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Sample records for pancreatitis trial protocol

  1. ChroPac-Trial: Duodenum-preserving pancreatic head resection versus pancreatoduodenectomy for chronic pancreatitis. Trial protocol of a randomised controlled multicentre trial

    Directory of Open Access Journals (Sweden)

    Schlitt Hans

    2010-04-01

    Full Text Available Abstract Background A recently published systematic review indicated superiority of duodenum-preserving techniques when compared with pancreatoduodenectomy, for the treatment of patients with chronic pancreatitis in the head of the gland. A multicentre randomised trial to confirm these results is needed. Methods/Design ChroPac aims to investigate differences in quality of life, mortality and morbidity during 24 months after surgery (duodenum-preserving pancreatic head resection versus pancreatoduodenectomy in patients with chronic pancreatitis of the pancreatic head. ChroPac is a randomised, controlled, observer and patient blinded multicentre surgical trial with two parallel comparison groups. The primary outcome measure will be the average quality of life during 24 months after surgery. Statistical analysis is based on the intention-to-treat population. Analysis of covariance will be applied for the intervention group comparison adjusting for age, centre and quality of life before surgery. Level of significance is set at 5% (two-sided and sample size (n = 100 per group is determined to assure a power of 90%. Discussion The ChroPac trial will explore important outcomes from different perspectives (e.g. surgeon, patient, health care system. Its pragmatic approach promises high external validity allowing a comprehensive evaluation of the surgical strategy for treatment of patients with chronic pancreatitis. Trial registration Controlled-trials.com ISRCTN38973832

  2. Pancreatitis of biliary origin, optimal timing of cholecystectomy (PONCHO trial: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Bouwense Stefan A

    2012-11-01

    Full Text Available Abstract Background After an initial attack of biliary pancreatitis, cholecystectomy minimizes the risk of recurrent biliary pancreatitis and other gallstone-related complications. Guidelines advocate performing cholecystectomy within 2 to 4 weeks after discharge for mild biliary pancreatitis. During this waiting period, the patient is at risk of recurrent biliary events. In current clinical practice, surgeons usually postpone cholecystectomy for 6 weeks due to a perceived risk of a more difficult dissection in the early days following pancreatitis and for logistical reasons. We hypothesize that early laparoscopic cholecystectomy minimizes the risk of recurrent biliary pancreatitis or other complications of gallstone disease in patients with mild biliary pancreatitis without increasing the difficulty of dissection and the surgical complication rate compared with interval laparoscopic cholecystectomy. Methods/Design PONCHO is a randomized controlled, parallel-group, assessor-blinded, superiority multicenter trial. Patients are randomly allocated to undergo early laparoscopic cholecystectomy, within 72 hours after randomization, or interval laparoscopic cholecystectomy, 25 to 30 days after randomization. During a 30-month period, 266 patients will be enrolled from 18 hospitals of the Dutch Pancreatitis Study Group. The primary endpoint is a composite endpoint of mortality and acute re-admissions for biliary events (that is, recurrent biliary pancreatitis, acute cholecystitis, symptomatic/obstructive choledocholithiasis requiring endoscopic retrograde cholangiopancreaticography including cholangitis (with/without endoscopic sphincterotomy, and uncomplicated biliary colics occurring within 6 months following randomization. Secondary endpoints include the individual endpoints of the composite endpoint, surgical and other complications, technical difficulty of cholecystectomy and costs. Discussion The PONCHO trial is designed to show that early

  3. Rectally administered indomethacin to prevent post-ESWL-pancreatitis (RIPEP): study protocol for a randomized controlled trial.

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    Qian, Yang-Yang; Chen, Hui; Tang, Xin-Ying; Jiang, Xi; Qian, Wei; Zou, Wen-Bin; Xin, Lei; Li, Bo; Qi, Yan-Fen; Hu, Liang-Hao; Zou, Duo-Wu; Jin, Zhen-Dong; Wang, Dong; Du, Yi-Qi; Wang, Luo-Wei; Liu, Feng; Li, Zhao-Shen; Liao, Zhuan

    2017-11-02

    Pancreatic extracorporeal shock wave lithotripsy (P-ESWL) is the first-line therapy for large pancreatic duct stones. Although it is a highly effective and safe procedure for the fragmentation of pancreatic stones, it is still not complication-free. Just like endoscopic retrograde cholangiopancreatography (ERCP), pancreatitis is the most common complication. To date, nonsteroidal anti-inflammatory drugs (NSAIDs) have proven to be the only effective prophylactic medication for post-ERCP pancreatitis and the European, American and Japanese Society for Gastrointestinal Endoscopy guidelines have recommended prophylactic rectally administered indomethacin for all patients undergoing ERCP. Given the little research about effective prevention for post P-ESWL pancreatitis, we aim to determine whether rectally administered indomethacin can reduce post-ESWL-pancreatitis. The RIPEP study is a prospective, randomized, double-blinded, placebo-controlled trial. One thousand three hundred and seventy patients with chronic pancreatitis and pancreatic stones (>5 mm in diameter) treated with P-ESWL at Changhai Hospital will be randomly allocated to rectally administered indomethacin or placebo therapy before the procedure. The primary endpoint is the incidence of post-ESWL pancreatitis. Secondary endpoints include the severity of pancreatitis, occurrence rate of asymptomatic hyperamylasemia and other complications. The RIPEP trial is designed to show that rectally administered indomethacin reduces the development and severity of post-ESWL pancreatitis and benefits patients treated with P-ESWL. ClinicalTrials.gov, ID: NCT02797067 . Registered on 17 November 2016.

  4. Pancreatic cancer clinical trials and accrual in the United States.

    Science.gov (United States)

    Hoos, William A; James, Porsha M; Rahib, Lola; Talley, Anitra W; Fleshman, Julie M; Matrisian, Lynn M

    2013-09-20

    Pancreatic cancer clinical trials open in the United States and their accrual were examined to identify opportunities to accelerate progress in the treatment of pancreatic cancer. Pancreatic cancer-specific clinical trials open in the United States in the years 2011 and 2012 were obtained from the Pancreatic Cancer Action Network database. Accrual information was obtained from trial sponsors. The portfolio of pancreatic cancer clinical trials identified by type (adenocarcinoma or neuroendocrine), phase, disease stage, and treatment approach is reported. More than half of trials for patients with pancreatic ductal adenocarcinoma applied biologic insights to new therapeutic approaches, and 38% focused on optimization of radiation or chemotherapy delivery or regimens. In 2011, pancreatic cancer trials required total enrollment of 11,786 patients. Actual accrual to 93.2% of trials was 1,804 patients, an estimated 4.57% of the patients with pancreatic cancer alive in that year. The greatest need was for patients with resectable cancer. Trials open in 2011 enrolled an average of 15% of their total target accrual. Physician recommendations greatly influenced patients' decision to enroll or not enroll onto a clinical trial. Matching to a clinical trial within a 50-mile radius and identifying trials for recurrent/refractory disease were documented as challenges for patient accrual. Overall trial enrollment indicates that pancreatic cancer trials open in 2011 would require 6.7 years on average to complete accrual. These results suggest that harmonizing patient supply and demand for clinical trials is required to accelerate progress toward improving survival in pancreatic cancer.

  5. Acute pancreatitis: recent advances through randomised trials.

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    van Dijk, Sven M; Hallensleben, Nora D L; van Santvoort, Hjalmar C; Fockens, Paul; van Goor, Harry; Bruno, Marco J; Besselink, Marc G

    2017-11-01

    Acute pancreatitis is one of the most common GI conditions requiring acute hospitalisation and has a rising incidence. In recent years, important insights on the management of acute pancreatitis have been obtained through numerous randomised controlled trials. Based on this evidence, the treatment of acute pancreatitis has gradually developed towards a tailored, multidisciplinary effort, with distinctive roles for gastroenterologists, radiologists and surgeons. This review summarises how to diagnose, classify and manage patients with acute pancreatitis, emphasising the evidence obtained through randomised controlled trials. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  6. A phase-I trial of pre‐operative, margin intensive, stereotactic body radiation therapy for pancreatic cancer: the ‘SPARC’ trial protocol

    International Nuclear Information System (INIS)

    Holyoake, Daniel L. P.; Ward, Elizabeth; Grose, Derek; McIntosh, David; Sebag-Montefiore, David; Radhakrishna, Ganesh; Patel, Neel; Silva, Michael; Mukherjee, Somnath; Strauss, Victoria Y.; Odondi, Lang’o; Fokas, Emmanouil; Melcher, Alan; Hawkins, Maria A.

    2016-01-01

    analyses of the cytological and humoral immunological responses to stereotactic radiotherapy in pancreatic cancer. Radiotherapy quality assurance of target definition and radiotherapy planning is enforced with pre-trial test cases and on-trial review. Recruitment began in April 2015. This prospective multi-centre study aims to establish the maximum tolerated dose of pre-operative margin-intensified stereotactic radiotherapy in pancreatic cancer at high risk of positive resection margins with a view to subsequent definitive comparison with other neoadjuvant treatment options

  7. Duodenum preserving pancreatectomy in chronic pancreatitis: Design of a randomized controlled trial comparing two surgical techniques [ISRCTN50638764

    Directory of Open Access Journals (Sweden)

    Reidel Margot A

    2006-05-01

    Full Text Available Abstract Background Chronic pancreatitis is an inflammatory disease which is characterized by an irreversible conversion of pancreatic parenchyma to fibrous tissue. Beside obstructive jaundice and pseudocyst formation, about half of the patients need surgical intervention due to untreatable chronic pain during the course of the disease. In most of the patients with chronic pancreatitis, the head of the pancreas is the trigger of the chronic inflammatory process. Therefore, resection of pancreatic head tissue must be the central part of any surgical intervention. However, it is unclear to which extent the surgical procedure must be radical in order to obtain a favourable outcome for the patients. Design A single centre randomized controlled, superiority trial to compare two techniques of duodenum preserving pancreatic head resection. Sample size: 65 patients will be included and randomized intraoperatively. Eligibility criteria: All patients with chronic pancreatitis and indication for surgical resection and signed informed consent. Cumulative primary endpoint (hierarchical model: duration of surgical procedure, quality of life after one year, duration of intensive care unit stay, duration of hospital stay. Reference treatment: Resection of the pancreatic head with dissection of the pancreas from the portal vein and transsection of the gland (Beger procedure. Intervention: Partial Resection of the pancreatic head without transsection of the organ and visualization of the portal vein (Berne procedure. Duration: September 2003-October 2007. Organisation/responsibility The trial is conducted in compliance with the protocol and in accordance with the moral, ethical, regulatory and scientific principles governing clinical research as set out in the Declaration of Helsinki (1989 and the Good Clinical Practice guideline (GCP. The Center for Clinical Studies of the Department of Surgery Heidelberg is responsible for planning, conducting and final

  8. Comparison of investigator-delineated gross tumor volumes and quality assurance in pancreatic cancer: Analysis of the pretrial benchmark case for the SCALOP trial.

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    Fokas, Emmanouil; Clifford, Charlotte; Spezi, Emiliano; Joseph, George; Branagan, Jennifer; Hurt, Chris; Nixon, Lisette; Abrams, Ross; Staffurth, John; Mukherjee, Somnath

    2015-12-01

    To evaluate the variation in investigator-delineated volumes and assess plans from the radiotherapy trial quality assurance (RTTQA) program of SCALOP, a phase II trial in locally advanced pancreatic cancer. Participating investigators (n=25) outlined a pre-trial benchmark case as per RT protocol, and the accuracy of investigators' GTV (iGTV) and PTV (iPTV) was evaluated, against the trials team-defined gold standard GTV (gsGTV) and PTV (gsPTV), using both qualitative and geometric analyses. The median Jaccard Conformity Index (JCI) and Geographical Miss Index (GMI) were calculated. Participating RT centers also submitted a radiotherapy plan for this benchmark case, which was centrally reviewed against protocol-defined constraints. Twenty-five investigator-defined contours were evaluated. The median JCI and GMI of iGTVs were 0.57 (IQR: 0.51-0.65) and 0.26 (IQR: 0.15-0.40). For iPTVs, these were 0.75 (IQR: 0.71-0.79) and 0.14 (IQR: 0.11-0.22) respectively. Qualitative analysis showed largest variation at the tumor edges and failure to recognize a peri-pancreatic lymph node. There were no major protocol deviations in RT planning, but three minor PTV coverage deviations were identified. . SCALOP demonstrated considerable variation in iGTV delineation. RTTQA workshops and real-time central review of delineations are needed in future trials. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  9. Fluid hydration to prevent post-ERCP pancreatitis in average- to high-risk patients receiving prophylactic rectal NSAIDs (FLUYT trial): study protocol for a randomized controlled trial.

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    Smeets, Xavier J N M; da Costa, David W; Fockens, Paul; Mulder, Chris J J; Timmer, Robin; Kievit, Wietske; Zegers, Marieke; Bruno, Marco J; Besselink, Marc G H; Vleggaar, Frank P; van der Hulst, Rene W M; Poen, Alexander C; Heine, Gerbrand D N; Venneman, Niels G; Kolkman, Jeroen J; Baak, Lubbertus C; Römkens, Tessa E H; van Dijk, Sven M; Hallensleben, Nora D L; van de Vrie, Wim; Seerden, Tom C J; Tan, Adriaan C I T L; Voorburg, Annet M C J; Poley, Jan-Werner; Witteman, Ben J; Bhalla, Abha; Hadithi, Muhammed; Thijs, Willem J; Schwartz, Matthijs P; Vrolijk, Jan Maarten; Verdonk, Robert C; van Delft, Foke; Keulemans, Yolande; van Goor, Harry; Drenth, Joost P H; van Geenen, Erwin J M

    2018-04-02

    Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common complication of ERCP and may run a severe course. Evidence suggests that vigorous periprocedural hydration can prevent PEP, but studies to date have significant methodological drawbacks. Importantly, evidence for its added value in patients already receiving prophylactic rectal non-steroidal anti-inflammatory drugs (NSAIDs) is lacking and the cost-effectiveness of the approach has not been investigated. We hypothesize that combination therapy of rectal NSAIDs and periprocedural hydration would significantly lower the incidence of post-ERCP pancreatitis compared to rectal NSAIDs alone in moderate- to high-risk patients undergoing ERCP. The FLUYT trial is a multicenter, parallel group, open label, superiority randomized controlled trial. A total of 826 moderate- to high-risk patients undergoing ERCP that receive prophylactic rectal NSAIDs will be randomized to a control group (no fluids or normal saline with a maximum of 1.5 mL/kg/h and 3 L/24 h) or intervention group (lactated Ringer's solution with 20 mL/kg over 60 min at start of ERCP, followed by 3 mL/kg/h for 8 h thereafter). The primary endpoint is the incidence of post-ERCP pancreatitis. Secondary endpoints include PEP severity, hydration-related complications, and cost-effectiveness. The FLUYT trial design, including hydration schedule, fluid type, and sample size, maximize its power of identifying a potential difference in post-ERCP pancreatitis incidence in patients receiving prophylactic rectal NSAIDs. EudraCT: 2015-000829-37 . Registered on 18 February 2015. 13659155 . Registered on 18 May 2015.

  10. Targeted agents for patients with advanced/metastatic pancreatic cancer: A protocol for systematic review and network meta-analysis.

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    Di, Baoshan; Pan, Bei; Ge, Long; Ma, Jichun; Wu, Yiting; Guo, Tiankang

    2018-03-01

    Pancreatic cancer (PC) is a devastating malignant tumor. Although surgical resection may offer a good prognosis and prolong survival, approximately 80% patients with PC are always diagnosed as unresectable tumor. National Comprehensive Cancer Network's (NCCN) recommended gemcitabine-based chemotherapy as efficient treatment. While, according to recent studies, targeted agents might be a better available option for advanced or metastatic pancreatic cancer patients. The aim of this systematic review and network meta-analysis will be to examine the differences of different targeted interventions for advanced/metastatic PC patients. We will conduct this systematic review and network meta-analysis using Bayesian method and according to Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement. To identify relevant studies, 6 electronic databases including PubMed, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of science, CNKI (Chinese National Knowledge Infrastructure), and CBM (Chinese Biological Medical Database) will be searched. The risk of bias in included randomized controlled trials (RCTs) will be assessed using the Cochrane Handbook version 5.1.0. And we will use GRADE approach to assess the quality of evidence from network meta-analysis. Data will be analyzed using R 3.4.1 software. To the best of our knowledge, this systematic review and network meta-analysis will firstly use both direct and indirect evidence to compare the differences of different targeted agents and targeted agents plus chemotherapy for advanced/metastatic pancreatic cancer patients. This is a protocol of systematic review and meta-analysis, so the ethical approval and patient consent are not required. We will disseminate the results of this review by submitting to a peer-reviewed journal.

  11. SU-E-J-07: A Functional MR Protocol for the Pancreatic Tumor Delineation

    International Nuclear Information System (INIS)

    Andreychenko, A; Heerkens, H; Meijer, G; Vulpen, M van; Lagendijk, J; Berg, C van den

    2014-01-01

    Purpose: Pancreatic cancer is one of the cancers with the poorest survival prognosis. At the time of diagnosis most of pancreatic cancers are unresectable and those patients can be treated by radiotherapy. Radiotherapy for pancreatic cancer is limited due to uncertainties in CT-based delineations. MRI provides an excellent soft tissue contrast. Here, an MR protocol is developed to improve delineations for radiotherapy treatment of pancreatic cancer. In a later stage this protocol can also be used for on-line visualization of the pancreas during MRI guided treatments. Methods: Nine pancreatic cancer patients were included. The MR protocol included T2 weighted(T2w), T1 weighted(T1w), diffusion weighted(DWI) and dynamic contrast enhanced(DCE) techniques. The tumor was delineated on T2w and T1w MRI by an experienced radiation oncologist. Healthy pancreas or pancreatitis (assigned by the oncologist based on T2w) areas were also delineated. Apparent diffusion coefficient(ADC), and area under the curve(AUC)/time to peak(TTP) maps were obtained from DWI and DCE scans, respectively. Results: A clear demarcation of tumor area was visible on b800 DWI images in 5 patients. ADC maps of those patients characterized tumor as an area with restricted water diffusion. Tumor delineations based on solely DCE were possible in 7 patients. In 6 of those patients AUC maps demonstrated tumor heterogeneity: a hypointense area with a hyperintense ring. TTP values clearly discriminated the tumor and the healthy pancreas but could not distinguish tumor and the pancreatitis accurately. Conclusion: MR imaging results in a more pronounced tumor contrast than contrast enhanced CT. The addition of quantitative, functional MRI provides valuable, additional information to the radiation oncologist on the spatial tumor extent by discriminating tumor from the healthy pancreas(TTP, DWI) and characterizing the tumor(ADC). Our findings indicate that tumor delineation in pancreatic cancer can greatly

  12. SU-E-J-07: A Functional MR Protocol for the Pancreatic Tumor Delineation

    Energy Technology Data Exchange (ETDEWEB)

    Andreychenko, A; Heerkens, H; Meijer, G; Vulpen, M van; Lagendijk, J; Berg, C van den [UMC Utrecht, Utrecht, Utrecht (Netherlands)

    2014-06-01

    Purpose: Pancreatic cancer is one of the cancers with the poorest survival prognosis. At the time of diagnosis most of pancreatic cancers are unresectable and those patients can be treated by radiotherapy. Radiotherapy for pancreatic cancer is limited due to uncertainties in CT-based delineations. MRI provides an excellent soft tissue contrast. Here, an MR protocol is developed to improve delineations for radiotherapy treatment of pancreatic cancer. In a later stage this protocol can also be used for on-line visualization of the pancreas during MRI guided treatments. Methods: Nine pancreatic cancer patients were included. The MR protocol included T2 weighted(T2w), T1 weighted(T1w), diffusion weighted(DWI) and dynamic contrast enhanced(DCE) techniques. The tumor was delineated on T2w and T1w MRI by an experienced radiation oncologist. Healthy pancreas or pancreatitis (assigned by the oncologist based on T2w) areas were also delineated. Apparent diffusion coefficient(ADC), and area under the curve(AUC)/time to peak(TTP) maps were obtained from DWI and DCE scans, respectively. Results: A clear demarcation of tumor area was visible on b800 DWI images in 5 patients. ADC maps of those patients characterized tumor as an area with restricted water diffusion. Tumor delineations based on solely DCE were possible in 7 patients. In 6 of those patients AUC maps demonstrated tumor heterogeneity: a hypointense area with a hyperintense ring. TTP values clearly discriminated the tumor and the healthy pancreas but could not distinguish tumor and the pancreatitis accurately. Conclusion: MR imaging results in a more pronounced tumor contrast than contrast enhanced CT. The addition of quantitative, functional MRI provides valuable, additional information to the radiation oncologist on the spatial tumor extent by discriminating tumor from the healthy pancreas(TTP, DWI) and characterizing the tumor(ADC). Our findings indicate that tumor delineation in pancreatic cancer can greatly

  13. Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol

    DEFF Research Database (Denmark)

    Raja, Raheel A; Schmiegelow, Kjeld; Albertsen, BK

    2014-01-01

    L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re-exposure to L-asparginase after pancreatitis and risk of recurrent pancreatitis...... within an asparaginase-intensive protocol has been poorly reported. Children (1-17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase-associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO...... ALL toxicity registry. NOPHO ALL2008 includes eight or 15 doses of intramuscular pegylated L-asparginase (PEG-asparaginase) 1000 iu/m(2) /dose at 2-6 weeks intervals, with a total of 30 weeks of exposure to PEG-asparaginase (clinicaltrials.gov no: NCT00819351). Of 786 children, 45 were diagnosed...

  14. Stem cell Transplantation for Eradication of Minimal PAncreatic Cancer persisting after surgical Excision (STEM PACE Trial, ISRCTN47877138): study protocol for a phase II study

    International Nuclear Information System (INIS)

    Schmitz-Winnenthal, Friedrich H; Schmidt, Thomas; Lehmann, Monika; Beckhove, Philipp; Kieser, Meinhard; Ho, Anthony D; Dreger, Peter; Büchler, Markus W

    2014-01-01

    Pancreatic cancer is the third most common cancer related cause of death. Even in the 15% of patients who are eligible for surgical resection the outlook is dismal with less than 10% of patients surviving after 5 years. Allogeneic hematopoietic (allo-HSCT) stem cell transplantation is an established treatment capable of to providing cure in a variety of hematopoietic malignancies. Best results are achieved when the underlying neoplasm has been turned into a stage of minimal disease by chemotherapy. Allo-HSCT in advanced solid tumors including pancreatic cancer have been of limited success, however studies of allo-HSCT in solid tumors in minimal disease situations have never been performed. The aim of this trial is to provide evidence for the clinical value of allo-HSCT in pancreatic cancer put into a minimal disease status by effective surgical resection and standard adjuvant chemotherapy. The STEM PACE trial is a single center, phase II study to evaluate adjuvant allogeneic hematopoietic stem cell transplantation in pancreatic cancer after surgical resection. The study will evaluate as primary endpoint 2 year progression free survival and will generate first time state-of-the-art scientific clinical evidence if allo-HSCT is feasible and if it can provide long term disease control in patients with effectively resected pancreatic cancer. Screened eligible patients after surgical resection and standard adjuvant chemotherapy with HLA matched related stem cell donor can participate. Patients without a matched donor will be used as a historical control. Study patients will undergo standard conditioning for allo-HSCT followed by transplantation of allogeneic unmanipulated peripheral blood stem cells. The follow up of the patients will continue for 2 years. Secondary endpoints will be evaluated on 7 postintervention visits. The principal question addressed in this trial is whether allo-HSCT can change the unfavourable natural course of this disease. The underlying

  15. A randomized trial of rectal indomethacin to prevent post-ERCP pancreatitis.

    Science.gov (United States)

    Elmunzer, B Joseph; Scheiman, James M; Lehman, Glen A; Chak, Amitabh; Mosler, Patrick; Higgins, Peter D R; Hayward, Rodney A; Romagnuolo, Joseph; Elta, Grace H; Sherman, Stuart; Waljee, Akbar K; Repaka, Aparna; Atkinson, Matthew R; Cote, Gregory A; Kwon, Richard S; McHenry, Lee; Piraka, Cyrus R; Wamsteker, Erik J; Watkins, James L; Korsnes, Sheryl J; Schmidt, Suzette E; Turner, Sarah M; Nicholson, Sylvia; Fogel, Evan L

    2012-04-12

    Preliminary research suggests that rectally administered nonsteroidal antiinflammatory drugs may reduce the incidence of pancreatitis after endoscopic retrograde cholangiopancreatography (ERCP). In this multicenter, randomized, placebo-controlled, double-blind clinical trial, we assigned patients at elevated risk for post-ERCP pancreatitis to receive a single dose of rectal indomethacin or placebo immediately after ERCP. Patients were determined to be at high risk on the basis of validated patient- and procedure-related risk factors. The primary outcome was post-ERCP pancreatitis, which was defined as new upper abdominal pain, an elevation in pancreatic enzymes to at least three times the upper limit of the normal range 24 hours after the procedure, and hospitalization for at least 2 nights. A total of 602 patients were enrolled and completed follow-up. The majority of patients (82%) had a clinical suspicion of sphincter of Oddi dysfunction. Post-ERCP pancreatitis developed in 27 of 295 patients (9.2%) in the indomethacin group and in 52 of 307 patients (16.9%) in the placebo group (P=0.005). Moderate-to-severe pancreatitis developed in 13 patients (4.4%) in the indomethacin group and in 27 patients (8.8%) in the placebo group (P=0.03). Among patients at high risk for post-ERCP pancreatitis, rectal indomethacin significantly reduced the incidence of the condition. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT00820612.).

  16. Incidental pancreatic cysts: natural history and diagnostic accuracy of a limited serial pancreatic cyst MRI protocol

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    Nougaret, Stephanie; Escal, Laure; Guiu, Boris [Saint Eloi University Hospital, Department of Abdominal Imaging, Montpellier Cedex 5 (France); Reinhold, Caroline; Chong, Jaron [McGill University, Department of Abdominal Imaging, MUHC, Montreal (Canada); Mercier, Gregoire; Molinari, Nicolas [CHU Montpellier, Department of Biostatistics, Montpellier (France); Fabre, Jean Michel [CHU Montpellier, Department of Surgery, Saint Eloi University Hospital, Montpellier (France)

    2014-05-15

    To examine the natural history of incidentally detected pancreatic cysts and whether a simplified MRI protocol without gadolinium is adequate for lesion follow-up. Over a 10-year period, 301-patients with asymptomatic pancreatic cysts underwent follow-up (45 months ± 30). The magnetic resonance imaging (MRI) protocol included axial, coronal T2-weighted images, MR cholangiopancreatographic and fat suppressed T1-weighted sequences before and after gadolinium. Three radiologists independently reviewed the initial MRI, the follow-up studies using first only unenhanced images, then secondly gadolinium-enhanced-sequences. Lesion changes during follow-up were recorded and the added value of gadolinium-enhanced sequences was determined by classifying the lesions into risk categories. Three hundred and one patients (1,174 cysts) constituted the study population. Only 35/301 patients (12 %) showed significant lesion change on follow-up. Using multivariate analysis the only independent factor of lesion growth (OR = 2.4; 95 % CI, 1.7-3.3; P < 0.001) and mural nodule development (OR = 1.9; 95 % CI, 1.1-3.4, P = 0.03) during follow-up was initial lesion size. No patient with a lesion initial size less than 2 cm developed cancer during follow-up. Intra-observer agreement with and without gadolinium enhancement ranged from 0.86 to 0.97. After consensus review of discordant cases, gadolinium-enhanced sequences demonstrated no added value. Most incidental pancreatic cystic lesions did not demonstrate change during follow-up. The addition of gadolinium-enhanced-sequences had no added-value for risk assignment on serial follow-up. (orig.)

  17. Quality assurance of the PREOPANC trial (2012-003181-40) for preoperative radiochemotherapy in pancreatic cancer. The dummy run

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    Versteijne, Eva; Lens, Eelco; Horst, Astrid van der; Bel, Arjan; Visser, Jorrit; Tienhoven, Geertjan van [Academic Medical Center, University of Amsterdam, Department of Radiation Oncology, Amsterdam (Netherlands); Punt, Cornelis J.A. [Academic Medical Center, University of Amsterdam, Department of Medical Oncology, Amsterdam (Netherlands); Suker, Mustafa; Eijck, Casper H.J. van [Erasmus Medical Center, Erasmus University, Department of Surgery, Rotterdam (Netherlands)

    2017-08-15

    The Dutch Pancreatic Cancer Group initiated the national, multicentre, controlled PREOPANC trial, randomising between preoperative radiochemotherapy and direct explorative laparotomy for patients with (borderline) resectable pancreatic cancer. The aim of this dummy run is to evaluate compliance with the radiotherapy protocol of this trial, and the quality of delineation and radiation plans. Eleven radiation oncology departments open for accrual of patients in the PREOPANC trial were provided with all necessary information of a selected 'dummy' patient. Each institute was asked to delineate the target volumes, including gross tumour volume, internal gross tumour volume (iGTV), internal clinical target volume, and planning target volume. The institutions were also asked to provide a radiation treatment plan in accordance with the PREOPANC trial protocol. The range of the iGTV was 19.3-77.2 cm{sup 3} with a mean iGTV of 41.5 cm{sup 3} (standard deviation 14.8 cm{sup 3}). Nine institutions made a treatment plan using an arc technique for treatment delivery, one an intensity modulated technique and one a 3-field conformal technique. All institutions reached the prescribed target coverage, without exceeding the organs at risk constraints. The institution with the 3-field conformal technique was advised to use a more sophisticated technique (e. g. volumetric modulated arc therapy) to reduce the dose to the spinal cord. All institutions showed acceptable deviations from the PREOPANC trial protocol and achieved an acceptable quality of delineation and radiation technique. All institutions were allowed to continue participation in the PREOPANC trial. (orig.) [German] Die niederlaendische Gruppe fuer Bauchspeicheldruesenkrebs (Dutch Pancreatic Cancer Group, DPCG) initiierte die nationale und multizentral kontrollierte PREOPANC-Studie, worin die praeoperative Radiochemotherapie mit der direkten explorativen Laparotomie fuer Patienten mit (grenzwertig) resektablen

  18. SPIRIT 2013 Statement: defining standard protocol items for clinical trials.

    Science.gov (United States)

    Chan, An-Wen; Tetzlaff, Jennifer M; Altman, Douglas G; Laupacis, Andreas; Gøtzsche, Peter C; Krle A-Jerić, Karmela; Hrobjartsson, Asbjørn; Mann, Howard; Dickersin, Kay; Berlin, Jesse A; Dore, Caroline J; Parulekar, Wendy R; Summerskill, William S M; Groves, Trish; Schulz, Kenneth F; Sox, Harold C; Rockhold, Frank W; Rennie, Drummond; Moher, David

    2015-12-01

    The protocol of a clinical trial serves as the foundation for study planning, conduct, reporting, and appraisal. However, trial protocols and existing protocol guidelines vary greatly in content and quality. This article describes the systematic development and scope of SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) 2013, a guideline for the minimum content of a clinical trial protocol. The 33-item SPIRIT checklist applies to protocols for all clinical trials and focuses on content rather than format. The checklist recommends a full description of what is planned; it does not prescribe how to design or conduct a trial. By providing guidance for key content, the SPIRIT recommendations aim to facilitate the drafting of high-quality protocols. Adherence to SPIRIT would also enhance the transparency and completeness of trial protocols for the benefit of investigators, trial participants, patients, sponsors, funders, research ethics committees or institutional review boards, peer reviewers, journals, trial registries, policymakers, regulators, and other key stakeholders.

  19. Study protocol for a randomised, double-blinded, placebo-controlled, clinical trial of S-ketamine for pain treatment in patients with chronic pancreatitis (RESET trial).

    Science.gov (United States)

    Juel, Jacob; Olesen, Søren Schou; Olesen, Anne Estrup; Poulsen, Jakob Lykke; Dahan, Albert; Wilder-Smith, Oliver; Madzak, Adnan; Frøkjær, Jens Brøndum; Drewes, Asbjørn Mohr

    2015-03-10

    Chronic pancreatitis (CP) is an inflammatory disease that causes irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In the absence of pathology suitable for endoscopic or surgical interventions, pain treatment usually includes opioids. However, opioids often have limited efficacy. Moreover, side effects are common and bothersome. Hence, novel approaches to control pain associated with CP are highly desirable. Sensitisation of the central nervous system is reported to play a key role in pain generation and chronification. Fundamental to the process of central sensitisation is abnormal activation of the N-methyl-D-aspartate receptor, which can be antagonised by S-ketamine. The RESET trial is investigating the analgaesic and antihyperalgesic effect of S-ketamine in patients with CP. 40 patients with CP will be enrolled. Patients are randomised to receive 8 h of intravenous S-ketamine followed by oral S-ketamine, or matching placebo, for 4 weeks. To improve blinding, 1 mg of midazolam will be added to active and placebo treatment. The primary end point is clinical pain relief as assessed by a daily pain diary. Secondary end points include changes in patient-reported outcome measures, opioid consumption and rates of side effects. The end points are registered through the 4-week medication period and for an additional follow-up period of 8 weeks to investigate long-term effects. In addition, experimental pain measures also serves as secondary end points, and neurophysiological imaging parameters are collected. Furthermore, experimental baseline recordings are compared to recordings from a group of healthy controls to evaluate general aspects of pain processing in CP. The protocol is approved by the North Denmark Region Committee on Health Research Ethics (N-20130040) and the Danish Health and Medicines Authorities (EudraCT number: 2013-003357-17). The results will be disseminated in peer-reviewed journals and at scientific conferences

  20. A percutaneous drainage protocol for severe and moderately severe acute pancreatitis.

    Science.gov (United States)

    Sugimoto, Motokazu; Sonntag, David P; Flint, Greggory S; Boyce, Cody J; Kirkham, John C; Harris, Tyler J; Carr, Sean M; Nelson, Brent D; Barton, Joshua G; Traverso, L William

    2015-11-01

    According to the revised Atlanta classification, severe and moderately severe acute pancreatitis (AP) includes patients with pancreatic and peripancreatic collections with or without organ failure. These collections suggest the presence of pancreatic juice leakage. The aim of this study was to evaluate the efficacy of a percutaneous catheter drainage (PCD) protocol designed to control leakage and decrease disease severity. Among 663 patients with clinical AP, 122 were classified as moderately severe or severe AP (all had collections). The computed tomography severity index (CTSI) score was calculated. The indication for PCD was based on progressive clinical signs and symptoms. Drain patency, position, and need for additional drainage sites were assessed using CT scans and drain studies initially every 3 days using a proactive protocol. Drain fluid was examined for amylase concentration and microbiological culture. Clinicopathological variables for patients with and without PCD were compared. Since there was no mortality, we used prolonged drainage time to measure the success of PCD. Within the group treated with PCD, variables that resulted in prolonged drainage time were analyzed. PCD was used in 47/122 (39 %) patients of which 33/47 (70 %) had necrosis. PCD cases had a median CTSI of 8 and were classified as moderately severe AP (57 %) and severe AP (43 %). Inhospital mortality was zero. Surgical necrosectomy was not required for patients with necrosis. Independent risk factors for prolonged drainage time were persistent organ failure >48 h (P = 0.001), CTSI 8-10 (P = 0.038), prolonged duration of amylase-rich fluid in drains (P drainage fluid resulting in a mortality rate of zero.

  1. Subgroup analyses in randomised controlled trials: cohort study on trial protocols and journal publications.

    Science.gov (United States)

    Kasenda, Benjamin; Schandelmaier, Stefan; Sun, Xin; von Elm, Erik; You, John; Blümle, Anette; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J; Stegert, Mihaela; Olu, Kelechi K; Tikkinen, Kari A O; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M; Mertz, Dominik; Akl, Elie A; Bassler, Dirk; Busse, Jason W; Ferreira-González, Ignacio; Lamontagne, Francois; Nordmann, Alain; Gloy, Viktoria; Raatz, Heike; Moja, Lorenzo; Rosenthal, Rachel; Ebrahim, Shanil; Vandvik, Per O; Johnston, Bradley C; Walter, Martin A; Burnand, Bernard; Schwenkglenks, Matthias; Hemkens, Lars G; Bucher, Heiner C; Guyatt, Gordon H; Briel, Matthias

    2014-07-16

    To investigate the planning of subgroup analyses in protocols of randomised controlled trials and the agreement with corresponding full journal publications. Cohort of protocols of randomised controlled trial and subsequent full journal publications. Six research ethics committees in Switzerland, Germany, and Canada. 894 protocols of randomised controlled trial involving patients approved by participating research ethics committees between 2000 and 2003 and 515 subsequent full journal publications. Of 894 protocols of randomised controlled trials, 252 (28.2%) included one or more planned subgroup analyses. Of those, 17 (6.7%) provided a clear hypothesis for at least one subgroup analysis, 10 (4.0%) anticipated the direction of a subgroup effect, and 87 (34.5%) planned a statistical test for interaction. Industry sponsored trials more often planned subgroup analyses compared with investigator sponsored trials (195/551 (35.4%) v 57/343 (16.6%), P<0.001). Of 515 identified journal publications, 246 (47.8%) reported at least one subgroup analysis. In 81 (32.9%) of the 246 publications reporting subgroup analyses, authors stated that subgroup analyses were prespecified, but this was not supported by 28 (34.6%) corresponding protocols. In 86 publications, authors claimed a subgroup effect, but only 36 (41.9%) corresponding protocols reported a planned subgroup analysis. Subgroup analyses are insufficiently described in the protocols of randomised controlled trials submitted to research ethics committees, and investigators rarely specify the anticipated direction of subgroup effects. More than one third of statements in publications of randomised controlled trials about subgroup prespecification had no documentation in the corresponding protocols. Definitive judgments regarding credibility of claimed subgroup effects are not possible without access to protocols and analysis plans of randomised controlled trials. © The DISCO study group 2014.

  2. Asparaginase-associated pancreatitis: a study on phenotype and genotype in the NOPHO ALL2008 protocol

    DEFF Research Database (Denmark)

    Wolthers, B. O.; Frandsen, Thomas L.; Abrahamsson, Jonas

    2016-01-01

    Asparaginase (ASP)-associated pancreatitis (AAP) occurs during acute lymphoblastic leukemia treatment. Among 1285 children (1.0-17.9 years) diagnosed during July 2008-December 2014 and treated according to the Nordic/Baltic ALL2008 protocol, 86 (cumulative incidence = 6.8%) developed AAP. Seventy...

  3. Early surgery versus optimal current step-up practice for chronic pancreatitis (ESCAPE): design and rationale of a randomized trial.

    Science.gov (United States)

    Ahmed Ali, Usama; Issa, Yama; Bruno, Marco J; van Goor, Harry; van Santvoort, Hjalmar; Busch, Olivier R C; Dejong, Cornelis H C; Nieuwenhuijs, Vincent B; van Eijck, Casper H; van Dullemen, Hendrik M; Fockens, Paul; Siersema, Peter D; Gouma, Dirk J; van Hooft, Jeanin E; Keulemans, Yolande; Poley, Jan W; Timmer, Robin; Besselink, Marc G; Vleggaar, Frank P; Wilder-Smith, Oliver H; Gooszen, Hein G; Dijkgraaf, Marcel G W; Boermeester, Marja A

    2013-03-18

    In current practice, patients with chronic pancreatitis undergo surgical intervention in a late stage of the disease, when conservative treatment and endoscopic interventions have failed. Recent evidence suggests that surgical intervention early on in the disease benefits patients in terms of better pain control and preservation of pancreatic function. Therefore, we designed a randomized controlled trial to evaluate the benefits, risks and costs of early surgical intervention compared to the current stepwise practice for chronic pancreatitis. The ESCAPE trial is a randomized controlled, parallel, superiority multicenter trial. Patients with chronic pancreatitis, a dilated pancreatic duct (≥5 mm) and moderate pain and/or frequent flare-ups will be registered and followed monthly as potential candidates for the trial. When a registered patient meets the randomization criteria (i.e. need for opioid analgesics) the patient will be randomized to either early surgical intervention (group A) or optimal current step-up practice (group B). An expert panel of chronic pancreatitis specialists will oversee the assessment of eligibility and ensure that allocation to either treatment arm is possible. Patients in group A will undergo pancreaticojejunostomy or a Frey-procedure in case of an enlarged pancreatic head (≥4 cm). Patients in group B will undergo a step-up practice of optimal medical treatment, if needed followed by endoscopic interventions, and if needed followed by surgery, according to predefined criteria. Primary outcome is pain assessed with the Izbicki pain score during a follow-up of 18 months. Secondary outcomes include complications, mortality, total direct and indirect costs, quality of life, pancreatic insufficiency, alternative pain scales, length of hospital admission, number of interventions and pancreatitis flare-ups. For the sample size calculation we defined a minimal clinically relevant difference in the primary endpoint as a difference of at least

  4. Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis

    NARCIS (Netherlands)

    Cahen, Djuna L.; Gouma, Dirk J.; Nio, Yung; Rauws, Erik A. J.; Boermeester, Marja A.; Busch, Olivier R.; Stoker, Jaap; Lameris, Johan S.; Dijkgraaf, Marcel G. W.; Huibregtse, Kees; Bruno, Marco J.

    2007-01-01

    BACKGROUND: For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. METHODS: All symptomatic patients with chronic pancreatitis and a distal

  5. Endoscopic versus surgical drainage of the pancreatic duct in chronic pancreatitis.

    Science.gov (United States)

    Cahen, Djuna L; Gouma, Dirk J; Nio, Yung; Rauws, Erik A J; Boermeester, Marja A; Busch, Olivier R; Stoker, Jaap; Laméris, Johan S; Dijkgraaf, Marcel G W; Huibregtse, Kees; Bruno, Marco J

    2007-02-15

    For patients with chronic pancreatitis and a dilated pancreatic duct, ductal decompression is recommended. We conducted a randomized trial to compare endoscopic and surgical drainage of the pancreatic duct. All symptomatic patients with chronic pancreatitis and a distal obstruction of the pancreatic duct but without an inflammatory mass were eligible for the study. We randomly assigned patients to undergo endoscopic transampullary drainage of the pancreatic duct or operative pancreaticojejunostomy. The primary end point was the average Izbicki pain score during 2 years of follow-up. The secondary end points were pain relief at the end of follow-up, physical and mental health, morbidity, mortality, length of hospital stay, number of procedures undergone, and changes in pancreatic function. Thirty-nine patients underwent randomization: 19 to endoscopic treatment (16 of whom underwent lithotripsy) and 20 to operative pancreaticojejunostomy. During the 24 months of follow-up, patients who underwent surgery, as compared with those who were treated endoscopically, had lower Izbicki pain scores (25 vs. 51, Psurgical drainage (P=0.007). Rates of complications, length of hospital stay, and changes in pancreatic function were similar in the two treatment groups, but patients receiving endoscopic treatment required more procedures than did patients in the surgery group (a median of eight vs. three, PSurgical drainage of the pancreatic duct was more effective than endoscopic treatment in patients with obstruction of the pancreatic duct due to chronic pancreatitis. (Current Controlled Trials number, ISRCTN04572410 [controlled-trials.com].). Copyright 2007 Massachusetts Medical Society.

  6. SPIRIT 2013 explanation and elaboration: guidance for protocols of clinical trials.

    Science.gov (United States)

    Chan, An-Wen; Tetzlaff, Jennifer M; Gøtzsche, Peter C; Altman, Douglas G; Mann, Howard; Berlin, Jesse A; Dickersin, Kay; Hróbjartsson, Asbjørn; Schulz, Kenneth F; Parulekar, Wendy R; Krleza-Jeric, Karmela; Laupacis, Andreas; Moher, David

    2013-01-08

    High quality protocols facilitate proper conduct, reporting, and external review of clinical trials. However, the completeness of trial protocols is often inadequate. To help improve the content and quality of protocols, an international group of stakeholders developed the SPIRIT 2013 Statement (Standard Protocol Items: Recommendations for Interventional Trials). The SPIRIT Statement provides guidance in the form of a checklist of recommended items to include in a clinical trial protocol. This SPIRIT 2013 Explanation and Elaboration paper provides important information to promote full understanding of the checklist recommendations. For each checklist item, we provide a rationale and detailed description; a model example from an actual protocol; and relevant references supporting its importance. We strongly recommend that this explanatory paper be used in conjunction with the SPIRIT Statement. A website of resources is also available (www.spirit-statement.org). The SPIRIT 2013 Explanation and Elaboration paper, together with the Statement, should help with the drafting of trial protocols. Complete documentation of key trial elements can facilitate transparency and protocol review for the benefit of all stakeholders.

  7. Electroacupuncture treatment for pancreatic cancer pain: a randomized controlled trial.

    Science.gov (United States)

    Chen, Hao; Liu, Tang-Yi; Kuai, Le; Zhu, Ji; Wu, Cai-Jun; Liu, Lu-Ming

    2013-01-01

    Pancreatic cancer is often accompanied by severe abdominal or back pain. It's the first study to evaluate the analgesic effect of electroacupuncture on pancreatic cancer pain. A randomized controlled trial compared electroacupuncture with control acupuncture using the placebo needle. Sixty patients with pancreatic cancer pain were randomly assigned to the electroacupuncture group (n = 30) and the placebo control group (n = 30). Patients were treated on Jiaji (Ex-B2) points T8-T12 bilaterally for 30 min once a day for 3 days. Pain intensity was assessed with numerical rated scales (NRS) before the treatment (Baseline), after 3 treatments, and 2 days follow-up. Baseline characteristics were similar in the two groups. After 3 treatment, pain intensity on NRS decreased compared with Baseline (-1.67, 95% confidence interval [CI] -1.46 to -1.87) in the electroacupuncture group; there was little change (-0.13, 95% CI 0.08 to -0.35) in control group; the difference between two groups was statistically significant (P electroacupuncture group compared with the control group (P Electroacupuncture was an effective treatment for relieving pancreatic cancer pain. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  8. Redactions in protocols for drug trials: what industry sponsors concealed.

    Science.gov (United States)

    Marquardsen, Mikkel; Ogden, Michelle; Gøtzsche, Peter C

    2018-04-01

    Objective To describe the redactions in contemporary protocols for industry-sponsored randomised drug trials with patient relevant outcomes and to evaluate whether there was a legitimate rationale for the redactions. Design Cohort study. Under the Freedom of Information Act, we requested access to trial protocols approved by a research ethics committee in Denmark from October 2012 to March 2013. We received 17 consecutive protocols, which had been redacted before we got them, and nine protocols without redactions. In five additional cases, the companies refused to let the committees give us access, and in three other cases, documents were missing. Participants Not applicable. Setting Not applicable. Main outcome measure Amount and nature of redactions in 22 predefined key protocol variables. Results The redactions were most widespread in those sections of the protocol where there is empirical evidence of substantial problems with the trustworthiness of published drug trials: data analysis, handling of missing data, detection and analysis of adverse events, definition of the outcomes, interim analyses and premature termination of the study, sponsor's access to incoming data while the study is running, ownership to the data and investigators' publication rights. The parts of the text that were redacted differed widely, both between companies and within the same company. Conclusions We could not identify any legitimate rationale for the redactions. The current mistrust in industry-sponsored drug trials can only change if the industry offers unconditional access to its trial protocols and other relevant documents and data.

  9. Evaluating Protocol Lifecycle Time Intervals in HIV/AIDS Clinical Trials

    Science.gov (United States)

    Schouten, Jeffrey T.; Dixon, Dennis; Varghese, Suresh; Cope, Marie T.; Marci, Joe; Kagan, Jonathan M.

    2014-01-01

    Background Identifying efficacious interventions for the prevention and treatment of human diseases depends on the efficient development and implementation of controlled clinical trials. Essential to reducing the time and burden of completing the clinical trial lifecycle is determining which aspects take the longest, delay other stages, and may lead to better resource utilization without diminishing scientific quality, safety, or the protection of human subjects. Purpose In this study we modeled time-to-event data to explore relationships between clinical trial protocol development and implementation times, as well as identify potential correlates of prolonged development and implementation. Methods We obtained time interval and participant accrual data from 111 interventional clinical trials initiated between 2006 and 2011 by NIH’s HIV/AIDS Clinical Trials Networks. We determined the time (in days) required to complete defined phases of clinical trial protocol development and implementation. Kaplan-Meier estimates were used to assess the rates at which protocols reached specified terminal events, stratified by study purpose (therapeutic, prevention) and phase group (pilot/phase I, phase II, and phase III/ IV). We also examined several potential correlates to prolonged development and implementation intervals. Results Even though phase grouping did not determine development or implementation times of either therapeutic or prevention studies, overall we observed wide variation in protocol development times. Moreover, we detected a trend toward phase III/IV therapeutic protocols exhibiting longer developmental (median 2 ½ years) and implementation times (>3years). We also found that protocols exceeding the median number of days for completing the development interval had significantly longer implementation. Limitations The use of a relatively small set of protocols may have limited our ability to detect differences across phase groupings. Some timing effects

  10. Contrast-enhanced magnetic resonance imaging for the detection of acute haemorrhagic necrotizing pancreatitis

    International Nuclear Information System (INIS)

    Piironen, A.; Kivisaari, R.; Pitkaeranta, P.; Poutanen, V.P.; Laippala, P.; Laurila, P.; Kivisaari, L.

    1997-01-01

    Eleven piglets with haemorrhagic necrotizing pancreatitis and nine piglets with oedematous pancreatitis were imaged using a multi-breath-hold TurboFLASH (TR 6.5 ms, TE 3 ms, TI 300 ms, flip angle 8 , three slices) pre-excited T1-weighted sequence with an IV bolus injection of gadopentetate dimeglumine (Gd-DTPA, 0.3 mmol/kg) as a contrast agent to show dynamic contrast enhancement of the pancreas by MRI. All piglets were imaged according to the same protocol before inducing the disease. Following the IV Gd-DTPA bolus, time-enhancement curve of the pancreas during haemorrhagic necrotizing pancreatitis was significantly lower than during oedematous pancreatitis. The enhancement curves for the healthy piglets and piglets with oedematous pancreatitis did not differ significantly. Each piglet served as its own control. Because the results of this initial study are similar to those obtained with contrast-enhanced CT, we conclude that our results may encourage further clinical trials, and contrast-enhanced dynamic MRI may be an alternative to the established method of CT for diagnosing acute haemorrhagic necrotizing pancreatitis. (orig.). With 3 figs

  11. Patient-reported outcome (PRO assessment in clinical trials: a systematic review of guidance for trial protocol writers.

    Directory of Open Access Journals (Sweden)

    Melanie Calvert

    Full Text Available Evidence suggests there are inconsistencies in patient-reported outcome (PRO assessment and reporting in clinical trials, which may limit the use of these data to inform patient care. For trials with a PRO endpoint, routine inclusion of key PRO information in the protocol may help improve trial conduct and the reporting and appraisal of PRO results; however, it is currently unclear exactly what PRO-specific information should be included. The aim of this review was to summarize the current PRO-specific guidance for clinical trial protocol developers.We searched the MEDLINE, EMBASE, CINHAL and Cochrane Library databases (inception to February 2013 for PRO-specific guidance regarding trial protocol development. Further guidance documents were identified via Google, Google scholar, requests to members of the UK Clinical Research Collaboration registered clinical trials units and international experts. Two independent investigators undertook title/abstract screening, full text review and data extraction, with a third involved in the event of disagreement. 21,175 citations were screened and 54 met the inclusion criteria. Guidance documents were difficult to access: electronic database searches identified just 8 documents, with the remaining 46 sourced elsewhere (5 from citation tracking, 27 from hand searching, 7 from the grey literature review and 7 from experts. 162 unique PRO-specific protocol recommendations were extracted from included documents. A further 10 PRO recommendations were identified relating to supporting trial documentation. Only 5/162 (3% recommendations appeared in ≥50% of guidance documents reviewed, indicating a lack of consistency.PRO-specific protocol guidelines were difficult to access, lacked consistency and may be challenging to implement in practice. There is a need to develop easily accessible consensus-driven PRO protocol guidance. Guidance should be aimed at ensuring key PRO information is routinely included in

  12. L-Carnitine-supplementation in advanced pancreatic cancer (CARPAN - a randomized multicentre trial

    Directory of Open Access Journals (Sweden)

    Kraft Matthias

    2012-07-01

    Full Text Available Abstract Background Cachexia, a >10% loss of body-weight, is one factor determining the poor prognosis of pancreatic cancer. Deficiency of L-Carnitine has been proposed to cause cancer cachexia. Findings We screened 152 and enrolled 72 patients suffering from advanced pancreatic cancer in a prospective, multi-centre, placebo-controlled, randomized and double-blinded trial to receive oral L-Carnitine (4 g or placebo for 12 weeks. At entry patients reported a mean weight loss of 12 ± 2,5 (SEM kg. During treatment body-mass-index increased by 3,4 ± 1,4% under L-Carnitine and decreased (−1,5 ± 1,4% in controls (p  Conclusion While these data are preliminary and need confirmation they indicate that patients with pancreatic cancer may have a clinically relevant benefit from the inexpensive and well tolerated oral supplementation of L-Carnitine.

  13. Clinicopathologic characteristics, laboratory parameters, treatment protocols, and outcomes of pancreatic cancer: a retrospective cohort study of 1433 patients in China

    Directory of Open Access Journals (Sweden)

    Shuisheng Zhang

    2018-05-01

    Full Text Available Objectives The prognosis of people with pancreatic cancer is extremely unfavorable. However, the prognostic factors remain largely undefined. We aimed to perform comprehensive analyses of clinicopathologic characteristics, laboratory parameters, and treatment protocols for exploring their role as prognostic factors of pancreatic cancer. Methods Patients diagnosed with pancreatic cancer and hospitalized at the China National Cancer Center between April 2006 and May 2016 were enrolled in this retrospective cohort study. Clinicopathologic characteristics, laboratory parameters, and treatment protocols were compared among patients at different stages of the disease. The association between these factors and overall survival (OS was analyzed using the Kaplan–Meier method and Cox proportional hazards model. Results The present study included 1,433 consecutive patients with pancreatic cancer. Median OS was 10.6 months (95% confidence interval [CI] 9.8–11.3 months, with 1-, 3-, and 5-year survival rates of 43.7%, 14.8%, and 8.8%, respectively. Cox multivariate analysis findings identified the following factors as independent predictors of OS: gender (female vs male, hazard ratio 0.72, 95% CI [0.54–0.95]; elevated total bilirubin (TBil; 1.82, 1.34–2.47; elevated carbohydrate antigen 19-9 (CA19-9; 1.72, 1.17–2.54; tumor being located in pancreatic body and tail (1.52, 1.10–2.10; advanced T stage (T3-4 vs T1-2, 1.62, 1.15–2.27; lymph node metastasis (1.57, 1.20–2.07; distant metastasis (1.59, 1.12–2.27; the presence of surgical resection (0.53, 0.34–0.81; and the presence of systemic chemotherapy (0.62, 0.45–0.82. Conclusions Being male, elevated TBil and carcinoembryonic antigen, tumor being located in pancreatic body and tail, advanced T stage, lymph node and distant metastasis, the absence of surgical resection, and the absence of systematic chemotherapy were associated with worse OS in patients with pancreatic cancer.

  14. Early biliary decompression versus conservative treatment in acute biliary pancreatitis (APEC trial): study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    Schepers, N.J.; Bakker, O.J.; Besselink, M.G.; Bollen, T.L.; Dijkgraaf, M.G.; Eijck, C.H. van; Fockens, P.; Geenen, E.J. van; Grinsven, J. van; Hallensleben, N.D.; Hansen, B.E.; Santvoort, H.C. van; Timmer, R.; Anten, M.P.; Bolwerk, C.J.; Delft, F. von; Dullemen, H.M. van; Erkelens, G.W.; Hooft, J.E. van; Laheij, R.; Hulst, R.W. van der; Jansen, J.M.; Kubben, F.J.; Kuiken, S.D.; Perk, L.E.; Ridder, R.J. de; Rijk, M.C. de; Romkens, T.E.; Schoon, E.J.; Schwartz, M.P.; Spanier, B.W.; Tan, A.C.; Thijs, W.J.; Venneman, N.G.; Vleggaar, F.P.; Vrie, W. van de; Witteman, B.J.; Gooszen, H.G.; Bruno, M.J.

    2016-01-01

    BACKGROUND: Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these patients. Whereas current guidelines recommend early ERC in patients with concomitant

  15. Early biliary decompression versus conservative treatment in acute biliary pancreatitis (APEC trial): Study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    N.J. Schepers (Nicolien); O.J. Bakker (Olaf ); M.G. Besselink (Marc); T.L. Bollen (Thomas); M.G.W. Dijkgraaf (Marcel); C.H.J. van Eijck (Casper); P. Fockens (Paul); E-J.M. Geenen (Erwin-Jan); J. van Grinsven (Janneke); N.D.L. Hallensleben (Nora D.L.); B.E. Hansen (Bettina); H.C. van Santvoort (Hjalmar); R. Timmer (Robin); M.-P.G.F. Anten (Marie-Paule G.F.); C.L. Bolwerk (Clemens); F. van Delft (Foke); H.M. van Dullemen (Hendrik); G.W. Erkelens (G.Willemien); J.E. van Hooft (Jeanin); C. Laheij (Claudia); R.W.M. van der Hulst (René); J.M. Jansen (Jeroen); F.J. Kubben; S.D. Kuiken (Sjoerd D.); L.E. Perk (Lars E.); R. de Ridder (Rogier); M.C.M. Rijk; T.E.H. Römkens; E.J. Schoon (Erik); M.P. Schwartz (Matthijs P.); B.W.M. Spanier (Marcel); A.C. Tan (Adriaan); W.J. Thijs; N.G. Venneman (Niels); F.P. Vleggaar (Frank); W. van de Vrie (Wim); B.J.M. Witteman (Ben); H.G. Gooszen (Hein); M.J. Bruno (Marco)

    2016-01-01

    textabstractBackground: Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these patients. Whereas current guidelines recommend early ERC in patients with

  16. Early biliary decompression versus conservative treatment in acute biliary pancreatitis (APEC trial) : Study protocol for a randomized controlled trial

    NARCIS (Netherlands)

    Schepers, Nicolien J.; Bakker, Olaf J.; Besselink, Marc G H; Bollen, Thomas L.; Dijkgraaf, Marcel G W; van Eijck, Casper H J; Fockens, Paul; van Geenen, Erwin J M; van Grinsven, Janneke; Hallensleben, Nora D L; Hansen, Bettina E.; van Santvoort, Hjalmar C.; Timmer, Robin; Anten, Marie Paule G F; Bolwerk, Clemens J M; van Delft, Foke; van Dullemen, Hendrik M.; Erkelens, G. Willemien; van Hooft, Jeanin E.; Laheij, Robert; van der Hulst, René W M; Jansen, Jeroen M.; Kubben, Frank J G M; Kuiken, Sjoerd D.; Perk, Lars E.; de Ridder, Rogier J J; Rijk, Marno C M; Römkens, Tessa E H; Schoon, Erik J.; Schwartz, Matthijs P.; Spanier, B. W Marcel; Tan, Adriaan C I T L; Thijs, Willem J.; Venneman, Niels G.; Vleggaar, Frank P.; van de Vrie, Wim; Witteman, Ben J.; Gooszen, Hein G.; Bruno, Marco J.

    2016-01-01

    Background: Acute pancreatitis is mostly caused by gallstones or sludge. Early decompression of the biliary tree by endoscopic retrograde cholangiography (ERC) with sphincterotomy may improve outcome in these patients. Whereas current guidelines recommend early ERC in patients with concomitant

  17. Pancreatic head cryosurgery: safety and efficiency in vivo--a pilot study.

    Science.gov (United States)

    Li, Jialiang; Zhou, Liang; Chen, Jibing; Wu, Binghui; Zeng, Jianying; Fang, Gang; Deng, Chunjuan; Huang, Shengquan; Yao, Fei; Chen, Zhixian; Leng, Yin; Deng, Min; Deng, Chunmei; Zhang, Bo; Zhou, Gang; He, Lihua; Liao, Maoxin; Chiu, David; Niu, Lizhi; Zuo, Jiansheng; Xu, Kecheng

    2012-11-01

    Pancreatic cancer is the fourth leading cause of cancer-related death. Cryosurgery has emerged as a promising new technique for treatment. Although 80% of pancreatic cancers are located in the pancreatic head, no research has been conducted on the safety and efficacy of cryosurgery for these tumors. Two groups of Tibetan miniature pigs (n = 4 per group) underwent cryosurgery to the pancreatic head with either the deep freezing protocol (100% argon output) or shallow freezing protocol (10% argon output), and compared to sham-operated pigs. Serum inflammatory factors and amylase increased during the 5 days after cryoablation in both groups but acute pancreatitis did not occur. Adhesions were observed between the pancreatic head and adjacent organs, and only minor trauma was caused to the stomach, duodenum, small intestine, and liver. Ice balls with a radius of 0.5 cm beyond the tumor edge were sufficient to cause complete necrosis of the pancreatic tissue, and decreased the degree of cold injury to surrounding tissues. Shallow freezing protocol seemed to be safer than, and just as effective as, the deep freezing protocol. This preliminary study suggests that cryosurgery could potentially be an effective treatment of cancer of the pancreatic head.

  18. Low-fat Dietary Pattern and Pancreatic Cancer Risk in the Women's Health Initiative Dietary Modification Randomized Controlled Trial.

    Science.gov (United States)

    Jiao, Li; Chen, Liang; White, Donna L; Tinker, Lesley; Chlebowski, Rowan T; Van Horn, Linda V; Richardson, Peter; Lane, Dorothy; Sangi-Haghpeykar, Haleh; El-Serag, Hashem B

    2018-01-01

    Observational studies suggest that diet may influence pancreatic cancer risk. We investigated the effect of a low-fat dietary intervention on pancreatic cancer incidence. The Women's Health Initiative Dietary Modification (WHI-DM) trial is a randomized controlled trial conducted in 48 835 postmenopausal women age 50 to 79 years in the United States between 1993 and 1998. Women were randomly assigned to the intervention group (n = 19 541), with the goal of reducing total fat intake and increasing intake of vegetables, fruits, and grains, or to the usual diet comparison group (n = 29 294). The intervention concluded in March 2005. We evaluated the effect of the intervention on pancreatic cancer incidence with the follow-up through 2014 using the log-rank test and multivariable Cox proportional hazards regression model. All statistical tests were two-sided. In intention-to-treat analyses including 46 200 women, 92 vs 165 pancreatic cancer cases were ascertained in the intervention vs the comparison group (P = .23). The multivariable hazard ratio (HR) of pancreatic cancer was 0.86 (95% confidence interval [CI] = 0.67 to 1.11). Risk was statistically significantly reduced among women with baseline body mass indexes (BMIs) of 25 kg/m2 or higher (HR = 0.71, 95% CI = 0.53 to 0.96), but not among women with BMIs of less than 25 kg/m2 (HR = 1.62, 95% CI = 0.97 to 2.71, Pinteraction = .01). A low-fat dietary intervention was associated with reduced pancreatic cancer incidence in women who were overweight or obese in the WHI-DM trial. Caution needs to be taken in interpreting the findings based on subgroup analyses. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  19. Development of a manualized protocol of massage therapy for clinical trials in osteoarthritis

    Directory of Open Access Journals (Sweden)

    Ali Ather

    2012-10-01

    Full Text Available Abstract Background Clinical trial design of manual therapies may be especially challenging as techniques are often individualized and practitioner-dependent. This paper describes our methods in creating a standardized Swedish massage protocol tailored to subjects with osteoarthritis of the knee while respectful of the individualized nature of massage therapy, as well as implementation of this protocol in two randomized clinical trials. Methods The manualization process involved a collaborative process between methodologic and clinical experts, with the explicit goals of creating a reproducible semi-structured protocol for massage therapy, while allowing some latitude for therapists’ clinical judgment and maintaining consistency with a prior pilot study. Results The manualized protocol addressed identical specified body regions with distinct 30- and 60-min protocols, using standard Swedish strokes. Each protocol specifies the time allocated to each body region. The manualized 30- and 60-min protocols were implemented in a dual-site 24-week randomized dose-finding trial in patients with osteoarthritis of the knee, and is currently being implemented in a three-site 52-week efficacy trial of manualized Swedish massage therapy. In the dose-finding study, therapists adhered to the protocols and significant treatment effects were demonstrated. Conclusions The massage protocol was manualized, using standard techniques, and made flexible for individual practitioner and subject needs. The protocol has been applied in two randomized clinical trials. This manualized Swedish massage protocol has real-world utility and can be readily utilized both in the research and clinical settings. Trial registration Clinicaltrials.gov NCT00970008 (18 August 2009

  20. Pharmacological interventions for acute pancreatitis.

    Science.gov (United States)

    Moggia, Elisabetta; Koti, Rahul; Belgaumkar, Ajay P; Fazio, Federico; Pereira, Stephen P; Davidson, Brian R; Gurusamy, Kurinchi Selvan

    2017-04-21

    In people with acute pancreatitis, it is unclear what the role should be for medical treatment as an addition to supportive care such as fluid and electrolyte balance and organ support in people with organ failure. To assess the effects of different pharmacological interventions in people with acute pancreatitis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2016, Issue 9), MEDLINE, Embase, Science Citation Index Expanded, and trial registers to October 2016 to identify randomised controlled trials (RCTs). We also searched the references of included trials to identify further trials. We considered only RCTs performed in people with acute pancreatitis, irrespective of aetiology, severity, presence of infection, language, blinding, or publication status for inclusion in the review. Two review authors independently identified trials and extracted data. We did not perform a network meta-analysis as planned because of the lack of information on potential effect modifiers and differences of type of participants included in the different comparisons, when information was available. We calculated the odds ratio (OR) with 95% confidence intervals (CIs) for the binary outcomes and rate ratios with 95% CIs for count outcomes using a fixed-effect model and random-effects model. We included 84 RCTs with 8234 participants in this review. Six trials (N = 658) did not report any of the outcomes of interest for this review. The remaining 78 trials excluded 210 participants after randomisation. Thus, a total of 7366 participants in 78 trials contributed to one or more outcomes for this review. The treatments assessed in these 78 trials included antibiotics, antioxidants, aprotinin, atropine, calcitonin, cimetidine, EDTA (ethylenediaminetetraacetic acid), gabexate, glucagon, iniprol, lexipafant, NSAIDs (non-steroidal anti-inflammatory drugs), octreotide, oxyphenonium, probiotics, activated protein C, somatostatin, somatostatin plus omeprazole, somatostatin

  1. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition : A Randomized Controlled Trial

    NARCIS (Netherlands)

    Bartels, Rosalie H.; Bourdon, Celine; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Kobold, Anneke C. Muller; Bandsma, Robert H.; van Hensbroek, Michael Boele; Voskuijl, Wieger P.

    Objective: To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design: We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth

  2. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial

    NARCIS (Netherlands)

    Bartels, Rosalie H.; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A.; Mponda, John S.; Muller Kobold, Anneke C.; Bandsma, Robert H.; Boele van Hensbroek, Michael; Voskuijl, Wieger P.

    2017-01-01

    Objective To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. Study design We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central

  3. Optimizing the multimodal approach to pancreatic cyst fluid diagnosis: developing a volume-based triage protocol.

    Science.gov (United States)

    Chai, Siaw Ming; Herba, Karl; Kumarasinghe, M Priyanthi; de Boer, W Bastiaan; Amanuel, Benhur; Grieu-Iacopetta, Fabienne; Lim, Ee Mun; Segarajasingam, Dev; Yusoff, Ian; Choo, Chris; Frost, Felicity

    2013-02-01

    The objective of this study was to develop a triage algorithm to optimize diagnostic yield from cytology, carcinoembryonic antigen (CEA), and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) testing on different components of a single pancreatic cyst fluid specimen. The authors also sought to determine whether cell block supernatant was suitable for CEA and KRAS testing. Fifty-four pancreatic cysts were triaged according to a volume-dependent protocol to generate fluid (neat and supernatant) and cell block specimens for cytology, comparative CEA, and KRAS testing. Follow-up histology, diagnostic cytology, or a combined clinicopathologic interpretation was recorded as the final diagnosis. There were 26 mucinous cystic lesions and 28 nonmucinous cystic lesions with volumes ranging from 0.3 mL to 55 mL. Testing different components of the specimens (cell block, neat, and/or supernatant) enabled all laboratory investigations to be performed on 50 of 54 cyst fluids (92.6%). Interpretive concordance was observed in 17 of 17 cases (100%) and in 35 of 40 cases (87.5%) that had multiple components tested for CEA and KRAS mutations, respectively. An elevated CEA level (>192 ng/mL) was the most sensitive test for the detection of a mucinous cystic lesion (62.5%) versus KRAS mutation (56%) and "positive" cytology (61.5%). KRAS mutations were identified in 2 of 25 mucinous cystic lesions (8%) in which cytology and CEA levels were not contributory. A volume-based protocol using different components of the specimen was able to optimize diagnostic yield in pancreatic cyst fluids. KRAS mutation testing increased diagnostic yield when combined with cytology and CEA analysis. The current results demonstrated that supernatant is comparable to neat fluid and cell block material for CEA and KRAS testing. Copyright © 2012 American Cancer Society.

  4. Incretin-based therapies and risk of pancreatic cancer in patients with type 2 diabetes: A meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Wang, Haining; Liu, Ye; Tian, Qing; Yang, Jin; Lu, Ran; Zhan, Siyan; Haukka, Jari; Hong, Tianpei

    2018-04-01

    To perform a meta-analysis of randomized controlled trials (RCTs), including 6 recently published large-scale cardiovascular outcome trials (CVOTs), to evaluate the risk of pancreatic cancer with incretin-based therapies in patients with type 2 diabetes (T2DM). For the period January 1, 2007 to May 1, 2017, the PubMed, Embase, Cochrane Central Register and ClininalTrials.gov databases were searched for RCTs in people with T2DM that compared incretin drugs with placebo or other antidiabetic drugs, with treatment and follow-up durations of ≥52 weeks. Two reviewers screened the studies, extracted the data and assessed the risk of bias independently and in duplicate. A total of 33 studies (n = 79 971), including the 6 CVOTs, with 87 pancreatic cancer events were identified. Overall, the pancreatic cancer risk was not increased in patients administered incretin drugs compared with controls (Peto odds ratio [OR] 0.67, 95% confidence interval [CI] 0.44-1.02). In the 6 CVOTs, 79 pancreatic cancer events were identified in 55 248 participants. Pooled estimates of the 6 CVOTs showed an identical tendency (Peto OR 0.65, 95% CI 0.42-1.01). Notably, in the subgroup of participants who received treatment and follow-up for ≥104 weeks, 84 pancreatic cancer events were identified in 59 919 participants, and a lower risk of pancreatic cancer was associated with incretin-based therapies (Peto OR 0.62, 95% CI 0.41-0.95). Treatment with incretin drugs was not associated with an increased risk of pancreatic cancer in people with T2DM. Instead, it might protect against pancreatic malignancy in patients treated for ≥104 weeks. © 2017 John Wiley & Sons Ltd.

  5. Pharmacological approach to acute pancreatitis

    DEFF Research Database (Denmark)

    Bang, U.C.; Semb, S.; Nøjgaard, Camilla

    2008-01-01

    The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may...... be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL...

  6. Comparison of investigator-delineated gross tumour volumes and quality assurance in pancreatic cancer: Analysis of the on-trial cases for the SCALOP trial.

    Science.gov (United States)

    Fokas, Emmanouil; Spezi, Emiliano; Patel, Neel; Hurt, Chris; Nixon, Lisette; Chu, Kwun-Ye; Staffurth, John; Abrams, Ross; Mukherjee, Somnath

    2016-08-01

    We performed a retrospective central review of tumour outlines in patients undergoing radiotherapy in the SCALOP trial. The planning CT scans were reviewed retrospectively by a central review team, and the accuracy of investigators' GTV (iGTV) and PTV (iPTV) was compared to the trials team-defined gold standard (gsGTV and gsPTV) using the Jaccard Conformity Index (JCI) and Geographical Miss Index (GMI). The prognostic value of JCI and GMI was also assessed. The RT plans were also reviewed against protocol-defined constraints. 60 patients with diagnostic-quality planning scans were included. The median whole volume JCI for GTV was 0.64 (IQR: 0.43-0.82), and the median GMI was 0.11 (IQR: 0.05-0.22). For PTVs, the median JCI and GMI were 0.80 (IQR: 0.71-0.88) and 0.04 (IQR: 0.02-0.12) respectively. Tumour was completely missed in 1 patient, and⩾50% of the tumour was missed in 3. Patients with JCI for GTV⩾0.7 had 7.12 (95% CIs: 1.83-27.67, p=0.005) higher odds of progressing by 9months in multivariate analysis. Major deviations in RT planning were noted in 4.5% of cases. Radiotherapy workshops and real-time central review of contours are required in RT trials of pancreatic cancer. Copyright © 2016 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  7. Pancreatic enzyme supplementation after gastrectomy for gastric cancer: a randomized controlled trial.

    Science.gov (United States)

    Catarci, Marco; Berlanda, Manuele; Grassi, Giovanni Battista; Masedu, Francesco; Guadagni, Stefano

    2018-05-01

    Gastrectomy for gastric cancer is a significant cause of secondary exocrine pancreatic insufficiency. Pancreatic enzyme replacement therapy may influence nutritional status and quality of life after gastrectomy, but the pertinent clinical research to date remains controversial. A randomized controlled trial to test this hypothesis was carried out. After gastrectomy, 43 patients with gastric cancer were randomly assigned to a normal diet (Normal-d; n = 21) or to a pancreatic enzyme supplementation diet (PES-d; n = 22) and were followed up during a 12-month period, assessing nutritional status and quality of life through body mass index (BMI), instant nutritional assessment (INA) class status, serum pre-albumin (SPA) values, and GastroiIntestinal Quality of Life Index (GIQLI). BMI was not significantly influenced by the type of diet; INA class status was significantly improved in the PES-d arm, particularly during the first 3 months after gastrectomy; SPA levels increased in both arms at 6 months after gastrectomy, reaching significantly higher values in the PES-d arm at 12 months. GIQLI was not significantly influenced by the type of diet throughout the follow-up period; however, this index significantly improved in the PES-d arm between the first and third month after gastrectomy. PES-d improves nutritional status and quality of life after gastrectomy for gastric cancer, particularly within 3 months from the operation. A larger, multicenter trial is necessary to address the potential influence of several confounding variables such as disease stage and adjuvant treatments.

  8. Pancreatic MRI for the surveillance of cystic neoplasms: Comparison of a short with a comprehensive imaging protocol

    Energy Technology Data Exchange (ETDEWEB)

    Pozzi-Mucelli, Raffaella Maria; Kartalis, Nikolaos [C1-46 Karolinska University Hospital, Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Department of Radiology, Stockholm (Sweden); Rinta-Kiikka, Irina [Tampere University Hospital, Department of Radiology, Medical Imaging Centre of Pirkanmaa Hospital District, Tampere (Finland); Wuensche, Katharina [St. Olavs University Hospital, Department of Radiology, Trondheim (Norway); Laukkarinen, Johanna [Tampere University Hospital, Department of Gastroenterology and Alimentary Tract Surgery, Tampere (Finland); Labori, Knut Joergen [Oslo University Hospital, Department of Hepato-Pancreato-Biliary Surgery, Oslo (Norway); Aanonsen, Kim [Oslo University Hospital, Department of Gastroenterology, Oslo (Norway); Verbeke, Caroline [Oslo University Hospital, Institute of Clinical Medicine, Oslo (Norway); Karolinska University Hospital, Department of Pathology, Stockholm (Sweden); Del Chiaro, Marco [Karolinska University Hospital, Division of Surgery, Department of Clinical Science, Intervention and Technology (CLINTEC), Karolinska Institutet and Center for Digestive Diseases, Stockholm (Sweden)

    2017-01-15

    The study aims were to evaluate: (1) whether a short-protocol (SP) MRI for the surveillance of pancreatic cystic neoplasms (PCN) provides equivalent clinical information as a comprehensive-protocol (CP), and (2) the cost reduction from substituting CP with SP for patient surveillance. This retrospective study included 154 consecutive patients (median age: 66, 52 % men) with working-diagnosis of PCN and available contrast-enhanced MRI/MRCP. Three radiologists evaluated independently two imaging sets (SP/CP) per patient. The CP included: T2-weighted (HASTE/MRCP), DWI and T1-weighted (chemical-shift/pre-/post-contrast) images [acquisition time (AT) ∼ 35 min], whereas the SP included: T2-weighted HASTE and T1-weighted pre-contrast images (AT ∼ 8 min). Mean values of largest cyst/main pancreatic duct diameter (D{sub C}/D{sub MPD}) were compared. Agreement regarding presence/absence of cystic/MPD mural nodules (MN{sub C}/MN{sub MPD}), inter-observer agreement and cost differences between SP/CP were calculated. For D{sub C} and D{sub MPD}, mean values with SP/CP were 21.4/21.7 mm and 3.52/3.58 mm, while mean differences SP-CP were 0.3 mm (p = 0.02) and 0.06 mm (p = 0.12), respectively. For presence/absence of MN{sub C} and MN{sub MPD}, SP/CP coincided in 93 % and 98 % of cases, respectively. Inter-observer agreement was strong for SP/CP. SP-cost was 25 % of CP-cost. For the surveillance of PCN, short-protocol MRI provides information equivalent to the more time-consuming and costly comprehensive-protocol. (orig.)

  9. Pancreatic MRI for the surveillance of cystic neoplasms: Comparison of a short with a comprehensive imaging protocol

    International Nuclear Information System (INIS)

    Pozzi-Mucelli, Raffaella Maria; Kartalis, Nikolaos; Rinta-Kiikka, Irina; Wuensche, Katharina; Laukkarinen, Johanna; Labori, Knut Joergen; Aanonsen, Kim; Verbeke, Caroline; Del Chiaro, Marco

    2017-01-01

    The study aims were to evaluate: (1) whether a short-protocol (SP) MRI for the surveillance of pancreatic cystic neoplasms (PCN) provides equivalent clinical information as a comprehensive-protocol (CP), and (2) the cost reduction from substituting CP with SP for patient surveillance. This retrospective study included 154 consecutive patients (median age: 66, 52 % men) with working-diagnosis of PCN and available contrast-enhanced MRI/MRCP. Three radiologists evaluated independently two imaging sets (SP/CP) per patient. The CP included: T2-weighted (HASTE/MRCP), DWI and T1-weighted (chemical-shift/pre-/post-contrast) images [acquisition time (AT) ∼ 35 min], whereas the SP included: T2-weighted HASTE and T1-weighted pre-contrast images (AT ∼ 8 min). Mean values of largest cyst/main pancreatic duct diameter (D_C/D_M_P_D) were compared. Agreement regarding presence/absence of cystic/MPD mural nodules (MN_C/MN_M_P_D), inter-observer agreement and cost differences between SP/CP were calculated. For D_C and D_M_P_D, mean values with SP/CP were 21.4/21.7 mm and 3.52/3.58 mm, while mean differences SP-CP were 0.3 mm (p = 0.02) and 0.06 mm (p = 0.12), respectively. For presence/absence of MN_C and MN_M_P_D, SP/CP coincided in 93 % and 98 % of cases, respectively. Inter-observer agreement was strong for SP/CP. SP-cost was 25 % of CP-cost. For the surveillance of PCN, short-protocol MRI provides information equivalent to the more time-consuming and costly comprehensive-protocol. (orig.)

  10. Stereotactic body radiotherapy for renal cell cancer and pancreatic cancer. Literature review and practice recommendations of the DEGRO Working Group on Stereotactic Radiotherapy

    International Nuclear Information System (INIS)

    Panje, Cedric; Andratschke, Nikolaus; Guckenberger, Matthias; Brunner, Thomas B.; Niyazi, Maximilian

    2016-01-01

    This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a literature review and practice recommendations for stereotactic body radiotherapy (SBRT) of primary renal cell cancer and primary pancreatic cancer. A literature search on SBRT for both renal cancer and pancreatic cancer was performed with focus on prospective trials and technical aspects for clinical implementation. Data on renal and pancreatic SBRT are limited, but show promising rates of local control for both treatment sites. For pancreatic cancer, fractionated SBRT should be preferred to single-dose treatment to reduce the risk of gastrointestinal toxicity. Motion-compensation strategies and image guidance are paramount for safe SBRT delivery in both tumor entities. SBRT for renal cancer and pancreatic cancer have been successfully evaluated in phase I and phase II trials. Pancreatic SBRT should be practiced carefully and only within prospective protocols due to the risk of severe gastrointestinal toxicity. SBRT for primary renal cell cancer appears a viable option for medically inoperable patients but future research needs to better define patient selection criteria and the detailed practice of SBRT. (orig.) [de

  11. Endoscopic or surgical step-up approach for infected necrotising pancreatitis: a multicentre randomised trial.

    Science.gov (United States)

    van Brunschot, Sandra; van Grinsven, Janneke; van Santvoort, Hjalmar C; Bakker, Olaf J; Besselink, Marc G; Boermeester, Marja A; Bollen, Thomas L; Bosscha, Koop; Bouwense, Stefan A; Bruno, Marco J; Cappendijk, Vincent C; Consten, Esther C; Dejong, Cornelis H; van Eijck, Casper H; Erkelens, Willemien G; van Goor, Harry; van Grevenstein, Wilhelmina M U; Haveman, Jan-Willem; Hofker, Sijbrand H; Jansen, Jeroen M; Laméris, Johan S; van Lienden, Krijn P; Meijssen, Maarten A; Mulder, Chris J; Nieuwenhuijs, Vincent B; Poley, Jan-Werner; Quispel, Rutger; de Ridder, Rogier J; Römkens, Tessa E; Scheepers, Joris J; Schepers, Nicolien J; Schwartz, Matthijs P; Seerden, Tom; Spanier, B W Marcel; Straathof, Jan Willem A; Strijker, Marin; Timmer, Robin; Venneman, Niels G; Vleggaar, Frank P; Voermans, Rogier P; Witteman, Ben J; Gooszen, Hein G; Dijkgraaf, Marcel G; Fockens, Paul

    2018-01-06

    Infected necrotising pancreatitis is a potentially lethal disease and an indication for invasive intervention. The surgical step-up approach is the standard treatment. A promising alternative is the endoscopic step-up approach. We compared both approaches to see whether the endoscopic step-up approach was superior to the surgical step-up approach in terms of clinical and economic outcomes. In this multicentre, randomised, superiority trial, we recruited adult patients with infected necrotising pancreatitis and an indication for invasive intervention from 19 hospitals in the Netherlands. Patients were randomly assigned to either the endoscopic or the surgical step-up approach. The endoscopic approach consisted of endoscopic ultrasound-guided transluminal drainage followed, if necessary, by endoscopic necrosectomy. The surgical approach consisted of percutaneous catheter drainage followed, if necessary, by video-assisted retroperitoneal debridement. The primary endpoint was a composite of major complications or death during 6-month follow-up. Analyses were by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN09186711. Between Sept 20, 2011, and Jan 29, 2015, we screened 418 patients with pancreatic or extrapancreatic necrosis, of which 98 patients were enrolled and randomly assigned to the endoscopic step-up approach (n=51) or the surgical step-up approach (n=47). The primary endpoint occurred in 22 (43%) of 51 patients in the endoscopy group and in 21 (45%) of 47 patients in the surgery group (risk ratio [RR] 0·97, 95% CI 0·62-1·51; p=0·88). Mortality did not differ between groups (nine [18%] patients in the endoscopy group vs six [13%] patients in the surgery group; RR 1·38, 95% CI 0·53-3·59, p=0·50), nor did any of the major complications included in the primary endpoint. In patients with infected necrotising pancreatitis, the endoscopic step-up approach was not superior to the surgical step-up approach in reducing major

  12. A randomized trial of rectal indomethacin and sublingual nitrates to prevent post-ERCP pancreatitis.

    Science.gov (United States)

    Sotoudehmanesh, Rasoul; Eloubeidi, Mohamad Ali; Asgari, Ali Ali; Farsinejad, Maryam; Khatibian, Morteza

    2014-06-01

    Acute pancreatitis is the most common adverse event of endoscopic retrograde cholangiopancreatography (ERCP). Recent data suggest that indomethacin can reduce the risk of post-ERCP pancreatitis (PEP) in high-risk individuals. However, whether the combination of indomethacin and sublingual nitrates is superior to indomethacin alone is unknown. Therefore, we aimed to evaluate the efficacy of rectally administered indomethacin plus sublingual nitrate compared with indomethacin alone to prevent PEP. During a 17-month period, all eligible patients who underwent ERCP were enrolled in this study. We excluded patients who had undergone a prior endoscopic sphincterotomy. In a double-blind controlled randomized trial, patients received a suppository containing 100 mg of indomethacin, plus 5 mg of sublingual nitrate (group A), or a suppository containing 100 mg of indomethacin, plus sublingual placebo (group B), before ERCP. Serum amylase levels and clinically pertinent evaluations were measured in all patients after ERCP. Of the 300 enrolled patients, 150 received indomethacin plus nitrate. Thirty-three patients developed pancreatitis: 10 (6.7%) in group A and 23 (15.3%) in group B (P=0.016, risk ratio=0.39, 95% confidence intervals (CI): 0.18-0.86). More than 80% of the patients were at high risk of developing pancreatitis after ERCP. Absolute risk reduction, relative risk reduction, and number needed to treat for the prevention of PEP were 8.6% (95% CI: 4.7-14.5), 56.2% (95% CI: 50.6-60.8), and 12 (95% CI: 7-22), respectively. Combination of rectal indomethacin and sublingual nitrate given before ERCP was significantly more likely to reduce the incidence of PEP than indomethacin suppository alone. Multicenter trials to confirm these promising findings are needed.

  13. MDCT of acute pancreatitis: Intraindividual comparison of single-phase versus dual-phase MDCT for initial assessment of acute pancreatitis using different CT scoring systems

    Energy Technology Data Exchange (ETDEWEB)

    Avanesov, Maxim, E-mail: m.avanesov@uke.de [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Weinrich, Julius M.; Kraus, Thomas [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Derlin, Thorsten [Department of Nuclear Medicine, Hannover Medical School (Germany); Adam, Gerhard; Yamamura, Jin [Department of Diagnostic and Interventional Radiology and Nuclear Medicine, University Medical Center Hamburg-Eppendorf, Hamburg (Germany); Karul, Murat [Department of Diagnostic and Interventional Radiology, Marienkrankenhaus Hamburg (Germany)

    2016-11-15

    Objectives: The purpose of the retrospective study was to evaluate the additional value of dual-phase multidetector computed tomography (MDCT) protocols over a single-phase protocol on initial MDCT in patients with acute pancreatitis using three CT-based pancreatitis severity scores with regard to radiation dose. Methods: In this retrospective, IRB approved study MDCT was performed in 102 consecutive patients (73 males; 55years, IQR48–64) with acute pancreatitis. Inclusion criteria were CT findings of interstitial edematous pancreatitis (IP) or necrotizing pancreatitis (NP) and a contrast-enhanced dual-phase (arterial phase and portal-venous phase) abdominal CT performed at ≥72 h after onset of symptoms. The severity of pancreatic and extrapancreatic changes was independently assessed by 2 observers using 3 validated CT-based scoring systems (CTSI, mCTSI, EPIC). All scores were applied to arterial phase and portal venous phase scans and compared to score results of portal venous phase scans, assessed ≥14 days after initial evaluation. For effective dose estimation, volume CT dose index (CTDIvol) and dose length product (DLP) were recorded in all examinations. Results: In neither of the CT severity scores a significant difference was observed after application of a dual-phase protocol compared with a single-phase protocol (IP: CTSI: 2.7 vs. 2.5, p = 0.25; mCTSI: 4.0 vs. 4.0, p = 0.10; EPIC: 2.0 vs. 2.0, p = 0.41; NP: CTSI: 8.0 vs. 7.0, p = 0.64; mCTSI: 8.0 vs. 8.0, p = 0.10; EPIC: 3.0 vs. 3.0, p = 0.06). The application of a single-phase CT protocol was associated with a median effective dose reduction of 36% (mean dose reduction 31%) compared to a dual-phase CT scan. Conclusions: An initial dual-phase abdominal CT after ≥72 h after onset of symptoms of acute pancreatitis was not superior to a single-phase protocol for evaluation of the severity of pancreatic and extrapancreatic changes. However, the effective radiation dose may be reduced by 36% using a

  14. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Wolthers, Benjamin O.; Frandsen, Thomas L.; Baruchel, André

    2017-01-01

    BACKGROUND: Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re......-exposing patients with asparaginase-associated pancreatitis to asparaginase, 18 acute lymphoblastic leukaemia trial groups merged data for this observational study. METHODS: Patient files from 26 trials run by 18 trial groups were reviewed on children (aged 1·0-17·9 years) diagnosed with t(9;22)-negative acute...... lymphoblastic leukaemia between June 1, 1996, and Jan 1, 2016, who within 50 days of asparaginase exposure developed asparaginase-associated pancreatitis. Asparaginase-associated pancreatitis was defined by at least two criteria: abdominal pain, pancreatic enzymes at least three times the upper limit of normal...

  15. Acute pancreatitis.

    Science.gov (United States)

    Talukdar, Rupjyoti; Vege, Santhi S

    2015-09-01

    To summarize recent data on classification systems, cause, risk factors, severity prediction, nutrition, and drug treatment of acute pancreatitis. Comparison of the Revised Atlanta Classification and Determinant Based Classification has shown heterogeneous results. Simvastatin has a protective effect against acute pancreatitis. Young black male, alcohol, smoldering symptoms, and subsequent diagnosis of chronic pancreatitis are risk factors associated with readmissions after acute pancreatitis. A reliable clinical or laboratory marker or a scoring system to predict severity is lacking. The PYTHON trial has shown that oral feeding with on demand nasoenteric tube feeding after 72 h is as good as nasoenteric tube feeding within 24 h in preventing infections in predicted severe acute pancreatitis. Male sex, multiple organ failure, extent of pancreatic necrosis, and heterogeneous collection are factors associated with failure of percutaneous drainage of pancreatic collections. The newly proposed classification systems of acute pancreatitis need to be evaluated more critically. New biomarkers are needed for severity prediction. Further well designed studies are required to assess the type of enteral nutritional formulations for acute pancreatitis. The optimal minimally invasive method or combination to debride the necrotic collections is evolving. There is a great need for a drug to treat the disease early on to prevent morbidity and mortality.

  16. Blockchain protocols in clinical trials: Transparency and traceability of consent

    Science.gov (United States)

    Benchoufi, Mehdi; Porcher, Raphael; Ravaud, Philippe

    2018-01-01

    Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again.  We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security, transparency and could be

  17. Blockchain protocols in clinical trials: Transparency and traceability of consent.

    Science.gov (United States)

    Benchoufi, Mehdi; Porcher, Raphael; Ravaud, Philippe

    2017-01-01

    Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients' informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient's consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again.  We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security, transparency and could be a

  18. Environmental risk factors for chronic pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Nitsche, Claudia; Simon, Peter; Weiss, F Ulrich; Fluhr, Gabriele; Weber, Eckhard; Gärtner, Simone; Behn, Claas O; Kraft, Matthias; Ringel, Jörg; Aghdassi, Ali; Mayerle, Julia; Lerch, Markus M

    2011-01-01

    Chronic pancreatitis has long been thought to be mainly associated with immoderate alcohol consumption. The observation that only ∼10% of heavy drinkers develop chronic pancreatitis not only suggests that other environmental factors, such as tobacco smoke, are potent additional risk factors, but also that the genetic component of pancreatitis is more common than previously presumed. Either disease-causing or protective traits have been indentified for mutations in different trypsinogen genes, the gene for the trypsin inhibitor SPINK1, chymotrypsinogen C, and the cystic fibrosis transmembane conductance regulator (CFTR). Other factors that have been proposed to contribute to pancreatitis are obesity, diets high in animal protein and fat, as well as antioxidant deficiencies. For the development of pancreatic cancer, preexisting chronic pancreatitis, more prominently hereditary pancreatitis, is a risk factor. The data on environmental risk factors for pancreatic cancer are, with the notable exception of tobacco smoke, either sparse, unconfirmed or controversial. Obesity appears to increase the risk of pancreatic cancer in the West but not in Japan. Diets high in processed or red meat, diets low in fruits and vegetables, phytochemicals such as lycopene and flavonols, have been proposed and refuted as risk or protective factors in different trials. The best established and single most important risk factor for cancer as well as pancreatitis and the one to clearly avoid is tobacco smoke. Copyright © 2011 S. Karger AG, Basel.

  19. Mesenchymal Stromal Cell Therapy for Pancreatitis: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Sara M. Ahmed

    2018-01-01

    Full Text Available Background. Based on animal studies, adult mesenchymal stromal cells (MSCs are promising for the treatment of pancreatitis. However, the best type of this form of cell therapy and its mechanism of action remain unclear. Methods. We searched the PubMed, Web of Science, Scopus, Google Scholar, and Clinical Trials.gov websites for studies using MSCs as a therapy for both acute and chronic pancreatitis published until September 2017. Results. We identified 276 publications; of these publications, 18 met our inclusion criteria. In animal studies, stem cell therapy was applied more frequently for acute pancreatitis than for chronic pancreatitis. No clinical trials were identified. MSC therapy ameliorated pancreatic inflammation in acute pancreatitis and pancreatic fibrosis in chronic pancreatitis. Bone marrow and umbilical cord MSCs were the most frequently administered cell types. Due to the substantial heterogeneity among the studies regarding the type, source, and dose of MSCs used, conducting a meta-analysis was not feasible to determine the best type of MSCs. Conclusion. The available data were insufficient for determining the best type of MSCs for the treatment of acute or chronic pancreatitis; therefore, clinical trials investigating the use of MSCs as therapy for pancreatitis are not warranted.

  20. Questions about the use of antibiotics in acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Assef Jose

    2006-07-01

    Full Text Available Abstract Background and objective The use of antibiotics in acute pancreatitis despite recent clinical trials remains controversial. The aim of this study is to review the latest clinical trials and guidelines about antibiotics in acute pancreatitis and determine its proper use. Methods Through a Medline search, we selected and analyzed pertinent randomized clinical trials and guidelines that evaluated the use of antibiotics in acute pancreatitis. We answered the most frequent questions about this topic. Results and conclusion Based on these clinical trials and guidelines, we conclude that the best treatment currently is the use of antibiotics in patients with severe acute pancreatitis with more than 30% of pancreatic necrosis. The best option for the treatment is Imipenem 3 × 500 mg/day i.v. for 14 days. Alternatively, Ciprofloxacin 2 × 400 mg/day i.v. associated with Metronidazole 3 × 500 mg for 14 days can also be considered as an option.

  1. Minimally invasive 'step-up approach' versus maximal necrosectomy in patients with acute necrotising pancreatitis (PANTER trial): design and rationale of a randomised controlled multicenter trial [ISRCTN13975868].

    Science.gov (United States)

    Besselink, Marc G H; van Santvoort, Hjalmar C; Nieuwenhuijs, Vincent B; Boermeester, Marja A; Bollen, Thomas L; Buskens, Erik; Dejong, Cornelis H C; van Eijck, Casper H J; van Goor, Harry; Hofker, Sijbrand S; Lameris, Johan S; van Leeuwen, Maarten S; Ploeg, Rutger J; van Ramshorst, Bert; Schaapherder, Alexander F M; Cuesta, Miguel A; Consten, Esther C J; Gouma, Dirk J; van der Harst, Erwin; Hesselink, Eric J; Houdijk, Lex P J; Karsten, Tom M; van Laarhoven, Cees J H M; Pierie, Jean-Pierre E N; Rosman, Camiel; Bilgen, Ernst Jan Spillenaar; Timmer, Robin; van der Tweel, Ingeborg; de Wit, Ralph J; Witteman, Ben J M; Gooszen, Hein G

    2006-04-11

    The initial treatment of acute necrotizing pancreatitis is conservative. Intervention is indicated in patients with (suspected) infected necrotizing pancreatitis. In the Netherlands, the standard intervention is necrosectomy by laparotomy followed by continuous postoperative lavage (CPL). In recent years several minimally invasive strategies have been introduced. So far, these strategies have never been compared in a randomised controlled trial. The PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach) was conceived to yield the evidence needed for a considered policy decision. 88 patients with (suspected) infected necrotizing pancreatitis will be randomly allocated to either group A) minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD) or group B) maximal necrosectomy by laparotomy. Both procedures are followed by CPL. Patients will be recruited from 20 hospitals, including all Dutch university medical centres, over a 3-year period. The primary endpoint is the proportion of patients suffering from postoperative major morbidity and mortality. Secondary endpoints are complications, new onset sepsis, length of hospital and intensive care stay, quality of life and total (direct and indirect) costs. To demonstrate that the 'step-up approach' can reduce the major morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total sample size of 88 patients was calculated. The PANTER-study is a randomised controlled trial that will provide evidence on the merits of a minimally invasive 'step-up approach' in patients with (suspected) infected necrotizing pancreatitis.

  2. A multicenter randomized controlled trial comparing pancreatic leaks after TissueLink versus SEAMGUARD after distal pancreatectomy (PLATS) NCT01051856.

    Science.gov (United States)

    Shubert, Christopher R; Ferrone, Christina R; Fernandez-Del Castillo, Carlos; Kendrick, Michael L; Farnell, Michael B; Smoot, Rory L; Truty, Mark J; Que, Florencia G

    2016-11-01

    Pancreatic leak is common after distal pancreatectomy. This trial sought to compare TissueLink closure of the pancreatic stump to that of SEAMGUARD. A multicenter, prospective, trial of patients undergoing distal pancreatectomy randomized to either TissueLink or SEAMGUARD. Enrollment was closed early due to poor accrual. Overall, 67 patients were enrolled, 35 TissueLink and 32 SEAMGUARD. The two groups differed in American Society of Anesthesiologist class and diagnosis at baseline and were relatively balanced otherwise. Overall, 37 of 67 patients (55%) experienced a leak of any grade, 15 (46.9%) in the SEAMGUARD arm and 22 (62.9%) in the TissueLink arm (P = 0.19). The clinically significant leak rate was 17.9%; 22.9% for TissueLink and 12.5% for SEAMGUARD (P = 0.35). There were no statistically significant differences in major or any pancreatic fistula-related morbidity between the two groups. This is the first multicentered randomized trial evaluating leak rate after distal pancreatectomy between two common transection methods. Although a difference in leak rates was observed, it was not statistically significant and therefore does not provide evidence of the superiority of one technique over the other. Choice should remain based on surgeon comfort, experience, and pancreas characteristics. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Minimally invasive 'step-up approach' versus maximal necrosectomy in patients with acute necrotising pancreatitis (PANTER trial): design and rationale of a randomised controlled multicenter trial [ISRCTN38327949

    Science.gov (United States)

    Besselink, Marc GH; van Santvoort, Hjalmar C; Nieuwenhuijs, Vincent B; Boermeester, Marja A; Bollen, Thomas L; Buskens, Erik; Dejong, Cornelis HC; van Eijck, Casper HJ; van Goor, Harry; Hofker, Sijbrand S; Lameris, Johan S; van Leeuwen, Maarten S; Ploeg, Rutger J; van Ramshorst, Bert; Schaapherder, Alexander FM; Cuesta, Miguel A; Consten, Esther CJ; Gouma, Dirk J; van der Harst, Erwin; Hesselink, Eric J; Houdijk, Lex PJ; Karsten, Tom M; van Laarhoven, Cees JHM; Pierie, Jean-Pierre EN; Rosman, Camiel; Bilgen, Ernst Jan Spillenaar; Timmer, Robin; van der Tweel, Ingeborg; de Wit, Ralph J; Witteman, Ben JM; Gooszen, Hein G

    2006-01-01

    Background The initial treatment of acute necrotizing pancreatitis is conservative. Intervention is indicated in patients with (suspected) infected necrotizing pancreatitis. In the Netherlands, the standard intervention is necrosectomy by laparotomy followed by continuous postoperative lavage (CPL). In recent years several minimally invasive strategies have been introduced. So far, these strategies have never been compared in a randomised controlled trial. The PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach) was conceived to yield the evidence needed for a considered policy decision. Methods/design 88 patients with (suspected) infected necrotizing pancreatitis will be randomly allocated to either group A) minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD) or group B) maximal necrosectomy by laparotomy. Both procedures are followed by CPL. Patients will be recruited from 20 hospitals, including all Dutch university medical centres, over a 3-year period. The primary endpoint is the proportion of patients suffering from postoperative major morbidity and mortality. Secondary endpoints are complications, new onset sepsis, length of hospital and intensive care stay, quality of life and total (direct and indirect) costs. To demonstrate that the 'step-up approach' can reduce the major morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total sample size of 88 patients was calculated. Discussion The PANTER-study is a randomised controlled trial that will provide evidence on the merits of a minimally invasive 'step-up approach' in patients with (suspected) infected necrotizing pancreatitis. PMID:16606471

  4. Minimally invasive 'step-up approach' versus maximal necrosectomy in patients with acute necrotising pancreatitis (PANTER trial: design and rationale of a randomised controlled multicenter trial [ISRCTN13975868

    Directory of Open Access Journals (Sweden)

    Houdijk Lex PJ

    2006-04-01

    Full Text Available Abstract Background The initial treatment of acute necrotizing pancreatitis is conservative. Intervention is indicated in patients with (suspected infected necrotizing pancreatitis. In the Netherlands, the standard intervention is necrosectomy by laparotomy followed by continuous postoperative lavage (CPL. In recent years several minimally invasive strategies have been introduced. So far, these strategies have never been compared in a randomised controlled trial. The PANTER study (PAncreatitis, Necrosectomy versus sTEp up appRoach was conceived to yield the evidence needed for a considered policy decision. Methods/design 88 patients with (suspected infected necrotizing pancreatitis will be randomly allocated to either group A minimally invasive 'step-up approach' starting with drainage followed, if necessary, by videoscopic assisted retroperitoneal debridement (VARD or group B maximal necrosectomy by laparotomy. Both procedures are followed by CPL. Patients will be recruited from 20 hospitals, including all Dutch university medical centres, over a 3-year period. The primary endpoint is the proportion of patients suffering from postoperative major morbidity and mortality. Secondary endpoints are complications, new onset sepsis, length of hospital and intensive care stay, quality of life and total (direct and indirect costs. To demonstrate that the 'step-up approach' can reduce the major morbidity and mortality rate from 45 to 16%, with 80% power at 5% alpha, a total sample size of 88 patients was calculated. Discussion The PANTER-study is a randomised controlled trial that will provide evidence on the merits of a minimally invasive 'step-up approach' in patients with (suspected infected necrotizing pancreatitis.

  5. Therapy of pancreatic cancer

    International Nuclear Information System (INIS)

    Takeda, Yutaka; Kitagawa, Toru; Nakamori, Shoji

    2009-01-01

    Pancreatic cancer remains one of the most difficult diseases to cure. Japan pancreas society guidelines for management of pancreatic cancer indicate therapeutic algorithm according to the clinical stage. For locally limited pancreatic cancer (cStage I, II, III in Japanese classification system), surgical resection is recommended, however prognosis is still poor. Major randomized controlled trials of resected pancreatic cancer indicates that adjuvant chemotherapy is superior to observation and gemcitabine is superior to 5-fluorouracil (FU). For locally advanced resectable pancreatic cancer (cStage IVa in Japanese classification system (JCS)), we perform neoadjuvant chemoradiotherapy. Phase I study established a recommended dose of 800 mg gemcitabine and radiation dose of 36 Gy. For locally advanced nonresectable pancreatic cancer (cStage IVa in JCS), chemoradiotherapy followed by chemotherapy is recommended. Although pancreatic cancer is chemotherapy resistant tumor, systemic chemotherapy is recommended for metastatic pancreatic cancer (cStage IVb in JCS). Single-agent gemcitabine is the standard first line agent for the treatment of advanced pancreatic cancer. Meta-analysis of chemotherapy showed possibility of survival benefit of gemcitabine combination chemotherapy over gemcitabine alone. We hope gemcitabine combination chemotherapy or molecular targeted therapy will improve prognosis of pancreatic cancer in the future. (author)

  6. Endoscopic or surgical intervention for painful obstructive chronic pancreatitis.

    Science.gov (United States)

    Ahmed Ali, Usama; Pahlplatz, Johanna M; Nealon, Wiliam H; van Goor, Harry; Gooszen, Hein G; Boermeester, Marja A

    2015-03-19

    Endoscopy and surgery are the treatment modalities of choice for patients with chronic pancreatitis and dilated pancreatic duct (obstructive chronic pancreatitis). Physicians face, without clear consensus, the choice between endoscopy or surgery for this group of patients. To assess and compare the effects and complications of surgical and endoscopic interventions in the management of pain for obstructive chronic pancreatitis. We searched the following databases in The Cochrane Library: CENTRAL (2014, Issue 2), the Cochrane Database of Systematic Reviews (2014, Issue 2), and DARE (2014, Issue 2). We also searched the following databases up to 25 March 2014: MEDLINE (from 1950), Embase (from 1980), and the Conference Proceedings Citation Index - Science (CPCI-S) (from 1990). We performed a cross-reference search. Two review authors independently performed the selection of trials. All randomised controlled trials (RCTs) of endoscopic or surgical interventions in obstructive chronic pancreatitis. We included trials comparing endoscopic versus surgical interventions as well as trials comparing either endoscopic or surgical interventions to conservative treatment (i.e. non-invasive treatment modalities). We included relevant trials irrespective of blinding, the number of participants randomised, and the language of the article. We used standard methodological procedures expected by The Cochrane Collaboration. Two authors independently extracted data from the articles. We evaluated the methodological quality of the included trials and requested additional information from study authors in the case of missing data. We identified three eligible trials. Two trials compared endoscopic intervention with surgical intervention and included a total of 111 participants: 55 in the endoscopic group and 56 in the surgical group. Compared with the endoscopic group, the surgical group had a higher proportion of participants with pain relief, both at middle/long-term follow-up (two to

  7. Guidelines for Inclusion of Patient-Reported Outcomes in Clinical Trial Protocols: The SPIRIT-PRO Extension.

    Science.gov (United States)

    Calvert, Melanie; Kyte, Derek; Mercieca-Bebber, Rebecca; Slade, Anita; Chan, An-Wen; King, Madeleine T; Hunn, Amanda; Bottomley, Andrew; Regnault, Antoine; Chan, An-Wen; Ells, Carolyn; O'Connor, Daniel; Revicki, Dennis; Patrick, Donald; Altman, Doug; Basch, Ethan; Velikova, Galina; Price, Gary; Draper, Heather; Blazeby, Jane; Scott, Jane; Coast, Joanna; Norquist, Josephine; Brown, Julia; Haywood, Kirstie; Johnson, Laura Lee; Campbell, Lisa; Frank, Lori; von Hildebrand, Maria; Brundage, Michael; Palmer, Michael; Kluetz, Paul; Stephens, Richard; Golub, Robert M; Mitchell, Sandra; Groves, Trish

    2018-02-06

    Patient-reported outcome (PRO) data from clinical trials can provide valuable evidence to inform shared decision making, labeling claims, clinical guidelines, and health policy; however, the PRO content of clinical trial protocols is often suboptimal. The SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) statement was published in 2013 and aims to improve the completeness of trial protocols by providing evidence-based recommendations for the minimum set of items to be addressed, but it does not provide PRO-specific guidance. To develop international, consensus-based, PRO-specific protocol guidance (the SPIRIT-PRO Extension). The SPIRIT-PRO Extension was developed following the Enhancing Quality and Transparency of Health Research (EQUATOR) Network's methodological framework for guideline development. This included (1) a systematic review of existing PRO-specific protocol guidance to generate a list of potential PRO-specific protocol items (published in 2014); (2) refinements to the list and removal of duplicate items by the International Society for Quality of Life Research (ISOQOL) Protocol Checklist Taskforce; (3) an international stakeholder survey of clinical trial research personnel, PRO methodologists, health economists, psychometricians, patient advocates, funders, industry representatives, journal editors, policy makers, ethicists, and researchers responsible for evidence synthesis (distributed by 38 international partner organizations in October 2016); (4) an international Delphi exercise (n = 137 invited; October 2016 to February 2017); and (5) consensus meeting (n = 30 invited; May 2017). Prior to voting, consensus meeting participants were informed of the results of the Delphi exercise and given data from structured reviews evaluating the PRO protocol content of 3 defined samples of trial protocols. The systematic review identified 162 PRO-specific protocol recommendations from 54 sources. The ISOQOL Taskforce (n

  8. Protocol adherence for continuously titrated interventions in randomized trials: an overview of the current methodology and case study.

    Science.gov (United States)

    Lauzier, F; Adhikari, N K; Seely, A; Koo, K K Y; Belley-Côté, E P; Burns, K E A; Cook, D J; D'Aragon, F; Rochwerg, B; Kho, M E; Oczkowksi, S J W; Duan, E H; Meade, M O; Day, A G; Lamontagne, F

    2017-07-17

    The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration. Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75-80 mmHg) versus lower (60-65 mmHg) mean arterial pressure (MAP) targets for vasopressor therapy in shock. In this trial, potential protocol deviations were defined as MAP values outside the targeted range for >4 consecutive hours during vasopressor therapy without synchronous and consistent adjustments of vasopressor doses. An adjudication committee reviewed each potential deviation to determine if it was clinically-justified or not. There are four reasons for this contextual measurement and reporting of protocol adherence. First, between-arm separation is a robust measure of adherence to complex protocols. Second, adherence assessed by protocol deviations varies in function of the definition of deviations and the frequency of measurements. Third, distinguishing clinically-justified vs. not clinically-justified protocol deviations acknowledges clinically sensible bedside decision-making and offers a clear terminology before the trial begins. Finally, multiple metrics exist to report protocol deviations, which provides different information but complementary information on protocol adherence. In trials of interventions requiring continuous titration, metrics used for defining protocol deviations have a considerable impact on the interpretation of protocol adherence. Definitions for protocol deviations should be prespecified and correlated with between-arm separation, if it can be measured.

  9. Guidelines for time-to-event end-point definitions in trials for pancreatic cancer. Results of the DATECAN initiative (Definition for the Assessment of Time-to-event End-points in CANcer trials).

    Science.gov (United States)

    Bonnetain, Franck; Bonsing, Bert; Conroy, Thierry; Dousseau, Adelaide; Glimelius, Bengt; Haustermans, Karin; Lacaine, François; Van Laethem, Jean Luc; Aparicio, Thomas; Aust, Daniela; Bassi, Claudio; Berger, Virginie; Chamorey, Emmanuel; Chibaudel, Benoist; Dahan, Laeticia; De Gramont, Aimery; Delpero, Jean Robert; Dervenis, Christos; Ducreux, Michel; Gal, Jocelyn; Gerber, Erich; Ghaneh, Paula; Hammel, Pascal; Hendlisz, Alain; Jooste, Valérie; Labianca, Roberto; Latouche, Aurelien; Lutz, Manfred; Macarulla, Teresa; Malka, David; Mauer, Muriel; Mitry, Emmanuel; Neoptolemos, John; Pessaux, Patrick; Sauvanet, Alain; Tabernero, Josep; Taieb, Julien; van Tienhoven, Geertjan; Gourgou-Bourgade, Sophie; Bellera, Carine; Mathoulin-Pélissier, Simone; Collette, Laurence

    2014-11-01

    Using potential surrogate end-points for overall survival (OS) such as Disease-Free- (DFS) or Progression-Free Survival (PFS) is increasingly common in randomised controlled trials (RCTs). However, end-points are too often imprecisely defined which largely contributes to a lack of homogeneity across trials, hampering comparison between them. The aim of the DATECAN (Definition for the Assessment of Time-to-event End-points in CANcer trials)-Pancreas project is to provide guidelines for standardised definition of time-to-event end-points in RCTs for pancreatic cancer. Time-to-event end-points currently used were identified from a literature review of pancreatic RCT trials (2006-2009). Academic research groups were contacted for participation in order to select clinicians and methodologists to participate in the pilot and scoring groups (>30 experts). A consensus was built after 2 rounds of the modified Delphi formal consensus approach with the Rand scoring methodology (range: 1-9). For pancreatic cancer, 14 time to event end-points and 25 distinct event types applied to two settings (detectable disease and/or no detectable disease) were considered relevant and included in the questionnaire sent to 52 selected experts. Thirty experts answered both scoring rounds. A total of 204 events distributed over the 14 end-points were scored. After the first round, consensus was reached for 25 items; after the second consensus was reached for 156 items; and after the face-to-face meeting for 203 items. The formal consensus approach reached the elaboration of guidelines for standardised definitions of time-to-event end-points allowing cross-comparison of RCTs in pancreatic cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  10. Hypermutation In Pancreatic Cancer.

    Science.gov (United States)

    Humphris, Jeremy L; Patch, Ann-Marie; Nones, Katia; Bailey, Peter J; Johns, Amber L; McKay, Skye; Chang, David K; Miller, David K; Pajic, Marina; Kassahn, Karin S; Quinn, Michael C J; Bruxner, Timothy J C; Christ, Angelika N; Harliwong, Ivon; Idrisoglu, Senel; Manning, Suzanne; Nourse, Craig; Nourbakhsh, Ehsan; Stone, Andrew; Wilson, Peter J; Anderson, Matthew; Fink, J Lynn; Holmes, Oliver; Kazakoff, Stephen; Leonard, Conrad; Newell, Felicity; Waddell, Nick; Wood, Scott; Mead, Ronald S; Xu, Qinying; Wu, Jianmin; Pinese, Mark; Cowley, Mark J; Jones, Marc D; Nagrial, Adnan M; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Chou, Angela; Scarlett, Christopher J; Pinho, Andreia V; Rooman, Ilse; Giry-Laterriere, Marc; Samra, Jaswinder S; Kench, James G; Merrett, Neil D; Toon, Christopher W; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Jamieson, Nigel B; McKay, Colin J; Carter, C Ross; Dickson, Euan J; Graham, Janet S; Duthie, Fraser; Oien, Karin; Hair, Jane; Morton, Jennifer P; Sansom, Owen J; Grützmann, Robert; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Rusev, Borislav; Corbo, Vincenzo; Salvia, Roberto; Cataldo, Ivana; Tortora, Giampaolo; Tempero, Margaret A; Hofmann, Oliver; Eshleman, James R; Pilarsky, Christian; Scarpa, Aldo; Musgrove, Elizabeth A; Gill, Anthony J; Pearson, John V; Grimmond, Sean M; Waddell, Nicola; Biankin, Andrew V

    2017-01-01

    Pancreatic cancer is molecularly diverse, with few effective therapies. Increased mutation burden and defective DNA repair are associated with response to immune checkpoint inhibitors in several other cancer types. We interrogated 385 pancreatic cancer genomes to define hypermutation and its causes. Mutational signatures inferring defects in DNA repair were enriched in those with the highest mutation burdens. Mismatch repair deficiency was identified in 1% of tumors harboring different mechanisms of somatic inactivation of MLH1 and MSH2. Defining mutation load in individual pancreatic cancers and the optimal assay for patient selection may inform clinical trial design for immunotherapy in pancreatic cancer. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Radiosensitization of pancreatic cancer cells by 2',2'-difluoro-2'-deoxycytidine

    International Nuclear Information System (INIS)

    Lawrence, Theodore S.; Chang, Emily Y.; Hahn, Tina M.; Hertel, Larry W.; Shewach, Donna S.

    1996-01-01

    Purpose: We have reported that the deoxycytidine analog 2',2'-difluoro-2'-deoxycytidine (dFdCyd) is a potent radiosensitizer of HT29 human colon cancer cells probably through its effects on intracellular deoxyribonucleotide (dNTP) pools. Because dFdCyd has activity against pancreatic cancer in clinical trials, we wished to determine if dFdCyd would radiosensitize human pancreatic cancer cells. Methods and Materials: We assessed the effect of dFdCyd on radiation sensitivity of two human pancreatic cancer cell lines, Panc-1 and BxPC-3. To begin to investigate the mechanism of sensitization, we determined the effect of dFdCyd on dNTP pools and cell cycle distribution. Results: We found that dFdCyd produced radiation enhancement ratios of 1.7-1.8 under noncytotoxic conditions in both cell lines. Sensitization was not associated with intracellular levels of 2',2'-difluoro-2'-deoxycytidine triphosphate, the cytotoxic metabolite of dFdCyd, but occurred when dATP pools were depleted below the level of approximately 1 μM. Although both cell lines showed substantial cell cycle redistribution after drug treatment, the flow cytogram of the BxPC-3 cells would not, by itself, be anticipated to result in increased radiation sensitivity. Conclusions: These findings demonstrate that dFdCyd is a potent radiation sensitizer of human pancreatic cancer cells and support the development of a clinical protocol using combined dFdCyd and radiation therapy in the treatment of pancreatic cancer

  12. Comparison between publicly accessible publications, registries, and protocols of phase III trials indicated persistence of selective outcome reporting.

    Science.gov (United States)

    Zhang, Sheng; Liang, Fei; Li, Wenfeng

    2017-11-01

    The decision to make protocols of phase III randomized controlled trials (RCTs) publicly accessible by leading journals was a landmark event in clinical trial reporting. Here, we compared primary outcomes defined in protocols with those in publications describing the trials and in trial registration. We identified phase III RCTs published between January 1, 2012, and June 30, 2015, in The New England Journal of Medicine, The Lancet, The Journal of the American Medical Association, and The BMJ with available protocols. Consistency in primary outcomes between protocols and registries (articles) was evaluated. We identified 299 phase III RCTs with available protocols in this analysis. Out of them, 25 trials (8.4%) had some discrepancy for primary outcomes between publications and protocols. Types of discrepancies included protocol-defined primary outcome reported as nonprimary outcome in publication (11 trials, 3.7%), protocol-defined primary outcome omitted in publication (10 trials, 3.3%), new primary outcome introduced in publication (8 trials, 2.7%), protocol-defined nonprimary outcome reported as primary outcome in publication (4 trials, 1.3%), and different timing of assessment of primary outcome (4 trials, 1.3%). Out of trials with discrepancies in primary outcome, 15 trials (60.0%) had discrepancies that favored statistically significant results. Registration could be seen as a valid surrogate of protocol in 237 of 299 trials (79.3%) with regard to primary outcome. Despite unrestricted public access to protocols, selective outcome reporting persists in a small fraction of phase III RCTs. Only studies from four leading journals were included, which may cause selection bias and limit the generalizability of this finding. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Rational drug use in acute pancreatitis: Case report

    Directory of Open Access Journals (Sweden)

    Rosić Nikola

    2011-01-01

    Full Text Available Acute pancreatitis is a sudden inflammation of pancreas where its enzymes autodigest the gland. Two main causes of acute pancreatitis are alcoholism and billiar calculosis. Treatment consists of preventing dehydration, analgesia, decrease of pancreatic exocrine function, enteral nutritional support , respiratory and renal function support and surgery. The patient presents with abdominal pain that lasts for few days and is followed by vomiting. Laboratory tests first revealed abnormal values of blood count and pancreas enzymes (leucocytes -19,7 x 109/L, hematocrit - 0,32, amylase - 52569 IU/L, lypase - 4750 IU/L, CRP - 152 IU/L, albumins - 25 g/L, followed by abnormal values of liver enzymes (AST - 80 IU/L, ALT - 127 IU/L, GGT - 362 IU/L. Further diagnostic procedures showed billiary calculosis, pleural effusion and acute pancreatitis with ascites. No surgery was performed, due to the lack of infect ion and the signs of the patient going into recovery. It was observed that not all diagnostic procedures that exist in the protocol of treatment, such as ERCP or biopsy of pancreatic t issue with microbiological investigation, were performed. Considering the rules of rat ional drug therapy, as well as the protocols that are to be applied in Clinical center 'Kragujevac' in Kragujevac, it was observed that some drugs (antibiotics and albumin were not used in a proper manner, i.e. in compliance with the protocol, which increased the cost of the treatment without improving the patient health or shortening the hospital stay.

  14. Protocol adherence for continuously titrated interventions in randomized trials: an overview of the current methodology and case study

    Directory of Open Access Journals (Sweden)

    F. Lauzier

    2017-07-01

    Full Text Available Abstract Background The standard definition for protocol adherence is the proportion of all scheduled doses that are delivered. In clinical research, this definition has several limitations when evaluating protocol adherence in trials that study interventions requiring continuous titration. Discussion Building upon a specific case study, we analyzed a recent trial of a continuously titrated intervention to assess the impact of different definitions of protocol deviations on the interpretation of protocol adherence. The OVATION pilot trial was an open-label randomized controlled trial of higher (75–80 mmHg versus lower (60–65 mmHg mean arterial pressure (MAP targets for vasopressor therapy in shock. In this trial, potential protocol deviations were defined as MAP values outside the targeted range for >4 consecutive hours during vasopressor therapy without synchronous and consistent adjustments of vasopressor doses. An adjudication committee reviewed each potential deviation to determine if it was clinically-justified or not. There are four reasons for this contextual measurement and reporting of protocol adherence. First, between-arm separation is a robust measure of adherence to complex protocols. Second, adherence assessed by protocol deviations varies in function of the definition of deviations and the frequency of measurements. Third, distinguishing clinically-justified vs. not clinically-justified protocol deviations acknowledges clinically sensible bedside decision-making and offers a clear terminology before the trial begins. Finally, multiple metrics exist to report protocol deviations, which provides different information but complementary information on protocol adherence. Conclusions In trials of interventions requiring continuous titration, metrics used for defining protocol deviations have a considerable impact on the interpretation of protocol adherence. Definitions for protocol deviations should be prespecified and correlated

  15. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

    International Nuclear Information System (INIS)

    Golcher, Henriette; Merkel, Susanne; Hohenberger, Werner; Brunner, Thomas B.; Witzigmann, Helmut; Marti, Lukas; Bechstein, Wolf-Otto; Bruns, Christiane; Jungnickel, Henry; Schreiber, Stefan; Grabenbauer, Gerhard G.; Meyer, Thomas; Fietkau, Rainer

    2015-01-01

    In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.) [de

  16. Chronic Pancreatitis in the 21st Century - Research Challenges and Opportunities

    Science.gov (United States)

    Uc, Aliye; Andersen, Dana K.; Bellin, Melena D.; Bruce, Jason I.; Drewes, Asbjørn M.; Engelhardt, John F.; Forsmark, Christopher E.; Lerch, Markus M.; Lowe, Mark E.; Neuschwander-Tetri, Brent A.; O’Keefe, Stephen J.; Palermo, Tonya M.; Pasricha, Pankaj; Saluja, Ashok K.; Singh, Vikesh K.; Szigethy, Eva M.; Whitcomb, David C.; Yadav, Dhiraj; Conwell, Darwin L.

    2016-01-01

    A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) to focus on research gaps and opportunities in chronic pancreatitis (CP) and its sequelae. This conference marked the 20th year anniversary of the discovery of the cationic trypsinogen (PRSS1) gene mutation for hereditary pancreatitis. The event was held on July 27, 2016, and structured into 4 sessions: (1) pathophysiology; (2) exocrine complications; (3) endocrine complications; and (4) pain. The current state of knowledge was reviewed; many knowledge gaps and research needs were identified that require further investigation. Common themes included the need to design better tools to diagnose CP and its sequelae early and reliably, identify predisposing risk factors for disease progression, develop standardized protocols to distinguish type 3c diabetes mellitus from other types of diabetes and design effective therapeutic strategies through novel cell culture technologies, animal models mimicking human disease, and pain management tools. Gene therapy and cystic fibrosis conductance regulator (CFTR) potentiators as possible treatments for CP were discussed. Importantly, the need for chronic pancreatitis endpoints and intermediate targets for future drug trials was emphasized. PMID:27748719

  17. Phase I study evaluating the treatment of patients with locally advanced pancreatic cancer with carbon ion radiotherapy: the PHOENIX-01 trial

    International Nuclear Information System (INIS)

    Combs, Stephanie E; Debus, Jürgen; Habermehl, Daniel; Kieser, Meinhard; Dreher, Constantin; Werner, Jens; Haselmann, Renate; Jäkel, Oliver; Jäger, Dirk; Büchler, Markus W

    2013-01-01

    Treatment options for patients with locally advanced pancreatic cancer include surgery, chemotherapy as well as radiotherapy. In many cases, surgical resection is not possible, and therefore treatment alternatives have to be performed. Chemoradiation has been established as a convincing treatment alternative for locally advanced pancreatic cancer. Carbon ions offer physical and biological characteristics. Due to their inverted dose profile and the high local dose deposition within the Bragg peak precise dose application and sparing of normal tissue is possible. Moreover, in comparison to photons, carbon ions offer an increased relative biological effectiveness (RBE), which can be calculated between 1.16 and 2.46 depending on the pancreatic cancer cell line as well as the endpoint analyzed. Japanese Data on the evaluation of carbon ion radiation therapy showed promising results for patients with pancreatic cancer. The present PHOENIX-01 trial evaluates carbon ion radiotherapy using the active rasterscanning technique in patients with advanced pancreatic cancer in combination with weekly gemcitabine and adjuvant gemcitabine. Primary endpoint is toxicity, secondary endpoints are overall survival, progression-free survival and response. The physical and biological properties of the carbon ion beam promise to improve the therapeutic ratio in patients with pancreatic cancer: Due to the inverted dose profile dose deposition in the entry channel of the beam leads to sparing of normal tissue; the Bragg peak can be directed into the defined target volume, and the sharp dose fall-off thereafter again spares normal tissue behind the target volume. The higher RBE of carbon ions, which has been shown also for pancreatic cancer cell lines in the preclinical setting, is likely to contribute to an increase in local control, and perhaps in OS. Early data from Japanese centers have shown promising results. In conclusion, this is the first trial to evaluate actively delivered carbon

  18. Generation of polyhormonal and multipotent pancreatic progenitor lineages from human pluripotent stem cells.

    Science.gov (United States)

    Korytnikov, Roman; Nostro, Maria Cristina

    2016-05-15

    Generation of pancreatic β-cells from human pluripotent stem cells (hPSCs) has enormous importance in type 1 diabetes (T1D), as it is fundamental to a treatment strategy based on cellular therapeutics. Being able to generate β-cells, as well as other mature pancreatic cells, from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) will also enable the development of platforms that can be used for disease modeling and drug testing for a variety of pancreas-associated diseases, including cystic fibrosis. For this to occur, it is crucial to develop differentiation strategies that are robust and reproducible across cell lines and laboratories. In this article we describe two serum-free differentiation protocols designed to generate specific pancreatic lineages from hPSCs. Our approach employs a variety of cytokines and small molecules to mimic developmental pathways active during pancreatic organogenesis and allows for the in vitro generation of distinct pancreatic populations. The first protocol is designed to give rise to polyhormonal cells that have the potential to differentiate into glucagon-producing cells. The second protocol is geared to generate multipotent pancreatic progenitor cells, which harbor the potential to generate all pancreatic lineages including: monohormonal endocrine cells, acinar, and ductal cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Discrepancies in sample size calculations and data analyses reported in randomised trials: comparison of publications with protocols

    DEFF Research Database (Denmark)

    Chan, A.W.; Hrobjartsson, A.; Jorgensen, K.J.

    2008-01-01

    OBJECTIVE: To evaluate how often sample size calculations and methods of statistical analysis are pre-specified or changed in randomised trials. DESIGN: Retrospective cohort study. Data source Protocols and journal publications of published randomised parallel group trials initially approved...... in 1994-5 by the scientific-ethics committees for Copenhagen and Frederiksberg, Denmark (n=70). MAIN OUTCOME MEASURE: Proportion of protocols and publications that did not provide key information about sample size calculations and statistical methods; proportion of trials with discrepancies between...... of handling missing data was described in 16 protocols and 49 publications. 39/49 protocols and 42/43 publications reported the statistical test used to analyse primary outcome measures. Unacknowledged discrepancies between protocols and publications were found for sample size calculations (18/34 trials...

  20. Management strategies for autoimmune pancreatitis.

    Science.gov (United States)

    Kamisawa, Terumi; Takuma, Kensuke; Hara, Seiichi; Tabata, Taku; Kuruma, Sawako; Inaba, Yoshihiko; Gopalakrishna, Rajesh; Egawa, Naoto; Itokawa, Fumihide; Itoi, Takao

    2011-10-01

    Autoimmune pancreatitis (AIP) is a newly developed concept for a peculiar type of pancreatitis, and at present is recognized as a pancreatic lesion reflecting IgG4-related systemic disease. It is of utmost importance to differentiate AIP from pancreatic cancer to avoid unnecessary surgery. The current management strategies for AIP, including its clinical features, diagnostic criteria, clinical subtypes, steroid therapy and prognosis are discussed, based on our 66 AIP cases and papers searched in PubMed from 1992 to March 2011, using the term 'autoimmune pancreatitis'. A new clinicopathological entity, an 'IgG4-related sclerosing disease' is also mentioned. AIP should be considered in the differential diagnosis in elderly male patients presented with obstructive jaundice and pancreatic mass. Steroids are a standard therapy for AIP, but their regimen including maintenance therapy should be evaluated in prospective trials.

  1. Pancreatic enzyme replacement therapy for people with cystic fibrosis.

    Science.gov (United States)

    Somaraju, Usha Rani; Solis-Moya, Arturo

    2016-11-23

    Most people with cystic fibrosis (80% to 90%) need pancreatic enzyme replacement therapy to prevent malnutrition. Enzyme preparations need to be taken whenever food is taken, and the dose needs to be adjusted according to the food consumed. A systematic review on the efficacy and safety of pancreatic enzyme replacement therapy is needed to guide clinical practice, as there is variability between centres with respect to assessment of pancreatic function, time of commencing treatment, dose and choice of supplements. This is an updated version of a published review. To evaluate the efficacy and safety of pancreatic enzyme replacement therapy in children and adults with cystic fibrosis and to compare the efficacy and safety of different formulations of this therapy and their appropriateness in different age groups. Also, to compare the effects of pancreatic enzyme replacement therapy in cystic fibrosis according to different diagnostic subgroups (e.g. different ages at introduction of therapy and different categories of pancreatic function). We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Most recent search: 15 July 2016.We also searched an ongoing trials website and the websites of the pharmaceutical companies who manufacture pancreatic enzyme replacements for any additional trials. Most recent search: 22 July 2016. Randomised and quasi-randomised controlled trials in people of any age, with cystic fibrosis and receiving pancreatic enzyme replacement therapy, at any dosage and in any formulation, for a period of not less than four weeks, compared to placebo or other pancreatic enzyme replacement therapy preparations. Two authors independently assessed trials and extracted outcome data. They also assessed the risk of bias of the trials included in the review. One

  2. Asparaginase-associated pancreatitis is not predicted by hypertriglyceridemia or pancreatic enzyme levels in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Raja, Raheel Altaf; Schmiegelow, Kjeld; Sørensen, Ditte Nørbo

    2017-01-01

    Background: l-Asparaginase is an important drug for treatment of childhood acute lymphoblastic leukemia (ALL), but is associated with serious toxicities, including pancreatitis and hypertriglyceridemia (HTG). Asparaginase-associated pancreatitis (AAP) is a common reason for stopping asparaginase...... treatment. The aim of this study was to explore if HTG or early elevations in pancreatic enzymes were associated with the subsequent development of AAP. Method: Children (1.0–17.9 years) diagnosed with ALL, treated with asparaginase for 30 weeks, according to the NOPHO ALL2008 protocol at the University...

  3. Reporting on blinding in trial protocols and corresponding publications was often inadequate but rarely contradictory

    DEFF Research Database (Denmark)

    Hróbjartsson, Asbjørn; Pildal, Julie; Chan, An-Wen

    2009-01-01

    OBJECTIVE: To compare the reporting on blinding in protocols and articles describing randomized controlled trials. STUDY DESIGN AND SETTING: We studied 73 protocols of trials approved by the scientific/ethical committees for Copenhagen and Frederiksberg, 1994 and 1995, and their corresponding...... publications. RESULTS: Three out of 73 trials (4%) reported blinding in the protocol that contradicted that in the publication (e.g., "open" vs. "double blind"). The proportion of "double-blind" trials with a clear description of the blinding of participants increased from 11 out of 58 (19%) when based...... on publications alone to 39 (67%) when adding the information in the protocol. The similar proportions for the blinding of health care providers were 2 (3%) and 22 (38%); and for the blinding of data collectors, they were 8 (14%) and 14 (24%). In 52 of 58 publications (90%), it was unclear whether all patients...

  4. Dietary fat intake and risk of pancreatic cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

    Science.gov (United States)

    Arem, Hannah; Mayne, Susan T; Sampson, Joshua; Risch, Harvey; Stolzenberg-Solomon, Rachael Z

    2013-09-01

    Epidemiologic and experimental studies suggest that dietary fat intake may affect risk of pancreatic cancer, but published results are inconsistent. We examined risk associations for specific types of dietary fat intakes and related food sources among 111,416 participants in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. We used Cox proportional hazards regression to examine associations between fat intake and pancreatic cancer risk. Over a mean 8.4 years of follow-up, 411 pancreatic cancer cases were identified. We observed an inverse association between saturated fat intake and pancreatic cancer risk (hazard ratio [HR], 0.64 comparing extreme quintiles; 95% confidence interval [CI], 0.46-0.88), but the association became weaker and nonsignificant when individuals with fewer than 4 years of follow-up were excluded to avoid possible reverse causation (HR, 0.88; 95% CI, 0.58-1.33). Total fat intake showed a similar pattern of association, whereas intakes of monounsaturated and polyunsaturated fats and fats from animal or plant sources showed no associations with risk. These results do not support the hypothesis of increased pancreatic cancer risk with higher fat consumption overall or by specific fat type or source. Dietary changes owing to undetected disease may explain the observed inverse association with saturated fat. Published by Elsevier Inc.

  5. Precision Medicine for Advanced Pancreas Cancer: The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) Trial.

    Science.gov (United States)

    Chantrill, Lorraine A; Nagrial, Adnan M; Watson, Clare; Johns, Amber L; Martyn-Smith, Mona; Simpson, Skye; Mead, Scott; Jones, Marc D; Samra, Jaswinder S; Gill, Anthony J; Watson, Nicole; Chin, Venessa T; Humphris, Jeremy L; Chou, Angela; Brown, Belinda; Morey, Adrienne; Pajic, Marina; Grimmond, Sean M; Chang, David K; Thomas, David; Sebastian, Lucille; Sjoquist, Katrin; Yip, Sonia; Pavlakis, Nick; Asghari, Ray; Harvey, Sandra; Grimison, Peter; Simes, John; Biankin, Andrew V

    2015-05-01

    Personalized medicine strategies using genomic profiling are particularly pertinent for pancreas cancer. The Individualized Molecular Pancreatic Cancer Therapy (IMPaCT) trial was initially designed to exploit results from genome sequencing of pancreatic cancer under the auspices of the International Cancer Genome Consortium (ICGC) in Australia. Sequencing revealed small subsets of patients with aberrations in their tumor genome that could be targeted with currently available therapies. The pilot stage of the IMPaCT trial assessed the feasibility of acquiring suitable tumor specimens for molecular analysis and returning high-quality actionable genomic data within a clinically acceptable timeframe. We screened for three molecular targets: HER2 amplification; KRAS wild-type; and mutations in DNA damage repair pathways (BRCA1, BRCA2, PALB2, ATM). Tumor biopsy and archived tumor samples were collected from 93 patients and 76 were screened. To date 22 candidate cases have been identified: 14 KRAS wild-type, 5 cases of HER2 amplification, 2 mutations in BRCA2, and 1 ATM mutation. Median time from consent to the return of validated results was 21.5 days. An inability to obtain a biopsy or insufficient tumor content in the available specimen were common reasons for patient exclusion from molecular analysis while deteriorating performance status prohibited a number of patients from proceeding in the study. Documenting the feasibility of acquiring and screening biospecimens for actionable molecular targets in real time will aid other groups embarking on similar trials. Key elements include the need to better prescreen patients, screen more patients, and offer more attractive clinical trial options. ©2015 American Association for Cancer Research.

  6. Progression of pancreatic adenocarcinoma is significantly impeded with a combination of vaccine and COX-2 inhibition.

    Science.gov (United States)

    Mukherjee, Pinku; Basu, Gargi D; Tinder, Teresa L; Subramani, Durai B; Bradley, Judy M; Arefayene, Million; Skaar, Todd; De Petris, Giovanni

    2009-01-01

    With a 5-year survival rate of <5%, pancreatic cancer is one of the most rapidly fatal malignancies. Current protocols for the treatment of pancreas cancer are not as effective as we desire. In this study, we show that a novel Mucin-1 (MUC1)-based vaccine in combination with a cyclooxygenase-2 inhibitor (celecoxib), and low-dose chemotherapy (gemcitabine) was effective in preventing the progression of preneoplastic intraepithelial lesions to invasive pancreatic ductal adenocarcinomas. The study was conducted in an appropriate triple transgenic model of spontaneous pancreatic cancer induced by the KRAS(G12D) mutation and that expresses human MUC1 as a self molecule. The combination treatment elicited robust antitumor cellular and humoral immune responses and was associated with increased apoptosis in the tumor. The mechanism for the increased immune response was attributed to the down-regulation of circulating prostaglandin E(2) and indoleamine 2, 3,-dioxygenase enzymatic activity, as well as decreased levels of T regulatory and myeloid suppressor cells within the tumor microenvironment. The preclinical data provide the rationale to design clinical trials with a combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment of pancreatic cancer.

  7. Surgical Treatment of Acute Pancreatitis.

    Science.gov (United States)

    Werner, Jens; Uhl, Waldemar; Büchler, Markus W.

    2003-10-01

    Patients with predicted severe necrotizing pancreatitis as diagnosed by C-reactive protein (>150 mg/L) and/or contrast-enhanced computed tomography should be managed in the intensive care unit. Prophylactic broad-spectrum antibiotics reduce infection rates and survival in severe necrotizing pancreatitis. Endoscopic retrograde cholangiopancreatography and endoscopic sphincterotomy is a causative therapy for gallstone pancreatitis with impacted stones, biliary sepsis, or obstructive jaundice. Fine needle aspiration for bacteriology should be performed to differentiate between sterile and infected pancreatic necrosis in patients with sepsis syndrome. Infected pancreatic necrosis in patients with clinical signs and symptoms of sepsis is an indication for surgery. Patients with sterile pancreatic necrosis should be managed conservatively. Surgery in patients with sterile necrosis may be indicated in cases of persistent necrotizing pancreatitis and in the rare cases of "fulminant acute pancreatitis." Early surgery, within 14 days after onset of the disease, is not recommended in patients with necrotizing pancreatitis. The surgical approach should be organ-preserving (debridement/necrosectomy) and combined with a postoperative management concept that maximizes postoperative evacuation of retroperitoneal debris and exudate. Minimally invasive surgical procedures have to be regarded as an experimental approach and should be restricted to controlled trials. Cholecystectomy should be performed to avoid recurrence of gallstone-associated acute pancreatitis.

  8. Study protocol for a randomised, double-blinded, placebo-controlled, clinical trial of S-ketamine for pain treatment in patients with chronic pancreatitis (RESET trial)

    DEFF Research Database (Denmark)

    Juel, Jacob; Olesen, Søren Schou; Olesen, Anne Estrup

    2015-01-01

    are randomised to receive 8 h of intravenous S-ketamine followed by oral S-ketamine, or matching placebo, for 4 weeks. To improve blinding, 1 mg of midazolam will be added to active and placebo treatment. The primary end point is clinical pain relief as assessed by a daily pain diary. Secondary end points......INTRODUCTION: Chronic pancreatitis (CP) is an inflammatory disease that causes irreversible damage to pancreatic tissue. Pain is its most prominent symptom. In the absence of pathology suitable for endoscopic or surgical interventions, pain treatment usually includes opioids. However, opioids often...... have limited efficacy. Moreover, side effects are common and bothersome. Hence, novel approaches to control pain associated with CP are highly desirable. Sensitisation of the central nervous system is reported to play a key role in pain generation and chronification. Fundamental to the process...

  9. Current knowledge on pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Juan eIovanna

    2012-01-01

    Full Text Available Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6 months and a dismal 5-year survival rate of 3-5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes and the deregulation of many signalling pathways. Therefore, the strategies targeting these molecules as well as their downstream signalling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical and therapeutic aspects of pancreatic cancer.

  10. Current Knowledge on Pancreatic Cancer

    International Nuclear Information System (INIS)

    Iovanna, Juan; Mallmann, Maria Cecilia; Gonçalves, Anthony; Turrini, Olivier; Dagorn, Jean-Charles

    2012-01-01

    Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6 months and a dismal 5-year survival rate of 3–5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways. Therefore, the strategies targeting these molecules as well as their downstream signaling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical, and therapeutic aspects of pancreatic cancer.

  11. Current Knowledge on Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Iovanna, Juan [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, Marseille (France); Mallmann, Maria Cecilia [Centre d’Investigation Clinique de Marseille, Marseille (France); Gonçalves, Anthony [Département d’Oncologie Médicale, Institut Paoli-Calmettes, Marseille (France); Turrini, Olivier [Département de Chirurgie Oncologique, Institut Paoli-Calmettes, Marseille (France); Dagorn, Jean-Charles, E-mail: juan.iovanna@inserm.fr [INSERM U624, Stress Cellulaire, Parc Scientifique et Technologique de Luminy, Marseille (France)

    2012-01-31

    Pancreatic cancer is the fourth leading cause of cancer death with a median survival of 6 months and a dismal 5-year survival rate of 3–5%. The development and progression of pancreatic cancer are caused by the activation of oncogenes, the inactivation of tumor suppressor genes, and the deregulation of many signaling pathways. Therefore, the strategies targeting these molecules as well as their downstream signaling could be promising for the prevention and treatment of pancreatic cancer. However, although targeted therapies for pancreatic cancer have yielded encouraging results in vitro and in animal models, these findings have not been translated into improved outcomes in clinical trials. This failure is due to an incomplete understanding of the biology of pancreatic cancer and to the selection of poorly efficient or imperfectly targeted agents. In this review, we will critically present the current knowledge regarding the molecular, biochemical, clinical, and therapeutic aspects of pancreatic cancer.

  12. Necrotizing pancreatitis: new definitions and a new era in surgical management.

    Science.gov (United States)

    Rosenberg, Andrew; Steensma, Elizabeth A; Napolitano, Lena M

    2015-02-01

    Necrotizing pancreatitis is a challenging condition that requires surgical treatment commonly and is associated with substantial morbidity and mortality. Over the past decade, new definitions have been developed for standardization of severity of acute and necrotizing pancreatitis, and new management techniques have emerged based on prospective, randomized clinical trials. Review of English-language literature. A new international classification of acute pancreatitis has been developed by PANCREA (Pancreatitis Across Nations Clinical Research and Education Alliance) to replace the Atlanta Classification. It is based on the actual local (whether pancreatic necrosis is present or not, whether it is sterile or infected) and systemic determinants (whether organ failure is present or not, whether it is transient or persistent) of severity. Early management requires goal-directed fluid resuscitation (with avoidance of over-resuscitation and abdominal compartment syndrome), assessment of severity of pancreatitis, diagnostic computed tomography (CT) imaging to assess for necrotizing pancreatitis, consideration of endoscopic retrograde cholangiopancreatography (ERCP) for biliary pancreatitis and early enteral nutrition support. Antibiotic prophylaxis is not recommended. Therapeutic antibiotics are required for treatment of documented infected pancreatic necrosis. The initial treatment of infected pancreatic necrosis is percutaneous catheter or endoscopic (transgastric/transduodenal) drainage with a second drain placement as required. Lack of clinical improvement after these initial procedures warrants consideration of minimally invasive techniques for pancreatic necrosectomy including video-assisted retroperitoneal debridement (VARD), minimally invasive retroperitoneal pancreatectomy (MIRP), or transluminal direct endoscopic necrosectomy (DEN). Open necrosectomy is associated with substantial morbidity, but to date no randomized trial has documented superiority of either

  13. Diffusion weighted MR imaging of pancreatic islet cell tumors

    International Nuclear Information System (INIS)

    Bakir, Baris; Salmaslioglu, Artur; Poyanli, Arzu; Rozanes, Izzet; Acunas, Bulent

    2010-01-01

    Purpose: The aim of our study is to demonstrate the feasibility of body diffusion weighted (DW) MR imaging in the evaluation of pancreatic islet cell tumors (ICTs) and to define apparent diffusion coefficient (ADC) values for these tumors. Materials and methods: 12 normal volunteers and 12 patients with histopathologically proven pancreatic ICT by surgery were included in the study. DW MR images were obtained by a body-phased array coil using a multisection single-shot echo planar sequence on the axial plane without breath holding. In addition, the routine abdominal imaging protocol for pancreas was applied in the patient group. We measured the ADC value within the normal pancreas in control group, pancreatic ICT, and surrounding pancreas parenchyma. Mann-Whitney U-test has been used to compare ADC values between tumoral tissues and normal pancreatic tissues of the volunteers. Wilcoxon Signed Ranks Test was preferred to compare ADC values between tumoral tissues and surrounding pancreatic parenchyma of the patients. Results: In 11 patients out of 12, conventional MR sequences were able to demonstrate ICTs successfully. In 1 patient an indistinct suspicious lesion was noted at the pancreatic tail. DW sequence was able to demonstrate the lesions in all of the 12 patients. On the DW images, all ICTs demonstrated high signal intensity relative to the surrounding pancreatic parenchyma. The mean and standard deviations of the ADC values (x10 -3 mm 2 /s) were as follows: ICT (n = 12), 1.51 ± 0.35 (0.91-2.11), surrounding parenchyma (n = 11) 0.76 ± 0.15 (0.51-1.01) and normal pancreas in normal volunteers (n = 12), 0.80 ± 0.06 (0.72-0.90). ADC values of the ICT were significantly higher compared with those of surrounding parenchyma (p < 0.01) and normal pancreas (p < 0.001). Conclusion: DW MR imaging does not appear to provide significant contribution to routine MR imaging protocol in the evaluation of pancreatic islet cell tumors. But it can be added to MR imaging

  14. Bounding the per-protocol effect in randomized trials: An application to colorectal cancer screening

    NARCIS (Netherlands)

    S.A. Swanson (Sonja); Holme (Øyvind); M. Løberg (Magnus); M. Kalager (Mette); M. Bretthauer (Michael); G. Hoff (G.); E. Aas (Eline); M.A. Hernán (M.)

    2015-01-01

    textabstractBackground: The per-protocol effect is the effect that would have been observed in a randomized trial had everybody followed the protocol. Though obtaining a valid point estimate for the per-protocol effect requires assumptions that are unverifiable and often implausible, lower and upper

  15. Progression of Pancreatic Adenocarcinoma Is Significantly Impeded with a Combination of Vaccine and COX-2 Inhibition1

    Science.gov (United States)

    Mukherjee, Pinku; Basu, Gargi D.; Tinder, Teresa L.; Subramani, Durai B.; Bradley, Judy M.; Arefayene, Million; Skaar, Todd; De Petris, Giovanni

    2013-01-01

    With a 5-year survival rate of <5%, pancreatic cancer is one of the most rapidly fatal malignancies. Current protocols for the treatment of pancreas cancer are not as effective as we desire. In this study, we show that a novel Mucin-1 (MUC1)-based vaccine in combination with a cyclooxygenase-2 inhibitor (celecoxib), and low-dose chemotherapy (gemcitabine) was effective in preventing the progression of preneoplastic intraepithelial lesions to invasive pancreatic ductal adenocarcinomas. The study was conducted in an appropriate triple transgenic model of spontaneous pancreatic cancer induced by the KRASG12D mutation and that expresses human MUC1 as a self molecule. The combination treatment elicited robust antitumor cellular and humoral immune responses and was associated with increased apoptosis in the tumor. The mechanism for the increased immune response was attributed to the down-regulation of circulating prostaglandin E2 and indoleamine 2, 3,-dioxygenase enzymatic activity, as well as decreased levels of T regulatory and myeloid suppressor cells within the tumor microenvironment. The preclinical data provide the rationale to design clinical trials with a combination of MUC1-based vaccine, celecoxib, and gemcitabine for the treatment of pancreatic cancer. PMID:19109152

  16. Targeted full energy and protein delivery in critically ill patients: a study protocol for a pilot randomised control trial (FEED Trial

    Directory of Open Access Journals (Sweden)

    Kate Fetterplace

    2018-02-01

    Full Text Available Abstract Background Current guidelines for the provision of protein for critically ill patients are based on incomplete evidence, due to limited data from randomised controlled trials. The present pilot randomised controlled trial is part of a program of work to expand knowledge about the clinical effects of protein delivery to critically ill patients. The primary aim of this pilot study is to determine whether an enteral feeding protocol using a volume target, with additional protein supplementation, delivers a greater amount of protein and energy to mechanically ventilated critically ill patients than a standard nutrition protocol. The secondary aims are to evaluate the potential effects of this feeding strategy on muscle mass and other patient-centred outcomes. Methods This prospective, single-centred, pilot, randomised control trial will include 60 participants who are mechanically ventilated and can be enterally fed. Following informed consent, the participants receiving enteral nutrition in the intensive care unit (ICU will be allocated using a randomisation algorithm in a 1:1 ratio to the intervention (high-protein daily volume-based feeding protocol, providing 25 kcal/kg and 1.5 g/kg protein or standard care (hourly rate-based feeding protocol providing 25 kcal/kg and 1 g/kg protein. The co-primary outcomes are the average daily protein and energy delivered to the end of day 15 following randomisation. The secondary outcomes include change in quadriceps muscle layer thickness (QMLT from baseline (prior to randomisation to ICU discharge and other nutritional and patient-centred outcomes. Discussion This trial aims to examine whether a volume-based feeding protocol with supplemental protein increases protein and energy delivery. The potential effect of such increases on muscle mass loss will be explored. These outcomes will assist in formulating larger randomised control trials to assess mortality and morbidity. Trial registration

  17. Pancreatic Enzyme Replacement Therapy in Children with Severe Acute Malnutrition: A Randomized Controlled Trial.

    Science.gov (United States)

    Bartels, Rosalie H; Bourdon, Céline; Potani, Isabel; Mhango, Brian; van den Brink, Deborah A; Mponda, John S; Muller Kobold, Anneke C; Bandsma, Robert H; Boele van Hensbroek, Michael; Voskuijl, Wieger P

    2017-11-01

    To assess the benefits of pancreatic enzyme replacement therapy (PERT) in children with complicated severe acute malnutrition. We conducted a randomized, controlled trial in 90 children aged 6-60 months with complicated severe acute malnutrition at the Queen Elizabeth Central Hospital in Malawi. All children received standard care; the intervention group also received PERT for 28 days. Children treated with PERT for 28 days did not gain more weight than controls (13.7 ± 9.0% in controls vs 15.3 ± 11.3% in PERT; P = .56). Exocrine pancreatic insufficiency was present in 83.1% of patients on admission and fecal elastase-1 levels increased during hospitalization mostly seen in children with nonedematous severe acute malnutrition (P Children who died had low fecal fatty acid split ratios at admission. Exocrine pancreatic insufficiency was not improved by PERT, but children receiving PERT were more likely to be discharged with every passing day (P = .02) compared with controls. PERT does not improve weight gain in severely malnourished children but does increase the rate of hospital discharge. Mortality was lower in patients on PERT, a finding that needs to be investigated in a larger cohort with stratification for edematous and nonedematous malnutrition. Mortality in severe acute malnutrition is associated with markers of poor digestive function. ISRCTN.com: 57423639. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Surgical strategies in the treatment of chronic pancreatitis: An updated systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Zhao, Xin; Cui, Naiqiang; Wang, Ximo; Cui, Yunfeng

    2017-03-01

    Chronic pancreatitis (CP) is a common and frequently occurring disease. Pancreaticoduodenectomy (PD), pylorus-preserving pancreaticoduodenectomy (PPPD), and duodenum-preserving pancreatic head resection (DPPHR) are important treatment options for patients with chronic pancreatitis. The Beger and Frey procedures are 2 main duodenum-preserving techniques in duodenum-preserving pancreatic head resection (DPPHR) strategies. We conducted this systematic review and meta-analysis to compare the clinical efficacy of DPPHR versus PD, the Beger procedure versus PD, the Frey procedure versus PD, and the Beger procedure versus the Frey procedure in the treatment of pancreatitis. The optimal surgical option for chronic pancreatitis is still under debate. The aim of this systematic review and meta-analysis was to evaluate the clinical efficacy of different surgical strategies for chronic pancreatitis. Five databases (PubMed, Medline, SinoMed, Embase, and Cochrane Library) were searched with the limitations of human subjects and randomized controlled trials (RCTs) text. Data were extracted by 2 of the coauthors independently and analyzed using the RevMan statistical software, version 5.3. Weighted mean differences (WMDs), risk ratios (RRs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool was used to assess the risk of bias. Seven studies involving a total of 385 patients who underwent the surgical treatments were assessed. The methodological quality of the trials ranged from low to moderate and included PD (n = 134) and DPPHR (n = 251 [Beger procedure = 100; Frey procedure = 109; Beger or Frey procedure = 42]). There were no significant differences between DPPHR and PD in post-operation mortality (RR = 2.89, 95% CI = 0.31-26.87, P = 0.36), pain relief (RR = 1.09, 95% CI = 0.94-1.25, P = 0.26), exocrine insufficiency (follow-up time > 60 months: RR = 0.91, 95% CI = 0.72-1.15, P

  19. A randomized trial of microdose leuprolide acetate protocol versus luteal phase ganirelix protocol in predicted poor responders.

    Science.gov (United States)

    DiLuigi, Andrea J; Engmann, Lawrence; Schmidt, David W; Benadiva, Claudio A; Nulsen, John C

    2011-06-30

    We performed a randomized trial to compare IVF outcomes in 54 poor responder patients undergoing a microdose leuprolide acetate (LA) protocol or a GnRH antagonist protocol incorporating a luteal phase E(2) patch and GnRH antagonist in the preceding menstrual cycle. Cancellation rates, number of oocytes retrieved, clinical pregnancy rates (PR), and ongoing PRs were similar between the two groups. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  20. Effect of endoscopic transpapillary biliary drainage with/without endoscopic sphincterotomy on post-endoscopic retrograde cholangiopancreatography pancreatitis in patients with biliary stricture (E-BEST): a protocol for a multicentre randomised controlled trial.

    Science.gov (United States)

    Kato, Shin; Kuwatani, Masaki; Sugiura, Ryo; Sano, Itsuki; Kawakubo, Kazumichi; Ono, Kota; Sakamoto, Naoya

    2017-08-11

    The effect of endoscopic sphincterotomy prior to endoscopic biliary stenting to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis remains to be fully elucidated. The aim of this study is to prospectively evaluate the non-inferiority of non-endoscopic sphincterotomy prior to stenting for naïve major duodenal papilla compared with endoscopic sphincterotomy prior to stenting in patients with biliary stricture. We designed a multicentre randomised controlled trial, for which we will recruit 370 patients with biliary stricture requiring endoscopic biliary stenting from 26 high-volume institutions in Japan. Patients will be randomly allocated to the endoscopic sphincterotomy group or the non-endoscopic sphincterotomy group. The main outcome measure is the incidence of pancreatitis within 2 days of initial transpapillary biliary drainage. Data will be analysed on completion of the study. We will calculate the 95% confidence intervals (CIs) of the incidence of pancreatitis in each group and analyse weather the difference in both groups with 95% CIs is within the non-inferiority margin (6%) using the Wald method. This study has been approved by the institutional review board of Hokkaido University Hospital (IRB: 016-0181). Results will be submitted for presentation at an international medical conference and published in a peer-reviewed journal. The University Hospital Medical Information Network ID: UMIN000025727 Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  1. The effect of prophylactic peripapillary administration of methylprednisolone in reducing the risk and severity of postendoscopic retrograde cholangiopancreatography pancreatitis: A double blind clinical trial

    Directory of Open Access Journals (Sweden)

    Ahmad Shavakhi

    2015-01-01

    Full Text Available Background : The most common complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP is acute pancreatitis. A number of therapeutic trials have been studied due to reduce the occurrence of postendoscopic retrograde cholangiopancreatography pancreatitis (PEP but many of them were unsuccessful. Periampullary corticosteroid injection was proposed to use as prophylactic agents for PEP because of its anti-inflammatory property with relative low systemic side effects. Materials and Methods : By conducting a double blinded clinical trial study in a single center university hospital, all patients undergoing therapeutic or diagnostic ERCP in our gastrointestinal endoscopy ward, enrolled the study. During ERCP, we randomly assigned the patients in blocks of 40 to undergo a locally injection of methylprednisolone acetate (corticosteroid group or saline (control group on the major papilla and prospectively evaluated the occurrence of PEP pancreatitis in each groups. Clinical and laboratory findings of acute pancreatitis were collected by means of a validated questionnaire during the procedure and before discharge. At baseline and end of the study, were compared pancreatitis prevalence and also its severity by using Chi-square and t-test statistics. Results : The frequency of moderate to severe PEP pain was not significantly between the placebo and corticosteroid receiving group (13.7% ± 3.2% vs. 9.3% ± 2.1%, respectively; P = 0.8. There is no significant difference in the mean concentration of lipase and amylase between corticosteroid receiving group and placebo receiving group at the first, second, and third time. In the corticosteroid receiving group, 3 patients (10.3% while in the control group, 11 patients (11.3% developed pancreatitis. Conclusion: We found no significant difference in PEP rates and also severity between the corticosteroid and placebo groups. The mean increase in serum amylase and amylase level

  2. Vitamins in Pancreatic Cancer: A Review of Underlying Mechanisms and Future Applications12

    Science.gov (United States)

    Davis-Yadley, Ashley H; Malafa, Mokenge P

    2015-01-01

    Although there is increasing evidence that vitamins influence pancreatic adenocarcinoma biology and carcinogenesis, a comprehensive review is lacking. In this study, we performed a PubMed literature search to review the anticancer mechanisms and the preclinical and clinical studies that support the development of the bioactive vitamins A, C, D, E, and K in pancreatic cancer intervention. Preclinical studies have shown promising results for vitamin A in pancreatic cancer prevention, with clinical trials showing intriguing responses in combination with immunotherapy. For vitamin C, preclinical studies have shown slower tumor growth rates and/or increased survival when used alone or in combination with gemcitabine, with clinical trials with this combination revealing decreased primary tumor sizes and improved performance status. Preclinical studies with vitamin D analogues have shown potent antiproliferative effects and repression of migration and invasion of pancreatic cancer cells, with a clinical trial showing increased time to progression when calciferol was added to docetaxel. For vitamin E, preclinical studies have shown that δ-tocotrienol and γ-tocotrienol inhibited tumor cell growth and survival and augmented gemcitabine activity. Early-phase clinical trials with δ-tocotrienol are ongoing. Vitamin K demonstrates activation of apoptosis and inhibition of cellular growth in pancreatic tumor cells; however, there are no clinical studies available for further evaluation. Although preclinical and clinical studies are encouraging, randomized controlled trials with endpoints based on insights gained from mechanistic and preclinical studies and early-phase clinical trials are required to determine the efficacy of bioactive vitamin interventions in pancreatic cancer. PMID:26567201

  3. Current status and outlook of pancreatic islets transplantation research

    International Nuclear Information System (INIS)

    Wang Wei; Ye Bin

    2006-01-01

    Diabetes is a common disease, severely harmful to the human's health and life quality. The pancreatic islets transplantation can correct the patient's hyperglycemia, stop or even reverse the progress of the complication and thus decrease the mortality of diabetic patients. It is the most safe and efficient therapy for diabetes. Since the Edmonton Protocol got success in pancreatic islet transplantation in 2000, it has been more and more interested because of its great clinical curative effect. Research strategy of islet transplantation is now focussed on increasing the acquired islets with normal viability, selecting the best transplantation pathway, and improving the immunosuppression protocol. The shortage of human pancreatic donor is an ever unsolved problem in clinical application. The potential resolutions may include acquisition from xenogenic-islets; islets originated from stem cells, and islets from the living-donor human pancreas. The islets transplantation will open a new application field for interventional radiology. (authors)

  4. Towards consistent generation of pancreatic lineage progenitors from human pluripotent stem cells.

    Science.gov (United States)

    Rostovskaya, Maria; Bredenkamp, Nicholas; Smith, Austin

    2015-10-19

    Human pluripotent stem cells can in principle be used as a source of any differentiated cell type for disease modelling, drug screening, toxicology testing or cell replacement therapy. Type I diabetes is considered a major target for stem cell applications due to the shortage of primary human beta cells. Several protocols have been reported for generating pancreatic progenitors by in vitro differentiation of human pluripotent stem cells. Here we first assessed one of these protocols on a panel of pluripotent stem cell lines for capacity to engender glucose sensitive insulin-producing cells after engraftment in immunocompromised mice. We observed variable outcomes with only one cell line showing a low level of glucose response. We, therefore, undertook a systematic comparison of different methods for inducing definitive endoderm and subsequently pancreatic differentiation. Of several protocols tested, we identified a combined approach that robustly generated pancreatic progenitors in vitro from both embryo-derived and induced pluripotent stem cells. These findings suggest that, although there are intrinsic differences in lineage specification propensity between pluripotent stem cell lines, optimal differentiation procedures may consistently direct a substantial fraction of cells into pancreatic specification. © 2015 The Authors.

  5. Role of bedside index for severity of acute pancreatitis (bisap score in predicting outcome in acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Shahnawaz Bashir Bhat

    2015-12-01

    Full Text Available Objective: To investigate the role of Bedside index for severity of acute pancreatitis (BISAP score in predicting the outcome of acute pancreatitis. Methods: This single hospital based prospective study included fifty patients of acute pancreatitis admitted within 48 hours of onset of symptoms, who were divided into two groups according to admission BISAP score. BISAP score 3 (severe acute pancreatitis. The ability of BISAP score to predict mortality, morbidity and hospital stay in acute pancreatitis patients was analyzed. Results: A BISAP score of >3 was associated with increased risk of development of transient organ failure, persistent organ failure and pancreatic necrosis (Statistically significant. Mortality in group with BISAP and #8805;3 was 23.5% (4 patients which was statistically higher than group with BISAP score and #706;3 (0 patients (p=0.019.The mean duration of hospital stay of patients in group with BISAP score < 3 was 7.58 +/- 4.04 days and in group with BISAP score and #8805;3 was 15.35 +/- 1.66.(p=0.02. Conclusion: Bedside index for severity in acute pancreatitis (BISAP score, at admission is an excellent score in predicting the mortality, morbidity and hospital stay and hence management protocol in patients admitted with acute pancreatitis. [J Contemp Med 2015; 5(4.000: 215-220

  6. High versus low energy administration in the early phase of acute pancreatitis (GOULASH trial): protocol of a multicentre randomised double-blind clinical trial

    OpenAIRE

    Márta, Katalin; Szabó, Anikó N; Pécsi, Dániel; Varjú, Péter; Bajor, Judit; Gódi, Szilárd; Sarlós, Patrícia; Mikó, Alexandra; Szemes, Kata; Papp, Mária; Tornai, Tamás; Vincze, Áron; Márton, Zsolt; Vincze, Patrícia A; Lankó, Erzsébet

    2017-01-01

    Introduction Acute pancreatitis (AP) is an inflammatory disease with no specific treatment. Mitochondrial injury followed by ATP depletion in both acinar and ductal cells is a recently discovered early event in its pathogenesis. Importantly, preclinical research has shown that intracellular ATP delivery restores the physiological function of the cells and protects from cell injury, suggesting that restoration of energy levels in the pancreas is therapeutically beneficial. Despite several high...

  7. A Suspicious Pancreatic Mass in Chronic Pancreatitis: Pancreatic Actinomycosis

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    F. de Clerck

    2015-01-01

    Full Text Available Introduction. Pancreatic actinomycosis is a chronic infection of the pancreas caused by the suppurative Gram-positive bacterium Actinomyces. It has mostly been described in patients following repeated main pancreatic duct stenting in the context of chronic pancreatitis or following pancreatic surgery. This type of pancreatitis is often erroneously interpreted as pancreatic malignancy due to the specific invasive characteristics of Actinomyces. Case. A 64-year-old male with a history of chronic pancreatitis and repeated main pancreatic duct stenting presented with weight loss, fever, night sweats, and abdominal pain. CT imaging revealed a mass in the pancreatic tail, invading the surrounding tissue and resulting in splenic vein thrombosis. Resectable pancreatic cancer was suspected, and pancreatic tail resection was performed. Postoperative findings revealed pancreatic actinomycosis instead of neoplasia. Conclusion. Pancreatic actinomycosis is a rare type of infectious pancreatitis that should be included in the differential diagnosis when a pancreatic mass is discovered in a patient with chronic pancreatitis and prior main pancreatic duct stenting. Our case emphasizes the importance of pursuing a histomorphological confirmation.

  8. Surgical and endoscopic treatment of pain in chronic pancreatitis: a multidisciplinary update

    NARCIS (Netherlands)

    Issa, Y.; van Santvoort, H. C.; van Goor, H.; Cahen, D. L.; Bruno, M. J.; Boermeester, M. A.

    2013-01-01

    Chronic pancreatitis is an inflammatory disease of the pancreas with abdominal pain as the most prominent symptom. Adequate treatment of patients with chronic pancreatitis remains a major challenge, mainly because of the lack of evidence-based treatment protocols. The primary goal of treatment is to

  9. Surgical and Endoscopic Treatment of Pain in Chronic Pancreatitis : A Multidisciplinary Update

    NARCIS (Netherlands)

    Issa, Y.; van Santvoort, H. C.; van Goor, H.; Cahen, D. L.; Bruno, M. J.; Boermeester, M. A.

    2013-01-01

    Chronic pancreatitis is an inflammatory disease of the pancreas with abdominal pain as the most prominent symptom. Adequate treatment of patients with chronic pancreatitis remains a major challenge, mainly because of the lack of evidence-based treatment protocols. The primary goal of treatment is to

  10. Does glyceryl nitrate prevent post-ERCP pancreatitis? A prospective, randomized, double-blind, placebo-controlled multicenter trial

    DEFF Research Database (Denmark)

    Nøjgaard, Camilla; Hornum, Mads; Elkjaer, Margarita

    2009-01-01

    OBJECTIVE: Acute pancreatitis is the most dreaded complication of ERCP. Two studies have shown a significant effect of glyceryl nitrate (GN) in preventing post-ERCP pancreatitis (PEP). We wanted to evaluate this promising effect in a larger study with a realistically precalculated incidence of PEP...... (PL) was an identical-looking patch applied before ERCP. A total of 401 patients received GN; 405 received PL. RESULTS: Forty-seven patients had PEP (5.8%), 18 (4.5%) in the GN group and 29 (7.1%) in the PL group. The relative risk reduction of PEP in the GN group of 36% (95% CI, 11%-65%) compared...... (P = .006) were more common in the GN group. Significant variables predictive of PEP were not having biliary stones extracted; hypotension after ERCP; morphine, propofol, glucagon, and general anesthesia during the procedure; or no sufentanil during the procedure. CONCLUSIONS: The trial showed...

  11. Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials.

    Directory of Open Access Journals (Sweden)

    Benjamin Kasenda

    2016-06-01

    Full Text Available Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i the existence and types of publication agreements in trial protocols, (ii the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii the frequency of co-authorship by industry employees.We used a retrospective cohort of randomized clinical trials (RCTs based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5% mentioned an agreement regarding publication of results. Of these 456, 393 (86.2% documented an industry partner's right to disapprove or at least review proposed manuscripts; 39 (8.6% agreements were without constraints of publication. The remaining 24 (5.3% protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0% trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]. Of 71 agreements reported in publications, 52 (73.2% were concordant with those documented in the protocol. In 14 of 37 (37.8% publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements.Publication agreements constraining academic authors' independence are common. Journal articles seldom report on publication agreements, and, if they do

  12. Agreements between Industry and Academia on Publication Rights: A Retrospective Study of Protocols and Publications of Randomized Clinical Trials

    Science.gov (United States)

    Kasenda, Benjamin; von Elm, Erik; You, John J.; Tomonaga, Yuki; Saccilotto, Ramon; Amstutz, Alain; Bengough, Theresa; Meerpohl, Joerg J.; Stegert, Mihaela; Olu, Kelechi K.; Tikkinen, Kari A. O.; Neumann, Ignacio; Carrasco-Labra, Alonso; Faulhaber, Markus; Mulla, Sohail M.; Mertz, Dominik; Akl, Elie A.; Bassler, Dirk; Busse, Jason W.; Nordmann, Alain; Gloy, Viktoria; Ebrahim, Shanil; Schandelmaier, Stefan; Sun, Xin; Vandvik, Per O.; Johnston, Bradley C.; Walter, Martin A.; Burnand, Bernard; Hemkens, Lars G.; Bucher, Heiner C.; Guyatt, Gordon H.; Briel, Matthias

    2016-01-01

    Background Little is known about publication agreements between industry and academic investigators in trial protocols and the consistency of these agreements with corresponding statements in publications. We aimed to investigate (i) the existence and types of publication agreements in trial protocols, (ii) the completeness and consistency of the reporting of these agreements in subsequent publications, and (iii) the frequency of co-authorship by industry employees. Methods and Findings We used a retrospective cohort of randomized clinical trials (RCTs) based on archived protocols approved by six research ethics committees between 13 January 2000 and 25 November 2003. Only RCTs with industry involvement were eligible. We investigated the documentation of publication agreements in RCT protocols and statements in corresponding journal publications. Of 647 eligible RCT protocols, 456 (70.5%) mentioned an agreement regarding publication of results. Of these 456, 393 (86.2%) documented an industry partner’s right to disapprove or at least review proposed manuscripts; 39 (8.6%) agreements were without constraints of publication. The remaining 24 (5.3%) protocols referred to separate agreement documents not accessible to us. Of those 432 protocols with an accessible publication agreement, 268 (62.0%) trials were published. Most agreements documented in the protocol were not reported in the subsequent publication (197/268 [73.5%]). Of 71 agreements reported in publications, 52 (73.2%) were concordant with those documented in the protocol. In 14 of 37 (37.8%) publications in which statements suggested unrestricted publication rights, at least one co-author was an industry employee. In 25 protocol-publication pairs, author statements in publications suggested no constraints, but 18 corresponding protocols documented restricting agreements. Conclusions Publication agreements constraining academic authors’ independence are common. Journal articles seldom report on

  13. Optimization of RNA Extraction from Rat Pancreatic Tissue

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    Sanaz Dastgheib

    2014-05-01

    Full Text Available Background: Optimized RNA extraction from tissues and cell lines consists of four main stages regardless of the method of extraction: 1 homogenizing, 2 effective denaturation of proteins from RNA, 3 inactivation of ribonuclease, and 4 removal of any DNA, protein, and carbohydrate contamination. Isolation of undamaged intact RNA is challenging when the related tissue contains high levels of RNase. Various technical difficulties occur during extraction of RNA from pancreatic tissue due to spontaneous autolysis. Since standard routine protocols yield unacceptable results in pancrease, we have designed a simple method for RNA extraction by comparing different protocols. Methods: We obtained 20-30 mg pancreatic tissues in less than 2 min from 30 rats. Several methods were performed to extract RNA from pancreatic tissue and evaluate its integrity. All methods were performed three times to obtain reproducible results. Results: Immersing pancreatic tissue in RNA-later for 24 h at -80ºC yielded high quality RNA by using the TriPure reagent which was comparable to the commercial RNeasy Micro Kit. The quality of RNA was evaluated by spectrophotometer, electrophoresis and RT-PCR. We separated intact 28S and 18S ribosomal RNA (rRNA when our procedure was compared with the RNeasy Micro Kit. Finally, full length of the actin gene was amplified by RT-PCR. Conclusion: We designed a simple, fast, cost-effective method for complete RNA extraction from the least amount of quantitatively intact pancreatic tissue

  14. A non-invasive method of quantifying pancreatic volume in mice using micro-MRI.

    Directory of Open Access Journals (Sweden)

    Jose L Paredes

    Full Text Available In experimental models of pancreatic growth and recovery, changes in pancreatic size are assessed by euthanizing a large cohort of animals at varying time points and measuring organ mass. However, to ascertain this information in clinical practice, patients with pancreatic disorders routinely undergo non-invasive cross-sectional imaging of the pancreas using magnetic resonance imaging (MRI or computed tomography (CT. The aim of the current study was to develop a thin-sliced, optimized sequence protocol using a high field MRI to accurately calculate pancreatic volumes in the most common experimental animal, the mouse. Using a 7 Telsa Bruker micro-MRI system, we performed abdominal imaging in whole-fixed mice in three standard planes: axial, sagittal, and coronal. The contour of the pancreas was traced using Vitrea software and then transformed into a 3-dimensional (3D reconstruction, from which volumetric measurements were calculated. Images were optimized using heart perfusion-fixation, T1 sequence analysis, and 0.2 to 0.4 mm thick slices. As proof of principle, increases in pancreatic volume among mice of different ages correlated tightly with increasing body weight. In summary, this is the first study to measure pancreatic volumes in mice, using a high field 7 Tesla micro-MRI and a thin-sliced, optimized sequence protocol. We anticipate that micro-MRI will improve the ability to non-invasively quantify changes in pancreatic size and will dramatically reduce the number of animals required to serially assess pancreatic growth and recovery.

  15. Current options for palliative treatment in patients with pancreatic cancer.

    Science.gov (United States)

    Ridwelski, K; Meyer, F

    2001-01-01

    Palliative treatment is often the only remaining option in the management of pancreatic carcinoma, but its efficacy is poor due to low tumor sensitivity and inadequate treatment protocols. There are several options of palliative treatment with antitumor or supportive intention. Classical end points of palliative treatment are survival, tumor response, and quality of life. A decade ago, palliative chemotherapy consisted mainly of 5-fluorouracil as the standard agent in combination with either other agents and/or radiotherapy. Only the new antineoplastic drug gemcitabine, which was introduced simultaneously with the definition of novel end points of chemotherapy such as clinical benefit, allowed to achieve some progress. However, while gemcitabine monotherapy appeared to be superior to 5-fluorouracil and improved important parameters of quality of life, it could not provide a significant improvement of survival. A novel concept, therefore, is to improve this beneficial cytostatic response in pancreatic carcinoma using a gemcitabine-based protocol by combining it with antineoplastic drugs such as taxanes or platin analogs. This strategy may have the potential to improve the outcome in palliative chemotherapy of pancreatic carcinoma patients with advanced tumor growth or metastases. Best supportive care in pancreatic cancer consists of the treatment of symptoms, such as pain, jaundice, duodenal obstruction, weight loss, exocrine pancreatic insufficiency, and tumor-associated depression. Copyright 2001 S. Karger AG, Basel

  16. Sphincter of Oddi botulinum toxin injection to prevent pancreatic fistula after distal pancreatectomy.

    Science.gov (United States)

    Hackert, Thilo; Klaiber, Ulla; Hinz, Ulf; Kehayova, Tzveta; Probst, Pascal; Knebel, Phillip; Diener, Markus K; Schneider, Lutz; Strobel, Oliver; Michalski, Christoph W; Ulrich, Alexis; Sauer, Peter; Büchler, Markus W

    2017-05-01

    Postoperative pancreatic fistula represents the most important complication after distal pancreatectomy. The aim of this study was to evaluate the use of a preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula (German Clinical Trials Register number: DRKS00007885). This was an investigator-initiated, prospective clinical phase I/II trial with an exploratory study design. We included patients who underwent preoperative endoscopic sphincter botulinum toxin injection (100 units of Botox). End points were the feasibility, safety, and postoperative outcomes, including postoperative pancreatic fistula within 30 days after distal pancreatectomy. Botulinum toxin patients were compared with a control collective of patients undergoing distal pancreatectomy without botulinum toxin injection by case-control matching in a 1:1 ratio. Between February 2015 and February 2016, 29 patients were included. All patients underwent successful sphincter of Oddi botulinum toxin injection within a median of 6 (range 0-10) days before operation. One patient had an asymptomatic, self-limiting (48 hours) increase in serum amylase and lipase after injection. Distal pancreatectomy was performed in 24/29 patients; 5 patients were not resectable. Of the patients receiving botulinum toxin, 7 (29%) had increased amylase levels in drainage fluid on postoperative day 3 (the International Study Group of Pancreatic Surgery definition of postoperative pancreatic fistula grade A) without symptoms or need for reintervention. Importantly, no clinically relevant fistulas (International Study Group of Pancreatic Surgery grades B/C) were observed in botulinum toxin patients compared to 33% postoperative pancreatic fistula grade B/C in case-control patients (P botulinum toxin injection is a novel and safe approach to decrease the incidence of clinically relevant postoperative pancreatic fistula after distal pancreatectomy. The results of

  17. Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial-PROSPECT: protocol for a feasibility randomized pilot trial.

    Science.gov (United States)

    Johnstone, Jennie; Meade, Maureen; Marshall, John; Heyland, Daren K; Surette, Michael G; Bowdish, Dawn Me; Lauzier, Francois; Thebane, Lehana; Cook, Deborah J

    2015-01-01

    Probiotics are defined as live microorganisms that may confer health benefits when ingested. Meta-analysis of probiotic trials suggests a 25 % lower ventilator-associated pneumonia (VAP) and 18 % lower infection rates overall when administered to patients in the intensive care unit (ICU). However, prior trials are small, largely single center, and at high risk of bias. Before a large rigorous trial is launched, testing whether probiotics confer benefit, harm, or have no impact, a pilot trial is needed. The aim of the PROSPECT Pilot Trial is to determine the feasibility of performing a larger trial in mechanically ventilated critically ill patients investigating Lactobacillus rhamnosus GG. A priori, we determined that the feasibility of the larger trial would be based on timely recruitment, high protocol adherence, minimal contamination, and an acceptable VAP rate. Patients ≥18 years old in the ICU who are anticipated to receive mechanical ventilation for ≥72 hours will be included. Patients are excluded if they are at increased risk of probiotic-associated infection, have strict enteral medication contraindications, are pregnant, previously enrolled in a related trial, or are receiving palliative care. Following informed consent, patients are randomized in variable unspecified block sizes in a fixed 1:1 ratio, stratified by ICU, and medical, surgical, or trauma admitting diagnosis. Patients receive 1 × 10 10 colony forming units of L. rhamnosus GG (Culturelle, Locin Industries Ltd) or an identical placebo suspended in tap water administered twice daily via nasogastric tube in the ICU. Clinical and research staff, patients, and families are blinded. The primary outcomes for this pilot trial are the following: (1) recruitment success, (2) ≥90 % protocol adherence, (3) ≤5 % contamination, and (4) ~10 % VAP rate. Additional clinical outcomes are VAP, other infections, diarrhea (total, antibiotic associated, and Clostridium difficile), ICU and

  18. Pancreatic Tuberculosis or Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Ayesha Salahuddin

    2014-01-01

    Full Text Available Introduction. Isolated pancreatic and peripancreatic tuberculosis is a challenging diagnosis due to its rarity and variable presentation. Pancreatic tuberculosis can mimic pancreatic carcinoma. Similarly, autoimmune pancreatitis can appear as a focal lesion resembling pancreatic malignancy. Endoscopic ultrasound-guided fine needle aspiration provides an effective tool for differentiating between benign and malignant pancreatic lesions. The immune processes involved in immunoglobulin G4 related systemic diseases and tuberculosis appear to have some similarities. Case Report. We report a case of a 59-year-old Southeast Asian male who presented with fever, weight loss, and obstructive jaundice. CT scan revealed pancreatic mass and enlarged peripancreatic lymph nodes. Endoscopic ultrasound-guided fine needle aspiration confirmed the presence of mycobacterium tuberculosis. Patient also had high immunoglobulin G4 levels suggestive of autoimmune pancreatitis. He was started on antituberculosis medications and steroids. Clinically, he responded to treatment. Follow-up imaging showed findings suggestive of chronic pancreatitis. Discussion. Pancreatic tuberculosis and autoimmune pancreatitis can mimic pancreatic malignancy. Accurate diagnosis is imperative as unnecessary surgical intervention can be avoided. Endoscopic ultrasound-guided fine needle aspiration seems to be the diagnostic test of choice for pancreatic masses. Long-term follow-up is warranted in cases of chronic pancreatitis.

  19. Nationwide prospective audit of pancreatic surgery: design, accuracy, and outcomes of the Dutch Pancreatic Cancer Audit.

    Science.gov (United States)

    van Rijssen, L Bengt; Koerkamp, Bas G; Zwart, Maurice J; Bonsing, Bert A; Bosscha, Koop; van Dam, Ronald M; van Eijck, Casper H; Gerhards, Michael F; van der Harst, Erwin; de Hingh, Ignace H; de Jong, Koert P; Kazemier, Geert; Klaase, Joost; van Laarhoven, Cornelis J; Molenaar, I Quintus; Patijn, Gijs A; Rupert, Coen G; van Santvoort, Hjalmar C; Scheepers, Joris J; van der Schelling, George P; Busch, Olivier R; Besselink, Marc G

    2017-10-01

    Auditing is an important tool to identify practice variation and 'best practices'. The Dutch Pancreatic Cancer Audit is mandatory in all 18 Dutch centers for pancreatic surgery. Performance indicators and case-mix factors were identified by a PubMed search for randomized controlled trials (RCT's) and large series in pancreatic surgery. In addition, data dictionaries of two national audits, three institutional databases, and the Dutch national cancer registry were evaluated. Morbidity, mortality, and length of stay were analyzed of all pancreatic resections registered during the first two audit years. Case ascertainment was cross-checked with the Dutch healthcare inspectorate and key-variables validated in all centers. Sixteen RCT's and three large series were found. Sixteen indicators and 20 case-mix factors were included in the audit. During 2014-2015, 1785 pancreatic resections were registered including 1345 pancreatoduodenectomies. Overall in-hospital mortality was 3.6%. Following pancreatoduodenectomy, mortality was 4.1%, Clavien-Dindo grade ≥ III morbidity was 29.9%, median (IQR) length of stay 12 (9-18) days, and readmission rate 16.0%. In total 97.2% of >40,000 variables validated were consistent with the medical charts. The Dutch Pancreatic Cancer Audit, with high quality data, reports good outcomes of pancreatic surgery on a national level. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  20. Development of a dynamic quality assurance testing protocol for multisite clinical trial DCE-CT accreditation

    Energy Technology Data Exchange (ETDEWEB)

    Driscoll, B. [Department of Radiation Physics, Princess Margaret Cancer Center, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada); Keller, H. [Department of Radiation Physics, Princess Margaret Cancer Center, 610 University Avenue, Toronto, Ontario M5G 2M9, Canada and Department of Radiation Oncology, University of Toronto, 150 College Street, Toronto, Ontario M5S 3E2 (Canada); Jaffray, D.; Coolens, C. [Department of Radiation Physics, Princess Margaret Cancer Center, 610 University Avenue, Toronto, Ontario M5G 2M9 (Canada); Department of Radiation Oncology, University of Toronto, 150 College Street, Toronto, Ontario M5S 3E2 (Canada); Techna Institute, University Health Network, 124-100 College Street, Toronto, Ontario M5G 1L5 (Canada)

    2013-08-15

    Purpose: Credentialing can have an impact on whether or not a clinical trial produces useful quality data that is comparable between various institutions and scanners. With the recent increase of dynamic contrast enhanced-computed tomography (DCE-CT) usage as a companion biomarker in clinical trials, effective quality assurance, and control methods are required to ensure there is minimal deviation in the results between different scanners and protocols at various institutions. This paper attempts to address this problem by utilizing a dynamic flow imaging phantom to develop and evaluate a DCE-CT quality assurance (QA) protocol.Methods: A previously designed flow phantom, capable of producing predictable and reproducible time concentration curves from contrast injection was fully validated and then utilized to design a DCE-CT QA protocol. The QA protocol involved a set of quantitative metrics including injected and total mass error, as well as goodness of fit comparison to the known truth concentration curves. An additional region of interest (ROI) sensitivity analysis was also developed to provide additional details on intrascanner variability and determine appropriate ROI sizes for quantitative analysis. Both the QA protocol and ROI sensitivity analysis were utilized to test variations in DCE-CT results using different imaging parameters (tube voltage and current) as well as alternate reconstruction methods and imaging techniques. The developed QA protocol and ROI sensitivity analysis was then applied at three institutions that were part of clinical trial involving DCE-CT and results were compared.Results: The inherent specificity of robustness of the phantom was determined through calculation of the total intraday variability and determined to be less than 2.2 ± 1.1% (total calculated output contrast mass error) with a goodness of fit (R{sup 2}) of greater than 0.99 ± 0.0035 (n= 10). The DCE-CT QA protocol was capable of detecting significant deviations from

  1. Sensitivity Analysis of Per-Protocol Time-to-Event Treatment Efficacy in Randomized Clinical Trials

    Science.gov (United States)

    Gilbert, Peter B.; Shepherd, Bryan E.; Hudgens, Michael G.

    2013-01-01

    Summary Assessing per-protocol treatment effcacy on a time-to-event endpoint is a common objective of randomized clinical trials. The typical analysis uses the same method employed for the intention-to-treat analysis (e.g., standard survival analysis) applied to the subgroup meeting protocol adherence criteria. However, due to potential post-randomization selection bias, this analysis may mislead about treatment efficacy. Moreover, while there is extensive literature on methods for assessing causal treatment effects in compliers, these methods do not apply to a common class of trials where a) the primary objective compares survival curves, b) it is inconceivable to assign participants to be adherent and event-free before adherence is measured, and c) the exclusion restriction assumption fails to hold. HIV vaccine efficacy trials including the recent RV144 trial exemplify this class, because many primary endpoints (e.g., HIV infections) occur before adherence is measured, and nonadherent subjects who receive some of the planned immunizations may be partially protected. Therefore, we develop methods for assessing per-protocol treatment efficacy for this problem class, considering three causal estimands of interest. Because these estimands are not identifiable from the observable data, we develop nonparametric bounds and semiparametric sensitivity analysis methods that yield estimated ignorance and uncertainty intervals. The methods are applied to RV144. PMID:24187408

  2. Neonatal pancreatic pericytes support β-cell proliferation

    Directory of Open Access Journals (Sweden)

    Alona Epshtein

    2017-10-01

    Conclusions: This study introduces pancreatic pericytes as regulators of neonatal β-cell proliferation. In addition to advancing current understanding of the physiological β-cell replication process, these findings could facilitate the development of protocols aimed at expending these cells as a potential cure for diabetes.

  3. From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology

    Science.gov (United States)

    Raghav, Kanwal Pratap Singh; Mahajan, Sminil; Yao, James C.; Hobbs, Brian P.; Berry, Donald A.; Pentz, Rebecca D.; Tam, Alda; Hong, Waun K.; Ellis, Lee M.; Abbruzzese, James; Overman, Michael J.

    2015-01-01

    Purpose The decision by journals to append protocols to published reports of randomized trials was a landmark event in clinical trial reporting. However, limited information is available on how this initiative effected transparency and selective reporting of clinical trial data. Methods We analyzed 74 oncology-based randomized trials published in Journal of Clinical Oncology, the New England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of reporting, we compared published reports with their respective appended protocols with regard to primary end points, nonprimary end points, unplanned end points, and unplanned analyses. Results A total of 86 primary end points were reported in 74 randomized trials; nine trials had greater than one primary end point. Nine trials (12.2%) had some discrepancy between their planned and published primary end points. A total of 579 nonprimary end points (median, seven per trial) were planned, of which 373 (64.4%; median, five per trial) were reported. A significant positive correlation was found between the number of planned and nonreported nonprimary end points (Spearman r = 0.66; P < .001). Twenty-eight studies (37.8%) reported a total of 65 unplanned end points; 52 (80.0%) of which were not identified as unplanned. Thirty-one (41.9%) and 19 (25.7%) of 74 trials reported a total of 52 unplanned analyses involving primary end points and 33 unplanned analyses involving nonprimary end points, respectively. Studies reported positive unplanned end points and unplanned analyses more frequently than negative outcomes in abstracts (unplanned end points odds ratio, 6.8; P = .002; unplanned analyses odd ratio, 8.4; P = .007). Conclusion Despite public and reviewer access to protocols, selective outcome reporting persists and is a major concern in the reporting of randomized clinical trials. To foster credible evidence-based medicine, additional initiatives are needed to minimize selective reporting. PMID:26304898

  4. From Protocols to Publications: A Study in Selective Reporting of Outcomes in Randomized Trials in Oncology.

    Science.gov (United States)

    Raghav, Kanwal Pratap Singh; Mahajan, Sminil; Yao, James C; Hobbs, Brian P; Berry, Donald A; Pentz, Rebecca D; Tam, Alda; Hong, Waun K; Ellis, Lee M; Abbruzzese, James; Overman, Michael J

    2015-11-01

    The decision by journals to append protocols to published reports of randomized trials was a landmark event in clinical trial reporting. However, limited information is available on how this initiative effected transparency and selective reporting of clinical trial data. We analyzed 74 oncology-based randomized trials published in Journal of Clinical Oncology, the New England Journal of Medicine, and The Lancet in 2012. To ascertain integrity of reporting, we compared published reports with their respective appended protocols with regard to primary end points, nonprimary end points, unplanned end points, and unplanned analyses. A total of 86 primary end points were reported in 74 randomized trials; nine trials had greater than one primary end point. Nine trials (12.2%) had some discrepancy between their planned and published primary end points. A total of 579 nonprimary end points (median, seven per trial) were planned, of which 373 (64.4%; median, five per trial) were reported. A significant positive correlation was found between the number of planned and nonreported nonprimary end points (Spearman r = 0.66; P medicine, additional initiatives are needed to minimize selective reporting. © 2015 by American Society of Clinical Oncology.

  5. Antibiotics in acute necrotizing pancreatitis --- perspective of a developing country

    International Nuclear Information System (INIS)

    Khan, A.; Khan, S.

    2010-01-01

    Prophylactic antibiotics in acute necrotizing pancreatitis is controversial. The mortality of acute necrotizing pancreatitis is 8-25% in the western world. In view of the limited resources available for managing the complications of infected pancreatitis in developing countries, the use of prophylactic antibiotics may be recommended in selected cases. Various antibiotics show good penetration into the pancreatic tissue; imipenem and quinolones have better penetration. Clinical trials on the use of prophylactic antibiotics in necrotizing pancreatitis have been reviewed. Prophylactic antibiotics have been considered if greater than 30% pancreatic necrosis as documented by CT scan. Imipenem can be given for a duration of 10 to 14 days if no systemic complications are present. In a developing country where the cost of managing complications of pancreatitis can be a limiting factor for patients, the use of prophylactic antibiotics early on in the disease in selected cases can be beneficial. (author)

  6. Treatment outcome of advanced pancreatic cancer patients who are ineligible for a clinical trial

    Directory of Open Access Journals (Sweden)

    Ueda A

    2013-05-01

    Full Text Available Akira Ueda, Ayumu Hosokawa, Kohei Ogawa, Hiroki Yoshita, Takayuki Ando, Shinya Kajiura, Haruka Fujinami, Kengo Kawai, Jun Nishikawa, Kazuto Tajiri, Masami Minemura, Toshiro SugiyamaDepartment of Gastroenterology and Hematology, Faculty of Medicine, University of Toyama, Toyama, JapanObjective: The aim of this study was to evaluate the outcome of patients with advanced pancreatic cancer in clinical practice, and assess whether chemotherapy provided a clinical benefit for patients who did not meet the eligibility criteria of the clinical trial.Methods: We retrospectively analyzed the medical records of 75 patients who received first-line chemotherapy for pancreatic cancer between April 2006 and September 2011. Patients were treated with gemcitabine (GEM alone, S-1 (tegafur, gimeracil, and oteracil potassium alone, or GEM plus S-1. Patients were divided into the clinical trial eligible group (arm eligible or the ineligible group (arm ineligible. We evaluated the efficacy and the safety of the chemotherapy.Results: A total of 23 patients out of 75 (31% belonged to the ineligible group, for the following reasons: 20 patients had poor performance status, eight had massive ascites, one had synchronous malignancy, and one had icterus. The median progression-free survival (PFS was 3.5 months, and the median overall survival (OS was 6.7 months in all patients. In arm eligible, median PFS was 4.5 months, and median OS was 10.5 months. In arm ineligible, median PFS was 1.1 months, and median OS was 2.9 months.Conclusion: The outcome of the patients who did not meet the eligibility criteria was very poor. It is important to select the patients that could benefit from either chemotherapy or optimal supportive care.Keywords: gemcitabine, S-1, clinical practice

  7. Incremental value of secretin-enhanced magnetic resonance cholangiopancreatography in detecting ductal communication in a population with high prevalence of small pancreatic cysts

    International Nuclear Information System (INIS)

    Rastegar, Neda; Matteoni-Athayde, Luciana G.; Eng, John; Takahashi, Naoki; Tamm, Eric P.; Mortele, Koenraad J.; Syngal, Sapna; Margolis, Daniel; Lennon, Anne Marie; Wolfgang, Christopher L.; Fishman, Elliot K.; Hruban, Ralph H.; Goggins, Michael; Canto, Marcia I.; Kamel, Ihab R.

    2015-01-01

    Highlights: •Secretin improved visualization of ductal communication of a cystic pancreatic lesion. •No association between cysts and gender, ethnicity or type of high risk. •Incremental value of secretin could offset the added cost and time. -- Abstract: Purpose: We investigated the incremental diagnostic yield of S-MRCP in a population with high prevalence of small pancreatic cysts. Methods: Standard MRCP protocol was performed with and without secretin using 1.5 T units in subjects undergoing pancreatic screening because of a strong family history of pancreatic cancer as part of the multicenter Cancer of the Pancreas Screening-3 trial (CAPS 3). All studies were reviewed prospectively by two independent readers who recorded the presence and number of pancreatic cysts, the presence of visualized ductal communication before and after secretin, and the degree of confidence in the diagnoses. Result: Of 202 individuals enrolled (mean age 56 years, 46% males), 93 (46%) had pancreatic cysts detected by MRCP, and 64 of the 93 had pre-and post-secretin MRCP images available for comparison. Data from the 128 readings show that 6 (6/128 = 4.7%) had ductal communication visualized only on the secretin studies compared to pre-secretin studies (odds ratio 1.28, p = 0.04). In addition, there was a statistically significant increase in confidence in reporting ductal communication after secretin compared to before secretin (p < 0.0005). Conclusion: At 1.5 T MRI, the use of secretin can improve the visualization of ductal communication of cystic pancreatic lesions

  8. Incremental value of secretin-enhanced magnetic resonance cholangiopancreatography in detecting ductal communication in a population with high prevalence of small pancreatic cysts

    Energy Technology Data Exchange (ETDEWEB)

    Rastegar, Neda; Matteoni-Athayde, Luciana G.; Eng, John [Departments of Medicine (Gastroenterology) and Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions (United States); Takahashi, Naoki [Mayo Clinic (United States); Tamm, Eric P. [MD Anderson Cancer Center (United States); Mortele, Koenraad J. [Beth Israel Deaconess Medical Center (United States); Syngal, Sapna [Dana Farber Cancer Institute (United States); Margolis, Daniel [University of California, Los Angeles (United States); Lennon, Anne Marie; Wolfgang, Christopher L.; Fishman, Elliot K.; Hruban, Ralph H.; Goggins, Michael; Canto, Marcia I. [Departments of Medicine (Gastroenterology) and Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions (United States); Kamel, Ihab R., E-mail: ikamel@jhmi.edu [Departments of Medicine (Gastroenterology) and Radiology, The Sol Goldman Pancreatic Cancer Research Center, Johns Hopkins Medical Institutions (United States)

    2015-04-15

    Highlights: •Secretin improved visualization of ductal communication of a cystic pancreatic lesion. •No association between cysts and gender, ethnicity or type of high risk. •Incremental value of secretin could offset the added cost and time. -- Abstract: Purpose: We investigated the incremental diagnostic yield of S-MRCP in a population with high prevalence of small pancreatic cysts. Methods: Standard MRCP protocol was performed with and without secretin using 1.5 T units in subjects undergoing pancreatic screening because of a strong family history of pancreatic cancer as part of the multicenter Cancer of the Pancreas Screening-3 trial (CAPS 3). All studies were reviewed prospectively by two independent readers who recorded the presence and number of pancreatic cysts, the presence of visualized ductal communication before and after secretin, and the degree of confidence in the diagnoses. Result: Of 202 individuals enrolled (mean age 56 years, 46% males), 93 (46%) had pancreatic cysts detected by MRCP, and 64 of the 93 had pre-and post-secretin MRCP images available for comparison. Data from the 128 readings show that 6 (6/128 = 4.7%) had ductal communication visualized only on the secretin studies compared to pre-secretin studies (odds ratio 1.28, p = 0.04). In addition, there was a statistically significant increase in confidence in reporting ductal communication after secretin compared to before secretin (p < 0.0005). Conclusion: At 1.5 T MRI, the use of secretin can improve the visualization of ductal communication of cystic pancreatic lesions.

  9. Algenpantucel-L immunotherapy in pancreatic adenocarcinoma.

    Science.gov (United States)

    Coveler, Andrew L; Rossi, Gabriela R; Vahanian, Nicholas N; Link, Charles; Chiorean, E Gabriela

    2016-02-01

    Pancreatic adenocarcinoma is the 4th leading cause of cancer death in the USA and the EU. A minority of patients presents with surgically resectable and potentially curable disease, but among these, 80% are destined to relapse and overall survival rates with adjuvant chemotherapy average 24 months. Immunotherapy is a promising therapeutic option and a potential paradigm shift in the treatment of patients with pancreatic cancer, and may be particularly effective when used early in the disease course to prevent metastatic spread. Algenpantucel-L (HyperAcute Pancreas, NewLink Genetics, Ames, IA, USA) is a whole-cell immunotherapy consisting of irradiated allogeneic pancreatic cancer cells genetically engineered to express the murine enzyme α-GT, which results in hyperacute rejection of the tumor cells with complement- and antibody-dependent cytotoxicity. Phase II clinical trial data has been encouraging, particularly for patients who demonstrated humoral immunologic responses. Here, we report preliminary results and biomarkers correlations with clinical activity of algenpantucel-L in pancreatic cancer.

  10. Therapeutic Potential of Curcumin in Treatment of Pancreatic Cancer: Current Status and Future Perspectives.

    Science.gov (United States)

    Hosseini, Mina; Hassanian, Seyed Mahdi; Mohammadzadeh, Elham; ShahidSales, Soodabeh; Maftouh, Mina; Fayazbakhsh, Hasan; Khazaei, Majid; Avan, Amir

    2017-07-01

    Pancreatic cancer is among the leading cause of deaths due to cancer with extremely poor prognosis. Gemcitabine is being used in the treatment of patient with pancreatic ductal adenocarcinoma (PDAC), although, the response rate is bellow 12%. A recent phase III trial revealed that FOLFIRINOX could be an option for the treatment of metastatic PDAC patients, although it is associated with increased toxicity. Therefore, identification of novel agents that either improves gemcitabine activity, within novel combinatorial approaches, or with a better efficacy than gemcitabine is warranted. The antitumor activity of curcumin in several tumors, including prostate, breast and colorectal cancers have investigated. A recent phase II trial explored the effects of curcumin in advanced pancreatic cancer patient. They found that oral curcumin was well tolerated. Another trial showed the activity of 8,000 mg of curcumin in combination with gemcitabine in patients with advanced pancreatic cancer. This review summarizes the current knowledge about possible molecular mechanisms of curcumin in PDAC with particular emphasis on preclinical/clinical studies in pancreatic cancer treatment. J. Cell. Biochem. 118: 1634-1638, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

    Directory of Open Access Journals (Sweden)

    P. V. Novokhatny

    2014-02-01

    Full Text Available Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study the endocrine function of pancreas in acute pancreatitis. To define the role of endocrine pancreatic function in the etiology and pathogenesis of the acute pancreatitis. To assess the prospects of the use of pancreatic hormones in the treatment and predicting the outcomes of acute pancreatitis. Materials and methods of the research Survey of publications in specialized periodical medical journals, PubMed sources developed by the National Center for Biotechnology Information. Search in PubMed was carried out in the following databases: MEDLINE, Pre MEDLINE. Results of the research. In a significant proportion of patients who recovered from acute pancreatitis, exocrine and endocrine functional impairments were found. This finding was not detected only in patients after severe acute pancreatitis. Routine evaluation of pancreatic function after acute pancreatitis should be considered. The comparative analysis of the synthetic analogues (somatostatin, calcitonin, leu-enkefalin-dalargin influence on the glucose metabolism of rats in acute pancreatitis of was made. Physiological reaction of beta-cells is preserved in infusion of somatostatin. However, infusion of calcitonin results in the distortion of counterregulatory action of insulin and glucagon. It was detected that pancreatic renin-angiotensin system is markedly activated in the experimental rat models of chronic hypoxia and acute pancreatitis. The activation of the pancreatic renin-angiotensin system by

  12. Antioxidant drugs to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis: What does evidence suggest?

    Science.gov (United States)

    Fuentes-Orozco, Clotilde; Dávalos-Cobián, Carlos; García-Correa, Jesús; Ambriz-González, Gabriela; Macías-Amezcua, Michel Dassaejv; García-Rentería, Jesús; Rendón-Félix, Jorge; Chávez-Tostado, Mariana; Cuesta-Márquez, Lizbeth Araceli; Alvarez-Villaseñor, Andrea Socorro; Cortés-Flores, Ana Olivia; González-Ojeda, Alejandro

    2015-06-07

    To determine whether or not the use of antioxidant supplementation aids in the prevention of post- endoscopic retrograde cholangiopancreatography pancreatitis. A systematic review of randomized controlled trials (RCTs) was made to evaluate the preventive effect of prophylactic antioxidant supplementation in post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The inclusion criteria included: acute post-endoscopic retrograde cholangiopancreatography pancreatitis in adults; randomized clinical trials with the use of any antioxidant as an intervention compared with placebo, to reduce PEP. The outcome measure was the incidence and severity of PEP. Twelve RCTs involving 3110 patients since 1999 were included. The antioxidants used were selenite, β-carotene, and pentoxifylline (each one in one trial), N-acetylcysteine (NAC) in three trials, and allopurinol in six trials. The group of patients treated with NAC received different doses; either oral or intravenous, and allopurinol-treated patients received five different oral doses in two different administration periods. The results are expressed with raw numbers, proportions, as well as mean and standard deviations. The incidence of pancreatitis between groups was analyzed with Pearson's χ(2) test or Fisher's exact test (F). The main outcome is expressed as relative risks and 95%CI. The incidence of pancreatitis in all antioxidant treatment groups was 8.6%, whereas it was 9.7% in the control group. The antioxidants used were selenite, β-carotene, and pentoxifylline (each one in one trial), NAC in three trials, and allopurinol in six trials. In allopurinol trials, three different dosifications were used; two trials reported a low dosage (of less than 400 mg), two trials reported a moderate dose (600 mg) and the remaining two employed higher doses (more than 900 mg). Supplementation was not associated with a significant reduction in the incidence of PEP [relative risk (RR) = 0.93; 95%CI: 0.82-1.06; P

  13. Glyceryl trinitrate for prevention of post-ERCP pancreatitis and improve the rate of cannulation: a meta-analysis of prospective, randomized, controlled trials.

    Directory of Open Access Journals (Sweden)

    Jiexia Ding

    Full Text Available BACKGROUND: Acute pancreatitis is the most common complication of diagnostic and therapeutic endoscopic retrograde cholangiopancreatography (ERCP. Several clinical trials used glyceryl trinitrate (GTN to prevent the incidence of post-ERCP pancreatitis (PEP. However, the results were still controversial. OBJECTIVE: To conduct a meta-analysis of published, full-length, randomized controlled trials evaluating the effect of prophylactic GTN on the prevention of PEP, improve the rate of cannulation and the prevention of hyperamylasemia. METHODS: Literature searches were conducted using PubMed, EMBASE, The Cochrane Library and Web of Knowledge databases, using keywords "post-ERCP" and "pancreatitis" and limited in randomized controlled trials. RESULTS: Twelve RCTs involving 2649 patients were included. Eleven RCTs compared GTN with placebo for PEP prevention. Meta-analysis showed the overall incidence of PEP was significantly reduced by GTN treatment (RR 0.67; 95% CI, 0.52-0.87. Nevertheless, GTN administration did not decrease the incidence of moderate to severe PEP (RR 0.70; 95% CI, 0.42-1.15. Subgroup analyses revealed that GTN administered by sublingual was more effective than transdermal and topical in reducing the incidence of PEP. Besides, the prophylactic effect of GTN was far more obvious in the group of high PEP incidence than in the group of low PEP incidence. Additionally, the incidence of hyperamylasemia was significantly reduced by GTN treatment (RR 0.69; 95% CI, 0.54-0.90. No differences of the successful cannulation rate of bile ducts (RR 1.03; 95% CI, 0.99-1.06 attributable to GTN were observed. CONCLUSION: Prophylactic use of GTN reduced the overall incidence of PEP and hyperamylasemia. However, GTN was not helpful for the severity of PEP and the rate of cannulation.

  14. Screening Technologies for Target Identification in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Michl, Patrick, E-mail: michlp@med.uni-marburg.de; Ripka, Stefanie; Gress, Thomas; Buchholz, Malte [Department of Gastroenterology and Endocrinology, University Hospital, Philipps-University Marburg, Baldinger Strasse, D-35043 Marburg (Germany)

    2010-12-29

    Pancreatic cancer exhibits an extraordinarily high level of resistance to almost any kind of systemic therapy evaluated in clinical trials so far. Therefore, the identification of novel therapeutic targets is urgently required. High-throughput screens have emerged as an important tool to identify putative targets for diagnosis and therapy in an unbiased manner. More than a decade ago, microarray technology was introduced to identify differentially expressed genes in pancreatic cancer as compared to normal pancreas, chronic pancreatitis and other cancer types located in close proximity to the pancreas. In addition, proteomic screens have facilitated the identification of differentially secreted proteins in body fluids of pancreatic cancer patients, serving as possible biomarkers. Recently, RNA interference-based loss-of-function screens have been used to identify functionally relevant genes, whose knock-down has impact on pancreatic cancer cell viability, thereby representing potential new targets for therapeutic intervention. This review summarizes recent results of transcriptional, proteomic and functional screens in pancreatic cancer and discusses potentials and limitations of the respective technologies as well as their impact on future therapeutic developments.

  15. New developments in endoscopic treatment of chronic pancreatitis.

    Science.gov (United States)

    Didden, P; Bruno, M; Poley, J W

    2012-12-01

    The aim of endoscopic therapy of chronic pancreatitis (CP) is to treat pain by draining the pancreatic duct or managing loco-regional complications. Recent decennia were characterized by continuous improvement of endoscopic techniques and devices, resulting in a better clinical outcome. Novel developments now also provide the opportunity to endoscopically treat refractory CP-related complications. Especially suboptimal surgical candidates could potentially benefit from these new developments, consequently avoiding invasive surgery. The use of fully covered self-expandable metal stents (SEMS) has been explored in pancreatic and CP-related biliary duct strictures, resistant to conventional treatment with plastic endoprotheses. Furthermore, endosonography-guided transmural drainage of the main pancreatic duct via duct-gastrostomy is an alternative treatment option in selected cases. Pancreatic pseudocysts represent an excellent indication for endoscopic therapy with some recent case series demonstrating effective drainage with the use of a fully covered SEMS. Although results of these new endoscopic developments are promising, high quality randomized trials are required to determine their definite role in the management of chronic pancreatitis.

  16. Screening Technologies for Target Identification in Pancreatic Cancer

    International Nuclear Information System (INIS)

    Michl, Patrick; Ripka, Stefanie; Gress, Thomas; Buchholz, Malte

    2010-01-01

    Pancreatic cancer exhibits an extraordinarily high level of resistance to almost any kind of systemic therapy evaluated in clinical trials so far. Therefore, the identification of novel therapeutic targets is urgently required. High-throughput screens have emerged as an important tool to identify putative targets for diagnosis and therapy in an unbiased manner. More than a decade ago, microarray technology was introduced to identify differentially expressed genes in pancreatic cancer as compared to normal pancreas, chronic pancreatitis and other cancer types located in close proximity to the pancreas. In addition, proteomic screens have facilitated the identification of differentially secreted proteins in body fluids of pancreatic cancer patients, serving as possible biomarkers. Recently, RNA interference-based loss-of-function screens have been used to identify functionally relevant genes, whose knock-down has impact on pancreatic cancer cell viability, thereby representing potential new targets for therapeutic intervention. This review summarizes recent results of transcriptional, proteomic and functional screens in pancreatic cancer and discusses potentials and limitations of the respective technologies as well as their impact on future therapeutic developments

  17. Clinical Trials

    Medline Plus

    Full Text Available ... Trial Protocol Each clinical trial has a master plan called a protocol (PRO-to-kol). This plan explains how the trial will work. The trial ... clinical trial; and detailed information about the treatment plan. Eligibility Criteria A clinical trial's protocol describes what ...

  18. Individual Patient Data Meta-Analysis of Organ Failure in Acute Pancreatitis: Protocol of the PANCREA II Study

    OpenAIRE

    Stephanie LM Das; John A Windsor; Maxim S Petrov; George I Papachristou; Tercio De Campos,; Jozefa Panek,; Ignasi Poves Prim; Alejandro Serrablo,; Rowan W Parks; Generoso Uomo

    2013-01-01

    Context Organ failure is a major determinant of mortality in patients with acute pancreatitis. These patients usually requireadmission to high dependency or intensive care units and consume considerable health care resources. Given a low incidence rate of organ failure and a lack of large non-interventional studies in the field of acute pancreatitis, the characteristics of organ failure that influence outcomes of patients with acute pancreatitis remain largely unknown. Therefore, the Pancreat...

  19. The evolution of the surgical treatment of chronic pancreatitis.

    Science.gov (United States)

    Andersen, Dana K; Frey, Charles F

    2010-01-01

    To establish the current status of surgical therapy for chronic pancreatitis, recent published reports are examined in the context of the historical advances in the field. The basis for decompression (drainage), denervation, and resection strategies for the treatment of pain caused by chronic pancreatitis is reviewed. These divergent approaches have finally coalesced as the head of the pancreas has become apparent as the nidus of chronic inflammation. The recent developments in surgical methods to treat the complications of chronic pancreatitis and the results of recent prospective randomized trials of operative approaches were reviewed to establish the current best practices. Local resection of the pancreatic head, with or without duct drainage, and duodenum-preserving pancreatic head resection offer outcomes as effective as pancreaticoduodenectomy, with lowered morbidity and mortality. Local resection or excavation of the pancreatic head offers the advantage of lowest cost and morbidity and early prevention of postoperative diabetes. The late incidences of recurrent pain, diabetes, and exocrine insufficiency are equivalent for all 3 surgical approaches. Local resection of the pancreatic head appears to offer best outcomes and lowest risk for the management of the pain of chronic pancreatitis.

  20. Five Year Results of US Intergroup/RTOG 9704 With Postoperative CA 19-9 {<=}90 U/mL and Comparison to the CONKO-001 Trial

    Energy Technology Data Exchange (ETDEWEB)

    Berger, Adam C., E-mail: adam.berger@jefferson.edu [Thomas Jefferson University Hospital, Philadelphia, Pennsylvania (United States); Winter, Kathryn [RTOG Statistical Center, Philadelphia, Pennsylvania (United States); Hoffman, John P. [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Regine, William F. [University of Maryland Medical Systems, Baltimore, Maryland (United States); Abrams, Ross A. [Rush University Medical Center, Chicago, Illinois (United States); Safran, Howard [Division of Hematology/Oncology, The Miriam Hospital, Providence, Rhode Island (United States); Freedman, Gary M. [Fox Chase Cancer Center, Philadelphia, Pennsylvania (United States); Benson, Alan B. [Northwestern Memorial Hospital, Chicago, Illinois (United States); MacDonald, John [St. Vincent' s Comprehensive Cancer Center, New York, New York (United States); Willett, Christopher G. [Duke University Medical Center, Durham, North Carolina (United States)

    2012-11-01

    Purpose: Radiation Therapy Oncology Group (RTOG) trial 9704 was the largest randomized trial to use adjuvant chemoradiation therapy for patients with pancreatic cancer. This report analyzes 5-year survival by serum level of tumor marker CA 19-9 of {<=}90 vs >90 U/mL and compares results to the those of the CONKO-001 trial. Methods and Materials: CA 19-9 expression was analyzed as a dichotomized variable ({<=}90 vs >90 U/mL). Cox proportional hazard models were used to identify the impact of the CA 19-9 value on overall survival (OS). Actuarial estimates of OS were calculated using the Kaplan-Meier method. Results: Both univariate (hazard ratio [HR] = 3.2; 95% confidence interval [CI], 2.3-4.3, P<.0001) and multivariate (HR = 3.1; 95% CI, 2.2-4.2, P<.0001) analyses demonstrated a statistically significant decrease in OS for CA 19-9 serum level of {>=}90 U/mL. For patients in the gemcitabine (Gem) treatment arm with CA 19-9 <90 U/mL, median survival was 21 months. For patients with CA 19-9 {>=}90 U/mL, this number dropped to 10 months. In patients with pancreatic head tumors in the Gem treatment arm with RT quality assurance per protocol and CA 19-9 of <90 U/mL, median survival and 5-year rate were 24 months and 34%. In comparison, the median survival and 5-year OS rate for patients in the Gem arm of the CONKO trial were 22 months and 21%. Conclusions: This analysis demonstrates that patients with postresection CA 19-9 values {>=}90 U/mL had a significantly worse survival. Patients with pancreatic head tumors treated with Gem with CA 19-9 serum level of <90 U/mL and per protocol RT had favorable survival compared to that seen in the CONKO trial. CA 19-9 is a stratification factor for the current RTOG adjuvant pancreas trial (0848).

  1. Natural Products as Adjunctive Treatment for Pancreatic Cancer: Recent Trends and Advancements

    Directory of Open Access Journals (Sweden)

    Qingxi Yue

    2017-01-01

    Full Text Available Pancreatic cancer is a type of common malignant tumors with high occurrence in the world. Most patients presented in clinic had pancreatic cancer at advanced stages. Furthermore, chemotherapy or radiotherapy had very limited success in treating pancreatic cancer. Complementary and alternative medicines, such as natural products/herbal medicines, represent exciting adjunctive therapies. In this review, we summarize the recent advances of using natural products/herbal medicines, such as Chinese herbal medicine, in combination with conventional chemotherapeutic agents to treat pancreatic cancer in preclinical and clinical trials.

  2. Investigation of the Study Characteristics Affecting Clinical Trial Quality Using the Protocol Deviations Leading to Exclusion of Subjects From the Per Protocol Set Data in Studies for New Drug Application: A Retrospective Analysis.

    Science.gov (United States)

    Kohara, Norihito; Kaneko, Masayuki; Narukawa, Mamoru

    2018-01-01

    The concept of the risk-based approach has been introduced as an effort to secure the quality of clinical trials. In the risk-based approach, identification and evaluation of risk in advance are considered important. For recently completed clinical trials, we investigated the relationship between study characteristics and protocol deviations leading to the exclusion of subjects from Per Protocol Set (PPS) efficacy analysis. New drugs approved in Japan in the fiscal year 2014-2015 were targeted in the research. The reasons for excluding subjects from the PPS efficacy analysis were described in 102 trials out of 492 in the summary of new drug application documents, which was publicly disclosed after the drug's regulatory approval. The author extracted these reasons along with the numbers of the cases and the study characteristics of each clinical trial. Then, the direct comparison, univariate regression analysis, and multivariate regression analysis was carried out based on the exclusion rate. The study characteristics for which exclusion of subjects from the PPS efficacy analysis were frequently observed was multiregional clinical trials in study region; inhalant and external use in administration route; Anti-infective for systemic use; Respiratory system, Dermatologicals, and Nervous system in therapeutic drug under the Anatomical Therapeutic Chemical Classification. In the multivariate regression analysis, the clinical trial variables of inhalant, Respiratory system, or Dermatologicals were selected as study characteristics leading to a higher exclusion rate. The characteristics of the clinical trial that is likely to cause protocol deviations that will affect efficacy analysis were suggested. These studies should be considered for specific attention and priority observation in the trial protocol or its monitoring plan and execution, such as a clear description of inclusion/exclusion criteria in the protocol, development of training materials to site staff, and

  3. Long-term follow-up of a randomized clinical trial comparing Beger with pylorus-preserving Whipple procedure for chronic pancreatitis.

    Science.gov (United States)

    Müller, M W; Friess, H; Martin, D J; Hinz, U; Dahmen, R; Büchler, M W

    2008-03-01

    Duodenum-preserving pancreatic head resection according to Beger and the pylorus-preserving Whipple (ppWhipple) procedure were compared in patients with chronic pancreatitis (CP) in a randomized clinical trial. Perioperative data and short-term outcome have been reported previously. The present study evaluated long-term follow-up. Forty patients were enrolled originally, 20 in each group. Long-term follow-up included mortality, morbidity, pain status, occupational rehabilitation, quality of life (QoL), and endocrine and exocrine function at median follow-up of 7 and 14 years. One patient who had a ppWhipple procedure was lost to follow-up. There were five late deaths in each group. No differences were noted in pain status and exocrine pancreatic function. Loss of appetite was significantly worse in the ppWhipple group at 14 years' follow-up, but there were no other differences in QoL parameters examined. After 14 years, diabetes mellitus was present in seven of 15 patients who had the Beger procedure and 11 of 14 patients after ppWhipple resection (P = 0.128). After long-term follow-up of up to 14 years early advantages of the Beger procedure were no longer present. 2007 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  4. A modified fast-track program for pancreatic surgery: a prospective single-center experience.

    Science.gov (United States)

    di Sebastiano, Pierluigi; Festa, Leonardina; De Bonis, Antonio; Ciuffreda, Andrea; Valvano, Maria Rosa; Andriulli, Angelo; di Mola, F Francesco

    2011-03-01

    The objective of this study is to evaluate the impact of a fast-track protocol in a high-volume center for patients with pancreatic disorders. The concept of fast-track surgery allowing accelerated postoperative recovery is accepted in colorectal surgery, but efficacy data are only preliminary for patients undergoing major pancreatic surgery. We aimed to evaluate the impact of a modified fast-track protocol in a high-volume center for patients with pancreatic disorders. Between February 2005 and January 2010, 145 subjects had resective pancreatic surgery and were enrolled in the program. Essential features of the program were no preanaesthetic medication, upper and lower air-warming device, avoidance of excessive i.v. fluids perioperatively, effective control of pain, early reinstitution of oral feeding, and immediate mobilization and restoration of bowel function following surgery. Outcome measures were postoperative complications such as pancreatic fistula, delayed gastric emptying, biliary leak, intra-abdominal abscess, post-pancreatectomy hemorrhage, acute pancreatitis, wound infection, 30-day mortality, postoperative hospital stay, and readmission rates. On average, patients were discharged on postoperative day 10 (range 6-69), with a 30-day readmission rate of 6.2%. Percentage of patients with at least one complication was 38.6%. Pancreatic anastomotic leakage occurred in seven of 101 pancreatico-jejunostomies, and biliary leak in three of 109 biliary jejunostomies. Postoperative hemorrhage occurred in ten (6.9%) patients and wound infection in nine (6.2%) cases. In-hospital mortality was 2.7%. Fast-track parameters, such as normal food and first stool, correlated significantly with early discharge (jaundice, and resumption of normal diet by the 5th postoperative day were independent factors of early discharge. Fast-track programs are feasible, easy, and also applicable for patients undergoing a major surgery such as pancreatic resection.

  5. The Epidemiology of Pancreatitis and Pancreatic Cancer

    Science.gov (United States)

    Yadav, Dhiraj; Lowenfels, Albert B.

    2013-01-01

    Acute pancreatitis is one of the most frequent gastrointestinal causes for hospital admission in the US. Chronic pancreatitis, although lower in incidence, significantly reduces patients’ quality of life. Pancreatic cancer has high mortality and is 1 of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect Blacks more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. PMID:23622135

  6. Nutrition management in enhanced recovery after abdominal pancreatic surgery.

    Science.gov (United States)

    Márquez Mesa, Elena; Baz Figueroa, Caleb; Suárez Llanos, José Pablo; Sanz Pereda, Pablo; Barrera Gómez, Manuel Ángel

    Multimodal rehabilitation programs are perioperative standardized strategies with the objective of improving patient recovery, and decreasing morbidity, hospital stay and health cost. The nutritional aspect is an essential component of multimodal rehabilitation programs and therefore nutritional screening is recommended prior to hospital admission, avoiding pre-surgical fasting, with oral carbohydrate overload and early initiation of oral intake after surgery. However, there are no standardized protocols of diet progression after pancreatic surgery. A systematic review was been performed of papers published between 2006 and 2016, describing different nutritional strategies after pancreatic surgery and its possible implications in postoperative outcome. The studies evaluated are very heterogeneous, so conclusive results could not be drawn on the diet protocol to be implemented, its influence on clinical variables, or the need for concomitant artificial nutrition. Copyright © 2017 AEC. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Targeting Epidermal Growth Factor Receptor-Related Signaling Pathways in Pancreatic Cancer.

    Science.gov (United States)

    Philip, Philip A; Lutz, Manfred P

    2015-10-01

    Pancreatic cancer is aggressive, chemoresistant, and characterized by complex and poorly understood molecular biology. The epidermal growth factor receptor (EGFR) pathway is frequently activated in pancreatic cancer; therefore, it is a rational target for new treatments. However, the EGFR tyrosine kinase inhibitor erlotinib is currently the only targeted therapy to demonstrate a very modest survival benefit when added to gemcitabine in the treatment of patients with advanced pancreatic cancer. There is no molecular biomarker to predict the outcome of erlotinib treatment, although rash may be predictive of improved survival; EGFR expression does not predict the biologic activity of anti-EGFR drugs in pancreatic cancer, and no EGFR mutations are identified as enabling the selection of patients likely to benefit from treatment. Here, we review clinical studies of EGFR-targeted therapies in combination with conventional cytotoxic regimens or multitargeted strategies in advanced pancreatic cancer, as well as research directed at molecules downstream of EGFR as alternatives or adjuncts to receptor targeting. Limitations of preclinical models, patient selection, and trial design, as well as the complex mechanisms underlying resistance to EGFR-targeted agents, are discussed. Future clinical trials must incorporate translational research end points to aid patient selection and circumvent resistance to EGFR inhibitors.

  8. Antioxidant therapy for patients with chronic pancreatitis: A systematic review and meta-analysis.

    Science.gov (United States)

    Zhou, Dongkai; Wang, Weilin; Cheng, Xiaofei; Wei, Jianfeng; Zheng, Shusen

    2015-08-01

    Chronic pancreatitis is a progressive, inflammatory disease of pancreas characterized by significant abdominal pain, malabsorption, and diabetes mellitus. Antioxidant therapy has been proposed as an effective treatment for painful chronic pancreatitis. We performed a meta-analysis of trials in which antioxidant therapy was compared with placebo in chronic pancreatitis. We searched six databases to identify relevant trials. Results are expressed as risk ratio (RR) or standardized mean difference (SMD) with accompanying 95% confidence intervals (CI). The meta-analysis was performed with the fixed-effects model or random-effects model according to heterogeneity. Eight studies including 573 patients met the inclusion criteria. A meta-analysis of these studies revealed that the intervention of antioxidants was associated with a significant increase in patients with pain relief (RR, 2.15; 95% CI, 1.72-2.69; P chronic pancreatitis patients (SMD: -0.41; 95% CI: -0.83 to -0.10; P = 0.0005). Additionally, antioxidants may cause some adverse reactions (RR, 4.22; 95% CI: 2.17-8.20; P pathophysiology of chronic pancreatitis, and administration of antioxidants to patients with painful chronic pancreatitis is effective in relieving pain. Antioxidant supplements may be advocated as one medical therapy for chronic pancreatitis patients with low antioxidant capacity in their blood. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

  9. Gene Therapy for Pancreatic Cancer: Specificity, Issues and Hopes.

    Science.gov (United States)

    Rouanet, Marie; Lebrin, Marine; Gross, Fabian; Bournet, Barbara; Cordelier, Pierre; Buscail, Louis

    2017-06-08

    A recent death projection has placed pancreatic ductal adenocarcinoma as the second cause of death by cancer in 2030. The prognosis for pancreatic cancer is very poor and there is a great need for new treatments that can change this poor outcome. Developments of therapeutic innovations in combination with conventional chemotherapy are needed urgently. Among innovative treatments the gene therapy offers a promising avenue. The present review gives an overview of the general strategy of gene therapy as well as the limitations and stakes of the different experimental in vivo models, expression vectors (synthetic and viral), molecular tools (interference RNA, genome editing) and therapeutic genes (tumor suppressor genes, antiangiogenic and pro-apoptotic genes, suicide genes). The latest developments in pancreatic carcinoma gene therapy are described including gene-based tumor cell sensitization to chemotherapy, vaccination and adoptive immunotherapy (chimeric antigen receptor T-cells strategy). Nowadays, there is a specific development of oncolytic virus therapies including oncolytic adenoviruses, herpes virus, parvovirus or reovirus. A summary of all published and on-going phase-1 trials is given. Most of them associate gene therapy and chemotherapy or radiochemotherapy. The first results are encouraging for most of the trials but remain to be confirmed in phase 2 trials.

  10. Treatment of severe acute pancreatitis

    Directory of Open Access Journals (Sweden)

    Praznik Ivan

    2014-01-01

    Full Text Available Acute pancreatitis is an acute inflammatory process of the pancreas with variable involvement of other regional tissues or other organ systems. The severe form of the disease occurs in 10-20% of cases, and usually requires prolonged hospitalization due to a frequent local and systemic complications. Additionally, considerable mortality despite diagnostic and therapeutic advances, makes this disease a serious health problem nowadays. The aim of this study was to conduct a review of randomized controlled trials to determine differences in the efficiency between standard methods of treatment for severe acute pancreatitis and new treatment ways in terms of decreased mortality. Search of the 'Medline' database of original scientific papers and systematic review articles was made, using a combination of the following keywords: acute pancreatitis, treatment, mortality. In total 914 papers were found, published in the last 13 years; 14 of 64 randomized controlled clinical trials met the selection criteria and were eligible for inclusion. From a total of 16 papers, the conservative treatment was related to 11, which includes some of the new treatment methods, while the effects of new methods of treatment have been the subject of research in the four studies. Combined endoscopic and surgical treatment was applied in only one study. The largest sample of 290 patients was included in the study with platelet activation factor antagonist, while the smallest sample of 22 patients was used in the study that compared total parenteral with enteral nutrition. Continuous regional arterial infusion of protease inhibitors in combination with antibiotics, intravenous supplementation of alanyl-glutamine dipeptide and the early, high-volume continuous veno-venous hemofiltration showed the best results in the treatment of patients with severe acute pancreatitis. Also, the use of low molecular weight heparin and enteral nutrition significantly reduced mortality.

  11. Advances in treatment of autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    LI Ji

    2013-07-01

    Full Text Available Autoimmune pancreatitis (AIP is a type of chronic pancreatitis characterized by an autoimmune inflammatory process. Treatment protocols for AIP are still evolving. According to the articles about AIP treatment in recent years, the indications for steroid therapy include specific clinical manifestations (jaundice, abdominal pain, etc., markedly abnormal imaging findings, and extrapancreatic organ involvement. The initial dose of steroid (prednisone is usually 0.6 mg·kg-1·d-1 or 30-40 mg/d; after 3 weeks to 1 month of treatment with the initial dose, the dose is decreased by 5-10 mg every 1-2 weeks until it drops to 2.5-5 mg/d; this dose is maintained for 6 months to 3 years. No consensus has been reached on the adverse effect of steroid on diabetes mellitus complicating AIP. Immunosuppressive agents should be used for the patients with disease relapses or with important extrapancreatic organs involved. Rituximab might become one of the therapies for refractory AIP. Although some patients achieved remission after surgical treatment, surgery is still not recommended as a routine treatment protocol due to the complications after surgery.

  12. Regulatory challenges in manufacturing of pancreatic islets.

    Science.gov (United States)

    Linetsky, E; Ricordi, C

    2008-03-01

    At the present time, transplantation of pancreatic islet cells is considered an experimental therapy for a selected cohort of patients with type 1 diabetes, and is conducted under an Investigational New Drug (IND) application. Encouraging results of the Edmonton Protocol published in the year 2000 sparked a renewed interest in clinical transplantation of allogeneic islets, triggering a large number of IND applications for phase I clinical trials. Promising results reported by a number of centers since then prompted the Food and Drug Administration (FDA) to consider the possibility of licensing allogeneic islets as a therapeutic treatment for patients with type 1 diabetes. However, prior to licensure, issues such as safety, purity, efficacy, and potency of the islet product must be addressed. This is complicated by the intricate nature of pancreatic islets and limited characterization prior to transplantation. In this context, control of the manufacturing process plays a critical role in the definition of the final product. Despite significant progress made in standardization of the donor organ preservation methods, reagents used, and characterization assays performed to qualify an islet cell product, control of the isolation process remains a challenge. Within the scope of the FDA regulations, islet cells meet the definition of a biologic product, somatic cell therapy, and a drug. In addition, AABB standards that address cellular therapy products apply to manufacturing facilities accredited by this organization. Control of the source material, isolation process, and final product are critical issues that must be addressed in the context of FDA and other relevant regulations applicable to islet cell products.

  13. Optimizing Adjuvant Therapy for Resected Pancreatic Cancer

    Science.gov (United States)

    In this clinical trial, patients with resected pancreatic head cancer will be randomly assigned to receive either gemcitabine with or without erlotinib for 5 treatment cycles. Patients who do not experience disease progression or recurrence will then be r

  14. The epidemiology of pancreatitis and pancreatic cancer.

    Science.gov (United States)

    Yadav, Dhiraj; Lowenfels, Albert B

    2013-06-01

    Acute pancreatitis is one of the most frequent gastrointestinal causes of hospital admission in the United States. Chronic pancreatitis, although lower in incidence, significantly reduces patients' quality of life. Pancreatic cancer is associated with a high mortality rate and is one of the top 5 causes of death from cancer. The burden of pancreatic disorders is expected to increase over time. The risk and etiology of pancreatitis differ with age and sex, and all pancreatic disorders affect the black population more than any other race. Gallstones are the most common cause of acute pancreatitis, and early cholecystectomy eliminates the risk of future attacks. Alcohol continues to be the single most important risk factor for chronic pancreatitis. Smoking is an independent risk factor for acute and chronic pancreatitis, and its effects could synergize with those of alcohol. Significant risk factors for pancreatic cancer include smoking and non-O blood groups. Alcohol abstinence and smoking cessation can alter the progression of pancreatitis and reduce recurrence; smoking cessation is the most effective strategy to reduce the risk of pancreatic cancer. Copyright © 2013 AGA Institute. Published by Elsevier Inc. All rights reserved.

  15. Pancreatic and duodenal injuries: keep it simple.

    Science.gov (United States)

    Rickard, Matthew J F X; Brohi, Karim; Bautz, Peter C

    2005-07-01

    The management of pancreatic and duodenal trauma has moved away from complex reconstructive procedures to simpler methods in keeping with the trend towards organ-specific, damage control surgery. A retrospective case note review was undertaken over a 30-month period to evaluate a simplified protocol for the management of these injuries. Of 100 consecutive patients there were 51 with pancreatic injury, 30 with a duodenal injury and 19 with combined pancreaticoduodenal trauma. Overall mortality was 18.0%, with a late mortality (after 24 h) of 9.9%. This is comparable to previous studies. Morbidity from abscesses, fistulas and anastomotic breakdown was acceptably low. The concept of staged laparotomy can be successfully applied to wounds of the pancreas and duodenum. Debridement of devitalized tissue and drainage can be employed for most cases of pancreatic trauma. Most duodenal injuries can be managed with debridement and primary repair. Temporary exclusion and reoperation should be employed for unstable patients.

  16. Focal pancreatic enlargement: differentiation between pancreatic adenocarcinoma and focal pancreatitis on CT and ERCP

    International Nuclear Information System (INIS)

    Kim, Eun Kyung; Kim, Ki Whang; Lee, Jong Tae; Kim, Hee Soo; Yoo, Hyung Sik; Yu, Jeong Sik; Yoon, Sang Wook

    1995-01-01

    To differentiate the pancreatic adenocarcinoma from focal pancreatitis on CT and ERCP in cases of focal pancreatic enlargement. We analysed CT findings of 66 patients of pancreatic adenocarcinoma (n = 45) or focal pancreatitis (n = 21) with respect to size, density, calcification, pancreatic or biliary duct dilatation, fat plane obliteration around the vessels, direction of retroperitoneal extension, lymphadenopathy, pseudocyst formation and atrophy of pancreas. ERCP available in 48 patients were analysed in respect to morphologic appearance of CBD and pancreatic duct, and distance between the two ducts. The patients in focal pancreatitis were younger with more common history of alcohol drinking. There was no statistical difference in calcifications of the mass (18% in the adenocarcinoma, 33% in the focal pancreatitis), but a tendency of denser, larger number of calcifications was noted in focal pancreatitis. The finding of fat plane obliteration around the vessels were more common in pancreatic adenocarcinoma, and fascial thickenings were more prominent in focal pancreatitis, although not statistically significant. On ERCP, there were no differential points of CBD, pancreatic duct morphology, but distance between the two ducts at the lesion center was more wider in focal pancreatitis. Differentiating focal pancreatitis from pancreatic adenocarcinoma is difficult. However, we should consider the possibility of focal pancreatitis in cases of patients with young age, having alcoholic history in association with CT findings of large numbers of and dense calcifications, and ERCP findings of prominent separation of two duct at the lesion center

  17. Trends in the number and the quality of trial protocols involving children submitted to a French Institutional Review Board

    Directory of Open Access Journals (Sweden)

    Isabelle Gautier

    2017-08-01

    Full Text Available Abstract Background There is a great need for high quality clinical research for children. The European Pediatric Regulation aimed to improve the quality of clinical trials in order to increase the availability of treatments for children. The main purpose of this study was to assess the evolution of both the number and the quality of pediatric trial protocols that were submitted to a French Institutional Review Board (IRB00009118 before and after the initiation of the EU Pediatric Regulation. Methods All protocols submitted to the IRB00009118 between 2003 and 2014 and conducting research on subjects under eighteen years of age were eligible. The quality of randomized clinical trials was assessed according to the guidelines developed by the Enhancing the QUAlity and Transparency Of health Research (EQUATOR Network and ranked using the Jadad score. Results Out of 622 protocols submitted to the Institutional Review Board (IRB, 21% (133/622 included children. Among these 133 pediatric protocols, the number of submitted pediatric protocols doubled between the two studied periods. From 2003 to 2008, 47 protocols including 21 institutionally sponsored were submitted to the IRB and from 2009 until 2014, 86 protocols including 48 institutionally sponsored were submitted. No significant trend was observed on the quality of RCTs. The overall median score of RCTs on the Jadad scale was high (3.5, 70.0% of protocols had a Jadad score ≥ 3, and 30.0% had a score < 3. Conclusion Following the EU Pediatric Regulation, the number of pediatric protocols submitted to the IRB00009118 tends to increase, but no change was noticed regarding their quality.

  18. Generation of insulin-producing cells from human bone marrow-derived mesenchymal stem cells: comparison of three differentiation protocols.

    Science.gov (United States)

    Gabr, Mahmoud M; Zakaria, Mahmoud M; Refaie, Ayman F; Khater, Sherry M; Ashamallah, Sylvia A; Ismail, Amani M; El-Badri, Nagwa; Ghoneim, Mohamed A

    2014-01-01

    Many protocols were utilized for directed differentiation of mesenchymal stem cells (MSCs) to form insulin-producing cells (IPCs). We compared the relative efficiency of three differentiation protocols. Human bone marrow-derived MSCs (HBM-MSCs) were obtained from three insulin-dependent type 2 diabetic patients. Differentiation into IPCs was carried out by three protocols: conophylline-based (one-step protocol), trichostatin-A-based (two-step protocol), and β -mercaptoethanol-based (three-step protocol). At the end of differentiation, cells were evaluated by immunolabeling for insulin production, expression of pancreatic endocrine genes, and release of insulin and c-peptide in response to increasing glucose concentrations. By immunolabeling, the proportion of generated IPCs was modest ( ≃ 3%) in all the three protocols. All relevant pancreatic endocrine genes, insulin, glucagon, and somatostatin, were expressed. There was a stepwise increase in insulin and c-peptide release in response to glucose challenge, but the released amounts were low when compared with those of pancreatic islets. The yield of functional IPCs following directed differentiation of HBM-MSCs was modest and was comparable among the three tested protocols. Protocols for directed differentiation of MSCs need further optimization in order to be clinically meaningful. To this end, addition of an extracellular matrix and/or a suitable template should be attempted.

  19. The Interface of Clinical Decision-Making With Study Protocols for Knowledge Translation From a Walking Recovery Trial.

    Science.gov (United States)

    Hershberg, Julie A; Rose, Dorian K; Tilson, Julie K; Brutsch, Bettina; Correa, Anita; Gallichio, Joann; McLeod, Molly; Moore, Craig; Wu, Sam; Duncan, Pamela W; Behrman, Andrea L

    2017-01-01

    Despite efforts to translate knowledge into clinical practice, barriers often arise in adapting the strict protocols of a randomized, controlled trial (RCT) to the individual patient. The Locomotor Experience Applied Post-Stroke (LEAPS) RCT demonstrated equal effectiveness of 2 intervention protocols for walking recovery poststroke; both protocols were more effective than usual care physical therapy. The purpose of this article was to provide knowledge-translation tools to facilitate implementation of the LEAPS RCT protocols into clinical practice. Participants from 2 of the trial's intervention arms: (1) early Locomotor Training Program (LTP) and (2) Home Exercise Program (HEP) were chosen for case presentation. The two cases illustrate how the protocols are used in synergy with individual patient presentations and clinical expertise. Decision algorithms and guidelines for progression represent the interface between implementation of an RCT standardized intervention protocol and clinical decision-making. In each case, the participant presents with a distinct clinical challenge that the therapist addresses by integrating the participant's unique presentation with the therapist's expertise while maintaining fidelity to the LEAPS protocol. Both participants progressed through an increasingly challenging intervention despite their own unique presentation. Decision algorithms and exercise progression for the LTP and HEP protocols facilitate translation of the RCT protocol to the real world of clinical practice. The two case examples to facilitate translation of the LEAPS RCT into clinical practice by enhancing understanding of the protocols, their progression, and their application to individual participants.Video Abstract available for more insights from the authors (see Supplemental Digital Content 1, available at: http://links.lww.com/JNPT/A147).

  20. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

    Science.gov (United States)

    Zhan, Xianbao; Wang, Fan; Bi, Yan

    2016-01-01

    Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. PMID:27418683

  1. Pain severity reduces life quality in chronic pancreatitis: Implications for design of future outcome trials

    NARCIS (Netherlands)

    Olesen, S.S.; Juel, J.; Nielsen, A.K.; Frokjaer, J.B.; Wilder-Smith, O.H.G.; Drewes, A.M.

    2014-01-01

    BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a disabling disease characterised by abdominal pain, and various pancreatic and extra-pancreatic complications. We investigated the interactions between pain characteristics (i.e. pain severity and its pattern in time), complications, and quality

  2. Autoimmune pancreatitis can develop into chronic pancreatitis

    Science.gov (United States)

    2014-01-01

    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung’s and Santorini’s ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct. PMID:24884922

  3. Autoimmune pancreatitis can develop into chronic pancreatitis.

    Science.gov (United States)

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

    2014-05-21

    Autoimmune pancreatitis (AIP) has been recognized as a distinct type of pancreatitis that is possibly caused by autoimmune mechanisms. AIP is characterized by high serum IgG4 and IgG4-positive plasma cell infiltration in affected pancreatic tissue. Acute phase AIP responds favorably to corticosteroid therapy and results in the amelioration of clinical findings. However, the long-term prognosis and outcome of AIP remain unclear. We have proposed a working hypothesis that AIP can develop into ordinary chronic pancreatitis resembling alcoholic pancreatitis over a long-term course based on several clinical findings, most notably frequent pancreatic stone formation. In this review article, we describe a series of study results to confirm our hypothesis and clarify that: 1) pancreatic calcification in AIP is closely associated with disease recurrence; 2) advanced stage AIP might have earlier been included in ordinary chronic pancreatitis; 3) approximately 40% of AIP patients experience pancreatic stone formation over a long-term course, for which a primary risk factor is narrowing of both Wirsung's and Santorini's ducts; and 4) nearly 20% of AIP patients progress to confirmed chronic pancreatitis according to the revised Japanese Clinical Diagnostic Criteria, with independent risk factors being pancreatic head swelling and non-narrowing of the pancreatic body duct.

  4. Pancreatic Exocrine Insufficiency in Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Miroslav Vujasinovic

    2017-02-01

    Full Text Available Abstract: Cancer patients experience weight loss for a variety of reasons, commencing with the tumor’s metabolism (Warburg effect and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  5. Pancreatic Exocrine Insufficiency in Pancreatic Cancer.

    Science.gov (United States)

    Vujasinovic, Miroslav; Valente, Roberto; Del Chiaro, Marco; Permert, Johan; Löhr, J-Matthias

    2017-02-23

    Abstract : Cancer patients experience weight loss for a variety of reasons, commencing with the tumor's metabolism (Warburg effect) and proceeding via cachexia to loss of appetite. In pancreatic cancer, several other factors are involved, including a loss of appetite with a particular aversion to meat and the incapacity of the pancreatic gland to function normally when a tumor is present in the pancreatic head. Pancreatic exocrine insufficiency is characterized by a deficiency of the enzymes secreted from the pancreas due to the obstructive tumor, resulting in maldigestion. This, in turn, contributes to malnutrition, specifically a lack of fat-soluble vitamins, antioxidants, and other micronutrients. Patients with pancreatic cancer and pancreatic exocrine insufficiency have, overall, an extremely poor prognosis with regard to surgical outcome and overall survival. Therefore, it is crucial to be aware of the mechanisms involved in the disease, to be able to diagnose pancreatic exocrine insufficiency early on, and to treat malnutrition appropriately, for example, with pancreatic enzymes.

  6. External pancreatic duct stent reduces pancreatic fistula: a meta-analysis and systematic review.

    Science.gov (United States)

    Patel, Krishen; Teta, Anthony; Sukharamwala, Prashant; Thoens, Jonathan; Szuchmacher, Mauricio; DeVito, Peter

    2014-01-01

    Postoperative pancreatic fistula formation (POPF) remains one of the most common and detrimental complications following pancreaticojejunostomy (PJ). The aim of this meta-analysis is to analyze the efficacy of external pancreatic duct stent placement in preventing POPF formation following PJ. The primary end-point was the incidence of POPF formation following pancreaticoduodenectomy (PD) in the presence and absence of external stent placement. Secondary outcomes examined were the incidence of perioperative mortality, delayed gastric emptying, postoperative wound infection, operative time, blood loss, and length of hospital stay. Four trials were included comprising 416 patients. External pancreatic duct stenting was found to reduce the incidence of both any grade POPF formation (OR 0.37, 95% CI = 0.23 to 0.58, p = 0.0001) and clinically significant (grade B or C) POPF formation (OR 0.50, 95% CI = 0.30 to 0.84, p = 0.0009) following PD. The use of an external stent was also found to significantly lessen length of hospital stay (SMD -0.39, 95% CI = -0.63 to -0.15, p = 0.001). This analysis has shown that external pancreatic duct stenting is indeed efficacious in the incidence of both any grade as well as clinically significant POPF formation following PD. Length of hospital stay was also found to be significantly less by external duct stenting. Copyright © 2014 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

  7. CT diagnosis of pancreatic carcinoma and chronic pancreatitis

    International Nuclear Information System (INIS)

    Luan Baoqing; Jin Erhu; Zhang Lizhen; Jiang Haibin

    1997-01-01

    To improve the diagnostic accuracy of pancreatic carcinoma and chronic pancreatitis. The CT findings of 154 cases with pancreatic carcinoma, chronic pancreatitis and mis-diagnosed other pancreatic diseases proven clinically and pathologically were analysed. Slice thickness of 8 mm and slice interval of 8 mm were used and thin-section scan and enhancement study were performed in some cases. The main signs in degassing and differential diagnosis between pancreatic carcinoma and chronic pancreatitis included: (1) focal or diffuse enlargement and density abnormality of pancreas; (2) dilated common bile duct was suddenly obstructed, peripancreatic blood vessels were invaded and cancerous thrombus was revealed, enlargement of abdominal lymph nodes and metastasis in the liver were discovered; (3) calcium deposit in the pancreatic duct area and dilated pancreatic duct which passed through the lesion or not; (4) presence and location of pancreatic cyst and its relationship to pancreatic contour. CT is the imaging modality of choice in the diagnosis of pancreatic carcinoma and chronic pancreatitis at present. The diagnostic accuracy of CT was over 90% in this series

  8. Individual patient data meta-analysis of organ failure in acute pancreatitis: protocol of the PANCREA II study.

    Science.gov (United States)

    Das, Stephanie L M; Papachristou, George I; De Campos, Tercio; Panek, Jozefa; Poves Prim, Ignasi; Serrablo, Alejandro; Parks, Rowan W; Uomo, Generoso; Windsor, John A; Petrov, Maxim S

    2013-09-10

    Organ failure is a major determinant of mortality in patients with acute pancreatitis. These patients usually require admission to high dependency or intensive care units and consume considerable health care resources. Given a low incidence rate of organ failure and a lack of large non-interventional studies in the field of acute pancreatitis, the characteristics of organ failure that influence outcomes of patients with acute pancreatitis remain largely unknown. Therefore, the Pancreatitis Across Nations Clinical Research and Education Alliance (PANCREA) aims to conduct a meta-analysis of individual patient data from prospective non-interventional studies to determine the influence of timing, duration, sequence, and combination of different organ failures on mortality in patients with acute pancreatitis. Pancreatologists currently active with acute pancreatitis clinical research will be invited to contribute. To be eligible for inclusion patients will have to meet the criteria of acute pancreatitis, develop at least one organ failure during the first week of hospitalization, and not be enrolled into an intervention study. Raw data will then be collated and checked. Individual patient data analysis based on a logistic regression model with adjustment for confounding variables will be done. For all analyses, corresponding 95% confidence intervals and P values will be reported. This collaborative individual patient data meta-analysis will answer important clinical questions regarding patients with acute pancreatitis that develop organ failure. Information derived from this study will be used to optimize routine clinical management and improve care strategies. It can also help validate outcome definitions, allow comparability of results and form a more accurate basis for patient allocation in further clinical studies.

  9. Standardized terminology for clinical trial protocols based on top-level ontological categories.

    Science.gov (United States)

    Heller, B; Herre, H; Lippoldt, K; Loeffler, M

    2004-01-01

    This paper describes a new method for the ontologically based standardization of concepts with regard to the quality assurance of clinical trial protocols. We developed a data dictionary for medical and trial-specific terms in which concepts and relations are defined context-dependently. The data dictionary is provided to different medical research networks by means of the software tool Onto-Builder via the internet. The data dictionary is based on domain-specific ontologies and the top-level ontology of GOL. The concepts and relations described in the data dictionary are represented in natural language, semi-formally or formally according to their use.

  10. Chronic pancreatitis

    Science.gov (United States)

    Chronic pancreatitis - chronic; Pancreatitis - chronic - discharge; Pancreatic insufficiency - chronic; Acute pancreatitis - chronic ... abuse over many years. Repeated episodes of acute pancreatitis can lead to chronic pancreatitis. Genetics may be ...

  11. Use of probiotics in the treatment of severe acute pancreatitis: a systematic review and meta-analysis of randomized controlled trials

    Science.gov (United States)

    2014-01-01

    Introduction Necrotic tissue infection can worsen the prognosis of severe acute pancreatitis (SAP), and probiotics have been shown to be beneficial in reducing the infection rate in animal experiments and primary clinical trials. However, the results of multicenter randomized clinical trials have been contradictory. Our aim in this study was to systematically review and quantitatively analyze all randomized controlled trials with regard to important outcomes in patients with predicted SAP who received probiotics. Methods A systematic literature search of the PubMed, Embase and Cochrane Library databases was conducted using specific search terms. Eligible studies were randomized controlled trials that compared the effects of probiotic with placebo treatment in patients with predicted SAP. Mean difference (MD), risk ratio (RR) and 95% confidence interval (95% CI) were calculated using the Mantel-Haenszel fixed- and random-effects models. A meta-analysis on the use of probiotics in the treatment of critically ill patients was also performed to serve as a reference. Results In this study, 6 trials comprising an aggregate total of 536 patients were analyzed. Significant heterogeneities were observed in the type, dose, treatment duration and clinical effects of probiotics in these trials. Systematic analysis showed that probiotics did not significantly affect the pancreatic infection rate (RR = 1.19, 95% CI = 0.74 to 1.93; P = 0.47), total infections (RR = 1.09, 95% CI = 0.80 to 1.48; P = 0.57), operation rate (RR = 1.42, 95% CI = 0.43 to 3.47; P = 0.71), length of hospital stay (MD = 2.45, 95% CI = −2.71 to 7.60; P = 0.35) or mortality (RR = 0.72, 95% CI = 0.42 to 1.45; P = 0.25). Conclusions Probiotics showed neither beneficial nor adverse effects on the clinical outcomes of patients with predicted SAP. However, significant heterogeneity was noted between the trials reviewed with regard to the type, dose and

  12. FGF7 and cell density are required for final differentiation of pancreatic amylase-positive cells from human ES cells.

    Science.gov (United States)

    Takizawa-Shirasawa, Sakiko; Yoshie, Susumu; Yue, Fengming; Mogi, Akimi; Yokoyama, Tadayuki; Tomotsune, Daihachiro; Sasaki, Katsunori

    2013-12-01

    The major molecular signals of pancreatic exocrine development are largely unknown. We examine the role of fibroblast growth factor 7 (FGF7) in the final induction of pancreatic amylase-containing exocrine cells from induced-pancreatic progenitor cells derived from human embryonic stem (hES) cells. Our protocol consisted in three steps: Step I, differentiation of definitive endoderm (DE) by activin A treatment of hES cell colonies; Step II, differentiation of pancreatic progenitor cells by re-plating of the cells of Step I onto 24-well plates at high density and stimulation with all-trans retinoic acid; Step III, differentiation of pancreatic exocrine cells with a combination of FGF7, glucagon-like peptide 1 and nicotinamide. The expression levels of pancreatic endodermal markers such as Foxa2, Sox17 and gut tube endoderm marker HNF1β were up-regulated in both Step I and II. Moreover, in Step III, the induced cells expressed pancreatic markers such as amylase, carboxypeptidase A and chymotrypsinogen B, which were similar to those in normal human pancreas. From day 8 in Step III, cells immunohistochemically positive for amylase and for carboxypeptidase A, a pancreatic exocrine cell product, were induced by FGF7. Pancreatic progenitor Pdx1-positive cells were localized in proximity to the amylase-positive cells. In the absence of FGF7, few amylase-positive cells were identified. Thus, our three-step culture protocol for human ES cells effectively induces the differentiation of amylase- and carboxypeptidase-A-containing pancreatic exocrine cells.

  13. Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy.

    Science.gov (United States)

    Tran, T C K; van 't Hof, G; Kazemier, G; Hop, W C; Pek, C; van Toorenenbergen, A W; van Dekken, H; van Eijck, C H J

    2008-01-01

    Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Fifty-five patients who were treated for pancreatic and periampullary carcinoma and 19 patients with chronic pancreatitis were evaluated. Exocrine pancreatic function was evaluated by fecal elastase-1 test, while endocrine pancreatic function was assessed by plasma glucose level. The extent of fibrosis, duct dilation and endocrine tissue loss was examined histopathologically. A strong correlation was found between pancreatic fibrosis and elastase-1 level less than 100 microg/g (p pancreatic insufficiency. A strong correlation was found between pancreatic fibrosis and endocrine tissue loss (p pancreatic fibrosis nor endocrine tissue loss were correlated with the development of postoperative diabetes mellitus. Duct dilation alone was neither correlated with exocrine nor with endocrine function loss. The majority of patients develop severe exocrine pancreatic insufficiency after pancreatoduodenectomy. The extent of exocrine pancreatic insufficiency is strongly correlated with preoperative fibrosis. The loss of endocrine tissue does not correlate with postoperative diabetes mellitus. Preoperative dilation of the pancreatic duct per se does not predict exocrine or endocrine pancreatic insufficiency postoperatively. Copyright 2008 S. Karger AG, Basel.

  14. Chronic Pancreatitis.

    Science.gov (United States)

    Stram, Michelle; Liu, Shu; Singhi, Aatur D

    2016-12-01

    Chronic pancreatitis is a debilitating condition often associated with severe abdominal pain and exocrine and endocrine dysfunction. The underlying cause is multifactorial and involves complex interaction of environmental, genetic, and/or other risk factors. The pathology is dependent on the underlying pathogenesis of the disease. This review describes the clinical, gross, and microscopic findings of the main subtypes of chronic pancreatitis: alcoholic chronic pancreatitis, obstructive chronic pancreatitis, paraduodenal ("groove") pancreatitis, pancreatic divisum, autoimmune pancreatitis, and genetic factors associated with chronic pancreatitis. As pancreatic ductal adenocarcinoma may be confused with chronic pancreatitis, the main distinguishing features between these 2 diseases are discussed. Copyright © 2016 Elsevier Inc. All rights reserved.

  15. A quality analysis of clinical anaesthesia study protocols from the Chinese clinical trials registry according to the SPIRIT statement.

    Science.gov (United States)

    Yang, Lei; Chen, Shouming; Yang, Di; Li, Jiajin; Wu, Taixiang; Zuo, Yunxia

    2018-05-15

    To learn about the overall quality of clinical anaesthesia study protocols from the Chinese Clinical Trials Registry and to discuss the way to improve study protocol quality. We defined completeness of each sub-item in SPIRIT as N/A (not applicable) or with a score of 0, 1, or 2. For each protocol, we calculated the proportion of adequately reported items (score = 2 and N/A) and unreported items (score = 0). Protocol quality was determined according to the proportion of reported items, with values >50% indicating high quality. Protocol quality was determined according to the proportion of reported items. For each sub-item in SPIRIT, we calculated the adequately reported rate (percentage of all protocols with score 2 and NA on one sub-item) as well as the unreported rate (percentage of all protocols with score 0 on one sub-item). Total 126 study protocols were available for assessment. Among these, 88.1% were assessed as being of low quality. By comparison, the percentage of low-quality protocols was 88.9% after the publication of the SPIRIT statement. Among the 51 SPIRIT sub-items, 18 sub-items had an unreported rate above 90% while 16 had a higher adequately reported rate than an unreported rate. The overall quality of clinical anaesthesia study protocols registered in the ChiCTR was poor. A mandatory protocol upload and self-check based on the SPIRIT statement during the trial registration process may improve protocol quality in the future.

  16. Initiating change locally in bullying and aggression through the school environment (INCLUSIVE) trial: update to cluster randomised controlled trial protocol.

    Science.gov (United States)

    Bonell, Chris; Mathiot, Anne; Allen, Elizabeth; Bevilacqua, Leonardo; Christie, Deborah; Elbourne, Diana; Fletcher, Adam; Grieve, Richard; Legood, Rosa; Scott, Stephen; Warren, Emily; Wiggins, Meg; Viner, Russell M

    2017-05-25

    Systematic reviews suggest that multi-component interventions are effective in reducing bullying victimisation and perpetration. We are undertaking a phase III randomised trial of the INCLUSIVE multi-component intervention. This trial aims to assess the effectiveness and cost-effectiveness of the INCLUSIVE intervention in reducing aggression and bullying victimisation in English secondary schools. This paper updates the original trial protocol published in 2014 (Trials 15:381, 2014) and presents the changes in the process evaluation protocol and the secondary outcome data collection. The methods are summarised as follows. cluster randomised trial. 40 state secondary schools. Outcomes assessed among the cohort of students at the end of year 7 (n = 6667) at baseline. INCLUSIVE is a multi-component school intervention including a social and emotional learning curriculum, changes to school environment (an action group comprising staff and students reviews local data on needs to review rules and policies and determine other local actions) and staff training in restorative practice. The intervention will be delivered by schools supported in the first two years by educational facilitators independent of the research team, with a third intervention year involving no external facilitation but all other elements. Comparator: normal practice. Primary: Two primary outcomes at student level assessed at baseline and at 36 months: 1. Aggressive behaviours in school: Edinburgh Study of Youth Transitions and Crime school misbehaviour subscale (ESYTC) 2. Bullying and victimisation: Gatehouse Bullying Scale (GBS) Secondary outcomes assessed at baseline, 24 and 36 months will include measures relating to the economic evaluation, psychosocial outcomes in students and staff and school-level truancy and exclusion rates. 20 schools per arm will provide 90% power to identify an effect size of 0.25 SD with a 5% significance level. Randomisation: eligible consenting schools were

  17. Pancreatic cancer risk in hereditary pancreatitis

    Directory of Open Access Journals (Sweden)

    Frank Ulrich Weiss

    2014-02-01

    Full Text Available Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1 gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic pancreatic inflammation with an early onset, mostly during childhood. Hereditary pancreatitis often starts with recurrent episodes of acute pancreatitis and the clinical phenotype is not very much different from other etiologies of the disease. The long-lasting inflammation however generates a tumor promoting environment and represents a major risk factor for tumor development This review will reflect our knowledge concerning the specific risk of hereditary pancreatitis patients to develop pancreatic cancer.

  18. [Development of clinical trial education program for pharmaceutical science students through small group discussion and role-playing using protocol].

    Science.gov (United States)

    Imakyure, Osamu; Shuto, Hideki; Nishikawa, Fumi; Hagiwara, Yoshifuka; Inoue, Sachiko; Koyanagi, Taeko; Hirakawa, Masaaki; Kataoka, Yasufumi

    2010-08-01

    The acquirement of basic knowledge of clinical trials and professional attitude in their practices is a general instructional objective in the Model Core Curriculum for Pharmaceutical Education. Unfortunately, the previous program of clinical trial education was not effective in the acquirement of a professional attitude in their practices. Then, we developed the new clinical trial education program using protocol through small group discussion (SGD) and roll-playing. Our program consists of 7 steps of practical training. In step 1, the students find some problems after presentation of the protocol including case and prescription. In step 2, they analyse the extracted problems and share the information obtained in SGD. In steps 3 and 5, five clinical case scenarios are presented to the students and they discuss which case is suitable for entry to the clinical trial or which case corresponds to the discontinuance criteria in the present designed protocol. In steps 4 and 6, the roll-playing is performed by teachers and students as doctors and clinical research coordinators (CRC) respectively. Further, we conducted a trial practice based on this program for the students. In the student's self-evaluation into five grades, the average score of the skill acquisition level in each step was 3.8-4.7 grade. Our clinical trial education program could be effective in educating the candidates for CRC or clinical pharmacists.

  19. Role of the immune system in pancreatic cancer progression and immune modulating treatment strategies.

    Science.gov (United States)

    Sideras, K; Braat, H; Kwekkeboom, J; van Eijck, C H; Peppelenbosch, M P; Sleijfer, S; Bruno, M

    2014-05-01

    Traditional chemotherapeutics have largely failed to date to produce significant improvements in pancreatic cancer survival. One of the reasons for the resilience of pancreatic cancer towards intensive treatment is that the cancer is capable of high jacking the immune system: during disease progression the immune system is converted from a system that attacks tumor cells into a support structure for the cancer, exerting trophic actions on the cancer cells. This turn-around of immune system action is achieved through mobilization and activation of regulatory T cells, myeloid derived suppressor cells, tumor-associated macrophages and fibroblasts, all of which suppress CD8 T cells and NK cells. This immune suppression occurs both through the expression of tolerance-inducing cell surface molecules, such as PD-L1, as well as through the production of "tolerogenic" cytokines, such as IL-10 and TGF-β. Based on the accumulating insight into the importance of the immune system for the outcome of pancreatic cancer patients multiple new immunotherapeutic approaches against pancreatic cancer are being currently tested in clinical trials. In this review we give an overview of both the immune escaping mechanisms of pancreatic cancer as well as the new immune related therapeutic strategies currently being tested in pancreatic cancer clinical trials. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer

    International Nuclear Information System (INIS)

    Hurt, Christopher N.; Mukherjee, Somnath; Bridgewater, John; Falk, Stephen; Crosby, Tom; McDonald, Alec; Joseph, George; Staffurth, John; Abrams, Ross A.; Blazeby, Jane M.; Bridges, Sarah; Dutton, Peter; Griffiths, Gareth; Maughan, Tim; Johnson, Colin

    2015-01-01

    Purpose: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. Methods and Materials: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). Results: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. Conclusions: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.

  1. Health-Related Quality of Life in SCALOP, a Randomized Phase 2 Trial Comparing Chemoradiation Therapy Regimens in Locally Advanced Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hurt, Christopher N., E-mail: hurtcn@cardiff.ac.uk [Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales (United Kingdom); Mukherjee, Somnath [Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Oxford University, NIHR Biomedical Research, Oxford (United Kingdom); Bridgewater, John [UCL Cancer Institute, London (United Kingdom); Falk, Stephen [Bristol Haematology and Oncology Centre, Bristol (United Kingdom); Crosby, Tom [Velindre Cancer Centre, Velindre Hospital, Cardiff, Wales (United Kingdom); McDonald, Alec [Beatson West of Scotland Cancer Centre, Glasgow, Scotland (United Kingdom); Joseph, George [Velindre Cancer Centre, Velindre Hospital, Cardiff, Wales (United Kingdom); Staffurth, John [Institute of Cancer and Genetics, Cardiff University, Cardiff, Wales (United Kingdom); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois (United States); Blazeby, Jane M. [Division of Surgery, Head and Neck, University Hospitals Bristol National Health Service Foundation Trust, Bristol and School of Social and Community Medicine, University of Bristol, Bristol (United Kingdom); Bridges, Sarah [Wales Cancer Trials Unit, College of Biomedical and Life Sciences, Cardiff University, Cardiff, Wales (United Kingdom); Dutton, Peter [Centre for Statistics in Medicine, University of Oxford, Oxford (United Kingdom); Griffiths, Gareth [Southampton Clinical Trials Unit, Faculty of Medicine, Southampton University, Southampton General Hospital, Southampton (United Kingdom); Maughan, Tim [Cancer Research UK/MRC Oxford Institute for Radiation Oncology, Oxford University, NIHR Biomedical Research, Oxford (United Kingdom); Johnson, Colin [University Surgical Unit, Faculty of Medicine, University Hospital Southampton, Southampton (United Kingdom)

    2015-11-15

    Purpose: Chemoradiation therapy (CRT) for patients with locally advanced pancreatic cancer (LAPC) provides survival benefits but may result in considerable toxicity. Health-related quality of life (HRQL) measurements during CRT have not been widely reported. This paper reports HRQL data from the Selective Chemoradiation in Advanced Localised Pancreatic Cancer (SCALOP) trial, including validation of the QLQ-PAN26 tool in CRT. Methods and Materials: Patients with locally advanced, inoperable, nonmetastatic carcinoma of the pancreas were eligible. Following 12 weeks of induction gemcitabine plus capecitabine (GEMCAP) chemotherapy, patients with stable and responding disease were randomized to a further cycle of GEMCAP followed by capecitabine- or gemcitabine-based CRT. HRQL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and the EORTC Pancreatic Cancer module (PAN26). Results: A total of 114 patients from 28 UK centers were registered and 74 patients randomized. There was improvement in the majority of HRQL scales during induction chemotherapy. Patients with significant deterioration in fatigue, appetite loss, and gastrointestinal symptoms during CRT recovered within 3 weeks following CRT. Differences in changes in HRQL scores between trial arms rarely reached statistical significance; however, where they did, they favored capecitabine therapy. PAN26 scales had good internal consistency and were able to distinguish between subgroups of patients experiencing toxicity. Conclusions: Although there is deterioration in HRQL following CRT, this resolves within 3 weeks. HRQL data support the use of capecitabine- over gemcitabine-based chemoradiation. The QLQ-PAN26 is a reliable and valid tool for use in patients receiving CRT.

  2. Surgical management of acute necrotizing pancreatitis: a 13-year experience and a systematic review

    NARCIS (Netherlands)

    Nieuwenhuijs, V. B.; Besselink, M. G. H.; van Minnen, L. P.; Gooszen, H. G.

    2003-01-01

    BACKGROUND: The course of acute pancreatitis (AP) is unpredictable and can vary from mild to lethal. Mortality varies from low ( <2%) in mild cases to high (20%-70%) in the case of infected pancreatic necrosis. Surgical management has not been investigated in well-designed trials. Based on

  3. Assessment of Adverse Events in Protocols, Clinical Study Reports, and Published Papers of Trials of Orlistat: A Document Analysis.

    Directory of Open Access Journals (Sweden)

    Jeppe Bennekou Schroll

    2016-08-01

    Full Text Available Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs from the European Medicines Agency through the Freedom of Information Act. The CSRs describe the results of studies conducted as part of the application for marketing authorisation for the slimming pill orlistat. The purpose of this study was to study how adverse events were summarised and reported in study protocols, CSRs, and published papers of orlistat trials.We received the CSRs from seven randomised placebo controlled orlistat trials (4,225 participants submitted by Roche. The CSRs consisted of 8,716 pages and included protocols. Two researchers independently extracted data on adverse events from protocols and CSRs. Corresponding published papers were identified on PubMed and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about adverse events. In CSRs, gastrointestinal adverse events were only coded if the participant reported that they were "bothersome," a condition that was not specified in the protocol for two of the trials. Serious adverse events were assessed for relationship to the drug by the sponsor, and all adverse events were coded by the sponsor using a glossary that could be updated by the sponsor. The criteria for withdrawal due to adverse events were in one case related to efficacy (high fasting glucose led to withdrawal, which meant that one trial had more withdrawals due to adverse events in the placebo group. Finally, only between 3% and 33% of the total number of investigator-reported adverse events from the trials were reported in the publications because of post hoc filters, though six of

  4. Long-Term Culture of Self-renewing Pancreatic Progenitors Derived from Human Pluripotent Stem Cells

    Directory of Open Access Journals (Sweden)

    Jamie Trott

    2017-06-01

    Full Text Available Pluripotent stem cells have been proposed as an unlimited source of pancreatic β cells for studying and treating diabetes. However, the long, multi-step differentiation protocols used to generate functional β cells inevitably exhibit considerable variability, particularly when applied to pluripotent cells from diverse genetic backgrounds. We have developed culture conditions that support long-term self-renewal of human multipotent pancreatic progenitors, which are developmentally more proximal to the specialized cells of the adult pancreas. These cultured pancreatic progenitor (cPP cells express key pancreatic transcription factors, including PDX1 and SOX9, and exhibit transcriptomes closely related to their in vivo counterparts. Upon exposure to differentiation cues, cPP cells give rise to pancreatic endocrine, acinar, and ductal lineages, indicating multilineage potency. Furthermore, cPP cells generate insulin+ β-like cells in vitro and in vivo, suggesting that they offer a convenient alternative to pluripotent cells as a source of adult cell types for modeling pancreatic development and diabetes.

  5. Combination therapy versus gemcitabine monotherapy in the treatment of elderly pancreatic cancer: a meta-analysis of randomized controlled trials

    Directory of Open Access Journals (Sweden)

    Jin JM

    2018-03-01

    Full Text Available Jiamin Jin, Chunbo Teng, Tao Li College of Life Science, Northeast Forestry University, Harbin, China Purpose: We aimed to compare the efficacy of combination therapy versus gemcitabine monotherapy in the treatment of elderly pancreatic cancer (PC by using a meta-analysis.Materials and methods: Databases were searched to identify relevant clinical trials. Hazard ratios (HRs were used to estimate overall survival (OS and progression-free survival (PFS. Statistical analyses were conducted by using Comprehensive Meta Analysis software (version 2.0.Results: A total of 3,401 elderly PC patients from six randomized controlled trials were included for analysis. In comparison with gemcitabine alone, combination therapy in elderly PC patients did not significantly improve OS (HR 0.93, 95% CI: 0.82–1.06, p=0.29. Sub-group analysis according to treatment regimens showed that combined chemotherapy significantly improved OS in comparison with gemcitabine alone (HR 0.73, 95% CI: 0.56–0.94, p=0.016, while gemcitabine plus targeted agents did not improve OS (HR 1.02, 95% CI: 0.87–1.19, p=0.83. Additionally, gemcitabine plus nab-paclitaxel significantly improved PFS in elderly PC patients (HR 0.69, 95% CI: 0.52–0.91, p=0.009 in comparison with gemcitabine alone. No publication bias was detected by Begg’s and Egger’s tests for OS.Conclusion: The findings of this study suggest that combined chemotherapy, but not for gemcitabine plus targeted agents, could be recommended for elderly PC patients due to its survival benefits. Further studies are still needed to assess the treatment tolerance of combination chemotherapy in these patient populations. Keywords: pancreatic cancer, elderly, randomized controlled trials, meta-analysis, targeted agents

  6. Effectiveness of a healthy lifestyle intervention for low back pain and osteoarthritis of the knee: protocol and statistical analysis plan for two randomised controlled trials

    Directory of Open Access Journals (Sweden)

    Kate M. O’Brien

    Full Text Available ABSTRACT Background These trials are the first randomised controlled trials of telephone-based weight management and healthy lifestyle interventions for low back pain and knee osteoarthritis. This article describes the protocol and statistical analysis plan. Method These trials are parallel randomised controlled trials that investigate and compare the effect of a telephone-based weight management and healthy lifestyle intervention for improving pain intensity in overweight or obese patients with low back pain or knee osteoarthritis. The analysis plan was finalised prior to initiation of analyses. All data collected as part of the trial were reviewed, without stratification by group, and classified by baseline characteristics, process of care and trial outcomes. Trial outcomes were classified as primary and secondary outcomes. Appropriate descriptive statistics and statistical testing of between-group differences, where relevant, have been planned and described. Conclusions A protocol for standard analyses was developed for the results of two randomised controlled trials. This protocol describes the data, and the pre-determined statistical tests of relevant outcome measures. The plan demonstrates transparent and verifiable use of the data collected. This a priori protocol will be followed to ensure rigorous standards of data analysis are strictly adhered to.

  7. Effectiveness of a healthy lifestyle intervention for low back pain and osteoarthritis of the knee: protocol and statistical analysis plan for two randomised controlled trials

    Science.gov (United States)

    O’Brien, Kate M.; Williams, Amanda; Wiggers, John; Wolfenden, Luke; Yoong, Serene; Campbell, Elizabeth; Kamper, Steven J.; McAuley, James; Attia, John; Oldmeadow, Chris; Williams, Christopher M.

    2016-01-01

    ABSTRACT Background These trials are the first randomised controlled trials of telephone-based weight management and healthy lifestyle interventions for low back pain and knee osteoarthritis. This article describes the protocol and statistical analysis plan. Method These trials are parallel randomised controlled trials that investigate and compare the effect of a telephone-based weight management and healthy lifestyle intervention for improving pain intensity in overweight or obese patients with low back pain or knee osteoarthritis. The analysis plan was finalised prior to initiation of analyses. All data collected as part of the trial were reviewed, without stratification by group, and classified by baseline characteristics, process of care and trial outcomes. Trial outcomes were classified as primary and secondary outcomes. Appropriate descriptive statistics and statistical testing of between-group differences, where relevant, have been planned and described. Conclusions A protocol for standard analyses was developed for the results of two randomised controlled trials. This protocol describes the data, and the pre-determined statistical tests of relevant outcome measures. The plan demonstrates transparent and verifiable use of the data collected. This a priori protocol will be followed to ensure rigorous standards of data analysis are strictly adhered to. PMID:27683839

  8. Expression of the DNA repair gene MLH1 correlates with survival in patients who have resected pancreatic cancer and have received adjuvant chemoradiation: NRG Oncology RTOG Study 9704.

    Science.gov (United States)

    Lawrence, Yaacov R; Moughan, Jennifer; Magliocco, Anthony M; Klimowicz, Alexander C; Regine, William F; Mowat, Rex B; DiPetrillo, Thomas A; Small, William; Simko, Jeffry P; Golan, Talia; Winter, Kathryn A; Guha, Chandan; Crane, Christopher H; Dicker, Adam P

    2018-02-01

    The majority of patients with pancreatic cancer who undergo curative resection experience rapid disease recurrence. In previous small studies, high expression of the mismatch-repair protein mutL protein homolog 1 (MLH1) in pancreatic cancers was associated with better outcomes. The objective of this study was to validate the association between MLH1 expression and survival in patients who underwent resection of pancreatic cancer and received adjuvant chemoradiation. Samples were obtained from the NRG Oncology Radiation Therapy Oncology Group 9704 prospective, randomized trial (clinicaltrials.gov identifier NCT00003216), which compared 2 adjuvant protocols in patients with pancreatic cancer who underwent resection. Tissue microarrays were prepared from formalin-fixed, paraffin-embedded, resected tumor tissues. MLH1 expression was quantified using fluorescence immunohistochemistry and automated quantitative analysis, and expression was dichotomized above and below the median value. Immunohistochemical staining was successfully performed on 117 patients for MLH1 (60 and 57 patients from the 2 arms). The characteristics of the participants who had tissue samples available were similar to those of the trial population as a whole. At the time of analysis, 84% of participants had died, with a median survival of 17 months. Elevated MLH1 expression levels in tumor nuclei were significantly correlated with longer disease-free and overall survival in each arm individually and in both arms combined. Two-year overall survival was 16% in patients who had low MLH1 expression levels and 53% in those who had high MLH1 expression levels (P MLH1 expression was correlated with long-term survival. Further studies should assess whether MLH1 expression predicts which patients with localized pancreatic cancer may benefit most from aggressive, multimodality treatment. Cancer 2018;124:491-8. © 2017 American Cancer Society. © 2017 American Cancer Society.

  9. Generation of Insulin-Producing Cells from Human Bone Marrow-Derived Mesenchymal Stem Cells: Comparison of Three Differentiation Protocols

    Directory of Open Access Journals (Sweden)

    Mahmoud M. Gabr

    2014-01-01

    Full Text Available Introduction. Many protocols were utilized for directed differentiation of mesenchymal stem cells (MSCs to form insulin-producing cells (IPCs. We compared the relative efficiency of three differentiation protocols. Methods. Human bone marrow-derived MSCs (HBM-MSCs were obtained from three insulin-dependent type 2 diabetic patients. Differentiation into IPCs was carried out by three protocols: conophylline-based (one-step protocol, trichostatin-A-based (two-step protocol, and β-mercaptoethanol-based (three-step protocol. At the end of differentiation, cells were evaluated by immunolabeling for insulin production, expression of pancreatic endocrine genes, and release of insulin and c-peptide in response to increasing glucose concentrations. Results. By immunolabeling, the proportion of generated IPCs was modest (≃3% in all the three protocols. All relevant pancreatic endocrine genes, insulin, glucagon, and somatostatin, were expressed. There was a stepwise increase in insulin and c-peptide release in response to glucose challenge, but the released amounts were low when compared with those of pancreatic islets. Conclusion. The yield of functional IPCs following directed differentiation of HBM-MSCs was modest and was comparable among the three tested protocols. Protocols for directed differentiation of MSCs need further optimization in order to be clinically meaningful. To this end, addition of an extracellular matrix and/or a suitable template should be attempted.

  10. Radiotherapy Technical Considerations in the Management of Locally Advanced Pancreatic Cancer: American-French Consensus Recommendations

    International Nuclear Information System (INIS)

    Huguet, Florence; Goodman, Karyn A.; Azria, David; Racadot, Severine; Abrams, Ross A.

    2012-01-01

    Summary: Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose

  11. Radiotherapy technical considerations in the management of locally advanced pancreatic cancer: American-French consensus recommendations.

    Science.gov (United States)

    Huguet, Florence; Goodman, Karyn A; Azria, David; Racadot, Severine; Abrams, Ross A

    2012-08-01

    Pancreatic carcinoma is a leading cause of cancer-related mortality. Approximately 30% of pancreatic cancer patients present with locally advanced, unresectable nonmetastatic disease. For these patients, two therapeutic options exist: systemic chemotherapy or chemoradiotherapy. Within this context, the optimal technique for pancreatic irradiation is not clearly defined. A search to identify relevant studies was undertaken using the Medline database. All Phase III randomized trials evaluating the modalities of radiotherapy in locally advanced pancreatic cancer were included, as were some noncontrolled Phase II and retrospective studies. An expert panel convened with members of the Radiation Therapy Oncology Group and GERCOR cooperative groups to review identified studies and prepare the guidelines. Each member of the working group independently evaluated five endpoints: total dose, target volume definition, radiotherapy planning technique, dose constraints to organs at risk, and quality assurance. Based on this analysis of the literature, we recommend either three-dimensional conformal radiation therapy or intensity-modulated radiation therapy to a total dose of 50 to 54 Gy at 1.8 to 2 Gy per fraction. We propose gross tumor volume identification to be followed by an expansion of 1.5 to 2 cm anteriorly, posteriorly, and laterally, and 2 to 3 cm craniocaudally to generate the planning target volume. The craniocaudal margins can be reduced with the use of respiratory gating. Organs at risk are liver, kidneys, spinal cord, stomach, and small bowel. Stereotactic body radiation therapy should not be used for pancreatic cancer outside of clinical trials. Radiotherapy quality assurance is mandatory in clinical trials. These consensus recommendations are proposed for use in the development of future trials testing new chemotherapy combinations with radiotherapy. Not all of these recommendations will be appropriate for trials testing radiotherapy dose or dose intensity

  12. Pancreatitis - discharge

    Science.gov (United States)

    Chronic pancreatitis - discharge; Pancreatitis - chronic - discharge; Pancreatic insufficiency - discharge; Acute pancreatitis - discharge ... You were in the hospital because you have pancreatitis. This is a swelling of the pancreas. You ...

  13. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.

    Science.gov (United States)

    Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

    2016-09-01

    Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mainly focus on rodent models because of their popularity. Autoimmune pancreatitis and genetically engineered animal models will be reviewed elsewhere. Copyright © 2016 the American Physiological Society.

  14. Chemotherapy Regimen Extends Survival in Advanced Pancreatic Cancer Patients

    Science.gov (United States)

    A four-drug chemotherapy regimen has produced the longest improvement in survival ever seen in a phase III clinical trial of patients with metastatic pancreatic cancer, one of the deadliest types of cancer.

  15. Prevention of abdominal wound infection (PROUD trial, DRKS00000390: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Heger Ulrike

    2011-11-01

    Full Text Available Abstract Background Wound infection affects a considerable portion of patients after abdominal operations, increasing health care costs and postoperative morbidity and affecting quality of life. Antibacterial coating has been suggested as an effective measure to decrease postoperative wound infections after laparotomies. The INLINE metaanalysis has recently shown the superiority of a slowly absorbable continuous suture for abdominal closure; with PDS plus® such a suture has now been made available with triclosan antibacterial coating. Methods/Design The PROUD trial is designed as a randomised, controlled, observer, surgeon and patient blinded multicenter superiority trial with two parallel groups and a primary endpoint of wound infection during 30 days after surgery. The intervention group will receive triclosan coated polydioxanone sutures, whereas the control group will receive the standard polydioxanone sutures; abdominal closure will otherwise be standardized in both groups. Statistical analysis is based on intention-to-treat population via binary logistic regression analysis, the total sample size of n = 750 is sufficient to ensure alpha = 5% and power = 80%, an interim analysis will be carried out after data of 375 patients are available. Discussion The PROUD trial will yield robust data to determine the effectiveness of antibacterial coating in one of the standard sutures for abdominal closure and potentially lead to amendment of current guidelines. The exploration of clinically objective parameters as well as quality of life holds immediate relevance for clinical management and the pragmatic trial design ensures high external validity. Trial Registration The trial protocol has been registered with the German Clinical Trials Register (DRKS00000390.

  16. Nanomedicine developments in the treatment of metastatic pancreatic cancer: focus on nanoliposomal irinotecan

    Directory of Open Access Journals (Sweden)

    Ko AH

    2016-03-01

    Full Text Available Andrew H KoDivision of Hematology/Oncology, Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, CA, USA Abstract: Nanoliposomal irinotecan (nal-IRI was originally developed using an efficient and high-loading capacity system to encapsulate irinotecan within a liposomal carrier, producing a therapeutic agent with improved biodistribution and pharmacokinetic characteristics compared to free drug. Specifically, administration of nal-IRI results in prolonged exposure of SN-38, the active metabolite of irinotecan, within tumors, while at the same time offering the advantage of less systemic toxicity than traditional irinotecan. These favorable properties of nal-IRI, confirmed in a variety of tumor xenograft models, led to its clinical evaluation in a number of disease indications for which camptothecins have proven activity, including in colorectal, gastric, and pancreatic cancers. The culmination of these clinical trials was the NAPOLI-1 (Nanoliposomal irinotecan with fluorouracil and folinic acid in metastatic pancreatic cancer after previous gemcitabine-based therapy trial, an international Phase III study evaluating nal-IRI both alone and in combination with 5-fluorouracil and leucovorin in patients with metastatic pancreatic adenocarcinoma following progression on gemcitabine-based chemotherapy. Positive results from NAPOLI-1 led to approval of nal-IRI (with 5-fluorouracil/leucovorin in October 2015 by the US Food and Drug Administration specifically for the treatment of metastatic pancreatic cancer in the second-line setting and beyond, a clinical context in which there had previously been no accepted standard of care. As such, nal-IRI represents an important landmark in cancer drug development, and potentially ushers in a new era where a greater number of patients with advanced pancreatic cancer can be sequenced through multiple lines of therapy translating into meaningful improvements in

  17. Pancreatic Enzymes

    Science.gov (United States)

    ... Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Pancreatic enzymes Home Facing Pancreatic Cancer Living with Pancreatic Cancer ... and see a registered dietitian. What are pancreatic enzymes? Pancreatic enzymes help break down fats, proteins and ...

  18. Imaging of the pancreas. Acute and chronic pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Balthazar, Emil J.; Megibow, Alec J. [NYU-Langone Medical Center, New York, NY (United States). Dept. of Radiology; Pozzi Mucelli, Roberto (eds.) [Policlinico ' ' GB Rossi' ' Verona Univ. (Italy). Dept. of Radiology

    2009-07-01

    With the aid of numerous high-quality illustrations, this volume explains the strengths and limitations of the different techniques employed in the imaging of pancreatitis. Ultrasound, computed tomography, magnetic resonance imaging and interventional imaging are each considered separately in the settings of acute and chronic pancreatitis. A further section is devoted to imaging of the complications of these conditions. Throughout, care has been taken to ensure that the reader will achieve a sound understanding of how the imaging findings derive from the pathophysiology of the disease processes. The significance of the imaging findings for clinical and therapeutic decision making is clearly explained, and protocols are provided that will assist in obtaining the best possible images. (orig.)

  19. Imaging of the pancreas. Acute and chronic pancreatitis

    International Nuclear Information System (INIS)

    Balthazar, Emil J.; Megibow, Alec J.; Pozzi Mucelli, Roberto

    2009-01-01

    With the aid of numerous high-quality illustrations, this volume explains the strengths and limitations of the different techniques employed in the imaging of pancreatitis. Ultrasound, computed tomography, magnetic resonance imaging and interventional imaging are each considered separately in the settings of acute and chronic pancreatitis. A further section is devoted to imaging of the complications of these conditions. Throughout, care has been taken to ensure that the reader will achieve a sound understanding of how the imaging findings derive from the pathophysiology of the disease processes. The significance of the imaging findings for clinical and therapeutic decision making is clearly explained, and protocols are provided that will assist in obtaining the best possible images. (orig.)

  20. Pancreatic injuries after blunt abdominal trauma: an analysis of 110 ...

    African Journals Online (AJOL)

    Background and objective. Injuries to the pancreas are uncommon, but may result in considerable morbidity and mortality. This study evaluated the management of blunt pancreatic injuries using a previously defined protocol to determine which factors predicted morbidity and mortality. Methods. The study design was a ...

  1. Pancreatic tumors in children and young adults with tuberous sclerosis complex

    International Nuclear Information System (INIS)

    Koc, Gonca; Sugimoto, Sam; Kammen, Bamidele F.; Karakas, S.P.; Kuperman, Rachel

    2017-01-01

    Pancreatic neuroendocrine tumors are not included in the diagnostic criteria for tuberous sclerosis complex, although an association has been described. To investigate the association of pancreatic neuroendocrine tumor in children and young adults with tuberous sclerosis complex and define MRI characteristics of the tumor. We retrospectively evaluated the abdominal MRI scans of 55 children and young adults with tuberous sclerosis complex for the presence of a pancreatic mass. The scans were performed over a period of 7 years to monitor renal pathology. We obtained each patient's clinical history and treatment protocol from the hospital's electronic medical records. A solid pancreatic mass was identified in 5/55 (9%, 95% confidence interval [CI] 3-20%) patients (4 male) with a mean age of 12.6 years. Four of the lesions were located in the pancreatic tail and one in the pancreatic body. All of the lesions were solid, ovoid and well demarcated, with a mean diameter of 3.1 cm. The masses uniformly demonstrated T1 and T2 prolongation, but their diffusion behavior and post-contrast enhancement varied. The two surgically resected lesions were synaptophysin (+) non-functional pancreatic neuroendocrine tumors on pathology. Two of the patients who did not have surgery were treated with everolimus; one of the lesions has shown interval decrease in size and the other has remained stable. Pancreatic tumor is relatively common in children and young adults with tuberous sclerosis complex. (orig.)

  2. Pancreatic tumors in children and young adults with tuberous sclerosis complex

    Energy Technology Data Exchange (ETDEWEB)

    Koc, Gonca [Erciyes University, School of Medicine, Department of Pediatric Radiology, Melikgazi, Kayseri (Turkey); Sugimoto, Sam; Kammen, Bamidele F.; Karakas, S.P. [UCSF Benioff Children' s Hospital, Department of Diagnostic Imaging, Oakland, CA (United States); Kuperman, Rachel [UCSF Benioff Children' s Hospital, Department of Pediatric Neurology, Oakland, CA (United States)

    2017-01-15

    Pancreatic neuroendocrine tumors are not included in the diagnostic criteria for tuberous sclerosis complex, although an association has been described. To investigate the association of pancreatic neuroendocrine tumor in children and young adults with tuberous sclerosis complex and define MRI characteristics of the tumor. We retrospectively evaluated the abdominal MRI scans of 55 children and young adults with tuberous sclerosis complex for the presence of a pancreatic mass. The scans were performed over a period of 7 years to monitor renal pathology. We obtained each patient's clinical history and treatment protocol from the hospital's electronic medical records. A solid pancreatic mass was identified in 5/55 (9%, 95% confidence interval [CI] 3-20%) patients (4 male) with a mean age of 12.6 years. Four of the lesions were located in the pancreatic tail and one in the pancreatic body. All of the lesions were solid, ovoid and well demarcated, with a mean diameter of 3.1 cm. The masses uniformly demonstrated T1 and T2 prolongation, but their diffusion behavior and post-contrast enhancement varied. The two surgically resected lesions were synaptophysin (+) non-functional pancreatic neuroendocrine tumors on pathology. Two of the patients who did not have surgery were treated with everolimus; one of the lesions has shown interval decrease in size and the other has remained stable. Pancreatic tumor is relatively common in children and young adults with tuberous sclerosis complex. (orig.)

  3. Stereotactic body radiotherapy for renal cell cancer and pancreatic cancer. Literature review and practice recommendations of the DEGRO Working Group on Stereotactic Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Panje, Cedric; Andratschke, Nikolaus; Guckenberger, Matthias [Zurich University Hospital, Department of Radiation Oncology, Zurich (Switzerland); Brunner, Thomas B. [Freiburg University Hospital, Department of Radiation Oncology, Freiburg (Germany); Niyazi, Maximilian [University of Munich, Department of Radiation Oncology, Munich (Germany)

    2016-12-15

    This report of the Working Group on Stereotactic Radiotherapy of the German Society of Radiation Oncology (DEGRO) aims to provide a literature review and practice recommendations for stereotactic body radiotherapy (SBRT) of primary renal cell cancer and primary pancreatic cancer. A literature search on SBRT for both renal cancer and pancreatic cancer was performed with focus on prospective trials and technical aspects for clinical implementation. Data on renal and pancreatic SBRT are limited, but show promising rates of local control for both treatment sites. For pancreatic cancer, fractionated SBRT should be preferred to single-dose treatment to reduce the risk of gastrointestinal toxicity. Motion-compensation strategies and image guidance are paramount for safe SBRT delivery in both tumor entities. SBRT for renal cancer and pancreatic cancer have been successfully evaluated in phase I and phase II trials. Pancreatic SBRT should be practiced carefully and only within prospective protocols due to the risk of severe gastrointestinal toxicity. SBRT for primary renal cell cancer appears a viable option for medically inoperable patients but future research needs to better define patient selection criteria and the detailed practice of SBRT. (orig.) [German] Die Arbeitsgruppe ''Stereotaktische Radiotherapie'' der Deutschen Gesellschaft fuer Radioonkologie (DEGRO) legt eine Zusammenfassung der aktuellen Literatur und daraus resultierende Empfehlungen zur Durchfuehrung der stereotaktischen Strahlentherapie (SBRT) beim Nierenzellkarzinom und beim Pankreaskarzinom vor. Es erfolgte eine Literaturrecherche zur Evidenz der SBRT beim Nierenzell- und Pankreaskarzinom, wobei der Schwerpunkt auf prospektive Studien und technische Aspekte fuer die klinische Umsetzung gelegt wurde. Fuer die SBRT beim Pankreaskarzinom und Nierenzellkarzinom sind bisher nur wenige Studien veroeffentlicht worden, die jedoch konsistent eine hohe Rate an lokaler Tumorkontrolle

  4. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis

    OpenAIRE

    Zhan, Xianbao; Wang, Fan; Bi, Yan; Ji, Baoan

    2016-01-01

    Animal models of pancreatitis are useful for elucidating the pathogenesis of pancreatitis and developing and testing novel interventions. In this review, we aim to summarize the most commonly used animal models, overview their pathophysiology, and discuss their strengths and limitations. We will also briefly describe common animal study procedures and refer readers to more detailed protocols in the literature. Although animal models include pigs, dogs, opossums, and other animals, we will mai...

  5. Evidence-Based Surgical Treatments for Chronic Pancreatitis.

    Science.gov (United States)

    Kleeff, Jörg; Stöß, Christian; Mayerle, Julia; Stecher, Lynne; Maak, Matthias; Simon, Peter; Nitsche, Ulrich; Friess, Helmut

    2016-07-25

    If conservative treatment of chronic pancreatitis is unsuccessful, surgery is an option. The choice of the most suitable surgical method can be difficult, as the indications, advantages, and disadvantages of the available methods have not yet been fully documented with scientific evidence. In April 2015, we carried out a temporally unlimited systematic search for publications on surgery for chronic pancreatitis. The target parameters were morbidity, mortality, pain, endocrine and exocrine insuffi - ciency, weight gain, quality of life, length of hospital stay, and duration of urgery. Differences between surgical methods were studied with network meta-analysis, and duodenum-preserving operations were compared with partial duodenopancreatectomy with standard meta-analysis. Among the 326 articles initially identified, 8 randomized controlled trials on a total of 423 patients were included in the meta-analysis. The trials were markedly heterogeneous in some respects. There was no significant difference among surgical methods with respect to perioperative morbidity, pain, endocrine and exocrine insufficiency, or quality of life. Duodenumpreserving procedures, compared to duodenopancreatectomy, were associated with a long-term weight gain that was 3 kg higher (p chronic pancreatitis is superior to partial duodenopancreatectomy in multiple respects. Only limited recommendations can be given, however, on the basis of present data. The question of the best surgical method for the individual patient, in view of the clinical manifestations, anatomy, and diagnostic criteria, remains open.

  6. Pancreatic fibrosis correlates with exocrine pancreatic insufficiency after pancreatoduodenectomy

    NARCIS (Netherlands)

    T.C. Tran; G. van 't Hof; G. Kazemier (Geert); W.C.J. Hop (Wim); C.J. Pek (Chulja); A.W. van Toorenenbergen (Albert); H. van Dekken (Herman); C.H.J. van Eijck (Casper)

    2008-01-01

    textabstractBackground: Obstruction of the pancreatic duct can lead to pancreatic fibrosis. We investigated the correlation between the extent of pancreatic fibrosis and the postoperative exocrine and endocrine pancreatic function. Methods: Fifty-five patients who were treated for pancreatic and

  7. Diagnosis and classification of pancreatic and duodenal injuries in emergency radiology.

    Science.gov (United States)

    Linsenmaier, Ulrich; Wirth, Stefan; Reiser, Maximilian; Körner, Markus

    2008-10-01

    Pancreatic and duodenal injuries after blunt abdominal trauma are rare; however, delays in diagnosis and treatment can significantly increase morbidity and mortality. Multidetector computed tomography (CT) has a major role in early diagnosis of pancreatic and duodenal injuries. Detecting the often subtle signs of injury with whole-body CT can be difficult because this technique usually does not include a dedicated protocol for scanning the pancreas. Specific injury patterns in the pancreas and duodenum often have variable expression at early posttraumatic multidetector CT: They may be hardly visible, or there may be considerable exudate, hematomas, organ ruptures, or active bleeding. An accurate multidetector CT technique allows optimized detection of subtle abnormalities. In duodenal injuries, differentiation between a contusion of the duodenal wall or mural hematoma and a duodenal perforation is vital. In pancreatic injuries, determination of involvement of the pancreatic duct is essential. The latter conditions require immediate surgical intervention. Use of organ injury scales and a surgical classification adapted for multidetector CT enables classification of organ injuries for trauma scoring, treatment planning, and outcome control. In addition, multidetector CT reliably demonstrates potential complications of duodenal and pancreatic injuries, such as posttraumatic pancreatitis, pseudocysts, fistulas, exudates, and abscesses. (c) RSNA, 2008.

  8. Regional intra-arterial vs. systemic chemotherapy for advanced pancreatic cancer: a systematic review and meta-analysis of randomized controlled trials.

    Directory of Open Access Journals (Sweden)

    Fenghua Liu

    Full Text Available OBJECTIVE: To investigate the efficacy and safety of regional intra-arterial chemotherapy (RIAC versus systemic chemotherapy for stage III/IV pancreatic cancer. METHODS: Randomized controlled trials of patients with advanced pancreatic cancer treated by regional intra-arterial or systemic chemotherapy were identified using PubMed, ISI, EMBASE, Cochrane Library, Google, Chinese Scientific Journals Database (VIP, and China National Knowledge Infrastructure (CNKI electronic databases, for all publications dated between 1960 and December 31, 2010. Data was independently extracted by two reviewers. Odds ratios and relative risks were pooled using either fixed- or random-effects models, depending on I(2 statistic and Q test assessments of heterogeneity. Statistical analysis was performed using RevMan 5.0. RESULTS: Six randomized controlled trials comprised of 298 patients met the standards for inclusion in the meta-analysis, among 492 articles that were identified. Eight patients achieved complete remission (CR with regional intra-arterial chemotherapy (RIAC, whereas no patients achieved CR with systemic chemotherapy. Compared with systemic chemotherapy, patients receiving RIAC had superior partial remissions (RR = 1.99, 95% CI: 1.50, 2.65; 58.06% with RIAC and 29.37% with systemic treatment, clinical benefits (RR = 2.34, 95% CI: 1.84, 2.97; 78.06% with RAIC and 29.37% with systemic treatment, total complication rates (RR = 0.72, 95% CI: 0.60, 0.87; 49.03% with RIAC and 71.33% with systemic treatment, and hematological side effects (RR = 0.76, 95% CI: 0.63, 0.91; 60.87% with RIAC and 85.71% with systemic treatment. The median survival time with RIAC (5-21 months was longer than for systemic chemotherapy (2.7-14 months. Similarly, one year survival rates with RIAC (28.6%-41.2% were higher than with systemic chemotherapy (0%-12.9%.. CONCLUSION: Regional intra-arterial chemotherapy is more effective and has fewer complications than

  9. Regional intra-arterial vs. systemic chemotherapy for advanced pancreatic cancer: a systematic review and meta-analysis of randomized controlled trials.

    Science.gov (United States)

    Liu, Fenghua; Tang, Yong; Sun, Junwei; Yuan, Zhanna; Li, Shasha; Sheng, Jun; Ren, He; Hao, Jihui

    2012-01-01

    To investigate the efficacy and safety of regional intra-arterial chemotherapy (RIAC) versus systemic chemotherapy for stage III/IV pancreatic cancer. Randomized controlled trials of patients with advanced pancreatic cancer treated by regional intra-arterial or systemic chemotherapy were identified using PubMed, ISI, EMBASE, Cochrane Library, Google, Chinese Scientific Journals Database (VIP), and China National Knowledge Infrastructure (CNKI) electronic databases, for all publications dated between 1960 and December 31, 2010. Data was independently extracted by two reviewers. Odds ratios and relative risks were pooled using either fixed- or random-effects models, depending on I(2) statistic and Q test assessments of heterogeneity. Statistical analysis was performed using RevMan 5.0. Six randomized controlled trials comprised of 298 patients met the standards for inclusion in the meta-analysis, among 492 articles that were identified. Eight patients achieved complete remission (CR) with regional intra-arterial chemotherapy (RIAC), whereas no patients achieved CR with systemic chemotherapy. Compared with systemic chemotherapy, patients receiving RIAC had superior partial remissions (RR = 1.99, 95% CI: 1.50, 2.65; 58.06% with RIAC and 29.37% with systemic treatment), clinical benefits (RR = 2.34, 95% CI: 1.84, 2.97; 78.06% with RAIC and 29.37% with systemic treatment), total complication rates (RR = 0.72, 95% CI: 0.60, 0.87; 49.03% with RIAC and 71.33% with systemic treatment), and hematological side effects (RR = 0.76, 95% CI: 0.63, 0.91; 60.87% with RIAC and 85.71% with systemic treatment). The median survival time with RIAC (5-21 months) was longer than for systemic chemotherapy (2.7-14 months). Similarly, one year survival rates with RIAC (28.6%-41.2%) were higher than with systemic chemotherapy (0%-12.9%.). Regional intra-arterial chemotherapy is more effective and has fewer complications than systemic chemotherapy for treating advanced

  10. Pregnancy outcome of “delayed start” GnRH antagonist protocol versus GnRH antagonist protocol in poor responders: A clinical trial study

    Directory of Open Access Journals (Sweden)

    Abbas Aflatoonian

    2017-08-01

    Full Text Available Background: Management of poor-responding patients is still major challenge in assisted reproductive techniques (ART. Delayed-start GnRH antagonist protocol is recommended to these patients, but little is known in this regards. Objective: The goal of this study was assessment of delayed-start GnRH antagonist protocol in poor responders, and in vitro fertilization (IVF outcomes. Materials and Methods: This randomized clinical trial included sixty infertile women with Bologna criteria for ovarian poor responders who were candidate for IVF. In case group (n=30, delayed-start GnRH antagonist protocol administered estrogen priming followed by early follicular-phase GnRH antagonist treatment for 7 days before ovarian stimulation with gonadotropin. Control group (n=30 treated with estrogen priming antagonist protocol. Finally, endometrial thickness, the rates of oocytes maturation, , embryo formation, and pregnancy were compared between two groups. Results: Rates of implantation, chemical, clinical, and ongoing pregnancy in delayed-start cycles were higher although was not statistically significant. Endometrial thickness was significantly higher in case group. There were no statistically significant differences in the rates of oocyte maturation, embryo formation, and IVF outcomes between two groups. Conclusion: There is no significant difference between delayed-start GnRH antagonist protocol versus GnRH antagonist protocol.

  11. Examining the impact of genetic testing for type 2 diabetes on health behaviors: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Voils Corrine I

    2012-08-01

    Full Text Available Abstract Background We describe the study design, procedures, and development of the risk counseling protocol used in a randomized controlled trial to evaluate the impact of genetic testing for diabetes mellitus (DM on psychological, health behavior, and clinical outcomes. Methods/Design Eligible patients are aged 21 to 65 years with body mass index (BMI ≥27 kg/m2 and no prior diagnosis of DM. At baseline, conventional DM risk factors are assessed, and blood is drawn for possible genetic testing. Participants are randomized to receive conventional risk counseling for DM with eye disease counseling or with genetic test results. The counseling protocol was pilot tested to identify an acceptable graphical format for conveying risk estimates and match the length of the eye disease to genetic counseling. Risk estimates are presented with a vertical bar graph denoting risk level with colors and descriptors. After receiving either genetic counseling regarding risk for DM or control counseling on eye disease, brief lifestyle counseling for prevention of DM is provided to all participants. Discussion A standardized risk counseling protocol is being used in a randomized trial of 600 participants. Results of this trial will inform policy about whether risk counseling should include genetic counseling. Trial registration ClinicalTrials.gov Identifier NCT01060540

  12. Telerehabilitation Versus Traditional Care Following Total Hip Replacement: A Randomized Controlled Trial Protocol.

    Science.gov (United States)

    Nelson, Mark; Bourke, Michael; Crossley, Kay; Russell, Trevor

    2017-03-02

    Total hip replacement (THR) is the gold standard treatment for severe hip osteoarthritis. Effectiveness of physical rehabilitation for THR patients following discharge from hospital is supported by evidence; however, barriers such as geographical location and transport can limit access to appropriate health care. One solution to this issue is using an alternative model of care using telerehabilitation technology to deliver rehabilitation programs directly into patients' homes. A telerehabilitation model may also have potential health care cost savings for health care providers. This study aims to determine if a telerehabilitation model of care delivered remotely is as effective as face-to-face rehabilitation in the THR population and cost effective for health care providers and patients. A total of 70 people undergoing THR will be recruited to participate in a randomized, single-blind, controlled noninferiority clinical trial. The trial will compare a technology-based THR rehabilitation program to in-person care. On discharge from hospital, participants randomized to the in-person group will receive usual care, defined as a paper home exercise program (HEP) targeting strengthening exercises for quadriceps, hip abductors, extensors, and flexors; they will be advised to perform their HEP 3 times per day. At 2, 4, and 6 weeks postoperatively, they will receive a 30-minute in-person physiotherapy session with a focus on gait retraining and reviewing and progressing their HEP. The telerehabilitation protocol will involve a program similar in content to the in-person rehabilitation program, except delivery will be directly into the homes of the participants via telerehabilitation technology on an iPad. Outcomes will be evaluated preoperatively, day of discharge from in-patient physiotherapy, 6 weeks and 6 months postoperatively. The primary outcome will be the quality of life subscale of the hip disability and osteoarthritis outcome score, measured at 6 weeks. Both

  13. Animal models of pancreatic cancer for drug research.

    Science.gov (United States)

    Kapischke, Matthias; Pries, Alexandra

    2008-10-01

    The operative and conservative results of therapy in pancreatic ductal adenocarcinoma remain appallingly poor. This underlines the demand for further research for effective anticancer drugs. The various animal models remain the essential method for the determination of efficacy of substances during preclinical phase. Unfortunately, most of these tested substances showed a good efficacy in pancreatic carcinoma in the animal model but were not confirmed during the clinical phase. The available literature in PubMed, Medline, Ovid and secondary literature was searched regarding the available animal models for drug testing against pancreatic cancer. The models were analyzed regarding their pros and cons in anticancer drug testing. The different modifications of the orthotopic model (especially in mice) seem at present to be the best model for anticancer testing in pancreatic carcinoma. The value of genetically engineered animal model (GEM) and syngeneic models is on debate. A good selection of the model concerning the questions supposed to be clarified may improve the comparability of the results of animal experiments compared to clinical trials.

  14. Long-term outcomes of endoscopic vs surgical drainage of the pancreatic duct in patients with chronic pancreatitis.

    Science.gov (United States)

    Cahen, Djuna L; Gouma, Dirk J; Laramée, Philippe; Nio, Yung; Rauws, Erik A J; Boermeester, Marja A; Busch, Olivier R; Fockens, Paul; Kuipers, Ernst J; Pereira, Stephen P; Wonderling, David; Dijkgraaf, Marcel G W; Bruno, Marco J

    2011-11-01

    A randomized trial that compared endoscopic and surgical drainage of the pancreatic duct in patients with advanced chronic pancreatitis reported a significant benefit of surgery after a 2-year follow-up period. We evaluated the long-term outcome of these patients after 5 years. Between 2000 and 2004, 39 symptomatic patients were randomly assigned to groups that underwent endoscopic drainage or operative pancreaticojejunostomy. In 2009, information was collected regarding pain, quality of life, morbidity, mortality, length of hospital stay, number of procedures undergone, changes in pancreatic function, and costs. Analysis was performed according to an intention-to-treat principle. During the 79-month follow-up period, one patient was lost and 7 died from unrelated causes. Of the patients treated by endoscopy, 68% required additional drainage compared with 5% in the surgery group (P = .001). Hospital stay and costs were comparable, but overall, patients assigned to endoscopy underwent more procedures (median, 12 vs 4; P = .001). Moreover, 47% of the patients in the endoscopy group eventually underwent surgery. Although the mean difference in Izbicki pain scores was no longer significant (39 vs 22; P = .12), surgery was still superior in terms of pain relief (80% vs 38%; P = .042). Levels of quality of life and pancreatic function were comparable. In the long term, symptomatic patients with advanced chronic pancreatitis who underwent surgery as the initial treatment for pancreatic duct obstruction had more relief from pain, with fewer procedures, than patients who were treated endoscopically. Importantly, almost half of the patients who were treated with endoscopy eventually underwent surgery. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  15. [Chronic pancreatitis diagnosed after the first attack of acute pancreatitis].

    Science.gov (United States)

    Bojková, Martina; Dítě, Petr; Uvírová, Magdalena; Dvořáčková, Nina; Kianička, Bohuslav; Kupka, Tomáš; Svoboda, Pavel; Klvaňa, Pavel; Martínek, Arnošt

    2016-02-01

    One of the diseases involving a potential risk of developing chronic pancreatitis is acute pancreatitis. Of the overall number of 231 individuals followed with a diagnosis of chronic pancreatitis, 56 patients were initially treated for acute pancreatitis (24.2 %). Within an interval of 12- 24 months from the first attack of acute pancreatitis, their condition gradually progressed to reached the picture of chronic pancreatitis. The individuals included in the study abstained (from alcohol) following the first attack of acute pancreatitis and no relapse of acute pancreatitis was proven during the period of their monitoring. The etiology of acute pancreatitis identified alcohol as the predominant cause (55.3 %), biliary etiology was proven in 35.7 %. According to the revised Atlanta classification, severe pancreatitis was established in 69.6 % of the patients, the others met the criterion for intermediate form, those with the light form were not included. Significant risk factors present among the patients were smoking, obesity and 18 %, resp. 25.8 % had pancreatogenous diabetes mellitus identified. 88.1 % of the patients with acute pancreatitis were smokers. The majority of individuals with chronic pancreatitis following an attack of acute pancreatitis were of a productive age from 25 to 50 years. It is not only acute alcoholic pancreatitis which evolves into chronic pancreatitis, we have also identified this transition for pancreatitis of biliary etiology.

  16. 64-section multidetector CT of the upper abdomen: optimization of a saline chaser injection protocol for improved vascular and parenchymal contrast enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Marin, Daniele [Duke University Medical Center, Department of Radiology, Durham, NC (United States); University of Rome Sapienza, Department of Radiological Sciences, Rome (Italy); Nelson, Rendon C. [Duke University Medical Center, Department of Radiology, Durham, NC (United States); Guerrisi, Antonino; Passariello, Roberto; Catalano, Carlo [University of Rome Sapienza, Department of Radiological Sciences, Rome (Italy); Barnhart, Huiman [Duke University Medical Center, Department of Biostatistics and Bioinformatics, Durham, NC (United States); Schindera, Sebastian T. [University Hospital of Bern, Institute for Diagnostic, Interventional and Pediatric Radiology, Bern (Switzerland)

    2011-09-15

    To prospectively investigate the effect of varying the injection flow rates of a saline chaser on vascular and parenchymal contrast enhancement during abdominal MDCT. 100 consecutive patients were randomly assigned to four injection protocols. A fixed dose of contrast medium was administered followed by no saline (Protocol A) or 50 mL of saline at 2, 4, or 8 mL/s (Protocols B, C, and D). Peak, time-to-peak, and duration of 90% peak enhancement were determined for aorta, pancreas, and liver. Aortic peak enhancement was significantly higher for Protocol D (369.5 HU) compared with Protocols A and B (332.9 HU and 326.0 HU, respectively; P < 0.05). Pancreatic peak enhancement was significantly higher for Protocols C and D (110.6 HU and 110.9 HU, respectively) compared to Protocol A (92.5 HU; P < 0.05). Aortic and pancreatic time-to-peak enhancement occurred significantly later for Protocol D compared with Protocol A (42.8 s vs. 36.1 s [P < 0.001] and 49.7 s vs. 45.3 s [P = 0.003]). Injecting a saline chaser at high flow rates yields significantly higher peak aortic and pancreatic enhancement, with a slight longer time-to-peak enhancement. (orig.)

  17. Development of the PANVAC-VF vaccine for pancreatic cancer.

    Science.gov (United States)

    Petrulio, Christian A; Kaufman, Howard L

    2006-02-01

    PANVAC-VF is a vaccine regimen composed of a priming dose of recombinant vaccinia virus and booster doses of recombinant fowlpox virus expressing carcinoembryonic antigen, mucin-1 and a triad of costimulatory molecules (TRICOM), which include B7.1, intercellular adhesion molecule-1 and leukocyte function-associated antigen-3. Vaccination is administered by subcutaneous injection followed by 4 days of local recombinant adjuvant granulocyte-macrophage colony-stimulating factor at the vaccination site. The vaccine has been developed for patients with advanced pancreatic cancer and has now entered a randomized Phase III clinical trial. This review will describe the background of recombinant poxvirus technology for tumor vaccine development, detail the key preclinical studies supporting the regimen, review the clinical trials supporting the current Phase III study, and highlight the key challenges and future obstacles to successful implementation of PANVAC-VF for pancreatic cancer.

  18. Robotic transgastric cystgastrostomy and pancreatic debridement in the management of pancreatic fluid collections following acute pancreatitis.

    Science.gov (United States)

    Kirks, Russell C; Sola, Richard; Iannitti, David A; Martinie, John B; Vrochides, Dionisios

    2016-01-01

    Pancreatic and peripancreatic fluid collections may develop after severe acute pancreatitis. Organized fluid collections such as pancreatic pseudocyst and walled-off pancreatic necrosis (WOPN) that mature over time may require intervention to treat obstructive or constitutional symptoms related to the size and location of the collection as well as possible infection. Endoscopic, open surgical and minimally invasive techniques are described to treat post-inflammatory pancreatic fluid collections. Surgical intervention may be required to treat collections containing necrotic pancreatic parenchyma or in locations not immediately apposed to the stomach or duodenum. Comprising a blend of the surgical approach and the clinical benefits of minimally invasive surgery, the robot-assisted technique of pancreatic cystgastrostomy with pancreatic debridement is described.

  19. Minimally invasive versus open distal pancreatectomy (LEOPARD): study protocol for a randomized controlled trial.

    Science.gov (United States)

    de Rooij, Thijs; van Hilst, Jony; Vogel, Jantien A; van Santvoort, Hjalmar C; de Boer, Marieke T; Boerma, Djamila; van den Boezem, Peter B; Bonsing, Bert A; Bosscha, Koop; Coene, Peter-Paul; Daams, Freek; van Dam, Ronald M; Dijkgraaf, Marcel G; van Eijck, Casper H; Festen, Sebastiaan; Gerhards, Michael F; Groot Koerkamp, Bas; Hagendoorn, Jeroen; van der Harst, Erwin; de Hingh, Ignace H; Dejong, Cees H; Kazemier, Geert; Klaase, Joost; de Kleine, Ruben H; van Laarhoven, Cornelis J; Lips, Daan J; Luyer, Misha D; Molenaar, I Quintus; Nieuwenhuijs, Vincent B; Patijn, Gijs A; Roos, Daphne; Scheepers, Joris J; van der Schelling, George P; Steenvoorde, Pascal; Swijnenburg, Rutger-Jan; Wijsman, Jan H; Abu Hilal, Moh'd; Busch, Olivier R; Besselink, Marc G

    2017-04-08

    Observational cohort studies have suggested that minimally invasive distal pancreatectomy (MIDP) is associated with better short-term outcomes compared with open distal pancreatectomy (ODP), such as less intraoperative blood loss, lower morbidity, shorter length of hospital stay, and reduced total costs. Confounding by indication has probably influenced these findings, given that case-matched studies failed to confirm the superiority of MIDP. This accentuates the need for multicenter randomized controlled trials, which are currently lacking. We hypothesize that time to functional recovery is shorter after MIDP compared with ODP even in an enhanced recovery setting. LEOPARD is a randomized controlled, parallel-group, patient-blinded, multicenter, superiority trial in all 17 centers of the Dutch Pancreatic Cancer Group. A total of 102 patients with symptomatic benign, premalignant or malignant disease will be randomly allocated to undergo MIDP or ODP in an enhanced recovery setting. The primary outcome is time (days) to functional recovery, defined as all of the following: independently mobile at the preoperative level, sufficient pain control with oral medication alone, ability to maintain sufficient (i.e. >50%) daily required caloric intake, no intravenous fluid administration and no signs of infection. Secondary outcomes are operative and postoperative outcomes, including clinically relevant complications, mortality, quality of life and costs. The LEOPARD trial is designed to investigate whether MIDP reduces the time to functional recovery compared with ODP in an enhanced recovery setting. Dutch Trial Register, NTR5188 . Registered on 9 April 2015.

  20. an extended pancreatic normal subjects and ~in pancreatItIs In ...

    African Journals Online (AJOL)

    function . . patIents. N. H. GILlNSKY, A. S. MEE, I. N. MARKS. Summary. Exocrine pancreatic response was evaluated in patients with varying degrees of pancreatic damage and in control subjects by ... hormones, the Lundh meal and an oral pancreatic function test .... is any different from that of the cells in me normal gland.

  1. Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis

    Directory of Open Access Journals (Sweden)

    Sala Abdalla

    2016-01-01

    Full Text Available Extra-abdominal complications of pancreatitis such as pancreaticopleural fistulae are rare. A pancreaticopleural fistula occurs when inflammation of the pancreas and pancreatic ductal disruption lead to leakage of secretions through a fistulous tract into the thorax. The underlying aetiology in the majority of cases is alcohol-induced chronic pancreatitis. The diagnosis is often delayed given that the majority of patients present with pulmonary symptoms and frequently have large, persistent pleural effusions. The diagnosis is confirmed through imaging and the detection of significantly elevated amylase levels in the pleural exudate. Treatment options include somatostatin analogues, thoracocentesis, endoscopic retrograde cholangiopancreatography (ERCP with pancreatic duct stenting, and surgery. The authors present a case of pancreatic pseudocyst pleural fistula in a woman with gallstone pancreatitis presenting with recurrent pneumonias and bilateral pleural effusions.

  2. The Key Genes of Chronic Pancreatitis which Bridge Chronic Pancreatitis and Pancreatic Cancer Can be Therapeutic Targets.

    Science.gov (United States)

    Li, Shuang; Li, Rui; Wang, Heping; Li, Lisha; Li, Huiyu; Li, Yulin

    2018-04-01

    An important question in systems biology is what role the underlying molecular mechanisms play in disease progression. The relationship between chronic pancreatitis and pancreatic cancer needs further exploration in a system view. We constructed the disease network based on gene expression data and protein-protein interaction. We proposed an approach to discover the underlying core network and molecular factors in the progression of pancreatic diseases, which contain stages of chronic pancreatitis and pancreatic cancer. The chronic pancreatitis and pancreatic cancer core network and key factors were revealed and then verified by gene set enrichment analysis of pathways and diseases. The key factors provide the microenvironment for tumor initiation and the change of gene expression level of key factors bridge chronic pancreatitis and pancreatic cancer. Some new candidate genes need further verification by experiments. Transcriptome profiling-based network analysis reveals the importance of chronic pancreatitis genes and pathways in pancreatic cancer development on a system level by computational method and they can be therapeutic targets.

  3. Pancreatic islet transplantation

    Directory of Open Access Journals (Sweden)

    Corrêa-Giannella Maria

    2009-09-01

    Full Text Available Abstract Background No formulation of exogenous insulin available to date has yet been able to mimic the physiological nictemeral rhythms of this hormone, and despite all engineering advancements, the theoretical proposal of developing a mechanical replacement for pancreatic β cell still has not been reached. Thus, the replacement of β cells through pancreas and pancreatic islet transplantation are the only concrete alternatives for re-establishing the endogenous insulin secretion in type 1 diabetic patients. Since only 1 to 1.5% of the pancreatic mass corresponds to endocrine tissue, pancreatic islets transplantation arises as a natural alternative. Data from the International Islet Transplant Registry (ITR from 1983 to December 2000 document a total of 493 transplants performed around the world, with progressively worse rates of post-transplant insulin independence. In 2000, the "Edmonton Protocol" introduced several modifications to the transplantation procedure, such as the use of a steroid-free immunosuppression regimen and transplantation of a mean islet mass of 11,000 islet equivalents per kilogram, which significantly improved 1-year outcomes. Although the results of a 5-year follow-up in 65 patients demonstrated improvement in glycemic instability in a significant portion of them, only 7.5% of the patients have reached insulin independence, indicating the need of further advances in the preservation of the function of transplanted islet. In addition to the scarcity of organs available for transplantation, islets transplantation still faces major challenges, specially those related to cell loss during the process of islet isolation and the losses related to the graft site, apoptosis, allorejection, autoimmunity, and immunosuppression. The main strategies to optimize islet transplantation aim at improving all these aspects. Conclusion Human islet transplantation should be regarded as an intervention that can decrease the frequency of

  4. Study Protocol: Phase III single-blinded fast-track pragmatic randomised controlled trial of a complex intervention for breathlessness in advanced disease

    Directory of Open Access Journals (Sweden)

    Brafman-Kennedy Barbara

    2011-05-01

    Full Text Available Abstract Background Breathlessness in advanced disease causes significant distress to patients and carers and presents management challenges to health care professionals. The Breathlessness Intervention Service (BIS seeks to improve the care of breathless patients with advanced disease (regardless of cause through the use of evidence-based practice and working with other healthcare providers. BIS delivers a complex intervention (of non-pharmacological and pharmacological treatments via a multi-professional team. BIS is being continuously developed and its impact evaluated using the MRC's framework for complex interventions (PreClinical, Phase I and Phase II completed. This paper presents the protocol for Phase III. Methods/Design Phase III comprises a pragmatic, fast-track, single-blind randomised controlled trial of BIS versus standard care. Due to differing disease trajectories, the service uses two broad service models: one for patients with malignant disease (intervention delivered over two weeks and one for patients with non-malignant disease (intervention delivered over four weeks. The Phase III trial therefore consists of two sub-protocols: one for patients with malignant conditions (four week protocol and one for patients with non-malignant conditions (eight week protocol. Mixed method interviews are conducted with patients and their lay carers at three to five measurement points depending on randomisation and sub-protocol. Qualitative interviews are conducted with referring and non-referring health care professionals (malignant disease protocol only. The primary outcome measure is 'patient distress due to breathlessness' measured on a numerical rating scale (0-10. The trial includes economic evaluation. Analysis will be on an intention to treat basis. Discussion This is the first evaluation of a breathlessness intervention for advanced disease to have followed the MRC framework and one of the first palliative care trials to use fast

  5. Surgical and endoscopic treatment of pain in chronic pancreatitis: a multidisciplinary update.

    Science.gov (United States)

    Issa, Y; van Santvoort, H C; van Goor, H; Cahen, D L; Bruno, M J; Boermeester, M A

    2013-01-01

    Chronic pancreatitis is an inflammatory disease of the pancreas with abdominal pain as the most prominent symptom. Adequate treatment of patients with chronic pancreatitis remains a major challenge, mainly because of the lack of evidence-based treatment protocols. The primary goal of treatment is to achieve long-term pain relief, control of the complications associated with the disease, and to restore the quality of life. Currently, a conservative step-up approach is often used for the treatment of pain; progression to severe and intractable pain is considered necessary before invasive treatment is considered. Recent studies, however, suggest that surgical intervention should not be considered only as last-resort treatment, since it can mitigate disease progression, achieve excellent pain control, and preserve pancreatic function. In this review, we present a state-of-the art overview of endoscopic and surgical treatment options for patients with painful chronic pancreatitis, and elaborate on the timing of surgery. Copyright © 2013 S. Karger AG, Basel.

  6. Pancreatic trauma.

    Science.gov (United States)

    Lahiri, R; Bhattacharya, S

    2013-05-01

    Pancreatic trauma occurs in approximately 4% of all patients sustaining abdominal injuries. The pancreas has an intimate relationship with the major upper abdominal vessels, and there is significant morbidity and mortality associated with severe pancreatic injury. Immediate resuscitation and investigations are essential to delineate the nature of the injury, and to plan further management. If main pancreatic duct injuries are identified, specialised input from a tertiary hepatopancreaticobiliary (HPB) team is advised. A comprehensive online literature search was performed using PubMed. Relevant articles from international journals were selected. The search terms used were: 'pancreatic trauma', 'pancreatic duct injury', 'radiology AND pancreas injury', 'diagnosis of pancreatic trauma', and 'management AND surgery'. Articles that were not published in English were excluded. All articles used were selected on relevance to this review and read by both authors. Pancreatic trauma is rare and associated with injury to other upper abdominal viscera. Patients present with non-specific abdominal findings and serum amylase is of little use in diagnosis. Computed tomography is effective in diagnosing pancreatic injury but not duct disruption, which is most easily seen on endoscopic retrograde cholangiopancreaticography or operative pancreatography. If pancreatic injury is suspected, inspection of the entire pancreas and duodenum is required to ensure full evaluation at laparotomy. The operative management of pancreatic injury depends on the grade of injury found at laparotomy. The most important prognostic factor is main duct disruption and, if found, reconstructive options should be determined by an experienced HPB surgeon. The diagnosis of pancreatic trauma requires a high index of suspicion and detailed imaging studies. Grading pancreatic injury is important to guide operative management. The most important prognostic factor is pancreatic duct disruption and in these cases

  7. Autoimmune pancreatitis

    Directory of Open Access Journals (Sweden)

    Davorin Dajčman

    2007-05-01

    Full Text Available Background: Autoimmune pancreatitis is a recently described type of pancreatitis of presumed autoimmune etiology. Autoimmune pancreatitis is often misdiagnosed as pancreatic cancer difficult, since their clinical presentations are often similar. The concept of autoimmune pancreatitis was first published in 1961. Since then, autoimmune pancreatitis has often been treated not as an independent clinical entity but rather as a manifestation of systemic disease. The overall prevalence and incidence of the disease have yet to be determined, but three series have reported the prevalence as between 5 and 6 % of all patients with chronic pancreatitis. Patient vary widely in age, but most are older than 50 years. Patients with autoimmune pancreatitis usually complain of the painless jaundice, mild abdominal pain and weight loss. There is no laboratory hallmark of the disease, even if cholestatic profiles of liver dysfunction with only mild elevation of amylase and lipase levels have been reported.Conclusions: Proposed diagnostic criteria contains: (1 radiologic imaging, diffuse enlargement of the pancreas and diffusely irregular narrowing of the main pancreatic duct, (2 laboratory data, elevated levels of serum ã-globulin and/or IgG, specially IgG4, or the presence of autoantibodies and (3 histopathologic examination, fibrotic change with dense lymphoplasmacytic infiltration in the pancreas. For correct diagnosis of autoimmune pancreatitis, criterion 1 must be present with criterion 2 and/or 3. Autoimmune pancreatitis is frequently associated with rheumatoid arthritis, Sjogren’s syndrome, inflammatory bowel disease, tubulointersticial nephritis, primary sclerosing cholangitis and idiopathic retroperitoneal fibrosis. Pancreatic biopsy using an endoscopic ultrasound-guided fine needle aspiration biopsy is the most important diagnostic method today. Treatment with corticosteroids leads to the and resolution of pancreatic inflamation, obstruction and

  8. Difference gel electrophoresis (DiGE) identifies differentially expressed proteins in endoscopically-collected pancreatic fluid

    Science.gov (United States)

    Paulo, Joao A.; Lee, Linda S.; Banks, Peter A.; Steen, Hanno; Conwell, Darwin L.

    2012-01-01

    Alterations in the pancreatic fluid proteome of individuals with chronic pancreatitis may offer insights into the development and progression of the disease. The endoscopic pancreas function test (ePFT) can safely collect large volumes of pancreatic fluid that are potentially amenable to proteomic analyses using difference gel electrophoresis (DiGE) coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pancreatic fluid was collected endoscopically using the ePFT method following secretin stimulation from three individuals with severe chronic pancreatitis and three chronic abdominal pain controls. The fluid was processed to minimize protein degradation and the protein profiles of each cohort, as determined by DiGE and LC-MS/MS, were compared. This DiGE-LC-MS/MS analysis reveals proteins that are differentially expressed in chronic pancreatitis compared to chronic abdominal pain controls. Proteins with higher abundance in pancreatic fluid from chronic pancreatitis individuals include: actin, desmoplankin, alpha-1-antitrypsin, SNC73, and serotransferrin. Those of relatively lower abundance include carboxypeptidase B, lipase, alpha-1-antichymotrypsin, alpha-2-macroglobulin, Arp2/3 subunit 4, glyceraldehyde-3-phosphate dehydrogenase, and protein disulfide isomerase. Endoscopic collection (ePFT) in tandem with DiGE-LC-MS/MS is a suitable approach for pancreatic fluid proteome analysis, however, further optimization of our protocol, as outlined herein, may improve proteome coverage in future analyses. PMID:21792986

  9. [Oligometastasis in pancreatic cancer : Current state of knowledge and spectrum of local therapy].

    Science.gov (United States)

    Gebauer, F; Damanakis, A I; Bruns, C

    2018-03-20

    Several case series reported results of surgical resection in patients with pancreatic ductal adenocarcinoma in a metastasized stage. A summarized overview of the current state of knowledge and a summary of the results of currently available studies. A systematic search was carried out in MEDLINE and PubMed with respect to metastasized pancreatic cancer and surgical resection. The evidence level for surgical resection in the metastasized stage is weak and so far no prospective trials are available. The largest single-arm trial included 85 patients with hepatic metastasis. In cases of hepatic oligometastasis an overall survival of 11-14 months was observed. In the presence of pulmonary metastasis, overall survival seems to be prolonged compared to intra-abdominal metastasis, although the evidence level is relatively weak. According to the available results, a general recommendation for surgical resection in a metastasized stage cannot be given; however, the results show a possible benefit for some well-selected patient subgroups. Prospective trials must validate these data and investigate the use of combined surgical and systemic treatments in the case of resectable metastatic pancreatic cancer.

  10. Endocrine pancreatic function changes after acute pancreatitis.

    Science.gov (United States)

    Wu, Deqing; Xu, Yaping; Zeng, Yue; Wang, Xingpeng

    2011-10-01

    This study aimed to investigate the impairment of pancreatic endocrine function and the associated risk factors after acute pancreatitis (AP). Fifty-nine patients were subjected to tests of pancreatic function after an attack of pancreatitis. The mean time after the event was 3.5 years. Pancreatic endocrine function was evaluated by fasting blood glucose (FBG), glycosylated hemoglobin, fasting blood insulin, and C-peptide. Homeostasis model assessment was used to evaluate insulin resistance and islet β-cell function. Pancreatic exocrine function was evaluated by fecal elastase 1. Factors that could influence endocrine function were also investigated. Nineteen patients (32%) were found to have elevated FBG, whereas 5 (8%) had abnormal glycosylated hemoglobin levels. The levels of FBG, fasting blood insulin, and C-peptide were higher in patients than in controls (P endocrine insufficiency. Pancreatic exocrine functional impairment was found at the same time. Endocrine functional impairment with insulin resistance was found in patients after AP. Obesity, hyperlipidemia, and diabetes-related symptoms increased the likelihood of developing functional impairment after AP.

  11. Pancreatitis in Children.

    Science.gov (United States)

    Sathiyasekaran, Malathi; Biradar, Vishnu; Ramaswamy, Ganesh; Srinivas, S; Ashish, B; Sumathi, B; Nirmala, D; Geetha, M

    2016-11-01

    Pancreatic disease in children has a wide clinical spectrum and may present as Acute pancreatitis (AP), Acute recurrent pancreatitis (ARP), Chronic pancreatitis (CP) and Pancreatic disease without pancreatitis. This article highlights the etiopathogenesis and management of pancreatitis in children along with clinical data from five tertiary care hospitals in south India [Chennai (3), Cochin and Pune].

  12. The prevalence of small intestinal bacterial overgrowth in non-surgical patients with chronic pancreatitis and pancreatic exocrine insufficiency (PEI).

    Science.gov (United States)

    Ní Chonchubhair, Hazel M; Bashir, Yasir; Dobson, Mark; Ryan, Barbara M; Duggan, Sinead N; Conlon, Kevin C

    2018-02-24

    Small intestinal bacterial overgrowth (SIBO) is a condition characterised by symptoms similar to pancreatic exocrine insufficiency (PEI) in chronic pancreatitis patients. SIBO is thought to complicate chronic pancreatitis in up to 92% of cases; however, studies are heterogeneous and protocols non-standardised. SIBO may be determined by measuring lung air-expiration of either hydrogen or methane which are by-products of small bowel bacterial fermentation of intraluminal substrates such as carbohydrates. We evaluated the prevalence of SIBO among a defined cohort of non-surgical chronic pancreatitics with mild to severe PEI compared with matched healthy controls. Thirty-five patients and 31 age-, gender- and smoking status-matched healthy controls were evaluated for SIBO by means of a fasting glucose hydrogen breath test (GHBT). The relationship between SIBO and clinical symptoms in chronic pancreatitis was evaluated. SIBO was present in 15% of chronic pancreatitis patients, while no healthy controls tested positive (P = 0.029). SIBO was more prevalent in those taking pancreatic enzyme replacement therapy (PERT) (P = 0.016), with proton pump inhibitor use (PPI) (P = 0.022) and in those with alcohol aetiology (P = 0.023). Patients with concurrent diabetes were more often SIBO-positive and this was statistically significant (P = 0.009). There were no statistically significant differences in reported symptoms between patients with and without SIBO, with the exception of 'weight loss', with patients reporting weight loss more likely to have SIBO (P = 0.047). The prevalence of SIBO in this study was almost 15% and consistent with other studies of SIBO in non-surgical chronic pancreatitis patients. These data support the testing of patients with clinically-relevant PEI unresolved by adequate doses of PERT, particularly in those patients with concurrent diabetes. SIBO can be easily diagnosed therefore allowing more specific and more targeted symptom

  13. Early ERCP is an essential part of the management of all cases of acute pancreatitis.

    OpenAIRE

    Gupta, R.; Toh, S. K.; Johnson, C. D.

    1999-01-01

    The role of early endoscopic retrograde cholangiopancreatography (ERCP) and sphincterotomy in acute pancreatitis is controversial. Recent randomised controlled trials mostly support the value of this procedure, but concerns remain as to its safety, efficacy and practicability. This debate critically assesses the evidence for and against the use of early ERCP in acute pancreatitis.

  14. Pain in Patients with Pancreatic Cancer: Prevalence, Mechanisms, Management and Future Developments.

    Science.gov (United States)

    Koulouris, Andreas I; Banim, Paul; Hart, Andrew R

    2017-04-01

    Pain affects approximately 80% of patients with pancreatic cancer, with half requiring strong opioid analgesia, namely: morphine-based drugs on step three of the WHO analgesic ladder (as opposed to the weak opioids: codeine and tramadol). The presence of pain is associated with reduced survival. This article reviews the literature regarding pain: prevalence, mechanisms, pharmacological, and endoscopic treatments and identifies areas for research to develop individualized patient pain management pathways. The online literature review was conducted through: PubMed, Clinical Key, Uptodate, and NICE Evidence. There are two principal mechanisms for pain: pancreatic duct obstruction and pancreatic neuropathy which, respectively, activate mechanical and chemical nociceptors. In pancreatic neuropathy, several histological, molecular, and immunological changes occur which correlate with pain including: transient receptor potential cation channel activation and mast cell infiltration. Current pain management is empirical rather etiology-based and is informed by the WHO analgesic ladder for first-line therapies, and then endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in patients with resistant pain. For EUS-CPN, there is only one clinical trial reporting a benefit, which has limited generalizability. Case series report pancreatic duct stenting gives effective analgesia, but there are no clinical trials. Progress in understanding the mechanisms for pain and when this occurs in the natural history, together with assessing new therapies both pharmacological and endoscopic, will enable individualized care and may improve patients' quality of life and survival.

  15. Optimizing 4-Dimensional Magnetic Resonance Imaging Data Sampling for Respiratory Motion Analysis of Pancreatic Tumors

    Energy Technology Data Exchange (ETDEWEB)

    Stemkens, Bjorn, E-mail: b.stemkens@umcutrecht.nl [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Tijssen, Rob H.N. [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands); Senneville, Baudouin D. de [Imaging Division, University Medical Center Utrecht, Utrecht (Netherlands); L' Institut de Mathématiques de Bordeaux, Unité Mixte de Recherche 5251, Centre National de la Recherche Scientifique/University of Bordeaux, Bordeaux (France); Heerkens, Hanne D.; Vulpen, Marco van; Lagendijk, Jan J.W.; Berg, Cornelis A.T. van den [Department of Radiotherapy, University Medical Center Utrecht, Utrecht (Netherlands)

    2015-03-01

    Purpose: To determine the optimum sampling strategy for retrospective reconstruction of 4-dimensional (4D) MR data for nonrigid motion characterization of tumor and organs at risk for radiation therapy purposes. Methods and Materials: For optimization, we compared 2 surrogate signals (external respiratory bellows and internal MRI navigators) and 2 MR sampling strategies (Cartesian and radial) in terms of image quality and robustness. Using the optimized protocol, 6 pancreatic cancer patients were scanned to calculate the 4D motion. Region of interest analysis was performed to characterize the respiratory-induced motion of the tumor and organs at risk simultaneously. Results: The MRI navigator was found to be a more reliable surrogate for pancreatic motion than the respiratory bellows signal. Radial sampling is most benign for undersampling artifacts and intraview motion. Motion characterization revealed interorgan and interpatient variation, as well as heterogeneity within the tumor. Conclusions: A robust 4D-MRI method, based on clinically available protocols, is presented and successfully applied to characterize the abdominal motion in a small number of pancreatic cancer patients.

  16. Biomarker-driven trial in metastatic pancreas cancer: feasibility in a multicenter study of saracatinib, an oral Src inhibitor, in previously treated pancreatic cancer

    International Nuclear Information System (INIS)

    Arcaroli, John; Quackenbush, Kevin; Dasari, Arvind; Powell, Rebecca; McManus, Martine; Tan, Aik-Choon; Foster, Nathan R; Picus, Joel; Wright, John; Nallapareddy, Sujatha; Erlichman, Charles; Hidalgo, Manuel; Messersmith, Wells A

    2012-01-01

    Src tyrosine kinases are overexpressed in pancreatic cancers, and the oral Src inhibitor saracatinib has shown antitumor activity in preclinical models of pancreas cancer. We performed a CTEP-sponsored Phase II clinical trial of saracatinib in previously treated pancreas cancer patients, with a primary endpoint of 6-month survival. A Simon MinMax two-stage phase II design was used. Saracatinib (175 mg/day) was administered orally continuously in 28-day cycles. In the unselected portion of the study, 18 patients were evaluable. Only two (11%) patients survived for at least 6 months, and three 6-month survivors were required to move to second stage of study as originally designed. The study was amended as a biomarker-driven trial (leucine rich repeat containing protein 19 [LRRC19] > insulin-like growth factor-binding protein 2 [IGFBP2] “top scoring pairs” polymerase chain reaction [PCR] assay, and PIK3CA mutant) based on preclinical data in a human pancreas tumor explant model. In the biomarker study, archival tumor tissue or fresh tumor biopsies were tested. Biomarker-positive patients were eligible for the study. Only one patient was PIK3CA mutant in a 3′ untranslated region (UTR) portion of the gene. This patient was enrolled in the study and failed to meet the 6-month survival endpoint. As the frequency of biomarker-positive patients was very low (<3%), the study was closed. Although we were unable to conclude whether enriching for a subset of second/third line pancreatic cancer patients treated with a Src inhibitor based on a biomarker would improve 6-month survival, we demonstrate that testing pancreatic tumor samples for a biomarker-driven, multicenter study in metastatic pancreas cancer is feasible

  17. Neoadjuvant chemoradiation therapy with gemcitabine/cisplatin and surgery versus immediate surgery in resectable pancreatic cancer. Results of the first prospective randomized phase II trial

    Energy Technology Data Exchange (ETDEWEB)

    Golcher, Henriette; Merkel, Susanne; Hohenberger, Werner [University Hospital Erlangen, Department of Surgery, Erlangen (Germany); Brunner, Thomas B. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); University Hospital Freiburg, Department of Radiation Oncology, Freiburg (Germany); Witzigmann, Helmut [University Hospital Leipzig, Department of Surgery, Leipzig (Germany); Hospital Dresden-Friedrichstadt, General Surgery, Dresden (Germany); Marti, Lukas [Hospital of Kanton St. Gallen, General Surgery, St. Gallen (Switzerland); Bechstein, Wolf-Otto [University Hospital Frankfurt, Department of Surgery, Frankfurt/Main (Germany); Bruns, Christiane [University Hospital Munich, Department of Surgery - Hospital Campus Grosshadern, Munich (Germany); University Hospital Magdeburg, Department of Surgery, Magdeburg (Germany); Jungnickel, Henry [Hospital Dresden-Friedrichstadt, General Surgery, Dresden (Germany); Schreiber, Stefan [University Hospital Leipzig, Department of Surgery, Leipzig (Germany); Grabenbauer, Gerhard G. [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany); Hospital Coburg, Department of Radiation Oncology, Coburg (Germany); Meyer, Thomas [University Hospital Erlangen, Department of Surgery, Erlangen (Germany); Hospital Ansbach, General Surgery, Ansbach (Germany); Fietkau, Rainer [University Hospital Erlangen, Department of Radiation Oncology, Erlangen (Germany)

    2014-09-25

    In nonrandomized trials, neoadjuvant treatment was reported to prolong survival in patients with pancreatic cancer. As neoadjuvant chemoradiation is established for the treatment of rectal cancer we examined the value of neoadjuvant chemoradiotherapy in pancreatic cancer in a randomized phase II trial. Radiological staging defining resectability was basic information prior to randomization in contrast to adjuvant therapy trials resting on pathological staging. Patients with resectable adenocarcinoma of the pancreatic head were randomized to primary surgery (Arm A) or neoadjuvant chemoradiotherapy followed by surgery (Arm B), which was followed by adjuvant chemotherapy in both arms. A total of 254 patients were required to detect a 4.33-month improvement in median overall survival (mOS). The trial was stopped after 73 patients; 66 patients were eligible for analysis. Twenty nine of 33 allocated patients received chemoradiotherapy. Radiotherapy was completed in all patients. Chemotherapy was changed in 3 patients due to toxicity. Tumor resection was performed in 23 vs. 19 patients (A vs. B). The R0 resection rate was 48 % (A) and 52 % (B, P = 0.81) and (y)pN0 was 30 % (A) vs. 39 % (B, P = 0.44), respectively. Postoperative complications were comparable in both groups. mOS was 14.4 vs. 17.4 months (A vs. B; intention-to-treat analysis; P = 0.96). After tumor resection, mOS was 18.9 vs. 25.0 months (A vs. B; P = 0.79). This worldwide first randomized trial for neoadjuvant chemoradiotherapy in pancreatic cancer showed that neoadjuvant chemoradiation is safe with respect to toxicity, perioperative morbidity, and mortality. Nevertheless, the trial was terminated early due to slow recruiting and the results were not significant. ISRCTN78805636; NCT00335543. (orig.) [German] Mehrere nichtrandomisierte Studien zeigten, dass eine neoadjuvante Therapie das Ueberleben bei Patienten mit Pankreaskarzinom verlaengert. Beim lokal fortgeschrittenen Rektumkarzinom gehoert die

  18. Early management of acute pancreatitis: A review of the best evidence.

    Science.gov (United States)

    Stigliano, Serena; Sternby, Hanna; de Madaria, Enrique; Capurso, Gabriele; Petrov, Maxim S

    2017-06-01

    In the 20th century early management of acute pancreatitis often included surgical intervention, despite overwhelming mortality. The emergence of high-quality evidence (randomized controlled trials and meta-analyses) over the past two decades has notably shifted the treatment paradigm towards predominantly non-surgical management early in the course of acute pancreatitis. The present evidence-based review focuses on contemporary aspects of early management (which include analgesia, fluid resuscitation, antibiotics, nutrition, and endoscopic retrograde cholangiopancreatography) with a view to providing clear and succinct guidelines on early management of patients with acute pancreatitis in 2017 and beyond. Copyright © 2017 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  19. Risk of Pancreatic Cancer After a Primary Episode of Acute Pancreatitis.

    Science.gov (United States)

    Rijkers, Anton P; Bakker, Olaf J; Ahmed Ali, Usama; Hagenaars, Julia C J P; van Santvoort, Hjalmar C; Besselink, Marc G; Bollen, Thomas L; van Eijck, Casper H

    2017-09-01

    Acute pancreatitis may be the first manifestation of pancreatic cancer. The aim of this study was to assess the risk of pancreatic cancer after a first episode of acute pancreatitis. Between March 2004 and March 2007, all consecutive patients with a first episode of acute pancreatitis were prospectively registered. Follow-up was based on hospital records audit, radiological imaging, and patient questionnaires. Outcome was stratified based on the development of chronic pancreatitis. We included 731 patients. The median follow-up time was 55 months. Progression to chronic pancreatitis was diagnosed in 51 patients (7.0%). In this group, the incidence rate per 1000 person-years for developing pancreatic cancer was 9.0 (95% confidence interval, 2.3-35.7). In the group of 680 patients who did not develop chronic pancreatitis, the incidence rate per 1000 person-years for developing pancreatic cancer in this group was 1.1 (95% confidence interval, 0.3-3.3). Hence, the rate ratio of pancreatic cancer was almost 9 times higher in patients who developed chronic pancreatitis compared with those who did not (P = 0.049). Although a first episode of acute pancreatitis may be related to pancreatic cancer, this risk is mainly present in patients who progress to chronic pancreatitis.

  20. Dry needling in a manual physiotherapy and therapeutic exercise protocol for patients with chronic mechanical shoulder pain of unspecific origin: a protocol for a randomized control trial.

    Science.gov (United States)

    Tejera-Falcón, Emma; Toledo-Martel, Nuria Del Carmen; Sosa-Medina, Francisco Manuel; Santana-González, Fátima; Quintana-de la Fe, Miriam Del Pino; Gallego-Izquierdo, Tomás; Pecos-Martín, Daniel

    2017-09-18

    Shoulder pain of musculoskeletal origin is the main cause of upper limb pain of non-traumatic origin. Despite being one of the most common reasons for consultation, there is no established protocol for treatment due to the complexity of its etiology. However, it has been shown that the presence of myofascial trigger points on the shoulder muscles is a common condition associated with patients suffering from shoulder pain. This protocol has been created which describes the design of a randomized controlled trial to evaluate the effectiveness of the inclusion of dry needling (DN) within a protocol of manual physiotherapy and therapeutic exercise in the treatment of chronic shoulder pain of unspecific origin. Thirty-six participants aged 18-65 years will be recruited having mechanical chronic shoulder pain on unspecific origin and meeting the inclusion criteria. These will be randomized to one of two interventions, (i) DN, manual physiotherapy and therapeutic exercise or (ii) sham DN, manual physiotherapy and therapeutic exercise. The protocol will cover 6 weeks of treatment, with a 6-month follow-up. Our main outcome measure will be the Visual Analogue Scale for pain. This is the first study to combine the use of DN, manual physiotherapy and an exercise program with a 6-month follow-up, thus becoming a new contribution to the treatment of chronic shoulder pain, while new lines of research may be established to help determine the effects of DN on chronic shoulder pain and the frequency and proper dosage. International Standard Randomized Controlled Trial Number Register: ISRCTN30604244 ( http://www.controlled-trials.com ) 29 June 2016.

  1. nab-Paclitaxel plus gemcitabine for metastatic pancreatic cancer: a subgroup analysis of the Western European cohort of the MPACT trial

    Directory of Open Access Journals (Sweden)

    Tabernero J

    2017-02-01

    Full Text Available Josep Tabernero,1 Volker Kunzmann,2 Werner Scheithauer,3 Michele Reni,4 Jack Shiansong Li,5 Stefano Ferrara,6 Kamel Djazouli7 1Medical Oncology Department, Vall d’Hebron University Hospital, Barcelona, Spain; 2Medizinische Klinik und Poliklinik II, University of Würzburg, Würzburg, Germany; 3Medizinische Universität Wien, Wien, Austria; 4San Raffaele Scientific Institute, Milan, Italy; 5Celgene Corporation, Summit, NJ, USA; 6Celgene Corporation, Boudry, Switzerland; 7Celgene Corporation, Paris, France Purpose: The global Phase III MPACT trial demonstrated superior efficacy of nab-paclitaxel plus gemcitabine over gemcitabine alone as first-line treatment for metastatic pancreatic cancer. Region was a randomization stratification factor in the MPACT trial. This subgroup analysis of MPACT examined efficacy and safety of patients treated in Western Europe.Patients and methods: Patients received nab-paclitaxel plus gemcitabine or gemcitabine alone as first-line treatment for metastatic pancreatic cancer as previously described. A total of 76 patients were included in this analysis (n=38 for each arm.Results: Differences between the overall Western European cohort and the intention-to-treat population included lower percentages of male patients (46% and 58%, respectively and patients with biliary stents (8% and 17%, and higher percentages of patients with Karnofsky performance status of 90–100 (78% and 60% and primary tumors in the body of the pancreas (48% and 31%. The median overall survival was 10.7 months with nab-paclitaxel plus gemcitabine vs 6.9 months with gemcitabine alone (hazard ratio [HR]: 0.82 [95% confidence interval (CI: 0.48–1.40]; P=0.471. Median progression-free survival was 5.3 vs 3.7 months, respectively (HR: 0.70 [95% CI: 0.37–1.33]; P=0.277. The independently assessed overall response rate was 18% vs 5% (response rate ratio, 3.50 [95% CI: 0.78–15.78]; P=0.076. The most common grade ≥3 adverse events with nab

  2. Occlusion of the pancreatic duct versus pancreaticojejunostomy: a prospective randomized trial.

    NARCIS (Netherlands)

    K.T. Tran; C.H.J. van Eijck (Casper); V. di Carlo (Valerio); W.C.J. Hop (Wim); A. Zerbi (Alessandro); G. Balzano (Gianpaolo); J. Jeekel (Hans)

    2002-01-01

    textabstractOBJECTIVE: Using a prospective randomized study to assess postoperative morbidity and pancreatic function after pancreaticoduodenectomy with pancreaticojejunostomy and duct occlusion without pancreaticojejunostomy. SUMMARY BACKGROUND DATA: Postoperative complications

  3. Future long-term trials of postmenopausal hormone replacement therapy - what is possible and what is the optimal protocol and regimen?

    Science.gov (United States)

    Purbrick, B; Stranks, K; Sum, C; MacLennan, A H

    2012-06-01

    The ideal long-term, randomized, placebo-controlled trial of hormone replacement therapy (HRT) from near menopause for up to 30 years to assess major morbidity and mortality is impractical because of high cost, participant retention, therapy compliance, and continuity of research staff and funding. Also the trial regimen may become outdated. It is nihilistic to demand such a long-term trial before endorsing HRT. However, medium-term trials using surrogate measures for long-term morbidity and mortality are possible and two are near completion. If these studies have been able to maintain reasonable participant retention, therapy compliance and minimal breach of protocol, they will set standards for trials of new HRT regimens. This paper discusses lessons learnt from past attempts at long-term trials and suggests the currently optimal protocol and cost of assessing new HRT regimens to optimize potential benefits and minimize adverse effects. A 5-7-year randomized, placebo-controlled trial of a flexible transdermal estrogen regimen ± either a selective estrogen receptor modulator, e.g. bazedoxifene, or micronized progesterone is discussed. Mild to moderately symptomatic women, 1-4 years post menopause, can be recruited via general practice and group meetings. Future trials should be funded by independent agencies and are high priority in women's health.

  4. Solitary main pancreatic ductal calculus of possible biliary origin causing acute pancreatitis.

    Science.gov (United States)

    Chaparala, Ramakrishna Prasad Chowdary; Patel, Rafiuddin; Guthrie, James Ahsley; Davies, Mervyn Huw; Guillou, Pierre J; Menon, Krishna V

    2005-09-10

    Pancreatic ductal calculi are most often associated with chronic pancreatitis. Radiological features of chronic pancreatitis are readily evident in the presence of these calculi. However, acute pancreatitis due to a solitary main pancreatic ductal calculus of biliary origin is rare. A 59-year-old man presented with a first episode of acute pancreatitis. Contrast enhanced computerized tomography (CT) scan and endoscopic retrograde cholangiopancreatography (ERCP) revealed a calculus in the main pancreatic duct in the head of the pancreas causing acute pancreatitis. There were no features suggestive of chronic pancreatitis on CT scanning. The episode acute pancreatitis was managed conservatively. ERCP extraction of the calculus failed as the stone was impacted in the main pancreatic duct resulting in severe acute pancreatitis. Once this resolved, a transduodenal exploration and extraction of the pancreatic ductal calculus was performed successfully. Crystallographic analysis revealed the composition of the calculus was different to that seen in chronic pancreatitis, but more in keeping with a calculus of biliary origin. This could be explained by migration of the biliary calculus via the common channel into the main pancreatic duct. Following the operation the patient made an uneventful recovery and was well at two-year follow up. Acute pancreatitis due to a solitary main pancreatic ductal calculus of biliary origin is rare. Failing endoscopic extraction, transduodenal exploration and extraction is a safe option after resolution of acute pancreatitis.

  5. Quantifying motion for pancreatic radiotherapy margin calculation

    International Nuclear Information System (INIS)

    Whitfield, Gillian; Jain, Pooja; Green, Melanie; Watkins, Gillian; Henry, Ann; Stratford, Julie; Amer, Ali; Marchant, Thomas; Moore, Christopher; Price, Patricia

    2012-01-01

    Background and purpose: Pancreatic radiotherapy (RT) is limited by uncertain target motion. We quantified 3D patient/organ motion during pancreatic RT and calculated required treatment margins. Materials and methods: Cone-beam computed tomography (CBCT) and orthogonal fluoroscopy images were acquired post-RT delivery from 13 patients with locally advanced pancreatic cancer. Bony setup errors were calculated from CBCT. Inter- and intra-fraction fiducial (clip/seed/stent) motion was determined from CBCT projections and orthogonal fluoroscopy. Results: Using an off-line CBCT correction protocol, systematic (random) setup errors were 2.4 (3.2), 2.0 (1.7) and 3.2 (3.6) mm laterally (left–right), vertically (anterior–posterior) and longitudinally (cranio-caudal), respectively. Fiducial motion varied substantially. Random inter-fractional changes in mean fiducial position were 2.0, 1.6 and 2.6 mm; 95% of intra-fractional peak-to-peak fiducial motion was up to 6.7, 10.1 and 20.6 mm, respectively. Calculated clinical to planning target volume (CTV–PTV) margins were 1.4 cm laterally, 1.4 cm vertically and 3.0 cm longitudinally for 3D conformal RT, reduced to 0.9, 1.0 and 1.8 cm, respectively, if using 4D planning and online setup correction. Conclusions: Commonly used CTV–PTV margins may inadequately account for target motion during pancreatic RT. Our results indicate better immobilisation, individualised allowance for respiratory motion, online setup error correction and 4D planning would improve targeting.

  6. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis.

    Science.gov (United States)

    Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C; Bakker, Olaf J; van Goor, Harry; Nieuwenhuijs, Vincent B; Bollen, Thomas L; van Ramshorst, Bert; Witteman, Ben J; Brink, Menno A; Schaapherder, Alexander F; Dejong, Cornelis H; Spanier, B W Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H; Besselink, Marc G; Gooszen, Hein G; van Santvoort, Hjalmar C; Boermeester, Marja A

    2016-05-01

    Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. We performed a cross-sectional study of 669 patients with a first episode of acute pancreatitis admitted to 15 Dutch hospitals from December 2003 through March 2007. We collected information on disease course, outpatient visits, and hospital readmissions, as well as results from imaging, laboratory, and histology studies. Standardized follow-up questionnaires were sent to all available patients to collect information on hospitalizations and interventions for pancreatic disease, abdominal pain, steatorrhea, diabetes mellitus, medications, and alcohol and tobacco use. Patients were followed up for a median time period of 57 months. Primary end points were recurrent pancreatitis and CP. Risk factors were evaluated using regression analysis. The cumulative risk was assessed using Kaplan-Meier analysis. Recurrent pancreatitis developed in 117 patients (17%), and CP occurred in 51 patients (7.6%). Recurrent pancreatitis developed in 12% of patients with biliary disease, 24% of patients with alcoholic etiology, and 25% of patients with disease of idiopathic or other etiologies; CP occurred in 3%, 16%, and 10% of these patients, respectively. Etiology, smoking, and necrotizing pancreatitis were independent risk factors for recurrent pancreatitis and CP. Acute Physiology and Chronic Health Evaluation II scores at admission also were associated independently with recurrent pancreatitis. The cumulative risk for recurrent pancreatitis over 5 years was highest among smokers at 40% (compared with 13% for nonsmokers). For alcohol abusers and current smokers, the cumulative risks for CP were similar-approximately 18%. In contrast, the cumulative risk of CP increased to 30% in patients who smoked and abused alcohol. Based on a retrospective analysis of patients admitted to Dutch hospitals, a first

  7. Blockchain protocols in clinical trials: Transparency and traceability of consent [version 5; referees: 1 approved, 2 approved with reservations, 2 not approved

    Directory of Open Access Journals (Sweden)

    Mehdi Benchoufi

    2018-02-01

    Full Text Available Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again.  We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security

  8. Blockchain protocols in clinical trials: Transparency and traceability of consent [version 4; referees: 1 approved, 2 approved with reservations, 2 not approved

    Directory of Open Access Journals (Sweden)

    Mehdi Benchoufi

    2017-12-01

    Full Text Available Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing for collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we build a consent workflow using a trending technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain, thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each protocol revision, consent was sought again.  We obtained a single document, in an open format, that accounted for the whole consent collection process: a time-stamped consent status regarding each version of the protocol. This document cannot be corrupted and can be checked on any dedicated public website. It should be considered a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened to remove the need for third parties, here trial stakeholders, and give participative control to the peer users. In the future, the complex data flow of a clinical trial could be tracked by using Blockchain, which core functionality, named Smart Contract, could help prevent clinical trial events not occurring in the correct chronological order, for example including patients before they consented or analysing case report form data before freezing the database. Globally, Blockchain could help with reliability, security

  9. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is defined as ... pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for almost 1 ...

  10. A Randomized Trial Comparing Two Tongue-Pressure Resistance Training Protocols for Post-Stroke Dysphagia.

    Science.gov (United States)

    Steele, Catriona M; Bayley, Mark T; Peladeau-Pigeon, Melanie; Nagy, Ahmed; Namasivayam, Ashwini M; Stokely, Shauna L; Wolkin, Talia

    2016-06-01

    The objective of this study was to compare the outcomes of two tongue resistance training protocols. One protocol ("tongue-pressure profile training") emphasized the pressure-timing patterns that are typically seen in healthy swallows by focusing on gradual pressure release and saliva swallowing tasks. The second protocol ("tongue-pressure strength and accuracy training") emphasized strength and accuracy in tongue-palate pressure generation and did not include swallowing tasks. A prospective, randomized, parallel allocation trial was conducted. Of 26 participants who were screened for eligibility, 14 received up to 24 sessions of treatment. Outcome measures of posterior tongue strength, oral bolus control, penetration-aspiration and vallecular residue were made based on videofluoroscopy analysis by blinded raters. Complete data were available for 11 participants. Significant improvements were seen in tongue strength and post-swallow vallecular residue with thin liquids, regardless of treatment condition. Stage transition duration (a measure of the duration of the bolus presence in the pharynx prior to swallow initiation, which had been chosen to capture impairments in oral bolus control) showed no significant differences. Similarly, significant improvements were not seen in median scores on the penetration-aspiration scale. This trial suggests that tongue strength can be improved with resistance training for individuals with tongue weakness following stroke. We conclude that improved penetration-aspiration does not necessarily accompany improvements in tongue strength; however, tongue-pressure resistance training does appear to be effective for reducing thin liquid vallecular residue.

  11. Circumportal Pancreas-a Must Know Pancreatic Anomaly for the Pancreatic Surgeon.

    Science.gov (United States)

    Luu, Andreas Minh; Braumann, C; Herzog, T; Janot, M; Uhl, W; Chromik, A M

    2017-02-01

    Circumportal pancreas is a rare congenital pancreatic anomaly with encasement of the portal vein and/or the superior mesenteric vein by pancreatic tissue. It is often overlooked on cross-sectional imaging studies and can be encountered during pancreatic surgery. Pancreatic head resection with circumportal pancreas is technically difficult and bears an increased risk of postoperative pancreatic fistula. A retrospective chart review of our data base for all patients who had undergone pancreatic head resection between 2004 and 2015 was performed. We identified six patients out of 1102 patients who had undergone pancreatic head surgery in the study period. CT-scan and MRI were never able to identify circumportal pancreas prior to surgery. The right hepatic an artery derived from the superior mesenteric artery in four cases (67%). Additional resection of the pancreatic body was always performed. Postoperative course was uneventful in all cases without occurrence of pancreatic fistula. Circumportal pancreas is a rare entity every pancreatic surgeon should be aware of. It is difficult to identify on cross-sectional imaging studies. A right hepatic artery arising from the superior mesenteric artery should raise suspicion of circumportal pancreas. Additional pancreatic tissue resection should be performed during pancreatic head resections to avoid pancreatic fistula.

  12. Chronic Pancreatitis and Pancreatic Cancer Risk: A Systematic Review and Meta-analysis.

    Science.gov (United States)

    Kirkegård, Jakob; Mortensen, Frank Viborg; Cronin-Fenton, Deirdre

    2017-09-01

    Chronic pancreatitis is a putative risk factor for pancreatic cancer. The aim of this study was to examine the magnitude and temporality of this association. We searched MEDLINE and EMBASE for observational studies investigating the association between chronic pancreatitis and pancreatic cancer. We computed overall effect estimates (EEs) with associated 95% confidence intervals (CIs) using a random-effects meta-analytic model. The EEs were stratified by length of follow-up from chronic pancreatitis diagnosis to pancreatic cancer (lag period). Robustness of the results was examined in sensitivity analyses. We identified 13 eligible studies. Pooled EEs for pancreatic cancer in patients with chronic pancreatitis were 16.16 (95% CI: 12.59-20.73) for patients diagnosed with pancreatic cancer within 2 years from their chronic pancreatitis diagnosis. The risk of pancreatic cancer in patients with chronic pancreatitis decreased when the lag period was increased to 5 years (EE: 7.90; 95% CI: 4.26-14.66) or a minimum of 9 years (EE: 3.53; 95% CI: 1.69-7.38). In conclusion, chronic pancreatitis increases the risk of pancreatic cancer, but the association diminishes with long-term follow-up. Five years after diagnosis, chronic pancreatitis patients have a nearly eight-fold increased risk of pancreatic cancer. We suggest that common practice on inducing a 2-year lag period in these studies may not be sufficient. We also recommend a close follow-up in the first years following a diagnosis of chronic pancreatitis to avoid overlooking a pancreatic cancer.

  13. Pancreatic Cancer

    Science.gov (United States)

    ... hormones that help control blood sugar levels. Pancreatic cancer usually begins in the cells that produce the juices. Some risk factors for developing pancreatic cancer include Smoking Long-term diabetes Chronic pancreatitis Certain ...

  14. Targeted Inhibition of Pancreatic Acinar Cell Calcineurin Is a Novel Strategy to Prevent Post-ERCP PancreatitisSummary

    Directory of Open Access Journals (Sweden)

    Abrahim I. Orabi

    2017-01-01

    Full Text Available Background & Aims: There is a pressing need to develop effective preventative therapies for post–endoscopic retrograde cholangiopancreatography pancreatitis (PEP. We showed that early PEP events are induced through the calcium-activated phosphatase calcineurin and that global calcineurin deletion abolishes PEP in mice. A crucial question is whether acinar cell calcineurin controls the initiation of PEP in vivo. Methods: We used a mouse model of PEP and examined the effects of in vivo acinar cell-specific calcineurin deletion by either generating a conditional knockout line or infusing a novel adeno-associated virus–pancreatic elastase improved Cre (I–iCre into the pancreatic duct of a calcineurin floxed line. Results: We found that PEP is dependent on acinar cell calcineurin in vivo, and this led us to determine that calcineurin inhibitors, infused within the radiocontrast, largely can prevent PEP. Conclusions: These results provide the impetus for launching clinical trials to test the efficacy of intraductal calcineurin inhibitors to prevent PEP. Keywords: Adeno-Associated Virus, Calcineurin B1, FK506, Cyclosporine A, Intraductal Delivery

  15. Soluble E-Cadherin: An Early Marker of Severity in Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    A. Sewpaul

    2009-01-01

    Full Text Available Background/Aims. At present, there is no simple test for predicting severity in acute pancreatitis. We investigated the use of an assay of soluble E-cadherin (sE-cadherin. Methods. Concentrations of sE-cadherin, from 19 patients with mild acute pancreatitis, 7 patients with severe acute pancreatitis, 11 patients with other acute gastrointestinal pathologies, and 12 healthy subjects were measured using a commercially available sandwich ELISA kit based on two monoclonal antibodies specific to the extracellular fragment of human E-cadherin. Measurements were made at 12 hours or less from onset of pain and also at 24 and 48 hours after onset of pain. Results. Mean (standard deviation concentration of sE-cadherin in patients with severe acute pancreatitis at <12 hours was 17780 ng/mL (7853, significantly higher than that of healthy volunteers 5180 ng/mL (1350, =.0039, patients with other gastrointestinal pathologies 7358 ng/mL (6655, =.0073, and also significantly higher than that of patients with mild pancreatitis, 7332 ng/mL (2843, =.0019. Discussion. Serum sE-cadherin could be an early (within 12 hours objective marker of severity in acute pancreatitis. This molecule warrants further investigation in the form of a large multicentre trial.

  16. Pancreatic Cysts

    Science.gov (United States)

    ... enzymes become prematurely active and irritate the pancreas (pancreatitis). Pseudocysts can also result from injury to the ... alcohol use and gallstones are risk factors for pancreatitis, and pancreatitis is a risk factor for pseudocysts. ...

  17. Dendritic Cells Promote Pancreatic Viability in Mice with Acute Pancreatitis

    Science.gov (United States)

    Bedrosian, Andrea S.; Nguyen, Andrew H.; Hackman, Michael; Connolly, Michael K.; Malhotra, Ashim; Ibrahim, Junaid; Cieza-Rubio, Napoleon E.; Henning, Justin R.; Barilla, Rocky; Rehman, Adeel; Pachter, H. Leon; Medina-Zea, Marco V.; Cohen, Steven M.; Frey, Alan B.; Acehan, Devrim; Miller, George

    2011-01-01

    Background & Aims Acute pancreatitis increases morbidity and mortality from organ necrosis by mechanisms that are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. Methods Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier analysis. Results Numbers of MHC II+CD11c+DC increased 100-fold in pancreas of mice with acute pancreatitis, to account for nearly 15% of intra-pancreatic leukocytes. Intra-pancreatic DC acquired an immune phenotype in mice with acute pancreatitis; they expressed higher levels of MHC II and CD86 and increased production of interleukin-6, membrane cofactor protein (MCP)-1, and tumor necrosis factor (TNF)-α. However, rather than inducing an organ-destructive inflammatory process, DC were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DC and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DC died from acinar cell death within 4 days. Depletion of DC from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DC did not require infiltrating neutrophils, activation of NF-κB, or signaling by mitogen-activated protein kinase or TNF-α. Conclusions DC are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress. PMID:21801698

  18. The effect of moderate sedation on exocrine pancreas function in normal healthy subjects: a prospective, randomized, cross-over trial using the synthetic porcine secretin stimulated Endoscopic Pancreatic Function Test (ePFT).

    Science.gov (United States)

    Conwell, Darwin L; Zuccaro, Gregory; Purich, Edward; Fein, Seymor; Vanlente, Frederick; Vargo, John; Dumot, John; O'laughlin, Cathy; Trolli, Patricia

    2005-05-01

    We have developed a purely endoscopic collection method for the assessment of pancreatic secretory function (ePFT). The pancreatic secretory effects of sedation medications utilized during endoscopic procedures are not completely known. To study the effect of moderate sedation on the exocrine pancreas gland in a prospective, randomized trial. Healthy volunteers were randomized by computers to one of two treatments (A-no sedation, B-sedation) in period 1 and crossed-over to the other treatment in period 2 with a minimal washout interval of 7 days. Sedation dosage was standardized for each patient based on age, gender and weight from a previously published dosing nomogram. Synthetic porcine secretin (ChiRhoClin, Inc., Burtonsville, Maryland) was used as the pancreatic stimulant. Duodenal fluid samples were aspirated via the endoscope every 5 min for 1 h and sent on ice to our hospital laboratory for the measurement of pancreatic secretory electrolyte concentrations by autoanalyzer. A total of 17 healthy volunteers were enrolled. Sixteen subjects (8 males and 8 females) completed the randomized prospective trial. Median intravenous meperidine and midazolam sedation dose was 62.5 mg and 2.5 mg, respectively. Maximum pancreatic juice flow occurred during the early phase of secretion and maximum bicarbonate concentration occurred during the late phase of secretion. Analysis of the electrolyte composition of the endoscopically collected duodenal drainage fluid revealed a constant cation concentration for both sodium and potassium over the 1 h collection period. The anions, chloride and bicarbonate, exhibited a reciprocal relationship identical to that seen in traditional gastroduodenal tube collection studies. There was no statistical difference observed between the sedation and no sedation groups. The estimated total bicarbonate output (area under curve, AUC) for the sedated and non-sedated groups were 5,017 meq + 724 (range 3,663-6,173) and 5,364 meq +/- 583 (range 4

  19. Laparoscopic pancreatic cystogastrostomy.

    Science.gov (United States)

    Obermeyer, Robert J; Fisher, William E; Salameh, Jihad R; Jeyapalan, Manjula; Sweeney, John F; Brunicardi, F Charles

    2003-08-01

    The purpose of the review was to evaluate the feasibility and outcome of laparoscopic pancreatic cystogastrostomy for operative drainage of symptomatic pancreatic pseudocysts. A retrospective review of all patients who underwent laparoscopic pancreatic cystogastrostomy between June 1997 and July 2001 was performed. Data regarding etiology of pancreatitis, size of pseudocyst, operative time, complications, and pseudocyst recurrence were collected and reported as median values with ranges. Laparoscopic pancreatic cystogastrostomy was attempted in 6 patients. Pseudocyst etiology included gallstone pancreatitis (3), alcohol-induced pancreatitis (2), and post-ERCP pancreatitis (1). The cystogastrostomy was successfully performed laparoscopically in 5 of 6 patients. However, the procedure was converted to open after creation of the cystgastrostomy in 1 of these patients. There were no complications in the cases completed laparoscopically and no deaths in the entire group. No pseudocyst recurrences were observed with a median followup of 44 months (range 4-59 months). Laparoscopic pancreatic cystgastrostomy is a feasible surgical treatment of pancreatic pseudocysts with a resultant low pseudocyst recurrence rate, length of stay, and low morbidity and mortality.

  20. [Surgical treatment of chronic pancreatitis, 2010].

    Science.gov (United States)

    Farkas, Gyula

    2011-04-01

    Chronic pancreatitis (CP) is a benign inflammatory process, which can cause enlargement of the pancreatic head accompanied by severe pain and weight loss, and often leads to a significant reduction in quality of life (QoL). Basically, the disease is characterised by pain and functional disorders which are initially treated with conservative therapy, but in case of complications (uncontrollable pain or obstruction) surgical treatment is required. This article reviews the relevant literature of CP treatment, in particular randomized controlled trials and meta-analyses were involved with a comparison of different surgical treatment options for the management of CP complications. Recent studies have demonstrated that surgical procedures are superior to endoscopic therapy as regards long-term results of QoL and pain control. There was no significant difference found in postoperative pain relief and overall mortality when duodenum-preserving pancreatic head resection (DPPHR) of Beger and its modification (duodenum and organ-preserving pancreatic head resection [DOPPHR]) were compared with pancreatoduodenectomy (PD), but hospital stay, weight gain, exocrine and endocrine insufficiency, and QoL were significantly better in the DPPHR and DOPPHR groups. DPPHR and PD seem to be equally effective in terms of postoperative pain relief and overall mortality. However, recent data suggest that DOPPHR is superior in the treatment of CP with regard to several peri- and postoperative outcome parameters and QoL. Therefore, this should be the preferable treatment option for CP complications.

  1. [Pancreatic anastomosis in operative treatment of chronic pancreatitis].

    Science.gov (United States)

    Bellon, E; Izbicki, J R; Bockhorn, M

    2017-01-01

    Chronic pancreatitis (CP) is an irreversible, inflammatory process, which is characterized by progressive fibrosis of the pancreas and leads to abdominal pain, endocrine and exocrine insufficiency. Surgical therapy is indicated by the absence of pain relief and local complications. The target of the surgical approach is to relieve the pancreatic and bile ducts and resection of the fibrotic and calcified parenchyma. Drainage procedures, such as the Partington-Rochelle method, are used in patients with isolated congestion of the pancreatic duct without further organ complications, such as inflammatory processes of the pancreatic head; however, patients with CP often have an inflammatory swelling of the pancreatic head. In this case classical pancreatoduodenectomy (PD) or organ-sparing duodenum-preserving pancreatic head resection (DPPHR) with its various techniques (e.g. Beger, Frey, Bern and V‑shape) can be applied. Due to similar long-term results PD should be carried out in cases of suspicion or detection of malignancies and DPPHR for treatment of CP.

  2. Aberrant glycogen synthase kinase 3β in the development of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Takeo Shimasaki

    2012-01-01

    Full Text Available Development and progression of pancreatic cancer involves general metabolic disorder, local chronic inflammation, and multistep activation of distinct oncogenic molecular pathways. These pathologic processes result in a highly invasive and metastatic tumor phenotype that is a major obstacle to curative surgical intervention, infusional gemcitabine-based chemotherapy, and radiation therapy. Many clinical trials with chemical compounds and therapeutic antibodies targeting growth factors, angiogenic factors, and matrix metalloproteinases have failed to demonstrate definitive therapeutic benefits to refractory pancreatic cancer patients. Glycogen synthase kinase 3β (GSK3β, a serine/threonine protein kinase, has emerged as a therapeutic target in common chronic and progressive diseases, including cancer. Here we review accumulating evidence for a pathologic role of GSK3β in promoting tumor cell survival, proliferation, invasion, and resistance to chemotherapy and radiation in pancreatic cancer. We also discuss the putative involvement of GSK3β in mediating metabolic disorder, local inflammation, and molecular alteration leading to pancreatic cancer development. Taken together, we highlight potential therapeutic as well as preventive effects of GSK3β inhibition in pancreatic cancer.

  3. Incidence of and risk factors for developing pancreatic cancer in patients with chronic pancreatitis.

    Science.gov (United States)

    Kudo, Yujin; Kamisawa, Terumi; Anjiki, Hajime; Takuma, Kensuke; Egawa, Naoto

    2011-01-01

    Pancreatic cancer sometimes occurs during the course of chronic pancreatitis. This study aimed to identify risk factors for developing pancreatic cancer associated with chronic pancreatitis. The incidence of pancreatic cancer developing in 218 patients with chronic pancreatitis and clinical features of the chronic pancreatitis patients who developed pancreatic cancer were studied. Nine patients developed pancreatic cancer. Average period from the diagnosis of chronic pancreatitis to the diagnosis of pancreatic cancer was 9.6 years. All pancreatic cancers were diagnosed at an advanced stage. Only 2 patients had been followed-up periodically. There were no significant differences between chronic pancreatitis patients who developed pancreatic cancer and those who did not in male/female ratio (3.5 vs. 8), average age on diagnosis (65.0 vs. 56.5), alcoholic/non-alcoholic chronic pancreatitis (1.6 vs. 2.6), smoking habits (62.5% vs. 70.7%), diabetes mellitus (77.8% vs. 54.4%), and continued alcohol drinking (37.5% vs. 53.1%). Over the period examined, 4% of chronic pancreatitis patients developed pancreatic cancer. Sex ratio, onset age, etiology, smoking habits, diabetes mellitus, and continued alcohol drinking were not significant risk factors for developing pancreatic cancer in chronic pancreatitis patients. Periodic follow-up due to the possibility of pancreatic cancer is necessary in chronic pancreatitis patients.

  4. Normal pancreatic exocrine function does not exclude MRI/MRCP chronic pancreatitis findings.

    Science.gov (United States)

    Alkaade, Samer; Cem Balci, Numan; Momtahen, Amir Javad; Burton, Frank

    2008-09-01

    Abnormal pancreatic function tests have been reported to precede the imaging findings of chronic pancreatitis. Magnetic resonance imaging (MRI) with magnetic resonance cholangiopancreatography (MRCP) is increasingly accepted as the primary imaging modality for the detection of structural changes of early mild chronic pancreatitis. The aim of this study was to evaluate MRI/MRCP findings in patients with symptoms consistent with chronic pancreatitis who have normal Secretin Endoscopic Pancreatic Function test. A retrospective study of 32 patients referred for evaluation of chronic abdominal pain consistent with chronic pancreatitis and reported normal standard abdominal imaging (ultrasound, computed tomography, or MRI). All patients underwent Secretin Endoscopic Pancreatic Function testing and pancreatic MRI/MRCP at our institution. We reviewed the MRI/MRCP images in patients who had normal Secretin Endoscopic Pancreatic Function testing. MRI/MRCP images were assessed for pancreatic duct morphology, gland size, parenchymal signal and morphology, and arterial contrast enhancement. Of the 32 patients, 23 had normal Secretin Endoscopic Pancreatic Function testing, and 8 of them had mild to marked spectrum of abnormal MRI/MRCP findings that were predominantly focal. Frequencies of the findings were as follows: pancreatic duct stricture (n=3), pancreatic duct dilatation (n=3), side branch ectasia (n=4), atrophy (n=5), decreased arterial enhancement (n=5), decreased parenchymal signal (n=1), and cavity formation (n=1). The remaining15 patients had normal pancreatic structure on MRI/MRCP. Normal pancreatic function testing cannot exclude abnormal MRI/MRCP especially focal findings of chronic pancreatitis. Further studies needed to verify significance of these findings and establish MRI/MRCP imaging criteria for the diagnosis of chronic pancreatitis.

  5. Efficacy of pancreatic enzyme replacement therapy in chronic pancreatitis: systematic review and meta-analysis.

    Science.gov (United States)

    de la Iglesia-García, Daniel; Huang, Wei; Szatmary, Peter; Baston-Rey, Iria; Gonzalez-Lopez, Jaime; Prada-Ramallal, Guillermo; Mukherjee, Rajarshi; Nunes, Quentin M; Domínguez-Muñoz, J Enrique; Sutton, Robert

    2017-08-01

    The benefits of pancreatic enzyme replacement therapy (PERT) in chronic pancreatitis (CP) are inadequately defined. We have undertaken a systematic review and meta-analysis of randomised controlled trials of PERT to determine the efficacy of PERT in exocrine pancreatic insufficiency (EPI) from CP. Major databases were searched from 1966 to 2015 inclusive. The primary outcome was coefficient of fat absorption (CFA). Effects of PERT versus baseline and versus placebo, and of different doses, formulations and schedules were determined. A total of 17 studies (511 patients with CP) were included and assessed qualitatively (Jadad score). Quantitative data were synthesised from 14 studies. PERT improved CFA compared with baseline (83.7±6.0 vs 63.1±15.0, pregression analyses revealed that sample size, CP diagnostic criteria, study design and enzyme dose contributed to heterogeneity; data on health inequalities were lacking. PERT is indicated to correct EPI and malnutrition in CP and may be improved by higher doses, enteric coating, administration during food and acid suppression. Further studies are required to determine optimal regimens, the impact of health inequalities and long-term effects on nutrition. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

  6. Surgery of malignant pancreatic tumors

    International Nuclear Information System (INIS)

    Loos, M.; Friess, H.; Kleeff, J.

    2009-01-01

    Ductal adenocarcinoma is the most common malignant tumor of the pancreas. Despite great efforts in basic and clinical pancreatic cancer research, the prognosis remains poor with an overall 5-year survival rate of less than 5%. Complete surgical resection represents the only curative treatment option and 5-year survival rates of 20-25% can be achieved following curative resection and adjuvant chemotherapy. Although pancreatic surgery is considered one of the most technically demanding and challenging procedures, there has been constant progress in surgical techniques and advances in perioperative care with a modern interdisciplinary approach including anesthesiology, oncology, radiology and nursing. This has reduced morbidity and especially mortality rates in high-volume centers. Among extended resection procedures multivisceral and venous resections are technically feasible and should be considered if a complete tumor resection can be achieved. Multimodal regimens have shown promising results, however, only adjuvant chemotherapy is supported by solid evidence from randomized controlled trials. (orig.) [de

  7. Simultaneous characterization of pancreatic stellate cells and other pancreatic components within three-dimensional tissue environment during chronic pancreatitis

    Science.gov (United States)

    Hu, Wenyan; Fu, Ling

    2013-05-01

    Pancreatic stellate cells (PSCs) and other pancreatic components that play a critical role in exocrine pancreatic diseases are generally identified separately by conventional studies, which provide indirect links between these components. Here, nonlinear optical microscopy was evaluated for simultaneous characterization of these components within a three-dimensional (3-D) tissue environment, primarily based on multichannel detection of intrinsic optical emissions and cell morphology. Fresh rat pancreatic tissues harvested at 1 day, 7 days, and 28 days after induction of chronic pancreatitis were imaged, respectively. PSCs, inflammatory cells, blood vessels, and collagen fibers were identified simultaneously. The PSCs at day 1 of chronic pancreatitis showed significant enlargement compared with those in normal pancreas (ppancreatic components coincidently within 3-D pancreatic tissues. It is a prospect for intravital observation of dynamic events under natural physiological conditions, and might help uncover the key mechanisms of exocrine pancreatic diseases, leading to more effective treatments.

  8. Determining the Optimal Protocol for Measuring an Albuminuria Class Transition in Clinical Trials in Diabetic Kidney Disease

    DEFF Research Database (Denmark)

    Kröpelin, Tobias F; de Zeeuw, Dick; Remuzzi, Giuseppe

    2016-01-01

    Albuminuria class transition (normo- to micro- to macroalbuminuria) is used as an intermediate end point to assess renoprotective drug efficacy. However, definitions of such class transition vary between trials. To determine the most optimal protocol, we evaluated the approaches used in four...... effect increased (decreased precision) with stricter end point definitions, resulting in a loss of statistical significance. In conclusion, the optimal albuminuria transition end point for use in drug intervention trials can be determined with a single urine collection for albuminuria assessment per...... clinical trials testing the effect of renin-angiotensin-aldosterone system intervention on albuminuria class transition in patients with diabetes: the BENEDICT, the DIRECT, the ALTITUDE, and the IRMA-2 Trial. The definition of albuminuria class transition used in each trial differed from the definitions...

  9. Pancreatic stellate cells promote epithelial-mesenchymal transition in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Kikuta, Kazuhiro; Masamune, Atsushi; Watanabe, Takashi; Ariga, Hiroyuki; Itoh, Hiromichi; Hamada, Shin; Satoh, Kennichi; Egawa, Shinichi; Unno, Michiaki; Shimosegawa, Tooru

    2010-01-01

    Research highlights: → Recent studies have shown that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. → Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and scattered, fibroblast-like appearance. → PSCs decreased the expression of epithelial markers but increased that of mesenchymal markers, along with increased migration. → This study suggests epithelial-mesenchymal transition as a novel mechanism by which PSCs contribute to the aggressive behavior of pancreatic cancer cells. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Because epithelial-mesenchymal transition (EMT) plays a critical role in the progression of pancreatic cancer, we hypothesized that PSCs promote EMT in pancreatic cancer cells. Panc-1 and SUIT-2 pancreatic cancer cells were indirectly co-cultured with human PSCs isolated from patients undergoing operation for pancreatic cancer. The expression of epithelial and mesenchymal markers was examined by real-time PCR and immunofluorescent staining. The migration of pancreatic cancer cells was examined by scratch and two-chamber assays. Pancreatic cancer cells co-cultured with PSCs showed loose cell contacts and a scattered, fibroblast-like appearance. The expression of E-cadherin, cytokeratin 19, and membrane-associated β-catenin was decreased, whereas vimentin and Snail (Snai-1) expression was increased more in cancer cells co-cultured with PSCs than in mono-cultured cells. The migration of pancreatic cancer cells was increased by co-culture with PSCs. The PSC-induced decrease of E-cadherin expression was not altered by treatment with anti

  10. Protective effect of bacillopeptidase CFR5 from Bacillus subtilis CFR5 on cerulein-induced pancreatitis.

    Science.gov (United States)

    Sharmila, G R; Venkateswaran, G

    2017-09-16

    Bacillopeptidase is a serine peptidase, known for its fibrinolytic activity. However, a very little information is known about its in vivo inflammatory and/or anti-inflammatory properties. Thus, to understand whether bacillopeptidase incorporation can regulate pancreatitis or not, the cerulein-induced pancreatitis model was used, and the role of bacillopeptidase on pancreatitis was studied. In this study, 46 kDa protein was purified from Bacillus subtilis and identified as bacillopeptidase CFR5 (BPC) through MS/MS analysis. The nutritional prophylactic group was orally fed with two doses of BPC (100 μg/Kg/BW of rat) 6 h before cerulein administration and analyzed for its effect on intestine and pancreas inflammation, cytokines, and pancreatitis marker gene expression. BPC administration significantly reduced the severity of pancreatitis by decreasing serum amylase, lipase, pancreatic edema and myeloperoxidase activity. The pretreatment with BPC suppressed the pancreatic pro-inflammatory and inflammatory cytokines production including IL-6, IL-1β, TNF-α, IL-2, IL-4, IL-5, IL-10, and IL-13 in both pancreas and serum samples. Moreover, BPC supplementation restored pancreatitis mediated disruption of intestinal barrier integrity by upregulating tight junction proteins (ZO-1, occludin), antimicrobial peptides (DEFB1, CRAMP), MUC-2, TFF3 expression and by enhancing SCFA's production. Pretreatment with BPC suppressed the intestinal inflammation with reduced cytokines production in the colon and ileal region of cerulein-induced pancreatitis. Thus, BPC based pretreatment protocol is a novel intervention to prevent acute pancreatitis. Copyright © 2017 Elsevier Inc. All rights reserved.

  11. Chinese Herbal Medicines as an Adjunctive Therapy for Unresectable Pancreatic Cancer: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Bin Li

    2015-01-01

    Full Text Available Pancreatic cancer is a common malignancy with a high mortality. Most patients present clinically with advanced pancreatic cancer. Moreover, the effect of radiotherapy or chemotherapy is limited. Complementary and alternative medicines represent exciting adjunctive therapies. In this study, we ascertained the beneficial and adverse effects of Chinese herbal medicine (CHM in combination with conventional therapy for inoperable pancreatic cancer by using meta-analysis methods for controlled clinical trials. We extracted data for studies searched from six electronic databases that were searched and also assessed the methodological quality of the included studies. We evaluated the following outcome measures: 6-month and 1-year survival rate, objective response rate, disease control rate, quality of life, and adverse effects. The final analysis showed CHM is a promising strategy as an adjunctive therapy to treat advanced or inoperable pancreatic cancer and that CHM in combination with conventional therapy is a promising strategy for resistant disease. However, convincing evidence must be obtained and confirmed by high-quality trials in future studies.

  12. The Effect of Preoperative Oral Immunonutrition on Complications and Length of Hospital Stay After Elective Surgery for Pancreatic Cancer--A Randomized Controlled Trial

    DEFF Research Database (Denmark)

    Gade, Josephine; Wilkens, Trine Levring; Hillingsø, Jens

    2016-01-01

    Major gastrointestinal surgery is associated with immune suppression and a high risk of postoperative complications. The aim of this open, randomized controlled trial was to examine the effect of supplementary per oral immunonutrition (IN) seven days before surgery for pancreatic cancer (PC......) on postoperative complications and length of hospital stay (LOS). Secondary outcomes were the changes in functional capability and body weight (BW). Consecutive patients referred for surgery for diagnosed or plausible PC were included. The patients in the intervention group received supplementary IN (Oral Impact...

  13. [External pancreatic fistulas management].

    Science.gov (United States)

    Stepan, E V; Ermolov, A S; Rogal', M L; Teterin, Yu S

    The main principles of treatment of external postoperative pancreatic fistulas are viewed in the article. Pancreatic trauma was the reason of pancreatic fistula in 38.7% of the cases, operations because of acute pancreatitis - in 25.8%, and pancreatic pseudocyst drainage - in 35.5%. 93 patients recovered after the treatment. Complex conservative treatment of EPF allowed to close fistulas in 74.2% of the patients with normal patency of the main pancreatic duct (MPD). The usage of octreotide 600-900 mcg daily for at least 5 days to decrease pancreatic secretion was an important part of the conservative treatment. Endoscopic papillotomy was performed in patients with major duodenal papilla obstruction and interruption of transporting of pancreatic secretion to duodenum. Stent of the main pancreatic duct was indicated in patients with extended pancreatic duct stenosis to normalize transport of pancreatic secretion to duodenum. Surgical formation of anastomosis between distal part of the main pancreatic duct and gastro-intestinal tract was carried out when it was impossible to fulfill endoscopic stenting of pancreatic duct either because of its interruption and diastasis between its ends, or in the cases of unsuccessful conservative treatment of external pancreatic fistula caused by drainage of pseudocyst.

  14. A cluster randomised controlled trial of advice, exercise or multifactorial assessment to prevent falls and fractures in community-dwelling older adults: protocol for the prevention of falls injury trial (PreFIT).

    Science.gov (United States)

    Bruce, Julie; Lall, Ranjit; Withers, Emma J; Finnegan, Susanne; Underwood, Martin; Hulme, Claire; Sheridan, Ray; Skelton, Dawn A; Martin, Finbarr; Lamb, Sarah E

    2016-01-18

    Falls are the leading cause of accident-related mortality in older adults. Injurious falls are associated with functional decline, disability, healthcare utilisation and significant National Health Service (NHS)-related costs. The evidence base for multifactorial or exercise interventions reducing fractures in the general population is weak. This protocol describes a large-scale UK trial investigating the clinical and cost-effectiveness of alternative falls prevention interventions targeted at community dwelling older adults. A three-arm, pragmatic, cluster randomised controlled trial, conducted within primary care in England, UK. Sixty-three general practices will be randomised to deliver one of three falls prevention interventions: (1) advice only; (2) advice with exercise; or (3) advice with multifactorial falls prevention (MFFP). We aim to recruit over 9000 community-dwelling adults aged 70 and above. Practices randomised to deliver advice will mail out advice booklets. Practices randomised to deliver 'active' interventions, either exercise or MFFP, send all trial participants the advice booklet and a screening survey to identify participants with a history of falling or balance problems. Onward referral to 'active' intervention will be based on falls risk determined from balance screen. The primary outcome is peripheral fracture; secondary outcomes include number with at least one fracture, falls, mortality, quality of life and health service resource use at 18 months, captured using self-report and routine healthcare activity data. The study protocol has approval from the National Research Ethics Service (REC reference 10/H0401/36; Protocol V.3.1, 21/May/2013). User groups and patient representatives were consulted to inform trial design. Results will be reported at conferences and in peer-reviewed publications. A patient-friendly summary of trial findings will be published on the prevention of falls injury trial (PreFIT) website. This protocol adheres to the

  15. Eosinophilic Pancreatitis: A Rare Cause of Recurrent Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Jennifer Reppucci

    2017-03-01

    Full Text Available Eosinophilic pancreatitis is a rare form of recurrent acute pancreatitis that demonstrates distinct histologic features, including diffuse, periductal, acinar, and septal inflammatory infiltrates comprised of a pure or predominant population of eosinophils, eosinophilic phlebitis and arteritis, and localized eosinophilic infiltrates with pseudocyst formation. It is associated with elevated serum immunoglobulin E levels, an elevated eosinophil count with systemic manifestations, and eosinophilic infiltrates in other organs of the gastrointestinal tract. We present a case of eosinophilic pancreatitis in a 44-year-old man who was diagnosed after pancreatic resection for recurrent bouts of acute pancreatitis. While the gross and histologic evaluations matched other reported cases of eosinophilic pancreatitis, our patient had only minimal peripheral eosinophilia, no reported history of symptoms related to elevated eosinophilia or immunoglobulin E, and only mild eosinophilic infiltrates in his gallbladder.

  16. Progressive loss of pancreatic function in chronic pancreatitis is delayed by main pancreatic duct decompression. A longitudinal prospective analysis of the modified puestow procedure.

    Science.gov (United States)

    Nealon, W H; Thompson, J C

    1993-05-01

    This study evaluated the effect of operative drainage of the main pancreatic duct (MPD) on functional derangements associated with chronic pancreatitis (CP). The author previously reported delayed functional impairment in an evaluation of the impact of operative drainage in patients with CP. The author now reports on a prospective study of 143 patients with this diagnosis. Each patient underwent 1) ERCP, 2) the Bentiromide PABA, 3) 72-hour fecal fat test, 4) oral glucose tolerance test (OGTT) and 5) fat meal (LIPOMUL)--stimulated pancreatic polypeptide release (PP). All patients were stratified as mild/moderate (M/M) or severe CP on the basis of a 5-point system that was developed by the author. Patients were studied at 16-month intervals. All 143 patients underwent initial and follow-up evaluations in a mean follow-up of 47.3 months; 83 of 143 patients had M/M grade at initial evaluation. Eighty-seven patients underwent (MPD) decompression to relieve abdominal pain. In a separate prospective 17 patients with a diagnosis of CP, a grade of M/M and non-disabling abdominal pain were randomized to operative or non-operative treatment; 9 of these randomized patients were operated upon and 8 were not. No patient improved their grade during follow-up; 47 of 83 M/M patients had operative drainage and 36 did not. This grade was preserved in 41 of 47 (87%) operated patients but in only 8 of the 36 non-operated patients (22%). In the randomized trial, seven of nine operated patients retained their functional status in follow-up, whereas only two of eight patients (25%) randomized to non-operation preserved their functional grade. These data in this large study as well as among a previous randomized sample, support a policy of early operative drainage before the development of irreversible functional impairment in patients with chronic pancreatitis and associated dilation of the main pancreatic duct.

  17. Pancreatic panniculitis associated with acute pancreatitis and hemorrhagic pseudocysts: A case report

    International Nuclear Information System (INIS)

    Jang, Yong Suk; Kim, Mi Sung; Park, Chan Sub; Park, Ji Yeon; Park, Noh Hyuck

    2012-01-01

    Pancreatic panniculitis is an inflammation and necrosis of fat at distant foci in patients with pancreatic disorders, most frequently, pancreatitis and pancreatic carcinoma. Clinically, pancreatic panniculitis is manifested by painless or painful subcutaneous nodules on the legs, buttocks, or trunk. The usual sites are the distal parts of the lower extremities. To the best of our knowledge, there have not been many reports for the radiologic findings of pancreatic panniculitis. In this article, we report a case of pancreatic panniculitis, including radiologic findings of CT and ultrasonography. The patient was presented with painful subcutaneous nodules on the trunk, and had underlying acute pancreatitis and hemorrhagic pseudocysts

  18. Pancreatic panniculitis associated with acute pancreatitis and hemorrhagic pseudocysts: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Yong Suk; Kim, Mi Sung; Park, Chan Sub; Park, Ji Yeon; Park, Noh Hyuck [Kwandong Univ., Myongji Hospital, Goyang (Korea, Republic of)

    2012-10-15

    Pancreatic panniculitis is an inflammation and necrosis of fat at distant foci in patients with pancreatic disorders, most frequently, pancreatitis and pancreatic carcinoma. Clinically, pancreatic panniculitis is manifested by painless or painful subcutaneous nodules on the legs, buttocks, or trunk. The usual sites are the distal parts of the lower extremities. To the best of our knowledge, there have not been many reports for the radiologic findings of pancreatic panniculitis. In this article, we report a case of pancreatic panniculitis, including radiologic findings of CT and ultrasonography. The patient was presented with painful subcutaneous nodules on the trunk, and had underlying acute pancreatitis and hemorrhagic pseudocysts.

  19. Lateral Pancreaticojejunostomy for Chronic Pancreatitis and Pancreatic Ductal Dilation in Children.

    Science.gov (United States)

    Shah, Adil A; Petrosyan, Mikael; Kane, Timothy D

    2018-06-06

    Pancreatic ductal obstruction leading to ductal dilation and recurrent pancreatitis is uncommon in children. Treatment is dependent upon etiology but consists of decompression of the pancreatic duct (PD) proximally, if possible, by endoscopic retrograde cholangiopancreatography (ERCP) intervention or surgical decompression with pancreaticojejunal anastomosis. After institutional review board approval, we retrospectively reviewed the records for 2 children who underwent lateral pancreaticojejunostomy for pancreatic ductal dilation. Data, including demographics, diagnostic studies, operative details, complications, outcomes, and follow-up, were analyzed. Case 1 was a 4-year-old female with pancreatic ductal obstruction with multiple episodes of recurrent pancreatitis and failure of ERCP to clear her PD of stones. She underwent a laparoscopic cholecystectomy with a lateral pancreaticojejunostomy (Puestow procedure). She recovered well with no further episodes of pancreatitis and normal pancreatic function 4 years later. Case 2 was a 2-year-old female who developed recurrent pancreatitis and was found to have papillary stenosis and long common bile-PD channel. Despite multiple sphincterotomies, laparoscopic cholecystectomy, and laparoscopic hepaticoduodenostomy, she continued to experience episodes of pancreatitis. She underwent a laparoscopy converted to open lateral pancreaticojejunostomy. Her recovery was also smooth having had no episodes of pancreatitis or hospital admissions for over 2 years following the Puestow. Indication for lateral pancreaticojejunostomy or Puestow procedure is rare in children and even less often performed using laparoscopy. In our small experience, both patients with pancreatic ductal obstruction managed with Puestow's procedure enjoy durable symptom and pain relief in the long term.

  20. From Pathogenesis, Clinical Manifestation, and Diagnosis to Treatment: An Overview on Autoimmune Pancreatitis

    Directory of Open Access Journals (Sweden)

    Ou Cai

    2017-01-01

    Full Text Available Autoimmune pancreatitis (AIP is a special type of chronic pancreatitis which is autoimmune mediated. The international consensus diagnostic criteria (ICDC 2011 proposed two types of AIP: type I is associated with histological pattern of lymphoplasmacytic sclerosing pancreatitis (LPSP, characterized by serum IgG4 elevation, whereas type 2 is named idiopathic duct-centric pancreatitis (IDCP, with granulocytic epithelial lesion (GEL and immunoglobulin G4 (IgG4 negative. The pathogenic mechanism is unclear now; based on genetic factors, disease specific or related antigens, innate and adaptive immunity may be involved. The most common clinical manifestations of AIP are obstructive jaundice and upper abdominal pain. The diagnosis can be made by a combination of parenchymal and ductal imaging, serum IgG4 concentrations, pancreatic histology, extrapancreatic disease, and glucocorticoid responsiveness according to ICDC 2011. Because of the clinical and imaging similarities with pancreatic cancer, general work-up should be done carefully to exclude pancreatic malignant tumor before empirical trial of glucocorticoid treatment. Glucocorticoid is the most common drug for AIP to induce remission, while there still exists controversy on steroid maintenance and treatment for relapse. Further studies should be done to identify more specific serum biomarkers for AIP, the pathogenic mechanisms, and the treatment for relapse.

  1. Possibilities of radiologic diagnosis of pancreatic calcinosis and chronic calculous pancreatics

    International Nuclear Information System (INIS)

    Loginov, A.S.; Sivash, Eh.S.; Kudryavtseva, G.V.

    1982-01-01

    X-ray diagnosis of the pancreatic gland calculous damage as well as chronic pancreatitis have been studied in 23 patients. A methodologic approach to examination of this group of patients was defined. Posteroanterior radiography has been shown to be of decisive importance in diagnosis of the calcified pancreatic gland. Duodenography and choleduodenography both considerably promote recognition of chronic pancreatitis. The radiologic method also allows one to reveal a series of complications: the common bile duct compression, duodenal stenosis, pancreatic tumor in the presence of chronic pancreatitis, malabsorption syndrome

  2. Assessment of Adverse Events in Protocols, Clinical Study Reports, and Published Papers of Trials of Orlistat

    DEFF Research Database (Denmark)

    Schroll, Jeppe Bennekou; Penninga, Elisabeth I; Gøtzsche, Peter C

    2016-01-01

    BACKGROUND: Little is known about how adverse events are summarised and reported in trials, as detailed information is usually considered confidential. We have acquired clinical study reports (CSRs) from the European Medicines Agency through the Freedom of Information Act. The CSRs describe......Med and adverse event data were extracted from this source as well. All three sources were compared. Individual adverse events from one trial were summed and compared to the totals in the summary report. None of the protocols or CSRs contained instructions for investigators on how to question participants about...

  3. Blockchain protocols in clinical trials: Transparency and traceability of consent [version 3; referees: 1 approved, 2 approved with reservations, 1 not approved

    Directory of Open Access Journals (Sweden)

    Mehdi Benchoufi

    2017-07-01

    Full Text Available Clinical trial consent for protocols and their revisions should be transparent for patients and traceable for stakeholders. Our goal is to implement a process allowing the collection of patients’ informed consent, which is bound to protocol revisions, storing and tracking the consent in a secure, unfalsifiable and publicly verifiable way, and enabling the sharing of this information in real time. For that, we will built a consent workflow using a rising technology called Blockchain. This is a distributed technology that brings a built-in layer of transparency and traceability. From a more general and prospective point of view, we believe Blockchain technology brings a paradigmatical shift to the entire clinical research field. We designed a Proof-of-Concept protocol consisting of time-stamping each step of the patient’s consent collection using Blockchain; thus archiving and historicising the consent through cryptographic validation in a securely unfalsifiable and transparent way. For each revision of the protocol, consent was sought again. We obtained a single document, in a standard open format, that accounted for the whole consent collection process: timestamped consent status with regards to each version of the protocol. This document cannot be corrupted, and can be checked on any dedicated public website. It should be considered as a robust proof of data. However, in a live clinical trial, the authentication system should be strengthened in order to remove the need for third parties, here the trial stakeholders, and give participative control to the peer-to-peer users. In the future, we think that the complex data flow of a clinical trial can be tracked using Blockchain, that a blockchain core functionality, named Smart Contract, could help prevent clinical trial events not to happen in the right chronological order: for example including patients before they consented or analysing case report forms data before freezing the database

  4. Pancreatic differentiation of Pdx1-GFP reporter mouse induced pluripotent stem cells.

    Science.gov (United States)

    Porciuncula, Angelo; Kumar, Anujith; Rodriguez, Saray; Atari, Maher; Araña, Miriam; Martin, Franz; Soria, Bernat; Prosper, Felipe; Verfaillie, Catherine; Barajas, Miguel

    2016-12-01

    Efficient induction of defined lineages in pluripotent stem cells constitutes the determinant step for the generation of therapeutically relevant replacement cells to potentially treat a wide range of diseases, including diabetes. Pancreatic differentiation has remained an important challenge in large part because of the need to differentiate uncommitted pluripotent stem cells into highly specialized hormone-secreting cells, which has been shown to require a developmentally informed step-by-step induction procedure. Here, in the framework of using induced pluripotent stem cells (iPSCs) to generate pancreatic cells for pancreatic diseases, we have generated and characterized iPSCs from Pdx1-GFP transgenic mice. The use of a GFP reporter knocked into the endogenous Pdx1 promoter allowed us to monitor pancreatic induction based on the expression of Pdx1, a pancreatic master transcription factor, and to isolate a pure Pdx1-GFP + population for downstream applications. Differentiated cultures timely expressed markers specific to each stage and end-stage progenies acquired a rather immature beta-cell phenotype, characterized by polyhormonal expression even among cells highly expressing the Pdx1-GFP reporter. Our findings highlight the utility of employing a fluorescent protein reporter under the control of a master developmental gene in order to devise novel differentiation protocols for relevant cell types for degenerative diseases such as pancreatic beta cells for diabetes. Copyright © 2016 International Society of Differentiation. Published by Elsevier B.V. All rights reserved.

  5. Pancreatitis-imaging approach

    Science.gov (United States)

    Busireddy, Kiran K; AlObaidy, Mamdoh; Ramalho, Miguel; Kalubowila, Janaka; Baodong, Liu; Santagostino, Ilaria; Semelka, Richard C

    2014-01-01

    Pancreatitis is defined as the inflammation of the pancreas and considered the most common pancreatic disease in children and adults. Imaging plays a significant role in the diagnosis, severity assessment, recognition of complications and guiding therapeutic interventions. In the setting of pancreatitis, wider availability and good image quality make multi-detector contrast-enhanced computed tomography (MD-CECT) the most used imaging technique. However, magnetic resonance imaging (MRI) offers diagnostic capabilities similar to those of CT, with additional intrinsic advantages including lack of ionizing radiation and exquisite soft tissue characterization. This article reviews the proposed definitions of revised Atlanta classification for acute pancreatitis, illustrates a wide range of morphologic pancreatic parenchymal and associated peripancreatic changes for different types of acute pancreatitis. It also describes the spectrum of early and late chronic pancreatitis imaging findings and illustrates some of the less common types of chronic pancreatitis, with special emphasis on the role of CT and MRI. PMID:25133027

  6. Surgery for chronic pancreatitis decreases the risk for pancreatic cancer: a multicenter retrospective analysis.

    Science.gov (United States)

    Ueda, Junji; Tanaka, Masao; Ohtsuka, Takao; Tokunaga, Shoji; Shimosegawa, Tooru

    2013-03-01

    Chronic pancreatitis is suggested to be one of the risk factors for the development of pancreatic cancer. The aim of this study was to confirm the high incidence of pancreatic cancer in patients with chronic pancreatitis in Japan and to determine the factors associated with the risk for pancreatic cancer in patients with chronic pancreatitis. The working group of the Research Committee of Intractable Disease supported by the Ministry of Health, Labour and Welfare of Japan carried out a nationwide survey to investigate the relationship between chronic pancreatitis and pancreatic cancer. This retrospective study included patients diagnosed with chronic pancreatitis who had had at least 2 years of follow-up. They were contacted through 22 Japanese referral centers experienced in the management of chronic pancreatitis. The standardized incidence ratio (95 CI) of pancreatic cancer was 11.8 (7.1-18.4). The incidence of pancreatic cancer was significantly lower in patients who had received surgery for chronic pancreatitis than in those who had not undergone surgery (hazard ratio estimated by Cox regression 0.11; 95% CI, 0.0014-0.80; P = .03). Patients who continued to drink alcohol after diagnosis of chronic pancreatitis showed a significantly higher incidence of pancreatic cancer than those who stopped drinking after diagnosis of chronic pancreatitis (hazard ratio, 5.07; 95% CI, 1.13-22.73; P = .03). This study confirmed that chronic pancreatitis is an important risk factor for the development of pancreatic cancer in Japan. Patients who underwent surgery for the treatment of chronic pancreatitis had significantly lower incidences of pancreatic cancer. Surgery for chronic pancreatitis may inhibit the development of pancreatic cancer in patients with chronic pancreatitis. Copyright © 2013 Mosby, Inc. All rights reserved.

  7. Is the Whipple procedure harmful for long-term outcome in treatment of chronic pancreatitis? 15-years follow-up comparing the outcome after pylorus-preserving pancreatoduodenectomy and Frey procedure in chronic pancreatitis.

    Science.gov (United States)

    Bachmann, Kai; Tomkoetter, Lena; Kutup, Asad; Erbes, Johannes; Vashist, Yogesh; Mann, Oliver; Bockhorn, Maximilian; Izbicki, Jakob R

    2013-11-01

    The aim of this study was to report on 15-year long-term results of a randomized controlled trial comparing extended drainage procedure (Frey) and classical resectional procedure [pylorus-preserving pancreatoduodenectomy (PD)] in patients with chronic pancreatitis. Chronic pancreatitis is a common inflammatory disease with a prevalence of 10 to 30 cases per 100,000 inhabitants. It is characterized by the progressive conversion of pancreatic parenchyma to fibrous tissue. Different surgical procedures are used in treatment of persistent pain. Sixty-four patients suffering from chronic pancreatitis with inflammatory mass in the pancreatic head were randomly assigned in 2 treatment groups (PD, n = 32) and (Frey, n = 32). The perioperative course of the randomized controlled trial and the 7 years follow-up have been previously published. All participating patients were contacted with a standardized, validated questionnaire (EORTC QLQ C30) to evaluate the long-term survival, quality-of-life pain, and exocrine and endocrine function. In the 15-year long-term follow-up, the pain control was good and comparable between both groups, but the quality of life was better after Frey procedure in regard of the physical status [PD: 100 (0-100) vs PD: 60 (0-100) (P = 0.011)]. No significant differences in terms of the Pain Score were detected between both groups [PD: 7 (0-100) vs Frey 4 (0-100) P = 0.258]. Seven patients after Frey OP and 6 patients after PD were free of pain. Analyzing the postoperative overall survival, a higher long-term mortality was found after PD (53%) than that found after Frey procedure (30%) resulting in a longer mean survival (14.5 ± 0.8 vs 11.3 ± 0.8 years; P = 0.037). No correlation between endocrine or exocrine pancreatic function and pain was found, whereas continuous alcohol consumption was associated with poorer outcome regarding quality of life (P treatment of chronic pancreatitis.

  8. [Optimizing the managment of patients with diabetes mellitus: selected clinical trials from the 2004 Congress of the American Diabetes Association].

    Science.gov (United States)

    Scheen, A J; Radermecker, R P; Philips, J C

    2004-06-01

    The 64th scientific congress of the American Diabetes Association had a special session devoted to the presentation of the results from three clinical trials: 1) the first multicentre international trial of pancreatic islet transplantation according to the so-called Edmonton protocol with the primary endpoint of restoring insulin independence in type 1 diabetic patients; 2) three pivotal studies of 30 weeks testing both the efficacy and safety of exenatide (exendin-4), a new insulin secretagogue that is a long-acting analogue of glucagon-like peptide-1, in patients with type 2 diabetes treated with either metformin, or a sulfonylurea, or a metformin-sulfonylurea combination; and 3) the "Collaborative AtoRvastatin Diabetes Study" (CARDS), a placebo-controlled primary prevention trial of cardiovascular complications using atorvastatin 10 mg in 2 838 at risk patients with type 2 diabetes. The main results and conclusions of these trials are briefly presented as they open new perspectives in the management of patients with type 1 or type 2 diabetes mellitus.

  9. The effect of pancreatic polypeptide and peptide YY on pancreatic blood flow and pancreatic exocrine secretion in the anesthetized dog

    International Nuclear Information System (INIS)

    DeMar, A.R.; Lake, R.; Fink, A.S.

    1991-01-01

    Pancreatic polypeptide (PP) and peptide YY (PYY) are inhibitors of pancreatic exocrine secretion in vivo but not in vitro, which suggests intermediate mechanisms of action. To examine the role of pancreatic blood flow in these inhibitory effects, xenon-133 gas clearance was used to measure pancreatic blood flow while simultaneously measuring pancreatic exocrine secretion. PP or PYY (400 pmol/kg/h) was administered during the intermediate hour of a 3-h secretin (125 ng/kg/h)/cholecystokinin octapeptide (CCK-8) (50 ng/kg/h) infusion. Exocrine secretion and pancreatic blood flow during the PP or PYY hours were compared with that observed in the first and third hours of the secretin/CCK-8 infusion. PP and PYY significantly inhibited secretin/CCK-8-induced pancreatic exocrine secretion. In addition, PYY (but not PP) significantly reduced pancreatic blood flow during secretin/CCK-8 stimulation. Nevertheless, there was no correlation between pancreatic blood flow and bicarbonate or protein outputs. It is concluded that changes in pancreatic blood flow do not mediate the inhibitory effects of PP or PYY on the exocrine pancreas

  10. Fast neutron irradiation for locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Smith, F.P.; Schein, P.S.; MacDonald, J.S.; Woolley, P.V.; Ornitz, R.; Rogers, C.

    1981-01-01

    Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore, caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials

  11. Fast neutron irradiation for locally advanced pancreatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Smith, F.P. (Georgetown Univ. Medical Center, Washington, DC); Schein, P.S.; MacDonald, J.S.; Woolley, P.V.; Ornitz, R.; Rogers, C.

    1981-11-01

    Nineteen patients with locally advanced pancreatic cancer and one patient with islet cell cancer were treated with 1700-1500 neutron rad alone or in combination with 5-fluorouracil to exploit the theoretic advantages of higher linear energy of transfer, and lower oxygen enhancement ratio of neutrons. Only 5 of 14 (36%) obtained partial tumor regression. The median survival for all patients with pancreatic cancer was 6 months, which is less than that reported with 5-fluorouracil and conventional photon irradiation. Gastrointestinal toxicity was considerable; hemorhagic gastritis in five patients, colitis in two and esophagitis in one. One patient developed radiation myelitis. We therefore, caution any enthusiasm for this modality of therapy until clear evidence of a therapeutic advantage over photon therapy is demonstrated in controlled clinical trials.

  12. A prospective evaluation of pancreatic exocrine function in patients with acute pancreatitis: correlation with extent of necrosis and pancreatic endocrine insufficiency.

    Science.gov (United States)

    Boreham, B; Ammori, B J

    2003-01-01

    The aim of this prospective study was to assess pancreatic exocrine function in patients recovering from a first attack of acute pancreatitis, and to evaluate its relationship to severity of attack, extent of pancreatic necrosis and severity of pancreatic endocrine insufficiency. Between December 2000 and November 2001, 23 patients were prospectively evaluated. Pancreatic exocrine function was measured by the faecal elastase-1 test and insufficiency was classified as moderately impaired or severely impaired. Pancreatic necrosis was determined by contrast-enhanced CT scan, and its extent was categorised according to Balthazar's classification. The severity of pancreatic endocrine insufficiency was categorised according to insulin dependence. Attacks were classified as mild (n = 16) or severe (n = 7) according to the Atlanta criteria. Pancreatic exocrine insufficiency was significantly more frequent in patients recovering from severe attacks than mild (n = 6, 86% vs. n = 2, 13%; p = 0.002), and in those who developed pancreatic necrosis or pseudocyst than those who did not (6 of 7 patients vs. 2 of 16 patients, and 5 of 5 patients vs. 3 of 18 patients respectively; p = 0.002). The development of exocrine insufficiency correlated strongly with the extent of pancreatic necrosis (r = -0.754, p pancreatic endocrine insufficiency (n = 4, r = -0.453, p = 0.03). Pancreatic exocrine insufficiency is a common occurrence in patients recovering from severe acute pancreatitis, and its severity correlates with the extent of pancreatic necrosis and the severity of concomitant pancreatic endocrine insufficiency. Copyright 2003 S. Karger AG, Basel and IAP

  13. Pancreatitis

    Science.gov (United States)

    ... the hormones insulin and glucagon into the bloodstream. Pancreatitis is inflammation of the pancreas. It happens when digestive enzymes start digesting the pancreas itself. Pancreatitis can be acute or chronic. Either form is ...

  14. Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees.

    Science.gov (United States)

    Li, Rebecca H; Wacholtz, Mary C; Barnes, Mark; Boggs, Liam; Callery-D'Amico, Susan; Davis, Amy; Digilova, Alla; Forster, David; Heffernan, Kate; Luthin, Maeve; Lynch, Holly Fernandez; McNair, Lindsay; Miller, Jennifer E; Murphy, Jacquelyn; Van Campen, Luann; Wilenzick, Mark; Wolf, Delia; Woolston, Cris; Aldinger, Carmen; Bierer, Barbara E

    2016-04-01

    A novel Protocol Ethics Tool Kit ('Ethics Tool Kit') has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews. It may also streamline ethics review and may facilitate and expedite the review process by anticipating the concerns of ethics committee reviewers. Specific attention was given to issues arising in multinational settings. With the use of this Tool Kit, researchers have the opportunity to address critical research ethics issues proactively, potentially speeding the time and easing the process to final protocol approval. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  15. Safety of intrathecal transplantation of human umbilical cord mesenchymal stem cells for treating hereditary cerebellar ataxia: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Yi-hua An

    2016-01-01

    Trial registration: ClinicalTrials.gov identifier: NCT01489267; registered on 30 October 2011. The study protocol has been approved by the ethics committee of the General Hospital of Chinese Armed Police Forces, China (approval No. 201117.

  16. Sequential changes from minimal pancreatic inflammation to advanced alcoholic pancreatitis.

    Science.gov (United States)

    Noronha, M; Dreiling, D A; Bordalo, O

    1983-11-01

    A correlation of several clinical parameters and pancreatitis morphological alterations observed in chronic alcoholics with and without pancreatic is presented. Three groups of patients were studied: asymptomatic chronic alcoholics (24); non-alcoholic controls (10); and cases with advanced chronic pancreatitis (6). Clinical, biochemical and functional studies were performed. Morphological studies were made on surgical biopsy specimens in light and electron microscopy. The results of this study showed: 1) fat accumulates within pancreatic acinar cells in alcoholics drinking more than 80 g of ethanol per day; 2) ultrastructural changes found in acinar cells of the alcoholics are similar to those described for liver cells; 3) the alterations found in alcoholics without pancreatitis are also observed in those with advanced chronic pancreatitis. An attempt to correlate the sequential changes in the histopathology of alcoholic pancreatic disease with the clinical picture and secretory patterns was made. According to these observations, admitting the ultrastructural similarities between the liver and the pancreas and the recently demonstrated abnormalities of lipid metabolism in pancreatic cells in experimental animal research, the authors postulate a toxic-metabolic mechanism as a likely hypothesis for the pathogenesis of chronic alcoholic inflammation of the pancreas.

  17. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia: an observational Ponte di Legno Toxicity Working Group study.

    Science.gov (United States)

    Wolthers, Benjamin O; Frandsen, Thomas L; Baruchel, André; Attarbaschi, Andishe; Barzilai, Shlomit; Colombini, Antonella; Escherich, Gabriele; Grell, Kathrine; Inaba, Hiroto; Kovacs, Gábor; Liang, Der-Cherng; Mateos, Marion; Mondelaers, Veerle; Möricke, Anja; Ociepa, Tomasz; Samarasinghe, Sujith; Silverman, Lewis B; van der Sluis, Inge M; Stanulla, Martin; Vrooman, Lynda M; Yano, Michihiro; Zapotocka, Ester; Schmiegelow, Kjeld

    2017-09-01

    Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re-exposing patients with asparaginase-associated pancreatitis to asparaginase, 18 acute lymphoblastic leukaemia trial groups merged data for this observational study. Patient files from 26 trials run by 18 trial groups were reviewed on children (aged 1·0-17·9 years) diagnosed with t(9;22)-negative acute lymphoblastic leukaemia between June 1, 1996, and Jan 1, 2016, who within 50 days of asparaginase exposure developed asparaginase-associated pancreatitis. Asparaginase-associated pancreatitis was defined by at least two criteria: abdominal pain, pancreatic enzymes at least three times the upper limit of normal (ULN), and imaging compatible with pancreatitis. Patients without sufficient data for diagnostic criteria were excluded. Primary outcomes were defined as acute and persisting complications of asparaginase-associated pancreatitis and risk of re-exposing patients who suffered an episode of asparaginase-associated pancreatitis to asparaginase. Data were collected from Feb 2, 2015, to June 30, 2016, and analysed and stored in a common database at Rigshospitalet, Copenhagen, Denmark. Of 465 patients with asparaginase-associated pancreatitis, 33 (8%) of 424 with available data needed mechanical ventilation, 109 (26%) of 422 developed pseudocysts, acute insulin therapy was needed in 81 (21%) of 393, and seven (2%) of 458 patients died. Risk of assisted mechanical ventilation, need for insulin, pseudocysts, or death was associated with older age (median age for patients with complications 10·5 years [IQR 6·4-13·8] vs without complications 6·1 years [IQR 3·6-12·2], ppancreatitis, 31 (11%) of 275 patients still needed insulin or had recurrent abdominal pain or both. Both the risk of persisting

  18. Quality of Life in a Prospective, Multicenter Phase 2 Trial of Neoadjuvant Full-Dose Gemcitabine, Oxaliplatin, and Radiation in Patients With Resectable or Borderline Resectable Pancreatic Adenocarcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Serrano, Pablo E. [Department of Surgery, University Health Network, University of Toronto, Toronto, ON (Canada); Herman, Joseph M. [Department of Radiation Oncology and Molecular Radiation Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland (United States); Griffith, Kent A.; Zalupski, Mark M. [Center for Cancer Biostatistics, Biostatistics Unit, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan (United States); Kim, Edward J. [Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan (United States); Bekaii-Saab, Tanios S. [Division of Medical Oncology, Department of Internal Medicine, The Ohio State University Medical Center, Columbus, Ohio (United States); Ben-Josef, Edgar [Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan (United States); University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan (United States); Dawson, Laura A. [Princess Margaret Cancer Center, University Health Network, Toronto, ON (Canada); Ringash, Jolie [Princess Margaret Cancer Center, University Health Network, Toronto, ON (Canada); Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON (Canada); Wei, Alice C., E-mail: alice.wei@uhn.ca [Department of Surgery, University Health Network, University of Toronto, Toronto, ON (Canada); Princess Margaret Cancer Center, University Health Network, Toronto, ON (Canada); Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, ON (Canada)

    2014-10-01

    Purpose: To determine the health-related quality of life (QOL) during and after neoadjuvant chemoradiation therapy and surgery for patients with pancreatic adenocarcinoma. Methods and Materials: Participants of a prospective, phase 2 multi-institutional trial treated with neoadjuvant chemoradiation followed by surgery completed QOL questionnaires (European Organization for Research and Treatment in Cancer Quality of Life Questionnaire version 3.0 [EORTC-QLQ C30], EORTC-Pancreatic Cancer module [EORTC-PAN 26], and Functional Assessment of Cancer Therapy Hepatobiliary and Pancreatic subscale [FACT-Hep]) at baseline, after 2 cycles of neoadjuvant therapy, after surgery, at 6 months from initiation of therapy, and at 6-month intervals for 2 years. Mean scores were compared with baseline. A change >10% was considered a minimal clinically important difference. Results: Of 71 participants in the trial, 55 were eligible for QOL analysis. Compliance ranged from 32% to 74%. The EORTC-QLQ C30 global QOL did not significantly decline after neoadjuvant therapy, whereas the Functional Assessment of Cancer Therapy global health measure showed a statistically, but not clinically significant decline (−8, P=.02). This was in parallel with deterioration in physical functioning (−14.1, P=.001), increase in diarrhea (+16.7, P=.044), and an improvement in pancreatic pain (−13, P=.01) as per EORTC-PAN 26. Because of poor patient compliance in the nonsurgical group, long-term analysis was performed only from surgically resected participants (n=36). Among those, global QOL returned to baseline levels after 6 months, remaining near baseline through the 24-month visit. Conclusions: The study regimen consisting of 2 cycles of neoadjuvant therapy was completed without a clinically significant QOL deterioration. A transient increase in gastrointestinal symptoms and a decrease in physical functioning were seen after neoadjuvant chemoradiation. In those patients who underwent surgical

  19. Quality of Life in a Prospective, Multicenter Phase 2 Trial of Neoadjuvant Full-Dose Gemcitabine, Oxaliplatin, and Radiation in Patients With Resectable or Borderline Resectable Pancreatic Adenocarcinoma

    International Nuclear Information System (INIS)

    Serrano, Pablo E.; Herman, Joseph M.; Griffith, Kent A.; Zalupski, Mark M.; Kim, Edward J.; Bekaii-Saab, Tanios S.; Ben-Josef, Edgar; Dawson, Laura A.; Ringash, Jolie; Wei, Alice C.

    2014-01-01

    Purpose: To determine the health-related quality of life (QOL) during and after neoadjuvant chemoradiation therapy and surgery for patients with pancreatic adenocarcinoma. Methods and Materials: Participants of a prospective, phase 2 multi-institutional trial treated with neoadjuvant chemoradiation followed by surgery completed QOL questionnaires (European Organization for Research and Treatment in Cancer Quality of Life Questionnaire version 3.0 [EORTC-QLQ C30], EORTC-Pancreatic Cancer module [EORTC-PAN 26], and Functional Assessment of Cancer Therapy Hepatobiliary and Pancreatic subscale [FACT-Hep]) at baseline, after 2 cycles of neoadjuvant therapy, after surgery, at 6 months from initiation of therapy, and at 6-month intervals for 2 years. Mean scores were compared with baseline. A change >10% was considered a minimal clinically important difference. Results: Of 71 participants in the trial, 55 were eligible for QOL analysis. Compliance ranged from 32% to 74%. The EORTC-QLQ C30 global QOL did not significantly decline after neoadjuvant therapy, whereas the Functional Assessment of Cancer Therapy global health measure showed a statistically, but not clinically significant decline (−8, P=.02). This was in parallel with deterioration in physical functioning (−14.1, P=.001), increase in diarrhea (+16.7, P=.044), and an improvement in pancreatic pain (−13, P=.01) as per EORTC-PAN 26. Because of poor patient compliance in the nonsurgical group, long-term analysis was performed only from surgically resected participants (n=36). Among those, global QOL returned to baseline levels after 6 months, remaining near baseline through the 24-month visit. Conclusions: The study regimen consisting of 2 cycles of neoadjuvant therapy was completed without a clinically significant QOL deterioration. A transient increase in gastrointestinal symptoms and a decrease in physical functioning were seen after neoadjuvant chemoradiation. In those patients who underwent surgical

  20. Rational combinations of immunotherapy for pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Blair, Alex B; Zheng, Lei

    2017-06-01

    The complex interaction between the immune system, the tumor and the microenvironment in pancreatic ductal adenocarcinoma (PDA) leads to the resistance of PDA to immunotherapy. To overcome this resistance, combination immunotherapy is being proposed. However, rational combinations that target multiple aspects of the complex anti-tumor immune response are warranted. Novel clinical trials will investigate and optimize the combination immunotherapy for PDA.

  1. Single dental implant retained mandibular complete dentures – influence of the loading protocol: study protocol for a randomized controlled trial

    Science.gov (United States)

    2014-01-01

    Background Over the years, there has been a strong consensus in dentistry that at least two implants are required to retain a complete mandibular denture. It has been shown in several clinical trials that one single median implant can retain a mandibular overdenture sufficiently well for up to 5 years without implant failures, when delayed loading was used. However, other trials have reported conflicting results with in part considerable failure rates when immediate loading was applied. Therefore it is the purpose of the current randomized clinical trial to test the hypothesis that immediate loading of a single mandibular midline implant with an overdenture will result in a comparable clinical outcome as using the standard protocol of delayed loading. Methods/design This prospective nine-center randomized controlled clinical trial is still ongoing. The final patient will complete the trial in 2016. In total, 180 edentulous patients between 60 and 89 years with sufficient complete dentures will receive one median implant in the edentulous mandible, which will retain the existing complete denture using a ball attachment. Loading of the median implant is either immediately after implant placement (experimental group) or delayed by 3 months of submerged healing at second-stage surgery (control group). Follow-up of patients will be performed for 24 months after implant loading. The primary outcome measure is non-inferiority of implant success rate of the experimental group compared to the control group. The secondary outcome measures encompass clinical, technical and subjective variables. The study was funded by the Deutsche Forschungsgemeinschaft (German research foundation, KE 477/8-1). Discussion This multi-center clinical trial will give information on the ability of a single median implant to retain a complete mandibular denture when immediately loaded. If viable, this treatment option will strongly improve everyday dental practice. Trial registration The trial

  2. Management of pancreatic cancer in the elderly.

    Science.gov (United States)

    Higuera, Oliver; Ghanem, Ismael; Nasimi, Rula; Prieto, Isabel; Koren, Laura; Feliu, Jaime

    2016-01-14

    Currently, pancreatic adenocarcinoma mainly occurs after 60 years of age, and its prognosis remains poor despite modest improvements in recent decades. The aging of the population will result in a rise in the incidence of pancreatic adenocarcinoma within the next years. Thus, the management of pancreatic cancer in the elderly population is gaining increasing relevance. Older cancer patients represent a heterogeneous group with different biological, functional and psychosocial characteristics that can modify the usual management of this disease, including pharmacokinetic and pharmacodynamic changes, polypharmacy, performance status, comorbidities and organ dysfunction. However, the biological age, not the chronological age, of the patient should be the limiting factor in determining the most appropriate treatment for these patients. Unfortunately, despite the increased incidence of this pathology in older patients, there is an underrepresentation of these patients in clinical trials, and the management of older patients is thus determined by extrapolation from the results of studies performed in younger patients. In this review, the special characteristics of the elderly, the multidisciplinary management of localized and advanced ductal adenocarcinoma of the pancreas and the most recent advances in the management of this condition will be discussed, focusing on surgery, chemotherapy, radiation and palliative care.

  3. Endosonography of groove pancreatitis

    NARCIS (Netherlands)

    Tio, T. L.; Luiken, G. J.; Tytgat, G. N.

    1991-01-01

    Groove pancreatitis is a rare form of chronic pancreatitis. Distinction between pancreatitis and pancreatic carcinoma is often difficult. Two cases of groove pancreatitis diagnosed by endosonography are described. A hypoechoic pattern between the duodenal wall and pancreas was clearly imaged in both

  4. Characteristic findings in images of extra-pancreatic lesions associated with autoimmune pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Fujinaga, Yasunari, E-mail: fujinaga@shinshu-u.ac.jp [Department of Radiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621 (Japan); Kadoya, Masumi [Department of Radiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621 (Japan); Kawa, Shigeyuki [Center of Health, Safety and Environmental Management, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621 (Japan); Hamano, Hideaki [Department of Medicine, Gastroenterology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621 (Japan); Ueda, Kazuhiko; Momose, Mitsuhiro; Kawakami, Satoshi; Yamazaki, Sachie; Hatta, Tomoko; Sugiyama, Yukiko [Department of Radiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621 (Japan)

    2010-11-15

    Purpose: Autoimmune pancreatitis is a unique form of chronic pancreatitis characterized by a variety of extra-pancreatic involvements which are frequently misdiagnosed as lesions of corresponding organs. The purpose of this study was to clarify the diagnostic imaging features of extra-pancreatic lesions associated with autoimmune pancreatitis. Materials and methods: We retrospectively analyzed diagnostic images of 90 patients with autoimmune pancreatitis who underwent computer-assisted tomography, magnetic resonance imaging, and/or gallium-67 scintigraphy before steroid therapy was initiated. Results: AIP was frequently (92.2%) accompanied by a variety of extra-pancreatic lesions, including swelling of lachrymal and salivary gland lesions (47.5%), lung hilar lymphadenopathy (78.3%), a variety of lung lesions (51.2%), wall thickening of bile ducts (77.8%), peri-pancreatic or para-aortic lymphadenopathy (56.0%), retroperitoneal fibrosis (19.8%), a variety of renal lesions (14.4%), and mass lesions of the ligamentum teres (2.2%). Characteristic findings in CT and MRI included lymphadenopathies of the hilar, peri-pancreatic, and para-aortic regions; wall thickening of the bile duct; and soft tissue masses in the kidney, ureters, aorta, paravertebral region, ligamentum teres, and orbit. Conclusions: Recognition of the diagnostic features in the images of various involved organs will assist in the diagnosis of autoimmune pancreatitis and in differential diagnoses between autoimmune pancreatitis-associated extra-pancreatic lesions and lesions due to other pathologies.

  5. TRAUMATIC PANCREATITIS

    Science.gov (United States)

    Berne, Clarence J.; Walters, Robert L.

    1953-01-01

    Traumatic pancreatitis should be considered as a diagnostic possibility when trauma to the epigastrium is followed by phenomena suggestive of intra-abdominal injury. The presence or absence of hyperamylasemia should be established immediately. Even when traumatic pancreatitis is believed to exist, any suggestion of injury to other viscera should indicate laparotomy. Retroperitoneal rupture of the duodenum may simulate traumatic pancreatitis in all respects, including hyperamylasemia. X-ray studies may be of value in differentiation. Non-complicated traumatic pancreatitis is best treated conservatively. Gunshot and knife wounds of the pancreas should be drained. PMID:13094537

  6. PROPOSAL OF GUIDELINE FOR CLINICAL TRIAL PROTOCOLS WITH HERBAL DRUGS

    Directory of Open Access Journals (Sweden)

    Migdacelys Arboláez Estrada.

    2007-04-01

    Full Text Available SUMMARYCuba has extensive experience about herbal drugs, however only a few products get to the clinical phase of drug development. Our objective was to design new guidelines for clinical trials with herbal drugs.A detailed bibliographic search about regulatory aspects about clinical trials in Cuba and the world was done for development of the guideline. The guideline's proposed format includes: 1 Index, including the classification of the content. 2 Summary, 3 Fifteen chapters, related to the clinical trials. The guideline also propose the inclusion of annexes.A new guideline containing 15 chapters allows for writing more clear and detailed clinical trial protocols. The guideline contains the information required to guide the research staff who is interested in the validation of herbal drugs pharmacological activations from the perspective of clinical trials. RESUMEN Cuba tiene experiencia extensa sobre plantas medicinales, aunque solo algunos productos llegan a una fase clínica del desarrollo. Nuestro objetivo fué diseñar una nueva guía para ensayos clínicos con plantas medicinales.Hemos realizado una detallada búsqueda bibliográfica sobre aspectos reguladores de ensayos clínicos en Cuba y el resto del mundo para el desarrollo de la guía. El formato propuesto de la guia incluye: 1 Índice, incluyendo la clasificación de los contenidos. 2 Resumen, 3 Quince capítulos, relacionados con los ensayos clínicos. La guía también propone la inclusión de anexos.La nueva guía que contiene 15 capítulos que orientan la redacción de protocolos de ensayos clínicos más claros y más detallados. La guía contiene la información requerida para orientar al personal investigador interesado en la validación de la actividad farmacológica de las plantas medicinales desde la perspectiva de los ensayos clínicos.

  7. Amylase, Lipase, and Acute Pancreatitis in People With Type 2 Diabetes Treated With Liraglutide: Results From the LEADER Randomized Trial.

    Science.gov (United States)

    Steinberg, William M; Buse, John B; Ghorbani, Marie Louise Muus; Ørsted, David D; Nauck, Michael A

    2017-07-01

    To evaluate serum amylase and lipase levels and the rate of acute pancreatitis in patients with type 2 diabetes and high cardiovascular risk randomized to liraglutide or placebo and observed for 3.5-5.0 years. A total of 9,340 patients with type 2 diabetes were randomized to either liraglutide or placebo (median observation time 3.84 years). Fasting serum lipase and amylase were monitored. Acute pancreatitis was adjudicated in a blinded manner. Compared with the placebo group, liraglutide-treated patients had increases in serum lipase and amylase of 28.0% and 7.0%, respectively. Levels were increased at 6 months and then remained stable. During the study, 18 (0.4% [1.1 events/1,000 patient-years of observation] [PYO]) liraglutide-treated and 23 (0.5% [1.7 events/1,000 PYO]) placebo patients had acute pancreatitis confirmed by adjudication. Most acute pancreatitis cases occurred ≥12 months after randomization. Liraglutide-treated patients with prior history of pancreatitis ( n = 147) were not more likely to develop acute pancreatitis than similar patients in the placebo group ( n = 120). Elevations of amylase and lipase levels did not predict future risk of acute pancreatitis (positive predictive value pancreatitis among liraglutide-treated patients (regardless of previous history of pancreatitis) compared with the placebo group. Liraglutide was associated with increases in serum lipase and amylase, which were not predictive of an event of subsequent acute pancreatitis. © 2017 by the American Diabetes Association.

  8. Risk of Recurrent Pancreatitis and Progression to Chronic Pancreatitis After a First Episode of Acute Pancreatitis

    NARCIS (Netherlands)

    Ahmed Ali, Usama; Issa, Yama; Hagenaars, Julia C.; Bakker, Olaf J.; van Goor, Harry; Nieuwenhuijs, Vincent B.; Bollen, Thomas L.; van Ramshorst, Bert; Witteman, Ben J.; Brink, Menno A.; Schaapherder, Alexander F.; Dejong, Cornelis H.; Spanier, B. W. Marcel; Heisterkamp, Joos; van der Harst, Erwin; van Eijck, Casper H.; Besselink, Marc G.; Gooszen, Hein G.; van Santvoort, Hjalmar C.; Boermeester, Marja A.

    2016-01-01

    Patients with a first episode of acute pancreatitis can develop recurrent or chronic pancreatitis (CP). However, little is known about the incidence or risk factors for these events. We performed a cross-sectional study of 669 patients with a first episode of acute pancreatitis admitted to 15 Dutch

  9. Pancreatic tissue fluid pressure during drainage operations for chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P

    1990-01-01

    Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results...... a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings....

  10. Treatment of Middle East Respiratory Syndrome with a combination of lopinavir-ritonavir and interferon-β1b (MIRACLE trial): study protocol for a randomized controlled trial.

    Science.gov (United States)

    Arabi, Yaseen M; Alothman, Adel; Balkhy, Hanan H; Al-Dawood, Abdulaziz; AlJohani, Sameera; Al Harbi, Shmeylan; Kojan, Suleiman; Al Jeraisy, Majed; Deeb, Ahmad M; Assiri, Abdullah M; Al-Hameed, Fahad; AlSaedi, Asim; Mandourah, Yasser; Almekhlafi, Ghaleb A; Sherbeeni, Nisreen Murad; Elzein, Fatehi Elnour; Memon, Javed; Taha, Yusri; Almotairi, Abdullah; Maghrabi, Khalid A; Qushmaq, Ismael; Al Bshabshe, Ali; Kharaba, Ayman; Shalhoub, Sarah; Jose, Jesna; Fowler, Robert A; Hayden, Frederick G; Hussein, Mohamed A

    2018-01-30

    It had been more than 5 years since the first case of Middle East Respiratory Syndrome coronavirus infection (MERS-CoV) was recorded, but no specific treatment has been investigated in randomized clinical trials. Results from in vitro and animal studies suggest that a combination of lopinavir/ritonavir and interferon-β1b (IFN-β1b) may be effective against MERS-CoV. The aim of this study is to investigate the efficacy of treatment with a combination of lopinavir/ritonavir and recombinant IFN-β1b provided with standard supportive care, compared to treatment with placebo provided with standard supportive care in patients with laboratory-confirmed MERS requiring hospital admission. The protocol is prepared in accordance with the SPIRIT (Standard Protocol Items: Recommendations for Interventional Trials) guidelines. Hospitalized adult patients with laboratory-confirmed MERS will be enrolled in this recursive, two-stage, group sequential, multicenter, placebo-controlled, double-blind randomized controlled trial. The trial is initially designed to include 2 two-stage components. The first two-stage component is designed to adjust sample size and determine futility stopping, but not efficacy stopping. The second two-stage component is designed to determine efficacy stopping and possibly readjustment of sample size. The primary outcome is 90-day mortality. This will be the first randomized controlled trial of a potential treatment for MERS. The study is sponsored by King Abdullah International Medical Research Center, Riyadh, Saudi Arabia. Enrollment for this study began in November 2016, and has enrolled thirteen patients as of Jan 24-2018. ClinicalTrials.gov, ID: NCT02845843 . Registered on 27 July 2016.

  11. Pathogenic mechanisms of pancreatitis

    Science.gov (United States)

    Manohar, Murli; Verma, Alok Kumar; Venkateshaiah, Sathisha Upparahalli; Sanders, Nathan L; Mishra, Anil

    2017-01-01

    Pancreatitis is inflammation of pancreas and caused by a number of factors including pancreatic duct obstruction, alcoholism, and mutation in the cationic trypsinogen gene. Pancreatitis is represented as acute pancreatitis with acute inflammatory responses and; chronic pancreatitis characterized by marked stroma formation with a high number of infiltrating granulocytes (such as neutrophils, eosinophils), monocytes, macrophages and pancreatic stellate cells (PSCs). These inflammatory cells are known to play a central role in initiating and promoting inflammation including pancreatic fibrosis, i.e., a major risk factor for pancreatic cancer. A number of inflammatory cytokines are known to involve in promoting pancreatic pathogenesis that lead pancreatic fibrosis. Pancreatic fibrosis is a dynamic phenomenon that requires an intricate network of several autocrine and paracrine signaling pathways. In this review, we have provided the details of various cytokines and molecular mechanistic pathways (i.e., Transforming growth factor-β/SMAD, mitogen-activated protein kinases, Rho kinase, Janus kinase/signal transducers and activators, and phosphatidylinositol 3 kinase) that have a critical role in the activation of PSCs to promote chronic pancreatitis and trigger the phenomenon of pancreatic fibrogenesis. In this review of literature, we discuss the involvement of several pro-inflammatory and anti-inflammatory cytokines, such as in interleukin (IL)-1, IL-1β, IL-6, IL-8 IL-10, IL-18, IL-33 and tumor necrosis factor-α, in the pathogenesis of disease. Our review also highlights the significance of several experimental animal models that have an important role in dissecting the mechanistic pathways operating in the development of chronic pancreatitis, including pancreatic fibrosis. Additionally, we provided several intermediary molecules that are involved in major signaling pathways that might provide target molecules for future therapeutic treatment strategies for

  12. Remotely-Supervised Transcranial Direct Current Stimulation (tDCS for Clinical Trials: Guidelines for Technology and Protocols

    Directory of Open Access Journals (Sweden)

    Leigh E Charvet

    2015-03-01

    Full Text Available The effect of transcranial direct current stimulation (tDCS is cumulative. Treatment protocols typically require multiple consecutive sessions spanning weeks or months. However, traveling to clinic for a tDCS session can present an obstacle to subjects and their caregivers. With modified devices and headgear, tDCS treatment can be administered remotely under clinical supervision, potentially enhancing recruitment, throughput, and convenience. Here we propose standards and protocols for clinical trials utilizing remotely-supervised tDCS with the goal of providing safe, reproducible and well-tolerated stimulation therapy outside of the clinic. The recommendations include: 1 training of staff in tDCS treatment and supervision, 2 assessment of the user’s capability to participate in tDCS remotely, 3 ongoing training procedures and materials including assessments of the user and/or caregiver, 4 simple and fail-safe electrode preparation techniques and tDCS headgear, 5 strict dose control for each session, 6 ongoing monitoring to quantify compliance (device preparation, electrode saturation/placement, stimulation protocol, with corresponding corrective steps as required, 7 monitoring for treatment-emergent adverse effects, 8 guidelines for discontinuation of a session and/or study participation including emergency failsafe procedures tailored to the treatment population’s level of need. These guidelines are intended to provide a minimal level of methodological rigor for clinical trials seeking to apply tDCS outside a specialized treatment center. We outline indication-specific applications (Attention Deficit Hyperactivity Disorder, Depression, Multiple Sclerosis, Palliative Care following these recommendations that support a standardized framework for evaluating the tolerability and reproducibility of remote-supervised tDCS that, once established, will allow for translation of tDCS clinical trials to a greater size and range of patient populations.

  13. An update on pancreatic pathophysiology (do we have to rewrite pancreatic pathophysiology?).

    Science.gov (United States)

    Hammer, Heinz F

    2014-02-01

    This review focuses on seven aspects of physiology and pathophysiology of the exocrine pancreas that have been intensively discussed and studied within the past few years: (1) the role of neurohormonal mechanisms like melatonin, leptin, or ghrelin in the stimulation of pancreatic enzyme secretion; (2) the initiation processes of acute pancreatitis, like fusion of zymogen granules with lysosomes leading to intracellular activation of trypsinogen by the lysosomal enzyme cathepsin B, or autoactivation of trypsinogen; (3) the role of genes in the pathogenesis of acute pancreatitis; (4) the role of alcohol and constituents of alcoholic beverages in the pathogenesis of acute pancreatitis; (5) the role of pancreatic hypertension, neuropathy, and central mechanisms for the pathogenesis of pain in chronic pancreatitis; (6) the relation between exocrine pancreatic function and diabetes mellitus; and (7) pathophysiology, diagnosis and treatment of pancreatic steatorrhea.

  14. Hereditary chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Mössner Joachim

    2007-01-01

    Full Text Available Abstract Hereditary chronic pancreatitis (HCP is a very rare form of early onset chronic pancreatitis. With the exception of the young age at diagnosis and a slower progression, the clinical course, morphological features and laboratory findings of HCP do not differ from those of patients with alcoholic chronic pancreatitis. As well, diagnostic criteria and treatment of HCP resemble that of chronic pancreatitis of other causes. The clinical presentation is highly variable and includes chronic abdominal pain, impairment of endocrine and exocrine pancreatic function, nausea and vomiting, maldigestion, diabetes, pseudocysts, bile duct and duodenal obstruction, and rarely pancreatic cancer. Fortunately, most patients have a mild disease. Mutations in the PRSS1 gene, encoding cationic trypsinogen, play a causative role in chronic pancreatitis. It has been shown that the PRSS1 mutations increase autocatalytic conversion of trypsinogen to active trypsin, and thus probably cause premature, intrapancreatic trypsinogen activation disturbing the intrapancreatic balance of proteases and their inhibitors. Other genes, such as the anionic trypsinogen (PRSS2, the serine protease inhibitor, Kazal type 1 (SPINK1 and the cystic fibrosis transmembrane conductance regulator (CFTR have been found to be associated with chronic pancreatitis (idiopathic and hereditary as well. Genetic testing should only be performed in carefully selected patients by direct DNA sequencing and antenatal diagnosis should not be encouraged. Treatment focuses on enzyme and nutritional supplementation, pain management, pancreatic diabetes, and local organ complications, such as pseudocysts, bile duct or duodenal obstruction. The disease course and prognosis of patients with HCP is unpredictable. Pancreatic cancer risk is elevated. Therefore, HCP patients should strongly avoid environmental risk factors for pancreatic cancer.

  15. Acute Pancreatitis and Pancreatic Cancer Risk: A Nationwide Matched-cohort Study in Denmark

    DEFF Research Database (Denmark)

    Kirkegård, Jakob; Cronin Fenton, Deirdre; Heide-Jørgensen, Uffe

    2018-01-01

    . Pancreatic cancer risk was expressed as hazard ratios (HRs) with 95% CIs, calculated using the Cox proportional hazards model. Cox models were stratified by age, sex, and year of pancreatitis diagnosis and adjusted for alcohol- and smoking-related conditions, and Charlson Comorbidity Index score. Results We...... included 41,669 patients diagnosed with incident acute pancreatitis and 208,340 comparison individuals. Patients with acute pancreatitis had an increased risk of pancreatic cancer compared with the age- and sex-matched general population throughout the follow-up period. The risk decreased over time......Background & Aims Acute pancreatitis may be a risk factor for pancreatic cancer. However, findings from studies on this association are conflicting. We investigated the association between acute pancreatitis and increased risk of pancreatic cancer. Methods We conducted a nationwide, population...

  16. The evaluation of complex clinical trial protocols: resources available to research ethics committees and the use of clinical trial registries--a case study.

    Science.gov (United States)

    Homedes, Núria; Ugalde, Antonio

    2015-06-01

    To assess the potential role of clinical trial (CT) registries and other resources available to research ethics committees (RECs) in the evaluation of complex CT protocols in low-income and middle-income countries. Using a case study approach, the authors examined the decision-making process of a REC in Argentina and its efforts to use available resources to decide on a complex protocol. We also analysed the information in the USA and other CT registries and consulted 24 CT experts in seven countries. Information requested by the Argentinean REC from other national RECs and ethics' experts was not useful to verify the adequacy of the REC's decision whether or not to approve the CT. The responses from the national regulatory agency and the sponsor were not helpful either. The identification of international resources that could assist was beyond the REC's capability. The information in the USA and other CT registries is limited, and at times misleading; and its accuracy is not verified by register keepers. RECs have limited access to experts and institutions that could assist them in their deliberations. Sponsors do not always answer RECs' request for information to properly conduct the ethical and methodological assessment of CT protocols. The usefulness of the CT registries is curtailed by the lack of appropriate codes and by data errors. Information about reasons for rejection, withdrawal or suspension of the trial should be included in the registries. Establishing formal channels of communication among national and foreign RECs and with independent international reference centres could strengthen the ethical review of CT protocols. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  17. The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial.

    Science.gov (United States)

    Leslie, Wilma S; Ford, Ian; Sattar, Naveed; Hollingsworth, Kieren G; Adamson, Ashley; Sniehotta, Falko F; McCombie, Louise; Brosnahan, Naomi; Ross, Hazel; Mathers, John C; Peters, Carl; Thom, George; Barnes, Alison; Kean, Sharon; McIlvenna, Yvonne; Rodrigues, Angela; Rehackova, Lucia; Zhyzhneuskaya, Sviatlana; Taylor, Roy; Lean, Mike E J

    2016-02-16

    Despite improving evidence-based practice following clinical guidelines to optimise drug therapy, Type 2 diabetes (T2DM) still exerts a devastating toll from vascular complications and premature death. Biochemical remission of T2DM has been demonstrated with weight loss around 15kg following bariatric surgery and in several small studies of non-surgical energy-restriction treatments. The non-surgical Counterweight-Plus programme, running in Primary Care where obesity and T2DM are routinely managed, produces >15 kg weight loss in 33% of all enrolled patients. The Diabetes UK-funded Counterpoint study suggested that this should be sufficient to reverse T2DM by removing ectopic fat in liver and pancreas, restoring first-phase insulin secretion. The Diabetes Remission Clinical Trial (DiRECT) was designed to determine whether a structured, intensive, weight management programme, delivered in a routine Primary Care setting, is a viable treatment for achieving durable normoglycaemia. Other aims are to understand the mechanistic basis of remission and to identify psychological predictors of response. Cluster-randomised design with GP practice as the unit of randomisation: 280 participants from around 30 practices in Scotland and England will be allocated either to continue usual guideline-based care or to add the Counterweight-Plus weight management programme, which includes primary care nurse or dietitian delivery of 12-20weeks low calorie diet replacement, food reintroduction, and long-term weight loss maintenance. Main inclusion criteria: men and women aged 20-65 years, all ethnicities, T2DM 0-6years duration, BMI 27-45 kg/m(2). Tyneside participants will undergo Magnetic Resonance (MR) studies of pancreatic and hepatic fat, and metabolic studies to determine mechanisms underlying T2DM remission. Co-primary endpoints: weight reduction ≥ 15 kg and HbA1c <48 mmol/mol at one year. Further follow-up at 2 years. This study will establish whether a structured weight

  18. Chronic pancreatitis.

    Science.gov (United States)

    Kleeff, Jorg; Whitcomb, David C; Shimosegawa, Tooru; Esposito, Irene; Lerch, Markus M; Gress, Thomas; Mayerle, Julia; Drewes, Asbjørn Mohr; Rebours, Vinciane; Akisik, Fatih; Muñoz, J Enrique Domínguez; Neoptolemos, John P

    2017-09-07

    Chronic pancreatitis is defined as a pathological fibro-inflammatory syndrome of the pancreas in individuals with genetic, environmental and/or other risk factors who develop persistent pathological responses to parenchymal injury or stress. Potential causes can include toxic factors (such as alcohol or smoking), metabolic abnormalities, idiopathic mechanisms, genetics, autoimmune responses and obstructive mechanisms. The pathophysiology of chronic pancreatitis is fairly complex and includes acinar cell injury, acinar stress responses, duct dysfunction, persistent or altered inflammation, and/or neuro-immune crosstalk, but these mechanisms are not completely understood. Chronic pancreatitis is characterized by ongoing inflammation of the pancreas that results in progressive loss of the endocrine and exocrine compartment owing to atrophy and/or replacement with fibrotic tissue. Functional consequences include recurrent or constant abdominal pain, diabetes mellitus (endocrine insufficiency) and maldigestion (exocrine insufficiency). Diagnosing early-stage chronic pancreatitis is challenging as changes are subtle, ill-defined and overlap those of other disorders. Later stages are characterized by variable fibrosis and calcification of the pancreatic parenchyma; dilatation, distortion and stricturing of the pancreatic ducts; pseudocysts; intrapancreatic bile duct stricturing; narrowing of the duodenum; and superior mesenteric, portal and/or splenic vein thrombosis. Treatment options comprise medical, radiological, endoscopic and surgical interventions, but evidence-based approaches are limited. This Primer highlights the major progress that has been made in understanding the pathophysiology, presentation, prevalence and management of chronic pancreatitis and its complications.

  19. Altered central pain processing after pancreatic surgery for chronic pancreatitis

    NARCIS (Netherlands)

    Bouwense, S. A.; Ahmed Ali, U.; ten Broek, R. P.; Issa, Y.; van Eijck, C. H.; Wilder-Smith, O. H.; van Goor, H.

    2013-01-01

    Chronic abdominal pain is common in chronic pancreatitis (CP) and may involve altered central pain processing. This study evaluated the relationship between pain processing and pain outcome after pancreatic duct decompression and/or pancreatic resection in patients with CP. Patients with CP

  20. Long-term follow-up of nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children.

    Science.gov (United States)

    Sugito, Kiminobu; Furuya, Takeshi; Kaneda, Hide; Masuko, Takayuki; Ohashi, Kensuke; Inoue, Mikiya; Ikeda, Taro; Koshinaga, Tsugumichi; Tomita, Ryouichi; Maebayashi, Toshiya

    2012-05-01

    The objectives of the present study were to determine nutritional status, pancreatic function, and morphological changes of the pancreatic remnant after pancreatic tumor resection in children. The nutritional status was evaluated by the patterns of growth. Pancreatic function was evaluated by using a questionnaire, the Bristol stool form chart, the serum levels of fasting blood glucose, and hemoglobin A1c (HbA1c). Morphological changes of the pancreatic remnant were evaluated by computed tomography, magnetic resonance image, or magnetic resonance cholangiopancreatography. The present study consisted of 6 patients with pancreatic tumor (5 solid pseudopapillary tumors of the pancreas and 1 pancreatoblastoma) who underwent the following operations: tumor enucleation (3), distal pancreatectomy with splenectomy (1), and pylorus-preserving pancreatoduodenectomy (PPPD [2]). The serum levels of HbA1c have been gradually elevated in 2 patients with PPPD. A significant decrease in pancreatic parenchymal thickness and dilatation of the main pancreatic duct were observed in 2 patients with PPPD. Endocrine pancreatic insufficiency after PPPD may be explainable by obstructive pancreatitis after operation. Taking together the results of pancreatic endocrine function and morphological changes of pancreatic remnant after PPPD, tumor enucleation should be considered as surgical approach in children with pancreas head tumor whenever possible.

  1. Low tube voltage CT for improved detection of pancreatic cancer: detection threshold for small, simulated lesions

    International Nuclear Information System (INIS)

    Holm, Jon; Loizou, Louiza; Albiin, Nils; Kartalis, Nikolaos; Leidner, Bertil; Sundin, Anders

    2012-01-01

    Pancreatic ductal adenocarcinoma is associated with dismal prognosis. The detection of small pancreatic tumors which are still resectable is still a challenging problem. The aim of this study was to investigate the effect of decreasing the tube voltage from 120 to 80 kV on the detection of pancreatic tumors. Three scanning protocols was used; one using the standard tube voltage (120 kV) and current (160 mA) and two using 80 kV but with different tube currents (500 and 675 mA) to achieve equivalent dose (15 mGy) and noise (15 HU) as that of the standard protocol. Tumors were simulated into collected CT phantom images. The attenuation in normal parenchyma at 120 kV was set at 130 HU, as measured previously in clinical examinations, and the tumor attenuation was assumed to differ 20 HU and was set at 110HU. By scanning and measuring of iodine solution with different concentrations the corresponding tumor and parenchyma attenuation at 80 kV was found to be 185 and 219 HU, respectively. To objectively evaluate the differences between the three protocols, a multi-reader multi-case receiver operating characteristic study was conducted, using three readers and 100 cases, each containing 0–3 lesions. The highest reader averaged figure-of-merit (FOM) was achieved for 80 kV and 675 mA (FOM = 0,850), and the lowest for 120 kV (FOM = 0,709). There was a significant difference between the three protocols (p < 0,0001), when making an analysis of variance (ANOVA). Post-hoc analysis (students t-test) shows that there was a significant difference between 120 and 80 kV, but not between the two levels of tube currents at 80 kV. We conclude that when decreasing the tube voltage there is a significant improvement in tumor conspicuity

  2. Pancreaticojejunostomy versus pancreaticogastrostomy reconstruction for the prevention of postoperative pancreatic fistula following pancreaticoduodenectomy.

    Science.gov (United States)

    Cheng, Yao; Briarava, Marta; Lai, Mingliang; Wang, Xiaomei; Tu, Bing; Cheng, Nansheng; Gong, Jianping; Yuan, Yuhong; Pilati, Pierluigi; Mocellin, Simone

    2017-09-12

    Pancreatoduodenectomy is a surgical procedure used to treat diseases of the pancreatic head and, less often, the duodenum. The most common disease treated is cancer, but pancreatoduodenectomy is also used for people with traumatic lesions and chronic pancreatitis. Following pancreatoduodenectomy, the pancreatic stump must be connected with the small bowel where pancreatic juice can play its role in food digestion. Pancreatojejunostomy (PJ) and pancreatogastrostomy (PG) are surgical procedures commonly used to reconstruct the pancreatic stump after pancreatoduodenectomy. Both of these procedures have a non-negligible rate of postoperative complications. Since it is unclear which procedure is better, there are currently no international guidelines on how to reconstruct the pancreatic stump after pancreatoduodenectomy, and the choice is based on the surgeon's personal preference. To assess the effects of pancreaticogastrostomy compared to pancreaticojejunostomy on postoperative pancreatic fistula in participants undergoing pancreaticoduodenectomy. We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 9), Ovid MEDLINE (1946 to 30 September 2016), Ovid Embase (1974 to 30 September 2016) and CINAHL (1982 to 30 September 2016). We also searched clinical trials registers (ClinicalTrials.gov and WHO ICTRP) and screened references of eligible articles and systematic reviews on this subject. There were no language or publication date restrictions. We included all randomized controlled trials (RCTs) assessing the clinical outcomes of PJ compared to PG in people undergoing pancreatoduodenectomy. We used standard methodological procedures expected by The Cochrane Collaboration. We performed descriptive analyses of the included RCTs for the primary (rate of postoperative pancreatic fistula and mortality) and secondary outcomes (length of hospital stay, rate of surgical re-intervention, overall rate of surgical complications, rate of postoperative

  3. Nutrition Following Pancreatic Surgery

    Science.gov (United States)

    ... BACK Contact Us DONATE NOW GENERAL DONATION PURPLESTRIDE Nutrition Following Pancreatic Surgery Home Facing Pancreatic Cancer Living with Pancreatic Cancer Diet and Nutrition Nutrition Following Pancreatic Surgery Ver esta página en ...

  4. Recurrent pancreatitis in pregnancy after preconception Whipple for pseudopapillary pancreatic tumor.

    Science.gov (United States)

    Dray, Danielle; Dahlke, Joshua D; Rouse, Dwight J

    2014-08-01

    Solid pseudopapillary pancreatic tumor is a rare tumor affecting young women. Case reports have presented pregnancy outcomes after pancreaticoduodenectomy (Whipple procedure) in pregnancy for this neoplasm. We report a case of a woman who underwent a preconception Whipple procedure for a solid pseudopapillary pancreatic tumor who experienced recurrent pancreatitis confined to pregnancy. A 28-year-old gravida 2 para 1 woman with a history of a Whipple procedure for a solid pseudopapillary pancreatic tumor 2 years prior had three episodes of severe pancreatitis in pregnancy. She was managed conservatively with each episode. She delivered at term and did not have a recurrence in the 8 months since her delivery. Recurrent pancreatitis in pregnancy after a preconception Whipple procedure can be managed conservatively without surgical intervention.

  5. Pancreatic Cancer Gene Therapy: From Molecular Targets to Delivery Systems

    Energy Technology Data Exchange (ETDEWEB)

    Fillat, Cristina, E-mail: cristina.fillat@crg.es; Jose, Anabel; Ros, Xavier Bofill-De; Mato-Berciano, Ana; Maliandi, Maria Victoria; Sobrevals, Luciano [Programa Gens i Malaltia, Centre de Regulació Genòmica-CRG, UPF, Parc de Recerca Biomedica de Barcelona-PRBB and Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona (Spain)

    2011-01-18

    The continuous identification of molecular changes deregulating critical pathways in pancreatic tumor cells provides us with a large number of novel candidates to engineer gene-targeted approaches for pancreatic cancer treatment. Targets—both protein coding and non-coding—are being exploited in gene therapy to influence the deregulated pathways to facilitate cytotoxicity, enhance the immune response or sensitize to current treatments. Delivery vehicles based on viral or non-viral systems as well as cellular vectors with tumor homing characteristics are a critical part of the design of gene therapy strategies. The different behavior of tumoral versus non-tumoral cells inspires vector engineering with the generation of tumor selective products that can prevent potential toxic-associated effects. In the current review, a detailed analysis of the different targets, the delivery vectors, the preclinical approaches and a descriptive update on the conducted clinical trials are presented. Moreover, future possibilities in pancreatic cancer treatment by gene therapy strategies are discussed.

  6. Acute Pancreatitis in Children

    Science.gov (United States)

    ... a feeding tube or an IV to prevent malnutrition and improve healing. Does my child have to ... Acute Pancreatitis in Children Chronic Pancreatitis in Children Childhood Inherited Disorders Pancreatic Cancer Pancreatic Cancer Risks and ...

  7. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection.

    Science.gov (United States)

    Gilliland, Taylor M; Villafane-Ferriol, Nicole; Shah, Kevin P; Shah, Rohan M; Tran Cao, Hop S; Massarweh, Nader N; Silberfein, Eric J; Choi, Eugene A; Hsu, Cary; McElhany, Amy L; Barakat, Omar; Fisher, William; Van Buren, George

    2017-03-07

    Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL). The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI) manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995-2016) addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC). We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1) patients with albumin 10% should postpone surgery and begin aggressive nutrition supplementation; (2) patients with albumin endocrine and exocrine pancreatic insufficiency alongside implementation of appropriate treatment to improve the patient's quality of life.

  8. Markers of angiogenesis and epidermal growth factor receptor signalling in patients with pancreatic and gastroesophageal junction cancer

    DEFF Research Database (Denmark)

    Rohrberg, Kristoffer Staal; Skov, Birgit Guldhammer; Lassen, Ulrik

    2010-01-01

    The epidermal growth factor receptor (EGFR) and angiogenesis are well established targets in anti-cancer therapy. Several targeted anti-cancer therapies are in clinical trials in pancreatic and gastroesophageal (GEJ) cancer. However, many patients do not respond to these targeted therapies...... in pancreatic and GEJ cancer patients, and could be investigated further as predictive biomarkers in such patients treated with EGFR or angiogenesis targeted therapies....

  9. Phase 1 trial evaluating cisplatin, gemcitabine, and veliparib in 2 patient cohorts: Germline BRCA mutation carriers and wild-type BRCA pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    O'Reilly, Eileen M; Lee, Jonathan W; Lowery, Maeve A; Capanu, Marinela; Stadler, Zsofia K; Moore, Malcolm J; Dhani, Neesha; Kindler, Hedy L; Estrella, Hayley; Maynard, Hannah; Golan, Talia; Segal, Amiel; Salo-Mullen, Erin E; Yu, Kenneth H; Epstein, Andrew S; Segal, Michal; Brenner, Robin; Do, Richard K; Chen, Alice P; Tang, Laura H; Kelsen, David P

    2018-04-01

    A phase 1 trial was used to evaluate a combination of cisplatin, gemcitabine, and escalating doses of veliparib in patients with untreated advanced pancreatic ductal adenocarcinoma (PDAC) in 2 cohorts: a germline BRCA1/2-mutated (BRCA+) cohort and a wild-type BRCA (BRCA-) cohort. The aims were to determine the safety, dose-limiting toxicities (DLTs), maximum tolerated dose, and recommended phase 2 dose (RP2D) of veliparib combined with cisplatin and gemcitabine and to assess the antitumor efficacy (Response Evaluation Criteria in Solid Tumors, version 1.1) and overall survival. Gemcitabine and cisplatin were dosed at 600 and 25 mg/m 2 , respectively, over 30 minutes on days 3 and 10 of a 21-day cycle. Four dose levels of veliparib were evaluated: 20 (dose level 0), 40 (dose level 1), and 80 mg (dose level 2) given orally twice daily on days 1 to 12 and 80 mg given twice daily on days 1 to 21 (dose level 2A [DL2A]). Seventeen patients were enrolled: 9 BRCA+ patients, 7 BRCA- patients, and 1 patient with an unknown status. DLTs were reached at DL2A (80 mg twice daily on days 1 to 21). Two of the 5 patients in this cohort (40%) experienced grade 4 neutropenia and thrombocytopenia. Two grade 5 events occurred on protocol. The objective response rate in the BRCA+ cohort was 7 of 9 (77.8%). The median overall survival for BRCA+ patients was 23.3 months (95% confidence interval [CI], 3.8-30.2 months). The median overall survival for BRCA- patients was 11 months (95% CI, 1.5-12.1 months). The RP2D of veliparib was 80 mg by mouth twice daily on days 1 to 12 in combination with cisplatin and gemcitabine; the DLT was myelosuppression. Substantial antitumor activity was seen in BRCA+ PDAC. A randomized phase 2 trial is currently evaluating cisplatin and gemcitabine with and without veliparib for BRCA+ PDAC (NCT01585805). Cancer 2018;124:1374-82. © 2018 American Cancer Society. © 2018 American Cancer Society.

  10. [Pancreatic trauma].

    Science.gov (United States)

    Arvieux, C; Guillon, F; Létoublon, Ch; Oughriss, M

    2003-10-01

    Early diagnosis of pancreatic trauma has always been challenging because of the lack of correlation between the initial clinical symptomatology, radiologic and laboratory findings, and the severity of the injury. Thanks to the improved performance of spiral CT scanning and magnetic resonance pancreatography, it is now often possible to make an early diagnosis of pancreatic contusion, to localize the site of the injury, and (most importantly) to identify injury to the main pancreatic duct which has major implications for the management of the case. When the trauma victim is unstable, radiologic work-up may be impossible and urgent laparotomy is required. Control of hemorrhage is the primary concern here and a damage control approach with packing may be appropriate; if the pancreatic head has been destroyed, a pancreaticoduodenectomy with delayed reconstruction may be required. If the trauma victim is stable, the treatment strategy will be governed by a variety of parameters--age, clinical condition, associated local anatomic findings (pancreatitis, injury to the duodenum or biliary tract), involvement of the pancreatic duct, and localization of the injury within the gland (to right or left of the mesenteric vessels).

  11. Which dressing do donor site wounds need?: study protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Ubbink Dirk T

    2011-10-01

    Full Text Available Abstract Background Donor site wounds after split-skin grafting are rather 'standard' wounds. At present, lots of dressings and topical agents for donor site wounds are commercially available. This causes large variation in the local care of these wounds, while the optimum 'standard' dressing for local wound care is unclear. This protocol describes a trial in which we investigate the effectiveness of various treatment options for these donor site wounds. Methods A 14-center, six-armed randomized clinical trial is being carried out in the Netherlands. An a-priori power analysis and an anticipated dropout rate of 15% indicates that 50 patients per group are necessary, totaling 300 patients, to be able to detect a 25% quicker mean time to complete wound healing. Randomization has been computerized to ensure allocation concealment. Adult patients who need a split-skin grafting operation for any reason, leaving a donor site wound of at least 10 cm2 are included and receive one of the following dressings: hydrocolloid, alginate, film, hydrofiber, silicone dressing, or paraffin gauze. No combinations of products from other intervention groups in this trial are allowed. Optimum application and changes of these dressings are pursued according to the protocol as supplied by the dressing manufacturers. Primary outcomes are days to complete wound healing and pain (using a Visual Analogue Scale. Secondary outcomes are adverse effects, scarring, patient satisfaction, and costs. Outcome assessors unaware of the treatment allocation will assess whether or not an outcome has occurred. Results will be analyzed according to the intention to treat principle. The first patient was randomized October 1, 2009. Discussion This study will provide comprehensive data on the effectiveness of different treatment options for donor site wounds. The dressing(s that will prevail in effectiveness, satisfaction and costs will be promoted among clinicians dealing with such

  12. Evaluation of pancreatic scintigram in the diagnosis of pancreatic diseases

    International Nuclear Information System (INIS)

    Takai, Yukihiro; Ueda, Noriyuki; Takasago, Noritsugu; Minemoto, Hiromasa; Namiki, Masayoshi

    1981-01-01

    The classification of accumulative patterns with the pancreatic scintigram findings of chronic pancreatitis and carcinoma of the pancreas were compared with endoscopic retrograde pancreatography (ERP) findings and Pancreozymin-Secretin test (P-S test). I) The frequency of pancreatic cancer was 93%, whilst, the chronic pancreatitis was 88% in the abnormal pancreatic scintigram. II) In the scintigram the type II (localyzed defect shadows) of pancreatic cancer was comparatively high and it is proportional to evidence. derived from ERP. Localized diagnostic certainty is helpful, although the two tests are related. The P-S test is only restricted to the carcinoma of head, whilst, scintigram is more useful to detect the carcinoma of the body and tail of the pancreas. III) As for the chronic pancreatitis, there are various accumulative patterns. This is resemblance to that of ERP findings, but in the P-S normal test, it showed discrepancy in part of the result. Particularly, in the type I (slightly generalized low uptake with density silhouette) and type II. Therefore in order to obtain an accurate diagnosis, it is essential to have both the P-S test and scintigram. (author)

  13. Differentiation of autoimmune pancreatitis from suspected pancreatic cancer by fluorine-18 fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Ozaki, Yayoi; Hamano, Hideaki; Oguchi, Kazuhiro

    2008-01-01

    Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG-PET) has been widely used for the diagnosis of pancreatic cancer. Because autoimmune pancreatitis is easily misdiagnosed as pancreatic cancer and can be tested for by FDG-PET analysis based on the presence of suspected pancreatic cancer, we attempted to clarify the differences in FDG-PET findings between the two conditions. We compared FDG-PET findings between 15 patients with autoimmune pancreatitis and 26 patients with pancreatic cancer. The findings were evaluated visually or semiquantitatively using the maximum standardized uptake value and the accumulation pattern of FDG. FDG uptake was found in all 15 patients with autoimmune pancreatitis, whereas it was found in 19 of 26 patients (73.1%) with pancreatic cancer. An accumulation pattern characterized by nodular shapes was significantly more frequent in pancreatic cancer, whereas a longitudinal shape indicated autoimmune pancreatitis. Heterogeneous accumulation was found in almost all cases of autoimmune pancreatitis, whereas homogeneous accumulation was found in pancreatic cancer. Significantly more cases of pancreatic cancer showed solitary localization, whereas multiple localization in the pancreas favored the presence of autoimmune pancreatitis. FDG uptake by the hilar lymph node was significantly more frequent in autoimmune pancreatitis than in pancreatic cancer, and uptake by the lachrymal gland, salivary gland, biliary duct, retroperitoneal space, and prostate were seen only in autoimmune pancreatitis. FDG-PET is a useful tool for differentiating autoimmune pancreatitis from suspected pancreatic cancer, if the accumulation pattern and extrapancreatic involvement are considered. IgG4 measurement and other current image tests can further confirm the diagnosis. (author)

  14. South African Research Ethics Committee Review of Standards of Prevention in HIV Vaccine Trial Protocols.

    Science.gov (United States)

    Essack, Zaynab; Wassenaar, Douglas R

    2018-04-01

    HIV prevention trials provide a prevention package to participants to help prevent HIV acquisition. As new prevention methods are proven effective, this raises ethical and scientific design complexities regarding the prevention package or standard of prevention. Given its high HIV incidence and prevalence, South Africa has become a hub for HIV prevention research. For this reason, it is critical to study the implementation of relevant ethical-legal frameworks for such research in South Africa. This qualitative study used in-depth interviews to explore the practices and perspectives of eight members of South African research ethics committees (RECs) who have reviewed protocols for HIV vaccine trials. Their practices and perspectives are compared with ethics guideline requirements for standards of prevention.

  15. Dynamic computed tomography of the pancreas in normal dogs and in a dog with pancreatic insulinoma.

    Science.gov (United States)

    Iseri, Toshie; Yamada, Kazutaka; Chijiwa, Kousaku; Nishimura, Ryohei; Matsunaga, Satoru; Fujiwara, Reina; Sasaki, Nobuo

    2007-01-01

    To establish optimal imaging conditions for enhanced computed tomography (CT) for canine pancreatic tumors, 10 healthy beagles were subjected to dynamic CT. This technique was then applied to a dog with suspected insulinoma. The changes in mean peak enhancement and the delay time of the aorta and pancreas were determined. In normal beagles, maximal arterial and pancreatic CT enhancement was observed at 15 +/- 2 s (795 +/- 52 Housfield unit [HU]) and 28 +/- 9 s (118 +/- 16HU) after contrast medium injection, respectively. Multiphase enhanced CT was performed in a pug with suspected insulinoma using the CT protocol defined for the normal beagles with some parameters modified; the images were acquired at the arterial (14 s after contrast medium injection), pancreatic (after 28 s), and equilibrium (after 90 s) phases; scanning was followed by exploratory laparotomy. CT images were characterized by an enhanced mass in the left pancreatic lobe at the arterial phase, during which the difference between the CT values of the mass and normal pancreas was the highest. Histopathologic diagnosis of the pancreatic mass was insulinoma. Thus, it appears that enhanced CT imaging can be used to delineate the pancreas from a pancreatic mass, and it may be helpful in deciding the need for surgery.

  16. Effectiveness of a transdiagnostic internet-based protocol for the treatment of emotional disorders versus treatment as usual in specialized care: study protocol for a randomized controlled trial.

    Science.gov (United States)

    González-Robles, Alberto; García-Palacios, Azucena; Baños, Rosa; Riera, Antonio; Llorca, Ginés; Traver, Francisco; Haro, Gonzalo; Palop, Vicente; Lera, Guillem; Romeu, José Enrique; Botella, Cristina

    2015-10-31

    Emotional disorders (depression and anxiety disorders) are highly prevalent mental health problems. Although evidence showing the effectiveness of disorder-specific treatments exists, high comorbidity rates among emotional disorders limit the utility of these protocols. This has led some researchers to focus their interest on transdiagnostic interventions, a treatment perspective that might be more widely effective across these disorders. Also, the current way of delivering treatments makes it difficult provide assistance to all of the population in need. The use of the Internet in the delivery of evidence-based treatments may help to disseminate treatments among the population. In this study, we aim to test the effectiveness of EmotionRegulation, a new transdiagnostic Internet-based protocol for unipolar mood disorders, five anxiety disorders (panic disorder, agoraphobia, social anxiety disorder, generalized anxiety disorder and anxiety disorder not otherwise specified), and obsessive-compulsive disorder in comparison to treatment as usual as provided in Spanish public specialized mental health care. We will also study its potential impact on basic temperament dimensions (neuroticism/behavioral inhibition and extraversion/behavioral activation). Expectations and opinions of patients about this protocol will also be studied. The study is a randomized controlled trial. 200 participants recruited in specialized care will be allocated to one of two treatment conditions: a) EmotionRegulation or b) treatment as usual. Primary outcome measures will be the BAI and the BDI-II. Secondary outcomes will include a specific measure of the principal disorder, and measures of neuroticism/behavioral inhibition and extraversion/behavioral activation. Patients will be assessed at baseline, post-treatment, and 3- and 12-month follow-ups. Intention to treat and per protocol analyses will be performed. Although the effectiveness of face-to-face transdiagnostic protocols has been

  17. Protocol for the Osteoporosis Choice trial. A pilot randomized trial of a decision aid in primary care practice

    Directory of Open Access Journals (Sweden)

    Tulledge-Scheitel Sidna M

    2009-12-01

    Full Text Available Abstract Background Bisphosphonates can reduce fracture risk in patients with osteoporosis, but many at-risk patients do not start or adhere to these medications. The aims of this study are to: (1 preliminarily evaluate the effect of an individualized 10-year osteoporotic fracture risk calculator and decision aid (OSTEOPOROSIS CHOICE for postmenopausal women at risk for osteoporotic fractures; and (2 assess the feasibility and validity (i.e., absence of contamination of patient-level randomization (vs. cluster randomization in pilot trials of decision aid efficacy. Methods/Design This is a protocol for a parallel, 2-arm, randomized trial to compare an intervention group receiving OSTEOPOROSIS CHOICE to a control group receiving usual primary care. Postmenopausal women with bone mineral density T-scores of STEOPOROSIS CHOICE on five outcomes: (a patient knowledge regarding osteoporosis risk factors and treatment; (b quality of the decision-making process for both the patient and clinician; (c patient and clinician acceptability and satisfaction with the decision aid; (d rate of bisphosphonate use and adherence, and (e trial processes (e.g., ability to recruit participants, collect patient outcomes. To capture these outcomes, we will use patient and clinician surveys following each visit and video recordings of the clinical encounters. These video recordings will also allow us to determine the extent to which clinicians previously exposed to the decision aid were able to recreate elements of the decision aid with control patients (i.e., contamination. Pharmacy prescription profiles and follow-up phone interviews will assess medication start and adherence at 6 months. Discussion This pilot trial will provide evidence of feasibility, validity of patient randomization, and preliminary efficacy of a novel approach -- decision aids -- to improving medication adherence for postmenopausal women at risk of osteoporotic fractures. The results will inform

  18. Nab-paclitaxel plus gemcitabine in the treatment of metastatic pancreatic cancer: utility and experience from the clinic

    Directory of Open Access Journals (Sweden)

    Kundranda MN

    2016-01-01

    Full Text Available Madappa N Kundranda, Tomislav Dragovich Division of Hematology and Oncology, Banner MD Anderson Cancer Center, Gilbert, AZ, USA Abstract: Pancreatic ductal adenocarcinoma remains one of the deadliest epithelial cancers, primarily due to late diagnosis, early metastasis and the lack of effective treatments. With recent advances in systemic therapies, the median survival for metastatic disease has essentially doubled to approximately 1 year, and a significant number of patients are receiving multiple lines of therapy. One such first-line therapy is the combination of gemcitabine with nab-paclitaxel, which was approved by the US Food and Drug Administration in 2013. This standard option is now serving as a backbone to other novel combinations. In this review, we focus on the development of this combination, its clinical utility, and real-life experiences of managing patients with metastatic pancreatic ductal adenocarcinoma receiving gemcitabine and nab-paclitaxel. Keywords: pancreatic ductal adenocarcinoma, nab-paclitaxel, MPACT trial, PRODIGE 4/ACCORD 11 trial

  19. From protocol to published report

    DEFF Research Database (Denmark)

    Berendt, Louise; Callréus, Torbjörn; Petersen, Lene Grejs

    2016-01-01

    and published reports of academic clinical drug trials. METHODS: A comparison was made between study protocols and their corresponding published reports. We assessed the overall consistency, which was defined as the absence of discrepancy regarding study type (categorized as either exploratory or confirmatory...... in 1999, 2001, and 2003, 95 of which fulfilled the eligibility criteria and had at least one corresponding published report reporting data on trial subjects. Overall consistency was observed in 39% of the trials (95% CI: 29 to 49%). Randomized controlled trials (RCTs) constituted 72% (95% CI: 63 to 81......%) of the sample, and 87% (95% CI: 80 to 94%) of the trials were hospital based. CONCLUSIONS: Overall consistency between protocols and their corresponding published reports was low. Motivators for the inconsistencies are unknown but do not seem restricted to economic incentives....

  20. Short and long-term post-operative outcomes of duodenum preserving pancreatic head resection for chronic pancreatitis affecting the head of pancreas: a systematic review and meta-analysis.

    Science.gov (United States)

    Jawad, Zaynab A R; Tsim, Nicole; Pai, Madhava; Bansi, Dev; Westaby, David; Vlavianos, Panagiotis; Jiao, Long R

    2016-02-01

    To evaluate the short and long term outcomes of duodenum preserving pancreatic head resection (DPPHR) procedures in the treatment of painful chronic pancreatitis. A systematic literature search was performed to identify all comparative studies evaluating long and short term postoperative outcomes (pain relief, morbidity and mortality, pancreatic exocrine and endocrine function). Five published studies fulfilled the inclusion criteria including 1 randomized controlled trial comparing the Beger and Frey procedure. In total, 323 patients underwent surgical procedures for chronic pancreatitis, including Beger (n = 138) and Frey (n = 99), minimal Frey (n = 32), modified Frey (n = 25) and Berne's modification (n = 29). Two studies comparing the Beger and Frey procedure were entered into a meta-analysis and showed no difference in post-operative pain (RD = -0.06; CI -0.21 to 0.09), mortality (RD = 0.01; CI -0.03 to 0.05), morbidity (RD = 0.12; CI -0.00 to 0.24), exocrine insufficiency (RD = 0.04; CI -0.10 to 0.18) and endocrine insufficiency (RD = -0.14 CI -0.28 to 0.01). All procedures are equally effective for the management of pain for chronic pancreatitis. The choice of procedure should be determined by other factors including the presence of secondary complications of pancreatitis and intra-operative findings. Registration number CRD42015019275. Centre for Reviews and Dissemination, University of York, 2009. Copyright © 2015 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

  1. Evaluating Data Abstraction Assistant, a novel software application for data abstraction during systematic reviews: protocol for a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Ian J. Saldanha

    2016-11-01

    abstraction approaches. Trial registration The trial is registered at National Information Center on Health Services Research and Health Care Technology (NICHSR under Registration # HSRP20152269: https://wwwcf.nlm.nih.gov/hsr_project/view_hsrproj_record.cfm?NLMUNIQUE_ID=20152269&SEARCH_FOR=Tianjing%20Li . All items from the World Health Organization Trial Registration Data Set are covered at various locations in this protocol. Protocol version and date: This is version 2.0 of the protocol, dated September 6, 2016. As needed, we will communicate any protocol amendments to the Institutional Review Boards (IRBs of Johns Hopkins Bloomberg School of Public Health (JHBSPH and Brown University. We also will make appropriate as-needed modifications to the NICHSR website in a timely fashion.

  2. 'Be active, eat right', evaluation of an overweight prevention protocol among 5-year-old children: design of a cluster randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Veldhuis Lydian

    2009-06-01

    Full Text Available Abstract Background The prevalence of overweight and obesity in children has at least doubled in the past 25 years with a major impact on health. In 2005 a prevention protocol was developed applicable within Youth Health Care. This study aims to assess the effects of this protocol on prevalence of overweight and health behaviour among children. Methods and design A cluster randomised controlled trial is conducted among 5-year-old children included by 44 Youth Health Care teams randomised within 9 Municipal Health Services. The teams are randomly allocated to the intervention or control group. The teams measure the weight and height of all children. When a child in the intervention group is detected with overweight according to the international age and gender specific cut-off points of BMI, the prevention protocol is applied. According to this protocol parents of overweight children are invited for up to three counselling sessions during which they receive personal advice about a healthy lifestyle, and are motivated for and assisted in behavioural change. The primary outcome measures are Body Mass Index and waist circumference of the children. Parents will complete questionnaires to assess secondary outcome measures: levels of overweight inducing/reducing behaviours (i.e. being physically active, having breakfast, drinking sweet beverages and watching television/playing computer games, parenting styles, parenting practices, and attitudes of parents regarding these behaviours, health-related quality of life of the children, and possible negative side effects of the prevention protocol. Data will be collected at baseline (when the children are aged 5 years, and after 12 and 24 months of follow-up. Additionally, a process and a cost-effectiveness evaluation will be conducted. Discussion In this study called 'Be active, eat right' we evaluate an overweight prevention protocol for use in the setting of Youth Health Care. It is hypothesized that the

  3. 78 FR 52929 - Scientific Information Request on Imaging Tests for the Diagnosis and Staging of Pancreatic...

    Science.gov (United States)

    2013-08-27

    ... submitting information from the list to upload your documents. Email submissions: src.org ">SIPS@epc- src.org... Email: src.org ">SIPS@epc- src.org . SUPPLEMENTARY INFORMATION: The Agency for Healthcare Research and... Pancreatic Adenocarcinoma, including those that describe adverse events. The entire research protocol...

  4. Imaging of pancreatitis

    International Nuclear Information System (INIS)

    Prassopoulos, P.

    2012-01-01

    Full text: Acute pancreatitis (AP) is an acute inflammatory process of the pancreas with variable involvement of peripancreatic tissues or remote organ systems. Mild AP accounts for 75-80% of the cases and it is characterized by interstitial oedema, absent or minimal organ dysfunction, lack of complications and, usually, uneventful recovery. Severe AP is characterized by pancreatic necrosis, protracted clinical course, high incidence of complications, and high mortality rate. The diagnosis of acute pancreatitis (AP) is generally based on clinical and laboratory findings. The role of imaging is to confirm diagnosis, to assess disease severity - especially by detecting pancreatic necrosis-, to reveal complications of the disease and to guide interventions). Contrast- enhanced multidetector CT is the current 'gold standard' imaging modality in the evaluation of patients with AP. The spectrum of findings seen on CT ranges from a normal appearance to diffuse pancreatic enlargement with poorly defined pancreatic contour and heterogeneous attenuation. Stranding of the fat surrounding the pancreas and fluid collections in the anterior pararenal space, the peritoneal cavity or elsewhere, acquiring the form of the anatomic space where they are developed, may also be disclosed. Lack of pancreatic parenchyma enhancement is indicative of the presence of pancreatic necrosis. CT may reveal biliary tract calculi, calcifications in patients with AP combined with chronic pancreatitis- and air in an inflamed pancreas. Pancreatic abscess is usually seen on CT as a focal low attenuation area with a thick wall that may exhibit enhancement following i.v. contrast media administration. Haemorrhage, pseudoaneurysms, renal and splenic parenchyma complications can also be demonstrated by CT. Balthazar et.al have developed CT classification and severity scores based on the presence of fluid collections and pancreatic necrosis. These scores correlate with the incidence of morbidity and

  5. Next generation sequencing of pancreatic ductal adenocarcinoma: right or wrong?

    Science.gov (United States)

    Connor, Ashton A; Gallinger, Steven

    2017-07-01

    Pancreatic ductal adenocarcinoma (PDAC) has the highest mortality rate of all epithelial malignancies and a paradoxically rising incidence rate. Clinical translation of next generation sequencing (NGS) of tumour and germline samples may ameliorate outcomes by identifying prognostic and predictive genomic and transcriptomic features in appreciable fractions of patients, facilitating enrolment in biomarker-matched trials. Areas covered: The literature on precision oncology is reviewed. It is found that outcomes may be improved across various malignancies, and it is suggested that current issues of adequate tissue acquisition, turnaround times, analytic expertise and clinical trial accessibility may lessen as experience accrues. Also reviewed are PDAC genomic and transcriptomic NGS studies, emphasizing discoveries of promising biomarkers, though these require validation, and the fraction of patients that will benefit from these outside of the research setting is currently unknown. Expert commentary: Clinical use of NGS with PDAC should be used in investigational contexts in centers with multidisciplinary expertise in cancer sequencing and pancreatic cancer management. Biomarker directed studies will improve our understanding of actionable genomic variation in PDAC, and improve outcomes for this challenging disease.

  6. Study protocol for a randomized controlled trial: tongue strengthening exercises in head and neck cancer patients, does exercise load matter?

    Science.gov (United States)

    Van Nuffelen, Gwen; Van den Steen, Leen; Vanderveken, Olivier; Specenier, Pol; Van Laer, Carl; Van Rompaey, Diane; Guns, Cindy; Mariën, Steven; Peeters, Marc; Van de Heyning, Paul; Vanderwegen, Jan; De Bodt, Marc

    2015-09-04

    Reduced tongue strength is an important factor contributing to early and late dysphagia in head and neck cancer patients previously treated with chemoradiotherapy. The evidence is growing that tongue strengthening exercises can improve tongue strength and swallowing function in both healthy and dysphagic subjects. However, little is known about the impact of specific features of an exercise protocol for tongue strength on the actual outcome (strength or swallowing function). Previous research originating in the fields of sports medicine and physical rehabilitation shows that the degree of exercise load is an influential factor for increasing muscle strength in the limb skeletal muscles. Since the tongue is considered a muscular hydrostat, it remains to be proven whether the same concepts will apply. This ongoing randomized controlled trial in chemoradiotherapy-treated patients with head and neck cancer investigates the effect of three tongue strengthening exercise protocols, with different degrees of exercise load, on tongue strength and swallowing. At enrollment, 51 patients whose dysphagia is primarily related to reduced tongue strength are randomly assigned to a training schedule of 60, 80, or 100% of their maximal tongue strength. Patients are treated three times a week for 8 weeks, executing 120 repetitions of the assigned exercise once per training day. Exercise load is progressively adjusted every 2 weeks. Patients are evaluated before, during and after treatment by means of tongue strength measurements, fiber-optic endoscopic evaluation of swallowing and quality-of-life questionnaires. This randomized controlled trial is the first to systematically investigate the effect of different exercise loads in tongue strengthening exercise protocols. The results will allow the development of more efficacious protocols. Current Controlled Trials ISRCTN14447678.

  7. Rapid Evolution from the First Episode of Acute Pancreatitis to Chronic Pancreatitis in Human Subjects

    OpenAIRE

    Elie Aoun; Adam Slivka; Dionysios J Papachristou; David C Whitcomb; Ferga C Gleeson; Georgios I Papachristou

    2007-01-01

    Context Growing evidence suggests that recurrent acute pancreatitis leads to chronic pancreatitis, but this sequence is seldom reported in human subjects. The sentinel acute pancreatitis event hypothesis suggests that an initial episode of acute pancreatitis is the first step in a complicated series of events ultimately leading to chronic pancreatitis. Objective To identify patients who evolved from recurrent acute pancreatitis to chronic pancreatitis. Setting The Severity of Acute Pancreatit...

  8. Maturation and function of human embryonic stem cell-derived pancreatic progenitors in macroencapsulation devices following transplant into mice.

    Science.gov (United States)

    Bruin, Jennifer E; Rezania, Alireza; Xu, Jean; Narayan, Kavitha; Fox, Jessica K; O'Neil, John J; Kieffer, Timothy J

    2013-09-01

    Islet transplantation is a promising cell therapy for patients with diabetes, but it is currently limited by the reliance upon cadaveric donor tissue. We previously demonstrated that human embryonic stem cell (hESC)-derived pancreatic progenitor cells matured under the kidney capsule in a mouse model of diabetes into glucose-responsive insulin-secreting cells capable of reversing diabetes. However, the formation of cells resembling bone and cartilage was a major limitation of that study. Therefore, we developed an improved differentiation protocol that aimed to prevent the formation of off-target mesoderm tissue following transplantation. We also examined how variation within the complex host environment influenced the development of pancreatic progenitors in vivo. The hESCs were differentiated for 14 days into pancreatic progenitor cells and transplanted either under the kidney capsule or within Theracyte (TheraCyte, Laguna Hills, CA, USA) devices into diabetic mice. Our revised differentiation protocol successfully eliminated the formation of non-endodermal cell populations in 99% of transplanted mice and generated grafts containing >80% endocrine cells. Progenitor cells developed efficiently into pancreatic endocrine tissue within macroencapsulation devices, despite lacking direct contact with the host environment, and reversed diabetes within 3 months. The preparation of cell aggregates pre-transplant was critical for the formation of insulin-producing cells in vivo and endocrine cell development was accelerated within a diabetic host environment compared with healthy mice. Neither insulin nor exendin-4 therapy post-transplant affected the maturation of macroencapsulated cells. Efficient differentiation of hESC-derived pancreatic endocrine cells can occur in a macroencapsulation device, yielding glucose-responsive insulin-producing cells capable of reversing diabetes.

  9. Incidental intraoperative discovery of a pancreatic neuroendocrine tumor associated with chronic pancreatitis

    Directory of Open Access Journals (Sweden)

    Surlin Valeriu

    2012-09-01

    Full Text Available Abstract Pancreatic neuroendocrine tumors are a rare entity with an incidence between 2 per million to 5 per 100 000. Association with pancreatitis (acute or chronic is rare and is considered to be determined by the tumoral obstruction of pancreatic ducts, but sometimes occurs without any apparent relationship between them. Non-functional neuroendocrine pancreatic tumors are usually diagnosed when either very large or metastatic. Small ones are occasionally diagnosed when imagery is performed for other diagnostic reasons. Intraoperative discovery is even rarer and poses problems of differential diagnosis with other pancreatic tumors. Association with chronic pancreatitis is rare and usually due to pancreatic duct obstruction by the tumor. We describe the case of a patient with a small non-functioning neuroendocrine tumor in the pancreatic tail accidentally discovered during surgery for delayed traumatic splenic rupture associated with chronic alcoholic pancreatitis. The tumor of 1.5cm size was well differentiated and confined to the pancreas, and was resected by a distal splenopancreatectomy. Conclusions Surgeons should be well aware of the rare possibility of a non-functional neuroendocrine tumor in the pancreas, associated with chronic pancreatitis, surgical resection being the optimal treatment for cure. Histopathology is of utmost importance to establish the correct diagnosis, grade of differentiation, malignancy and prognosis. Virtual slides The virtual slide(s for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/2114470176676003.

  10. Chronic Pancreatitis and Systemic Inflammatory Response Syndrome Prevent Impact of Chemotherapy with Gemcitabine in a Genetically Engineered Mouse Model of Pancreatic Cancer

    Directory of Open Access Journals (Sweden)

    Richard F. Knoop

    2014-06-01

    CONCLUSION: We could demonstrate for the first time that an improvement in median overall survival with gemcitabine is significantly abolished by a persistent mild chronic pancreatitis and a systemic inflammatory response syndrome. In particular, the inflammation biomarkers C-reactive protein, IL-6, and IL-1α could indicate the prognostic benefit of gemcitabine chemotherapy and should now be tested in prospective patient-controlled trials.

  11. Medicinal Plants and Their Inhibitory Activities against Pancreatic Lipase: A Review

    Directory of Open Access Journals (Sweden)

    Atefehalsadat Seyedan

    2015-01-01

    Full Text Available Obesity is recognized as a major life style disorder especially in developing countries and it is prevailing at an alarming speed in new world countries due to fast food intake, industrialization, and reduction of physical activity. Furthermore, it is associated with a vast number of chronic diseases and disabilities. To date, relatively effective drugs, from either natural or synthetic sources, are generally associated with serious side effects, often leading to cessation of clinical trials or even withdrawal from the market. In order to find new compounds which are more effective or with less adverse effects compared to orlistat, the drug that has been approved for obesity, new compounds isolated from natural products are being identified and screened for antiobesity effects, in particular, for their pancreatic lipase inhibitory effect. Pancreatic lipase inhibitory activity has been extensively used for the determination of potential efficacy of natural products as antiobesity agents. In attempts to identify natural products for overcoming obesity, more researches have been focused on the identification of newer pancreatic lipase inhibitors with less unpleasant adverse effects. In this review, we consider the potential role of plants that have been investigated for their pancreatic lipase inhibitory activity.

  12. A clinical trial protocol to treat massive Africanized honeybee (Apis mellifera) attack with a new apilic antivenom.

    Science.gov (United States)

    Barbosa, Alexandre Naime; Boyer, Leslie; Chippaux, Jean-Philippe; Medolago, Natalia Bronzatto; Caramori, Carlos Antonio; Paixão, Ariane Gomes; Poli, João Paulo Vasconcelos; Mendes, Mônica Bannwart; Dos Santos, Lucilene Delazari; Ferreira, Rui Seabra; Barraviera, Benedito

    2017-01-01

    Envenomation caused by multiple stings from Africanized honeybees Apis mellifera constitutes a public health problem in the Americas. In 2015, the Brazilian Ministry of Health reported 13,597 accidents (incidence of seven cases per 100,000 inhabitants) with 39 deaths (lethality of 0.25%). The toxins present in the venom, which include melittin and phospholipase A 2 , cause lesions in diverse organs and systems that may be fatal. As there has been no specific treatment to date, management has been symptomatic and supportive only. In order to evaluate the safety and neutralizing capacity of a new apilic antivenom, as well as to confirm its lowest effective dose, a clinical protocol was developed to be applied in a multicenter, non-randomized and open phase I/II clinical trial. Twenty participants with more than five stings, aged more than 18 years, of both sexes, who have not previously received the heterologous serum against bee stings, will be included for 24 months. The proposed dose was based on the antivenom neutralizing capacity and the number of stings. Treatment will be administered only in a hospital environment and the participants will be evaluated for a period up to 30 days after discharge for clinical and laboratory follow-up. This protocol, approved by the Brazilian regulatory agencies for ethics (National Commission for Ethics on Research - CONEP) and sanitation (National Health Surveillance Agency - ANVISA), is a guideline constituted by specific, adjuvant, symptomatic and complementary treatments, in addition to basic orientations for conducting a clinical trial involving heterologous sera. This is the first clinical trial protocol designed specifically to evaluate the preliminary efficacy and safety of a new antivenom against stings from the Africanized honeybee Apis mellifera . The results will support future studies to confirm a new treatment for massive bee attack that has a large impact on public health in the Americas.

  13. Ny klassifikation af pancreatitis acuta

    DEFF Research Database (Denmark)

    Hansen, Benny Østerbye; Schmidt, Palle Nordblad

    2011-01-01

    The course of acute pancreatitis is in the initial phase dominated by a systemic inflammatory response, later by local complications. A new classification defines three specific types of pancreatitis: 1) interstitial oedematous pancreatitis and 2) necrotizing pancreatitis with pancreatic...

  14. The "Healthy Habits, Healthy Girls" randomized controlled trial for girls: study design, protocol, and baseline results.

    Science.gov (United States)

    Leme, Ana Carolina Barco; Philippi, Sonia Tucunduva

    2015-07-01

    The purpose of this article is to describe the study design, protocol, and baseline results of the "Healthy Habits, Healthy Girls" program. The intervention is being evaluated through a randomized controlled trial in 10 public schools in the city of São Paulo, Brazil. Data on the following variables were collected and assessed at baseline and will be reevaluated at 7 and 12 months: body mass index, waist circumference, dietary intake, nutrition, physical activity, social cognitive mediators, physical activity level, sedentary behaviors, self-rated physical status, and overall self-esteem. According to the baseline results, 32.4% and 23.4% of girls were overweight in the intervention and control groups, respectively, and in both groups a higher percentage failed to meet daily recommendations for moderate and vigorous physical activity and maximum screen time (TV, computer, mobile devices). There were no significant differences between the groups for most of the variables, except age (p = 0.000) and waist circumference (p = 0.014). The study showed a gap in the Brazilian literature on protocols for randomized controlled trials to prevent obesity among youth. The current study may thus be an important initial contribution to the field.

  15. Clinical Trials

    Medline Plus

    Full Text Available ... to-kol). This plan explains how the trial will work. The trial is led by a principal ... for the clinical trial. The protocol outlines what will be done during the clinical trial and why. ...

  16. The significance of pancreatic juice trace-element concentration in chronic pancreatitis

    International Nuclear Information System (INIS)

    Persigehl, M.; Loeffler, A.; Hoeck, A.

    1979-01-01

    The diagnosis of exocrine pancreas insufficiency in patients with chronic pancreatitis is still not easy. The best-suited method to confirm the diagnosis seems to be the secretin pancreozymin test (SPT). As previous results have shown, the determination of trace elements in the pancreatic juice can improve the diagnostic value of the SPT. During the SPT, the concentrations of Zn, Fe, Rb, Co, Cr, Se, Sb, Cs, Sc and Ag were measured in the duodenal aspirate of 50 patients by instrumental neutron activation analysis. Of the 50 patients, 24 suffered from pancreatic insufficiency in chronic pancreatitis and 26 had no signs of pancreatic insufficiency. Only the concentration of zinc differed significantly in the two groups; the other elements showed a similar behaviour. In patients without disease of the exocrine pancreas the zinc content of the pancreatic juice during the SPT ws 0.46+-0.13μg/ml, whereas in patients with pancreatic insufficiency it was only 0.18+-0.07μg/ml. The corresponding output was 171+-49.3μg zinc in controls and 41+-17.4μg in patients. After stimulation with pancreozymin the concentrations of zinc increased in normal patients to 1.13+-0.14μg/ml and to 0.22+-0.12μg/ml in patients with pancreatic insufficiency. The data demonstrate that the measurement of zinc in the duodenal juice during the SPT improves the diagnostic value of the test and that zinc should also be determined in doubtful cases of pancreatic insufficiency. (author)

  17. Human pancreatic islet-derived extracellular vesicles modulate insulin expression in 3D-differentiating iPSC clusters.

    Directory of Open Access Journals (Sweden)

    Diana Ribeiro

    Full Text Available It has been suggested that extracellular vesicles (EVs can mediate crosstalk between hormones and metabolites within pancreatic tissue. However, the possible effect of pancreatic EVs on stem cell differentiation into pancreatic lineages remains unknown. Herein, human islet-derived EVs (h-Islet-EVs were isolated, characterized and subsequently added to human induced pluripotent stem cell (iPSC clusters during pancreatic differentiation. The h-islet-EVs had a mean size of 117±7 nm and showed positive expression of CD63 and CD81 EV markers as measured by ELISA. The presence of key pancreatic transcription factor mRNA, such as NGN3, MAFA and PDX1, and pancreatic hormone proteins such as C-peptide and glucagon, were confirmed in h-Islet-EVs. iPSC clusters were differentiated in suspension and at the end stages of the differentiation protocol, the mRNA expression of the main pancreatic transcription factors and pancreatic hormones was increased. H-Islet-EVs were supplemented to the iPSC clusters in the later stages of differentiation. It was observed that h-Islet-EVs were able to up-regulate the intracellular levels of C-peptide in iPSC clusters in a concentration-dependent manner. The effect of h-Islet-EVs on the differentiation of iPSC clusters cultured in 3D-collagen hydrogels was also assessed. Although increased mRNA expression for pancreatic markers was observed when culturing the iPSC clusters in 3D-collagen hydrogels, delivery of EVs did not affect the insulin or C-peptide intracellular content. Our results provide new information on the role of h-Islet-EVs in the regulation of insulin expression in differentiating iPSC clusters, and are highly relevant for pancreatic tissue engineering applications.

  18. Differential diagnosis of groove pancreatic carcinomas vs. groove pancreatitis: Usefulness of the portal venous phase

    International Nuclear Information System (INIS)

    Ishigami, Kousei; Tajima, Tsuyoshi; Nishie, Akihiro; Kakihara, Daisuke; Fujita, Nobuhiro; Asayama, Yoshiki; Ushijima, Yasuhiro; Irie, Hiroyuki; Nakamura, Masafumi; Takahata, Shunichi; Ito, Tetsuhide; Honda, Hiroshi

    2010-01-01

    Purpose: To clarify if the portal venous phase is helpful for the differential diagnosis of groove pancreatic carcinomas and groove pancreatitis. Materials and methods: MDCT and MRI of groove pancreatic carcinomas (n = 7) and groove pancreatitis (n = 15) were retrospectively reviewed by two radiologists independently. The signal intensity on T2-weighted images was subjectively assessed. The presence or absence of common bile duct (CBD) and main pancreatic duct (MPD) strictures, calcifications, and cystic lesions was evaluated. Additionally, the appearance of groove pancreatic carcinoma and that of groove pancreatitis in the portal venous phase on dynamic MDCT and MRI were compared. Results: There were no significant differences in the signal intensity on T2-weighted images and in the presence or absence of CBD and MPD strictures, calcifications, and cystic lesions between groove pancreatic carcinomas and groove pancreatitis. However, patchy focal enhancement in the portal venous phase was more commonly observed in groove pancreatitis than groove pancreatic carcinoma (Reviewers 1 and 2: 14/15 [93.3%] vs. 1/7 [14.3%], P < 0.0001). In addition, peripheral enhancement was only seen in groove pancreatic carcinomas (Reviewer 1: 4/7 [57.1%] vs. 0/15 [0%], P < 0.005, and Reviewer 2: 3/7 [42.9%] vs. 0/15 [0%], P < 0.05). Conclusion: The portal venous phase may be helpful for the differential diagnosis of groove pancreatic carcinomas and groove pancreatitis.

  19. Diagnosing autoimmune pancreatitis with the Unifying-Autoimmune-Pancreatitis-Criteria.

    Science.gov (United States)

    Schneider, Alexander; Michaely, Henrik; Rückert, Felix; Weiss, Christel; Ströbel, Philipp; Belle, Sebastian; Hirth, Michael; Wilhelm, Torsten J; Haas, Stephan L; Jesenofsky, Ralf; Schönberg, Stefan; Marx, Alexander; Singer, Manfred V; Ebert, Matthias P; Pfützer, Roland H; Löhr, J Matthias

    We had developed the Unifying-Autoimmune-Pancreatitis-Criteria (U-AIP) to diagnose autoimmune pancreatitis (AiP) within the M-ANNHEIM classification of chronic pancreatitis. In 2011, International-Consensus-Diagnostic-Criteria (ICDC) to diagnose AiP have been published. We had applied the U-AIP long before the ICDC were available. The aims of the study were, first, to describe patients with AiP diagnosed by the U-AIP; second, to compare diagnostic accuracies of the U-AIP and other diagnostic systems; third, to evaluate the clinical applicability of the U-AIP. From 1998 until 2008, we identified patients with AiP using U-AIP, Japanese-, Korean-, Asian-, Mayo-HISORt-, Revised-Mayo-HISORt- and Italian-criteria. We retrospectively verified the diagnosis by ICDC and Revised-Japanese-2011-criteria, compared diagnostic accuracies of all systems and evaluated all criteria in consecutive patients with pancreatitis (2009 until 2010, Pancreas-Outpatient-Clinic-Cohort, n = 84). We retrospectively validated our diagnostic approach in consecutive patients with a pancreatic lesion requiring surgery (Surgical-Cohort, n = 98). Overall, we identified 21 patients with AiP. Unifying-Autoimmune-Pancreatitis-Criteria and ICDC presented the highest diagnostic accuracies (each 98.8%), highest Youden indices (each 0.95238), and highest proportions of diagnosed patients (each n = 20/21, U-AIP/ICDC vs. other diagnostic systems, p Pancreatitis-Criteria revealed a satisfactory clinical applicability and offered an additional approach to diagnose AiP. Copyright © 2017 IAP and EPC. Published by Elsevier B.V. All rights reserved.

  20. Assessment value of quantitative indexes of pancreatic CT perfusion scanning for malignant degree of pancreatic cancer

    Directory of Open Access Journals (Sweden)

    Jiang-Xia Lei

    2016-10-01

    Full Text Available Objective: To analyze the assessment value of the quantitative indexes of pancreatic CT perfusion scanning for malignant degree of pancreatic cancer. Methods: A total of 58 patients with space-occupying pancreatic lesions were divided into 20 patients with pancreatic cancer and 38 patients with benign pancreatic lesions after pancreatic CT perfusion. Patients with pancreatic cancer received palliative surgery, and the cancer tissue and para-carcinoma tissue specimens were collected during operation. The differences in pancreatic CT perfusion scanning parameter values and serum tumor marker levels were compared between patients with pancreatic cancer and patients with benign pancreatic lesions, mRNA expression levels of malignant molecules in pancreatic cancer tissue and para-carcinoma tissue were further determined, and the correlation between pancreatic CT perfusion scanning parameter values and malignant degree of pancreatic cancer was analyzed. Results: CT perfusion scanning BF, BV and Per values of patients with pancreatic cancer were lower than those of patients with benign pancreatic lesions; serum CA19-9, CEA, CA125 and CA242 levels were higher than those of patients with benign pancreatic lesions (P<0.05; mRNA expression levels of Bcl-2, Bcl-xL and survivin in pancreatic cancer tissue samples were higher than those in paracarcinoma tissue samples, and mRNA expression levels of P53 and Bax were lower than those in para-carcinoma tissue samples (P<0.05; CT perfusion scanning parameters BF, BV and Per values of patients with pancreatic cancer were negatively correlated with CA19-9, CEA, CA125 and CA242 levels in serum as well as mRNA expression levels of Bcl-2, Bcl-xL and survivin in pancreatic cancer tissue, and positively correlated with mRNA expression levels of P53 and Bax in pancreatic cancer tissue (P<0.05. Conclusions: Pancreatic CT perfusion scanning is a reliable way to judge the malignant degree of pancreatic cancer and plays a

  1. Pancreatic stellate cells enhance stem cell-like phenotypes in pancreatic cancer cells

    International Nuclear Information System (INIS)

    Hamada, Shin; Masamune, Atsushi; Takikawa, Tetsuya; Suzuki, Noriaki; Kikuta, Kazuhiro; Hirota, Morihisa; Hamada, Hirofumi; Kobune, Masayoshi; Satoh, Kennichi; Shimosegawa, Tooru

    2012-01-01

    Highlights: ► Pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. ► Pancreatic cancer cells co-cultured with PSCs showed enhanced spheroid formation. ► Expression of stem cell-related genes ABCG2, Nestin and LIN28 was increased. ► Co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. ► This study suggested a novel role of PSCs as a part of the cancer stem cell niche. -- Abstract: The interaction between pancreatic cancer cells and pancreatic stellate cells (PSCs), a major profibrogenic cell type in the pancreas, is receiving increasing attention. There is accumulating evidence that PSCs promote the progression of pancreatic cancer by increasing cancer cell proliferation and invasion as well as by protecting them from radiation- and gemcitabine-induced apoptosis. Recent studies have identified that a portion of cancer cells, called “cancer stem cells”, within the entire cancer tissue harbor highly tumorigenic and chemo-resistant phenotypes, which lead to the recurrence after surgery or re-growth of the tumor. The mechanisms that maintain the “stemness” of these cells remain largely unknown. We hypothesized that PSCs might enhance the cancer stem cell-like phenotypes in pancreatic cancer cells. Indirect co-culture of pancreatic cancer cells with PSCs enhanced the spheroid-forming ability of cancer cells and induced the expression of cancer stem cell-related genes ABCG2, Nestin and LIN28. In addition, co-injection of PSCs enhanced tumorigenicity of pancreatic cancer cells in vivo. These results suggested a novel role of PSCs as a part of the cancer stem cell niche.

  2. Risk of pancreatitis after pancreatic duct guidewire placement during endoscopic retrograde cholangiopancreatography.

    Directory of Open Access Journals (Sweden)

    Yuki Ishikawa-Kakiya

    Full Text Available Advanced techniques have been developed to overcome difficult cannulation cases in endoscopic retrograde cholangiopancreatography (ERCP. Pancreatic duct guidewire placement method (PGW is performed in difficult cannulation cases; it is possible that it places patients at risk of post-ERCP pancreatitis (PEP. The mechanism of PEP is still unclear, but pancreatic duct pressure and injury of pancreatic duct are known causes of PEP. Therefore, we hypothesized a relationship between pancreatic duct diameter and PEP and predicted that PGW would increase the risk of PEP in patients with non-dilated pancreatic ducts. This study aimed to investigate whether PGW increased the risk of PEP in patients with pancreatic duct diameter ≤ 3 mm.We analyzed 332 patients with pancreatic duct ≤ 3 mm who performed first time ERCP session. The primary endpoint was the rate of adverse event of PEP. We evaluated the risk of PEP in patients who had undergone PGW compared to those who had not, using the inverse probability of treatment weighting (IPTW analysis.PGW was found to be an independent risk factor for PEP by univariate analysis (odds ratio [OR], 2.45; 95% confidence interval [CI], 1.12-5.38; p = 0.03 after IPTW in patients with pancreatic duct diameter ≤ 3 mm. Adjusted for all covariates, PGW remained an independent risk factor for PEP (OR, 3.12; 95% CI, 1.33-7.33; p = 0.01.Our results indicate that PGW in patients with pancreatic duct diameter ≤ 3 mm increases the risk of PEP.

  3. Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology.

    Science.gov (United States)

    Ferri, María José; Saez, Marc; Figueras, Joan; Fort, Esther; Sabat, Miriam; López-Ben, Santiago; de Llorens, Rafael; Aleixandre, Rosa Núria; Peracaula, Rosa

    2016-01-01

    There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9) is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies. CA 19-9, carcinoembryonic antigen (CEA), C-reactive protein, albumin, insulin growth factor-1 (IGF-1) and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls. The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC) of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients. Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.

  4. Improved Pancreatic Adenocarcinoma Diagnosis in Jaundiced and Non-Jaundiced Pancreatic Adenocarcinoma Patients through the Combination of Routine Clinical Markers Associated to Pancreatic Adenocarcinoma Pathophysiology.

    Directory of Open Access Journals (Sweden)

    María José Ferri

    Full Text Available There is still no reliable biomarker for the diagnosis of pancreatic adenocarcinoma. Carbohydrate antigen 19-9 (CA 19-9 is a tumor marker only recommended for pancreatic adenocarcinoma follow-up. One of the clinical problems lies in distinguishing between this cancer and other benign pancreatic diseases such as chronic pancreatitis. In this study we will assess the value of panels of serum molecules related to pancreatic cancer physiopathology to determine whether alone or in combination could help to discriminate between these two pathologies.CA 19-9, carcinoembryonic antigen (CEA, C-reactive protein, albumin, insulin growth factor-1 (IGF-1 and IGF binding protein-3 were measured using routine clinical analyzers in a cohort of 47 pancreatic adenocarcinoma, 20 chronic pancreatitis and 15 healthy controls.The combination of CA 19-9, IGF-1 and albumin resulted in a combined area under the curve (AUC of 0.959 with 93.6% sensitivity and 95% specificity, much higher than CA 19-9 alone. An algorithm was defined to classify the patients as chronic pancreatitis or pancreatic cancer with the above specificity and sensitivity. In an independent validation group of 20 pancreatic adenocarcinoma and 13 chronic pancreatitis patients, the combination of the four molecules classified correctly all pancreatic adenocarcinoma and 12 out of 13 chronic pancreatitis patients.Although this panel of markers should be validated in larger cohorts, the high sensitivity and specificity values and the convenience to measure these parameters in clinical laboratories shows great promise for improving pancreatic adenocarcinoma diagnosis.

  5. Differential diagnosis of focal pancreatitis and pancreatic cancer

    NARCIS (Netherlands)

    van Gulik, T. M.; Moojen, T. M.; van Geenen, R.; Rauws, E. A.; Obertop, H.; Gouma, D. J.

    1999-01-01

    The differentiation of focal, chronic pancreatitis (CP) and pancreatic cancer (PAC) poses a diagnostic dilemma. Both conditions may present with the same symptoms and signs. The complexity of differential diagnosis is enhanced because PAC is frequently associated with secondary inflammatory changes

  6. [Duodenum-preserving total pancreatic head resection and pancreatic head resection with segmental duodenostomy].

    Science.gov (United States)

    Takada, Tadahiro; Yasuda, Hideki; Nagashima, Ikuo; Amano, Hodaka; Yoshiada, Masahiro; Toyota, Naoyuki

    2003-06-01

    A duodenum-preserving pancreatic head resection (DPPHR) was first reported by Beger et al. in 1980. However, its application has been limited to chronic pancreatitis because of it is a subtotal pancreatic head resection. In 1990, we reported duodenum-preserving total pancreatic head resection (DPTPHR) in 26 cases. This opened the way for total pancreatic head resection, expanding the application of this approach to tumorigenic morbidities such as intraductal papillary mucinous tumor (IMPT), other benign tumors, and small pancreatic cancers. On the other hand, Nakao et al. reported pancreatic head resection with segmental duodenectomy (PHRSD) as an alternative pylorus-preserving pancreatoduodenectomy technique in 24 cases. Hirata et al. also reported this technique as a new pylorus-preserving pancreatoduodenostomy with increased vessel preservation. When performing DPTPHR, the surgeon should ensure adequate duodenal blood supply. Avoidance of duodenal ischemia is very important in this operation, and thus it is necessary to maintain blood flow in the posterior pancreatoduodenal artery and to preserve the mesoduodenal vessels. Postoperative pancreatic functional tests reveal that DPTPHR is superior to PPPD, including PHSRD, because the entire duodenum and duodenal integrity is very important for postoperative pancreatic function.

  7. Remnant pancreatic parenchymal volume predicts postoperative pancreatic exocrine insufficiency after pancreatectomy.

    Science.gov (United States)

    Okano, Keisuke; Murakami, Yoshiaki; Nakagawa, Naoya; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Takahashi, Shinya; Sueda, Taijiro

    2016-03-01

    Pancreatectomy, including pancreatoduodenectomy and distal pancreatectomy, often causes postoperative pancreatic exocrine insufficiency (PEI). Our aim was to clarify a relationship between remnant pancreatic volume and postoperative PEI. A total of 227 patients who underwent pancreatoduodenectomy or distal pancreatectomy were enrolled in this study. All patients underwent a (13)C-labeled mixed triglyceride breath test to assess pancreatic exocrine function and abdominal dynamic computed tomography for assessing remnant pancreatic volume after pancreatectomy at a median of 7 months postoperatively. The percent (13)CO2 cumulative dose at 7 hours (% dose (13)C cum 7 h) pancreatectomy were performed in 174 (76.7%) and 53 (23.3%) patients, respectively. Of the 227 patients, 128 (56.3%) developed postoperative PEI. Postoperative % dose (13)C cum 7 h was strongly correlated with remnant pancreatic volume (r = .509, P pancreatectomy (P pancreatectomy. Remnant pancreatic volume may predict postoperative PEI in patients who undergo pancreatectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

  8. A meta-analysis of gemcitabine containing chemotherapy for locally advanced and metastatic pancreatic adenocarcinoma

    Directory of Open Access Journals (Sweden)

    Ma Yue

    2011-03-01

    Full Text Available Abstract Background The objectives of the present study are to investigate the efficacy and safety profile of gemcitabine-based combinations in the treatment of locally advanced and metastatic pancreatic adenocarcinoma (LA/MPC. Methods We performed a computerized search using combinations of the following keywords: "chemotherapy", "gemcitabine", "trial", and "pancreatic cancer". Results Thirty-five trials were included in the present analysis, with a total of 9,979 patients accrued. The analysis showed that the gemcitabine-based combination therapy was associated with significantly better overall survival (OS (ORs, 1.15; p = 0.011, progression-free survival (PFS (ORs, 1.27; p Conclusions Gemcitabine in combination with capecitabine or oxaliplatin was associated with enhanced OS and ORR as compared with gemcitabine in monotherapy, which are likely to become the preferred standard first-line treatment of LA/MPC.

  9. Lysosome associated membrane proteins maintain pancreatic acinar cell homeostasis: LAMP-2 deficient mice develop pancreatitis.

    Science.gov (United States)

    Mareninova, Olga A; Sendler, Matthias; Malla, Sudarshan Ravi; Yakubov, Iskandar; French, Samuel W; Tokhtaeva, Elmira; Vagin, Olga; Oorschot, Viola; Lüllmann-Rauch, Renate; Blanz, Judith; Dawson, David; Klumperman, Judith; Lerch, Markus M; Mayerle, Julia; Gukovsky, Ilya; Gukovskaya, Anna S

    2015-11-01

    The pathogenic mechanism of pancreatitis is poorly understood. Recent evidence implicates defective autophagy in pancreatitis responses; however, the pathways mediating impaired autophagy in pancreas remain largely unknown. Here, we investigate the role of lysosome associated membrane proteins (LAMPs) in pancreatitis. We analyzed changes in LAMPs in experimental models and human pancreatitis, and the underlying mechanisms: LAMP de-glycosylation and degradation. LAMP cleavage by cathepsin B (CatB) was analyzed by mass spectrometry. We used mice deficient in LAMP-2 to assess its role in pancreatitis. Pancreatic levels of LAMP-1 and LAMP-2 greatly decrease across various pancreatitis models and in human disease. Pancreatitis does not trigger LAMPs' bulk de-glycosylation, but induces their degradation via CatB-mediated cleavage of LAMP molecule close to the boundary between luminal and transmembrane domains. LAMP-2 null mice spontaneously develop pancreatitis that begins with acinar cell vacuolization due to impaired autophagic flux, and progresses to severe pancreas damage characterized by trypsinogen activation, macrophage-driven inflammation, and acinar cell death. LAMP-2 deficiency causes a decrease in pancreatic digestive enzymes content, stimulates the basal and inhibits CCK-induced amylase secretion by acinar cells. The effects of LAMP-2 knockout and acute cerulein pancreatitis overlap, which corroborates the pathogenic role of LAMP decrease in experimental pancreatitis models. The results indicate a critical role for LAMPs, particularly LAMP-2, in maintaining pancreatic acinar cell homeostasis, and provide evidence that defective lysosomal function, resulting in impaired autophagy, leads to pancreatitis. Mice with LAMP-2 deficiency present a novel genetic model of human pancreatitis caused by lysosomal/autophagic dysfunction.

  10. Pancreatic tissue fluid pressure and pain in chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N

    1992-01-01

    A casual relation between pancreatic pressure and pain has been searched for decades but lack of appropriate methods for pressure measurements has hindered progress. During the 1980's the needle method has been used for direct intraoperative pancreatic tissue fluid pressure measurements and later...... for percutaneous sonographically-guided pressure measurements. Clinical and experimental evaluation of the method showed comparable results at intraoperative and percutaneous measurements and little week-to-week variation. Furthermore, comparable pressures in duct and adjacent pancreatic tissue were found, i.......e. the needle pressure mirrors the intraductal pressure. Comparisons of pain registrations, morphological and functional parameters with pancreatic tissue fluid pressure measurements have revealed a relation between pressure and pain which probably is causal. In patients with pain the high pressures previously...

  11. Incidence and risk factors for post-ERCP pancreatitis in chronic pancreatitis.

    Science.gov (United States)

    Zhao, Zhen-Hua; Hu, Liang-Hao; Ren, Hong-Bo; Zhao, An-Jing; Qian, Yang-Yang; Sun, Xiao-Tian; Su, Song; Zhu, Shu-Guang; Yu, Jin; Zou, Wen-Bin; Guo, Xiao-Rong; Wang, Lei; Li, Zhao-Shen; Liao, Zhuan

    2017-09-01

    Almost all studies on post-ERCP pancreatitis (PEP) have mainly involved patients with biliary diseases rather than chronic pancreatitis (CP), and the concept that CP seems to be a protective factor associated with PEP has not been studied in detail. The aim of this study was to determine the incidence of PEP in patients with CP at different clinical stages and to identify the predictive and protective factors of PEP in a large cohort. In this observational cohort study, medical records of patients with CP (CP group) and biliary diseases (BD group) in a tertiary hospital from January 2011 to May 2015 were examined. The difference in the incidence of PEP between CP group and BD group and the risk of PEP at different clinical stages of CP were calculated by the χ 2 test or the Fisher exact test. The predictive and protective factors for PEP were investigated by univariate and multivariate analysis. In total, 2028 ERCP procedures were performed in 1301 patients with CP and 2000 procedures in 1655 patients with BD. The overall incidence of PEP in CP group (4.5%) was similar to that in the BD group (4.8%; P = .747). However, CP patients had significantly lower rates of moderate and severe attacks (0% vs 1.3%, P pancreatitis, and prior PEP were independent risk factors of PEP, whereas extracorporeal shock wave lithotripsy was a protective factor. Compared with BD patients, CP patients had similar incidence of PEP overall but lower grades of severity. The incidence of PEP in CP patients decreased significantly with disease progression. (Clinical trial registration number: NCT02781987.). Copyright © 2017 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.

  12. Early low volume oral synbiotic/prebiotic supplemented enteral stimulation of the gut in patients with severe acute pancreatitis: a prospective feasibility study.

    Science.gov (United States)

    Plaudis, H; Pupelis, G; Zeiza, K; Boka, V

    2012-01-01

    Experience with administration of synbiotics (prebiotics/probiotics) in patients with severe acute pancreatitis (SAP) has demonstrated immunomodulatory capacity. The aim of this trial was evaluation of the feasibility and perspective of early clinical application of oral synbiotic/prebiotic supplements in patients with SAP. 90 SAP patients were enrolled during the period from 2005-2008. Patients were stratified according to the feeding mode. CONTROL (n = 32) group received standard whole protein feeding formula. SYNBIO (n = 30) and FIBRE groups (n = 28) received early (within first 24-48 hours) synbiotic or prebiotic supplements. Oral administration of synbiotics or prebiotics was commenced when patients were able to sip water. Daily provided average volume and calories of synbiotic/prebiotic blends were smaller compared to the CONTROL, p = 0.001. Oral administration of synbiotic/prebiotic supplements was associated with lower infection rate (pancreatic and peripancreatic necrosis) compared to the CONTROL, (p = 0.03; p = 0.001), lower rate of surgical interventions, p = 0.005, shorter ICU (p = 0.05) and hospital stay (p = 0.03). Synbiotic supplemented enteral stimulation of the gut resulted in reduced mortality rate compared to the CONTROL, p = 0.02. Early low volume oral synbiotic/prebiotic supplemented enteral stimulation of the gut seems to be a potentially valuable complement to the routine treatment protocol of SAP.

  13. Pancreatic adenocarcinoma, chronic pancreatitis, and MODY-8 diabetes: is bile salt-dependent lipase (or carboxyl ester lipase) at the crossroads of pancreatic pathologies?

    Science.gov (United States)

    Lombardo, Dominique; Silvy, Françoise; Crenon, Isabelle; Martinez, Emmanuelle; Collignon, Aurélie; Beraud, Evelyne; Mas, Eric

    2018-02-23

    Pancreatic adenocarcinomas and diabetes mellitus are responsible for the deaths of around two million people each year worldwide. Patients with chronic pancreatitis do not die directly of this disease, except where the pathology is hereditary. Much current literature supports the involvement of bile salt-dependent lipase (BSDL), also known as carboxyl ester lipase (CEL), in the pathophysiology of these pancreatic diseases. The purpose of this review is to shed light on connections between chronic pancreatitis, diabetes, and pancreatic adenocarcinomas by gaining an insight into BSDL and its variants. This enzyme is normally secreted by the exocrine pancreas, and is diverted within the intestinal lumen to participate in the hydrolysis of dietary lipids. However, BSDL is also expressed by other cells and tissues, where it participates in lipid homeostasis. Variants of BSDL resulting from germline and/or somatic mutations (nucleotide insertion/deletion or nonallelic homologous recombination) are expressed in the pancreas of patients with pancreatic pathologies such as chronic pancreatitis, MODY-8, and pancreatic adenocarcinomas. We discuss the possible link between the expression of BSDL variants and these dramatic pancreatic pathologies, putting forward the suggestion that BSDL and its variants are implicated in the cell lipid metabolism/reprogramming that leads to the dyslipidemia observed in chronic pancreatitis, MODY-8, and pancreatic adenocarcinomas. We also propose potential strategies for translation to therapeutic applications.

  14. Surgical Approaches to Chronic Pancreatitis

    Directory of Open Access Journals (Sweden)

    Daniel Hartmann

    2015-01-01

    Full Text Available Chronic pancreatitis is a progressive inflammatory disease resulting in permanent structural damage of the pancreas. It is mainly characterized by recurring epigastric pain and pancreatic insufficiency. In addition, progression of the disease might lead to additional complications, such as pseudocyst formation or development of pancreatic cancer. The medical and surgical treatment of chronic pancreatitis has changed significantly in the past decades. With regard to surgical management, pancreatic head resection has been shown to be a mainstay in the treatment of severe chronic pancreatitis because the pancreatic head mass is known to trigger the chronic inflammatory process. Over the years, organ-preserving procedures, such as the duodenum-preserving pancreatic head resection and the pylorus-preserving Whipple, have become the surgical standard and have led to major improvements in pain relief, preservation of pancreatic function, and quality of life of patients.

  15. Food-Induced Acute Pancreatitis.

    Science.gov (United States)

    Manohar, Murli; Verma, Alok K; Upparahalli Venkateshaiah, Sathisha; Goyal, Hemant; Mishra, Anil

    2017-12-01

    Food allergy, a commonly increasing problem worldwide, defined as an adverse immune response to food. A variety of immune-related effector cells such as mast cells, eosinophils, neutrophils, and T cells are involved in food-related allergic responses categorized as IgE mediated, non-IgE mediated, and mixed (IgE and non-IgE) depending upon underlying immunological mechanisms. The dietary antigens mainly target the gastrointestinal tract including pancreas that gets inflamed due to food allergy and leads acute pancreatitis. Reports indicate several food proteins induce pancreatitis; however, detailed underlying mechanism of food-induced pancreatitis is unexplored. The aim of the review is to understand and update the current scenario of food-induced pancreatitis. A comprehensive literature search of relevant research articles has been performed through PubMed, and articles were chosen based on their relevance to food allergen-mediated pancreatitis. Several cases in the literature indicate that acute pancreatitis has been provoked after the consumption of mustard, milk, egg, banana, fish, and kiwi fruits. Food-induced pancreatitis is an ignored and unexplored area of research. The review highlights the significance of food in the development of pancreatitis and draws the attention of physicians and scientists to consider food allergies as a possible cause for initiation of pancreatitis pathogenesis.

  16. Surgical therapy in chronic pancreatitis.

    Science.gov (United States)

    Neal, C P; Dennison, A R; Garcea, G

    2012-12-01

    Chronic pancreatitis (CP) is an inflammatory disease of the pancreas which causes chronic pain, as well as exocrine and endocrine failure in the majority of patients, together producing social and domestic upheaval and a very poor quality of life. At least half of patients will require surgical intervention at some stage in their disease, primarily for the treatment of persistent pain. Available data have now confirmed that surgical intervention may produce superior results to conservative and endoscopic treatment. Comprehensive individual patient assessment is crucial to optimal surgical management, however, in order to determine which morphological disease variant (large duct disease, distal stricture with focal disease, expanded head or small duct/minimal change disease) is present in the individual patient, as a wide and differing range of surgical approaches are possible depending upon the specific abnormality within the gland. This review comprehensively assesses the evidence for these differing approaches to surgical intervention in chronic pancreatitis. Surgical drainage procedures should be limited to a small number of patients with a dilated duct and no pancreatic head mass. Similarly, a small population presenting with a focal stricture and tail only disease may be successfully treated by distal pancreatectomy. Long-term results of both of these procedure types are poor, however. More impressive results have been yielded for the surgical treatment of the expanded head, for which a range of surgical options now exist. Evidence from level I studies and a recent meta-analysis suggests that duodenum-preserving resections offer benefits compared to pancreaticoduodenectomy, though the results of the ongoing, multicentre ChroPac trial are awaited to confirm this. Further data are also needed to determine which of the duodenum-preserving procedures provides optimal results. In relation to small duct/minimal change disease total pancreatectomy represents the only

  17. Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer.

    Science.gov (United States)

    Fujioka, Rumi; Mochizuki, Nobuo; Ikeda, Masafumi; Sato, Akihiro; Nomura, Shogo; Owada, Satoshi; Yomoda, Satoshi; Tsuchihara, Katsuya; Kishino, Satoshi; Esumi, Hiroyasu

    2018-01-01

    Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.

  18. Change in plasma lactate concentration during arctigenin administration in a phase I clinical trial in patients with gemcitabine-refractory pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Rumi Fujioka

    Full Text Available Arctigenin is evaluated for antitumor efficacy in patients with pancreatic cancer. It has an inhibitory activity on mitochondrial complex I.Therefore, plasma lactate level of patients after arctigenin administration was evaluated for biomarker of clinical response and/or adverse effect. Plasma lactate level in 15 patients enrolled in a Phase I clinical trial of GBS-01 rich in arctigenin was analyzed by colorimetric assay. Statistical analyses for association of plasma lactate and clinical responses, pharmacokinetics of arctigenin, and background factors of each patient by multivariate and univariate analyses.In about half of the patients, transient increase of lactate was observed. Correlation between plasma lactate level and pharmacokinetic parameters of arctigenin and its glucuronide conjugate, and clinical outcome was not detected. Regarding to the determinant of lactate level, only slight association with liver function test was detected. Plasma lactate level is primary determined by reutilization rather than production for antitumor effect and dose not serve as a biomarker. Arctigenin, inhibition of mitochondrial complex I, plasma lactate concentration, phase I clinical trial of GBS-01, Cori cycle.

  19. Correction: PAIS: paracetamol (acetaminophen in stroke; protocol for a randomized, double blind clinical trial. [ISCRTN74418480

    Directory of Open Access Journals (Sweden)

    Kappelle L Jaap

    2008-11-01

    Full Text Available Abstract Background The Paracetamol (Acetaminophen In Stroke (PAIS study is a phase III multicenter, double blind, randomized, placebo-controlled clinical trial of high-dose acetaminophen in patients with acute stroke. The trial compares treatment with a daily dose of 6 g acetaminophen, started within 12 hours after the onset of symptoms, with matched placebo. The purpose of this study is to assess whether treatment with acetaminophen for 3 days will result in improved functional outcome through a modest reduction in body temperature and prevention of fever. The previously planned statistical analysis based on a dichotomization of the scores on the modified Rankin Scale (mRS may not make the most efficient use of the available baseline information. Therefore, the planned primary analysis of the PAIS study has been changed from fixed dichotomization of the mRS to a sliding dichotomy analysis. Methods Instead of taking a single definition of good outcome for all patients, the definition is tailored to each individual patient's baseline prognosis on entry into the trial. Conclusion The protocol change was initiated because of both advances in statistical approaches and to increase the efficiency of the trial by improving statistical power. Trial Registration Current Controlled Trials [ISCRTN74418480

  20. Imaging of pancreatic diseases

    International Nuclear Information System (INIS)

    Akisada, Masayoshi; Hiramatsu, Yoshihiro; Ishikawa, Nobuyoshi; Tatezawa, Akira; Matsumoto, Kunihiko

    1982-01-01

    There has been no definite examining technique for the early diagnosis of pancreatic diseases, especially small cancers of the pancreas less than 3 cm. Plain abdominal X-rays do not produce reliable roentgenological signs of acute pancreatitis, but the advent of CT has elucidated the condition to some extent. Upper gastrointestinal series are alleged to demonstrate abnormal findings in 80% of cases of pancreatic cancer or cyst. Pancreatic RI scintigraphy expresses the function and anatomy, and the sensitivity with 75 Se is 88%, similar to 87% by US and 80% by CT. Although endoscopic retrograde cholangiopancreatography visualizes extrapancreatic secretory function, as well as the morphology of pancreas, differentiation is not easy in many cases. The greatest indication for US was cysts. The detection rate of pancreatic cancers is similar between plain and contrast CTs, and pancreatic angiography is not specific for pancreatic cancers. (Chiba, N.)

  1. Pancreatic tissue fluid pressure during drainage operations for chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P

    1990-01-01

    Pancreatic tissue fluid pressure was measured in 10 patients undergoing drainage operations for painful chronic pancreatitis. The pressure was measured by the needle technique in the three anatomic regions of the pancreas before and at different stages of the drainage procedure, and the results...... were compared with preoperative endoscopic retrograde cholangiopancreatography (ERCP) morphology. The preoperatively elevated pressure decreased in all patients but one, to normal or slightly elevated values. The median pressure decrease was 50% (range, 0-90%; p = 0.01). The drainage anastomosis (a...... a decrease in pancreatic tissue fluid pressure during drainage operations for pain in chronic pancreatitis. Regional pressure decrease were apparently unrelated to ERCP findings....

  2. Study protocol for a pragmatic randomised controlled trial evaluating efficacy of a smoking cessation e-‘Tabac Info Service’: ee-TIS trial

    Science.gov (United States)

    Cambon, L; Bergman, P; Le Faou, Al; Vincent, I; Le Maitre, B; Pasquereau, A; Arwidson, P; Thomas, D; Alla, F

    2017-01-01

    Introduction A French national smoking cessation service, Tabac Info Service, has been developed to provide an adapted quitline and a web and mobile application involving personalised contacts (eg, questionnaires, advice, activities, messages) to support smoking cessation. This paper presents the study protocol of the evaluation of the application (e-intervention Tabac Info Service (e-TIS)). The primary objective is to assess the efficacy of e-TIS. The secondary objectives are to (1) describe efficacy variations with regard to users' characteristics, (2) analyse mechanisms and contextual conditions of e-TIS efficacy. Methods and analyses The study design is a two-arm pragmatic randomised controlled trial including a process evaluation with at least 3000 participants randomised to the intervention or to the control arm (current practices). Inclusion criteria are: aged 18 years or over, current smoker, having completed the online consent forms, possessing a mobile phone with android or apple systems and using mobile applications, wanting to stop smoking sooner or later. The primary outcome is the point prevalence abstinence of 7 days at 6 months later. Data will be analysed in intention to treat (primary) and per protocol analyses. A logistic regression will be carried out to estimate an OR (95% CI) for efficacy. A multivariate multilevel analysis will explore the influence on results of patients' characteristics (sex, age, education and socioprofessional levels, dependency, motivation, quit experiences) and contextual factors, conditions of use, behaviour change techniques. Ethics and dissemination The study protocol was reviewed by the ethical and deontological institutional review board of the French Institute for Public Health Surveillance on 18 April 2016. The findings of this study will allow us to characterise the efficacy of e-TIS and conditions of its efficacy. These findings will be disseminated through peer-reviewed articles. Trial registration

  3. A Phase I Safety, Pharmacokinetic, and Pharmacodynamic Presurgical Trial of Vitamin E δ-tocotrienol in Patients with Pancreatic Ductal Neoplasia

    Directory of Open Access Journals (Sweden)

    Gregory M. Springett

    2015-12-01

    Interpretation: VEDT from 200 to 1600 mg daily taken orally for 2 weeks before pancreatic surgery was well tolerated, reached bioactive levels in blood, and significantly induced apoptosis in the neoplastic cells of patients with pancreatic ductal neoplasia. These promising results warrant further clinical investigation of VEDT for chemoprevention and/or therapy of pancreatic cancer.

  4. Role of pancreatic polypeptide in the regulation of pancreatic exocrine secretion in dogs

    International Nuclear Information System (INIS)

    Shiratori, Keiko; Lee, K.Y.; Chang, Tamin; Jo, Y.H.; Coy, D.H.; Chey, W.Y.

    1988-01-01

    The effect of intravenous infusion of synthetic human pancreatic polypeptide (HPP) or a rabbit anti-PP serum on pancreatic exocrine secretion was studied in 10 dogs with gastric and Thomas duodenal cannulas. The infusion of HPP, achieved a plasma PP concentration that mimicked the peak plasma concentration of PP in both interdigestive and postprandial states. This dose of HPP significantly inhibited pancreatic secretion in the interdigestive state. By contrast, immunoneutralization of circulating PP by a rabbit anti-PP serum resulted in significant increases in both interdigestive and postprandial pancreatic secretion, including water, bicarbonate, and protein. The increase in the pancreatic secretion paralleled a decrease in circulating PP level, which lasted for as long as 5 days. Furthermore, the anti-PP serum blocked the inhibitory action of exogenous HPP on pancreatic exocrine secretion. The present study indicates that endogenous PP plays a significant role in the regulation of the pancreatic exocrine secretion in both interdigestive and digestive states. Thus the authors conclude that PP is another hormone regulating pancreatic exocrine secretion in dogs

  5. Hereditary pancreatitis: current perspectives

    Directory of Open Access Journals (Sweden)

    Raphael KL

    2016-07-01

    Full Text Available Kara L Raphael, Field F Willingham Division of Digestive Diseases, Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA Abstract: Hereditary pancreatitis (HP is a rare cause of acute, recurrent acute, and chronic pancreatitis. It may present similarly to other causes of acute and chronic pancreatitis, and often there has been a protracted evaluation prior to the diagnosis of HP. Since it was first described in 1952, multiple genetic defects that affect the action of digestive enzymes in the pancreas have been implicated. The most common mutations involve the PRSS1, CFTR, SPINK1, and CTRC genes. New mutations in these genes and previously unrecognized mutations in other genes are being discovered due to the increasing use of next-generation genomic sequencing. While the inheritance pathways of these genetic mutations may be variable and complex, sometimes involving coinheritance of other mutations, the clinical presentation of patients tends to be similar. Interactions with environmental triggers often play a role. Patients tend to present at an early age (prior to the second decade of life and have a significantly increased risk for the development of pancreatic adenocarcinoma. Patients with HP may develop sequelae of chronic pancreatitis such as strictures and fluid collections as well as exocrine and endocrine insufficiency. Management of patients with HP involves avoidance of environmental triggers, surveillance for pancreatic adenocarcinoma, medical therapy for endocrine and exocrine insufficiency, pain management, and endoscopic or surgical treatment for complications. Care for affected patients should be individualized, with an emphasis on early diagnosis and multidisciplinary involvement to develop a comprehensive treatment strategy. Keywords: pancreatic cancer, chronic pancreatitis, idiopathic pancreatitis, pancreatitis, familial pancreatitis, genetic mutations

  6. Role of chymotrypsin C in development and progression of pancreatitis and pancreatic cancer

    Directory of Open Access Journals (Sweden)

    LIU Zejie

    2016-11-01

    Full Text Available Chymotrypsin C (CTRC is a trypsinogen synthesized by pancreatic acinar cells and secreted by pancreatic duct cells and belongs to the family of serine chymotrypsin. The main function of CTRC is to regulate the balance between activation and degradation of trypsin and maintain the structural and functional integrity of the pancreas. CTRC gene mutations can cause abnormal activation of trypsinogen and abnormal degradation of trypsin and then lead to the development of pancreatitis. The downregulation or absence of CTRC expression may be associated with the development and metastasis of pancreatic cancer. This article introduces the structure and biological function of CTRC and its mechanism of action in the development and progression of pancreatitis and pancreatic cancer.

  7. Endocrine and exocrine pancreatic insufficiency after acute pancreatitis: long-term follow-up study.

    Science.gov (United States)

    Tu, Jianfeng; Zhang, Jingzhu; Ke, Lu; Yang, Yue; Yang, Qi; Lu, Guotao; Li, Baiqiang; Tong, Zhihui; Li, Weiqin; Li, Jieshou

    2017-10-27

    Patients could develop endocrine and exocrine pancreatic insufficiency after acute pancreatitis (AP), but the morbidity, risk factors and outcome remain unclear. The aim of the present study was to evaluate the incidence of endocrine and exocrine pancreatic insufficiency after AP and the risk factors of endocrine pancreatic insufficiency through a long-term follow-up investigation. Follow-up assessment of the endocrine and exocrine function was conducted for the discharged patients with AP episodes. Oral Glucose Tolerance Test (OGTT) and faecal elastase-1(FE-1) test were used as primary parameters. Fasting blood-glucose (FBG), fasting insulin (FINS), glycosylated hemoglobin HBA1c, 2-h postprandial blood glucose (2hPG), Homa beta cell function index (HOMA-β), homeostasis model assessment of insulin resistance (HOMA-IR) and FE-1 were collected. Abdominal contrast-enhanced computed tomography (CECT) was performed to investigate the pancreatic morphology and the other related data during hospitalization was also collected. One hundred thirteen patients were included in this study and 34 of whom (30.1%) developed diabetes mellitus (DM), 33 (29.2%) suffered impaired glucose tolerance (IGT). Moreover, 33 patients (29.2%) developed mild to moderate exocrine pancreatic insufficiency with 100μg/gpancreatic insufficiency with FE-1pancreatic necrosis was significant higher than that in the non-pancreatic necrosis group (X 2  = 13.442,P = 0.001). The multiple logistic regression analysis showed that extent of pancreatic necrosisendocrine pancreatic insufficiency. HOMA-IR (P = 0.002, OR = 6.626), Wall-off necrosis (WON) (P = 0.013, OR = 184.772) were the risk factors. The integrated morbidity of DM and IGT after AP was 59.25%, which was higher than exocrine pancreatic insufficiency. 6.2% and 29.2% of patients developed severe and mild to moderate exocrine pancreatic insufficiency, respectively. The extent of pancreatic necrosis>50%, WON and insulin resistance were

  8. Ketamine Use for Successful Resolution of Post-ERCP Acute Pancreatitis Abdominal Pain

    Directory of Open Access Journals (Sweden)

    Suneel M. Agerwala

    2017-01-01

    Full Text Available We report a case in which a patient with intractable pain secondary to post-endoscopic retrograde cholangiopancreatography (ERCP acute pancreatitis is successfully treated with a subanesthetic ketamine infusion. Shortly after ERCP, the patient reported severe stabbing epigastric pain. She exhibited voluntary guarding and tenderness without distension. Amylase and lipase levels were elevated. Pain persisted for hours despite hydromorphone PCA, hydromorphone boluses, fentanyl boluses, and postprocedure anxiolytics. Pain management was consulted and a ketamine infusion was trialed, leading to a dramatic reduction in pain. This case suggests that ketamine may be a promising option in treating intractable pain associated with ERCP acute pancreatitis.

  9. Protocol for a scoping review of post-trial extensions of randomised controlled trials using individually linked administrative and registry data.

    Science.gov (United States)

    Fitzpatrick, Tiffany; Perrier, Laure; Tricco, Andrea C; Straus, Sharon E; Jüni, Peter; Zwarenstein, Merrick; Lix, Lisa M; Smith, Mark; Rosella, Laura C; Henry, David A

    2017-02-17

    Well-conducted randomised controlled trials (RCTs) provide the least biased estimates of intervention effects. However, RCTs are costly and time-consuming to perform and long-term follow-up of participants may be hampered by lost contacts and financial constraints. Advances in computing and population-based registries have created new possibilities for increasing the value of RCTs by post-trial extension using linkage to routinely collected administrative/registry data in order to determine long-term interventional effects. There have been recent important examples, including 20+ years follow-up studies of trials of pravastatin and mammography. Despite the potential value of post-trial extension, there has been no systematic study of this literature. This scoping review aims to characterise published post-trial extension studies, assess their value, and identify any potential challenges associated with this approach. This review will use the recommended methods for scoping reviews. We will search MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. A draft search strategy is included in this protocol. Review of titles and abstracts, full texts of potentially eligible studies and data/information extraction will be conducted independently by pairs of investigators. Eligible studies will be RCTs that investigated healthcare interventions that were extended by individual linkage to administrative/registry/electronic medical records data after the completion of the planned follow-up period. Information concerning the original trial, characteristics of the extension study, any clinical, policy or ethical implications and methodological or practical challenges will be collected using standardised forms. As this study uses secondary data, and does not include person-level data, ethics approval is not required. We aim to disseminate these findings through journals and conferences targeting triallists and researchers involved in health data linkage. We

  10. Acute pancreatitis: staging with CT

    International Nuclear Information System (INIS)

    Gialeli, E.; Petrocheilou, G.; Georgaki, S.; Tzemailas, I.; Adraktas, A.; Charilas, G.; Patsiogiannis, V.

    2012-01-01

    Full text: Introduction: Computed Tomography (CT) is the imaging modality of choice for the diagnosis and staging of acute pancreatitis and its complications. Objectives and tasks: The purpose of this presentation is to demonstrate the findings in CT images which are useful for staging acute pancreatitis according to Balthazar, their significance and restrictions. Materials and methods: CT images from patients who were referred to our Department for an abdominal CT scan for the diagnosis or/and staging of acute pancreatitis were retrospectively studied. Results: In acute pancreatitis, CT helps to stage the severity of inflammatory process, to detect pancreatic necrosis and to depict local complications. CT severity index (CTSI), which was proposed by Balthazar et al, combines the grade of pancreatitis with the extent of pancreatic necrosis assigning points to the patients in order to find the severity index which scales from 0-10. More points are given for a higher grade of pancreatitis and for more extensive necrosis. Types of pancreatitis according to CTSI are: interstitial (Balthazar grade A-C), exudative (Balthazar grade D or E), necrotising (Balthazar grade E, CTSI:10) and central gland necrotising. Patients with pancreatitis but no collections or necrosis have an interstitial (mild) pancreatitis. In exudative pancreatitis there is normal enhancement of the entire pancreas associated with extensive peripancreatic collections. Necrotizing (severe) pancreatitis is characterized by protacted clinical course, high incidence of local complications and high mortality rate. Central gland necrosis is a subtype of necrotizing pancreatitis. Conclusions: The combination of CT imaging and clinical and laboratory evaluation allows the early diagnosis of acute pancreatitis. Acute pancreatitis may vary from a mild uneventful disease to a severe life-threatening illness with multisystemic organ failure. Thus, it is crucial to identify patients who are at high risk of severe

  11. Morphohistological features of pancreatic stump are the main determinant of pancreatic fistula after pancreatoduodenectomy.

    Science.gov (United States)

    Ridolfi, Cristina; Angiolini, Maria Rachele; Gavazzi, Francesca; Spaggiari, Paola; Tinti, Maria Carla; Uccelli, Fara; Madonini, Marco; Montorsi, Marco; Zerbi, Alessandro

    2014-01-01

    Pancreatic surgery is challenging and associated with high morbidity, mainly represented by postoperative pancreatic fistula (POPF) and its further consequences. Identification of risk factors for POPF is essential for proper postoperative management. Evaluation of the role of morphological and histological features of pancreatic stump, other than main pancreatic duct diameter and glandular texture, in POPF occurrence after pancreaticoduodenectomy. Between March 2011 and April 2013, we performed 145 consecutive pancreaticoduodenectomies. We intraoperatively recorded morphological features of pancreatic stump and collected data about postoperative morbidity. Our dedicated pathologist designed a score to quantify fibrosis and inflammation of pancreatic tissue. Overall morbidity was 59,3%. Mortality was 4,1%. POPF rate was 28,3%, while clinically significant POPF were 15,8%. Male sex (P = 0.009), BMI ≥ 25 (P = 0.002), prolonged surgery (P = 0.001), soft pancreatic texture (P < 0.001), small pancreatic duct (P < 0.001), pancreatic duct decentralization on stump anteroposterior axis, especially if close to the posterior margin (P = 0.031), large stump area (P = 0.001), and extended stump mobilization (P = 0.001) were related to higher POPF rate. Our fibrosis-and-inflammation score is strongly associated with POPF (P = 0.001). Pancreatic stump features evaluation, including histology, can help the surgeon in fitting postoperative management to patient individual risk after pancreaticoduodenectomy.

  12. Comparison of regional pancreatic tissue fluid pressure and endoscopic retrograde pancreatographic morphology in chronic pancreatitis

    DEFF Research Database (Denmark)

    Ebbehøj, N; Borly, L; Madsen, P

    1990-01-01

    The relation between pancreatic tissue fluid pressure measured by the needle method and pancreatic duct morphology was studied in 16 patients with chronic pancreatitis. After preoperative endoscopic retrograde pancreatography (ERP) the patients were submitted to a drainage operation. The predrain......The relation between pancreatic tissue fluid pressure measured by the needle method and pancreatic duct morphology was studied in 16 patients with chronic pancreatitis. After preoperative endoscopic retrograde pancreatography (ERP) the patients were submitted to a drainage operation...

  13. Asparaginase-associated pancreatitis in children.

    Science.gov (United States)

    Raja, Raheel Altaf; Schmiegelow, Kjeld; Frandsen, Thomas Leth

    2012-10-01

    l-asparaginase has been an element in the treatment for acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma since the late 1960s and remains an essential component of their combination chemotherapy. Among the major toxicities associated with l-asparaginase therapy are pancreatitis, allergic reactions, thrombotic events, hepatotoxicity and hyperlipidaemia. Acute pancreatitis is one of the most common reasons for stopping treatment with l-asparaginase. Short-term complications of asparaginase-associated pancreatitis include development of pseudocysts and pancreatic necrosis. Long-term complications include chronic pancreatitis and diabetes. The pathophysiology of asparaginase-associated pancreatitis remains to be uncovered. Individual clinical and genetic risk factors have been identified, but they are only weak predictors of pancreatitis. This review explores the definition, possible risk factors, treatment and complications of asparaginase-associated pancreatitis. © 2012 Blackwell Publishing Ltd.

  14. Nutritional and Metabolic Derangements in Pancreatic Cancer and Pancreatic Resection

    Directory of Open Access Journals (Sweden)

    Taylor M. Gilliland

    2017-03-01

    Full Text Available Pancreatic cancer is an aggressive malignancy with a poor prognosis. The disease and its treatment can cause significant nutritional impairments that often adversely impact patient quality of life (QOL. The pancreas has both exocrine and endocrine functions and, in the setting of cancer, both systems may be affected. Pancreatic exocrine insufficiency (PEI manifests as weight loss and steatorrhea, while endocrine insufficiency may result in diabetes mellitus. Surgical resection, a central component of pancreatic cancer treatment, may induce or exacerbate these dysfunctions. Nutritional and metabolic dysfunctions in patients with pancreatic cancer lack characterization, and few guidelines exist for nutritional support in patients after surgical resection. We reviewed publications from the past two decades (1995–2016 addressing the nutritional and metabolic status of patients with pancreatic cancer, grouping them into status at the time of diagnosis, status at the time of resection, and status of nutritional support throughout the diagnosis and treatment of pancreatic cancer. Here, we summarize the results of these investigations and evaluate the effectiveness of various types of nutritional support in patients after pancreatectomy for pancreatic adenocarcinoma (PDAC. We outline the following conservative perioperative strategies to optimize patient outcomes and guide the care of these patients: (1 patients with albumin < 2.5 mg/dL or weight loss > 10% should postpone surgery and begin aggressive nutrition supplementation; (2 patients with albumin < 3 mg/dL or weight loss between 5% and 10% should have nutrition supplementation prior to surgery; (3 enteral nutrition (EN should be preferred as a nutritional intervention over total parenteral nutrition (TPN postoperatively; and, (4 a multidisciplinary approach should be used to allow for early detection of symptoms of endocrine and exocrine pancreatic insufficiency alongside implementation of

  15. Conservative treatment of chronic pancreatitis.

    Science.gov (United States)

    Löhr, J-Matthias; Haas, Stephen L; Lindgren, Fredrik; Enochsson, Lars; Hedström, Aleksandra; Swahn, Fredrik; Segersvärd, Ralf; Arnelo, Urban

    2013-01-01

    Chronic pancreatitis is a progressive inflammatory disease giving rise to several complications that need to be treated accordingly. Because pancreatic surgery has significant morbidity and mortality, less invasive therapy seems to be an attractive option. This paper reviews current state-of-the-art strategies to treat chronic pancreatitis without surgery and the current guidelines for the medical therapy of chronic pancreatitis. Endoscopic therapy of complications of chronic pancreatitis such as pain, main pancreatic duct strictures and stones as well as pseudocysts is technically feasible and safe. The long-term outcome, however, is inferior to definitive surgical procedures such as resection or drainage. On the other hand, the medical therapy of pancreatic endocrine and exocrine insufficiency is well established and evidence based. Endoscopic therapy may be an option to bridge for surgery and in children/young adolescents and those unfit for surgery. Pain in chronic pancreatitis as well as treatment of pancreatic exocrine insufficiency follows established guidelines. Copyright © 2013 S. Karger AG, Basel.

  16. Pseudocyst in the pancreatic tail associated with chronic pancreatitis successfully treated by transpapillary cyst drainage.

    Science.gov (United States)

    Naitoh, Itaru; Ohara, Hirotaka; Okayama, Yasutaka; Nakazawa, Takahiro; Ando, Tomoaki; Hayashi, Kazuki; Okumura, Fumihiro; Kitajima, Yasuhiro; Ban, Tessin; Miyabe, Katsuyuki; Ueno, Koichiro; Joh, Takashi; Sano, Hitoshi

    2008-09-01

    We report a 50-year-old male with pseudocysts in the pancreatic tail associated with chronic pancreatitis successfully treated by transpapillary cyst drainage. He had previously undergone ultrasonography-guided percutaneous cyst drainage for a pancreatic pseudocyst in our hospital. He was readmitted due to abdominal pain and fever. Computed tomography showed recurrence of a pseudocyst in the pancreatic tail measuring 5 cm in diameter. Since conservative treatment failed, endoscopic retrograde pancreatography was performed. There was communication between the pseudocyst and the main pancreatic duct, and pancreatic duct stenosis proximal to the pseudocyst. First, transpapillary pancreatic duct drainage was performed using a plastic stent, but the pseudocyst did not decrease in size and became infected. After removal of the stent, a pigtail type nasocystic catheter was placed in the pseudocyst via the pancreatic duct. The pseudocyst infection immediately disappeared, and the pseudocyst gradually decreased and disappeared. After removal of the nasocystic catheter, no recurrence was observed. As transpapillary drainage of pancreatic pseudocyst, cyst drainage and pancreatic duct drainage have been reported. In our patient with pseudocyst in the pancreatic tail, duct drainage was ineffective and the pseudocyst was infected, whereas cyst drainage was very effective. We considered that cyst drainage by a nasocystic catheter was the first-line therapy as the transpapillary drainage of the pancreatic pseudocyst.

  17. Pseudocyst in the Pancreatic Tail Associated with Chronic Pancreatitis Successfully Treated by Transpapillary Cyst Drainage

    Directory of Open Access Journals (Sweden)

    Itaru Naitoh

    2008-11-01

    Full Text Available We report a 50-year-old male with pseudocysts in the pancreatic tail associated with chronic pancreatitis successfully treated by transpapillary cyst drainage. He had previously undergone ultrasonography-guided percutaneous cyst drainage for a pancreatic pseudocyst in our hospital. He was readmitted due to abdominal pain and fever. Computed tomography showed recurrence of a pseudocyst in the pancreatic tail measuring 5 cm in diameter. Since conservative treatment failed, endoscopic retrograde pancreatography was performed. There was communication between the pseudocyst and the main pancreatic duct, and pancreatic duct stenosis proximal to the pseudocyst. First, transpapillary pancreatic duct drainage was performed using a plastic stent, but the pseudocyst did not decrease in size and became infected. After removal of the stent, a pigtail type nasocystic catheter was placed in the pseudocyst via the pancreatic duct. The pseudocyst infection immediately disappeared, and the pseudocyst gradually decreased and disappeared. After removal of the nasocystic catheter, no recurrence was observed. As transpapillary drainage of pancreatic pseudocyst, cyst drainage and pancreatic duct drainage have been reported. In our patient with pseudocyst in the pancreatic tail, duct drainage was ineffective and the pseudocyst was infected, whereas cyst drainage was very effective. We considered that cyst drainage by a nasocystic catheter was the first-line therapy as the transpapillary drainage of the pancreatic pseudocyst.

  18. Acute pancreatitis: clinical vs. CT findings

    International Nuclear Information System (INIS)

    Hill, M.C.; Barkin, J.; Isikoff, M.B.; Silver stein, W.; Kalser, M.

    1982-01-01

    In a prospective study of 91 patients with acute pancreatitis, computed tomographic (CT) findings were correlated with the clinical type of acute pancreatitis. In acute edematous pancreatitis (63 patients; 16 with repeat CT), CT was normal (28%) or showed inflammation limited to the pancreas (61%). Phlegmonous changes were present in 11%, including one patient with focal pancreatic hemorrhage, indicating that clinically unsuspected hemorrhagic pancreatitis can occur. In acute necrotizing (hemorrhagic, suppurative) pancreatitis (nine patients; eight with repeat CT), no patient had a normal CT scan and 89% had phlegmonous changes. One patient had hemorrhagic pancreatitis and three had abscesses. In acute exacerbation of chronic pancreatitis (10 patients; three with repeat CT), there were pancreatic calcifications (70%), a focal mass (40%), and pancreatic ductal dilation (30%). On follow-up CT, the findings of acute pancreatitis did not always disappear with resolution of the clinical symptons. This was especialy true of phlegmonous pancreatitis, where the CT findings could persist for months

  19. [Robot-assisted pancreatic resection].

    Science.gov (United States)

    Müssle, B; Distler, M; Weitz, J; Welsch, T

    2017-06-01

    Although robot-assisted pancreatic surgery has been considered critically in the past, it is nowadays an established standard technique in some centers, for distal pancreatectomy and pancreatic head resection. Compared with the laparoscopic approach, the use of robot-assisted surgery seems to be advantageous for acquiring the skills for pancreatic, bile duct and vascular anastomoses during pancreatic head resection and total pancreatectomy. On the other hand, the use of the robot is associated with increased costs and only highly effective and professional robotic programs in centers for pancreatic surgery will achieve top surgical and oncological quality, acceptable operation times and a reduction in duration of hospital stay. Moreover, new technologies, such as intraoperative fluorescence guidance and augmented reality will define additional indications for robot-assisted pancreatic surgery.

  20. A clinical examination of antibiotics in continuous regional arterial infusion (CRAI) therapy for severe acute pancreatitis (SAP). A prospective randomized controlled trial of BIPM and IPM/CS

    International Nuclear Information System (INIS)

    Yamasaki, Shigemichi; Ishikura, Hiroyasu; Kamitani, Takanori

    2011-01-01

    Continuous regional arterial infusion (CRAI) therapy using both protease inhibitors and antibiotics are one of the specific therapeutic methods for severe acute pancreatitis (SAP). As for the administered antibiotics, imipenem/cilastatin sodium (IPM/CS) is generally chosen as a first step, but there are only a few reports comparing IPM/CS with other antibiotics. Therefore, we performed a prospective randomized controlled trial between biapenem (BIPM) and IPM/CS as CRAI antibiotics. Twelve patients with SAP were admitted to our institution during April, 2009 since August, 2006, and were randomized into two groups. They were treated with 120 mg/day of nafamostat mesilate and either 1.2 g/day of BIPM (n=6) or 2.0 g/day of IPM/CS (n=6) for CRAI therapy within 48 hours after the administration. The clinical data, inflammatory markers (WBC, CRP), serum pancreatic enzymes (lipase, tripsin, phospholipase A2, elastase 1 and pancreatic secretory trypsin inhibitor (PSTI) and contrast-enhanced abdominal Computed Tomography findings were compared between the two groups and the adverse effects were monitored. CRAI therapy was performed for seven days. The curative effect of this therapy was evaluated at the beginning of the treatment, the day 7 and the day 14. Our results suggested that BIPM was a non-recessive antibiotic which had an equal effect in CRAI therapy in comparison with IPM/CS. (author)

  1. Study protocol for the evaluation of an Infant Simulator based program delivered in schools: a pragmatic cluster randomised controlled trial

    OpenAIRE

    Brinkman, Sally A; Johnson, Sarah E; Lawrence, David; Codde, James P; Hart, Michael B; Straton, Judith AY; Silburn, Sven

    2010-01-01

    Abstract Background This paper presents the study protocol for a pragmatic randomised controlled trial to evaluate the impact of a school based program developed to prevent teenage pregnancy. The program includes students taking care of an Infant Simulator; despite growing popularity and an increasing global presence of such programs, there is no published evidence of their long-term impact. The aim of this trial is to evaluate the Virtual Infant Parenting (VIP) program by investigating pre-c...

  2. Groove Pancreatitis – A Mimic of Pancreatic and Periampullary Tumors

    Directory of Open Access Journals (Sweden)

    Sivakami R Pradheepkumar

    2017-10-01

    Full Text Available Groove Pancreatitis (GP is a rare form of focal chronic pancreatitis involving the pancreatico-duodenal groove (PDG. GP was first described by Becker in 1973. Though, GP has been described so many years ago, it is still unfamiliar among most physicians because of lack of sufficient case studies and clinical similarity of GP to conventional pancreatitis. Imaging based differentiation of GP from other lesions, like pancreatic and periampullary adenocarcinoma is also not possible in all the cases, unless there are typical findings favoring GP. Since, the line of treatment and outcome is totally different in these two conditions, appreciation of the fine differences between these two entities is very significant. Groove pancreatitis is symptomatically treated with medicines and only for patients with continuous and severe symptoms which are not amenable to medical treatment surgical management is considered. Radiological differentiation of GP from pancreatic and periampullary malignancies will help to avoid unnecessary surgery in the initial stages. We report two cases of GP, one of pure and other of segmental form where we found typical imaging features which pointed to the diagnosis of GP with a small discussion about the Computed tomography (CT and Magnetic Resonance Imaging (MRI appearance of this entity as well as its differential diagnosis.

  3. Pancreatic duct stones in patients with chronic pancreatitis: surgical outcomes.

    Science.gov (United States)

    Liu, Bo-Nan; Zhang, Tai-Ping; Zhao, Yu-Pei; Liao, Quan; Dai, Meng-Hua; Zhan, Han-Xiang

    2010-08-01

    Pancreatic duct stone (PDS) is a common complication of chronic pancreatitis. Surgery is a common therapeutic option for PDS. In this study we assessed the surgical procedures for PDS in patients with chronic pancreatitis at our hospital. Between January 2004 and September 2009, medical records from 35 patients diagnosed with PDS associated with chronic pancreatitis were retrospectively reviewed and the patients were followed up for up to 67 months. The 35 patients underwent ultrasonography, computed tomography, or both, with an overall accuracy rate of 85.7%. Of these patients, 31 underwent the modified Puestow procedure, 2 underwent the Whipple procedure, 1 underwent simple stone removal by duct incision, and 1 underwent pancreatic abscess drainage. Of the 35 patients, 28 were followed up for 4-67 months. There was no postoperative death before discharge or during follow-up. After the modified Puestow procedure, abdominal pain was reduced in patients with complete or incomplete stone clearance (P>0.05). Steatorrhea and diabetes mellitus developed in several patients during a long-term follow-up. Surgery, especially the modified Puestow procedure, is effective and safe for patients with PDS associated with chronic pancreatitis. Decompression of intraductal pressure rather than complete clearance of all stones predicts postoperative outcome.

  4. Protocol for the BAG-RECALL clinical trial: a prospective, multi-center, randomized, controlled trial to determine whether a bispectral index-guided protocol is superior to an anesthesia gas-guided protocol in reducing intraoperative awareness with explicit recall in high risk surgical patients

    Directory of Open Access Journals (Sweden)

    Villafranca Alex

    2009-11-01

    Full Text Available Abstract Background Awareness with explicit recall of intra-operative events is a rare and distressing complication that may lead to severe psychological symptoms. Candidate depth of anesthesia monitors have been developed, partly with the aim of preventing this complication. Despite conflicting results from clinical trials and the lack of incisive validation, such monitors have enjoyed widespread clinical adoption, in particular the bispectral index. The American Society of Anesthesiologists has called for adequately powered and rigorously designed clinical trials to determine whether the use of such monitors decreases the incidence of awareness in various settings. The aim of this study is to determine with increased precision whether incorporating the bispectral index into a structured general anesthesia protocol decreases the incidence of awareness with explicit recall among a subset of surgical patients at increased risk for awareness and scheduled to receive an inhalation gas-based general anesthetic. Methods/Design BAG-RECALL is a multi-center, randomized, controlled clinical trial, in which 6,000 patients are being assigned to bispectral index-guided anesthesia (target range, 40 to 60 or end-tidal anesthetic gas-guided anesthesia (target range, 0.7 to 1.3 age-adjusted minimum alveolar concentration. Postoperatively, patients are being assessed for explicit recall at two intervals (0 to 72 hours, and 30 days after extubation. The primary outcome of the trial is awareness with explicit recall. Secondary outcomes include postoperative mortality, psychological symptoms, intensive care and hospital length of stay, average anesthetic gas administration, postoperative pain and nausea and vomiting, duration of stay in the recovery area, intra-operative dreaming, and postoperative delirium. Discussion This trial has been designed to complement two other clinical trials: B-Unaware and MACS (ClinicalTrials.gov numbers, NCT00281489 and NCT00689091

  5. Targeting pancreatic expressed PAX genes for the treatment of diabetes mellitus and pancreatic neuroendocrine tumors.

    Science.gov (United States)

    Martin-Montalvo, Alejandro; Lorenzo, Petra I; López-Noriega, Livia; Gauthier, Benoit R

    2017-01-01

    Four members of the PAX family, PAX2, PAX4, PAX6 and PAX8 are known to be expressed in the pancreas. Accumulated evidences indicate that several pancreatic expressed PAX genes play a significant role in pancreatic development/functionality and alterations in these genes are involved in the pathogenesis of pancreatic diseases. Areas covered: In this review, we summarize the ongoing research related to pancreatic PAX genes in diabetes mellitus and pancreatic neuroendocrine tumors. We dissect the current knowledge at different levels; from mechanistic studies in cell lines performed to understand the molecular processes controlled by pancreatic PAX genes, to in vivo studies using rodent models that over-express or lack specific PAX genes. Finally, we describe human studies associating variants on pancreatic-expressed PAX genes with pancreatic diseases. Expert opinion: Based on the current literature, we propose that future interventions to treat pancreatic neuroendocrine tumors and diabetes mellitus could be developed via the modulation of PAX4 and/or PAX6 regulated pathways.

  6. Metabolic pancreatitis: Etiopathogenesis and management

    Directory of Open Access Journals (Sweden)

    Sunil Kumar Kota

    2013-01-01

    Full Text Available Acute pancreatitis is a medical emergency. Alcohol and gallstones are the most common etiologies accounting for 60%-75% cases. Other important causes include postendoscopic retrograde cholangiopancreatography procedure, abdominal trauma, drug toxicity, various infections, autoimmune, ischemia, and hereditary causes. In about 15% of cases the cause remains unknown (idiopathic pancreatitis. Metabolic conditions giving rise to pancreatitis are less common, accounting for 5%-10% cases. The causes include hypertriglyceridemia, hypercalcemia, diabetes mellitus, porphyria, and Wilson′s disease. The episodes of pancreatitis tend to be more severe. In cases of metabolic pancreatitis, over and above the standard routine management of pancreatitis, careful management of the underlying metabolic abnormalities is of paramount importance. If not treated properly, it leads to recurrent life-threatening bouts of acute pancreatitis. We hereby review the pathogenesis and management of various causes of metabolic pancreatitis.

  7. Effectiveness of Chinese massage therapy (Tui Na) for chronic low back pain: study protocol for a randomized controlled trial.

    Science.gov (United States)

    Yang, Mingxiao; Feng, Yue; Pei, Hong; Deng, Shufang; Wang, Minyu; Xiao, Xianjun; Zheng, Hui; Lai, Zhenhong; Chen, Jiao; Li, Xiang; He, Xiaoguo; Liang, Fanrong

    2014-10-29

    Low back pain is a common, disabling musculoskeletal disorder in both developing and developed countries. Although often recommended, the potential efficacy of massage therapy in general, and Chinese massage (tuina) in particular, for relief of chronic low back pain (CLBP) has not been fully established due to inadequate sample sizes, low methodological quality, and subclinical dosing regimens of trials to date. Thus, the purpose of this randomized controlled trial (RCT) is to evaluate the comparative effectiveness of tuina massage therapy versus conventional analgesics for CLBP. The present study is a single center, two-arm, open-label RCT. A total of 150 eligible CLBP patients will be randomly assigned to either a tuina treatment group or a conventional drug control group in a 1:1 ratio. Patients in the tuina group receive a 20 minutes, 4-step treatment protocol which includes both structural and relaxation massage, administered in 20 sessions over a period of 4 weeks. Patients in the conventional drug control group are instructed to take a specific daily dose of ibuprofen. The primary outcome measure is the change from baseline back pain and function, measured by Roland-Morris Disability Questionnaire, at two months. Secondary outcome measures include the visual analogue scale, Japanese orthopedic association score (JOAS), and McGill pain questionnaire. The design and methodological rigor of this trial will allow for collection of valuable data to evaluate the efficacy of a specific tuina protocol for treating CLBP. This trial will therefore contribute to providing a solid foundation for clinical treatment of CLBP, as well as future research in massage therapy. This trial was registered with ClinicalTrials.gov of the National Institute of Health on 22 October 2013 (http://NCT01973010).

  8. [Delayed complications after pancreatic surgery: Pancreatic insufficiency, malabsorption syndrome, pancreoprivic diabetes mellitus and pseudocysts].

    Science.gov (United States)

    Nitsche, U; Siveke, J; Friess, H; Kleeff, J

    2015-06-01

    Benign and malignant pathologies of the pancreas can result in a relevant chronic disease burden. This is aggravated by morbidities resulting from surgical resections as well as from progression of the underlying condition. The aim was to summarize the current evidence regarding epidemiology, pathophysiology, diagnosis and treatment of endocrine and exocrine pancreatic insufficiency, as well as of pancreatic pseudocysts. A selective literature search was performed and a summary of the currently available data on the surgical sequelae after pancreatic resection is given. Reduction of healthy pancreatic parenchyma down to 10-15 % leads to exocrine insufficiency with malabsorption and gastrointestinal complaints. Orally substituted pancreatic enzymes are the therapy of choice. Loss of pancreatic islets and/or islet function leads to endocrine insufficiency and pancreoprivic diabetes mellitus. Inflammatory, traumatic and iatrogenic injuries of the pancreas can lead to pancreatic pseudocysts, which require endoscopic, interventional or surgical drainage if symptomatic. Finally, pancreatic surgery harbors the long-term risk of gastrointestinal anastomotic ulcers, bile duct stenosis, portal vein thrombosis and chronic pain syndrome. As the evidence is limited, an interdisciplinary and individually tailored approach for delayed pancreatic morbidity is recommended.

  9. Chronic Pancreatitis in Children

    Science.gov (United States)

    ... E-News Sign-Up Home Patient Information Children/Pediatric Chronic Pancreatitis in Children Chronic Pancreatitis in Children What symptoms would my child have? Frequent or chronic abdominal pain is the most common symptom of pancreatitis. The ...

  10. Phase II trial of sorafenib and erlotinib in advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Cardin, Dana B; Goff, Laura; Li, Chung-I; Shyr, Yu; Winkler, Charles; DeVore, Russell; Schlabach, Larry; Holloway, Melanie; McClanahan, Pam; Meyer, Krista; Grigorieva, Julia; Berlin, Jordan; Chan, Emily

    2014-01-01

    This trial was designed to assess efficacy and safety of erlotinib with sorafenib in the treatment of patients with advanced pancreatic adenocarcinoma. An exploratory correlative study analyzing pretreatment serum samples using a multivariate protein mass spectrometry-based test (VeriStrat®), previously shown to correlate with outcomes in lung cancer patients treated with erlotinib, was performed. Patients received sorafenib 400 mg daily along with erlotinib 150 mg daily with a primary endpoint of 8-week progression free survival (PFS) rate. Pretreatment serum sample analysis by VeriStrat was done blinded to clinical and outcome data; the endpoints were PFS and overall survival (OS). Difference between groups (by VeriStrat classification) was assessed using log-rank P values; hazard ratios (HR) were obtained from Cox proportional hazards model. Thirty-six patients received study drug and were included in the survival analysis. Eight-week PFS rate of 46% (95% confidence interval (CI): 0.32–0.67) did not meet the primary endpoint of a rate ≥70%. Thirty-two patients were included in the correlative analysis, and VeriStrat “Good” patients had superior PFS (HR = 0.18, 95% CI: 0.06–0.57; P = 0.001) and OS (HR = 0.31 95% CI: 0.13–0.77, P = 0.008) compared to VeriStrat “Poor” patients. Grade 3 toxicities of this regimen included fever, anemia, diarrhea, dehydration, rash, and altered liver function. This study did not meet the primary endpoint, and this combination will not be further pursued. In this small retrospective analysis, the proteomic classification was significantly associated with clinical outcomes and is being further evaluated in ongoing studies

  11. [Autoimmune pancreatitis. Evidence based management guidelines of the Hungarian Pancreatic Study Group].

    Science.gov (United States)

    Dubravcsik, Zsolt; Farkas, Gyula; Hegyi, Péter; Hritz, István; Kelemen, Dezső; Lásztity, Natália; Morvay, Zita; Oláh, Attila; Pap, Ákos; Párniczky, Andrea; Sahin-Tóth, Miklós; Szentkereszti, Zsolt; Szmola, Richárd; Takács, Tamás; Tiszlavicz, László; Szücs, Ákos; Czakó, László

    2015-02-22

    Autoimmune pancreatitis is a rare disease which can even mimic pancreatic tumor, however, unlike the latter, it requires not surgical but conservative management. Correct diagnosis and differential diagnosis of autoimmune pancreatitis and treatment of these patients requires up-to-date and evidence based management guidelines. The Hungarian Pancreatic Study Group proposed to prepare an evidence based guideline based on the available international guidelines and evidences. The preparatory and consultation task force appointed by the Hungarian Pancreatic Study Group translated and complemented and/or modified the international guidelines if it was necessary. 29 relevant clinical questions in 4 topics were defined (Basics; Diagnosis; Differential diagnostics; Therapy). Evidence was classified according to the UpToDate(®) grading system. The draft of the guidelines was presented and discussed at the consensus meeting on September 12, 2014. All clinial questions were accepted with almost total (more than 95%) agreement. The present guideline is the first evidence based autoimmune pancreatitis guideline in Hungary. The guideline may provide very important and helpful data for tuition of autoimmune pancreatitis, for everyday practice and for establishing proper finance. Therefore, the authors believe that these guidelines will widely become a basic reference in Hungary.

  12. Clinical Trials

    Medline Plus

    Full Text Available ... criteria differ from trial to trial. They include factors such as a patient's age and gender, the ... bias. "Bias" means that human choices or other factors not related to the protocol affect the trial's ...

  13. Clinical Trials

    Medline Plus

    Full Text Available ... protocol affect the trial's results. Comparison Groups In most clinical trials, researchers use comparison groups. This means ... study before you agree to take part. Randomization Most clinical trials that have comparison groups use randomization. ...

  14. MRI findings of pancreatic lymphoma and autoimmune pancreatitis: A comparative study

    Energy Technology Data Exchange (ETDEWEB)

    Ishigami, Kousei, E-mail: Ishigamikousei@aol.co [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 (Japan); Tajima, Tsuyoshi; Nishie, Akihiro; Ushijima, Yasuhiro [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 (Japan); Fujita, Nobuhiro [Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University (Japan); Asayama, Yoshiki; Kakihara, Daisuke; Irie, Hiroyuki [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 (Japan); Ito, Tetsuhide; Igarashi, Hisato [Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University (Japan); Nakamura, Masafumi [Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University (Japan); Honda, Hiroshi [Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582 (Japan)

    2010-06-15

    Purpose: To clarify whether there are differences in MRI findings between pancreatic lymphomas and autoimmune pancreatitis (AIP). Materials and methods: MRI of 8 patients with pancreatic lymphomas and 21 patients with AIP were retrospectively reviewed. For multifocal pancreatic lymphomas (n = 2) and AIP (n = 4), the largest 2 lesions were evaluated. Ten pancreatic lymphomas and 25 AIP were compared on three bases: the signal intensity on T2-weighted images, internal homogeneity, and presence or absence of capsule-like rim. In 8 lymphomas and 19 AIP, the enhancement pattern on dynamic MRI was compared, as well. Results: On T2-weighted images, pancreatic lymphomas comprised 5, 5 and 4 lesions with low (iso), slightly high, and moderately high intensity, respectively, while the numbers for AIP were 14, 10, and 1 (P < 0.01). Nine of 10 (90%) lymphomas appeared homogenous, and 11 of 25 (44%) AIP were homogenous (P < 0.05). A capsule-like rim was present in 9 of 25 (36%) AIP, but was not seen in lymphomas (P < 0.05). On dynamic MRI, 18 of 19 (94.7%) AIP showed persistent (n = 5) or delayed enhancement (n = 13), and 6 of 8 (75%) lymphomas showed low intensity without delayed enhancement (P < 0.001). Conclusion: MRI findings for pancreatic lymphomas and AIP were significantly different, which may be helpful for the differential diagnosis of these two diseases.

  15. Segmental pancreatic autotransplantation for chronic pancreatitis. A preliminary report

    Energy Technology Data Exchange (ETDEWEB)

    Rossi, R.L.; Braasch, J.W.; O' Bryan, E.M.; Watkins, E. Jr.

    1983-03-01

    A patient who underwent 95% pancreatectomy with autotransplantation of the body and tail of the gland to the femoral area for chronic pancreatitis is presented. The pain resolved, and the patient's blood glucose level remained within normal limits. High levels of insulin were found in the iliac vein on the transplanted side. Patency of the graft was demonstrated by technetium scan and arteriography and followed by a color-coded Doppler imaging system. Segmental pancreatic autotransplantation offers a method of relieving pain with preservation of endocrine function in selected patients with chronic pancreatitis.

  16. Morphohistological Features of Pancreatic Stump Are the Main Determinant of Pancreatic Fistula after Pancreatoduodenectomy

    Directory of Open Access Journals (Sweden)

    Cristina Ridolfi

    2014-01-01

    Full Text Available Introduction. Pancreatic surgery is challenging and associated with high morbidity, mainly represented by postoperative pancreatic fistula (POPF and its further consequences. Identification of risk factors for POPF is essential for proper postoperative management. Aim of the Study. Evaluation of the role of morphological and histological features of pancreatic stump, other than main pancreatic duct diameter and glandular texture, in POPF occurrence after pancreaticoduodenectomy. Patients and Methods. Between March 2011 and April 2013, we performed 145 consecutive pancreaticoduodenectomies. We intraoperatively recorded morphological features of pancreatic stump and collected data about postoperative morbidity. Our dedicated pathologist designed a score to quantify fibrosis and inflammation of pancreatic tissue. Results. Overall morbidity was 59,3%. Mortality was 4,1%. POPF rate was 28,3%, while clinically significant POPF were 15,8%. Male sex (P=0.009, BMI≥25 (P=0.002, prolonged surgery (P=0.001, soft pancreatic texture (P<0.001, small pancreatic duct (P<0.001, pancreatic duct decentralization on stump anteroposterior axis, especially if close to the posterior margin (P=0.031, large stump area (P=0.001, and extended stump mobilization (P=0.001 were related to higher POPF rate. Our fibrosis-and-inflammation score is strongly associated with POPF (P=0.001. Discussion and Conclusions. Pancreatic stump features evaluation, including histology, can help the surgeon in fitting postoperative management to patient individual risk after pancreaticoduodenectomy.

  17. The effects of a tailored intensive care unit delirium prevention protocol: A randomized controlled trial.

    Science.gov (United States)

    Moon, Kyoung-Ja; Lee, Sun-Mi

    2015-09-01

    A decreased incidence of delirium following the application of non-pharmacologic intervention protocols to several patient populations has been previously reported. However, few studies have been conducted to examine the effects of their application to intensive care unit (ICU) patients. To examine the effects of applying a tailored delirium preventive protocol, developed by the authors, to ICU patients by analyzing its effects on delirium incidence, in-hospital mortality, ICU readmission, and length of ICU stay in a Korean hospital. A single-blind randomized controlled trial. A 1049-bed general hospital with a 105-bed ICU. Sixty and 63 ICU patients were randomly assigned to the intervention and control groups, respectively. The researchers applied the delirium prevention protocol to the intervention group every day for the first 7 days of ICU hospitalization. Delirium incidence, mortality, and re-admission to the ICU during the same hospitalization period were analyzed by logistic regression analysis; the 7- and 30-day in-hospital mortality by Kaplan-Meier survival and Cox proportional hazard regression analysis; and length of ICU stay was assessed by linear regression analysis. Application of the protocol had no significant effect on delirium incidence, in-hospital mortality, re-admission to the ICU, or length of ICU stay. Whereas the risk of 30-day in-hospital mortality was not significantly lower in the intervention than in the control group (OR: 0.33; 95% CI: 0.10-1.09), we found a significantly decreased 7-day in-hospital mortality in the intervention group after protocol application (HR: 0.09; 95% CI: 0.01-0.72). Application of a tailored delirium prevention protocol to acute stage patients during the first 7 days of ICU hospitalization appeared to reduce the 7-day in-hospital risk of mortality only for this patient population. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Pancreatic cancer risk in hereditary pancreatitis

    OpenAIRE

    Weiss, Frank U.

    2014-01-01

    Inflammation is part of the body’s immune response in order to remove harmful stimuli – like pathogens, irritants or damaged cells - and start the healing process. Recurrent or chronic inflammation on the other side seems a predisposing factor for carcinogenesis and has been found associated with cancer development. In chronic pancreatitis mutations of the cationic trypsinogen (PRSS1) gene have been identified as risk factors of the disease. Hereditary pancreatitis is a rare cause of chronic...

  19. ENDOCRINE PANCREATIC FUNCTION IN ACUTE PANCREATITIS

    OpenAIRE

    P. V. Novokhatny

    2014-01-01

    Introduction Among the organs of internal secretion pancreas has a special place thanks to active exocrine function and a wide range of physiological actions of produced hormones. Violations of endocrine pancreas arises in 6.5-38 % of patients with acute pancreatitis. However, there is still no clear understanding of the pathogenetic mechanisms of hormonal dysfunction of the pancreas in acute pancreatitis, there is no uniform algorithms for its correction. Aim of the research was to study...

  20. Management of acute pancreatitis in children.

    Science.gov (United States)

    Abu-El-Haija, Maisam; Lin, Tom K; Nathan, Jaimie D

    2017-10-01

    Pediatric acute pancreatitis has been on the rise in the last decades, with an incidence close to adult pancreatitis. In the majority of cases acute pancreatitis resolves spontaneously, but in a subset of children the disease progresses to severe acute pancreatitis with attendant morbidity and mortality. Pediatric acute pancreatitis in this era is recognized as a separate entity from adult acute pancreatitis given that the causes and disease outcomes are different. There are slow but important advances made in understanding the best management for acute pancreatitis in children from medical, interventional, and surgical aspects. Supportive care with fluids, pain medications, and nutrition remain the mainstay for acute pancreatitis management. For complicated or severe pancreatitis, specialized interventions may be required with endoscopic or drainage procedures. Surgery has an important but limited role in pediatric acute pancreatitis.

  1. Lack of consensus on the role of endoscopic retrograde cholangiography in acute biliary pancreatitis in published meta-analyses and guidelines: a systematic review

    NARCIS (Netherlands)

    Geenen, E.J.M. van; Santvoort, H.C. van; Besselink, M.G.; Peet, D.L. van der; Erpecum, K.J. van; Fockens, P.; Mulder, C.J.; Bruno, M.J.

    2013-01-01

    OBJECTIVES: Several randomized controlled trials studied the role of endoscopic retrograde cholangiopancreaticography (ERCP) and endoscopic sphincterotomy (ES) in acute biliary pancreatitis (ABP). No study assessed whether these trials resulted in international consensus in published meta-analyses

  2. Lack of Consensus on the Role of Endoscopic Retrograde Cholangiography in Acute Biliary Pancreatitis in Published Meta-Analyses and Guidelines A Systematic Review

    NARCIS (Netherlands)

    van Geenen, Erwin-Jan M.; van Santvoort, Hjalmar C.; Besselink, Marc G. H.; van der Peet, Donald L.; van Erpecum, Karel J.; Fockens, Paul; Mulder, Chris J. J.; Bruno, Marco J.

    2013-01-01

    Objectives: Several randomized controlled trials studied the role of endoscopic retrograde cholangiopancreaticography (ERCP) and endoscopic sphincterotomy (ES) in acute biliary pancreatitis (ABP). No study assessed whether these trials resulted in international consensus in published meta-analyses

  3. Everolimus for Advanced Pancreatic Neuroendocrine Tumours: A Subgroup Analysis Evaluating Japanese Patients in the RADIANT-3 Trial

    Science.gov (United States)

    Ito, Tetsuhide; Okusaka, Takuji; Ikeda, Masafumi; Igarashi, Hisato; Morizane, Chigusa; Nakachi, Kohei; Tajima, Takeshi; Kasuga, Akio; Fujita, Yoshie; Furuse, Junji

    2012-01-01

    Objective Everolimus, an inhibitor of the mammalian target of rapamycin, has recently demonstrated efficacy and safety in a Phase III, double-blind, randomized trial (RADIANT-3) in 410 patients with low- or intermediate-grade advanced pancreatic neuroendocrine tumours. Everolimus 10 mg/day provided a 2.4-fold improvement compared with placebo in progression-free survival, representing a 65% risk reduction for progression. The purpose of this analysis was to investigate the efficacy and safety of everolimus in the Japanese subgroup enrolled in the RADIANT-3 study. Methods Subgroup analysis of the Japanese patients was performed comparing efficacy and safety between everolimus 10 mg/day orally (n = 23) and matching placebo (n = 17). The primary endpoint was progression-free survival. Safety was evaluated on the basis of the incidence of adverse drug reactions. Results Progression-free survival was significantly prolonged with everolimus compared with placebo. The median progression-free survival was 19.45 months (95% confidence interval, 8.31–not available) with everolimus vs 2.83 months (95% confidence interval, 2.46–8.34) with placebo, resulting in an 81% risk reduction in progression (hazard ratio, 0.19; 95% confidence interval, 0.08–0.48; P< 0.001). Adverse drug reactions occurred in all 23 (100%) Japanese patients receiving everolimus and in 13 (77%) patients receiving placebo; most were grade 1/2 in severity. The most common adverse drug reactions in the everolimus group were rash (n = 20; 87%), stomatitis (n = 17; 74%), infections (n = 15; 65%), nail disorders (n = 12; 52%), epistaxis (n = 10; 44%) and pneumonitis (n = 10; 44%). Conclusions These results support the use of everolimus as a valuable treatment option for Japanese patients with advanced pancreatic neuroendocrine tumours. PMID:22859827

  4. Isolated Roux-en-Y anastomosis of the pancreatic stump in a duct-to-mucosa fashion in patients with distal pancreatectomy with en-bloc celiac axis resection.

    Science.gov (United States)

    Okada, Ken-Ichi; Kawai, Manabu; Tani, Masaji; Hirono, Seiko; Miyazawa, Motoki; Shimizu, Atsushi; Kitahata, Yuji; Yamaue, Hiroki

    2014-03-01

    A pancreatic fistula is one of the most serious complications in distal pancreatectomy with en bloc celiac axis resection (DP-CAR), because the pancreatic transection is performed on the right side of the portal vein, which results in a large cross-section surface, and because post-pancreatectomy hemorrhage is hard to treat by interventional radiology. Therefore, a procedure to decrease the incidence of postoperative pancreatic fistula is urgently needed. Twenty-six consecutive patients who underwent DP-CAR between April 2008 and August 2012 were reviewed retrospectively. The first 13 consecutive patients underwent DP-CAR with no anastomosis, and the subsequent 13 consecutive patients were treated with Roux-en-Y pancreaticojejunostomy (PJ) in a duct-to-mucosa fashion. Extremely high amylase levels (>4000 IU/l) of all drainage fluid specimens on postoperative day (POD) 1, 3 and 4 were detected more frequently in cases with no anastomosis (n = 7) compared to those with PJ (n = 1) (P = 0.056). The incidence of grade B/C pancreatic fistulas was 15.4% in cases with isolated Roux-en-Y anastomosis of the pancreatic stump performed in a duct-to-mucosa fashion, and we are currently examining whether this anastomosis method reduces the pancreatic fistula rate in a multicenter, randomized controlled trial for distal pancreatectomy patients (ClinicalTrials.gov NCT01384617). © 2013 Japanese Society of Hepato-Biliary-Pancreatic Surgery.

  5. Secretin-stimulated MRI characterization of pancreatic morphology and function in patients with chronic pancreatitis.

    Science.gov (United States)

    Madzak, Adnan; Olesen, Søren Schou; Haldorsen, Ingfrid Salvesen; Drewes, Asbjørn Mohr; Frøkjær, Jens Brøndum

    Chronic pancreatitis (CP) is characterized by abnormal pancreatic morphology and impaired endocrine and exocrine function. However, little is known about the relationship between pancreatic morphology and function, and also the association with the etiology and clinical manifestations of CP. The aim was to explore pancreatic morphology and function with advanced MRI in patients with CP and hea