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Background: Management and palliation of pancreatic head adenocarcinoma is challenging. End-of-life decision-making is a variable process involving multiple factors., Methods: We conducted a qualitative, physician-based, 40-question international survey characterizing the impact of medical, religious, social, training and system factors on care., Results: A total of 258 international clinicians completed the survey. Respondents were typically fellowship-trained (78%), with a mean of 16 years' experience in a university-affiliated (93%) hepato-pancreato-biliary group (96%) practice. Most (91%) believed resection is potentially curative. Most patients were discussed preoperatively by multidisciplinary teams (94%) and medical assessment clinics (68%), but rarely critical care (21%). Intraoperative surgical palliation included double bypass or no intervention for locally advanced nonresectable tumours (41% and 49% v. 14% and 85%, respectively, for patients with hepatic metastases). Postoperative admission to the intensive care unit was frequent (58%). Severe postoperative complications were often treated with aggressive cardiopulmonary resuscitation, intubation and critical care (96%), with no defined time points for futility (74%). Admitting surgeons guided most end-of-life decisions (97%). Formal medical futility laws were rarely available (26%). Insurance status did not alter treatment (97%) or palliation (95%) in non-universal care regions. Clinician experience, regional culture and training background impacted treatment (all p < 0.05)., Conclusion: Despite remarkable overall agreement, geographic and training differences are evident in the treatment and palliation of pancreatic head adenocarcinoma.

Objective: A Phase II study was conducted at Indiana University to evaluate the safety and efficacy of combined weekly Gemcitabine (GEM) with external beam radiotherapy (RT) in unresectable, locally advanced pancreatic cancer (LAPC)., Methods: Eligible patients had biopsy-proven LAPC without evidence of metastatic disease. In part A of the treatment plan, patients received GEM 600 mg/m(2) IV weekly, with concurrent RT (50.4 Gy in 28 fractions, 1.8 Gy/d, 5 days per week). Part B of the treatment plan began approximately 4 weeks after completing part A: patients without disease progression received weekly GEM 1000 mg/m(2) on days 1, 8, and 15 of a 28-day cycle for 6 cycles or until disease progression., Results: From April 2001 to June 2003, of 28 patients evaluated, 24 (86%) completed part A. About 22 patients had grade 3 toxicities, primarily hematologic (43%) and gastrointestinal (36%). Three patients (11%) had grade 4 toxicities (one each for hyperbilirubinemia, infection, and dyspnea). The median follow-up was 10 months (1-63 months) for all enrolled patients. Six patients (21%) had a radiologic partial response, 16 (57%) had stable disease, 5 (18%) had progressive disease, and 1 patient (4%) had an unevaluable response at last follow-up. Four patients (14%) underwent surgical resection (2 with R0 resection). Median time to progression was 6 months (0-36 months). Median survival time was 10.3 months (95% confidence interval, 7.9-14.6 months). The 1- and 2-year actuarial survival rates were 30% and 11%. At last analysis, all but 2 patients died., Conclusion: The activity and toxicity profile of combination GEM and RT indicates that this can be safely administered for patients with LAPC.

Unlabelled: In patients undergoing pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PC), conversion to total pancreatectomy (TP) may be necessary to achieve R0 resection., Hypothesis: We sought to examine the oncologic benefit of conversion of PD to TP to achieve an R0 resection in patients with an isolated positive neck margin., Methods: We conducted a retrospective analysis of prospectively collected data at Indiana University and Johns Hopkins Medical Institutions. A review of 1,579 patients who underwent PD or TP for PC at these institutions between 1992 and 2006 was performed. Sixty-one patients were eligible., Results: Twenty-eight patients underwent PD with an isolated positive neck margin found on pathologic examination; 33 patients had conversion to TP for isolated neck margin involvement to achieve R0 resection. Patients undergoing TP versus PD had a greater median survival (18 vs 10 months; P = .04). Mortality (6% vs 7%) and morbidity (36% vs 54%; P = .20) for TP versus PD were comparable. Multivariate analysis revealed PD and greater tumor size as the only independent predictors of poor long-term survival (hazard ratio [HR], 2.2; P = .01 and HR, 1.3; P = .005)., Conclusions: Conversion of PD to TP to achieve an R0 resection in patients with pancreatic adenocarcinoma is associated with a survival benefit.

Pancreatic cancer has a poor prognosis with complete surgical resection being the only therapy to offer a realistic chance for long-term survival. The aim of this study is to identify surgery-related variables that influence long-term survival. Between 1990 and 2002, 226 consecutive patients (mean age of 64+/-11 years) had resection for pancreatic adenocarcinoma. Prognostic variables in these patients were analyzed using univariate and multivariate analysis. Two hundred four patients (90%) had pancreaticoduodenectomy, 13 patients (6%) had distal pancreatectomy, and 9 patients (4%) had a TP. Stage I disease was present in 50 (22%), stage II disease in 170 (75%), and stage III disease in 6 (3%). R0 resections were achieved in 70%. Operative morbidity was 36% and 30-day mortality was 6%. Actual 1-year, 3-year, and 5-year survival rates were 49% (n=111), 14% (n=31), and 4% (n=9). Using multivariate analysis: tumor size, tumor differentiation, obtaining an R0 resection, and lack of postoperative complications were variables associated with long-term survival. Long-term survival in patients with pancreatic cancer after resection remains poor. Achieving a margin negative resection (R0) with no postoperative complications are prognostic variables that can be affected by the surgeon.

Hypothesis: Pancreaticoduodenectomy (PD) is a safe procedure for a variety of periampullary conditions., Design: Retrospective review of a prospectively collected database., Setting: Academic tertiary care hospital., Patients: A total of 516 consecutive patients who underwent PD., Main Outcome Measures: Patient outcomes and survival factors., Results: Pathological examination demonstrated 57% periampullary cancers, 22% chronic pancreatitis, 12% cystic neoplasms, 4% islet cell neoplasms, and 5% other. Fifty-one percent of patients underwent pylorus preservation. Median operating time was 5 hours; blood loss, 1300 mL; and transfusion requirement, 1.5 U. Postoperative complications occurred in 43% of patients, including cardiopulmonary events (15%), fistula (9%), delayed gastric emptying (7%), and sepsis (6%). Additional surgery was required in 3% of patients, most commonly because of bleeding. Perioperative mortality was 3.9% overall but only 1.8% in patients with chronic pancreatitis; 25% of patients who died had preoperative complications associated with their periampullary condition. Three-year survival was 15% after resection for pancreatic cancer, 42% for duodenal cancer, 53% for ampullary cancer, and 62% for bile duct cancer. Univariate predictors of long-term survival in patients with periampullary adenocarcinoma included elevated glucose levels, liver function test results, abnormal tumor markers, blood loss, transfusion requirement, type of operation, and pathologic findings (periampullary adenocarcinoma type, differentiation, and margin and node status). Multivariate predictors were serum total bilirubin level, blood loss, operation type, diagnosis, and lymph node status., Conclusions: Pancreaticoduodenectomy continues to be associated with considerable morbidity. With careful patient selection, PD can be performed safely. Long-term survival in patients with periampullary adenocarcinoma can be predicted by preoperative laboratory values, intraoperative factors, and pathologic findings.

Pancreaticoduodenectomy is often avoided in patients with portal or superior mesenteric venous involvement due to the perception that venous resection is complex, morbid, and carries a poor long-term survival. Our recent experience using state-of-the-art imaging and strict resection criteria show that venous reconstruction increases operative time, transfusion requirements, intensive care unit stay, and total hospital length of stay, but has no significant impact on operative morbidity rates, mortality rates, or the incidence of positive histologic margins. Kalpan-Meier life table analysis shows similar survival curves when compared to a contemporary cohort of patients who do not undergo venous reconstruction.

Current management of intraductal papillary mucinous neoplasm (IPMN) according to recently published International Consensus Guidelines depends upon distinguishing it from mucinous cystic neoplasms (MCNs). We have previously shown that prostaglandin E(2) (PGE(2)) is increased in pancreatic cancer tissue over normal controls. Thus, we hypothesized that PGE(2) level in pancreatic fluid differentiates IPMN and MCN and is a biomarker of IPMN dysplasia. Pancreatic fluid was collected in 65 patients at the time of endoscopy (EUS or ERCP) or operation (OR) and analyzed by PGE(2) enzyme-linked immunosorbent assay (ELISA). PGE(2) level was correlated with surgical pathologic diagnosis and dysplastic stage. Mean PGE(2) level (pg/microl) in IPMNs (2.2 +/- 0.6) was greater than in MCNs (0.2 +/- 0.1) (p < 0.05). Mean PGE(2) level of IPMN by dysplastic stage was 0.1 +/- 0.01 (low grade), 1.2 +/- 0.6 (medium grade), 4.4 +/- 0.9 (high grade), and 5.0 +/- 2.3 (invasive). Among invasive IPMN, PGE(2) level dropped in advanced cases with pancreatic ductal obstruction by tumor (0.3 +/- 0) vs non-obstructed (8.6 +/- 2.9). PGE(2) level may help in distinguishing IPMN from MCN in patients with known mucinous lesions. PGE(2) level may also be an indicator of malignant progression of IPMN before ductal obstruction by tumor. Prospective evaluation will be necessary to evaluate the clinical role of PGE(2) level in pancreatic fluid. [ABSTRACT FROM AUTHOR]

Current management of intraductal papillary mucinous neoplasm (IPMN) according to recently published International Consensus Guidelines depends upon distinguishing it from mucinous cystic neoplasms (MCNs). We have previously shown that prostaglandin E2 (PGE2) is increased in pancreatic cancer tissue over normal controls. Thus, we hypothesized that PGE2 level in pancreatic fluid differentiates IPMN and MCN and is a biomarker of IPMN dysplasia. Pancreatic fluid was collected in 65 patients at the time of endoscopy (EUS or ERCP) or operation (OR) and analyzed by PGE2 enzyme-linked immunosorbent assay (ELISA). PGE2 level was correlated with surgical pathologic diagnosis and dysplastic stage. Mean PGE2 level (pg/µl) in IPMNs (2.2±0.6) was greater than in MCNs (0.2±0.1) (p<0.05). Mean PGE2 level of IPMN by dysplastic stage was 0.1±0.01 (low grade), 1.2±0.6 (medium grade), 4.4±0.9 (high grade), and 5.0±2.3 (invasive). Among invasive IPMN, PGE2 level dropped in advanced cases with pancreatic ductal obstruction by tumor (0.3±0) vs non-obstructed (8.6±2.9). PGE2 level may help in distinguishing IPMN from MCN in patients with known mucinous lesions. PGE2 level may also be an indicator of malignant progression of IPMN before ductal obstruction by tumor. Prospective evaluation will be necessary to evaluate the clinical role of PGE2 level in pancreatic fluid. [ABSTRACT FROM AUTHOR]