the Clinical Nurse Specialist/Neonatal Nurse Practitioner in the role as consultant to Lactation Consultants in a large breastfeeding clinic. The role of the Clinical Nurse Specialist/Neonatal Nurse Practitioner in this ambulatory setting encompasses all the dimensions of the advanced practice model including research, leadership, education, and clinical practice. The evolution of this model of care is described. A conceptual framework of this advanced practice model is presented, supported by examples of the role in the clinic.

  6. A robust two-stage design identifying the optimal biological dose for phase I/II clinical trials.

    PubMed

    Zang, Yong; Lee, J Jack

    2017-01-15

    We propose a robust two-stage design to identify the optimal biological dose for phase I/II clinical trials evaluating both toxicity and efficacy outcomes. In the first stage of dose finding, we use the Bayesian model averaging continual reassessment method to monitor the toxicity outcomes and adopt an isotonic regression method based on the efficacy outcomes to guide dose escalation. When the first stage ends, we use the Dirichlet-multinomial distribution to jointly model the toxicity and efficacy outcomes and pick the candidate doses based on a three-dimensional volume ratio. The selected candidate doses are then seamlessly advanced to the second stage for dose validation. Both toxicity and efficacy outcomes are continuously monitored so that any overly toxic and/or less efficacious dose can be dropped from the study as the trial continues. When the phase I/II trial ends, we select the optimal biological dose as the dose obtaining the minimal value of the volume ratio within the candidate set. An advantage of the proposed design is that it does not impose a monotonically increasing assumption on the shape of the dose-efficacy curve. We conduct extensive simulation studies to examine the operating characteristics of the proposed design. The simulation results show that the proposed design has desirable operating characteristics across different shapes of the underlying true dose-toxicity and dose-efficacy curves. The software to implement the proposed design is available upon request. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  7. Dual-Fuel Propulsion in Single-Stage Advanced Manned Launch System Vehicle

    NASA Technical Reports Server (NTRS)

    Lepsch, Roger A., Jr.; Stanley, Douglas O.; Unal, Resit

    1995-01-01

    As part of the United States Advanced Manned Launch System study to determine a follow-on, or complement, to the Space Shuttle, a reusable single-stage-to-orbit concept utilizing dual-fuel rocket propulsion has been examined. Several dual-fuel propulsion concepts were investigated. These include: a separate-engine concept combining Russian RD-170 kerosene-fueled engines with space shuttle main engine-derivative engines: the kerosene- and hydrogen-fueled Russian RD-701 engine; and a dual-fuel, dual-expander engine. Analysis to determine vehicle weight and size characteristics was performed using conceptual-level design techniques. A response-surface methodology for multidisciplinary design was utilized to optimize the dual-fuel vehicles with respect to several important propulsion-system and vehicle design parameters, in order to achieve minimum empty weight. The tools and methods employed in the analysis process are also summarized. In comparison with a reference hydrogen- fueled single-stage vehicle, results showed that the dual-fuel vehicles were from 10 to 30% lower in empty weight for the same payload capability, with the dual-expander engine types showing the greatest potential.

  8. Tracking Patient Encounters and Clinical Skills to Determine Competency in Ambulatory Care Advanced Pharmacy Practice Experiences

    PubMed Central

    Pereira, Chrystian R.; Harris, Ila M.; Moon, Jean Y.; Westberg, Sarah M.; Kolar, Claire

    2016-01-01

    Objective. To determine if the amount of exposure to patient encounters and clinical skills correlates to student clinical competency on ambulatory care advanced pharmacy practice experiences (APPEs). Design. Students in ambulatory care APPEs tracked the number of patients encountered by medical condition and the number of patient care skills performed. At the end of the APPE, preceptors evaluated students’ competency for each medical condition and skill, referencing the Dreyfus model for skill acquisition. Assessment. Data was collected from September 2012 through August 2014. Forty-six responses from a student tracking tool were matched to preceptor ratings. Students rated as competent saw more patients and performed more skills overall. Preceptors noted minimal impact on workload. Conclusions. Increased exposure to patient encounters and skills performed had a positive association with higher Dreyfus stage, which may represent a starting point in the conversation for more thoughtful design of ambulatory care APPEs. PMID:26941440

  9. [Perimetric changes in advanced glaucoma].

    PubMed

    Feraru, Crenguta Ioana; Pantalon, Anca

    2011-01-01

    The evaluation of various perimetric aspects in advanced glaucoma stages correlated to morpho-functional changes. MATHERIAL AND METHOD: Retrospective clinical trial over a 10 months time period that included patients with advanced glaucoma stages, for which there have been recorded several computerised visual field tests (central 24-2 strategy, 10-2 strategy with either III or V--Goldman stimulus spot size) along with other morpho-funtional ocular paramaters: VA, lOP optic disk analysis. We included in our study 56 eyes from 45 patients. In most cases 89% it was an open angle glaucoma (either primary or secondary) Mean visual acuity was 0.45 +/- 0.28. Regarding the perimetric deficit 83% had advanced deficit, 9% moderate and 8% early visual changes. As perimetric type of defect we found a majority with general reduction of sensitivity (33 eyes) + ring shape scotoma. In 6 eyes (10.7%) having left only a central isle of vision we performed the central 10-2 strategy with III or V Goldmann stimulus spot size. Statistic analysis showed scarce correlation between the visual acuity and the quantitative perimetric parameters (MD and PSD), and variance analysis found present a multiple correlation parameter p = 0.07 that proves there is no liniary correspondence between the morpho-functional parameters: VA-MD(PSD) and C/D ratio. In advanced glaucoma stages, the perimetric changes are mostly severe. Perimetric evaluation is essential in these stages and needs to be individualised.

  10. Are we ready to use biomarkers for staging, prognosis and treatment selection in early-stage non-small-cell lung cancer?

    PubMed

    Massuti, Bartomeu; Sanchez, Jose Miguel; Hernando-Trancho, Florentino; Karachaliou, Niki; Rosell, Rafael

    2013-06-01

    Lung cancer accounts for the majority of cancer-related deaths worldwide. At present, platinum-based therapy represents the standard of care in fit stage II and IIIA non-small cell lung cancer (NSCLC) patients following surgical resection. In advanced disease, personalized chemotherapy and targeted biologic therapy based on histological and molecular tumor profiling have already shown promise in terms of optimizing treatment efficacy. While disease stage is associated with outcome and is commonly used to determine adjuvant treatment eligibility, it is known that a subset of patients with early stage disease experience shorter survival than others with the same clinicopathological characteristics. Improved methods for identifying these individuals, at or near the time of initial diagnosis, may inform the decision to pursue adjuvant therapy options. Among the numerous candidate molecular biomarkers, only few gene-expression profiling signatures provide clinically relevant information, while real-time quantitative polymerase-chain reaction (RT-qPCR) strategy involving relatively small numbers of genes offers a practical alternative with high cross-platform performance. mRNA and/or protein expression levels of excision repair cross-complementation group 1 (ERCC1), ribonucleotide reductase M subunit 1 (RRM1) and breast cancer susceptibility gene 1 (BRCA1) are among the most promising potential biomarkers for early disease and their clinical utility is currently being evaluated in randomized phase II and III clinical trials. This review describes the most promising clinicopathological and molecular biomarkers with predictive and prognostic significance in lung cancer that have been identified through advanced research and which could influence adjuvant and neoadjuvant chemotherapy decisions for operable NSCLC in routine clinical practice.

  11. Histogram analysis of diffusion kurtosis imaging of nasopharyngeal carcinoma: Correlation between quantitative parameters and clinical stage.

    PubMed

    Xu, Xiao-Quan; Ma, Gao; Wang, Yan-Jun; Hu, Hao; Su, Guo-Yi; Shi, Hai-Bin; Wu, Fei-Yun

    2017-07-18

    To evaluate the correlation between histogram parameters derived from diffusion-kurtosis (DK) imaging and the clinical stage of nasopharyngeal carcinoma (NPC). High T-stage (T3/4) NPC showed significantly higher Kapp-mean (P = 0.018), Kapp-median (P = 0.029) and Kapp-90th (P = 0.003) than low T-stage (T1/2) NPC. High N-stage NPC (N2/3) showed significantly lower Dapp-mean (P = 0.002), Dapp-median (P = 0.002) and Dapp-10th (P < 0.001) than low N-stage NPC (N0/1). High AJCC-stage NPC (III/IV) showed significantly lower Dapp-10th (P = 0.038) than low AJCC-stage NPC (I/II). ROC analyses indicated that Kapp-90th was optimal for predicting high T-stage (AUC, 0.759; sensitivity, 0.842; specificity, 0.607), while Dapp-10th was best for predicting high N- and AJCC-stage (N-stage, AUC, 0.841; sensitivity, 0.875; specificity, 0.807; AJCC-stage, AUC, 0.671; sensitivity, 0.800; specificity, 0.588). DK imaging data of forty-seven consecutive NPC patients were retrospectively analyzed. Apparent diffusion for Gaussian distribution (Dapp) and apparent kurtosis coefficient (Kapp) were generated using diffusion-kurtosis model. Histogram parameters, including mean, median, 10th, 90th percentiles, skewness and kurtosis of Dapp and Kapp were calculated. Patients were divided into low and high T, N and clinical stage based on American Joint Committee on Cancer (AJCC) staging system. Differences of histogram parameters between low and high T, N and AJCC stages were compared using t test. Multiple receiver operating characteristic (ROC) curves were used to determine and compare the value of significant parameters in predicting high T, N and AJCC stage, respectively. DK imaging-derived parameters correlated well with clinical stage of NPC, therefore could serve as an adjunctive imaging technique for evaluating NPC.

  12. A Novel Therapeutic Modality for Advanced-Stage Prostate Cancer Treatment

    DTIC Science & Technology

    2015-10-01

    as an oral contraceptive [6, 7]. Recently, its anti-cancer activity has been reported against advanced breast cancer [8] and head and neck squamous...profile of Centchroman--a new post-coital contraceptive . Indian J Exp Biol, 1977. 15(12): p. 1144-50. 7. Misra, N.C., et al., Centchroman--a non-steroidal... contraceptive and for the management of hormone-related clinical disorders. Med Res Rev, 2001. 21(4): p. 302-47. 11. Jaggi, M., et al., Bryostatin 1 modulates

  13. Advances in clinical immunology in 2015.

    PubMed

    Chinen, Javier; Notarangelo, Luigi D; Shearer, William T

    2016-12-01

    Advances in clinical immunology in the past year included the report of practice parameters for the diagnosis and management of primary immunodeficiencies to guide the clinician in the approach to these relatively uncommon disorders. We have learned of new gene defects causing immunodeficiency and of new phenotypes expanding the spectrum of conditions caused by genetic mutations such as a specific regulator of telomere elongation (RTEL1) mutation causing isolated natural killer cell deficiency and mutations in ras-associated RAB (RAB27) resulting in immunodeficiency without albinism. Advances in diagnosis included the increasing use of whole-exome sequencing to identify gene defects and the measurement of serum free light chains to identify secondary hypogammaglobulinemias. For several primary immunodeficiencies, improved outcomes have been reported after definitive therapy with hematopoietic stem cell transplantation and gene therapy. Copyright © 2016 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  14. Evaluation of 122 advanced-stage cutaneous squamous cell carcinomas by comprehensive genomic profiling opens the door for new routes to targeted therapies.

    PubMed

    Al-Rohil, Rami N; Tarasen, Ashley J; Carlson, J Andrew; Wang, Kai; Johnson, Adrienne; Yelensky, Roman; Lipson, Doron; Elvin, Julia A; Vergilio, Jo-Anne; Ali, Siraj M; Suh, James; Miller, Vincent A; Stephens, Philip J; Ganesan, Prasanth; Janku, Filip; Karp, Daniel D; Subbiah, Vivek; Mihm, Martin C; Ross, Jeffrey S

    2016-01-15

    The authors hypothesized that comprehensive genomic profiling of advanced-stage cutaneous squamous cell carcinoma (cSCC) could identify genomic-derived drug targets of therapy for patients with conventional therapy-resistant disease. Comprehensive genomic profiling of 315 cancer genes was applied to 50 ng of DNA from 122 cSCC cases for the evaluation of all classes of genomic alterations (GAs). Clinically relevant genomic alterations (CRGAs) were defined as those identifying anticancer drugs on the market or in registered clinical trials. There were 21 women (17%) and 101 men (83%) with a median age of 64.9 years (range, 21-87 years). Eleven cSCC cases (9%) were histologic AJCC grade 1, 69 (57%) were grade 2, and 42 (34%) were grade 3. The primary cSCC was used for sequencing in 77 cases (63%). Metastatic lesions were sequenced in 37% of cases. There were 1120 total GAs identified (average of 9.2 GAs per tumor), with 100% of cases harboring at least 1 alteration. Of the 122 cSCCs, 107 (88%) harbored at least 1 CRGA (2.5 CRGAs per cSCC) includingNOTCH1 (43%); patched 1 (PTCH1) (11%); BRCA2 (10%); HRAS (8%); ataxia telangiectasia mutated (ATM) (7%); erb-B2 receptor tyrosine kinase 4 (ERBB4) (7%); neurofibromatosis type 1 (NF1) (7%); erb-B2 receptor tyrosine kinase 2 (ERBB2) (6%); phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha (PIK3CA) (6%); cyclin D1 (CCND1) (6%); epidermal growth factor receptor (EGFR) (5%); and F-box and WD repeat domain containing 7, E3 ubiquitin protein ligase (FBXW7) (5%). In the current study, approximately 88% of patients with cSCC were found to harbor clinically relevant GAs that have the potential to guide the treatment of patients with advanced-stage tumors with targeted therapeutic agents. Cancer 2016;122:249-257. © 2015 American Cancer Society. © 2015 American Cancer Society.

  15. Construction of databases: advances and significance in clinical research.

    PubMed

    Long, Erping; Huang, Bingjie; Wang, Liming; Lin, Xiaoyu; Lin, Haotian

    2015-12-01

    Widely used in clinical research, the database is a new type of data management automation technology and the most efficient tool for data management. In this article, we first explain some basic concepts, such as the definition, classification, and establishment of databases. Afterward, the workflow for establishing databases, inputting data, verifying data, and managing databases is presented. Meanwhile, by discussing the application of databases in clinical research, we illuminate the important role of databases in clinical research practice. Lastly, we introduce the reanalysis of randomized controlled trials (RCTs) and cloud computing techniques, showing the most recent advancements of databases in clinical research.

  16. Optimized ex-ovo culturing of chick embryos to advanced stages of development.

    PubMed

    Cloney, Kellie; Franz-Odendaal, Tamara Anne

    2015-01-24

    Research in anatomy, embryology, and developmental biology has largely relied on the use of model organisms. In order to study development in live embryos model organisms, such as the chicken, are often used. The chicken is an excellent model organism due to its low cost and minimal maintenance, however they present observational challenges because they are enclosed in an opaque eggshell. In order to properly view the embryo as it develops, the shell must be windowed or removed. Both windowing and ex ovo techniques have been developed to assist researchers in the study of embryonic development. However, each of the methods has limitations and challenges. Here, we present a simple, optimized ex ovo culture technique for chicken embryos that enables the observation of embryonic development from stage HH 19 into late stages of development (HH 40), when many organs have developed. This technique is easy to adopt in both undergraduate classes and more advanced research laboratories where embryo manipulations are conducted.

  17. Preoperative N Staging of Gastric Cancer by Stomach Protocol Computed Tomography

    PubMed Central

    Kim, Se Hoon; Kim, Jeong Jae; Lee, Jeong Sub; Kim, Seung Hyoung; Kim, Bong Soo; Maeng, Young Hee; Hyun, Chang Lim; Kim, Min Jeong

    2013-01-01

    Purpose Clinical stage of gastric cancer is currently assessed by computed tomography. Accurate clinical staging is important for the tailoring of therapy. This study evaluated the accuracy of clinical N staging using stomach protocol computed tomography. Materials and Methods Between March 2004 and November 2012, 171 patients with gastric cancer underwent preoperative stomach protocol computed tomography (Jeju National University Hospital; Jeju, Korea). Their demographic and clinical characteristics were reviewed retrospectively. Two radiologists evaluated cN staging using axial and coronal computed tomography images, and cN stage was matched with pathologic results. The diagnostic accuracy of stomach protocol computed tomography for clinical N staging and clinical characteristics associated with diagnostic accuracy were evaluated. Results The overall accuracy of stomach protocol computed tomography for cN staging was 63.2%. Computed tomography images of slice thickness 3.0 mm had a sensitivity of 60.0%; a specificity of 89.6%; an accuracy of 78.4%; and a positive predictive value of 78.0% in detecting lymph node metastases. Underestimation of cN stage was associated with larger tumor size (P<0.001), undifferentiated type (P=0.003), diffuse type (P=0.020), more advanced pathologic stage (P<0.001), and larger numbers of harvested and metastatic lymph nodes (P<0.001 each). Tumor differentiation was an independent factor affecting underestimation by computed tomography (P=0.045). Conclusions Computed tomography with a size criterion of 8 mm is highly specific but relatively insensitive in detecting nodal metastases. Physicians should keep in mind that computed tomography may not be an appropriate tool to detect nodal metastases for choosing appropriate treatment. PMID:24156034

  18. Hepatocellular carcinoma: early-stage management challenges

    PubMed Central

    Erstad, Derek J; Tanabe, Kenneth K

    2017-01-01

    Hepatocellular carcinoma (HCC) is a major cause of cancer death and is increasing in incidence. This review focuses on HCC surveillance and treatment of early-stage disease, which are essential to improving outcomes. Multiple societies have published HCC surveillance guidelines, but screening efforts have been limited by noncompliance and overall lack of testing for patients with undiagnosed chronic liver disease. Treatment of early-stage HCC has become increasingly complex due to expanding therapeutic options and better outcomes with established treatments. Surgical indications for HCC have broadened with improved preoperative liver testing, neoadjuvant therapy, portal vein embolization, and perioperative care. Advances in post-procedural monitoring have improved efficacies of transarterial chemoembolization and radiofrequency ablation, and novel therapies involving delivery of radiochemicals are being studied in small trials. Finally, advances in liver transplantation have allowed for expanded indications beyond Milan criteria with non-inferior outcomes. More clinical trials evaluating new therapies and multimodal regimens are necessary to help clinicians design better treatment algorithms and improve outcomes. PMID:28721349

  19. The ideas about advanced life support and affecting factors at the end-stage of life in a hospital in Turkey.

    PubMed

    Albayrak, Turgay; Şencan, İrfan; Akça, Ömer; Koç, Esra Meltem; Aksoy, Hilal; Ünsal, Selim; Bülbül, İskender; Bahadır, Adem; Kasım, İsmail; Kahveci, Rabia; Özkara, Adem

    2017-01-01

    The participation of the people in health decisions may be structured in various levels. One of these is participation in decisions for the treatment. "Advanced directives" is one of the examples for the participation in decisions for the treatment. We wanted to determine the decisions on advanced life support at the end-stage of life in case of a life-threatening illness for the people themselves and their first degree relatives and the factors effecting these decisions. The cross-sectional study was conducted with volunteers among patients and patient relatives who applied to all polyclinics of the Ankara Numune Training and Research Hospital except the emergency, oncology and psychiatry polyclinics between 15.12.2012 and 15.03.2013. A questionnaire, the Hospital Anxiety Depression (HAD) scale, and Templer's Death Anxiety Scale (TDA) were applied to all individuals. SPSS for Win. Ver. 17.0 and MS-Excel 2010 Starter software bundles were used for all statistical analysis and calculations. The participants want both themselves and their first degree relatives included in end-stage decision-making process. Therefore, the patients and their families should be informed adequately during decision making process and quality communication must be provided. Participants who have given their end-stage decisions previously want to be treated according to these decisions. This desire can just be possible by advanced directives.When moral and material loads of end-stage process are taken into consideration, countries, in which advanced directives are practiced, should be examined well and participants' desire should be evaluated in terms of practicability.

  20. Complete response in 5 out of 38 patients with advanced hepatocellular carcinoma treated with stem cell differentiation stage factors: case reports from a single centre.

    PubMed

    Livraghi, Tito; Ceriani, R; Palmisano, A; Pedicini, V; Pich, M G; Tommasini, M A; Torzilli, G

    2011-02-01

    Hepatocellular carcinoma (HCC) represents the third cause of cancer-related death. Because HCC is multi-centric with time, excluding the few transplanted patients, sooner or later it becomes untreatable with loco-regional therapies and, until some years ago, it was not responsive to systemic therapies. In 2005 a randomized trial indicated the efficacy of a product containing stem cell differentiation stage factors (SCDSF) taken from zebra fish embryos during the stage in which the totipotent stem cells are differentiating into the pluripotent adult stem cells. In such a trial the patients, with "intermediate" and "advanced" HCC according to BCLC/AASLD guidelines, presented benefit in terms of performance status (PS) and objective tumoral response, with some cases (2.4%) of complete response (CR). The aim of this cohort study is to report the experience of a tertiary referral center on the evidence of cases of CR in patients with "advanced" stage HCC treated with SCDSF as supportive care. CR was regarded as sustained disappearance of the neoplastic areas or blood supply therein, accompanied by normalization of AFP levels. Out of 49 patients consecutively recruited and retrospectively evaluated, 38 had "advanced" stage and 11 "terminal" stage. In 5 patients with "advanced" stage a sustained CR was reported (13.1%). Improvement on PS was obtained in 17 patients (34.6%). No side effects occurred. SCDSF treatment confirmed its efficacy in patients with "advanced" HCC, in terms of PS and tumoral response.

  1. Serum antioxidant levels and nutritional status in early and advanced stage lung cancer patients.

    PubMed

    Klarod, Kultida; Hongsprabhas, Pranithi; Khampitak, Tueanjit; Wirasorn, Kosin; Kiertiburanakul, Sasisopin; Tangrassameeprasert, Roongpet; Daduang, Jureerut; Yongvanit, Puangrat; Boonsiri, Patcharee

    2011-01-01

    Malnutrition frequently occurs in lung cancer patients. We aimed to determine nutritional status and antioxidant and mineral levels in Thai patients with lung cancer. A prospective study with matched case-control was conducted. Nutritional status was assessed by body mass index (BMI) and subjective global assessment (SGA). Eastern Cooperative Oncology Group (ECOG) performance status was used to assess the performance. The serum antioxidant and mineral levels were determined. Forty-nine patients with a mean age of 58.8 (range, 35-82) who were first diagnosed with lung cancer were enrolled. They were compared with 60 healthy controls, and levels of retinol, α-tocopherol, β-carotene, lycopene, β-cryptoxanthin, selenium, and zinc were lower (P < 0.05). However, peroxidase activity was higher (P = 0.002) in patients. Selenium levels were higher in early stage compared to advanced stage patients (P = 0.041). Overweight patients had higher selenium levels (0.04 mg/L) than normal BMI patients (β = 0.04, P = 0.035). Patients with SGA class C had lower selenium levels (0.03 mg/L) than those with class A (β = -0.03, P = 0.035). The poorer ECOG performance patients had significantly lower β-carotene (β = -0.192, P = 0.003) and selenium (β = -0.031, P = 0.011) levels compared with those with good ECOG performance status. Significantly lower levels of antioxidants and selenium were found in lung cancer patients compared to healthy controls. Levels of some antioxidants and minerals differed among categories of BMI, SGA categories, or ECOG performance status. These findings may be helpful for further studies, such as the effect of nutritional supplementation on clinical outcomes. Copyright © 2011 Elsevier Inc. All rights reserved.

  2. Evaluation of pelvic posterior exenteration in the management of advanced-stage ovarian cancer.

    PubMed

    Tixier, Hervé; Fraisse, Jean; Chauffert, Bruno; Mayer, Françoise; Causeret, Sylvain; Loustalot, Catherine; Deville, Coralie; Bonnetain, Franck; Sagot, Paul; Douvier, Serge; Cuisenier, Jean

    2010-03-01

    The main aim of this study was to show the interest of pelvic posterior exenteration to obtain complete resection of the tumor in case of invasion of the rectum by contiguity in advanced-stage ovarian cancer. The secondary aim was to determine the morbidity of this surgery. It is a multicentric, retrospective study of a series of 41 patients, who underwent posterior pelvectomy for advanced-stage ovarian cancer, over a period of 18 years, from July 1989 to July 2007. The surgery resulted in macroscopically complete resection in 19 patients (46.34%), a residual tumor <2 cm in 19 patients (46.34%) and >2 cm in 3 patients (7.32%). In 34 patients (34/41), digestive continuity with satisfactory anal sphincter function was restored immediately or in the short term. The mean delay to the start of complementary treatment was 36 days. Median overall survival was 33 months. The main aim of surgery for ovarian peritoneal carcinomatosis is to obtain a complete resection. In the case of direct invasion of the rectum by contiguity, when there is no cleavage plane between the uterus and the rectum, pelvic posterior exenteration is an effective method to achieve this objective. Morbidity is relatively high, but acceptable given the poor prognosis of this disease, the improved survival after surgery, and improvements in post-operative quality of life and functions.

  3. Melanoma costs: a dynamic model comparing estimated overall costs of various clinical stages.

    PubMed

    Alexandrescu, Doru Traian

    2009-11-15

    The rapidly increasing incidence of melanoma occurs at the same time as an increase in general healthcare costs, particularly the expenses associated with cancer care. Previous cost estimates in melanoma have not utilized a dynamic model considering the evolution of the disease and have not integrated the multiple costs associated with different aspects of medical interventions and patient-related factors. Futhermore, previous calculations have not been updated to reflect the modern tendencies in healthcare costs. We designed a comprehensive model of expenses in melanoma that considers the dynamic costs generated by the natural progression of the disease, which produces costs associated with treatment, surveillance, loss of income, and terminal care. The complete range of initial clinical (TNM) stages of the disease and initial tumor stages were analyzed in this model and the total healthcare costs for the five years following melanoma presentation at each particular stage were calculated. We have observed dramatic incremental total costs associated with progressively higher initial stages of the disease, ranging from a total of $4,648.48 for in situ tumors to $159,808.17 for Stage IV melanoma. By stage, early lesions associate 30-55 percent of their costs for the treatment of the primary tumor, due to a low rate of recurrence (local, regional, or distant), which limits the need for additional interventions. For in situ melanoma, T1a, and T1b, surveillance is an important contributor to the medical costs, accounting for more than 25 percent of the total cost over 5 years. In contrast, late lesions incur a much larger proportion of their associated costs (up to 80-85%) from the diagnosis and treatment of metastatic disease because of the increased propensity of those lesions to disseminate. This cost increases with increasing tumor stage (from $2,442.17 for T1a to $6,678.00 for T4b). The most expensive items in the medical care of patients with melanoma consist of

  4. Comparative effectiveness studies to improve clinical outcomes in end stage renal disease: the DEcIDE patient outcomes in end stage renal disease study

    PubMed Central

    2012-01-01

    Background Evidence is lacking to inform providers’ and patients’ decisions about many common treatment strategies for patients with end stage renal disease (ESRD). Methods/design The DEcIDE Patient Outcomes in ESRD Study is funded by the United States (US) Agency for Health Care Research and Quality to study the comparative effectiveness of: 1) antihypertensive therapies, 2) early versus later initiation of dialysis, and 3) intravenous iron therapies on clinical outcomes in patients with ESRD. Ongoing studies utilize four existing, nationally representative cohorts of patients with ESRD, including (1) the Choices for Healthy Outcomes in Caring for ESRD study (1041 incident dialysis patients recruited from October 1995 to June 1999 with complete outcome ascertainment through 2009), (2) the Dialysis Clinic Inc (45,124 incident dialysis patients initiating and receiving their care from 2003–2010 with complete outcome ascertainment through 2010), (3) the United States Renal Data System (333,308 incident dialysis patients from 2006–2009 with complete outcome ascertainment through 2010), and (4) the Cleveland Clinic Foundation Chronic Kidney Disease Registry (53,399 patients with chronic kidney disease with outcome ascertainment from 2005 through 2009). We ascertain patient reported outcomes (i.e., health-related quality of life), morbidity, and mortality using clinical and administrative data, and data obtained from national death indices. We use advanced statistical methods (e.g., propensity scoring and marginal structural modeling) to account for potential biases of our study designs. All data are de-identified for analyses. The conduct of studies and dissemination of findings are guided by input from Stakeholders in the ESRD community. Discussion The DEcIDE Patient Outcomes in ESRD Study will provide needed evidence regarding the effectiveness of common treatments employed for dialysis patients. Carefully planned dissemination strategies to the ESRD

  5. Cognitive benefits of memantine in Alzheimer's 5XFAD model mice decline during advanced disease stages.

    PubMed

    Devi, Latha; Ohno, Masuo

    2016-05-01

    Memantine, a noncompetitive NMDA receptor antagonist with neuroprotective properties, has been used for the treatment of Alzheimer's disease (AD). Administration of memantine to various transgenic AD mice has been reported to improve cognitive deficits, very often completely back to normal wild-type control levels. However, such great benefits of memantine in preclinical studies do not translate into clinical results of this drug, showing only marginal and transient efficacy in moderate to severe AD. To further address in vivo efficacy, we compared the effects of memantine at different disease stages in 5XFAD mice, one of the rapid-onset and most aggressive amyloid models. Specifically, we administered memantine once daily for 30 days to 5XFAD mice, which showed moderate (6-7 months of age) and robust (12-15 months) β-amyloid (Aβ) accumulation. Treatments with memantine (10mg/kg, i.p.) reversed memory impairments in the younger 5XFAD mice, as tested by the contextual fear conditioning and spontaneous alternation Y-maze paradigms. Memantine had no effects on soluble Aβ oligomer or total Aβ42 levels in 5XFAD mouse brains. In contrast, subchronic treatments with memantine showed no behavioral benefits in the older 5XFAD group, which exhibited more profound memory deficits concomitant with highly increased concentrations of Aβ as compared with those of the younger 5XFAD group. Since subchronic memantine at the higher dose (30 mg/kg) impaired memory performances in wild-type controls, we further tested acute administration of 50mg/kg memantine, which was reported to enhance hippocampal adult neurogenesis and memory function. However, this treatment also failed to rescue memory deficits in 12-15-month-old 5XFAD mice. Collectively, our results demonstrate that cognitive benefits of memantine independent of Aβ reductions were no longer observed in the 5XFAD Alzheimer mouse model during advanced stages, which may be reflective of the limited efficacy of memantine in

  6. Point estimation following two-stage adaptive threshold enrichment clinical trials.

    PubMed

    Kimani, Peter K; Todd, Susan; Renfro, Lindsay A; Stallard, Nigel

    2018-05-31

    Recently, several study designs incorporating treatment effect assessment in biomarker-based subpopulations have been proposed. Most statistical methodologies for such designs focus on the control of type I error rate and power. In this paper, we have developed point estimators for clinical trials that use the two-stage adaptive enrichment threshold design. The design consists of two stages, where in stage 1, patients are recruited in the full population. Stage 1 outcome data are then used to perform interim analysis to decide whether the trial continues to stage 2 with the full population or a subpopulation. The subpopulation is defined based on one of the candidate threshold values of a numerical predictive biomarker. To estimate treatment effect in the selected subpopulation, we have derived unbiased estimators, shrinkage estimators, and estimators that estimate bias and subtract it from the naive estimate. We have recommended one of the unbiased estimators. However, since none of the estimators dominated in all simulation scenarios based on both bias and mean squared error, an alternative strategy would be to use a hybrid estimator where the estimator used depends on the subpopulation selected. This would require a simulation study of plausible scenarios before the trial. © 2018 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

  7. [Clinical observation on acupuncture by stages combined with exercise therapy for treatment of Bell palsy at acute stage].

    PubMed

    Qu, Yong

    2005-08-01

    To find out a method for increasing clinical therapeutic effect on Bell palsy at acute stage. Ninety cases of Bell palsy were randomly divided into an observation group, a control group I and a control group II, 30 cases in each group. They were treated respectively with acupuncture plus exercise therapy, simple acupuncture therapy, and simple exercise therapy, and their therapeutic effects were observed. The cured rate was 66.7% in the observation group, 53.3% in the control group I and 46.70% in the control group II, the observation group being better than the two control groups (P<0.05). Acupuncture by stage combined with exercise therapy can increase the therapeutic effect on Bell palsy at acute stage, and it is a better therapy for Bell palsy.

  8. Advances in Probes and Methods for Clinical EPR Oximetry

    PubMed Central

    Hou, Huagang; Khan, Nadeem; Jarvis, Lesley A.; Chen, Eunice Y.; Williams, Benjamin B.; Kuppusamy, Periannan

    2015-01-01

    EPR oximetry, which enables reliable, accurate, and repeated measurements of the partial pressure of oxygen in tissues, provides a unique opportunity to investigate the role of oxygen in the pathogenesis and treatment of several diseases including cancer, stroke, and heart failure. Building on significant advances in the in vivo application of EPR oximetry for small animal models of disease, we are developing suitable probes and instrumentation required for use in human subjects. Our laboratory has established the feasibility of clinical EPR oximetry in cancer patients using India ink, the only material presently approved for clinical use. We now are developing the next generation of probes, which are both superior in terms of oxygen sensitivity and biocompatibility including an excellent safety profile for use in humans. Further advances include the development of implantable oxygen sensors linked to an external coupling loop for measurements of deep-tissue oxygenations at any depth, overcoming the current limitation of 10 mm. This paper presents an overview of recent developments in our ability to make meaningful measurements of oxygen partial pressures in human subjects under clinical settings. PMID:24729217

  9. Relationship between primary lesion metabolic parameters and clinical stage in lung cancer.

    PubMed

    Sahiner, I; Atasever, T; Akdemir, U O; Ozturk, C; Memis, L

    2013-01-01

    The relation of PET-derived parameters as maximum standardized uptake value (SUVmax), total lesion glycolysis (TLG), metabolic tumor volume (MTV) with clinical stage in lung cancer and correlation of SUVmax of primary tumor and that of metastatic lesion was studied in lung cancer patients. Patients with lung cancer who were referred for FDG PET/CT were included in the study. PET/CT scans and pathology reports of 168 patients were assessed. A total of 146 (86.9%) of these patients had a diagnosis of non-small cell lung cancer (NSCLC) and 22 (13.1%) had small cell lung cancer (SCLC). Metabolic parameters such as SUVmax, TLG and MTV showed significant differences in all the stages in NSCLC patients (p<0.001). However, after tumors sizes <25 mm were excluded, no significant differences in SUVmax between stages were observed. No significant differences were found between these metabolic parameters and limited or extended disease SCLC. Tumor diameter correlated with primary tumor SUVmax and significant correlations between primary lesion SUVmax and metastatic lesion SUVmax were found. Although differences were found regarding indices between stages of NSCLC cases, SUVmax differences between stages seem to be caused by underestimation of SUVmax in small lesions. Other glucose metabolism indexes such as MTV and TLG show promising results in terms of prognostic stratification. Future studies are needed for better understanding of their contribution to clinical cases. Copyright © 2013 Elsevier España, S.L. and SEMNIM. All rights reserved.

  10. Clinical cancer advances 2008: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

    PubMed

    Winer, Eric; Gralow, Julie; Diller, Lisa; Karlan, Beth; Loehrer, Patrick; Pierce, Lori; Demetri, George; Ganz, Patricia; Kramer, Barnett; Kris, Mark; Markman, Maurie; Mayer, Robert; Pfister, David; Raghavan, Derek; Ramsey, Scott; Reaman, Gregory; Sandler, Howard; Sawaya, Raymond; Schuchter, Lynn; Sweetenham, John; Vahdat, Linda; Schilsky, Richard L

    2009-02-10

    A message from ASCO'S president: Nearly 40 years ago, President Richard Nixon signed the National Cancer Act, mobilizing the country's resources to make the "conquest of cancer a national crusade." That declaration led to a major investment in cancer research that has significantly improved cancer prevention, treatment, and survival. As a result, two thirds of people diagnosed with cancer today will live at least 5 years after diagnosis, compared with just half in the 1970s. In addition, there are now more than 12 million cancer survivors in the United States--up from 3 million in 1971. Scientifically, we have never been in a better position to advance cancer treatment. Basic scientific research, fueled in recent years by the tools of molecular biology, has generated unprecedented knowledge of cancer development. We now understand many of the cellular pathways that can lead to cancer. We have learned how to develop drugs that block those pathways; increasingly, we know how to personalize therapy to the unique genetics of the tumor and the patient. Yet in 2008, 1.4 million people in the United States will still be diagnosed with cancer, and more than half a million will die as a result of the disease. Some cancers remain stubbornly resistant to treatment, whereas others cannot be detected until they are in their advanced, less curable stages. Biologically, the cancer cell is notoriously wily; each time we throw an obstacle in its path, it finds an alternate route that must then be blocked. To translate our growing basic science knowledge into better treatments for patients, a new national commitment to cancer research is urgently needed. However, funding for cancer research has stagnated. The budgets of the National Institutes of Health and the National Cancer Institute have failed to keep pace with inflation, declining up to 13% in real terms since 2004. Tighter budgets reduce incentives to support high-risk research that could have the largest payoffs. The most

  11. Weekly Cisplatin and Volumetric-Modulated Arc Therapy With Simultaneous Integrated Boost for Radical Treatment of Advanced Cervical Cancer in Elderly Patients: Feasibility and Clinical Preliminary Results.

    PubMed

    Mazzola, Rosario; Ricchetti, Francesco; Fiorentino, Alba; Levra, Niccolò Giaj; Fersino, Sergio; Di Paola, Gioacchino; Ruggieri, Ruggero; Alongi, Filippo

    2017-06-01

    To evaluate the feasibility and clinical preliminary results of weekly cisplatin and volumetric-modulated arc therapy to the pelvis with simultaneous integrated boost to macroscopic disease in a cohort of elderly patients. Inclusion criteria of this prospective study were age ≥70 years, Karnofsky performance status 70 to 100, locally advanced histologically proven squamous cervical carcinoma, and patients unable to undergo brachytherapy. Radiation doses prescribed were 66 Gy to the macroscopic disease and 54 Gy to the pelvic nodes in 30 fractions. Weekly cisplatin dose was 40 mg/mq. A total of 30 patients were recruited. Median follow-up was 32 months (range: 8-48 months). Median age was 72 years (range: 70-84 years). The 3-year overall survival and local control were 93% and 80%, respectively. The median time to progression was 24 months (range: 6-30 months). Analyzing clinical outcome grouping based on the stage of disease, II versus III, the 3-year overall survival was 100% and 85%, respectively. The 3-year local control was 91% for stage II and 67% for stage III. Acute and late toxicities were acceptable without severe events. Weekly cisplatin and volumetric-modulated arc therapy-simultaneous integrated boost for radical treatment of advanced cervical cancer in the current cohort of elderly patients were feasible. Long-term results and prospective randomized trials are advocated.

  12. Weekly Cisplatin and Volumetric-Modulated Arc Therapy With Simultaneous Integrated Boost for Radical Treatment of Advanced Cervical Cancer in Elderly Patients: Feasibility and Clinical Preliminary Results

    PubMed Central

    Mazzola, Rosario; Ricchetti, Francesco; Fiorentino, Alba; Levra, Niccolò Giaj; Fersino, Sergio; Di Paola, Gioacchino; Ruggieri, Ruggero

    2016-01-01

    Background: To evaluate the feasibility and clinical preliminary results of weekly cisplatin and volumetric-modulated arc therapy to the pelvis with simultaneous integrated boost to macroscopic disease in a cohort of elderly patients. Materials and Methods: Inclusion criteria of this prospective study were age ≥70 years, Karnofsky performance status 70 to 100, locally advanced histologically proven squamous cervical carcinoma, and patients unable to undergo brachytherapy. Radiation doses prescribed were 66 Gy to the macroscopic disease and 54 Gy to the pelvic nodes in 30 fractions. Weekly cisplatin dose was 40 mg/mq. Results: A total of 30 patients were recruited. Median follow-up was 32 months (range: 8-48 months). Median age was 72 years (range: 70-84 years). The 3-year overall survival and local control were 93% and 80%, respectively. The median time to progression was 24 months (range: 6-30 months). Analyzing clinical outcome grouping based on the stage of disease, II versus III, the 3-year overall survival was 100% and 85%, respectively. The 3-year local control was 91% for stage II and 67% for stage III. Acute and late toxicities were acceptable without severe events. Conclusion: Weekly cisplatin and volumetric-modulated arc therapy–simultaneous integrated boost for radical treatment of advanced cervical cancer in the current cohort of elderly patients were feasible. Long-term results and prospective randomized trials are advocated. PMID:27402633

  13. Fixed dose-rate gemcitabine infusion as first-line treatment for advanced-stage carcinoma of the pancreas and biliary tree.

    PubMed

    Gelibter, Alain; Malaguti, Paola; Di Cosimo, Serena; Bria, Emilio; Ruggeri, Enzo Maria; Carlini, Paolo; Carboni, Fabio; Ettorre, Giuseppe Maria; Pellicciotta, Mario; Giannarelli, Diana; Terzoli, Edmondo; Cognetti, Francesco; Milella, Michele

    2005-09-15

    Gemcitabine infusion at the fixed dose rate of 10 mg/m(2) per minute (FDR-gemcitabine) has pharmacokinetic advantages and may result in improved therapeutic efficacy. Between April 2002 and September 2003, 40 patients with advanced-stage pancreatic adenocarcinoma (PDAC; n = 27) or biliary tree carcinoma (BTC; n = 13) were treated with weekly FDR-gemcitabine (1000 mg/m(2)). The primary end point was the response rate. The secondary end points were progression-free and overall survival (PFS and OS), tumor marker response, and clinical benefit response (CBR). The overall response rate (ORR) on an intent-to-treat basis was 15% (95% confidence interval [95% CI], 4-26%). A positive CBR was obtained in 14 of 29 (48%) patients. Seventeen of 25 (68%) patients had a reduction in carbohydrate antigen 19-9 (CA 19-9) of > 25%. The median time to treatment failure and the median PFS were 17 weeks (95% CI, 13-22 weeks) and 19 weeks (95% CI, 15-23 weeks), respectively. The median OS was 40 weeks (95% CI, 36-45 weeks) and the 1-year actuarial survival rate was 25.8%. Multivariate analysis showed that a performance status score of 0-1 at study entry and locally advanced disease were the only independent predictors of longer PFS and OS, whereas a reduction in CA 19-9 serum levels > 75% was an independent predictor of longer PFS, but had no impact on OS. Toxicity was mild with Grade 3-4 neutropenia (according to the National Cancer Institute-Common Toxicity Criteria [version 2.0]) in 18 of 427 treatment weeks (4.2%), and Grade 3 anemia and thrombocytopenia in 6 of 427 treatment weeks (1.4%) and 9 of 427 treatment weeks (2.1%), respectively, and asymptomatic Grade 3-4 transaminase elevation in 21 of 427 treatment weeks (4.9%). FDR-gemcitabine at the weekly dose of 1000 mg/m(2) demonstrated promising activity, despite negligible toxicity, in patients with advanced-stage PDAC and BTC. Copyright 2005 American Cancer Society.

  14. New advances in focal therapy for early stage prostate cancer.

    PubMed

    Tay, Kae Jack; Schulman, Ariel A; Sze, Christina; Tsivian, Efrat; Polascik, Thomas J

    2017-08-01

    Prostate focal therapy offers men the opportunity to achieve oncological control while preserving sexual and urinary function. The prerequisites for successful focal therapy are to accurately identify, localize and completely ablate the clinically significant cancer(s) within the prostate. We aim to evaluate the evidence for current and upcoming technologies that could shape the future of prostate cancer focal therapy in the next five years. Areas covered: Current literature on advances in patient selection using imaging, biopsy and biomarkers, ablation techniques and adjuvant treatments for focal therapy are summarized. A literature search of major databases was performed using the search terms 'focal therapy', 'focal ablation', 'partial ablation', 'targeted ablation', 'image guided therapy' and 'prostate cancer'. Expert commentary: Advanced radiological tools such as multiparametric magnetic resonance imaging (mpMRI), multiparametric ultrasound (mpUS), prostate-specific-membrane-antigen positron emission tomography (PSMA-PET) represent a revolution in the ability to understand cancer function and biology. Advances in ablative technologies now provide a menu of modalities that can be rationalized based on lesion location, size and perhaps in the near future, pre-determined resistance to therapy. However, these need to be carefully studied to establish their safety and efficacy parameters. Adjuvant strategies to enhance focal ablation are under development.

  15. Clinical outcome of fresh and vitrified-warmed blastocyst and cleavage-stage embryo transfers in ethnic Chinese ART patients

    PubMed Central

    2012-01-01

    Objectives This study sought to evaluate the outcome of fresh and vitrified-warmed cleavage-stage and blastocyst-stage embryo transfers in patients undergoing ART treatment within an ethnic Chinese population. Study design We compared the clinical results of embryo transfer on the 3rd (cleavage stage) or 5th (blastocyst stage) day after oocyte retrieval, including clinical pregnancy rates, implantation rates and multiple pregnancy rates. Results Our data showed that blastocyst transfer on day 5 did not significantly increase clinical pregnancy rate (41.07% vs 47.08%, p>0.05) and implantation rate (31.8% vs 31.2%, p>0.05) in patients under 35 years of age, in comparison with day 3 cleavage stage embryo transfer. In patients older than 35 years of age, the clinical pregnancy rate after blastocyst transfer was slightly decreased compared with cleavage stage embryo transfer (33.33% vs 42.31%, p>0.05). Unexpectedly, It was found that vitrified-warmed blastocyst transfer resulted in significantly higher clinical pregnancy rate (56.8%) and implantation rate (47%) compared with fresh blastocyst transfer in controlled stimulation cycles (41.07% and 31.8%, respectively). For patients under 35 years of age, the cumulative clinical pregnancy rate combining fresh and vitrified-warmed blastocyst transfer cycles were significantly higher compared to just cleavage-stage embryo transfer (70.1% versus 51.8%, p<0.05). However, the cumulative multiple pregnancy rates showed no significant difference between the two groups. Conclusions In an ethnic Chinese patient population, fresh blastocyst transfer does not significantly increase clinical pregnancy rate. However, subsequent vitrified-warmed blastocyst transfer in a non-controlled ovarian hyperstimulation cycle dramatically improves clinical outcomes. Therefore, blastocyst culture in tandem with vitrified-warmed blastocyst transfer is recommended as a favourable and promising protocol in human ART treatment, particularly for ethnic

  16. Clinical outcome of fresh and vitrified-warmed blastocyst and cleavage-stage embryo transfers in ethnic Chinese ART patients.

    PubMed

    Tong, Guo Qing; Cao, Shan Ren; Wu, Xun; Zhang, Jun Qiang; Cui, Ji; Heng, Boon Chin; Ling, Xiu Feng

    2012-10-05

    This study sought to evaluate the outcome of fresh and vitrified-warmed cleavage-stage and blastocyst-stage embryo transfers in patients undergoing ART treatment within an ethnic Chinese population. We compared the clinical results of embryo transfer on the 3rd (cleavage stage) or 5th (blastocyst stage) day after oocyte retrieval, including clinical pregnancy rates, implantation rates and multiple pregnancy rates. Our data showed that blastocyst transfer on day 5 did not significantly increase clinical pregnancy rate (41.07% vs 47.08%, p>0.05) and implantation rate (31.8% vs 31.2%, p>0.05) in patients under 35 years of age, in comparison with day 3 cleavage stage embryo transfer. In patients older than 35 years of age, the clinical pregnancy rate after blastocyst transfer was slightly decreased compared with cleavage stage embryo transfer (33.33% vs 42.31%, p>0.05). Unexpectedly, It was found that vitrified-warmed blastocyst transfer resulted in significantly higher clinical pregnancy rate (56.8%) and implantation rate (47%) compared with fresh blastocyst transfer in controlled stimulation cycles (41.07% and 31.8%, respectively). For patients under 35 years of age, the cumulative clinical pregnancy rate combining fresh and vitrified-warmed blastocyst transfer cycles were significantly higher compared to just cleavage-stage embryo transfer (70.1% versus 51.8%, p<0.05). However, the cumulative multiple pregnancy rates showed no significant difference between the two groups. In an ethnic Chinese patient population, fresh blastocyst transfer does not significantly increase clinical pregnancy rate. However, subsequent vitrified-warmed blastocyst transfer in a non-controlled ovarian hyperstimulation cycle dramatically improves clinical outcomes. Therefore, blastocyst culture in tandem with vitrified-warmed blastocyst transfer is recommended as a favourable and promising protocol in human ART treatment, particularly for ethnic Chinese patients.

  17. Treatment-related mortality in patients with advanced-stage hodgkin lymphoma: an analysis of the german hodgkin study group.

    PubMed

    Wongso, Diana; Fuchs, Michael; Plütschow, Annette; Klimm, Beate; Sasse, Stephanie; Hertenstein, Bernd; Maschmeyer, Georg; Vieler, Tom; Dührsen, Ulrich; Lindemann, Walter; Aulitzky, Walter; Diehl, Volker; Borchmann, Peter; Engert, Andreas

    2013-08-01

    The introduction of BEACOPP(escalated) (escalated-dose bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone) has significantly improved tumor control and overall survival in patients with advanced-stage Hodgkin lymphoma. However, this regimen has also been associated with higher treatment-related mortality (TRM). Thus, we analyzed clinical course and risk factors associated with TRM during treatment with BEACOPP(escalated). In this retrospective analysis, we investigated incidence, clinical features, and risk factors for BEACOPP(escalated)-associated TRM in the German Hodgkin Study Group trials HD9, HD12, and HD15. Among a total of 3,402 patients, TRM of 1.9% (64 of 3,402) was mainly related to neutropenic infections (n = 56; 87.5%). Twenty of 64 events occurred during the first course of BEACOPP(escalated) (31.3%). Higher risk of TRM was seen in patients age ≥ 40 years with poor performance status (PS) and in patients age ≥ 50 years. PS and age were then used to construct a new risk score; those with a score ≥ 2 had TRM of 7.1%, whereas patients who scored 0 or 1 had TRM of 0.9%. The individual risk of TRM associated with BEACOPP(escalated) can be predicted by a simple algorithm based on age and PS. High-risk patients should receive special clinical attention.

  18. Sublobar resection is equivalent to lobectomy for clinical stage 1A lung cancer in solid nodules.

    PubMed

    Altorki, Nasser K; Yip, Rowena; Hanaoka, Takaomi; Bauer, Thomas; Aye, Ralph; Kohman, Leslie; Sheppard, Barry; Thurer, Richard; Andaz, Shahriyour; Smith, Michael; Mayfield, William; Grannis, Fred; Korst, Robert; Pass, Harvey; Straznicka, Michaela; Flores, Raja; Henschke, Claudia I

    2014-02-01

    A single randomized trial established lobectomy as the standard of care for the surgical treatment of early-stage non-small cell lung cancer. Recent advances in imaging/staging modalities and detection of smaller tumors have once again rekindled interest in sublobar resection for early-stage disease. The objective of this study was to compare lung cancer survival in patients with non-small cell lung cancer with a diameter of 30 mm or less with clinical stage 1 disease who underwent lobectomy or sublobar resection. We identified 347 patients diagnosed with lung cancer who underwent lobectomy (n = 294) or sublobar resection (n = 53) for non-small cell lung cancer manifesting as a solid nodule in the International Early Lung Cancer Action Program from 1993 to 2011. Differences in the distribution of the presurgical covariates between sublobar resection and lobectomy were assessed using unadjusted P values determined by logistic regression analysis. Propensity scoring was performed using the same covariates. Differences in the distribution of the same covariates between sublobar resection and lobectomy were assessed using adjusted P values determined by logistic regression analysis with adjustment for the propensity scores. Lung cancer-specific survival was determined by the Kaplan-Meier method. Cox survival regression analysis was used to compare sublobar resection with lobectomy, adjusted for the propensity scores, surgical, and pathology findings, when adjusted and stratified by propensity quintiles. Among 347 patients, 10-year Kaplan-Meier for 53 patients treated by sublobar resection compared with 294 patients treated by lobectomy was 85% (95% confidence interval, 80-91) versus 86% (confidence interval, 75-96) (P = .86). Cox survival analysis showed no significant difference between sublobar resection and lobectomy when adjusted for propensity scores or when using propensity quintiles (P = .62 and P = .79, respectively). For those with cancers 20 mm or less in

  19. TEN-YEAR FOLLOW UP OF A PHASE II STUDY OF DOSE-INTENSE PACLITAXEL WITH CISPLATIN AND CYCLOPHOSPHAMIDE AS INITIAL THERAPY FOR POOR-PROGNOSIS ADVANCED-STAGE EPITHELIAL OVARIAN CANCER

    PubMed Central

    Sarosy, Gisele A.; Hussain, Mahrukh M.; Seiden, Michael V.; Fuller, A.F.; Nikrui, N.; Goodman, Annekathryn; Minasian, Lori; Reed, Eddie; Steinberg, Seth M.; Kohn, Elise C.

    2009-01-01

    SUMMARY Background To assess activity and toxicity in newly diagnosed advanced stage epithelial ovarian cancer (EOC) patients receiving dose-intense paclitaxel, cyclophosphamide, cisplatin, and filgrastim delivered with a flexible dosing schedule. Methods Patients with Stage III/IV EOC received cyclophosphamide 750 mg/m2, followed by 24 hr infusion of paclitaxel 250 mg/m2, and cisplatin 75 mg/m2 on day 2. Filgrastim began on day 3 at 10 μg/kg/d × 9d. Patients received six cycles of all drugs. Those with pathologic complete response or microscopic residual disease at the conclusion of six cycles of therapy received an additional cycles two to four cycles of paclitaxel with cyclophosphamide. Patients with objective response continued cyclophosphamide and paclitaxel. Results 62 patients were enrolled. Thirty-two of these 62 patients had stage IIIC disease, and 26 of 62 had stage IV disease. Using an intent to treat analysis, 55 (89%) experienced clinical complete remission (CCR). With a median potential follow-up of 11.4 years, the median progression free survival is 18.9 months and median survival is 5.4 years. The most serious toxicity was grade 3/4 neutropenic fever (35%). Although all participants developed peripheral neuropathy, improvement in neuropathic symptoms began with decrease or cessation of paclitaxel. Conclusions This regimen yielded a high response rate and encouraging overall survival. These data and those of the Japanese Gynecologic Oncology Group suggest that further study of dose dense or intense paclitaxel regimens in women with newly diagnosed advanced stage EOC is warranted. PMID:20091841

  20. Implementation status and explanatory analysis of early advance care planning for Stage IV non-small cell lung cancer patients.

    PubMed

    Tokito, Takaaki; Murakami, Haruyasu; Mori, Keita; Osaka, Iwao; Takahashi, Toshiaki

    2015-03-01

    The American Society of Clinical Oncology published the goals of individualized care including advance care planning for advanced cancer patients in 2011. However, no data are available on the implementation status of advance care planning. We retrospectively reviewed the electronic medical records and informed consent forms of consecutive Stage IV non-small cell lung cancer patients treated with chemotherapy between January 2010 and December 2012 at our institution. Two outcomes were defined to investigate the advance care planning implementation status: C-D, the duration from the last day of chemotherapy to death and D-D, that from the day of confirmed do-not-attempt-resuscitation order to death. The study included 136 eligible patients. The advance care planning implementation status in participating patients was as follows: 96 (70%) patients received information on 'incurable disease before first-line chemotherapy', 69 (50%) were informed about 'supportive care before first-line chemotherapy', whereas 43 (32%) learned about their prognosis. The do-not-attempt-resuscitation decision was reflected in 29 patients' will (21%). The median C-D was 64 days. Receipt of ≤2 chemotherapy regimens and provision of prognosis information to patients were significantly associated with long C-D in multivariate analysis. The median D-D was 25 days. Provision of information on supportive care before first-line chemotherapy and provision of prognosis information to patients were significantly associated with long D-D in multivariate analysis. Our results suggest that there is possible benefit from providing information on supportive care before first-line chemotherapy and informing patients about their prognosis in prolonging the duration of supportive care. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  1. Ocriplasmin for treatment of stage 2 macular holes: early clinical results.

    PubMed

    Miller, John B; Kim, Leo A; Wu, David M; Vavvas, Demetrios G; Eliott, Dean; Husain, Deeba

    2014-01-01

    To review clinical and structural outcomes of ocriplasmin for treatment of stage 2 macular holes. A retrospective review of the first patients with stage 2 macular holes to be treated with ocriplasmin at Massachusetts Eye and Ear Infirmary. All patients were imaged with spectral-domain optical coherence tomography (SD-OCT). Eight patients with stage 2 macular holes received a single injection of 125 μg of ocriplasmin. One patient (12.5%) demonstrated macular hole closure. The posterior hyaloid separated from the macula in six eyes (75%). All seven holes that remained open showed enlargement in hole diameters (narrowest, apical, and basal) at 1 week and 1 month. All seven were successfully closed with surgery. Ellipsoid zone disruptions were observed by OCT in four eyes (50%) and persisted throughout follow-up (more than 6 months on average). In early clinical results, the authors found a lower macular hole closure rate with ocriplasmin than previously reported. Enlargement was observed in all holes that failed to close with ocriplasmin. The authors found ellipsoid zone disruptions that persisted through 6 months of follow-up after ocriplasmin injection. Further work is needed to investigate the cause for these ellipsoid zone changes. Copyright 2014, SLACK Incorporated.

  2. [Chronic pancreatitis: which is the role of 320-row CT for the staging?].

    PubMed

    Stabile Ianora, Amato Antonio; Rubini, Giuseppe; Lorusso, Filomenamila; Ambriola, Angela; Rella, Leonarda; Di Crescenzo, Vincenzo; Moschetta, Marco

    2013-01-01

    The purpose of this study was to evaluate the diagnostic potential of multi-planar and volumetric reconstructions obtained from isotropic data by using 16-slice computed tomography (CT) in the diagnosis and staging of chronic pancreatitis. In a group of 42 patients CT images were evaluated searching for alterations in morphology and structure of the pancreas, alterations of the Wirsung duct, dilatation of the bile ducts, fluid collections, and vascular involvement of the digestive tract. The disease was then staged in mild, moderate and severe and correlated with the clinical staging. CT allowed the recognition of chronic pancreatitis in all cases. The staging was correct in 25/42 patients, with an accuracy rate of 59.5%. In the staging of moderate and severe forms, CT correlation with clinical and laboratory data was valid, but in mild forms it appeared less significant. Multi-detector CT is accurate in the recognition of moderate, advanced forms of chronic pancreatitis and in the identification of its complications, while it is poorly correlated with the clinical staging in mild forms of the disease.

  3. Does Radiation Have a Role in Advanced Stage Hodgkin's or Non-Hodgkin Lymphoma?

    PubMed

    Specht, Lena

    2016-01-01

    Radiation therapy (RT) is one of the most effective agents available in the treatment of lymphomas. However, it is a local treatment, and today, with systemic treatments assuming a primary role for induction of response, RT is primarily used for consolidation. For advanced stage lymphomas, the indications for the use of RT have been questioned and debated, and proper randomized evidence is sparse. RT has significant long-term side effects, and the very extended RT fields of the past yielded unacceptable toxicity in many patients. Modern advanced imaging and conformal RT techniques now enable treatment of larger and anatomically more challenging target volumes with much less radiation to normal tissues and consequently much lower risks of long-term complications. The modern concept of involved site radiation therapy (ISRT) has now been accepted as standard in lymphomas. In advanced Hodgkin lymphoma (HL), RT to residual disease and/or initial bulk benefits some patients, depending on the chemotherapy regimen used. The more intensive the chemotherapy regimen, the fewer patients benefit from RT. In advanced aggressive non-Hodgkin lymphoma (NHL), most of the evidence comes from the most common type, the diffuse large B cell lymphoma (DLBCL). In patients treated with modern immunochemotherapy, RT to initial bulky disease or extralymphatic involvement is beneficial. For both HL and aggressive NHL, RT to residual masses after systemic treatment is of benefit. The role of PET in the evaluation and indication for RT to residual masses has not been tested in randomized trials. In advanced indolent NHL, very low dose RT offers excellent palliation with very few side effects. Modern RT in advanced lymphomas warrants further evaluation in randomized trials.

  4. The ideas about advanced life support and affecting factors at the end-stage of life in a hospital in Turkey

    PubMed Central

    Albayrak, Turgay; Şencan, İrfan; Akça, Ömer; Aksoy, Hilal; Ünsal, Selim; Bülbül, İskender; Bahadır, Adem; Kasım, İsmail; Kahveci, Rabia; Özkara, Adem

    2017-01-01

    Background The participation of the people in health decisions may be structured in various levels. One of these is participation in decisions for the treatment. “Advanced directives” is one of the examples for the participation in decisions for the treatment. Aim We wanted to determine the decisions on advanced life support at the end-stage of life in case of a life-threatening illness for the people themselves and their first degree relatives and the factors effecting these decisions. Design and setting The cross-sectional study was conducted with volunteers among patients and patient relatives who applied to all polyclinics of the Ankara Numune Training and Research Hospital except the emergency, oncology and psychiatry polyclinics between 15.12.2012 and 15.03.2013. Method A questionnaire, the Hospital Anxiety Depression (HAD) scale, and Templer’s Death Anxiety Scale (TDA) were applied to all individuals. SPSS for Win. Ver. 17.0 and MS-Excel 2010 Starter software bundles were used for all statistical analysis and calculations. Results The participants want both themselves and their first degree relatives included in end-stage decision-making process. Therefore, the patients and their families should be informed adequately during decision making process and quality communication must be provided. Conclusion Participants who have given their end-stage decisions previously want to be treated according to these decisions. This desire can just be possible by advanced directives.When moral and material loads of end-stage process are taken into consideration, countries, in which advanced directives are practiced, should be examined well and participants’ desire should be evaluated in terms of practicability. PMID:28732071

  5. Advanced Stage Mucinous Adenocarcinoma of the Ovary is both Rare and Highly Lethal: A Gynecologic Oncology Group Study

    PubMed Central

    Zaino, Richard J.; Brady, Mark F.; Lele, Subodh M.; Michael, Helen; Greer, Benjamin; Bookman, Michael A.

    2010-01-01

    Background Primary mucinous adenocarcinomas of the ovary are uncommon and their biologic behavior uncertain. Retrospective studies suggest that many mucinous carcinomas diagnosed as primary to the ovary were actually metastatic from another site. A prospective randomized trial provided an opportunity to estimate the frequency of mucinous tumors, diagnostic reproducibility, and clinical outcomes. Methods A phase III trial enrolled 4000 women with stage III or IV ovarian carcinoma, treated by surgical staging and debulking, with randomization to one of five chemotherapeutic arms. Slides and pathology reports classified as primary mucinous carcinoma were reviewed independently by three pathologists. Cases were re-classified as primary or metastatic to the ovary according to two methods. Overall survival (OS) of reclassified groups was compared with each other and with that of patients with serous carcinomas. Results Forty-four cases were classified as mucinous adenocarcinoma at review. Using either method, only about one third were interpreted by the three reviewers as primary mucinous carcinomas. Reproducibility of interpretations among the reviewers was high with unanimity of opinion in 30 of the 44 (68%) cases. The median survival (MS) did not differ significantly between the groups interpreted as primary or metastatic, but the OS was significantly less than that for women with serous carcinoma (14 vs 42 months, p<0.001). Conclusion Advanced stage mucinous carcinoma of the ovary is very rare and is associated with poor OS. Many mucinous adenocarcinomas that are diagnosed as primary ovarian neoplasms appear to be metastatic to the ovary. PMID:20862744

  6. In utero stem cell transplantation and gene therapy: rationale, history, and recent advances toward clinical application

    PubMed Central

    Almeida-Porada, Graça; Atala, Anthony; Porada, Christopher D

    2016-01-01

    Recent advances in high-throughput molecular testing have made it possible to diagnose most genetic disorders relatively early in gestation with minimal risk to the fetus. These advances should soon allow widespread prenatal screening for the majority of human genetic diseases, opening the door to the possibility of treatment/correction prior to birth. In addition to the obvious psychological and financial benefits of curing a disease in utero, and thereby enabling the birth of a healthy infant, there are multiple biological advantages unique to fetal development, which provide compelling rationale for performing potentially curative treatments, such as stem cell transplantation or gene therapy, prior to birth. Herein, we briefly review the fields of in utero transplantation (IUTx) and in utero gene therapy and discuss the biological hurdles that have thus far restricted success of IUTx to patients with immunodeficiencies. We then highlight several recent experimental breakthroughs in immunology, hematopoietic/marrow ontogeny, and in utero cell delivery, which have collectively provided means of overcoming these barriers, thus setting the stage for clinical application of these highly promising therapies in the near future. PMID:27069953

  7. Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD

    PubMed Central

    Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A.; Kleiner, David; Brunt, Elizabeth M.; Wilson, Laura; Doo, Ed; Lavine, Joel; Tonascia, James

    2015-01-01

    OBJECTIVE Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. RESEARCH DESIGN AND METHODS This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. RESULTS The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m2, respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75–0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit

  8. Comparative Study of Clinical Staging of Oral Submucous Fibrosis with Qualitative Analysis of Collagen Fibers Under Polarized Microscopy.

    PubMed

    Modak, Neha; Tamgadge, Sandhya; Tamgadge, Avinash; Bhalerao, Sudhir

    2015-01-01

    Oral submucous fibrosis (OSMF) is a condition where excessive deposition of dense collagen fibers occurred in the connective tissue of oral mucosa. An alteration of collagen necessitates an in depth understanding of collagen in oral tissues as no breakthrough studies have been reported. T herefore the aim was to correlate the clinical, functional and histopathological staging and to analyze the polarization colors and thickness of the collagen fibers in different stages of OSMF using picrosirius red stain under polarizing microscopy so as to assess the severity of disease. The study was conducted in the department of Oral Pathology and Microbiology at Padm. Dr. D. Y Patil Dental and Hospital, Navi Mumbai, India (2012-13). A sample size was of a total 40 subjects, of which 30 patients had OSMF, and 10 were in control group. Clinical, functional and histopathological staging were done depending upon definite criteria. Collagen fibers were analyzed for polarizing colors and thickness. Further clinical, functional and histopathological stages as well as qualitative parameters of collagen fibers were compared. The correlation between clinical and functional staging was not significant ( P >0.05) whereas the comparison of the functional staging with histopathological staging was more reliable ( P <0.01) as an indication to the severity of the disease rather than clinical staging. One-way ANOVA analysis showed highly significant correlation between functional staging and polarization colors and thickness of collagen fibers ( P <0.001). The qualitative change in the collagen fibers of OSMF patients using polarized microscopy would help to assess its role in diagnostic evaluation, to determine the prognosis of the disease as well as to provide useful predictive treatment modalities to them.

  9. Survival after yttrium-90 resin microsphere radioembolization of hepatocellular carcinoma across Barcelona clinic liver cancer stages: a European evaluation.

    PubMed

    Sangro, Bruno; Carpanese, Livio; Cianni, Roberto; Golfieri, Rita; Gasparini, Daniele; Ezziddin, Samer; Paprottka, Philipp M; Fiore, Francesco; Van Buskirk, Mark; Bilbao, Jose Ignacio; Ettorre, Giuseppe Maria; Salvatori, Rita; Giampalma, Emanuela; Geatti, Onelio; Wilhelm, Kai; Hoffmann, Ralf Thorsten; Izzo, Francesco; Iñarrairaegui, Mercedes; Maini, Carlo Ludovico; Urigo, Carlo; Cappelli, Alberta; Vit, Alessandro; Ahmadzadehfar, Hojjat; Jakobs, Tobias Franz; Lastoria, Secondo

    2011-09-02

    A multicenter analysis was conducted to evaluate the main prognostic factors driving survival after radioembolization using yttrium-90-labeled resin microspheres in patients with hepatocellular carcinoma at eight European centers. In total, 325 patients received a median activity of 1.6 GBq between September 2003 and December 2009, predominantly as whole-liver (45.2%) or right-lobe (38.5%) infusions. Typically, patients were Child-Pugh class A (82.5%), had underlying cirrhosis (78.5%), and had good Eastern Cooperative Oncology Group (ECOG) performance status (ECOG 0-1; 87.7%), but many had multinodular disease (75.9%) invading both lobes (53.1%) and/or portal vein occlusion (13.5% branch; 9.8% main). Over half had advanced Barcelona Clinic Liver Cancer (BCLC) staging (BCLC C, 56.3%) and one-quarter had intermediate staging (BCLC B, 26.8%). The median overall survival was 12.8 months (95% confidence interval, 10.9-15.7), which varied significantly by disease stage (BCLC A, 24.4 months [95% CI, 18.6-38.1 months]; BCLC B, 16.9 months [95% CI, 12.8-22.8 months]; BCLC C, 10.0 months [95% CI, 7.7-10.9 months]). Consistent with this finding , survival varied significantly by ECOG status, hepatic function (Child-Pugh class, ascites, and baseline total bilirubin), tumor burden (number of nodules, alpha-fetoprotein), and presence of extrahepatic disease. When considered within the framework of BCLC staging, variables reflecting tumor burden and liver function provided additional prognostic information. The most significant independent prognostic factors for survival upon multivariate analysis were ECOG status, tumor burden (nodules >5), international normalized ratio >1.2, and extrahepatic disease. Common adverse events were: fatigue, nausea/vomiting, and abdominal pain. Grade 3 or higher increases in bilirubin were reported in 5.8% of patients. All-cause mortality was 0.6% and 6.8% at 30 and 90 days, respectively. This analysis provides robust evidence of the survival

  10. Prognosis for advanced-stage primary peritoneal serous papillary carcinoma and serous ovarian cancer in Taiwan.

    PubMed

    Chao, Kuan-Chong; Chen, Yi-Jen; Juang, Chi-Mou; Lau, Hei-Yu; Wen, Kuo-Chang; Sung, Pi-Lin; Fang, Feng-Ying; Twu, Nae-Fang; Yen, Ming-Shyen

    2013-03-01

    To compare the prognosis of patients with advanced-stage primary peritoneal serous papillary carcinoma (PSPC) or papillary serous ovarian cancer (PSOC). This was a retrospective case-control study and included two study groups: one with stage III/IV PSPC (n = 38) patients and the other with PSOC (n = 53) patients. Patients were matched for histologic subtype (serous tumor), tumor stage, tumor grade, residual disease at the end of debulking surgery (primary or interval), and age (±5 years). Mean age was significantly greater for patients with PSPC (63.03 ± 11.88 years) than for patients with PSOC (55.92 ± 12.56 years, p = 0.008). Optimal debulking surgery was performed initially in 71.9% of PSPC patients and 66.0% of PSOC patients. In addition, 93.9% of PSPC patients and 92.3% of PSOC patients were treated with platinum-paclitaxel chemotherapy. The frequency of high-grade tumors was significantly higher in the PSPC (100%) than in the PSOC group (68.3%; p < 0.001). Progression-free survival (PFS) was similar in the PSPC [median 12 months, 95% confidence interval (CI) 7.3-16.7] and PSOC groups (median 16.7 months, 95% CI 12.9-20.4; p = 0.470). Overall survival was shorter in the PSPC (median 62 months, 95% CI 19.6-104.4) than in the PSOC group (median 77.5 months, 95% CI 69.7-85.2; p = 0.006, log-rank statistic). PFS was similar for advanced-stage PSPC and PSOC patients. Since the PSPC patients tended to be older and have more high-grade tumors, OS was shorter for PSPC than for POSC patients. Thus, management of the two types of cancer should not differ. Copyright © 2013. Published by Elsevier B.V.

  11. Urinary Tract Resections in Advanced-stage Cervical Cancer - A Series of Eight Cases.

    PubMed

    Oprescu, Dana Nuti; Bacalbasa, Nicolae; Balescu, Irina; Filipescu, Alexandru

    2017-06-01

    Cervical cancer is one of the most frequent malignancies in women worldwide and is unfortunately diagnosed in advanced stages of the disease. Whenever local invasion is present, neoadjuvant therapy might be needed in order to limit the degree of local invasion. However, in certain cases local invasion persists even after completing the neoadjuvant radiochemotherapy; in these patients more extensive resections might be needed in order to achieve a radical resection. We present a case series of eight patients in whom segmental ureteral or uretero-vesical resections were performed as part of the radical resections for locally advanced cervical tumors. The continuity of the urinary tract was re-established by performing ureteral reimplantation via uretero-neocystostomy, augmentation cystoplasties with ureteral reimplantations. In a single case ureteral reimplantation was not feasible, a definitive cutaneous ureterostomy being performed. The postoperative course was uneventful in seven cases while in a single case urinary leak occurred, necessitating the exteriorization of the ureter in terminal cutaneous ureterostomy. Ureteral resections can be safely performed in patients with locally advanced cervical cancer. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  12. Clinical and radiographic evaluation of maxillary central incisors exposure in patients undergoing maxillary advancement

    PubMed Central

    Trento, Guilherme dos Santos; Bernabé, Felipe Bueno Rosettti; da Costa, Delson João; Rebellato, Nelson Luis Barbosa; Klüppel, Leandro Eduardo; Scariot, Rafaela

    2015-01-01

    Abstract Introduction: Patients with dentofacial deformities may undergo orthodontic or orthodontic-surgical treatment. Both modalities can affect esthetics. Objective: This study aims to evaluate clinical and radiographic changes in exposure of maxillary central incisors occurring after orthognathic surgery for maxillary advancement. Methods: A total of 17 patients who underwent orthognathic surgery for maxillary advancement between September, 2010 and July, 2011 were selected. Exposure of maxillary central incisors was evaluated clinically and by lateral cephalograms. Measurements were taken one week before and three months after surgery. Data were paired in terms of sex, age, nasolabial angle, height and thickness of the upper lip, the amount of maxillary advancement, clinical exposure and inclination of maxillary central incisor by statistical tests (CI 95%). Results: After maxillary advancement, incisor clinical exposure had increased even with relaxed lips and under forced smile. Moreover, there was a mean increase of 23.33% revealed by lateral cephalograms. There was an inverse correlation between upper lip thickness and incisors postsurgical exposure revealed by radiographic images (p = 0.002). Conclusions: Significant changes in the exposure of maxillary central incisors occur after maxillary advancement, under the influence of some factors, especially lip thickness. PMID:26691970

  13. Content of Advance Directives for Individuals with Advanced Dementia

    PubMed Central

    Black, Betty S.; Phillips, Hilary; Fahrendorf, Sarah Richardson; Schwartz, Jack; Angelino, Andrew F.; Anderson, Danielle; Rabins, Peter V.

    2010-01-01

    Objectives To examine how people with end-stage dementia have conveyed their wishes for end-of-life care in advance directives. Methods The documents of 123 residents of three Maryland nursing homes, all with end-stage dementia, were reviewed. Results More years of education and White race were significantly associated with having an advance directive. With the exceptions of comfort care and pain treatment, advance directives were used primarily to restrict, not request, many forms of care at the end-of-life. Decisions about care for end-stage conditions such as Alzheimer's dementia are less often addressed in these documents than for terminal conditions and persistent vegetative state. Discussion In order for advance directives to better reflect a person's wishes, discussions with individuals and families about advance directives should include a range of care issues in the settings of terminal illness, persistent vegetative state or end-stage illness. These documents should be reviewed periodically to make certain they convey accurately the person's treatment preferences. PMID:18625761

  14. Prognostic values of common clinical parameters in advanced pancreatic ductal adenocarcinoma: a large multicenter cohort study of ten years.

    PubMed

    Zhang, Chenyue; Dong, Shu; Wang, Lei; Yu, Songlin; Zheng, Yuwei; Geng, Yanyan; Shen, Xiaoheng; Ying, Haifeng; Guo, Yuanbiao; Yu, Jinming; Deng, Qinglong; Meng, Zhiqiang; Li, Zhaoshen; Chen, Hao; Shen, Yehua; Chen, Qiwen

    2018-03-01

    We conducted a multicenter cohort study to investigate the prognostic value of some commonly-used laboratory indices in advanced pancreatic ductal adenocarcinoma (PDAC). A multicenter cohort study was conducted from 2004 to 2013. The associations between laboratory indices and prognosis of advanced PDAC were examined. This cohort consisted of 553 females (36.2%) and 973 males (63.8%). Patients at cancer stage III and IV were 595 (39.0%) and 931 (61.0%), respectively. The median survival of stage III patients was 9.0 months, with 3-, 6-, and 12-month survival rates of 94.5%, 73.4%, and 28.5%, respectively. The median survival of stage IV patients was 5.4 months, with 3-, 6-, and 12-month survival rates of 79.3%, 42.9%, and 15.0%, respectively. In multivariate analyses, primary tumor diameter, low albumin, and elevated CA19-9 were associated with decreased survival for stage III patients. Age, smoking, primary tumor diameter, elevated ALT or AST, low albumin, and elevated CA19-9 were associated with decreased survival for stage IV patients. Elevated CA19-9 level, decreased albumin level, and tumor size were associated with worse survival in stage III patients. Meanwhile, advanced age, smoking, and ALT or AST level were negatively correlated to prognosis in stage IV patients.

  15. Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence.

    PubMed

    Rothschild, Sacha I

    2014-01-01

    The therapeutic landscape in non-small-cell lung cancer (NSCLC) is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations) and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here.

  16. Clinical potential of nintedanib for the second-line treatment of advanced non-small-cell lung cancer: current evidence

    PubMed Central

    Rothschild, Sacha I

    2014-01-01

    The therapeutic landscape in non-small-cell lung cancer (NSCLC) is changing. The description of molecular alterations leading to NSCLC carcinogenesis and progression (so-called oncogenic driver mutations) and the development of targeted agents interfering with the tumor-promoting intracellular signaling pathways have improved the outcome for many patients with advanced/metastatic NSCLC. However, many patients with stage IV NSCLC do not have one of the targetable predictive biomarkers, and are therefore in need of classical chemotherapy. This especially applies to squamous cell cancer. A platinum-based doublet chemotherapy is the standard of care for patients with stage IV NSCLC. As second-line therapies, docetaxel, pemetrexed, and the EGFR tyrosine-kinase inhibitor erlotinib have demonstrated benefit in Phase III randomized trials. Recently, the addition of the angiokinase inhibitor nintedanib to docetaxel has proven efficacious, and is a new treatment option in the second-line setting. Preclinical and clinical data of nintedanib for the treatment of lung cancer patients are reviewed here. PMID:28210142

  17. Cell-free DNA levels and correlation to stage and outcome following treatment of locally advanced rectal cancer.

    PubMed

    Boysen, Anders Kindberg; Wettergren, Yvonne; Sorensen, Boe Sandahl; Taflin, Helena; Gustavson, Bengt; Spindler, Karen-Lise Garm

    2017-11-01

    Accurate staging of rectal cancer remains essential for optimal patient selection for combined modality treatment, including radiotherapy, chemotherapy and surgery. We aimed at examining the correlation of cell free DNA with the pathologic stage and subsequent risk of recurrence for patients with locally advanced rectal cancer undergoing preoperative chemoradiation. We examined 75 patients with locally advanced rectal cancer receiving preoperative chemoradiation. Blood samples for translational use were drawn prior to rectal surgery. The level of cell free DNA was quantified by digital droplet PCR and expressed as copy number of beta 2 microglobulin. We found a median level of cell free DNA in the AJCC stages I-III of 3100, 8300, and 10,700 copies/mL respectively. For patients with 12 sampled lymph nodes or above, the median level of cell free DNA were 2400 copies/mL and 4400 copies/mL (p = 0.04) for node negative and node positive disease respectively. The median follow-up was 39 months and 11 recurrences were detected (15%). The median level for patients with recurrent disease was 13,000 copies/mL compared to 5200 copies/mL for non-recurrent patients (p = 0.08). We have demonstrated a correlation between the level of total cell free DNA and the pathologic stage and nodal involvement. Furthermore, we have found a trend towards a correlation with the risk of recurrence following resection of localized rectal cancer.

  18. Smooth Transition for Advancement to Graduate Education (STAGE) for Underrepresented Groups in the Mathematical Sciences Pilot Project: Broadening Participation through Mentoring

    ERIC Educational Resources Information Center

    Eubanks-Turner, Christina; Beaulieu, Patricia; Pal, Nabendu

    2018-01-01

    The Smooth Transition for Advancement to Graduate Education (STAGE) project was a three-year pilot project designed to mentor undergraduate students primarily from under-represented groups in the mathematical sciences. The STAGE pilot project focused on mentoring students as they transitioned from undergraduate education to either graduate school…

  19. Advances in Retinal Prosthetic Research: A Systematic Review of Engineering and Clinical Characteristics of Current Prosthetic Initiatives.

    PubMed

    Cheng, Derrick L; Greenberg, Paul B; Borton, David A

    2017-03-01

    To date, reviews of retinal prostheses have focused primarily on devices undergoing human trials in the Western Hemisphere and fail to capture significant advances in materials and engineering research in countries such as Japan and Korea, as well as projects in early stages of development. To address these gaps, this systematic review examines worldwide advances in retinal prosthetic research, evaluates engineering characteristics and clinical progress of contemporary device initiatives, and identifies potential directions for future research in the field of retinal prosthetics. A literature search using PubMed, Google Scholar, and IEEExplore was conducted following the PRISMA Guidelines for Systematic Review. Inclusion criteria were peer-reviewed papers demonstrating progress in human or animal trials and papers discussing the prosthetic engineering design. For each initiative, a description of the device, its engineering considerations, and recent clinical results were provided. Ten prosthetic initiatives met our inclusion criteria and were organized by stimulation location. Of these initiatives, four have recently completed human trials, three are undergoing multi- or single-center human trials, and three are undergoing preclinical animal testing. Only the Argus II (FDA 2013, CE 2011) has obtained FDA approval for use in the United States; the Alpha-IMS (CE 2013) has achieved the highest visual acuity using a Landolt-C test to date and is the only device presently undergoing a multicenter clinical trial. Several distinct approaches to retinal stimulation have been successful in eliciting visual precepts in animals and/or humans. However, many clinical needs are still not met and engineering challenges must be addressed before a retinal prosthesis with the capability to fully and safely restore functional vision can be realized.

  20. Exploring the scope of expanding advanced nursing practice in nurse-led clinics: a multiple-case study.

    PubMed

    Shiu, Ann T Y; Lee, Diana T F; Chau, Janita P C

    2012-08-01

    This article is a report on a study to explore the development of expanding advanced nursing practice in nurse-led clinics in Hong Kong. Nurse-led clinics serviced by advanced practice nurses, a common international practice, have been adopted in Hong Kong since 1990s. Evaluations consistently show that this practice has good clinical outcomes and contributes to containing healthcare cost. However, similar to the international literature, it remains unclear as to what the elements of good advanced nursing practice are, and which directions Hong Kong should adopt for further development of such practice. A multiple-case study design was adopted with six nurse-led clinics representing three specialties as six case studies, and including two clinics each from continence, diabetes and wound care. Each case had four embedded units of analysis. They included non-participant observation of nursing activities (9 days), nurse interviews (N = 6), doctor interviews (N = 6) and client interviews (N = 12). The data were collected in 2009. Within- and cross-case analyses were conducted. The cross-case analysis demonstrated six elements of good advanced nursing practice in nurse-led clinics, and showed a great potential to expand the practice by reshaping four categories of current boundaries, including community-hospital, wellness-illness, public-private and professional-practice boundaries. From these findings, we suggest a model to advance the scope of advanced nursing practice in nurse-led clinics. The six elements may be applied as audit criteria for evaluation of advanced nursing practice in nurse-led clinics, and the proposed model provides directions for expanding such practice in Hong Kong and beyond. © 2011 Blackwell Publishing Ltd.

  1. One-Stage versus Two-Stage Repair of Asymmetric Bilateral Cleft Lip: A 20-Year Retrospective Study of Clinical Outcome.

    PubMed

    Chung, Kyung Hoon; Lo, Lun-Jou

    2018-05-01

    Both one- and two-stage approaches have been widely used for patients with asymmetric bilateral cleft lip. There are insufficient long-term outcome data for comparison of these two methods. The purpose of this retrospective study was to compare the clinical outcome over the past 20 years. The senior author's (L.J.L.) database was searched for patients with asymmetric bilateral cleft lip from 1995 to 2015. Qualified patients were divided into two groups: one-stage and two-stage. The postoperative photographs of patients were evaluated subjectively by surgical professionals and laypersons. Ratios of the nasolabial region were calculated for objective analysis. Finally, the revision procedures in the nasolabial area were reviewed. Statistical analyses were performed. A total of 95 consecutive patients were qualified for evaluation. Average follow-up was 13.1 years. A two-stage method was used in 35 percent of the patients, and a one-stage approach was used in 65 percent. All underwent primary nasal reconstruction. Among the satisfaction rating scores, the one-stage repair was rated significantly higher than two-stage reconstruction (p = 0.0001). Long-term outcomes of the two-stage patients and the unrepaired mini-microform deformities were unsatisfactory according to both professional and nonprofessional evaluators. The revision rate was higher in patients with a greater-side complete cleft lip and palate as compared with those without palatal involvement. The results suggested that one-stage repair provided better results with regard to achieving a more symmetric and smooth lip and nose after primary reconstruction. The revision rate was slightly higher in the two-stage patient group. Therapeutic, III.

  2. [The initial (I and II) and advanced (III and IV) stages of juvenile patellar chondromalacia. Its diagnosis by magnetic resonance using a 1.5-T magnet with FLASH sequences].

    PubMed

    Macarini, L; Rizzo, A; Martino, F; Zaccheo, N; Angelelli, G; Rotondo, A

    1998-06-01

    Juvenile patellar chondromalacia is a common orthopedic disorder which can mimic other conditions; early diagnosis is mandatory to prevent its evolution into osteoarthrosis. In the early stages of patellar chondromalacia (I and II), the lesions originate in the deep cartilage layer and the joint surface is not affected. Arthroscopy can demonstrate joint surface changes only and give indirect information about deeper lesions. We investigated the yield of 2D FLASH MRI with 30 degrees flip angle and a dedicated coil in the diagnosis of patellar chondromalacia, especially in its early stages. Eighteen patients (mean age: 21 years) with clinically suspected patellar chondromalacia were examined with MRI; 13 of them were also submitted to arthroscopy. A 1.5 T unit with a transmit-and-receive extremity coil was used. We acquired T1 SE sequences (TR/TE: 500-700/15/20) and 2D T2* FLASH sequence (TR/TE/FA: 500-800/18/30 degrees). The field of view was 160-180 mm and the matrix 192 x 256, with 2-3 NEX. The images were obtained on the axial plane. The lesions were classified in 4 stages according to Shahriaree classification. Agreement between MR and arthroscopic findings was good in both early and advanced lesions in 12/13 cases. Early lesions appeared as hyperintense focal thickening of the hyaline cartilage (stage I) or as small cystic lesions within the cartilage and no articular surface involvement (stage II). The medial patellar facet was the most frequent site. Advanced lesions appeared as articular surface ulcerations, thinning and cartilage hypointensity (stage III); stage IV lesions presented as complete erosions of the hyaline cartilage and hypointense underlying bone. 2D FLASH MRI with 30 degrees flip angle can show the differences in water content in the cartilage and thus permit to detect early chondromalacia lesions in the deep cartilage.

  3. Low-Noise Potential of Advanced Fan Stage Stator Vane Designs Verified in NASA Lewis Wind Tunnel Test

    NASA Technical Reports Server (NTRS)

    Hughes, Christopher E.

    1999-01-01

    With the advent of new, more stringent noise regulations in the next century, aircraft engine manufacturers are investigating new technologies to make the current generation of aircraft engines as well as the next generation of advanced engines quieter without sacrificing operating performance. A current NASA initiative called the Advanced Subsonic Technology (AST) Program has set as a goal a 6-EPNdB (effective perceived noise) reduction in aircraft engine noise relative to 1992 technology levels by the year 2000. As part of this noise program, and in cooperation with the Allison Engine Company, an advanced, low-noise, high-bypass-ratio fan stage design and several advanced technology stator vane designs were recently tested in NASA Lewis Research Center's 9- by 15-Foot Low-Speed Wind Tunnel (an anechoic facility). The project was called the NASA/Allison Low Noise Fan.

  4. Elective nodal irradiation (ENI) vs. involved field radiotherapy (IFRT) for locally advanced non-small cell lung cancer (NSCLC): A comparative analysis of toxicities and clinical outcomes.

    PubMed

    Fernandes, Annemarie T; Shen, Jason; Finlay, Jarod; Mitra, Nandita; Evans, Tracey; Stevenson, James; Langer, Corey; Lin, Lilie; Hahn, Stephen; Glatstein, Eli; Rengan, Ramesh

    2010-05-01

    Elective nodal irradiation (ENI) and involved field radiotherapy (IFRT) are definitive radiotherapeutic approaches used to treat patients with locally advanced non-small cell lung cancer (NSCLC). ENI delivers prophylactic radiation to clinically uninvolved lymph nodes, while IFRT only targets identifiable gross nodal disease. Because clinically uninvolved nodal stations may harbor microscopic disease, IFRT raises concerns for increased nodal failures. This retrospective cohort analysis evaluates failure rates and treatment-related toxicities in patients treated at a single institution with ENI and IFRT. We assessed all patients with stage III locally advanced or stage IV oligometastatic NSCLC treated with definitive radiotherapy from 2003 to 2008. Each physician consistently treated with either ENI or IFRT, based on their treatment philosophy. Of the 108 consecutive patients assessed (60 ENI vs. 48 IFRT), 10 patients had stage IV disease and 95 patients received chemotherapy. The median follow-up time for survivors was 18.9 months. On multivariable logistic regression analysis, patients treated with IFRT demonstrated a significantly lower risk of high grade esophagitis (Odds ratio: 0.31, p = 0.036). The differences in 2-year local control (39.2% vs. 59.6%), elective nodal control (84.3% vs. 84.3%), distant control (47.7% vs. 52.7%) and overall survival (40.1% vs. 43.7%) rates were not statistically significant between ENI vs. IFRT. Nodal failure rates in clinically uninvolved nodal stations were not increased with IFRT when compared to ENI. IFRT also resulted in significantly decreased esophageal toxicity, suggesting that IFRT may allow for integration of concurrent systemic chemotherapy in a greater proportion of patients. Copyright 2010 Elsevier Ireland Ltd. All rights reserved.

  5. The Prognostic Value of Plasma Epstein-Barr Viral DNA and Tumor Response to Neoadjuvant Chemotherapy in Advanced-Stage Nasopharyngeal Carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Liu, Li-Ting; Tang, Lin-Quan; Chen, Qiu-Yan

    Purpose: To explore the prognostic value of the plasma load of Epstein-Barr viral (EBV) DNA and the tumor response to neoadjuvant chemotherapy (NACT) in advanced-stage nasopharyngeal carcinoma (NPC). Patients and Methods: In all, 185 consecutive patients with stage III to IVb NPC treated with NACT followed by concurrent chemoradiation therapy (CCRT) were prospectively enrolled. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included locoregional relapse–free survival (LRFS) and distant metastasis–free survival (DMFS). Results: EBV DNA was detected in 165 (89%) patients before treatment but was undetectable in 127 (69%) patients after NACT. Detectable EBV DNA levels aftermore » NACT were correlated with poor prognosis (3-year PFS 71.8% vs 85.2%, P=.008 and 3-year DMFS 82.5% vs 92.3%, P=.013). An unsatisfactory tumor response (stable disease or disease progression) after NACT was also correlated with poor clinical outcome (3-year PFS 71.1% vs 85.9%, P=.005 and 3-year LRFS 82.7% vs 93.5%, P=.012). Multivariate analysis showed that the EBV DNA level after NACT (hazard ratio [HR] 2.31, 95% CI 1.18-4.54, P=.015) and the tumor response to NACT (HR 2.84, 95% CI 1.42-5.67, P=.003) were both significant prognostic factors for PFS. Multivariate analysis also showed that EBV DNA after NACT was the only significant predictor of DMFS (HR 2.99, 95% CI 1.25-7.15, P=.014) and that tumor response to NACT was the only significant predictor of LRFS (HR 3.31, 95% CI 1.21-9.07, P=.020). Conclusion: Detectable EBV DNA levels and an unsatisfactory tumor response (stable disease or disease progression) after NACT serve as predictors of poor prognosis for patients with advanced-stage NPC. These findings will facilitate further risk stratification, early treatment modification, or both before CCRT.« less

  6. Novel histopathologic feature identified through image analysis augments stage II colorectal cancer clinical reporting

    PubMed Central

    Caie, Peter D.; Zhou, Ying; Turnbull, Arran K.; Oniscu, Anca; Harrison, David J.

    2016-01-01

    A number of candidate histopathologic factors show promise in identifying stage II colorectal cancer (CRC) patients at a high risk of disease-specific death, however they can suffer from low reproducibility and none have replaced classical pathologic staging. We developed an image analysis algorithm which standardized the quantification of specific histopathologic features and exported a multi-parametric feature-set captured without bias. The image analysis algorithm was executed across a training set (n = 50) and the resultant big data was distilled through decision tree modelling to identify the most informative parameters to sub-categorize stage II CRC patients. The most significant, and novel, parameter identified was the ‘sum area of poorly differentiated clusters’ (AreaPDC). This feature was validated across a second cohort of stage II CRC patients (n = 134) (HR = 4; 95% CI, 1.5– 11). Finally, the AreaPDC was integrated with the significant features within the clinical pathology report, pT stage and differentiation, into a novel prognostic index (HR = 7.5; 95% CI, 3–18.5) which improved upon current clinical staging (HR = 4.26; 95% CI, 1.7– 10.3). The identification of poorly differentiated clusters as being highly significant in disease progression presents evidence to suggest that these features could be the source of novel targets to decrease the risk of disease specific death. PMID:27322148

  7. Recent Advances in Clinical Natural Language Processing in Support of Semantic Analysis.

    PubMed

    Velupillai, S; Mowery, D; South, B R; Kvist, M; Dalianis, H

    2015-08-13

    We present a review of recent advances in clinical Natural Language Processing (NLP), with a focus on semantic analysis and key subtasks that support such analysis. We conducted a literature review of clinical NLP research from 2008 to 2014, emphasizing recent publications (2012-2014), based on PubMed and ACL proceedings as well as relevant referenced publications from the included papers. Significant articles published within this time-span were included and are discussed from the perspective of semantic analysis. Three key clinical NLP subtasks that enable such analysis were identified: 1) developing more efficient methods for corpus creation (annotation and de-identification), 2) generating building blocks for extracting meaning (morphological, syntactic, and semantic subtasks), and 3) leveraging NLP for clinical utility (NLP applications and infrastructure for clinical use cases). Finally, we provide a reflection upon most recent developments and potential areas of future NLP development and applications. There has been an increase of advances within key NLP subtasks that support semantic analysis. Performance of NLP semantic analysis is, in many cases, close to that of agreement between humans. The creation and release of corpora annotated with complex semantic information models has greatly supported the development of new tools and approaches. Research on non-English languages is continuously growing. NLP methods have sometimes been successfully employed in real-world clinical tasks. However, there is still a gap between the development of advanced resources and their utilization in clinical settings. A plethora of new clinical use cases are emerging due to established health care initiatives and additional patient-generated sources through the extensive use of social media and other devices.

  8. Recent Advances in Clinical Natural Language Processing in Support of Semantic Analysis

    PubMed Central

    Mowery, D.; South, B. R.; Kvist, M.; Dalianis, H.

    2015-01-01

    Summary Objectives We present a review of recent advances in clinical Natural Language Processing (NLP), with a focus on semantic analysis and key subtasks that support such analysis. Methods We conducted a literature review of clinical NLP research from 2008 to 2014, emphasizing recent publications (2012-2014), based on PubMed and ACL proceedings as well as relevant referenced publications from the included papers. Results Significant articles published within this time-span were included and are discussed from the perspective of semantic analysis. Three key clinical NLP subtasks that enable such analysis were identified: 1) developing more efficient methods for corpus creation (annotation and de-identification), 2) generating building blocks for extracting meaning (morphological, syntactic, and semantic subtasks), and 3) leveraging NLP for clinical utility (NLP applications and infrastructure for clinical use cases). Finally, we provide a reflection upon most recent developments and potential areas of future NLP development and applications. Conclusions There has been an increase of advances within key NLP subtasks that support semantic analysis. Performance of NLP semantic analysis is, in many cases, close to that of agreement between humans. The creation and release of corpora annotated with complex semantic information models has greatly supported the development of new tools and approaches. Research on non-English languages is continuously growing. NLP methods have sometimes been successfully employed in real-world clinical tasks. However, there is still a gap between the development of advanced resources and their utilization in clinical settings. A plethora of new clinical use cases are emerging due to established health care initiatives and additional patient-generated sources through the extensive use of social media and other devices. PMID:26293867

  9. Lost in Translation: The Unintended Consequences of Advance Directive Law on Clinical Care

    PubMed Central

    Castillo, Lesley S.; Williams, Brie A.; Hooper, Sarah M.; Sabatino, Charles P.; Weithorn, Lois A.; Sudore, Rebecca L.

    2011-01-01

    Background Advance directive law may compromise the clinical effectiveness of advance directives. Purpose To identify unintended legal consequences of advance directive law that may prevent patients from communicating end-of-life preferences. Data Sources Advance directive legal statutes for all 50 U.S. states and the District of Columbia and English-language searches of LexisNexis, Westlaw, and MEDLINE from 1966 to August 2010. Study Selection Two independent reviewers selected 51 advance directive statutes and 20 articles. Three independent legal reviewers selected 105 legal proceedings. Data Extraction Two reviewers independently assessed data sources and used critical content analysis to determine legal barriers to the clinical effectiveness of advance directives. Disagreements were resolved by consensus. Data Synthesis Legal and content-related barriers included poor readability (that is, laws in all states were written above a 12th-grade reading level), health care agent or surrogate restrictions (for example, 40 states did not include same-sex or domestic partners as default surrogates), and execution requirements needed to make forms legally valid (for example, 35 states did not allow oral advance directives, and 48 states required witness signatures, a notary public, or both). Vulnerable populations most likely to be affected by these barriers included patients with limited literacy, limited English proficiency, or both who cannot read or execute advance directives; same-sex or domestic partners who may be without legally valid and trusted surrogates; and unbefriended, institutionalized, or homeless patients who may be without witnesses and suitable surrogates. Limitation Only appellate-level legal cases were available, which may have excluded relevant cases. Conclusion Unintended negative consequences of advance directive legal restrictions may prevent all patients, and particularly vulnerable patients, from making and communicating their end

  10. Clinical translation of handheld optical coherence tomography: practical considerations and recent advancements

    NASA Astrophysics Data System (ADS)

    Monroy, Guillermo L.; Won, Jungeun; Spillman, Darold R.; Dsouza, Roshan; Boppart, Stephen A.

    2017-12-01

    Since the inception of optical coherence tomography (OCT), advancements in imaging system design and handheld probes have allowed for numerous advancements in disease diagnostics and characterization of the structural and optical properties of tissue. OCT system developers continue to reduce form factor and cost, while improving imaging performance (speed, resolution, etc.) and flexibility for applicability in a broad range of fields, and nearly every clinical specialty. An extensive array of components to construct customized systems has also become available, with a range of commercial entities that produce high-quality products, from single components to full systems, for clinical and research use. Many advancements in the development of these miniaturized and portable systems can be linked back to a specific challenge in academic research, or a clinical need in medicine or surgery. Handheld OCT systems are discussed and explored for various applications. Handheld systems are discussed in terms of their relative level of portability and form factor, with mention of the supporting technologies and surrounding ecosystem that bolstered their development. Additional insight from our efforts to implement systems in several clinical environments is provided. The trend toward well-designed, efficient, and compact handheld systems paves the way for more widespread adoption of OCT into point-of-care or point-of-procedure applications in both clinical and commercial settings.

  11. Multivariable normal-tissue complication modeling of acute esophageal toxicity in advanced stage non-small cell lung cancer patients treated with intensity-modulated (chemo-)radiotherapy.

    PubMed

    Wijsman, Robin; Dankers, Frank; Troost, Esther G C; Hoffmann, Aswin L; van der Heijden, Erik H F M; de Geus-Oei, Lioe-Fee; Bussink, Johan

    2015-10-01

    The majority of normal-tissue complication probability (NTCP) models for acute esophageal toxicity (AET) in advanced stage non-small cell lung cancer (AS-NSCLC) patients treated with (chemo-)radiotherapy are based on three-dimensional conformal radiotherapy (3D-CRT). Due to distinct dosimetric characteristics of intensity-modulated radiation therapy (IMRT), 3D-CRT based models need revision. We established a multivariable NTCP model for AET in 149 AS-NSCLC patients undergoing IMRT. An established model selection procedure was used to develop an NTCP model for Grade ⩾2 AET (53 patients) including clinical and esophageal dose-volume histogram parameters. The NTCP model predicted an increased risk of Grade ⩾2 AET in case of: concurrent chemoradiotherapy (CCR) [adjusted odds ratio (OR) 14.08, 95% confidence interval (CI) 4.70-42.19; p<0.001], increasing mean esophageal dose [Dmean; OR 1.12 per Gy increase, 95% CI 1.06-1.19; p<0.001], female patients (OR 3.33, 95% CI 1.36-8.17; p=0.008), and ⩾cT3 (OR 2.7, 95% CI 1.12-6.50; p=0.026). The AUC was 0.82 and the model showed good calibration. A multivariable NTCP model including CCR, Dmean, clinical tumor stage and gender predicts Grade ⩾2 AET after IMRT for AS-NSCLC. Prior to clinical introduction, the model needs validation in an independent patient cohort. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Advanced clinical insights & practice: ischemic heart disease.

    PubMed

    Benner, Randall W; Zavarella, Matthew S

    2008-03-01

    This issue sees the debut of a new series of continuing education articles. The series, Advanced Clinical Insights & Practice, is designed to provide continuing education to an ever-expanding realm of paramedicine that needs more of it: the critical care transport paramedic. Secondly, and equally important, are the benefits that can be reaped by other certification levels reading this feature. For EMT-Basics and Intermediates, it will provide a great enhancement to your core knowledge, although most of the interventions discussed will be beyond your traditional scope. For paramedics, it will augment both your pathophysiological understanding and clinical assessment/management skills of diseases and injuries discussed. Ultimately though, it is hoped that anyone who reads these articles will become a better clinician. The next article will appear in the July issue.

  13. Major clinical research advances in gynecologic cancer in 2013.

    PubMed

    Suh, Dong Hoon; Kim, Jae-Weon; Kang, Sokbom; Kim, Hak Jae; Lee, Kyung-Hun

    2014-07-01

    In 2013, 10 topics were selected for major clinical research advances in gynecologic oncology; these included three topics regarding cervical cancer, three regarding ovarian cancer, two regarding endometrial cancer, and one each regarding breast cancer and radiation oncology. For cervical cancer, bevacizumab was first demonstrated to exhibit outstanding clinical efficacy in a recurrent, metastatic setting. Regarding cervical cancer screening, visual inspections with acetic acid in low-resource settings, p16/Ki-67 double staining, and the follow-up results of four randomized controlled trials of human papillomavirus-based screening methods were reviewed. Laparoscopic para-aortic lymphadenectomy before chemoradiation for locally advanced cervical cancer was the final topic for cervical cancer. Regarding front-line ovarian cancer therapies, dose-dense paclitaxel and carboplatin, intraperitoneal chemotherapy, and other targeted agents administered according to combination or maintenance schedules were discussed. Regarding recurrent ovarian cancer treatment, cediranib, olaparib, and farletuzumab were discussed for platinum-sensitive disease. The final overall survival data associated with a combination of bevacizumab and chemotherapy for platinum-resistant disease were briefly summarized. For endometrial cancer, the potential clinical efficacy of metformin, an antidiabetic drug, in obese patients was followed by integrated genomic analyses from the Cancer Genome Atlas Research Network. For breast cancer, three remarkable advances were reviewed: the long-term effects of continued adjuvant tamoxifen for 10 years, the effects of 2-year versus 1-year adjuvant trastuzumab for human epidermal growth factor receptor 2-positive disease, and the approval of pertuzumab in a neoadjuvant setting with a pathologic complete response as the surrogate endpoint. Finally, the recent large studies of intensity-modulated radiotherapy for gynecologic cancer were briefly summarized.

  14. P38 mitogen-activated protein kinase (p38 MAPK) overexpression in clinical staging of nasopharyngeal carcinoma

    NASA Astrophysics Data System (ADS)

    Farhat; Asnir, R. A.; Yudhistira, A.; Daulay, E. R.; Muzakkir, M. M.; Yulius, S.

    2018-03-01

    Molecular biological research on nasopharyngeal carcinoma has been widely practiced, such as VEGF, EGFR, COX-2 expression and so on. MAPK plays a role in cell growth such as proliferation, differentiation, and apoptosis, primarily contributing to gene expression, where p38 MAPK pathway mostly associate with anti-apoptosis and cause cell transformation. The aim of this study is to determine the expression of p38 MAPK in clinical stage of nasopharyngeal carcinoma so that the result can be helpful in prognosis and adjunctive therapy in nasopharyngeal carcinoma. The research design is descriptive. It was done in THT- KL Department of FK USU/RSUP Haji Adam Malik, Medan and Pathology Anatomical Department of FK USU. The study was conducted from December 2011 to May 2012. The Samples are all patients who diagnosed with nasopharyngeal carcinoma in oncology division of Otorhinolaryngology Department. p38 MAPK overexpression was found in 21 samples (70%) from 30 nasopharyngeal carcinoma samples. The elevated of p38 MAPK expression most found on T4 by eight samples (38.1%), N3 lymph node group by nine samples (42.9%), stage IV of clinical staging is as many as 15 samples (71.4%). p38 MAPK most expressed in stage IV clinical staging of patients with nasopharyngeal carcinoma.

  15. Contemporary Treatment Patterns and Outcomes for Clinical Stage IS Testicular Cancer.

    PubMed

    Kamran, Sophia C; Seisen, Thomas; Markt, Sarah C; Preston, Mark A; Trinh, Quoc-Dien; Frazier, Lindsay A; Choueiri, Toni K; Martin, Neil E; Nguyen, Paul L; Beard, Clair J

    2018-02-01

    Controversy exists regarding the optimal management strategy for clinical stage IS seminomatous (SGCT) and nonseminomatous germ cell tumors (NSGCT) of the testis. To assess contemporary treatment patterns and outcomes for clinical stage IS testicular cancer. Using the National Cancer Data Base (2004-2012), we identified 1362 patients with clinical stage IS SGCT and NSGCT of the testis, treated with either adjuvant treatment (AT) or observation. We calculated the annual percent change (APC) to assess treatment trends. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier curves and Cox regression analyses were used to compare overall survival (OS) between AT and observation groups. Analyses were stratified by histologic type. Overall, there were 581 (43%) and 781 (57%) men with SGCT and NSGCT, respectively. Among men with SGCT, the use of AT decreased over the study period (APC=-2.7, 95% confidence interval [CI]: -4.4, -1.1, p=0.001). The 5-yr IPTW-adjusted rates of OS were 99% and 97% in the AT and observation groups, respectively (hazard ratio = 0.36, 95% CI: 0.12, 1.14, p=0.08). Among men with NSGCT, the use of AT remained stable over the study period (APC = +0.8, 95% CI: -0.7, +2.2, p=0.29). The 5-yr IPTW-adjusted rates of OS were 97% and 95% in the AT and observation groups, respectively (HR=0.66, 95% CI: 0.27, 1.61, p=0.36). Limitations include the lack of full treatment details and cancer-specific survival information. Trends in the use of AT significantly decreased over time for SGCT, while it remained stable for NSGCT. Nonetheless, we report 5-yr OS rates of ≥95% for both histologies without any significant benefit with the use of AT. Further studies are warranted to confirm these findings. We evaluated treatment trends and outcomes for stage IS testicular cancer. We found that treatment changed over time for seminoma and remained stable for nonseminoma; there was no significant survival benefit in the use of adjuvant treatment versus

  16. Clinical Model for NASH and Advanced Fibrosis in Adult Patients With Diabetes and NAFLD: Guidelines for Referral in NAFLD.

    PubMed

    Bazick, Jessica; Donithan, Michele; Neuschwander-Tetri, Brent A; Kleiner, David; Brunt, Elizabeth M; Wilson, Laura; Doo, Ed; Lavine, Joel; Tonascia, James; Loomba, Rohit

    2015-07-01

    Approximately 18 million people in the U.S. have coexisting type 2 diabetes and nonalcoholic fatty liver disease (NAFLD). It is not known who among these patients has nonalcoholic steatohepatitis (NASH) with advanced fibrosis. Therefore, we aimed to determine factors that are associated with both NASH and advanced fibrosis in patients with diabetes and NAFLD in order to identify who should be prioritized for referral to a hepatologist for further diagnostic evaluation and treatment. This study was derived from the NASH Clinical Research Network studies and included 1,249 patients with biopsy-proven NAFLD (including a model development cohort of 346 patients and an independent validation cohort of 100 patients with type 2 diabetes as defined by the American Diabetes Association criteria). Outcome measures were presence of NASH or advanced fibrosis (stage 3 or 4) using cross-validated, by jackknife method, multivariable-adjusted area under the receiver operating characteristic curve (AUROC) and 95% CI. The mean ± SD age and BMI of patients with diabetes and NAFLD was 52.5 ± 10.3 years and 35.8 ± 6.8 kg/m(2), respectively. The prevalence of NASH and advanced fibrosis was 69.2% and 41.0%, respectively. The model for NASH included white race, BMI, waist, alanine aminotransferase (ALT), Aspartate aminotransferase (AST), albumin, HbA1c, HOMA of insulin resistance, and ferritin with an AUROC of 0.80 (95% CI 0.75-0.84, P = 0.007). The specificity, sensitivity, negative predictive values (NPVs), and positive predictive values (PPVs) were 90.0%, 56.8%, 47.7%, and 93.2%, respectively, and the model correctly classified 67% of patients as having NASH. The model for predicting advanced fibrosis included age, Hispanic ethnicity, BMI, waist-to-hip ratio, hypertension, ALT-to-AST ratio, alkaline phosphatase, isolated abnormal alkaline phosphatase, bilirubin (total and direct), globulin, albumin, serum insulin, hematocrit, international normalized ratio, and platelet count with

  17. Lymph node metastasis in grossly apparent clinical stage Ia epithelial ovarian cancer: Hacettepe experience and review of literature

    PubMed Central

    2010-01-01

    Background Lymphadenectomy is an integral part of the staging system of epithelial ovarian cancer. However, the extent of lymphadenectomy in the early stages of ovarian cancer is controversial. The objective of this study was to identify the lymph node involvement in unilateral epithelial ovarian cancer apparently confined to the one ovary (clinical stage Ia). Methods A prospective study of clinical stage I ovarian cancer patients is presented. Patient's characteristics and tumor histopathology were the variables evaluated. Results Thirty three ovarian cancer patients with intact ovarian capsule were evaluated. Intraoperatively, neither of the patients had surface involvement, adhesions, ascites or palpable lymph nodes (supposed to be clinical stage Ia). The mean age of the study group was 55.3 ± 11.8. All patients were surgically staged and have undergone a systematic pelvic and paraaortic lymphadenectomy. Final surgicopathologic reports revealed capsular involvement in seven patients (21.2%), contralateral ovarian involvement in two (6%) and omental metastasis in one (3%) patient. There were two patients (6%) with lymph node involvement. One of the two lymph node metastasis was solely in paraaortic node and the other metastasis was in ipsilateral pelvic lymph node. Ovarian capsule was intact in all of the patients with lymph node involvement and the tumor was grade 3. Conclusion In clinical stage Ia ovarian cancer patients, there may be a risk of paraaortic and pelvic lymph node metastasis. Further studies with larger sample size are needed for an exact conclusion. PMID:21114870

  18. An update on the role of advanced diagnostic bronchoscopy in the evaluation and staging of lung cancer

    PubMed Central

    Belanger, Adam R.; Akulian, Jason A.

    2017-01-01

    Lung cancer remains a common and deadly disease. Many modalities are available to the bronchoscopist to evaluate and stage lung cancer. We review the role of bronchoscopy in the staging of the mediastinum with convex endobronchial ultrasound (EBUS) and discuss emerging role of esophageal ultrasonography as a complementary modality. In addition, we discuss advances in scope technology and elastography. We review the bronchoscopic methods available for the diagnosis of peripheral lung nodules including radial EBUS and navigational bronchoscopy (NB) with a consideration of the basic methodologies and diagnostic accuracies. We conclude with a discussion of the comparison of the various methodologies. PMID:28470104

  19. Endemic chronic kidney disease of unknown etiology in Sri Lanka: Correlation of pathology with clinical stages.

    PubMed

    Wijetunge, S; Ratnatunga, N V I; Abeysekera, T D J; Wazil, A W M; Selvarajah, M

    2015-01-01

    Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy.

  20. Evidence-based use of electronic clinical tracking systems in advanced practice registered nurse education: an integrative review.

    PubMed

    Branstetter, M Laurie; Smith, Lynette S; Brooks, Andrea F

    2014-07-01

    Over the past decade, the federal government has mandated healthcare providers to incorporate electronic health records into practice by 2015. This technological update in healthcare documentation has generated a need for advanced practice RN programs to incorporate information technology into education. The National Organization of Nurse Practitioner Faculties created core competencies to guide program standards for advanced practice RN education. One core competency is Technology and Information Literacy. Educational programs are moving toward the utilization of electronic clinical tracking systems to capture students' clinical encounter data. The purpose of this integrative review was to evaluate current research on advanced practice RN students' documentation of clinical encounters utilizing electronic clinical tracking systems to meet advanced practice RN curriculum outcome goals in information technology as defined by the National Organization of Nurse Practitioner Faculties. The state of the science depicts student' and faculty attitudes, preferences, opinions, and data collections of students' clinical encounters. Although electronic clinical tracking systems were utilized to track students' clinical encounters, these systems have not been evaluated for meeting information technology core competency standards. Educational programs are utilizing electronic clinical tracking systems with limited evidence-based literature evaluating the ability of these systems to meet the core competencies in advanced practice RN programs.

  1. Predictors of clinical-pathologic stage discrepancy in oral cavity squamous cell carcinoma: A National Cancer Database study.

    PubMed

    Kılıç, Sarah S; Kılıç, Suat; Crippen, Meghan M; Varughese, Denny; Eloy, Jean Anderson; Baredes, Soly; Mahmoud, Omar M; Park, Richard Chan Woo

    2018-04-01

    Few studies have examined the frequency and survival implications of clinicopathologic stage discrepancy in oral cavity squamous cell carcinoma (SCC). Oral cavity SCC cases with full pathologic staging information were identified in the National Cancer Database (NCDB). Clinical and pathologic stages were compared. Multivariate logistic regressions were performed to identify factors associated with stage discrepancy. There were 9110 cases identified, of which 67.3% of the cases were stage concordant, 19.9% were upstaged, and 12.8% were downstaged. The N classification discordance (28.5%) was more common than T classification discordance (27.6%). In cases of T classification discordance, downstaging is more common than upstaging (15.4% vs 12.1% of cases), but in cases of N classification discordance, the reverse is true; upstaging is much more common than downstaging (20.1 vs 8.4% of cases). Clinicopathologic stage discrepancy in oral cavity SCC is a common phenomenon that is associated with a number of clinical factors and has survival implications. © 2018 Wiley Periodicals, Inc.

  2. A Bayesian predictive two-stage design for phase II clinical trials.

    PubMed

    Sambucini, Valeria

    2008-04-15

    In this paper, we propose a Bayesian two-stage design for phase II clinical trials, which represents a predictive version of the single threshold design (STD) recently introduced by Tan and Machin. The STD two-stage sample sizes are determined specifying a minimum threshold for the posterior probability that the true response rate exceeds a pre-specified target value and assuming that the observed response rate is slightly higher than the target. Unlike the STD, we do not refer to a fixed experimental outcome, but take into account the uncertainty about future data. In both stages, the design aims to control the probability of getting a large posterior probability that the true response rate exceeds the target value. Such a probability is expressed in terms of prior predictive distributions of the data. The performance of the design is based on the distinction between analysis and design priors, recently introduced in the literature. The properties of the method are studied when all the design parameters vary.

  3. Evidence of prostate cancer "reverse stage migration" toward more advanced disease at diagnosis: Data from the Pennsylvania Cancer Registry.

    PubMed

    Reese, Adam C; Wessel, Sean R; Fisher, Susan G; Mydlo, Jack H

    2016-08-01

    The widespread adoption of prostate-specific antigen-based prostate cancer screening caused a stage migration toward earlier stage disease at diagnosis. We investigated whether this stage migration has persisted in a contemporary analysis of a population-based statewide cancer registry. We analyzed the Pennsylvania Cancer Registry, a statewide registry of all newly diagnosed cancers. Data were collected on prostate cancers diagnosed between 1992 and 2012. We determined age-adjusted prostate cancer incidence and mortality rates, as well as the distribution of tumor stage (localized, regional, or metastatic) at diagnosis, and assessed for changes in these variables over time using joinpoint analysis. Between 1992 and 2012, 210,831 new cases of prostate cancer were diagnosed in Pennsylvania, and 33,948 men died of disease. Age-adjusted prostate cancer incidence rates, and specifically the incidence of localized disease, have decreased dramatically since 2007 to 2008. Due to the decreased diagnosis of localized disease, regional and metastatic tumors have made up a greater percentage of all prostate cancer diagnoses in recent years, despite a relatively stable incidence of these advanced stage tumors. Over the past 2 decades, age-adjusted prostate cancer incidence rates in Pennsylvania have decreased, primarily because of the decreased detection of early-stage disease. There has been a corresponding shift toward more advanced disease at diagnosis. These findings may be explained by the decreased use of prostate-specific antigen-based screening, among other factors. The 2012 United States Preventative Services Task Force recommendations against prostate cancer screening may exacerbate this concerning trend, potentially resulting in an increase in prostate cancer-specific mortality. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Irreversible electroporation of stage 3 locally advanced pancreatic cancer: optimal technique and outcomes

    PubMed Central

    2015-01-01

    Objective Irreversible electroporation (IRE) of stage 3 pancreatic adenocarcinoma has been used to provide quality of life time in patients who have undergone appropriate induction therapy. The optimal technique has been reported within the literature, but not in video form. IRE of locally advanced pancreatic cancer is technically demanding requiring precision ultrasound use for continuous imaging in multiple needle placements and during IRE energy delivery. Methods Appropriate patients with locally advanced pancreatic cancer should have undergone appropriate induction chemotherapy for a reasonable duration. The safe and effective technique for irreversible electroporation is preformed through an open approach with the emphasis on intra-operative ultrasound and intra-operative electroporation management. Results The technique of open irreversible electroporation of the pancreas involves bracketing the target tumor with IRE probes and any and all invaded vital structures including the celiac axis, superior mesenteric artery (SMA), superior mesenteric-portal vein, and bile duct with continuous intraoperative ultrasound imaging through a caudal to cranial approach. Optimal IRE delivery requires a change in amperage of at least 12 amps from baseline tissue conductivity in order to achieve technical success. Multiple pull-backs are necessary since the IRE ablation probe lengths are 1 cm and thus needed to achieve technical success along the caudal to cranial plane. Conclusions Irreversible electroporation in combination with multi-modality therapy for locally advanced pancreatic carcinoma is feasible for appropriate patients with locally advanced cancer. Technical demands are high and require the highest quality ultrasound for precise spacing measurements and optimal delivery to ensure adequate change in tissue resistance. PMID:29075594

  5. A heartrending burden of gynaecological cancers in advance stage at nuclear institute of medicine and radiotherapy Jamshoro Sindh

    PubMed Central

    Bibi, Seema; Ashfaque, Sanober; Laghari, Naeem Ahmed

    2016-01-01

    Objectives: In Pakistan gynaecological cancers are among the leading causes of women’s morbidity and mortality posing huge financial burden on families, communities and state. Due to lack of national cancer registry exact facts and figures are unknown therefore this study was planned to find out prevalence, age, site and stage of presentation of gynaecological cancers at Nuclear Institute of Medicine and Radiotherapy (NIMRA), Jamshoro. Methods: A retrospective, cross sectional study was conducted from 1st January 2011 to 31st December 2011 at NIMRA Jamshoro. All cases of genital tract cancers were evaluated, required data was entered on predesigned performa and results were analyzed manually. Results: Out of 2401 total registered cancer cases, 231 (9.6%) patients were suffering from gynaecological cancer making it third most common cancer. Ovary was commonest site followed by cervix and uterus. More than 60% cases presented in advanced stage, mostly during 4th and 5th decade of life. Conclusion: Gynecological cancer was among top three cancers at one of the busiest public sector cancer institute in Sindh province and significant number presented in advance stage making treatment difficult and expensive. There is urgent need for development and implementation of an effective health policy regarding cancer prevention and treatment. PMID:27022358

  6. [Clinical significance of prognostic nutritional index in patients with advanced gastric cancer].

    PubMed

    Song, Shubin; Liu, Honggang; Xue, Yingwei

    2018-02-25

    To investigate the relationship of prognostic nutritional index (PNI) with clinicopathological factors and the clinical significance of PNI in predicting the survival in patients with advanced gastric cancer. Clinicopathological and follow-up data of 1150 patients with advanced gastric cancer who underwent radical gastrectomy from January 2007 to December 2010 at the Department of Gastrointestinal Surgery, Harbin Medical University Cancer Hospital were analyzed retrospectively. The PNI value was calculated [PNI=absolute value of lymphocyte(10 9 /L)×5 + serum albumin (g/L)] and was grouped according to the mean value of PNI. Relationships of PNI with gender, age, tumor size, depth of invasion, tumor differentiation, tumor stage, tumor location, lymph node metastasis and tumor marker detection level were analyzed. At the same time, for the survival analysis of patients, log-rank method was used for univariate analysis, and Cox method was used for multivariate analysis. Of 1150 cases, 846 were males and 304 were females with an average age of 62 (24 to 88) years. The average maximum diameter of tumor was 5.4(1.0 to 20.0) cm. Tumor of 159 cases located in the gastric fundus, 221 cases in the gastric body, 705 cases in the gastric antrum and 65 cases in the whole stomach. Well differentiated tumors were found in 198 cases and poorly differentiated tumors in 952 cases. As for depth of tumor invasion, 165 cases were T2, 343 cases were T3 and 642 cases were T4. According to TNM stage, 53 cases were stage I(, 397 cases were stage II( and 700 cases were stage III(. The average lymph node metastasis rate was 25.0%, meanwhile lymph node metastasis was N0 in 296 cases, N1 in 246 cases, N2 in 277 cases and N3 in 331 cases. Blood examination showed hemoglobin ≤130 g/L in 544 cases and >130 g/L in 606 cases; carcinoembryonic antigen ≤5 μg/L in 903 cases and >5 μg /L in 247 cases; carbohydrate antigen 19-9 ≤37 kU/L in 927 cases and >37 kU/L in 223 cases. In whole patients

  7. Clinically advancing and promising polymer-based therapeutics.

    PubMed

    Souery, Whitney N; Bishop, Corey J

    2018-02-01

    In this review article, we will examine the history of polymers and their evolution from provisional World War II materials to medical therapeutics. To provide a comprehensive look at the current state of polymer-based therapeutics, we will classify technologies according to targeted areas of interest, including central nervous system-based and intraocular-, gastrointestinal-, cardiovascular-, dermal-, reproductive-, skeletal-, and neoplastic-based systems. Within each of these areas, we will consider several examples of novel, clinically available polymer-based therapeutics; in addition, this review will also include a discussion of developing therapies, ranging from the in vivo to clinical trial stage, for each targeted area of treatment. Finally, we will emphasize areas of patient care in need of more effective, accessible, and targeted treatment approaches where polymer-based therapeutics may offer potential solutions. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  8. Impact of advanced monitoring variables on intraoperative clinical decision-making: an international survey.

    PubMed

    Joosten, Alexandre; Desebbe, Olivier; Suehiro, Koichi; Essiet, Mfonobong; Alexander, Brenton; Ricks, Cameron; Rinehart, Joseph; Faraoni, David; Cecconi, Maurizio; Van der Linden, Philippe; Cannesson, Maxime

    2017-02-01

    To assess the relationship between the addition of advanced monitoring variables and changes in clinical decision-making. A 15-questions survey was anonymously emailed to international experts and physician members of five anesthesia societies which focused on assessing treatment decisions of clinicians during three realistic clinical scenarios measured at two distinct time points. The first is when typical case information and basic monitoring (T1) were provided, and then once again after the addition of advanced monitoring variables (T2). We hypothesized that the addition of advanced variables would increase the incidence of an optimal therapeutic decision (a priori defined as the answer with the highest percentage of expert agreement) and decrease the variability among the physician's suggested treatments. The survey was completed by 18 experts and 839 physicians. Overall, adding advanced monitoring did not significantly increase physician response accuracy, with the least substantial changes noted on questions related to volume expansion or vasopressor administration. Moreover, advanced monitoring data did not significantly decrease the high level of initial practice variability in physician suggested treatments (P = 0.13), in contrast to the low variability observed within the expert group (P = 0.039). Additionally, 5-10 years of practice (P < 0.0001) and a cardiovascular subspecialty (P = 0.048) were both physician characteristics associated with a higher rate of optimal therapeutic decisions. The addition of advanced variables was of limited benefit for most physicians, further indicating the need for more in depth education on the clinical value and technical understanding of such variables.

  9. Endemic chronic kidney disease of unknown etiology in Sri Lanka: Correlation of pathology with clinical stages

    PubMed Central

    Wijetunge, S.; Ratnatunga, N. V. I.; Abeysekera, T. D. J.; Wazil, A. W. M.; Selvarajah, M.

    2015-01-01

    Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy. PMID:26628792

  10. Liquid biopsy and its role in an advanced clinical trial for lung cancer.

    PubMed

    Johann, Donald J; Steliga, Mathew; Shin, Ik J; Yoon, Donghoon; Arnaoutakis, Konstantinos; Hutchins, Laura; Liu, Meeiyueh; Liem, Jason; Walker, Karl; Pereira, Andy; Yang, Mary; Jeffus, Susanne K; Peterson, Erich; Xu, Joshua

    2018-02-01

    Liquid biopsy methodologies, for the purpose of plasma genotyping of cell-free DNA (cfDNA) of solid tumors, are a new class of novel molecular assays. Such assays are rapidly entering the clinical sphere of research-based monitoring in translational oncology, especially for thoracic malignancies. Potential applications for these blood-based cfDNA assays include: (i) initial diagnosis, (ii) response to therapy and follow-up, (iii) tumor evolution, and (iv) minimal residual disease evaluation. Precision medicine will benefit from cutting-edge molecular diagnostics, especially regarding treatment decisions in the adjuvant setting, where avoiding over-treatment and unnecessary toxicity are paramount. The use of innovative genetic analysis techniques on individual patient tumor samples is being pursued in several advanced clinical trials. Rather than using a categorical treatment plan, the next critical step of therapeutic decision making is providing the "right" cancer therapy for an individual patient, including correct dose and timeframe based on the molecular analysis of the tumor in question. Per the 21st Century Cures Act, innovative clinical trials are integral for biomarker and drug development. This will include advanced clinical trials utilizing: (i) innovative assays, (ii) molecular profiling with cutting-edge bioinformatics, and (iii) clinically relevant animal or tissue models. In this paper, a mini-review addresses state-of-the-art liquid biopsy approaches. Additionally, an on-going advanced clinical trial for lung cancer with novelty through synergizing liquid biopsies, co-clinical trials, and advanced bioinformatics is also presented. Impact statement Liquid biopsy technology is providing a new source for cancer biomarkers, and adds new dimensions in advanced clinical trials. Utilizing a non-invasive routine blood draw, the liquid biopsy provides abilities to address perplexing issues of tumor tissue heterogeneity by identifying mutations in both primary

  11. Phase I/II study of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma.

    PubMed

    Song, Y-P; Ma, J-B; Hu, L-K; Zhou, W; Chen, E-C; Zhang, W

    2011-02-01

    Compared to conventional fractionated-dose radiotherapy, high hypofractionated-dose radiotherapy could yield tumoricidal effects. However, few clinical trials of hypofractionated radiotherapy in loco-regionally advanced incurable esophageal cancer at present have yet been performed. The purpose of the current study was to evaluate the efficacy and toxicity of hypofractioned radiation with three-dimensional conformal radiotherapy for clinical T3-4N0-1M0 stage esophageal carcinoma. From September 2003 to December 2005, 45 patients with locally advanced esophageal carcinoma were grouped and received three-dimensional conformal hypofractioned radiotherapy (3D-CRT) whose fractionated dose was gradually increase per group. Radiotherapy was administered to a total dose of from 50 to 54 Gy (fractionated dose of from 3.0 to 6.0 Gy, 3 times weekly), over a 3-4 week period. And patients received 4 cycles chemotherapy. The median follow-up period for survivors was 38 months. Treatment tolerance rate was 78.8% with daily dose of from 3 to 5 Gy. There are 21.2% patients occurring Grade ≥ 3 acute toxicities. But patients couldn't tolerate daily dose of 6 Gy (55.6%). The 1-year, 2-year and 3-year local control rates were 62%, 49% and 39% respectively. And the 1-year, 2-year and 3-year overall survival rates were 34%, 21% and 9% respectively. The median overall survival time was 17 months. At the time of following up, 13 patients (31.0%) had occurred esophageal late complications, with mainly esophageal perforation, hemorrhage or stenosis, including initial stenosis aggravation. Therefore hypofractionated irradiation was thought to be feasible for clinical T3-4N0-1M0 stage esophageal carcinoma. And daily dose of ≤5 Gy was comparatively suitable in hypofractionated irradiation for esophageal carcinoma, and the patients tolerated well. But further research was in need also.

  12. ranibizumab in the management of advanced Coats disease Stages 3B and 4: long-term outcomes.

    PubMed

    Gaillard, Marie-Claire; Mataftsi, Assimina; Balmer, Aubin; Houghton, Susan; Munier, Francis L

    2014-11-01

    Laser photocoagulation and cryotherapy to completely destroy telangiectatic vessels and ischemic retina in Coats disease is barely applicable in advanced cases with total retinal detachment, and globe survival is notoriously poor in Stages 3B and 4. Anti-vascular endothelial growth factor intravitreal injections may offer new prospects for these patients. This study is a retrospective review of all consecutive patients with Coats disease treated with neoadjuvant or adjuvant intravitreal ranibizumab plus conventional and amblyopia treatment as appropriate. Nine patients (median age, 13 months) presenting Coats Stages 3B and 4 (5 and 4 eyes, respectively) were included. Iris neovascularization resolved within 2 weeks and retinal reapplication within 4 months in all patients. At last follow-up, globe survival was 100% with anatomical success in 8 of the 9 eyes. With a median follow-up of 50 months, fibrotic vitreoretinopathy was developed in 5 of the 9 cases, one leading to tractional retinal detachment and ultimately phthisis bulbi. The remaining 4 of the 9 eyes achieved some vision (range, 0.02-0.063). To the best of the authors' knowledge, this is the largest reported series of late-stage Coats undergoing anti-vascular endothelial growth factor therapy, a homogenous cohort of patients treated with a single agent and with the longest follow-up. This study supports the role of ranibizumab in advanced disease by transient restoration of the hemato-retinal barrier and suppression of neovascularization to facilitate classic treatment. At the last follow-up, the authors report unprecedented anatomical success and functional outcome.

  13. Recent advances in treating Parkinson’s disease

    PubMed Central

    Oertel, Wolfgang H.

    2017-01-01

    This article summarizes (1) the recent achievements to further improve symptomatic therapy of motor Parkinson’s disease (PD) symptoms, (2) the still-few attempts to systematically search for symptomatic therapy of non-motor symptoms in PD, and (3) the advances in the development and clinical testing of compounds which promise to offer disease modification in already-manifest PD. However, prevention (that is, slowing or stopping PD in a prodromal stage) is still a dream and one reason for this is that we have no consensus on primary endpoints for clinical trials which reflect the progression in prodromal stages of PD, such as in rapid eye movement sleep behavior disorder (RBD) —a methodological challenge to be met in the future. PMID:28357055

  14. Pathway Profiling and Rational Trial Design for Studies in Advanced Stage Cervical Carcinoma: A Review and a Perspective

    PubMed Central

    Scholl, Susy M. E.; Kenter, Gemma; Kurzeder, Christian; Beuzeboc, Philippe

    2011-01-01

    Multiple genetic abnormalities will have occurred in advanced cervical cancer and multiple targeting is likely to be needed to control tumor growth. To date, dominant therapeutic targets under scrutiny for cervical cancer treatment have been EGFR pathway and angiogenesis inhibition as well as anti-HPV vaccines. The potentially most effective targets to be blocked may be downstream from the membrane receptor or at the level of the nucleus. Alterations of the pathways involved in DNA repair and in checkpoint activations, as well as the specific site of HPV genome integration, appear worth assessing. For genetic mutational analysis, complete exon sequencing may become the norm in the future but at this stage frequent mutations (that matter) can be verified by PCR analysis. A precise documentation of relevant alterations of a large spectrum of protein biomarkers can be carried out by reverse phase protein array (RPPA) or by multiplex analysis. Clinical decision-making on the drug(s) of choice as a function of the biological alteration will need input from bio-informatics platforms as well as novel statistical designs. Endpoints are yet to be defined such as the loss (or reappearance) of a predictive biomarker. Single or dual targeting needs to be explored first in relevant preclinical animal and in xenograft models prior to clinical deployment. PMID:22091418

  15. Advanced Parkinson's or "complex phase" Parkinson's disease? Re-evaluation is needed.

    PubMed

    Titova, Nataliya; Martinez-Martin, Pablo; Katunina, Elena; Chaudhuri, K Ray

    2017-12-01

    Holistic management of Parkinson's disease, now recognised as a combined motor and nonmotor disorder, remains a key unmet need. Such management needs relatively accurate definition of the various stages of Parkinson's from early untreated to late palliative as each stage calls for personalised therapies. Management also needs to have a robust knowledge of the progression pattern and clinical heterogeneity of the presentation of Parkinson's which may manifest in a motor dominant or nonmotor dominant manner. The "advanced" stages of Parkinson's disease qualify for advanced treatments such as with continuous infusion or stereotactic surgery yet the concept of "advanced Parkinson's disease" (APD) remains controversial in spite of growing knowledge of the natural history of the motor syndrome of PD. Advanced PD is currently largely defined on the basis of consensus opinion and thus with several caveats. Nonmotor aspects of PD may also reflect advancing course of the disorder, so far not reflected in usual scale based assessments which are largely focussed on motor symptoms. In this paper, we discuss the problems with current definitions of "advanced" PD and also propose the term "complex phase" Parkinson's disease as an alternative which takes into account a multimodal symptoms and biomarker based approach in addition to patient preference.

  16. Phase 0 Trial of Itraconazole for Early-Stage Non-Small Cell Lung Cancer

    DTIC Science & Technology

    2015-10-01

    63 Male Caucasian T1bN0M0 Stage IA Undifferentiated carcinoma , favor Large cell 63 Female Caucasian T1aN0N0 Stage IA squamous cell carcinoma ... carcinoma ; and possibly prolongs survival in advanced non-small cell lung cancer (NSCLC). Insight into itraconazole mechanism and biomarkers will...study team members in which itraconazole resulted in tumor regression and Hh pathway antagonism in basal cell carcinoma ; and (3) a clinical trial in

  17. Disorganization at the stage of schizophrenia clinical outcome: Clinical-biological study.

    PubMed

    Nestsiarovich, A; Obyedkov, V; Kandratsenka, H; Siniauskaya, M; Goloenko, I; Waszkiewicz, N

    2017-05-01

    According to the multidimensional model of schizophrenia, three basic psychopathological dimensions constitute its clinical structure: positive symptoms, negative symptoms and disorganization. The latter one is the newest and the least studied. Our aim was to discriminate disorganization in schizophrenia clinical picture and to identify its distinctive biological and socio-psychological particularities and associated genetic and environmental factors. We used SAPS/SANS psychometrical scales, scales for the assessment of patient's compliance, insight, social functioning, life quality. Neuropsychological tests included Wisconsin Card Sorting Test (WCST), Stroop Color-Word test. Neurophysiological examination included registration of P300 wave of the evoked cognitive auditory potentials. Environmental factors related to patient's education, family, surrounding and nicotine use, as well as subjectively significant traumatic events in childhood and adolescence were assessed. Using PCR we detected SNP of genes related to the systems of neurotransmission (COMT, SLC6A4 and DRD2), inflammatory response (IL6, TNF), cellular detoxification (GSTM1, GSTT1), DNA methylation (MTHFR, DNMT3b, DNMT1). Disorganization is associated with early schizophrenia onset and history of psychosis in family, low level of insight and compliance, high risk of committing delicts, distraction errors in WCST, lengthened P300 latency of evoked cognitive auditory potentials, low-functional alleles of genes MTHFR (rs1801133) and DNMT3b (rs2424913), high level of urbanicity and psychotraumatic events at early age. Severe disorganization at the stage of schizophrenia clinical outcome is associated with the set of specific biological and social-psychological characteristics that indicate its epigenetic nature and maladaptive social significance. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  18. Clinical potentials of methylator phenotype in stage 4 high-risk neuroblastoma: an open challenge.

    PubMed

    Banelli, Barbara; Merlo, Domenico Franco; Allemanni, Giorgio; Forlani, Alessandra; Romani, Massimo

    2013-01-01

    Approximately 20% of stage 4 high-risk neuroblastoma patients are alive and disease-free 5 years after disease onset while the remaining experience rapid and fatal progression. Numerous findings underline the prognostic role of methylation of defined target genes in neuroblastoma without taking into account the clinical and biological heterogeneity of this disease. In this report we have investigated the methylation of the PCDHB cluster, the most informative member of the "Methylator Phenotype" in neuroblastoma, hypothesizing that if this epigenetic mark can predict overall and progression free survival in high-risk stage 4 neuroblastoma, it could be utilized to improve the risk stratification of the patients, alone or in conjunction with the previously identified methylation of the SFN gene (14.3.3sigma) that can accurately predict outcome in these patients. We have utilized univariate and multivariate models to compare the prognostic power of PCDHB methylation in terms of overall and progression free survival, quantitatively determined by pyrosequencing, with that of other markers utilized for the patients' stratification utilizing methylation thresholds calculated on neuroblastoma at stage 1-4 and only on stage 4, high-risk patients. Our results indicate that PCDHB accurately distinguishes between high- and intermediate/low risk stage 4 neuroblastoma in agreement with the established risk stratification criteria. However PCDHB cannot predict outcome in the subgroup of stage 4 patients at high-risk whereas methylation levels of SFN are suggestive of a "methylation gradient" associated with tumor aggressiveness as suggested by the finding of a higher threshold that defines a subset of patients with an extremely severe disease (OS <24 months). Because of the heterogeneity of neuroblastoma we believe that clinically relevant methylation markers should be selected and tested on homogeneous groups of patients rather than on patients at all stages.

  19. Collaborative communication: learning from advanced clinical practice patient consultations.

    PubMed

    Barratt, Julian

    2018-04-28

    Advanced nurse practitioners, and nurses aspiring to this role, are required to understand how to communicate effectively and on a collaborative basis with patients and carers during consultations, with the aim of enhancing patient outcomes such as improved patient satisfaction, ability to self-manage healthcare needs and adherence to care plans. This article explores collaborative communication in consultations and how best to achieve this, using the author's doctoral observational research based on the findings of a mixed methods observational study of communication in advanced clinical practice patient consultations. ©2018 RCN Publishing Company Ltd. All rights reserved. Not to be copied, transmitted or recorded in any way, in whole or part, without prior permission of the publishers.

  20. Appendiceal goblet cell carcinoid: common errors in staging and clinical interpretation with a proposal for an improved terminology.

    PubMed

    Wen, Kwun Wah; Hale, Gillian; Shafizadeh, Nafis; Hosseini, Mojgan; Huang, Anne; Kakar, Sanjay

    2017-07-01

    Goblet cell carcinoid (GCC) is staged and treated as adenocarcinoma (AC) and not as neuroendocrine tumor (NET) or neuroendocrine carcinoma. The term carcinoid may lead to incorrect interpretation as NET. The aim of the study was to explore pitfalls in staging and clinical interpretation of GCC and mixed GCC-AC, and propose strategies to avoid common errors. Diagnostic terminology, staging, and clinical interpretation were evaluated in 58 cases (27 GCCs, 31 mixed GCC-ACs). Opinions were collected from 23 pathologists using a survey. Clinical notes were reviewed to assess the interpretation of pathology diagnoses by oncologists. NET staging was incorrectly used for 25% of GCCs and 5% of mixed GCC-ACs. In the survey, 43% of pathologists incorrectly indicated that NET staging is applicable to GCCs, and 43% incorrectly responded that Ki-67 proliferation index is necessary for GCC grading. Two cases each of GCC and mixed GCC-AC were incorrectly interpreted as neuroendocrine neoplasms by oncologists, and platinum-based therapy was considered for 2 GCC-AC cases because of the mistaken impression of neuroendocrine carcinoma created by use of the World Health Organization 2010 term mixed adenoneuroendocrine carcinoma. The term carcinoid in GCC and use of mixed adenoneuroendocrine carcinoma for mixed GCC-AC lead to errors in staging and treatment. We propose that goblet cell carcinoid should be changed to goblet cell carcinoma, whereas GCC with AC should be referred to as mixed GCC-AC with a comment about the proportion of each component and the histologic subtype of AC. This terminology will facilitate appropriate staging and clinical management, and avoid errors in interpretation. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

    PubMed

    Mohammadianpanah, Mohammad; Ashouri, Yaghoub; Hoseini, Sare; Amadloo, Niloofar; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Nasrolahi, Hamid; Mosalaei, Ahmad; Omidvari, Shapour; Ansari, Mansour; Mosleh-Shirazi, Mohammad Amin

    2012-04-01

    This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

  2. Development and testing of a de novo clinical staging system for podoconiosis (endemic non-filarial elephantiasis)

    PubMed Central

    Tekola, Fasil; Ayele, Zewdu; HaileMariam, Dereje; Fuller, Claire; Davey, Gail

    2010-01-01

    Summary Background Podoconiosis (endemic non-filarial elephantiasis) is a geochemical disease in individuals exposed to red-clay soil. Despite the prevalence and public health importance of podoconiosis, there is as yet no accepted clinical staging system. Objective We aimed to develop and test a robust clinical staging system for podoconiosis. Methods We adapted the Dreyer system for staging filarial lymphoedema and tested it in four re-iterative field tests conducted in an area of high podoconiosis prevalence in Southern Ethiopia. The system finally arrived at has five stages according to proximal spread of disease and presence of dermal nodules, ridges and bands. We measured the one-week repeatability and the inter-observer agreement of the final staging system. Results We have developed a five-stage system that is readily understood by community workers with little health training. Kappa for one-week repeatability was 0.88 (95% CI 0.80 to 0.96), Kappa for agreement between health professionals was 0.71 (95% CI 0.60 to 0.82), while that between health professionals and community podoconiosis agents without formal health training averaged 0.64 (95% CI 0.52 to 0.78). Conclusions A simple staging system with good inter-observer agreement and repeatability has been developed to assist in the management and further study of podoconiosis. PMID:18721188

  3. Baseline clinical predictors of antitumor response to the PARP inhibitor olaparib in germline BRCA1/2 mutated patients with advanced ovarian cancer.

    PubMed

    Rafii, Saeed; Gourley, Charlie; Kumar, Rajiv; Geuna, Elena; Ern Ang, Joo; Rye, Tzyvia; Chen, Lee-May; Shapira-Frommer, Ronnie; Friedlander, Michael; Matulonis, Ursula; De Greve, Jacques; Oza, Amit M; Banerjee, Susana; Molife, L Rhoda; Gore, Martin E; Kaye, Stan B; Yap, Timothy A

    2017-07-18

    The PARP inhibitor olaparib was recently granted Food and Drug Administration (FDA) accelerated approval in patients with advanced BRCA1/2 mutation ovarian cancer. However, antitumor responses are observed in only approximately 40% of patients and the impact of baseline clinical factors on response to treatment remains unclear. Although platinum sensitivity has been suggested as a marker of response to PARP inhibitors, patients with platinum-resistant disease still respond to olaparib. 108 patients with advanced BRCA1/2 mutation ovarian cancers were included. The interval between the end of the most recent platinum chemotherapy and PARPi (PTPI) was used to predict response to olaparib independent of conventional definition of platinum sensitivity. RECIST complete response (CR) and partial response (PR) rates were 35% in patients with platinum-sensitive versus 13% in platinum-resistant (p<0.005). Independent of platinum sensitivity status, the RECIST CR/PR rates were 42% in patients with PTPI greater than 52 weeks and 18% in patients with PTPI less than 52 weeks (p=0.016). No association was found between baseline clinical factors such as FIGO staging, debulking surgery, BRCA1 versus BRCA2 mutations, prior history of breast cancer and prior chemotherapy for breast cancer, and the response to olaparib. We conducted an international multicenter retrospective study to investigate the association between baseline clinical characteristics of patients with advanced BRCA1/2 mutation ovarian cancers from eight different cancer centers and their antitumor response to olaparib. PTPI may be used to refine the prediction of response to PARP inhibition based on the conventional categorization of platinum sensitivity.

  4. Advances in bioartificial liver assist devices.

    PubMed

    Patzer, J F

    2001-11-01

    Rapid advances in development of bioartificial liver assist devices (BLADs) are exciting clinical interest in the application of BLAD technology for support of patients with acute liver failure. Four devices (Circe Biomedical HepatAssist, Vitagen ELAD, Gerlach BELS, and Excorp Medical BLSS) that rely on hepatocytes cultured in hollow-fiber membrane technology are currently in various stages of clinical evaluation. Several alternative approaches for culture and perfusion of hepatocytes have been evaluated in preclinical, large animal models of liver failure, or at a laboratory scale. Engineering design issues with respect to xenotransplantation, BLAD perfusion, hepatocyte functionality and culture maintenance, and ultimate distribution of a BLAD to a clinical site are delineated.

  5. Staging of breast cancer and the advanced applications of digital mammogram: what the physician needs to know?

    PubMed

    Helal, Maha H; Mansour, Sahar M; Zaglol, Mai; Salaleldin, Lamia A; Nada, Omniya M; Haggag, Marwa A

    2017-03-01

    To study the role of advanced applications of digital mammogram, whether contrast-enhanced spectral mammography (CESM) or digital breast tomosynthesis (DBT), in the "T" staging of histologically proven breast cancer before planning for treatment management. In this prospective analysis, we evaluated 98 proved malignant breast masses regarding their size, multiplicity and the presence of associated clusters of microcalcifications. Evaluation methods included digital mammography (DM), 3D tomosynthesis and CESM. Traditional DM was first performed then in a period of 10-14-day interval; breast tomosynthesis and contrast-based mammography were performed for the involved breast only. Views at tomosynthesis were acquired in a "step-and-shoot" tube motion mode to produce multiple (11-15), low-dose images and in contrast-enhanced study, low-energy (22-33 kVp) and high-energy (44-49 kVp) exposures were taken after the i.v. injection of the contrast agent. Operative data were the gold standard reference. Breast tomosynthesis showed the highest accuracy in size assessment (n = 69, 70.4%) than contrast-enhanced (n = 49, 50%) and regular mammography (n = 59, 60.2%). Contrast-enhanced mammography presented the least performance in assessing calcifications, yet it was most sensitive in the detection of multiplicity (92.3%), followed by tomosynthesis (77%) and regular mammography (53.8%). The combined analysis of the three modalities provided an accuracy of 74% in the "T" staging of breast cancer. The combined application of tomosynthesis and contrast-enhanced digital mammogram enhanced the performance of the traditional DM and presented an informative method in the staging of breast cancer. Advances in knowledge: Staging and management planning of breast cancer can divert according to tumour size, multiplicity and the presence of microcalcifications. DBT shows sharp outlines of the tumour with no overlap tissue and spots microcalcifications. Contrast

  6. Staging of breast cancer and the advanced applications of digital mammogram: what the physician needs to know?

    PubMed Central

    Helal, Maha H; Zaglol, Mai; Salaleldin, Lamia A; Nada, Omniya M; Haggag, Marwa A

    2017-01-01

    Objective: To study the role of advanced applications of digital mammogram, whether contrast-enhanced spectral mammography (CESM) or digital breast tomosynthesis (DBT), in the “T” staging of histologically proven breast cancer before planning for treatment management. Methods: In this prospective analysis, we evaluated 98 proved malignant breast masses regarding their size, multiplicity and the presence of associated clusters of microcalcifications. Evaluation methods included digital mammography (DM), 3D tomosynthesis and CESM. Traditional DM was first performed then in a period of 10–14-day interval; breast tomosynthesis and contrast-based mammography were performed for the involved breast only. Views at tomosynthesis were acquired in a “step-and-shoot” tube motion mode to produce multiple (11–15), low-dose images and in contrast-enhanced study, low-energy (22–33 kVp) and high-energy (44–49 kVp) exposures were taken after the i.v. injection of the contrast agent. Operative data were the gold standard reference. Results: Breast tomosynthesis showed the highest accuracy in size assessment (n = 69, 70.4%) than contrast-enhanced (n = 49, 50%) and regular mammography (n = 59, 60.2%). Contrast-enhanced mammography presented the least performance in assessing calcifications, yet it was most sensitive in the detection of multiplicity (92.3%), followed by tomosynthesis (77%) and regular mammography (53.8%). The combined analysis of the three modalities provided an accuracy of 74% in the “T” staging of breast cancer. Conclusion: The combined application of tomosynthesis and contrast-enhanced digital mammogram enhanced the performance of the traditional DM and presented an informative method in the staging of breast cancer. Advances in knowledge: Staging and management planning of breast cancer can divert according to tumour size, multiplicity and the presence of microcalcifications. DBT shows sharp outlines of the tumour with no overlap

  7. Comparison of Oral Contrast-Enhanced Transabdominal Ultrasound Imaging With Transverse Contrast-Enhanced Computed Tomography in Preoperative Tumor Staging of Advanced Gastric Carcinoma.

    PubMed

    He, Xuemei; Sun, Jing; Huang, Xiaoling; Zeng, Chun; Ge, Yinggang; Zhang, Jun; Wu, Jingxian

    2017-12-01

    This study assessed the diagnostic performance of transabdominal oral contrast-enhanced ultrasound (US) imaging for preoperative tumor staging of advanced gastric carcinoma by comparing it with transverse contrast-enhanced computed tomography (CT). This retrospective study included 42 patients with advanced gastric cancer who underwent laparoscopy, radical surgery, or palliative surgery because of serious complications and had a body mass index of less than 25 kg/m 2 . A cereal-based oral contrast agent was used for transabdominal oral contrast-enhanced US. Retrospective analyses were conducted using preoperative tumor staging data acquired by either transabdominal oral contrast-enhanced US or transverse contrast-enhanced CT. Both contrast-enhanced US and contrast-enhanced CT examinations were reviewed by 2 experienced radiologists independently for preoperative tumor staging according to the seventh edition of the TNM classification. The accuracy, sensitivity, and specificity were calculated by comparing the results of contrast-enhanced US and contrast-enhanced CT with pathologic findings. The overall accuracies of the imaging modalities were compared by the McNemar test. No significant difference was noted in the overall accuracy of transabdominal oral contrast-enhanced US (86% [36 of 42]) and transverse contrast-enhanced CT (83% [35 of 42] P > .999). For stage T2 to T4 gastric cancer, the accuracies of transabdominal oral contrast-enhanced US were 88%, 86%, and 98%, respectively, and those of transverse contrast-enhanced CT were 93%, 83%, and 90%. The overall accuracy of transabdominal oral contrast-enhanced US was comparable with that of transverse contrast-enhanced CT for preoperative tumor staging of advanced gastric cancer. © 2017 by the American Institute of Ultrasound in Medicine.

  8. Esophageal cancer: anatomic particularities, staging, and imaging techniques.

    PubMed

    Encinas de la Iglesia, J; Corral de la Calle, M A; Fernández Pérez, G C; Ruano Pérez, R; Álvarez Delgado, A

    2016-01-01

    Cancer of the esophagus is a tumor with aggressive behavior that is usually diagnosed in advanced stages. The absence of serosa allows it to spread quickly to neighboring mediastinal structures, and an extensive lymphatic drainage network facilitates tumor spread even in early stages. The current TNM classification, harmonized with the classification for gastric cancer, provides new definitions for the anatomic classification, adds non-anatomic characteristics of the tumor, and includes tumors of the gastroesophageal junction. Combining endoscopic ultrasound, computed tomography, positron emission tomography, and magnetic resonance imaging provides greater accuracy in determining the initial clinical stage, and these imaging techniques play an essential role in the selection, planning, and evaluation of treatment. In this article, we review some particularities that explain the behavior of this tumor and we describe the current TNM staging system; furthermore, we discuss the different imaging tests available for its evaluation and include a diagnostic algorithm. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Does aggressive surgical resection improve survival in advanced stage 3 and 4 neuroblastoma? A systematic review and meta-analysis.

    PubMed

    Mullassery, Dhanya; Farrelly, Paul; Losty, Paul D

    2014-11-01

    The role of surgery in the management of advanced staged neuroblastoma (NBL) is controversial. A systematic review and meta-analysis is reported to address robust evidence for curative "gross total tumor resection" (GTR) in Stage 3 and Stage 4 neuroblastoma. Studies were identified using Medline, Embase, and Cochrane databases using pre-specified search terms. Primary outcomes were 5-year overall (OS) and disease-free survival (DFS) after GTR and subtotal resection (STR) in Stage 3 or 4 NBL. Data were analyzed using Review Manager. The Mantel-Haenszel method and a random effects model was utilized to calculate odds ratios (95% CI). Fifteen studies (five Stage 3 and 13 Stage 4) met full inclusion criteria. The pooled odds ratio for 5 year OS in Stage 3 following GTR compared to STR was 2.4 (95% CI 1.19-4.85). In Stage 4 disease, the pooled odds ratio for 5 year overall survival (OS) following GTR compared to STR was 1.65 (95% CI 0.96-1.91); a pooled odds ratio for 5 year DFS following GTR compared to STR was 1.55 (95% CI 1.12-2.14). A clear survival benefit is shown for GTR over STR in Stage 3 NBL only. Though some advantage can be demonstrated for GTR as defined by DFS in Stage 4 NBL GTR did not significantly improve OS in Stage 4 disease.

  10. Use and Yield of Baseline Imaging and Laboratory Testing in Stage II Breast Cancer

    PubMed Central

    Guo, Hao; Sutton, Jazmine; Spring, Laura; Faig, Jennifer; Dagogo-Jack, Ibiayi; Battelli, Chiara; Houlihan, Mary Jane; Yeh, Tsai-Chu; Come, Steven E.; Lin, Nancy U.

    2016-01-01

    Background. Despite guideline recommendations, baseline laboratory testing and advanced imaging are widely ordered in clinical practice to stage asymptomatic patients with clinical stage II breast cancer (BC). Materials and Methods. A retrospective study at two academic centers in Boston, Massachusetts, between 2006 and 2007 explored the use, results, and implications of laboratory tests, tumor markers, and imaging in patients with clinical stage II BC. Results. Among 411 patients, 233 (57%) had liver function testing, 134 (33%) had tumor marker tests, and 237 (58%) had computed tomography (CT) as part of their initial diagnostic workup. Median age was 52 (range, 23–90 years). On multivariable analysis, young age, more advanced stage, and tumor subtype (human epidermal growth receptor-positive [HER2+] and triple-negative breast cancer [TNBC]) were significantly associated with baseline CT. The rate of detection of true metastatic disease with use of baseline staging imaging was 2.1% (95% confidence interval, 0.7%–5%). It was 2.2% (3 of 135) for estrogen receptor/progesterone receptor-positive disease, 1.9% (1 of 54) for HER2+ disease, and 2.1% (1 of 48) for TNBC. At 5 years of follow-up, 46 of 406 patients were diagnosed with metastatic breast cancer. Thirty-four of 46 (73.9%) who developed recurrent disease had imaging at their initial diagnosis, and of these, five had abnormalities on their initial imaging that was correlated with where they developed metastatic disease. Conclusion. In this cohort of women with stage II BC, staging imaging at diagnosis had a low yield in detecting distant metastases (2.1%). The detection rate was not higher with HER2+ disease or TNBC, despite the trend that patients with these subtypes were more likely to undergo imaging. Implications for Practice: Despite guideline recommendations, asymptomatic patients with stage II breast cancer (BC) often undergo staging imaging with computed tomography, bone scanning, or positron

  11. Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging

    PubMed Central

    Gomaa, Asmaa I; Al-Khatib, Alzhraa; Abdel-Razek, Wael; Hashim, Mohammed Saad; Waked, Imam

    2015-01-01

    AIM: To assess how ascites and alpha-fetoprotein (AFP) added to the Barcelona Clinic Liver Cancer (BCLC) staging predict hepatocellular carcinoma survival. METHODS: The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh (CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data (including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed. RESULTS: At the time the data were censored, 123/496 (24.8%) and 218/564 (38.6%) patients with BCLC stages A and B, respectively, had died. Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo [95% confidence interval (95%CI): 29.7-32.3] and 22.7 mo (95%CI: 20.7-24.8), respectively. The presence of ascites, multiple focal lesions, large tumor size, AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis (P < 0.001). Among stage A patients, 18% had ascites, 33% had AFP ≥ 200 ng/mL, and 8% had both. Their median survival in the presence of ascites was shorter if AFP was ≥ 200 ng/mL (19 mo vs 24 mo), and in the absence of ascites

  12. Ascites and alpha-fetoprotein improve prognostic performance of Barcelona Clinic Liver Cancer staging.

    PubMed

    Gomaa, Asmaa I; Al-Khatib, Alzhraa; Abdel-Razek, Wael; Hashim, Mohammed Saad; Waked, Imam

    2015-05-14

    To assess how ascites and alpha-fetoprotein (AFP) added to the Barcelona Clinic Liver Cancer (BCLC) staging predict hepatocellular carcinoma survival. The presence of underlying cirrhosis, ascites and encephalopathy, Child-Turcotte-Pugh (CTP) score, the number of nodules, and the maximum diameter of the largest nodule were determined at diagnosis for 1060 patients with hepatocellular carcinoma at a tertiary referral center for liver disease in Egypt. Demographic information, etiology of liver disease, and biochemical data (including serum bilirubin, albumin, international normalized ratio, alanine and aspartate aminotransferases, and AFP) were evaluated. Staging of the tumor was determined at the time of diagnosis using the BCLC staging system; 496 patients were stage A and 564 patients were stage B. Patients with mild ascites on initial ultrasound, computed tomography, or clinical examination, and who had a CTP score ≤ 9 were included in this analysis. All patients received therapy according to the recommended treatment based on the BCLC stage, and were monitored from the time of diagnosis to the date of death or date of data collection. The effect of the presence of ascites and AFP level on survival was analyzed. At the time the data were censored, 123/496 (24.8%) and 218/564 (38.6%) patients with BCLC stages A and B, respectively, had died. Overall mean survival of the BCLC A and B patients during a three-year follow-up period was 31 mo [95% confidence interval (95%CI): 29.7-32.3] and 22.7 mo (95%CI: 20.7-24.8), respectively. The presence of ascites, multiple focal lesions, large tumor size, AFP level and CTP score were independent predictors of survival for the included patients on multivariate analysis (P < 0.001). Among stage A patients, 18% had ascites, 33% had AFP ≥ 200 ng/mL, and 8% had both. Their median survival in the presence of ascites was shorter if AFP was ≥ 200 ng/mL (19 mo vs 24 mo), and in the absence of ascites, patients with AFP ≥ 200

  13. Magnetic Resonance Imaging (MRI) and Positron Emission Tomography (PET)/MRI for Lung Cancer Staging.

    PubMed

    Ohno, Yoshiharu; Koyama, Hisanobu; Lee, Ho Yun; Yoshikawa, Takeshi; Sugimura, Kazuro

    2016-07-01

    Tumor, lymph node, and metastasis (TNM) classification of lung cancer is typically performed with the TNM staging system, as recommended by the Union Internationale Contre le Cancer (UICC), the American Joint Committee on Cancer (AJCC), and the International Association for the Study of Lung Cancer (IASLC). Radiologic examinations for TNM staging of lung cancer patients include computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography with 2-[fluorine-18] fluoro-2-deoxy-D-glucose (FDG-PET), and FDG-PET combined with CT (FDG-PET/CT) and are used for pretherapeutic assessments. Recent technical advances in MR systems, application of fast and parallel imaging and/or introduction of new MR techniques, and utilization of contrast media have markedly improved the diagnostic utility of MRI in this setting. In addition, FDG-PET can be combined or fused with MRI (PET/MRI) for clinical practice. This review article will focus on these recent advances in MRI as well as on PET/MRI for lung cancer staging, in addition to a discussion of their potential and limitations for routine clinical practice in comparison with other modalities such as CT, FDG-PET, and PET/CT.

  14. Methods for Surgical Targeting of the STN in Early-Stage Parkinson’s Disease

    PubMed Central

    Camalier, Corrie R.; Konrad, Peter E.; Gill, Chandler E.; Kao, Chris; Remple, Michael R.; Nasr, Hana M.; Davis, Thomas L.; Hedera, Peter; Phibbs, Fenna T.; Molinari, Anna L.; Neimat, Joseph S.; Charles, David

    2013-01-01

    Patients with Parkinson’s disease (PD) experience progressive neurological decline, and future interventional therapies are thought to show most promise in early stages of the disease. There is much interest in therapies that target the subthalamic nucleus (STN) with surgical access. While locating STN in advanced disease patients (Hoehn–Yahr Stage III or IV) is well understood and routinely performed at many centers in the context of deep brain stimulation surgery, the ability to identify this nucleus in early-stage patients has not previously been explored in a sizeable cohort. We report surgical methods used to target the STN in 15 patients with early PD (Hoehn–Yahr Stage II), using a combination of image guided surgery, microelectrode recordings, and clinical responses to macrostimulation of the region surrounding the STN. Measures of electrophysiology (firing rates and root mean squared activity) have previously been found to be lower than in later-stage patients, however, the patterns of electrophysiology seen and dopamimetic macrostimulation effects are qualitatively similar to those seen in advanced stages. Our experience with surgical implantation of Parkinson’s patients with minimal motor symptoms suggest that it remains possible to accurately target the STN in early-stage PD using traditional methods. PMID:24678307

  15. Student and Preceptor Advancement in a Dedicated Education Site: Innovation in Clinical Education for Advanced Practice Nurses.

    PubMed

    Hall, Katherine C; Diffenderfer, Sandy K; Stidham, April; Mullins, Christine M

    2018-04-19

    In the 1990s, dedicated education units transformed undergraduate preceptorships, but graduate preceptorships remain static. The dyadic nurse practitioner preceptorship model supports an environment where faculty, students, and preceptors may overlook nuances that affect the teaching-learning process. This article describes an innovative clinical education model, Student and Preceptor Advancement in a Dedicated Education Site, designed to improve preceptorships for advanced practice nurses. The focus is on adaptations made to facilitate use in advanced practice nursing programs.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal.

  16. Single stage, low noise, advanced technology fan. Volume 1: Aerodynamic design

    NASA Technical Reports Server (NTRS)

    Sullivan, T. J.; Younghans, J. L.; Little, D. R.

    1976-01-01

    The aerodynamic design for a half-scale fan vehicle, which would have application on an advanced transport aircraft, is described. The single stage advanced technology fan was designed to a pressure ratio of 1.8 at a tip speed of 503 m/sec 11,650 ft/sec). The fan and booster components are designed in a scale model flow size convenient for testing with existing facility and vehicle hardware. The design corrected flow per unit annulus area at the fan face is 215 kg/sec sq m (44.0 lb m/sec sq ft) with a hub-tip ratio of 0.38 at the leading edge of the fan rotor. This results in an inlet corrected airflow of 117.9 kg/sec (259.9 lb m/sec) for the selected rotor tip diameter if 90.37 cm (35.58 in.). The variable geometry inlet is designed utilizing a combination of high throat Mach number and acoustic treatment in the inlet diffuser for noise suppression (hybrid inlet). A variable fan exhaust nozzle was assumed in conjunction with the variable inlet throat area to limit the required area change of the inlet throat at approach and hence limit the overall diffusion and inlet length. The fan exit duct design was primarily influenced by acoustic requirements, including length of suppressor wall treatment; length, thickness and position on a duct splitter for additional suppressor treatment; and duct surface Mach numbers.

  17. Frequency, predictors, and outcomes of urine drug testing among patients with advanced cancer on chronic opioid therapy at an outpatient supportive care clinic.

    PubMed

    Arthur, Joseph A; Edwards, Tonya; Lu, Zhanni; Reddy, Suresh; Hui, David; Wu, Jimin; Liu, Diane; Williams, Janet L; Bruera, Eduardo

    2016-12-01

    Data are limited on the use and outcomes of urine drug tests (UDTs) among patients with advanced cancer. The main objective of this study was to determine the factors associated with UDT ordering and results in outpatients with advanced cancer. A retrospective chart review was conducted of 1058 patients who attended an outpatient supportive care clinic from March 2014 to November 2015. Sixty-one patients who were receiving chronic opioid therapy and underwent UDTs were identified. A control group of 120 patients who did not undergo UDTs was selected for comparison. Sixty-one of 1058 patients (6%) underwent UDTs, and 33 of 61 patients (54%) had abnormal results. Multivariate analysis indicated that the odds ratio for UDT ordering was 3.9 in patients who had positive Cut Down, Annoyed, Guilty, and Eye Opener (CAGE) questionnaire results (P = .002), 4.41 in patients aged < 45 years (P < .001), 5.58 in patients who had moderate-to-severe pain (Edmonton Symptom Assessment Scale pain scores ≥4; P < .001), 0.27 in patients with advanced-stage cancer, (P = .008), and 0.25 in patients who had moderate-to-severe fatigue (P = .001). Among 52 abnormal UDT results in 33 patients, the most common opioid findings were prescribed opioids absent in urine (14 of 52 tests; 27%) and unprescribed opioids in urine (13 of 52 tests; 25%). UDTs were used infrequently among outpatients with advanced cancer who were receiving chronic opioid therapy. Younger age, positive CAGE questionnaire results, early stage cancer or no evidence of disease status, higher pain intensity, and lower fatigue scores were significant predictors of UDT ordering. More than 50% of UDT results were abnormal. More research is necessary to better characterize aberrant opioid use in patients with advanced cancer. Cancer 2016;122:3732-9. © 2016 American Cancer Society. © 2016 American Cancer Society.

  18. A prospective evaluation of the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography staging on survival for patients with locally advanced esophageal cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Blackstock, A. William; Farmer, Michael R.; Lovato, James

    2006-02-01

    Purpose: To determine the impact of 18-F-fluoro-deoxy-D-glucose positron emission tomography (FDG-PET) in the staging and prognosis of patients with locally advanced esophageal cancer (LAEC). Methods and Materials: Between January 2000 and October 2004, all patients with LAEC evaluated in the Department of Radiation Oncology were considered for enrollment into a Phase II trial of preoperative chemoradiation. Entry required a staging whole-body FDG-PET scan. Results: One hundred ten consecutive patients were evaluated; 38 were ineligible for reasons including treatment elsewhere, prior malignancy, or refusal of treatment. After conventional staging (clinical examination, endoscopic ultrasound, and chest/abdominal computerized tomography), 33 patients were ineligiblemore » because of metastatic disease or poor performance status. Of the remaining 39 patients, 23 were confirmed to have LAEC after FDG-PET staging and were treated in the Phase II trial (Cohort I). Sixteen patients, however, had FDG-PET findings consistent with occult metastatic disease and were deemed ineligible for the trial but were treated with curative intent (Cohort II). The 2-year survival rate for the 23 patients in Cohort I was 64%, compared with 17% (p = 0.003) for patients in Cohort II (FDG-PET positive). Conclusions: More than one-third of patients determined to have LAEC with conventional staging were upstaged with the use of FDG-PET. Despite comparable therapy, upstaging with FDG-PET predicts poor 2-year survival.« less

  19. Estimation of Direct Melanoma-related Costs by Disease Stage and by Phase of Diagnosis and Treatment According to Clinical Guidelines.

    PubMed

    Buja, Alessandra; Sartor, Gino; Scioni, Manuela; Vecchiato, Antonella; Bolzan, Mario; Rebba, Vincenzo; Sileni, Vanna Chiarion; Palozzo, Angelo Claudio; Montesco, Maria; Del Fiore, Paolo; Baldo, Vincenzo; Rossi, Carlo Riccardo

    2018-02-07

    Cutaneous melanoma is a major concern in terms of healthcare systems and economics. The aim of this study was to estimate the direct costs of melanoma by disease stage, phase of diagnosis, and treatment according to the pre-set clinical guidelines drafted by the AIOM (Italian Medical Oncological Association). Based on the AIOM guidelines for malignant cutaneous melanoma, a highly detailed decision-making model was developed describing the patient's pathway from diagnosis through the subsequent phases of disease staging, surgical and medical treatment, and follow-up. The model associates each phase potentially involving medical procedures with a likelihood measure and a cost, thus enabling an estimation of the expected costs by disease stage and clinical phase of melanoma diagnosis and treatment according to the clinical guidelines. The mean per-patient cost of the whole melanoma pathway (including one year of follow-up) ranged from €149 for stage 0 disease to €66,950 for stage IV disease. The costs relating to each phase of the disease's diagnosis and treatment depended on disease stage. It is essential to calculate the direct costs of managing malignant cutaneous melanoma according to clinical guidelines in order to estimate the economic burden of this disease and to enable policy-makers to allocate appropriate resources.

  20. Treatment of Locally Advanced Vaginal Cancer With Radiochemotherapy and Magnetic Resonance Image-Guided Adaptive Brachytherapy: Dose-Volume Parameters and First Clinical Results

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dimopoulos, Johannes C.A.; Schmid, Maximilian P., E-mail: maximilian.schmid@akhwien.at; Fidarova, Elena

    2012-04-01

    Purpose: To investigate the clinical feasibility of magnetic resonance image-guided adaptive brachytherapy (IGABT) for patients with locally advanced vaginal cancer and to report treatment outcomes. Methods and Materials: Thirteen patients with vaginal cancer were treated with external beam radiotherapy (45-50.4 Gy) plus IGABT with or without chemotherapy. Distribution of International Federation of Gynecology and Obstetrics stages among patients were as follows: 4 patients had Stage II cancer, 5 patients had Stage III cancer, and 4 patients had Stage IV cancer. The concept of IGABT as developed for cervix cancer was transferred and adapted for vaginal cancer, with corresponding treatment planningmore » and reporting. Doses were converted to the equivalent dose in 2 Gy, applying the linear quadratic model ({alpha}/{beta} = 10 Gy for tumor; {alpha}/{beta} = 3 for organs at risk). Endpoints studied were gross tumor volume (GTV), dose-volume parameters for high-risk clinical target volume (HRCTV), and organs at risk, local control (LC), adverse side effects, and survival. Results: The mean GTV ({+-} 1 standard deviation) at diagnosis was 45.3 ({+-}30) cm{sup 3}, and the mean GTV at brachytherapy was 10 ({+-}14) cm{sup 3}. The mean D90 for the HRCTV was 86 ({+-}13) Gy. The mean D2cc for bladder, urethra, rectum, and sigmoid colon were 80 ({+-}20) Gy, 76 ({+-}16) Gy, 70 ({+-}9) Gy, and 60 ({+-}9) Gy, respectively. After a median follow-up of 43 months (range, 19-87 months), one local recurrence and two distant metastases cases were observed. Actuarial LC and overall survival rates at 3 years were 92% and 85%. One patient with Stage IVA and 1 patient with Stage III disease experienced fistulas (one vesicovaginal, one rectovaginal), and 1 patient developed periurethral necrosis. Conclusions: The concept of IGABT, originally developed for treating cervix cancer, appears to be applicable to vaginal cancer treatment with only minor adaptations. Dose-volume parameters for

  1. Advancing the educational and career pathway for clinical trials nurses.

    PubMed

    Scott, Kathleen; White, Kathryn; Roydhouse, Jessica K

    2013-04-01

    Clinical trials nurses play a pivotal role in the conduct of clinical research, but the educational and career pathway for these nurses remains unclear. This article reports findings from a survey of nurses working in cancer clinical trials research in Australia. Most participants held postgraduate qualifications (42 of 61); however, clinical trials education was primarily attained through short professional development courses. Interest in pursuing trial-specific postgraduate education was high, but barriers were identified, including cost, time, and unclear benefit for career advancement. Job titles varied substantially, which is indicative of an unclear employment pathway. These findings suggest that initiatives to improve the educational and career pathway for clinical trials nurses are needed and should include the following: formal educational preparation, greater consistency in employment status, and clearer career progression. These strategies should be underpinned by broad professional recognition of the clinical trials nurse as a specialized nursing role. Copyright 2013, SLACK Incorporated.

  2. Efficacy and safety of crizotinib among Chinese EML4-ALK-positive, advanced-stage non-small cell lung cancer patients.

    PubMed

    Cao, Yabing; Xiao, Guangli; Qiu, Xibin; Ye, Sheng; Lin, Tongyu

    2014-01-01

    We report the efficacy and safety of crizotinib treatment among Chinese patients with advanced-stage NSCLC. We retrospectively analyzed patients with EML4-ALK positive advanced NSCLC who were treated with crizotinib from May 2012 to Aug 2013. Baseline clinical parameters, treatment protocol, response to therapy and survival were noted. The primary goal was to evaluate the efficacy of crizotinib in patients who were previously treated patients or who had poor ECOG performance status (PS). Forty patients were evaluable for safety and efficacy. Median age was 43 years, 100% had adenocarcinoma and stage IV disease, and 42.5% were female. Six patients received frontline treatment with crizotinib, 17 patients had 1 prior treatment, and 17 patients had more than 2 lines of prior treatment. Patients received a median of 5 cycles of treatment (range 1-15 cycles). After the first cycle, 92.5% (37/40) patients archived partial remission (PR). At the end of the follow-up period, the overall PR rate was 70% (28/40), and progression of disease (PD) occurred in 30% of patients (12/40). The median PFS was 28 weeks (95% CI 15.4 to 40.5 weeks), and median OS was 40 weeks (95% CI 38.6 to 49.3 weeks). The most frequent treatment-related AEs were vomiting (47.5%), vision disorder (27.5%) and increased ALT/AST (42%); most toxicities were Grade 1/2. Observed treatment-related Grade 3/4 AEs included increased ALT/AST (10%) and vomiting (5%). The EML4-ALK fusion rate and number of prior chemotherapy cycles did not appear to significantly affect the efficacy of crizotinib. However, PS 0-2 patients had improved PFS (50 weeks vs. 24 weeks, p = 0.015). Crizotinib was safe, well-tolerated, and effective in Chinese patients with pre-treated ALK-rearranged NSCLC. QOL was improved and PS appears to have an effect on the efficacy of crizotinib, but prior treatment and ALK fusion rate do not.

  3. Using large-scale Granger causality to study changes in brain network properties in the Clinically Isolated Syndrome (CIS) stage of multiple sclerosis

    NASA Astrophysics Data System (ADS)

    Abidin, Anas Z.; Chockanathan, Udaysankar; DSouza, Adora M.; Inglese, Matilde; Wismüller, Axel

    2017-03-01

    Clinically Isolated Syndrome (CIS) is often considered to be the first neurological episode associated with Multiple sclerosis (MS). At an early stage the inflammatory demyelination occurring in the CNS can manifest as a change in neuronal metabolism, with multiple asymptomatic white matter lesions detected in clinical MRI. Such damage may induce topological changes of brain networks, which can be captured by advanced functional MRI (fMRI) analysis techniques. We test this hypothesis by capturing the effective relationships of 90 brain regions, defined in the Automated Anatomic Labeling (AAL) atlas, using a large-scale Granger Causality (lsGC) framework. The resulting networks are then characterized using graph-theoretic measures that quantify various network topology properties at a global as well as at a local level. We study for differences in these properties in network graphs obtained for 18 subjects (10 male and 8 female, 9 with CIS and 9 healthy controls). Global network properties captured trending differences with modularity and clustering coefficient (p<0.1). Additionally, local network properties, such as local efficiency and the strength of connections, captured statistically significant (p<0.01) differences in some regions of the inferior frontal and parietal lobe. We conclude that multivariate analysis of fMRI time-series can reveal interesting information about changes occurring in the brain in early stages of MS.

  4. Placental cord drainage in the third stage of labor: Randomized clinical trial.

    PubMed

    Vasconcelos, Fernanda Barros; Katz, Leila; Coutinho, Isabela; Lins, Vanessa Laranjeiras; de Amorim, Melania Maria

    2018-01-01

    An open randomized clinical trial was developed at Instituto de Medicina Integral Prof. Fernando Figueira (IMIP) in Recife and at Petronila Campos Municipal Hospital in São Lourenço da Mata, both in Pernambuco, northeastern Brazil, including 226 low-risk pregnant women bearing a single, full-term, live fetus after delayed cord clamping, 113 randomized to placental cord drainage and 113 to a control group not submitted to this procedure. Women incapable of understanding the study objectives and those who went on to have an instrumental or cesarean delivery were excluded. Duration of the third stage of labor did not differ between the two groups (14.2±12.9 versus 13.7±12.1 minutes (mean ± SD), p = 0.66). Likewise, there was no significant difference in mean blood loss (248±254 versus 208±187ml, p = 0.39) or in postpartum hematocrit levels (32.3±4.06 versus 32.8±4.25mg/dl, p = 0.21). Furthermore, no differences were found between the groups for any of the secondary outcomes (postpartum hemorrhage >500 or >1000ml, therapeutic use of oxytocin, third stage >30 or 60 minutes, digital evacuation of the uterus or curettage, symptoms of postpartum anemia and maternal satisfaction). Placental cord drainage had no effect in reducing duration or blood loss during the third stage of labor. ClinicalTrials.gov: www.clinicaltrial.gov, NCT01655576.

  5. Comprehensive Clinical Staging for Resectable Lung Cancer: Clinicopathological Correlations and the Role of Brain MRI.

    PubMed

    Vernon, Jordyn; Andruszkiewicz, Nicole; Schneider, Laura; Schieman, Colin; Finley, Christian J; Shargall, Yaron; Fahim, Christine; Farrokhyar, Forough; Hanna, Waël C

    2016-11-01

    In our model of comprehensive clinical staging (CCS) for lung cancer, patients with a computerized tomography scan of the chest and upper abdomen not showing distant metastases will then routinely undergo whole body positron emission tomography/computerized tomography and magnetic resonance imaging (MRI) of the brain before any therapeutic decision. Our aim was to determine the accuracy of CCS and the value of brain MRI in this population. A retrospective analysis of a prospectively entered database was performed for all patients who underwent lung cancer resection from January 2012 to June 2014. Demographics, clinical and pathological stage (seventh edition of the American Joint Committee on Cancer/Union for International Cancer Control tumor, node, and metastasis staging manual), and costs of staging were collected. Correlation between clinical and pathological stage was determined. Of 315 patients with primary lung cancer, 55.6% were female and the mean age was 70 ± 9.6 years. When correlation was analyzed without consideration for substages A and B, 49.8% of patients (158 of 315) were staged accurately, 39.7% (125 of 315) were overstaged, and 10.5% (32 of 315) were understaged. Only 4.7% of patients (15 of 315) underwent surgery without appropriate neoadjuvant treatment. Preoperative brain MRI detected asymptomatic metastases in four of 315 patients (1.3%). At a median postoperative follow-up of 19 months (range 6-43), symptomatic brain metastases developed in seven additional patients. The total cost of CCS in Canadian dollars was $367,292 over the study period, with $117,272 (31.9%) going toward brain MRI. CCS is effective for patients with resectable lung cancer, with less than 5% of patients being denied appropriate systemic treatment before surgery. Brain MRI is a low-yield and high-cost intervention in this population, and its routine use should be questioned. Copyright © 2016 International Association for the Study of Lung Cancer. Published by

  6. Mechanical design of a precision linear flexural stage for 3D x-ray diffraction microscope at the Advanced Photon Source

    NASA Astrophysics Data System (ADS)

    Shu, D.; Liu, W.; Kearney, S.; Anton, J.; Tischler, J. Z.

    2015-09-01

    The 3-D X-ray diffraction microscope is a new nondestructive tool for the three-dimensional characterization of mesoscopic materials structure. A flexural-pivot-based precision linear stage has been designed to perform a wire scan as a differential aperture for the 3-D diffraction microscope at the Advanced Photon Source, Argonne National Laboratory. The mechanical design and finite element analyses of the flexural stage, as well as its initial mechanical test results with laser interferometer are described in this paper.

  7. Genome-Level Determination of Plasmodium falciparum Blood-Stage Targets of Malarial Clinical Immunity in the Peruvian Amazon

    PubMed Central

    Torres, Katherine J.; Castrillon, Carlos E.; Moss, Eli L.; Saito, Mayuko; Tenorio, Roy; Molina, Douglas M.; Davies, Huw; Neafsey, Daniel E.; Felgner, Philip; Vinetz, Joseph M.; Gamboa, Dionicia

    2015-01-01

    Background. Persons with blood-stage Plasmodium falciparum parasitemia in the absence of symptoms are considered to be clinically immune. We hypothesized that asymptomatic subjects with P. falciparum parasitemia would differentially recognize a subset of P. falciparum proteins on a genomic scale. Methods and Findings. Compared with symptomatic subjects, sera from clinically immune, asymptomatically infected individuals differentially recognized 51 P. falciparum proteins, including the established vaccine candidate PfMSP1. Novel, hitherto unstudied hypothetical proteins and other proteins not previously recognized as potential vaccine candidates were also differentially recognized. Genes encoding the proteins differentially recognized by the Peruvian clinically immune individuals exhibited a significant enrichment of nonsynonymous nucleotide variation, an observation consistent with these genes undergoing immune selection. Conclusions. A limited set of P. falciparum protein antigens was associated with the development of naturally acquired clinical immunity in the low-transmission setting of the Peruvian Amazon. These results imply that, even in a low-transmission setting, an asexual blood-stage vaccine designed to reduce clinical malaria symptoms will likely need to contain large numbers of often-polymorphic proteins, a finding at odds with many current efforts in the design of vaccines against asexual blood-stage P. falciparum. PMID:25381370

  8. Design and overall performance of four highly loaded, high speed inlet stages for an advanced high-pressure-ratio core compressor

    NASA Technical Reports Server (NTRS)

    Reid, L.; Moore, R. D.

    1978-01-01

    The detailed design and overall performances of four inlet stages for an advanced core compressor are presented. These four stages represent two levels of design total pressure ratio (1.82 and 2.05), two levels of rotor aspect ratio (1.19 and 1.63), and two levels of stator aspect ratio (1.26 and 1.78). The individual stages were tested over the stable operating flow range at 70, 90, and 100 percent of design speeds. The performances of the low aspect ratio configurations were substantially better than those of the high aspect ratio configurations. The two low aspect ratio configurations achieved peak efficiencies of 0.876 and 0.872 and corresponding stage efficiencies of 0.845 and 0.840. The high aspect ratio configurations achieved peak ratio efficiencies of 0.851 and 0.849 and corresponding stage efficiencies of 0.821 and 0.831.

  9. Clinical Trial Results Vary Widely, But Always Advance Research | NIH MedlinePlus the Magazine

    MedlinePlus

    ... turn Javascript on. Feature: Clinical Trials Clinical Trial Results Vary Widely, But Always Advance Research Past Issues / ... members met with his surgeon to learn the results: 'When we first met, I told you it ...

  10. Staging Dementia Using Clinical Dementia Rating Scale Sum of Boxes Scores

    PubMed Central

    O'Bryant, Sid E.; Waring, Stephen C.; Cullum, C. Munro; Hall, James; Lacritz, Laura; Massman, Paul J.; Lupo, Philip J.; Reisch, Joan S.; Doody, Rachelle

    2012-01-01

    Background The Clinical Dementia Rating Scale Sum of Boxes (CDR-SOB) score is commonly used, although the utility regarding this score in staging dementia severity is not well established. Obiective To investigate the effectiveness of CDRSOB scores in staging dementia severity compared with the global CDR score. Design Retrospective study. Setting Texas Alzheimer's Research Consortium minimum data set cohort. Participants A total of 1577 participants (110 controls, 202 patients with mild cognitive impairment, and 1265 patients with probable Alzheimer disease) were available for analysis. Main Outcome Measures Receiver operating characteristic curves were generated from a derivation sample to determine optimal cutoff scores and ranges, which were then applied to the validation sample. Results Optimal ranges of CDR-SOB scores corresponding to the global CDR scores were 0.5 to 4.0 for a global score of 0.5, 4.5 to 9.0 for a global score of 1.O, 9.5 to 15.5 for a global score of 2.0, and 16.0 to 18.0 for a global score of 3.0. When applied to the validation sample, κ scores ranged from 0.86 to 0.94 (P <.001 for all), with 93.0% of the participants falling within the new staging categories. Conclusions The CDR-SOB score compares well with the global CDR score for dementia staging. Owing to the increased range of values, the CDR-SOB score offers several advantages over the global score, including increased utility in tracking changes within and between stages of dementia severity. Interpretive guidelines for CDR-SOB scores are provided. PMID:18695059

  11. Effect of Habits and Nutritional Status on Clinical Grading and Histopathological Staging in Patients with Oral Sub Mucous Fibrosis.

    PubMed

    Singh, Abhayjeet; Lanke, Rama Brahmam; Shetty, Rakhith; Akifuddin, Syed; Sahu, Manish; Singh, Navneet; Kaur, Gagandeep; Goyal, Garish

    2015-10-01

    Oral submucous fibrosis (OSMF) is a chronic progressive debilitating disease affecting the oral, oropharyngeal and sometimes the oesophageal mucosa resulting in inability to eat due to burning, ulcers and stiffness. The study was undertaken, to evaluate the correlation of clinical staging, histological grading and nutritional status using body mass index (BMI) with gutkha (habit) index in OSMF patients. The study group comprised of 50 patients clinically diagnosed and histopathologically confirmed cases of OSMF. Habit (gutkha) index was calculated by multiplying duration and frequency. Body mass index was calculated by dividing weight in kilograms and height in centimetres of the patient. Male to female ratio was 2.8:1. Clinical grading increased with increase in gutkha index, patients with gutkha index 1-50, maximum were in mild stage; with gutkha index 51-100, maximum in moderate and patients with gutkha index 101-150, all were in severe stage. Histological staging showed direct correlation with gutkha index, it increased with increase in gutkha index with p <0.05. Site analysis showed that buccal mucosa and retromolar area were involved in all the patient and floor of mouth in 46% of patients Body mass index analysis revealed that out of 27 patients with moderate clinical staging 3 was underweight; out of 3 with severe clinical staging, 2 was underweight. The duration and frequency of areca nut product use effects on the incidence and severity of OSMF and the patient becomes unable to eat due to burning, ulcers and inability to open mouth which affect the health of the individual. Thus it is important to access the nutritional status to improve the survival rate of patients.

  12. Perspectives on current tumor-node-metastasis (TNM) staging of cancers of the colon and rectum.

    PubMed

    Hu, Huankai; Krasinskas, Alyssa; Willis, Joseph

    2011-08-01

    Improvements in classifications of cancers based on discovery and validation of important histopathological parameters and new molecular markers continue unabated. Though still not perfect, recent updates of classification schemes in gastrointestinal oncology by the American Joint Commission on Cancer (tumor-node-metastasis [TNM] staging) and the World Health Organization further stratify patients and guide optimization of treatment strategies and better predict patient outcomes. These updates recognize the heterogeneity of patient populations with significant subgrouping of each tumor stage and use of tumor deposits to significantly "up-stage" some cancers; change staging parameters for subsets of IIIB and IIIC cancers; and introduce of several new subtypes of colon carcinomas. By the nature of the process, recent discoveries that are important to improving even routine standards of patient care, especially new advances in molecular medicine, are not incorporated into these systems. Nonetheless, these classifications significantly advance clinical standards and are welcome enhancements to our current methods of cancer reporting. Copyright © 2011 Elsevier Inc. All rights reserved.

  13. Perceptions of mistreatment among trainees vary at different stages of clinical training.

    PubMed

    Kulaylat, Afif N; Qin, Danni; Sun, Susie X; Hollenbeak, Christopher S; Schubart, Jane R; Aboud, Antone J; Flemming, Donald J; Dillon, Peter W; Bollard, Edward R; Han, David C

    2017-01-14

    Mistreatment of trainees remains a frequently reported phenomenon in medical education. One barrier to creating an educational culture of respect and professionalism may be a lack of alignment in the perceptions of mistreatment among different learners. Through the use of clinical vignettes, our aim was to assess the perceptions of trainees toward themes of potential mistreatment at different stages of training. Based on observations from external experts embedded in the clinical learning environment, six thematic areas of potential mistreatment were identified: verbal abuse, specialty-choice discrimination, non-educational tasks, withholding/denying learning opportunities, neglect and gender/racial insensitivity. Corresponding clinical vignettes were created and distributed to 1) medical students, 2) incoming interns, 3) residents/fellows. Perceptions of the appropriateness of the interactions depicted in the vignettes were measured on a 5-point Likert scale. Scores were categorized into neutral or appropriate (≤3) or inappropriate (i.e. mistreatment) (>3) and compared using chi-squared tests. Four hundred twenty seven trainees participated (182 students, 120 interns, 125 residents/fellows). Proportions of students perceiving mistreatment differed significantly from those of interns and residents/fellows in domains of verbal abuse, specialty discrimination and gender/racial insensitivity (p < 0.05). In scenarios comparing interns to residents/fellows, no significant differences were noted in perceptions of mistreatment in the domains of non-educational tasks, withholding learning and neglect. Perceptions of mistreatment differ at different developmental stages of medical training. After exposure to the clinical learning environment, perceptions of incoming interns did not differ from those of residents/fellows, implicating clinical rotations as a key period in indoctrinating students into the prevailing culture. More longitudinal studies are needed to

  14. Recommendations for Initial Evaluation, Staging, and Response Assessment of Hodgkin and Non-Hodgkin Lymphoma: The Lugano Classification

    PubMed Central

    Cheson, Bruce D.; Fisher, Richard I.; Barrington, Sally F.; Cavalli, Franco; Schwartz, Lawrence H.; Zucca, Emanuele; Lister, T. Andrew

    2014-01-01

    The purpose of this work was to modernize recommendations for evaluation, staging, and response assessment of patients with Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A workshop was held at the 11th International Conference on Malignant Lymphoma in Lugano, Switzerland, in June 2011, that included leading hematologists, oncologists, radiation oncologists, pathologists, radiologists, and nuclear medicine physicians, representing major international lymphoma clinical trials groups and cancer centers. Clinical and imaging subcommittees presented their conclusions at a subsequent workshop at the 12th International Conference on Malignant Lymphoma, leading to revised criteria for staging and of the International Working Group Guidelines of 2007 for response. As a result, fluorodeoxyglucose (FDG) positron emission tomography (PET)–computed tomography (CT) was formally incorporated into standard staging for FDG-avid lymphomas. A modification of the Ann Arbor descriptive terminology will be used for anatomic distribution of disease extent, but the suffixes A or B for symptoms will only be included for HL. A bone marrow biopsy is no longer indicated for the routine staging of HL and most diffuse large B-cell lymphomas. However, regardless of stage, general practice is to treat patients based on limited (stages I and II, nonbulky) or advanced (stage III or IV) disease, with stage II bulky disease considered as limited or advanced disease based on histology and a number of prognostic factors. PET-CT will be used to assess response in FDG-avid histologies using the 5-point scale. The product of the perpendicular diameters of a single node can be used to identify progressive disease. Routine surveillance scans are discouraged. These recommendations should improve evaluation of patients with lymphoma and enhance the ability to compare outcomes of clinical trials. PMID:25113753

  15. Introducing Advanced Clinical Reasoning to an Adult Learning Disability Service

    ERIC Educational Resources Information Center

    Stansfield, Jois; Matthews, Alison

    2014-01-01

    The advanced clinical reasoning approach is widely adopted in speech and language therapy practice. This article reports on the introduction of the approach across a multidisciplinary adult learning disability service and staff reports on the impact of this initiative. Staff and team managers reported that the training had a positive impact on…

  16. Legal Briefing: Medicare Coverage of Advance Care Planning.

    PubMed

    Pope, Thaddeus Mason

    2015-01-01

    This issue's "Legal Briefing" column covers the recent decision by the Centers for Medicare and Medicaid Services (CMS) to expand Medicare coverage of advance care planning, beginning 1 January 2016. Since 2009, most "Legal Briefings" in this journal have covered a wide gamut of judicial, legislative, and regulatory developments concerning a particular topic in clinical ethics. In contrast, this "Legal Briefing" is more narrowly focused on one single legal development. This concentration on Medicare coverage of advance care planning seems warranted. Advance care planning is a frequent subject of articles in JCE. After all, it has long been seen as an important, albeit only partial, solution to a significant range of big problems in clinical ethics. These problems range from medical futility disputes to decision making for incapacitated patients who have no available legally authorized surrogate. Consequently, expanded Medicare coverage of advance care planning is a potentially seismic development. It may materially reduce both the frequency and severity of key problems in clinical ethics. Since the sociological, medical, and ethical literature on advance care planning is voluminous, I will not even summarize it here. Instead, I focus on Medicare coverage. I proceed, chronologically, in six stages: 1. Prior Medicare Coverage of Advance Care Planning 2. Proposed Expanded Medicare Coverage in 2015 3. Proposed Expanded Medicare Coverage in 2016 4. The Final Rule Expanding Medicare Coverage in 2016 5. Remaining Issues for CMS to Address in 2017 6. Pending Federal Legislation. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

  17. The Prognostic Influence of BRAF Mutation and other Molecular, Clinical and Laboratory Parameters in Stage IV Colorectal Cancer.

    PubMed

    Karadima, Maria L; Saetta, Angelica A; Chatziandreou, Ilenia; Lazaris, Andreas C; Patsouris, Efstratios; Tsavaris, Nikolaos

    2016-10-01

    Our aim was to evaluate the predictive and prognostic influence of BRAF mutation and other molecular, clinical and laboratory parameters in stage IV colorectal cancer (CRC). 60 patients were included in this retrospective analysis, and 17 variables were examined for their relation with treatment response and survival. KRAS mutation was identified in 40.3 % of cases, BRAF and PIK3CA in 8.8 % and 10.5 % respectively. 29.8 % of patients responded to treatment. Median survival time was 14.3 months. Weight loss, fever, abdominal metastases, blood transfusion, hypoalbuminaimia, BRAF and PIK3CA mutations, CRP and DNA Index were associated with survival. In multivariate analysis, male patients had 3.8 times higher probability of response, increased DNA Index was inversely correlated with response and one unit raise of DNA Index augmented 6 times the probability of death. Our findings potentiate the prognostic role of BRAF, PIK3CA mutations and ploidy in advanced CRC.

  18. Major clinical research advances in gynecologic cancer in 2015

    PubMed Central

    2016-01-01

    In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7–9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review. PMID:27775259

  19. Major clinical research advances in gynecologic cancer in 2015.

    PubMed

    Suh, Dong Hoon; Kim, Miseon; Kim, Hak Jae; Lee, Kyung Hun; Kim, Jae Weon

    2016-11-01

    In 2015, fourteen topics were selected as major research advances in gynecologic oncology. For ovarian cancer, high-level evidence for annual screening with multimodal strategy which could reduce ovarian cancer deaths was reported. The best preventive strategies with current status of evidence level were also summarized. Final report of chemotherapy or upfront surgery (CHORUS) trial of neoadjuvant chemotherapy in advanced stage ovarian cancer and individualized therapy based on gene characteristics followed. There was no sign of abating in great interest in immunotherapy as well as targeted therapies in various gynecologic cancers. The fifth Ovarian Cancer Consensus Conference which was held in November 7-9 in Tokyo was briefly introduced. For cervical cancer, update of human papillomavirus vaccines regarding two-dose regimen, 9-valent vaccine, and therapeutic vaccine was reviewed. For corpus cancer, the safety concern of power morcellation in presumed fibroids was explored again with regard to age and prevalence of corpus malignancy. Hormone therapy and endometrial cancer risk, trabectedin as an option for leiomyosarcoma, endometrial cancer and Lynch syndrome, and the radiation therapy guidelines were also discussed. In addition, adjuvant therapy in vulvar cancer and the updated of targeted therapy in gynecologic cancer were addressed. For breast cancer, palbociclib in hormone-receptor-positive advanced disease, oncotype DX Recurrence Score in low-risk patients, regional nodal irradiation to internal mammary, supraclavicular, and axillary lymph nodes, and cavity shave margins were summarized as the last topics covered in this review.

  20. Risk Factors for Predicting Occult Lymph Node Metastasis in Patients with Clinical Stage I Non-small Cell Lung Cancer Staged by Integrated Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography.

    PubMed

    Kaseda, Kaoru; Asakura, Keisuke; Kazama, Akio; Ozawa, Yukihiko

    2016-12-01

    Lymph nodes in patients with non-small cell lung cancer (NSCLC) are often staged using integrated 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT). However, this modality has limited ability to detect micrometastases. We aimed to define risk factors for occult lymph node metastasis in patients with clinical stage I NSCLC diagnosed by preoperative integrated FDG-PET/CT. We retrospectively reviewed the records of 246 patients diagnosed with clinical stage I NSCLC based on integrated FDG-PET/CT between April 2007 and May 2015. All patients were treated by complete surgical resection. The prevalence of occult lymph node metastasis in patients with clinical stage I NSCLC was analysed according to clinicopathological factors. Risk factors for occult lymph node metastasis were defined using univariate and multivariate analyses. Occult lymph node metastasis was detected in 31 patients (12.6 %). Univariate analysis revealed CEA (P = 0.04), SUV max of the primary tumour (P = 0.031), adenocarcinoma (P = 0.023), tumour size (P = 0.002) and pleural invasion (P = 0.046) as significant predictors of occult lymph node metastasis. Multivariate analysis selected SUV max of the primary tumour (P = 0.049), adenocarcinoma (P = 0.003) and tumour size (P = 0.019) as independent predictors of occult lymph node metastasis. The SUV max of the primary tumour, adenocarcinoma and tumour size were risk factors for occult lymph node metastasis in patients with NSCLC diagnosed as clinical stage I by preoperative integrated FDG-PET/CT. These findings would be helpful in selecting candidates for mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration.

  1. Effects of facilitated family case conferencing for advanced dementia: A cluster randomised clinical trial

    PubMed Central

    2017-01-01

    Background Palliative care planning for nursing home residents with advanced dementia is often suboptimal. This study compared effects of facilitated case conferencing (FCC) with usual care (UC) on end-of-life care. Methods A two arm parallel cluster randomised controlled trial was conducted. The sample included people with advanced dementia from 20 Australian nursing homes and their families and professional caregivers. In each intervention nursing home (n = 10), Palliative Care Planning Coordinators (PCPCs) facilitated family case conferences and trained staff in person-centred palliative care for 16 hours per week over 18 months. The primary outcome was family-rated quality of end-of-life care (End-of-Life Dementia [EOLD] Scales). Secondary outcomes included nurse-rated EOLD scales, resident quality of life (Quality of Life in Late-stage Dementia [QUALID]) and quality of care over the last month of life (pharmacological/non-pharmacological palliative strategies, hospitalization or inappropriate interventions). Results Two-hundred-eighty-six people with advanced dementia took part but only 131 died (64 in UC and 67 in FCC which was fewer than anticipated), rendering the primary analysis under-powered with no group effect seen in EOLD scales. Significant differences in pharmacological (P < 0.01) and non-pharmacological (P < 0.05) palliative management in last month of life were seen. Intercurrent illness was associated with lower family-rated EOLD Satisfaction with Care (coefficient 2.97, P < 0.05) and lower staff-rated EOLD Comfort Assessment with Dying (coefficient 4.37, P < 0.01). Per protocol analyses showed positive relationships between EOLD and staff hours to bed ratios, proportion of residents with dementia and staff attitudes. Conclusion FCC facilitates a palliative approach to care. Future trials of case conferencing should consider outcomes and processes regarding decision making and planning for anticipated events and acute illness. Trial registration

  2. Management of clinical stage I testicular pure seminoma. Report on 42 patients and review of the literature.

    PubMed

    Porcaro, Antonio B; Antoniolli, Stefano Zecchini; Schiavone, Dionisio; Maffei, Nicola; Bassetto, Maria A; Curti, Pierpaolo

    2002-06-01

    Testis cancer is the most common tumor detected in men aged from 20 to 35 years accounting for 1-2%. About 20-30% of patients presenting with clinical stage I pure seminoma of the testis, which accounts for 45-50% of all germ cell tumors, present with occult metastases in the retroperitoneal lymph nodes. Currently, treatment options for clinical stage I seminoma include adjuvant radiotherapy (RT) as well as surveillance and adjuvant single agent chemotherapy. Herein, we review our experience in the management of 42 patients with clinical stage I pure seminoma of the testis and review the literature concerning this topic. Between January 1977 and December 2000, of 56 patients with pure seminoma of the testis 42 (75%) were assessed as clinical stage I disease. Adjuvant RT was performed in 41 patients and surveillance in 1. Radiations fields included the para-aortic and ipsilateral pelvic lymph nodes. A radiation dose of 25 Gy in 20 daily fractions was given. All patients were followed up. Average age was 41.2 years (range 24-67). Mean follow-up was 85.3 months (range 12-279). Histopathology assessed classic seminoma in 41 cases (98%) and spermatocytic seminoma in 1 (2%). Small vessel invasion was detected in 8 cases (19%). Overall relapse rate was 4.7%. Overall survival rate resulted 97%. Adjuvant radiotherapy (RT) is a safe standard of care in controlling microscopic retroperitoneal disease in patients with clinical stage I seminoma. About 3 to 5% of patients undergo relapses, mostly after the first 18 months after orchiectomy. Overall cause-specific survival rates range between 96% to 100%. An alternative optional treatment for compliant patients presenting with low risk factors for relapse is surveillance with recurrences rates ranging between 15% to 20%. Surveillance avoids unnecessary treatment in about 80% of patients, thus it could be offered as a safe alternative option to adjuvant RT since imaging detects relapses at their early stages. Adjuvant chemotherapy

  3. Technological advances in perioperative monitoring: Current concepts and clinical perspectives

    PubMed Central

    Chilkoti, Geetanjali; Wadhwa, Rachna; Saxena, Ashok Kumar

    2015-01-01

    Minimal mandatory monitoring in the perioperative period recommended by Association of Anesthetists of Great Britain and Ireland and American Society of Anesthesiologists are universally acknowledged and has become an integral part of the anesthesia practice. The technologies in perioperative monitoring have advanced, and the availability and clinical applications have multiplied exponentially. Newer monitoring techniques include depth of anesthesia monitoring, goal-directed fluid therapy, transesophageal echocardiography, advanced neurological monitoring, improved alarm system and technological advancement in objective pain assessment. Various factors that need to be considered with the use of improved monitoring techniques are their validation data, patient outcome, safety profile, cost-effectiveness, awareness of the possible adverse events, knowledge of technical principle and ability of the convenient routine handling. In this review, we will discuss the new monitoring techniques in anesthesia, their advantages, deficiencies, limitations, their comparison to the conventional methods and their effect on patient outcome, if any. PMID:25788767

  4. Technological advances in perioperative monitoring: Current concepts and clinical perspectives.

    PubMed

    Chilkoti, Geetanjali; Wadhwa, Rachna; Saxena, Ashok Kumar

    2015-01-01

    Minimal mandatory monitoring in the perioperative period recommended by Association of Anesthetists of Great Britain and Ireland and American Society of Anesthesiologists are universally acknowledged and has become an integral part of the anesthesia practice. The technologies in perioperative monitoring have advanced, and the availability and clinical applications have multiplied exponentially. Newer monitoring techniques include depth of anesthesia monitoring, goal-directed fluid therapy, transesophageal echocardiography, advanced neurological monitoring, improved alarm system and technological advancement in objective pain assessment. Various factors that need to be considered with the use of improved monitoring techniques are their validation data, patient outcome, safety profile, cost-effectiveness, awareness of the possible adverse events, knowledge of technical principle and ability of the convenient routine handling. In this review, we will discuss the new monitoring techniques in anesthesia, their advantages, deficiencies, limitations, their comparison to the conventional methods and their effect on patient outcome, if any.

  5. Realization of Real-Time Clinical Data Integration Using Advanced Database Technology

    PubMed Central

    Yoo, Sooyoung; Kim, Boyoung; Park, Heekyong; Choi, Jinwook; Chun, Jonghoon

    2003-01-01

    As information & communication technologies have advanced, interest in mobile health care systems has grown. In order to obtain information seamlessly from distributed and fragmented clinical data from heterogeneous institutions, we need solutions that integrate data. In this article, we introduce a method for information integration based on real-time message communication using trigger and advanced database technologies. Messages were devised to conform to HL7, a standard for electronic data exchange in healthcare environments. The HL7 based system provides us with an integrated environment in which we are able to manage the complexities of medical data. We developed this message communication interface to generate and parse HL7 messages automatically from the database point of view. We discuss how easily real time data exchange is performed in the clinical information system, given the requirement for minimum loading of the database system. PMID:14728271

  6. No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients

    PubMed Central

    Hoogendam, Jacob P.; Zweemer, Ronald P.; Verkooijen, Helena M.; de Jong, Pim A.; van den Bosch, Maurice A. A. J.; Verheijen, René H. M.; Veldhuis, Wouter B.

    2015-01-01

    Aim Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. Methods All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 – September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. Results Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman – with advanced pre-radiograph stage (IVA) disease – showed findings consistent with pulmonary metastases. Radiographs of 7 other women – 4 early, 3 advanced stage disease – were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. Conclusion Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years. PMID:26135733

  7. No Value for Routine Chest Radiography in the Work-Up of Early Stage Cervical Cancer Patients.

    PubMed

    Hoogendam, Jacob P; Zweemer, Ronald P; Verkooijen, Helena M; de Jong, Pim A; van den Bosch, Maurice A A J; Verheijen, René H M; Veldhuis, Wouter B

    2015-01-01

    Evidence supporting the recommendation to include chest radiography in the work-up of all cervical cancer patients is limited. We investigated the diagnostic value of routine chest radiography in cervical cancer staging. All consecutive cervical cancer patients who presented at our tertiary referral center in the Netherlands (January 2006 - September 2013), and for whom ≥6 months follow-up was available, were included. As part of the staging procedure, patients underwent a routine two-directional digital chest radiograph. Findings were compared to a composite reference standard consisting of all imaging studies and histology obtained during the 6 months following radiography. Of the 402 women who presented with cervical cancer, 288 (71.6%) underwent chest radiography and had ≥6 months follow-up. Early clinical stage (I/II) cervical cancer was present in 244/288 (84.7%) women, while 44 (15.3%) presented with advanced disease (stage III/IV). The chest radiograph of 1 woman - with advanced pre-radiograph stage (IVA) disease - showed findings consistent with pulmonary metastases. Radiographs of 7 other women - 4 early, 3 advanced stage disease - were suspicious for pulmonary metastases which was confirmed by additional imaging in only 1 woman (with pre-radiograph advanced stage (IIIB) disease) and excluded in 6 cases, including all women with early stage disease. In none of the 288 women were thoracic skeletal metastases identified on imaging or during 6 months follow up. Radiography was unremarkable in 76.4% of the study population, and showed findings unrelated to the cervical carcinoma in 21.2%. Routine chest radiography was of no value for any of the early stage cervical cancer patients presenting at our tertiary center over a period of 7.7 years.

  8. Histology-based Combination Induction Chemotherapy for Elderly Patients with Clinical Stage III Non-small Cell Lung Cancer.

    PubMed

    Banna, Giuseppe L; Parra, Hector Josè Soto; Castaing, Marine; Dieci, Maria Vittoria; Anile, Giuseppe; Nicolosi, Maurizio; Strano, Salvatore; Marletta, Francesco; Guarneri, Valentina; Conte, Pierfranco; Lal, Rohit

    2017-07-01

    To explore the feasibility and activity of a histology-based induction combination chemotherapy for elderly patients with clinical stage III non-small cell lung cancer (NSCLC). Patients aged ≥70 years with stage IIIA and IIIB lung squamous cell carcinoma (SCC) or adenocarcinoma were treated with three cycles of carboplatin and gemcitabine or pemetrexed, respectively, followed by definitive radiotherapy or surgery. The primary endpoint was the overall response rate (ORR) following induction. Twenty-seven patients, with a median age of 74 years (range=70-80 years) were treated for adenocarcinoma in 14 (52%) and SCC in 13 (48%), clinical stage IIIA in eight (30%) and IIIB in 19 (70%). Grade 3 or 4 toxicity was reported for five patients (18.5%). The ORR was 46% in 12 (partial responses) out of 26 assessable patients. Histology-based induction combination chemotherapy is active and feasible in elderly patients with stage III NSCLC. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  9. Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology.

    PubMed

    Patel, Jyoti D; Krilov, Lada; Adams, Sylvia; Aghajanian, Carol; Basch, Ethan; Brose, Marcia S; Carroll, William L; de Lima, Marcos; Gilbert, Mark R; Kris, Mark G; Marshall, John L; Masters, Gregory A; O'Day, Steven J; Polite, Blasé; Schwartz, Gary K; Sharma, Sunil; Thompson, Ian; Vogelzang, Nicholas J; Roth, Bruce J

    2014-01-10

    Since its founding in 1964, the American Society of Clinical Oncology (ASCO) has been committed to improving cancer outcomes through research and the delivery of quality care. Research is the bedrock of discovering better treatments--providing hope to the millions of individuals who face a cancer diagnosis each year. The studies featured in "Clinical Cancer Advances 2013: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology" represent the invaluable contributions of thousands of patients who participate in clinical trials and the scientists who conduct basic and clinical research. The insights described in this report, such as how cancers hide from the immune system and why cancers may become resistant to targeted drugs, enable us to envision a future in which cancer will be even more controllable and preventable. The scientific process is thoughtful, deliberate, and sometimes slow, but each advance, while helping patients, now also points toward new research questions and unexplored opportunities. Both dramatic and subtle breakthroughs occur so that progress against cancer typically builds over many years. Success requires vision, persistence, and a long-term commitment to supporting cancer research and training. Our nation's longstanding investment in federally funded cancer research has contributed significantly to a growing array of effective new treatments and a much deeper understanding of the drivers of cancer. But despite this progress, our position as a world leader in advancing medical knowledge and our ability to attract the most promising and talented investigators are now threatened by an acute problem: Federal funding for cancer research has steadily eroded over the past decade, and only 15% of the ever-shrinking budget is actually spent on clinical trials. This dismal reality threatens the pace of progress against cancer and undermines our ability to address the continuing needs of our patients. Despite this

  10. Diffusion-weighted MR imaging in thymic epithelial tumors: correlation with World Health Organization classification and clinical staging.

    PubMed

    Abdel Razek, Ahmed Abdel Khalek; Khairy, Mohamed; Nada, Nadia

    2014-10-01

    To assess thymic epithelial tumors with diffusion-weighted magnetic resonance (MR) imaging. Informed consent from patients and institutional review board approval were obtained. Prospective study was conducted on 30 consecutive patients (21 men and nine women; age range, 35-71 years) with thymic epithelial tumors. They underwent true fast imaging with steady-state precession and single-shot echo-planar diffusion-weighted MR imaging of the mediastinum with b values of 0, 400, and 800 sec/mm(2). Apparent diffusion coefficient (ADC) of the thymic epithelial tumors was calculated by the same observer at two settings and was correlated with World Health Organization classification and clinical staging. There was significant difference in longest diameter (P = .001) and necrotic part of the tumor (P = .014) between low-risk thymoma, high-risk thymoma, and thymic carcinoma. Mean ADC value of both readings of thymic epithelial tumors (n = 30) was 1.24 × 10(-3) mm(2)/sec and 1.22 × 10(-3) mm(2)/sec, with good intraobserver agreement (κ = 0.732). There was significant difference in both readings (P = .01 and .20) of low-risk thymoma (1.30 × 10(-3) mm(2)/sec and 1.29 × 10(-3) mm(2)/sec), high-risk thymoma (1.16 × 10(-3) mm(2)/sec and 1.14 × 10(-3) mm(2)/sec), and thymic carcinoma (1.18 × 10(-3) mm(2)/sec and 1.06 × 10(-3) mm(2)/sec). Cutoff ADC values of both readings used to differentiate low-risk thymoma from high-risk thymoma and thymic carcinoma were 1.25 and 1.22 × 10(-3) mm(2)/sec with area under the curve of 0.804 and 0.851, respectively. There was significant difference in both readings of ADC value of early (stage I, II) and advanced stages (stage III, IV) of thymic epithelial tumors (P = .006 and .005, respectively). ADC value is a noninvasive, reliable, and reproducible imaging parameter that may help to assess and characterize thymic epithelial tumors. © RSNA, 2014.

  11. Erlotinib as single agent first line treatment in locally advanced or metastatic activating EGFR mutation-positive lung adenocarcinoma (CEETAC): an open-label, non-randomized, multicenter, phase IV clinical trial.

    PubMed

    Markóczy, Zsolt; Sárosi, Veronika; Kudaba, Iveta; Gálffy, Gabriella; Turay, Ülkü Yilmaz; Demirkazik, Ahmet; Purkalne, Gunta; Somfay, Attila; Pápai-Székely, Zsolt; Rásó, Erzsébet; Ostoros, Gyula

    2018-05-25

    Erlotinib is approved for the first line treatment of epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer. Since the number of prospective studies in Caucasian patients treated in routine clinical setting is limited we conducted a multicenter, phase IV clinical trial to determine the efficacy and safety of erlotinib and to demonstrate the feasibility of the validated standardized companion diagnostic method of EGFR mutation detection. 651 chemonaive, cytologically or histologically verified advanced stage lung adenocarcinoma patients from Hungary, Turkey and Latvia were screened for exon19 microdeletions and exon21 L858R EGFR mutations using the companion diagnostic EGFR test. EGFR mutation-positive, locally advanced or metastatic lung adenocarcinoma patients received as first line treatment erlotinib at 150 mg/day. The primary endpoint was progression-free survival (PFS). 62 EGFR mutation-positive patients (9.5% of screened) were included in the safety/intent-to-treat cohort. Median PFS was 12.8 months (95%CI, 9.9-15.8), objective response rate and one-year survival was 66.1% and 82.5%, respectively. Most frequent treatment related adverse events were diarrhoea and rash. Eastern Oncology Cooperative Group Performance Status (ECOG PS), smoking status and M1a/M1b disease stage were significant prognosticators of PFS (p = 0.017, p = 0.045 and p = 0.002, respectively). There was no significant difference in PFS between the subgroups stratified by gender, age or exon19 vs exon21 mutation. Our study confirmed the efficacy and safety of first line erlotinib monotherapy in Caucasian patients with locally advanced or metastatic lung adenocarcinoma carrying activating EGFR mutations based on the screening with the approved companion diagnostic procedure. ClinicalTrials.gov Identifier: NCT01609543.

  12. Bevacizumab, Carboplatin and Paclitaxel Combination Treatment in Advanced Stage Ovarian Cancer: The First Experience in Thammasat University Hospital, Thailand: A Case Report.

    PubMed

    Suwannarurk, Komsun; Thaweekul, Yudthadej; Mairaing, Karicha; Poomtavorn, Yenrudee; Tangtiang, Kaan; Piyawang, Wichet; Bhamarapravatana, Kornkarn

    2015-04-01

    Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growthfactor (VEGF), has been approvedfor concurrent treatment with first line chemotherapy in advanced epithelial ovarian cancer. A case of an advanced stage epithelial ovarian cancer (EOC) receiving a combination of bevacizumab, carboplatin andpaclitaxel chemotherapy was reported. A 44-year-old woman was presented with abdominal discomfort and distention for 4 months. Bilateral 12 cm diameter ovarian tumors were diagnosed as FIGO stage IIIc after surgical staging operation. Histopathology report showed the mixed type of serous and endometriod adenocarcinoma. The patient was then started on carboplatin/paclitaxel combination chemotherapy for 6 cycles after surgery every 3 weeks. Bevacizumab (7.5 mg/ m2) was concurrently administered with chemotherapy every 3 weeks startingfrom the 2nd cycle. A complete remission was achieved after the end of the chemotherapy treatment. Bevacizumab was continued for one year after the completion of the standard chemotherapy. Bone marrow suppression, hypertension and proteinuria were not found during Bevacizumab treatment. At bevacizumab treatment completion, a platinum-sensitive recurrent ovarian cancer was diagnosed at the two weeks postprogram routine check-up. The patient was counseled to start second line chemotherapy treatment and has yet to come back with her decision. Combination of bevacizumab, carboplatin and paclitaxelfor first line chemotherapy in advanced EOC in this case had no serious side effects and need further study.

  13. Could the clinical interpretability of subgroups detected using clustering methods be improved by using a novel two-stage approach?

    PubMed

    Kent, Peter; Stochkendahl, Mette Jensen; Christensen, Henrik Wulff; Kongsted, Alice

    2015-01-01

    Recognition of homogeneous subgroups of patients can usefully improve prediction of their outcomes and the targeting of treatment. There are a number of research approaches that have been used to recognise homogeneity in such subgroups and to test their implications. One approach is to use statistical clustering techniques, such as Cluster Analysis or Latent Class Analysis, to detect latent relationships between patient characteristics. Influential patient characteristics can come from diverse domains of health, such as pain, activity limitation, physical impairment, social role participation, psychological factors, biomarkers and imaging. However, such 'whole person' research may result in data-driven subgroups that are complex, difficult to interpret and challenging to recognise clinically. This paper describes a novel approach to applying statistical clustering techniques that may improve the clinical interpretability of derived subgroups and reduce sample size requirements. This approach involves clustering in two sequential stages. The first stage involves clustering within health domains and therefore requires creating as many clustering models as there are health domains in the available data. This first stage produces scoring patterns within each domain. The second stage involves clustering using the scoring patterns from each health domain (from the first stage) to identify subgroups across all domains. We illustrate this using chest pain data from the baseline presentation of 580 patients. The new two-stage clustering resulted in two subgroups that approximated the classic textbook descriptions of musculoskeletal chest pain and atypical angina chest pain. The traditional single-stage clustering resulted in five clusters that were also clinically recognisable but displayed less distinct differences. In this paper, a new approach to using clustering techniques to identify clinically useful subgroups of patients is suggested. Research designs, statistical

  14. Advancing Early Detection of Autism Spectrum Disorder by Applying an Integrated Two-Stage Screening Approach

    ERIC Educational Resources Information Center

    Oosterling, Iris J.; Wensing, Michel; Swinkels, Sophie H.; van der Gaag, Rutger Jan; Visser, Janne C.; Woudenberg, Tim; Minderaa, Ruud; Steenhuis, Mark-Peter; Buitelaar, Jan K.

    2010-01-01

    Background: Few field trials exist on the impact of implementing guidelines for the early detection of autism spectrum disorders (ASD). The aims of the present study were to develop and evaluate a clinically relevant integrated early detection programme based on the two-stage screening approach of Filipek et al. (1999), and to expand the evidence…

  15. Genome-level determination of Plasmodium falciparum blood-stage targets of malarial clinical immunity in the Peruvian Amazon.

    PubMed

    Torres, Katherine J; Castrillon, Carlos E; Moss, Eli L; Saito, Mayuko; Tenorio, Roy; Molina, Douglas M; Davies, Huw; Neafsey, Daniel E; Felgner, Philip; Vinetz, Joseph M; Gamboa, Dionicia

    2015-04-15

    Persons with blood-stage Plasmodium falciparum parasitemia in the absence of symptoms are considered to be clinically immune. We hypothesized that asymptomatic subjects with P. falciparum parasitemia would differentially recognize a subset of P. falciparum proteins on a genomic scale. Compared with symptomatic subjects, sera from clinically immune, asymptomatically infected individuals differentially recognized 51 P. falciparum proteins, including the established vaccine candidate PfMSP1. Novel, hitherto unstudied hypothetical proteins and other proteins not previously recognized as potential vaccine candidates were also differentially recognized. Genes encoding the proteins differentially recognized by the Peruvian clinically immune individuals exhibited a significant enrichment of nonsynonymous nucleotide variation, an observation consistent with these genes undergoing immune selection. A limited set of P. falciparum protein antigens was associated with the development of naturally acquired clinical immunity in the low-transmission setting of the Peruvian Amazon. These results imply that, even in a low-transmission setting, an asexual blood-stage vaccine designed to reduce clinical malaria symptoms will likely need to contain large numbers of often-polymorphic proteins, a finding at odds with many current efforts in the design of vaccines against asexual blood-stage P. falciparum. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  16. High-volume ovarian cancer care: survival impact and disparities in access for advanced-stage disease.

    PubMed

    Bristow, Robert E; Chang, Jenny; Ziogas, Argyrios; Randall, Leslie M; Anton-Culver, Hoda

    2014-02-01

    To characterize the impact of hospital and physician ovarian cancer case volume on survival for advanced-stage disease and investigate socio-demographic variables associated with access to high-volume providers. Consecutive patients with stage IIIC/IV epithelial ovarian cancer (1/1/96-12/31/06) were identified from the California Cancer Registry. Disease-specific survival analysis was performed using Cox-proportional hazards model. Multivariate logistic regression analyses were used to evaluate for differences in access to high-volume hospitals (HVH) (≥20 cases/year), high-volume physicians (HVP) (≥10 cases/year), and cross-tabulations of high- or low-volume hospital (LVH) and physician (LVP) according to socio-demographic variables. A total of 11,865 patients were identified. The median ovarian cancer-specific survival for all patients was 28.2 months, and on multivariate analysis the HVH/HVP provider combination (HR = 1.00) was associated with superior ovarian cancer-specific survival compared to LVH/LVP (HR = 1.31, 95%CI = 1.16-1.49). Overall, 2119 patients (17.9%) were cared for at HVHs, and 1791 patients (15.1%) were treated by HVPs. Only 4.3% of patients received care from HVH/HVP, while 53.1% of patients were treated by LVH/LVP. Both race and socio-demographic characteristics were independently associated with an increased likelihood of being cared for by the LVH/LVP combination and included: Hispanic race (OR = 1.72, 95%CI = 1.22-2.42), Asian/Pacific Islander race (OR = 1.57, 95%CI = 1.07-2.32), Medicaid insurance (OR = 2.51, 95%CI = 1.46-4.30), and low socioeconomic status (OR = 2.84, 95%CI = 1.90-4.23). Among patients with advanced-stage ovarian cancer, the provider combination of HVH/HVP is an independent predictor of improved disease-specific survival. Access to high-volume ovarian cancer providers is limited, and barriers are more pronounced for patients with low socioeconomic status, Medicaid insurance, and racial minorities. Copyright © 2013

  17. Changes in Protein Structure and Distribution Observed at Pre-Clinical Stages of Scrapie Pathogenesis

    PubMed Central

    Kretlow, Ariane; Wang, Qi; Beekes, Michael; Naumann, Dieter; Miller, Lisa M.

    2011-01-01

    Scrapie is a neurodegenerative disorder that involves the misfolding, aggregation and accumulation of the prion protein (PrP). The normal cellular PrP (PrPC) is rich in α-helical secondary structure, whereas the disease-associated pathogenic form of the protein (PrPSc) has an anomalously high β-sheet content. In this study, protein structural changes were examined in situ in the dorsal root ganglia from perorally 263K scrapie-infected and mock-infected hamsters using synchrotron Fourier Transform InfraRed Microspectroscopy (FTIRM) at four time points over the course of the disease (preclinical, 100 & 130 days post-infection (dpi); first clinical signs (~145 dpi); and terminal (~170 dpi)). Results showed clear changes in the total protein content, structure, and distribution as the disease progressed. At pre-clinical time points, the scrapie-infected animals exhibited a significant increase in protein expression, but the β-sheet protein content was significantly lower than controls. Based on these findings, we suggest that the pre-clinical stages of scrapie are characterized by an overexpression of proteins low in β-sheet content. As the disease progressed, the β-sheet content increased significantly. Immunostaining with a PrP-specific antibody, 3F4, confirmed that this increase was partly – but not solely – due to the formation of PrPSc in the tissue and indicated that other proteins high in β-sheet were produced, either by overexpression or misfolding. Elevated β-sheet was observed near the cell membrane at pre-clinical time points and also in the cytoplasm of infected neurons at later stages of infection. At the terminal stage of the disease, the protein expression declined significantly, likely due to degeneration and death of neurons. These dramatic changes in protein content and structure, especially at pre-clinical time points, emphasize the possibility for identifying other proteins involved in early pathogenesis, which are important for further

  18. Clinical Placement Before or After Simulated Learning Environments?: A Naturalistic Study of Clinical Skills Acquisition Among Early-Stage Paramedicine Students.

    PubMed

    Mills, Brennen W; Carter, Owen B J; Rudd, Cobie J; Ross, Nathan P; Claxton, Louise A

    2015-10-01

    There is conflicting evidence surrounding the merit of clinical placements (CPs) for early-stage health-profession students. Some contend that early-stage CPs facilitate contextualization of a subsequently learned theory. Others argue that training in simulated-learning experiences (SLEs) should occur before CP to ensure that students possess at least basic competency. We sought to investigate both claims. First-year paramedicine students (n = 85) undertook 3 days of CP and SLEs as part of course requirements. Students undertook CP either before or after participation in SLEs creating 2 groups (Clin → Sim/Sim → Clin). Clinical skills acquisition was measured via direct scenario-based clinical assessments with expert observers conducted at 4 intervals during the semester. Perceptions of difficulty of CP and SLE were measured via the National Aeronautics and Space Administration Task Load Index. Students' clinical assessment scores in both groups improved significantly from beginning to end of semester (P < 0.001). However, at semester's end, clinical assessment scores for the Sim → Clin group were statistically significantly greater than those of the Clin → Sim group (P = 0.021). Both groups found SLEs more demanding than CP (P < 0.001). However, compared with the Sim → Clin group, the Clin → Sim group rated SLE as substantially more time-demanding than CP (P = 0.003). Differences in temporal demand suggest that the Clin → Sim students had fewer opportunities to practice clinical skills during CP than the Sim → Clin students due to a more limited scope of practice. The Sim → Clin students contextualized SLE within subsequent CP resulting in greater improvement in clinical competency by semester's end in comparison with the Clin → Sim students who were forced to contextualize skills retrospectively.

  19. Increased AAA-TOB3 correlates with lymph node metastasis and advanced stage of lung adenocarcinoma.

    PubMed

    Liu, Yanfeng; Bu, Lina; Li, Wei; Wu, Wei; Wang, Shengyu; Diao, Xin; Zhou, Jing; Chen, Guoan; Yang, Shuanying

    2017-07-24

    This study was to investigate the differential mitochondrial protein expressions in human lung adenocarcinoma and provide preliminary data for further exploration of the carcinogenic mechanism. Total proteins of A549 and 16HBE mitochondria were extracted through 2D polyacrylamide gel electrophoresis (2-DE). The differential mitochondria proteins were identified by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and were further confirmed by Western blot, immunoelectron microscopy and immunohistochemistry (IHC) in A549 cells as well as lung adenocarcinoma tissues. A total of 41 differentially expressed protein spots were found in A549 mitochondria. Of them, 15 proteins were highly expressed and 26 proteins were lowly expressed in the mitochondria of A549 (by more than 1.5 times). Among the 15 more highly expressed proteins, AAA-TOB3 (by more than 3 times) was highly expressed in the mitochondria of A549 compared with the 16HBE, by LC-MS/MS identification. High electron density and clear circular colloidal gold-marked AAA-TOB3 particles were observed in the A549 cells via immunoelectron microscopy. Besides, AAA-TOB3 was confirmed to be elevated in lung adenocarcinoma by Western blot and IHC. Moreover, increased AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma (p<0.05). AAA-TOB3 was highly expressed in lung adenocarcinoma, and the up-regulation of AAA-TOB3 correlated with lymph node metastasis and advanced stage of lung adenocarcinoma, which suggested that it could serve as a potential molecular marker for lung adenocarcinoma.

  20. Clinical Significance of the Champagne Bottle Neck Sign in the Extracranial Carotid Arteries of Patients with Moyamoya Disease.

    PubMed

    Yasuda, C; Arakawa, S; Shimogawa, T; Kanazawa, Y; Sayama, T; Haga, S; Morioka, T

    2016-05-26

    The champagne bottle neck sign represents a rapid reduction in the extracranial ICA diameters and is a characteristic feature of Moyamoya disease. However, the clinical significance of the champagne bottle neck sign is unclear. We investigated the relationship between the champagne bottle neck sign and the clinical and hemodynamic stages of Moyamoya disease. We analyzed 14 patients with Moyamoya disease before revascularization (5 men, 9 women; age, 43.2 ± 19.3 years). The ratio of the extracranial ICA and common carotid artery diameters was determined using carotid ultrasonography or cerebral angiography; a ratio of < 0.5 was considered champagne bottle neck sign-positive. The clinical disease stage was determined using the Suzuki angiographic grading system. CBF and cerebral vasoreactivity also were measured. The ICA/common carotid artery ratio (expressed as median [interquartile range]) decreased as the clinical stage advanced (stages I-II, 0.71 [0.60-0.77]; stages III-IV, 0.49 [0.45-0.57]; stages V-VI, 0.38 [0.34-0.47]; P < .001). Lower ICA/common carotid artery ratio tended to occur in symptomatic versus asymptomatic arteries (0.47 [0.40-0.53] versus 0.57 [0.40-0.66], respectively; P = .06). Although the ICA/common carotid artery ratio was not related to cerebral perfusion, it decreased as cerebral vasoreactivity decreased (P < .01). All champagne bottle neck sign-positive arteries were classified as Suzuki stage ≥III, 73% were symptomatic, and 89% exhibited reduced cerebral vasoreactivity. In contrast, all champagne bottle neck sign-negative arteries were Suzuki stage ≤III, 67% were asymptomatic, and all showed preserved cerebral vasoreactivity. The champagne bottle neck sign was related to advanced clinical stage, clinical symptoms, and impaired cerebral vasoreactivity. Thus, detection of the champagne bottle neck sign might be useful in determining the clinical and hemodynamic stages of Moyamoya disease. © 2016 American Society of Neuroradiology.

  1. Epidemiology and Clinical Aspects of Genetic Cardiomyopathies.

    PubMed

    Masarone, Daniele; Kaski, Juan Pablo; Pacileo, Giuseppe; Elliott, Perry M; Bossone, Eduardo; Day, Sharlene M; Limongelli, Giuseppe

    2018-04-01

    Cardiomyopathies (CMPs) are an increasingly recognized cause of heart failure and sudden death, particularly in young patients. Since their original description, major advances were achieved in the phenotype knowledge, natural history, and nosography of CMPs leading to different classification systems and therapies. However, a deeper knowledge of different causes, genotype-phenotype link, and natural history in different disease stages (preclinical, overt disease, and end-stage disease) according to a recognized standard of care (ie, international guidelines) is needed. Clinical registries can fill gaps in our knowledge regarding the uncovered issues on cause, clinical course, and management of CMPs. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Advance directives: the clinical nurse specialist as a change agent.

    PubMed

    Meehan, Karen Anne

    2009-01-01

    The purpose of this article is to describe the impact the clinical nurse specialist (CNS) has on the advance directive process within the cardiac surgery patient population. As a change agent, the CNS needs to be able to increase the number of advance directives obtained and increase the provision of dignified, self-directed, quality patient care. With requirements from The Joint Commission and the Patient Self-determination Act, the change in process must take place to ensure that healthcare professionals are doing all they can do to carry out a patient's wishes. The 6-Source Influencer Model is applied to a case study to illustrate the role of the CNS as a change agent. Following this model, the CNS can facilitate lasting institutional change in the advance directive process. Based on the example, it is possible that a CNS can act as a change agent for other patient populations within the healthcare setting.

  3. Do the Trajectories of Bipolar Disorder and Schizophrenia Follow a Universal Staging Model?

    PubMed

    Duffy, Anne; Malhi, Gin S; Grof, Paul

    2017-02-01

    The purpose of this study is to address the question of whether a universal staging model of severe psychiatric disorders is a viable direction for future research by examining the extant literature. A narrative review was conducted of the relevant historical, conceptual, and empirical literature pertaining to the clinical trajectory of bipolar disorder and schizophrenia and issues relevant to staging. There is substantive evidence that classic recurrent bipolar disorder is separable from schizophrenia on the basis of family history, developmental and clinical course, treatment response, and neurobiological findings. However, because of the intrinsic heterogeneity of diagnostic categories that has been amplified by recent changes in psychiatric taxonomy, key distinctions between the groups have become obfuscated. While mapping risk and illness markers to emerging psychopathology is a logical approach and may be of value for some psychiatric disorders and/or their clinical subtypes, robust evidence supporting identifiable stages per se is still lacking. Presently, even rudimentary stages such as prodromes cannot be meaningfully applied across different disorders and no commonalities can be found for the basis of universal staging. Advances in the prediction of risk, accurate early illness detection, and tailored intervention will require mapping biomarkers and other risk indicators to reliable clinical phases of illness progression. Given the capricious nature of mood and psychotic disorders, this task is likely to yield success only if conducted in narrowly defined subgroups of individuals at high risk for specific illnesses. This approach is diametrically opposite to that being promulgated by proponents of a universal staging model.

  4. [Comparison of the Masaoka-Koga Classification with the New TNM Staging of the IASLC/ITMIG for Thymoma and Thymic Carcinoma].

    PubMed

    Ried, Michael; Eicher, Maria-Magdalena; Neu, Reiner; Kraus, Dietmar; Inderhees, Sebastian; Marx, Alexander; Hofmann, Hans-Stefan

    2018-05-18

    The Masaoka-Koga classification describes the extent and spread of thymic epithelial malignancies. The objective of this study was to evaluate the Masaoka-Koga and the new TNM-staging system regarding differences in stage distributions, clinical implementation and therapeutic consequences. Retrospective analysis of all patients who underwent surgery between January 2005 and December 2015 for thymoma/thymic carcinoma in two centres for thoracic surgery. The final tumour stages were determined on the basis of preoperative imaging, surgical reports and histological findings. A total of 118 patients (male 51%) with a mean age of 56 ± 14.8 years were included. Indications for surgery were primary mediastinal tumour (n = 97), pleura dissemination (n = 15) or mediastinal recurrence (n = 7). Radical tumour resection was performed in 92% of patients (n = 109) within one operation, whereas 8% of patients (n = 9) underwent two operations. Surgical revision was necessary in 12 patients (10.1%) and in-hospital mortality was 1.7% (n = 2). Early Masaoka-Koga stages I (n = 34) and II (n = 16) shifted to the new UICC stage I (T1: n = 58). Locally advanced stages (Masaoka-Koga stage III n = 22 vs. UICC stage IIIA + IIIB n = 20) and metastasised stages (Masaoka-Koga stage IV n = 36 vs. UICC stage IV n = 39) remained very similar. The new TNM staging system gave rise to changes, especially in early stages (downstaging), but these had no therapeutic implications. Although advanced stages were very similar, the new TNM staging provides more clinically relevant differentiation. Georg Thieme Verlag KG Stuttgart · New York.

  5. An education and motivation intervention to change clinical management of the third stage of labor - the GIRMMAHP Initiative.

    PubMed

    Figueras, Albert; Narváez, Edgar; Valsecia, Mabel; Vásquez, Susana; Rojas, Germán; Camilo, Angiolina; del Valle, José-María; Aguilera, Cristina

    2008-12-01

    Hemorrhage and hypertensive disorders are major contributors to death after delivery in developing countries. The GIRMMAHP Initiative was designed to describe the actual delivery care in five Latin American countries and to educate and motivate clinical staff at 17 hospitals with the purpose of implementing their own clinical practice guidelines to prevent postpartum hemorrhage. A multicountry education intervention was developed in four consecutive stages, using two analyses: (a) an observational study of the clinical records in eight teaching and nine nonteaching hospitals and (b) a study of the long-term changes measured 12 months after completion of an education intervention and writing a local clinical guideline. Data from 2,247 pregnant women showed that only 23.3 percent had an active management of the third stage of labor and that 22.7 percent received no prenatal care visit. These data were used to prepare local clinical practice guidelines in each participant hospital. The proportion of active management increased to 72.6 percent of deliveries at 3 months and 58.7 percent 1 year later. Use of oxytocin during the third stage of labor increased to 85.9 percent of included deliveries. The proportion of women who had postpartum hemorrhage decreased from 12.7 percent at baseline to 5 percent at 1 year after the intervention. An education intervention and discussion of actual clinical practice problems with health professionals and their involvement in drafting clinical guidelines helped improve health care quality and practitioners' adherence to these guidelines.

  6. FOCIS goes south: advances in translational and clinical immunology.

    PubMed

    Kalergis, Alexis M; Anegon, Ignacio; González, Pablo A

    2017-09-01

    FOCIS goes South: Advances in Translational and Clinical Immunology was the first Federation of Clinical Immunology Societies (FOCIS) ( www.focisnet.org ) meeting held in Latin America (May 15-17, 2017, Santiago de Chile, Chile). The meeting was organized as a 3-day workshop and was fostered by the Millennium Institute on Immunology and Immunotherapy, a recently nominated FOCIS Center of Excellence. The workshop brought together FOCIS associates, such as members of the FOCIS Board of Directors, Directors of different Centers of Excellence, regional speakers and 350 attendees. The Meeting covered aspects of immune regulation and modulation, as well as immunotherapy in areas of autoimmunity, transplantation, cancer and infectious diseases, among others. The activity also had a full-day immunology course and a day-long flow cytometry course.

  7. Regulation of immunotherapeutic products for cancer and FDA’s role in product development and clinical evaluation

    PubMed Central

    2013-01-01

    Immunotherapeutics include drugs and biologics that render therapeutic benefit by harnessing the power of the immune system. The promise of immune-mediated therapies is target specificity with a consequent reduction in off-target side effects. Recent scientific advances have led to clinical trials of both active and passive immunotherapeutic products that have the potential to convert life-ending diseases into chronic but manageable conditions. Clinical trials investigating immunotherapeutics are ongoing with some trials at advanced stages of development. However, as with many products involving novel mechanisms of action, major regulatory and scientific issues arising with clinical use of immunotherapeutic products remain to be addressed. In this review, we address issues related to different immunotherapeutics and provide recommendations for the characterization and evaluation of these products during various stages of product and clinical development. PMID:24764535

  8. Rethinking the Food and Drug Administration's 2013 guidance on developing drugs for early-stage Alzheimer's disease.

    PubMed

    Schneider, Lon S

    2014-03-01

    The February 2013 Food and Drug Administration (FDA) draft guidance for developing drugs for early-stage Alzheimer's disease (AD) creates certain challenges as they guide toward the use of one cognitive outcome to gain accelerated marketing approval for preclinical AD drugs, and a composite clinical scale - the Clinical Dementia Rating Scale in particular - for the primary outcome for prodromal AD clinical trials. In light of the developing knowledge regarding early stage diagnoses and clinical trials outcomes, we recommend that FDA describe its requirements for validating preclinical AD diagnoses for drug development purposes, maintain the principle for requiring coprimary outcomes, and encourage the advancement of outcomes for early stage AD trials. The principles for drug development for early stage AD should not differ from those for clinical AD, especially as the diagnoses of prodromal and early AD impinge on each other. The FDA should not recommend that a composite scale be used as a sole primary efficacy outcome to support a marketing claim unless it requires that the cognitive and functional components of such a scale are demonstrated to be individually meaningful. The current draft guidelines may inadvertently constrain efforts to better assess the clinical effects of new drugs and inhibit innovation in an area where evidence-based clinical research practices are still evolving. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  9. A two-stage clinical decision support system for early recognition and stratification of patients with sepsis: an observational cohort study.

    PubMed

    Amland, Robert C; Lyons, Jason J; Greene, Tracy L; Haley, James M

    2015-10-01

    To examine the diagnostic accuracy of a two-stage clinical decision support system for early recognition and stratification of patients with sepsis. Observational cohort study employing a two-stage sepsis clinical decision support to recognise and stratify patients with sepsis. The stage one component was comprised of a cloud-based clinical decision support with 24/7 surveillance to detect patients at risk of sepsis. The cloud-based clinical decision support delivered notifications to the patients' designated nurse, who then electronically contacted a provider. The second stage component comprised a sepsis screening and stratification form integrated into the patient electronic health record, essentially an evidence-based decision aid, used by providers to assess patients at bedside. Urban, 284 acute bed community hospital in the USA; 16,000 hospitalisations annually. Data on 2620 adult patients were collected retrospectively in 2014 after the clinical decision support was implemented. 'Suspected infection' was the established gold standard to assess clinical decision support clinimetric performance. A sepsis alert activated on 417 (16%) of 2620 adult patients hospitalised. Applying 'suspected infection' as standard, the patient population characteristics showed 72% sensitivity and 73% positive predictive value. A postalert screening conducted by providers at bedside of 417 patients achieved 81% sensitivity and 94% positive predictive value. Providers documented against 89% patients with an alert activated by clinical decision support and completed 75% of bedside screening and stratification of patients with sepsis within one hour from notification. A clinical decision support binary alarm system with cross-checking functionality improves early recognition and facilitates stratification of patients with sepsis.

  10. Upper stage technology evaluation studies

    NASA Technical Reports Server (NTRS)

    1972-01-01

    Studies to evaluate advanced technology relative to chemical upper stages and orbit-to-orbit stages are reported. The work described includes: development of LH2/LOX stage data, development of data to indicate stage sensitivity to engine tolerance, modified thermal routines to accommodate storable propellants, added stage geometries to computer program for monopropellant configurations, determination of the relative gain obtainable through improvement of stage mass fraction, future propulsion concepts, effect of ultrahigh chamber-pressure increases, and relative gains obtainable through improved mass fraction.

  11. [Revision of the TNM Stage Grouping in the Forthcoming Eighth Edition of the TNM Classification for Lung Cancer].

    PubMed

    Ye, Bo; Zhao, Heng

    2016-06-20

    The currently adopted staging system for lung cancer is the seventh edition of the TNM staging edited by Union for International Cancer Control (UICC) in January, 2009. In recent years, with the advances of techniques in lung cancer diagnosis and the treatment trends towards precision treatment modalities such as individualized therapy and molecular targeted therapy, the survival and prognosis of lung cancer has been significantly improved. The old staging standard is difficult to satisfy the currentrapidly developing clinical needs. Therefore, the International Lung Cancer Research Society (International Association for the Study of Lung Cancer, IASLC) updated the stage of lung cancer in 2015, and the forthcoming eighth edition of the TNM Classification for Lung Cancer, which will be formally adopted in Jan. 2017, has been published in Journal of Thoracic Oncology. The new staging system has adopted 35 databases from 16 countries, including 94,708 cases treated between 1999 and 2010. The advantages of the new staging lies in its higher prognosis prediction and clinical guidance value.

  12. OUR EXPERIENCES WITH ERLOTINIB IN SECOND AND THIRD LINE TREATMENT PATIENTS WITH ADVANCED STAGE IIIB/ IV NON-SMALL CELL LUNG CANCER

    PubMed Central

    Mehić, Bakir; Stanetić, Mirko; Tinjić, Ljuljeta; Smoljanović, Vlatka

    2008-01-01

    HeadHER1/EGFR is known to play a pivotal role in tumorigenesis and is overexpressed in up to 80% of NSCLCs. The study of an Expanded Access Clinical Program of Erlotinib in NSCLC is a phase IV openlabel, non-randomized, multicenter trial in patients with advanced (inoperable stage IIIb/IV) NSCLC who were eligible for treatment with erlotinib but had no access to trial participation. Patients for the study from Bosnia and Herzegovina (B&H) were selected from two Clinical centres (Sarajevo and Banja Luka). The aim of study was to evaluated efficacy and tolerability of erlotinib monotherapy in this setting. All patients who received at least one dose of erlotinib and data were entered in the database as of the CRF cut-off date of 14th May 2008 were included in analysis of data (n = 19). This population is defined as the Intent to Treat (ITT) population and includes all patients who had at least one dose of erlotinib regardless of whether major protocol violations were incurred. The findings are consistent with the results of the randomized, placebo-controlled BR.21 study. Indicating that erlotinib is an effective option for patients with advanced NSCLC who are unsuitable for, or who have previously failed standard chemotherapy. In B&H group of patients DCR was almost 84%, and PFS was approximately 24,7 weeks (compared with 44% and 9,7 weeks for erlotinib reported in phase III). Almost three quarter of the patients received erlotinib as their second line of therapy. Overall, erlotinib was well tolerated; there were no patients who withdrew due to a treatment-related AE (mainly rash) and there were few dose reductions. 24% of patients experienced an SAE (most commonly gastrointestinal (GI) disorders). PMID:19125714

  13. Single stage, low noise, advanced technology fan. Volume 5: Fan acoustics. Section 1: Results and analysis

    NASA Technical Reports Server (NTRS)

    Jutras, R. R.

    1976-01-01

    The acoustic tests and data analysis for a 0.508-scale fan vehicle of a 111,300 newton (25,000 pound) thrust, full-size engine, which would have application on an advanced transport aircraft, is described. The single-stage advanced technology fan was designed to a pressure ratio of 1.8 at a tip speed of 503 m/sec (1,650 ft/sec) to achieve the desired pressure ratio in a single-stage fan with low radius ratio (0.38), and to maintain adequate stall margin. The fan has 44 tip-shrouded rotor blades and 90 outlet guide vanes. The two basic approaches taken in the acoustic design were: (1) minimization of noise at the source, and (2) suppression of the generated noise in the inlet and bypass exhaust duct. Suppression of the generated noise was accomplished in the inlet through use of the hybrid concept (wall acoustic treatment plus airflow acceleration suppression) and in the exhaust duct with extensive acoustic treatment including a splitter. The goal of the design was attainment of twenty effective perceived noise decibels (20 EPNdB) below current Federal Air Regulation noise standards for a full-scale fan at the takeoff, cutback, and approach conditions. The suppression goal of FAR 36-20 was not reached, but improvements in the technology of both front and aft fan-noise suppression were realized. The suppressed fan noise was shown to be consistent with the proposed federal regulation on aircraft noise.

  14. Recent advances in managing differentiated thyroid cancer.

    PubMed

    Lamartina, Livia; Grani, Giorgio; Durante, Cosimo; Filetti, Sebastiano

    2018-01-01

    The main clinical challenge in the management of thyroid cancer is to avoid over-treatment and over-diagnosis in patients with lower-risk disease while promptly identifying those patients with more advanced or high-risk disease requiring aggressive treatment. In recent years, novel clinical and molecular data have emerged, allowing the development of new staging systems, predictive and prognostic tools, and treatment approaches. There has been a notable shift toward more conservative management of low- and intermediate-risk patients, characterized by less extensive surgery, more selective use of radioisotopes (for both diagnostic and therapeutic purposes), and less intensive follow-up. Furthermore, the histologic classification; tumor, node, and metastasis (TNM) staging; and American Thyroid Association risk stratification systems have been refined, and this has increased the number of patients in the low- and intermediate-risk categories. There is now a need for new, prospective data to clarify how these changing practices will impact long-term outcomes of patients with thyroid cancer, and new follow-up strategies and biomarkers are still under investigation. On the other hand, patients with more advanced or high-risk disease have a broader portfolio of options in terms of treatments and therapeutic agents, including multitarget tyrosine kinase inhibitors, more selective BRAF or MEK inhibitors, combination therapies, and immunotherapy.

  15. Advances in the delivery of RNA therapeutics: from concept to clinical reality.

    PubMed

    Kaczmarek, James C; Kowalski, Piotr S; Anderson, Daniel G

    2017-06-27

    The rapid expansion of the available genomic data continues to greatly impact biomedical science and medicine. Fulfilling the clinical potential of genetic discoveries requires the development of therapeutics that can specifically modulate the expression of disease-relevant genes. RNA-based drugs, including short interfering RNAs and antisense oligonucleotides, are particularly promising examples of this newer class of biologics. For over two decades, researchers have been trying to overcome major challenges for utilizing such RNAs in a therapeutic context, including intracellular delivery, stability, and immune response activation. This research is finally beginning to bear fruit as the first RNA drugs gain FDA approval and more advance to the final phases of clinical trials. Furthermore, the recent advent of CRISPR, an RNA-guided gene-editing technology, as well as new strides in the delivery of messenger RNA transcribed in vitro, have triggered a major expansion of the RNA-therapeutics field. In this review, we discuss the challenges for clinical translation of RNA-based therapeutics, with an emphasis on recent advances in delivery technologies, and present an overview of the applications of RNA-based drugs for modulation of gene/protein expression and genome editing that are currently being investigated both in the laboratory as well as in the clinic.

  16. Laser immunotherapy for treatment of patients with advanced breast cancer and melanoma

    NASA Astrophysics Data System (ADS)

    Li, Xiaosong; Hode, Tomas; Guerra, Maria C.; Ferrel, Gabriela L.; Nordquist, Robert E.; Chen, Wei R.

    2011-02-01

    Laser immunotherapy (LIT) was developed for the treatment of metastatic tumors. It combines local selective photothermal interaction and active immunological stimulation to induce a long-term, systemic anti-tumor immunity. During the past sixteen years, LIT has been advanced from bench-top to bedside, with promising outcomes. In our pre-clinical and preliminary clinical studies, LIT has demonstrated the capability in inducing immunological responses, which not only can eradicate the treated primary tumors, but also can eliminate untreated metastases at distant sites. Specifically, LIT has been used to treat advanced melanoma and breast cancer patients during the past five years. LIT was shown to be effective in controlling both primary tumors and distant metastases in late-stage patients, who have failed conventional therapies such as surgery, chemotherapy, radiation, and other more advanced approaches. The methodology and the development of LIT are presented in this paper. The patients' responses to LIT are also reported in this paper. The preliminary results obtained in these studies indicated that LIT could be an effective modality for the treatment of patients with late-stage, metastatic cancers, who are facing severely limited options.

  17. A Severity-Based Clinical Staging Model for the Psychosis Prodrome: Longitudinal Findings From the New York Recognition and Prevention Program.

    PubMed

    Carrión, Ricardo E; Correll, Christoph U; Auther, Andrea M; Cornblatt, Barbara A

    2017-01-01

    Clinical staging improved the possibility of intervening during the psychosis prodrome to limit progression of illness. The current study aimed to validate a novel 4-stage severity-based model with a focus on clinical change over time and risk for conversion to psychosis. One hundred seventy-one individuals at clinical high risk (CHR) for psychosis were followed prospectively (3 ± 1.6 y) as part of the Recognition and Prevention (RAP) program and divided into 4 diagnostic stages according to absence/presence and severity of attenuated positive symptoms. Twenty-two percent of the combined sample recovered (no prodromal symptoms) by study outcome. The negative symptoms only subgroup had the highest symptom stability (70%), but the lowest conversion rate at 5.9%. The subgroup with more severe baseline attenuated positive symptom levels had a higher conversion rate (28%) and a more rapid onset when compared to the moderate attenuated positive symptom subgroup (11%). Finally, the Schizophrenia-Like Psychosis (SLP) subgroup showed low stability (3%), with 49% developing a specific psychotic disorder. The proposed stage model provides a more finely grained classification system than the standard diagnostic approach for prodromal individuals. All 4 stages are in need of early intervention because of low recovery rates. The negative symptom only stage is possibly a separate clinical syndrome, with an increased risk of functional disability. Both subgroups with attenuated positive symptoms are appropriate for studying the mechanisms of psychosis risk, however, individuals with more severe baseline positive symptoms appear better suited to clinical trials. Finally, the SLP category represents an intermediate outcome group appropriate for preventative intervention research but questionable for inclusion in prodromal studies of mechanisms. © The Author 2016. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For

  18. Clinical Cancer Advances 2018: Annual Report on Progress Against Cancer From the American Society of Clinical Oncology.

    PubMed

    Heymach, John; Krilov, Lada; Alberg, Anthony; Baxter, Nancy; Chang, Susan Marina; Corcoran, Ryan; Dale, William; DeMichele, Angela; Magid Diefenbach, Catherine S; Dreicer, Robert; Epstein, Andrew S; Gillison, Maura L; Graham, David L; Jones, Joshua; Ko, Andrew H; Lopez, Ana Maria; Maki, Robert G; Rodriguez-Galindo, Carlos; Schilsky, Richard L; Sznol, Mario; Westin, Shannon Neville; Burstein, Harold

    2018-04-01

    A MESSAGE FROM ASCO'S PRESIDENT I remember when ASCO first conceived of publishing an annual report on the most transformative research occurring in cancer care. Thirteen reports later, the progress we have chronicled is remarkable, and this year is no different. The research featured in ASCO's Clinical Cancer Advances 2018 report underscores the impressive gains in our understanding of cancer and in our ability to tailor treatments to tumors' genetic makeup. The ASCO 2018 Advance of the Year, adoptive cell immunotherapy, allows clinicians to genetically reprogram patients' own immune cells to find and attack cancer cells throughout the body. Chimeric antigen receptor (CAR) T-cell therapy-a type of adoptive cell immunotherapy-has led to remarkable results in young patients with acute lymphoblastic leukemia (ALL) and in adults with lymphoma and multiple myeloma. Researchers are also exploring this approach in other types of cancer. This advance would not be possible without robust federal investment in cancer research. The first clinical trial of CAR T-cell therapy in children with ALL was funded, in part, by grants from the National Cancer Institute (NCI), and researchers at the NCI Center for Cancer Research were the first to report on possible CAR T-cell therapy for multiple myeloma. These discoveries follow decades of prior research on immunology and cancer biology, much of which was supported by federal dollars. In fact, many advances that are highlighted in the 2018 Clinical Cancer Advances report were made possible thanks to our nation's support for biomedical research. Funding from the US National Institutes of Health and the NCI helps researchers pursue critical patient care questions and addresses vital, unmet needs that private industry has little incentive to take on. Federally supported cancer research generates the biomedical innovations that fuel the development and availability of new and improved treatments for patients. We need sustained federal

  19. Laparoscopic common hepatic artery ligation and staging followed by distal pancreatectomy with en bloc resection of celiac artery for advanced pancreatic cancer.

    PubMed

    Raut, V; Takaori, K; Kawaguchi, Y; Mizumoto, M; Kawaguchi, M; Koizumi, M; Kodama, S; Kida, A; Uemoto, S

    2011-11-01

    Adeno-carcinomas of pancreatic body are usually asymptomatic and progress to advanced stage with involvement of major arteries. Resection of advanced cancer along with en bloc resection of a common hepatic artery and celiac trunk enables a "curative" resections and only possible treatment. However, the celiac axis resection always has a risk of compromising blood supply to liver, resulting in the hepatic insufficiency. We evaluated practicability of a two-stage procedure for the advanced pancreases body cancer, laparoscopic clamping of a common hepatic artery followed by open distal pancreatectomy with en bloc celiac arterial resection to prevent the hepatic insufficiency. Seventy-five-year-old woman diagnosed with a 50-mm pancreatic body mass, invading splenic artery, common hepatic artery, splenic vein, and portal vein at the confluence. STAGE-1: At laparoscopy, after confirming absence of the peritoneal, superficial liver metastases and negative peritoneal cytology; we approached the common hepatic artery through the lesser sac and ligated. STAGE-2: Her liver function tests were normal after 2 weeks, and CT angiography showed complete blockage of the common hepatic artery with sufficient collateral circulation to the liver through inferior pancreatico-duodenal artery and gastro-duodenal artery. We performed an open distal pancreatectomy with en bloc resection of celiac artery. Histopathology examination confirmed R0 resection. The celiac axis resection with distal pancreatectomy improves the chance of R0 resection and potentially, survival of the patient. Preoperative laparoscopic ligation of the common hepatic artery is a safe, effective, and in-expensive technique to prevent postoperative hepatic insufficiency and improves the safety of en bloc celiac artery resection with a distal pancreatectomy. Also these patients have high risk of peritoneal dissemination. Diagnostic laparoscopy is useful to detect occult metastasis, which are missed by per-operative CT

  20. Continuous Low-Dose Oral Cyclophosphamide and Methotrexate as Maintenance Therapy in Patients With Advanced Ovarian Carcinoma After Complete Clinical Response to Platinum and Paclitaxel Chemotherapy.

    PubMed

    El-Husseiny, Khalid; Motawei, Helmy; Ali, Mohamad Sayed

    2016-03-01

    The aim of this study was to evaluate efficacy and safety of continuous, low dose of oral, metronomic chemotherapy as maintenance therapy in patients with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy. In this nonrandomized study, patients older than 18 years, with Eastern Cooperative Oncology Group performance status less than 2, with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy were enrolled in 2 arms--arm A (maintenance arm), treated with continuous low-dose oral cyclophosphamide 50 mg and methotrexate 2.5 mg, and arm B (observation arm). Both arms were followed up for progression-free survival and toxicity. Thirty patients were accrued in each arm from January 2009 to December 2010 in Ain Shams University Hospitals, where they received the treatment and followed up for disease progression and toxicity. Patients had a median age of 53 years in maintenance arm and 52.5 years in the observational arm, respectively. Over 80% had papillary serous adenocarcinoma, and over 40% of them had a stage IV disease in both arms. After median follow-up of 27 months, patients achieved median progression-free survival of 18 months in maintenance arm (A) and 15.5 months in observational arm (B), respectively. Toxicity profile was excellent with no grade 3 or 4 toxicity reported. Current study may provide an evidence of efficacy and tolerability of continuous low-dose oral cyclophosphamide and methotrexate as a maintenance therapy in patients with advanced ovarian carcinoma after complete clinical response to platinum and paclitaxel chemotherapy.

  1. Barriers and strategies for the clinical translation of advanced orthopaedic tissue engineering protocols.

    PubMed

    Madry, H; Alini, M; Stoddart, M J; Evans, C; Miclau, T; Steiner, S

    2014-05-06

    Research in orthopaedic tissue engineering has intensified over the last decade and new protocols continue to emerge. The clinical translation of these new applications, however, remains associated with a number of obstacles. This report highlights the major issues that impede the clinical translation of advanced tissue engineering concepts, discusses strategies to overcome these barriers, and examines the need to increase incentives for translational strategies. The statements are based on presentations and discussions held at the AO Foundation-sponsored symposium "Where Science meets Clinics 2013" held at the Congress Center in Davos, Switzerland, in September, 2013. The event organisers convened a diverse group of over one hundred stakeholders involved in clinical translation of orthopaedic tissue engineering, including scientists, clinicians, healthcare industry professionals and regulatory agency representatives. A major point that emerged from the discussions was that there continues to be a critical need for early trans-disciplinary communication and collaboration in the development and execution of research approaches. Equally importantly was the need to address the shortage of sustained funding programs for multidisciplinary teams conducting translational research. Such detailed discussions between experts contribute towards the development of a roadmap to more successfully advance the clinical translation of novel tissue engineering concepts and ultimately improve patient care in orthopaedic and trauma surgery.

  2. Advances in clinical studies of cardiopulmonary resuscitation

    PubMed Central

    Chen, Shou-quan

    2015-01-01

    BACKGROUND: The survival rate of patients after cardiac arrest (CA) remains lower since 2010 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care (ECC) was published. In clinical trials, the methods and techniques for CPR have been overly described. This article gives an overview of the progress in methods and techniques for CPR in the past years. DATA SOURCES: Original articles about cardiac arrest and CPR from MEDLINE (PubMed) and relevant journals were searched, and most of them were clinical randomized controlled trials (RCTs). RESULTS: Forty-two articles on methods and techniques of CPR were reviewed, including chest compression and conventional CPR, chest compression depth and speed, defibrillation strategies and priority, mechanical and manual chest compression, advanced airway management, impedance threshold device (ITD) and active compression-decompression (ACD) CPR, epinephrine use, and therapeutic hypothermia. The results of studies and related issues described in the international guidelines had been testified. CONCLUSIONS: Although large multicenter studies on CPR are still difficult to carry out, progress has been made in the past 4 years in the methods and techniques of CPR. The results of this review provide evidences for updating the 2015 international guidelines. PMID:26056537

  3. [ilin Pills for oligoasthenospermia: Advances in clinical studies].

    PubMed

    Zhang, Kai-Shu; Fu, Long-Long; Shang, Xue-Jun; Gu, Yi-Qun

    2017-10-01

    Industrialization and environmental pollution are bringing more problems to human reproduction and increasing the prevalence of male infertility. Western medicine has shown its limitations in the management of male infertility, especially that of oligoasthenospermia. Traditional Chinese medicine (TCM), however, has long and rich experiences in the treatment of oligoasthenospermia, with a large variety of medicinal prescriptions based on the TCM theories, among which Qilin Pills shows a particularly significant therapeutic effect on oligoasthenospermia, especially when combined with Western medicine. At present, published studies on Qilin Pills are mainly in the stage of clinical observation, while basic researches and studies on its relevant mechanisms are rarely seen.

  4. Initial Misdiagnosis of Proximal Pancreatic Adenocarcinoma Is Associated with Delay in Diagnosis and Advanced Stage at Presentation.

    PubMed

    Swords, Douglas S; Mone, Mary C; Zhang, Chong; Presson, Angela P; Mulvihill, Sean J; Scaife, Courtney L

    2015-10-01

    Delay in diagnosis of pancreatic ductal adenocarcinoma (PDAC) is associated with decreased survival. The effect of an initial misdiagnosis on delay in diagnosis and stage of PDAC is unknown. This study is a retrospective review (2000-2010) from a University-based cancer center of new diagnoses of proximal PDAC. Of 313 patients, 98 (31.3 %) had an initial misdiagnosis. Misdiagnosed patients were younger, 62.8 ± 12.6 vs. 68.0 ± 10.1 (p < 0.001). The most common initial misdiagnoses were: gallbladder disease, gastroesophageal reflux disease, and peptic ulcer disease. After excluding patients with prior cholecystectomy, 14.2 % were misdiagnosed with gallbladder disease and underwent cholecystectomy before PDAC diagnosis. Misdiagnosed patients had higher rates of abdominal pain (p < 0.001), weight loss (p = 0.04), and acute pancreatitis (p < 0.001) and lower rate of jaundice (p < 0.001). Median time between symptoms to PDAC diagnosis was longer in misdiagnosed: 4.2 months vs. 1.4 (p < 0.001). Median time from contact with medical provider to axial imaging was longer in misdiagnosed (p < 0.001). Rate of stages III-IV disease at diagnosis was higher in misdiagnosed: 61.2 vs. 43.7 % (p = 0.004), with a 1.4 (95 % confidence interval (CI), 1.12-1.74) higher risk of stages III-IV disease at diagnosis; however, there was no difference in median overall survival in misdiagnosed patients (9.6 months in misdiagnosed vs. 10.3 months in correctly diagnosed, p = 0.69). Initial misdiagnosis of patients with proximal PDAC is associated with delay in diagnosis and higher risk of locally advanced or advanced disease at time of PDAC diagnosis.

  5. Adjuvant Therapy for Stage II Colorectal Cancer: Who and with What?

    PubMed

    Chung, Ki-Young Y; Kelsen, David

    2006-06-01

    The role of adjuvant chemotherapy for patients with stage II colon adenocarcinoma remains controversial. The high surgical cure rate for patients with "low-risk" stage II colon cancer, ranging from 75% to 80%, and the available clinical trials and meta-analyses provide conflicting recommendations for or against adjuvant chemotherapy for this group of patients. For fit "high-risk" stage II patients with clinical obstruction or perforation at presentation, in which the 5-year survival rate is 60% to 70%, there is little controversy, as these patients are routinely treated with adjuvant chemotherapy. Other potential high-risk factors, including high histologic grade, microsatellite instability, and loss of 18q, have yet to be validated in prospective trials. Patients with fewer than 12 regional lymph nodes identified in the surgical specimen have a statistically unclear risk of lymph node involvement. These patients may have stage III disease and should receive adjuvant therapy. The decision to use adjuvant chemotherapy to treat low-risk stage II colon cancer patients (no obstruction or perforation) should be an informed decision weighing the magnitude of a net 2% to 5% survival benefit, a 0.5% to 1.0% risk of mortality with chemotherapy in addition to 6 months of chemotherapy-related toxicities, other coexisting patient morbidities, and the anticipated life expectancy of each patient. As adjuvant chemotherapy is therapy addressing local or metastatic microscopic disease, and the effectiveness of systemic and biologically targeted therapy for advanced macroscopic colon cancer continues to improve rapidly, it remains to be determined by clinical trials whether therapies including newer agents such as cetuximab and bevacizumab administered in the adjuvant setting may affect survival for stage II cancer patients.

  6. Advanced abdominal pregnancy: an increasingly challenging clinical concern for obstetricians

    PubMed Central

    Huang, Ke; Song, Lei; Wang, Longxia; Gao, Zhiying; Meng, Yuanguang; Lu, Yanping

    2014-01-01

    Advanced abdominal pregnancy is rare. The low incidence, high misdiagnosis rate, and lack of specific clinical signs and symptoms explain the fact that there are no standard diagnostic and treatment options available for advanced abdominal pregnancy. We managed a case of abdominal pregnancy in a woman who was pregnant for the first time. This case was further complicated by a concurrent singleton intrauterine pregnancy; the twin pregnancy was not detected until 20 weeks of pregnancy. The case was confirmed at 26 weeks gestational age using MRI to be an abdominal combined with intrauterine pregnancy. The pregnancy was terminated by cesarean section at 33 + 5 weeks gestation. We collected the relevant data of the case while reviewing the advanced abdominal pregnancy-related English literature in the Pubmed, Proquest, and OVID databases. We compared and analyzed the pregnancy history, gestational age when the diagnosis was confirmed, the placental colonization position, the course of treatment and surgical processes, related concurrency rate, post-operative drug treatment programs, and follow-up results with the expectation to provide guidance for other physicians who might encounter similar cases. PMID:25337188

  7. Recent Advances towards the Clinical Application of Stem Cells for Retinal Regeneration

    PubMed Central

    Becker, Silke; Jayaram, Hari; Limb, G. Astrid

    2012-01-01

    Retinal degenerative diseases constitute a major cause of irreversible blindness in the world. Stem cell-based therapies offer hope for these patients at risk of or suffering from blindness due to the deterioration of the neural retina. Various sources of stem cells are currently being investigated, ranging from human embryonic stem cells to adult-derived induced pluripotent stem cells as well as human Müller stem cells, with the first clinical trials to investigate the safety and tolerability of human embryonic stem cell-derived retinal pigment epithelium cells having recently commenced. This review aims to summarize the latest advances in the development of stem cell strategies for the replacement of retinal neurons and their supportive cells, the retinal pigment epithelium (RPE) affected by retinal degenerative conditions. Particular emphasis will be given to the advances in stem cell transplantation and the challenges associated with their translation into clinical practice. PMID:24710533

  8. Optimal debulking targets in women with advanced stage ovarian cancer: a retrospective study of immediate versus interval debulking surgery.

    PubMed

    Altman, Alon D; Nelson, Gregg; Chu, Pamela; Nation, Jill; Ghatage, Prafull

    2012-06-01

    The objective of this study was to examine both overall and disease-free survival of patients with advanced stage ovarian cancer after immediate or interval debulking surgery based on residual disease. We performed a retrospective chart review at the Tom Baker Cancer Centre in Calgary, Alberta of patients with pathologically confirmed stage III or IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer between 2003 and 2007. We collected data on the dates of diagnosis, recurrence, and death; cancer stage and grade, patients' age, surgery performed, and residual disease. One hundred ninety-two patients were included in the final analysis. The optimal debulking rate with immediate surgery was 64.8%, and with interval surgery it was 85.9%. There were improved overall and disease-free survival rates for optimally debulked disease (< 1 cm) with both immediate and interval surgery (P < 0.001) compared to suboptimally debulked disease. Overall survival rates for optimally debulked disease were not significantly different in patients having immediate and interval surgery (P = 0.25). In the immediate surgery group, patients with microscopic residual disease had better disease-free survival (P = 0.015) and overall survival (P = 0.005) than patients with < 1 cm residual disease. In patients who had interval surgery, those who had microscopic residual disease had more improved disease-free survival than those with < 1 cm disease (P = 0.05), but they did not have more improved overall survival (P = 0.42). Patients with microscopic residual disease who had immediate surgery had a significantly better overall survival rate than those who had interval surgery (P = 0.034). In women with advanced stage ovarian cancer, the goal of surgery should be resection of disease to microscopic residual at the initial procedure. This results in improved overall survival than lesser degrees of resection. Further studies are required to determine optimal surgical management.

  9. Lymphatic vessel invasion and lymph node metastasis in patients with clinical stage I non-small cell lung cancer.

    PubMed

    Kang, Du-Young; Lee, Sungsoo

    2014-09-01

    The aim of this study was to investigate the association between the presence of lymphatic vessel invasion (LVI) in primary tumors and lymph node (LN) metastasis in clinical stage I non-small cell lung cancer (NSCLC) patients. A total of 76 patients who underwent complete resection for clinical stage I adenocarcinoma and squamous cell carcinoma were retrospectively examined. Tumors consisted of 51 cases of adenocarcinoma and 25 cases of squamous cell carcinoma as determined by histology. LN metastasis was detected in 24.4% (19/76) of patients. Factors associated with LN metastasis on univariate analysis included LVI (p < 0.001) and increased tumor dimensions (p < 0.05). Binary logistic regression analysis showed that the presence of LVI (p < 0.001) was the only predictor of LN metastasis. LVI is significantly associated with LN metastasis in patients with clinical stage I NSCLC. These findings may be helpful in determining the most appropriate operative strategy for patients if preoperative detection of LVI becomes feasible. Georg Thieme Verlag KG Stuttgart · New York.

  10. Imaging in the evaluation and follow-up of early and advanced breast cancer: When, why, and how often?

    PubMed

    Bychkovsky, Brittany L; Lin, Nancy U

    2017-02-01

    Imaging in the evaluation and follow-up of patients with early or advanced breast cancer is an important aspect of cancer care. The role of imaging in breast cancer depends on the goal and should only be performed to guide clinical decisions. Imaging is valuable if a finding will change the course of treatment and improve outcomes, whether this is disease-free survival, overall survival or quality-of-life. In the last decade, imaging is often overused in oncology and contributes to rising healthcare costs. In this context, we review the data that supports the appropriate use of imaging for breast cancer patients. We will discuss: 1) the optimal use of staging imaging in both early (Stage 0-II) and locally advanced (Stage III) breast cancer, 2) the role of surveillance imaging to detect recurrent disease in Stage 0-III breast cancer and 3) how patients with metastatic breast cancer should be followed with advanced imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Hui; Shi, Tujin; Qian, Wei-Jun

    2015-12-04

    Mass spectrometry-based proteomics has become an indispensable tool in biomedical research with broad applications ranging from fundamental biology, systems biology, and biomarker discovery. Recent advances in LC-MS have made it become a major technology in clinical applications, especially in cancer biomarker discovery and verification. To overcome the challenges associated with the analysis of clinical samples, such as extremely wide dynamic range of protein concentrations in biofluids and the need to perform high throughput and accurate quantification, significant efforts have been devoted to improve the overall performance of LC-MS bases clinical proteomics. In this review, we summarize the recent advances inmore » LC-MS in the aspect of cancer biomarker discovery and quantification, and discuss its potentials, limitations, and future perspectives.« less

  12. The clinical impact of recent advances in LC-MS for cancer biomarker discovery and verification.

    PubMed

    Wang, Hui; Shi, Tujin; Qian, Wei-Jun; Liu, Tao; Kagan, Jacob; Srivastava, Sudhir; Smith, Richard D; Rodland, Karin D; Camp, David G

    2016-01-01

    Mass spectrometry (MS) -based proteomics has become an indispensable tool with broad applications in systems biology and biomedical research. With recent advances in liquid chromatography (LC) and MS instrumentation, LC-MS is making increasingly significant contributions to clinical applications, especially in the area of cancer biomarker discovery and verification. To overcome challenges associated with analyses of clinical samples (for example, a wide dynamic range of protein concentrations in bodily fluids and the need to perform high throughput and accurate quantification of candidate biomarker proteins), significant efforts have been devoted to improve the overall performance of LC-MS-based clinical proteomics platforms. Reviewed here are the recent advances in LC-MS and its applications in cancer biomarker discovery and quantification, along with the potentials, limitations and future perspectives.

  13. Improving quality and patient satisfaction in a pediatric resident continuity clinic through advanced access scheduling.

    PubMed

    Tuli, Sanjeev Y; Thompson, Lindsay A; Ryan, Kathleen A; Srinivas, Ganga L; Fillipps, Donald J; Young, Christopher M; Tuli, Sonal S

    2010-06-01

    To evaluate the impact of advanced access scheduling in a pediatric residency clinic on resident and patient satisfaction, medical education, practice quality, and efficiency. Residents were assigned to either the advanced access template (10 appointments available to patients and 2 physician overbooks) or the prior template (5 available and 8 overbooks). Outcomes included resident and patient satisfaction, appointment availability, and continuity of care and clinic costs. Patient satisfaction improved in 7 areas (P < .001). Residents in either template did not report an impact on medical education experiences. Significant increases were realized with appointment availability and the number of patients seen. Continuity also increased as the overflow/acute visits decreased (P < .001). Overall costs per visit decreased 22%. Because of the significant improvements in access, continuity, and efficiency, all residents were switched to the advanced access template after completion of the study. Improvement in access to the primary physician has a significant impact on patient satisfaction with health care delivery. This model optimizes the limited time that residents have in continuity clinic, and it has implications for health care delivery quality improvement.

  14. Advancing description and explanation in clinical linguistics: a legacy of Martin J. Ball.

    PubMed

    Damico, Jack S; Damico, Holly L; Nelson, Ryan L

    2011-11-01

    This article asserts the importance of explication of order and disorder in language as a privileged objective of clinical linguistics and service delivery and reviews the contributions of Martin Ball in advancing this agenda.

  15. Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

    PubMed

    Diaz Beveridge, Robert; Alcolea, Vicent; Aparicio, Jorge; Segura, Ángel; García, Jose; Corbellas, Miguel; Fonfría, María; Giménez, Alejandra; Montalar, Joaquin

    2014-01-10

    The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

  16. Reducing by half the percentage of late-stage presentation for breast and cervix cancer over 4 years: a pilot study of clinical downstaging in Sarawak, Malaysia.

    PubMed

    Devi, B C R; Tang, T S; Corbex, M

    2007-07-01

    The registry of the Oncology Departmental in Sarawak General Hospital showed that 79% of nasopharyngeal, 77% of breast and 70% of cervix cancer patients were diagnosed at an advanced stage (stages III and IV) for year 1993. Hence, a low cost Early Cancer Surveillance Program was started in 1994, with the intent of downstaging these three most common cancers in Sarawak. The program consisted of (i) training health staff in hospital and rural clinics to improve their skills in early cancer detection, (ii) raising public awareness through pamphlets, posters and sensitization by health staff. Data analysis revealed that the program achieved downstaging in two of the cancers. Breast cancer in stage III and IV was reduced from 60% (1994) to 35% (1998) (P < 0.0001) and cervical cancer in stage III and IV from 60% (1994) to 26% (1998) (P < 0.0001). No reduction was observed for nasopharyngeal cancer at 88% (1994) to 91% (1998). The overall cost of this program was stage (III and IV) where screening programs meet important difficulties. Our data analyses revealed important shortcomings in the PAP smear screening program where inadequate groups of women were screened. It resulted in a pick up rate of only 5% of the cases. This finding confirmed the need for the simple and complementary downstaging approach.

  17. Enhanced liver fibrosis test using ELISA assay accurately discriminates advanced stage of liver fibrosis as determined by transient elastography fibroscan in treatment naïve chronic HCV patients.

    PubMed

    Omran, Dalia; Yosry, Ayman; Darweesh, Samar K; Nabeel, Mohammed M; El-Beshlawey, Mohammed; Saif, Sameh; Fared, Azza; Hassany, Mohamed; Zayed, Rania A

    2018-02-01

    Evaluation of liver fibrosis stage is crucial in the assessment of chronic HCV patients, regarding decision to start treatment and during follow-up. Our aim was to assess the validity of the enhanced liver fibrosis (ELF) score in discrimination of advanced stage of liver fibrosis in naïve chronic HCV patients. We prospectively evaluated liver fibrosis stage in one hundred eighty-one naïve chronic HCV Egyptian patients by transient elastography (TE)-FibroScan. Patients were categorized into mild to moderate fibrosis (≤F2) group and advanced fibrosis (≥F3) group. The ELF score components, hyaluronic acid (HA), amino-terminal propeptide of type-III-procollagen (PIIINP) and tissue inhibitor of metalloproteinase type-1 (TIMP-1), were done using ELISA test. The mean values of ELF and its individual components significantly correlated with the hepatic fibrosis stage as measured by TE-FibroScan (P value 0.001). ELF cutoff value of 9.8 generated a sensitivity of 77.8%, specificity of 67.1%, area under the receiver operator characteristic curve (AUROC) of 0.76 with 95% confidence interval [CI] (0.68-0.83) for detecting advanced fibrosis (F ≥ 3). ELF panel is a good, reliable noninvasive test and showed comparable results to TE-FibroScan in detecting liver fibrosis stage in treatment naïve chronic HCV patients.

  18. Clinical Implementation of Integrated Genomic Profiling in Patients with Advanced Cancers.

    PubMed

    Borad, Mitesh J; Egan, Jan B; Condjella, Rachel M; Liang, Winnie S; Fonseca, Rafael; Ritacca, Nicole R; McCullough, Ann E; Barrett, Michael T; Hunt, Katherine S; Champion, Mia D; Patel, Maitray D; Young, Scott W; Silva, Alvin C; Ho, Thai H; Halfdanarson, Thorvardur R; McWilliams, Robert R; Lazaridis, Konstantinos N; Ramanathan, Ramesh K; Baker, Angela; Aldrich, Jessica; Kurdoglu, Ahmet; Izatt, Tyler; Christoforides, Alexis; Cherni, Irene; Nasser, Sara; Reiman, Rebecca; Cuyugan, Lori; McDonald, Jacquelyn; Adkins, Jonathan; Mastrian, Stephen D; Valdez, Riccardo; Jaroszewski, Dawn E; Von Hoff, Daniel D; Craig, David W; Stewart, A Keith; Carpten, John D; Bryce, Alan H

    2016-12-23

    DNA focused panel sequencing has been rapidly adopted to assess therapeutic targets in advanced/refractory cancer. Integrated Genomic Profiling (IGP) utilising DNA/RNA with tumour/normal comparisons in a Clinical Laboratory Improvement Amendments (CLIA) compliant setting enables a single assay to provide: therapeutic target prioritisation, novel target discovery/application and comprehensive germline assessment. A prospective study in 35 advanced/refractory cancer patients was conducted using CLIA-compliant IGP. Feasibility was assessed by estimating time to results (TTR), prioritising/assigning putative therapeutic targets, assessing drug access, ascertaining germline alterations, and assessing patient preferences/perspectives on data use/reporting. Therapeutic targets were identified using biointelligence/pathway analyses and interpreted by a Genomic Tumour Board. Seventy-five percent of cases harboured 1-3 therapeutically targetable mutations/case (median 79 mutations of potential functional significance/case). Median time to CLIA-validated results was 116 days with CLIA-validation of targets achieved in 21/22 patients. IGP directed treatment was instituted in 13 patients utilising on/off label FDA approved drugs (n = 9), clinical trials (n = 3) and single patient IND (n = 1). Preliminary clinical efficacy was noted in five patients (two partial response, three stable disease). Although barriers to broader application exist, including the need for wider availability of therapies, IGP in a CLIA-framework is feasible and valuable in selection/prioritisation of anti-cancer therapeutic targets.

  19. der(11)t(11;17): a distinct cytogenetic pathway of advanced stage neuroblastoma (NBL) - detected by spectral karyotyping (SKY).

    PubMed

    Stark, Batia; Jeison, Marta; Glaser-Gabay, Leticia; Bar-Am, Irit; Mardoukh, Jacques; Ash, Shifra; Atias, Dina; Stein, Jerry; Zaizov, Rina; Yaniv, Isaac

    2003-07-18

    Conventional cytogenetic, molecular cytogenic and genetic methods disclosed a broad spectrum of genetic abnormalities leading to gain and loss of chromosomal segments in advanced stage neuroblastoma (NBL). Specific correlation between the genetic findings could delineate distinct genetic pathways, of which the biology and prognostic significance is as yet undetermined. Using spectral karyotyping (SKY) and fluorescence in situ hybridization (FISH) on metaphases from 16 patients with advanced stage NBL, it was possible to explore the whole spectrum of rearrangement within complex karyotypes and to detect hidden recurrent translocations. All translocations were unbalanced. The most prevalent recurrent unbalanced translocations resulted in 17q gain in 12 patients (75%), 11q loss in nine patients (56%), and 1p deletion/imbalance in eight patients (50%). The most frequent recurrent translocation was der(11)t(11;17) in six patients. Three cytogenetic pathways could be delineated. The first, with six patients, was characterized by the unbalanced translocation der(11)t(11;17), detected only by SKY, resulting in the concomitant 17q gain and 11q loss. No MYCN amplification or 1p deletion (except one patient with 1p imbalance) were found, while 3p deletion, and complex karyotypes were common. The second subgroup, with four patients, had 17q gain and 1p deletion, and in two patients 11q loss, that was apparent only by FISH. 1p deletion occurred through der(1)t(1;17) or del(1p). The third subgroup of four patients was characterized by MYCN amplification with 17q gain and 1p deletion, very rarely with 11q loss (one patient) through a translocation with a non-17q partner. The SKY subclassifications were in accordance with the findings reported by molecular genetic techniques, and may indicate that distinct oncogenes and suppressor genes are involved in the der(11)t(11;17) pathway of advanced stage NBL.

  20. Biweekly irinotecan plus bolus 5-fluorouracil and folinic acid in patients with advanced stage colorectal cancer.

    PubMed

    Yalcin, Suayib; Oksuzoglu, Berna; Tekuzman, Gülten; Engin, Hüseyin; Celik, Ismail; Turker, Alev; Barista, Ibrahim; Gullu, Ibrahim; Guler, Nilufer; Altundag, Kadri; Ozisik, Yavuz; Kars, Ayse

    2003-11-01

    In this study, we evaluated the efficacy and tolerability of biweekly irinotecan (CPT-11) plus 5-fluorouracil (5-FU) and folinic acid (FA) regimen (IFL) in patients with advanced stage colorectal cancer. A total of 28 patients were examined. The median age was 51 years (range, 30-74 years). One treatment cycle consisted of CPT-11 180 mg/m(2) on days 1 and 15; 5-FU 425 mg/m(2) on days 1, 2, 15 and 16; and FA 20 mg/m(2) on days 1, 2, 15 and 16, every 4 weeks. A total of 119 cycles (median, 4.0 cycles) were administered. Of the 28 patients, 18 received the chemotherapy as first line treatment, seven received it as second line and three received it as third line. An overall objective response rate of 21.5% was achieved in the patient group. However, the overall response rate for the 18 patients receiving first line treatment was 27.7%. The median response duration was 10.5 months (range, 3-19 months). An additional 28.6% of the patients had stable disease for a median duration of 6.5 months (range, 3-8 months). Median time to disease progression was 4.5 months (range, 1-22+ months) and median overall survival time was 11+ months (95% confidence interval, 9-15 months). Toxicities were mild and manageable. We conclude that biweekly IFL is a practical and tolerable treatment option with a disease control rate of 50.1% in patients with advanced stage colorectal cancer.

  1. Developing clinical leaders: the impact of an action learning mentoring programme for advanced practice nurses.

    PubMed

    Leggat, Sandra G; Balding, Cathy; Schiftan, Dan

    2015-06-01

    To determine whether a formal mentoring programme assists nurse practitioner candidates to develop competence in the clinical leadership competencies required in their advanced practice roles. Nurse practitioner candidates are required to show evidence of defined clinical leadership competencies when they apply for endorsement within the Australian health care system. Aiming to assist the candidates with the development or enhancement of these leadership skills, 18 nurse practitioner candidates participated in a mentoring programme that matched them with senior nurse mentors. A pre-postlongitudinal intervention study. Eighteen nurse practitioner candidates and 17 senior nurses participated in a voluntary mentoring programme that incorporated coaching and action learning over 18 months in 2012 and 2013. Participants completed a pen and paper questionnaire to document baseline measures of self-reported leadership practices prior to commencement of the programme and again at the end of the programme. The mentors and the nurse practitioner candidates qualitatively evaluated the programme as successful and quantitative data illustrated significant improvement in self-reported leadership practices among the nurse practitioner candidates. In particular, the nurse practitioner candidates reported greater competence in the transformational aspects of leadership, which is directly related to the nurse practitioner candidate clinical leadership standard. A formal, structured mentoring programme based on principles of action learning was successful in assisting Australian advanced practice nurses enhance their clinical leadership skills in preparation for formal endorsement as a nurse practitioner and for success in their advanced practice role. Mentoring can assist nurses to transition to new roles and develop knowledge and skills in clinical leadership essential for advanced practice roles. Nurse managers should make greater use of mentoring programmes to support nurses in

  2. National Trends and Predictors of Locally Advanced Penile Cancer in the United States (1998-2012).

    PubMed

    Chipollini, Juan; Chaing, Sharon; Peyton, Charles C; Sharma, Pranav; Kidd, Laura C; Giuliano, Anna R; Johnstone, Peter A; Spiess, Philippe E

    2017-08-12

    We analyzed the trends in presentation of squamous cell carcinoma (SCC) of the penis and determined the socioeconomic predictors for locally advanced (cT3-cT4) disease in the United States. The National Cancer Database was queried for patients with clinically nonmetastatic penile SCC and staging available from 1998 to 2012. Temporal trends per tumor stage were evaluated, and a multivariable logistic regression model was used to identify predictors for advanced presentation during the study period. A total of 5767 patients with stage ≤ T1-T2 (n = 5423) and T3-T4 (n = 344) disease were identified. Increasing trends were noted in all stages of penile SCC with a greater proportion of advanced cases over time (P = .001). Significant predictors of advanced presentation were age > 55 years, the presence of comorbidities, and Medicaid or no insurance (P < .05 for all). More penile SCC is being detected in the United States. Our results have demonstrated older age, presence of comorbidities, and Medicaid or no insurance as potential barriers to early access of care in the male population. Understanding the current socioeconomic gaps could help guide targeted interventions in vulnerable populations. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Coronary Stents: The Impact of Technological Advances on Clinical Outcomes.

    PubMed

    Mennuni, Marco G; Pagnotta, Paolo A; Stefanini, Giulio G

    2016-02-01

    Percutaneous coronary interventions (PCI) were proposed in the late 1970s as an alternative to surgical coronary artery bypass grafting for the treatment of coronary artery disease. Important technological progress has been made since. Balloon angioplasty was replaced by bare metal stents, which allowed to permanently scaffold the coronary vessel avoiding acute recoil and abrupt occlusion. Thereafter, the introduction of early generation drug-eluting stents (DES) has significantly improved clinical outcomes, primarily by markedly reducing the risk of restenosis. New generation DES with thinner stent struts, novel durable or biodegradable polymer coatings, and new limus antiproliferative agents, have further improved upon the safety and efficacy profile of early generation DES. The present article aims to review the impact of technological advances on clinical outcomes in the field of PCI with coronary stents, and to provide a brief overview on clinical margins of improvement and unmet needs of available DES.

  4. [Diagnosis and treatment of depression in the advanced stage of cancer].

    PubMed

    Ronson, A

    2002-10-01

    The diagnosis of depression in patients with advanced cancer is a particularly complex task. The lack of diagnostic tools specifically developed for this patient population, the difficulty of interpreting neurovegetative symptoms of depression--which can result from the neoplastic disease--and the "normal and understandable" nature of many symptoms or signs of psychological distress are among the main obstacles to a clear-cut diagnosis of depression. Things go even more complex when it comes about to discuss whether one should treat patients displaying psychological distress that does not meet established criteria for the diagnosis of a depressive illness. When the indication to treat is finally acknowledged, the choice of the optimal antidepressant will depend upon a series of parameters including survival expectancy, tolerance profile and drug interactions. Though we currently lack prospective data about the efficacy and safety of antidepressants in depressed patients with advanced cancer, extrapolation of data available from other patient populations with severe medical conditions and clinical experience allow to draw guidelines aimed at helping healthcare professionals faced with those problems to improve the quality of life of their patients. These elements are presented and discussed in this paper in the light of the recent developments resulting from the growing interest of the medical community to the care to patients with terminal illness.

  5. [Advance directives in clinical practice : Living will, healthcare power of attorney and care directive].

    PubMed

    Hack, J; Buecking, B; Lopez, C L; Ruchholtz, S; Kühne, C A

    2017-06-01

    In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

  6. [Advance directives in clinical practice : Living will, healthcare power of attorney and care directive].

    PubMed

    Hack, J; Buecking, B; Lopez, C L; Ruchholtz, S; Kühne, C A

    2017-02-01

    In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

  7. [Advance directives in clinical practice : Living will, healthcare power of attorney and care directive].

    PubMed

    Hack, J; Buecking, B; Lopez, C L; Ruchholtz, S; Kühne, C A

    2017-12-01

    In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

  8. [Advance directives in clinical practice : Living will, healthcare power of attorney and care directive].

    PubMed

    Hack, J; Buecking, B; Lopez, C L; Ruchholtz, S; Kühne, C A

    2017-04-01

    In clinical practice, situations continuously occur in which medical professionals and family members are confronted with decisions on whether to extend or limit treatment for severely ill patients in end of life treatment decisions. In these situations, advance directives are helpful tools in decision making according to the wishes of the patient; however, not every patient has made an advance directive and in our experience medical staff as well as patients are often not familiar with these documents. The purpose of this article is therefore to explain the currently available documents (e.g. living will, healthcare power of attorney and care directive) and the possible (legal) applications and limitations in the routine clinical practice.

  9. Mild versus moderate stages of Alzheimer's disease: three-year outcomes in a routine clinical setting of cholinesterase inhibitor therapy.

    PubMed

    Wattmo, Carina; Minthon, Lennart; Wallin, Åsa K

    2016-02-17

    There is an increasing interest in cognitive and functional outcomes in the respective stages of Alzheimer's disease (AD) and in novel therapies particularly for the milder phases of AD. Our aim was to describe and compare various aspects of disease progression in patients with mild versus moderate AD in routine clinical practice of cholinesterase inhibitor (ChEI) therapy. This 3-year, prospective, observational, multicentre study included 1021 participants. Of these, 734 had mild AD (Mini-Mental State Examination (MMSE) score, 20-26) and 287 had moderate AD (MMSE score, 10-19) at the start of ChEI treatment. At baseline and every 6 months, patients were assessed using cognitive, global, instrumental and basic activities of daily living (ADL) scales. Potential predictors of deterioration in moderate AD were analysed using mixed-effects models. The change from baseline between participants with mild and moderate stages of AD after 3 years of ChEI therapy differed significantly on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and basic ADL, but not using the MMSE and instrumental ADL scales. Protective independent factors for better cognitive long-term outcome in the group with moderate AD were older age, higher instrumental ADL ability, no antipsychotics, usage of non-steroidal anti-inflammatory drugs/acetylsalicylic acid, living with family member, lower education and a higher mean dose of ChEI. Apolipoprotein E genotype did not influence the rates of disease progression or the longitudinal outcomes. Prediction models were provided for moderate AD. More sensitive cognitive measures, such as the ADAS-cog scale, are required to detect a possibly faster deterioration among the participants with moderate AD. This study highlighted the clinical importance of instrumental ADL evaluations in patients at a mild stage of AD, and the importance of optimizing the ChEI dose even for individuals with moderate AD. Solitary living was a risk factor for

  10. Is heterogeneity in stage 3 non-small cell lung cancer obscuring the potential benefits of dose-escalated concurrent chemo-radiotherapy in clinical trials?

    PubMed

    Hudson, Andrew; Chan, Clara; Woolf, David; McWilliam, Alan; Hiley, Crispin; O'Connor, James; Bayman, Neil; Blackhall, Fiona; Faivre-Finn, Corinne

    2018-04-01

    The current standard of care for the management of inoperable stage 3 non-small cell lung cancer (NSCLC) is concurrent chemoradiotherapy (cCRT) using radiotherapy dose-fractionation and chemotherapy regimens that were established 3 decades ago. In an attempt to improve the chances of long-term control from cCRT, dose-escalation of the radiotherapy dose was assessed in the RTOG 0617 randomised control study comparing the standard 60 Gy in 30 fractions with a high-dose arm receiving 74 Gy in 37 fractions. Following the publication of this trial the thoracic oncology community were surprised to learn that there was worse survival in the dose-escalated arm and that for now the standard of care must remain with the lower dose. In this article we review the RTOG 0617 paper with subsequent analyses and studies to explore why the use of dose-escalated cCRT in stage 3 NSCLC has not shown the benefits that were expected. The overarching theme of this opinion piece is how heterogeneity between stage 3 NSCLC cases in terms of patient, tumour, and clinical factors may obscure the potential benefits of dose-escalation by causing imbalances in the arms of studies such as RTOG 0617. We also examine recent advances in the staging, management, and technological delivery of radiotherapy in NSCLC and how these may be employed to optimise cCRT trials in the future and ensure that any potential benefits of dose-escalation can be detected. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Establishing a Multicenter Longitudinal Clinical Cohort Study in Ethiopia: Advanced Clinical Monitoring of Antiretroviral Treatment Project.

    PubMed

    Teklu, Alula M; Tsegaye, Eyuel; Fekade, Daniel; Hailemelak, Abraham; Weiss, William; Hassen, Elham; Simmons, Nicole; Zewdu, Solomon; Berhan, Yifru; Getachew, Assefa; Hagos, Tesfalem; Alebachew, Achamyeleh; Damena, Melake; Sitotaw, Yohannes; Assefa, Yibeltal; Medhin, Girmay; Ruff, Andrea

    2017-02-01

    The purpose of this paper is to describe the establishment of the Advanced Clinical Monitoring of ART Project in Ethiopia for monitoring and evaluation of the longitudinal effectiveness of the ART program and to show the opportunities it presents. This cohort was established in response to the 2005 call by WHO for establishing additional mechanisms for stronger monitoring of ART and the need for creating the platform to generate evidence to guide the care given for the ever increasing number of patients on ART in Ethiopia. A participatory and multi-stage process which started from a consensus building workshop and steered by a mother protocol as well as guiding documents which dictated the degree of engagement and expectations was followed. The primary and secondary aims of the study were agreed upon. A multi-site longitudinal observational clinical cohort was established by a consortium of stakeholders including seven Ethiopian medical schools and their affiliated referral hospitals, John Hopkins University, Ethiopian Public Health Institute, Ministry of Science and Technology, US Centers for Disease Prevention and Control - CDC-Ethiopia, and the Federal Ministry of Health. Adult and adolescent cohorts covering the age range of 14+ years) and pediatric cohorts covering those below age 14 years were the two main cohorts. During the initial recruitment of these cohorts information was extracted from existing documents for a total of 2,100 adult participants. In parallel, a prospective cohort of 1,400 adult and adolescent patients were enrolled for ART initiation and follow-up. Using similar recruitment procedures, a total of 120 children were enrolled in each of retrospective and prospective cohorts. Replacement of participants were made in subsequent years based on lost follow up and death rates to maintain adequacy of the sample to be followed-up. Between January 2005 and August 2013 a total of 4,339 patients were followed for a median of 41.6 months and data on

  12. Prognostic significance of cell cycle proteins and genomic instability in borderline, early and advanced stage ovarian carcinomas.

    PubMed

    Blegen, H.; Einhorn, N.; Sjövall, K.; Roschke, A.; Ghadimi, B. M.; McShane, L. M.; Nilsson, B.; Shah, K.; Ried, T.; Auer, G.

    2000-11-01

    Disturbed cell cycle-regulating checkpoints and impairment of genomic stability are key events during the genesis and progression of malignant tumors. We analyzed 80 epithelial ovarian tumors of benign (n = 10) and borderline type (n = 18) in addition to carcinomas of early (n = 26) and advanced (n = 26) stages for the expression of Ki67, cyclin A and cyclin E, p21WAF-1, p27KIP-1 and p53 and correlated the results with the clinical course. Genomic instability was assessed by DNA ploidy measurements and, in 35 cases, by comparative genomic hybridization. Overexpression of cyclin A and cyclin E was observed in the majority of invasive carcinomas, only rarely in borderline tumors and in none of the benign tumors. Similarly, high expression of p53 together with undetectable p21 or loss of chromosome arm 17p were frequent events only in adenocarcinomas. Both borderline tumors and adenocarcinomas revealed a high number of chromosomal gains and losses. However, regional chromosomal amplifications were found to occur 13 times more frequently in the adenocarcinomas than in the borderline tumors. The expression pattern of low p27 together with high Ki67 was found to be an independent predictor of poor outcome in invasive carcinomas. The results provide a link between disturbed cell cycle regulatory proteins, chromosomal aberrations and survival in ovarian carcinomas.

  13. Stage-directed individualized therapy in esophageal cancer.

    PubMed

    Goense, Lucas; van Rossum, Peter S N; Kandioler, Daniela; Ruurda, Jelle P; Goh, Khean-Lee; Luyer, Misha D; Krasna, Mark J; van Hillegersberg, Richard

    2016-10-01

    Esophageal cancer is the eighth most common cancer worldwide, and the incidence of esophageal carcinoma is rapidly increasing. With the advent of new staging and treatment techniques, esophageal cancer can now be managed through various strategies. A good understanding of the advances and limitations of new staging techniques and how these can guide in individualizing treatment is important to improve outcomes for esophageal cancer patients. This paper outlines the recent progress in staging and treatment of esophageal cancer, with particularly attention to endoscopic techniques for early-stage esophageal cancer, multimodality treatment for locally advanced esophageal cancer, assessment of response to neoadjuvant treatment, and the role of cervical lymph node dissection. Furthermore, advances in robot-assisted surgical techniques and postoperative recovery protocols that may further improve outcomes after esophagectomy are discussed. © 2016 The Authors. Annals of the New York Academy of Sciences published by Wiley Periodicals Inc. on behalf of The New York Academy of Sciences.

  14. Extraperitoneal lymph node dissection in locally advanced cervical cancer; the prognostic factors associated with survival

    PubMed Central

    Köse, Mehmet Faruk; Kiseli, Mine; Kimyon, Günsu; Öcalan, Reyhan; Yenen, Müfit Cemal; Tulunay, Gökhan; Turan, Ahmet Taner; Üreyen, Işın; Boran, Nurettin

    2017-01-01

    Objective: Surgical staging was recently recommended for the decision of treatment in locally advanced cervical cancer. We aimed to investigate clinical outcomes as well as factors associated with overall survival (OS) in patients with locally advanced cervical cancer who had undergone extraperitoneal lymph node dissection and were managed according to their lymph node status. Material and Methods: The medical records of 233 women with stage IIb-IVa cervical cancer who were clinically staged and underwent extraperitoneal lymph node dissection were retrospectively reviewed. Paraaortic lymph node status determined the appropriate radiotherapeutic treatment field. Surgery-related complications and clinical outcomes were evaluated. Results: The median age of the patients was 52 years (range, 26-88 years) and the median follow-up time was 28.4 months (range, 3-141 months). Thirty-one patients had laparoscopic extraperitoneal lymph node dissection and 202 patients underwent laparotomy. The number of paraaortic lymph nodes extracted was similar for both techniques. Sixty-two (27%) of the 233 patients had paraaortic lymph node metastases. The 3-year and 5-year OS rates were 55.1% and 46.5%, respectively. The stage of disease, number of metastatic paraaortic lymph nodes, tumor type, and paraaortic lymph node status were associated with OS. In multivariate Cox regression analyses, tumor type, stage, and presence of paraaortic lymph node metastases were the independent prognostic factors of OS. Conclusion: Paraaortic lymph node metastasis is the most important prognostic factor affecting survival. Surgery would give hints about the prognosis and treatment planning of the patient. PMID:28400350

  15. Advanced Launch Vehicle Upper Stages Using Liquid Propulsion and Metallized Propellants

    NASA Technical Reports Server (NTRS)

    Palaszewski, Bryan A.

    1990-01-01

    Metallized propellants are liquid propellants with a metal additive suspended in a gelled fuel or oxidizer. Typically, aluminum (Al) particles are the metal additive. These propellants provide increase in the density and/or the specific impulse of the propulsion system. Using metallized propellant for volume-and mass-constrained upper stages can deliver modest increases in performance for low earth orbit to geosynchronous earth orbit (LEO-GEO) and other earth orbital transfer missions. Metallized propellants, however, can enable very fast planetary missions with a single-stage upper stage system. Trade studies comparing metallized propellant stage performance with non-metallized upper stages and the Inertial Upper Stage (IUS) are presented. These upper stages are both one- and two-stage vehicles that provide the added energy to send payloads to altitudes and onto trajectories that are unattainable with only the launch vehicle. The stage designs are controlled by the volume and the mass constraints of the Space Transportation System (STS) and Space Transportation System-Cargo (STS-C) launch vehicles. The influences of the density and specific impulse increases enabled by metallized propellants are examined for a variety of different stage and propellant combinations.

  16. Antiretroviral Therapy in Advanced HIV Disease: Which is the Best Regimen?

    PubMed

    Burgos, Joaquin; Ribera, Esteban; Falcó, Vicenç

    2018-01-01

    Advanced HIV disease, defined as a CD4 cell count below 200 cells/μl or the presence of an AIDS-defining illness, remains common among HIV-infected individuals who first present for medical care. In developed countries, nearly 30% of new HIV diagnoses occurred at advanced stages of the disease, and it is important because advanced HIV disease has been associated with worse clinical outcomes, including lower rates of virological response, higher morbidity, and higher mortality. However, there are scarce data regarding which is the best antiretroviral regimen in these patients. Nowadays, integrase inhibitor-based regimens are widely recommended as the best initial therapy for treatment-naïve HIV-infected patients by all international guidelines. However, these guidelines hardly mention the recommended regimens in individuals with advanced HIV disease. Otherwise, recent data indicating a higher risk of immune reconstitution inflammatory syndrome associated to the use of integrase inhibitors have raised concerns on the use of these drugs in patients with advanced HIV disease. The aim of this article is to review the available evidence from randomized clinical trials for the best treatment in patients with advanced HIV disease.

  17. Development and testing of a de novo clinical staging system for podoconiosis (endemic non-filarial elephantiasis).

    PubMed

    Tekola, Fasil; Ayele, Zewdu; Mariam, Dereje Haile; Fuller, Claire; Davey, Gail

    2008-10-01

    To develop and test a robust clinical staging system for podoconiosis, a geochemical disease in individuals exposed to red clay soil. We adapted the Dreyer system for staging filarial lymphoedema and tested it in four re-iterative field tests conducted in an area of high-podoconiosis prevalence in Southern Ethiopia. The system has five stages according to proximal spread of disease and presence of dermal nodules, ridges and bands. We measured the 1-week repeatability and the inter-observer agreement of the final staging system. The five-stage system is readily understood by community workers with little health training. Kappa for 1-week repeatability was 0.88 (95% CI 0.80-0.96), for agreement between health professionals was 0.71 (95% CI 0.60-0.82), while that between health professionals and community podoconiosis agents without formal health training averaged 0.64 (95% CI 0.52-0.78). This simple staging system with good inter-observer agreement and repeatability can assist in the management and further study of podoconiosis.

  18. Correlation between clinical fetal head station and sonographic angle of progression during the second stage of labor.

    PubMed

    Perlman, Sharon; Kivilevitch, Zvi; Moran, Orit; Katorza, Eldad; Kees, Salim; Achiron, Reuven; Gilboa, Yinon

    2017-08-04

    To investigate the correlation between the angle of progression and the clinical fetal head station (FHS) during the second stage of labor, and to build reference range. A prospective, observational study was conducted. Women carrying singleton term pregnancies were enrolled during the second stage of labor. FHS was assessed manually by a senior obstetrician, while the angle of progression (AOP) was assessed by transperineal ultrasound (TPU). Both examiners were blinded to each others results. The correlation between the sonographic AOP and the clinical FHS was analyzed. Seventy patients comprised the study group. Clinical FHS demonstrated an excellent correlation with the sonographic measurement of AOP (Pearson's Correlation 0.642, p < 0.001). This correlation was best described by a cubic regression according to the formula: 123.800 + 10.290 × FHS -2.889 * FHS +0.910, (r 2  = 0.423, p < .001). After aggregation of the mean AOP per FHS, the relative predicted centiles values and standard deviation were calculated. The mean Z score between measured and predicted values of the AOP for a given FHS was 0.007 (range -0.13 to +0.006). Our results demonstrate a significant correlation between the clinical FHS and the TPU measured AOP. These standardized sonographic values may serve the obstetrician as a reliable, objective auxiliary tool for the evaluation of the FHS during the second stage of labor.

  19. Association of serum ferritin levels with immunological status and clinical staging of HIV patients: a retrospective study

    NASA Astrophysics Data System (ADS)

    Saragih, R. H.; Mardia, A. I.; Purba, G. C. F.; Syahrini, H.

    2018-03-01

    Serum ferritin has long known as an acute phase reactant during inflammation. It works as an oxidative stress marker beside its role in the storage of intracellular iron. The increase of serum ferritin levels (SFL) has been reported found in HIV patients. It remains unclear though whether it causes, or is the cause, to the progressivity of the disease. The purpose of this study was to find the association between the SFL and the progressivity of the HIV disease. A retrospective study of 91 patients was carried out at the Haji Adam Malik Central General Hospital. All of the study population were HIV positive inpatients admitted from January to December 2016. The data needed to be all obtained from the patient’s medical records. The WHO Clinical Staging System was used to assess the HIV clinical staging. An inverse relationship was found between the SFL with the immunological status of the HIV patients (r=-0.213) based on their CD4+ count. There was no association found between the SFL with the clinical staging of the HIV patients (p=0.953). The elevated SFL is a feature found in HIV-diagnosed patients with the low CD4+ count, and it affects the progressivity of the disease.

  20. Clinical and dosimetric implications of intensity-modulated radiotherapy for early-stage glottic carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ward, Matthew Christopher, E-mail: wardm3@ccf.org; Pham, Yvonne D.; Kotecha, Rupesh

    2016-04-01

    Conventional parallel-opposed radiotherapy (PORT) is the established standard technique for early-stage glottic carcinoma. However, case reports have reported the utility of intensity-modulated radiotherapy (IMRT) and volumetric-modulated arc therapy (VMAT) with or without image guidance (image-guided radiotherapy, IGRT) in select patients. The proposed advantages of IMRT/VMAT include sparing of the carotid artery, thyroid gland, and the remaining functional larynx, although these benefits remain unclear. The following case study presents a patient with multiple vascular comorbidities treated with VMAT for early-stage glottic carcinoma. A detailed explanation of the corresponding treatment details, dose-volume histogram (DVH) analysis, and a review of the relevant literaturemore » are provided. Conventional PORT remains the standard of care for early-stage glottic carcinoma. IMRT or VMAT may be beneficial for select patients, although great care is necessary to avoid a geographical miss. Clinical data supporting the benefit of CRT are lacking. Therefore, these techniques should be used with caution and only in selected patients.« less

  1. Midwives׳ clinical reasoning during second stage labour: Report on an interpretive study.

    PubMed

    Jefford, Elaine; Fahy, Kathleen

    2015-05-01

    clinical reasoning was once thought to be the exclusive domain of medicine - setting it apart from 'non-scientific' occupations like midwifery. Poor assessment, clinical reasoning and decision-making skills are well known contributors to adverse outcomes in maternity care. Midwifery decision-making models share a common deficit: they are insufficiently detailed to guide reasoning processes for midwives in practice. For these reasons we wanted to explore if midwives actively engaged in clinical reasoning processes within their clinical practice and if so to what extent. The study was conducted using post structural, feminist methodology. to what extent do midwives engage in clinical reasoning processes when making decisions in the second stage labour? twenty-six practising midwives were interviewed. Feminist interpretive analysis was conducted by two researchers guided by the steps of a model of clinical reasoning process. Six narratives were excluded from analysis because they did not sufficiently address the research question. The midwives narratives were prepared via data reduction. A theoretically informed analysis and interpretation was conducted. using a feminist, interpretive approach we created a model of midwifery clinical reasoning grounded in the literature and consistent with the data. Thirteen of the 20 participant narratives demonstrate analytical clinical reasoning abilities but only nine completed the process and implemented the decision. Seven midwives used non-analytical decision-making without adequately checking against assessment data. over half of the participants demonstrated the ability to use clinical reasoning skills. Less than half of the midwives demonstrated clinical reasoning as their way of making decisions. The new model of Midwifery Clinical Reasoning includes 'intuition' as a valued way of knowing. Using intuition, however, should not replace clinical reasoning which promotes through decision-making can be made transparent and be

  2. The Impact of Local and Regional Disease Extent on Overall Survival in Patients With Advanced Stage IIIB/IV Non-Small Cell Lung Carcinoma

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Higginson, Daniel S., E-mail: daniel.higginson@gmail.com; Chen, Ronald C.; Tracton, Gregg

    2012-11-01

    Purpose: Patients with advanced stage IIIB or stage IV non-small cell lung carcinoma are typically treated with initial platinum-based chemotherapy. A variety of factors (eg, performance status, gender, age, histology, weight loss, and smoking history) are generally accepted as predictors of overall survival. Because uncontrolled pulmonary disease constitutes a major cause of death in these patients, we hypothesized that clinical and radiographic factors related to intrathoracic disease at diagnosis may be prognostically significant in addition to conventional factors. The results have implications regarding the selection of patients for whom palliative thoracic radiation therapy may be of most benefit. Methods andmore » Materials: We conducted a pooled analysis of 189 patients enrolled at a single institution into 9 prospective phase II and III clinical trials involving first-line, platinum-based chemotherapy. Baseline clinical and radiographic characteristics before trial enrollment were analyzed as possible predictors for subsequent overall survival. To assess the relationship between anatomic location and volume of disease within the thorax and its effect on survival, the pre-enrollment computed tomography images were also analyzed by contouring central and peripheral intrapulmonary disease. Results: On univariate survival analysis, multiple pulmonary-related factors were significantly associated with worse overall survival, including pulmonary symptoms at presentation (P=.0046), total volume of intrathoracic disease (P=.0006), and evidence of obstruction of major bronchi or vessels on prechemotherapy computed tomography (P<.0001). When partitioned into central and peripheral volumes, central (P<.0001) but not peripheral (P=.74) disease was associated with worse survival. On multivariate analysis with known factors, pulmonary symptoms (hazard ratio, 1.46; P=.042), central disease volume (hazard ratio, 1.47; P=.042), and bronchial/vascular compression (hazard

  3. Association of code status discussion with invasive procedures among advanced-stage cancer and noncancer patients.

    PubMed

    Sasaki, Akinori; Hiraoka, Eiji; Homma, Yosuke; Takahashi, Osamu; Norisue, Yasuhiro; Kawai, Koji; Fujitani, Shigeki

    2017-01-01

    Code status discussion is associated with a decrease in invasive procedures among terminally ill cancer patients. We investigated the association between code status discussion on admission and incidence of invasive procedures, cardiopulmonary resuscitation (CPR), and opioid use among inpatients with advanced stages of cancer and noncancer diseases. We performed a retrospective cohort study in a single center, Ito Municipal Hospital, Japan. Participants were patients who were admitted to the Department of Internal Medicine between October 1, 2013 and August 30, 2015, with advanced-stage cancer and noncancer. We collected demographic data and inquired the presence or absence of code status discussion within 24 hours of admission and whether invasive procedures, including central venous catheter placement, intubation with mechanical ventilation, and CPR for cardiac arrest, and opioid treatment were performed. We investigated the factors associated with CPR events by using multivariate logistic regression analysis. Among the total 232 patients, code status was discussed with 115 patients on admission, of which 114 (99.1%) patients had do-not-resuscitate (DNR) orders. The code status was not discussed with the remaining 117 patients on admission, of which 69 (59%) patients had subsequent code status discussion with resultant DNR orders. Code status discussion on admission decreased the incidence of central venous catheter placement, intubation with mechanical ventilation, and CPR in both cancer and noncancer patients. It tended to increase the rate of opioid use. Code status discussion on admission was the only factor associated with the decreased use of CPR ( P <0.001, odds ratio =0.03, 95% CI =0.004-0.21), which was found by using multivariate logistic regression analysis. Code status discussion on admission is associated with a decrease in invasive procedures and CPR in cancer and noncancer patients. Physicians should be educated about code status discussion to

  4. Esophageal dysfunction in different stages of Parkinson's disease.

    PubMed

    Suttrup, I; Suttrup, J; Suntrup-Krueger, S; Siemer, M-L; Bauer, J; Hamacher, C; Oelenberg, S; Domagk, D; Dziewas, R; Warnecke, T

    2017-01-01

    Dysphagia is a clinically relevant symptom in patients with Parkinson's disease (PD) leading to pronounced reduction in quality of life and other severe complications. Parkinson's disease-related dysphagia may affect the oral and pharyngeal, as well as the esophageal phase of swallowing. To examine the nature and extend of esophageal dysphagia in different stages of PD and their relation to oropharyngeal dysfunction, we examined 65 PD patients (mean age 66.3±9.7 years, mean disease duration 7.9±5.8 years, mean Hoehn & Yahr [H&Y] stage 2.89±0.91) and divided into three groups (early [H&Y I+II; n=21], intermediate [H&Y III; n=25], and advanced stadium [H&Y IV+V; n=19]), using esophageal high-resolution manometry (HRM) to detect esophageal motor disorders. Oropharyngeal impairment was assessed using fiberoptic endoscopic evaluation of swallowing. Major esophageal motor disorders were detected in nearly one third of the PD patients. Minor impairment of the esophageal body was present in 95% of participants and throughout all disease stages with pathological findings especially in peristalsis and intrabolus pressure (IBP). The IBP was found to significantly increase in the advanced stadium. Although dysfunction of the upper and lower esophageal sphincters was observed in individual patients, alterations in these esophageal segments revealed no statistical significance compared with normative data. No clear association was found between the occurrence of oropharyngeal dysphagia and esophageal impairment. Esophageal body impairment in PD is a frequent phenomenon during all disease stages, which possibly reflects α-synucleinopathy in the enteric nervous system. © 2016 John Wiley & Sons Ltd.

  5. Evaluation of the appropriateness of the preclinical phase (stage A and stage B) of heart failure Management in Outpatient clinics in Italy rationale and design of the 'VASTISSIMO' study.

    PubMed

    Mureddu, Gian F; Nistri, Stefano; Faggiano, Pompilio; Fimiani, Biagio; Misuraca, Gianfranco; Maggi, Antonio; Gori, Anna M; Uguccioni, Massimo; Tavazzi, Luigi; Zito, Giovanni B

    2016-07-01

    Early detection of heart failure, when still preclinical, is fundamental. Therefore, it is important to assess whether preclinical heart failure management by cardiologists is adequate. The VASTISSIMO study ('EValuation of the AppropriateneSs of The preclInical phase (Stage A and Stage B) of heart failure Management in Outpatient clinics in Italy') is a prospective nationwide study aimed to evaluate the appropriateness of diagnosis and management of preclinical heart failure (stages A and B) by cardiologists working in outpatient clinics in Italy. Secondary goals are to verify if an online educational course for cardiologists can improve management of preclinical heart failure, and evaluate how well cardiologists are aware of patients' adherence to medications. The study involves 80 outpatient cardiology clinics distributed throughout Italy, affiliated either to the Hospital Cardiologists Association or to the Regional Association of Outpatient Cardiologists, and is designed with two phases of consecutive outpatient enrolment each lasting 1 month. In phase 1, physicians' awareness of the risk of heart failure and their decision-making process are recorded. Subsequently, half of the cardiologists are randomized to undergo an online educational course aimed to improve preclinical heart failure management through implementation of guideline recommendations. At the end of the course, all cardiologists are evaluated (phase 2) to see whether changes in clinical management have occurred in those who underwent the educational program versus those who did not. Patients' adherence to prescribed medications will be assessed through the Morisky Self-report Questionnaire. This study should provide valuable information about cardiologists' awareness of preclinical heart failure and the appropriateness of clinical practice in outpatient cardiology clinics in Italy.

  6. Method and apparatus for advanced staged combustion utilizing forced internal recirculation

    DOEpatents

    Rabovitser, Iosif K.; Knight, Richard A.; Cygan, David F.; Nester, Serguei; Abbasi, Hamid A.

    2003-12-16

    A method and apparatus for combustion of a fuel in which a first-stage fuel and a first-stage oxidant are introduced into a combustion chamber and ignited, forming a primary combustion zone. At least about 5% of the total heat output produced by combustion of the first-stage fuel and the first-stage oxidant is removed from the primary combustion zone, forming cooled first-stage combustion products. A portion of the cooled first-stage combustion products from a downstream region of the primary combustion zone is recirculated to an upstream region of primary combustion zone. A second-stage fuel is introduced into the combustion chamber downstream of the primary combustion zone and ignited, forming a secondary combustion zone. At least about 5% of the heat from the secondary combustion zone is removed. In accordance with one embodiment, a third-stage oxidant is introduced into the combustion chamber downstream of the secondary combustion zone, forming a tertiary combustion zone.

  7. The reliability of clinical decisions based on the cervical vertebrae maturation staging method.

    PubMed

    Sohrabi, Aydin; Babay Ahari, Sahar; Moslemzadeh, Hossein; Rafighi, Ali; Aghazadeh, Zahra

    2016-02-01

    Of the various techniques used to determine the optimum timing for growth modification treatments, the cervical vertebrae maturation method has great advantages, including validity and no need for extra X-ray exposure. Recently, the reproducibility of this method has been questioned. The aim of this study was to investigate the cause of poor reproducibility of this method and to assess the reproducibility of the clinical decisions made based on it. Seventy lateral cephalograms of Iranian patients aged 9‒15 years were observed twice by five experienced orthodontists. In addition to determining the developmental stage, each single parameter involved in this method was assessed in terms of inter- and intra-observer reproducibility. In order to evaluate the reproducibility of clinical decisions based on this method, cervical vertebrae maturation staging (CVMS) I and II were considered as phase 1 and CVMS IV and V were considered as phase 3. By considering the clinical approach of the CVMS method, inter-observer reproducibility of this method increased from 0.48 to 0.61 (moderate to substantial) and intra-observer reproducibility enhanced from 0.72 to 0.74. 1. Complete visualization of the first four cervical vertebrae was an inclusion criterion, which also limits the clinical application of CVMS method. 2. These results can be generalized when determining growth modification treatments solely for Class II patients. Difficulty in determining the morphology of C3 and C4 leads to poor reproducibility of the CVMS method. Despite this, it has acceptable reproducibility in determining the timing of functional treatment for Class II patients. © The Author 2015. Published by Oxford University Press on behalf of the European Orthodontic Society. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  8. Predicting distant failure in early stage NSCLC treated with SBRT using clinical parameters.

    PubMed

    Zhou, Zhiguo; Folkert, Michael; Cannon, Nathan; Iyengar, Puneeth; Westover, Kenneth; Zhang, Yuanyuan; Choy, Hak; Timmerman, Robert; Yan, Jingsheng; Xie, Xian-J; Jiang, Steve; Wang, Jing

    2016-06-01

    The aim of this study is to predict early distant failure in early stage non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) using clinical parameters by machine learning algorithms. The dataset used in this work includes 81 early stage NSCLC patients with at least 6months of follow-up who underwent SBRT between 2006 and 2012 at a single institution. The clinical parameters (n=18) for each patient include demographic parameters, tumor characteristics, treatment fraction schemes, and pretreatment medications. Three predictive models were constructed based on different machine learning algorithms: (1) artificial neural network (ANN), (2) logistic regression (LR) and (3) support vector machine (SVM). Furthermore, to select an optimal clinical parameter set for the model construction, three strategies were adopted: (1) clonal selection algorithm (CSA) based selection strategy; (2) sequential forward selection (SFS) method; and (3) statistical analysis (SA) based strategy. 5-cross-validation is used to validate the performance of each predictive model. The accuracy was assessed by area under the receiver operating characteristic (ROC) curve (AUC), sensitivity and specificity of the system was also evaluated. The AUCs for ANN, LR and SVM were 0.75, 0.73, and 0.80, respectively. The sensitivity values for ANN, LR and SVM were 71.2%, 72.9% and 83.1%, while the specificity values for ANN, LR and SVM were 59.1%, 63.6% and 63.6%, respectively. Meanwhile, the CSA based strategy outperformed SFS and SA in terms of AUC, sensitivity and specificity. Based on clinical parameters, the SVM with the CSA optimal parameter set selection strategy achieves better performance than other strategies for predicting distant failure in lung SBRT patients. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Lung cancer staging now and in the future.

    PubMed

    Liam, Chong-Kin; Andarini, Sita; Lee, Pyng; Ho, James Chung-Man; Chau, Ngo Quy; Tscheikuna, Jamsak

    2015-05-01

    For a long time lung cancer was associated with a fatalistic approach by healthcare professionals. In recent years, advances in imaging, improved diagnostic techniques and more effective treatment modalities are reasons for optimism. Accurate lung cancer staging is vitally important because treatment options and prognosis differ significantly by stage. The staging algorithm should include a contrast computed tomography (CT) of the chest and the upper abdomen including adrenals, positron emission tomography/CT for staging the mediastinum and to rule out extrathoracic metastasis in patients considered for surgical resection, endosonography-guided needle sampling procedure replacing mediastinoscopy for near complete mediastinal staging, and brain imaging as clinically indicated. Applicability of evidence-based guidelines for staging of lung cancer depends on the available expertise and level of resources and is directly impacted by financial issues. Considering the diversity of healthcare infrastructure and economic performance of Asian countries, optimal and cost-effective use of staging methods appropriate to the available resources is prudent. The pulmonologist plays a central role in the multidisciplinary approach to lung cancer diagnosis, staging and management. Regional respiratory societies such as the Asian Pacific Society of Respirology should work with national respiratory societies to strive for uniform standards of care. For developing countries, a minimum set of care standards should be formulated. Cost-effective delivery of optimal care for lung cancer patients, including staging within the various healthcare systems, should be encouraged and most importantly, tobacco control implementation should receive an absolute priority status in all countries in Asia. © 2015 Asian Pacific Society of Respirology.

  10. HCV clearance after direct-acting antivirals in patients with cirrhosis by stages of liver impairment: The ITAL-C network study.

    PubMed

    Ippolito, Antonio Massimo; Milella, Michele; Messina, Vincenzo; Conti, Fabio; Cozzolongo, Raffaele; Morisco, Filomena; Brancaccio, Giuseppina; Barone, Michele; Santantonio, Teresa; Masetti, Chiara; Tundo, Paolo; Smedile, Antonina; Carretta, Vito; Gatti, Pietro; Termite, Antonio Patrizio; Valvano, Maria Rosa; Bruno, Giuseppe; Fabrizio, Claudia; Andreone, Pietro; Zappimbulso, Marianna; Gaeta, Giovanni Battista; Napoli, Nicola; Fontanella, Luca; Lauletta, Gianfranco; Cuccorese, Giuseppe; Metrangolo, Antonio; Francavilla, Ruggiero; Ciracì, Emanuela; Rizzo, Salvatore; Andriulli, Angelo

    2017-09-01

    Sustained virological response (SVR12) rates at 12 weeks after treatment for HCV-infected patients with decompensated cirrhosis are used when referring to those with moderate functional impairment, while few data are available for those with more severe impairment. The use of the cirrhosis staging system proposed by D'Amico might provide new insights on timing for antiviral therapy. We investigated efficacy (SVR12), safety, and post-treatment variations in clinical and laboratory parameters in 2612 patients with advanced fibrosis (n=575) or cirrhosis (n=2037). Cirrhosis was in the compensated phase (without/with varices) or had previously been in the decompensated stage. Different direct-acting antiviral (DAA) regimens were administered in accordance with scientific guidelines. The SVR12 rate was 97.6% in patients with advanced fibrosis. For patients with cirrhosis, the rate was 96.5% in stage 1, 95.1% in stage 2, 100% in stage 3, 95.7% in stage 4, and 93.6% in stage 5. These rates were independent of gender, age, HCV genotype, and treatment schedule. Positive changes in biochemical parameters and CPT classes following therapy were evident in compensated and previously decompensated patients. Our findings support the use of DAAs in patients with advanced cirrhosis (stages 3-5) who are at greatest risk and have the most to gain from therapy. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  11. The Impact of a Multidimensional Exercise Intervention on Physical and Functional Capacity, Anxiety, and Depression in Patients With Advanced-Stage Lung Cancer Undergoing Chemotherapy.

    PubMed

    Quist, Morten; Adamsen, Lis; Rørth, Mikael; Laursen, Jørgen H; Christensen, Karl B; Langer, Seppo W

    2015-07-01

    Patients with advanced-stage lung cancer face poor survival and experience co-occurring chronic physical and psychosocial symptoms. Despite several years of research in exercise oncology, few exercise studies have targeted advanced lung cancer patients undergoing chemotherapy. The aim of the present study was to investigate the benefits of a 6-week supervised group exercise intervention and to outline the effect on aerobic capacity, strength, health-related quality of life (HRQoL), anxiety, and depression. VO2peak was assessed using an incremental exercise test. Muscle strength was measured with one repetition maximum test (1RM). HRQoL, anxiety, and depression were assessed using Functional Assessment of Cancer Therapy-Lung (FACT-L) scale and the Hospital Anxiety and Depression Scale (HADS). One hundred and forthteen patients with advanced stage lung cancer were recruited. Forty-three patients dropped out. No serious adverse events were reported. Exercise adherence in the group training was 68%. Improvements in VO2peak (P < .001) and 6-minute walk distance (P < .001) and muscle strength measurements (P < .05) were seen. There was a reduction in anxiety level (P = .0007) and improvement in the emotional well-being parameter (FACT-L) but no statistically significant changes in HRQoL were observed. The results of the present study show that during a 6-week hospital-based supervised, structured, and group-based exercise program, patients with advanced-stage lung cancer (NSCLC IIIb-IV, ED-SCLC) improve their physical capacity (VO2peak, 1RM), functional capacity, anxiety level, and emotional well-being, but not their overall HRQoL. A randomized controlled trial testing the intervention including 216 patients is currently being carried out. © The Author(s) 2015.

  12. Advances in pancreatic cancer research: moving towards early detection.

    PubMed

    He, Xiang-Yi; Yuan, Yao-Zong

    2014-08-28

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer. Substantial progress has been made in the understanding of the biology of pancreatic cancer, and advances in patient management have been significant. However, most patients (nearly 80%) who present with locally advanced or metastatic disease have an extremely poor prognosis. Survival is better for those with malignant disease localized to the pancreas, because surgical resection at present offers the only chance of cure. Therefore, the early detection of pancreatic cancer may benefit patients with PDAC. However, its low rate of incidence and the limitations of current screening strategies make early detection difficult. Recent advances in the understanding of the pathogenesis of PDAC suggest that it is possible to detect PDAC in early stages and even identify precursor lesions. The presence of new-onset diabetes mellitus in the early phase of pancreatic cancer may provide clues for its early diagnosis. Advances in the identification of novel circulating biomarkers including serological signatures, autoantibodies, epigenetic markers, circulating tumor cells and microRNAs suggest that they can be used as potential tools for the screening of precursors and early stage PDAC in the future. However, proper screening strategies based on effective screening methodologies need to be tested for clinical application.

  13. Circulating CD147 predicts mortality in advanced hepatocellular carcinoma.

    PubMed

    Lee, Aimei; Rode, Anthony; Nicoll, Amanda; Maczurek, Annette E; Lim, Lucy; Lim, Seok; Angus, Peter; Kronborg, Ian; Arachchi, Niranjan; Gorelik, Alexandra; Liew, Danny; Warner, Fiona J; McCaughan, Geoffrey W; McLennan, Susan V; Shackel, Nicholas A

    2016-02-01

    The glycoprotein CD147 has a role in tumor progression, is readily detectable in the circulation, and is abundantly expressed in hepatocellular carcinoma (HCC). Advanced HCC patients are a heterogeneous group with some individuals having dismal survival. The aim of this study was to examine circulating soluble CD147 levels as a prognostic marker in HCC patients. CD147 was measured in 277 patients (110 HCC, 115 chronic liver disease, and 52 non-liver disease). Clinical data included etiology, tumor progression, Barcelona Clinic Liver Cancer (BCLC) stage, and treatment response. Patients with HCC were stratified into two groups based upon the 75th percentile of CD147 levels (24 ng/mL). CD147 in HCC correlated inversely with poor survival (P = 0.031). Increased CD147 predicted poor survival in BCLC stages C and D (P = 0.045), and CD147 levels >24 ng/mL predicted a significantly diminished 90-day and 180-day survival time (hazard ratio [HR] = 6.1; 95% confidence interval [CI]: 2.1-63.2; P = 0.0045 and HR = 2.8; 95% CI: 1.2-12.6; P = 0.028, respectively). In BCLC stage C, CD147 predicted prognosis; levels >24 ng/mL were associated with a median survival of 1.5 months compared with 6.5 months with CD147 levels ≤24 ng/mL (P = 0.03). CD147 also identified patients with a poor prognosis independent from treatment frequency, modality, and tumor size. Circulating CD147 is an independent marker of survival in advanced HCC. CD147 requires further evaluation as a potential new prognostic measure in HCC to identify patients with advanced disease who have a poor prognosis. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

  14. SU-E-J-87: Ventilation Weighting Effect On Mean Doses of Both Side Lungs for Patients with Advanced Stage Lung Cancer

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Qu, H; Xia, P; Yu, N

    Purpose: To study ventilation weighting effect on radiation doses to both side lungs for patients with advanced stage lung cancer. Methods: Fourteen patients with advanced stage lung cancer were included in this retrospective study. Proprietary software was developed to calculate the lung ventilation map based on 4DCT images acquired for radiation therapy. Two phases of inhale (0%) and exhale (50%) were used for the lung ventilation calculations. For each patient, the CT images were resampled to the same dose calculation resolution of 3mmx3mmx3mm. The ventilation distribution was then normalized by the mean value of the ventilation. The ventilation weighted dosemore » was calculated by applying linearly weighted ventilation to the dose of each pixel. The lung contours were automatically delineated from patient CT image with lung window, excluding the tumor and high density tissues. For contralateral and ipsilateral lungs, the mean lung doses from the original plan and ventilation weighted mean lung doses were compared using two tail t-Test. Results: The average of mean dose was 6.1 ±3.8Gy for the contralateral lungs, and 26.2 ± 14.0Gy for the ipsilateral lungs. The average of ventilation weighted dose was 6.3± 3.8Gy for the contralateral lungs and 24.6 ± 13.1Gy for the ipsilateral lungs. The statistics analysis shows the significance of the mean dose increase (p<0.015) for the contralateral lungs and decrease (p<0.005) for the ipsilateral lungs. Conclusion: Ventilation weighted doses were greater than the un-weighted doses for contralateral lungs and smaller for ipsilateral lungs. This Result may be helpful to understand the radiation dosimetric effect on the lung function and provide planning guidance for patients with advance stage lung cancer.« less

  15. Routine conventional karyotyping of lymphoma staging bone marrow samples does not contribute clinically relevant information.

    PubMed

    Nardi, Valentina; Pulluqi, Olja; Abramson, Jeremy S; Dal Cin, Paola; Hasserjian, Robert P

    2015-06-01

    Bone marrow (BM) evaluation is an important part of lymphoma staging, which guides patient management. Although positive staging marrow is defined as morphologically identifiable disease, such samples often also include flow cytometric analysis and conventional karyotyping. Cytogenetic analysis is a labor-intensive and costly procedure and its utility in this setting is uncertain. We retrospectively reviewed pathological reports of 526 staging marrow specimens in which conventional karyotyping had been performed. All samples originated from a single institution from patients with previously untreated Hodgkin and non-Hodgkin lymphomas presenting in an extramedullary site. Cytogenetic analysis revealed clonal abnormalities in only eight marrow samples (1.5%), all of which were positive for lymphoma by morphologic evaluation. Flow cytometry showed a small clonal lymphoid population in three of the 443 morphologically negative marrow samples (0.7%). Conventional karyotyping is rarely positive in lymphoma staging marrow samples and, in our cohort, the BM karyotype did not contribute clinically relevant information in the vast majority of cases. Our findings suggest that karyotyping should not be performed routinely on BM samples taken to stage previously diagnosed extramedullary lymphomas unless there is pathological evidence of BM involvement by lymphoma. © 2015 Wiley Periodicals, Inc.

  16. [Application of clinical nursing path in standard management of advanced schistosomiasis patients with splenomegaly].

    PubMed

    Yang, Liu; Liu, Juan-Juan

    2013-04-01

    To study the feasibility and effect of clinical nursing path in the standard management of advanced schistosomiasis patients with splenomegaly. A total of 64 advanced schistosomiasis patients with splenomegaly were randomly divided into a routine nursing group (control group) and a clinical nursing pathway group (CNP group), and the postoperative situation, average hospitalization days, cost of hospitalization and the satisfaction of the patients of the 2 groups were compared. The complications, average hospitalization days, costs of hospitalization in the CNP group were significantly decreased compared with those in the control group, and satisfaction rate of the patients in the CNP group increased from 81.25% to 100%. The implementation of CNP effectively reduces the length of hospitalization, costs and complications, and improves the satisfaction of the patients.

  17. Squalene epoxidase, located on chromosome 8q24.1, is upregulated in 8q+ breast cancer and indicates poor clinical outcome in stage I and II disease.

    PubMed

    Helms, M W; Kemming, D; Pospisil, H; Vogt, U; Buerger, H; Korsching, E; Liedtke, C; Schlotter, C M; Wang, A; Chan, S Y; Brandt, B H

    2008-09-02

    Gains of chromosomes 7p and 8q are associated with poor prognosis among oestrogen receptor-positive (ER+) stage I/II breast cancer. To identify transcriptional changes associated with this breast cancer subtype, we applied suppression subtractive hybridisation method to analyse differentially expressed genes among six breast tumours with and without chromosomal 7p and 8q gains. Identified mRNAs were validated by real-time RT-PCR in tissue samples obtained from 186 patients with stage I/II breast cancer. Advanced statistical methods were applied to identify associations of mRNA expression with distant metastasis-free survival (DMFS). mRNA expression of the key enzyme of cholesterol biosynthesis, squalene epoxidase (SQLE, chromosomal location 8q24.1), was associated with ER+ 7p+/8q+ breast cancer. Distant metastasis-free survival in stage I/II breast cancer cases was significantly inversely related to SQLE mRNA in multivariate Cox analysis (P<0.001) in two independent patient cohorts of 160 patients each. The clinically favourable group associated with a low SQLE mRNA expression could be further divided by mRNA expression levels of the oestrogen-regulated zinc transporter LIV-1. The data strongly support that SQLE mRNA expression might indicate high-risk ER+ stage I/II breast cancers. Further studies on tumour tissue from standardised treated patients, for example with tamoxifen, may validate the role of SQLE as a novel diagnostic parameter for ER+ early stage breast cancers.

  18. Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty.

    PubMed Central

    Tanner, J M; Whitehouse, R H

    1976-01-01

    New charts for height, weight, height velocity, and weight velocity are presented for clinical (as opposed to population survey) use. They are based on longitudinal-type growth curves, using the same data as in the British 1965 growth standards. In the velocity standards centiles are given for children who are early- and late-maturing as well as for those who mature at the average age (thus extending the use of the previous charts). Limits of normality for the age of occurrence of the adolescent growth spurt are given and also for the successive stages of penis, testes, and pubic hair development in boys, and for stages of breast and pubic hair development in girls. PMID:952550

  19. Influence of Preoperative Chemoradiotherapy on the Surgical Strategy According to the Clinical T Stage of Patients With Rectal Cancer

    PubMed Central

    Park, In Ja; Lee, Jong Lyul; Yoon, Yong Sik; Kim, Chan Wook; Lim, Seok-Byung; Lee, Jong Seok; Park, Seong Ho; Park, Jin Hong; Kim, Jong Hoon; Yu, Chang Sik; Kim, Jin Cheon

    2015-01-01

    Abstract The aim of this study was to evaluate the pathologic responses and changes to surgical strategies following preoperative chemoradiotherapy (PCRT) in rectal cancer patients according to their clinical T stage (cT). The use of PCRT has recently been extended to less advanced disease. The authors enrolled 650 patients with cT2 to 4 mid and low rectal cancer who received both PCRT and surgical resection. The rate of total regression and the proportion of local excision were compared according to the cT category. The 3-year recurrence-free survival (RFS) rate was compared using the log-rank test according to patient cT category, pathologic stage, and type of surgical treatment. Patients with cT2 were older (P = 0.001), predominately female (P = 0.028), and had low-lying rectal cancer (P = 0.008). Pathologic total regression was achieved most frequently in cT2 patients (54% of cT2 versus 17.6% of cT3 versus 8.2% of cT4; P < 0.001). Local excision was performed on 42 cT2 (42%) and 24 cT3 (5.2%) patients (P < 0.001). The 3-year RFS rates differed according to both cT (P < 0.001) and ypT stage (P < 0.001). Among patients with ypT0 to 1 disease, the 3-year RFS did not differ according to the type of surgical treatment received (P = 0.5). Total regression of the primary tumor and a change in the surgical strategy after PCRT are most commonly seen in cT2 disease. Although PCRT is not generally indicated for cT2 rectal cancer, optimal surgical treatment may be achieved with the tailored use of PCRT. PMID:26717384

  20. Clinical Implementation of Novel Targeted Therapeutics in Advanced Breast Cancer.

    PubMed

    Chamberlin, Mary D; Bernhardt, Erica B; Miller, Todd W

    2016-11-01

    The majority of advanced breast cancers have genetic alterations that are potentially targetable with drugs. Through initiatives such as The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), data can be mined to provide context for next-generation sequencing (NGS) results in the landscape of advanced breast cancer. Therapies for targets other than estrogen receptor alpha (ER) and HER2, such as cyclin-dependent kinases CDK4 and CDK6, were recently approved based on efficacy in patient subpopulations, but no predictive biomarkers have been found, leaving clinicians to continue a trial-and-error approach with each patient. Next-generation sequencing identifies potentially actionable alterations in genes thought to be drivers in the cancerous process including phosphatidylinositol 3-kinase (PI3K), AKT, fibroblast growth factor receptors (FGFRs), and mutant HER2. Epigenetically directed and immunologic therapies have also shown promise for the treatment of breast cancer via histone deacetylases (HDAC) 1 and 3, programmed T cell death 1 (PD-1), and programmed T cell death ligand 1 (PD-L1). Identifying biomarkers to predict primary resistance in breast cancer will ultimately affect clinical decisions regarding adjuvant therapy in the first-line setting. However, the bulk of medical decision-making is currently made in the secondary resistance setting. Herein, we review the clinical potential of PI3K, AKT, FGFRs, mutant HER2, HDAC1/3, PD-1, and PD-L1 as therapeutic targets in breast cancer, focusing on the rationale for therapeutic development and the status of clinical testing. J. Cell. Biochem. 117: 2454-2463, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. The Effect of Two-Staged Warm Compress on the Pain Duration of First and Second Labor Stages and Apgar Score in Prim Gravida Women: a Randomized Clinical Trial

    PubMed Central

    Akbarzadeh, Marzieh; Nematollahi, Azar; Farahmand, Mahnaz; Amooee, Sedigheh

    2018-01-01

    Introduction: The aim of this study was to assess the effect of two-stage warm compress technique on the pain duration of the first and second labor stages and neonatal outcomes. Methods: The clinical trial was done on 150 women (75 subjects in each groups) in Shiraz-affiliated hospitals in 2012 A two-staged warm compress was done for 15-20 minutes in the first and second labor phase (cervical dilatation of 7 and 10 cm with zero status) while the control group received hospital routine care. The duration of labor and Apgar score were evaluated. Results: According to t-test, the average of labor duration was lower in the intervention group compared to the control group at the second stage. However, there was no significant difference for labor duration at the first stage and the first and fifth minute Apgar score. Conclusion: According to the result, this intervention seems a good method for decreasing labor duration at the second stage of parturition. PMID:29637053

  2. CD30 expression utilization for the accuracy of classical Hodgkin's lymphoma staging.

    PubMed

    Flangea, Corina; Potencz, Elena; Mihăescu, Rodica; Anghel, A; Gîju, S; Motoc, Marilena; Dogaru, C

    2006-01-01

    The presence of Reed-Sternberg malignant cells is absolutely necessary for Hodgkin's lymphoma diagnostic, but it is not always sufficient because can be observed Reed-Sternberg-like cells in other malignant and benign diseases, too. The CD30 expression at Hodgkin and Reed-Sternberg level can give us supplementary information in differential diagnostic and can be used as progressive disease factor. Our study was composed from 63 cases histopathological diagnosed with Hodgkin's lymphoma and hospitalized in Hematology Department of County Hospital Timişoara. CD30 expression was immunohistochemical semi-quantitative evaluated using clone BerH2 as primary antibody and APAAP-New Fuchsin as visualization system. The increasing of CD30 expression occurs in the same time with advanced stages and the disease progression (p =0.001). For I and II stages CD30 expression does not overcome (-/+) category while the III and IV stages, all the cases are situated in (+/-) and (+) categories. No connection can be noticed between histological type and CD30 expression (p < or = 1). We consider that using this staining, although less used in Romania, must be done in all Hodgkin's lymphoma and Hodgkin's lymphoma-like cases. We say that because the main cause of relapses is represented by inadequate clinical staging and diagnostic. In our study, the increasing of CD30 expression is associated with advanced disease stage. We recommend reinvestigating and restaging all cases that was included into an incipient stages and they have a CD30 expression situated in (+/-) and (+) intervals because some lymph nodes could be overlooked.

  3. Ultra-wide-field scanning laser ophthalmoscopy assists in the clinical detection and evaluation of asymptomatic early-stage familial exudative vitreoretinopathy.

    PubMed

    Lyu, Jiao; Zhang, Qi; Wang, Shi-Yuan; Chen, Yi-Ye; Xu, Yu; Zhao, Pei-Quan

    2017-01-01

    This study aims to investigate the ability of the ultra-wide-field scanning laser ophthalmoscope (UWF SLO) in clinically detecting and evaluating asymptomatic early-stage familial exudative vitreoretinopathy (FEVR). We retrospectively reviewed 163 eyes of 83 asymptomatic family members of 48 patients with FEVR. UWF SLO imaging (Optos® PLC, Scotland, UK) was performed on asymptomatic family members as a preliminary screening test for fundus anomalies, and the findings were compared with subsequent examinations using indirect fundus ophthalmoscopy in full mydriasis, fluorescein angiography (FA), fundus autoflourescence, and genetic sequencing. A total of 86 eyes of 43 asymptomatic family members were clinically diagnosed with early-stage FEVR, and 17 of the affected 43 family members were also genetically diagnosed. Compared with FA as a standard, the UWF SLO was highly effective in diagnosing FEVR with a sensitivity and specificity of 93.0 % and 97.5 %, respectively. The UWF SLO was able to diagnose early-stage FEVR in 93.0 % of eyes, and guided the selection of therapies in 46.5 % of the eyes studied. UWF SLO is a valuable imaging tool for detecting fundus anomalies related to early-stage FEVR, and this tool can assist in the clinical diagnosis and evaluation of early-stage FEVR in asymptomatic family members of patients with FEVR.

  4. Elevated circulating level of osteopontin is associated with advanced disease state of non-small cell lung cancer.

    PubMed

    Chang, Yoon Soo; Kim, Hyung Jung; Chang, Joon; Ahn, Chul Min; Kim, Sung Kyu; Kim, Se Kyu

    2007-09-01

    Osteopontin (OPN) plays important roles in tumor progression and metastasis through binding to OPN receptors such as alpha(v)beta(beta) integrin and CD44, and its overexpression in tumor is associated poor clinical outcome of NSCLC patients. Circulating OPN levels, measured by ELISA in 130 NSCLC cases that had not been treated for cancer at the time of sampling, were analyzed according to clinical, pathologic parameters and single nucleotide polymorphisms (SNPs) in the OPN gene promoter. Advanced disease states had higher circulating levels of OPN (T4 versus T1-3, N3 versus N0-2, and M1 versus M0, P=.029, .001, and .001, respectively, Kruskal-Wallis H-test), reflected by higher level of OPN in stage IV than stage I-III (P=.029, Kruskal-Wallis H-test). Among the clinical and pathological parameters including age, gender, smoking status, histologic subtypes and grade of differentiation, smoking status influences circulating OPN level showing higher level of OPN in ex-smokers than current and non-smokers (P=.038, Kruskal-Wallis H-test). Variation at nucleotide (nt) -443 of the OPN gene promoter had no influence on circulating OPN levels, however, patients with G/G at nt -156 showed higher concentrations of OPN than those with G/GG or GG/GG (P=.003, Kruskal-Wallis H-test). A patient with G/G at nt -156 was more frequently diagnosed with advanced stage (IIIB-IV) than with early stage (I-IIIA) NSCLC (P=.048, Mantel-Haenszel-test). In multivariate analysis, stage is the only independent factor influencing circulating level of OPN. Although circulating level of OPN in the patients with bone metastasis was higher than in those without bone metastasis (P=.028, Mann-Whitney U-test), there was no difference in the OPN levels between bone metastasis group and non-bone metastasis group. Given that the elevated levels of OPN is associated with advanced stages of NSCLC, elucidating OPN regulatory mechanisms may contribute to the development of a new therapeutic modality for NSCLC.

  5. Clinical cancer advances 2011: Annual Report on Progress Against Cancer from the American Society of Clinical Oncology.

    PubMed

    Vogelzang, Nicholas J; Benowitz, Steven I; Adams, Sylvia; Aghajanian, Carol; Chang, Susan Marina; Dreyer, Zoann Eckert; Janne, Pasi A; Ko, Andrew H; Masters, Greg A; Odenike, Olatoyosi; Patel, Jyoti D; Roth, Bruce J; Samlowski, Wolfram E; Seidman, Andrew D; Tap, William D; Temel, Jennifer S; Von Roenn, Jamie H; Kris, Mark G

    2012-01-01

    A message from ASCO'S President. It has been forty years since President Richard Nixon signed the National Cancer Act of 1971, which many view as the nation's declaration of the "War on Cancer." The bill has led to major investments in cancer research and significant increases in cancer survival. Today, two-thirds of patients survive at least five years after being diagnosed with cancer compared with just half of all diagnosed patients surviving five years after diagnosis in 1975. The research advances detailed in this year's Clinical Cancer Advances demonstrate that improvements in cancer screening, treatment, and prevention save and improve lives. But although much progress has been made, cancer remains one of the world's most serious health problems. In the United States, the disease is expected to become the nation's leading cause of death in the years ahead as our population ages. I believe we can accelerate the pace of progress, provided that everyone involved in cancer care works together to achieve this goal. It is this viewpoint that has shaped the theme for my presidential term: Collaborating to Conquer Cancer. In practice, this means that physicians and researchers must learn from every patient's experience, ensure greater collaboration between members of a patient's medical team, and involve more patients in the search for cures through clinical trials. Cancer advocates, insurers, and government agencies also have important roles to play. Today, we have an incredible opportunity to improve the quality of cancer care by drawing lessons from the real-world experiences of patients. The American Society of Clinical Oncology (ASCO) is taking the lead in this area, in part through innovative use of health information technology. In addition to our existing quality initiatives, ASCO is working with partners to develop a comprehensive rapid-learning system for cancer care. When complete, this system will provide physicians with personalized, real

  6. Trousseau's syndrome in a patient with advanced stage gastric cancer.

    PubMed

    Chien, Tai-Long; Rau, Kung-Ming; Chung, Wen-Jung; Tai, Wei-Chen; Wang, Shih-Ho; Chiu, Yi-Chun; Wu, Keng-Liang; Chou, Yeh-Pin; Wu, Chia-Che; Chen, Yen-Hao; Chuah, Seng-Kee

    2015-09-14

    Patients with cancer are at high risk for thrombotic events, which are known collectively as Trousseau's syndrome. Herein, we report a 66-year-old male patient who was diagnosed with terminal stage gastric cancer and liver metastasis and who had an initial clinical presentation of upper gastrointestinal bleeding. Acute ischemia of the left lower leg that resulted in gangrenous changes occurred during admission. Subsequent angiography of the left lower limb was then performed. This procedure revealed arterial thrombosis of the left common iliac artery with extension to the external iliac artery, the left common iliac artery, the posterior tibial artery, and the peroneal artery, which were occluded by thrombi. Aspiration of the thrombi demonstrated that these were not tumor thrombi. The interesting aspect of our case was that the disease it presented as arterial thrombotic events, which may correlate with gastric adenocarcinoma. In summary, we suggested that the unexplained thrombotic events might be one of the initial presentations of occult malignancy and that thromboprophylaxis should always be considered.

  7. Clinical Factors and Outcomes of Dialysis-Dependent End-Stage Renal Disease Patients with Emergency Department Septic Shock.

    PubMed

    Lowe, Kevin M; Heffner, Alan C; Karvetski, Colleen H

    2018-01-01

    Infection is the second leading cause of death in end-stage renal disease (ESRD) patients. Prior investigations of acute septic shock in this specific population are limited. We aimed to evaluate the clinical presentation and factors associated with outcome among ESRD patients with acute septic shock. We reviewed patients prospectively enrolled in an emergency department (ED) septic shock treatment pathway registry between January 2014 and May 2016. Clinical and treatment variables for ESRD patients were compared with non-ESRD patients. A second analysis focused on ESRD septic shock survivors and nonsurvivors. Among 4126 registry enrollees, 3564 (86.4%) met inclusion for the study. End-stage renal disease was present in 3.8% (n = 137) of ED septic shock patients. Hospital mortality was 20.4% and 17.1% for the ESRD and non-ESRD septic shock patient groups (p = 0.31). Septic shock patients with ESRD had a higher burden of chronic illness, but similar admission clinical profiles to non-ESRD patients. End-stage renal disease status was independently associated with lower fluid resuscitation dose, even when controlling for severity of illness. Age and admission lactate were independently associated with mortality in ESRD septic shock patients. ESRD patients comprise a small but important portion of patients with ED septic shock. Although presentation clinical profiles are similar to patients without ESRD, ESRD status is independently associated with lower fluid dose and compliance with the 30-mL/kg fluid goal. Hyperlactatemia is a marker of mortality in ESRD septic shock. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Is there a benefit to operating on patients (bedridden or in wheelchairs) with advanced stage cervical spondylotic myelopathy?

    PubMed

    Scardino, Fabrizio Borges; Rocha, Leonardo Poubel; Barcelos, Alécio Cristino Evangelista Santos; Rotta, José Marcus; Botelho, Ricardo Vieira

    2010-05-01

    Surgical treatment of cervical spondylotic myelopathy (CSM) aims to prevent or delay the progression of the disease. Many patients are diagnosed in advanced stages of the disease, presenting severe functional disability and extensive radiologic changes, which suggests clinical irreversibility. There are doubts about the real benefit of surgery in patients who are seriously ill, bedridden or in a wheelchair. The objective of the study is to evaluate the effects of surgical treatment in the clinical outcomes of patients severely affected by CSM. We analyzed patients with CSM who received an operation at a single institution between 1996 and 2008. Cases with a preoperative Nurick score equal to 5 were studied. We describe postoperative clinical improvement and compare the demographics and clinical data between the patients who improved and those who had no improvement. Radiological findings were also analyzed. We evaluated 55 patients operated on. Nine presented with preoperative Nurick score of 5 (16.3%). The mean age was 69.77 +/- 6.6 years (95% CI 64.65-79.90). The mean follow-up was 53.44 +/- 35.09 months (CI 26.46-80.42). Six patients (66.6%) achieved functional improvement when assessed by the Nurick scale, regaining the ability to walk. All patients improved on the JOAm scale, except one. The mean preoperative Nurick score was 5, while the mean postoperative Nurick score was 4.11 +/- 0.92 (95% CI 3.39-4.82) (Wilcoxon p = 0.027). The mean preoperative JOAm score was 6.4, and postoperative was 9.88 +/- 2.31 (CI 95% 8.10-11.66) (Wilcoxon p = 0.011). All spinal cords presented high-intensity signal on T2-weighted images. There was no correlation between the number of spinal cord high-intensity signal levels and clinical improvement. Three out of seven patients (whose image was adequate for analysis) had evident spinal cord atrophy, and two of them did not improve clinically. In the whole sample of patients, the mean length of disease for those who improved was 9

  9. Oestrogen receptors, nodes and stage as predictors of post-recurrence survival in 457 breast cancer patients.

    PubMed

    Shek, L L; Godolphin, W; Spinelli, J J

    1987-12-01

    The relationship to survival after first recurrence of oestrogen receptor (ER), nodal status and TNM stage at diagnosis, and treatment for advanced disease was studied in 457 females whose primary breast cancer was diagnosed in 1975 to 1981. Receptor concentration was the most important predictor of post-recurrence survival, with some additional information conveyed by nodal status. ER predicted survival after recurrence independently of nodal status, clinical stage or mode of therapy. Response to endocrine therapy is only a facet of the generally favourable prognosis of ER positive patients, rather than the sole explanation.

  10. Simulation of multi-stage nonlinear bone remodeling induced by fixed partial dentures of different configurations: a comparative clinical and numerical study.

    PubMed

    Liao, Zhipeng; Yoda, Nobuhiro; Chen, Junning; Zheng, Keke; Sasaki, Keiichi; Swain, Michael V; Li, Qing

    2017-04-01

    This paper aimed to develop a clinically validated bone remodeling algorithm by integrating bone's dynamic properties in a multi-stage fashion based on a four-year clinical follow-up of implant treatment. The configurational effects of fixed partial dentures (FPDs) were explored using a multi-stage remodeling rule. Three-dimensional real-time occlusal loads during maximum voluntary clenching were measured with a piezoelectric force transducer and were incorporated into a computerized tomography-based finite element mandibular model. Virtual X-ray images were generated based on simulation and statistically correlated with clinical data using linear regressions. The strain energy density-driven remodeling parameters were regulated over the time frame considered. A linear single-stage bone remodeling algorithm, with a single set of constant remodeling parameters, was found to poorly fit with clinical data through linear regression (low [Formula: see text] and R), whereas a time-dependent multi-stage algorithm better simulated the remodeling process (high [Formula: see text] and R) against the clinical results. The three-implant-supported and distally cantilevered FPDs presented noticeable and continuous bone apposition, mainly adjacent to the cervical and apical regions. The bridged and mesially cantilevered FPDs showed bone resorption or no visible bone formation in some areas. Time-dependent variation of bone remodeling parameters is recommended to better correlate remodeling simulation with clinical follow-up. The position of FPD pontics plays a critical role in mechanobiological functionality and bone remodeling. Caution should be exercised when selecting the cantilever FPD due to the risk of overloading bone resorption.

  11. New idea for treatment strategies for Barcelona Clinic Liver Cancer stages based on a network meta-analysis.

    PubMed

    Li, Kun; Wang, Hai-Tao; He, Yu-Kun; Guo, Tao

    2017-05-01

    Currently, the Barcelona Clinic Liver Cancer staging (BCLC) system still remains controversies in the management of hepatocellular carcinoma. We are trying to determine the best therapeutic strategy for each BCLC stage through a network meta-analysis and provide a new treatment idea. We conducted a systematic literature search of the PubMed, EMBASE, and Cochrane Library databases and extracted data from randomized controlled trials (RCTs) that compared various strategies. Network meta-analyses were conducted in ADDIS by evaluating different overall survival of each stage. Cumulative probability was used to rank the included strategies. A node-splitting model assessed whether direct and indirect evidence on a specific node was in agreement. Of the 24 included RCTs, 3667 patients were included. Based on the probability P values, the results showed that TACE plus surgical resection (SR) was the first choice for BCLC Stage A (P = .38 and P = .52 for 3- and 5-year OS, respectively). The application of SR was the best strategy for BCLC Stage B (P = .51 and P = .95 for 1- and 3-year OS, respectively). For Stage C, whole net connections could not be established in this research, but combined therapy seemed to produce better results based on 3 separated net connections (P = .92, P = .80, and P = .69 for 1-year OS). The updated therapy strategies discussed in this study are recommended. More importantly, we deemed that the recommended strategy for each patient may be subject to adjustment due to individual clinical factors. The applicable scope of each strategy should also be evaluated before application.

  12. ADVANCED MANUFACTURING TEAM

    NASA Image and Video Library

    2014-01-16

    ZACK JONES AND JIM LYDON OF MSFC’S ADVANCED MANUFACTURING TEAM, WITH MSFC’S M2 SELECTIVE LASER MELTING SYSTEM. THE M2 IS CURRENTLY DEDICATED TO ADVANCED COPPER MATERIAL DEVELOPMENT FOR THE LOW COST UPPER STAGE PROGRAM.

  13. Long-term Outcomes of Laparoscopic Versus Open Surgery for Clinical Stage II/III Gastric Cancer: A Multicenter Cohort Study in Japan (LOC-A Study).

    PubMed

    Kinoshita, Takahiro; Uyama, Ichiro; Terashima, Masanori; Noshiro, Hirokazu; Nagai, Eishi; Obama, Kazutaka; Tamamori, Yutaka; Nabae, Toshinaga; Honda, Michitaka; Abe, Takayuki

    2018-04-24

    A large-scale multicenter historical cohort study was conducted to investigate the efficacy of laparoscopic gastrectomy (LG) in comparison to open gastrectomy (OG) for locally advanced gastric cancer. LG is now practiced widely, but its applicability for advanced gastric cancer is still controversial. As oncologic outcomes of randomized trials are still pending, there is an urgent need for information that would be relevant to current practice. Through a consensus meeting involving surgeons and biostatisticians, 30 preoperative variables possibly influencing the choice of surgical approach and associated with outcome were identified to enable rigorous estimation of propensity scores. A total of 1948 consecutive patients who underwent gastrectomy for clinical stage II/III gastric adenocarcinoma between 2008 and 2014 were identified, and their clinical data were collected from 8 participating hospitals. After propensity score matching, 610 cases (OG = 305, LG = 305) were finally selected for comparison of long-term outcomes. In the propensity-matched OG and LG populations, the mean observation period was 3.5 and 3.4 years, and the 5-year overall survival was 53.0% and 54.2%, respectively. The hazard ratio (LG/OG) for overall survival was 1.01 (95% confidence interval, 0.80-1.29), and noninferiority of LG was demonstrated statistically as the upper 95% confidence limit was less than the prespecified margin (1.33). The recurrence rate was 30.8% and 29.8% for OG and LG, respectively, and the hazard ratio for recurrence was 0.98 (95% confidence interval, 0.74-1.31). The patterns of recurrence in the 2 groups were similar. This observational study strictly adjusted for confounding factors has provided evidence to suggest that LG is oncologically comparable to OG for locally advanced gastric cancer. The validity of this result will be examined in ongoing randomized trials.

  14. BRAF Mutations in Advanced Cancers: Clinical Characteristics and Outcomes

    PubMed Central

    El-Osta, Hazem; Falchook, Gerald; Tsimberidou, Apostolia; Hong, David; Naing, Aung; Kim, Kevin; Wen, Sijin; Janku, Filip; Kurzrock, Razelle

    2011-01-01

    Background Oncogenic BRAF mutations have been found in diverse malignancies and activate RAF/MEK/ERK signaling, a critical pathway of tumorigenesis. We examined the clinical characteristics and outcomes of patients with mutant (mut) BRAF advanced cancer referred to phase 1 clinic. Methods We reviewed the records of 80 consecutive patients with mutBRAF advanced malignancies and 149 with wild-type (wt) BRAF (matched by tumor type) referred to the Clinical Center for Targeted Therapy and analyzed their outcome. Results Of 80 patients with mutBRAF advanced cancer, 56 had melanoma, 10 colorectal, 11 papillary thyroid, 2 ovarian and 1 esophageal cancer. Mutations in codon 600 were found in 77 patients (62, V600E; 13, V600K; 1, V600R; 1, unreported). Multivariate analysis showed less soft tissue (Odds ratio (OR) = 0.39, 95%CI: 0.20–0.77, P = 0.007), lung (OR = 0.38, 95%CI: 0.19–0.73, p = 0.004) and retroperitoneal metastases (OR = 0.34, 95%CI: 0.13–0.86, p = 0.024) and more brain metastases (OR = 2.05, 95%CI: 1.02–4.11, P = 0.043) in patients with mutBRAF versus wtBRAF. Comparing to the corresponding wtBRAF, mutBRAF melanoma patients had insignificant trend to longer median survival from diagnosis (131 vs. 78 months, p = 0.14), while mutBRAF colorectal cancer patients had an insignificant trend to shorter median survival from diagnosis (48 vs. 53 months, p = 0.22). In melanoma, V600K mutations in comparison to other BRAF mutations were associated with more frequent brain (75% vs. 36.3%, p = 0.02) and lung metastases (91.6% vs. 47.7%, p = 0.007), and shorter time from diagnosis to metastasis and to death (19 vs. 53 months, p = 0.046 and 78 vs. 322 months, p = 0.024 respectively). Treatment with RAF/MEK targeting agents (Hazard ratio (HR) = 0.16, 95%CI: 0.03–0.89, p = 0.037) and any decrease in tumor size after referral (HR = 0.07, 95%CI: 0.015–0.35, p = 0.001) correlated with longer

  15. Management of Locally Advanced Cancer Cervix an Indian Perspective.

    PubMed

    Singh, J K; Chauhan, Richa

    2015-01-01

    Cervical cancer has a major impact on the lives of Indian women with an estimated 122, 844 new cases of cervical cancer in the year 2012. About 80% of these cases present in a locally advanced stage leading to high morbidity and mortality. Because of lack of public awareness and infrastructure for screening and early detection in developing countries, this late presentation is likely to continue in the coming years. Radiation therapy has been the treatment of choice for patients with locally advanced cancer cervix. Many clinical trials and meta-analyses have shown a significant improvement in overall and progression-free survival with decreased local and distant recurrences with the use of concurrent chemotherapy with radiation. Most of these trials have been done in women from developed countries where the patient and disease profile are entirely different from ours. Recently, few trials from India have also shown promising results in locally advanced cancer cervix with concurrent chemoradiotherapy but toxicities remain a major concern. Further exploration is required for the use of concurrent chemo radiation prior to incorporating it into routine clinical practice.

  16. Neurofibrillary Tangle Stage and the Rate of Progression of Alzheimer Symptoms: Modeling Using an Autopsy Cohort and Application to Clinical Trial Design

    PubMed Central

    Qian, Jing; T.Hyman, Bradley; Betensky, Rebecca A.

    2017-01-01

    Importance The heterogeneity of rate of clinical progression among patients with Alzheimer disease leads to difficulty in providing clinical counseling and diminishes the power of clinical trials using disease-modifying agents. Objective To gain a better understanding of the factors that affect the natural history of progression in Alzheimer disease for the purpose of improving both clinical care and clinical trial design. Design, Setting, and Participants A longitudinal cohort study of aging from 2005 to 2014 in the National Alzheimer Coordinating Center. Clinical evaluation of the participants was conducted in 31 National Institute on Aging’s Alzheimer Disease Centers. Nine hundred eighty-four participants in the National Alzheimer Coordinating Center cohort study who died and underwent autopsy and met inclusion and exclusion criteria. Main Outcomes and Measures We sought to model the possibility that knowledge of neurofibrillary tangle burden in the presence of moderate or frequent plaques would add to the ability to predict clinical rate of progression during the ensuing 2 to 3 years. We examined the National Alzheimer Coordinating Center autopsy data to evaluate the effect of different neurofibrillary tangle stages on the rates of progression on several standard clinical instruments: the Clinical Dementia Rating Scale sum of boxes, a verbal memory test (logical memory), and a controlled oral word association task (vegetable naming), implementing a reverse-time longitudinal modeling approach in conjunction with latent class estimation to adjust for unmeasured sources of heterogeneity. Results Several correlations between clinical variables and neurocognitive performance suggest a basis for heterogeneity: Higher education level was associated with lower Clinical Dementia Rating Scale sum of boxes (β = −0.19; P < .001), and frequent vs moderate neuritic plaques were associated with higher Clinical Dementia Rating Scale sum of boxes (β = 1.64; P

  17. Advancing understanding of executive function impairments and psychopathology: bridging the gap between clinical and cognitive approaches

    PubMed Central

    Snyder, Hannah R.; Miyake, Akira; Hankin, Benjamin L.

    2015-01-01

    Executive function (EF) is essential for successfully navigating nearly all of our daily activities. Of critical importance for clinical psychological science, EF impairments are associated with most forms of psychopathology. However, despite the proliferation of research on EF in clinical populations, with notable exceptions clinical and cognitive approaches to EF have remained largely independent, leading to failures to apply theoretical and methodological advances in one field to the other field and hindering progress. First, we review the current state of knowledge of EF impairments associated with psychopathology and limitations to the previous research in light of recent advances in understanding and measuring EF. Next, we offer concrete suggestions for improving EF assessment. Last, we suggest future directions, including integrating modern models of EF with state of the art, hierarchical models of dimensional psychopathology as well as translational implications of EF-informed research on clinical science. PMID:25859234

  18. [Application of clinical nursing path integrated with holistic nursing in advanced schistosomiasis patients with ascites].

    PubMed

    Mei-Zhi, Yuan; Jing-Ru, Sun; Tao, Chen; Xiao-Yu, Zhang; Liang-Cai, He; Jia-Song, Wang

    2016-05-12

    To evaluate the effect of the clinical nursing path integrated with the holistic nursing on advanced schistosomiasis patients with ascites. A total of 226 advanced schistosomiasis patients with ascites were randomly divided into a control group and an experimental group (113 cases each group). The subjects in the experimental group were nursed by the clinical nursing path integrated with the holistic nursing, while those in the control group were nursed only by the holistic nursing. Then the clinical relevant indexes of the two groups were observed, and the quality of life of the patients before and after hospital discharge was assessed. The improvement rate, satisfaction degree, and awareness rate of health knowledge of the patients in the experiment group were 93.8%, 100% and 97.4%, respectively, which were significantly higher than those of the control group (all P < 0.05). The mortality rate and the complication rate of the patients in the experimental group were 0 and 2.7%, respectively, which were significantly lower than those of the control group (both P < 0.05). In addition, the average hospitalization days and the hospitalization cost of the experiment group were (12.2 ± 0.7) d and (4 725.0 ± 310.1) Yuan respectively, which were less than those of the control group (both P < 0.01). When 6 months after the discharge from hospital, the quality of life of the patients in the experimental group in various fields was significantly better than that of the control group (all P < 0.05). The clinical nursing pathway integrated with holistic nursing can effectively improve the improvement rate and decrease the mortality of the advanced schistosomiasis patients with ascites; meanwhile, it can shorten the hospitalization time and save the hospitalization cost. Therefore, this nursing model is suitable for popularization and application in the treatment and nursing work of the advanced schistosomiasis assistance.

  19. Low intensity laser therapy: the clinical approach

    NASA Astrophysics Data System (ADS)

    Kahn, Fred

    2006-02-01

    Recently, there has been significant improvement in the process of research and application of Low Intensity Laser Therapy (LILT). Despite this positive direction, a wide discrepancy between the research component and clinical understanding of the technology remains. In our efforts to achieve better clinical results and more fully comprehend the mechanisms of interaction between light and cells, further studies are required. The clinical results presented in this paper are extrapolated from a wide range of musculoskeletal problems including degenerative osteoarthritis, repetitive motion injuries, sports injuries, etc. The paper includes three separate clinical studies comprising 151, 286 and 576 consecutive patient discharges at our clinic. Each patient studied received a specific course of treatment that was designed for that individual and was modified on a continuing basis as the healing process advanced. On each visit, clinical status correlation with the duration, dosage and other parameters was carried out. The essentials of the treatment consisted of a three stage approach. This involved a photon stream emanating from a number of specified gallium-aluminum-arsenide diodes; stage one, red light array, stage two consisting of an array of infrared diodes and stage three consisting of the application of an infrared laser diode probe. On average, each of these groups required less than 10 treatments per patient and resulted in a significant improvement / cure rate greater than 90% in all conditions treated. This report clearly demonstrates the benefits of LILT, indicating that it should be more widely adapted in all medical therapeutic settings.

  20. Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care

    Cancer.gov

    Cancer Pharmacogenomics: Integrating Discoveries in Basic, Clinical and Population Sciences to Advance Predictive Cancer Care, a 2010 workshop sponsored by the Epidemiology and Genomics Research Program.

  1. Nutritional status according to the stages of Alzheimer's disease.

    PubMed

    Marino, Larissa Vieira; Ramos, Liliana Figueiredo Andrade de Oliveira; Chiarello, Paula Garcia

    2015-08-01

    To assess the nutritional status of Alzheimer's disease (AD) patients with no other associated dementia, according to disease stage. Cross-sectional observational study. Neurobehavioral Diseases Outpatient Clinic, Clinical Hospital, Ribeirao Preto Medical School (University of São Paulo). The sample consisted of 36 individuals of both genders with AD diagnosis, and no other associated type of dementia, in various stages of the disease, according to the Clinical Dementia Rating (CDR 0.5-3). Nutritional status was evaluated using the Mini Nutritional Assessment (MNA) and anthropometric measurements such as weight, body mass index (BMI) and arm, waist, abdomen and hip circumferences. In addition, body composition was assessed by bioelectrical impedance analysis (BIA). The mean age of the group was 74.2 ± 10.1 years, 72.2 % of them were women. The MNA showed that most of these individuals were at risk for malnutrition (55.5 %) and many of them (43.7 %) were underweight according to BMI. Data from BIA analysis revealed that 41.7 % of these individuals had a quantity of body fat classified as malnutrition and 11.1 % had a phase angle (PA) below recommended values for age group. There was a negative and significant correlation of lean mass and PA with age, and of global MNA evaluation with CDR, as well as a positive correlation of MNA total score with fat mass and BMI. Worse classifications of nutritional status obtained by MNA scores were also observed in the more severe stages of the disease, according to the CDR. Patients with AD are mostly elderly with changes in body composition that are typical of aging, with signs of peripheral malnutrition and preservation of abdominal fat. However, greater impairment of general nutritional status was observed in the more advanced stages of AD, creating a situation of greater vulnerability for these patients.

  2. ADVANCED MANUFACTURING TEAM

    NASA Image and Video Library

    2014-01-16

    QUINCY BEAN, JIM LYDON, AND ZACK JONES OF MSFC’S ADVANCED MANUFACTURING TEAM, WITH MSFC’S M2 SELECTIVE LASER MELTING SYSTEM. THE M2 IS CURRENTLY DEDICATED TO ADVANCED COPPER MATERIAL DEVELOPMENT FOR THE LOW COST UPPER STAGE PROGRAM.

  3. Clinical Value of Vestibular Evoked Myogenic Potential in Assessing the Stage and Predicting the Hearing Results in Ménière's Disease.

    PubMed

    Kim, Min-Beom; Choi, Jeesun; Park, Ga Young; Cho, Yang-Sun; Hong, Sung Hwa; Chung, Won-Ho

    2013-06-01

    Our goal was to find the clinical value of cervical vestibular evoked myogenic potential (VEMP) in Ménière's disease (MD) and to evaluate whether the VEMP results can be useful in assessing the stage of MD. Furthermore, we tried to evaluate the clinical effectiveness of VEMP in predicting hearing outcomes. The amplitude, peak latency and interaural amplitude difference (IAD) ratio were obtained using cervical VEMP. The VEMP results of MD were compared with those of normal subjects, and the MD stages were compared with the IAD ratio. Finally, the hearing changes were analyzed according to their VEMP results. In clinically definite unilateral MD (n=41), the prevalence of cervical VEMP abnormality in the IAD ratio was 34.1%. When compared with normal subjects (n=33), the VEMP profile of MD patients showed a low amplitude and a similar latency. The mean IAD ratio in MD was 23%, which was significantly different from that of normal subjects (P=0.01). As the stage increased, the IAD ratio significantly increased (P=0.09). After stratification by initial hearing level, stage I and II subjects (hearing threshold, 0-40 dB) with an abnormal IAD ratio showed a decrease in hearing over time compared to those with a normal IAD ratio (P=0.08). VEMP parameters have an important clinical role in MD. Especially, the IAD ratio can be used to assess the stage of MD. An abnormal IAD ratio may be used as a predictor of poor hearing outcomes in subjects with early stage MD.

  4. Clinical Value of Vestibular Evoked Myogenic Potential in Assessing the Stage and Predicting the Hearing Results in Ménière's Disease

    PubMed Central

    Kim, Min-Beom; Choi, Jeesun; Park, Ga Young; Cho, Yang-Sun; Hong, Sung Hwa

    2013-01-01

    Objectives Our goal was to find the clinical value of cervical vestibular evoked myogenic potential (VEMP) in Ménière's disease (MD) and to evaluate whether the VEMP results can be useful in assessing the stage of MD. Furthermore, we tried to evaluate the clinical effectiveness of VEMP in predicting hearing outcomes. Methods The amplitude, peak latency and interaural amplitude difference (IAD) ratio were obtained using cervical VEMP. The VEMP results of MD were compared with those of normal subjects, and the MD stages were compared with the IAD ratio. Finally, the hearing changes were analyzed according to their VEMP results. Results In clinically definite unilateral MD (n=41), the prevalence of cervical VEMP abnormality in the IAD ratio was 34.1%. When compared with normal subjects (n=33), the VEMP profile of MD patients showed a low amplitude and a similar latency. The mean IAD ratio in MD was 23%, which was significantly different from that of normal subjects (P=0.01). As the stage increased, the IAD ratio significantly increased (P=0.09). After stratification by initial hearing level, stage I and II subjects (hearing threshold, 0-40 dB) with an abnormal IAD ratio showed a decrease in hearing over time compared to those with a normal IAD ratio (P=0.08). Conclusion VEMP parameters have an important clinical role in MD. Especially, the IAD ratio can be used to assess the stage of MD. An abnormal IAD ratio may be used as a predictor of poor hearing outcomes in subjects with early stage MD. PMID:23799160

  5. In situ photoimmunotherapy for melanoma: an ongoing phase I clinical trial

    NASA Astrophysics Data System (ADS)

    Naylor, Mark F.; Nordquist, Robert E.; Teague, T. Kent; Perry, Lisa A.; Chen, Wei R.

    2007-02-01

    In situ Photoimmunotherapy (ISPI) was developed to treat metastatic tumors using a combination of phototherapy and immunotherapy. It utilizes local intervention through photothermal destruction of existing solid tumors and through immune response modifier to elicit host anti-tumor responses. Such combination in pre-clinical studies has shown promise in cancer treatment by eradicating the primary tumors and also controlling metastases at distant sites. ISPI has been used in our preliminary clinical studies for melanoma patients and the outcome has been extremely encouraging. In 2006, we began enrolling patients in a new phase I immunotherapy trial for advanced cutaneous melanoma. This trial is based on our previous results which indicated that we had developed an effective treatment for advanced melanoma. Of the first six patients treated, (4 stage IV, and 2 surgically unresectable stage III), 2 of the stage IV patients are still alive, one tumor free, and one with a possible treatable recurrence after 2 1/2 years. We have also discovered that recurrences of the skin cancer can be retreated by the same technique and that treatment seems to blunt the virulence of the disease and make it more treatable. These initial results indicate that ISPI probably will have the ability to prolong survival in selected cases of advanced melanoma, and potentially cure a significant percentage of treated patients.

  6. Ten years of iPSC: clinical potential and advances in vitro hematopoietic differentiation.

    PubMed

    Paes, Bárbara Cristina Martins Fernandes; Moço, Pablo Diego; Pereira, Cristiano Gonçalves; Porto, Geciane Silveira; de Sousa Russo, Elisa Maria; Reis, Luiza Cunha Junqueira; Covas, Dimas Tadeu; Picanço-Castro, Virginia

    2017-06-01

    Ten years have passed since the first publication announcing the generation of induced pluripotent stem cells (iPSCs). Issues related to ethics, immune rejection, and cell availability seemed to be solved following this breakthrough. The development of iPSC technology allows advances in in vitro cell differentiation for cell therapy purpose and other clinical applications. This review provides a perspective on the iPSC potential for cell therapies, particularly for hematological applications. We discuss the advances in in vitro hematopoietic differentiation, the possibilities to employ iPSC in hematology studies, and their potential clinical application in hematologic diseases. The generation of red blood cells and functional T cells and the genome editing technology applied to mutation correction are also covered. We highlight some of the requirements and obstacles to be overcome before translating these cells from research to the clinic, for instance, iPSC variability, genotoxicity, the differentiation process, and engraftment. Also, we evaluate the patent landscape and compile the clinical trials in the field of pluripotent stem cells. Currently, we know much more about iPSC than in 2006, but there are still challenges that must be solved. A greater understanding of molecular mechanisms underlying the generation of hematopoietic stem cells is necessary to produce suitable and transplantable hematopoietic stem progenitor cells from iPSC.

  7. Performance of FDG PET/CT in the clinical management of breast cancer.

    PubMed

    Groheux, David; Espié, Marc; Giacchetti, Sylvie; Hindié, Elif

    2013-02-01

    In this analysis, the role of metabolic imaging with fluorine 18 fluorodeoxyglucose (FDG) in breast cancer is reviewed. The analysis was limited to recent works by using state-of-the-art positron emission tomography (PET)/computed tomography (CT) technology. The strengths and limitations of FDG PET/CT are examined in various clinical settings, and the following questions are answered: Is FDG PET/CT useful to differentiate malignant from benign breast lesions? Can FDG PET/CT replace sentinel node biopsy for axillary staging? What is the role of FDG PET/CT in initial staging of inflammatory or locally advanced breast cancer? What is the role of FDG PET/CT in initial staging of clinical stage IIA and IIB and primary operable stage IIIA breast cancer? How does FDG PET/CT compare with conventional techniques in the restaging of cancer in patients who are suspected of having disease recurrence? What is the role of FDG PET/CT in the assessment of early response to neoadjuvant therapy and of response to therapy for metastatic disease? Some recommendations for clinical practice are given.

  8. Two stage launch vehicle

    NASA Technical Reports Server (NTRS)

    1987-01-01

    The Advanced Space Design project for 1986-87 was the design of a two stage launch vehicle, representing a second generation space transportation system (STS) which will be needed to support the space station. The first stage is an unmanned winged booster which is fully reusable with a fly back capability. It has jet engines so that it can fly back to the landing site. This adds safety as well as the flexibility to choose alternate landing sites. There are two different second stages. One of the second stages is a manned advanced space shuttle called Space Shuttle II. Space Shuttle II has a payload capability of delivering 40,000 pounds to the space station in low Earth orbit (LEO), and returning 40,000 pounds to Earth. Servicing the space station makes the ability to return a heavy payload to Earth as important as being able to launch a heavy payload. The other second stage is an unmanned heavy lift cargo vehicle with ability to deliver 150,000 pounds of payload to LEO. This vehicle will not return to Earth; however, the engines and electronics can be removed and returned to Earth in the Space Shuttle II. The rest of the vehicle can then be used on orbit for storage or raw materials, supplies, and space manufactured items awaiting transport back to Earth.

  9. Tumor Stage-Related Role of Radiotherapy in Patients with an External Auditory Canal and Middle Ear Carcinoma.

    PubMed

    Choi, Jinhyun; Kim, Se-Heon; Koh, Yoon Woo; Choi, Eun Chang; Lee, Chang Geol; Keum, Ki Chang

    2017-01-01

    The purpose of this study was to evaluate the clinical outcomes of patients treated with radiotherapy (RT) for a carcinoma of the external auditory canal (EAC) and middle ear. The records of 32 patients who received RT from 1990 to 2013 were reviewed retrospectively. The Pittsburgh classification was used to stage all the cancers (early stage, T1/T2 [n=12]; advanced stage, T3/T4 or N positive [n=20]). Twenty-one patients (65.6%) were treated with postoperative RT and 11 patients (34.4%) were treated with definitive RT. The median radiation doses for postoperative and definitive RT were 60 Gy and 64.8 Gy, respectively. Chemotherapy was administered to seven patients (21.9%). The 5-year overall survival and disease-free survival rates for all patients were 57% and 52%, respectively. The disease control rates for the patients with early stage versus advanced stage carcinomawere 55.6% (5/9) and 50% (6/12) in the postoperative RT group and 66.7% (2/3) and 37.5% (3/8) in the definitive RT group, respectively. Overall, 15 cases (14 patients, 46.7%) experienced treatment failure; these failures were classified as local in four cases, regional in one case, and distant in 10 cases. The median follow-up period after RT was 51 months (range, 7 to 286 months). Patients with early stage carcinoma achieved better outcomes when definitive RT was used. Advanced stage carcinoma patients experienced better outcomes with postoperative RT. The high rate of distant failure after RT, with or without surgery, reflected the lack of a consensus regarding the best therapeutic approach for treating carcinoma of the EAC and middle ear.

  10. Facial affect recognition in early and late-stage schizophrenia patients.

    PubMed

    Romero-Ferreiro, María Verónica; Aguado, Luis; Rodriguez-Torresano, Javier; Palomo, Tomás; Rodriguez-Jimenez, Roberto; Pedreira-Massa, José Luis

    2016-04-01

    Prior studies have shown deficits in social cognition and emotion perception in first-episode psychosis (FEP) and multi-episode schizophrenia (MES) patients. These studies compared patients at different stages of the illness with only a single control group which differed in age from at least one clinical group. The present study provides new evidence of a differential pattern of deficit in facial affect recognition in FEP and MES patients using a double age-matched control design. Compared to their controls, FEP patients only showed impaired recognition of fearful faces (p=.007). In contrast to this, the MES patients showed a more generalized deficit compared to their age-matched controls, with impaired recognition of angry, sad and fearful faces (ps<.01) and an increased misattribution of emotional meaning to neutral faces. PANSS scores of FEP patients on Depressed factor correlated positively with the accuracy to recognize fearful expressions (r=.473). For the MES group fear recognition correlated positively with negative PANSS factor (r=.498) and recognition of sad and neutral expressions was inversely correlated with disorganized PANSS factor (r=-.461 and r=-.541, respectively). These results provide evidence that a generalized impairment of affect recognition is observed in advanced-stage patients and is not characteristic of the early stages of schizophrenia. Moreover, the finding that anomalous attribution of emotional meaning to neutral faces is observed only in MES patients suggests that an increased attribution of salience to social stimuli is a characteristic of social cognition in advanced stages of the disorder. Copyright © 2016 Elsevier B.V. All rights reserved.

  11. World Workshop on Oral Medicine VI: an international validation study of clinical competencies for advanced training in oral medicine.

    PubMed

    Steele, John C; Clark, Hadleigh J; Hong, Catherine H L; Jurge, Sabine; Muthukrishnan, Arvind; Kerr, A Ross; Wray, David; Prescott-Clements, Linda; Felix, David H; Sollecito, Thomas P

    2015-08-01

    To explore international consensus for the validation of clinical competencies for advanced training in Oral Medicine. An electronic survey of clinical competencies was designed. The survey was sent to and completed by identified international stakeholders during a 10-week period. To be validated, an individual competency had to achieve 90% or greater consensus to keep it in its current format. Stakeholders from 31 countries responded. High consensus agreement was achieved with 93 of 101 (92%) competencies exceeding the benchmark for agreement. Only 8 warranted further attention and were reviewed by a focus group. No additional competencies were suggested. This is the first international validated study of clinical competencies for advanced training in Oral Medicine. These validated clinical competencies could provide a model for countries developing an advanced training curriculum for Oral Medicine and also inform review of existing curricula. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. [Eyeball salvage treatment or enucleation for advanced retinoblastoma].

    PubMed

    Qian, J; Xue, K

    2016-10-11

    The management of retinoblastoma (RB) has dramatically changed over the past two decades. The introduction of chemotherapy has transformed treatment algorithms completely. Chemotherapy is currently used as a first line approach for children with RB and can be delivered by intravenous, intra-arterial and intravitreal routes. However, there still remains some controversy on the treatment of advanced RB, especially in eyeball salvage. This article described domestic and international approaches to eyeball salvage treatment. We would like to further discuss our opinion on the management of advanced RB based on our clinical experience for attracting more clinical concern on this issue. Many factors should be considered when choosing the appropriate conservative therapy. The choice of eyeball salvage treatment not only depends upon the tumor staging and laterality but also upon compliance and economic factors. Doctors and parents should not blindly pursue eye saving. However, there are still cases where enucleation is definitely the treatment of choice. (Chin J Ophthalmol, 2016, 52: 728-732) .

  13. Para-aortic nodal metastases in cervical cancer: a blind spot in the International Federation of Gynecology and Obstetrics staging system: current diagnosis and management.

    PubMed

    Hwang, Lindsay; Bailey, April; Lea, Jayanthi; Albuquerque, Kevin

    2015-01-01

    In cervical cancer, para-aortic nodal (PALN) metastases at presentation is a strong indicator of poor prognosis. Despite this, International Federation of Gynecology and Obstetrics staging system does not require evaluation of lymph node involvement and does not incorporate clinically detected PALN into the staging system. In the USA, despite screening, a significant number of women still present at an advanced stage often with nodal metastases. While the presence of PALN metastases often indicates occult systemic disease, it is possible with modern therapies to provide long-term control of disease in a percentage of patients. We review the epidemiology, diagnosis and treatment of PALN metastases in cervical cancer outlining advances in modern imaging and combined modality therapies (surgery, chemotherapy and radiation therapy).

  14. Linear Combinations of Multiple Outcome Measures to Improve the Power of Efficacy Analysis ---Application to Clinical Trials on Early Stage Alzheimer Disease

    PubMed Central

    Xiong, Chengjie; Luo, Jingqin; Morris, John C; Bateman, Randall

    2018-01-01

    Modern clinical trials on Alzheimer disease (AD) focus on the early symptomatic stage or even the preclinical stage. Subtle disease progression at the early stages, however, poses a major challenge in designing such clinical trials. We propose a multivariate mixed model on repeated measures to model the disease progression over time on multiple efficacy outcomes, and derive the optimum weights to combine multiple outcome measures by minimizing the sample sizes to adequately power the clinical trials. A cross-validation simulation study is conducted to assess the accuracy for the estimated weights as well as the improvement in reducing the sample sizes for such trials. The proposed methodology is applied to the multiple cognitive tests from the ongoing observational study of the Dominantly Inherited Alzheimer Network (DIAN) to power future clinical trials in the DIAN with a cognitive endpoint. Our results show that the optimum weights to combine multiple outcome measures can be accurately estimated, and that compared to the individual outcomes, the combined efficacy outcome with these weights significantly reduces the sample size required to adequately power clinical trials. When applied to the clinical trial in the DIAN, the estimated linear combination of six cognitive tests can adequately power the clinical trial. PMID:29546251

  15. C5b-9 Staining Correlates With Clinical and Tumor Stage in Gastric Adenocarcinoma.

    PubMed

    Chen, Jian; Yang, Wei-Jun; Sun, Hai-Jian; Yang, Xia; Wu, Yu-Zhang

    2016-08-01

    The complement system is a critical part of the immune response, acting in defense against viral infections, clearance of immune complexes, and maintenance of tissue homeostasis. Upregulated expression of the terminal complement complex, C5b-9, has been observed on various tumor cells, such as stomach carcinoma cells, and on cells in the necrotic regions of these tumors as well; however, whether and how C5b-9 is related to gastric cancer progression and severity remains unknown. In this study, human gastric adenocarcinoma (HGAC) tissues (n=47 cases) and patient-matched adjacent nontumoral parenchyma (n=20 cases) were evaluated by tissue microarray and immunohistochemistry. The HGAC tissues showed upregulated C5b-9 expression. Multinomial logistic regression and likelihood ratio testing showed that overexpression of C5b-9 in HGAC tissue was significantly correlated with clinical stage (P=0.007) and tumor stage (P=0.005), but not with tumor distant organ metastasis, lymphoid nodal status, sex, or age. Patients with late-stage gastric adenocarcinoma had a higher amount of tumor cells showing positive staining for C5b-9 than patients with early-stage disease. These results may help in diagnosis and assessment of disease severity of human gastric carcinoma.

  16. The development of leadership outcome-indicators evaluating the contribution of clinical specialists and advanced practitioners to health care: a secondary analysis.

    PubMed

    Elliott, Naomi; Begley, Cecily; Kleinpell, Ruth; Higgins, Agnes

    2014-05-01

    To report a secondary analysis of data collected from the case study phase of a national study of advanced practitioners and to develop leadership outcome-indicators appropriate for advanced practitioners. In many countries, advanced practitioners in nursing and midwifery have responsibility as leaders for health care development, but without having leadership outcome measures available they are unable to demonstrate the results of their activities. In Ireland, a sequential mixed method research study was used to develop a validated tool for the evaluation of clinical specialists and advanced practitioners. Despite strong evidence of leadership activities, few leadership-specific outcomes were generated from the primary analysis. Secondary analysis of a multiple case study data set. Data set comprised 23 case studies of advanced practitioner/clinical specialists from 13 sites across each region in Ireland from all divisions of the Nursing Board Register. Data were collected 2008-2010. Data sources included non-participant observation (n = 92 hours) of advanced practitioners in practice, interviews with clinicians (n = 21), patients (n = 20) and directors of nursing/midwifery (n = 13) and documents. Analysis focused on leadership outcome-indicator development in line with the National Health Service's Good Indicators Guide. The four categories of leadership outcomes for advanced practitioner developed were as follows: (i) capacity and capability building of multidisciplinary team; (ii) measure of esteem; (iii) new initiatives for clinical practice and healthcare delivery; and (iv) clinical practice based on evidence. The proposed set of leadership outcome-indicators derived from a secondary analysis captures the complexity of leadership in practice. They add to existing clinical outcomes measuring advanced practice. © 2013 John Wiley & Sons Ltd.

  17. Hormone profiling, WHO 2010 grading, and AJCC/UICC staging in pancreatic neuroendocrine tumor behavior

    PubMed Central

    Morin, Emilie; Cheng, Sonia; Mete, Ozgur; Serra, Stefano; Araujo, Paula B; Temple, Sara; Cleary, Sean; Gallinger, Steven; Greig, Paul D; McGilvray, Ian; Wei, Alice; Asa, Sylvia L; Ezzat, Shereen

    2013-01-01

    Pancreatic neuroendocrine tumors (pNETs) are the second most common pancreatic neoplasms, exhibiting a complex spectrum of clinical behaviors. To examine the clinico-pathological characteristics associated with long-term prognosis we reviewed 119 patients with pNETs treated in a tertiary referral center using the WHO 2010 grading and the American Joint Committee on Cancer/International Union Against Cancer (AJCC/UICC) staging systems, with a median follow-up of 38 months. Tumor size, immunohistochemistry (IHC) profiling and patient characteristics-determining stage were analyzed. Primary clinical outcomes were disease progression or death. The mean age at presentation was 52 years; 55% were female patients, 11% were associated with MEN1 (multiple endocrine neoplasia 1) or VHL (Von Hippel–Lindau); mean tumor diameter was 3.3 cm (standard deviation, SD) (2.92). The clinical presentation was incidental in 39% with endocrine hypersecretion syndromes in only 24% of cases. Nevertheless, endocrine hormone tissue immunoreactivity was identified in 67 (56.3%) cases. According to WHO 2010 grading, 50 (42%), 38 (31.9%), and 3 (2.5%) of tumors were low grade (G1), intermediate grade (G2), and high grade (G3), respectively. Disease progression occurred more frequently in higher WHO grades (G1: 6%, G2: 10.5%, G3: 67%, P = 0.026) and in more advanced AJCC stages (I: 2%, IV: 63%, P = 0.033). Shorter progression free survival (PFS) was noted in higher grades (G3 vs. G2; 21 vs. 144 months; P = 0.015) and in more advanced AJCC stages (stage I: 218 months, IV: 24 months, P < 0.001). Liver involvement (20 vs. 173 months, P < 0.001) or histologically positive lymph nodes (33 vs. 208 months, P < 0.001) were independently associated with shorter PFS. Conversely, tissue endocrine hormone immunoreactivity, independent of circulating levels was significantly associated with less aggressive disease. Age, gender, number of primary tumors, and heredity were not

  18. A clinical and pathologic comparison between stage-matched endometrial intraepithelial carcinoma and uterine serous carcinoma: is there a difference?

    PubMed

    Hou, June Y; McAndrew, Thomas C; Goldberg, Gary L; Whitney, Kathleen; Shahabi, Shohreh

    2014-04-01

    Endometrial intraepithelial carcinoma (EIC) is a rare pathologic variant of uterine serous carcinoma (USC). Our aim is to distinguish patterns of clinic-pathologic outcomes in patients with EIC and USC for disease limited to the endometrium (stage 1A) as well as with distant metastasis (stage 4B). Surgically staged patients were retrospectively identified and relevant variables were extracted and compared. Kaplan-Meier was used to generate the survival data. More USC (n = 29) exhibited lymphovascular invasion (stage 4, P = .01) and expressed higher levels of estrogen receptor-α than EIC (P = .0009 and .063 for stages 1 and 4, respectively). The survival is comparable, with 1 recurrence in each group for stage 1A disease. For stage 4 EIC and USC, the progression-free survival (14 vs10 months) and overall survival (19 vs 20 months) are similar to what is previously published. In conclusion, EIC, whether limited to the endometrium, or widely metastatic, imparts similar outcomes and should be treated comparably with stage-matched USC.

  19. Dilemmas in Lung Cancer Staging.

    PubMed

    Vlahos, Ioannis

    2018-05-01

    The advent of the 8th edition of the lung cancer staging system reflects a further meticulous evidence-based advance in the stratification of the survival of patients with lung cancer. Although addressing many limitations of earlier staging systems, several limitations in staging remain. This article reviews from a radiological perspective the limitations of the current staging system, highlighting the process of TNM restructuring, the residual issues with regards to the assignment of T, N, M descriptors, and their associated stage groupings and how these dilemmas impact guidance of multidisciplinary teams taking care of patients with lung cancer. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  20. Design options for advanced manned launch systems

    NASA Astrophysics Data System (ADS)

    Freeman, Delma C.; Talay, Theodore A.; Stanley, Douglas O.; Lepsch, Roger A.; Wilhite, Alan W.

    1995-03-01

    Various concepts for advanced manned launch systems are examined for delivery missions to space station and polar orbit. Included are single-and two-stage winged systems with rocket and/or air-breathing propulsion systems. For near-term technologies, two-stage reusable rocket systems are favored over single-stage rocket or two-stage air-breathing/rocket systems. Advanced technologies enable viable single-stage-to-orbit (SSTO) concepts. Although two-stage rocket systems continue to be lighter in dry weight than SSTO vehicles, advantages in simpler operations may make SSTO vehicles more cost-effective over the life cycle. Generally, rocket systems maintain a dry-weight advantage over air-breathing systems at the advanced technology levels, but to a lesser degree than when near-term technologies are used. More detailed understanding of vehicle systems and associated ground and flight operations requirements and procedures is essential in determining quantitative discrimination between these latter concepts.

  1. Clinical predictors of advanced sellar masses.

    PubMed

    Rambaldini, Gloria M; Butalia, Sonia; Ezzat, Shereen; Kucharczyk, Walter; Sawka, Anna M

    2007-10-01

    To identify clinical variables associated with the presence of a structurally advanced sellar mass (ASM). We performed a retrospective study of patients referred for evaluation of suspected new pituitary disease or sellar mass to the Endocrine Oncology Unit of Mount Sinai Hospital in Toronto, Ontario, Canada. By multivariate analysis, we examined predictors of a structurally ASM (a sellar lesion with any of the following characteristics: diameter of >or=1 cm on magnetic resonance imaging [MRI], optic chiasmal compression on MRI, or clinical or biochemical evidence of hypopituitarism). Data from 152 patients were analyzed. Of the 152 sellar masses, 142 (93%) were pituitary adenomas. An ASM was noted in 85 of the 152 patients (56%). In the final multivariate model, male sex (odds ratio [OR], 6.23; 95% confidence interval [CI], 2.84 to 13.56; P<0.001) and self-reported visual field defect (OR, 3.62; 95% CI, 1.07 to 12.25; P = 0.039) were significantly independently associated with the presence of an ASM. The presence of new or changed headaches also tended to be associated with an ASM (OR, 2.11; 95% CI, 0.96 to 4.64; P = 0.063). Age and self-reported galactorrhea were not independently associated with the presence of an ASM and were conditionally removed from the final model. In patients with suspected sellar or pituitary disease, male sex and self-reported visual field defects independently predict the presence of an ASM. New or changed headaches also tend to be related to the presence of an ASM. The presence of predictors of an ASM should prompt expedited sellar MRI and biochemical evaluation.

  2. Preoperative administration of polysaccharide Kureha and reduced plasma transforming growth factor-β in patients with advanced gastric cancer: A randomized clinical trial

    PubMed Central

    YAMASHITA, KEISHI; SAKURAMOTO, SHINICHI; MIENO, HIROAKI; NEMOTO, MASAYUKI; SHIBATA, TOMOTAKA; KATADA, NATSUYA; OHTSUKI, SHIGEAKI; SAKAMOTO, YASUTOSHI; HOSHI, KEIKA; WANG, GUOQIN; HEMMI, OSAMU; SATOH, TOSHIHIKO; KIKUCHI, SHIRO; WATANABE, MASAHIKO

    2015-01-01

    Systemic abrogation of TGF-β signaling results in tumor reduction through cytotoxic T lymphocytes activity in a mouse model. The administration of polysaccharide-Kureha (PSK) into tumor-bearing mice also showed tumor regression with reduced TGF-β. However, there have been no studies regarding the PSK administration to cancer patients and the association with plasma TGF-β. PSK (3 g/day) was administered as a neoadjuvant therapy for 2 weeks before surgery. In total, 31 advanced gastric cancer (AGC) patients were randomly assigned to group A (no neoadjuvant PSK; n=14) or B (neoadjuvant PSK therapy; n=17). Plasma TGF-β was measured pre- and postoperatively. The allocation factors were clinical stage (cStage) and gender. Plasma TGF-β ranged from 1.85–43.5 ng/ml (average, 9.50 ng/ml) in AGC, and 12 patients (38.7%) had a high value, >7.0 ng/ml. These patients were largely composed of poorly-differentiated adenocarcinoma with pathological stage III/IV. All the six elevated cases in group B showed a significant reduction of plasma TGF-β (from 21.6 to 4.5 ng/ml, on average), whereas this was not exhibited in group A. The cases within the normal limits of TGF-β remained unchanged irrespective of PSK treatment. Analysis of variance showed a statistically significant reduction in the difference of plasma TGF-β between groups A and B (P=0.019). PSK reduced the plasma TGF-β in AGC patients when the levels were initially high. The clinical advantage of PSK may, however, be restricted to specific histological types of AGC. Perioperative suppression of TGF-β by PSK may antagonize cancer immune evasion and improve patient prognosis in cases of AGC. PMID:26137253

  3. Innovation at the Intersection of Clinical Trials and Real-World Data Science to Advance Patient Care.

    PubMed

    Swift, Brandon; Jain, Lokesh; White, Craig; Chandrasekaran, Vasu; Bhandari, Aman; Hughes, Dyfrig A; Jadhav, Pravin R

    2018-05-16

    While efficacy and safety data collected from randomized clinical trials are the evidentiary standard for determining market authorization, this alone may no longer be sufficient to address the needs of key stakeholders (regulators, providers, and payers) and guarantee long-term success of pharmaceutical products. There is a heightened interest from stakeholders on understanding the use of real-world evidence (RWE) to substantiate benefit-risk assessment and support the value of a new drug. This review provides an overview of real-world data (RWD) and related advances in the regulatory framework, and discusses their impact on clinical research and development. A framework for linking drug development decisions with the value proposition of the drug, utilizing pharmacokinetic-pharmacodynamic-pharmacoeconomic models, is introduced. The summary presented here is based on the presentations and discussion at the symposium entitled Innovation at the Intersection of Clinical Trials and Real-World Data to Advance Patient Care at the American Society for Clinical Pharmacology and Therapeutics (ASCPT) 2017 Annual Meeting. © 2018 The Authors. Clinical and Translational Science published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  4. Germline determinants of clinical outcome of cutaneous melanoma

    PubMed Central

    Vogelsang, Matjaz; Wilson, Melissa; Kirchhoff, Tomas

    2016-01-01

    Cutaneous melanoma (CM) is the most lethal form of skin cancer. Despite the constant increase of melanoma incidence, which is in part due to incremental advances in early diagnostic modalities, mortality rates have not improved over the last decade and for advanced stages remain steadily high. While conventional prognostic biomarkers currently in use find significant utility for predicting overall general survival probabilities, they are not sensitive enough for a more personalized clinical assessment on an individual level. In recent years, the advent of genomic technologies has brought the promise of identification of germline DNA alterations that may associate with CM outcomes and hence represent novel biomarkers for clinical utilization. This review attempts to summarize the current state of knowledge of germline genetic factors studied for their impact on melanoma clinical outcomes. We also discuss ongoing problems and hurdles in validating such surrogates, and we also project future directions in discovery of more powerful germline genetic factors with clinical utility in melanoma prognostication. PMID:26342156

  5. "A palliative end-stage COPD patient does not exist": a qualitative study of barriers to and facilitators for early integration of palliative home care for end-stage COPD.

    PubMed

    Scheerens, Charlotte; Deliens, Luc; Van Belle, Simon; Joos, Guy; Pype, Peter; Chambaere, Kenneth

    2018-06-20

    Early integration of palliative home care (PHC) might positively affect people with chronic obstructive pulmonary disease (COPD). However, PHC as a holistic approach is not well integrated in clinical practice at the end-stage COPD. General practitioners (GPs) and community nurses (CNs) are highly involved in primary and home care and could provide valuable perspectives about barriers to and facilitators for early integrated PHC in end-stage COPD. Three focus groups were organised with GPs (n = 28) and four with CNs (n = 28), transcribed verbatim and comparatively analysed. Barriers were related to the unpredictability of COPD, a lack of disease insight and resistance towards care of the patient, lack of cooperation and experience with PHC for professional caregivers, lack of education about early integrated PHC, insufficient continuity of care from hospital to home, and lack of communication about PHC between professional caregivers and with end-stage COPD patients. Facilitators were the use of trigger moments for early integrating PHC, such as after a hospital admission or when an end-stage COPD patient becomes oxygen-dependent or housebound, positive attitudes towards PHC in informal caregivers, more focus on early integration of PHC in professional caregivers' education, implementing advance care planning in healthcare and PHC systems, and enhancing communication about care and PHC. The results provide insights for clinical practice and the development of key components for successful practice in a phase 0-2 Early Integration of PHC for end-stage COPD (EPIC) trial, such as improving care integration, patients' disease insight and training PHC nurses in care for end-stage COPD.

  6. Clinically Applicable Inhibitors Impacting Genome Stability.

    PubMed

    Prakash, Anu; Garcia-Moreno, Juan F; Brown, James A L; Bourke, Emer

    2018-05-13

    Advances in technology have facilitated the molecular profiling (genomic and transcriptomic) of tumours, and has led to improved stratification of patients and the individualisation of treatment regimes. To fully realize the potential of truly personalised treatment options, we need targeted therapies that precisely disrupt the compensatory pathways identified by profiling which allow tumours to survive or gain resistance to treatments. Here, we discuss recent advances in novel therapies that impact the genome (chromosomes and chromatin), pathways targeted and the stage of the pathways targeted. The current state of research will be discussed, with a focus on compounds that have advanced into trials (clinical and pre-clinical). We will discuss inhibitors of specific DNA damage responses and other genome stability pathways, including those in development, which are likely to synergistically combine with current therapeutic options. Tumour profiling data, combined with the knowledge of new treatments that affect the regulation of essential tumour signalling pathways, is revealing fundamental insights into cancer progression and resistance mechanisms. This is the forefront of the next evolution of advanced oncology medicine that will ultimately lead to improved survival and may, one day, result in many cancers becoming chronic conditions, rather than fatal diseases.

  7. The efficacy of self-directed modules for clinical learning: advanced competencies in entry-level physical therapy education.

    PubMed

    Peck, Kirk; Paschal, Karen; Black, Lisa; Nelson, Kelly

    2014-01-01

    Prior to graduation, students often express an interest to advance clinical and professional skills in teaching, research, administration, and various niche practice areas. The acquisition of advanced education in selected areas of practice is believed to improve employment opportunities, accelerate career advancement including eligibility for professional certifications, and contribute to personal satisfaction in the profession. The purpose of this paper is to (1) describe an innovative model of education, the Directed Practice Experience (DPE) elective, that incorporates a student-initiated learning process designed to achieve student-identified professional goals, and (2) report the outcomes for graduates who have completed the DPE in an entry-level program in physical therapy education. Students who met select criteria were eligible to complete a DPE. Applicants designed a 4- to 6-week clinical education experience consisting of stated rationale for personal and professional growth, examples of leadership and service, and self-directed objectives that are beyond entry-level expectations as measured by the revised Physical Therapist Clinical Performance Instrument, version 2006. Twenty-six students have completed DPEs since 2005. Fifty percent resulted in new academic partnerships. At least 25% of graduates now serve as clinical instructors for the entry-level program. Those who participated in DPEs have also completed post-graduate residencies, attained ABPTS Board certifications, authored peer-reviewed publications, and taught in both PT and residency programs. The DPE model allows qualified students to acquire advanced personal skills and knowledge prior to graduation in areas of professional practice that exceed entry-level expectations. The model is applicable to all CAPTE accredited physical therapy education programs and is especially beneficial for academic programs desiring to form new community partnerships for student clinical education.

  8. Clinical Application Of Advanced Infrared Thermography (IRT) In Locomotor Diseases

    NASA Astrophysics Data System (ADS)

    Engel, Joachim-Michael

    1983-11-01

    Locomotor diseases is a wide range of about 450 different illnesses with all different pathologies, clinical and prognostic features and response to treatment. No single method will be able to cover the whole spectrum of local and systemic signs and symptoms. Nevertheless there is a need for objective measurements at the site of disease: clinical examination is often enough depending from subjective estimations and personal experiance of the clinician. Laboratory tests only show the systemic effect of the disease, like inflammation. X-rays are restricted to the detection of structural changes appearing late during the pathological process, even when using different techniques. Here IRT offers several advantages to the clinician as well as to the patient. As a non invasive method it monitors the course of disease at the anatomic site of pathology. Quantitative figures calculated from the thermogram,either taken at steady-state or during dynamic tests, are essential for differential diagnosis and follow-up. Advanced IRT camera systems fulfill all requirements set up for medical thermography recently by the National Bureau of Standards. Although, the user should check his system daily with regard to precision of absolute temperature measurements. Standardisation of recording technique is essential as well,to get reliable results. Ambient conditions must be adapted to the locomotor disease pathology under study. Advanced IRT systems , e.g. ZEISS-IKOTHERM, together with image processing capability and special software, e.g. THERMOTOM package, are valuable tools to the rheumatologist for diagnosing and monitoring locomotor diseases.

  9. Clinical Advancements in the Targeted Therapies against Liver Fibrosis

    PubMed Central

    Nagórniewicz, Beata; Prakash, Jai

    2016-01-01

    Hepatic fibrosis, characterized by excessive accumulation of extracellular matrix (ECM) proteins leading to liver dysfunction, is a growing cause of mortality worldwide. Hepatocellular damage owing to liver injury leads to the release of profibrotic factors from infiltrating inflammatory cells that results in the activation of hepatic stellate cells (HSCs). Upon activation, HSCs undergo characteristic morphological and functional changes and are transformed into proliferative and contractile ECM-producing myofibroblasts. Over recent years, a number of therapeutic strategies have been developed to inhibit hepatocyte apoptosis, inflammatory responses, and HSCs proliferation and activation. Preclinical studies have yielded numerous targets for the development of antifibrotic therapies, some of which have entered clinical trials and showed improved therapeutic efficacy and desirable safety profiles. Furthermore, advancements have been made in the development of noninvasive markers and techniques for the accurate disease assessment and therapy responses. Here, we focus on the clinical developments attained in the field of targeted antifibrotics for the treatment of liver fibrosis, for example, small molecule drugs, antibodies, and targeted drug conjugate. We further briefly highlight different noninvasive diagnostic technologies and will provide an overview about different therapeutic targets, clinical trials, endpoints, and translational efforts that have been made to halt or reverse the progression of liver fibrosis. PMID:27999454

  10. Staged Hard and Soft Tissue Reconstruction Followed by Implant Supported Restoration in the Aesthetic Zone: A Case Report.

    PubMed

    Parthasarathy, Harinath; Ramachandran, Lakshmi; Tadepalli, Anupama; Ponnaiyan, Deepa

    2017-04-01

    Alveolar ridge deficiency is a common clinical consequence following tooth loss due to chronic periodontitis complicating ideal implant placement. Advanced hard and soft tissue augmentation procedures have been developed in the recent past with predictable clinical outcomes. A male patient presented with a Grade III mobile upper right central incisor associated with advanced bone loss and soft tissue deficit. Following extraction of tooth #11, socket augmentation was done using an autogenous cortico-cancellous block graft and subsequent soft tissue augmentation was done with palatal connective tissue graft. At the end of six months, a tapered self tapping implant fixture was placed with adequate primary stability and after eight weeks, second stage implant surgery was done with the Misch technique in order to recreate papillae and the implant was prosthetically restored. The alveolar ridge was adequately recontoured following the staged surgical protocol. The implant was well integrated at the end of 15 months. Execution of sequential surgical procedures in a highly deficient edentulous site made it possible to achieve of optimal pink and white aesthetics with stable implant supported fixed prosthesis.

  11. Axillary Ultrasound Accurately Excludes Clinically Significant Lymph Node Disease in Patients with Early Stage Breast Cancer

    PubMed Central

    Tucker, Natalia S.; Cyr, Amy E.; Ademuyiwa, Foluso O.; Tabchy, Adel; George, Krystl; Sharma, Piyush; Jin, Linda X.; Sanati, Souzan; Aft, Rebecca; Gao, Feng; Margenthaler, Julie A.; Gillanders, William E.

    2016-01-01

    Objective Assess the performance characteristics of axillary ultrasound (AUS) for accurate exclusion of clinically significant axillary lymph node (ALN) disease. Background Sentinel lymph node biopsy (SLNB) is currently the standard of care for staging the axilla in patients with clinical T1–T2, N0 breast cancer. AUS is a noninvasive alternative to SLNB for staging the axilla. Methods Patients were identified using a prospectively maintained database. Sensitivity, specificity, and negative predictive value (NPV) were calculated by comparing AUS findings to pathology results. Multivariate analyses were performed to identify patient and/or tumor characteristics associated with false negative (FN) AUS. A blinded review of FN and matched true negative cases was performed by two independent medical oncologists to compare treatment recommendations and actual treatment received. Recurrence-free survival was described using Kaplan-Meier product limit methods. Results 647 patients with clinical T1–T2, N0 breast cancer underwent AUS between January, 2008 and March, 2013. AUS had a sensitivity of 70%, NPV of 84% and PPV of 56% for the detection of ALN disease. For detection of clinically significant disease (> 2.0 mm), AUS had a sensitivity of 76% and NPV of 89%. FN AUS did not significantly impact adjuvant medical decision making. Patients with FN AUS had recurrence-free survival equivalent to patients with pathologic N0 disease. Conclusions AUS accurately excludes clinically significant ALN disease in patients with clinical T1–T2, N0 breast cancer. AUS may be an alternative to SLNB in these patients where axillary surgery is no longer considered therapeutic, and predictors of tumor biology are increasingly used to make adjuvant therapy decisions. PMID:26779976

  12. Differential impact of current diagnosis and clinical stage on attendance at a youth mental health service.

    PubMed

    Cross, Shane P M; Hermens, Daniel F; Scott, Jan; Salvador-Carulla, Luis; Hickie, Ian B

    2017-06-01

    To examine whether clinical stage of illness and current diagnosis influence appointment behaviour in a specialized primary-level youth mental health service. Factors associated with attendance at 8697 appointments made by 828 young people (females = 497) aged 12-25 years over a 1-year period were analysed. The number of appointments made did not correlate with the rates of attendance. However, those with more severe psychiatric morbidity made significantly more appointments and missed significantly more appointments than those with less severe presentations. Impaired social functioning was the best predictor of female attendance rates, whereas age and clinical stage of illness best predicted male attendance rates. Current diagnosis rather than functional impairment appeared to influence the level of input offered by clinicians. Age, gender, severity of illness, functioning and psychological distress had differential associations with both planned treatment intensity and attendance rates. These differences are likely to have implications for service provision in this youth population. © 2016 John Wiley & Sons Australia, Ltd.

  13. Macroscopic appearance of Type IV and giant Type III is a high risk for a poor prognosis in pathological stage II/III advanced gastric cancer with postoperative adjuvant chemotherapy

    PubMed Central

    Yamashita, Keishi; Ema, Akira; Hosoda, Kei; Mieno, Hiroaki; Moriya, Hiromitsu; Katada, Natsuya; Watanabe, Masahiko

    2017-01-01

    AIM To evaluate whether a high risk macroscopic appearance (Type IV and giant Type III) is associated with a dismal prognosis after curative surgery, because its prognostic relevance remains elusive in pathological stage II/III (pStage II/III) gastric cancer. METHODS One hundred and seventy-two advanced gastric cancer (defined as pT2 or beyond) patients with pStage II/III who underwent curative surgery plus adjuvant S1 chemotherapy were evaluated, and the prognostic relevance of a high-risk macroscopic appearance was examined. RESULTS Advanced gastric cancers with a high-risk macroscopic appearance were retrospectively identified by preoperative recorded images. A high-risk macroscopic appearance showed a significantly worse relapse free survival (RFS) (35.7%) and overall survival (OS) (34%) than an average risk appearance (P = 0.0003 and P < 0.0001, respectively). A high-risk macroscopic appearance was significantly associated with the 13th Japanese Gastric Cancer Association (JGCA) pT (P = 0.01), but not with the 13th JGCA pN. On univariate analysis for RFS and OS, prognostic factors included 13th JGCA pStage (P < 0.0001) and other clinicopathological factors including macroscopic appearance. A multivariate Cox proportional hazards model for univariate prognostic factors identified high-risk macroscopic appearance (P = 0.036, HR = 2.29 for RFS and P = 0.021, HR = 2.74 for OS) as an independent prognostic indicator. CONCLUSION A high-risk macroscopic appearance was associated with a poor prognosis, and it could be a prognostic factor independent of 13th JGCA stage in pStage II/III advanced gastric cancer. PMID:28451064

  14. Advanced stages of embryonic development and cotylocidial morphogenesis in the intrauterine eggs of Aspidogaster limacoides Diesing, 1835 (Aspidogastrea), with comments on their phylogenetic implications.

    PubMed

    Świderski, Zdzisław; Poddubnaya, Larisa G; Gibson, David I; Młocicki, Daniel

    2012-06-01

    Ultrastructural aspects of the advanced embryonic development and cotylocidial morphogenesis of the aspidogastrean Aspidogaster limacoides are described. The posterior or distal regions of the uterus are filled with eggs containing larvae at advanced stages of morphogenesis and fully-formed cotylocidia. Various stages and organs of this larva are described in detail, including the aspects of the developing and fully-differentiated cotylocidium, the body wall (tegument and musculature), glandular regions and the protonephridial excretory system. Blastomere multiplication by means of mitotic divisions takes place simultaneously with the degeneration or apoptosis of some micromeres; this frequently observed characteristic is compared and discussed in relation to corresponding reports for other neodermatans. During the advanced stages of the embryonic development of A. limacoides, the vitelline syncytium disappears and the size of the embryo increases rapidly. Evident polarization of the differentiating larva was observed; towards one pole of the egg, cytodifferentiation of the mouth, surrounded by the oral sucker and cephalic glands, takes place, whereas, towards the opposite pole, differentiation of the posterior sucker (incipient ventral disc) occurs. The oral and posterior suckers are formed from numerous embryonic cells which have differentiated into myocytes. The central part of the oral sucker undergoes invagination and forms the future pharynx and intestine. Fully-developed cotylocidia of A. limacoides have a neodermatan type of tegument, flame cells and two types of glandular structures. These results suggest a sister relationship between the Aspidogastrea and the Digenea, although the systematic position of aspidogastreans in relation to other platyhelminth taxa remains somewhat equivocal.

  15. Endoscopic Criteria for Evaluating Tumor Stage after Preoperative Chemoradiation Therapy in Locally Advanced Rectal Cancer.

    PubMed

    Han, Kyung Su; Sohn, Dae Kyung; Kim, Dae Yong; Kim, Byung Chang; Hong, Chang Won; Chang, Hee Jin; Kim, Sun Young; Baek, Ji Yeon; Park, Sung Chan; Kim, Min Ju; Oh, Jae Hwan

    2016-04-01

    Local excision may be an another option for selected patients with markedly down-staged rectal cancer after preoperative chemoradiation therapy (CRT), and proper evaluation of post-CRT tumor stage (ypT) is essential prior to local excision of these tumors. This study was designed to determine the correlations between endoscopic findings and ypT of rectal cancer. In this study, 481 patients with locally advanced rectal cancer who underwent preoperative CRT followed by surgical resection between 2004 and 2013 at a single institution were evaluated retrospectively. Pathological good response (p-GR) was defined as ypT ≤ 1, and pathological minimal or no response (p-MR) as ypT ≥ 2. The patients were randomly classified according to two groups, a testing (n=193) and a validation (n=288) group. Endoscopic criteria were determined from endoscopic findings and ypT in the testing group and used in classifying patients in the validation group as achieving or not achieving p-GR. Based on findings in the testing group, the endoscopic criteria for p-GR included scarring, telangiectasia, and erythema, whereas criteria for p-MR included nodules, ulcers, strictures, and remnant tumors. In the validation group, the kappa statistic was 0.965 (p < 0.001), and the sensitivity, specificity, positive predictive value, and negative predictive value were 0.362, 0.963, 0.654, and 0.885, respectively. The endoscopic criteria presented are easily applicable for evaluation of ypT after preoperative CRT for rectal cancer. These criteria may be used for selection of patients for local excision of down-staged rectal tumors, because patients with p-MR could be easily ruled out.

  16. Advances in basic and clinical immunology in 2016.

    PubMed

    Chinen, Javier; Badran, Yousef R; Geha, Raif S; Chou, Janet S; Fried, Ari J

    2017-10-01

    Advances in basic immunology in 2016 included studies that further characterized the role of different proteins in the differentiation of effector T and B cells, including cytokines and proteins involved in the actin cytoskeleton. Regulation of granule formation and secretion in cytotoxic cells was also further described by examining patients with familial hemophagocytic lymphohistiocytosis. The role of prenylation in patients with mevalonate kinase deficiency leading to inflammation has been established. We reviewed advances in clinical immunology, as well as new approaches of whole-genome sequencing and genes newly reported to be associated with immunodeficiency, such as linker of activation of T cells (LAT); B-cell CLL/lymphoma 11B (BCL11B); RGD, leucine-rich repeat, tropomodulin domain, and proline-rich domain-containing protein (RLTPR); moesin; and Janus kinase 1 (JAK1). Trials of hematopoietic stem cell transplantation and gene therapy for primary immunodeficiency have had relative success; the use of autologous virus-specific cytotoxic T cells has proved effective as well. New medications are being explored, such as pioglitazone, which is under study for its role in enhancing the oxidative burst in patients with chronic granulomatous disease. Development of vaccines for HIV infection continues to provide insight into the immune response against a virus with an extraordinary mutation rate. Copyright © 2017 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

  17. The 3 faces of clinical reasoning: Epistemological explorations of disparate error reduction strategies.

    PubMed

    Monteiro, Sandra; Norman, Geoff; Sherbino, Jonathan

    2018-06-01

    There is general consensus that clinical reasoning involves 2 stages: a rapid stage where 1 or more diagnostic hypotheses are advanced and a slower stage where these hypotheses are tested or confirmed. The rapid hypothesis generation stage is considered inaccessible for analysis or observation. Consequently, recent research on clinical reasoning has focused specifically on improving the accuracy of the slower, hypothesis confirmation stage. Three perspectives have developed in this line of research, and each proposes different error reduction strategies for clinical reasoning. This paper considers these 3 perspectives and examines the underlying assumptions. Additionally, this paper reviews the evidence, or lack of, behind each class of error reduction strategies. The first perspective takes an epidemiological stance, appealing to the benefits of incorporating population data and evidence-based medicine in every day clinical reasoning. The second builds on the heuristic and bias research programme, appealing to a special class of dual process reasoning models that theorizes a rapid error prone cognitive process for problem solving with a slower more logical cognitive process capable of correcting those errors. Finally, the third perspective borrows from an exemplar model of categorization that explicitly relates clinical knowledge and experience to diagnostic accuracy. © 2018 John Wiley & Sons, Ltd.

  18. Report of a consultation on the optimization of clinical challenge trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, Bethesda, MD, USA.

    PubMed

    Moorthy, V S; Diggs, C; Ferro, S; Good, M F; Herrera, S; Hill, A V; Imoukhuede, E B; Kumar, S; Loucq, C; Marsh, K; Ockenhouse, C F; Richie, T L; Sauerwein, R W

    2009-09-25

    Development and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing pre-erythrocytic stage vaccines, some researchers believe that the sporozoite challenge model is less appropriate for testing blood stage vaccines. Here we report a consultation, co-sponsored by PATH MVI, USAID, EMVI and WHO, where scientists from all institutions globally that have conducted such clinical challenges in recent years and representatives from regulatory agencies and funding agencies met to discuss clinical malaria challenge models. Participants discussed strengthening and harmonizing the sporozoite challenge model and considered the pros and cons of further developing a blood stage challenge possibly better suited for evaluating the efficacy of blood stage vaccines. This report summarizes major findings and recommendations, including an update on the Plasmodium vivax clinical challenge model, the prospects for performing experimental challenge trials in malaria endemic countries and an update on clinical safety data. While the focus of the meeting was on the optimization of clinical challenge models for evaluation of blood stage candidate malaria vaccines, many of the considerations are relevant for the application of challenge trials to other purposes.

  19. Treatment for stage 4A retinopathy of prematurity: laser and/or ranibizumab.

    PubMed

    Sukgen, Emine Alyamaç; Koçluk, Yusuf

    2017-02-01

    Stage 4A retinopathy of prematurity (ROP) is a critical phase where retinal detachment develops, but fovea is preserved. The present study aims to evaluate the effect of the first treatment choice (laser photocoagulation (LPC) or intravitreal ranibizumab (IVR)) applied in this critical phase on the prognosis of the disease. Records of patients diagnosed with stage 4A ROP and whose first treatment was applied in our clinic were evaluated retrospectively. All patients were referred to our clinic for the treatment of advanced ROP . While group 1 was composed of the patients who were administered LPC as first treatment, group 2 included patients where IVR was applied as first treatment. The patients in both groups were referred to surgical treatment in the presence of progression. The present study included a total of 31 eyes in 16 patients with stage 4A ROP. Eighteen eyes of nine patients in group 1 were first applied LPC, and 13 eyes of seven patients in group 2 were first applied intravitreal ranibizumab. While anatomic outcomes of ten eyes in both groups were favorable, eight eyes in group 1 and three eyes in group 2 displayed progression and were referred to vitreoretinal surgery. Laser and/or IVR treatment may be effective as a non-surgical treatment for stage 4A ROP. Especially stage 4A ROP until 6 clock hours can regress without surgical treatment. However, in stage 4A with involvement wider than 6 clock hours, non-surgical regression is difficult. Prospective controlled large series studies are necessary.

  20. Nuclear Cryogenic Propulsion Stage

    NASA Technical Reports Server (NTRS)

    Houts, Michael G.; Borowski, S. K.; George, J. A.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Adams, R. B.

    2012-01-01

    The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced NEP.