Science.gov

Sample records for advanced clinical staging

  1. Advances take stage - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Regulatory advances in proteomics will be taking center stage at a Symposia scheduled to occur at the 2011 American Association for Clinical Chemistry (AACC) Annual Meeting. The symposium entitled "Enabling Translational Proteomics with NCI's Clinical Proteomic Technologies for Cancer" is scheduled for July 25, 2011 at AACC's annual Meeting.

  2. Advances take stage - Office of Cancer Clinical Proteomics Research

    Cancer.gov

    Regulatory advances in proteomics will be taking center stage at a Symposia scheduled to occur at the 2011 American Association for Clinical Chemistry (AACC) Annual Meeting. The symposium entitled "Enabling Translational Proteomics with NCI's Clinical Proteomic Technologies for Cancer" is scheduled for July 25, 2011 at AACC's annual Meeting.

  3. The cachexia clinic: from staging to managing nutritional and functional problems in advanced cancer patients.

    PubMed

    Vigano, Antonio; Del Fabbro, Egidio; Bruera, Eduardo; Borod, Manuel

    2012-01-01

    Panels of experts have agreed on the definition of cancer cachexia stages (CCS). We evaluated the clinical relevance of these stages and proposed ways to apply the CCSs to the clinical practice via standardized methods. The CCS were applied to 207 patients with advanced non-small-cell lung or gastrointestinal cancers from the Human Cancer Cachexia Database via consensus among the coauthors. Patients were categorized as noncachectic, precachectic, cachectic, and in refractory cachexia. Through analysis of variance, χ2, and Kaplan-Meier analyses, we tested the relationships between CCSs and selected outcomes. The CCS were significantly correlated (P < 0.05) with patient-centered indicators, including overall symptom burden, quality of life, tolerability to chemotherapy, body composition, hospital stay, and survival. However, precachectic and cachectic patients behaved similarly in all these outcomes but were significantly different from noncachectic and refractory cachectic patients. The average scores for the abridged Patient-Generated Subjective Global Assessment (aPG-SGA) corresponded well with the CCSs and reflected nicely the cut-off scores recommended for the nutritional triage of cancer patients. In addition to the aPG-SGA, we proposed the Edmonton Symptom Assessment System and routine laboratory tests for the triage of patients with refractory cachexia, for whom comfort care is the primary goal. The cachexia clinic hosted by the McGill Nutrition and Performance Laboratory offers a model for diagnosing more precisely the pathophysiology and severity of precachectic and cachectic conditions. The cachexia clinic, by working closely with palliative care programs, may offer the best environment for a comprehensive and personalized approach to the nutritional and functional problems in advanced cancer patients.

  4. IGF-IEc expression is associated with advanced clinical and pathological stage of prostate cancer.

    PubMed

    Savvani, Argyro; Petraki, Constantina; Msaouel, Pavlos; Diamanti, Evangelia; Xoxakos, Ioannis; Koutsilieris, Michael

    2013-06-01

    Recent evidence suggests a role for the insulin-like growth factor-1Ec (IGF-IEc) transcript variant in cancer biology. The aim of the present study was to investigate whether IGF-IEc expression is associated with prostate cancer stage. Formalin-fixed and paraffin-embedded prostate cancer surgical specimens from 83 patients were assessed by immunohistochemistry for IGF-IEc expression. Normal prostate epithelium was negative or demonstrated mild IGF-IEc cytoplasmic expression whereas prostate cancer exhibited mild to strong cytoplasmic immunoexpression. The mean IGF-1Ec expression, was significantly lower (p=0.004) in localized (stage ≤ IIb) prostate cancer, compared to locally advanced tumors (stage ≥ III). Only one out of 83 (1.2%) prostate cancer samples was completely negative for IGF-IEc. A weak-positive correlation was also observed between IGF-IEc expression levels and Gleason score (r=0.247; p=0.024). The present data demonstrate that the expression of IGF-IEc is positively-associated with more advanced stage and higher Gleason score of prostate carcinomas.

  5. Relationship of Clinical and Pathologic Nodal Staging in Locally Advanced Breast Cancer: Current Controversies in Daily Practice?

    PubMed Central

    De Felice, Francesca; Musio, Daniela; Bulzonetti, Nadia; Raffetto, Nicola; Tombolini, Vincenzo

    2014-01-01

    Systemic neo-adjuvant therapy plays a primary role in the management of locally advanced breast cancer. Without having any negative effect in overall survival, induction chemotherapy potentially assures a surgery approach in unresectable disease or a conservative treatment in technically resectable disease and acts on a well-vascularized tumor bed, without the modifications induced by surgery. A specific issue has a central function in the neo-adjuvant setting: lymph nodes status. It still represents one of the strongest predictors of long-term prognosis in breast cancer. The discussion of regional radiation therapy should be a matter of debate, especially in a pathological complete response. Currently, the indication for radiotherapy is based on the clinical stage before the surgery, even for the irradiation of the loco-regional lymph nodes. Regardless of pathological down-staging, radiation therapy is accepted as standard adjuvant treatment in locally advanced breast cancer. PMID:25247013

  6. Latest research and clinical treatment of advanced-stage epithelial ovarian cancer

    PubMed Central

    Coleman, Robert L.; Monk, Bradley J.; Sood, Anil K.; Herzog, Thomas J.

    2013-01-01

    The natural history of ovarian cancer continues to be characterized by late-stage presentation, metastatic bulky disease burden and stagnant mortality statistics despite prolific drug development. Robust clinical investigation, particularly with modifications to primary treatment surgical goals and adjuvant therapy are increasing median progression-free and overall survival, although the cure rates have only modestly been affected. Maintenance therapy holds promise, but studies have yet to identify an agent and/or strategy that can affect survival. Recurrent disease is largely an incurable state; however, current intervention with selected surgery, combination and targeted therapy and investigational protocols are impacting progression-free survival. Ovarian cancer is a diverse and genomically complex disease, which commands global attention. Rational investigation must balance the high rate of discovery with lagging clinical investigation and limited patient resources. Nevertheless, armamentarium growth offers unprecedented opportunities for patients suffering with this disease. This Review presents and reviews the contemporary management of the disease spectrum termed epithelial ‘ovarian’ cancer and introduces the direction and early results of clinical investigation. PMID:23381004

  7. Clinical outcomes of advanced-stage glassy cell carcinoma of the uterine cervix: a need for reappraisal

    PubMed Central

    Yoon, Nara; Kim, Ji-Ye; Kim, Hyun-Soo

    2016-01-01

    We performed a retrospective analysis of the clinical features and patient outcomes for advanced-stage glassy cell carcinoma of the uterine cervix. The study was restricted to cases in which the glassy cell features constituted at least 95% of the biopsied specimen. During the study period, 675 patients were diagnosed with primary cervical carcinoma. Five (0.7%) of the 675 patients had cervical glassy cell carcinoma; of these, three were premenopausal, and two were postmenopausal. Abnormal vaginal bleeding was the most frequent presenting symptom. Glassy cell carcinoma presented as a fungating, exophytic, or infiltrative mass. The greatest tumor dimension ranged from 3 to 9 cm. All patients had parametrial extension. Four patients had stage IIB tumors, and one had a stage IIIB tumor. All patients received concurrent chemoradiation therapy. The patient with a stage IIIB tumor died of hypovolemic shock caused by upper gastrointestinal bleeding during radiation therapy. Three patients with stage IIB tumors survived for more than 8 years without tumor recurrence or metastasis. One of these three patients died of pelvic recurrence 10 years after the initial diagnosis. Cervical glassy cell carcinoma has traditionally been considered an aggressive, highly malignant tumor with poor prognosis, but our data suggest that patient survival is not significantly decreased compared with other histological types of cervical carcinoma. It will be necessary to analyze patient outcomes using a larger number of cervical glassy cell carcinoma cases to confirm our findings. PMID:27793022

  8. "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.

  9. 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.

  10. Clinical Impact of Education Provision on Determining Advance Care Planning Decisions among End Stage Renal Disease Patients Receiving Regular Hemodialysis in University Malaya Medical Centre

    PubMed Central

    Hing (Wong), Albert; Chin, Loh Ee; Ping, Tan Li; Peng, Ng Kok; Kun, Lim Soo

    2016-01-01

    Introduction: Advance care planning (ACP) is a process of shared decision-making about future health-care plans between patients, health care providers, and family members, should patients becomes incapable of participating in medical treatment decisions. ACP discussions enhance patient's autonomy, focus on patient's values and treatment preferences, and promote patient-centered care. ACP is integrated as part of clinical practice in Singapore and the United States. Aim: To assess the clinical impact of education provision on determining ACP decisions among end-stage renal disease patients on regular hemodialysis at University Malaya Medical Centre (UMMC). To study the knowledge and attitude of patients toward ACP and end-of-life issues. Materials and Methods: Fifty-six patients were recruited from UMMC. About 43 questions pretest survey adapted from Lyon's ACP survey and Moss's cardiopulmonary resuscitation (CPR) attitude survey was given to patients to answer. An educational brochure is then introduced to these patients, and a posttest survey carried out after that. The results were analyzed using SPSS version 22.0. Results: Opinion on ACP, including CPR decisions, showed an upward trend on the importance percentage after the educational brochure exposure, but this was statistically not significant. Seventy-five percent of participants had never heard of ACP before, and only 3.6% had actually prepared a written advanced directive. Conclusion: The ACP educational brochure clinically impacts patients’ preferences and decisions toward end-of-life care; however, this is statistically not significant. Majority of patients have poor knowledge on ACP. This study lays the foundation for execution of future larger scale clinical trials, and ultimately, the incorporation of ACP into clinical practice in Malaysia. PMID:27803566

  11. Using data from studies of health-related quality of life to describe clinical issues examples from a longitudinal study of patients with advanced stages of cervical cancer.

    PubMed

    Klee, M; Groenvold, M; Machin, D

    1999-12-01

    The focus of the paper is to describe how to present data from studies on health-related quality of life (H-QoL) in a way that is simple and clinically relevant. Data from a longitudinal study of patients with advanced stages of cervix cancer are used. One hundred and eighteen patients filled out questionnaires (including EORTC QLQ-C30) 7 times over a period of 2 years. The following issues are considered: (1) The use of a panel for an initial overview of data. (2) The visual difference between using mean and median values. (3) Box-whisker plots to illustrate the variability of the data. (4) The effect of combining categorical data into fewer categories. (5) Individual patient profiles showing the wide variability among patients. (6) A table showing the change of scores over a one-year period. (7) "Prognostic plots" dividing the initial scores and the following scores. (8) Plotting changes over time. (9) Illustration of the impact of non-random dropout. (10) The effect of drop-out for the patients who fill out two sequential assessments. (11) The use of healthy controls to help answer the question "what is normal?".

  12. 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

  13. 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.

  14. Advanced staged combustion system for power generation

    SciTech Connect

    Rehmat, A.; Goyal, A.

    1993-12-31

    To respond to the increasing market need for a new generation of plants with a substantial improvement in efficiency and a reduction in capital cost, the Institute of Gas Technology has developed an advanced staged, fluidized-bed combustion system concept. The staged fluidized-bed partial combustor produces the fuel gas at about 1500 F. The fuel gas, after particulate removal, is directed to a gas turbine followed by a steam cycle. Adequate sulfur capture and solids waste stabilization are attained by separating calcination, carbonization, and gasification/combustion steps in the staged fluidized beds. Intermediate gas cooling is avoided during the process to maximize the power production. The coal-to-electricity conversion efficiency of the system approaches 49 percent, which exceeds the efficiencies of the other emerging technologies.

  15. 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.

  16. Stages of the clinical course of schizophrenia - staging concept.

    PubMed

    Wójciak, Paweł; Remlinger-Molenda, Agnieszka; Rybakowski, Janusz

    2016-01-01

    Clinical staging is a tool useful in medical sciences. It assumes the presence of three key elements. Firstly, pathologic indices are progressing in subsequent stages. Secondly, the patients in the individual stages present similar pathological changes. Thirdly, treatment should be most effective in the earlier stages. Such model is particularly well established in the treatment of malignancies. Staging is useful here to define prognosis, to evaluate the results of treatment, facilitate the exchange and comparison of information among treatment centres. There is much data describing a similar model for mental illnesses including schizophrenia. There are two theories supporting the staging model for schizophrenia: the neurodevelopmental hypothesis and allostatic load concept. Both theories make a theoretical premise for creating the staging model for schizophrenia. We can describe at least three stages in the development of a schizophrenic illness: the prodrome, the first episode and chronic phase. Each stage is reflected by anatomical and functional changes in the brain. Therefore, a clinical staging model can describe a development of schizophrenia over time, to help selecting adequate treatments that are particularly relevant to a given stage and to show the relations between known biological markers and psychosocial risk factors and the stage of the illness.

  17. 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.

  18. Three-dimensional conformal radiotherapy for locally advanced (Stage II and worse) head-and-neck cancer: Dosimetric and clinical evaluation

    SciTech Connect

    Portaluri, Maurizio . E-mail: portaluri@hotmail.com; Fucilli, Fulvio I.M.; Castagna, Roberta; Bambace, Santa; Pili, Giorgio; Tramacere, Francesco; Russo, Donatella; Francavilla, Maria Carmen

    2006-11-15

    Purpose: To evaluate the dosimetric parameters of three-dimensional conformal radiotherapy (3D-CRT) in locally advanced head-and-neck tumors (Stage II and above) and the effects on xerostomia. Methods and Materials: A total of 49 patients with histologically proven squamous cell cancer of the head and neck were consecutively treated with 3D-CRT using a one-point setup technique; 17 had larynx cancer, 12 oropharynx, 12 oral cavity, and 6 nasopharynx cancer; 2 had other sites of cancer. Of the 49 patients, 41 received postoperative RT and 8 definitive treatment. Also, 13 were treated with cisplatin-based chemotherapy before and during RT; in 6 cases, 5-fluorouracil was added. The follow-up time was 484-567 days (median, 530 days). Results: One-point setup can deliver 96% of the prescribed dose to the isocenter, to the whole planning target volume, including all node levels of the neck and without overdosages. The mean dose to the primary planning target volume was 49.54 {+-} 4.82 Gy (51.53 {+-} 5.47 Gy for larynx cases). The average dose to the contralateral parotid gland was approximately 38 Gy (30 Gy for larynx cases). The maximal dose to the spinal cord was 46 Gy. A Grade 0 Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer xerostomia score corresponded to a mean dose of 30 Gy to one parotid gland. A lower xerostomia score with a lower mean parotid dose and longer follow-up seemed to give rise to a sort of functional recovery phenomenon. Conclusion: Three dimensional-CRT in head-and-neck cancers permits good coverage of the planning target volume with about 10-11 segments and one isocenter. With a mean dose of approximately 30 Gy to the contralateral parotid, we observed no or mild xerostomia.

  19. Efficacy and feasibility of docetaxel, cisplatin, and 5-fluorouracil induction chemotherapy for locally advanced head and neck squamous cell carcinoma classified as clinical nodal stage N2c, N3, or N2b with supraclavicular lymph node metastases.

    PubMed

    Izawa, Naoki; Onozawa, Yusuke; Hikosaka, Tomomi; Hamauchi, Satoshi; Tsushima, Takahiro; Todaka, Akiko; Machida, Nozomu; Haraguchi, Yutaka; Ogawa, Hirofumi; Nishimura, Tetsuo; Nakagawa, Masahiro; Fuke, Tomohito; Iida, Yoshiyuki; Kamijo, Tomoyuki; Onitsuka, Tetsuro; Boku, Narikazu; Yasui, Hirofumi; Yokota, Tomoya

    2015-06-01

    We evaluated the efficacy and feasibility of docetaxel, cisplatin, and 5-fluorouracil (TPF) induction chemotherapy followed by concurrent chemoradiotherapy (CRT) for locally advanced head and neck squamous cell carcinoma (HNSCC) with a high risk of distant metastases compared with CRT alone. We retrospectively analyzed 29 HNSCC patients with clinical nodal stage N2c, N3, or N2b disease and supraclavicular lymph node metastases receiving CRT alone (CRT group; n = 16) or TPF induction chemotherapy followed by CRT (TPF group; n = 13) between April 2008 and May 2012. The median follow-up periods were 14.5 (range 5.0-65.0) and 25.0 (range 14.0-32.0) months for CRT and TPF groups, respectively. A greater proportion of patient characteristics in the CRT group had advanced T and N stages. The overall response rate to induction TPF was 50.0%; grade 3-4 toxicities included neutropenia, febrile neutropenia, anorexia, and hyponatremia. Complete response rates after CRT completion were 55.5% in the TPF and 42.9% in the CRT group; median overall survival was not reached in the TPF group and was 14.0 months in the CRT group (p = 0.037). Multivariate analysis revealed that induction TPF and T stage were independent prognostic factors [hazard ratio (HR) = 0.196; 95% confidence interval (CI) 0.043-0.898; p = 0.036, HR = 9.966; 95% CI 2.270-43.75; p = 0.002, respectively). TPF followed by CRT is tolerated and may be an option for the treatment of locally advanced stage N2c, N3, or N2b HNSCC.

  20. Accuracy of preoperative CT T staging of renal cell carcinoma: which features predict advanced stage?

    PubMed

    Bradley, A J; MacDonald, L; Whiteside, S; Johnson, R J; Ramani, V A C

    2015-08-01

    To characterise CT findings in renal cell carcinoma (RCC), and establish which features are associated with higher clinical T stage disease, and to evaluate patterns of discrepancy between radiological and pathological staging of RCC. Preoperative CT studies of 92 patients with 94 pathologically proven RCCs were retrospectively reviewed. CT stage was compared with pathological stage using the American Joint Committee on Cancer (AJCC), 7(th) edition (2010). The presence or absence of tumour necrosis, perinephric fat standing, thickening of Gerota's fascia, collateral vessels were noted, and correlated with pT stage. The sensitivity, specificity, and positive (PPV) and negative predictive values (NPV) for predicting pT stage ≥pT3a were derived separately for different predictors using cross-tabulations. Twenty-four lesions were pathological stage T1a, 21 were T1b, seven were T2a, 25 were T3a, 11 were T3b, four were T3c, and two were T4. There were no stage T2b. Sixty-three (67%) patients had necrosis, 27 (29%) thickening of Gerota's fascia (1 T1a), 25 had collateral vessels (0 T1a), 28 (30%) had fat stranding of <2 mm, 20 (21%) of 2-5mm and one (1%) of >5 mm. For pT stage ≥pT3a, the presence of perinephric fat stranding had a sensitivity, specificity, PPV and NPV of 74%, 65%, 63%, and 76%, respectively. Presence of tumour necrosis had a sensitivity, specificity, PPV, and NPV of 81%, 44%, 54%, and 72%, respectively. Thickening of Gerota's fascia had a sensitivity, specificity, PPV, and NPV of 52%, 90%, 81% and 70%, respectively; and enlarged collateral vessels had a sensitivity, specificity, PPV, and NPV value of 52%, 94%, 88%, and 71% respectively. The presence of perinephric stranding and tumour necrosis were not reliable signs for pT stage >T3a. Thickening of Gerota's fascia and the presence of collateral vessels in the peri- or paranephric fat had 90% and 94% specificity, with 82% and 88% PPV, respectively, for the presence of tumour stage for pT stage >T3a

  1. Cyberknife treatment for advanced or terminal stage hepatocellular carcinoma

    PubMed Central

    Kato, Hiroyuki; Yoshida, Hideo; Taniguch, Hiroyoshi; Nomura, Ryutaro; Sato, Kengo; Suzuki, Ichiro; Nakata, Ryo

    2015-01-01

    AIM: To investigate the safety and efficacy of the Cyberknife treatment for patients with advanced or terminal stage hepatocellular carcinoma (HCC). METHODS: Patients with HCC with extrahepatic metastasis or vascular or bile duct invasion were enrolled between May 2011 and June 2015. The Cyberknife was used to treat each lesion. Treatment response scores were based on Response Evaluation Criteria in Solid Tumors v1.1. The trends of tumor markers, including alpha fetoprotein (AFP) and proteins induced by vitamin K absence II (PIVKA II) were assessed. Prognostic factors for tumor response and tumor markers were evaluated with Fisher’s exact test and a logistic regression model. Survival was evaluated with the Kaplan-Meier method and multivariate analysis was performed using the Cox proportional hazards model. RESULTS: Sixty-five patients with 95 lesions were enrolled. Based on the Barcelona Clinic Liver Cancer classification, all patients were either in the advanced or terminal stage of the disease. The target lesions were as follows: 52 were bone metastasis; 9, lung metastasis; 7, brain metastasis; 9, portal vein invasion; 4, hepatic vein invasion; 4, bile duct invasion; and 10 other lesion types. The response rate and disease control rate were 34% and 53%, respectively. None of the clinical factors correlated significantly with tumor response. Fiducial marker implantation was associated with better control of both AFP (HR = 0.152; 95%CI: 0.026-0.887; P = 0.036) and PIVKA II (HR = 0.035; 95%CI: 0.003-0.342; P = 0.004). The median survival time was 9 mo (95%CI: 5-15 mo). Terminal stage disease (HR = 9.809; 95%CI: 2.589-37.17, P < 0.001) and an AFP of more than 400 ng/mL (HR = 2.548; 95%CI: 1.070-6.068, P = 0.035) were associated with worse survival. A radiation dose higher than 30 Gy (HR = 0.274; 95%CI: 0.093-0.7541, P = 0.012) was associated with better survival. In the 52 cases of bone metastasis, 36 patients (69%) achieved pain relief. One patient had cerebral

  2. Clinical manifestations and stages of Rett syndrome.

    PubMed

    Hagberg, Bengt

    2002-01-01

    The presentation and clinical diagnosis of Rett syndrome at various ages and stages are reviewed. In addition to the classical form, variability in phenotype between different atypical Rett forms is given. Obligatory, supportive, and differential diagnostic criteria are summarized. Long-term follow-up findings in ageing Rett women are addressed.

  3. The mRNA expression of inhibitors of DNA binding-1 and -2 is associated with advanced tumour stage and adverse clinical outcome in human breast cancer.

    PubMed

    Wazir, Umar; Jiang, Wen G; Sharma, Anup K; Newbold, Robert F; Mokbel, Kefah

    2013-05-01

    Inhibitors of DNA binding (ID) are known to have a role in embryogenesis and oncogenesis. In this study, we analyzed the role of ID1 and ID2 in breast cancer, by assessing associations of mRNA expression with clinicopathological parameters. Breast cancer tissues (n=152) and adjacent normal tissues (n=31) underwent reverse transcription and quantitative- polymerase chain reaction (qPCR). Transcript levels were correlated with clinicopathological data. Patients who were disease-free had significantly lower ID1 mRNA expression than all other patients (p=0.0033). Higher expression was associated with worse disease-free (p=0.001) and overall survival (p=0.02). ID2 expression was directly associated with the Nottingham Prognostic Index (NPI) (NPI 2 vs. 3; p=0.0062) and worsening clinical outcome (disease-free vs. mortality: p=0.0004), and with worse disease-free (p=0.01) and overall survival (p=0.005). Our findings are suggestive of a role for ID1 and ID2 in human breast cancer as possible prognostic markers and therapeutic targets meriting further validating investigations, by immunohistochemistry and mechanistic studies.

  4. Evolving molecularly targeted therapies for advanced-stage thyroid cancers.

    PubMed

    Bible, Keith C; Ryder, Mabel

    2016-07-01

    Increased understanding of disease-specific molecular targets of therapy has led to the regulatory approval of two drugs (vandetanib and cabozantinib) for the treatment of medullary thyroid cancer (MTC), and two agents (sorafenib and lenvatinib) for the treatment of radioactive- iodine refractory differentiated thyroid cancer (DTC) in both the USA and in the EU. The effects of these and other therapies on overall survival and quality of life among patients with thyroid cancer, however, remain to be more-clearly defined. When applied early in the disease course, intensive multimodality therapy seems to improve the survival outcomes of patients with anaplastic thyroid cancer (ATC), but salvage therapies for ATC are of uncertain benefit. Additional innovative, rationally designed therapeutic strategies are under active development both for patients with DTC and for patients with ATC, with multiple phase II and phase III randomized clinical trials currently ongoing. Continued effort is being made to identify further signalling pathways with potential therapeutic relevance in thyroid cancers, as well as to elaborate on the complex interactions between signalling pathways, with the intention of translating these discoveries into effective and personalized therapies. Herein, we summarize the progress made in molecular medicine for advanced-stage thyroid cancers of different histotypes, analyse how these developments have altered - and might further refine - patient care, and identify open questions for future research.

  5. Prognostic significance of tumour progression and human papillomavirus in advanced tonsillar cancer classified as stage IVa.

    PubMed

    Park, E; Jung, K-Y; Kwon, S-Y; Woo, J-S; Cho, J-G; Park, M W; Kim, I S; Kim, S J; Baek, S-K

    2015-01-01

    To identify clinical factors that can explain the differences in treatment outcome, and examine the value of human papillomavirus infection as a prognostic biomarker in stage IVa tonsillar carcinomas. Fifty-nine patients with tonsillar carcinoma classified as stage IVa were retrospectively analysed for survival outcomes according to various clinical factors. Human papillomavirus infection was evaluated using a human papillomavirus DNA chip test and immunohistochemical staining for p16 and p53. Lower disease-free survival rates were associated with increasing local invasiveness and nodal status. Although human papillomavirus positivity and p16 expression was more common in locally advanced tonsillar carcinomas with advanced nodal status, the overall survival rate was better for patients with human papillomavirus positive, p16-positive tumours. The disease-free survival rate may differ according to local tumour invasiveness and nodal status, even for stage IVa tonsillar cancers. Human papillomavirus infection may be a useful biomarker for predicting treatment outcomes for stage VIa tumours.

  6. Are active surveillance criteria sufficient for predicting advanced stage prostate cancer patients?

    PubMed

    Ongun, S; Celik, S; Gül-Niflioglu, G; Aslan, G; Tuna, B; Mungan, U; Uner, S; Yörükoğlu, K

    2014-10-01

    To examine the treatment outcomes of the prostate cancer (PCa) patients treated by radical prostatectomy (RP) who could be good candidates for active surveillance (AS) and test the confidence and reliability of the AS criterias for predicting advanced stage disease (RP Gleason score≥7 or Pathological stage T3). Between 2005 and 2012 the records of the 401 patients who underwent RP with a diagnosis of PCa were examined. Of these patients, 173 were found to be candidates of AS. The inclusion criteria were as follows; clinical stage T2a or less, PSA<10ng/ml, 2 or fewer cores involved with cancer, no single core with 50% or greater maximum involvement of cancer, and no Gleason grade greater than 3 in the specimen. Univariate analyzes revealed that patients with advanced stage disease have higher prostate specific antigen density (PSAD), higher maximum percent (max%) in positive cores and higher RP tumor volumes. In multivariate analyzes PSAD, max% in positive cores and RP tumor volumes were statistically significant determinants for advanced stage disease. ROC analyzes revealed that the RP tumor volume is a good test on advanced stage disease. Decreasing the cutoff values for PSAD and max% in positive cores should be considered for AS inclusion criteria. If we could calculate the tumor volume before RP, we can minimize the treatment failures (over or undertreatment) of PCa. Perhaps new biopsy protocols, tissue biomarkers, and molecular imaging technology may refine AS criteria. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  7. [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.

  8. 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.

  9. Advances in clinical analysis 2012.

    PubMed

    Couchman, Lewis; Mills, Graham A

    2013-01-01

    A report on the meeting organized by The Chromatographic Society and the Separation Science Group, Analytical Division of the Royal Society of Chemistry. Over 60 delegates and commercial exhibitors attended this event, held to celebrate the careers of Robert Flanagan and David Perrett, and acknowledge their extensive contributions in the field of clinical analysis.

  10. Placebo Effects: Biological, Clinical and Ethical Advances

    PubMed Central

    Kaptchuk, Ted J; Miller, Franklin; Benedetti, Fabrizio

    2010-01-01

    For many years, placebos have been conceptualised by their inert content and their use as controls in clinical trials and treatments in clinical practice. Recent research demonstrates that placebo effects are genuine psychobiological phenomenon attributable to the overall therapeutic context, and that placebo effects can be robust in both laboratory and clinical settings. Evidence has also emerged that placebo effects can exist in clinical practice, even if no placebo is given. Further promotion and integration of laboratory and clinical research will allow advances in the ethical harnessing of placebo mechanisms that are inherent in routine clinical care and the potential use of treatments to primarily promote placebo effects. PMID:20171404

  11. 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.

  12. Nutrition Intervention for Advanced Stages of Diabetic Kidney Disease

    PubMed Central

    Kalantar-Zadeh, Kamyar

    2015-01-01

    IN BRIEF For the goals of reducing diabetic kidney disease (DKD) onset and progression, approaches to nutritional therapy are a subject of much debate. This article discusses selected nutrients that have a role in affecting DKD outcomes and introduces application of newer, individualized concepts for healthful eating, as supported by clinical evidence relevant to patients with DKD. Selected aspects of management of advanced DKD are also reviewed. PMID:26300611

  13. Nutrition Intervention for Advanced Stages of Diabetic Kidney Disease.

    PubMed

    Goldstein-Fuchs, Jordi; Kalantar-Zadeh, Kamyar

    2015-08-01

    IN BRIEF For the goals of reducing diabetic kidney disease (DKD) onset and progression, approaches to nutritional therapy are a subject of much debate. This article discusses selected nutrients that have a role in affecting DKD outcomes and introduces application of newer, individualized concepts for healthful eating, as supported by clinical evidence relevant to patients with DKD. Selected aspects of management of advanced DKD are also reviewed.

  14. Towards advanced OCT clinical applications

    NASA Astrophysics Data System (ADS)

    Kirillin, Mikhail; Panteleeva, Olga; Agrba, Pavel; Pasukhin, Mikhail; Sergeeva, Ekaterina; Plankina, Elena; Dudenkova, Varvara; Gubarkova, Ekaterina; Kiseleva, Elena; Gladkova, Natalia; Shakhova, Natalia; Vitkin, Alex

    2015-07-01

    In this paper we report on our recent achievement in application of conventional and cross-polarization OCT (CP OCT) modalities for in vivo clinical diagnostics in different medical areas including gynecology, dermatology, and stomatology. In gynecology, CP OCT was employed for diagnosing fallopian tubes and cervix; in dermatology OCT for monitoring of treatment of psoriasis, scleroderma and atopic dermatitis; and in stomatology for diagnosis of oral diseases. For all considered application, we propose and develop different image processing methods which enhance the diagnostic value of the technique. In particular, we use histogram analysis, Fourier analysis and neural networks, thus calculating different tissue characteristics as revealed by OCT's polarization evolution. These approaches enable improved OCT image quantification and increase its resultant diagnostic accuracy.

  15. Prognostic significance of clusterin expression in advanced-stage cervical cancer treated with curative intended radiotherapy.

    PubMed

    Watari, Hidemichi; Kinoshita, Rumiko; Han, Yimin; Wang, Lei; Hosaka, Masayoshi; Taguchi, Hiroshi; Tsuchiya, Kazuhiko; Tanaka, Shinya; Shirato, Hiroki; Sakuragi, Noriaki

    2012-03-01

    Overexpression of clusterin (CLU), an antiapoptotic molecule, has been reported to induce resistance to radiotherapy (RT) in a variety of cancer cell types. The aim of this study was to evaluate the significance of CLU expression to predict survival of patients with advanced-stage cervical cancer who received curative intended RT. Biopsy tissue specimens of advanced-stage cervical cancer before curative intended RT were obtained from 34 patients who were treated at Hokkaido University Hospital between 1998 and 2008 and whose complete medical records were available. The expression of CLU protein was analyzed by immunohistochemistry. Findings were evaluated in relation to several clinicopathological factors. Survival analyses were performed using the Kaplan-Meier curves and the log-rank test. Independent prognostic factors were determined by multivariate Cox regression analysis. Clusterin protein was mainly present in the cytoplasm of cervical cancer cells. The expression of CLU protein in cervical cancer tissues before curative intended RT was not significantly related to any clinicopathological factors analyzed, including age, clinical stage, histologic type, and response to RT. Univariate analysis on prognostic factors showed that histologic type (P = 0.001), and CLU expression (P = 0.02) were related to survival. Multivariate analysis revealed that both histologic type (P = 0.002), and CLU expression (P = 0.02) were independent prognostic factors for overall survival. We conclude that CLU could be a new molecular marker to predict overall survival of patients with advanced-stage cervical cancer treated with curative intended RT.

  16. Clinical prognostic markers in stage IIIC melanoma.

    PubMed

    Madu, Max F; Schopman, Jaap H H; Berger, Danique M S; Klop, Willem M C; Jóźwiak, Katarzyna; Wouters, Michel W J M; van der Hage, Jos A; van Akkooi, Alexander C J

    2017-08-01

    Although the EORTC 18071-trial has shown a clear survival benefit for adjuvant ipilimumab, accurately selecting patients for this toxic adjuvant therapy is important. We aimed to identify prognostic factors for death and disease recurrence in AJCC stage IIIC melanoma patients. Retrospective analysis of patients who underwent lymph node dissection (LND) for stage IIIC melanoma in our institution between 2000 and 2016. Baseline characteristics, melanoma-specific survival (MSS), and disease-free survival (DFS) were assessed, and prognostic factors for recurrence and survival were analyzed using uni- and multivariable analysis. A total of 205 patients were included. Median follow-up was 20 months (interquartile range 11-43 months), median MSS was 28 months, and median DFS was 11 months. Five-year MSS was 33% and 5-year DFS was 23%. N3 (≥4 involved lymph nodes) and extracapsular extension (ECE) carried an increased risk of disease recurrence after LND and death by melanoma. Patients with both N3 and ECE had virtually no long-term survival. Although survival for patients with stage IIIC is poor in general, patients with both N3 disease and ECE constitute the group with the worst prognosis and should be considered for adjuvant therapy with ipilimumab or any other future effective adjuvant therapy (study). © 2017 Wiley Periodicals, Inc.

  17. Biophysical properties of the clinical-stage antibody landscape

    PubMed Central

    Jain, Tushar; Sun, Tingwan; Durand, Stéphanie; Hall, Amy; Houston, Nga Rewa; Nett, Juergen H.; Sharkey, Beth; Bobrowicz, Beata; Caffry, Isabelle; Yu, Yao; Cao, Yuan; Lynaugh, Heather; Brown, Michael; Baruah, Hemanta; Gray, Laura T.; Krauland, Eric M.; Xu, Yingda; Vásquez, Maximiliano; Wittrup, K. Dane

    2017-01-01

    Antibodies are a highly successful class of biological drugs, with over 50 such molecules approved for therapeutic use and hundreds more currently in clinical development. Improvements in technology for the discovery and optimization of high-potency antibodies have greatly increased the chances for finding binding molecules with desired biological properties; however, achieving drug-like properties at the same time is an additional requirement that is receiving increased attention. In this work, we attempt to quantify the historical limits of acceptability for multiple biophysical metrics of “developability.” Amino acid sequences from 137 antibodies in advanced clinical stages, including 48 approved for therapeutic use, were collected and used to construct isotype-matched IgG1 antibodies, which were then expressed in mammalian cells. The resulting material for each source antibody was evaluated in a dozen biophysical property assays. The distributions of the observed metrics are used to empirically define boundaries of drug-like behavior that can represent practical guidelines for future antibody drug candidates. PMID:28096333

  18. [Performing madness: the clinic as stage].

    PubMed

    Herrn, Rainer; Friedland, Alexander

    2014-12-01

    In the second half of the nine- teenth century, clinical demonstrations became the dominant teaching method in psychiatry, playing a key role in medical-professional disputes, as well. This paper traces this widely used though historiographically neglected practice of knowledge implementation and mediation, as demonstrated in the psychiatric clinic of the Berlin Charité (Psychiatrische und Nervenklinik der Berliner Charité) from 1881 to 1927. Documentation of this practice, found within individual medical records, forms the basis of this research. The concept of 'theatricality' assists in uncovering the dramatic quality of the clinical demonstration: Psychiatric knowledge was not simply disseminated through such a practice; rather, such knowledge was first performatively created through the very logic of its presentation of exemplary patient histories, as well as through the examination and diagnostic positioning of its patients. The 'success' of such presentations depended on many variables, related to staff, time, place, and other situational factors. These include the presence of appropriate lecture halls, the availability and calculated selection of patients, and the employment of specific performative techniques by doctors for the sake of producing desired results. As one effect, clinical demonstrations also encouraged patients to both learn and rehearse behavior considered relevant to the particular diagnosis that was to be demonstrated.

  19. Outcomes of concurrent chemoradiotherapy versus chemotherapy alone for advanced-stage unresectable intrahepatic cholangiocarcinoma.

    PubMed

    Kim, Young-Il; Park, Joong-Won; Kim, Bo Hyun; Woo, Sang Myung; Kim, Tae Hyun; Koh, Young Hwan; Lee, Woo Jin; Kim, Chang-Min

    2013-12-21

    A standard treatment for unresectable advanced-stage intrahepatic cholangiocarcinoma (IHCC) has not yet been established. Although neoadjuvant concurrent chemoradiotherapy (CCRT) and liver transplantation are associated with long-term survival in select patients, the outcomes of CCRT for advanced-stage unresectable IHCC remain unclear. The aim of our study was to evaluate the outcomes of CCRT in patients with unresectable advanced-stage IHCC. We retrospectively reviewed the records of all patients with unresectable advanced stage (stage IVa or IVb) IHCC who were pathologically diagnosed and treated at National Cancer Center, Korea, from June 2001 to March 2012. Of the total of 92 patients, 25 (27.1%) received capecitabine plus cisplatin (XP) chemotherapy with external radiotherapy (RT) (XP-CCRT group) and 67 (72.8%) received XP chemotherapy alone (XP group). The clinical characteristics and outcomes of the 2 groups were compared. The 92 patients comprised 72 male and 20 female patients, with a median age of 58 years (range 26-78 years). The baseline clinical characteristics of the 2 groups were similar. Patients in the XP-CCRT group received a mean 44.7 Gy of RT and a mean 5.6 cycles of XP chemotherapy, whereas patients in the XP group received a mean 4.0 cycles. The disease control rate was higher in the XP-CCRT group than in the XP group, but the difference was not statistically significant (56.0% vs. 41.5%, p = 0.217). Although neutropenia was significantly more frequent in the XP-CCRT than in the XP group (48% vs. 9%, p < 0.001), the rates of other toxicities and > grade 3 toxicities did not differ. At a median follow-up of 5.3 months, PFS (4.3 vs. 1.9 months, p = 0.001) and OS (9.3 vs. 6.2 months, p = 0.048) were significantly longer in the XP-CCRT than in the XP group. XP-CCRT was well tolerated and was associated with longer PFS and OS than XP chemotherapy alone in patients with unresectable advanced IHCC. Controlled randomized

  20. Molecular targeted therapy in the treatment of advanced stage non-small cell lung cancer (NSCLC).

    PubMed

    Kumarakulasinghe, Nesaretnam Barr; van Zanwijk, Nico; Soo, Ross A

    2015-04-01

    Historically, patients with advanced stage non-small cell lung cancer (NSCLC) were treated with chemotherapy alone, but a therapeutic plateau has been reached. Advances in the understanding of molecular genetics have led to the recognition of multiple molecularly distinct subsets of NSCLC. This in turn has led to the development of rationally directed molecular targeted therapy, leading to improved clinical outcomes. Tumour genotyping for EGFR mutations and ALK rearrangement has meant chemotherapy is no longer given automatically as first-line treatment but reserved for when patients do not have a 'druggable' driver oncogene. In this review, we will address the current status of clinically relevant driver mutations and emerging new molecular subsets in lung adenocarcinoma and squamous cell carcinoma, and the role of targeted therapy and mechanisms of acquired resistance to targeted therapy.

  1. Advanced Strategies for End-Stage Heart Failure: Combining Regenerative Approaches with LVAD, a New Horizon?

    PubMed Central

    Tseng, Cheyenne C. S.; Ramjankhan, Faiz Z.; de Jonge, Nicolaas; Chamuleau, Steven A. J.

    2015-01-01

    Despite the improved treatment of cardiovascular diseases, the population with end-stage heart failure (HF) is progressively growing. The scarcity of the gold standard therapy, heart transplantation, demands novel therapeutic approaches. For patients awaiting transplantation, ventricular-assist devices have been of great benefit on survival. To allow explantation of the assist device and obviate heart transplantation, sufficient and durable myocardial recovery is necessary. However, explant rates so far are low. Combining mechanical circulatory support with regenerative therapies such as cell (-based) therapy and biomaterials might give rise to improved long-term results. Although synergistic effects are suggested with mechanical support and stem cell therapy, evidence in both preclinical and clinical setting is lacking. This review focuses on advanced and innovative strategies for the treatment of end-stage HF and furthermore appraises clinical experience with combined strategies. PMID:25905105

  2. Combined Alzheimer's disease and cerebrovascular staging explains advanced dementia cognition.

    PubMed

    Zea-Sevilla, María Ascensión; Fernández-Blázquez, Miguel Angel; Calero, Miguel; Bermejo-Velasco, Pedro; Rábano, Alberto

    2015-11-01

    The absence of a consensus system for full neuropathological evaluation limits clinicopathological studies and comparability between laboratories. Combined staging for Alzheimer's type and cerebral vascular pathology may allow a better classification of cases for clinical and cognitive correlation. Cognitive and postmortem neuropathological data were obtained from 70 brains donated to the Tissue Bank of the Centro de Investigación de Enfermedades Neurológicas (CIEN) Foundation according to recently developed staging schemes for Alzheimer's type and vascular pathology. Subjects belonged to a cohort of institutionalized patients with moderate or severe dementia and a mean follow-up period of 7 years. Cases were classified into three groups: Alzheimer's predominant (64.1%), vascular predominant (6.3%) and mixed pathology (29.6%). Significant differences were observed in Severe Mini-Mental State Examination and verbal fluency between the vascular predominant and the other groups of patients. The combination of scales measuring cerebral vascular and Alzheimer's type pathology allowed a classification of patients that reveals differences between groups in premortem cognitive features. Copyright © 2015 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  3. Serum markers in early-stage and locally advanced melanoma.

    PubMed

    Lugowska, Iwona; Kowalska, Maria; Fuksiewicz, Małgorzata; Kotowicz, Beata; Mierzejewska, Ewa; Koseła-Paterczyk, Hanna; Szamotulska, Katarzyna; Rutkowski, Piotr

    2015-11-01

    The identification of prognostic factors in cutaneous melanoma allows choosing the most effective treatment, especially in group of patients with locoregional disease. Markers related to carcinogenesis and angiogenesis in particular have effect on the course of the disease. The aim of this study was to evaluate clinical utility of vascular endothelial growth factor (VEGF), matrix metalloproteinase 2 (MMP-2), MMP-9, tissue inhibitors of metalloproteinase 1 (TIMP-1), and YKL-40 in serum of melanoma patients at pathological stages I-III. We included 148 adult patients with melanoma. The median follow-up was 40 months. Disease recurrence was observed in 43 patients; 3-year disease-free survival (DFS) rate was 71.7%; 35 patients died; and the 3-year overall survival (OS) rate was 85%. Concentrations of VEGF, MMP-2, MMP-9, TIMP-1, and YKL-40 were measured by ELISA kits. VEGF, MMP-9, TIMP-1, and YKL-40 were significantly higher in group of patients than in controls. Increased concentrations of TIMP-1 were related to patient survival, which in the group of lower and increased TIMP-1, disease-free survival amounted to 81 vs. 61% (p = 0.014) and overall survival -88 vs. 82% (p = 0.050), respectively. An increased concentration of YKL-40 was observed in 59% of patients with ulceration and in 26% of patients without ulceration (p = 0.012). We have found a clinically significant correlation between YKL-40 and MMP-9 (rho = 0.363; p = 0.004) as well as YKL-40 and VEGF (rho = 0.306; p = 0.018). In melanoma patients at stages I-III, the high concentrations of TIMP-1 in serum predicted adverse prognosis. YKL-40 was associated with ulceration of primary tumor, which is a very important prognostic factor.

  4. Investigation of early and advanced stages in ovarian cancer using human plasma by differential scanning calorimetry and mass spectrometry.

    PubMed

    Kim, Nam Ah; Jin, Jing Hui; Kim, Kyung-Hee; Lim, Dae Gon; Cheong, Heesun; Kim, Yun Hwan; Ju, Woong; Kim, Seung Cheol; Jeong, Seong Hoon

    2016-05-01

    Ovarian cancer is recognized with high mortality due to asymptomatic nature of the disease and difficulties in diagnosing early stage of the cancer. The present study evaluates the use of differential scanning calorimetry (DSC) in differentiating the severity of ovarian cancer from healthy women. 47 diseased women were subdivided into four stages with respect to clinical relevance and severity. Stages I-II were regarded as early stages and stages III-IV were regarded as advanced stages. The two average transition temperatures (T m ) increased with disease severity from 64.84 and 70.32 °C (healthy) to 68.46 and 75.24 °C (stage IV), respectively. T m were increased depending on clinical groups. In addition, the change in heat capacity was also dependent on the disease severity. To further support and investigate the nature of the proposed interactions, matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis is employed. The results suggest the differences in peptide expression between early and advanced stage of ovarian cancer, affected abundant proteins in plasma. The combined DSC and MS approach was supportive in identifying a unique signature of ovarian cancer stages, and demonstrates the potential of DSC as a complementary diagnostic tool in the evaluation of early stage ovarian cancer.

  5. Oral squamous cell carcinoma among Yemenis: Onset in young age and presentation at advanced stage

    PubMed Central

    Al-Mohaya, Maha; Abdulhuq, Mahmoud; Al-Mandili, Ahmad; Al-Anazi, Yousef

    2012-01-01

    Objectives: Oral cancer represents a health burden worldwide. Up to 90% of oral cancer cases are squamous cell carcinomas (SCC). The data on oral SCC in Yemen are lacking. The objective of this study therefore was to describe and analyze the demographic, clinical and histological characteristics of Yemeni patients with oral SCC. Study Design: In this cross-sectional study, two sets of retrospective data for Yemeni cancer patients were obtained officially by two different registries. Patients with oral SCC were included. Their ages were dichotomized using 40 and 45 years alternately as individual cut-points for young and old patients. The patients` demographic, clinical and histological characteristics were statistically analyzed. Results: There were 457 Yemenis with oral SCC; 253 patients (55.4%) were men. The overall mean age was 58.15±14.11 years. The tongue was the most affected oral sub-site accounting for 53% of the reported cases. The well and moderately differentiated oral SCC accounted for 55.5% and 25.6% of the total cases respectively. Noteworthy, 62 patients (14%) were affected by the age of ?40; this increased to 105 patients (23%) aged ?45 years. Additionally, a high proportion of oral SCC patients (62%, 283) were diagnosed at advanced tumor stages (regional extension or metastasized). The distributions of histological grades and tumor stages in young and old patients were significantly different (P=0.006 and 0.026 respectively). Conclusion: The relative frequency of oral SCC among Yemeni young people is high. Unfortunately, most of oral SCC patients in Yemen were diagnosed at advanced stage. Key words:Oral squamous cell carcinoma, Yemen, young patients, advanced stage. PMID:24558559

  6. 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.

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

    DTIC Science & Technology

    2015-10-01

    There is an urgent need to develop effective therapies for the treatment of advanced stage prostate cancer (PrCa) due to their limited or no response to...Award Number: W81XWH-141-0154 TITLE: “A Novel Therapeutic Modality for Advanced-Stage Prostate Cancer Treatment” PRINCIPAL INVESTIGATOR...Novel Therapeutic Modality for Advanced-Stage Prostate Cancer Treatment” 5a. CONTRACT NUMBER: 5b. GRANT NUMBER: W81XWH-14-1-0154 5c. PROGRAM ELEMENT

  8. The changing hope trajectory in patients with advanced-stage cancer: a nursing perspective.

    PubMed

    Sanders, Judith Brown; Seda, Julie S; Kardinal, Carl G

    2012-06-01

    As patients with advanced-stage cancer move from the initial diagnosis through treatment, remission, recurrence, and advanced-stage disease, the hope trajectory undergoes a dynamic transformation. By identifying the hope trajectory, nurses can help patients focus on obtainable hope objects while balancing the need to present a realistic prognosis. This, in turn, may help patients find meaning and purpose in advanced-stage cancer and facilitate realistic hope when faced with a life-threatening illness.

  9. Advances in cardiology: clinical trial update.

    PubMed

    Howe, Andrew J; Shand, James A; Menown, Ian B A

    2011-05-01

    Multiple key cardiology trials have been presented or published over recent months, several with the potential to change clinical practice. In this article, we summarize and place in clinical context new trial findings regarding anticoagulation in the cardiac catheterization laboratory (enoxaparin, fondaparinux and unfractionated heparin), the implications of genetic polymorphisms and functional testing for antiplatelet therapy (clopidogrel and ticagrelor), new oral anticoagulants for use in atrial fibrillation (apixiban and rivaroxaban), optimal pacing strategies and pharmacological agents in heart failure (ivabradine, eplerenone, cardiac resynchronization therapy, telemonitoring and intracoronary bone marrow stem cell infusion). Clinical trials in percutaneous structural intervention (transcatheter aortic valve implantation, MONARC™ mitral annular implant, STARFlex(®) patent foramen ovale device) and advanced percutaneous coronary intervention (everolimus-eluting stents, biodegradable polymer/polymer-free technologies and contemporary use of intravascular ultrasound) are also discussed.

  10. Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer.

    PubMed

    Panis, C; Victorino, V J; Herrera, A C S A; Freitas, L F; De Rossi, T; Campos, F C; Simão, A N Colado; Barbosa, D S; Pinge-Filho, P; Cecchini, R; Cecchini, A L

    2012-06-01

    Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1β, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure

  11. Short-term clinical outcomes for stages of NIA-AA preclinical Alzheimer disease.

    PubMed

    Knopman, D S; Jack, C R; Wiste, H J; Weigand, S D; Vemuri, P; Lowe, V; Kantarci, K; Gunter, J L; Senjem, M L; Ivnik, R J; Roberts, R O; Boeve, B F; Petersen, R C

    2012-05-15

    Recommendations for the diagnosis of preclinical Alzheimer disease (AD) have been formulated by a workgroup of the National Institute on Aging and Alzheimer's Association. Three stages of preclinical AD were described. Stage 1 is characterized by abnormal levels of β-amyloid. Stage 2 represents abnormal levels of β-amyloid and evidence of brain neurodegeneration. Stage 3 includes the features of stage 2 plus subtle cognitive changes. Stage 0, not explicitly defined in the criteria, represents subjects with normal biomarkers and normal cognition. The ability of the recommended criteria to predict progression to cognitive impairment is the crux of their validity. Using previously developed operational definitions of the 3 stages of preclinical AD, we examined the outcomes of subjects from the Mayo Clinic Study of Aging diagnosed as cognitively normal who underwent brain MRI or [(18)F]fluorodeoxyglucose and Pittsburgh compound B PET, had global cognitive test scores, and were followed for at least 1 year. Of the 296 initially normal subjects, 31 (10%) progressed to a diagnosis of mild cognitive impairment (MCI) or dementia (27 amnestic MCI, 2 nonamnestic MCI, and 2 non-AD dementias) within 1 year. The proportion of subjects who progressed to MCI or dementia increased with advancing stage (stage 0, 5%; stage 1, 11%; stage 2, 21%; stage 3, 43%; test for trend, p < 0.001). Despite the short follow-up period, our operationalization of the new preclinical AD recommendations confirmed that advancing preclinical stage led to higher proportions of subjects who progressed to MCI or dementia.

  12. Novel therapeutic strategies for cutaneous T-cell lymphoma in advanced stages.

    PubMed

    Kun, Lillian; Hernandez-Ilizaliturri, Francisco J; Reddy, Nishitha M

    2014-01-01

    The term cutaneous T-cell lymphoma (CTCL), introduced in 1975, was used to describe a spectrum of skin-based malignant tumors of T-cell origin. Immunological studies identified the complex interaction of cytokines released from infiltrating accessory or malignant cells and how such cytokines aid in the maintenance and proliferation of malignant cells. Though the etiology remains unknown, an association with rare retrovirus in some cases has been described. The mainstay of therapy has been to control the cutaneous presentation with topical therapies in patients with early limited-stage disease. However, a significant number of patients develop refractory disease to skin-directed therapies with or without clinical progression to advanced stages requiring systemic therapy. Over the last two decades a wide number of novel agents such as monoclonal antibodies, small molecule inhibitors, and chemotherapy agents have been developed and are used in patients with advanced disease or those who have exhausted topical treatment options and/or radiation. In this contribution we review the results of clinical studies evaluating emerging therapeutic strategies for patients with CTCL that had developed from ongoing translational research programs focused on understanding the biology of different subtypes of CTCL and identifying disease-specific biomarkers suitable for targeting.

  13. Modified approach for extraperitoneal laparoscopic staging for locally advanced cervical cancer.

    PubMed

    Gil-Moreno, A; Maffuz, A; Díaz-Feijoo, B; Puig, O; Martínez-Palones, J M; Pérez, A; García, A; Xercavins, J

    2007-12-01

    Describe a modified approach to the technique for staging laparoscopic extraperitoneal aortic and common iliac lymph node dissection for locally advanced cervical cancer.Retrospective, nonrandomized clinical study. (Canadian Task Force classification II-2), setting in an acute-care, teaching hospital. Thirty-six patients with locally advanced cervical cancer underwent laparoscopic surgical staging via extraperitoneal approach with the conventional or the modified technique from August 2001 through September 2004. Clinical outcomes in 23 patients who were operated on with the conventional technique using index finger for first trocar entrance; 12 patients with the modified technique using direct trocar entrance, were compared. One patient was excluded due to peritoneal carcinomatosis. Technique, baseline characteristics, histopathologic variables and surgical outcome were measured. There were no significant differences in patients basal characteristics on comparative analysis between conventional and modified technique. With our proposed modified technique, we obtained a reduced surgical procedure duration and blood loss. The proposed modified surgical technique offers some advantages, is an easier approach because the parietal pelvic peritoneum is elastic and this helps to avoid its disruption at time of trocar insertion, size of incision is shorter, we achieved no CO2 leak through the trocar orifice, and wound suture is fast and simple.

  14. Long-Term Outcomes and Prognostic Factors in Advanced Gallbladder Cancer: Focus on the Advanced T Stage

    PubMed Central

    Shen, Haoxin; Song, Huwei; Zhao, Yaling; Zhang, Guanjun; Li, Wenzhi; Ma, Li; Wang, Lin

    2016-01-01

    Background Radical resection is an effective therapeutic method to increase the survival rate of patients with gallbladder cancer (GBC). In addition to the surgical approach, the relationships between various clinicopathologic factors and the outcome of patients with GBC remain controversial. Methods Clinical and laboratory examination characteristics, pathological and surgical data, and post-operative survival time of 338 patients with advanced GBC who received treatment at the First Affiliated Hospital of Xi'an Jiaotong University, China from January 2008 to December 2012 were analyzed retrospectively. Factors influencing the prognosis of GBC after surgery were analyzed by univariate and multivariate analysis. Results The overall survival rates for curative resection patients were significantly greater than those for non-curative resection patients (1-,3-,5-year survival rate and mean-survival time: 59.0%, 47.3%, 44.3% and 22.0 months vs. 12.7%, 8.3%, 7.7% and 3.0 months) (P < 0.001). For the curative resection patients, positive margin, lymph node metastasis, poorly pathological differentiation and the presence of ascites were all independent risk factors for poor prognosis. For patients with T3 stage, neither segmentectomy of IVb and V nor common bile duct resection improved the prognosis (P = 0.867 and P = 0.948). For patients with T4 stage, aggressive curative resection improved the prognosis (P = 0.007). Conclusions An advanced T stage does not preclude curative resection. Positive margin, lymph node metastasis, poorly pathological differentiation and the presence of ascites are all independent risk factors for poor prognosis in the curative intent resection patients. The range of liver resection and whether common bile duct resection is performed do not influence the prognosis as long as R0 resection is achieved. PMID:27846279

  15. An advanced clinical track within a doctor of pharmacy program.

    PubMed

    New, James; Garner, Sandra; Ragucci, Kelly; Spencer, Anne

    2012-04-10

    To evaluate the advanced clinical track, a curricular track designed to prepare doctor of pharmacy (PharmD) students for residency training and institutional practice. The advanced clinical track required completion of elective coursework, an additional advanced practice experience, 8 clinical experiences, and a skills checklist, and participation in a clinical skills competition. Thirty-two graduates of the advanced clinical track were surveyed. Of the 23 respondents, 95% of those who pursued residency training were successfully matched with a residency program. Ninety-one percent of respondents felt that the advanced clinical track increased their confidence and 74% felt it was definitely an advantage when applying to a residency program. All participants agreed that the advanced clinical track met their expectations or goals and would recommend it to other students. Completion of an advanced clinical track was viewed by PharmD graduates as valuable preparation for residency training and institutional practice and would be recommended to other students.

  16. 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

  17. 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.

  18. Advances in basic and clinical immunology.

    PubMed

    Chinen, Javier; Finkelman, Fred; Shearer, William T

    2006-08-01

    This review comments on basic and clinical immunology articles that were published in 2005, with a focus on those that appeared in the Journal of Allergy and Clinical Immunology. In the area of basic immunology, mechanisms of the innate immune system and its interaction with the adaptive immune system were described, with special consideration to applications in biodefense strategies. T regulatory cells were further characterized in their role for the control of allergic, autoimmune, and neoplastic disorders. The function of the thymus Hassall's corpuscles was reported to be the generation of T regulatory cells. Flavonoid molecules obtained from medicinal herbs, including astilbin and epigallocatechin gallate, were discovered to have immunomodulatory properties. Advances in clinical immunology resulted from efforts to develop a newborn screening test for severe combined immunodeficiency and the elucidation of the crystal structure of the IL-2 receptor gamma chain. Mutations in the membrane receptor transmembrane activator and calcium modulator and cyclophilin ligand interactor were found in patients with common variable immunodeficiency. New therapeutic options are described, such as the use of infliximab for granulomas and GM-CSF for chronic ulcers in patients with common variable immunodeficiency. The importance of mucosal immunity in acute HIV infection is cited, as is the role of CD8+ T-cell activation in HIV disease progression in children.

  19. Primary femininity: clinical advances and theoretical ambiguities.

    PubMed

    Kulish, N

    2000-01-01

    This paper examines the use of the term "primary femininity" in current psychoanalytic thinking. The concept of primary femininity arose in reaction to early theories about female sexuality and development; based on a model of male development, these presented problems when applied to females. The author attempts to demonstrate the clinical advances that have resulted from the idea of primary femininity. At the same time she argues that the idea has been used to carry widely differing meanings, and has reflected many writers' differing frames of reference, which range from gender identity through biological traits, object relations, genital anxieties, and bisexuality. Like the terms it originally was intended to replace or augment, it has come to be used reductionistically or loosely. The author warns against its misuse and argues that primary femininity is not a unitary concept, but rather encompasses a related group of ideas about the female body and mind.

  20. 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

  1. 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

  2. How to analyze tumor stage data in clinical research.

    PubMed

    Hu, Zhi-De; Zhou, Zhi-Rui; Qian, Shi

    2015-04-01

    Tumor staging serves as an important prognostic factor in cancer patient care. It also plays critical roles in cancer-related clinical research. Aimed to shed lights on how to analyze tumor staging related data and deliver proper interpretation, various statistical methods, from categorical data analysis to modeling techniques, were introduced through the examples. General guidelines were discussed for how to choose proper statistical test with key considerations of research aims, study design, measurement scale of data, proper data summary, type of associations, and underlying assumptions of statistical methods.

  3. Lymph node staging in colorectal cancer: Old controversies and recent advances

    PubMed Central

    Resch, Annika; Langner, Cord

    2013-01-01

    Outcome prediction based on tumor stage reflected by the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) tumor node metastasis (TNM) system is currently regarded as the strongest prognostic parameter for patients with colorectal cancer. For affected patients, the indication for adjuvant therapy is mainly guided by the presence of regional lymph node metastasis. In addition to the extent of surgical lymph node removal and the thoroughness of the pathologist in dissecting the resection specimen, several parameters that are related to the pathological work-up of the dissected nodes may affect the clinical significance of lymph node staging. These include changing definitions of lymph nodes, involved lymph nodes, and tumor deposits in different editions of the AJCC/UICC TNM system as well as the minimum number of nodes to be dissected. Methods to increase the lymph node yield in the fatty tissue include methylene blue injection and acetone compression. Outcome prediction based on the lymph node ratio, defined as the number of positive lymph nodes divided by the total number of retrieved nodes, may be superior to the absolute numbers of involved nodes. Extracapsular invasion has been identified as additional prognostic factor. Adding step sectioning and immunohistochemistry to the pathological work-up may result in higher accuracy of histological diagnosis. The clinical value of more recent technical advances, such as sentinel lymph node biopsy and molecular analysis of lymph nodes tissue still remains to be defined. PMID:24379568

  4. 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.

  5. 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.

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

    PubMed Central

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

    2015-01-01

    Background: 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. Methods: 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. Results: 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. Conclusions: 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. PMID:26021505

  7. Recent advances in limb lengthening. Part I: Clinical advances.

    PubMed

    Sproul, J T; Price, C T

    1992-03-01

    The discipline of limb lengthening has undergone numerous advances in recent years. An increased understanding of the biology of distraction osteogenesis, as well as technical advances, has made lengthening more feasible. However, significant problems remain unsolved, and complications--although less severe and long standing--still remain. Little is known about the effect of distraction on soft tissues. Lengthening in skeletally mature patients remains difficult. The myriad of conditions that require lengthening often confounds comparison of techniques. Uniform indications for limb lengthening may never exist, but increasing experience helps guide patient selection.

  8. StrandAdvantage test for early-line and advanced-stage treatment decisions in solid tumors.

    PubMed

    Sen, Manimala; Katragadda, Shanmukh; Ravichandran, Aarthi; Deshpande, Gouri; Parulekar, Minothi; Nayanala, Swetha; Vittal, Vikram; Shen, Weiming; Phooi Nee Yong, Melanie; Jacob, Jemima; Parchuru, Sravanthi; Dhanuskodi, Kalpana; Eyring, Kenneth; Agrawal, Pooja; Agarwal, Smita; Shanmugam, Ashwini; Gupta, Satish; Vishwanath, Divya; Kumari, Kiran; Hariharan, Arun K; Balaji, Sai A; Liang, Qiaoling; Robolledo, Belen; Gauribidanur Raghavendrachar, Vijayashree; Oomer Farooque, Mohammed; Buresh, Cary J; Ramamoorthy, Preveen; Bahadur, Urvashi; Subramanian, Kalyanasundaram; Hariharan, Ramesh; Veeramachaneni, Vamsi; Sankaran, Satish; Gupta, Vaijayanti

    2017-05-01

    Comprehensive genetic profiling of tumors using next-generation sequencing (NGS) is gaining acceptance for guiding treatment decisions in cancer care. We designed a cancer profiling test combining both deep sequencing and immunohistochemistry (IHC) of relevant cancer targets to aid therapy choices in both standard-of-care (SOC) and advanced-stage treatments for solid tumors. The SOC report is provided in a short turnaround time for four tumors, namely lung, breast, colon, and melanoma, followed by an investigational report. For other tumor types, an investigational report is provided. The NGS assay reports single-nucleotide variants (SNVs), copy number variations (CNVs), and translocations in 152 cancer-related genes. The tissue-specific IHC tests include routine and less common markers associated with drugs used in SOC settings. We describe the standardization, validation, and clinical utility of the StrandAdvantage test (SA test) using more than 250 solid tumor formalin-fixed paraffin-embedded (FFPE) samples and control cell line samples. The NGS test showed high reproducibility and accuracy of >99%. The test provided relevant clinical information for SOC treatment as well as more information related to investigational options and clinical trials for >95% of advanced-stage patients. In conclusion, the SA test comprising a robust and accurate NGS assay combined with clinically relevant IHC tests can detect somatic changes of clinical significance for strategic cancer management in all the stages. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  9. A two-stage, single-arm, phase II study of EGCG-enriched green tea drink as a maintenance therapy in women with advanced stage ovarian cancer.

    PubMed

    Trudel, Dominique; Labbé, David P; Araya-Farias, Monica; Doyen, Alain; Bazinet, Laurent; Duchesne, Thierry; Plante, Marie; Grégoire, Jean; Renaud, Marie-Claude; Bachvarov, Dimcho; Têtu, Bernard; Bairati, Isabelle

    2013-11-01

    A two-stage, single-arm, phase II study was conducted to assess the effectiveness and safety of an epigallocatechin gallate (EGCG)-enriched tea drink, the double-brewed green tea (DBGT), as a maintenance treatment in women with advanced stage serous or endometrioid ovarian cancer (clinicaltrials.gov, NCT00721890). Eligible women had FIGO stage III-IV serous or endometrioid ovarian cancer. They had to undergo complete response after debulking surgery followed by 6 to 8 cycles of platinum/taxane chemotherapy at the Centre Hospitalier Universitaire de Québec. They all had to drink the DBGT, 500 mL daily until recurrence or during a follow-up of 18 months. The primary endpoint was the absence of recurrence at 18 months. Statistical analyses were done according to the principle of intention to treat. Using a two-stage design, the first stage consisted of 16 enrolled patients. At the end of the follow-up, if 7 or fewer patients were free of recurrence, the trial stopped. Otherwise, accrual would continue to a total of 46 patients. During the first stage of the study, only 5 of the 16 women remained free of recurrence 18 months after complete response. Accordingly, the clinical trial was terminated. Women's adherence to DBGT was high (median daily intake during intervention, 98.1%, interquartile range: 89.7-100%), but 6 women discontinued the intervention before the end of their follow-up. No severe toxicity was reported. DBGT supplementation does not appear to be a promising maintenance intervention in women with advanced stage ovarian cancer after standard treatment. © 2013.

  10. 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

  11. Extracorporeal shock wave lithotripsy treatment of pancreatic stones complicated with advanced stage autoimmune pancreatitis.

    PubMed

    Maruyama, Masahiro; Watanabe, Takayuki; Kanai, Keita; Oguchi, Takaya; Asano, Jumpei; Ito, Tetsuya; Muraki, Takashi; Hamano, Hideaki; Arakura, Norikazu; Uehara, Takeshi; Kawa, Shigeyuki

    2015-03-10

    Although most patients with autoimmune pancreatitis (AIP) respond favorably to prednisolone therapy, some individuals who later suffer from pancreatic calculi may require additional extracorporeal shock wave lithotripsy (ESWL) treatment. This study compares the efficacy of ESWL for calculi in AIP with that in ordinary chronic pancreatitis (CP) and proposes a new treatment approach for pancreatic duct stones occurring in AIP. We examined the clinical records of 8 patients with chronic stage AIP and 92 patients with ordinary CP who received ESWL for pancreatic calculi. The AIP group was significantly older than the CP group (69.0 vs. 56.5 years, P = 0.018). With regard to the indications for ESWL, chronic pain was significantly less frequent in the chronic stage AIP group (0% vs. 45.7%, P = 0.001), whereas preservation of pancreatic function was significantly more frequent (75% vs. 19.6%, P = 0.001). Compared with the CP group, the AIP group tended to exhibit pancreatic duct stenosis proximal to pancreatic calculi and had a lower rate of complete extraction of stones from the main pancreatic duct. Histopathological analysis of a patient with chronic stage AIP revealed widely distributed nodular pancreatitis, which was characteristic of ordinary CP, along with isolated areas of lymphoplasmacytic sclerosing pancreatitis. Different approaches are needed for the treatment of pancreatic calculi in chronic stage AIP and ordinary CP. Specifically, it appears that intensive ESWL therapy can be avoided or delayed in AIP if the patient displays: (1) advanced age, (2) little or no chronic pain or pancreatitis, and (3) pancreatic duct stenosis proximal to pancreatic stones. In such cases, the benefit of ESWL treatment may be outweighed by the risks involved in this procedure.

  12. Serum adiponectin levels in advanced-stage Parkinson's disease patients.

    PubMed

    Cassani, Erica; Cancello, Raffaella; Cavanna, Ferruccio; Maestrini, Sabrina; Di Blasio, Anna Maria; Liuzzi, Antonio; Pezzoli, Gianni; Barichella, Michela

    2011-01-01

    Patients with advanced Parkinson's disease (PD) experience body weight loss and reductions in the most common cardiovascular risk factors. At present, the pathogenetic mechanisms involved have not been elucidated. Increased serum concentrations of adiponectin, which possesses antiatherogenic and anti-inflammatory properties, are associated with a reduction in cardiovascular risk. The objective of this study was to determine adiponectin serum concentrations in PD patients. Thirty PD patients underwent a full nutritional status assessment, including the determination of adiponectin serum concentrations. Mean ± SD adiponectin concentrations were 9.59 ± 5.9 μg/mL (interquartile range: 5.92-12.9 μg/mL). In PD patients, adiponectin serum levels were similar to those in normal-weight, healthy, young subjects and significantly higher than that in an aged-matched group of morbidly obese subjects. Further studies are warranted to establish the role of adiponectin in the management of PD patients.

  13. Response evaluation after chemoradiotherapy for advanced staged oropharyngeal squamous cell carcinoma: a nationwide survey in the Netherlands.

    PubMed

    Schouten, Charlotte S; Hoekstra, Otto S; Leemans, C René; Castelijns, Jonas A; de Bree, Remco

    2015-11-01

    Following failure of chemoradiotherapy (CRT) for advanced staged oropharyngeal squamous cell carcinomas (OPSCC), residual tumor can often be treated successfully with salvage surgery, if detected early. Current clinical practice in the VU University Medical Center is to perform routine response evaluation, i.e., examination under general anesthesia (EUA), 12 weeks after treatment. However, in the Netherlands there is no consensus on response evaluation in patients with advanced oropharyngeal cancer. Questionnaire on current clinical practice concerning response evaluation after CRT for advanced OPSCC in all eight head and neck cancer centers of the Dutch Head and Neck Oncology Cooperative Group. The response rate was 100%. Response evaluation was routinely performed with various methods in five institutions (62.5%) and in one institute (12.5%) only if clinical evaluation was difficult. Two centers (25%) did not perform response evaluation. In case of suspicion of residual disease during follow-up, six centers (75%) performed imaging prior to EUA and two centers (25%) only if clinical evaluation was difficult. Diagnostic techniques used prior to EUA were MRI (87.5%), diffusion-weighted MRI (37.5%), 18F-FDG-PET-CT (75-87.5%) and CT (37.5%). This survey shows a substantial variation in the diagnostic policy concerning response evaluation after CRT for advanced OPSCC in the Netherlands. There is a need for guidelines for response evaluation in patients with advanced oropharyngeal cancer.

  14. The Edmonton Obesity Staging System for Pediatrics: A proposed clinical staging system for paediatric obesity

    PubMed Central

    Hadjiyannakis, Stasia; Buchholz, Annick; Chanoine, Jean-Pierre; Jetha, Mary M; Gaboury, Laurie; Hamilton, Jill; Birken, Catherine; Morrison, Katherine M; Legault, Laurent; Bridger, Tracey; Cook, Stephen R; Lyons, John; Sharma, Arya M; Ball, Geoff DC

    2016-01-01

    Traditionally, clinical recommendations for assessing and managing paediatric obesity have relied on anthropometric measures, such as body mass index (BMI), BMI percentile and/or BMI z-score, to monitor health risks and determine weight management success. However, anthropometric measures do not always accurately and reliably identify children and youth with obesity-related health risks or comorbidities. The authors propose a new clinical staging system (the Edmonton Obesity Staging System for Pediatrics, EOSS-P), adapted from the adult-oriented EOSS. The EOSS-P is used to stratify patients according to severity of obesity-related comorbidities and barriers to weight management into four graded categories (0 to 3) within four main health domains: metabolic, mechanical, mental health and social milieu (the 4Ms). The EOSS-P is based on common clinical assessments that are widely available and routinely completed by clinicians, and has the potential to provide clinical and prognostic information to help evaluate and inform the management of paediatric obesity. PMID:26941556

  15. The Edmonton Obesity Staging System for Pediatrics: A proposed clinical staging system for paediatric obesity.

    PubMed

    Hadjiyannakis, Stasia; Buchholz, Annick; Chanoine, Jean-Pierre; Jetha, Mary M; Gaboury, Laurie; Hamilton, Jill; Birken, Catherine; Morrison, Katherine M; Legault, Laurent; Bridger, Tracey; Cook, Stephen R; Lyons, John; Sharma, Arya M; Ball, Geoff Dc

    2016-01-01

    Traditionally, clinical recommendations for assessing and managing paediatric obesity have relied on anthropometric measures, such as body mass index (BMI), BMI percentile and/or BMI z-score, to monitor health risks and determine weight management success. However, anthropometric measures do not always accurately and reliably identify children and youth with obesity-related health risks or comorbidities. The authors propose a new clinical staging system (the Edmonton Obesity Staging System for Pediatrics, EOSS-P), adapted from the adult-oriented EOSS. The EOSS-P is used to stratify patients according to severity of obesity-related comorbidities and barriers to weight management into four graded categories (0 to 3) within four main health domains: metabolic, mechanical, mental health and social milieu (the 4Ms). The EOSS-P is based on common clinical assessments that are widely available and routinely completed by clinicians, and has the potential to provide clinical and prognostic information to help evaluate and inform the management of paediatric obesity.

  16. A Clinicoimmunohistopathologic Study of Anetoderma: Is Protruding Type More Advanced in Stage Than Indented Type?

    PubMed Central

    Jeong, Kwan Ho; Lee, Jeong Deuk; Park, Chul Jong; Yu, Dong Soo

    2016-01-01

    Background. The clinical and histopathologic classification of anetoderma are not well characterized. Objective. We aimed to investigate the clinical and histopathologic characteristics of anetoderma and to correlate clinical phenotypes with immunohistopathologic findings. Methods. We retrospectively reviewed the medical records of 30 patients with anetoderma and performed immunohistochemistry for elastin, fibrillin-1, metalloproteinase- (MMP-) 2, MMP-7, MMP-9, and MMP-12, and tissue inhibitor of metalloproteinase- (TIMP-) 1 and TIMP-2. Results. Protruding type (n = 17) had a longer disease duration and more severe loss of elastin, without changes in fibrillin, than indented type (n = 13). MMP-2 and MMP-9 showed significantly higher expressions in the dermis compared with controls (p < 0.05). MMP-7 and MMP-12 showed little expressions in both anetoderma and control tissue. TIMP-1 was highly expressed in anetoderma lesions and controls. TIMP-2 expression was variable. Conclusions. Our findings suggest that protruding type anetoderma may represent a more advanced stage and that MMP-2 and MMP-9 could be responsible for elastic fiber degradation in anetoderma. PMID:28116317

  17. 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.

  18. A clinical staging system and treatment guidelines for maxillary osteoradionecrosis in irradiated nasopharyngeal carcinoma patients

    SciTech Connect

    Cheng, S.-J.; Lee, J.-J.; Ting, L.-L.; Tseng, I.-Y.; Chang, H.-H.; Chen, H.-M.; Kuo, Y.-S.; Hahn, L.-J.; Kok, S.-H. . E-mail: kok@ha.mc.ntu.edu.tw

    2006-01-01

    Purpose: To develop a clinical staging system for maxillary osteoradionecrosis (ORN) in irradiated nasopharyngeal carcinoma (NPC) patients. Methods and Materials: The data of maxillary ORN cases among 1,758 irradiated NPC patients were analyzed. A staging system based on the degrees of bone exposure (E), infection (I), and bleeding (B) was developed. Correlations between various clinical parameters and stages of maxillary ORN and relationships between treatment modalities and outcomes at each stage were evaluated. Cumulative success of treatment and risk factors that affect treatment outcomes were analyzed. Results: The incidence of maxillary ORN was 2.7% (48/1,758). TNM stage of NPC (p < 0.001), radiation dose (p = 0.029), and tooth extraction (p < 0.001) appeared to have significant influences on disease severity. Success rates between conservative therapy and surgical treatment were not significantly different for Stage I ORN but differed significantly for Stage II (p = 0.013) and Stage III (p = 0.008) lesions. Grade 3 infection and bleeding significantly jeopardized treatment success (p = 0.043 and 0.015, respectively). The risk ratios of treatment failure for Grade 3 infection and bleeding were 2.523 (p = 0.034) and 3.141 (p = 0.027), respectively. Conclusions: More serious maxillary ORN tended to occur in cases with more advanced NPC, higher radiation dose, and history of tooth extraction. Surgical treatment was usually required in Stage II and III ORN. The grades of infection and bleeding are important factors in guidance of treatment and prediction of outcomes.

  19. Gene Expression Profile for Predicting Survival in Advanced-Stage Serous Ovarian Cancer Across Two Independent Datasets

    PubMed Central

    Yoshihara, Kosuke; Tajima, Atsushi; Yahata, Tetsuro; Kodama, Shoji; Fujiwara, Hiroyuki; Suzuki, Mitsuaki; Onishi, Yoshitaka; Hatae, Masayuki; Sueyoshi, Kazunobu; Fujiwara, Hisaya; Kudo, Yoshiki; Kotera, Kohei; Masuzaki, Hideaki; Tashiro, Hironori; Katabuchi, Hidetaka; Inoue, Ituro; Tanaka, Kenichi

    2010-01-01

    Background Advanced-stage ovarian cancer patients are generally treated with platinum/taxane-based chemotherapy after primary debulking surgery. However, there is a wide range of outcomes for individual patients. Therefore, the clinicopathological factors alone are insufficient for predicting prognosis. Our aim is to identify a progression-free survival (PFS)-related molecular profile for predicting survival of patients with advanced-stage serous ovarian cancer. Methodology/Principal Findings Advanced-stage serous ovarian cancer tissues from 110 Japanese patients who underwent primary surgery and platinum/taxane-based chemotherapy were profiled using oligonucleotide microarrays. We selected 88 PFS-related genes by a univariate Cox model (p<0.01) and generated the prognostic index based on 88 PFS-related genes after adjustment of regression coefficients of the respective genes by ridge regression Cox model using 10-fold cross-validation. The prognostic index was independently associated with PFS time compared to other clinical factors in multivariate analysis [hazard ratio (HR), 3.72; 95% confidence interval (CI), 2.66–5.43; p<0.0001]. In an external dataset, multivariate analysis revealed that this prognostic index was significantly correlated with PFS time (HR, 1.54; 95% CI, 1.20–1.98; p = 0.0008). Furthermore, the correlation between the prognostic index and overall survival time was confirmed in the two independent external datasets (log rank test, p = 0.0010 and 0.0008). Conclusions/Significance The prognostic ability of our index based on the 88-gene expression profile in ridge regression Cox hazard model was shown to be independent of other clinical factors in predicting cancer prognosis across two distinct datasets. Further study will be necessary to improve predictive accuracy of the prognostic index toward clinical application for evaluation of the risk of recurrence in patients with advanced-stage serous ovarian cancer. PMID:20300634

  20. Serum Adiponectin Levels in Advanced-Stage Parkinson's Disease Patients

    PubMed Central

    Cassani, Erica; Cancello, Raffaella; Cavanna, Ferruccio; Maestrini, Sabrina; Di Blasio, Anna Maria; Liuzzi, Antonio; Pezzoli, Gianni; Barichella, Michela

    2011-01-01

    Patients with advanced Parkinson's disease (PD) experience body weight loss and reductions in the most common cardiovascular risk factors. At present, the pathogenetic mechanisms involved have not been elucidated. Increased serum concentrations of adiponectin, which possesses antiatherogenic and anti-inflammatory properties, are associated with a reduction in cardiovascular risk. The objective of this study was to determine adiponectin serum concentrations in PD patients. Thirty PD patients underwent a full nutritional status assessment, including the determination of adiponectin serum concentrations. Mean ± SD adiponectin concentrations were 9.59 ± 5.9 μg/mL (interquartile range: 5.92–12.9 μg/mL). In PD patients, adiponectin serum levels were similar to those in normal-weight, healthy, young subjects and significantly higher than that in an aged-matched group of morbidly obese subjects. Further studies are warranted to establish the role of adiponectin in the management of PD patients. PMID:21766000

  1. Advanced stages in the evolution of the sun

    NASA Astrophysics Data System (ADS)

    Jorgensen, U. G.

    1991-06-01

    The method of analytical fits to numerical results of stellar evolutionary tracks is used to estimate the effects of using different codes and input physics, as well as to gauge the effects of uncertainties in the knowledge of the sun's chemical composition, mixing-length parameter, and mass-loss parameter. The sun is found to be in a region of parameter space where solar models with only slightly different input will lead to widely different evolutionary ends, spanning from the end of nuclear burning before the helium core flash can occur, to evolution until enough nucleosynthesized material has been dredged up to turn the sun into a carbon star with C/O approximating 1.6. The most likely final stage is an oxygen-rich red giant Mira variable with a period of around 250 days and a luminosity and temperature of around 5000 solar luminosities and 3000 K, respectively, at an age of 11.6 x 10 to the 9th yr. Between 35 and 55 percent of the mass will be lost via wind during the solar lifetime, primarily shortly before the helium core flash and at the asymptotic giant branch.

  2. Carpal tunnel syndrome severity staging using sonographic and clinical measures.

    PubMed

    Roll, Shawn C; Volz, Kevin R; Fahy, Christine M; Evans, Kevin D

    2015-06-01

    Ultrasonography may be valuable in staging carpal tunnel syndrome severity, especially by combining multiple measures. This study aimed to develop a preliminary severity staging model using multiple sonographic and clinical measures. Measures were obtained in 104 participants. Multiple categorization structures for each variable were correlated to diagnostic severity based on nerve conduction. Goodness-of-fit was evaluated for models using iterative combinations of highly correlated variables. Using the best-fit model, a preliminary scoring system was developed, and frequency of misclassification was calculated. The severity staging model with best fit (rho 0.90) included patient-reported symptoms, functional deficits, provocative testing, nerve cross-sectional area, and nerve longitudinal appearance. An 8-point scoring scale classified severity accurately for 79.8% of participants. This severity staging model is a novel approach to carpal tunnel syndrome evaluation. Including more sensitive measures of nerve vascularity, nerve excursion, or other emerging techniques may refine this preliminary model. © 2014 Wiley Periodicals, Inc.

  3. Carpal tunnel syndrome severity staging using sonographic and clinical measures

    PubMed Central

    Roll, Shawn C.; Volz, Kevin R.; Fahy, Christine M.; Evans, Kevin D.

    2014-01-01

    Introduction Ultrasonography may be valuable in staging carpal tunnel syndrome severity, especially by combining multiple measures. This study aimed to develop a preliminary severity staging model using multiple sonographic and clinical measures. Methods Measures were obtained in 104 participants. Multiple categorization structures for each variable were correlated to diagnostic severity based on nerve conduction. Goodness-of-fit was evaluated for models using iterative combinations of highly correlated variables. Using the best-fit model, a preliminary scoring system was developed, and frequency of misclassification was calculated. Results The severity staging model with best fit (Rho 0.90) included patient-reported symptoms, functional deficits, provocative testing, nerve cross-sectional area, and nerve longitudinal appearance. An 8-point scoring scale classified severity accurately for 79.8% of participants. Discussion This severity staging model is a novel approach to carpal tunnel syndrome evaluation. Including more sensitive measures of nerve vascularity, nerve excursion, or other emerging techniques may refine this preliminary model. PMID:25287477

  4. Reduction of Advanced Breast Cancer Stages at Subsequent Participation in Mammography Screening.

    PubMed

    Weigel, S; Heindel, W; Heidrich, J; Heidinger, O; Hense, H W

    2016-01-01

    The decline in advanced breast cancer stages is presumably the most relevant surrogate parameter in mammography screening. It represents the last step in the causal cascade that is expected to affect breast cancer-related mortality. To assess the effectiveness of population-based screening, we analyzed the 2-year incidence rates of advanced breast cancers between women participating in the initial and in the first subsequent round. The study included data from 19,563 initial and 18,034 subsequent examinations of one digital screening unit (2008 - 2010). Data on tumor stages, detected by screening or within the following interval of two years (2-year incidence), were provided by the epidemiological cancer registry. Rates of all and combined UICC stages 2, 3 and 4 (advanced stages) were reported for a two-year period. Proportions were tested for significance by using chi-square tests (p < 0.001). The 2-year incidence rate of all stages was significantly lower in participants in subsequent screening than in initial screening (0.85 vs. 1.29 per 100 women (%); p < 0.0001). A significantly lower 2-year incidence of advanced stages was observed for subsequent screening compared to initial screening (0.26 % vs. 0.48 %; p = 0.0007). Among women aged 50 to 59 years, the incidence of advanced stages was less clearly different (0.21 % vs. 0.35 %; p = 0.07) than in women aged 60 to 69 years (0.31 % vs. 0.70 %; p = 0.0008). During the change from prevalent to incident phase mammography screening, a program impact is seen by a lower 2-year incidence of advanced breast cancers within subsequent compared to initial participants, predominately in women aged 60 to 69 years. • The incidence of advanced tumor stages represents the most relevant surrogate parameter for screening effectiveness. • For the first time the 2-year incidence of advanced breast cancer stages after subsequent mammography screening was analyzed. • We observed a

  5. Treatment of advanced stage gonarthrosis with prolotherapy: case report.

    PubMed

    Solmaz, Ilker; Deniz, Suleyman; Cifci, Onder Taylan

    2014-02-01

    This case report aims to discuss the clinical and radiological outcomes of prolotherapy at a patient whom to total knee prosthesis had been planned but surgery couldn't be performed due to co-morbidities. A 72 year old woman presented with severe pain at her knees for over 5 years. Treatment methods include weight loss, decreasing the weight bearing on the joint, stretching exercises, nonsteroid anti-inflammatory and steroid drugs, and physiotherapy. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale was applied to measure the osteoarthritis level of the patient: Pain level; 25 points, stiffness level; 10 points, Physical function loss; 80 points, and total WOMAC 115 points. At radiological evaluation, the patient was diagnosed as grade IV osteoarthritis due to significant osteophyte presence and complete joint space narrowing. Six sessions of knee prolotherapy protocol was applied to the patient, one session monthly. Significant improvement was noted at WOMAC scale (Pain level; 5 points, stiffness level; 2 points, Physical function loss; 15 points, and total WOMAC 22 points). Osteoarthritis level of the patient was improved to grade I at radiological evaluation after a year. Our case is the report that presents radiological evidence in addition to clinical findings of improvement of osteoarthritis level. As a result of this case report, further studies aiming to offer a different minimally invasive treatment option to the patients before surgery may be performed. We are in the opinion that prolotherapy may be preferred more commonly as an efficient method once the importance of ligamentous structures at pathogenesis of osteoarthritis is established.

  6. Treatment of Advanced Stage Gonarthrosis With Prolotherapy: Case Report

    PubMed Central

    Solmaz, Ilker; Deniz, Suleyman; Cifci, Onder Taylan

    2013-01-01

    Introduction This case report aims to discuss the clinical and radiological outcomes of prolotherapy at a patient whom to total knee prosthesis had been planned but surgery couldn’t be performed due to co-morbidities. Case Presentation A 72 year old woman presented with severe pain at her knees for over 5 years. Treatment methods include weight loss, decreasing the weight bearing on the joint, stretching exercises, nonsteroid anti-inflammatory and steroid drugs, and physiotherapy. The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scale was applied to measure the osteoarthritis level of the patient: Pain level; 25 points, stiffness level; 10 points, Physical function loss; 80 points, and total WOMAC 115 points. At radiological evaluation, the patient was diagnosed as grade IV osteoarthritis due to significant osteophyte presence and complete joint space narrowing. Six sessions of knee prolotherapy protocol was applied to the patient, one session monthly. Conclusions Significant improvement was noted at WOMAC scale (Pain level; 5 points, stiffness level; 2 points, Physical function loss; 15 points, and total WOMAC 22 points). Osteoarthritis level of the patient was improved to grade I at radiological evaluation after a year. Our case is the report that presents radiological evidence in addition to clinical findings of improvement of osteoarthritis level. As a result of this case report, further studies aiming to offer a different minimally invasive treatment option to the patients before surgery may be performed. We are in the opinion that prolotherapy may be preferred more commonly as an efficient method once the importance of ligamentous structures at pathogenesis of osteoarthritis is established. PMID:24660149

  7. 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.

  8. 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.

  9. Radionuclide scans not indicated for clinical Stage I melanoma

    SciTech Connect

    Evans, R.A.; Bland, K.I.; McMurtrey, M.J.; Ballantyne, A.J.

    1980-04-01

    One hundred and sixty-two scans of the liver and 160 scans of the brain were performed upon 230 patients with clinical Stage I melanoma. No patient was found to have a true-positive scan. However, there were two false-positive scans of the liver and two false-positive scans of the brain. One craniotomy, two arteriograms, and numerous follow-up scans were done to confirm that these scans were false-positive. The cost of the 322 screening scans was $23,964, and the expense of follow-up evaluation was considerably greater. The authors have discontinued the use of scans of the liver and brain in the evaluation of asymptomatic patients with Stage I melanoma.

  10. Malignant pheochromocytoma-paraganglioma: pathogenesis, TNM staging, and current clinical trials.

    PubMed

    Roman-Gonzalez, Alejandro; Jimenez, Camilo

    2017-06-01

    Pheochromocytomas and paragangliomas (PPGs) are rare neuroendocrine tumors. Over the last 15 years, substantial progress has been made toward understanding the clinical aspects and molecular origins of this disease. Nevertheless, predicting and managing malignancy remains the biggest challenge in clinical practice. The natural history of patients with malignant PPGs has not yet been described, and their prognosis varies. Currently, the diagnosis of malignant PPGs relies on the presence of metastases, by which time the disease is usually advanced. Better understanding of the clinical and molecular characteristics of patients with malignant PPGs has spurred several prospective clinical trials. Several molecular targeted therapies, a novel radiopharmaceutical medication that targets the catecholamine transporter, and immunotherapy are under evaluation for the treatment of patients with malignant PPGs. Furthermore, the identification of clinical predictors of malignancy and survival has led to the first TNM staging classification for PPGs. Prospective clinical trials are providing patients with therapeutic options beyond systemic chemotherapy. The knowledge derived from these trials and from the evaluation of the TNM staging in clinical practice will help to clarify how to most effectively treat malignant PPGs.

  11. Does extracellular matrix of the varicose vein wall change according to clinical stage?

    PubMed

    Demirkıran, Mehmet Ali; Köksoy, Cüneyt; Heper, Aylin Okçu; Bengisun, Uğur

    2014-01-01

    The etiology and pathophysiology of chronic venous disease is not fully understood. This study aimed to determine the variation of the extracellular matrix proteins in varicose vein wall according to clinical stage. Forty varicose and 10 control veins were sampled from the saphenofemoral junction. The Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification was used in patients with varicose veins. Samples were stained with hematoxylin-eosin, Masson's trichrome, EVG (Elastica-van Gieson) stain and with laminin, fibronectin, tenascin antibodies. Stained samples were examined immuno-histochemically. Changes in extracellular matrix were determined semi-quantitatively using light microscopy. It was observed that in the early stages (C2-C3) of chronic venous disease, fibrosis is increased in the intima and media layers, with fragmentation in lamina elastica interna, and increased tenascin expression in the intima layer. In advanced stages (C4-C6), the accumulation of tenascin in the intima continued along with fibrosis in the media layer, the thickness of the media layer increased and fibronectin deposition was observed. This study showed that changes first occur in the intima during the early stages of the disease with addition of alterations in the media layer at later stages.

  12. Does extracellular matrix of the varicose vein wall change according to clinical stage?

    PubMed Central

    Demirkıran, Mehmet Ali; Köksoy, Cüneyt; Heper, Aylin Okçu; Bengisun, Uğur

    2014-01-01

    Objective: The etiology and pathophysiology of chronic venous disease is not fully understood. This study aimed to determine the variation of the extracellular matrix proteins in varicose vein wall according to clinical stage. Material and Methods: Forty varicose and 10 control veins were sampled from the saphenofemoral junction. The Clinical Etiologic Anatomic Pathophysiologic (CEAP) classification was used in patients with varicose veins. Samples were stained with hematoxylin-eosin, Masson’s trichrome, EVG (Elastica-van Gieson) stain and with laminin, fibronectin, tenascin antibodies. Stained samples were examined immuno-histochemically. Changes in extracellular matrix were determined semi-quantitatively using light microscopy. Results: It was observed that in the early stages (C2–C3) of chronic venous disease, fibrosis is increased in the intima and media layers, with fragmentation in lamina elastica interna, and increased tenascin expression in the intima layer. In advanced stages (C4–C6), the accumulation of tenascin in the intima continued along with fibrosis in the media layer, the thickness of the media layer increased and fibronectin deposition was observed. Conclusion: This study showed that changes first occur in the intima during the early stages of the disease with addition of alterations in the media layer at later stages. PMID:25931926

  13. Clinical applications of advanced rotational radiation therapy

    NASA Astrophysics Data System (ADS)

    Nalichowski, Adrian

    Purpose: With a fast adoption of emerging technologies, it is critical to fully test and understand its limits and capabilities. In this work we investigate new graphic processing unit (GPU) based treatment planning algorithm and its applications in helical tomotherapy dose delivery. We explore the limits of the system by applying it to challenging clinical cases of total marrow irradiation (TMI) and stereotactic radiosurgery (SRS). We also analyze the feasibility of alternative fractionation schemes for total body irradiation (TBI) and TMI based on reported historical data on lung dose and interstitial pneumonitis (IP) incidence rates. Methods and Materials: An anthropomorphic phantom was used to create TMI plans using the new GPU based treatment planning system and the existing CPU cluster based system. Optimization parameters were selected based on clinically used values for field width, modulation factor and pitch. Treatment plans were also created on Eclipse treatment planning system (Varian Medical Systems Inc, Palo Alto, CA) using volumetric modulated arc therapy (VMAT) for dose delivery on IX treatment unit. A retrospective review was performed of 42 publications that reported IP rates along with lung dose, fractionation regimen, dose rate and chemotherapy. The analysis consisted of nearly thirty two hundred patients and 34 unique radiation regimens. Multivariate logistic regression was performed to determine parameters associated with IP and establish does response function. Results: The results showed very good dosimetric agreement between the GPU and CPU calculated plans. The results from SBRT study show that GPU planning system can maintain 90% target coverage while meeting all the constraints of RTOG 0631 protocol. Beam on time for Tomotherapy and flattening filter free RapidArc was much faster than for Vero or Cyberknife. Retrospective data analysis showed that lung dose and Cyclophosphomide (Cy) are both predictors of IP in TBI/TMI treatments. The

  14. Clinical predictors and recommendations for staging CT scan among men with prostate cancer

    PubMed Central

    Risko, Rachel; Merdan, Selin; Womble, Paul R.; Barnett, Christine; Ye, Zaojun; Linsell, Susan M.; Montie, James E.; Miller, David C.; Denton, Brian T.

    2016-01-01

    Objective To identify clinical variables associated with a positive CT scan and estimate the performance of imaging recommendations in patients from a diverse sample of urology practices. Materials and Methods This study comprised 2,380 men with newly diagnosed prostate cancer seen at 28 practices in the Michigan Urological Surgery Improvement Collaborative (MUSIC) from March 2012 through September 2013. Data included age, prostate-specific antigen (PSA) level, Gleason score (GS), clinical T-stage, total number of positive biopsy cores, whether or not the patient received a staging abdominal/pelvic CT scan, and the CT scan result. We fit a multivariable logistic regression model to identify clinical variables associated with metastases detected by CT scan. We estimated the sensitivity and specificity of existing imaging recommendations. Results Among 643 men (27.4%) who underwent a staging CT scan, 62 (9.6%) had a positive study. In the multivariable analysis, PSA, GS, and clinical T stage were independently associated with the occurrence of a positive CT scan (all p-values<0.05). American Urology Association Best Practice recommendations for imaging when PSA >20 or GS ≥8 or locally advanced cancer had a sensitivity of 87.3% and specificity of 82.6%. Compared to current practice, implementing this recommendation in the MUSIC population was estimated to result in approximately 0.5% of positive studies being missed, and 26.1% fewer studies overall. Conclusions Successful implementation of CT imaging criterion of PSA >20 or GS ≥8 or clinical stage ≥T3 would ensure that CT scans are performed for almost all men who would have positive studies while reducing the number of negative studies. PMID:25288575

  15. The relationship between clinical phenotype and early staged bilateral deep brain stimulation in Parkinson disease.

    PubMed

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

    2013-12-01

    While many centers place bilateral deep brain stimulation (DBS) systems simultaneously, unilateral subthalamic nucleus (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 STN will be required. The authors aimed to determine whether preoperative clinical phenotype predicts early staged placement of a second STN DBS electrode in patients who undergo unilateral STN DBS for Parkinson disease (PD). Eighty-two consecutive patients with advanced PD underwent unilateral STN DBS contralateral to the most affected hemibody and had at least 2 years of follow-up. Multivariate logistic regression analysis determined preoperative characteristics that predicted staged placement of a second electrode in the opposite STN. Preoperative measurements included aspects of the Unified Parkinson's Disease Rating Scale (UPDRS), motor asymmetry index, and body weight. At 2-year follow-up, 28 (34%) of the 82 patients 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 analysis showed that the most important predictors for early staged placement of a second subthalamic stimulator were low asymmetry index (OR 13.4, 95% CI 2.8-64.9), high tremor subscore (OR 7.2, CI 1.5-35.0), and low body weight (OR 5.5, 95% CI 1.4-22.3). This single-center study provides evidence that elements of the preoperative PD phenotype predict whether patients will require early staged bilateral STN DBS. These data may aid in the management of patients with advanced PD who undergo STN DBS.

  16. The prognostic relevance of tumor associated macrophages in advanced stage classical Hodgkin lymphoma.

    PubMed

    Jakovic, Ljubomir R; Mihaljevic, Biljana S; Perunicic Jovanovic, Maja D; Bogdanovic, Andrija D; Andjelic, Bosko M; Bumbasirevic, Vladimir Z

    2011-10-01

    Although the treatment of Hodgkin lymphoma (HL) has been improved, distinguishing reliable prognostic biomarkers could better stratify patients for more effective treatment. We analyzed the prognostic relevance of CD68+ tumor-associated macrophages (TAMs) by immunohistochemical analysis at diagnosis and standard clinical parameters in 52 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)-treated patients with advanced stage classical HL (cHL). Patients with >25% CD68+ TAMs compared to those with ≤25% had worse 5-year overall survival (45% vs. 77%, log-rank p = 0.019) and showed a trend toward shorter 5-year event-free survival (51% vs. 71%, log-rank p = 0.19). Additionally, no significant correlation with selected clinical features was found. Significantly shorter 5-year overall survival was associated with International Prognostic Score (IPS) >2, bulky disease, elevated erythrocyte sedimentation rate (log-rank test, p = 0.003, p = 0.049, p = 0.007, respectively). In multivariate analysis, increased CD68+TAMs, IPS >2, and bulky disease were identified as independent prognostic factors for overall survival (Cox multivariate model, p = 0.006, p = 0.007, p = 0.013, respectively). Tumor-associated macrophages represent a potential prognostic biomarker which could contribute to better risk stratification of patients with cHL.

  17. [The preoperative staging of rectal neoplasms: the clinical exam and diagnostic imaging].

    PubMed

    Grande, M; Danza, F M

    1999-01-01

    The management of rectal cancer remains an important clinical problem. Although there was been great progress in surgical management, the survival of patients with locally advanced disease has not improved significantly during the past decades. Preoperative staging and evaluation of the risk of recurrence may help in the choice of operation. It is difficult for clinicians to quantify reliably with digital examination the degree of fixation of the tumor, and they usually cannot distinguish nodal metastases except in advanced cases. The more frequent overstaging of small tumors within one quadrant of the rectum is a major drawback of digital examination. Computed tomography and magnetic resonance seems to underestimate the extension of rectal tumors, but both can be helpful in selecting patients with advanced tumors for whom preoperative adjuvant treatment is being considered. Endoluminal ultrasound is superior in staging tumors confined to the rectal wall, but is not the ideal tool for staging: the results are examiner dependent, the field of vision in depth is limited, and stricturing tumors cannot be passed by the ultrasound transducer. Imaging diagnostic attendibility confirms the preeminent role of intraoperative exploration in the assessment of neoplastic diffusion in order to plan a correct surgical treatment.

  18. Oxidized low-density lipoprotein is associated with advanced-stage prostate cancer.

    PubMed

    Wan, Fangning; Qin, Xiaojian; Zhang, Guiming; Lu, Xiaolin; Zhu, Yao; Zhang, Hailiang; Dai, Bo; Shi, Guohai; Ye, Dingwei

    2015-05-01

    Clinical and epidemiological data suggest coronary artery disease shares etiology with prostate cancer (PCa). The aim of this work was to assess the effects of several serum markers reported in cardiovascular disease on PCa. Serum markers (oxidized low-density lipoprotein [ox-LDL], apolipoprotein [apo] B100, and apoB48) in peripheral blood samples from 50 patients from Fudan University Shanghai Cancer Center (FUSCC) with localized or lymph node metastatic PCa were investigated in this study. Twenty-five samples from normal individuals were set as controls. We first conducted enzyme-linked immunosorbent assay analysis to select candidate markers that were significantly different between these patients and controls. Then, the clinical relevance between OLR1 (the ox-LDL receptor) expression and PCa was analyzed in The Cancer Genome Atlas (TCGA) cohort. We also investigated the function of ox-LDL in PCa cell lines in vitro. Phosphorylation protein chips were used to analyze cell signaling pathways in ox-LDL-treated PC-3 cells. The ox-LDL level was found to be significantly correlated with N stage of prostate cancer. OLR1 expression was correlated with lymph node metastasis in the TCGA cohort. In vitro, ox-LDL stimulated the proliferation, migration, and invasion of LNCaP and PC-3 in a dose-dependent manner. The results of phosphoprotein microarray illustrated that ox-LDL could influence multiple signaling pathways of PC-3. Activation of proliferation promoting signaling pathways (including β-catenin, cMyc, NF-κB, STAT1, STAT3) as well as apoptosis-associating signaling pathways (including p27, caspase-3) demonstrated that ox-LDL had complicated effects on prostate cancer. Increased serum ox-LDL level and OLR1 expression may indicate advanced-stage PCa and lymph node metastasis. Moreover, ox-LDL could stimulate PCa proliferation, migration, and invasion in vitro.

  19. Transcriptomic analysis of stage 1 versus advanced adult granulosa cell tumors

    PubMed Central

    Leung, Dilys; Gould, Jodee A.; Jobling, Tom; Fuller, Peter J.

    2016-01-01

    Ovarian granulosa cell tumors (GCT) are hormonally-active neoplasms characterized, in the adult-subtype, by a mutation in the FOXL2 gene (C134W). They exhibit an indolent course with an unexplained propensity for late recurrence; ∼80% of patients with aggressive, advanced stage tumors die from their disease; aside from surgery, therapeutic options are limited. To identify the molecular basis of advanced stage disease we have used whole transcriptome analysis of FOXL2 C134W mutation positive adult (a)GCT to identify genes that are differentially expressed between early (stage 1) and advanced (stage 3) aGCT. Transcriptome profiles for early (n = 6) and stage 3 (n = 6) aGCT, and for the aGCT-derived KGN, cell line identified 24 genes whose expression significantly differs between the early and stage 3 aGCT. Of these, 16 were more abundantly expressed in the stage 3 aGCT and 8 were higher in the stage 1 tumors. These changes were further examined for the genes which showed the greatest fold change: the cytokine CXCL14, microfibrillar-associated protein 5, insulin-like 3 and desmin. Gene Set Enrichment Analysis identified overexpression of genes on chromosome 7p15 which includes the homeobox A gene locus. The analysis therefore identifies a small number of genes with clearly discriminate patterns of expression arguing that the clinicopathological-derived distinction of the tumor stage is robust, whilst confirming the relative homogeneity of expression for many genes across the cohort and hence of aGCT. The expression profiles do however identify several overexpressed genes in both stage 1 and/or stage 3 aGCT which warrant further study as possible therapeutic targets. PMID:26893359

  20. Advanced primary pulmonary lymphoepithelioma-like carcinoma: clinical manifestations, treatment, and outcome

    PubMed Central

    Lin, Chun-Yu; Chen, Ying-Jen; Hsieh, Meng-Heng; Wang, Chih-Wei

    2017-01-01

    Background Primary pulmonary lymphoepithelioma-like carcinoma (LELC) is rare, with better clinical outcomes than other lung cancers. However, reports on advanced LELC characteristics and prognosis are lacking. Methods This retrospective study included adults diagnosed with advanced LELC (at least stage IIIA) between January 2003 and December 2015. Clinical characteristics, treatment modalities, and outcomes were recorded. Results Study population comprised 23 patients with a mean age of 63.7±10.6 years. The Eastern Cooperative Oncology Group status on diagnosis was 0 in five patients and 1 in the others. Most patients received multimodality treatment and all received cisplatin-based chemotherapy. Median follow-up duration was 28.8 months. The median progression free survival (PFS) was 14.6 months in patients received palliative chemotherapy. There were nine (39.1%) deaths. The median overall survival (OS) was not achieved. Until July 31, 2016, median OS was 54.1 months for stage IIIB and 27.6 months for stage IV. There was no significant difference in OS among all stages. No prognostic factors were found. Conclusions Advanced LELC responded well to cisplatin-based chemotherapy and/or radiotherapy. Main tumor resection is probably beneficial for advanced LELC. Long-term survival is possible for advanced LELC after multimodality treatment. PMID:28203414

  1. Martinique Crinkled Retinal Pigment Epitheliopathy: Clinical Stages and Pathophysiologic Insights.

    PubMed

    Jean-Charles, Albert; Merle, Harold; Audo, Isabelle; Desoudin, Catherine; Bocquet, Béatrice; Baudoin, Corinne; Sidibe, Moro; Mauget-Faÿsse, Martine; Wolff, Benjamin; Fichard, Agnès; Lenaers, Guy; Sahel, José-Alain; Gaudric, Alain; Cohen, Salomon Yves; Hamel, Christian P; Meunier, Isabelle

    2016-10-01

    To reappraise the autosomal dominant Martinique crinkled retinal pigment epitheliopathy (MCRPE) in light of the knowledge of its associated mutated gene mitogen-activated protein kinase-activated protein kinase 3 (MAPKAPK3), an actor in the p38 mitogen-activated protein kinase pathway. Clinical and molecular study. A total of 45 patients from 3 generations belonging to a family originating from Martinique with an autosomal dominant MCRPE were examined. Best-corrected visual acuity, fundus photographs, and spectral-domain optical coherence tomography (SD OCT) of all clinically affected patients and carriers for the causal mutation were reviewed at the initial visit and 4 years later for 10 of them. Histologic retinal lesions of Mapkapk3(-/-) mice were compared with those of the human disease. The MCRPE natural history in view of MAPKAPK3 function and Mapkapk3(-/-) mouse retinal lesions. Eighteen patients had the c.518T>C mutation. One heterozygous woman aged 20 years was asymptomatic with normal fundus and SD OCT (stage 0). All c.518T>C heterozygous patients older than 30 years of age had the characteristic dried-out soil fundus pattern (stages 1 and 2). Complications (stage 3) were observed in 7 cases, including polypoidal choroidal vasculopathy (PCV) and macular fibrosis or atrophy. One patient was homozygous and had a form with severe Bruch's membrane (BM) thickening and macular exudation with a dried-out soil pattern in the peripheral retina. The oldest heterozygous patient, who was legally blind, had peripheral nummular pigmentary changes (stage 4). After 4 years, visual acuity was unchanged in 6 of 10 patients. The dried-out soil elementary lesions radically enlarged in patients with a preferential macular extension and confluence. These findings are in line with the progressive thickening of BM noted with age in the mouse model. During follow-up, there was no occurrence of PCV. MCRPE is an autosomal dominant, fully penetrant retinal dystrophy with a

  2. Is obesity associated with advanced stage or grade of colon cancer?

    PubMed

    Neumann, Katerina; Mahmud, Salaheddin M; McKay, Andrew; Park, Jason; Metcalfe, Jennifer; Hochman, David J

    2015-04-01

    Population-based studies from Europe have suggested that obesity is associated with more advanced stage colorectal cancer on presentation. Obesity is an even more prevalent issue in North America, but comparable data on associations with cancer are lacking. We reviewed the cases of 672 patients with colon cancer diagnosed between 2004 and 2008 in the province of Manitoba who underwent surgical resection at a Winnipeg Regional Health Authority–affiliated hospital. We tested if obesity was associated with more advanced cancer stage or grade. On multivariate analysis, after adjusting for age, sex,tumour location and socioeconomic status, we were unable to show any significant associations between body mass index of 30 or more and advanced stage or grade cancer on presentation. The reasons for the lack of association are likely multifactorial, including the pathophysiology of the disease and process factors, such as screening habits and colonoscopic diagnostic success rates in obese patients.

  3. High copy number of mitochondrial DNA predicts poor prognosis in patients with advanced stage colon cancer.

    PubMed

    Wang, Yun; He, Shuixiang; Zhu, Xingmei; Qiao, Wei; Zhang, Juan

    2016-12-23

    The aim of this investigation was to determine whether alterations in mitochondrial DNA (mtDNA) copy number in colon cancer were associated with clinicopathological parameters and postsurgical outcome. By quantitative real-time PCR assay, the mtDNA copy number was detected in a cohort of colon cancer and matched adjacent colon tissues (n = 162). The majority of patients had higher mtDNA content in colon cancer tissues than matched adjacent colon tissues. Moreover, high mtDNA content in tumor tissues was associated with larger tumor size, higher serum CEA level, advanced TNM stage, vascular emboli, and liver metastases. Further survival curve analysis showed that high mtDNA content was related to the worst survival in patients with colon cancer at advanced TNM stage. High mtDNA content is a potential effective factor of poor prognosis in patients with advanced stage colon cancer.

  4. Two-stage design of clinical trials involving recurrent events.

    PubMed

    Cook, Richard J; Bergeron, Pierre-Jerome; Boher, Jean-Marie; Liu, Yang

    2009-09-20

    Mixed Poisson models are often used for the design of clinical trials involving recurrent events since they provide measures of treatment effect based on rate and mean functions and accommodate between individual heterogeneity in event rates. Planning studies based on these models can be challenging when there is a little information available on the population event rates, or the extent of heterogeneity characterized by the variance of individual-specific random effects. We consider methods for adaptive two-stage clinical trial design, which enable investigators to revise sample size estimates using data collected during the first phase of the study. We describe blinded procedures in which the group membership and treatment received by each individual are not revealed at the interim analysis stage, and a 'partially blinded' procedure in which group membership is revealed but not the treatment received by the groups. An EM algorithm is proposed for the interim analyses in both cases, and the performance is investigated through simulation. The work is motivated by the design of a study involving patients with immune thrombocytopenic purpura where the aim is to reduce bleeding episodes and an illustrative application is given using data from a cardiovascular trial.

  5. Single stage, low noise, advanced technology fan. Volume 2: Structural design

    NASA Technical Reports Server (NTRS)

    Schoener, J. L.; Black, G. R.; Roth, R. H.

    1976-01-01

    The structural 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 (1,650 ft/sec). This mechanical design report describes the fan rotor design and the design of various structures of the vehicle; eg, stators, casings, splitters, seals, adapters, etc.

  6. Atrophy patterns in early clinical stages across distinct phenotypes of Alzheimer's disease.

    PubMed

    Ossenkoppele, Rik; Cohn-Sheehy, Brendan I; La Joie, Renaud; Vogel, Jacob W; Möller, Christiane; Lehmann, Manja; van Berckel, Bart N M; Seeley, William W; Pijnenburg, Yolande A; Gorno-Tempini, Maria L; Kramer, Joel H; Barkhof, Frederik; Rosen, Howard J; van der Flier, Wiesje M; Jagust, William J; Miller, Bruce L; Scheltens, Philip; Rabinovici, Gil D

    2015-11-01

    Alzheimer's disease (AD) can present with distinct clinical variants. Identifying the earliest neurodegenerative changes associated with each variant has implications for early diagnosis, and for understanding the mechanisms that underlie regional vulnerability and disease progression in AD. We performed voxel-based morphometry to detect atrophy patterns in early clinical stages of four AD phenotypes: Posterior cortical atrophy (PCA, "visual variant," n=93), logopenic variant primary progressive aphasia (lvPPA, "language variant," n=74), and memory-predominant AD categorized as early age-of-onset (EOAD, <65 years, n=114) and late age-of-onset (LOAD, >65 years, n=114). Patients with each syndrome were stratified based on: (1) degree of functional impairment, as measured by the clinical dementia rating (CDR) scale, and (2) overall extent of brain atrophy, as measured by a neuroimaging approach that sums the number of brain voxels showing significantly lower gray matter volume than cognitively normal controls (n=80). Even at the earliest clinical stage (CDR=0.5 or bottom quartile of overall atrophy), patients with each syndrome showed both common and variant-specific atrophy. Common atrophy across variants was found in temporoparietal regions that comprise the posterior default mode network (DMN). Early syndrome-specific atrophy mirrored functional brain networks underlying functions that are uniquely affected in each variant: Language network in lvPPA, posterior cingulate cortex-hippocampal circuit in amnestic EOAD and LOAD, and visual networks in PCA. At more advanced stages, atrophy patterns largely converged across AD variants. These findings support a model in which neurodegeneration selectively targets both the DMN and syndrome-specific vulnerable networks at the earliest clinical stages of AD. © 2015 Wiley Periodicals, Inc.

  7. Clinical Outcome of Squamous Cell Carcinoma of the Tongue in Young Patients: A Stage-Matched Comparative Analysis

    PubMed Central

    Park, Jun-Ook; Sun, Dong-Il; Cho, Kwang-Jae; Joo, Young-Hoon; Yoo, Hwa-Jong

    2010-01-01

    Objectives The reported incidence of tongue cancer in young patients has recently increased. The aim of this study was to analyze the clinical characteristics of tongue cancer in a young group of patients, and to compare them with those of an older group of tongue cancer patients. Methods We retrospectively reviewed the records of 85 patients who were diagnosed with squamous cell carcinoma of the tongue. They were divided into two age groups: over 45 years of age and under 45 years. To compare the prognosis of similarly staged patients in the group, each age group was divided into the early (stage I, II) and advanced stage groups (stage III, IV), and then they were compared. The young group consisted of 23 patients and the older group had 62 patients. Results At the early stage, the clinical prognosis of the patients in both age groups was good, and no significant difference was observed. However, at the advanced stage, the overall and regional recurrence rates were significantly higher in the younger age group as compared to that in the old age group (P=0.007, P=0.001, respectively). The disease-specific survival rate of the patients in the young group was significantly lower than that in the old age group (P=0.025). Conclusion Tongue cancer in young subjects has significantly different clinical outcomes according to the stage. The clinical outcome of the advanced-stage tongue cancer in young subjects was poorer than that in the older subjects. Regional recurrence seemed to be the main cause of the poor prognosis. PMID:20978546

  8. A clinical advancement process revisited: a descriptive study.

    PubMed

    Ward, Cynthia W; Goodrich, Cynthia A

    2007-06-01

    Clinical advancement programs are not evaluated often for effectiveness and participant satisfaction. The advancement committee at this community hospital made the commitment to evaluate participant satisfaction periodically. Revisions were made in the program based on the evaluation findings and implemented in 2002. This re-evaluation was conducted to determine participant satisfaction.

  9. Advances in clinical study of curcumin.

    PubMed

    Yang, Chunfen; Su, Xun; Liu, Anchang; Zhang, Lin; Yu, Aihua; Xi, Yanwei; Zhai, Guangxi

    2013-01-01

    Curcumin has been estimated as a potential agent for many diseases and attracted great attention owing to its various pharmacological activities, including anti-cancer, and anti-inflammatory. Now curcumin is being applied to a number of patients with breast cancer, rheumatoid arthritis, Alzheimer's disease, colorectal cancer, psoriatic, etc. Several clinical trials have stated that curcumin is safe enough and effective. The objective of this article was to summarize the clinical studies of curcumin, and give a reference for future studies.

  10. 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.

  11. Management of clinical stage I nonseminomatous germ cell tumors.

    PubMed

    Isharwal, Sumit; Risk, Michael C

    2014-09-01

    Therapeutic options for clinical stage I nonseminomatous germ cell tumor include active surveillance, adjuvant chemotherapy and retroperitoneal lymph node dissection (RPLND). Lymphovascular invasion (LVI) determines risk of recurrence, as those without LVI have 15% risk of relapse on surveillance while those with LVI have a 50% risk. This stratifies patients into high risk(LVI+) and low risk(LVI-) groups which direct treatment recommendations. Surveillance is preferred for those with low risk disease, and is an option for those with high risk disease, as at least half are over-treated with other options. Adjuvant chemotherapy is an option for all patients as it can eradicate micrometastatic disease and reduce recurrence by at least 90%. RPLND benefits patients with low volume retroperitoneal disease with a cure rate of RPLND alone at approximately 70%. All three treatment modalities have similar survival rates approaching 100% but differing potential morbidities, which, along with patient preferences and compliance, should guide treatment decisions.

  12. The 2-stage liver transplant: 3 clinical scenarios.

    PubMed

    Gedik, Ender; Bıçakçıoğlu, Murat; Otan, Emrah; İlksen Toprak, Hüseyin; Işık, Burak; Aydın, Cemalettin; Kayaalp, Cüneyt; Yılmaz, Sezai

    2015-04-01

    The main goal of 2-stage liver transplant is to provide time to obtain a new liver source. We describe our experience of 3 patients with 3 different clinical conditions. A 57-year-old man was retransplanted successfully with this technique due to hepatic artery thrombosis. However, a 38-year-old woman with fulminant toxic hepatitis and a 5-year-old-boy with abdominal trauma had poor outcome. This technique could serve as a rescue therapy for liver transplant patients who have toxic liver syndrome or abdominal trauma. These patients required intensive support during long anhepatic states. The transplant team should decide early whether to use this technique before irreversible conditions develop.

  13. Staging and treatment of clinically occult breast cancer.

    PubMed

    Schwartz, G F; Feig, S A; Rosenberg, A L; Patchefsky, A S; Schwartz, A B

    1984-03-15

    Five hundred fifty-seven biopsies were performed for clinically occult mammary lesions, detected by mammography as clustered calcifications or nonpalpable masses within the breast. One hundred seventy-five cancers were demonstrated within this group, including 106 invasive carcinomas, 10 microinvasive carcinomas, 45 in situ ductal carcinomas, and 14 lobular carcinomas in situ (lobular neoplasia). No patient with in situ or microinvasive carcinoma had evidence of axillary node metastases in 33 specimens studied. However, a disturbingly high proportion of those patients with invasive carcinomas, approximately 35%, had histologically confirmed axillary node metastases, despite the small size of the primary tumors. These observations suggest that the use of the term "minimal" cancer is misleading when applied to invasive carcinoma. Staging systems for breast cancer have been imprecise when referring to nonpalpable lesions. Cancers detected as clustered calcifications only or as areas of parenchymal distortion without an accompanying mass are properly considered as T-0 cancers, with a suggested T-0(m) to indicate that the lesion was detected by mammography. However, when the mammogram indicates the presence of a mass that proves to be malignant, although the clinical examination may have been negative, the cancer should be staged according to the size of the mass on the mammogram, with the notation that it was detected by mammography, e.g., T-1(m), T-2(m), etc. The incidence of axillary node metastases even in these so-called occult cancers is significant, so that recommendations for treatment for any invasive cancer, regardless of its size, must take these observations into account. Similarly, the incidence of multifocal sites of cancer within the breast, even in the noninvasive cancers encountered, must be remembered when treatment is suggested.

  14. HLA-G Expression and Role in Advanced-Stage Classical Hodgkin Lymphoma

    PubMed Central

    Caocci, G.; Greco, M.; Fanni, D.; Senes, G.; Littera, R.; Lai, S.; Risso, P.; Carcassi, C.; Faa, G.; La Nasa, G.

    2016-01-01

    Non-classical human leucocyte antigen (HLA)-G class I molecules have an important role in tumor immune escape mechanisms. We investigated HLA-G expression in lymphonode biopsies taken from 8 controls and 20 patients with advanced-stage classical Hodgkin lymphoma (cHL), in relationship to clinical outcomes and the HLA-G 14-basepair (14-bp) deletion-insertion (del-ins) polymorphism. Lymphnode tissue sections were stained using a specific murine monoclonal HLA-G antibody. HLA-G protein expression was higher in cHL patients than controls. In the group of PET-2 positive (positron emission tomography carried out after 2 cycles of standard chemotherapy) patients with a 2-year progression-free survival rate (PFS) of 40%, we observed high HLA-G protein expression within the tumor microenvironment with low expression on Hodgkin and Reed-Sternberg (HRS) cells. Conversely, PET-2 negative patients with a PFS of 86% had higher HLA-G protein expression levels on HRS cells compared to the microenvironment. Lower expression on HRS cells was significantly associated with the HLA-G 14-bp ins/ins genotype. These preliminary data suggest that the immunohistochemical pattern of HLA-G protein expression may represent a useful tool for a tailored therapy in patients with cHL, based on the modulation of HLA-G expression in relation to achievement of negative PET-2. PMID:27349312

  15. Statin as a Combined Therapy for Advanced-Stage Ovarian Cancer: A Propensity Score Matched Analysis

    PubMed Central

    Chen, Hong-Yu; Wang, Qian; Xu, Qiu-Hong; Yan, Li; Gao, Xue-Feng; Lu, Yan-Hong

    2016-01-01

    Background. Despite the great achievements in the treatment of advanced-stage ovarian cancer, it is still a severe condition with an unfavorable 5-year survival rate. Statins have been suggested to reduce the risk of several cancers beyond their cholesterol-lowing effects. However, the prognostic significance of statins in patients with advanced-stage ovarian cancer remains controversial. Methods. A retrospective study was performed to evaluate the association between statin intake and overall survival (OS) among patients with advanced-stage ovarian cancer. Patients who underwent cytoreductive surgery followed by courses of intravenous chemotherapy were matched through a propensity score analysis. Results. A total of 60 propensity-matched patients were included. Women in statin group showed a similar OS than the nonstatin counterparts (P = 0.966), whereas residual tumor was significantly associated with better OS (P = 0.013) and was an independent factor that associated with OS (P = 0.002, hazard ratio = 5.460, and 95% confidence interval: 1.894 to 15.742) in multivariable analysis. Conclusions. Our results suggested that statin usage was not associated with improved OS in patients with advanced-stage ovarian cancer undergoing surgery and chemotherapy. Considering the retrospective nature and the relative small sample size of the study, further prospective studies and random control trials are needed. PMID:27975064

  16. PET-CT for staging and early response: results from the Response-Adapted Therapy in Advanced Hodgkin Lymphoma study.

    PubMed

    Barrington, Sally F; Kirkwood, Amy A; Franceschetto, Antonella; Fulham, Michael J; Roberts, Thomas H; Almquist, Helén; Brun, Eva; Hjorthaug, Karin; Viney, Zaid N; Pike, Lucy C; Federico, Massimo; Luminari, Stefano; Radford, John; Trotman, Judith; Fosså, Alexander; Berkahn, Leanne; Molin, Daniel; D'Amore, Francesco; Sinclair, Donald A; Smith, Paul; O'Doherty, Michael J; Stevens, Lindsey; Johnson, Peter W

    2016-03-24

    International guidelines recommend that positron emission tomography-computed tomography (PET-CT) should replace CT in Hodgkin lymphoma (HL). The aims of this study were to compare PET-CT with CT for staging and measure agreement between expert and local readers, using a 5-point scale (Deauville criteria), to adapt treatment in a clinical trial: Response-Adapted Therapy in Advanced Hodgkin Lymphoma (RATHL). Patients were staged using clinical assessment, CT, and bone marrow biopsy (RATHL stage). PET-CT was performed at baseline (PET0) and after 2 chemotherapy cycles (PET2) in a response-adapted design. PET-CT was reported centrally by experts at 5 national core laboratories. Local readers optionally scored PET2 scans. The RATHL and PET-CT stages were compared. Agreement among experts and between expert and local readers was measured. RATHL and PET0 stage were concordant in 938 (80%) patients. PET-CT upstaged 159 (14%) and downstaged 74 (6%) patients. Upstaging by extranodal disease in bone marrow (92), lung (11), or multiple sites (12) on PET-CT accounted for most discrepancies. Follow-up of discrepant findings confirmed the PET characterization of lesions in the vast majority. Five patients were upstaged by marrow biopsy and 7 by contrast-enhanced CT in the bowel and/or liver or spleen. PET2 agreement among experts (140 scans) with a κ (95% confidence interval) of 0.84 (0.76-0.91) was very good and between experts and local readers (300 scans) at 0.77 (0.68-0.86) was good. These results confirm PET-CT as the modern standard for staging HL and that response assessment using Deauville criteria is robust, enabling translation of RATHL results into clinical practice.

  17. Microvessel density and p53 mutations in advanced-stage epithelial ovarian cancer.

    PubMed

    Nadkarni, Niyati J; Geest, Koen De; Neff, Traci; Young, Barry De; Bender, David P; Ahmed, Amina; Smith, Brian J; Button, Anna; Goodheart, Michael J

    2013-04-30

    We planned to determine the relationship between angiogenesis and p53 mutational status in advanced-stage epithelial ovarian cancer. Using 190 tumor samples from patients with stage III and IV ovarian cancer we performed p53 sequencing, immunohistochemistry, and CD31 microvessel density (MVD) determination. MVD was elevated in tumors with p53 null mutations compared to p53 missense mutation or no mutation. Disease recurrence was increased with higher MVD in both unadjusted and adjusted analyses. In adjusted analysis, p53 null mutation was associated with increased recurrence and worse overall survival. Worse overall survival and increased recurrence risk were also associated with the combination of CD31 MVD values >25 vessels/HPF and any p53 mutation. P53 mutation status and MVD may have prognostic significance in patients with advanced-stage ovarian cancer. Tumors with p53 null mutations are likely to be more vascular, contributing to decreased survival and increased recurrence probability.

  18. Lung Cancer Clinical Trials: Advances in Immunotherapy

    Cancer.gov

    New treatments for lung cancer and aspects of joining a clinical trial are discussed in this 30-minute Facebook Live event, hosted by NCI’s Dr. Shakun Malik, head of thoracic oncology therapeutics, and Janet Freeman-Daily, lung cancer patient activist and founding member of #LCSM.

  19. Advances in Basic and Clinical Immunology 2009

    PubMed Central

    Chinen, Javier; Shearer, William T.

    2010-01-01

    In 2009, reports on basic and clinical immunology had an increased focus on human disease mechanisms and management. The molecular pathogenesis of familial angioedema associated with estrogen was further explored to find possible factors affecting severity, including polymorphisms in enzymes and receptors related to bradykinin pathways. A placebo-controlled clinical trial of C1INH concentrate in hereditary angioedema patients demonstrated the safety of its use and the efficacy to reduce duration of angioedema attacks. The interaction of innate immunity and adaptive responses was further examined in several reports establishing the significant role of toll-like receptor stimulation for the development of optimal specific antibody responses. The 2009 update of the classification of primary immunodeficiencies introduced over 15 new genetic defects related to the immune response, including DOCK8 mutations responsible for the autosomal recessive form of the hyper IgE syndrome. Other reports expanded the clinical spectrum of disease and improved the characterization of conditions such as warts, hypogammaglobulinemia and myelokathexis (WHIM) syndrome, or the occurrence of mucormycosis and Serratia infections in chronic granulomatous disease. The frequent presentation of gastrointestinal disorders in humoral immunodeficiencies was recognized and recommendations for management were reviewed. Clinical research focused in severe combined immunodeficiency included the development and implementation of a state-wide newborn screening program for this condition, a desired goal considering the significant reduction of mortality rate when diagnosis is made early before opportunistic infections occur. PMID:20226292

  20. Yield of Staging Laparoscopy for Incurable Factors in Chinese Patients with Advanced Gastric Cancer.

    PubMed

    Huang, Jun; Luo, Hongliang; Zhou, Chengliang; Zhan, Jianjun; Rao, Xionghui; Zhao, Gang; Zhu, Zhengming

    2017-06-26

    Although the role of staging laparoscopy (SL) in detecting radiologically occult M1 disease has been widely recognized, it is seldom used in China and its clinical value based on Chinese population has been rarely reported. The aim of this study is to identify the yield of SL for Chinese patients with advanced gastric cancer (AGC) and determine the proportions of patients in whom treatment plan is altered. The clinical data were retrospectively collected from 879 AGC patients who underwent SL without any definite signs of disseminated disease on imaging examination. The primary outcomes were the proportions of patients whose laparoscopy identified incurable factors (including M1 diseases and unresectable T4b diseases), and who had their treatment plan altered. SL revealed incurable factors in 130 (14.8%) patients, including macroscopic peritoneal metastasis (n = 92), positive peritoneal cytology (n = 10), liver metastasis (n = 12), para-aortic lymph node metastasis (n = 1), and unresectable T4b tumor (n = 18). After SL, treatment plans were altered in 123 (14.0%) patients, among which 82 (63.1%) patients were not offered any further procedure and referred for chemotherapy. Among 749 M0 patients who immediately proceeded to radical gastrectomy after SL, new incurable factors were found at subsequent operations in 21 (2.8%) patients. Multivariate analysis showed that tumor size ≥8 cm, Borrmann type III and IV, and tumor invasion of T4a and T4b in preoperative imaging examination were the predictive factors for peritoneal metastasis. SL detects additional incurable factors in Chinese AGC patients with potentially resectable disease and optimizes their treatments. A systematic and painstaking inspection of the whole abdominal cavity, including routine entry into the bursa omentalis, is necessary for improving the yield of SL.

  1. 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

  2. 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.

  3. Advanced management facilities for clinical laboratories.

    PubMed

    van Merode, G G; Hasman, A; Derks, J; Schoenmaker, B; Goldschmidt, H M

    1996-07-01

    As part of the OpenLabs (AIM 2028) programme a decision support system (DSS) for laboratory capacity management has been developed. This DSS contains a simulation module for determining the performance of planning rules given the equipment and staffing of the clinical laboratory and the demand for laboratory services. User requirements are discussed and a method is developed to (re-)define rules concerning various planning decisions. To show the functionality of the simulation module some simulation experiments are described.

  4. Integrative clinical genomics of advanced prostate cancer

    PubMed Central

    Dan, Robinson; Van Allen, Eliezer M.; Wu, Yi-Mi; Schultz, Nikolaus; Lonigro, Robert J.; Mosquera, Juan-Miguel; Montgomery, Bruce; Taplin, Mary-Ellen; Pritchard, Colin C; Attard, Gerhardt; Beltran, Himisha; Abida, Wassim M.; Bradley, Robert K.; Vinson, Jake; Cao, Xuhong; Vats, Pankaj; Kunju, Lakshmi P.; Hussain, Maha; Feng, Felix Y.; Tomlins, Scott A.; Cooney, Kathleen A.; Smith, David C.; Brennan, Christine; Siddiqui, Javed; Mehra, Rohit; Chen, Yu; Rathkopf, Dana E.; Morris, Michael J.; Solomon, Stephen B.; Durack, Jeremy C.; Reuter, Victor E.; Gopalan, Anuradha; Gao, Jianjiong; Loda, Massimo; Lis, Rosina T.; Bowden, Michaela; Balk, Stephen P.; Gaviola, Glenn; Sougnez, Carrie; Gupta, Manaswi; Yu, Evan Y.; Mostaghel, Elahe A.; Cheng, Heather H.; Mulcahy, Hyojeong; True, Lawrence D.; Plymate, Stephen R.; Dvinge, Heidi; Ferraldeschi, Roberta; Flohr, Penny; Miranda, Susana; Zafeiriou, Zafeiris; Tunariu, Nina; Mateo, Joaquin; Lopez, Raquel Perez; Demichelis, Francesca; Robinson, Brian D.; Schiffman, Marc A.; Nanus, David M.; Tagawa, Scott T.; Sigaras, Alexandros; Eng, Kenneth W.; Elemento, Olivier; Sboner, Andrea; Heath, Elisabeth I.; Scher, Howard I.; Pienta, Kenneth J.; Kantoff, Philip; de Bono, Johann S.; Rubin, Mark A.; Nelson, Peter S.; Garraway, Levi A.; Sawyers, Charles L.; Chinnaiyan, Arul M.

    2015-01-01

    SUMMARY Toward development of a precision medicine framework for metastatic, castration resistant prostate cancer (mCRPC), we established a multi-institutional clinical sequencing infrastructure to conduct prospective whole exome and transcriptome sequencing of bone or soft tissue tumor biopsies from a cohort of 150 mCRPC affected individuals. Aberrations of AR, ETS genes, TP53 and PTEN were frequent (40–60% of cases), with TP53 and AR alterations enriched in mCRPC compared to primary prostate cancer. We identified novel genomic alterations in PIK3CA/B, R-spondin, BRAF/RAF1, APC, β-catenin and ZBTB16/PLZF. Aberrations of BRCA2, BRCA1 and ATM were observed at substantially higher frequencies (19.3% overall) than seen in primary prostate cancers. 89% of affected individuals harbored a clinically actionable aberration including 62.7% with aberrations in AR, 65% in other cancer-related genes, and 8% with actionable pathogenic germline alterations. This cohort study provides evidence that clinical sequencing in mCRPC is feasible and could impact treatment decisions in significant numbers of affected individuals. PMID:26000489

  5. 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

  6. [Clinical stages of patients with Alzheimer disease treated in specialist clinics in Spain. The EACE study].

    PubMed

    Alom Poveda, J; Baquero, M; González-Adalid Guerreiro, M

    2013-10-01

    The diagnostic paradigm of Alzheimer disease (AD) is changing; there is a trend toward diagnosing the disease in its early stages, even before the complete syndrome of dementia is apparent. The clinical stage at which AD is usually diagnosed in our area is unknown. Therefore, the purpose of this study is to describe the clinical stages of AD patients at time of diagnosis. Multicentre, observational and cross-sectional study. Patients with probable AD according to NINCDS-ARDRA criteria, attended in specialist clinics in Spain, were included in the study. We recorded the symptom onset to evaluation and symptom onset to diagnosis intervals and clinical status of AD (based on MMSE, NPI questionnaire, and CDR scale). Participants in this study included 437 specialists representing all of Spain's autonomous communities and a total of 1,707 patients, of whom 1,694 were included in the analysis. Mean MMSE score was 17.6±4.8 (95% CI:17.4-17.9). Moderate cognitive impairment (MMSE between 10 and 20) was detected in 64% of the patients, and severe cognitive impairment (MMSE<10) in 6%. The mean interval between symptom onset and the initial primary care visit was 10.9±17.2 months (95% CI:9.9-11.8), and the interval between symptom onset and diagnosis with AD was 28.4±21.3 months. Results from the EACE show that most AD patients in our area have reached a moderate clinical stage by the time they are evaluated in a specialist clinic. Copyright © 2012 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  7. Clinical Research Informatics: Recent Advances and Future Directions

    PubMed Central

    2015-01-01

    Summary Objectives To summarize significant developments in Clinical Research Informatics (CRI) over the past two years and discuss future directions. Methods Survey of advances, open problems and opportunities in this field based on exploration of current literature. Results Recent advances are structured according to three use cases of clinical research: Protocol feasibility, patient identification/recruitment and clinical trial execution. Discussion CRI is an evolving, dynamic field of research. Global collaboration, open metadata, content standards with semantics and computable eligibility criteria are key success factors for future developments in CRI. PMID:26293865

  8. Public Funding of Clinical-Stage Antibiotic Development in the United States and European Union

    PubMed Central

    2015-01-01

    The health and national security challenge of antibiotic resistance has led governments to adopt policies to stimulate new antibiotic R&D. Government programs that directly fund late-stage clinical development of antibiotics have emerged, including the Broad Spectrum Antimicrobial Program of the Biomedical Advanced Research and Development Authority in the United States, and the New Drugs for Bad Bugs program of the Innovative Medicines Initiative in the European Union. These efforts are collectively investing nearly $1 billion and are supporting nearly 20% of the global antibiotic pipeline. This article describes these programs, including the antibiotics and their targeted pathogens and clinical indications, as well as program mechanisms for project eligibility, selection, governance, funding, and IP management. Preliminary assessment of the impact of these mechanisms on the success of the programs is provided. PMID:26042859

  9. Public funding of clinical-stage antibiotic development in the United States and European Union.

    PubMed

    Eichberg, Michael J

    2015-01-01

    The health and national security challenge of antibiotic resistance has led governments to adopt policies to stimulate new antibiotic R&D. Government programs that directly fund late-stage clinical development of antibiotics have emerged, including the Broad Spectrum Antimicrobial Program of the Biomedical Advanced Research and Development Authority in the United States, and the New Drugs for Bad Bugs program of the Innovative Medicines Initiative in the European Union. These efforts are collectively investing nearly $1 billion and are supporting nearly 20% of the global antibiotic pipeline. This article describes these programs, including the antibiotics and their targeted pathogens and clinical indications, as well as program mechanisms for project eligibility, selection, governance, funding, and IP management. Preliminary assessment of the impact of these mechanisms on the success of the programs is provided.

  10. Clinically relevant advances in rheumatoid arthritis therapy.

    PubMed

    Müller-Ladner, Ulf; Neumann, Elena; Tarner, Ingo H

    2009-09-14

    Owing to the success of biologics in the treatment of rheumatoid arthritis (RA), several novel drugs have been introduced in the therapeutic armamentarium, although not all of them have been approved in all countries worldwide. Among the drugs are tumour necrosis factor (TNF) inhibitors such as certolizumab pegol and golimumab (the latter of which was the first TNF blocker shown to be effective in patients who had been unsuccessfully treated with other TNF blockers and which can be applied only once a month), and the interleukin-6 receptor antagonist tocilizumab, which not only opens up a completely new field of anti-inflammatory modulation of RA pathophysiology, but also highlights the challenge of novel potential side effects. Moreover, aside from clinical studies showing efficacy in the inhibition of osteoclast activation by the anti-RANKL (receptor activator of nuclear factor-kappa B ligand) antibody denosumab, an improved form of steroid application known as slow-release 'tempus tablet' for treatment of RA and several developments in the small-molecule area have been addressed by clinical trials.

  11. Advanced Development Program for a 625 lbf thrust engine for Ares First Stage Roll Control System

    NASA Technical Reports Server (NTRS)

    Dawson, Matt; Chenevert, Blake; Brewster, Gerry; Frei, Tom; Bullard, Brad; Fuller, Ray

    2009-01-01

    NASA's new Ares Launch Vehicle will require twelve thrusters to provide roll control of the vehicle during the first stage firing. All twelve roll control thrusters will be located at the inter-stage segment that separates the solid rocket booster first stage from the second stage. NASA selected a mono propellant hydrazine solution and as a result awarded Aerojet-General a contract in 2007 for an advanced development program for an MR-80- series 625 Ibf vacuum thrust monopropellant hydrazine thruster. This thruster has heritage dating back to the 1976 Viking Landers and most recently for the 2011 Mars Science Laboratory. Prior to the Ares application, the MR-80-series thrusters had been equipped with throttle valves and not typically operated in pulse mode. The primary objective of the advanced development program was to increase the technology readiness level and retire major technical risks for the future flight qualification test program. Aerojet built on their heritage MR-80 rocket engine designs to achieve the design and performance requirements. Significant improvements to cost and lead-time were achieved by applying Design for Manufacturing and Assembly (DFMA) principles. AerojetGeneral has completed Preliminary and Critical Design Reviews, followed by two successful rocket engine development test programs. The test programs included qualification random vibration and firing lite that significantly exceed the flight qualification requirements. This paper discusses the advanced development program and the demonstrated capability of the MR-80C engine. Y;

  12. Advanced Development Program for a 625 lbf thrust engine for Ares First Stage Roll Control System

    NASA Technical Reports Server (NTRS)

    Dawson, Matt; Chenevert, Blake; Brewster, Gerry; Frei, Tom; Bullard, Brad; Fuller, Ray

    2009-01-01

    NASA's new Ares Launch Vehicle will require twelve thrusters to provide roll control of the vehicle during the first stage firing. All twelve roll control thrusters will be located at the inter-stage segment that separates the solid rocket booster first stage from the second stage. NASA selected a mono propellant hydrazine solution and as a result awarded Aerojet-General a contract in 2007 for an advanced development program for an MR-80- series 625 Ibf vacuum thrust monopropellant hydrazine thruster. This thruster has heritage dating back to the 1976 Viking Landers and most recently for the 2011 Mars Science Laboratory. Prior to the Ares application, the MR-80-series thrusters had been equipped with throttle valves and not typically operated in pulse mode. The primary objective of the advanced development program was to increase the technology readiness level and retire major technical risks for the future flight qualification test program. Aerojet built on their heritage MR-80 rocket engine designs to achieve the design and performance requirements. Significant improvements to cost and lead-time were achieved by applying Design for Manufacturing and Assembly (DFMA) principles. AerojetGeneral has completed Preliminary and Critical Design Reviews, followed by two successful rocket engine development test programs. The test programs included qualification random vibration and firing lite that significantly exceed the flight qualification requirements. This paper discusses the advanced development program and the demonstrated capability of the MR-80C engine. Y;

  13. Personalizing Drug Selection Using Advanced Clinical Decision Support.

    PubMed

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

    2009-06-23

    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.

  14. 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

  15. 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

  16. 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.

  17. Advances in Clinical PET/MRI Instrumentation.

    PubMed

    Herzog, Hans; Lerche, Christoph

    2016-04-01

    In 2010, the first whole-body PET/MRI scanners installed for clinical use were the sequential Philips PET/MRI with PMT-based, TOF-capable technology and the integrated simultaneous Siemens PET/MRI. Avalanche photodiodes as non-magneto-sensitive readout electronics allowed PET integrated within the MRI. The experiences with these scanners showed that improvements of software aspects, such as attenuation correction, were necessary and that efficient protocols combining optimally PET and MRI must be still developed. In 2014, General Electric issued an integrated PET/MRI with SiPM-based PET detectors, allowing TOF-PET. Looking at the MRI components of current PET/MR imaging systems, primary improvements come from sequences and new coils.

  18. Advance modern medicine with clinical case reports

    PubMed Central

    2014-01-01

    Randomized clinical trial (RCT) can fail to demonstrate the richness of individual patient characteristics. Given the unpredictable nature of medicine, a patient may present in an unusual way, have a strange new pathology, or react to a medical intervention in a manner not seen before. The publication of these novelties as case reports is a fundamental way of conveying medical knowledge. Throughout history there have been famous case studies that shaped the way we view health and disease. Case reports can have the following functions: (I) descriptions of new diseases; (II) study of mechanisms; (III) discovery new therapies; (IV) recognition of side effects; and (V) education. Before submitting a case report, it is worthwhile to refer to the Case Report Check Sheet described by Green and Johnson [2006]. PMID:25525572

  19. Advances in Clinical Management of Eosinophilic Esophagitis

    PubMed Central

    Dellon, Evan S.; Liacouras, Chris A.

    2014-01-01

    EoE is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. It is diagnosed based on symptoms of esophageal dysfunction, the presence of at least 15 eosinophils/high-power field in esophageal biopsies, and exclusion of competing causes of esophageal eosinophilia, including proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE). We review what we have recently learned about the clinical aspects of EoE, discussing the clinical, endoscopic, and histologic features of EoE in adults and children. We explain the current diagnostic criteria and challenges to diagnosis, including the role of gastroesophageal reflux disease and PPI-REE. It is also important to consider the epidemiology of EoE (current incidence of 1/10,000 new cases per year and prevalence of 0.5-1/1,000 cases per year) and disease progression. We review the main treatment approaches and new treatment options; EoE can be treated with topical corticosteroids such as fluticasone and budesonide, or dietary strategies, such as amino acid-based formulas, allergy test-directed elimination diets, and non-directed empiric elimination diets. Endoscopic dilation has also become an important tool for treatment of fibrostenostic complications of EoE. There are number of unresolved issues in EoE, including phenotypes, optimal treatment endpoints, the role of maintenance therapy, and treatment of refractory EoE. The care of patients with EoE and the study of the disease span many disciplines—EoE is ideally managed by a multidisciplinary team of gastroenterologists, allergists, pathologists, and dieticians. PMID:25109885

  20. Reusable launch vehicles, enabling technology for the development of advanced upper stages and payloads

    SciTech Connect

    Metzger, John D.

    1998-01-15

    In the near future there will be classes of upper stages and payloads that will require initial operation at a high-earth orbit to reduce the probability of an inadvertent reentry that could result in a detrimental impact on humans and the biosphere. A nuclear propulsion system, such as was being developed under the Space Nuclear Thermal Propulsion (SNTP) Program, is an example of such a potential payload. This paper uses the results of a reusable launch vehicle (RLV) study to demonstrate the potential importance of a Reusable Launch Vehicle (RLV) to test and implement an advanced upper stage (AUS) or payload in a safe orbit and in a cost effective and reliable manner. The RLV is a horizontal takeoff and horizontal landing (HTHL), two-stage-to-orbit (TSTO) vehicle. The results of the study shows that an HTHL is cost effective because it implements airplane-like operation, infrastructure, and flight operations. The first stage of the TSTO is powered by Rocket-Based-Combined-Cycle (RBCC) engines, the second stage is powered by a LOX/LH rocket engine. The TSTO is used since it most effectively utilizes the capability of the RBCC engine. The analysis uses the NASA code POST (Program to Optimize Simulated Trajectories) to determine trajectories and weight in high-earth orbit for AUS/advanced payloads. Cost and reliability of an RLV versus current generation expandable launch vehicles are presented.

  1. The Influence of Social Norms on Advancement Through Bystander Stages for Preventing Interpersonal Violence.

    PubMed

    Deitch-Stackhouse, Jacqueline; Kenneavy, Kristin; Thayer, Richard; Berkowitz, Alan; Mascari, Janine

    2015-10-01

    This research evaluates the impact of social norms on the advancement through the bystander stages toward prosocial (active) intervention in interpersonal violence (IPV): emotional abuse, physical violence, controlling behavior, sexual violence, and stalking. The influence of social norms on bystander behavior across stages and types of violence varies. Accurate social norms perceptions are associated with routine intervention, although social norms misperceptions are not always a strong deterrent to intervention. Interpretation of a violent situation as problematic predicts increased willingness to intervene. Implications for the development of social norms antiviolence campaigns and strategies for reducing barriers to prosocial intervention are discussed. © The Author(s) 2015.

  2. Analytical Protein Microarrays: Advancements Towards Clinical Applications.

    PubMed

    Sauer, Ursula

    2017-01-29

    Protein microarrays represent a powerful technology with the potential to serve as tools for the detection of a broad range of analytes in numerous applications such as diagnostics, drug development, food safety, and environmental monitoring. Key features of analytical protein microarrays include high throughput and relatively low costs due to minimal reagent consumption, multiplexing, fast kinetics and hence measurements, and the possibility of functional integration. So far, especially fundamental studies in molecular and cell biology have been conducted using protein microarrays, while the potential for clinical, notably point-of-care applications is not yet fully utilized. The question arises what features have to be implemented and what improvements have to be made in order to fully exploit the technology. In the past we have identified various obstacles that have to be overcome in order to promote protein microarray technology in the diagnostic field. Issues that need significant improvement to make the technology more attractive for the diagnostic market are for instance: too low sensitivity and deficiency in reproducibility, inadequate analysis time, lack of high-quality antibodies and validated reagents, lack of automation and portable instruments, and cost of instruments necessary for chip production and read-out. The scope of the paper at hand is to review approaches to solve these problems.

  3. Analytical Protein Microarrays: Advancements Towards Clinical Applications

    PubMed Central

    Sauer, Ursula

    2017-01-01

    Protein microarrays represent a powerful technology with the potential to serve as tools for the detection of a broad range of analytes in numerous applications such as diagnostics, drug development, food safety, and environmental monitoring. Key features of analytical protein microarrays include high throughput and relatively low costs due to minimal reagent consumption, multiplexing, fast kinetics and hence measurements, and the possibility of functional integration. So far, especially fundamental studies in molecular and cell biology have been conducted using protein microarrays, while the potential for clinical, notably point-of-care applications is not yet fully utilized. The question arises what features have to be implemented and what improvements have to be made in order to fully exploit the technology. In the past we have identified various obstacles that have to be overcome in order to promote protein microarray technology in the diagnostic field. Issues that need significant improvement to make the technology more attractive for the diagnostic market are for instance: too low sensitivity and deficiency in reproducibility, inadequate analysis time, lack of high-quality antibodies and validated reagents, lack of automation and portable instruments, and cost of instruments necessary for chip production and read-out. The scope of the paper at hand is to review approaches to solve these problems. PMID:28146048

  4. ADVANCES IN BASIC AND CLINICAL IMMUNOLOGY 2013

    PubMed Central

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

    2014-01-01

    A significant number of contributions to our understanding of primary immunodeficiencies in pathogenesis, diagnosis and treatment were published in the Journal in 2013. For example, deficiency of mast cell degranulation due to STAT3 deficiency was demonstrated to contribute to the difference on frequency of severe allergic reactions in AD-HIES patients, compared to atopic individuals with similar high IgE serum levels. High levels of non-glycosylated IgA were found in WAS patients and these abnormal antibodies might contribute to nephropathy in WAS. New described genes causing immunodeficiency included caspase recruitment domain 11 (CARD11), mucosa-associated lymphoid tissue 1 (MALT1) for combined immunodeficiencies, and tetratricopeptide repeat domain 7A (TTC7A) for mutations associated to multiple atresia with combined immunodeficiency. Other observations expand the spectrum of clinical presentation of specific genes. (e.g., adult onset idiopathic T-cell lymphopenia and early onset autoimmunity might be due to hypomorphic mutations of the RAG genes). Newborn screening in California established incidence of SCID at 1/66,250 live births. The use of HSCT for primary immunodeficiencies was reviewed, with recommendations to give priority to research oriented to establish best regimens to improve safety and efficacy of bone marrow transplantation. These represent only a fraction of significant research done in primary immunodeficiencies that has accelerated the quality of care of these patients. Genetic analysis of patients has demonstrated multiple phenotypic expressions of immune deficiency in patients with nearly identical genotypes, suggesting that additional genetic factors, possibly gene dosage, or environmental factors are responsible for this diversity. PMID:24589342

  5. Stereotactic ablative radiotherapy for stage I NSCLC: Recent advances and controversies

    PubMed Central

    Senan, Suresh; Palma, David A.; Lagerwaard, Frank J.

    2011-01-01

    Stereotactic ablative radiotherapy (SABR) is a technique that has rapidly entered routine care for early-stage peripheral non-small cell lung cancer in many countries in the last decade. The adoption of SABR was partly stimulated by advances in the so-called ‘image guided’ radiotherapy delivery. In the last 2 years, a growing body of publications has reported on clinical outcomes, acute and late radiological changes after SABR, and sub-acute and late toxicity. The local control rates in many publications have exceeded 90% when tumors of up to 5 cm have been treated, with corresponding regional nodal failure rates of approximately 10%. However, these results are not universal: lower control rates reported by some authors serve to emphasize the importance of quality assurance in all steps of SABR treatment planning and delivery. High-grade toxicity is uncommon when so-called ‘risk-adapted’ fractionation schemes are applied; an approach which involves the use of lower daily doses and more fractions when critical normal organs are in the proximity of the tumor volume. This review will address the new data available on a number of controversial topics such as the treatment of patients without a tissue diagnosis of malignancy, data on SABR outcomes in patients with severe chronic obstructive airways disease, use of a classification system for late radiological changes post-SABR, late treatment-related toxicity, and the evidence to support a need for expert multi-disciplinary teams in the follow-up of such patients. PMID:22263087

  6. Investigation of Advanced Propellants to Enable Single Stage to Orbit Launch Vehicles

    DTIC Science & Technology

    2006-10-30

    Jeigh Shelley Department of Mechanical Engineering Raymond Moszée Air Force Research Laboratory ABSTRACT INVESTIGATION OF ADVANCED...Engineering Raymond Moszée Air Force Research Laboratory For the University Graduate Committee: Dean, Division of Graduate Studies...September 2005. 33. Bayer , M.J., “Comparative Assessment of Rocket-Propelled Single-Stage-to- Orbit Concepts,” Journal of Spacecraft and Rockets, Vol. 40

  7. Phase I trial of daily triapine in combination with cisplatin chemotherapy for advanced-stage malignancies.

    PubMed

    Kunos, Charles A; Chu, Edward; Beumer, Jan H; Sznol, Mario; Ivy, S Percy

    2017-01-01

    Advanced-stage malignancies have increased deoxyribonucleotide demands in DNA replication and repair, making deoxyribonucleotide supply a potential exploitable target for therapy based on ribonucleotide reductase (RNR) inhibition. A dose-finding phase I trial was conducted of intravenous (i.v.) triapine, a small-molecule RNR inhibitor, and cisplatin chemotherapy in patients with advanced-stage solid tumor malignancies. Patients received dose-finding levels of i.v. triapine (48-96 mg/m(2)) and i.v. cisplatin (20-75 mg/m(2)) on 1 of 3 different schedules. The primary endpoint was to identify the maximum tolerated dose of a triapine-cisplatin combination. Secondary endpoints included the rate of triapine-cisplatin objective response and the pharmacokinetics and bioavailability of a single oral triapine dose. (Clinicaltrials.gov number, NCT00024323). The MTD was 96 mg/m(2) triapine daily days 1-4 and 75 mg/m(2) cisplatin split over day 2 and day 3. Frequent grade 3 or 4 adverse events included fatigue, dyspnea, leukopenia, thrombocytopenia, and electrolyte abnormalities. No objective responses were observed; 5 (50%) of 10 patients treated at the MTD had stable disease. Pharmacokinetics indicated an oral triapine bioavailability of 88%. The triapine-cisplatin combination may be given safely in patients with advanced-stage solid tumor malignancies. On the basis of these results, a phase I trial adequately powered to evaluate oral triapine bioavailability in women with advanced-stage uterine cervix or vulvar cancers is underway.

  8. Stages of Change for the Component Behaviors of Advance Care Planning

    PubMed Central

    Fried, Terri R.; Redding, Colleen; Robbins, Mark; Paiva, Andrea; O’Leary, John R.; Iannone, Lynne

    2010-01-01

    Objectives 1) To develop stages of change measures for advance care planning (ACP), conceptualized as a group of interrelated but separate behaviors. 2) To use these measures to characterize older persons’ engagement in and factors associated with readiness to participate in ACP. Design Observational cohort study. Setting Community. Participants Persons age ≥ 65 recruited from physician offices and a senior center. Measurements Stages of change for six ACP behaviors: completion of a living will and health care proxy, communication with loved ones regarding use of life-sustaining treatments and quantity versus quality of life (QOL), and communication with physicians about these same issues. Results Readiness to participate in ACP varied widely across behaviors. Whereas between approximately 50–60% of participants were in the action or maintenance stage for communicating with loved ones and completing a living will, 40% were in the precontemplation stage for communicating with loved ones about quantity versus QOL, and 70–75% were in the precontemplation stage for communicating with physicians. Participants were frequently in different stages for the different behaviors. Relatively few sociodemographic, health, or psychosocial factors were associated with stages of change for completing a living will, but a broader range of factors was associated with stages of change for communication with loved ones about quantity versus QOL. Conclusion Older persons show a range of readiness to engage in different aspects of ACP. Individualized assessment and interventions targeted to stage of behavior change for each component of ACP may be an effective strategy to increase participation in ACP. PMID:21143441

  9. Clinical update: communication issues and advance care planning.

    PubMed

    Moore, Crystal Dea; Reynolds, Ashley M

    2013-11-01

    To provide a clinical update on practical strategies to enhance the quality of communication in the palliative and end-of-life medical care settings. Published articles, textbooks, reports, and clinical experience. The components of effective and compassionate care throughout the advanced illness trajectory require thoughtful and strategic communication with patients, families, and members of the health care team. Unfortunately, few health care professionals are formally trained in communication skills. Nurses who possess self-awareness and are skilled in effective communication practices are integral to the provision of high-quality palliative care for patients and families coping with advanced malignancies. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. 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.

  11. Controversies on the prognostic value of interim FDG-PET in advanced-stage Hodgkin lymphoma.

    PubMed

    Adams, Hugo J A; Kwee, Thomas C

    2016-12-01

    Hodgkin lymphoma, even in advanced-stage, is a highly curable malignancy, but treatment is associated with short-term toxicity and long-term side effects. Early predictive markers are required to identify those patients who do not require the full-length standard therapy (and thus qualify for therapy de-escalation) and those patients who will not be cured by standard therapy (and thus qualify for therapy escalation). Multiple trials have assessed the value of (18) F-fluoro-2-deoxy-d-glucose positron emission tomography (FDG-PET) after a few cycles of chemotherapy (also known as 'interim FDG-PET') in predicting outcome in advanced-stage Hodgkin lymphoma. Furthermore, multiple interim FDG-PET-adapted trials, in which patients with positive interim FDG-PET scans are assigned to escalated therapies, and patients with negative interim FDG-PET scans are assigned to de-escalated therapies, have recently been published or are currently ongoing, with generally heterogeneous results. The present article reports the currently available evidence (and controversies) on the prognostic value of interim FDG-PET in advanced-stage Hodgkin lymphoma in patients with positive and negative interim FDG-PET findings following continuation of standard chemotherapy or escalated/de-escalated therapy. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. 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.

  13. Global strategies for the treatment of early-stage and advanced cervical cancer.

    PubMed

    Dueñas-González, Alfonso; Campbell, Sergio

    2016-02-01

    Recent peer-reviewed publications on the treatment of early, locally advanced and advanced cervical cancer patients are reviewed to gain insight into the main research done in the field. In early-stage patients where cure is offered to most patients, research focuses on more conservative or less morbid approaches to increase quality of life and reduce the treatment-related sexual dysfunction. No major advances have occurred for treating locally advanced disease since the introduction of concurrent chemoradiation, but efforts are directed to increase efficacy while reducing toxicity with the use of combination chemoradiation and modern radiation technologies. Molecular-targeted therapy and identification of targetable gene alterations as well as immunotherapy are actively pursued in patients with advanced disease. Although global statistics indicate a trend for decreased age-standardized incidence rates, social and economical factors impede the uptake of therapeutic advances achieved as many patients have no access even to basic resources for treating cancer. The adherence to quality indicators in delivery of optimized standard concurrent chemoradiation and adherence to guidelines in cervical cancer surgery must not be underestimated. Major efforts are needed in both the scientific and social aspects of cervical cancer treatment to reduce mortality.

  14. Treatment results in women with clinical stage I and pathologic stage II endometrial carcinoma.

    PubMed

    Jobsen, J J; Schutter, E M; Meerwaldt, J H; Van Der Palen, J; Van Der Sijde, R; Ten Cate, L N

    2001-01-01

    The aim of this study is to report survival and results of therapy and possible prognostic factors in women with pathologic stage II endometrial carcinoma. Forty-two patients with pathologic stage II endometrial carcinoma were treated at the department of Radiation Oncology of the Medisch Spectrum Twente between 1987 and 1998. All patients received external radiotherapy following standard surgical procedures and no adjuvant systemic therapy was given. From the 42 patients 21 had a pathologic stage IIA and 21 stage IIB. The median follow-up was 62 months. The overall recurrence rate was 21.5% (9/42). Seven patients had distant metastasis, of which three also had locoregional recurrence, vaginal vault and/or pelvic. The presence of myometrial invasion (> (1/2)) and/or lymph-angioinvasion showed a significant relation with distant metastasis (P = 0.017). Stage IIB showed more recurrences, 33% (7/21). There was a significant different 5-year disease specific survival for stage IIA and IIB, respectively, 95% and 74% (P = 0.0311). Patients with a differentiation grade 3 and stage IIB showed a significantly poorer (P = 0.003) 5-year survival of 48.6% (P = 0.003). Results obtained in the present series of patients are in accordance with the literature. The present treatment policy seems justified, except for patients with pathologic stage IIB and grade 3, in which a more aggressive treatment should be considered.

  15. Advanced clinical technology--clinical tool or expensive toy?

    PubMed

    Ganz, C H

    1995-10-01

    There should no longer be any doubt in dentists' minds when it comes to the importance of technology in the day-to-day activities of the dental office. But there is, and this doubt must be addressed if the profession is to grow and prosper to its full potential. Denying the importance of technology--or putting on blinders--only leads to complacency, and clearly does not support our professions goal of providing the finest dental care possible. This article addresses the use of technology in a clinically-related manner, and attempts to provide the practitioner with valuable practice management tools to allow for a prosperous and efficient dental practice.

  16. Symposium on research advances in clinical PET. Final performance report

    SciTech Connect

    J. Michael McGehee

    1992-01-01

    The Institute for Clinical PET and the U.S. Department of Energy (DOE) co-sponsored a symposium entitled 'Research in PET: International and Institutional Perspectives' that highlighted the activities of many leading investigators in the U.S. and throughout the world. Research programs at the DOE were discussed as were potential directions of PET research. International as well as institutional perspectives on PET research were presented. This symposium was successful in reaching those interested in research advances of clinical PET.

  17. 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…

  18. Extended surgical resections of advanced thymoma Masaoka stages III and IVa facilitate outcome.

    PubMed

    Ried, Michael; Potzger, Tobias; Sziklavari, Zsolt; Diez, Claudius; Neu, Reiner; Schalke, Berthold; Hofmann, Hans-Stefan

    2014-03-01

    Extended thymoma resections including adjacent structures and pleurectomy/decortication (P/D) with hyperthermic intrathoracic chemotherapy (HITHOC) perfusion were performed in a multidisciplinary treatment regime. Between July 2000 and February 2012, 22 patients with Masaoka stage III (n = 9; 41%) and Masaoka stage IVa (n = 13; 59%) thymic tumors were included. Mean age was 55 years (25-84 years) and 50% (11 out of 22) of patients were female. World Health Organization histological classification was as follows: B2 (n = 15), A (n = 1), B1 (n = 1), B3 (n = 2), and thymic carcinoma (C; n = 3). Radical thymectomy and partial resection of the mediastinal pleura and pericardium were performed. Of the 13, 9 patients with pleural involvement (stage IVa) received radical P/D followed by HITHOC (cisplatin). Macroscopic complete resection (R0/R1) was achieved in 19 (86%) patients. All patients received multimodality treatment depending on tumor stage, histology, and completeness of resection. Thirty-day mortality was 0% and three (13.6%) patients needed operative revision. Recurrence of thymoma was documented in five (22.7%) patients (stage III, n = 1; stage IVa, n = 4). Mean disease-free interval of patients with complete resection (n = 14 out of 22) was 30.2 months. After a mean follow-up of 29 months, 18 out of the 22 (82%) patients are alive. After P/D and HITHOC, 89% (8 out of 9 patients) are alive (current median survival is 25 months) without recurrence. Extended surgical resection of advanced thymic tumors infiltrating adjacent structures (stage III) or with pleural metastases (stage IVa) is safe and feasible. It provides a low recurrence rate and an acceptable survival. Additional HITHOC in patients with pleural thymoma spread seems to offer a better local tumor control. Georg Thieme Verlag KG Stuttgart · New York.

  19. Quality of life among long-term survivors of advanced stage ovarian cancer: A cross-sectional approach.

    PubMed

    Lutgendorf, Susan K; Shinn, Eileen; Carter, Jeanne; Leighton, Susan; Baggerly, Keith; Guindani, Michele; Fellman, Bryan; Matzo, Marianne; Slavich, George M; Goodman, Marc T; Tew, William; Lester, Jenny; Moore, Kathleen M; Karlan, Beth Y; Levine, Douglas A; Sood, Anil K

    2017-07-01

    Long-term survival of women with advanced-stage ovarian cancer is relatively rare. Little is known about quality of life (QOL) and survivorship concerns of these women. Here, we describe QOL of women with advanced-stage ovarian cancer surviving for 8.5 years or longer and compare women with 0-1 recurrence to those with multiple recurrences. Participants (n=56) recruited from 5 academic medical centers and the Ovarian Cancer Research Fund Alliance completed surveys regarding QOL (FACT-O), mood (CESD), social support (SPS), physical activity (IPAQ-SF), diet, and clinical characteristics. Median survival was 14.0 years (range 8.8-33.3). QOL and psychological adjustment of long-term survivors was relatively good, with mean FACT-G scores (multiple recurrences: 80.81±13.95; 0-1 recurrence: 89.05 ±10.80) above norms for healthy community samples (80.1±18.1). Survivors with multiple recurrences reported more compromised QOL in domains of physical and emotional well-being (p <.05), and endorsed a variety of physical and emotional concerns compared to survivors with 0-1 recurrence. Difficulties in sexual functioning were common in both groups. Almost half (43%) of the survivors reported low levels of physical activity. Overall, women with advanced-stage ovarian cancer who have survived at least 8.5 years report good QOL and psychological adjustment. QOL of survivors with multiple recurrences is somewhat impaired compared to those with 0-1 recurrence. Limitations include a possible bias towards participation by healthier survivors, thus under-representing the level of compromise in long-term survivors. Health care practitioners should be alert to psychosocial issues faced by these long-term survivors to provide interventions that enhance QOL. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. [Comparison between clinical and surgical-pathological TNM staging in patients with lung cancer].

    PubMed

    Wei, Bo; Wang, Tianyou; Gong, Min; Lv, Kejie; Tian, Feng; Wang, Zhicheng

    2005-02-20

    The accuracy of clinical TNM staging correlates with appropriate treatment in patients with lung cancer. The aim of this study is to evaluate the agreement between clinical and surgical-pathological staging in patients with lung cancer and analyze its cause in detail. One hundred and fifty patients with lung cancer treated surgically from 2000 were enrolled randomly. Clinical and surgical-pathological staging of them were made respectively according to the International System for Staging Lung Cancer newly revised by UICC. Then concordance was determined between the two staging results with Kappa value, and difference in coincident rate was analyzed among subgroups of T staging. For T staging, the agreement was excellent (Kappa value=0.729), however, the coincident rate of T3 or T4 was significantly lower than that in T1 or T2 group (P < 0.01). The agreement of N staging was poor (Kappa value=0.108), followed by a disappointed conformity of TNM staging (Kappa value=0.287). Clinical T staging based on CT can indicate the location and size of primary tumor precisely. But the borderline may be difficult to estimate when tumor site is near chest wall or mediastinum, so some patients with clinical T4 still have chances to receive complete resection. The conformity of N staging is rather poor. The key point to improve the accuracy of clinical TNM staging should be to seek more reliable techniques for evaluating N status.

  1. Prognostic value of programmed death ligand 1, p53, and Ki-67 in patients with advanced stage colorectal cancer.

    PubMed

    Wang, Lisha; Liu, Zebing; Fisher, Kurt W; Ren, Fei; Lv, Jiaojie; Davidson, Darrell D; Baldridge, Lee A; Du, Xiang; Cheng, Liang

    2017-08-04

    Current prognostic indicators are ineffective for identifying advanced stage colorectal cancer (CRC) patients with high risk of recurrence after surgical resection. We investigated the prognostic value of p53, Ki-67, and programmed death ligand 1 (PD-L1) in 254 patients with stage II and III CRC. The expression of p53 was positive in 63% of cases. Up-regulation of p53 was associated with smaller tumor size (P=.001) and higher Ki-67 labeling index (LI) (P=.031). The tumor Ki-67 LI was high (≥ 20%) in 197 (78%) of the patients. High Ki-67 LI was associated with higher TNM stage (P=.031), positive p53 expression (P=.031), and negative PD-L1 expression (P=.003). The five-year relapse-free survivals (RFS) were 53% and 89%, respectively, for the p53-positive and Ki-67 LI-high patients and the p53-negative and Ki-67 LI-low patients (P<.001). In univariate analysis, negative p53 (P=.001), low Ki-67 LI (P=.006), low PD-L1 expression (P=.044), low TNM stage (P<.001), recto-sigmoid location (P=.026), and small size (P=.013) were significantly related to RFS. In multivariate Cox regression analysis, positive p53 expression (hazard ratio [HR]: 2.48; 95% confidence interval: 1.34-4.59, P=.004), high Ki-67 LI (HR: 2.62; 95% CI: 1.12-6.14, P=.027) and high TNM stage (HR: 2.598, 95% CI: 1.55-4.37, P<.001,) were independent predictors of unfavorable prognosis. In summary, PD-L1, Ki-67, and p53 staining individually had significant prognostic value for patients with stage II and III CRC. Moreover, combining p53 H-score≥35 and Ki-67 LI≥20% identifies patients with poor clinical outcome. Copyright © 2017. Published by Elsevier Inc.

  2. 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…

  3. 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…

  4. Psychometric Advances in Measuring Clinical Problem-Solving Skills.

    ERIC Educational Resources Information Center

    Gross, Leon J.

    1981-01-01

    Advances have been made in testing optometrists' clinical skills, particularly with the use of simulation techniques. Further research into these techniques will probably receive the most attention, although a shift in research emphasis from correlational studies of test validity and reliability to test development studies is needed. (MSE)

  5. 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.

  6. 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.

  7. 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.

  8. Recent advances in dengue pathogenesis and clinical management.

    PubMed

    Simmons, Cameron P; McPherson, Kirsty; Van Vinh Chau, Nguyen; Hoai Tam, D T; Young, Paul; Mackenzie, Jason; Wills, Bridget

    2015-12-10

    This review describes and commentates on recent advances in the understanding of dengue pathogenesis and immunity, plus clinical research on vaccines and therapeutics. We expand specifically on the role of the dermis in dengue virus infection, the contribution of cellular and humoral immune responses to pathogenesis and immunity, NS1 and mechanisms of virus immune evasion. Additionally we review a series of therapeutic intervention trials for dengue, as well as recent clinical research aimed at improving clinical diagnosis, risk prediction and disease classification. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Bacteriophage Therapy: Advances in Formulation Strategies and Human Clinical Trials.

    PubMed

    Vandenheuvel, Dieter; Lavigne, Rob; Brüssow, Harald

    2015-11-01

    Recently, a number of phage therapy phase I and II safety trials have been concluded, showing no notable safety concerns associated with the use of phage. Though hurdles for efficient treatment remain, these trials hold promise for future phase III clinical trials. Interestingly, most phage formulations used in these clinical trials are straightforward phage suspensions, and not much research has focused on the processing of phage cocktails in specific pharmaceutical dosage forms. Additional research on formulation strategies and the stability of phage-based drugs will be of key importance, especially with phage therapy advancing toward phase III clinical trials.

  10. Analysis of Outcome of Intraplueral Streptokinase in Pediatric Empyema Thoracis even in Advanced Stages: A Prospective Study

    PubMed Central

    Bose, Kallol; Saha, Sudip; Mridha, Dhrubojyoti; Das, Kallol; Mondal, Piyasi; Das, Ira

    2015-01-01

    Background: Empyema thoracis in children causes significant morbidity. Standard treatment of Empyema thoracis includes tube drainage and antibiotics. But the tube drainage often fails. Intrapleural Streptokinase has been used in empyema thoracis with good success rate. Objectives: We evaluated the efficacy of intra-pleural Streptokinase in management of empyema thoracis even in advanced stages. Patients and Methods: A total of 28 patients with empyema thoracis requiring intercostal tube drainage aged zero to twelve years were included in the study who were admitted in Pediatric intensive care unit. 15,000 units/kg of Streptokinase was instilled into the pleural cavity. Response was assessed by clinical outcome, after unclamping and subsequent chest radiography and serial chest ultrasounds. Results: Streptokinase enhanced drainage in all patients with complete resolution of empyema thoracis in 26 patients. Two patients were referred for surgery. Only 7.2% required surgery. Streptokinase was equally effective if started before or after seven days. Conclusions: Intrapleural Streptokinase is the preferred treatment for treating pediatric empyema thoracis even in advanced stages and can avoid surgery. PMID:26495096

  11. 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.

  12. 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.

  13. Comparison of Lower Extremity Edema in Locally Advanced Cervical Cancer: Pretreatment Laparoscopic Surgical Staging with Tailored Radiotherapy Versus Primary Radiotherapy.

    PubMed

    Kim, Se Ik; Lim, Myong Cheol; Lee, Jeong Seon; Kim, Yeon-Joo; Seo, Sang-Soo; Kang, Sokbom; Yoo, Chong Woo; Nam, Byung-Ho; Kim, Joo-Young; Chung, Seung Hyun; Park, Sang-Yoon

    2016-01-01

    This study investigated the clinical manifestations of lower extremity edema (LEE) in locally advanced cervical cancer patients treated with two different strategies. In total, 79 cervical cancer survivors with International Federation of Gynecology and Obstetrics stage IB2-IIB were included. Six survivors with stage IB1 and who had been suspicious for lymph node metastasis on pretreatment image also were included. Forty-two patients received radiotherapy after pretreatment laparoscopic surgical staging (Group 1), and 43 patients received primary radiotherapy (Group 2). The patients' medical records and survey results of the Korean version of the Gynecologic Cancer Lymphedema Questionnaire (GCLQ-K) were analyzed. The incidence of LEE was higher in Group 1 than in Group 2 (69.0 vs. 11.6 %; P < 0.001). The duration of LEE was longer in Group 1 (mean 77.3 vs. 9.4 months). At the time of survey, 47.6 % of the patients in Group 1 were clinically diagnosed with lymphedema compared with no patients in Group 2. In GCLQ-K, the mean symptom cluster scores for general swelling (0.74 vs. 0.09; P < 0.001), limb swelling (0.22 vs. 0.00; P = 0.006), and heaviness (0.45 vs. 0.23; P = 0.033) were significantly higher in Group 1. One patient in Group 1 developed lymphedema-related angiosarcoma that was diagnosed at 7.8 years after surgery. Patients with cervical cancer who underwent radiotherapy after laparoscopic surgical staging more commonly experienced LEE and related symptoms than patients who underwent primary radiotherapy. As LEE decreases patients' quality of life, it should be considered during patient consultation and surveillance.

  14. Advanced MR Imaging in Pediatric Brain Tumors, Clinical Applications.

    PubMed

    Lequin, Maarten; Hendrikse, Jeroen

    2017-02-01

    Advanced MR imaging techniques, such as spectroscopy, perfusion, diffusion, and functional imaging, have improved the diagnosis of brain tumors in children and also play an important role in defining surgical as well as therapeutic responses in these patients. In addition to the anatomic or structural information gained with conventional MR imaging sequences, advanced MR imaging techniques also provide physiologic information about tumor morphology, metabolism, and hemodynamics. This article reviews the physiology, techniques, and clinical applications of diffusion-weighted and diffusion tensor imaging, MR spectroscopy, perfusion MR imaging, susceptibility-weighted imaging, and functional MR imaging in the setting of neuro-oncology.

  15. Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity!

    PubMed

    Kuchay, Mohammad Shafi; Mishra, Sunil Kumar; Farooqui, Khalid Jamal; Bansal, Beena; Wasir, Jasjeet Singh; Mithal, Ambrish

    2016-01-01

    Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them.

  16. Hypercalcemia of advanced chronic liver disease: a forgotten clinical entity!

    PubMed Central

    Kuchay, Mohammad Shafi; Mishra, Sunil Kumar; Farooqui, Khalid Jamal; Bansal, Beena; Wasir, Jasjeet Singh; Mithal, Ambrish

    2016-01-01

    Summary Hypercalcemia caused by advanced chronic liver disease (CLD) without hepatic neoplasia is uncommonly reported and poorly understood condition. We are reporting two cases of advanced CLD who developed hypercalcemia in the course of the disease. This diagnosis of exclusion was made only after meticulous ruling out of all causes of hypercalcemia. The unique feature of this type of hypercalcemia is its transient nature that may or may not require treatment. This clinical condition in patients with CLD should be kept in mind while evaluating the cause of hypercalcemia in them. PMID:27252737

  17. Prospective Cohort Study Depending on the Use of Palliative Care for Advanced Stage of Cancer Patients

    ClinicalTrials.gov

    2017-09-05

    Stage IV Breast Cancer; Stage IV Pancreatic Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Lung Cancer; Stage IV Liver Cancer; Malignant Hematologic Neoplasm; Biliary Cancer Metastatic; Pediatric Leukemia; Pediatric Lymphoma; Pediatric Brain Tumor; Pediatric Solid Tumor

  18. 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.

  19. [Clinical analysis of postoperative radiotherapy for stage I endometrial cancer].

    PubMed

    Li, Z; Shen, W; Wang, J

    1998-05-01

    To evaluate the role and complications of adjuvant radiotherapy for stage I endometrial cancer after surgery. From May, 1986 to December, 1995, 20 patients with stage I endometrial cancer received total abdominal hysterectomy with bilateral salpingo-oophorectomy(TAH/BSO), and additional pelvic lymph node dissection in 5 cases. Most of the patients received radio therapy in 2-4 weeks after surgery. The radiation fields included pelvic lymph nodes with a total dose of 40-50 Gy. All the patients had survived for 10 years. Only one patient developed distant metastases. Acute radiation reaction was observed in all patients. Late radiation-induced damage occured in six patients and was severe in two. Postoperative radiotherapy in the management of stage I endometrial cancer is beneficial for the controal of local recurrence but has relatively high frequency of late radiation injury.

  20. 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.

  1. 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.

  2. A Two Stage Solution Procedure for Production Planning System with Advance Demand Information

    NASA Astrophysics Data System (ADS)

    Ueno, Nobuyuki; Kadomoto, Kiyotaka; Hasuike, Takashi; Okuhara, Koji

    We model for ‘Naiji System’ which is a unique corporation technique between a manufacturer and suppliers in Japan. We propose a two stage solution procedure for a production planning problem with advance demand information, which is called ‘Naiji’. Under demand uncertainty, this model is formulated as a nonlinear stochastic programming problem which minimizes the sum of production cost and inventory holding cost subject to a probabilistic constraint and some linear production constraints. By the convexity and the special structure of correlation matrix in the problem where inventory for different periods is not independent, we propose a solution procedure with two stages which are named Mass Customization Production Planning & Management System (MCPS) and Variable Mesh Neighborhood Search (VMNS) based on meta-heuristics. It is shown that the proposed solution procedure is available to get a near optimal solution efficiently and practical for making a good master production schedule in the suppliers.

  3. In search of an advance directive that works for end-stage renal disease patients.

    PubMed

    Bartlow, Bruce

    2006-10-01

    Although loss, disability, and death are constant possibilities for any end-stage renal disease patient, very few have planned for the last of life. Currently available Advance Directives (ADs) are refusal of specific therapies in only specific but nebulous circumstances. They fail to provide positive guidance for a patient's remaining time. Without addressing goals, quality of life, reversibility of medical problems, and desired end-of-life (EOL) care, such ADs are useless. End-stage renal disease providers are generally untrained and unsupported in offering guidance. Financial, emotional, and structural factors collude to justify ignoring EOL planning. Several alternative ADs are offered, along with a goal-directed approach to EOL counseling for patients and staff.

  4. Ipilimumab in the treatment of advanced melanoma - a clinical update.

    PubMed

    Kim, Dae Won; Trinh, Van Anh; Hwu, Wen-Jen

    2014-11-01

    Ipilimumab has become an important treatment option for patients with advanced melanoma; however, active research perseveres to resolve many clinical practice issues and to further improve the therapeutic index of this agent. This article aims to provide an update on long-term data, current challenge and recent progress relating to the clinical application of ipilimumab in the treatment of advanced melanoma. A literature search using PubMed database was conducted using search words ipilimumab, melanoma, treatment sequencing, adjuvant therapy, combination therapy, and biomarkers. Data were also obtained from meeting abstracts and clinical trial registries. Signal of clinical activity as adjuvant therapy in patients with resected high-risk melanoma begins to emerge, but longer follow-up is required for confirmation. Many issues, such as optimal dosing schedules and therapeutic sequences, remain unraveled. At present, treatment should be individualized based on patient- and disease-specific factors. Immunotherapy like ipilimumab still represents the best treatment option for durable remission; however, targeted therapies are more appropriate for patients with BRAF V600-mutated tumor who are symptomatic or have rapidly growing disease. With novel therapeutic options in the pipeline, the role of ipilimumab continues to evolve in the rapidly changing treatment landscape of advanced melanoma. Most likely, this agent will be utilized in combinatorial or sequential approach.

  5. 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

  6. Comparison of maturation ponds and constructed wetlands as the final stage of an advanced pond system.

    PubMed

    Tanner, C C; Craggs, R J; Sukias, J P S; Park, J B K

    2005-01-01

    The treatment performance of a maturation pond (MP), the typical final polishing stage of an Advanced Pond System (APS), is compared with that of a surface-flow constructed wetland (CW) over 19 months. Both received approximately 67 mm d-1 of wastewater after passage through upstream stages of the APS. The MP, with greater sunlight exposure, had higher algal biomass (and associated suspended solids) than the CW, showed higher dissolved oxygen (DO) concentrations and greater diurnal variation in DO and pH. Neither polishing stages reduced nutrients markedly, with the CW exporting slightly more NH(3)-N and DRP, and less NO(3)-N than the MP. Disinfection was more efficient in the MP (geometric mean 1 log load removal, 12 MPN (100ml)-1) compared to the CW (0.47 log load removal, 53 MPN (100ml)-1). Incorporation of a final rock filter (28% of area) reduced median solids levels to < 10 g m(-3) in both the MP and CW. A hybrid between MPs and CWs with alternating zones of open-water (for enhanced disinfection and zooplankton grazing of algal solids) and wetland vegetation (promoting sedimentation and denitrification, and providing refugia for zooplankton) may provide more consistent effluent quality that either stage alone.

  7. 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.

  8. Clinical staging: a necessary step in the development of improved animal models of mood disturbance?

    PubMed

    Walker, Frederick Rohan; James, Morgan H; Hickie, Ian B; McGorry, Patrick D

    2014-03-01

    Recently, it has been suggested that the clinical staging approach be considered a serious alternative framework for conceptualising mood related psychopathology. The fundamental difference between clinical staging and the now dominant categorical diagnostic framework is that the entire illness trajectory becomes relevant, as opposed to simply the end-stage. The concept of disease trajectory has significant implications for animal models of psychopathology, and particularly for animal models of depression. This article will introduce and discuss the implications of the clinical staging approach for those undertaking research using animal models of mood disturbance.

  9. Confocal microscopy of skin cancers: Translational advances toward clinical utility

    PubMed Central

    Rajadhyaksha, Milind

    2014-01-01

    Recent advances in translational research in and technology for confocal microscopy of skin cancers, toward clinical applications, are described. Advances in translational research are in diagnosis of melanoma in vivo, pre-operative mapping of lentigo maligna melanoma margins to guide surgery and intra-operative imaging of residual basal cell carcinomas to guide shave-biopsy. Advances in technology include mosaicing microscopy for detection of basal cell carcinomas in large areas of excised tissue, toward rapid pathology-at-the-bedside, and development of small, simple and low-cost line-scanning confocal microscopes for worldwide use in diverse primary healthcare settings. Current limitations and future opportunities and challenges for both clinicians and technologists are discussed. PMID:19964286

  10. 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.

  11. 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

  12. Integrating first-line treatment options into clinical practice: what's new in advanced melanoma?

    PubMed

    Dummer, Reinhard; Schadendorf, Dirk; Ascierto, Paolo A; Larkin, James; Lebbé, Celeste; Hauschild, Axel

    2015-12-01

    Melanoma remains a serious form of skin cancer in Europe and worldwide. Localized, early-stage melanomas can usually be treated with surgical excision. However, the prognosis is poorer for patients with advanced disease. Before 2011, treatment for advanced melanoma included palliative surgery and/or radiotherapy, and chemotherapy with or without immunotherapy, such as interleukin-2. As none of these treatments had shown survival benefits in patients with advanced melanoma, European guidelines had recommended that patients be entered into clinical trials. The lack of approved first-line options and varying access to clinical trials meant that European clinicians relied on experimental regimens and chemotherapy-based treatments when no other options were available. Since 2011, ipilimumab, an immuno-oncology therapy, and vemurafenib and dabrafenib, targeted agents that inhibit mutant BRAF, have been approved by the European Medicines Agency for the treatment of advanced melanoma. More recently, the MEK inhibitor, trametinib, received European marketing authorization for use in patients with BRAF mutation-positive advanced melanoma. In 2014, the anti-PD-1 antibody nivolumab was approved as a first-line therapy in Japan. Whereas nivolumab and another anti-PD-1 antibody, pembrolizumab, were approved as second-line therapies in the USA, their recent approval in Europe are for first-line use based on new clinical trial data in this setting. Together these agents are changing clinical practice and making therapeutic decisions more complex. Here, we discuss current and emerging therapeutic options for the first-line treatment of advanced melanoma, and how these therapies can be optimized to provide the best possible outcomes for patients.

  13. One-stage and two-stage designs for phase II clinical trials with survival endpoints.

    PubMed

    Whitehead, John

    2014-09-28

    This work is motivated by trials in rapidly lethal cancers or cancers for which measuring shrinkage of tumours is infeasible. In either case, traditional phase II designs focussing on tumour response are unsuitable. Usually, tumour response is considered as a substitute for the more relevant but longer-term endpoint of death. In rapidly lethal cancers such as pancreatic cancer, there is no need to use a surrogate, as the definitive endpoint is (sadly) available so soon. In uveal cancer, there is no counterpart to tumour response, and so, mortality is the only realistic response available. Cytostatic cancer treatments do not seek to kill tumours, but to mitigate their effects. Trials of such therapy might also be based on survival times to death or progression, rather than on tumour shrinkage. Phase II oncology trials are often conducted with all study patients receiving the experimental therapy, and this approach is considered here. Simple extensions of one-stage and two-stage designs based on binary responses are presented. Outcomes based on survival past a small number of landmark times are considered: here, the case of three such times is explored in examples. This approach allows exact calculations to be made for both design and analysis purposes. Simulations presented here show that calculations based on normal approximations can lead to loss of power when sample sizes are small. Two-stage versions of the procedure are also suggested.

  14. A streamlined clinical advancement program improves RN participation and retention.

    PubMed

    Allen, Susan R; Fiorini, Pamela; Dickey, Michelle

    2010-01-01

    Retaining expert nurses in direct care is essential to quality patient outcomes. The goal of the clinical advancement program at Cincinnati Children's Hospital Medical Center has always been to recruit, retain, recognize, and reward nurses in direct care. A program revision in 2002 markedly increased nursing promotions and a higher retention rate for program participants versus their peers' retention rate of 88%. Nearly 40% of the hospital's nurses now participate in the program.

  15. [The relationship between GAPDH mRNA multiple location degradation and advanced stage postmortem intervals].

    PubMed

    Ren, Guang-Mu; Wang, Ying-Yuan; Liu, Ji

    2009-09-01

    To study the degradation regularity on different sites of housekeeping gene GAPDH in the same tissue in order to deduce advanced stage postmortem interval (PMI). Rat brain cortex was collected, and 6 sites from 5'-cap to 3'-end in GAPDH mRNA sequence were measured by SYBR Green I real-time RT-PCR to determine the degradation of GAPDH mRNA in brain cortex. Postmortem intervals were extended to 0, 1, 5, 9, 12 days. All the Ct values of GAPDH mRNA at different sites from the 5'-mRNA cap structure to the 3'-end (GAPDH mRNA 1-GAPDH mRNA 6) in brain correlate with the postmortem periods, while different sites showed different degradation rate. The rates of GAPDH mRNA 4-6 degradation were lower than those of GAPDH mRNA 1-3. If we used GAPDH mRNA 6 as external standard, the ratio of GAPDH mRNA 1-3/GAPDH mRNA 6 were correlated with postmortem periods. However, the relation between GAPDH mRNA 4-5/GAPDH mRNA 6 ratio and postmortem periods were not observed. Different sites of housekeeping gene GAPDH in the same tissue share different degradation rates. The degradation of those sites near to 3'-end of mRNA show more precise to deduce advanced stage PMI.

  16. Clinical trials in predementia stages of Alzheimer disease.

    PubMed

    Pillai, Jagan A; Cummings, Jeffrey L

    2013-05-01

    Effective treatments of Alzheimer disease (AD) dementia are an urgent necessity. There is a growing consensus that effective disease-modifying treatment before the onset of clinical dementia and slowing the progression of mild symptoms are needed after recent setbacks in AD therapeutics. The identification of at-risk and preclinical AD populations is becoming important for targeting primary and secondary prevention clinical trials in AD. This article reviews the strategies and challenges in targeting at-risk and preclinical AD populations for a new generation of AD clinical trials. Design, outcome measures, and complexities in successfully completing a clinical trial targeting this population are reviewed. Copyright © 2013 Elsevier Inc. All rights reserved.

  17. A Comparative Analysis of Clinical and Molecular Factors with the Stage of Cervical Cancer in a Brazilian Cohort

    PubMed Central

    Amaro-Filho, Sergio M.; Golub, Jonathan E.; Nuovo, Gerard J.; Cunha, Cynthia B.; Levi, José E.; Villa, Luisa L.; Andrade, Cecília V.; Russomano, Fabio B.; Tristão, Aparecida; Pires, Andrea; Nicol, Alcina F.

    2013-01-01

    Cell cycle protein expression plays an important role in the pathophysiology of cervical cancer. However, few studies have attempted to correlate the use of these biomarkers with the clinical progression of the tumor. Objectives 1) To analyze the expression of Ki-67, p53 and p16INK4a in cervical cancer, 2) to correlate the relative expression of these proteins as well as clinical parameters with the stage of disease, and 3) to determine the HPV DNA prevalence and subtype distribution. Methods Tissue Micro-Arrays (TMA) from patients with invasive cervical cancer (ICC) and controls were analyzed. HPV DNA detection was done by PCR and in situ hybridization. Ki-67, p53 and p16INK4a were analyzed by immunohistochemistry; clinical data was derived from the chart review. Results Advanced tumor stage (III and IV) was strongly associated (p<0.005) with advanced age (>55 years old), with more than four pregnancies and with the lack of formal education. HPV DNA was found in 94.3% of cases with the most prevalent types being HPV16 (67.5%), followed by HPV33 (12.0%) and HPV35 (3.6%). High expression of Ki-67 and p16 was more common in the advanced FIGO stages (p = 0.023). Women with HPV16 tended to be younger (50.9 years; SE 1.9) compared to women with other types (59.9 years; SE 2.8). Conclusion We found that Ki-67 and p16 expression were independently associated with the tumor stage. We also noted that about 1/3 of the cervical cancers in this Brazilian cohort were not associated with HPV types directly targeted by the current HPV vaccines. PMID:23505442

  18. 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

  19. Diagnostic Approach to Advanced Fibrotic Interstitial Lung Disease: Bringing Together Clinical, Radiologic, and Histologic Clues.

    PubMed

    Larsen, Brandon T; Smith, Maxwell L; Elicker, Brett M; Fernandez, Jessica M; de Morvil, Guillermo A Arbo-Oze; Pereira, Carlos A C; Leslie, Kevin O

    2017-07-01

    - Idiopathic pulmonary fibrosis (IPF) is a distinctive clinicopathologic entity and the most common form of progressive diffuse lung scarring in older adults. Idiopathic pulmonary fibrosis manifests histopathologically as the usual interstitial pneumonia pattern. The usual interstitial pneumonia pattern is distinguished by geographically and temporally heterogeneous fibrosis that is peripherally accentuated, often with honeycombing and traction bronchiectasis. Idiopathic pulmonary fibrosis is not the only disease that leads to end-stage lung fibrosis, however, and several other entities may also cause advanced fibrosis. Surgical lung biopsies often present a diagnostic dilemma when they show clear evidence of advanced fibrosis, but the clinical, imaging, and/or histopathologic subcharacteristics suggest something other than IPF. - To address this dilemma, we review several other fibrotic lung diseases, including connective tissue disease-associated interstitial lung disease, chronic hypersensitivity pneumonitis, advanced pulmonary Langerhans cell histiocytosis, end-stage pulmonary sarcoidosis, Erdheim-Chester disease, Hermansky-Pudlak syndrome, and others, detailing their clinical, radiologic, and histopathologic attributes and emphasizing similarities to and differences from IPF. - Data sources comprised published peer-reviewed literature and personal experience of the authors. - Often, clues in the lung biopsy may offer the first suggestion of a fibrotic lung disease other than IPF, and accurate classification is important for prognosis, treatment, and the development of future therapies.

  20. Prognostic factors of advanced stage non-small-cell lung cancer.

    PubMed

    Ben Amar, Jihen; Ben Safta, Boutheina; Zaibi, Haifa; Dhahri, Besma; Baccar, Mohamed Ali; Azzabi, Saloua

    2016-05-01

    Background Lung cancer is the main cause of death from cancer in the world. The 5-year survival is about 15%. Despite the progress of medicine the mortality rate decreased only marginally. This poor prognosis is due to late diagnosis. Aim To evaluate overall survival and prognostic factors in patients locally advanced or metastatic non small cell lung cancer (NSCLC). Methods Retrospective study including 180 patients with non-small cell lung cancer hospitalized in the department of Charles Nicolle Hospital of Tunis between January 2007 and December 2014. Results The mean age was 61.5 years with a male predominance (93.3%). The median overall survival was 6 months. The poor prognostic factors were the performans status (PS) and early delays of management (<30 days). The factors that improve survival were surgical treatment and delays of management more than 45 days.  Conclusion The prognostic factors in locally advanced and metastatic NSLC in our patient were: PS, management delay and treatment. These factors should be considered in management of patient with advanced stage NSCLC.

  1. Two-stage, low noise advanced technology fan. Volume 2: Aerodynamic data

    NASA Technical Reports Server (NTRS)

    Harley, K. G.; Odegard, P. A.

    1975-01-01

    Aerodynamic data from static tests of a two-stage advanced technology fan designed to minimize noise are presented. Fan design conditions include delivery of 209.1kg/sec/sq m (42.85 lbm/sec/sq ft) specific corrected flow at an overall pressure ratio of 1.9 and an adiabatic efficiency of 85.3 percent. The 0.836m (2.74ft) diameter first stage rotor has a hub/tip ratio of 0.4 and 365.8m/sec (1200ft/sec) design tip speed. In addition to the moderate tip speed and pressure rise per stage, other noise control design features involve widely spaced blade rows and proper selection of blade-vane ratios. Aerodynamic data are presented for tests with unifrom and with hub and tip radially distorted inlet flow. Aerodynamic data are also presented for tests of this fan with acoustic treatments, including acoustically treated casing walls, a flowpath exit acoustic ring, and a translating centerbody sonic inlet device. A complete tabulation of the overall performance data, the blade element data, and the power spectral density information relating to turbulence levels generated by the sonic inlet obtained during these tests is included. For vol. 1, see N74-33789.

  2. Advances in high-rate anaerobic treatment: staging of reactor systems.

    PubMed

    van Lier, J B; van der Zee, F P; Tan, N C; Rebac, S; Kleerebezem, R

    2001-01-01

    Anaerobic wastewater treatment (AnWT) is considered as the most cost-effective solution for organically polluted industrial waste streams. Particularly the development of high-rate systems, in which hydraulic retention times are uncoupled from solids retention times, has led to a world-wide acceptance of AnWT. In the last decade up to the present, the application potentials of AnWT are further explored. Research shows the feasibility of anaerobic reactors under extreme conditions, such as low and high temperatures. Also toxic and/or recalcitrant wastewaters, that were previously believed not to be suitable for anaerobic processes, are now effectively treated. The recent advances are made possible by adapting the conventional anaerobic high-rate concept to the more extreme conditions. Staged anaerobic reactor concepts show advantages under non-optimal temperature conditions as well as during the treatment of chemical wastewater. In other situations, a staged anaerobic-aerobic approach is required for biodegradation of specific pollutants, e.g. the removal of dyes from textile processing wastewaters. The current paper illustrates the benefits of reactor staging and the yet un-exploited potentials of high-rate AnWT.

  3. Transcriptome portrait of cellulose-enriched flax fibres at advanced stage of specialization.

    PubMed

    Gorshkov, Oleg; Mokshina, Natalia; Gorshkov, Vladimir; Chemikosova, Svetlana; Gogolev, Yuri; Gorshkova, Tatyana

    2017-03-01

    Functional specialization of cells is among the most fundamental processes of higher organism ontogenesis. The major obstacle to studying this phenomenon in plants is the difficulty of isolating certain types of cells at defined stages of in planta development for in-depth analysis. A rare opportunity is given by the developed model system of flax (Linum usitatissimum L.) phloem fibres that can be purified from the surrounding tissues at the stage of the tertiary cell wall deposition. The performed comparison of the whole transcriptome profile in isolated fibres and other portions of the flax stem, together with fibre metabolism characterization, helped to elucidate the general picture of the advanced stage of plant cell specialization and to reveal novel participants potentially involved in fibre metabolism regulation and cell wall formation. Down-regulation of all genes encoding proteins involved in xylan and lignin synthesis and up-regulation of genes for the specific set of transcription factors transcribed during tertiary cell wall formation were revealed. The increased abundance of transcripts for several glycosyltransferases indicated the enzymes that may be involved in synthesis of fibre-specific version of rhamnogalacturonan I.

  4. Comparison of vascularized supraclavicular lymph node transfer and lymphaticovenular anastomosis for advanced stage lower extremity lymphedema.

    PubMed

    Akita, Shinsuke; Mitsukawa, Nobuyuki; Kuriyama, Motone; Kubota, Yoshitaka; Hasegawa, Masakazu; Tokumoto, Hideki; Ishigaki, Tatsuya; Togawa, Takashi; Kuyama, Junpei; Satoh, Kaneshige

    2015-05-01

    Vascularized lymph node transfer has become a popular surgical option to improve lower extremity lymphedema (LEL), although potential donor sites are limited. The free supraclavicular flap with deep cervical lymph nodes has been recently associated with a minimal risk of secondary lymphedema caused by donor site dissection. However, the effectiveness of this procedure has not yet been evaluated. Vascularized supraclavicular lymph node transfer (VSLNT) was performed for patients with International Society of Lymphology late stage II or more severe LEL. The results were compared with lymphaticovenular anastomosis (LVA) performed for patients with the same stages of severity. To evaluate improvement in lymphatic function, indocyanine green lymphography and lymphoscintigraphy were performed. Vascularized supraclavicular lymph node transfer was performed in 13 limbs of 13 patients. The results were compared with 43 limbs of 33 patients who underwent multiple LVA. No severe complications were observed in either group. Improvement in lymphatic function, as measured by the LEL index, was 26.5 ± 4.4 and 21.2 ± 2.0 in the VSLNT and LVA groups, respectively. Lymphatic function was improved in 7 cases in the VSLNT group and 10 cases in the LVA group. Vascularized supraclavicular lymph node transfer is an effective technique for the treatment of advanced stage LEL. Lymphaticovenular anastomosis is also effective, but to a lesser degree than VSLNT. However, LVA is less invasive and requires a shorter hospital stay.

  5. Mentoring for retention and advancement in the multigenerational clinical laboratory.

    PubMed

    Laudicina, R J

    2001-01-01

    Retention of recent graduates and other laboratory practitioners in the workplace will play a key role in addressing current and projected shortages of clinical laboratory scientists (CLS) and technicians (CLT). In addition, with overrepresentation of the aging Baby Boomer generation in laboratory supervisory and management positions, it is crucial not only to retain younger practitioners, but to prepare them for assuming these important functions in the future. Mentoring, a practice commonly employed in other professions, is widely considered to be useful in employee retention and career advancement. Mentoring has probably been used in the clinical laboratory profession, but has not been well documented. In the clinical laboratory environment, potential mentors are in the Veteran and Baby Boomer generations, and new practitioners who could benefit from mentoring are in Generation X. Generational differences among these groups may present challenges to the use of mentoring. This article will attempt to provide a better understanding of generational differences and show how mentoring can be applied in the setting of the clinical laboratory in order to increase retention and promote career advancement of younger practitioners. A panel of five laboratory managers provided examples of mentoring strategies. Definitions, benefits, and examples of mentoring are addressed in the accompanying article, "Passing the Torch: Mentoring the Next Generation of Laboratory Professionals".

  6. Angiogenic inhibitors for older patients with advanced colorectal cancer: Does the age hold the stage?

    PubMed Central

    Aprile, Giuseppe; Fontanella, Caterina; Lutrino, Eufemia Stefania; Ferrari, Laura; Casagrande, Mariaelena; Cardellino, Giovanni Gerardo; Rosati, Gerardo; Fasola, Gianpiero

    2013-01-01

    Although major progress has been achieved in the treatment of advanced colorectal cancer (CRC) with the employment of antiangiogenic agents, several questions remain on the use of these drugs in older patients. Since cardiovascular, renal and other comorbidities are common in the elderly, an accurate assessment of the patients’ conditions should be performed before a treatment decision is made. Since most CRC patients enrolled in clinical trials testing antiangiogenic drugs were aged < 65 years, the efficacy and tolerability of these agents in elderly patients has not been adequately explored. Data suggest that patients with advanced CRC derive similar benefit from bevacizumab treatment regardless of age, but the advantage of other antiangiogenic drugs in the same class of patients appears more blurred. Literature data suggest that specific antiangiogenic-related toxicities such as hypertension or arterial thromboembolic events may be higher in the elderly than in the younger patients. In addition, it should be emphasized that the patients included in the clinical studies discussed herein were selected and therefore may not be representative of the usual elderly population. Advanced age alone should not discourage the use of bevacizumab. However, a careful patients’ selection and watchful monitoring of toxicities are required to optimize the use of antiangiogenics in this population. PMID:23847406

  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. 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

  9. 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.

  10. Association Between Clinically Staged Node-Negative Esophageal Adenocarcinoma and Overall Survival Benefit From Neoadjuvant Chemoradiation

    PubMed Central

    Gabriel, Emmanuel; Attwood, Kristopher; Du, William; Tuttle, Rebecca; Alnaji, Raed M.; Nurkin, Steven; Malhotra, Usha; Hochwald, Steven N.; Kukar, Moshim

    2017-01-01

    Importance While neoadjuvant chemoradiation for esophageal cancer improves oncologic outcomes for a broad group of patients with locally advanced and/or node-positive tumors, it is less clear which specific subset of patients derives most benefit in terms of overall survival (OS). Objective To determine whether neoadjuvant chemoradiation based on esophageal adenocarcinoma histology has similar oncologic outcomes for patients treated with surgery alone when stratified by clinical nodal status. Design, Setting, and Participants A retrospective analysis using the American College of Surgeons National Cancer Database from 1998 to 2006. Patients with esophageal adenocarcinoma histology and clinical stage T1bN1-N3 or T2-T4aN−/+M0 were divided into 2 treatment groups: (1) neoadjuvant chemoradiation followed by surgery and (2) surgery alone. Subset analysis within each treatment group was performed for clinically node-negative patients (cN−) vs node-positive patients (cN+) in conjunction with pathological nodal status. A propensity score–adjusted analysis, which included patient demographics, comorbidity status, and clinical T stage, was also performed. Main Outcome and measures The primary outcome was 3-year OS. Secondary outcomes included margin status, postoperative length of stay, unplanned readmission rate, and 30-day mortality. Results A total of 1309 patients were identified, of whom 539 received neoadjuvant chemoradiation followed by surgery and 770 received surgery alone. Of the 1309 patients, 41.2% (n = 539) received neoadjuvant chemoradiation and 47.2% (n = 618) were cN+. Median follow-up for the entire cohort was 73.3 months (interquartile range, 64.1-93.5 months). The 3-year OS was better for neoadjuvant chemoradiation followed by surgery compared with surgery alone (49% vs 38%, respectively; P < .001). Stratifying based on clinical nodal status, the propensity score–adjusted OS was significantly better for cN+ patients who received neoadjuvant

  11. Loss of flower bud vigour in the Mediterranean shrub, Cistus albidus L. at advanced developmental stages.

    PubMed

    Oñate, M; Munné-Bosch, S

    2010-05-01

    To better understand aging in perennials, age-related changes in the physiology of leaves and flower buds of the Mediterranean shrub, Cistus albidus L. were evaluated. Two groups of different ages (5 and 10 years old), both at advanced developmental stages but of similar size, were compared. Total plant biomass, biomass produced per apical meristem and levels of cytokinins, abscisic acid and jasmonic acid in leaves and flower buds, as well as flower production, were measured. No differences in plant size, vegetative growth rates and levels of phytohormones in leaves were observed between 5- and 10-year-old plants. However, they showed significant differences in flower bud development; the older plants having reduced vigour, with 29.6% of flowers reaching anthesis compared to 52.5% in the younger plants. Furthermore, endogenous concentrations of zeatin and abscisic acid in flower buds at stage I (start of flower organ formation) were 61% and 41%, respectively, smaller in 10- than in 5-year-old plants. At stage II (with all flower organs formed), zeatin and abscisic acid concentrations decreased by ca. 90% and 80%, respectively, but differences between age groups were still evident (60% and 29% for zeatin and abscisic acid, respectively). Jasmonic acid levels in flower buds decreased by 80% from stage I to II, but did not differ between age groups. Despite reductions in flower bud vigour, total number of flowers per individual was not significantly different between age groups, so that an age-related loss in reproductive vigour at the organ level did not lead to a decrease in flower production at the whole plant level.

  12. Association of peroxisome proliferator-activated receptor-gamma 2 Pro12Ala polymorphism with advanced-stage endometriosis.

    PubMed

    Hwang, Kyu Ri; Choi, Young Min; Kim, Jong Mee; Lee, Gyoung Hoon; Kim, Jin Ju; Chae, Soo Jin; Moon, Shin Yong

    2010-11-01

    To investigate whether the peroxisome proliferator-activated receptor (PPAR)-γ2 Pro12Ala polymorphism is associated with a risk of advanced-stage endometriosis in a Korean population.   Case-control study in a collective of 446 patients and 427 controls. The Pro12Ala polymorphism of PPAR-γ2 gene was genotyped using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) analysis. The distribution of the PPAR-γ2 Pro12Ala polymorphism was different between the advanced-stage endometriosis group and the control group (non-CC rates were 5.2% for patients with advanced endometriosis and 10.1% for the control group, respectively, P = 0.006). The frequency for the Ala-12 allele variant was significantly lower in patients with advanced stage of endometriosis (2.7%) than in the control group (5.3%) (P = 0.006). These findings suggest that the PPAR-γ2 Pro12Ala polymorphism is associated with advanced-stage endometriosis in the Korean population. Unlike results from other studies reported so far, the Ala-12 allele may have protective effects against advanced-stage endometriosis in the Korean population. © 2010 John Wiley & Sons A/S.

  13. Clinical applicability of staging small cell lung cancer according to the seventh edition of the TNM staging system.

    PubMed

    Jhun, Byung Woo; Lee, Kyung-Jong; Jeon, Kyeongman; Suh, Gee Young; Chung, Man Pyo; Kim, Hojoong; Kwon, O Jung; Sun, Jong-Mu; Ahn, Jin Seok; Ahn, Myung-Ju; Park, Keunchil; Choi, Joon Young; Lee, Kyung Soo; Han, Joungho; Um, Sang-Won

    2013-07-01

    The two-stage system of limited and extensive disease has been widely employed for small cell lung cancer (SCLC). However, the International Association for the Study of Lung Cancer has proposed that the TNM classification should be incorporated into clinical practice. The purpose of this study was to evaluate the applicability of the Union for International Cancer Control (UICC) 7th TNM staging system to SCLC. We retrospectively reviewed the medical records of consecutive patients with newly diagnosed histologically proven SCLC between March 2005 and January 2010. Patients who had other concurrent malignancies or had combined-type SCLC were excluded. We assessed overall survival (OS) according to the T descriptor, N descriptor, M descriptor, and TNM stage grouping. In total, 320 SCLC patients were included. Median age was 65 years and 286 patients (89.4%) were male. Median OS was 12.7 months. There were no significant differences in OS according to the T descriptor (P = 0.880). However, there were significant differences in OS according to the N (P < 0.001) and M (P < 0.001) descriptors and TNM stage grouping (P < 0.001). Hazard ratios for OS, adjusted for known prognostic factors, differed significantly according to the N and M descriptor, and TNM stage grouping, but not according to the T descriptors. The UICC 7th TNM staging system may contribute to a more precise prognosis in SCLC patients. Further studies are required to evaluate the applicability of the TNM staging system to SCLC. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  14. A systematic review of clinically available gene expression profiling assays for stage II colorectal cancer: initial steps toward genetic staging.

    PubMed

    Lopez, Nicole E; Weiss, Anna C; Robles, Julie; Fanta, Paul; Ramamoorthy, Sonia L

    2016-10-01

    In recent years, increasingly accessible and novel genetic technologies have spurred keen interest in the application of cancer genetics in predicting prognosis and response to treatment. In particular, investigators have eagerly sought to establish and validate genetic signatures that might improve the identification of patients with stage II colorectal cancer (CRC) who are at highest risk of recurrence. To better understand the evidence for incorporation of genetic assays into clinical practice, we have systematically reviewed those assays that have been validated and are available for clinical use in stage II CRC. A systematic review was performed using PubMed, Web of Science and Scopus databases. The GRADE system was used to evaluate level of evidence and strength of recommendations. After duplicates were removed and exclusion criteria were applied, there were 13 articles for review. Identifying high-risk patients with stage II CRC using molecular profiling has been the primary aim of many investigators, and the approach is translating into clinical utility. Published by Elsevier Inc.

  15. Dynamic changes of driver genes' mutations across clinical stages in nine cancer types.

    PubMed

    Li, Xia

    2016-07-01

    The driver genes play critical roles for tumorigenesis, and the number of identified driver genes reached plateau. But how they act during different cancer development stages is lack of knowledge. We investigated 138 driver genes' mutation changes across clinical stages using 3,477 cases in nine cancer types from the Cancer Genome Atlas (TCGA) and constructed their temporal order relationships. We also examined the codon changes for the widely mutated TP53 and PIK3CA in tumor stages. Combinations of one to three driver genes specifically dominated in each cancer. Across the clinical stages, we categorized three patterns for the behaviors of driver genes' mutation changes in the nine cancer types: recurrently mutated in all the stages and triggering other mutations; certain mutations lost meanwhile other mutations emerged; mutations dominated across entire stages, while other mutations gradually appeared or disappeared. We observed different codon changes dominated in different stages and revealed mutations recurrently occurring on the hotspot regions of the coding sequence may be the core factor for driver genes' tumorigenesis. Our results highlighted the dynamic changes of oncogenesis roles in different clinical stages and suggested different diagnostic decision making according to the clinical stages of patients.

  16. Prognostic and predictive significance of long interspersed nucleotide element-1 methylation in advanced-stage colorectal cancer.

    PubMed

    Kaneko, Mami; Kotake, Masanori; Bando, Hiroyuki; Yamada, Tetsuji; Takemura, Hirofumi; Minamoto, Toshinari

    2016-12-12

    Hypomethylation of Long Interspersed Nucleotide Element-1 (LINE-1) is associated with worse prognosis in colorectal cancer (CRC). However, little is known about the relevance of this marker for the prognosis and response to chemotherapy of metastatic and recurrent (advanced-stage) CRC. Our aim was therefore to investigate whether tumor LINE-1 hypomethylation correlates with patient survival and with response to 5-fluorouracil (5-FU)/ oxaliplatin (FOLFOX) chemotherapy in advanced-stage CRC. The study included 40 CRC patients who developed metastasis or local recurrence after surgery and subsequently underwent FOLFOX therapy. Progression-free and overall survival were estimated using the Kaplan-Meier method. LINE-1 methylation levels in formalin-fixed and paraffin-embedded primary tumor tissues were measured by MethyLight assay and correlated with patient survival. In vitro analyses were also conducted with human colon cancer cell lines having different LINE-1 methylation levels to examine the effects of 5-FU and oxaliplatin on LINE-1 activity and DNA double-strand-breaks. Patients with LINE-1 hypomethylation showed significantly worse progression-free (median: 6.6 vs 9.4 months; P = 0.02) and overall (median: 16.6 vs 23.2 months; P = 0.01) survival following chemotherapy compared to patients with high methylation. LINE-1 hypomethylation was an independent factor for poor prognosis (P = 0.018) and was associated with a trend for non-response to FOLFOX chemotherapy. In vitro analysis showed that oxaliplatin increased the LINE-1 score in LINE-1-expressing (hypomethylated) cancer cells, thereby enhancing and prolonging the effect of 5-FU against these cells. This finding supports the observed correlation between tumor LINE-1 methylation and response to chemotherapy in CRC patients. Tumor LINE-1 hypomethylation is an independent marker of poor prognosis in advanced-stage CRC and may also predict non-response to combination FOLFOX chemotherapy. Prospective

  17. 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.

  18. Effect of p53 codon 72 polymorphism on the survival outcome in advanced stage cervical cancer patients in India

    PubMed Central

    Bansal, Akanksha; Das, Poulami; Kannan, Sadhana; Mahantshetty, Umesh; Mulherkar, Rita

    2016-01-01

    Background & objectives: The Arg>Pro polymorphism in codon 72 of p53 gene is known to affect the susceptibility of cervical cancer differently in different population worldwide although information regarding its role in determining survival status and disease outcome in patients is lacking. The present study was conducted to determine the genotype frequency and prognostic role of p53 codon 72 Arg>Pro polymorphism in patients with advanced stage cervical cancer in India. Methods: The p53 codon 72 polymorphism was determined in tumour biopsies (n = 107) and matched blood samples (n = 19) in cervical cancer patients using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP). Effect of p53 genotype on the overall survival (OS) and recurrence-free survival (RFS) was analyzed. Individual Arg or Pro alleles were studied for their significance on survival as Pro carriers (Pro/Pro + Arg/Pro) versus Arg/Arg individuals or Arg carriers (Arg/Arg + Arg/Pro) versus Pro/Pro individuals. Results: The frequencies for Arg/Arg, Arg/Pro and Pro/Pro genotypes were 27.2, 49.5 and 23.3 per cent, respectively. There was no significant difference in the genotypes with respect to patients’ OS or RFS. Interpretation & conclusions: The findings of our study indicated that p53 codon 72 polymorphism might not be an independent marker in predicting clinical outcome in advanced stage cervical cancer patients. Further studies need to be done in larger samples to confirm these findings. PMID:28139534

  19. Advanced stage ovarian juvenile granuloza cell tumor causing acute abdomen: a case report.

    PubMed

    Bedir, Recep; Mürtezaoğlu, Afşin Rahman; Calapoğlu, Ahmet Salih; Şehitoğlu, İbrahim; Yurdakul, Cüneyt

    2014-09-01

    Ovary juvenile granulosa cell tumors (JGCT) are rare sex cord-stromal tumors that are most commonly encountered in prepubertal girls. These tumors can be of the adult type (95%) and juvenile type (5%). The main causes of complaint are abdominal distention and abdominal pain. Definitive diagnosis is confirmed by histopathologal and immunohistochemical examinations. A 10-year old girl presented with massive abdominal distention, acute abdomen findings and ascites. Abdominopelvic magnetic resonance imaging showed masses with multiple cysts and solid components in the left ovary. Tumor markers were normal, but serum estradiol level was elevated. The patient underwent mass resection with left salpingo-oophorectomy and total omentectomy. Final histopathological diagnosis was JGCT. We herein reporte an extremely rare case of advanced stage JGCT causing massive ascites and acute abdomen.

  20. Clinical staging in bitches with mammary tumors: Influence of type and histological grade

    PubMed Central

    Gundim, Lígia F.; de Araújo, Camila P.; Blanca, William T.; Guimarães, Ednaldo C.; Medeiros, Alessandra A.

    2016-01-01

    Breast tumors are the most common tumors in dogs and the study of disease prognostic factors is important for establishing the appropriate treatment protocols. The purpose of this study was to clinically stage mammary tumors of bitches and correlate the stages with histological type and grade. The tumors of 63 dogs were clinically staged based on the findings of tumor sizing, lymph node evaluation, and radiographic examination. After surgical excision, the tumors were classified histologically and graded. The relationship between the tumor grade, stage, and histological type was evaluated using a binomial test. Stage I tumors were the most numerous (31.75%), followed by tumors at stages II, III, IV, and V. Animals with histological grade I carcinomas presented stage I, II, or III tumors more frequently and stage IV and V tumors less frequently. The number of animals with simple carcinomas that were at stage I of the disease was greater than that at stage V. Carcinomas in the mixed tumors were less aggressive; however, the small number of animals in stage V of the disease made any statistical association impossible. The complex carcinomas presented with the invasion of the lymph nodes and less cellular differentiation in a larger number of animals than did simple carcinomas. Histological grading proved to be the best parameter for the prognostic evaluation of the breast carcinomas. PMID:27733787

  1. Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

    PubMed Central

    Peng, Jianhong; Lin, Junzhong; Qiu, Miaozhen; Wu, Xiaojun; Lu, Zhenhai; Chen, Gong; Li, Liren; Ding, Peirong; Gao, Yuanhong; Zeng, Zhifan; Zhang, Huizhong; Wan, Desen; Pan, Zhizhong

    2016-01-01

    OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical

  2. Clinical Cancer Advances 2005: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

    PubMed

    Herbst, Roy S; Bajorin, Dean F; Bleiberg, Harry; Blum, Diane; Hao, Desirée; Johnson, Bruce E; Ozols, Robert F; Demetri, George D; Ganz, Patricia A; Kris, Mark G; Levin, Bernard; Markman, Maurie; Raghavan, Derek; Reaman, Gregory H; Sawaya, Raymond; Schuchter, Lynn M; Sweetenham, John W; Vahdat, Linda T; Vokes, Everett E; Winn, Rodger J; Mayer, Robert J

    2006-01-01

    This year, for the first time, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances 2005: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant clinical research presented or published over the past year across all cancer types. ASCO embarked on this project to provide the public, patients, policymakers, and physicians with an accessible summary of the year's most important research advances. While not intended to serve as a comprehensive review, this report provides a year-end snapshot of research that will have the greatest impact on patient care. As you will read, there is much good news from the front lines of cancer research. These pages report on new chemotherapy regimens that sharply reduce the risk of recurrence for very common cancers; the "coming of age" of targeted cancer therapies; promising studies of drugs to prevent cancer; and improvements in quality of life for people living with the disease, among many other advances. Survival rates for cancer are on the rise, increasing from 50% to 64% over the last 30 years. Cancer still exacts an enormous toll, however. Nearly 1.4 million Americans will be diagnosed this year, and some 570,000 will die of the disease. Clearly, more research is needed to find effective therapies for the most stubborn cancer types and stages. We need to know more about the long-term effects of newer, more targeted cancer therapies, some of which need to be taken over long periods of time. And we need to devote far greater attention to tracking and improving the care of the nearly 10 million cancer survivors in the United States today. Despite these and other challenges, the message of this report is one of hope. Through the dedicated, persistent pursuit of clinical research and participation in clinical trials by people with cancer, we steadily uncover new and better ways of treating, diagnosing, and preventing a disease that touches the

  3. Clinical Trial Results Vary Widely, But Always Advance Research | NIH MedlinePlus the Magazine

    MedlinePlus

    ... of this page please turn Javascript on. Feature: Clinical Trials Clinical Trial Results Vary Widely, But Always Advance Research ... very emotional." Should You Be Interested in a Clinical Trial People volunteer to take part in clinical ...

  4. The meaning of life intervention for patients with advanced-stage cancer: development and pilot study.

    PubMed

    Mok, Esther; Lau, Ka-po; Lai, Theresa; Ching, Shirley

    2012-11-01

    To develop the Meaning of Life Intervention in response to the need for brief and meaning-focused interventions in palliative care and to establish potential effect sizes for future full-scale randomized, controlled trials. A randomized, controlled trial conducted to pilot test the Meaning of Life Intervention. A 68-bed oncology inpatient ward in an urban acute general hospital in Hong Kong. 84 patients with advanced-stage cancer. Fifty-eight completed the study. Assessments of outcome variables were conducted at baseline and one day and two weeks after the intervention. Patients were randomly allocated to the intervention group or the control group. Repeated measures analysis of covariance were conducted to assess the impact of the Meaning of Life Intervention on participants' quality of life. The primary outcome was quality of life and was measured by the Quality-of-Life Concerns in the End-of-Life (QOLC-E) questionnaire and with a single-item scale on global quality of life. The eight subscales of the QOLC-E served as secondary outcomes. Statistically significant main effects were noted for the group in the QOLC-E questionnaire total score, the single-item scale on global quality of life, and the existential distress subscale of the QOLC-E questionnaire. The effects represented a medium effect size. The results of this pilot study show that the Meaning of Life Intervention can improve quality of life, particularly existential distress. The Meaning of Life Intervention represents a potentially effective and efficient intervention that is feasible for implementation by nursing staff for patients with advanced-stage cancer in a palliative care setting.

  5. 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.

  6. A clinical trial adriamycin (NSC 123127) in advanced sarcomas.

    PubMed

    Creagan, E T; Hahn, R G; Ahmann, D L; Bisel, H F

    1977-01-01

    22 patients with advanced sarcomas received adriamycin, 20--25 mg/m2/day for three days each three weeks. Two patients manifested objective response for a median of five months. Eight patients had stable disease for a median of three months. Nausea and vomiting occurred in 21 of 22 patients; leukopenia in eleven of 22; thrombocytopenia in four of 22. There was no clinically significant cardiotoxicity. Our study indicates that this regimen for adriamycin was relatively ineffective in the management of these inoperable or metastatic malignancies.

  7. 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.

  8. Single stage, low noise advanced technology fan. Volume 3: Acoustic design

    NASA Technical Reports Server (NTRS)

    Kazin, S. B.; Mishler, R. B.

    1976-01-01

    The acoustic 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 (1,650 ft/sec). 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 is 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. Predicted unsuppressed and suppressed fore and aft maximum perceived noise levels indicate that the cutback condition is the most critical with respect to the goal, which is probably unattainable for that condition. This is also true for aft radiated noise in the approach condition.

  9. Surgical resection and vascularized bone reconstruction in advanced stage medication-related osteonecrosis of the jaw.

    PubMed

    Caldroney, S; Ghazali, N; Dyalram, D; Lubek, J E

    2017-07-01

    A retrospective review of all patients with stage 3 medication-related osteonecrosis of the jaw (MRONJ), treated by surgical resection and immediate vascularized bone reconstruction at a tertiary care medical center, was performed. Eleven patients were included, seven female and four male; their mean age was 65.8 years (range 56-73 years). Mean follow-up was 25 months. Ten patients had received intravenous bisphosphonates. The most common pathology was breast cancer (4/11). Pain (n=8) and pathological fracture (n=7) were the most common presenting symptoms. Microvascular free flaps consisted of seven fibula osteocutaneous flaps and four scapula osteocutaneous free flaps. All patients reported resolution of symptoms, with complete bone union identified radiographically (100%). Complications occurred in three patients (27%). One patient required removal of hardware at 8 months postoperative. Dental implant rehabilitation was completed in two patients. Ten patients are tolerating an oral diet. Ten patients are alive without evidence of MRONJ at any of the surgical sites. One patient died 28 months after surgery from progression of metastatic disease. Advanced MRONJ can be successfully treated in patients using vascularized tissue transfer, including those patients with significant peripheral vascular disease. Dental rehabilitation is a viable option for advanced MRONJ patients treated by vascularized flap reconstruction. Copyright © 2017 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

  10. 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.

  11. Differentiation stage of myeloma plasma cells: biological and clinical significance.

    PubMed

    Paiva, B; Puig, N; Cedena, M T; de Jong, B G; Ruiz, Y; Rapado, I; Martinez-Lopez, J; Cordon, L; Alignani, D; Delgado, J A; van Zelm, M C; Van Dongen, J J M; Pascual, M; Agirre, X; Prosper, F; Martín-Subero, J I; Vidriales, M-B; Gutierrez, N C; Hernandez, M T; Oriol, A; Echeveste, M A; Gonzalez, Y; Johnson, S K; Epstein, J; Barlogie, B; Morgan, G J; Orfao, A; Blade, J; Mateos, M V; Lahuerta, J J; San-Miguel, J F

    2017-02-01

    The notion that plasma cells (PCs) are terminally differentiated has prevented intensive research in multiple myeloma (MM) about their phenotypic plasticity and differentiation. Here, we demonstrated in healthy individuals (n=20) that the CD19-CD81 expression axis identifies three bone marrow (BM)PC subsets with distinct age-prevalence, proliferation, replication-history, immunoglobulin-production, and phenotype, consistent with progressively increased differentiation from CD19+CD81+ into CD19-CD81+ and CD19-CD81- BMPCs. Afterwards, we demonstrated in 225 newly diagnosed MM patients that, comparing to normal BMPC counterparts, 59% had fully differentiated (CD19-CD81-) clones, 38% intermediate-differentiated (CD19-CD81+) and 3% less-differentiated (CD19+CD81+) clones. The latter patients had dismal outcome, and PC differentiation emerged as an independent prognostic marker for progression-free (HR: 1.7; P=0.005) and overall survival (HR: 2.1; P=0.006). Longitudinal comparison of diagnostic vs minimal-residual-disease samples (n=40) unraveled that in 20% of patients, less-differentiated PCs subclones become enriched after therapy-induced pressure. We also revealed that CD81 expression is epigenetically regulated, that less-differentiated clonal PCs retain high expression of genes related to preceding B-cell stages (for example: PAX5), and show distinct mutation profile vs fully differentiated PC clones within individual patients. Together, we shed new light into PC plasticity and demonstrated that MM patients harbouring less-differentiated PCs have dismal survival, which might be related to higher chemoresistant potential plus different molecular and genomic profiles.

  12. Differentiation stage of myeloma plasma cells: biological and clinical significance

    PubMed Central

    Paiva, B; Puig, N; Cedena, MT; de Jong, BG; Ruiz, Y; Rapado, I; Martinez-Lopez, J; Cordon, L; Alignani, D; Delgado, JA; van Zelm, MC; Van Dongen, JJM; Pascual, M; Agirre, X; Prosper, F; Martín-Subero, JI; Vidriales, M-B; Gutierrez, NC; Hernandez, MT; Oriol, A; Echeveste, MA; Gonzalez, Y; Johnson, SK; Epstein, J; Barlogie, B; Morgan, GJ; Orfao, A; Blade, J; Mateos, MV; Lahuerta, JJ; San-Miguel, JF

    2017-01-01

    The notion that plasma cells (PCs) are terminally differentiated has prevented intensive research in multiple myeloma (MM) about their phenotypic plasticity and differentiation. Here, we demonstrated in healthy individuals (n = 20) that the CD19 − CD81 expression axis identifies three bone marrow (BM)PC subsets with distinct age-prevalence, proliferation, replication-history, immunoglobulin-production, and phenotype, consistent with progressively increased differentiation from CD19+CD81+ into CD19 − CD81+ and CD19 − CD81 − BMPCs. Afterwards, we demonstrated in 225 newly diagnosed MM patients that, comparing to normal BMPC counterparts, 59% had fully differentiated (CD19 − CD81 −) clones, 38% intermediate-differentiated (CD19 − CD81+) and 3% less-differentiated (CD19+CD81+) clones. The latter patients had dismal outcome, and PC differentiation emerged as an independent prognostic marker for progression-free (HR: 1.7; P = 0.005) and overall survival (HR: 2.1; P = 0.006). Longitudinal comparison of diagnostic vs minimal-residual-disease samples (n = 40) unraveled that in 20% of patients, less-differentiated PCs subclones become enriched after therapy-induced pressure. We also revealed that CD81 expression is epigenetically regulated, that less-differentiated clonal PCs retain high expression of genes related to preceding B-cell stages (for example: PAX5), and show distinct mutation profile vs fully differentiated PC clones within individual patients. Together, we shed new light into PC plasticity and demonstrated that MM patients harbouring less-differentiated PCs have dismal survival, which might be related to higher chemoresistant potential plus different molecular and genomic profiles. PMID:27479184

  13. Bacterial vectors for active immunotherapy reach clinical and industrial stages

    PubMed Central

    Le Gouëllec, Audrey; Chauchet, Xavier; Polack, Benoit; Buffat, Laurent; Toussaint, Bertrand

    2012-01-01

    Active immunotherapy based on live attenuated bacterial vectors has matured in terms of industrial development and develops through a combination of three phenomena. First, active immunotherapy that stimulates an antigen-specific cytotoxic T-cell immune response has become a reality after several years of work. Second, there is still a need to identify vectors that can deliver antigens to the cytosol of antigen-presenting cells in vivo. Third, the recent progress in the understanding of bacterial lifestyle and in developing genetic engineering tools has enabled the design of bioengineered bugs that are capable of delivering antigens. Here, we review the mechanisms by which clinical bacterial vectors deliver antigens into the cytosol of antigen-presenting cells and summarize the development strategy of the three identified firms in this field. PMID:22894945

  14. Polymeric nanotherapeutics: clinical development and advances in stealth functionalization strategies

    NASA Astrophysics Data System (ADS)

    Hu, Che-Ming J.; Fang, Ronnie H.; Luk, Brian T.; Zhang, Liangfang

    2013-12-01

    Long-circulating polymeric nanotherapeutics have garnered increasing interest in research and in the clinic owing to their ability to improve the solubility and pharmacokinetics of therapeutic cargoes. Modulation of carrier properties promises more effective drug localization at the disease sites and can lead to enhanced drug safety and efficacy. In the present review, we highlight the current development of polymeric nanotherapeutics in the clinic. In light of the importance of stealth properties in therapeutic nanoparticles, we also review the advances in stealth functionalization strategies and examine the performance of different stealth polymers in the literature. In addition, we discuss the recent development of biologically inspired ``self'' nanoparticles, which present a differing stealth concept from conventional approaches.

  15. 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.

  16. Stage IV Gastro-Entero-Pancreatic Neuroendocrine Neoplasms: A Risk Score to Predict Clinical Outcome.

    PubMed

    Panzuto, Francesco; Merola, Elettra; Pavel, Marianne Ellen; Rinke, Anja; Kump, Patrizia; Partelli, Stefano; Rinzivillo, Maria; Rodriguez-Laval, Victor; Pape, Ulrich Frank; Lipp, Rainer; Gress, Thomas; Wiedenmann, Bertram; Falconi, Massimo; Delle Fave, Gianfranco

    2017-04-01

    Several risk factors predict clinical outcome in gastro-entero-pancreatic neuroendocrine neoplasms (GEP-NENs); however, the impact of their combination has not been investigated so far. A retrospective analysis of stage IV GEP-NENs was performed. Multivariate analysis for progression of disease (PD) was performed by Cox proportional hazards method to obtain a risk score. Area under the curve obtained by receiver operating characteristic analysis was used to assess the score performance. Progression-free survival analysis was performed by Kaplan-Meier method. Two hundred eighty-three stage IV GEP-NENs were evaluated, including 93 grade 1 neuroendocrine tumors (32.9%), 153 grade 2 neuroendocrine tumors (54%), and 37 grade 3 neuroendocrine carcinomas (13.1%). Independent risk factors for PD were Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The risk score was calculated as follows: (0.025 × Ki67) + [(0 if no liver metastases or liver involvement <25%) OR (0.405 if liver involvement 25%-50%) OR (0.462 if liver involvement >50%)] + [(0 if no extra-abdominal metastases) OR (0.528 if extra-abdominal metastases present)]. The risk score accuracy to predict PD was superior compared with the G grading system (area under the curve: 0.705 and 0.622, respectively). Three subgroups of patients with low, intermediate, and high risk of PD according to risk score were identified, median progression-free survival being 26 months, 19 months, and 12 months, respectively. In stage IV GEP-NENs, a risk score able to predict PD was obtained by combining Ki67, proportion of metastatic liver involvement, and presence of extra-abdominal metastases. The score may help to discriminate patients with different progression risk level to plan tailored therapeutic approaches and follow-up programs. The Oncologist 2017;22:409-415Implications for Practice: Clinical outcome of patients with advanced gastro-entero-pancreatic neuroendocrine

  17. The future of drug development: advancing clinical trial design.

    PubMed

    Orloff, John; Douglas, Frank; Pinheiro, Jose; Levinson, Susan; Branson, Michael; Chaturvedi, Pravin; Ette, Ene; Gallo, Paul; Hirsch, Gigi; Mehta, Cyrus; Patel, Nitin; Sabir, Sameer; Springs, Stacy; Stanski, Donald; Evers, Matthias R; Fleming, Edd; Singh, Navjot; Tramontin, Tony; Golub, Howard

    2009-12-01

    Declining pharmaceutical industry productivity is well recognized by drug developers, regulatory authorities and patient groups. A key part of the problem is that clinical studies are increasingly expensive, driven by the rising costs of conducting Phase II and III trials. It is therefore crucial to ensure that these phases of drug development are conducted more efficiently and cost-effectively, and that attrition rates are reduced. In this article, we argue that moving from the traditional clinical development approach based on sequential, distinct phases towards a more integrated view that uses adaptive design tools to increase flexibility and maximize the use of accumulated knowledge could have an important role in achieving these goals. Applications and examples of the use of these tools--such as Bayesian methodologies--in early- and late-stage drug development are discussed, as well as the advantages, challenges and barriers to their more widespread implementation.

  18. 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

  19. Photodynamic therapy for locally advanced pancreatic cancer: early clinical results

    NASA Astrophysics Data System (ADS)

    Sandanayake, N. S.; Huggett, M. T.; Bown, S. G.; Pogue, B. W.; Hasan, T.; Pereira, S. P.

    2010-02-01

    Pancreatic adenocarcinoma ranks as the fourth most common cause of cancer death in the USA. Patients usually present late with advanced disease, limiting attempted curative surgery to 10% of cases. Overall prognosis is poor with one-year survival rates of less than 10% with palliative chemotherapy and/or radiotherapy. Given these dismal results, a minimally invasive treatment capable of local destruction of tumor tissue with low morbidity may have a place in the treatment of this disease. In this paper we review the preclinical photodynamic therapy (PDT) studies which have shown that it is possible to achieve a zone of necrosis in normal pancreas and implanted tumour tissue. Side effects of treatment and evidence of a potential survival advantage are discussed. We describe the only published clinical study of pancreatic interstitial PDT, which was carried out by our group (Bown et al Gut 2002), in 16 patients with unresectable locally advanced pancreatic adenocarcinoma. All patients had evidence of tumor necrosis on follow-up imaging, with a median survival from diagnosis of 12.5 months. Finally, we outline a phase I dose-escalation study of verteporfin single fibre PDT followed by standard gemcitabine chemotherapy which our group is currently undertaking in patients with locally advanced pancreatic cancer. Randomized controlled studies are also planned.

  20. Health utility decreases with increasing clinical stage in amyotrophic lateral sclerosis.

    PubMed

    Jones, Ashley R; Jivraj, Naheed; Balendra, Rubika; Murphy, Caroline; Kelly, Joanna; Thornhill, Marie; Young, Carolyn; Shaw, Pamela J; Leigh, P Nigel; Turner, Martin R; Steen, I Nick; McCrone, Paul; Al-Chalabi, Ammar

    2014-06-01

    Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease typically causing death within three years. Understanding the impact of disease on patients using health utility at different stages of ALS would allow meaningful cost-benefit analysis of new potential therapies. A common health-related quality of life measurement, developed and validated for the UK, is the EQ-5D. Using clinical trial data from the LiCALS study, we calculated health utility using the EQ-5D for each King's ALS clinical stage from 214 patients. We analysed whether health utility, and other health-related measures, significantly changed between each of the clinical stages. Results showed that mean health utility decreased by 0.487 (the scale runs from 1 to - 0.594) between clinical stages 2A and 4. Emotional states, measured using the Hospital Anxiety and Depression Scale (HADS), showed worsening depression and anxiety scores as ALS progressed. Age of onset, disease onset, gender and treatment group were not predictors of EQ-5D, depression or anxiety. In conclusion, increasing severity of King's ALS Clinical Stage is associated with a progressive decrease in EQ-5D health utility. This is useful for cost-benefit analysis of new therapies and validates this ALS clinical staging system.

  1. COPD, stage and treatment in a large outpatient clinic

    PubMed Central

    Holm, Claire Præst; Holm, Jakob; Nørgaard, Annette; Godtfredsen, Nina

    2017-01-01

    ABSTRACT Some COPD patients suffer from frequent exacerbations despite triple inhalation treatment. These frequent exacerbators should be identified, as exacerbations often lead to decreasing lung function and increasing mortality. Roflumilast reduces exacerbations in patients with a previous history of exacerbations. Our aim was to describe COPD patient characteristics and compare roflumilast treatment eligible to non-eligible patients. An observational cross-section study was conducted. Patients were included from a large COPD outpatient clinic. Information regarding COPD patient characteristics was registered on a standardized form and lung function was measured. Patients were categorized according to the GOLD classification. Eligibility for roflumilast treatment was assessed and patient characteristics compared between groups. 547 patients were included. Most patients (54%) were in GOLD group D. 62 patients (11.3%) met the criteria for treatment with roflumilast. Among the patients eligible for roflumilast treatment, only 14 patients (22.6%) were receiving treatment. There were no significant differences in FEV1, number of exacerbations, hospitalization due to exacerbation, MRC grade, age, smoking status and medication use between patients receiving roflumilast and not treated eligible patients. Our study documents low use of roflumilast treatment. In view of the established effect of roflumilast we think that this treatment should be considered more consistently as an option among COPD patients fulfilling the criteria for this therapy. PMID:28326174

  2. 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.

  3. The biology of infertility: research advances and clinical challenges

    PubMed Central

    Matzuk, Martin M; Lamb, Dolores J

    2013-01-01

    Reproduction is required for the survival of all mammalian species, and thousands of essential ‘sex’ genes are conserved through evolution. Basic research helps to define these genes and the mechanisms responsible for the development, function and regulation of the male and female reproductive systems. However, many infertile couples continue to be labeled with the diagnosis of idiopathic infertility or given descriptive diagnoses that do not provide a cause for their defect. For other individuals with a known etiology, effective cures are lacking, although their infertility is often bypassed with assisted reproductive technologies (ART), some accompanied by safety or ethical concerns. Certainly, progress in the field of reproduction has been realized in the twenty-first century with advances in the understanding of the regulation of fertility, with the production of over 400 mutant mouse models with a reproductive phenotype and with the promise of regenerative gonadal stem cells. Indeed, the past six years have witnessed a virtual explosion in the identification of gene mutations or polymorphisms that cause or are linked to human infertility. Translation of these findings to the clinic remains slow, however, as do new methods to diagnose and treat infertile couples. Additionally, new approaches to contraception remain elusive. Nevertheless, the basic and clinical advances in the understanding of the molecular controls of reproduction are impressive and will ultimately improve patient care. PMID:18989307

  4. [Advanced data analysis and visualization for clinical laboratory].

    PubMed

    Inada, Masanori; Yoneyama, Akiko

    2011-01-01

    This paper describes visualization techniques that help identify hidden structures in clinical laboratory data. The visualization of data is helpful for a rapid and better understanding of the characteristics of data sets. Various charts help the user identify trends in data. Scatter plots help prevent misinterpretations due to invalid data by identifying outliers. The representation of experimental data in figures is always useful for communicating results to others. Currently, flexible methods such as smoothing methods and latent structure analysis are available owing to the presence of advanced hardware and software. Principle component analysis, which is a well-known technique used to reduce multidimensional data sets, can be carried out on a personal computer. These methods could lead to advanced visualization with regard to exploratory data analysis. In this paper, we present 3 examples in order to introduce advanced data analysis. In the first example, a smoothing spline was fitted to a time-series from the control chart which is not in a state of statistical control. The trend line was clearly extracted from the daily measurements of the control samples. In the second example, principal component analysis was used to identify a new diagnostic indicator for Graves' disease. The multi-dimensional data obtained from patients were reduced to lower dimensions, and the principle components thus obtained summarized the variation in the data set. In the final example, a latent structure analysis for a Gaussian mixture model was used to draw complex density functions suitable for actual laboratory data. As a result, 5 clusters were extracted. The mixed density function of these clusters represented the data distribution graphically. The methods used in the above examples make the creation of complicated models for clinical laboratories more simple and flexible.

  5. Recent advances in targeted proteomics for clinical applications.

    PubMed

    Domon, Bruno; Gallien, Sebastien

    2015-04-01

    MS-based approaches using targeted methods have been widely adopted by the proteomics community to study clinical questions such as the evaluation of biomarkers. At present, the most widely used targeted MS method is the SRM technique typically performed on a triple quadrupole instrument. However, the high analytical demands for performing clinical studies in combination with the extreme complexity of the samples involved are a serious challenge. The segmentation of the biomarker evaluation workflow has only partially alleviated these issues by differently balancing the analytical requirements and throughput at different stages of the process. The recent introduction of targeted high-resolution and accurate-mass analyses on fast sequencing mass spectrometers operated in parallel reaction monitoring (PRM) mode offers new avenues to conduct clinical studies and thus overcome some of the limitations of the triple quadrupole instrument. This article discusses the attributes and specificities of the PRM technique, in terms of experimental design, execution, and data analysis, and the implications for biomarker evaluation. The benefits of PRM on data quality and the impact on the consistency of results are highlighted and the definitive progress on the overall output of clinical studies, including high throughput, is discussed.

  6. Current status of selected oral peptide technologies in advanced preclinical development and in clinical trials.

    PubMed

    Aguirre, T A S; Teijeiro-Osorio, D; Rosa, M; Coulter, I S; Alonso, M J; Brayden, D J

    2016-11-15

    The development of oral dosage forms that allows absorption of therapeutic peptides to the systemic circulation is one of the greatest challenges for the pharmaceutical industry. Currently, a number of technologies including either mixtures of penetration enhancers or protease inhibitors and/or nanotechnology-based products are under clinical development. Typically, these formulations are presented in the form of enteric-coated tablets or capsules. Systems undergoing preclinical investigation include further advances in nanotechnology, including intestinal microneedle patches, as well as their combination with regional delivery to the colon. This review critically examines four selected promising oral peptide technologies at preclinical stage and the twelve that have progressed to clinical trials, as indicated in www.clinicaltrials.gov. We examined these technologies under the criteria of peptide selection, formulation design, system components and excipients, intestinal mechanism of action, efficacy in man, and safety issues. The conclusion is that most of the technologies in clinical trials are incremental rather than paradigm-shifting and that even the more clinically advanced oral peptide drugs examples of oral bioavailability appear to yield oral bioavailability values of only 1-2% and are, therefore, only currently suitable for a limited range of peptides.

  7. Comparison of clinical and pathological tumor, node and metastasis staging of lung cancer: 15-year experience with 530 patients.

    PubMed

    Turk, F; Gursoy, S; Yaldiz, S; Yuncu, G; Yazgan, S; Basok, O

    2011-12-01

    The prognosis of patients with lung cancer depends on early diagnosis and accurate staging. The present staging system for lung cancer is tumor (T), node (N), and metastasis (M) staging (TNM). We compared the accuracy of preoperative (clinical) and postoperative (pathological) TNM staging of lung cancer in this study and emphasized the preoperative mediastinoscopy is useful in selected patients. We performed a retrospective comparison of the clinical and pathological TNM staging of 530 patients with lung cancer treated surgically. The preoperative clinical TNM staging of all patients was based on physical examination, radiological investigations and bronchoscopy. Mediastinoscopy was used routinely for all patients with an indication since 2000. We found the agreement between clinical and pathological TNM staging to be only 46.4%. The comparison between clinical and pathological TNM staging was 6.2-5.3% at stage Ia, 37.9%-36% at stage Ib, 0.7-0.9% at stage IIa, 23-25% at stage IIb, 27.1-16.2% at stage IIIa, and 3.2-14% at stage IIIb respectively. The frequency rates of the different clinical and pathologic stages were 6.2% and 5.3%, for stage Ia, 37.9% and 36% for stage Ib, 0.7% and 0.9% for stage IIa, 23% and 25% for stage IIb, 27.1% and 16.2% for stage IIIa, 3.2% and 14% for stage IIIb respectively. We compared the clinical and pathological staging in patients with non small cell lung cancer submitted to surgical treatment to identify the causes of any discordance. The clinical TNM and staging based on computerized tomography was found to be inaccurate.

  8. The relationship between cognitive reserve and the clinical stage of HIV infection.

    PubMed

    Alvarez-Tostado, Pablo; Inozemtseva, Olga; Aguiñiga, Miguel A; López, Enrique; Matute, Esmeralda

    2016-01-01

    The objective of this study was to determine whether the effect of cognitive reserve (CR) on neuropsychological functioning differs according to the clinical stage of HIV infection. A sample of 34 HIV-positive individuals aged 23-49, with a minimum of 9 years of formal education, was assessed. Participants were grouped according to the Centers for Disease Control and Prevention's (CDC) clinical stages (A = 10, B = 16, C = 8). CR was calculated for each clinical stage group in accordance with estimates of premorbid IQ, years of education, and occupational attainment. The sum of these three variables was then transformed into z-scores. Individuals above the median were classified as having "High" CR (HCR), those below the median were classified as "Low" CR (LCR). Participants completed an evaluation of cognitive and executive functions based on selected, modified tasks from the HIV University of Miami Annotated Neuropsychological test in Spanish (HUMANS). Assessment included the following domains: attention, memory (visual, verbal, and working memory), executive functions (cognitive flexibility, switching), language (naming), and visual constructive skills (block design). HCR outperformed LCR in all cognitive domains. Comparison of HCR and LCR in each clinical stage revealed that the effect of CR was stronger in stage B than in stages A and C, suggesting that this effect does indeed vary among stages.

  9. Improvement in clinical TNM staging documentation within a prostate cancer quality improvement collaborative.

    PubMed

    Filson, Christopher P; Boer, Brooke; Curry, Jon; Linsell, Susan; Ye, Zaojun; Montie, James E; Miller, David C

    2014-04-01

    To assess the effectiveness of a feedback and educational intervention to increase documentation of clinical tumor-node-metastasis (TNM) stage among urologists in a statewide quality improvement collaborative. The Michigan Urological Surgery Improvement Collaborative (MUSIC) is a consortium of urology practices that aims to improve the quality and cost-efficiency of prostate cancer care. In pilot data collection activities, trained abstractors recorded medical record documentation of clinical TNM stage by participating urologists. We compared levels of TNM stage documentation in 12 MUSIC practices at baseline and after performance feedback and a collaborative-wide educational intervention. We examined patient and practice characteristics associated with documentation of TNM stage. We accrued 491 and 581 men with newly diagnosed prostate cancer during the baseline and postfeedback phases of data collection, respectively. At baseline, 58% of patients had clinical TNM staging in the medical record, ranging from 19% to 96% across 12 practices (P <.05). After the intervention, documentation improved to 79% of patients overall, with 7 individual practices achieving significant improvements (all P <.05). The greatest improvements in documentation occurred among patients treated in smaller practices (ie, 1-4 urologists). After collaborative review of staging criteria and feedback of baseline performance, urologists in MUSIC practices dramatically improved documentation of clinical TNM stage. This finding underscores the behavioral change possible with the collaborative quality improvement model and ensures the necessary risk stratification data for our ongoing efforts to improve care. Copyright © 2014 Elsevier Inc. All rights reserved.

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

    PubMed

    Dong, Gaohong

    2014-04-15

    Currently, adaptive phase II/III clinical trials are typically carried out with a strict two-stage design. The first stage is a learning stage called phase II, and the second stage is a confirmatory stage called phase III. Following phase II analysis, inefficacious or harmful dose arms are dropped, then one or two promising dose arms are selected for the second stage. However, there are often situations in which researchers are in dilemma to make 'go or no-go' decision and/or to select 'best' dose arm(s), as data from the first stage may not provide sufficient information for their decision making. In this case, it is challenging to follow a strict two-stage plan. Therefore, we propose a varying-stage adaptive phase II/III clinical trial design, in which we consider whether there is a need to have an intermediate stage to obtain more data, so that a more informative decision could be made. Hence, the number of further investigational stages in our design is determined on the basis of data accumulated to the interim analysis. With respect to adaptations, we consider dropping dose arm(s), switching another plausible endpoint as the primary study endpoint, re-estimating sample size, and early stopping for futility. We use an adaptive combination test to perform final analyses. By applying closed testing procedure, we control family-wise type I error rate at the nominal level of α in the strong sense. We delineate other essential design considerations including the threshold parameters and the proportion of alpha allocated in the two-stage versus three-stage setting.

  11. 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.

  12. 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.

  13. Renewed interest in the role of consolidative radiotherapy in advanced stage diffuse large B-cell lymphoma.

    PubMed

    Shi, Zheng; Esiashvili, Natia; Flowers, Christopher; Das, Satya; Khan, Mohammad K

    2013-10-01

    Diffuse large B-cell lymphoma (DLBCL) represents the most common subtype of non-Hodgkin lymphoma (NHL) in the United States, and two-thirds of these patients will present with advanced stage (stage III-IV) disease. Although radiation therapy (RT) alone was the first curative therapy for limited stage DLBCL, the advancement of combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with the addition of the anti-CD20 antibody rituximab became the cornerstone of current management. The role of consolidative RT as part of first-line therapy in the management of patients with advanced stage DLBCL remains unclear, and represents an area of controversy with considerable differences in patterns of practice across different institutions. Emerging data now challenge the National Comprehensive Cancer Network (NCCN) guidelines, and give support to the use of consolidative RT in patients with advanced stage DLBCL. This review summarizes the major studies as reflected in our current practice and provides further insight into future directions for randomized trials which would help better define the role of consolidative RT in such a cohort.

  14. 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

  15. Rational Combination of Immunotherapies with Clinical Efficacy in Mice with Advanced Cancer.

    PubMed

    Bransi, Ali; Salgado, Oscar Camilo; Beffinger, Michal; Milo, Karim; Silina, Karina; Yagita, Hideo; Becher, Burkhard; Knuth, Alexander; van den Broek, Maries

    2015-11-01

    In the context of cancer, naïve T cells are insufficiently primed and become progressively dysfunctional. Boosting antitumor responses by blocking PD-1 or CTLA-4 results in durable clinical responses only in a limited proportion of cancer patients, suggesting that other pathways must be targeted to improve clinical efficacy. Our preclinical study in TRAMP mice comparing 14 different immune interventions identified anti-CD40 + IL2/anti-IL2 complexes + IL12Fc as a uniquely efficacious treatment that prevents tolerance induction, promotes priming of sustained, protective tumor-specific CD8(+) T cells, and cures late-stage cancer when given together with adoptively transferred tumor-specific T cells. We propose that improving signals 2 (costimulation) and 3 (cytokines) together with fresh tumor-specific, rather than boosting of dysfunctional preexisting memory, T cells represents a potent therapy for advanced cancer.

  16. Management for Elderly Women With Advanced-Stage, High-Grade Endometrial Cancer.

    PubMed

    Rauh-Hain, J Alejandro; Pepin, Kristen J; Meyer, Larissa A; Clemmer, Joel T; Lu, Karen H; Rice, Laurel W; Uppal, Shitanshu; Schorge, John O; Del Carmen, Marcela G

    2015-12-01

    To examine the treatment and survival of elderly women diagnosed with advanced-stage, high-grade endometrial cancer. We performed a retrospective cohort study of women diagnosed between 2003 and 2011 with advanced-stage, high-grade endometrial cancers (grade 3 adenocarcinoma, carcinosarcoma, clear-cell carcinoma, and uterine serous carcinoma) using the National Cancer Database. Women were stratified by age: younger than 55, 55-64, 65-74, 75-84, and 85 years old or older. Multivariate logistic regression models and Cox proportional hazards survival methods for all-cause mortality were used for analyses. Twenty thousand four hundred sixty-eight patients were included, 14.9% younger than 55 years, 30.9% 55-64 years, 31.1% 65-74 years, 18.8% 75-84 years, and 4.3% 85 years old or older. Patients younger than 55 years had surgery more frequently compared with patients 75-84 years (97.2% compared with 95.8%; P<.001) and 85 years or older (97.2% compared with 94.8%; P<.001) and a higher rate of lymph node dissection (78.7% compared with 70.5%; P<.001 and 78.7% compared with 59.5%; P<.001, respectively). Women younger than 55 years old were more likely to receive chemotherapy compared with those 75-84 years (63.9% compared with 42.2%; P<.001) and 85 years old or older (63.9% compared with 22%; P<.001). After adjusting for prognostic factors, women ages 75-84 and 85 years or older were less likely to have received chemotherapy compared with women younger than 55 years (odds ratio [OR] 0.34, 95% confidence interval [CI] 0.29-0.38 and OR 0.12, 95% CI 0.10-0.14). The same was true with surgery (OR 0.63, 95% CI 0.45-0.88 and OR 0.46, 95% CI 0.30-0.70) and radiotherapy (OR 0.61, 95% CI 0.53-0.70 and OR 0.45, 95% CI 0.37-0.56). The Cox regression model showed that in women with stage III disease, women 75-84 years had a twofold higher risk of death (hazard ratio [HR] 2.38, 95% CI 2.14-2.65) and those 85 years or older had a threefold higher risk (HR 3.16, 95% CI 2

  17. Interval estimation of binomial proportion in clinical trials with a two-stage design.

    PubMed

    Tsai, Wei-Yann; Chi, Yunchan; Chen, Chia-Min

    2008-01-15

    Generally, a two-stage design is employed in Phase II clinical trials to avoid giving patients an ineffective drug. If the number of patients with significant improvement, which is a binomial response, is greater than a pre-specified value at the first stage, then another binomial response at the second stage is also observed. This paper considers interval estimation of the response probability when the second stage is allowed to continue. Two asymptotic interval estimators, Wald and score, as well as two exact interval estimators, Clopper-Pearson and Sterne, are constructed according to the two binomial responses from this two-stage design, where the binomial response at the first stage follows a truncated binomial distribution. The mean actual coverage probability and expected interval width are employed to evaluate the performance of these interval estimators. According to the comparison results, the score interval is recommended for both Simon's optimal and minimax designs.

  18. Advances in designs for Alzheimer's disease clinical trials.

    PubMed

    Cummings, Jeffrey; Gould, Heath; Zhong, Kate

    2012-01-01

    There is an urgent need to identify new treatments for the rapidly growing population of people with Alzheimer's disease (AD). Innovations in clinical trial designs many help to reduce development time, provide more definitive answers regarding drug efficacy, and facilitate prioritizing compounds to be advanced to Phase III clinical trials. Standard designs compare drug and placebo changes from baseline on a rating scale. Baysian adaptive clinical trials allow the use of data collected in the trial to modify doses, sample size, trial duration, and entry criteria in an ongoing way as the data are collected. Disease-modification is supported by findings on staggered start and delayed withdrawal designs. Futility designs can use historical controls and may shorten trial duration. Combination therapy designs may allow investigation of additive or synergistic treatment effects. Novel trial selection criteria allow investigation of treatment effects in asymptomatic or minimally symptomatic, prodromal AD populations. The Clinical Dementia Rating-Sum of Boxes (CDR-SOB) can be considered as a single trial outcome in early disease populations. Alternate forms of the Alzheimer's Disease Assessment Scale-Cognitive Portion (ADAS-cog), computerized measures, and pharmacoeconomic scales provide new and relevant information on drug effects. Comparative dose strategies are used in trials of symptomatic agents, and novel methods including withdrawal designs, symptom emergence analyses, and sequential designs are being utilized to assess the efficacy of putative psychotropic agents. The choice of trial design is driven by the question to be answered by the clinical trial; an increasing number of design approaches are available and may be useful in accelerating and refining AD drug development.

  19. Advances in designs for Alzheimer’s disease clinical trials

    PubMed Central

    Cummings, Jeffrey; Gould, Heath; Zhong, Kate

    2012-01-01

    There is an urgent need to identify new treatments for the rapidly growing population of people with Alzheimer’s disease (AD). Innovations in clinical trial designs many help to reduce development time, provide more definitive answers regarding drug efficacy, and facilitate prioritizing compounds to be advanced to Phase III clinical trials. Standard designs compare drug and placebo changes from baseline on a rating scale. Baysian adaptive clinical trials allow the use of data collected in the trial to modify doses, sample size, trial duration, and entry criteria in an ongoing way as the data are collected. Disease-modification is supported by findings on staggered start and delayed withdrawal designs. Futility designs can use historical controls and may shorten trial duration. Combination therapy designs may allow investigation of additive or synergistic treatment effects. Novel trial selection criteria allow investigation of treatment effects in asymptomatic or minimally symptomatic, prodromal AD populations. The Clinical Dementia Rating-Sum of Boxes (CDR-SOB) can be considered as a single trial outcome in early disease populations. Alternate forms of the Alzheimer’s Disease Assessment Scale-Cognitive Portion (ADAS-cog), computerized measures, and pharmacoeconomic scales provide new and relevant information on drug effects. Comparative dose strategies are used in trials of symptomatic agents, and novel methods including withdrawal designs, symptom emergence analyses, and sequential designs are being utilized to assess the efficacy of putative psychotropic agents. The choice of trial design is driven by the question to be answered by the clinical trial; an increasing number of design approaches are available and may be useful in accelerating and refining AD drug development. PMID:23383393

  20. Critical advances in bridging personal health informatics and clinical informatics.

    PubMed

    Koch, S; Vimarlund, V

    2012-01-01

    To provide a survey over significant developments in the area of linking personal health informatics and clinical informatics, to give insights into critical advances and to discuss open problems and opportunities in this area. A scoping review over the literature published in scientific journals and relevant conference proceedings in the intersection between personal health informatics and clinical informatics over the years 2010 and 2011 was performed. The publications analyzed are related to two main topics, namely "Sharing information and collaborating through personal health records, portals and social networks" and "Integration of personal health systems with clinical information systems". For the first topic, results are presented according to five different themes: "Patient expectations and attitudes", "Real use experiences", "Changes for care providers", "Barriers to adoption" and "Proposed technical infrastructures". For the second topic, two different themes were found, namely "Technical architectures and interoperability" and "Security, safety and privacy issues". Results show a number of gaps between the information needs of patients and the information care provider organizations provide to them as well as the lack of a trusted technical, ethical and regulatory framework regarding information sharing. Despite recent developments in the areas of personal health informatics and clinical informatics both fields have diverging needs. To support both clinical work processes and empower patients to effectively handle self-care, a number of issues remain unsolved. Open issues include privacy and confidentiality, including trusted sharing of health information and building collaborative environments between patients, their families and care providers. There are further challenges to meet around health and technology literacy as well as to overcome structural and organizational barriers. Frameworks for evaluating personal health informatics applications and

  1. Changes in mortality and human longevity in Kerala: are they leading to the advanced stage?

    PubMed Central

    Thomas, Muttikkal B.; James, Kuriath S.

    2014-01-01

    Background During the last century, Kerala witnessed drastic mortality reduction and high improvement in longevity. This achievement is often compared with that of developed countries. However, how far the early advantages in mortality reduction have further enhanced in Kerala remains unknown. In most developed countries, advanced stage of mortality reduction and further increase in longevity was achieved mainly due to the mortality shift from adult and older ages to oldest ages (Olshansky and Ault 1986). Objectives Considering the lack of comprehensive study on the change in longevity in Kerala, this study focuses on discovering (i) the historical time-periods that provided the biggest gain to life expectancy and also the beneficiaries (by age group and sex) and (ii) the contributions of major groups of causes of death in mortality reduction and consequent improvement in longevity. Methodology and data The study uses the methodology proposed by Olshansky and Ault in 1986. It used methods such as Temporary Life Expectancy (TLE), Annual Relative Change in TLE, Decomposition of changes in longevity among different age groups (gender and spatial) and causes of deaths, for the analysis. It used data from various sources such as Census, Civil Registration System (CRS) and Directorate of Health Services (DHS), as well as survey data from Sample Registration System (SRS) and Medically Certified Causes of Deaths (MCCD) for this study. Finding and conclusion The study found that overall mortality dramatically declined in the state in the recent decades. Younger ages have contributed the most for this reduction. Therefore, further mortality reduction is possible in adult and early old ages. However, the contribution of these ages to life expectancy was lower than that of youngsters until 1991–2000 especially among males. This may indicate a slow progress towards the advanced stage of epidemiological transition characterized by high prevalence of non-communicable diseases

  2. Initial Stage Affects Survival Even After Complete Pathologic Remission is Achieved in Locally Advanced Esophageal Cancer: Analysis of 70 Patients With Pathologic Major Response After Preoperative Chemoradiotherapy

    SciTech Connect

    Kim, Min Kyoung; Cho, Kyung-Ja; Park, Seung-Il; Kim, Yong Hee; Kim, Jong Hoon; Song, Ho-Young; Shin, Ji Hoon; Jung, Hwoon Yong; Lee, Gin Hyug; Choi, Kee Don; Song, Ho June; Ryu, Jin-Sook; Kim, Sung-Bae

    2009-09-01

    Purpose: To analyze outcomes and factors predictive for recurrence and survival in patients with operable esophageal carcinoma who achieved pathologic complete response (PCR) or microscopic residual disease (MRD) after preoperative chemoradiotherapy (CRT). Materials and Methods: Outcomes were assessed in 70 patients with locally advanced esophageal cancer who achieved pathologic major response (53 with PCR and 17 with MRD) after preoperative CRT. Results: At a median follow-up of 38.6 months for surviving patients, 17 of 70 patients (24.3%) experienced disease recurrence and 31 (44.3%) died. Clinical stage (II vs III; p = 0.013) and pathologic response (PCR vs. MRD; p = 0.014) were independent predictors of disease recurrence. Median overall survival (OS) was 99.6 months (95% CI, 44.1-155.1 months) and the 5-year OS rate was 57%. Median recurrence-free survival (RFS) was 71.5 months (95% CI, 39.5-103.6 months) and the 5-year RFS rate was 51.3%. Median OS of patients with Stage II and Stage III disease was 108.8 months and 39.9 months, respectively, and the 5-year OS rates were 68.2% and 27.0%, respectively (p = 0.0003). In a subgroup of patients with PCR, median OS and RFS were also significantly different according to clinical stage. Multivariate analysis showed that clinical stage was an independent predictor of RFS (p = 0.01) and OS (p = 0.008). Conclusions: Even though patients achieved major response after preoperative CRT, pretreatment clinical stage is an important prognostic marker for recurrence and survival. Patients with MRD have an increased recurrence risk but similar survival compared with patients achieved PCR.

  3. The role of neoadjuvant chemotherapy in patients with advanced (stage IIIC) epithelial ovarian cancer

    PubMed Central

    Škof, Erik; Merlo, Sebastjan; Pilko, Gasper

    2016-01-01

    Abstract Background Primary treatment of patients with advanced epithelial ovarian cancer consists of chemotherapy either before (neoadjuvant chemotherapy, NACT) or after primary surgery (adjuvant chemotherapy). The goal of primary treatment is no residual disease after surgery (R0 resection) what is associated with an improvement in survival of patients. There is, however, no evidence of survival benefits in patients with R0 resections after prior NACT. Methods We retrospectively reviewed the records of patients who were treated with diagnosis of epithelial ovarian cancer at Institute of Oncology Ljubljana in the years 2005–2007. The differences in the rates of R0 resections, progression free survival (PFS), overall survival (OS) and in five-year and eight-year survival rates between patients treated with NACT and patients who had primary surgery were compared. Results Overall 160 patients had stage IIIC epithelial ovarian cancer. Eighty patients had NACT and eighty patients had primary surgery. Patients in NACT group had higher rates of R0 resection (42% vs. 20%; p = 0.011) than patients after primary surgery. PFS was 14.1 months in NACT group and 17.7 months after primary surgery (p = 0.213). OS was 24.8 months in NACT group and 31.6 months after primary surgery (p = 0.012). In patients with R0 resections five-year and eight-year survival rates were 20.6% and 17.6% in NACT group compared to 62.5% and 62.5% after primary surgery (p < 0.0001), respectively. Conclusions Despite higher rates of R0 resections achieved by NACT, survival of patients treated with NACT was inferior to survival of patients who underwent primary surgery. NACT should only be offered to patients with advanced epithelial cancer who are not candidates for primary surgery. PMID:27679552

  4. Results of two different surgical techniques in the treatment of advanced-stage Freiberg's disease

    PubMed Central

    Özkul, Emin; Gem, Mehmet; Alemdar, Celil; Arslan, Hüseyin; Boğatekin, Ferit; Kişin, Bülent

    2016-01-01

    Background: Freiberg's disease is an osteochondrosis most commonly seen in adolescent women and characterized by pain, swelling and motion restriction in the second metatarsal. The early stages of this disease can be managed with semirigid orthoses, metatarsal bars and short leg walking cast. Number of operative methods are suggested which can be used depending on the pathophysiology of the disease, including abnormal biomechanics, joint congruence and degenerative process. We evaluated the outcomes of the patients with Freiberg's disease who were treated with dorsal closing-wedge osteotomy and resection of the metatarsal head. Patients and Methods: 16 patients (11 female, 5 male) with a mean age of 24.5 (range 13–49 years) years who underwent dorsal closing wedge osteotomy or resection of the metatarsal head were included in this retrospective study. Second metatarsal was affected in 13 and third metatarsal in three patients. According to the Smillie's classification system, ten patients had type IV osteonecrosis and six patients had type V. The results of the patients were evaluated using the lesser metatarsophalangeal-interphalangeal (LMPI) scale. Results: According to the LMPI scale, the postoperative scores for the osteotomy and excision groups were 86 (range 64–100) and 72.6 (range 60–85), respectively. In the osteotomy group, mean passive flexion restriction was 18° (range 0°–35°) and mean passive extension restriction was 12° (range 0°–25°). Mean metatarsal shortening was 2.2 mm (range 2–4 mm) in the osteotomy group as opposed to 9.8 mm (range 7–14 mm) in the excision group. Significant pain relief was obtained in both groups following the surgery. Conclusions: The decision of performing osteotomy or resection arthroplasty in the patients with advanced-stage Freiberg's disease should be based on the joint injury and the patients should be informed about the cosmetic problems like shortening which may arise from resection. PMID:26955180

  5. Advances in functional magnetic resonance imaging: technology and clinical applications.

    PubMed

    Dickerson, Bradford C

    2007-07-01

    Functional MRI (fMRI) is a valuable method for use by clinical investigators to study task-related brain activation in patients with neurological or neuropsychiatric illness. Despite the relative infancy of the field, the rapid adoption of this functional neuroimaging technology has resulted from, among other factors, its ready availability, its relatively high spatial and temporal resolution, and its safety as a noninvasive imaging tool that enables multiple repeated scans over the course of a longitudinal study, and thus may lend itself well as a measure in clinical drug trials. Investigators have used fMRI to identify abnormal functional brain activity during task performance in a variety of patient populations, including those with neurodegenerative, demyelinating, cerebrovascular, and other neurological disorders that highlight the potential utility of fMRI in both basic and clinical spheres of research. In addition, fMRI studies reveal processes related to neuroplasticity, including compensatory hyperactivation, which may be a universally-occurring, adaptive neural response to insult. Functional MRI is being used to study the modulatory effects of genetic risk factors for neurological disease on brain activation; it is being applied to differential diagnosis, as a predictive biomarker of disease course, and as a means to identify neural correlates of neurotherapeutic interventions. Technological advances are rapidly occurring that should provide new applications for fMRI, including improved spatial resolution, which promises to reveal novel insights into the function of fine-scale neural circuitry of the human brain in health and disease.

  6. Recent advances in medical imaging: anatomical and clinical applications.

    PubMed

    Grignon, Bruno; Mainard, Laurence; Delion, Matthieu; Hodez, Claude; Oldrini, Guillaume

    2012-10-01

    The aim of this paper was to present an overview of the most important recent advances in medical imaging and their potential clinical and anatomical applications. Dramatic changes have been particularly observed in the field of computed tomography (CT) and magnetic resonance imaging (MRI). Computed tomography (CT) has been completely overturned by the successive development of helical acquisition, multidetector and large area-detector acquisition. Visualising brain function has become a new challenge for MRI, which is called functional MRI, currently based principally on blood oxygenation level-dependent sequences, which could be completed or replaced by other techniques such as diffusion MRI (DWI). Based on molecular diffusion due to the thermal energy of free water, DWI offers a spectrum of anatomical and clinical applications, ranging from brain ischemia to visualisation of large fibrous structures of the human body such as the anatomical bundles of white matter with diffusion tensor imaging and tractography. In the field of X-ray projection imaging, a new low-dose device called EOS has been developed through new highly sensitive detectors of X-rays, allowing for acquiring frontal and lateral images simultaneously. Other improvements have been briefly mentioned. Technical principles have been considered in order to understand what is most useful in clinical practice as well as in the field of anatomical applications. Nuclear medicine has not been included.

  7. Recent theoretical, neural, and clinical advances in sustained attention research.

    PubMed

    Fortenbaugh, Francesca C; DeGutis, Joseph; Esterman, Michael

    2017-03-05

    Models of attention often distinguish among attention subtypes, with classic models separating orienting, switching, and sustaining functions. Compared with other forms of attention, the neurophysiological basis of sustaining attention has received far less notice, yet it is known that momentary failures of sustained attention can have far-ranging negative effects in healthy individuals, and lasting sustained attention deficits are pervasive in clinical populations. In recent years, however, there has been increased interest in characterizing moment-to-moment fluctuations in sustained attention, in addition to the overall vigilance decrement, and understanding how these neurocognitive systems change over the life span and across various clinical populations. The use of novel neuroimaging paradigms and statistical approaches has allowed for better characterization of the neural networks supporting sustained attention and has highlighted dynamic interactions within and across multiple distributed networks that predict behavioral performance. These advances have also provided potential biomarkers to identify individuals with sustained attention deficits. These findings have led to new theoretical models explaining why sustaining focused attention is a challenge for individuals and form the basis for the next generation of sustained attention research, which seeks to accurately diagnose and develop theoretically driven treatments for sustained attention deficits that affect a variety of clinical populations.

  8. 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

  9. Advances and applications of molecular cloning in clinical microbiology.

    PubMed

    Sharma, Kamal; Mishra, Ajay Kumar; Mehraj, Vikram; Duraisamy, Ganesh Selvaraj

    2014-10-01

    Molecular cloning is based on isolation of a DNA sequence of interest to obtain multiple copies of it in vitro. Application of this technique has become an increasingly important tool in clinical microbiology due to its simplicity, cost effectiveness, rapidity, and reliability. This review entails the recent advances in molecular cloning and its application in the clinical microbiology in the context of polymicrobial infections, recombinant antigens, recombinant vaccines, diagnostic probes, antimicrobial peptides, and recombinant cytokines. Culture-based methods in polymicrobial infection have many limitation, which has been overcome by cloning techniques and provide gold standard technique. Recombinant antigens produced by cloning technique are now being used for screening of HIV, HCV, HBV, CMV, Treponema pallidum, and other clinical infectious agents. Recombinant vaccines for hepatitis B, cholera, influenza A, and other diseases also use recombinant antigens which have replaced the use of live vaccines and thus reduce the risk for adverse effects. Gene probes developed by gene cloning have many applications including in early diagnosis of hereditary diseases, forensic investigations, and routine diagnosis. Industrial application of this technology produces new antibiotics in the form of antimicrobial peptides and recombinant cytokines that can be used as therapeutic agents.

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

    PubMed Central

    Lee, Tae Young; Kim, Minah; Kim, Sung Nyun

    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. PMID:28096883

  11. Differences between clinical specialist and advanced practitioner clinical practice, leadership, and research roles, responsibilities, and perceived outcomes (the SCAPE study).

    PubMed

    Begley, Cecily; Elliott, Naomi; Lalor, Joan; Coyne, Imelda; Higgins, Agnes; Comiskey, Catherine M

    2013-06-01

    To report a study designed comparing the roles, responsibilities, and perceived outcomes of Clinical Nurse Specialists, Clinical Midwife Specialists, and Advanced Nurse Practitioners in Ireland. A clinical career pathway that encompasses progression from staff nurse or midwife through clinical specialist to advanced practitioner level was introduced in Ireland in 2000. Such roles are common internationally, but little evaluation has been conducted and few comparisons have been made between roles. A mixed-method case-study design was used. Following Research Ethics Committee Approval, data were collected in 2009-2010, using non-participant observation (92 hours) of 23 Clinical Specialists and Advanced Practitioners, interviews with 21 clinicians and 13 Directors of Nursing or Midwifery. A survey was completed by 154 service-users. A clear difference was seen between Clinical Specialist and Advanced Practitioners, with advanced practice roles providing improved service delivery, greater clinical and professional leadership, increased research, and a clear governance and accreditation structure. Clinical Midwife Specialists were rated at a similar level to Advanced Nurse Practitioners for certain aspects and rated more highly for 'continuity of care and carer'. Advanced Practitioners do give a higher level of care, particularly at a strategic level. Existing Clinical Specialists should therefore be encouraged to develop their skills and education to achieve advanced practice level and more specialist and advanced practice posts should be instituted. © 2012 Blackwell Publishing Ltd.

  12. Clinical Perspectives on Lupus Genetics: Advances and Opportunities

    PubMed Central

    James, Judith A.

    2014-01-01

    Synopsis In recent years, genome wide association studies have led to an explosion in the identification of regions containing confirmed genetic risk variants within complex human diseases, for example in systemic lupus erythematosus (SLE). Many of these strongest SLE genetic associations can be divided into groups based upon their potential roles in different processes implicated in lupus pathogenesis, including ubiquitination (a process of marking proteins for degradation), DNA degradation, innate immunity, cellular immunity (B cell, T cell, neutrophil, monocytes), lymphocyte development, and antigen presentation. Recent advances have also demonstrated several genetic associations with SLE subphenotypes and subcriteria, such as autoantibody production, lupus nephritis, serositis, and arthritis. Despite the broad range of lupus genetic studies to date, many areas for further exploration remain to move lupus genetic studies toward clinically informative endpoints, such as identifying individuals at the greatest risk of end-organ damage, early mortality or poor response to a specific therapeutic regimen. PMID:25034154

  13. [Anticoagulant therapy clinic: moving towards Advanced Nursing Practice].

    PubMed

    Romero Ruiz, Adolfo; Parrado Borrego, Gema; Rodríguez González, José; Caparrós Miranda, Isabel S; Vargas Lirio, M Isabel; Ortiz Fernández, Primitiva

    2014-01-01

    There is currently around one million people receiving oral anticoagulants in Spain. The drug most used is acenocoumarol, which requires coagulation monitoring to ensure that the patient is within its normal therapeutic range. Patients usually start this treatment in a hospital clinic and, when they are stabilised, they are referred to primary care, where they are followed-up by their community nurses. The usual practice is that nurses are responsible for changes in the dose when the patients are outside the range. This practice is not performed by hospital nurses, despite having sufficient experience and knowledge to adequately manage these types of patients. An Advanced Nursing Practice model has been introduced into the Haematology management unit of the Hospital Universitario Virgen de la Victoria, Málaga. This involves various aspects of attention and care of patients on anticoagulant therapy, and includes adjusting the doses of their treatment following a catalogue of therapeutic and diagnostic ranges.

  14. Clinical relevance of advanced glycation endproducts for vascular surgery.

    PubMed

    Meerwaldt, R; van der Vaart, M G; van Dam, G M; Tio, R A; Hillebrands, J-L; Smit, A J; Zeebregts, C J

    2008-08-01

    Atherosclerosis is the main contributor to cardiovascular disease and leads to intimal plaque formation, which may progress to plaque rupture with subsequent thromboembolic events and/or occlusion of the arterial lumen. There is increasing evidence that the development or progression of atherosclerosis is associated with advanced glycation endproducts (AGEs). AGEs are a heterogeneous group of compounds formed by the non-enzymatic reaction of reducing sugars with proteins, lipids, and nucleic acids. An increased understanding of the mechanisms of formation and interaction of AGEs has allowed the development of several potential anti-AGE strategies. This review summarizes AGE formation and biochemistry, the pathogeneic role of AGEs in cardiovascular disease, anti-AGE therapies and clinical relevance to vascular surgery.

  15. Pancreatic neuroendocrine tumors: clinical features, diagnosis and medical treatment: advances

    PubMed Central

    Ito, Tetsuhide; Igarashi, Hisato; Jensen, Robert T.

    2013-01-01

    Pancreatic neuroendocrine tumors (pNETs) comprise with gastrointestinal carcinoids, the main groups of gastrointestinal neuroendocrine tumors (GI-NETs). Although these two groups of GI-NETs share many features including histological aspects; over-/ectopic expression of somatostatin receptors; the ability to ectopically secrete hormones/peptides/amines which can result in distinct functional syndromes; similar approaches used for tumor localization and some aspects of treatment, it is now generally agreed they should be considered separate. They differ in their pathogenesis, hormonal syndromes produced, many aspects of biological behavior and most important, in their response to certain anti-tumor treatment (chemotherapy, molecular targeted therapies). In this chapter the clinical features of the different types of pNETs will be considered as well as aspects of their diagnosis and medical treatment of the hormone-excess state. Emphasis will be on controversial areas or recent advances. The other aspects of the management of these tumors (surgery, treatment of advanced disease, tumor localization) are not dealt with here, because they are covered in other chapters in this volume. PMID:23582916

  16. The clinical and economic impact of alternative staging strategies for adenocarcinoma of the pancreas.

    PubMed

    Tierney, W M; Fendrick, A M; Hirth, R A; Scheiman, J M

    2000-07-01

    Several innovative imaging modalities, including endoscopic ultrasound, have increased the number of available preoperative staging methods in patients with adenocarcinoma of the pancreas. Our goal was to estimate the clinical outcomes and cost-effectiveness of alternative staging strategies for pancreatic adenocarcinoma. Decision analysis was used to simulate alternative staging strategies. Cost inputs were based on Medicare reimbursements; clinical inputs were obtained from the available literature. Model endpoints of interest were cost per curative resection and appropriateness of treatment allocation based on pathological stage. Endoscopic ultrasound followed by laparoscopy yielded the lowest cost per curative resection ($37,600) and minimized the number of unnecessary surgical explorations (5.4 per 100 patients staged). Requiring angiographic confirmation when endoscopic ultrasound demonstrated an unresectable tumor yielded an intermediate cost-effectiveness ratio and virtually eliminated the risk of overstaging. Laparoscopy alone maximized the resection rate, but each additional resection would cost approximately $2 million relative to a strategy employing both endoscopic ultrasound and angiography. Staging strategies incorporating endoscopic ultrasound may improve treatment allocation and are cost-effective relative to angiography-based strategies. A staging protocol that does not incorporate an imaging modality to detect vascular invasion dramatically increases the cost per additional curative resection compared with more comprehensive staging protocols.

  17. Development of advanced heat pump. Part 2: Preliminary test of two-stage compression heat pump

    NASA Astrophysics Data System (ADS)

    Iwatsubo, Tetsushiro; Saikawa, Michinori; Hamamatsu, Teruhide

    1988-03-01

    A heat pump driven by electricity is one of the excellent electricity utilization systems and is promoted to be widely used. An advanced heat pump has been investigated to enlarge its applications in the field of hot water supply for domestic use which will be competitive with city gas and air conditioning in large scale buildings. An experimental unit with two-stage compression system was designed, which has the multi-function of air conditioning and hot water supply, and the trial system was fabricated. In the design, followings were considered; cooperative operations of two compressors by inverter driving, the temperature conditions of both the air for the air conditioning and the heat source, additional setting of the intermediate heat exchanger. The test operation was carried out with checking the start up procedure, the control sequence and so on. The probability of five operation modes: cooling, heating, hot water supply, cooling/hot water supply, and heating/hot water supply, were confirmed. In the mode of heating/hot water supply the hot water temperature was increased to 65 C, the excellent performance in hot water supply was demonstrated.

  18. Glacier advance during Marine Isotope Stage 11 in the McMurdo Dry Valleys of Antarctica

    NASA Astrophysics Data System (ADS)

    Swanger, Kate M.; Lamp, Jennifer L.; Winckler, Gisela; Schaefer, Joerg M.; Marchant, David R.

    2017-01-01

    We mapped six distinct glacial moraines alongside Stocking Glacier in the McMurdo Dry Valleys, Antarctica. Stocking Glacier is one of several alpine glaciers in the Dry Valleys fringed by multiple cold-based drop moraines. To determine the age of the outermost moraine, we collected 10 boulders of Ferrar Dolerite along the crest of the moraine and analyzed mineral separates of pyroxene for cosmogenic 3He. On the basis of these measurements, the exposure age for the outermost moraine is 391 ± 35 ka. This represents the first documented advance of alpine glacier ice in the Dry Valleys during Marine Isotope Stage (MIS) 11. At this time, Stocking Glacier was ~20–30% larger than today. The cause of ice expansion is uncertain, but most likely it is related to increased atmospheric temperature and precipitation, associated with reduced ice extent in the nearby Ross Embayment. The data suggest complex local environmental response to warm climates in Antarctica and have implications for glacial response to Holocene warming. The study also demonstrates the potential for using alpine glacier chronologies in the Transantarctic Mountains as proxies for retreat of grounded glacier ice in the Ross Embayment.

  19. Glacier advance during Marine Isotope Stage 11 in the McMurdo Dry Valleys of Antarctica.

    PubMed

    Swanger, Kate M; Lamp, Jennifer L; Winckler, Gisela; Schaefer, Joerg M; Marchant, David R

    2017-01-31

    We mapped six distinct glacial moraines alongside Stocking Glacier in the McMurdo Dry Valleys, Antarctica. Stocking Glacier is one of several alpine glaciers in the Dry Valleys fringed by multiple cold-based drop moraines. To determine the age of the outermost moraine, we collected 10 boulders of Ferrar Dolerite along the crest of the moraine and analyzed mineral separates of pyroxene for cosmogenic (3)He. On the basis of these measurements, the exposure age for the outermost moraine is 391 ± 35 ka. This represents the first documented advance of alpine glacier ice in the Dry Valleys during Marine Isotope Stage (MIS) 11. At this time, Stocking Glacier was ~20-30% larger than today. The cause of ice expansion is uncertain, but most likely it is related to increased atmospheric temperature and precipitation, associated with reduced ice extent in the nearby Ross Embayment. The data suggest complex local environmental response to warm climates in Antarctica and have implications for glacial response to Holocene warming. The study also demonstrates the potential for using alpine glacier chronologies in the Transantarctic Mountains as proxies for retreat of grounded glacier ice in the Ross Embayment.

  20. Glacier advance during Marine Isotope Stage 11 in the McMurdo Dry Valleys of Antarctica

    PubMed Central

    Swanger, Kate M.; Lamp, Jennifer L.; Winckler, Gisela; Schaefer, Joerg M.; Marchant, David R.

    2017-01-01

    We mapped six distinct glacial moraines alongside Stocking Glacier in the McMurdo Dry Valleys, Antarctica. Stocking Glacier is one of several alpine glaciers in the Dry Valleys fringed by multiple cold-based drop moraines. To determine the age of the outermost moraine, we collected 10 boulders of Ferrar Dolerite along the crest of the moraine and analyzed mineral separates of pyroxene for cosmogenic 3He. On the basis of these measurements, the exposure age for the outermost moraine is 391 ± 35 ka. This represents the first documented advance of alpine glacier ice in the Dry Valleys during Marine Isotope Stage (MIS) 11. At this time, Stocking Glacier was ~20–30% larger than today. The cause of ice expansion is uncertain, but most likely it is related to increased atmospheric temperature and precipitation, associated with reduced ice extent in the nearby Ross Embayment. The data suggest complex local environmental response to warm climates in Antarctica and have implications for glacial response to Holocene warming. The study also demonstrates the potential for using alpine glacier chronologies in the Transantarctic Mountains as proxies for retreat of grounded glacier ice in the Ross Embayment. PMID:28139676

  1. [Obstetrical prognosis of breech presentation admitted in advanced first stage of labour].

    PubMed

    Faivre, M; Mottet, N; Bourtembourg, A; Ramanah, R; Maillet, R; Riethmuller, D

    2016-06-01

    Fear of dystocia during breech delivery brings obstetrical teams to choose elective caesarean sections. However, some patients with breech presentations will be in labour before the date scheduled and caesarean delivery during labour increases maternal morbidity. Therefore, this situation raises the question about the relevance of labour trial for breech presentations admitted in labour. Our study aimed to determine the obstetrical prognosis of breech presentations on admission in the labour ward following their degree of cervical dilation. We conducted an observational retrospective study on 213 single breech presentations at ≥37 gestational weeks that delivered at our level 3 labour ward between1st January 2007 and 30th July 2013. Maternal, obstetrical and neonatal factors were analyzed. The total caesarean rate during labour was 23.4% and significantly less important (P<0.05) in patients with cervical dilation ≥5cm on admission (14% vs. 27%). Apgar scores, cordonal arterial pH and lactates, rate of transfer to intensive care were not significantly different between the two groups. In our study, any patient with a breech presentation at an advanced stage of labour on admission is of very good prognosis, although statistical power is insufficient. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. Two-stage, low noise advanced technology fan. 4: Aerodynamic final report

    NASA Technical Reports Server (NTRS)

    Harley, K. G.; Keenan, M. J.

    1975-01-01

    A two-stage research fan was tested to provide technology for designing a turbofan engine for an advanced, long range commercial transport having a cruise Mach number of 0.85 -0.9 and a noise level 20 EPNdB below current requirements. The fan design tip speed was 365.8m/sec (1200ft/sec);the hub/tip ratio was 0.4; the design pressure ratio was 1.9; and the design specific flow was 209.2 kg/sec/sq m(42.85lbm/sec/sq ft). Two fan-versions were tested: a baseline configuration, and an acoustically treated configuration with a sonic inlet device. The baseline version was tested with uniform inlet flow and with tip-radial and hub-radial inlet flow distortions. The baseline fan with uniform inlet flow attained an efficiency of 86.4% at design speed, but the stall margin was low. Tip-radial distortion increased stall margin 4 percentage points at design speed and reduced peak efficiency one percentage point. Hub-radial distortion decreased stall margin 4 percentage points at all speeds and reduced peak efficiency at design speed 8 percentage points. At design speed, the sonic inlet in the cruise position reduced stall margin one percentage point and efficiency 1.5 to 4.5 percentage points. The sonic inlet in the approach position reduced stall margin 2 percentage points.

  3. A clinical advancement program for registered nurses with an outpatient focus.

    PubMed

    Streeter, Bonnie L

    2007-01-01

    Clinical advancement programs have been in use for almost 30 years. Although clinical advancement programs have been designed for many areas, it appears that one has never been developed specific to the outpatient-focused registered nurse. This article describes the development of a clinical advancement program for non-hospital-based registered nurses employed at the Guthrie Clinic in Sayre, Pennsylvania and highlights recommendations for instituting this program in any outpatient setting.

  4. 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.

  5. Bisphosphonate-related osteonecrosis of jaws in advanced stage breast cancer was detected from bone scan: a case report

    PubMed Central

    Chirappapha, Prakasit; Thongjood, Thanaporn; Aroonroch, Rangsima

    2017-01-01

    Bisphosphonates (BPs) are indicated to treat skeletal-related events (SREs) for cancer patients with bone metastasis. We report a 79-year-old woman with advanced stage breast cancer with bone metastasis who was prescribed BPs (zoledronate), then developed osteonecrosis of jaw. We provide a brief review of the pathogenesis, diagnosis and treatment of this complication. PMID:28210558

  6. Advances in thyroid cancer treatment: latest evidence and clinical potential

    PubMed Central

    Alonso-Gordoa, T.; Díez, J.J.; Durán, M.

    2015-01-01

    Advanced thyroid carcinoma is an infrequent tumor entity with limited treatment possibilities until recently. The extraordinary improvement in the comprehension of genetic and molecular alterations involving the RAS/RAF/mitogen-activated protein kinase and phosphatidylinositide 3-kinase/Akt/mammalian target of rapamycin signaling and interacting pathways that are involved in tumor survival, proliferation, differentiation, motility and angiogenesis have been the rationale for the development of new effective targeted therapies. Data coming from phase II clinical trials have confirmed the efficacy of those targeted agents against receptors in cell membrane and cytoplasmic molecules. Moreover, four of those investigational drugs, vandetanib, cabozantinib, sorafenib and lenvatinib, have reached a phase III clinical trial with favorable results in progression-free survival and overall survival in medullary thyroid carcinoma and differentiated thyroid carcinoma. Further analysis for an optimal approach has been conducted according to mutational profile and tumor subtypes. However, consistent results are still awaited and the research for adequate prognostic and predictive biomarkers is ongoing. The following report offers a comprehensive review from the rationale to the basis of targeted agents in the treatment of thyroid carcinoma. In addition, current and future therapeutic developments by the inhibition of further molecular targets are discussed in this setting. PMID:25553081

  7. Gene therapy for hemophilia: advancing beyond the first clinical success.

    PubMed

    Monahan, Paul E; Gui, Tong

    2013-09-01

    Consistently measurable and persistent expression of circulating clotting factor activity, associated with decreased clinical bleeding, has been achieved for the first time in a hemophilia gene therapy trial. This review examines the successes and limitations of this clinical trial for hemophilia B and approaches to advance beyond this milestone. Although a self-complementary serotype 8 adeno-associated virus (scAAV8) vector approach directed factor IX expression of up to 6% in a human trial, the apparent need to suppress vector dose-dependent immune-mediated liver inflammation in some patients at the highest dose highlighted the next steps to optimize the risk-benefit of hemophilia gene therapy. The approaches being pursued include manufacturing modifications to eliminate contaminating empty vector capsids, the utilization of factor IX and factor VIII modified transgenes to improve secretion or function of the transgene product, and adjunctive pharmacologic and molecular approaches to overcome limitations imposed by naturally occurring antibodies against vectors and by the large size of the factor VIII gene. Preclinical data suggest strategies in development may build upon the first gene therapy success and achieve factor IX correction sufficient to prevent bleeding without toxicity and translate success to hemophilia A gene therapy.

  8. Major clinical research advances in gynecologic cancer in 2012.

    PubMed

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

    2013-01-01

    Ten topics were chosen among major clinical research achievements in gynecologic oncology in 2012. For ovarian cancer, comprehensive review of the history of bevacizumab studies was followed by poly adenosine diphosphate [ADP]-ribose polymerase (PARP) inhibitors and other molecular targeted agents such as epidermal growth factor receptor tyrosine kinase inhibitor and AMG 386. For the development of genomic study in gynecologic cancers, BRCA and DICER1 mutations were covered in epithelial and nonepithelial ovarian cancer, respectively. For endometrial cancer, targeted agents including mammalian target of rapamycin (mTOR) inhibitors and bevacizumab were discussed. Radiation therapy "sandwiched" between combination chemotherapy schedules for the treatment of uterine papillary serous carcinoma was also reviewed. Preoperative prediction of lymph node metastasis, definition of low-risk group, and recurrence and survival outcomes of laparoscopic approaches were addressed. For cervical cancer, we reviewed long-term benefit of human papillomavirus test and efficacy of paclitaxel/carboplatin versus paclitaxel/cisplatin in stage IVB, persistent or recurrent disease. In addition, the effect of three dimensional image-based high-dose rate brachytherapy was also reviewed. For vulvar cancer, the diagnostic value of sentinel lymph node biopsy was discussed. For breast cancer, positive results of three outstanding phase III randomized clinical trials, CLEOPATRA, EMILIA, and BOLERO-2 were introduced. Lastly, updates of major practice guidelines were summarized.

  9. Major clinical research advances in gynecologic cancer in 2012

    PubMed Central

    Suh, Dong Hoon; Kim, Kidong; Kim, Hak Jae; Lee, Kyung-Hun

    2013-01-01

    Ten topics were chosen among major clinical research achievements in gynecologic oncology in 2012. For ovarian cancer, comprehensive review of the history of bevacizumab studies was followed by poly adenosine diphosphate [ADP]-ribose polymerase (PARP) inhibitors and other molecular targeted agents such as epidermal growth factor receptor tyrosine kinase inhibitor and AMG 386. For the development of genomic study in gynecologic cancers, BRCA and DICER1 mutations were covered in epithelial and nonepithelial ovarian cancer, respectively. For endometrial cancer, targeted agents including mammalian target of rapamycin (mTOR) inhibitors and bevacizumab were discussed. Radiation therapy "sandwiched" between combination chemotherapy schedules for the treatment of uterine papillary serous carcinoma was also reviewed. Preoperative prediction of lymph node metastasis, definition of low-risk group, and recurrence and survival outcomes of laparoscopic approaches were addressed. For cervical cancer, we reviewed long-term benefit of human papillomavirus test and efficacy of paclitaxel/carboplatin versus paclitaxel/cisplatin in stage IVB, persistent or recurrent disease. In addition, the effect of three dimensional image-based high-dose rate brachytherapy was also reviewed. For vulvar cancer, the diagnostic value of sentinel lymph node biopsy was discussed. For breast cancer, positive results of three outstanding phase III randomized clinical trials, CLEOPATRA, EMILIA, and BOLERO-2 were introduced. Lastly, updates of major practice guidelines were summarized. PMID:23346316

  10. Advancing Clostridia to Clinical Trial: Past Lessons and Recent Progress

    PubMed Central

    Mowday, Alexandra M.; Guise, Christopher P.; Ackerley, David F.; Minton, Nigel P.; Lambin, Philippe; Dubois, Ludwig J.; Theys, Jan; Smaill, Jeff B.; Patterson, Adam V.

    2016-01-01

    Most solid cancers contain regions of necrotic tissue. The extent of necrosis is associated with poor survival, most likely because it reflects aggressive tumour outgrowth and inflammation. Intravenously injected spores of anaerobic bacteria from the genus Clostridium infiltrate and selectively germinate in these necrotic regions, providing cancer-specific colonisation. The specificity of this system was first demonstrated over 60 years ago and evidence of colonisation has been confirmed in multiple tumour models. The use of “armed” clostridia, such as in Clostridium Directed Enzyme Prodrug Therapy (CDEPT), may help to overcome some of the described deficiencies of using wild-type clostridia for treatment of cancer, such as tumour regrowth from a well-vascularised outer rim of viable cells. Successful preclinical evaluation of a transferable gene that metabolises both clinical stage positron emission tomography (PET) imaging agents (for whole body vector visualisation) as well as chemotherapy prodrugs (for conditional enhancement of efficacy) would be a valuable early step towards the prospect of “armed” clostridia entering clinical evaluation. The ability to target the immunosuppressive hypoxic tumour microenvironment using CDEPT may offer potential for synergy with recently developed immunotherapy strategies. Ultimately, clostridia may be most efficacious when combined with conventional therapies, such as radiotherapy, that sterilise viable aerobic tumour cells. PMID:27367731

  11. HIV/AIDS Clinical Manifestations and their Implication for Patient Clinical Staging in Resource Limited Settings in Tanzania.

    PubMed

    Boniphace, Idindili; Omari, Minzi; Susan Fred, Rumisha; Ferdinand, Mugusi; Marcel, Tanner

    2011-01-01

    Tanzania HIV/AIDS management follows WHO clinical staging which requires CD4 counts as complement. Lacking CD4 counts facilities in rural health facilities remains a challenge. Simplified and sensitive clinical staging based on local clinical patterns is useful to ensure effective care without CD4 counts. To assess whether local HIV clinical manifestations can be used to guide HIV management in settings with limited access to CD4 counts in Tanzania. A Cross-sectional study conducted at Tumbi and Chalinze health facilities documented clinical manifestations and CD4 counts in 360 HIV/AIDS patients. Simplified management groups comprised of severe and moderate disease were formed based on clinical manifestations and CD4 counts results. Symptoms with high frequency were used to predict severe disease. A Weight loss (48.3%) and chronic cough (40.8 %) were the most reported manifestations in the study population. More than 50% of patients presented with CD4≤200. Most symptoms were found to be highly sensitive (71% to 93%) in predicting severe immunosuppression using CD4<200 cut-off point as a 'Gold standard'. Chronic diarrhoea presented in 10.6%, and predicted well severe immunosuppression either alone (OR 1.95, 95%CI, 0.95-4.22) or in combination (OR 4.21, 95%CI 0.92-19.33) with other symptoms. Basing strictly on WHO clinical staging 30.8% of patients were detected to be severely immunosuppressed (Stage 4). While using our proposed management categories of severe and moderate immunosuppression 70% of patients were put into the severe immunosuppression group, consistent with CD4 cut-off count of≤350. HIV/AIDS clinics managing large cohorts should develop validated site specific guidelines based on local experiences. Simplified guidelines are useful for resource constrained settings without CD4 counting facilities.

  12. 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.

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

    PubMed Central

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

    2017-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:28203421

  14. Helicobacter pylori-negative gastric cancer: advanced-stage undifferentiated adenocarcinoma located in the pyloric gland area.

    PubMed

    Okano, Akihiro; Kato, Shigeru; Ohana, Masaya

    2017-02-01

    The incidence of Helicobacter pylori-negative gastric cancer (HpNGC) is extremely low. A 78-year old female without H. pylori infection was diagnosed with type 4 advanced-stage gastric prepylorus cancer. Distal gastrectomy was performed as for HpNGC (cT3N0M0). Histological findings of the resected specimen showed poorly differentiated adenocarcinoma and signet ring cell carcinoma, which were located in the pyloric gland area, diffusely invaded beyond the serosa without lymph node metastasis (pT4aN0M0). Most cases of undifferentiated-type HpNGC are diagnosed in the early stage and are located in the fundic gland area. We report the first case of advanced-stage undifferentiated HpNGC located in the pyloric gland area.

  15. 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

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

    PubMed

    Schneider, L S; Mangialasche, F; Andreasen, N; Feldman, H; Giacobini, E; Jones, R; Mantua, V; Mecocci, P; Pani, L; Winblad, B; Kivipelto, M

    2014-03-01

    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 6-12 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 of daily living

  17. Chemotherapy in advanced ovarian cancer: an overview of randomised clinical trials. Advanced Ovarian Cancer Trialists Group.

    PubMed Central

    1991-01-01

    OBJECTIVES--To consider the role of platinum and the relative merits of single agent and combination chemotherapy in the treatment of advanced ovarian cancer. DESIGN--Formal quantitative overview using updated individual patient data from all available randomised trials (published and unpublished). SUBJECTS--8139 patients (6408 deaths) included in 45 different trials. RESULTS--No firm conclusions could be reached. Nevertheless, the results suggest that in terms of survival immediate platinum based treatment was better than non-platinum regimens (overall relative risk 0.93; 95% confidence interval 0.83 to 1.05); platinum in combination was better than single agent platinum when used in the same dose (overall relative risk 0.85; 0.72 to 1.00); and cisplatin and carboplatin were equally effective (overall relative risk 1.05; 0.94 to 1.18). CONCLUSIONS--In the past, randomised clinical trials of chemotherapy in advanced ovarian cancer have been much too small to detect the degree of benefit which this overview suggests is realistic for currently available chemotherapeutic regimens. Hence a new trial comparing cisplatin, doxorubicin, and cyclophosphamide (CAP) with carboplatin has been launched and plans to accrue 2000 patients. PMID:1834291

  18. Risk of discontinuation of Advanced Therapy Medicinal Products clinical trials.

    PubMed

    Hanna, Eve; Rémuzat, Cecile; Auquier, Pascal; Toumi, Mondher

    2016-01-01

    Advanced therapy medicinal products (ATMPs) constitute a class of innovative products that encompasses gene therapy, somatic cell therapy, and tissue-engineered products (TEP). There is an increased investment of commercial and non-commercial sponsors in this field and a growing number of ATMPs randomized clinical trials (RCT) and patients enrolled in such trials. RCT generate data to prove the efficacy of a new therapy, but the discontinuation of RCTs wastes scarce resources. Our objective is to identify the number and characteristics of discontinued ATMPs trials in order to evaluate the rate of discontinuation. We searched for ATMPs trials conducted between 1999 to June 2015 using three databases, which are Clinicaltrials.gov, the International Clinical Trials Registry Platform (ICTRP), and the EU Drug Regulating Authorities Clinical Trials (EudraCT). We selected the ATMPs trials after elimination of the duplicates. We identified the disease areas and the sponsors as commercial or non-commercial organizations. We classified ATMPs by type and trial status, that is, ongoing, completed, terminated, discontinued, and prematurely ended. Then, we calculated the rate of discontinuation. Between 1999 and June 2015, 143 withdrawn, terminated, or prematurely ended ATMPs clinical trials were identified. Between 1999 and June 2013, 474 ongoing and completed clinical trials were identified. Therefore, the rate of discontinuation of ATMPs trials is 23.18%, similar to that for non-ATMPs drugs in development. The probability of discontinuation is, respectively, 27.35, 16.28, and 16.34% for cell therapies, gene therapies, and TEP. The highest discontinuation rate is for oncology (43%), followed by cardiology (19.2%). It is almost the same for commercial and non-commercial sponsors; therefore, the discontinuation reason may not be financially driven. No failure risk rate per development phase is available for ATMPs. The discontinuation rate may prove helpful when assessing the

  19. Design of adaptive two-stage double-arm clinical trials for dichotomous variables.

    PubMed

    Jiang, Zhiwei; Xue, Fubo; Li, Chanjuan; Wang, Ling; Cai, Hongwei; Zhang, Chunmao; Xia, Jielai

    2010-05-01

    It is well known that flexibility is one of the major advantages of an adaptive two-stage design, and the intended adaptation should be as preplanned as possible to maintain the integrity of the clinical trial. The design of adaptive two-stage double-arm clinical trials for dichotomous variables was proposed by simulation and forecasting procedure at the planning stage. To further ensure the integrity of the clinical trial, the sample size scheme for each scenario, which was supposed to be based on the first stage, was provided in the protocol by Monte Carlo simulation. In addition, the study parameters were determined by comparing the assessment indexes such as total sample size, expected sample size and the test power at the first stage. Furthermore, Fisher's combination test and pooled data analysis were considered and compared through the simulation. The latter, which has the larger overall power and the better overall type I error control, with the same sample size was adopted for further simulation and statistical analysis in the clinical trial.

  20. hMSH2 and GTBP expression in advanced stage epithelial ovarian cancer

    PubMed Central

    Ercoli, A; Ferrandina, G; Raspaglio, G; Marone, M; Maggiano, N; Mastro, P Del; Panici, P Benedetti; Mancuso, S; Scambia, G

    1999-01-01

    Defects in DNA mismatch repair have been associated with both hereditary and sporadic forms of human cancer. Most of the attention has been focused on the incidence and genetics of mismatch repair defects, while little is known about the expression levels of the mismatch repair proteins and their significance in cancer cell biology. In this study, both the expression levels of hMSH2 and GTBP proteins were investigated by Western blotting in 20 untreated epithelial ovarian cancers. For these analyses, a commercial anti-hMSH2 monoclonal antibody and a newly generated mouse monoclonal anti-GTBP antibody were used. hMSH2 and GTBP proteins were detected by Western blotting in 19 out of 20 (95%) samples analysed and were found to be directly correlated (r = +0.51, P = 0.025). hMSH2 expression was significantly higher in ovarian cancer cells originating from solid tumours than from ascites (H = 4.5, P = 0.033), whereas GTBP content did not significantly differ according to the origin of cancer cells. No statistically significant differences were found in the distribution of hMSH2 and GTBP levels according to the age of the patients, grade of differentiation, histotype and extent of surgical debulking. The amount of hMSH2 protein was demonstrated to be significantly lower in stage IV than in stage III patients (H = 7.35, P = 0.007). Moreover, significantly lower hMSH2 levels were observed in non-responding patients compared to patients who achieved complete or partial response to cisplatin-based chemotherapy (H = 4.88, P = 0.027). Conversely, GTBP levels were not distributed differently according to stage of disease and chemotherapy response. Our study suggests a possible involvement of hMSH2 in ovarian cancer cell biology and susceptibility to chemotherapy. The possible biological and/or clinical role of GTBP expression in ovarian cancer patients remains to be elucidated. © 1999 Cancer Research Campaign PMID:10408416

  1. Clinical implication of computed tomography findings in patients with locally advanced squamous cell carcinoma of the larynx and hypopharynx.

    PubMed

    Ryu, In Sun; Lee, Jeong Hyun; Roh, Jong-Lyel; Choi, Seung-Ho; Nam, Soon Yuhl; Kim, Sang Yoon; Cho, Kyung-Ja

    2015-10-01

    Accurate tumor staging including involvement of laryngeal cartilage is important to treatment planning. Clinicians rely on imaging findings and determine initial laryngectomy for T4-stage cancer with functionless larynx or extralaryngeal spread (ELS). We examined the accuracy and prognostic value of preoperative CT findings for tumor staging in patients with locally advanced laryngeal and hypopharyngeal cancer. Ninety-four consecutive patients with clinically T3-T4-stage squamous cell carcinoma of the larynx or hypopharynx who underwent curative resection of primary tumor were reviewed. Preoperative CT findings were interpreted by a radiologist without pathologic information. Pathologic findings were used as the gold standard for correlating radiographic findings. CT imaging identified 23 (72%) of 32 cases of pathologically documented thyroid cartilage penetration and 24 (73%) of 33 cases of pathologically documented ELS. The positive predictive values for thyroid cartilage penetration and ELS were 70 and 80%, respectively. Pretreatment CT imaging up-staged 6 of 46 pT3 cases and all of 8 pT2 cases, while it down-staged 7 of 40 pT4 cases. The accuracy for clinical staging by CT imaging was 78%. Subglottic extension of the CT image was an independent variable for predicting thyroid cartilage penetration and ELS (P = 0.014). Thyroid cartilage penetration with or without ELS on CT scans is significantly associated with unfavorable DFS outcome of patients (P = 0.020). CT imaging is suboptimal in diagnosing TCP or ELS of advanced laryngeal cancer, but may be useful to predict patient survival by identifying clinically TCP.

  2. Advances in management of adjuvant chemotherapy in rectal cancer: Consequences for clinical practice.

    PubMed

    Netter, Jeanne; Douard, Richard; Durdux, Catherine; Landi, Bruno; Berger, Anne; Taieb, Julien

    2016-11-01

    More than half the patients with rectal cancer present with locally advanced rectal disease at diagnosis with a high risk of recurrence. Preoperative chemoradiotherapy and standardized radical surgery with total mesorectal excision have been established as the 'gold standard' for treating these patients. Pathological staging using the ypTNM classification system to decide on adjuvant chemotherapy (ACT) is widely used in clinical practice, but the delivery of ACT is still controversial, as many discrepancies persist in the conclusions of different trials, due to heterogeneity of the inclusion criteria between studies, lack of statistical power, and variations in preoperative and adjuvant regimens. In 2014, a meta-analysis of four randomized phase-III trials (EORTC 22921, I-CNR-RT, PROCTOR-SCRIPT, CHRONICLE) failed to demonstrate any statistical efficacy of fluorouracil (5FU)-based ACT. Three recent randomized trials aimed to compare 5FU with 5FU plus oxaliplatin-based chemotherapy. Two of them (ADORE, CAO/ARO/AIO-04) appeared to find a disease-free survival benefit for patients treated with the combination therapy. Thus, while awaiting new data, it can be said that, as of 2015, patients with yp stage I tumors or histological complete response derived no benefit from adjuvant therapy. On the other hand, the FOLFOX chemotherapy regimen should be proposed for yp stage III patients, and may be considered for yp stage II tumors in fit patients with high-risk factors. Nevertheless, well-designed and sufficiently powered clinical trials dedicated to adjuvant treatments for rectal cancer remain justified in future to achieve a high level of proof in keeping with evidence-based medical standards. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  3. Comprehensive Genomic Profiling of Advanced Penile Carcinoma Suggests a High Frequency of Clinically Relevant Genomic Alterations.

    PubMed

    Ali, Siraj M; Pal, Sumanta K; Wang, Kai; Palma, Norma A; Sanford, Eric; Bailey, Mark; He, Jie; Elvin, Julia A; Chmielecki, Juliann; Squillace, Rachel; Dow, Edward; Morosini, Deborah; Buell, Jamie; Yelensky, Roman; Lipson, Doron; Frampton, Garrett M; Howley, Peter; Ross, Jeffrey S; Stephens, Philip J; Miller, Vincent A

    2016-01-01

    Advanced penile squamous cell carcinoma (PSCC) is associated with poor survival due to the aggressiveness of the disease and lack of effective systemic therapies. Comprehensive genomic profiling (CGP) was performed to identify clinically relevant genomic alterations (CRGAs). DNA was extracted from 40 μm of formalin-fixed, paraffin-embedded sections in patients with advanced PSCC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 692× for 3,769 exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. CRGAs were defined as genomic alterations (GAs) linked to targeted therapies on the market or under evaluation in mechanism-driven clinical trials. Twenty male patients with a median age of 60 years (range, 46-87 years) were assessed. Seventeen (85%) cases were stage IV and three cases (15%) were stage III. CGP revealed 109 GAs (5.45 per tumor), 44 of which were CRGAs (2.2 per tumor). At least one CRGA was detected in 19 (95%) cases, and the most common CRGAs were CDKN2A point mutations and homozygous deletion (40%), NOTCH1 point mutations and rearrangements (25%), PIK3CA point mutations and amplification (25%), EGFR amplification (20%), CCND1 amplification (20%), BRCA2 insertions/deletions (10%), RICTOR amplifications (10%), and FBXW7 point mutations (10%). CGP identified CRGAs in patients with advanced PSCC, including EGFR amplification and PIK3CA alterations, which can lead to the rational administration of targeted therapy and subsequent benefit for these patients. Few treatment options exist for patients with advanced penile squamous cell carcinoma (PSCC). Outcomes are dismal with platinum-based chemotherapy, with median survival estimated at 1 year or less across multiple series. Biological studies of patients with PSCC to date have principally focused on human papillomavirus status, but few studies have elucidated molecular drivers of the disease. To this end

  4. Comprehensive Genomic Profiling of Advanced Penile Carcinoma Suggests a High Frequency of Clinically Relevant Genomic Alterations

    PubMed Central

    Pal, Sumanta K.; Wang, Kai; Palma, Norma A.; Sanford, Eric; Bailey, Mark; He, Jie; Elvin, Julia A.; Chmielecki, Juliann; Squillace, Rachel; Dow, Edward; Morosini, Deborah; Buell, Jamie; Yelensky, Roman; Lipson, Doron; Frampton, Garrett M.; Howley, Peter; Ross, Jeffrey S.; Stephens, Philip J.; Miller, Vincent A.

    2016-01-01

    Background. Advanced penile squamous cell carcinoma (PSCC) is associated with poor survival due to the aggressiveness of the disease and lack of effective systemic therapies. Comprehensive genomic profiling (CGP) was performed to identify clinically relevant genomic alterations (CRGAs). Materials and Methods. DNA was extracted from 40 μm of formalin-fixed, paraffin-embedded sections in patients with advanced PSCC. CGP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of 692× for 3,769 exons of 236 cancer-related genes plus 47 introns from 19 genes frequently rearranged in cancer. CRGAs were defined as genomic alterations (GAs) linked to targeted therapies on the market or under evaluation in mechanism-driven clinical trials. Results. Twenty male patients with a median age of 60 years (range, 46–87 years) were assessed. Seventeen (85%) cases were stage IV and three cases (15%) were stage III. CGP revealed 109 GAs (5.45 per tumor), 44 of which were CRGAs (2.2 per tumor). At least one CRGA was detected in 19 (95%) cases, and the most common CRGAs were CDKN2A point mutations and homozygous deletion (40%), NOTCH1 point mutations and rearrangements (25%), PIK3CA point mutations and amplification (25%), EGFR amplification (20%), CCND1 amplification (20%), BRCA2 insertions/deletions (10%), RICTOR amplifications (10%), and FBXW7 point mutations (10%). Conclusion. CGP identified CRGAs in patients with advanced PSCC, including EGFR amplification and PIK3CA alterations, which can lead to the rational administration of targeted therapy and subsequent benefit for these patients. Implications for Practice: Few treatment options exist for patients with advanced penile squamous cell carcinoma (PSCC). Outcomes are dismal with platinum-based chemotherapy, with median survival estimated at 1 year or less across multiple series. Biological studies of patients with PSCC to date have principally focused on human papillomavirus status

  5. Cases of advanced visual field loss at referral to glaucoma clinics - more men than women?

    PubMed

    Crabb, David P; Saunders, Luke J; Edwards, Laura A

    2017-01-01

    In many medical conditions 'late presentation' of disease is more of a problem for men than women. Risk of sight loss from glaucoma is certainly greater in those detected with advanced disease. We performed a retrospective study to test the hypothesis that men are more likely than women to have advanced visual field loss at referral to glaucoma clinics. We used 152 918 Humphrey visual fields from 32 147 patients from three regionally different hospitals in England; no other clinical data were made available apart from patient's age, sex and examination dates. The study population was defined as patients with measureable visual field loss in at least one eye at referral to glaucoma clinics. Cases of advanced visual field loss as defined by the Enhanced Glaucoma Severity Staging method at the first visit to secondary care were used as a proxy measure for late presentation of glaucoma. Age-adjusted relative risk (RR) was calculated as the ratio of the proportion of men to women with this proxy measure. Median (interquartile range) age and MD (worse eye) for 3733 men and 4264 women was 72 (63, 79) and 74 (64, 81) years and -6.4 (-11.7, -3.8) and -6.3 (-11.0, -3.8) dB respectively. Overall proportion of patients with advanced visual field loss at referral to glaucoma clinics was slightly higher in men (25.0%) than in women (22.3%); this difference was statistically significant (p < 0.01). Overall age-standardised RR was statistically significant (1.16; p < 0.001); a person with late presentation of glaucoma is 16% (95% confidence interval: 7-25%) more likely to be a man than a woman. A large number of patients with glaucomatous visual field defects are estimated to have advanced loss in at least one eye on referral to secondary care in England; risk for men more likely presenting with late disease is slightly greater than for women. © 2016 The Authors Ophthalmic & Physiological Optics © 2016 The College of Optometrists.

  6. Anatomic Location of PET-Positive Aortocaval Nodes in Patients with Locally Advanced Cervical Cancer: Implications for Surgical Staging

    PubMed Central

    Frumovitz, Michael; Ramirez, Pedro T.; Macapinlac, Homer A.; Klopp, Ann H.; Nick, Alpa M.; Ramondetta, Lois M.; Jhingran, Anuja

    2014-01-01

    Objective Pathologic evaluation of aortocaval nodes in patients with locally advanced cervical cancer in an effort to better tailor radiotherapy has gained popularity. We sought to determine which aortocaval nodes should be sampled during surgical staging procedures. Methods From 2004 to 2011, 246 patients with locally advanced cervical cancer underwent positron emission tomography (PET) before definitive chemoradiation. We reviewed the imaging studies to determine the location of PET-positive aortocaval nodes in relationship to the inferior mesenteric artery (IMA). Results Forty-two patients (17%) had PET images suggesting aortocaval metastasis. Ten patients had stage IB, 1 had stage IIA, 13 had stage IIB, 13 had stage IIIB, and 5 had stage IV disease. Of these 42 patients, 39 (93%) had FDG-avid pelvic nodes, 1 (2%) had PET-negative pelvic nodes but FDG-avid common iliac nodes, and 2 (5%) had direct spread to the aortocaval nodes. Three patients (7%) had FDG-avid aortocaval nodes above the IMA without FDG-avid nodes between the aortic bifurcation and IMA. All 3 of these patients also had FDG-avid nodes in the pelvis. Nineteen patients (45%) had FDG-avid nodes above and below the IMA, and 20 (48%) had FDG-avid nodes below the IMA only. Conclusions This hypothesis-generating study revealed that a small number of patients have PET-positive aortocaval nodes above the IMA only. For patients undergoing surgical staging for locally advanced cervical cancer, dissection to the renal vessels may be necessary. A future international, randomized study will prospectively evaluate the locations of pathologically positive aortocaval lymph nodes. PMID:22810967

  7. Optimal adaptive two-stage designs for early phase II clinical trials.

    PubMed

    Shan, Guogen; Wilding, Gregory E; Hutson, Alan D; Gerstenberger, Shawn

    2016-04-15

    Simon's optimal two-stage design has been widely used in early phase clinical trials for Oncology and AIDS studies with binary endpoints. With this approach, the second-stage sample size is fixed when the trial passes the first stage with sufficient activity. Adaptive designs, such as those due to Banerjee and Tsiatis (2006) and Englert and Kieser (2013), are flexible in the sense that the second-stage sample size depends on the response from the first stage, and these designs are often seen to reduce the expected sample size under the null hypothesis as compared with Simon's approach. An unappealing trait of the existing designs is that they are not associated with a second-stage sample size, which is a non-increasing function of the first-stage response rate. In this paper, an efficient intelligent process, the branch-and-bound algorithm, is used in extensively searching for the optimal adaptive design with the smallest expected sample size under the null, while the type I and II error rates are maintained and the aforementioned monotonicity characteristic is respected. The proposed optimal design is observed to have smaller expected sample sizes compared to Simon's optimal design, and the maximum total sample size of the proposed adaptive design is very close to that from Simon's method. The proposed optimal adaptive two-stage design is recommended for use in practice to improve the flexibility and efficiency of early phase therapeutic development.

  8. Staging practice for prostate cancer varies and is not in line with clinical guidelines.

    PubMed

    Petersen, Lars J; Shuysky, Yuliya; Zacho, Helle D

    2016-12-01

    The objective was to describe regional variations in M-staging in patients with newly diagnosed prostate cancer within a Danish county and to compare clinical practice with guideline recommendations. Data were as captured from 1) a prospective, non-interventional study counting 635 consecutive patients referred for M-staging in the 2008-2009 period at three regional hospitals within one county, and 2) a questionnaire on M-staging practice completed by the five sites performing M-staging in the same county in 2015. All three sites referred patients for M-staging in 2008, irrespective of their risk factors. Two of the three sites maintained this practice in 2015. Furthermore, in 2015, three of five sites performed M-staging in intermediate and high-risk patients only. Planar whole-body bone scans were standard in all sites in 2008 with single photon emission computed tomography/computed tomography (SPECT/CT) being performed if required and if available. In 2015, two sites used choline positron emission tomography/CT for primary staging of high-risk patients against guideline recommendations. The use of SPECT/CT showed wide variations from "if required" to "mandatory" head-to-thigh imaging. There were notable variations between clinical practice and guidelines in 2008, and this was even more evident in 2015. Considerable variations existed with respect to the M-staging imaging practices in prostate cancer within a single Danish county. The variation was more pronounced in 2015 than in 2008. Clinical practice conflicted in part with European and national Danish guidelines. none. not relevant.

  9. 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

  10. Plasma EGFR Mutation Detection Associated With Survival Outcomes in Advanced-Stage Lung Cancer.

    PubMed

    Lam, David C L; Tam, Terence C C; Lau, Kenneth M K; Wong, Wai-Mui; Hui, Christopher K M; Lam, Jamie C M; Wang, Julie K L; Lui, Macy M S; Ho, James C M; Ip, Mary S M

    2015-11-01

    We confirmed the performance of an array method for plasma epidermal growth factor receptor (EGFR) mutation detection and showed the association of plasma EGFR mutation with survival outcomes. Noninvasive detection of epidermal growth factor receptor (EGFR) mutation in plasma is feasible and could be adjunct for therapeutic monitoring especially when repeated biopsy of tumor tissue is challenging. The aims of this study were to establish the diagnostic performance of peptide nucleic acid-locked nucleic acid polymerase chain reaction followed by custom array for plasma EGFR mutation and to evaluate the association of detection with clinical characteristics and survival outcomes. Plasma genomic DNA from consecutive advanced lung cancer subjects was tested for EGFR mutations before anticancer treatment, and compared with mutation status in tumor tissue. Clinical characteristics were compared between patients who were EGFR-mutant and wild type; and within EGFR mutants, whether EGFR mutations could be detected in plasma. In 74 lung cancer patients, the sensitivity, specificity, and positive and negative predictive values of plasma EGFR detection were 79.1%, 96.8%, 97.1%, and 76.9%, respectively. EGFR mutants with concomitant detection of plasma EGFR mutation showed worse survival compared with mutants with no concomitant plasma mutation detected in biopsy specimens. Plasma EGFR mutation detected using this method demonstrated high diagnostic performance. In EGFR mutants, plasma EGFR mutation detection correlated not only EGFR mutation status in biopsy but was also associated with worse prognosis compared with EGFR mutant without plasma EGFR mutation detection. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  11. Preclinical recapitulation of antiangiogenic drug clinical efficacies using models of early or late stage breast cancer metastatis.

    PubMed

    Kerbel, Robert S; Guerin, Eric; Francia, Giulio; Xu, Ping; Lee, Christina R; Ebos, John M L; Man, Shan

    2013-08-01

    Historically, preclinical tumor therapy models in mice have frequently been deficient in predicting subsequent clinical activity; over-prediction of clinical anti-tumor efficacy is common. Several approaches are being made in an attempt to improve the clinical relevance of preclinical models, and include the use of genetically engineered mouse models (GEMMs) of cancer or patient derived xenografts (PDXs). Here we summarize, in the context of breast cancer, another approach, namely, the development of postsurgical models of either macroscopic or microscopic metastatic disease to mimic metastatic or adjuvant therapy. To do so we used in vivo selected metastatic variants of established human breast cancer cell lines such as MDA-MB-231. Testing antiangiogenic drugs such as the oral tyrosine kinase inhibitor (TKI) sunitinib alone or combined with chemotherapy in models involving treatment of established primary tumors invariably resulted in demonstrable anti-tumor activity. In contrast, identical treatments of postsurgical mice with advanced metastatic disease did not: survival times were not prolonged. This reflects multiple failed phase III trials of sunitinib based therapies in metastatic breast cancer patients. However, using a VEGF pathway targeting antibody drug instead of a TKI, with (paclitaxel) chemotherapy, resulted in anti-tumor activity in the metastatic setting, partially reflecting prior clinical results of the E2100 phase III trial of weekly paclitaxel plus bevacizumab. Other experiments involving postsurgical adjuvant treatment of early stage disease foreshadowed the phase III clinical trial failures of adjuvant bevacizumab in colorectal or breast cancer. In contrast, some investigational metronomic oral chemotherapy protocols alone or in combination with an antiangiogenic drug demonstrated potent activity in the advanced metastatic setting; these encouraging results have yet to be validated in randomized phase III clinical trials, which are underway

  12. Implementation of an advanced clinical and administrative hospital information system.

    PubMed

    Vegoda, P R; Dyro, J F

    1986-01-01

    Over the last six years since University Hospital opened, the University Hospital Information System (UHIS) has continued to evolve to what is today an advanced administrative and clinical information system. At University Hospital UHIS is the way of conducting business. A wide range of patient care applications are operational including Patient Registration, ADT for Inpatient/Outpatient/Emergency Room visits, Advanced Order Entry/Result Reporting, Medical Records, Lab Automated Data Acquisition/Quality Control, Pharmacy, Radiology, Dietary, Respiratory Therapy, ECG, EEG, Cardiology, Physical/Occupational Therapy and Nursing. These systems and numerous financial systems have been installed in a highly tuned, efficient computer system. All applications are real-time, on-line, and data base oriented. Each system is provided with multiple data security levels, forward file recovery, and dynamic transaction backout of in-flight tasks. Sensitive medical information is safeguarded by job function passwords, identification codes, need-to-know master screens and terminal keylocks. University Hospital has an IBM 3083 CPU with five 3380 disk drives, four dual density tape drives, and a 3705 network controller. The network of 300 terminals and 100 printers is connected to the computer center by an RF broadband cable. The software is configured around the IBM/MVS operating system using CICS as the telecommunication monitor, IMS as the data base management system and PCS/ADS as the application enabling tool. The most extensive clinical system added to UHIS is the Physiological Monitoring/Patient Data Management System with serves 92 critical care beds. In keeping with the Hospital's philosophy of integrated computing, the PMS/PDMS with its network of minicomputers was linked to the UHIS system. In a pilot program, remote access to UHIS through the IBM personal computer has been implemented in several physician offices in the local community, further extending the communications

  13. 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

    SciTech Connect

    Blackstock, A. William . E-mail: ablackst@wfubmc.edu; Farmer, Michael R.; Lovato, James; Mishra, Girish; Melin, Susan A.; Oaks, Timothy; Aklilu, Mabea; Clark, Paige B.; Levine, Edward A.

    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 ineligible 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.

  14. 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.

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. Validity, reliability, and feasibility of clinical staging scales in dementia: a systematic review.

    PubMed

    Rikkert, Marcel G M Olde; Tona, Klodiana Daphne; Janssen, Lieneke; Burns, Alistair; Lobo, Anatonio; Robert, Philippe; Sartorius, Norman; Stoppe, Gabriela; Waldemar, Gunhild

    2011-08-01

    New staging systems of dementia require adaptation of disease management programs and adequate staging instruments. Therefore, we systematically reviewed the literature on validity and reliability of clinically applicable, multidomain, and dementia staging instruments. A total of 23 articles describing 12 staging instruments were identified (N = 6109 participants, age 65-87). Reliability was studied in most (91%) of the articles and was judged moderate to good. Approximately 78% of the articles evaluated concurrent validity, which was good to very good, while discriminant validity was assessed in only 25%. The scales can be applied in ±15 minutes. Clinical Dementia Rating (CDR), Global Deterioration scale (GDS), and Functional Assessment Staging (FAST) have been monitored on reliability and validity, and the CDR currently is the best-evidenced scale, also studied in international perspective, and is available in 14 languages. Taking into account the increasing differentiation of Alzheimer's disease in preclinical and predementia stages, there is an urgent need for global rating scales to be refined as well.

  20. Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances

    PubMed Central

    Varadkar, Sophia; Bien, Christian G; Kruse, Carol A; Jensen, Frances E; Bauer, Jan; Pardo, Carlos A; Vincent, Angela; Mathern, Gary W; Cross, J Helen

    2014-01-01

    Rasmussen’s encephalitis is a rare chronic neurological disorder, characterised by unilateral inflammation of the cerebral cortex, drug-resistant epilepsy, and progressive neurological and cognitive deterioration. Neuropathological and immunological studies support the notion that Rasmussen’s encephalitis is probably driven by a T-cell response to one or more antigenic epitopes, with potential additional contribution by autoantibodies. Careful analysis of the association between histopathology and clinical presentation suggests that initial damage to the brain is mediated by T cells and microglia, suggesting a window for treatment if Rasmussen’s encephalitis can be diagnosed early. Advances in neuroimaging suggest that progression of the inflammatory process seen with MRI might be a good biomarker in Rasmussen’s encephalitis. For many patients, families, and doctors, choosing the right time to move from medical management to surgery is a real therapeutic dilemma. Cerebral hemispherectomy remains the only cure for seizures, but there are inevitable functional compromises. Decisions of whether or when surgery should be undertaken are challenging in the absence of a dense neurological deficit, and vary by institutional experience. Further, the optimum time for surgery, to give the best language and cognitive outcome, is not yet well understood. Immunomodulatory treatments seem to slow rather than halt disease progression in Rasmussen’s encephalitis, without changing the eventual outcome. PMID:24457189

  1. Genetic and clinical advances in congenital long QT syndrome.

    PubMed

    Mizusawa, Yuka; Horie, Minoru; Wilde, Arthur A M

    2014-01-01

    Congenital long QT syndrome (LQTS) is an inherited arrhythmia syndrome characterized by a prolonged QT interval on the 12-lead ECG, torsades de pointes and a higher chance of sudden cardiac death. LQTS segregates in a Mendelian fashion, which includes Romano-Ward syndrome with an autosomal dominant pattern as well as a rare autosomal recessive pattern (Jervell and Lange-Nielsen syndrome). Since 1957 when Jervell and Lange-Nielsen reported the first familial LQTS with congenital deafness, progress in understanding the genetic and electrophysiological mechanisms of LQTS has tremendously improved diagnostic methods and treatments. In the meantime, it has become evident that LQTS may not always be explained by a single gene mutation, but seems to follow a more complex genetic model intertwined with genetic common polymorphisms that have a mild to moderate effect on disease expression. In this review, we summarize the characteristics of LQTS (mainly LQT1-3) and briefly describe the most recent advances in LQTS clinical diagnostics as well as genetics.

  2. Functional neuroimaging of traumatic brain injury: advances and clinical utility

    PubMed Central

    Irimia, Andrei; Van Horn, John Darrell

    2015-01-01

    Functional deficits due to traumatic brain injury (TBI) can have significant and enduring consequences upon patients’ life quality and expectancy. Although functional neuroimaging is essential for understanding TBI pathophysiology, an insufficient amount of effort has been dedicated to the task of translating functional neuroimaging findings into information with clinical utility. The purpose of this review is to summarize the use of functional neuroimaging techniques – especially functional magnetic resonance imaging, diffusion tensor imaging, positron emission tomography, magnetic resonance spectroscopy, and electroencephalography – for advancing current knowledge of TBI-related brain dysfunction and for improving the rehabilitation of TBI patients. We focus on seven core areas of functional deficits, namely consciousness, motor function, attention, memory, higher cognition, personality, and affect, and, for each of these, we summarize recent findings from neuroimaging studies which have provided substantial insight into brain function changes due to TBI. Recommendations are also provided to aid in setting the direction of future neuroimaging research and for understanding brain function changes after TBI. PMID:26396520

  3. Advanced launch vehicle upper stages using liquid propulsion and metallized propellants

    NASA Technical Reports Server (NTRS)

    Palaszewski, B. A.

    1990-01-01

    Metallized propellants are liquid propellants with a metal additive suspended in a gelled fuel or oxidizer. Typically, aluminum particles are the metal additives. These propellants provide increase in the density and/or the specific impulse of the propulsion system. Using metallized propellants for volume- and mass-constrained upper stages can deliver modest increases in performance for Low Earth Orbit to Geosynchronous Earth Orbit 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 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 and Space Transportation System-Cargo 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.

  4. Lung cancer staging: the value of PET depends on the clinical setting

    PubMed Central

    2014-01-01

    Background Although positron emission tomography (PET) imaging is widely recommended in the evaluation of patients with lung cancer, randomized controlled trials (RCTs) assessing this have demonstrated inconsistent results. We asked whether differences in the clinical context and endpoints could explain these discrepancies. Methods We used realist synthesis methods to analyze how contextual differences among RCTs affected the results. We focused on RCTs to minimize confounding yet permit evaluation of differences by comparing across studies. Results This analysis suggests that the impact of PET depends on the clinical setting. PET is of greatest benefit in identifying M1 disease in patients with a high chance of such involvement and when little traditional imaging [e.g., abdominal/pelvis computed tomography (CT) and bone scan] is used. Identification of N2,3 involvement by PET prior to resection is seen primarily when there is at least a moderate probability of such and the rate of invasive staging is high. The rate of N2 disease not identified preoperatively appears to increase if PET is used to avoid invasive mediastinal staging in clinical settings in which the risk of N2,3 involvement is moderately high. There is both a potential benefit in avoiding stage-inappropriate resection as well as a risk of missed (stage-appropriate) resection if PET findings are not evaluated carefully. Conclusions A blanket recommendation for PET may be too simplistic without considering nuances of the clinical setting. PMID:25589964

  5. Photoacoustic intra-operative nodal staging using clinically approved superparamagnetic iron oxide nanoparticles

    NASA Astrophysics Data System (ADS)

    Grootendorst, Diederik J.; Fratila, Raluca M.; Visscher, Martijn; Ten Haken, Bennie; van Wezel, Richard; Steenbergen, Wiendelt; Manohar, Srirang; Ruers, Theo J. M.

    2013-02-01

    Detection of tumor metastases in the lymphatic system is essential for accurate staging of various malignancies, however fast, accurate and cost-effective intra-operative evaluation of the nodal status remains difficult to perform with common available medical imaging techniques. In recent years, numerous studies have confirmed the additional value of superparamagnetic iron oxide dispersions (SPIOs) for nodal staging purposes, prompting the clearance of different SPIO dispersions for clinical practice. We evaluate whether a combination of photoacoustic (PA) imaging and a clinically approved SPIO dispersion, could be applied for intra-operative nodal staging. Metastatic adenocarcinoma was inoculated in Copenhagen rats for 5 or 8 days. After SPIO injection, the lymph nodes were photoacoustically imaged both in vivo and ex vivo whereafter imaging results were correlated with MR and histology. Results were compared to a control group without tumor inoculation. In the tumor groups clear irregularities, as small as 1 mm, were observed in the PA contrast pattern of the nodes together with an decrease of PA response. These irregularities could be correlated to the absence of contrast in the MR images and could be linked to metastatic deposits seen in the histological slides. The PA and MR images of the control animals did not show these features. We conclude that the combination of photoacoustic imaging with a clinically approved iron oxide nanoparticle dispersion is able to detect lymph node metastases in an animal model. This approach opens up new possibilities for fast intra-operative nodal staging in a clinical setting.

  6. Bioinformatics Methods and Tools to Advance Clinical Care

    PubMed Central

    Lecroq, T.

    2015-01-01

    Summary Objectives To summarize excellent current research in the field of Bioinformatics and Translational Informatics with application in the health domain and clinical care. Method We provide a synopsis of the articles selected for the IMIA Yearbook 2015, from which we attempt to derive a synthetic overview of current and future activities in the field. As last year, a first step of selection was performed by querying MEDLINE with a list of MeSH descriptors completed by a list of terms adapted to the section. Each section editor has evaluated separately the set of 1,594 articles and the evaluation results were merged for retaining 15 articles for peer-review. Results The selection and evaluation process of this Yearbook’s section on Bioinformatics and Translational Informatics yielded four excellent articles regarding data management and genome medicine that are mainly tool-based papers. In the first article, the authors present PPISURV a tool for uncovering the role of specific genes in cancer survival outcome. The second article describes the classifier PredictSNP which combines six performing tools for predicting disease-related mutations. In the third article, by presenting a high-coverage map of the human proteome using high resolution mass spectrometry, the authors highlight the need for using mass spectrometry to complement genome annotation. The fourth article is also related to patient survival and decision support. The authors present datamining methods of large-scale datasets of past transplants. The objective is to identify chances of survival. Conclusions The current research activities still attest the continuous convergence of Bioinformatics and Medical Informatics, with a focus this year on dedicated tools and methods to advance clinical care. Indeed, there is a need for powerful tools for managing and interpreting complex, large-scale genomic and biological datasets, but also a need for user-friendly tools developed for the clinicians in their

  7. Correlations Between the EGFR Mutation Status and Clinicopathological Features of Clinical Stage I Lung Adenocarcinoma

    PubMed Central

    Isaka, Tetsuya; Yokose, Tomoyuki; Ito, Hiroyuki; Nagata, Masashi; Furumoto, Hideyuki; Nishii, Teppei; Katayama, Kayoko; Yamada, Kouzo; Nakayama, Haruhiko; Masuda, Munetaka

    2015-01-01

    Abstract Advanced lung cancers with epidermal growth factor receptor (EGFR) exon 19 deletions (Ex19s) and EGFR exon 21 L858R point mutations (Ex21s) exhibit different clinical behavior. However, these differences are unclear in resectable primary lung tumors. The clinicopathological features of 88 (20.9%) Ex19, 124 (29.4%) Ex21, and 198 (46.9%) EGFR wild-type (Wt) clinical stage I primary adenocarcinomas resected between January 1, 2012 and October 31, 2014 were compared by using Chi-square tests, residual error analysis, analysis of variance, and Tukey tests. Ex21 lesions occurred more frequently in women and never-smokers and had a higher tumor disappearance rate (TDR: 59.6% vs 43.9%; P < 0.001) and lower maximum standardized uptake value (maxSUV: 2.0 vs 3.5; P < 0.01) than Wt lesions; Ex19 lesions had intermediate values (52.8% and 2.6). There was a low frequency of vascular invasion in Ex21 lesions (12.1%; P < 0.05) and a high frequency in Wt lesions (22.7%; P < 0.05). Most Ex19 lesions were intermediate-grade adenocarcinoma (lepidic, acinar, and papillary predominant: 73.9%; P < 0.05). Wt and Ex21 lesions were predominately high-grade (micropapillary or solid predominant, mucinous variant) and low-grade (adenocarcinoma in situ and minimally invasive adenocarcinoma) adenocarcinoma, respectively. Wt lesions had smaller lepidic components (42.1% vs 56.3%; P < 0.001) and larger papillary and solid components (papillary: 15.5% vs 9.0%; P < 0.05; solid: 13.2% vs 3.2%; P < 0.001) than Ex21 lesions. Most Ex19 lesions had intermediate component rates. Most Ex21 lesions were low-grade adenocarcinoma with lepidic growth patterns. Wt high-grade adenocarcinomas included solid and papillary components with vascular invasion. Ex19 lesions were intermediate grade between Ex21 and Wt. PMID:26496308

  8. Mutation Profiling of Clinically Advanced Cancers Using Next-Generation Sequencing for Targeted Therapy: A Lifespan Experience.

    PubMed

    Friedman, Kenneth; Resnick, Murray B; Safran, Howard

    2015-10-01

    The application of modern molecular tests such as next-generation sequencing (NGS) to human malignancies has led to better understanding of tumor biology and the design of targeted molecular therapies. In the research setting, important genomic alterations in tumors have been discovered with potential therapeutic implications but data regarding the impact of this technology in a real world oncology practice is limited. As a result, we decided to review the results of NGS in 144 advanced-stage cancer patients referred to the oncology practices of Lifespan-affiliated centers in Rhode Island. Most cancers revealed genomic alterations in genes commonly mutated in cancer. However, several unexpected genomic alterations were discovered in certain cancers with potential therapeutic intervention. Most cancers contained "actionable" genomic alterations despite being of advanced stage. Our experience demonstrates that application of NGS in the clinical setting contributes both to increasing the therapeutic armamentarium as well as our understanding of tumor biology.

  9. Clinical nurse research consultant: a clinical and academic role to advance practice and the discipline of nursing.

    PubMed

    Currey, Judy; Considine, Julie; Khaw, Damien

    2011-10-01

    This article presents a proposal for the Clinical Nurse Research Consultant, a new nursing role. Although healthcare delivery continues to evolve, nursing has lacked highly specialized clinical and research leadership that, as a primary responsibility, drives evidence-based practice change in collaboration with bedside clinicians. International literature published over the last 25 years in the databases of CINAHL, OVID, Medline Pubmed, Science Direct, Expanded Academic, ESBSCOhost, Scopus and Proquest is cited to create a case for the Clinical Nurse Research Consultant. The Clinical Nurse Research Consultant will address the research/practice gap and assist in facilitating evidence-based clinical practice. To fulfil the responsibilities of this proposed role, the Clinical Nurse Research Consultant must be a doctorally prepared recognized clinical expert, have educational expertise, and possess advanced interpersonal, teamwork and communication skills. This role will enable clinical nurses to maintain and share their clinical expertise, advance practice through research and role model the clinical/research nexus. Critically, the Clinical Nurse Research Consultant must be appointed in a clinical and academic partnership to provide for career progression and role support. The creation of the Clinical Nurse Research Consultant will advance nursing practice and the discipline of nursing. © 2011 The Authors. Journal of Advanced Nursing © 2011 Blackwell Publishing Ltd.

  10. Assessment of advanced hepatic MR elastography methods for susceptibility artifact suppression in clinical patients.

    PubMed

    Wang, Jin; Glaser, Kevin J; Zhang, Tianhui; Shan, Qungang; He, Bingjun; Chen, Jun; Yin, Meng; Dzyubak, Bogdan; Kugel, Jennifer L; Kruse, Scott A; Grimm, Roger C; Venkatesh, Sudhakar K; Ehman, Richard L

    2017-08-11

    To assess the success rate, image quality, and the ability to stage liver fibrosis of a standard 2D gradient-recalled echo (GRE) and four different spin-echo (SE) magnetic resonance elastography (MRE) sequences in patients with different liver iron concentrations. A total of 332 patients who underwent 3T MRE examinations that included liver fat and iron quantification were enrolled, including 136 patients with all five MRE techniques. Thirty-four patients had biopsy results for fibrosis staging. The liver stiffness, region of interest area, image quality, and success rate of the five sequences were compared in 115/136 patients. The area under the receiver operating characteristic curves (AUCs) and the accuracies for diagnosing early-stage fibrosis and advanced fibrosis were compared. The effect of BMI (body mass index), the R2* relaxation time, and fat fraction on the image quality and liver stiffness measurements were analyzed. The success rates were significantly higher in the four SE sequences (99.1-100%) compared with GRE MRE (85.3%) (all P < 0.001). There were significant differences of the mean ROI area between every pair of sequences (all P < 0.0001). There were no significant differences in the AUC of the five MRE sequences for discriminating advanced fibrosis (10 P-values ranging from 0.2410-0.9171). R2* had a significant effect on the success rate and image quality for the noniron 2D echo-planar imaging (EPI), 3D EPI and 2D GRE (all P < 0.001) sequences. BMI had a significant effect on the iron 2D EPI (P = 0.0230) and iron 2D SE (P = 0.0040) sequences. All five techniques showed good diagnostic performance in staging liver fibrosis. The SE MRE sequences had higher success rates and better image quality than GRE MRE in 3T clinical hepatic imaging. 3 Technical Efficacy Stage: 5 J. Magn. Reson. Imaging 2017. © 2017 International Society for Magnetic Resonance in Medicine.

  11. Advances in endodontics: Potential applications in clinical practice

    PubMed Central

    Kishen, Anil; Peters, Ove A.; Zehnder, Matthias; Diogenes, Anibal R.; Nair, Madhu K.

    2016-01-01

    Contemporary endodontics has seen an unprecedented advance in technology and materials. This article aimed to review some of the challenges and advances in the following sections: (1) endodontic imaging, (2) root canal preparation, (3) root canal disinfection, (4) root canal filling, and (4) regenerative endodontic procedures (REPs). Jointly, these advances are aimed at improving the state of the art and science of root canal treatment. PMID:27217630

  12. Advances in endodontics: Potential applications in clinical practice.

    PubMed

    Kishen, Anil; Peters, Ove A; Zehnder, Matthias; Diogenes, Anibal R; Nair, Madhu K

    2016-01-01

    Contemporary endodontics has seen an unprecedented advance in technology and materials. This article aimed to review some of the challenges and advances in the following sections: (1) endodontic imaging, (2) root canal preparation, (3) root canal disinfection, (4) root canal filling, and (4) regenerative endodontic procedures (REPs). Jointly, these advances are aimed at improving the state of the art and science of root canal treatment.

  13. Complete pathological response following down-staging chemoradiation in locally advanced pancreatic cancer: Challenging the boundaries

    PubMed Central

    Khan, AZ; Pitsinis, V; Mudan, SS

    2007-01-01

    Pancreatic cancer is an aggressive malignancy, relatively resistant to chemotherapy and radiotherapy, which usually presents late. Disease specific mortality approaches unity despite advances in adjuvant therapy. We present the first reported case of complete pathological response following neoadjuvant therapy in a locally advanced pancreatic adenocarcinoma. PMID:18081235

  14. 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.

  15. 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.

  16. 2011 Focused Update of 2009 American Society of Clinical Oncology Clinical Practice Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer

    PubMed Central

    Azzoli, Christopher G.; Temin, Sarah; Aliff, Timothy; Baker, Sherman; Brahmer, Julie; Johnson, David H.; Laskin, Janessa L.; Masters, Gregory; Milton, Daniel; Nordquist, Luke; Pao, William; Pfister, David G.; Piantadosi, Steven; Schiller, Joan H.; Smith, Reily; Smith, Thomas J.; Strawn, John R.; Trent, David; Giaccone, Giuseppe

    2011-01-01

    Purpose An American Society of Clinical Oncology (ASCO) focused update updates a single recommendation (or subset of recommendations) in advance of a regularly scheduled guideline update. This document updates one recommendation of the ASCO Guideline Update on Chemotherapy for Stage IV Non–Small-Cell Lung Cancer (NSCLC) regarding switch maintenance chemotherapy. Clinical Context Recent results from phase III clinical trials have demonstrated that in patients with stage IV NSCLC who have received four cycles of first-line chemotherapy and whose disease has not progressed, an immediate switch to alternative, single-agent chemotherapy can extend progression-free survival and, in some cases, overall survival. Because of limitations in the data, delayed treatment with a second-line agent after disease progression is also acceptable. Recent Data Seven randomized controlled trials of carboxyaminoimidazole, docetaxel, erlotinib, gefitinib, gemcitabine, and pemetrexed have evaluated outcomes in patients who received an immediate, non–cross resistant alternative therapy (switch maintenance) after first-line therapy. Recommendation In patients with stage IV NSCLC, first-line cytotoxic chemotherapy should be stopped at disease progression or after four cycles in patients whose disease is stable but not responding to treatment. Two-drug cytotoxic combinations should be administered for no more than six cycles. For those with stable disease or response after four cycles, immediate treatment with an alternative, single-agent chemotherapy such as pemetrexed in patients with nonsquamous histology, docetaxel in unselected patients, or erlotinib in unselected patients may be considered. Limitations of this data are such that a break from cytotoxic chemotherapy after a fixed course is also acceptable, with initiation of second-line chemotherapy at disease progression. PMID:21900105

  17. Low Level of Microsatellite Instability Correlates with Poor Clinical Prognosis in Stage II Colorectal Cancer Patients

    PubMed Central

    Mojarad, Ehsan Nazemalhosseini; Kashfi, Seyed Mohammad Hossein; Mirtalebi, Hanieh; Taleghani, Mohammad Yaghoob; Azimzadeh, Pedram; Savabkar, Sanaz; Pourhoseingholi, Mohammad Amin; Jalaeikhoo, Hasan; Asadzadeh Aghdaei, Hamid; Kuppen, Peter J. K.; Zali, Mohammad Reza

    2016-01-01

    The influence of microsatellite instability (MSI) on the prognosis of colorectal cancer (CRC) requires more investigation. We assessed the role of MSI status in survival of individuals diagnosed with primary colorectal cancer. In this retrospective cross-sectional study the MSI status was determined in 158 formalin-fixed paraffin-embedded tumors and their matched normal tissues from patients who underwent curative surgery. Cox proportional hazard modeling was performed to assess the clinical prognostic significance. In this study we found that MSI-H tumors were predominantly located in the colon versus rectum (p = 0.03), associated with poorer differentiation (p = 0.003) and TNM stage II/III of tumors (p = 0.02). In CRC patients with stage II, MSI-L cases showed significantly poorer survival compared with patients who had MSI-H or MSS tumors (p = 0.04). This study indicates that MSI-L tumors correlate with poorer clinical outcome in patients with stage II tumors (p = 0.04) or in tumors located in the colon (p = 0.02). MSI-L characterizes a distinct subgroup of CRC patients who have a poorer outcome. This study suggests that MSI status in CRC, as a clinical prognostic marker, is dependent on other factors, such as tumor stage and location. PMID:27429617

  18. Microscopic Omental Metastasis in Clinical Stage I Endometrial Cancer: A Meta-analysis.

    PubMed

    Joo, Won Duk; Schwartz, Peter E; Rutherford, Thomas J; Seong, Seok Ju; Ku, Junbeom; Park, Hyun; Jung, Sang Geun; Choi, Min Chul; Lee, Chan

    2015-10-01

    A patient with early-stage endometrial cancer may possibly have microscopic metastasis in the omentum, which is associated with a poor prognosis. The purpose of this study was to identify risk factors for microscopic omental metastasis in patients with clinical stage I endometrial cancer to establish the indications for selective omentectomy. We searched the PubMed, EMBASE, and Cochrane Library databases for published studies from inception to August 2014, using terms such as 'endometrial cancer' or 'uterine cancer' for disease, 'omentectomy' or 'omental biopsy' for intervention, and 'metastasis' for outcome. Two reviewers independently identified the studies that matched the selection criteria. We calculated the pooled risk ratios (RRs) with 95 % confidence intervals (CI) of each surgicopathologic finding for microscopic omental metastases in clinical stage I endometrial cancer. We also calculated the prevalence of microscopic omental metastases. Among 1163 patients from ten studies, 22 cases (1.9 %) of microscopic omental metastases were found, which accounted for 26.5 % of all omental metastases. Positive lymph nodes (RR 8.71, 95 % CI 1.38-54.95), adnexal metastases (RR 16.76, 95 % CI 2.60-107.97), and appendiceal implants (RR 161.67, 95 % CI 5.16-5061.03) were highly associated with microscopic omental metastases. Microscopic omental metastases were not negligible in patients with clinical stage I endometrial cancer. Those with a risk factor of microscopic omental metastases were recommended for selective omentectomy.

  19. Potential factors associated with clinical stage of nasopharyngeal carcinoma at diagnosis: a case-control study.

    PubMed

    Ren, Jun-Ting; Li, Meng-Yu; Wang, Xiao-Wen; Xue, Wen-Qiong; Ren, Ze-Fang; Jia, Wei-Hua

    2017-09-04

    In China, most patients with nasopharyngeal carcinoma (NPC) are diagnosed at a late stage and consequently have a poor prognosis. This study aimed to investigate potential factors associated with the clinical stage of NPC at diagnosis. Data were obtained from 118 patients with early-stage NPC and 274 with late-stage NPC who were treated at Sun Yat-sen University Cancer Center between August 2014 and July 2015. Patients were individually matched by age, sex, and residence, and a conditional logistic regression model was applied to assess the associations of clinical stage at diagnosis with socioeconomic status indicators, knowledge of NPC, physical examinations, patient interval, and risk factors for NPC. Although knowledge of early NPC symptoms, smoking cessation, and patient interval were important factors, the number of cigarettes smoked per day, motorbike ownership, and physical examination exhibited the strongest associations with the clinical stage of NPC at diagnosis. Compared with smoking fewer than ten cigarettes a day, smoking 10-30 cigarettes [odds ratio (OR) 4.03; 95% confidence interval (CI) 1.11-14.68] or more than 30 cigarettes (OR 11.46; 95% CI 1.26-103.91) was associated with an increased risk of late diagnosis. Compared with not owning a motorbike, owning a motorbike (OR 0.38; 95% CI 0.23-0.64) was associated with early diagnosis. Subjects who underwent physical examinations were less likely to receive a late diagnosis than those who did not undergo examinations (OR 0.50; 95% CI 0.28-0.89). However, indicators of wealth were not significant factors. Initiatives to improve NPC patient prognosis should aim to promote knowledge about early symptoms and detection, health awareness, and accessibility to health facilities among all patients, regardless of socioeconomic status.

  20. Optimization of two-stage production/inventory systems under order base stock policy with advance demand information

    NASA Astrophysics Data System (ADS)

    Nakade, Koichi; Yokozawa, Shiori

    2016-08-01

    It is important to share demand information among the members in supply chains. In recent years, production and inventory systems with advance demand information (ADI) have been discussed, where advance demand information means the information of demand which the decision maker obtains before the corresponding actual demand arrives. Appropriate production and inventory control using demand information leads to the decrease of inventory and backlog costs. For a single stage system, the optimal base stock and release lead time have been discussed in the literature. In practical production systems the manufacturing system has multiple processes. The multiple stage production and inventory system with ADI, however, has been analyzed by simulation or assuming exponential processing time. That is, their theoretical analysis and optimization of release lead time and base stock level have little been obtained because of its difficulty. In this paper, theoretical analysis of a two-stage production inventory system with advance demand information is developed, where the processing time is assumed deterministic and identical; demand arrival process is Poisson, and an order base stock policy is adopted. Using the analytical results, optimal release lead time and optimal base stock levels for minimizing the average cost on the holding and backlog costs are explicitly derived.

  1. Neoadjuvant chemoradiation therapy is beneficial for clinical stage T2 N0 esophageal cancer patients due to inaccurate preoperative staging.

    PubMed

    Zhang, Jennifer Q; Hooker, Craig M; Brock, Malcolm V; Shin, James; Lee, Sue; How, Remealle; Franco, Noreli; Prevas, Helen; Hulbert, Alicia; Yang, Stephen C

    2012-02-01

    It remains unclear if patients with clinical stage T2 N0 (cT2 N0) esophageal cancer should be offered induction therapy vs surgical intervention alone. This was a retrospective cohort study of cT2 N0 patients undergoing induction therapy, followed by surgical resection, or resection alone, at the Johns Hopkins Hospital from 1989 to 2009. Kaplan-Meier analysis was used to compare all-cause mortality in cT2 N0 patients who had resection alone vs those who had induction chemoradiation therapy, followed by resection. A study cohort of 69 patients was identified and divided into two groups: 55 patients (79.7%) received induction therapy and 14 (20.3%) did not. No statistically significant difference in 5-year survival rate was observed for the two groups: 49.5% for the resection-only group and 53.8% for the induction group. More than 50% of cT2 N0 patients were understaged. For cT2 N0 esophageal cancer patients, the benefit of neoadjuvant therapy is still unclear. Induction therapy for cT2 N0 did not translate into a statistically significant improvement in survival. However, due to the significant understaging of T2 N0 patients, we recommend neoadjuvant therapy to all cT2N0 patients before operation. Copyright © 2012 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

  2. Neoadjuvant Chemoradiation Therapy Is Beneficial for Clinical Stage T2 N0 Esophageal Cancer Patients Due to Inaccurate Preoperative Staging

    PubMed Central

    Zhang, Jennifer Q.; Hooker, Craig M.; Brock, Malcolm V.; Shin, James; Lee, Sue; How, Remealle; Franco, Noreli; Prevas, Helen; Hulbert, Alicia; Yang, Stephen C.

    2014-01-01

    Background It remains unclear if patients with clinical stage T2 N0 (cT2 N0) esophageal cancer should be offered induction therapy vs surgical intervention alone. Methods This was a retrospective cohort study of cT2 N0 patients undergoing induction therapy, followed by surgical resection, or resection alone, at the Johns Hopkins Hospital from 1989 to 2009. Kaplan-Meier analysis was used to compare all-cause mortality in cT2 N0 patients who had resection alone vs those who had induction chemoradiation therapy, followed by resection. Results A study cohort of 69 patients was identified and divided into two groups: 55 patients (79.7%) received induction therapy and 14 (20.3%) did not. No statistically significant difference in 5-year survival rate was observed for the two groups: 49.5% for the resection-only group and 53.8% for the induction group. More than 50% of cT2 N0 patients were understaged. Conclusions For cT2 N0 esophageal cancer patients, the benefit of neoadjuvant therapy is still unclear. Induction therapy for cT2 N0 did not translate into a statistically significant improvement in survival. However, due to the significant understaging of T2 N0 patients, we recommend neoadjuvant therapy to all cT2N0 patients before operation. PMID:22269708

  3. Recent advances in innovative therapeutic approaches for Duchenne muscular dystrophy: from discovery to clinical trials

    PubMed Central

    Shimizu-Motohashi, Yuko; Miyatake, Shouta; Komaki, Hirofumi; Takeda, Shin’ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked progressive degenerative muscle disorder caused by the absence of dystrophin. There is no curative therapy, although innovative therapeutic approaches have been aggressively investigated over recent years. Currently, the international clinical trial registry platform for this disease has been constructed and clinical trials for innovative therapeutic approaches are underway. Among these, exon skipping and read-through of nonsense mutations are in the most advanced stages, with exon skipping theoretically applicable to a larger number of patients. To date, exon skipping that targets exons 51, 44, 45, and 53 is being globally investigated including in USA, EU, and Japan. The latest announcement from Japan was made, demonstrating successful dystrophin production in muscles of patients with DMD after treating with exon 53 skipping antisense oligonucleotides (ASOs). However, the innovative therapeutic approaches have demonstrated limited efficacy. To address this issue in exon skipping, studies to unveil the mechanism underlying gymnotic delivery of ASO uptake in living cells have been conducted in an effort to improve in vivo delivery. Further, establishing the infrastructures to integrate multi-institutional clinical trials are needed to facilitate the development of successful therapies for DMD, which ultimately is applicable to other myopathies and neurodegenerative diseases, including spinal muscular atrophy and motor neuron diseases. PMID:27398133

  4. Recent advances in innovative therapeutic approaches for Duchenne muscular dystrophy: from discovery to clinical trials.

    PubMed

    Shimizu-Motohashi, Yuko; Miyatake, Shouta; Komaki, Hirofumi; Takeda, Shin'ichi; Aoki, Yoshitsugu

    2016-01-01

    Duchenne muscular dystrophy (DMD) is an X-linked progressive degenerative muscle disorder caused by the absence of dystrophin. There is no curative therapy, although innovative therapeutic approaches have been aggressively investigated over recent years. Currently, the international clinical trial registry platform for this disease has been constructed and clinical trials for innovative therapeutic approaches are underway. Among these, exon skipping and read-through of nonsense mutations are in the most advanced stages, with exon skipping theoretically applicable to a larger number of patients. To date, exon skipping that targets exons 51, 44, 45, and 53 is being globally investigated including in USA, EU, and Japan. The latest announcement from Japan was made, demonstrating successful dystrophin production in muscles of patients with DMD after treating with exon 53 skipping antisense oligonucleotides (ASOs). However, the innovative therapeutic approaches have demonstrated limited efficacy. To address this issue in exon skipping, studies to unveil the mechanism underlying gymnotic delivery of ASO uptake in living cells have been conducted in an effort to improve in vivo delivery. Further, establishing the infrastructures to integrate multi-institutional clinical trials are needed to facilitate the development of successful therapies for DMD, which ultimately is applicable to other myopathies and neurodegenerative diseases, including spinal muscular atrophy and motor neuron diseases.

  5. Evaluation and revision of a clinical advancement program.

    PubMed

    Goodrich, Cynthia A; Ward, Cynthia W

    2004-12-01

    Career advancement programs have been used for decades to provide promotion opportunities for bedside nurses. Few of the programs have been evaluated to determine their efficacy and the overall satisfaction to registered nurses. An evaluation of a career advancement system in a community hospital setting was conducted to identify the perceived lack of interest in pursuing promotion with the current process.

  6. 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…

  7. 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…

  8. 2nd ESMO Consensus Conference in Lung Cancer: locally advanced stage III non-small-cell lung cancer.

    PubMed

    Eberhardt, W E E; De Ruysscher, D; Weder, W; Le Péchoux, C; De Leyn, P; Hoffmann, H; Westeel, V; Stahel, R; Felip, E; Peters, S

    2015-08-01

    To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on Lung Cancer was held on 11-12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on locally advanced disease.

  9. Oral submucous fibrosis: A quantitative assessment of serum malondialdehyde, superoxide dismutase and correlation with clinical staging

    PubMed Central

    Bale, Ratnakar; Kattappagari, Kiran Kumar; Vidya, Desai; Vuddandi, Sivapradobh; Gummalla, Charani; Baddam, Venkata Ramana Reddy

    2017-01-01

    Background: Oral submucous fibrosis (OSMF) is a progressive disorder affecting the oral mucosa. OSMF predominantly seen in South-east Asian countries. There are some biochemicals parameters which are modify in oral submucous fibrosis; this alteration can be used as a tool for diseases progress and avert malignant transformation. Aims and Objectives: The aim of this study is to evaluate the serum malondialdehyde (malondialdehyde [MDA]), and Superoxide dismutase (SOD) in oral sub mucous fibrosis cases and compare clinical stages. Materials and Methods: Thirty cases of clinical and histopathological established oral submucous fibrosis and thirty cases of nonsymptomatic features of oral submucous fibrosis preferred as controls. Venous blood was collected and separation of serum for estimation of MDA and SOD levels was done using an ultraviolet spectrophotometer. Statistical Analysis: Data were analyzed using SPSS software using Student's t-test and Kruskal–Wallis ANOVA test. Results: Serum MDA levels were elevated when clinical staging increases, where as SOD levels were decreased when clinical stage increases when compared with control cases and it showed stastically significant. Conclusion: Estimation of serum MDA and SOD in patients with OSMF, we can assess the degree of oxidative damage of the disease. This can be used as an early diagnostic tool for preventing malignant transformation of oral submucous fibrosis. PMID:28479685

  10. Oral submucous fibrosis: A quantitative assessment of serum malondialdehyde, superoxide dismutase and correlation with clinical staging.

    PubMed

    Bale, Ratnakar; Kattappagari, Kiran Kumar; Vidya, Desai; Vuddandi, Sivapradobh; Gummalla, Charani; Baddam, Venkata Ramana Reddy

    2017-01-01

    Oral submucous fibrosis (OSMF) is a progressive disorder affecting the oral mucosa. OSMF predominantly seen in South-east Asian countries. There are some biochemicals parameters which are modify in oral submucous fibrosis; this alteration can be used as a tool for diseases progress and avert malignant transformation. The aim of this study is to evaluate the serum malondialdehyde (malondialdehyde [MDA]), and Superoxide dismutase (SOD) in oral sub mucous fibrosis cases and compare clinical stages. Thirty cases of clinical and histopathological established oral submucous fibrosis and thirty cases of nonsymptomatic features of oral submucous fibrosis preferred as controls. Venous blood was collected and separation of serum for estimation of MDA and SOD levels was done using an ultraviolet spectrophotometer. Data were analyzed using SPSS software using Student's t-test and Kruskal-Wallis ANOVA test. Serum MDA levels were elevated when clinical staging increases, where as SOD levels were decreased when clinical stage increases when compared with control cases and it showed stastically significant. Estimation of serum MDA and SOD in patients with OSMF, we can assess the degree of oxidative damage of the disease. This can be used as an early diagnostic tool for preventing malignant transformation of oral submucous fibrosis.

  11. Late-stage clinical development in lower urogenital targets: sexual dysfunction

    PubMed Central

    Azam, Usman

    2006-01-01

    In recent years, late-stage clinical drug development that primarily focuses on urogenital targets has centered around four areas of medical need (both unmet need and aiming to improve on existing therapies). These include male sexual dysfunction (MSD), female sexual dysfunction (FSD), prostatic pathology (neoplastic, pre-neoplasitic, and non-neoplastic), and improvement in lower urinary tract symptoms. Despite the regulatory approval of compounds to treat erectile dysfunction (ED), benign prostatic hyperplasia, a number of treatments for overactive bladder, and stress urinary incontinence, there remains a deficiency in addressing a number of conditions that arise out of pathophysiological dysfunction resulting in lower urogenital tract sexual conditions. In terms of late-stage clinical development, significant progress has most recently been made in MSD development, especially in understanding further a common and complex sexual dysfunction – that of premature ejaculation. The search also continues for compounds that improve ED in terms of better efficacy and superior safety profile compared to the currently marketed phosphodiesterase-5-inhibitors. Whilst there are no approved medications to treat the subtypes of FSD, there has been significant progress in attempting to better understand how to appropriately assess treatment benefit in clinical trial settings for this difficult to diagnose and treat condition. This review will focus on late-stage human clinical development pertaining to MSD and FSD. PMID:16465180

  12. Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up

    PubMed Central

    Colagrande, Stefano; Regini, Francesco; Taliani, Gian Giacomo; Nardi, Cosimo; Inghilesi, Andrea Lorenzo

    2015-01-01

    Advanced stage hepatocellular carcinoma (HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenib treatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments (many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters (cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of

  13. Advanced hepatocellular carcinoma and sorafenib: Diagnosis, indications, clinical and radiological follow-up.

    PubMed

    Colagrande, Stefano; Regini, Francesco; Taliani, Gian Giacomo; Nardi, Cosimo; Inghilesi, Andrea Lorenzo

    2015-05-18

    Advanced stage hepatocellular carcinoma (HCC) is a category of disease defined by radiological, clinical and hepatic function parameters, comprehending a wide range of patients with different general conditions. The main therapeutic option is represented by sorafenib treatment, a multi-kinase inhibitor with anti-proliferative and anti-angiogenic effect. Trans-arterial Radio Embolization also represents a promising new approach to intermediate/advanced HCC. Post-marketing clinical studies showed that only a portion of patients actually benefits from sorafenib treatment, and an even smaller percentage of patients treated shows partial/complete response on follow-up examinations, up against relevant costs and an incidence of drug related adverse effects. Although the treatment with sorafenib has shown a significant increase in mean overall survival in different studies, only a part of patients actually shows real benefits, while the incidence of drug related significant adverse effects and the economic costs are relatively high. Moreover, only a small percentage of patients also shows a response in terms of lesion dimensions reduction. Being able to properly differentiate patients who are responding to the therapy from non-responders as early as possible is then still difficult and could be a pivotal challenge for the future; in fact it could spare several patients a therapy often difficult to bear, directing them to other second line treatments (many of which are at the moment still under investigation). For this reason, some supplemental criteria to be added to the standard modified Response Evaluation Criteria in Solid Tumors evaluation are being searched for. In particular, finding some parameters (cellular density, perfusion grade and enhancement rate) able to predict the sensitivity of the lesions to anti-angiogenic agents could help in stratifying patients in terms of treatment responsiveness before the beginning of the therapy itself, or in the first weeks of

  14. Reconstruction of advanced-stage electrical hand injury in a one stage procedure using a prefabricated medial lateral crural composite flap.

    PubMed

    Jiang, Hao; Li, Qing Feng; Gu, Bin; Fu, Kaiding; Zheng, Danning; Liu, Kai; Shen, Guoxiong

    2008-06-01

    To explore the possibility of a one stage restoration of protective sensation and finger flexion after electrical burn of the hand, 5 patients with electrical injuries at the wrist were treated by a new free composite flap, originating from the medial lateral crural skin flap. This flap can repair skin, blood vessels, tendons, and nerves in a one-stage procedure. The harvest of the medial lateral crural flap is described. The posterior tibial vessels provide the arterial supply. The perforators to the flap and the branches to the plantaris tendon and the sural nerve were preserved, and the nerve and tendon were kept within the flap by careful dissection of the crural fascia. At the same time, 3 to 4 tendons of extensor digitorum longus were inserted into the layer between superficial and profundus crural fascia. Thus, blood vessels, nerves, and tendons were combined into the flap before transplantation. The composite flap was then transplanted into the recipient site of the injured hand to repair the complex defects in a single operation. Flexion and extension function of the fingers was evaluated. Sensory function was tested by the standards recommended by the British Medical Research Council System for evaluating sensibility. Follow-up ranged from 18 to 24 months. Results revealed all flaps survived. The flexion distance from tip to palmar crease and extension distance from tip to horizontal level of 3 patients were 4 to 5 cm and 3 to 4 cm, respectively. At 6 months, 2 patients improved from 6 cm and 5 cm to 4 cm and 4 cm, respectively. The sensation reached to S2 level, and skin temperature rose. The medial lateral crural composite flap is an ideal, one-stage method to restore protective sensation and finger flexion for advanced-stage patients who have suffered severe high voltage electrical injuries in the wrist.

  15. 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

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

    PubMed Central

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

    2015-01-01

    Introduction 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). Methods 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. Results 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. Conclusions 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

  17. Frontline rituximab monotherapy induction versus a watch and wait approach for asymptomatic advanced-stage follicular lymphoma: A cost-effectiveness analysis.

    PubMed

    Prica, Anca; Chan, Kelvin; Cheung, Matthew

    2015-08-01

    A watch and wait (WW) strategy is the standard of care for patients with asymptomatic advanced-stage follicular lymphoma. Recent data have demonstrated an improvement in the time to progression with rituximab induction (RI) with or without rituximab maintenance (RM) in comparison with a WW strategy wait in such patients. It remains unclear whether this is a cost-effective strategy. A Markov decision analysis model was developed to compare the clinical outcomes, costs, and cost-effectiveness of RI (4 weekly doses) plus RM (12 doses every 2 months), RI (4 weekly doses), and a WW strategy for patients newly diagnosed with low-burden, asymptomatic advanced-stage follicular lymphoma over a lifetime horizon. Baseline probabilities and utilities were derived from a systematic review of published studies, and they were evaluated on a 6-month cycle. A Canadian public health payer's perspective was adopted, and costs were presented in 2012 Canadian dollars. RI was the cheapest strategy. It was less costly at $59,953 versus $67,489 for the RM arm and $75,895 for the WW arm. It was also associated with a slightly lower quality-adjusted life expectancy at 6.16 quality-adjusted life years (QALYs) versus 6.28 QALYs for the RM strategy but was superior to WW (5.71 QALYs). In sensitivity analyses of key variables, this effectiveness was sensitive to the probability of first and second progression in the RI arm, and this indicated relatively neutral effectiveness between the 2 rituximab arms. RI without maintenance for asymptomatic advanced-stage follicular lymphoma is the preferred strategy: it minimizes costs per patient over a lifetime horizon. © 2015 American Cancer Society.

  18. Assessment of tumor size reduction improves outcome prediction of positron emission tomography/computed tomography after chemotherapy in advanced-stage Hodgkin lymphoma.

    PubMed

    Kobe, Carsten; Kuhnert, Georg; Kahraman, Deniz; Haverkamp, Heinz; Eich, Hans-Theodor; Franke, Mareike; Persigehl, Thorsten; Klutmann, Susanne; Amthauer, Holger; Bockisch, Andreas; Kluge, Regine; Wolf, Hans-Heinrich; Maintz, David; Fuchs, Michael; Borchmann, Peter; Diehl, Volker; Drzezga, Alexander; Engert, Andreas; Dietlein, Markus

    2014-06-10

    Positron emission tomography (PET) after chemotherapy can guide consolidating radiotherapy in advanced-stage Hodgkin lymphoma (HL). This analysis aims to improve outcome prediction by integrating additional criteria derived by computed tomography (CT). The analysis set consisted of 739 patients with residues≥2.5 cm after chemotherapy from a total of 2,126 patients treated in the HD15 trial (HD15 for advanced stage Hodgkin's disease: Quality assurance protocol for reduction of toxicity and the prognostic relevance of fluorodeoxyglucose-positron-emission tomography [FDG-PET] in the first-line treatment of advanced-stage Hodgkin's disease) performed by the German Hodgkin Study Group. A central panel performed image analysis and interpretation of CT scans before and after chemotherapy as well as PET scans after chemotherapy. Prognosis was evaluated by using progression-free survival (PFS); groups were compared with the log-rank test. Potential prognostic factors were investigated by using receiver operating characteristic analysis and logistic regression. In all, 548 (74%) of 739 patients had PET-negative residues after chemotherapy; these patients did not receive additional radiotherapy and showed a 4-year PFS of 91.5%. The 191 PET-positive patients (26%) receiving additional radiotherapy had a 4-year PFS of 86.1% (P=.022). CT alone did not allow further separation of patients in partial remission by risk of recurrence (P=.9). In the subgroup of the 54 PET-positive patients with a relative reduction of less than 40%, the risk of progression or relapse within the first year was 23.1% compared with 5.3% for patients with a larger reduction (difference, 17.9%; 95% CI, 5.8% to 30%). Patients with HL who have PET-positive residual disease after chemotherapy and poor tumor shrinkage are at high risk of progression or relapse. © 2014 by American Society of Clinical Oncology.

  19. 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

  20. 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

    2016-09-30

    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

  1. Full Mouth Implant Rehabilitation with Staged Approach: 6-Year Clinical Follow-Up.

    PubMed

    Papaspyridakos, Panos

    2015-01-01

    The transition of patients from failing dentition to complete arch implant rehabilitation often requires that the patient is rendered edentulous and has to wear a removable complete denture for varying periods of time. In order to avoid removable provisionalization, the staged treatment approach allows for fixed interim prosthesis throughout the rehabilitation process, patient comfort, and prosthodontic control. The purpose of this clinical report is to describe a combination of staged approach with guided flapless surgery for minimally invasive treatment. The patient had fixed interim prostheses during the entire rehabilitation process. The various implant prosthodontic stages are illustrated for the complete arch prosthetic rehabilitation and the 6-year follow-up outcome is reported. A patient with debilitated dentition was treated with this combined protocol and was followed for 6 years after definitive prosthesis insertion. Implant and prosthesis success rates were 100% with minor biologic and no technical complications encountered up to 6-year recall. Guided surgery has the advantage of prosthetically driven implant placement and minimal postoperative sequelae, whereas the staged approach allows for fixed provisionalization throughout the entire treatment period. As the computer-guided surgery protocols continue to evolve and improve, further clinical studies are necessary to assess accuracy and make this exciting technology even safer for the average clinician. The clinical significance of this case report lies in the treatment sequence combined with cutting edge technology for maximum patient comfort and prosthodontic control. Guided flapless surgery with prosthodontically driven implant placement led to predictable rehabilitation with no major complications after 6 years. A staged approach with fixed interim prostheses was used throughout the entire rehabilitation period, optimizing patient satisfaction and comfort. Natural canine guidance was the occlusal

  2. [Ways to improve efficiency of patient clinical examinations during early stage of cholelithiasis].

    PubMed

    Khokhlacheva, N A; Suchkova, E V; Vakhrushev, Ia M

    2013-01-01

    The aim of the work was to improve the organization and conduct of clinical examination of patients with gallstone disease (GSD). An integrated study of 396 patients with different pathologies of the hepatobiliary system and the medical check-up for three years for 101 patients. Built logistic model to predict the likelihood of developing gallstone disease and developed a predictive scoring table it possible to distinguish patients at risk of developing gall stones. The result of follow-up of the proposed method was prevented economic losses due to the lack of need for a cholecystectomy, which is made up of one patient 6766.22 rubles., The entire group of 1,004,966.63 rubles. Obtained to diagnose cholelithiasis at an early stage dokamennoy. Developed a screening questionnaire, predictive scoring table, the scheme of follow-up also improves clinical examination of patients with cholelithiasis dokamennoy stage.

  3. A review of the Mark 48-F, 3.50 pitch diameter, 2-stage reaction turbine designed for the staged combustion cycle requirements of an advanced space engine

    NASA Technical Reports Server (NTRS)

    Macaluso, S. B.

    1976-01-01

    The Mark 48-F two-stage reaction turbine was designed as a component for an advanced space engine propellant feed system, high-pressure liquid hydrogen turbopump. The turbine total inlet temperature and total inlet pressure were designed to be 1860 R and 3420 psia, respectively. At a design speed of 95,000 rpm, the turbine will develop 2543 horsepower with LO2/LH2 working fluid. The aerothermodynamic performance of a prototype turbine assembly was evaluated with gaseous nitrogen working fluid. Turbine performance was evaluated at turbine velocity ratios ranging from 0.250 to 0.782, and turbine speeds up to 25,250 rpm. Turbine test efficiency at the design velocity ratio of 0.483 was found to be 79.5% total-to-total.

  4. Visual disturbances in advanced cancer patients: clinical observations.

    PubMed

    Saita, L; Polastri, D; De Conno, F

    1999-03-01

    Visual disturbances in advanced cancer patients are very rarely signaled, evaluated, or adequately treated. The main causes of sight disturbances are primary eye tumors, ocular metastases, and some paraneoplastic syndromes. Sight alteration can also be associated with asthenia, fatigue, anemia, and hypovitaminosis. These symptoms can be monocular or binocular, and their gravity and evolution can vary. Based on a survey of 156 patients, we estimate the prevalence of visual disturbances to be 12% in advanced cancer patients.

  5. Defining features of advance directives in law and clinical practice.

    PubMed

    Olick, Robert S

    2012-01-01

    In the > 30 years since the New Jersey Supreme Court's seminal opinion in the case of Karen Ann Quinlan, all 50 states and the District of Columbia have enacted legislation to recognize the legal right of competent adults to write advance directives. The purpose of advance directives is to provide direction for health-care decisions near the end of life, when the ravages of illness, disease, or injury have taken the ability to decide for one's self. This article reviews the defining features of advance directives and the governing law, discusses some common practical concerns regarding the use and effectiveness of advance directives, and identifies several significant ethical-legal challenges for honoring advance directives at the bedside. With a primary focus on the health-care proxy, the anatomy of advance directives is analyzed under four general rubrics: formal requirements, decisional capacity and when the directive takes effect, rights and responsibilities of proxies and health-care providers, and the scope and limitations of decisions to forego life-sustaining treatment. There is much common ground among state laws, but particular legal provisions may vary from state to state. Physicians, nurses, social workers, and other health-care professionals should be familiar with the law of their home state.

  6. Advance Directives in Hospice Healthcare Providers: A Clinical Challenge.

    PubMed

    Luck, George R; Eggenberger, Terry; Newman, David; Cortizo, Jacqueline; Blankenship, Derek C; Hennekens, Charles H

    2017-08-07

    On a daily basis, healthcare providers, especially those dealing with terminally ill patients, such as hospice workers, witness how advance directives help ensure the wishes of patients. They also witness the deleterious consequences when patients fail to document the care they desire at their end of life. To the best of our knowledge there are no data concerning the prevalence of advance directives among hospice healthcare providers. We therefore explored the prevalence and factors influencing completion rates in a survey of hospice healthcare providers. Surveys that included 32 items to explore completion rates, as well as barriers, knowledge, and demographics, were e-mailed to 2097 healthcare providers, including employees and volunteers, at a nonprofit hospice. Of 890 respondents, 44% reported having completed an advance directive. Ethnicity, age, relationship status, and perceived knowledge were all significant factors influencing the completion rates, whereas years of experience or working directly with patients had no effect. Procrastination, fear of the subject, and costs were common reasons reported as barriers. Upon completion of the survey, 43% said they will now complete an advance directive, and 45% will talk to patients and families about their wishes. The majority of hospice healthcare providers have not completed an advance directive. These results are very similar to those for other healthcare providers treating patients with terminal diseases, specifically oncologists. Because, at completion, 43% said that they would now complete an advance directive, such a survey of healthcare providers may help increase completion rates. Copyright © 2017 Elsevier Inc. All rights reserved.

  7. 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

  8. Risk stratification in patients with advanced-stage breast cancer by pretreatment [(18) F]FDG PET/CT.

    PubMed

    Chen, Suyun; Ibrahim, Nuhad K; Yan, Yuanqing; Wong, Stephen T; Wang, Hui; Wong, Franklin C

    2015-11-15

    The objective of the current study was to investigate the prognostic value of pretreatment [(18) F] fluorodeoxyglucose position emission tomography/computed tomography ([(18) F]FDG PET/CT) in patients with advanced-stage breast cancer. Pretreatment PET/CT scans from 240 consecutive patients with American Joint Committee on Cancer stage III or stage IV BC were analyzed retrospectively. Clinicopathological factors and metabolic parameters of the primary tumor including maximum standardized uptake value (SUVmax ), metabolic tumor volume, and total lesion glycolysis (TLG) with a range of thresholds were compared to predict progression-free survival (PFS) and overall survival (OS) using a time-dependent receiver operating characteristic curve and Cox proportional hazards regression analyses. SUVmax with a cutoff value of 6.0, TLG30% with a cutoff value of 158 g, and phenotype associated with PFS and OS were analyzed using multivariate analysis. The mean TLG30% of primary tumors for patients with stage III and stage IV disease was 405 g and 750 g (P = .010), respectively. Patients with triple-negative breast cancer or a TLG30% >158 g or with both were categorized as being at high risk, and those with non-triple-negative breast cancer and a primary tumor with a TLG30% ≤158 g were defined as low risk. The 5-year PFS rates for stage III disease among patients with low-risk versus high-risk BC were 85% and 67.5%, respectively. For patients with stage IV disease, the 5-year PFS rates were 45% and 9%, respectively, for patients with low-risk versus high-risk disease. Patients with stage III and high-risk BC had OS rates that were similar to those for patients with stage IV and low-risk BC (P = .552). The TLG30% from pretreatment PET/CT was found to independently correlate with survival outcomes and appears to be able to effectively stratify both patients with stage III and those with stage IV BC. © 2015 American Cancer Society.

  9. Nuclear DNA content and p53 overexpression in stage I squamous cell carcinoma of the tongue compared with advanced tongue carcinomas.

    PubMed Central

    Högmo, A; Kuylenstierna, R; Lindholm, J; Nathansson, A; Auer, G; Munck-Wikland, E

    1998-01-01

    AIMS: To evaluate the predictive value of the nuclear DNA content (image cytometry) and p53 overexpression (immuno-histochemistry using antibody CM-1) in uniformly treated stage I carcinomas of the mobile tongue. Also, to compare stage I carcinomas with advanced tongue carcinomas (stages II-IV). METHODS: Archival formalin fixed, paraffin wax embedded tumour specimens from 54 patients with stage I squamous cell carcinoma and 37 patients with advanced squamous cell carcinoma were analysed. Mean follow up time of the stage I carcinomas was 71 months (median, 62.5; range, 6-175). RESULTS: Twenty three patients (stage I) had recurring disease: 10 had local recurrence (in the tongue) and 13 had regional recurrence (cervical metastases). Locally recurring stage I carcinomas had a more pronounced DNA deviation than the other stage I carcinomas and this degree of deviation was comparable with the DNA content of advanced carcinomas. Stage I carcinomas that developed regional recurrences overexpressed p53 more frequently. In Cox multivariate regression analysis of time to recurrence, DNA deviation was a significant parameter in tumours that recurred locally (p = 0.032). p53 overexpression was the only parameter close to significance for regional recurrence (p = 0.065). CONCLUSIONS: Nuclear DNA content and p53 immunostaining are of value for the prediction of recurrence of stage I squamous cell carcinomas of the mobile tongue. Stage I tongue carcinomas that are prone to local recurrence show the same DNA content as do advanced tongue carcinomas. PMID:10193521

  10. 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.

  11. Correlation analysis of urine metabolites and clinical staging in patients with ovarian cancer

    PubMed Central

    Jiang, Ting; Lin, Yunliang; Yin, Haiqin; Wang, Shanshan; Sun, Qinglei; Zhang, Peihai; Bi, Wenxiang

    2015-01-01

    This study is to investigate the correlation between urine metabolites and clinical staging in patients with ovarian cancer. The urina sanguinis from 56 cases of primary epithelial ovarian cancer patients and 15 healthy volunteers was collected and the urine metabolites were extracted. Ultra high performance liquid chromatography/time-of-flight mass spectrometry (UPLC-Q-TOF-MS) analysis was performed. Principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) were used to analyze the mass spectrometry data. Database retrieval and comparison of the screened metabolites were performed and one-way ANOVA and least significant difference (LSD) t test were carried out. PCA analysis of UPLC-Q-TOF-MS results showed that the score plots of samples from healthy people and patients with ovarian cancer at different clinical stages were separated. Further PLS-DA analysis significantly improved the classification results. The R2X was 0.757, the R2Y was 0.977 and the Q2Y was 0.87, indicating that the model stability and predictability were good. Eight metabolites, including N-acetylneuraminic acid-9-phosphate, 5’-methioadenosine, uric acid-3-nucleoside, pseudouridine, L-valine, succinic acid, L-proline and β-nicotinamide mononucleotide were identified. The contents of these metabolites increased with the development of the disease. There was correlation between urine metabolites and clinical staging in patients with ovarian cancer. PMID:26770415

  12. Clinical staging and electroencephalographic evolution of continuous spikes and waves during sleep.

    PubMed

    Fernández, Iván Sánchez; Peters, Jurriaan M; Hadjiloizou, Stavros; Prabhu, Sanjay P; Zarowski, Marcin; Stannard, Karen M; Takeoka, Masanori; Rotenberg, Alexander; Kothare, Sanjeev V; Loddenkemper, Tobias

    2012-07-01

    Currently, in continuous spikes and waves during sleep (CSWS) there is a lack of systematic assessments of the clinically relevant stages and the evolution of the electroencephalographic features. The aim of this study is to describe the evolution over time of clinical and electroencephalographic features in CSWS. We enrolled patients from our video-electroencephalography (EEG) monitoring unit with CSWS and with overnight EEG studies with at least one overnight assessment per year over a minimum period of 3 years. We studied clinical presentation and electroencephalographic features. We calculated the (1) spike-wave percentage (SWP) as the percentage of 1-s bins containing at least one spike-wave complex and (2) spike frequency (SF) as the number of spikes per 100 s. Nine children (six boys) met the inclusion criteria during a 15-year period. Seven (78%) had an abnormal development prior to the epilepsy onset, and in two (22%) seizures were the only presenting symptom. Median age at epilepsy onset was 2 years (range 2 days to 4 years), at neuropsychological regression 5.1 years (4-7.7 years), and at seizure freedom 8.6 years (6.5-11.4 years). Median duration and range of clinically relevant stages were as follows: dormant stage (birth-epilepsy onset median 2 years, range 2 days-4 years), prodromal stage (epilepsy onset-neuropsychological regression 3.9 years, range 0.9-7.7 years), acute stage (neuropsychological regression-seizure freedom 2.9 years, range 2.1-6.6 years), and residual stage (after seizure freedom). Seven patients (78%) had a structural lesion on neuroimaging. At last follow-up (median 11.4 years, range 7.2-20.3 years), eight patients (89%) were receiving antiepileptic treatment, and all patients had residual neurocognitive deficits. During the acute stage, SWP was <85% in 13 (42%) of 31 assessments, and after seizure freedom, 3 of 5 patients (60%) had SWP >85%. Evolution of electroencephalographic patterns included increasing

  13. Treatment patterns of advanced malignant melanoma (stage III-IV) - A review of current standards in Europe.

    PubMed

    Harries, Mark; Malvehy, Josep; Lebbe, Céleste; Heron, Louise; Amelio, Justyna; Szabo, Zsolt; Schadendorf, Dirk

    2016-06-01

    With the recent emergence of immunotherapies and novel targeted treatments for advanced and metastatic melanoma such as selective B-Raf inhibitors and checkpoint inhibitors, the treatment landscape in Europe has changed considerably. The aim of this review was to provide an overview of current treatment pathways in Europe for the treatment of advanced melanoma, unresectable stage III-IV. A literature search of four databases was conducted to identify publications reporting on the treatment patterns of advanced and metastatic melanoma (stage III-IV) in European populations. Seven full-text publications and two conference abstracts reported on observational studies of melanoma treatment practices in France, Italy and the United Kingdom. Treatment patterns were identified for two time periods: 2005-2009 and 2011-2012. Common treatments reported for both periods included chemotherapy with dacarbazine, fotemustine or temozolomide. The main differences between the two periods were the introduction and prescription of immunotherapy ipilimumab and targeted therapy vemurafenib between 2011 and 2012. Across the three countries studied, the types of treatments prescribed between 2005 and 2009 were relatively similar, however, with noticeable differences in the frequency and priority of administration. Treatment practices for advanced melanoma vary markedly across different European countries and continue to evolve with the introduction of new therapies. The results of this review highlight a considerable evidence gap with regards to recent treatment patterns for advanced melanoma in Europe, especially post-2011 after the introduction of novel therapeutic agents, and more recently with the introduction of programmed cell death 1 inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  14. Contemporary surgical management of advanced end stage emphysema: an evidence based review.

    PubMed

    Sachithanandan, Anand; Badmanaban, Balaji

    2012-06-01

    Emphysema is a progressive unrelenting component of chronic obstructive pulmonary disease and a major source of mortality and morbidity globally. The prevalence of moderate to severe emphysema is approximately 5% in Malaysia and likely to increase in the future. Hence advanced emphysema will emerge as a leading cause of hospital admission and a major consumer of healthcare resources in this country in the future. Patients with advanced disease have a poor quality of life and reduced survival. Medical therapy has been largely ineffective for many patients however certain subgroups have disease amenable to surgical palliation. Effective surgical therapies include lung volume reduction surgery, lung transplantation and bullectomy. This article is a comprehensive evidence based review of the literature evaluating the rationale, efficacy, safety and limitations of surgery for advanced emphysema highlighting the importance of meticulous patient selection and local factors relevant to Malaysia.

  15. Advances in quantitative UV-visible spectroscopy for clinical and pre-clinical application in cancer.

    PubMed

    Brown, J Quincy; Vishwanath, Karthik; Palmer, Gregory M; Ramanujam, Nirmala

    2009-02-01

    Methods of optical spectroscopy that provide quantitative, physically or physiologically meaningful measures of tissue properties are an attractive tool for the study, diagnosis, prognosis, and treatment of various cancers. Recent development of methodologies to convert measured reflectance and fluorescence spectra from tissue to cancer-relevant parameters such as vascular volume, oxygenation, extracellular matrix extent, metabolic redox states, and cellular proliferation have significantly advanced the field of tissue optical spectroscopy. The number of publications reporting quantitative tissue spectroscopy results in the UV-visible wavelength range has increased sharply in the past three years, and includes new and emerging studies that correlate optically measured parameters with independent measures such as immunohistochemistry, which should aid in increased clinical acceptance of these technologies.

  16. Advances in Quantitative UV-Visible Spectroscopy for Clinical and Pre-clinical Application in Cancer

    PubMed Central

    Brown, J. Quincy; Vishwanath, Karthik; Palmer, Gregory M.; Ramanujam, Nirmala

    2009-01-01

    Summary Methods of optical spectroscopy which provide quantitative, physically or physiologically meaningful measures of tissue properties are an attractive tool for the study, diagnosis, prognosis, and treatment of various cancers. Recent development of methodologies to convert measured reflectance and fluorescence spectra from tissue to cancer-relevant parameters such as vascular volume, oxygenation, extracellular matrix extent, metabolic redox states, and cellular proliferation have significantly advanced the field of tissue optical spectroscopy. The number of publications reporting quantitative tissue spectroscopy results in the UV-visible wavelength range has increased sharply in the last 3 years, and includes new and emerging studies which correlate optically-measured parameters with independent measures such as immunohistochemistry, which should aid in increased clinical acceptance of these technologies. PMID:19268567

  17. Photoselective laser vaporization of the prostate in the treatment of bladder outlet obstruction in advanced-stage prostate cancer: a single-center experience.

    PubMed

    Jin, ChongRui; Xu, Yue-Min; Fu, Qiang; Gu, BaoJun

    2012-10-01

    The study in China is the first on photoselective vaporization of the prostate (PVP) applied to bladder outlet obstruction (BOO) or urinary retention from advanced-stage prostate cancer (PCa). The aim is to evaluate the efficacy and safety of PVP in the treatment of patients with BOO secondary to advanced-stage PCa. Forty-five patients (mean age 76.13±5.88 years, range 62-89 years) with BOO or urinary retention secondary to advanced-stage PCa received PVP with a potassium-titanyl-phosphate laser. The treatment outcome was evaluated with subjective and objective tests at 1, 3, 6, and 12 months after PVP using the International Prostate Symptom Score (IPSS), quality of life (QoL) score, postvoid residual (PVR) urine volume, and maximum urinary flow rate (Qmax). The operative time, indwelling catheterization time, and operative complications were also observed. All 45 patients recovered without incident. The mean operative time was 50±7.6 minutes. The catheterization duration was 3.2 days (range 2-7 days). There was significant improvement in Qmax from 7.29±0.93 to 12.16±2.75 mL/sec after treatment at 12 months. Mean PVR volume decreased from 210.94±179.49 to 54.45±33.16 mL. Mean IPSS score decreased from preoperative 28.19±3.64 to postoperative 14.61±2.81 (P<0.05), QoL score decreased from 5.03±0.69 to 3.66±0.65 (P<0.05). There were no intraoperative adverse events. Postoperative complications included mild transient hematuria in 12 (26.7%) patients and mild dysuria in 11 (24.4%) patients within 4 weeks. The clinical results suggest that PVP is a safe, efficient, and less-invasive treatment for patients with BOO or urinary retention secondary to advanced-stage PCa.

  18. 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

  19. Clinical Cancer Advances 2008: Major Research Advances in Cancer Treatment, Prevention, and Screening—A Report From the American Society of Clinical Oncology

    PubMed Central

    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.

    2009-01-01

    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

  20. 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

  1. A population-based study of prognosis in advanced stage follicular lymphoma managed by watch and wait.

    PubMed

    El-Galaly, Tarec Christoffer; Bilgrau, Anders E; de Nully Brown, Peter; Mylam, Karen J; Ahmad, Syed A; Pedersen, Lars M; Gang, Anne O; Bentzen, Hans H; Juul, Maja B; Bergmann, Olav J; Pedersen, Robert S; Nielsen, Berit J; Johnsen, Hans E; Dybkaer, Karen; Bøgsted, Martin; Hutchings, Martin

    2015-05-01

    Watch and wait (WAW) is a common approach for asymptomatic, advanced stage follicular lymphoma (FL), but single-agent rituximab is an alternative for these patients. In this nationwide study we describe the outcome of patients selected for WAW. A cohort of 286 out of 849 (34%) stage III-IVA FL patients seen between 2000 and 2011, were managed expectantly and included. The 5-year progression-free survival (PFS) was 35% [95% confidence interval (CI) 29-42]. The 10-year overall survival (OS) was 65% (95%CI 54-78), and the cumulative risk of dying from lymphoma within 10 years of diagnosis was 13% (95%CI 7-20). Elevated lactate dehydrogenase and > four nodal regions involved were associated with a higher risk of lymphoma treatment and death from lymphoma. The WAW patients and a matched background population had similar OS during the first 50 months after diagnosis (P = 0·7), but WAW patients had increased risk of death after 50 months (P < 0·001). The estimated loss of residual life after 10 years was 6·8 months. The 10-year cumulative risk of histological transformation was 22% (95%CI 15-29) and the 3-year OS after transformation was 71% (95%CI 58-87%). In conclusion, advanced stage FL managed by WAW had a favourable outcome and abandoning this strategy could lead to overtreatment in some patients.

  2. Comparison of staging between the old (6th edition) and new (7th edition) TNM classifications in advanced gastric cancer.

    PubMed

    Kikuchi, Shiro; Futawatari, Nobue; Sakuramoto, Shinichi; Katada, Natsuya; Yamashita, Keishi; Shibata, Tomotaka; Nemoto, Masayuki; Watanabe, Masahiko

    2011-06-01

    The aims of the present study were to compare staging between the old (6th edition) and new (7th edition) TNM classifications, and to evaluate the prognostic impact of extended lymph node dissection according to the new nodal staging in advanced gastric cancer. A total of 609 patients with advanced gastric cancer who had undergone curative gastric resection combined with extended lymph node dissection were enrolled in the present study. Survival curves were analyzed according to staging based on the TNM 6th and 7th editions and the Japanese Classification of Gastric Carcinoma (JCGC) 14th edition. The 5-year survival rates and the consecutive stage survival with no significant differences were: IB 88%; II 74%; IIIA 53%; IIIB 39%; and IV 18% (IIIA vs. IIIB, p=0.1307) by the TNM 6th edition; IB 94%; IIA 85%; IIB 71%; IIIA 68%; IIIB 48%; IIIC 23%; and IV 13%; (IIB vs. IIIA, p=0.7665; IIIC vs. IV, p=0.4156) by the TNM 7th and JCGC 14th editions; N0 85%; N1 70%; N2 46%; N3 18%; and M1 13%; (N3 vs. M1, p=0.8640) by the TNM 6th edition; and N0 85%; N1 80%; N2 61%; N3a 46%; N3b 18%; and M1 13%; (N0 vs. N1, p=0.2735; N2 vs. N3a, p=0.0663; N3b vs. M1, p=0.8640) by the TNM 7th and JCGC 14th editions. The new classification according to the TNM 7th and the JCGC 14th editions does not always seem to be superior to the TNM 6th edition for the prognostic stratification of stages in patients who undergo curative resection for advanced gastric cancer. An extended lymph node dissection may be effective for N0-N3a, but not for N3b and M1 stages classified according to the new TNM 7th and JCGC 14th editions.

  3. [Clinical significance of the relationship between expression of survivin and effects of neoadjuvant chemotherapy in locally advanced breast cancer].

    PubMed

    Fuzhong, Tong; Nan, Lu; Jiajia, Guo; Miao, Liu; Deqi, Yang

    2008-08-01

    Explore the relationship between the expression intensity of survivin and the effectiveness of neoadjuvant chemotherapy in locally advanced breast cancer patients. Neoadjuvant chemotherapy with epirubicin plus paclitaxel was administered to 76 patients in locally advanced breast cancer (including 25 cases of stage IIa, 26 of stage IIb, 16 of stage IIIa, and 9 of stage IIIb), the mean age is 52.8(33-79)years old. All patients were female. They were treated with epirubicin 60 mg/m(2), on day 1, by i. v. followed paclitaxel 175 mg/m(2) by 3 hours continues infusion on day 2 and every 3 weeks repeatedly. Premedication of dexamethasone, ondansetron, diphenhydramine and cimetidine were administered to prevent gastroenteric and allergic reactions before chemotherapy. Four cycles were used. The expression of survivin in breast cancer tissue was detected with SDS-PAGE, western-immunoblotting and immunohistochemistry (IHC), and then that were immunological stained by anti survivin monoclonal antibody, and also the results were analyzed for the relationship between the expressed intensity of survivin and the effect of neoadjuvant chemotherapy in locally advanced breast cancer patients. Nineteen out of 76 patients had a clinical complete response, 36 had clinical partial response, and 21 had no change. The response rate was 72.37%(55/76). We found survivin could be differently expressed in 76 patients with SDS-PAGE, western-immunoblotting and IHC and then immune stain by anti survivin monoclonal antibody. Forty six patients were low expressed of survivin and 9 patients were high expressed in all response patients. Eight patients were low expressed, only 1 patient was high expressed of survivin in 9 patients had pCR. But no finding the relationship between the expression of survivin and TNM stage, ER, PgR, HER-2. The patients have high response rate of low expression of survivin after neoadjuvant chemotherapy with TE regimen in locally advanced breast cancer patients. This

  4. 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

  5. Feasibility, safety and clinical outcomes of cardiophrenic lymph node resection in advanced ovarian cancer.

    PubMed

    Cowan, Renee A; Tseng, Jill; Murthy, Vijayashree; Srivastava, Radhika; Long Roche, Kara C; Zivanovic, Oliver; Gardner, Ginger J; Chi, Dennis S; Park, Bernard J; Sonoda, Yukio

    2017-09-06

    Surgical resection of enlarged cardiophrenic lymph nodes (CPLNs) in primary treatment of advanced ovarian cancer has not been widely studied. We report on a cohort of patients undergoing CPLN resection during primary cytoreductive surgery (CRS), examining its feasibility, safety, and potential impact on clinical outcomes. We identified all patients undergoing primary CRS/CPLN resection for Stages IIIB-IV high-grade epithelial ovarian cancer at our institution from 1/2001-12/2013. Clinical and pathological data were collected. Statistical tests were performed. 54 patients underwent CPLN resection. All had enlarged CPLNs on preoperative imaging. Median diameter of an enlarged CPLN: 1.3cm (range 0.6-2.9). Median patient age: 59y (range 41-74). 48 (88.9%) underwent transdiaphragmatic resection; 6 (11.1%) underwent video-assisted thoracic surgery. A median of 3 nodes (range 1-23) were resected. A median of 2 nodes (range 0-22) were positive for metastasis. 51/54 (94.4%) had positive nodes. 51 (94.4%) had chest tube placement; median time to removal: 4d (range 2-12). 44 (81.4%) had peritoneal carcinomatosis. 19 (35%) experienced major postoperative complications; 4 of these (7%) were surgery-related. Median time to adjuvant chemotherapy: 40d (range 19-205). All patients were optimally cytoreduced, 30 (55.6%) without visible residual disease. Median progression-free survival: 17.2mos (95% CI 12.6-21.8); median overall survival: 70.1mos (95% CI 51.2-89.0). Enlarged CPLNs can be identified on preoperative imaging and may indicate metastases. Resection can identify extra-abdominal disease, confirm Stage IV disease, obtain optimal cytoreduction. In the proper setting it is feasible, safe, and does not delay chemotherapy. In select patients, it may improve survival. Copyright © 2017. Published by Elsevier Inc.

  6. Outcome of Men With Relapse After Adjuvant Carboplatin for Clinical Stage I Seminoma.

    PubMed

    Fischer, Stefanie; Tandstad, Torgrim; Wheater, Matthew; Porfiri, Emilio; Fléchon, Aude; Aparicio, Jorge; Klingbiel, Dirk; Skrbinc, Breda; Basso, Umberto; Shamash, Jonathan; Lorch, Anja; Dieckmann, Klaus-Peter; Cohn-Cedermark, Gabriella; Ståhl, Olof; Chau, Caroline; Arriola, Edurne; Marti, Kalena; Hutton, Paul; Laguerre, Brigitte; Maroto, Pablo; Beyer, Jörg; Gillessen, Silke

    2017-01-10

    Purpose Adjuvant carboplatin is one of three management strategies that may follow inguinal orchiectomy in clinical stage I seminoma. However, little is known about the outcome of patients who experience a relapse after such treatment. Patients and Methods Data from 185 patients who relapsed after adjuvant carboplatin between January 1987 and August 2013 at 31 centers/groups from 20 countries were collected and retrospectively analyzed. Primary outcomes were disease-free survival and overall survival. Secondary outcomes were time to, stage at, and treatment of relapse as well as rate of subsequent relapses. Results With a median follow-up of 53 months (95% CI, 48 to 60 months) the 5-year disease-free survival was 82% (95% CI, 77% to 89%), and the 5-year overall survival was 98% (95% CI, 95% to 100%). The median time from orchiectomy to relapse was 19 months (95% CI, 17 to 23 months); 15% (95% CI, 10% to 21%) of relapses occurred > 3 years after treatment. The majority of relapses were detected by computed tomography scan during routine follow-up, 98% in the International Germ Cell Cancer Collaborative Group good prognosis group. Chemotherapy was administered to 92% of patients, mostly as standard first-line treatment corresponding to stage; 8% of patients had additional local treatments. Only 28 patients experienced a second relapse. At last follow-up, 174 (94%) of 185 patients were alive without disease, and four patients with disease. Seven patients died, three of whom due to progressive disease. Conclusion Within the limitations of a retrospective analysis, the results suggest that the majority of patients who experience a relapse after adjuvant carboplatin for clinical stage I seminoma can be successfully treated with a cisplatin-based chemotherapy regimen adequate for stage. Because 15% of the relapses occurred > 3 years after adjuvant treatment, a minimum of 5 years follow-up is recommended.

  7. Advanced Parkinson's disease: clinical characteristics and treatment. Part II.

    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

    2013-01-01

    Many patients who have had Parkinson's disease (PD) for several years will present severe motor fluctuations and dyskinesias which require more aggressive therapies. The different approaches which are now available include deep brain stimulation of the subthalamic nucleus or medial globus pallidus, subcutaneous infusion of apomorphine, and intestinal infusion of levodopa-carbidopa. To define the indications and results for the 3 available therapies for advanced PD. Exhaustive review of the literature concerning the indications and results of deep brain stimulation, subcutaneous apomorphine infusion and duodenal infusion of levodopa/carbidopa gel to treat patients with advanced Parkinson disease. Although numerous studies have confirmed the efficacy of the 3 different therapies in advanced PD, there are no comparative studies that would allow us to define the best candidate for each technique. Copyright © 2013 Sociedad Española de Neurología. Published by Elsevier Espana. All rights reserved.

  8. Comparison of weight changes following unilateral and staged bilateral STN DBS for advanced PD.

    PubMed

    Lee, Eric M; Kurundkar, Ashish; Cutter, Gary R; Huang, He; Guthrie, Barton L; Watts, Ray L; Walker, Harrison C

    2011-09-01

    Unilateral and bilateral subthalamic nucleus deep brain stimulation (STN DBS) in Parkinson's disease (PD) result in weight gain in the initial postoperative months, but little is known about the changes in weight following unilateral and staged bilateral STN DBS over longer time intervals. A case-control comparison evaluated weight changes over 2 years in 43 consecutive unilateral STN DBS patients, among whom 25 elected to undergo staged bilateral STN DBS, and 21 age-matched and disease severity matched PD controls without DBS. Regression analyses incorporating age, gender, and baseline weight in case or control were conducted to assess weight changes 2 years after the initial unilateral surgery. Unilateral STN DBS and staged bilateral STN DBS patients gained 3.9 ± 2.0 kg and 5.6 ± 2.1 kg versus their preoperative baseline weight (P < 0.001, respectively) while PD controls without DBS lost 0.8 ± 1.1 kg. Although bilateral STN DBS patients gained 1.7 kg more than unilateral STN DBS patients at 2 years, this difference was not statistically significant (P = 0.885). Although there was a trend toward greater weight gain in staged bilateral STN DBS patients versus unilateral patients, we found no evidence for an equivalent or synergistic increase in body weight following placement of the second DBS electrode.

  9. Interobserver consistency of digital rectal examination in clinical staging of localized prostatic carcinoma.

    PubMed

    Angulo, J C; Montie, J E; Bukowsky, T; Chakrabarty, A; Grignon, D J; Sakr, W; Shamsa, F H; Edson Pontes, J

    1995-01-01

    A prospective study was undertaken to determine the reproducibility of clinical staging based on digital rectal examination (DRE) in prostate carcinoma. We evaluated 48 consecutive patients diagnosed with localized prostatic cancer. Four urologists performed DRE and sorted the patients according to the 1992 American Joint Committee on Cancer Classification for prostate cancer. Both the percentage observed total agreement among each couple of two different observers and the interobserver variability (Kappa index) were analyzed. The percentage observed total agreement among observers in distinguishing five clinical subcategories (T1c, T2a, T2b, T2c, and T3a) ranged between 38-60% (mean 49%) and the Kappa index showed interobserver agreement was poor (overall Kappa = 0.3 1). All four examiners agreed in assigning the same subcategory in only 21 % of cases, and 90% of them were T I. If only categories are distinguished (T I, T2, or T3), the percentage observed total agreement rises to 60-71% (mean 66%) and the interexaminer agreement improves to good (overall Kappa = 0.4 1). Accurate pathologic staging was obtained in every patient and the percentage observed agreement between every examiner and the pathologist was calculated, excluding cases interpreted as T I c. Regarding subcategories, clinicopathologic agreement ranges between 17-46%. If only categories T2 and9T3 are distinguished, agreement rises to 57-69%. In summary, the ability to reproduce clinical staging based on DRE among multiple examiners is disappointingly low and understandably correlates poorly with pathologic stage.

  10. 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

  11. Deep brain stimulation in early stage Parkinson's disease: operative experience from a prospective randomised clinical trial.

    PubMed

    Kahn, Elyne; D'Haese, Pierre-Francois; Dawant, Benoit; Allen, Laura; Kao, Chris; Charles, P David; Konrad, Peter

    2012-02-01

    Recent evidence suggests that deep brain stimulation of the subthalamic nucleus (STN-DBS) may have a disease modifying effect in early Parkinson's disease (PD). A randomised, prospective study is underway to determine whether STN-DBS in early PD is safe and tolerable. 15 of 30 early PD patients were randomised to receive STN-DBS implants in an institutional review board approved protocol. Operative technique, location of DBS leads and perioperative adverse events are reported. Active contact used for stimulation in these patients was compared with 47 advanced PD patients undergoing an identical procedure by the same surgeon. 14 of the 15 patients did not sustain any long term (>3 months) complications from the surgery. One subject suffered a stroke resulting in mild cognitive changes and slight right arm and face weakness. The average optimal contact used in symptomatic treatment of early PD patients was: anterior -1.1±1.7 mm, lateral 10.7±1.7 mm and superior -3.3±2.5 mm (anterior and posterior commissure coordinates). This location is statistically no different (0.77 mm, p>0.05) than the optimal contact used in the treatment of 47 advanced PD patients. The perioperative adverse events in this trial of subjects with early stage PD are comparable with those reported for STN-DBS in advanced PD. The active contact position used in early PD is not significantly different from that used in late stage disease. This is the first report of the operative experience from a randomised, surgical versus best medical therapy trial for the early treatment of PD.

  12. [Clinical application value of prognostic nutritional index for predicting survival in patients with advanced non-small cell lung cancer].

    PubMed

    Xu, W J; Kang, Y M; Zhou, L; Chen, F F; Song, Y H; Zhang, C Q

    2017-02-23

    Objective: To explore the clinical application value of prognostic nutritional index(PNI) for predicting overall survival(OS) in patients with advanced non-small cell lung cancer (NSCLC). Methods: 123 patients with histologically confirmed non-small cell lung cancer were enrolled in this study, and their clinical and laboratory data were reviewed. The PNI was calculated as 10×serum albumin value+ 5×total lymphocyte countin peripheral blood.Univariate and multivariate analyses were used to identify the potential prognostic factors for advanced NSCLC. Results: PNI of the 123 NSCLC patients was 46.24±6.56. PNI was significantly associated with age, weight loss and pleural effusion (P<0.05). However, it showed no relationship with sex, smoking, hemoptysis, chest pain, dyspnea, histological type, clinical stage, and administration of chemotherapy (P>0.05). The median OS of the 123 patients was 19.5 months. The median OS in the higher PNI group (PNI≥46.24) and lower PNI group(PNI<46.24) were 25.2 months and 16.4 months, respectively.The 1-year survival rates were 80.6% and 63.9%, and 2-year survival rates were 54.8% and 19.6%, respectively (P<0.01). Univariate analysis showed that PNI, age, dyspnea, and weight loss were related to the OS of the advanced NSCLC patients (P<0.05). Multivariate analysis identified PNI as an independent prognostic factor for OS of advanced NSCLC (P<0.001). Conclusion: PNI can be easily calculated, and may be used as a relatively new prognostic indicator for advanced NSCLC in clinical practice.

  13. Consequences of Advanced Glycation End Products Accumulation in Chronic Kidney Disease and Clinical Usefulness of Their Assessment Using a Non-invasive Technique - Skin Autofluorescence.

    PubMed

    Oleniuc, Mihaela; Secara, Irina; Onofriescu, Mihai; Hogas, Simona; Voroneanu, Luminita; Siriopol, Dimitrie; Covic, Adrian

    2011-10-01

    Accelerated formation and accumulation of advanced glycation end-products occur under circumstances of increased supply of substrates such as hyperglycaemic or oxidative stress and in age-related and chronic diseases like diabetes mellitus, chronic renal failure, neurodegenerative diseases, osteoarthritis and also non-diabetic atherosclerosis and chronic heart failure. Advanced glycation end-products accumulation occurs especially on long-lived proteins such as collagen in the skin and in vascular basement membranes leading to vascular damage. Adequate renal clearance capacity is an important factor in the effective removal of advanced glycation end-products. The Autofluorescence Reader was developed as a marker, representative for tissue advanced glycation end-products accumulation, easily applicable in a clinical setting, initially for predicting diabetes related complications. Studies have already shown a relationship between skin autofluorescence and diabetes complications, as well as its predictive value for total and cardiovascular mortality in type 2 diabetes. Moreover skin autofluorescence was demonstrated to be superior to Haemoglobin A1c and other conventional risk factors. Advanced glycation end-products have been proposed as a novel factor involved in the development and progression of chronic heart failure. Assessment of advanced glycation end-products accumulation in end-stage renal disease and undergoing renal replacement therapies patients has become of great importance. Cardiovascular and connective tissue disorders are very common in patients with end-stage renal disease, and the accumulation of advanced glycation end-products is significantly increased in these patients. Mortality is markedly increased in patients with decreased kidney function, particularly in patients with end-stage renal disease. Skin advanced glycation end-products levels are strong predictors of survival in haemodialysis patients independent of other established risk factors

  14. Optimal two-stage log-rank test for randomized phase II clinical trials.

    PubMed

    Kwak, Minjung; Jung, Sin-Ho

    2017-01-01

    Randomized controlled clinical trials are conducted to determine whether a new treatment is safe and efficacious compared to a standard therapy. We consider randomized clinical trials with right censored time to event endpoint, called survival time here. The two-sample log-rank test is popularly used to test if the experimental therapy has a longer survival distribution than the control therapy or not. We consider an early stopping for futility only or for both futility and efficacy. For planning such clinical trials, this article presents two-stage designs that are optimal in the sense that either the maximal sample size or the expected sample size when the experimental therapy is futile or superior is minimized under the given type I and II error rates. Optimal designs for a range of design parameters are tabulated and evaluated using simulations.

  15. Advanced Stage at Presentation Remains a Major Factor Contributing to Breast Cancer Survival Disparity between Public and Private Hospitals in a Middle-Income Country.

    PubMed

    Kong, Yek-Ching; Bhoo-Pathy, Nirmala; Subramaniam, Shridevi; Bhoo-Pathy, Nanthini; Taib, Nur Aishah; Jamaris, Suniza; Kaur, Kiran; See, Mee-Hoong; Ho, Gwo-Fuang; Yip, Cheng-Har

    2017-04-16

    Background: Survival disparities in cancer are known to occur between public and private hospitals. We compared breast cancer presentation, treatment and survival between a public academic hospital and a private hospital in a middle-income country. Methods: The demographics, clinical characteristics, treatment and overall survival (OS) of 2767 patients with invasive breast carcinoma diagnosed between 2001 and 2011 in the public hospital were compared with 1199 patients from the private hospital. Results: Compared to patients in the private hospital, patients from the public hospital were older at presentation, and had more advanced cancer stages. They were also more likely to receive mastectomy and chemotherapy but less radiotherapy. The five-year OS in public patients was significantly lower than in private patients (71.6% vs. 86.8%). This difference was largely attributed to discrepancies in stage at diagnosis and, although to a much smaller extent, to demographic differences and treatment disparities. Even following adjustment for these factors, patients in the public hospital remained at increased risk of mortality compared to their counterparts in the private hospital (Hazard Ratio: 1.59; 95% Confidence Interval: 1.36-1.85). Conclusion: Late stage at diagnosis appears to be a major contributing factor explaining the breast cancer survival disparity between public and private patients in this middle-income setting.

  16. The conjoint use of music therapy and reflexology with hospitalized advanced stage cancer patients and their families.

    PubMed

    Magill, Lucanne; Berenson, Susan

    2008-09-01

    Advanced stage cancer patients experience debilitating physical symptoms as well as profound emotional and spiritual struggles. Advanced disease is accompanied by multiple changes and losses for the patient and the family. Palliative care focuses on the relief of overall suffering of patients and families, including symptom control, psychosocial support, and the meeting of spiritual needs. Music therapy and reflexology are complementary therapies that can soothe and provide comfort. When used conjointly, they provide a multifaceted experience that can aid in the reduction of anxiety, pain, and isolation; facilitate communication between patients, family members, and staff; and provide the potential for a more peaceful dying experience for all involved. This article addresses the benefits of the combined use of music therapy and reflexology. Two case studies are presented to illustrate the application and benefits of this dual approach for patients and their families regarding adjustment to the end of life in the presence of anxiety and cognitive impairment.

  17. Mentoring clinical ladder advancement with a facilitated prep class.

    PubMed

    Winslow, Susan A; Blankenship, Jean

    2007-01-01

    The authors describe a strategy for encouraging participation and overcoming reluctance of staff to participate in an optional professional advancement career ladder program. A facilitated prep class in a computer skills laboratory provides nurses with the framework for completing application requirements in a casual, supportive atmosphere.

  18. Bmi-1 promotes invasion and metastasis, and its elevated expression is correlated with an advanced stage of breast cancer

    PubMed Central

    2011-01-01

    Background B-lymphoma Moloney murine leukemia virus insertion region-1 (Bmi-1) acts as an oncogene in various tumors, and its overexpression correlates with a poor outcome in several human cancers. Ectopic expression of Bmi-1 can induce epithelial-mesenchymal transition (EMT) and enhance the motility and invasiveness of human nasopharyngeal epithelial cells (NPECs), whereas silencing endogenous Bmi-1 expression can reverse EMT and reduce the metastatic potential of nasopharyngeal cancer cells (NPCs). Mouse xenograft studies indicate that coexpression of Bmi-1 and H-Ras in breast cancer cells can induce an aggressive and metastatic phenotype with an unusual occurrence of brain metastasis; although, Bmi-1 overexpression did not result in oncogenic transformation of MCF-10A cells. However, the underlying molecular mechanism of Bmi-1-mediated progression and the metastasis of breast cancer are not fully elucidated at this time. Results Bmi-1 expression is more pronouncedly increased in primary cancer tissues compared to matched adjacent non-cancerous tissues. High Bmi-1 expression is correlated with advanced clinicopathologic classifications (T, N, and M) and clinical stages. Furthermore, a high level of Bmi-1 indicates an unfavorable overall survival and serves as a high risk marker for breast cancer. In addition, inverse transcriptional expression levels of Bmi-1 and E-cadherin are detected between the primary cancer tissues and the matched adjacent non-cancerous tissues. Higher Bmi-1 levels are found in the cancer tissue, whereas the paired adjacent non-cancer tissue shows higher E-cadherin levels. Overexpression of Bmi-1 increases the motility and invasive properties of immortalized human mammary epithelial cells, which is concurrent with the increased expression of mesenchymal markers, the decreased expression of epithelial markers, the stabilization of Snail and the dysregulation of the Akt/GSK3β pathway. Consistent with these observations, the repression of Bmi

  19. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient.

    PubMed

    Fox, Joyce E; Volpe, Linda; Bullaro, Josephine; Kakkis, Emil D; Sly, William S

    2015-02-01

    Mucopolysaccharidosis type VII (MPS VII, Sly syndrome) is a very rare lysosomal storage disease caused by a deficiency of the enzyme β-glucuronidase (GUS), which is required for the degradation of three glycosaminoglycans (GAGs): dermatan sulfate, heparan sulfate, and chondroitin sulfate. Progressive accumulation of these GAGs in lysosomes leads to increasing dysfunction in numerous tissues and organs. Enzyme replacement therapy (ERT) has been used successfully for other MPS disorders, but there is no approved treatment for MPS VII. Here we describe the first human treatment with recombinant human GUS (rhGUS), an investigational therapy for MPS VII, in a 12-year old boy with advanced stage MPS VII. Despite a tracheostomy, nocturnal continuous positive airway pressure, and oxygen therapy, significant pulmonary restriction and obstruction led to oxygen dependence and end-tidal carbon dioxide (ETCO2) levels in the 60-80mmHg range, eventually approaching respiratory failure (ETCO2 of 100mmHg) and the need for full-time ventilation. Since no additional medical measures could improve his function, we implemented experimental ERT by infusing rhGUS at 2mg/kg over 4h every 2 weeks for 24 weeks. Safety was evaluated by standard assessments and observance for any infusion associated reactions (IARs). Urinary GAG (uGAG) levels, pulmonary function, oxygen dependence, CO2 levels, cardiac valve function, liver and spleen size, and growth velocity were assessed to evaluate response to therapy. rhGUS infusions were well tolerated. No serious adverse events (SAEs) or IARs were observed. After initiation of rhGUS infusions, the patient's uGAG excretion decreased by more than 50%. Liver and spleen size were reduced within 2 weeks of the first infusion and reached normal size by 24 weeks. Pulmonary function appeared to improve during the course of treatment based on reduced changes in ETCO2 after off-ventilator challenges and a reduced oxygen requirement. The patient regained the

  20. Cascaded interactions between Raman induced solitons and dispersive waves in photonic crystal fibers at the advanced stage of supercontinuum generation.

    PubMed

    Driben, Rodislav; Mitschke, Fedor; Zhavoronkov, Nickolai

    2010-12-06

    The complex mechanism of multiple interactions between solitary and dispersive waves at the advanced stage of supercontinuum generation in photonic crystal fiber is studied in experiment and numerical simulations. Injection of high power negatively chirped pulses near zero dispersion frequency results in an effective soliton fission process with multiple interactions between red shifted Raman solitons and dispersive waves. These interactions may result in relative acceleration of solitons with further collisions between them of quasi-elastic or quasi-plastic kinds. In the spectral domain these processes result in enhancement of certain wavelength regions within the spectrum or development of a new significant band at the long wavelength side of the spectrum.

  1. Clinical staging and survival in refractory celiac disease: a single center experience.

    PubMed

    Rubio-Tapia, Alberto; Kelly, Darlene G; Lahr, Brian D; Dogan, Ahmet; Wu, Tsung-Teh; Murray, Joseph A

    2009-01-01

    Refractory celiac disease (RCD) occurs when both symptoms and intestinal damage persist or recur despite strict adherence to a gluten-free diet. In RCD, the immunophenotype of intraepithelial lymphocytes may be normal and polyclonal (RCD I) or abnormal and monoclonal (RCD II). The aim is to describe the clinical characteristics, treatment, and long-term outcome in a large single-center cohort of patients with RCD. We compared the clinical characteristics and outcome in 57 patients with RCD: 42 with RCD I and 15 with RCD II. Fifteen of 57 patients died during follow-up (n=8 with RCD I and n=7 with RCD II), each within the first 2 years after RCD diagnosis. The overall 5-year cumulative survival is 70%, 80%, and 45% for the entire cohort, RCD I, and RCD II, respectively. The refractory state itself and enteropathy-associated T-cell lymphoma (EATL) were the most common causes of death, respectively. A new staging system is proposed based on the cumulative effect of 5 prognostic factors investigated at the time of the refractory state diagnosis: for patients in stages I, II, and III, the 5-year cumulative survival rate was 96%, 71%, and 19%, respectively (P< .0001). RCD is associated with high mortality with RCD II having an especially poor prognosis because of the development of EATL. A new staging model is proposed that may improve the precision of prognosis in patients with RCD.

  2. Clinical investigation into the initial diagnosis and treatment of 539 patients with stage IV lung cancer

    PubMed Central

    Shao, Qian; Liu, Shanshan; Wang, Wei; Zhang, Yingjie; Li, Fengxiang; Li, Jianbin

    2017-01-01

    Objective The aim of the study was to analyze clinical data, including the types of pathologic classification, metastatic organs, treatment strategy, and prognosis of patients with stage IV lung cancer. Methods A retrospective analysis of the clinical features of 539 patients with stage IV lung cancer who were initially diagnosed and treated in 2009 was conducted. There were 146 cases of single organ metastases and 393 cases of multiple organ metastases. The Kaplan-Meier method and multivariate Cox regression analysis were performed to analyze the influence of age, pathological classification, metastatic organs, and treatment strategy on overall survival. Results The 1-, 2-, and 3-year survival rates were 64.2% (n=346), 19.7% (n=106), and 1.5% (n=8), respectively. Metastases to the liver and pleura predicted poor prognosis, although bone metastases predicted relatively good prognosis. The prognosis of single brain metastasis was relatively better than that of multiple brain metastases. Multi-factor analysis showed that the patient’s age, different metastatic organs, the numbers of metastatic organs, and different treatment were independent risk factors for survival. Conclusion The prognosis for patients with stage IV lung cancer is poor. Patient’s age, the type and number of metastatic organs, and method of treatment are the main factors affecting survival. PMID:28203086

  3. C5b-9 Staining Correlates With Clinical and Tumor Stage in Gastric Adenocarcinoma

    PubMed Central

    Chen, Jian; Yang, Wei-jun; Sun, Hai-jian; Wu, Yu-zhang

    2016-01-01

    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. PMID:26186252

  4. Technology requirements for advanced earth-orbital transportation systems: Summary report. [single stage to orbit vehicles

    NASA Technical Reports Server (NTRS)

    Haefeli, R. C.; Littler, E. G.; Hurley, J. B.; Winter, M. G.

    1977-01-01

    Areas of advanced technology that are either critical or offer significant benefits to the development of future Earth-orbit transportation systems were identified. Technology assessment was based on the application of these technologies to fully reusable, single-state-to-orbit (SSTO) vehicle concepts with horizontal landing capability. Study guidelines included mission requirements similar to space shuttle, an operational capability beginning in 1995, and main propulsion to be advanced hydrogen-fueled rocket engines. The technical and economic feasibility of this class of SSTO concepts were evaluated as well as the comparative features of three operational take-off modes, which were vertical boost, horizontal sled launch, and horizontal take-off with subsequent inflight fueling. Projections of both normal and accelerated technology growth were made. Figures of merit were derived to provide relative rankings of technology areas. The influence of selected accelerated areas on vehicle design and program costs was analyzed by developing near-optimum point designs.

  5. Two stage low noise advanced technology fan. 1: Aerodynamic, structural, and acoustic design

    NASA Technical Reports Server (NTRS)

    Messenger, H. E.; Ruschak, J. T.; Sofrin, T. G.

    1974-01-01

    A two-stage fan was designed to reduce noise 20 db below current requirements. The first-stage rotor has a design tip speed of 365.8 m/sec and a hub/tip ratio of 0.4. The fan was designed to deliver a pressure ratio of 1.9 with an adiabatic efficiency of 85.3 percent at a specific inlet corrected flow of 209.2kg/sec/sq m. Noise reduction devices include acoustically treated casing walls, a flowpath exit acoustic splitter, a translating centerbody sonic inlet device, widely spaced blade rows, and the proper ratio of blades and vanes. Multiple-circular-arc rotor airfoils, resettable stators, split outer casings, and capability to go to close blade-row spacing are also included.

  6. An Academic-Business Partnership for Advancing Clinical Informatics.

    ERIC Educational Resources Information Center

    Connors, Helen R.; Weaver, Charlotte; Warren, Judith; Miller, Karen L.

    2002-01-01

    A partnership between a university school of nursing and a health care information technology supplier resulted in the Simulated E-hEalth Delivery System (SEEDS). This program enables nursing students to learn clinical skills in a state-of-the-art environment using a live-production, clinical information system designed for care delivery. (JOW)

  7. The treatment of advanced stage favorable histology non-Hodgkin's lymphoma: a preliminary report of a randomized trial comparing single agent chemotherapy, combination chemotherapy, and whole body irradiation

    SciTech Connect

    Hoppe, R.T.; Kushlan, P.; Kaplan, H.S.; Rosenberg, S.A.; Brown, B.W.

    1981-09-01

    Between 1975 and 1978, 51 patients with favorable histology non-Hodgkin's lymphomas, pathologic stage III-IV, were treated prospectively on a randomized treatment protocol. Treatment options were single alkylating agent chemotherapy, combination chemotherapy with cyclophosphamide, vincristine, and prednisone (CVP), or fractionated whole body irradiation followed by low dose involved field irradiation. The median follow-up interval in this group of patients is not 41 mo. Actuarial survival is excellent, 84% at 4 yr for the entire group, with similar survival observed for each of the three treatment options. Initial complete remission rates (64%, 88%, and 71%) were not significantly different in the three treatment arms. Frequent relapse after initial remission induction was noted, however, with a freedom from relapse at 4 yr of only 25%. The toxicities of the three therapies were acceptable. Acute complications of therapy were most numerous in the group of patients treated with CVP; however, long-term hematologic depression was most commonly observed in patients treated with whole body irradiation. In general, hematologic complications were more frequent among patients who had marrow involvement and intact spleens at the time of initial therapy. The relationship of this study to other clinical trials in the management of patients with advanced stage favorable histology lymphomas and its implications for future clinical trials are discussed.

  8. Extreme-Scale Computing Project Aims to Advance Precision Oncology | FNLCR Staging

    Cancer.gov

    Two government agencies and five national laboratories are collaborating to develop extremely high-performance computing capabilities that will analyze mountains of research and clinical data to improve scientific understanding of cancer, predict dru

  9. Therapeutic exercises for affecting post-treatment swallowing in people treated for advanced-stage head and neck cancers.

    PubMed

    Perry, Alison; Lee, Siew Hwa; Cotton, Susan; Kennedy, Catriona

    2016-08-26

    Head and neck cancer treatment has developed over the last decade, with improved mortality and survival rates, but the treatments often result in dysphagia (a difficulty in swallowing) as a side effect. This may be acute, resolving after treatment, or remain as a long-term negative sequela of head and neck cancer (HNC) treatment. Interventions to counteract the problems associated with dysphagia include swallowing exercises or modification of diet (bolus texture, size), or both. To determine the effects of therapeutic exercises, undertaken before, during and/or immediately after HNC treatment, on swallowing, aspiration and adverse events such as chest infections, aspiration pneumonia and profound weight loss, in people treated curatively for advanced-stage (stage III, stage IV) squamous cell carcinoma of the head and neck. The Cochrane ENT Information Specialist searched the ENT Trials Register; Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 6); MEDLINE; PubMed; Embase; CINAHL; LILACS; KoreaMed; IndMed; PakMediNet; Web of Science; ClinicalTrials.gov; ICTRP; speechBITE; Google Scholar; Google and additional sources for published and unpublished trials. The date of the search was 1 July 2016. We selected randomised controlled trials (RCTs) of adults with head and neck cancer (stage III, stage IV) who underwent therapeutic exercises for swallowing before, during and/or immediately after HNC treatment to help produce safe and efficient swallowing. The main comparison was therapeutic exercises versus treatment as usual (TAU). Other possible comparison pairs included: therapeutic exercises versus sham exercises and therapeutic exercises plus TAU versus TAU. TAU consisted of reactive management of a patient's dysphagia, when this occurred. When severe, this included insertion of either a percutaneous endoscopic gastroscopy or nasogastric tube for non-oral feeding. We used the standard methodological procedures expected by Cochrane. Our primary

  10. Dose and volume reduction for normal lung using intensity-modulated radiotherapy for advanced-stage non-small-cell lung cancer.

    PubMed

    Murshed, Hasan; Liu, H Helen; Liao, Zhongxing; Barker, Jerry L; Wang, Xiaochun; Tucker, Susan L; Chandra, Anurag; Guerrero, Thomas; Stevens, Craig; Chang, Joe Y; Jeter, Melinda; Cox, James D; Komaki, Ritsuko; Mohan, Radhe; Change, Joe Y

    2004-03-15

    To investigate dosimetric improvements with respect to tumor-dose conformity and normal tissue sparing using intensity-modulated radiotherapy (IMRT) compared with three-dimensional conformal radiotherapy (3D-CRT) for advanced-stage non-small-cell lung cancer (NSCLC). Forty-one patients with Stage III-IV and recurrent NSCLC who previously underwent 3D-CRT were included. IMRT plans were designed to deliver 63 Gy to 95% of the planning target volume using nine equidistant coplanar 6-MV beams. Inverse planning was performed to minimize the volumes of normal lung, heart, esophagus, and spinal cord irradiated above their tolerance doses. Dose distributions and dosimetric indexes for the tumors and critical structures in both plans were computed and compared. Using IMRT, the median absolute reduction in the percentage of lung volume irradiated to >10 and >20 Gy was 7% and 10%, respectively. This corresponded to a decrease of >2 Gy in the total lung mean dose and of 10% in the risk of radiation pneumonitis. The volumes of the heart and esophagus irradiated to >40-50 Gy and normal thoracic tissue volume irradiated to >10-40 Gy were reduced using the IMRT plans. A marginal increase occurred in the spinal cord maximal dose and lung volume >5 Gy in the IMRT plans, which could be have resulted from the significant increase in monitor units and thus leakage dose in IMRT. IMRT planning significantly improved target coverage and reduced the volume of normal lung irradiated above low doses. The spread of low doses to normal tissues can be controlled in IMRT with appropriately selected planning parameters. The dosimetric benefits of IMRT for advanced-stage non-small-cell lung cancer must be evaluated further in clinical trials.

  11. Human Leukocyte Antigen G Polymorphism and Expression Are Associated with an Increased Risk of Non-Small-Cell Lung Cancer and Advanced Disease Stage

    PubMed Central

    Ben Amor, Amira; Beauchemin, Karine; Faucher, Marie-Claude; Hamzaoui, Agnes; Hamzaoui, Kamel; Roger, Michel

    2016-01-01

    Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression may enable tumor cells to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G allelic variants and serum soluble HLA-G (sHLA-G) levels on risk of non-small-cell lung cancer (NSCLC). We analyzed 191 Caucasian adults with NSCLC and 191 healthy subjects recruited between January 2009 and March 2014 in Ariana (Tunisia). Serum sHLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. The heterozygous genotypes of HLA-G 010101 and -G 010401 were associated with increased risks of both NSCLC and advanced disease stages. In contrast, the heterozygous genotypes of HLA-G 0105N and -G 0106 were associated with decreased risks of NSCC and clinical disease stage IV, respectively. Serum sHLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. The area under the receiver-operating characteristic (ROC) curves was 0.82 for controls vs patients. Given 100% specificity, the highest sensitivity achieved to detect NSCLC was 52.8% at a cutoff value of 24.9 U/ml. Patients with the sHLA-G above median level (≥ 50 U/ml) had a significantly shorter survival time. This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum sHLA-G levels in NSCLC patients could be useful biomarkers for the diagnostic and prognosis of NSCLC. PMID:27517300

  12. Human Leukocyte Antigen G Polymorphism and Expression Are Associated with an Increased Risk of Non-Small-Cell Lung Cancer and Advanced Disease Stage.

    PubMed

    Ben Amor, Amira; Beauchemin, Karine; Faucher, Marie-Claude; Hamzaoui, Agnes; Hamzaoui, Kamel; Roger, Michel

    2016-01-01

    Human leukocyte antigen (HLA)-G acts as negative regulator of the immune responses and its expression may enable tumor cells to escape immunosurveillance. The purpose of this study was to investigate the influence of HLA-G allelic variants and serum soluble HLA-G (sHLA-G) levels on risk of non-small-cell lung cancer (NSCLC). We analyzed 191 Caucasian adults with NSCLC and 191 healthy subjects recruited between January 2009 and March 2014 in Ariana (Tunisia). Serum sHLA-G levels were measured by immunoassay and HLA-G alleles were determined using a direct DNA sequencing procedures. The heterozygous genotypes of HLA-G 010101 and -G 010401 were associated with increased risks of both NSCLC and advanced disease stages. In contrast, the heterozygous genotypes of HLA-G 0105N and -G 0106 were associated with decreased risks of NSCC and clinical disease stage IV, respectively. Serum sHLA-G levels were significantly higher in patients with NSCLC and particularly in those with advanced disease stages compared to healthy subjects. The area under the receiver-operating characteristic (ROC) curves was 0.82 for controls vs patients. Given 100% specificity, the highest sensitivity achieved to detect NSCLC was 52.8% at a cutoff value of 24.9 U/ml. Patients with the sHLA-G above median level (≥ 50 U/ml) had a significantly shorter survival time. This study demonstrates that HLA-G allelic variants are independent risk factors for NSCLC. Serum sHLA-G levels in NSCLC patients could be useful biomarkers for the diagnostic and prognosis of NSCLC.

  13. Single-stage osseointegrated implants for nasal prosthodontic rehabilitation: A clinical report.

    PubMed

    de Carvalho, Bruna M D F; Freitas-Pontes, Karina M; de Negreiros, Wagner A; Verde, Marcus A R L

    2015-08-01

    Malignant tumors in the nasal region may be treated by means of invasive surgical procedures, with large facial losses. Nasal prostheses, retained by osseointegrated facial implants, instead of plastic surgery, will, in most patients, offer good biomechanical and cosmetic results. This clinical report describes the prosthetic rehabilitation of a patient with nasal cancer who had the entire nasal vestibule removed in a single-stage surgical procedure in order to shorten the rehabilitation time. The nasal prosthesis was built on a 3-magnet bar and was made of platinum silicone with intrinsic pigmentation, thereby restoring the patient's appearance and self-esteem. The authors concluded that single-stage implants may reduce the rehabilitation time to as little as 1 month, and the correct use of materials and techniques may significantly improve the nasal prosthesis.

  14. The Advancing Clinical Impact of Molecular Imaging in Cardiovascular Disease

    PubMed Central

    Osborn, Eric A; Jaffer, Farouc A

    2013-01-01

    Molecular imaging seeks to unravel critical molecular and cellular events in living subjects by providing complementary biological information to current structural clinical imaging modalities. In recent years, molecular imaging efforts have marched forward into the clinical cardiovascular arena, and are now actively illuminating new biology in a broad range of conditions, including atherosclerosis, myocardial infarction, thrombosis, vasculitis, aneurysm, cardiomyopathy, and valvular disease. Development of novel molecular imaging reporters is occurring for many clinical cardiovascular imaging modalities (PET, SPECT, MRI), as well in translational platforms such as intravascular fluorescence imaging. The ability to image, track, and quantify molecular biomarkers in organs not routinely amenable to biopsy (e.g. the heart and vasculature) open new clinical opportunities to tailor therapeutics based on a cardiovascular disease molecular profile. In addition, molecular imaging is playing an increasing role in atherosclerosis drug development in Phase II clinical trials. Here we present state-of-the-art clinical cardiovascular molecular imaging strategies, and explore promising translational approaches positioned for clinical testing in the near term. PMID:24332285

  15. Distribution of Resistant Esophageal Adenocarcinoma in the Resected Specimens of Clinical Stage III Patients After Chemoradiation: Its Clinical Implications

    PubMed Central

    Neishaboori, Nastaran; Wadhwa, Roopma; Nogueras-González, Graciela M.; Elimova, Elena; Shiozaki, Hironori; Sudo, Kazuki; Charalampakis, Nikolaos; Hiremath, Adarsh; Lee, Jeffrey H.; Bhutani, Manoop S.; Weston, Brian; Blum, Mariela A.; Rogers, Jane E.; Garris, Jeana L.; Rice, David C.; Komaki, Ritsuko; Swisher, Stephen G.; Skinner, Heath D.; Hofstetter, Wayne L.; Ajani, Jaffer A.

    2015-01-01

    Background We have limited knowledge of the geographic distribution of resistant EAC in the resected specimen and its clinical importance can be enormous. Method We selected patients with baseline stage III EAC who had chemoradiation followed by surgery, and had residual EAC (resistant cases only). Outcomes were correlated with various endpoints (% of resistant EAC, anatomic distribution). Results 100 clinical stage III patients were studied. 90% had an R0 resection. 99% had either moderate or poorly differentiated EAC. 12% had >50% residual cancer, 31% had 11–50% residual cancer, 53% had 1–10% residual cancer, and 3% had positive nodes only. Each compartment was frequently involved: mucosa/submucosa=66%, muscularis propria=76%, serosa=62%, and all=35%. Lack of EAC (meaning response) was observed in mucosa/submucosa (34%), muscularis propria (24%), serosa (38%), and nodes (42%). Although the endoscopic biopsies prior to surgery had no EAC in 79% of patients, in the surgical specimen, however, resistant EAC was frequent (66%) in mucosa/submucosa. Conclusion Contrary to our belief that resistant EAC would be frequent in the nodes, our data show that its distribution is heterogeneous and unpredictable. Most importantly, the post-chemoradiation biopsies are misleading and a decision to delay/avoid surgery based on negative biopsies can be detrimental for the patients. PMID:25765719

  16. Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach

    PubMed Central

    Lewis, S; Foltynie, T; Blackwell, A; Robbins, T; Owen, A; Barker, R

    2005-01-01

    Objective: To investigate the heterogeneity of idiopathic Parkinson's disease (PD) in a data driven manner among a cohort of patients in the early clinical stages of the disease meeting established diagnostic criteria. Methods: Data on demographic, motor, mood, and cognitive measures were collected from 120 consecutive patients in the early stages of PD (Hoehn and Yahr I–III) attending a specialist PD research clinic. Statistical cluster analysis of the data allowed the existence of the patient subgroups generated to be explored. Results: The analysis revealed four main subgroups: (a) patients with a younger disease onset; (b) a tremor dominant subgroup of patients; (c) a non-tremor dominant subgroup with significant levels of cognitive impairment and mild depression; and (d) a subgroup with rapid disease progression but no cognitive impairment. Conclusions: This study complements and extends previous research by using a data driven approach to define the clinical heterogeneity of early PD. The approach adopted in this study for the identification of subgroups of patients within Parkinson's disease has important implications for generating testable hypotheses on defining the heterogeneity of this common condition and its aetiopathological basis and thus its treatment. PMID:15716523

  17. Genetics of deafness: recent advances and clinical implications.

    PubMed

    Goldfarb, Abraham; Avraham, Karen B

    2002-01-01

    Genetic research into the causes of deafness has advanced considerably in the last years. Progress has been made in both discovering loci and cloning genes associated with syndromic and non-syndromic hearing loss. To date, close to 75 loci have been identified and 29 genes have been cloned for non-syndromic deafness. The proteins these genes encode range from transcription factors to molecular motors to ion channels. We review the recent discoveries and discuss the impact of this research.

  18. 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.

  19. Safety and efficacy of a polyherbal formulation for the management of dyslipidemia and hyperglycemia in patients with advanced-stage of type-2 diabetes.

    PubMed

    Zarvandi, Mahdi; Rakhshandeh, Hassan; Abazari, Mohammad; Shafiee-Nick, Reza; Ghorbani, Ahmad

    2017-02-16

    The present clinical trial was designed to evaluate the safety and efficacy of a polyherbal formulation (PHF) consisted of Allium sativum, Aloe vera, Nigella sativa, Plantago psyllium, Silybum marianum and Trigonella foenum-graecum for controlling dyslipidemia and hyperglycemia in patients with advanced-stage of type-2 diabetes. An open-label phase I trial was carried out on 30 patients who had hyperlipidemia and hyperglycemia before the beginning of the trial in spite of receiving statins and oral hypoglycemic drugs. Patients were given one PHF sachet two times daily for 40 consecutive days. All subjects also continuously received their statins and oral hypoglycemic agents. Clinical assessments and laboratory findings were evaluated before starting treatment and at day 40. Treatment with PHF had no significant effects on serum biochemical parameters related to liver and kidney functions, on hematological parameters related to erythrocytes, leukocytes, and platelets, and on body weight and blood pressure. After consumption of PHF, 2 patients complained of mild nausea, and 2 patients reported diarrhea. PHF significantly decreased fasting blood glucose and HbA1c from 162±40mg/dL to 146±37mg/dL and from 8.4±1.5% to 7.7±1.1%, respectively. Also, it significantly decreased the level of LDL from 138±25mg/dL to 108±36mg/dL, and the level of triglycerides from 203±47mg/dL to 166±58mg/dL. In conclusion, the present results demonstrated that the PHF was safe and efficacious in lowering the levels of blood glucose and serum lipids in patients with advanced-stage of type-2 diabetes.

  20. Health-related quality of life and risk of colorectal cancer recurrence and All-cause death among advanced stages of colorectal cancer 1-year after diagnosis.

    PubMed

    Wong, Carlos K H; Law, Wai-Lun; Wan, Yuk-Fai; Poon, Jensen Tung-Chung; Lam, Cindy Lo-Kuen

    2014-05-17

    The study aimed to examine the association between health-related quality of life (HRQOL) assessed with overall survival (OS) and recurrence after diagnosis of colorectal cancer (CRC). Overall 160 patients with advanced stage CRC were recruited in an observational study and completed the generic and condition-specific HRQOL questionnaires at the colorectal specialist outpatient clinic in Hong Kong, between 10/2009 and 07/2010. Socio-demographic and clinical characteristics including duration since diagnosis, primary tumor location and treatment modality, were collected to serve as predictor variables in regression models. All-cause death or CRC recurrence was the event of interest. Association between HRQOL with OS was assessed using Cox regression. Association between HRQOL and CRC recurrence was further modeled by competing-risks regression adjusted for the competing-risks of death from any cause. After a median follow-up of 23 months, there were 22 (16.1%) incidents of CRC recurrence and 15 (9.4%) deaths. Decreased physical functioning (hazard ratios, HR = 0.917, 95% CI:0.889-0.981) and general health of domains in SF-12 (HR = 0.846, 95% CI:0.746-0.958) or SF-6D scores (HR = 0.010, 95% CI:0.000-0.573) were associated with an increased risk of death, with adjustment of patients' characteristics. Increased vitality (HR = 1.151, 95% CI:1.027-1.289) and mental health (HR = 1.128, 95% CI:1.005-1.265) were associated with an increased likelihood of death. In models adjusted for competing-risk of death, those with worse HRQOL was not associated with increased risk of CRC recurrence. Although self-reported HRQOL was not a significant prognostic factor for CRC recurrence, the HRQOL provided independent prognostic value about mortality in patients with advanced stage of CRC.

  1. Implementation of wireless technology in advanced clinical practice.

    PubMed

    Øyri, Karl; Balasingham, Ilangko; Høgetveit, Jan Olav

    2006-01-01

    The Wireless Sensors in Healthcare Project focused on the implementation of wireless technology in healthcare. Wireless biomedical sensors for monitoring of continuous invasive arterial blood pressure were developed and evaluated under controlled conditions during laparoscopic surgery. The project has resulted in the first publication of clinical use of a wireless biomedical sensor for invasive measurement of arterial blood pressure in a pilot study. A second demonstrator for wireless clinical decision support based on the first demonstrator was developed. Wireless technologies used were Bluetooth, wireless local area network and GPRS/mobile telephones. Further research is needed to evaluate the wireless clinical decision support system. Critical care nurses and nurse anesthetists are potential users of wireless technology. Their clinical expertise is important in development of-, and future use of wireless technology.

  2. Clinical analysis of the patients with single fair cleavage-stage embryo on day 3.

    PubMed

    Li, Mingzhao; Wang, Hui; Xue, Xia; Shi, Juanzi

    2017-09-23

    This study aimed to explore an appropriate selection for the patients with single fair cleavage-stage embryo on day 3. This study included 469 fresh transfers and 220 frozen-thawed transfers from January 2014 to June 2016. Furthermore, in 72 patients who have only 4-6 fair embryos (4-5 blastomeres) on day 3, the blastocysts were cultured to day 5 for transfer. In the fresh transfers, the clinical pregnancy rate of 4-5 blastomeres group was significantly lower than 6-7 and 8-10 blastomeres group (5.88 vs. 30.13%, p<.001and 5.88 vs. 26.09%, p < .001). In the frozen-thawed transfers, the clinical pregnancy rate of 4-5 blastomeres group was also significantly lower than 6-7 and 8-10 blastomeres group (10.00 vs. 28.57%, p = .040 and 10.00 vs. 33.33%, p = .005). For the blastocyst transfers derived from fair embryos with 4-5 blastomeres, the clinical pregnancy rate was significantly higher than single and double fair embryo transfers of similar quality (44.44 vs. 7.04%, p < .001 and 44.44 vs. 28.09%, p = .013). For the patients with single fair embryo (6-7 blastomeres or 8-10 blastomeres), transfer at the cleavage stage is feasible. For the patients with single fair embryo (4-5 blastomeres), transfer of single fair embryo at the blastocyst stage or accumulating two fair embryos might be worthy of consideration.

  3. Two-Stage Axial Compressor Rig Designed To Develop and Validate Advanced Aerodynamic Technologies

    NASA Technical Reports Server (NTRS)

    Larosiliere, Louis M.

    2003-01-01

    Future aeropropulsion gas turbine engines must be affordable in addition to being energy efficient and environmentally benign. Progress in aerodynamic design capability is required not only to maximize the specific thrust of next-generation engines without sacrificing fuel consumption, but also to reduce parts count by increasing the aerodynamic loading of the compression system. To meet future compressor requirements, the NASA Glenn Research Center is investigating advanced aerodynamic design concepts that will lead to more compact, higher efficiency, and wider operability configurations than are currently in operation.

  4. Durable left ventricular assist device therapy in advanced heart failure: Patient selection and clinical outcomes

    PubMed Central

    Shah, Sachin P.; Mehra, Mandeep R.

    2016-01-01

    The increasing adoption of left ventricular assist devices (LVADs) into clinical practice is related to a combination of engineering advances in pump technology and improvements in understanding the appropriate clinical use of these devices in the management of patients with advanced heart failure. This review intends to assist the clinician in identifying candidates for LVAD implantation, to examine long-term outcomes and provide an overview of the common complications related to use of these devices. PMID:27056652

  5. Experiences of pretreatment laparoscopic surgical staging in patients with locally advanced cervical cancer: results of a prospective study

    PubMed Central

    Lim, Myong Cheol; Bae, Jaeman; Park, Jeong-Yoel; Lim, Soyi; Kang, Sokbom; Seo, Sang-Soo; Kim, Joo-Yong; Rho, Ju-Won

    2008-01-01

    Objective To prospectively evaluate the feasibility, safety, and survival of laparoscopic surgical staging in patients with locally advanced cervical cancer. Methods From Oct 2001 to Jul 2006, a total of 83 consecutive patients were eligible for inclusion and underwent laparoscopic surgical staging. Results Three patients with intraoperative great vessel injury and 1 patient in whom the colpotomizer was unable to be inserted were excluded. Laparoscopic surgical staging was feasible in 95.2% (79/83). Immediate postoperative complications were noted in 12 (15.2%) patients. Prolonged complications directly related to operative procedures numbered 2 (2.5%), and were trocar site metastases. The mean time from surgery to the start of radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) was 11 (5-35) days. All patients tolerated the treatment well and completed scheduled RT or CCRT without disruption of treatment and additional admission. The rate of modification of the radiation field after surgical staging was 8.9% (7/79). Five-year progression-free survival and overall survival (OS) rates were 79% and 89%, respectively. The OS of patients with microscopic lymph node metastases, which were fully resected, were comparable to those of patients without lymph node metastasis. However, the OS of patients with macroscopic lymph node metastases that were fully resected were poorer compared with those of patients without lymph node metastasis. Conclusion Pretreatment laparoscopic surgical staging is a feasible and safe treatment modality. However the survival benefit of debulking lymph nodes or full lymph node dissection is not clear. PMID:19471562

  6. Induction chemotherapy followed by concurrent chemoradiotherapy for advanced stage oropharyngeal squamous cell carcinoma with HPV and P16 testing.

    PubMed

    Flavill, Eric; Fang, Yisheng V; Miles, Brett; Truelson, John; Perkins, Steve

    2014-05-01

    The objective was to report our experience with advanced stage oropharyngeal squamous cell carcinoma treated sequentially with induction chemotherapy followed by concurrent chemoradiotherapy. Retrospective chart review identified 49 eligible patients with advanced stage oropharyngeal squamous cell carcinoma treated with induction chemotherapy followed by concurrent chemoradiotherapy. HPV and p16(INK4A) testing was performed on pathology specimens. Follow-up of over 11 months was required unless a death or treatment failure occurred before that time. Treatment with induction chemotherapy followed by concurrent chemoradiotherapy resulted in 44/48 (90%) complete durable response. One death occurred from pulmonary embolism. Toxicity profiles were comparable to other published data. Average follow-up was 3.9 years. Oncologic failure rates among subgroups showed 5.7% failure for HPV+/p16+ cancer, 9.1% failure for HPV-/p16+ cancer, 100% failure for HPV-/p16- cancer, 0% failure for nonsmokers, and 17.9% failure for smokers. This study showed favorable outcomes in terms of durable oncologic response and acceptable toxicity profiles. It is notable that 36/49 patients were HPV+/p16+ and 11/49 were HPV-/p16+. Only 2 patients were HPV-/p16-, and both died as a result of oncologic failures. This highlights the importance of obtaining HPV and p16 testing in studies evaluating the efficacy of treatments for oropharyngeal squamous cell carcinoma.

  7. High expression of Wls is associated with lymph node metastasis and advanced TNM stage in gastric carcinomas.

    PubMed

    Zhang, Wei; Tao, Hong; Chen, Xiao; Sugimura, Haruhiko; Wang, Jiandong; Zhou, Ping

    2017-03-01

    The roles of Wnt protein in carcinogenesis have been well documented in human cancers. Wls is a key modulator for the secretion of Wnt protein. We previously found that Wls was aberrantly expressed in colorectal carcinomas. Studies have revealed that dysregulation of Wnt signal transduction plays an important role in gastric carcinoma. We hypothesized that Wls may play a role in the development and progression of gastric carcinoma. In this study, three gastric cancer cell lines MGC-803, SGC-7901, and AGS, and a set of gastric carcinoma tissue specimens were subjected to immunohistochemistry. The relationship between the expression of Wls and clinicopathological parameters was analyzed. Wls was negatively detected in MGC-803, positively detected in SGC-7901 and AGS cell lines. Wls was weakly expressed in 9.7% (15/154), moderately in 33.1% (51/154), and strongly in 57.1% (88/154) of tested gastric carcinoma specimens. High expression of Wls was positively associated with well and moderately differentiated tumors (P = 0.035, rs  = 0.170), lymph node metastasis (P = 0.001, rs  = 0.276), and advanced TNM stage (P = 0.006, rs  = 0.219). Our data suggest that Wls protein is related to tumor metastasis and advanced TNM stage, and may be used as a new marker for prognosis of gastric carcinoma.

  8. An evaluation of a Simon 2-Stage phase II clinical trial design incorporating toxicity monitoring.

    PubMed

    Ray, H E; Rai, S N

    2011-05-01

    Phase II clinical trials are usually designed to measure efficacy but patient safety is also a very important aspect. Previous authors suggested a methodology that allows one to monitor the cumulative number of toxic events after each patient is treated, which is also known as continuous toxicity monitoring. In this work we describe how to combine the continuous toxicity monitoring methodology with the Simon 2-Stage design for response. Then we investigate through simulation the combined procedure's type I and type II error rates under various combinations of design parameters. We include the underlying relationship between toxicity and response in our examination of the error rates.

  9. Vinflunine in the treatment of advanced urothelial cancer: clinical evidence and experience

    PubMed Central

    Gerullis, Holger; Wawroschek, Friedhelm; Köhne, Claus-Henning; Ecke, Thorsten Holger

    2016-01-01

    Vinflunine (VFL) has been approved in Europe for second-line treatment of metastatic and advanced urothelial cancer after failure of platin-containing therapy. Since approval, the drug has been investigated in few clinical trials. Most of the currently available reports describe experiences with VFL in a daily clinical setting. This review gives a short overview on clinical experiences and clinical trials involving VFL since the approval of this drug in 2009. PMID:28042310

  10. Clinically advanced and metastatic pure mucinous carcinoma of the breast: a comprehensive genomic profiling study.

    PubMed

    Ross, Jeffrey S; Gay, Laurie M; Nozad, Sahar; Wang, Kai; Ali, Siraj M; Boguniewicz, Ann; Khaira, Depinder; Johnson, Adrienne; Elvin, Julia A; Vergilio, Jo-Anne; Suh, James; Miller, Vincent A; Stephens, Philip J

    2016-01-01

    Pure mucinous breast carcinoma (pmucBC) is a distinctive variant of breast cancer (BC) featuring an excellent overall prognosis. However, on rare occasions, pmucBC pursues an aggressive clinical course. We queried whether comprehensive genomic profiling (CGP) would uncover clinically relevant genomic alterations (CRGA) that could lead to targeted therapy treatment for patients with an advanced and metastatic form of pmucBC. From a series of 51,238 total cancer samples, which included 5605 cases of clinically advanced BC and 22 cases of stage IV pmucBC, DNA was extracted from 40 microns of FFPE sections. Comprehensive genomic profiling was performed using a hybrid-capture, adaptor ligation-based next generation sequencing assay to a mean coverage depth of 564X. The results were analyzed for all classes of genomic alterations (GA) including base substitutions, insertions and deletions, select rearrangements, and copy number changes. Clinically relevant genomic alterations were defined as those indicating possible treatment with anti-cancer drugs on the market or in registered clinical trials. Samples were obtained from breast (11), lymph nodes (3), chest wall (2), liver (2), soft tissue (2), bone (1), and pleura (1). The median age of the 22 pmucBC patients was 57 years (range 32-79 years). Three pmucBCs were grade 1, 17 were grade 2, and 2 were grade 3. Twenty-one (95 %) pmucBC were ER+, 18 (82 %) were PR+, and 3 (14 %) were HER2+ by IHC and/or FISH. A total of 132 GA were identified (6.0 GA per tumor), including 53 CRGA, for a mean of 2.4 GA per tumor. Amplification of FGFR1 or ZNF703, located within the same amplicon, was found in 8 of 22 cases (36 %). This enrichment of FGFR1 amplification in 36 % of pmucBC versus 11 % of non-mucinous ER+ BC (601 cases) was significant (p < 0.005). Other frequently altered genes of interest in pmucBC were CCND1 and the FGF3/FGF4/FGF19 amplicon (27 %), often co-amplified together. ERBB2/HER2 alterations were identified in 5 pmuc

  11. Image Guided Hypofractionated 3-Dimensional Radiation Therapy in Patients With Inoperable Advanced Stage Non-Small Cell Lung Cancer

    SciTech Connect

    Osti, Mattia Falchetto; Agolli, Linda; Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi

    2013-03-01

    Purpose: Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Methods and Materials: Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. Results: The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Conclusions: Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized

  12. Image guided hypofractionated 3-dimensional radiation therapy in patients with inoperable advanced stage non-small cell lung cancer.

    PubMed

    Osti, Mattia Falchetto; Agolli, Linda; Valeriani, Maurizio; Falco, Teresa; Bracci, Stefano; De Sanctis, Vitaliana; Enrici, Riccardo Maurizi

    2013-03-01

    Hypofractionated radiation therapy (HypoRT) can potentially improve local control with a higher biological effect and shorter overall treatment time. Response, local control, toxicity rates, and survival rates were evaluated in patients affected by inoperable advanced stage non-small cell lung cancer (NSCLC) who received HypoRT. Thirty patients with advanced NSCLC were enrolled; 27% had stage IIIA, 50% had stage IIIB, and 23% had stage IV disease. All patients underwent HypoRT with a prescribed total dose of 60 Gy in 20 fractions of 3 Gy each. Radiation treatment was delivered using an image guided radiation therapy technique to verify correct position. Toxicities were graded according to Radiation Therapy Oncology Group morbidity score. Survival rates were estimated using the Kaplan-Meier method. The median follow-up was 13 months (range, 4-56 months). All patients completed radiation therapy and received the total dose of 60 Gy to the primary tumor and positive lymph nodes. The overall response rate after radiation therapy was 83% (3 patients with complete response and 22 patients with partial response). The 2-year overall survival and progression-free survival rates were 38.1% and 36%, respectively. Locoregional recurrence/persistence occurred in 11 (37%) patients. Distant metastasis occurred in 17 (57%) patients. Acute toxicities occurred consisting of grade 1 to 2 hematological toxicity in 5 patients (17%) and grade 3 in 1 patient; grade 1 to 2 esophagitis in 12 patients (40%) and grade 3 in 1 patient; and grade 1 to 2 pneumonitis in 6 patients (20%) and grade 3 in 2 patients (7%). Thirty-three percent of patients developed grade 1 to 2 late toxicities. Only 3 patients developed grade 3 late adverse effects: esophagitis in 1 patient and pneumonitis in 2 patients. Hypofractionated curative radiation therapy is a feasible and well-tolerated treatment for patients with locally advanced NSCLC. Randomized studies are needed to compare HypoRT to conventional

  13. Advances of multidetector computed tomography in the characterization and staging of renal cell carcinoma

    PubMed Central

    Tsili, Athina C; Argyropoulou, Maria I

    2015-01-01

    Renal cell carcinoma (RCC) accounts for approximately 90%-95% of kidney tumors. With the widespread use of cross-sectional imaging modalities, more than half of RCCs are detected incidentally, often diagnosed at an early stage. This may allow the planning of more conservative treatment strategies. Computed tomography (CT) is considered the examination of choice for the detection and staging of RCC. Multidetector CT (MDCT) with the improvement of spatial resolution and the ability to obtain multiphase imaging, multiplanar and three-dimensional reconstructions in any desired plane brought about further improvement in the evaluation of RCC. Differentiation of RCC from benign renal tumors based on MDCT features is improved. Tumor enhancement characteristics on MDCT have been found closely to correlate with the histologic subtype of RCC, the nuclear grade and the cytogenetic characteristics of clear cell RCC. Important information, including tumor size, localization, and organ involvement, presence and extent of venous thrombus, possible invasion of adjacent organs or lymph nodes, and presence of distant metastases are provided by MDCT examination. The preoperative evaluation of patients with RCC was improved by depicting the presence or absence of renal pseudocapsule and by assessing the possible neoplastic infiltration of the perirenal fat tissue and/or renal sinus fat compartment. PMID:26120380

  14. 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.

  15. 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.

  16. Pulmonary contusion: an update on recent advances in clinical management.

    PubMed

    Cohn, Stephen M; Dubose, Joseph J

    2010-08-01

    Pulmonary contusion is a common finding after blunt chest trauma. The physiologic consequences of alveolar hemorrhage and pulmonary parenchymal destruction typically manifest themselves within hours of injury and usually resolve within approximately 7 days. Clinical symptoms, including respiratory distress with hypoxemia and hypercarbia, peak at about 72 h after injury. The timely diagnosis of pulmonary contusion requires a high degree of clinical suspicion when a patient presents with trauma caused by an appropriate mechanism of injury. The clinical diagnosis of acute parenchymal lung injury is usually confirmed by thoracic computed tomography, which is both highly sensitive in identifying pulmonary contusion and highly predictive of the need for subsequent mechanical ventilation. Management of pulmonary contusion is primarily supportive. Associated complications such as pneumonia, acute respiratory distress syndrome, and long-term pulmonary disability, however, are frequent sequelae of these injuries.

  17. Clinical response of advanced cancer patients to cellular immunotherapy and intensity-modulated radiation therapy

    PubMed Central

    Hasumi, Kenichiro; Aoki, Yukimasa; Wantanabe, Ryuko; Mann, Dean L

    2013-01-01

    Patients afflicted with advanced cancers were treated with the intratumoral injection of autologous immature dendritic cells (iDCs) followed by activated T-cell infusion and intensity-modulated radiation therapy (IMRT). A second round of iDCs and activated T cells was then administered to patients after the last radiation cycle. This complete regimen was repeated for new and recurring lesions after 6 weeks of follow-up. One year post therapy, outcome analyses were performed to evaluate treatment efficacy. Patients were grouped according to both the number and size of tumors and clinical parameters at treatment initiation, including recurrent disease after standard cancer therapy, Stage IV disease, and no prior therapy. Irrespective of prior treatment status, 23/37 patients with ≤ 5 neoplastic lesions that were ≤ 3 cm in diameter achieved complete responses (CRs), and 5/37 exhibited partial responses (PRs). Among 130 individuals harboring larger and more numerous lesions, CRs were observed in 7/74 patients that had received prior SCT and in 2/56 previously untreated patients. Some patients manifested immune responses including an increase in CD8+CD56+ lymphocytes among circulating mononuclear cells in the course of treatment. To prospectively explore the therapeutic use of these cells, CD8+ cells were isolated from patients that had been treated with cellular immunotherapy and IMRT, expanded in vitro, and injected into recurrent metastatic sites in 13 individuals who underwent the same immunoradiotherapeutic regimens but failed to respond. CRs were achieved in 34 of 58 of such recurrent lesions while PRs in 17 of 58. These data support the expanded use of immunoradiotherapy in advanced cancer patients exhibiting progressive disease. PMID:24349874

  18. Overview of chemoradiation clinical trials for locally advanced non-small cell lung cancer in Japan.

    PubMed

    Okamoto, Isamu

    2008-04-01

    The standard of care for unresectable stage III non-small cell lung cancer (NSCLC) is combined-modality therapy with both chemotherapy and thoracic radiation therapy (TRT). A phase III trial by the West Japan Lung Cancer Group revealed that the combination of mitomycin, vindesine, and cisplatin (MVP) with concurrent TRT yielded a median survival time of 16.6 months and a 5-year survival rate of 16% in patients with unresectable stage III NSCLC. Although evidence indicates that concurrent chemotherapy and TRT (chemoradiation) increases survival to a moderately greater extent than sequential therapeutic approaches, the optimal strategies for such concurrent treatment remain to be defined, and differ between full-dose systemic and low-dose radio-enhancing protocols. Two phase III trials have been initiated in Japan to address these issues and they have recently reported preliminary data. Early results of the Okayama Lung Cancer Study Group (OLCSG) trial, comparing chemoradiation based on divided docetaxel and cisplatin chemotherapy with MVP-based chemoradiation, have been reported. The West Japan Oncology Group (WJOG) is comparing the efficacy and toxicity of TRT and concurrent chemotherapy with either carboplatin-paclitaxel or carboplatin-irinotecan, followed by full-dose consolidation chemotherapy, with the efficacy and toxicity of MVP-based chemoradiation. Several phase I/II studies to test the optimal use of new agents such as S-1 (an oral anticancer drug combining tegafur, 5-chloro-2, 4-dihydroxypyridine, and potassium oxonate) and gefitinib (an inhibitor of the tyrosine kinase activity of the epidermal growth factor receptor) are also ongoing. In addition, radiation dose intensification with three-dimensional planning approaches is currently under evaluation. A phase I clinical trial by WJOG to establish, prospectively, the maximum tolerated dose of three-dimensional hyperfractionated radiotherapy with concurrent weekly chemotherapy (carboplatin-paclitaxel) is

  19. 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.

  20. Can evidence-based prevention programs be sustained in community practice settings? The Early Risers' Advanced-Stage Effectiveness Trial.

    PubMed

    August, Gerald J; Bloomquist, Michael L; Lee, Susanne S; Realmuto, George M; Hektner, Joel M

    2006-06-01

    This study evaluated institutional sustainability of the Early Risers "Skills for Success" conduct problems prevention program. In a previous early-stage effectiveness trial Early Risers had been successfully implemented by a nonprofit community agency with guidance, supervision, technical assistance and fiscal support/oversight provided by program developers. The current advanced-stage effectiveness trial applied a randomized, control group design to determine whether this community agency could replicate earlier positive findings with a new cohort of participants, but with less direct involvement of program developers. An intent-to-intervene strategy was used to compare children randomly assigned to Early Risers or a no-intervention comparison group. Compared to results obtained in an early-stage effectiveness trial, program attendance rates were much lower and only one positive outcome was replicated. Failure to replicate program effects was not attributed to poor program implementation, because data collected pertaining to exposure, adherence and quality of delivery were acceptable, and a participation analysis showed that families who attended at higher levels did benefit. It was difficulties that the community agency experienced in engaging families in program components at recommended levels that primarily accounted for the results. Possible organizational barriers that impeded sustainability included unreliable transportation, poor collaboration between the agency and the local public school system, high staff turnover, agency downsizing, and fiduciary responsibility and accountability. It was concluded that both program developers and program providers need to be proactive in planning for sustainability.

  1. De novo sequencing of circulating miRNAs identifies novel markers predicting clinical outcome of locally advanced breast cancer

    PubMed Central

    2012-01-01

    Background MicroRNAs (miRNAs) have been recently detected in the circulation of cancer patients, where they are associated with clinical parameters. Discovery profiling of circulating small RNAs has not been reported in breast cancer (BC), and was carried out in this study to identify blood-based small RNA markers of BC clinical outcome. Methods The pre-treatment sera of 42 stage II-III locally advanced and inflammatory BC patients who received neoadjuvant chemotherapy (NCT) followed by surgical tumor resection were analyzed for marker identification by deep sequencing all circulating small RNAs. An independent validation cohort of 26 stage II-III BC patients was used to assess the power of identified miRNA markers. Results More than 800 miRNA species were detected in the circulation, and observed patterns showed association with histopathological profiles of BC. Groups of circulating miRNAs differentially associated with ER/PR/HER2 status and inflammatory BC were identified. The relative levels of selected miRNAs measured by PCR showed consistency with their abundance determined by deep sequencing. Two circulating miRNAs, miR-375 and miR-122, exhibited strong correlations with clinical outcomes, including NCT response and relapse with metastatic disease. In the validation cohort, higher levels of circulating miR-122 specifically predicted metastatic recurrence in stage II-III BC patients. Conclusions Our study indicates that certain miRNAs can serve as potential blood-based biomarkers for NCT response, and that miR-122 prevalence in the circulation predicts BC metastasis in early-stage patients. These results may allow optimized chemotherapy treatments and preventive anti-metastasis interventions in future clinical applications. PMID:22400902

  2. Vismodegib induces significant clinical response in locally advanced trichoblastic carcinoma.

    PubMed

    Lepesant, P; Crinquette, M; Alkeraye, S; Mirabel, X; Dziwniel, V; Cribier, B; Mortier, L

    2015-10-01

    Patients with advanced basal cell carcinoma due to local extension or metastatic disease were previously at a therapeutic impasse. Targeted inhibition of the sonic hedgehog pathway by vismodegib represents a new therapeutic strategy. Adnexal carcinomas are rare malignant skin tumours derived from epithelial annexes. Conventional treatment of adnexal tumours is based on surgical excision. Although the radiosensitivity of adnexal carcinomas has not been established, radiotherapy could be offered alone or in combination in locally advanced or inoperable disease. Chemotherapy represents a therapeutic option in the treatment of metastatic adnexal tumours. Currently there is no effective treatment for these tumours when they become metastatic or unresectable, and treatment is palliative. Sunitinib represents a new therapeutic strategy, with efficiency described in the literature for a small number of patients. However, its efficacy is partial, and its tolerance is not always good. We report a patient with trichoblastic carcinoma, initially diagnosed as basal cell carcinoma, treated effectively with vismodegib. The remarkable response we have observed in this patient suggests an encouraging therapeutic role of vismodegib in trichoblastic carcinoma that should be evaluated in a carefully designed trial.

  3. [Sample Size Calculation using SAS for PhaseⅡin Two-stage Clinical Trials of Anti-tumor Drugs].

    PubMed

    Li, Ji-Jie; Hou, Li-Sha; Zhu, Ping; Du, Xu-Dong; Zhu, Cai-Rong

    2017-07-01

    To compare Gehan two-stage design and Simon two-stage design in sample size calculations for phase Ⅱ clinical trials of anti-tumor drugs. We explained the sample size calculation methods with a single-stage design, Gehan two-stage design, and Simon optimal two-stage and minimax two-stage designs in line with the principle of exact binomial probability. By setting up different parameters in SAS macro program, the advantages and disadvantages of these designs were compared. The minimax two-stage design does not increase the maximum sample size compared with the single-stage design. Compared with the Gehan two-stage design, the Simon two-stage design has the advantage of being able to determine an early termination of trials when no or low anti-tumor activities are evident. Simon two-stage design is better than single-stage design and Gehan two-stage design. The minimax design is more popular than the optimal design.

  4. Receipt of Nephrology Care and Clinical Outcomes Among Veterans With Advanced CKD.

    PubMed

    Fung, Enrica; Chang, Tara I; Chertow, Glenn M; Thomas, I-Chun; Asch, Steven M; Kurella Tamura, Manjula

    2017-08-12

    Clinical practice guidelines recommend referral to nephrology when estimated glomerular filtration rate (eGFR) decreases to <30mL/min/1.73m(2); however, evidence for benefits of nephrology care are mixed. Observational cohort using landmark analysis. A national cohort of veterans with advanced chronic kidney disease, defined as an outpatient eGFR≤30mL/min/1.73m(2) for January 1, 2010, through December 31, 2010, and a prior eGFR<60mL/min/1.73m(2), using administrative and laboratory data from the Department of Veterans Affairs and the US Renal Data System. Receipt and frequency of outpatient nephrology care over 12 months. Survival and progression to end-stage renal disease (ESRD; receipt of dialysis or kidney transplantation) were the primary outcomes. In addition, control of associated clinical parameters over 12 months were intermediate outcomes. Of 39,669 patients included in the cohort, 14,983 (37.8%) received nephrology care. Older age, heart failure, dementia, depression, and rapidly declining kidney function were independently associated with the absence of nephrology care. During a mean follow-up of 2.9 years, 14,719 (37.1%) patients died and 4,310 (10.9%) progressed to ESRD. In models adjusting for demographics, comorbid conditions, and trajectory of kidney function, nephrology care was associated with lower risk for death (HR, 0.88; 95% CI, 0.85-0.91), but higher risk for ESRD (HR, 1.48; 95% CI, 1.38-1.58). Among patients with clinical parameters outside guideline recommendations at cohort entry, a significantly higher adjusted proportion of patients who received nephrology care had improvement in control of hemoglobin, potassium, albumin, calcium, and phosphorus concentrations compared with those who did not receive nephrology care. May not be generalizable to nonveterans. Among patients with advanced chronic kidney disease, nephrology care was associated with lower mortality, but was not associated with lower risk for progression to ESRD. Copyright

  5. Clinical and dosimetric implications of intensity-modulated radiotherapy for early-stage glottic carcinoma

    SciTech Connect

    Ward, Matthew Christopher Pham, Yvonne D.; Kotecha, Rupesh; Zakem, Sara J.; Murray, Eric; Greskovich, John F.

    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 literature 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.

  6. Adjuvant sorafenib after heptectomy for Barcelona Clinic Liver Cancer-stage C hepatocellular carcinoma patients.

    PubMed

    Xia, Feng; Wu, Li-Li; Lau, Wan-Yee; Huan, Hong-Bo; Wen, Xu-Dong; Ma, Kuan-Sheng; Li, Xiao-Wu; Bie, Ping

    2016-06-21

    To investigate the efficacy and safety of adjuvant sorafenib after curative resection for patients with Barcelona Clinic Liver Cancer (BCLC)-stage C hepatocellular carcinoma (HCC). Thirty-four HCC patients, classified as BCLC-stage C, received adjuvant sorafenib for high-risk of tumor recurrence after curative hepatectomy at a tertiary care university hospital. The study group was compared with a case-matched control group of 68 patients who received curative hepatectomy for HCC during the study period in a 1:2 ratio. The tumor recurrence rate was markedly lower in the sorafenib group (15/34, 44.1%) than in the control group (51/68, 75%, P = 0.002). The median disease-free survival was 12 mo in the study group and 10 mo in the control group. Tumor number more than 3, macrovascular invasion, hilar lymph nodes metastasis, and treatment with sorafenib were signi