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Objectives: Patient education and resources that address barriers to health literacy to improve understanding in pancreatic cancer are limited. We evaluated the impact and outcomes benefits of Animated Pancreas Patient (APP) cancer educational modules (APP website and YouTube)., Methods: A retrospective study of APP metrics and utilization data from September 2013 to February 2021 was conducted. We evaluated audience reach and calculated top views by media type (animation/expert video/patient video/slideshow) and top retention videos from the modules., Results: During the study period, APP had 4,551,079 views worldwide of which 2,757,064 unique visitors or 60% were from the United States. Of these, 54% were patients, 17% were family members or caregivers, 16% were health care providers, and 13% were other. The most popular topic viewed among the animations was "Understanding Clinical Trials" (n = 182,217), and the most common expert video viewed was "What are the different stages of pancreatic cancer?" (n = 15,357)., Conclusions: Pancreatic cancer patient education using APP's visual formats of learning demonstrated a wide reach and had a significant impact on improved understanding among patients, families, and caregivers. Continued efforts should be made to provide patient resources that address health literacy, better quality of life and improved health outcomes in pancreatic cancer., Competing Interests: The authors declare no conflict of interest. The Animated Pancreas Patient—An Animated Patient's Guide to Pancreatic Diseases is supported by unrestricted education grants from Abbvie Inc, Boston Scientific Corporation, Celgene Corporation, Ethicon US LLC, and Incyte Corporation. Mechanisms in Medicine, the developers of this resource, declare no conflict of interest in the development of the program., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: The aim of this study was to characterize an international cohort of resected cystic pancreatic neuroendocrine neoplasms (cPanNENs) and identify preoperative predictors of aggressive behavior., Background: The characteristics of cPanNENs are unknown and their clinical management remains unclear. An observational strategy for asymptomatic cPanNENs ≤2 cm has been proposed by recent guidelines, but evidence is scarce and limited to single-institutional series., Methods: Resected cPanNENs (1995-2017) from 16 institutions worldwide were included. Solid lesions (>50% solid component), functional tumors, and MEN-1 patients were excluded. Aggressiveness was defined as lymph node (LN) involvement, G3 grading, distant metastases, and/or recurrence., Results: Overall, 263 resected cPanNENs were included, among which 177 (63.5%) were >2 cm preoperatively. A preoperative diagnosis of cPanNEN was established in 162 cases (61.6%) and was more frequent when patients underwent endoscopic ultrasound [EUS, odds ratio (OR) 2.69, 95% confidence interval (CI) 1.52-4.77] and somatostatin-receptor imaging (OR 3.681, 95% CI 1.809-7.490), and for those managed in specialized institutions (OR 3.12, 95% CI 1.57-6.21). Forty-one cPanNENs (15.6%) were considered aggressive. In the whole cohort, LN involvement on imaging, age >65 years, preoperative size >2 cm, and pancreatic duct dilation were independently associated with aggressive behavior. In asymptomatic patients, older age and a preoperative size >2 cm remained independently associated with aggressiveness. Only 1 of 61 asymptomatic cPanNENs ≤2 cm displayed an aggressive behavior., Conclusions: The diagnostic accuracy of cPanNENs is increased by the use of EUS and somatostatin-receptor imaging and is higher in specialized institutions. Preoperative size >2 cm is independently associated with aggressive behavior. Consequently, a watch-and-wait policy for sporadic asymptomatic cPanNENs ≤2 cm seems justified and safe for most patients., Competing Interests: This work was performed and written as part of a project of the 8th Pancreas 2000 program funded and organized by the European Pancreatic Club (EPC). None of the authors have any financial or any other kind of personal conflicts of interest in relation to this study The authors report no conflicts of interest., (Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Periampullary malignancies are often unresectable tumors that frequently cause biliary or duodenal obstruction. Advances in endoscopic and percutaneous options have lessened the need for operative palliation. Nevertheless, many patients are still found to be unresectable at the time of exploration, making palliative bypass a consideration. Several prior studies have examined the morbidity of operative palliation, but many were conducted over lengthy time periods, and few have examined the impact of these procedures on future therapy. This study is a contemporary analysis of the short- and long-term outcomes of palliative bypass procedures for unresectable periampullary malignancies at a single high-volume institution., Methods: We identified a contemporary cohort of patients in whom a pancreatoduodenectomy was planned for periampullary malignancy but instead underwent an aborted procedure. Patients were divided into 5 procedure groups: laparoscopy only, laparotomy with or without cholecystectomy, gastrointestinal bypass, biliary bypass, and double bypass (gastrointestinal and biliary). Data regarding the patient cohort, procedures, morbidity/mortality, and the interval to initiation of systemic therapy were collected prospectively and reviewed retrospectively., Results: Between July 2011 and November 2018, 128 out of 615 (17%) patients had an aborted pancreatoduodenectomy; 113 out of 128 patients had pancreatic adenocarcinoma, and 86 (67.1%) had duodenal or biliary obstruction at the time of operation. Patients who underwent laparoscopy only (n = 34) had no operative complications and a 90-day mortality of 6%; 88% of these patients went on to receive systemic therapy (median 21 days postprocedure). Double bypass was associated with a far lesser complication rate than in prior studies; 17% of patients had some complication(s), but only 9% had a severe complication. The 90-day all-cause mortality was 13%, and only 71% of these patients went on to receive systemic therapy (median 47 days postprocedure). Notably, 27 out of 34 (79%) of patients who underwent laparoscopy alone needed additional procedures for local obstruction, whereas only 5 out of 42 (12%) double bypass patients needed additional interventions. Median survival for the entire cohort was 10.3 months., Conclusion: Palliative procedures in this cohort had a far lesser complication rate than that of historical series. Palliative procedures, however, delayed systemic therapy, and a fair number of patients never received additional treatments. Palliative procedures markedly decreased the need for future interventions. Intraoperative decisions regarding palliative procedures must incorporate the functional status and motivations of the patient; these procedures are increasingly safe but may still affect survival., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Weight change offers the simplest indication of a patient's recovery after an operation. There have been no studies that have thoroughly investigated postoperative weight dynamics after pancreatectomy. The aim of this study was to define postoperative weight change after a pancreatectomy and determine factors associated with optimal and poor weight trajectories., Methods: From 2004 to 2019, 1,090 proximal (65%) and distal (35%) pancreatectomies were performed in patients with adequate data in the medical records. Patient weights were acquired preoperatively and at postoperative months 1, 3, and 12. Optimal (top quartile, weight restoration) and poor (bottom quartile, persistent weight loss) postoperative weight cohorts were identified at 1 year postoperatively., Results: The median percentage weight change 1 year postpancreatectomy was -6.6% (interquartile range: -1.4% to -12.5%), -7.8% for proximal pancreatectomy, and -4.2% for distal pancreatectomy. For most patients (interquartile range cohort), the median percentage weight change at 1, 3, and 12 months was -6.2%, -7.2%, and -6.6%. The independent factors associated with weight restoration were age <65, nonobesity (body mass index <30kg/m 2 ), receiving total parenteral nutrition/total enteral nutrition preoperatively, experiencing preoperative weight loss >10%, distal pancreatectomy, not undergoing vascular resection, and no readmission within 30 days. Conversely, persistent weight loss was associated with American Society of Anesthesiologists classes III to IV, obesity, malignancy, proximal pancreatectomy, blood loss ≥350mL, and experiencing readmission within 30 days. Focusing on pancreatic ductal adenocarcinoma (n = 372) patients, the factors associated with persistent weight loss were obesity, proximal pancreatectomy, and experiencing recurrence within 1 year; however, weight cohorts were not associated with overall survival for pancreatic ductal adenocarcinoma patients., Conclusion: These data define weight kinetics after pancreatectomy. Ultimately, postoperative weight trajectories appear to be largely predetermined but may be mitigated by limiting readmissions and complications. Clinicians should use these data to identify patients who continue to lose weight between the first and third month postoperatively with a high suspicion for the requirement of nutritional monitoring or other interventions., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Recent data illustrates improved outcomes when adhering to early drain removal following pancreatoduodenectomy (PD). This study aims to explore the potential benefits of expanding the timeframe for early drain removal., Methods: Six hundred forty PDs were originally managed by selective drain placement and early removal. Outcomes were reappraised in the framework of a novel proposal; intraoperative drains were omitted based on a low-risk profile (Fistula Risk Score 0-2), followed by drain removal at PODs 1, 3, and 5 if drain fluid amylase (DFA) fell below specific cutoffs based on optimized negative predictive values (NPV) for clinically relevant postoperative pancreatic fistula (CR-POPF). Characteristics of the remaining cohort with drains in situ on POD5 were examined using multivariable analysis (MVA)., Results: Intraoperative FRS would preclude drains from 230 (35.9%) negligible/low-risk cases with a cohort CR-POPF rate of 1.7%. Of the remaining patients, 30.5% would have drains removed on POD1 based on a DFA threshold of 300 IU/L (NPV = 98.4%), demonstrating a 1.6% CR-POPF rate. On POD3, drains could be removed in the residual cohort from 21.1% of patients with DFA ≤ 150 IU/L (NPV = 96.6%), reflecting a 3.4% CR-POPF rate. On POD5, a DFA threshold of 50 IU/L (NPV = 84%) identified 16.3% more patients whose drains could be removed. The remaining cohort (POD5 DFA > 50 IU/L), "enriched" for fistula development and reflecting just 18.4% of the original patients, displays a 61% CR-POPF rate. Among these patients on POD5, a DFA threshold > 2000 IU/L best predicted subsequent CR-POPF (PPV = 89.5%), and MVA revealed a positive association between pancreatic cancer/pancreatitis (OR = 4.37, p = 0.022) and longer operations (OR = 3.74, p = 0.014) with CR-POPF development., Conclusion: Early drain removal is a dynamic concept and can be employed throughout the postoperative time course using conditional thresholds to better identify patients at risk for CR-POPF.

Objective: To evaluate surgical performance in pancreatoduodenectomy using clinically relevant postoperative pancreatic fistula (CR-POPF) occurrence as a quality indicator., Background: Accurate assessment of surgeon and institutional performance requires (1) standardized definitions for the outcome of interest and (2) a comprehensive risk-adjustment process to control for differences in patient risk., Methods: This multinational, retrospective study of 4301 pancreatoduodenectomies involved 55 surgeons at 15 institutions. Risk for CR-POPF was assessed using the previously validated Fistula Risk Score, and pancreatic fistulas were stratified by International Study Group criteria. CR-POPF variability was evaluated and hierarchical regression analysis assessed individual surgeon and institutional performance., Results: There was considerable variability in both CR-POPF risk and occurrence. Factors increasing the risk for CR-POPF development included increasing Fistula Risk Score (odds ratio 1.49 per point, P < 0.00001) and octreotide (odds ratio 3.30, P < 0.00001). When adjusting for risk, performance outliers were identified at the surgeon and institutional levels. Of the top 10 surgeons (≥15 cases) for nonrisk-adjusted performance, only 6 remained in this high-performing category following risk adjustment., Conclusions: This analysis of pancreatic fistulas following pancreatoduodenectomy demonstrates considerable variability in both the risk and occurrence of CR-POPF among surgeons and institutions. Disparities in patient risk between providers reinforce the need for comprehensive, risk-adjusted modeling when assessing performance based on procedure-specific complications. Furthermore, beyond inherent patient risk factors, surgical decision-making influences fistula outcomes.

The surgical management of pancreatic diseases is rapidly evolving, encompassing advances in evidence-driven selection of patients amenable for surgical therapy, preoperative risk stratification, refinements in the technical conduct of pancreatic operations, and quantification of postoperative morbidity. These advances have resulted in dramatic reductions in mortality following pancreatic surgery, particularly at high-volume pancreatic centers. Surgical decision making is complex, and requires an intimate understanding of disease pathobiology, host physiology, technical considerations, and evolving trends. This article highlights key developments in the contemporary surgical management of pancreatic diseases., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Although the outcomes for pancreatic ductal adenocarcinoma (PDAC) remain disappointing, there has been considerable improvement in the 5-year survival rate of patients with resectable disease. As such, an R0 surgical resection (microscopic tumor clearance) offers patients with PDAC the greatest survival benefit. Carbohydrate antigen 19-9, the only US Food and Drug Administration-approved biomarker for PDAC, is a poor screening tool and is most informative after PDAC resection. Consequently, there has been a tremendous initiative to discover novel biomarkers that may aid in detecting the disease earlier, improving prognosis, and predicting response to available chemotherapy. The number of implicated biomarkers in PDAC is indeed staggering, with >2500 proposed candidates presented in the recent literature. A vast majority of these biomarkers, however, remain in the investigational phase. This review categorizes the most promising biomarkers--those closest to potential clinical application--into diagnostic and prognostic/predictive groups. The greatest challenge likely lies in the search for an effective diagnostic biomarker that can accurately discriminate between malignant and benign disease, and thereby facilitate earlier identification of those patients with PDAC who may benefit most from surgical resection.

Introduction: Survival after a resected pancreatic ductal adenocarcinoma (PDAC) appears to be improving. Yet, in spite of advancements, prognosis remains disappointing. This study analyses a contemporary experience and identifies features associated with survival., Methods: Kaplan-Meier analysis was conducted for 424 PDAC resections performed at two institutions (2001-2011). Multivariate analysis was performed to elicit characteristics independently associated with survival., Results: The median, 1-, and 5-year survivals were 21.3 m, 76%, and 23%, with 30/90-day mortalities of 0.7%/1.7%. 76% of patients received adjuvant therapy. Patients with major complications (Clavien Grade IIIb-IV) survived equivalently to patients with no complications (P = 0.33). The median and 5-year survival for a total pancreatectomy was 32.2 m/49%; for 90 'favourable biology' patients (R0/N0/M0) was 37.3 m/40%; and for IPMN (9% of series) was 21.2 m/46%. Elderly (>75 yo) and nonelderly patients had similar survival. Favorable prognostic features by multivariate analysis include lower POSSUM physiology score, R0 resection, absence of operative transfusion, G1/G2 grade, absence of lymphovascular invasion, T1/T2 stage, smaller tumor size, LN ratio <0.3, and receipt of adjuvant therapy., Conclusion: This experience with resected PDAC shows decreasing morbidity and mortality rates along with modestly improving long-term survival, particularly for certain subgroups of patients. Survival is related to pathological features, pre-operative physiology, operative results and adjuvant therapy., (© 2012 International Hepato-Pancreato-Biliary Association.)

Introduction: Although mortality rates from pancreatectomy have decreased worldwide, death remains an infrequent but profound event at an individual practice level. Root-cause analysis is a retrospective method commonly employed to understand adverse events. We evaluate whether emerging mortality risk assessment tools sufficiently predict and account for actual clinical events that are often identified by root-cause analysis., Methods: We assembled a Pancreatic Surgery Mortality Study Group comprised of 36 pancreatic surgeons from 15 institutions in 4 countries. Mortalities after pancreatectomy (30 and 90 days) were accrued from 2000 to 2010. For root-cause analysis, each surgeon "deconstructed" the clinical events preceding a death to determine cause. We next tested whether mortality risk assessment tools (ASA, POSSUM, Charlson, SOAR, and NSQIP) could predict those patients who would die (n = 218) and compared their prognostic accuracy against a cohort of resections in which no patient died (n = 1,177)., Results: Two hundred eighteen deaths (184 Whipple's resection, 18 distal pancreatectomies, and 16 total pancreatectomies) were identified from 11,559 pancreatectomies performed by surgeons whose experience averaged 14.5 years. Overall 30- and 90-day mortalities were 0.96% and 1.89%, respectively. Individual surgeon rates ranged from 0% to 4.7%. Only 5 patients died intraoperatively, while the other 213 succumbed at a median of 29 days. Mean patient age was 70 years old (38% were >75 years old). Malignancy was the indication in 90% of cases, mostly pancreatic cancer (57%). Median operative time was 365 min and estimated blood loss was 700 cc (range, 100-16,000 cc). Vascular repair or multivisceral resections were required for 19.7% and 15.1%, respectively. Seventy-seven percent had a variety of major complications before death. Eighty-seven percent required intensive care unit care, 55% were transfused, and 35% were reoperated upon. Fifty percent died during the index admission, while another 11% died after a readmission. Almost half (n = 107) expired between 31 and 90 days. Only 11% had autopsies. Operation-related complications contributed to 40% of deaths, with pancreatic fistula being the most evident (14%). Technical errors (21%) and poor patient selection (15%) were cited by surgeons. Of deaths, 5.5% had associated cancer progression-all occurring between 31 and 90 days. Even after root-cause scrutiny, the ultimate cause of death could not be determined for a quarter of the patients-most often between 31 and 90 days. While assorted risk models predicted mortality with variable discrimination from nonmortalities, they consistently underestimated the actual mortality events we report., Conclusion: Root-cause analysis suggests that risk prediction should include, if not emphasize, operative factors related to pancreatectomy. While risk models can distinguish between mortalities and nonmortalities in a collective fashion, they vastly miscalculate the actual chance of death on an individual basis. This study reveals the contributions of both comorbidities and aggressive surgical decisions to mortality.

Background: Traditional survival estimates after resection for pancreatic cancer are based on clinicopathological variables at the time of diagnosis. Estimates have not reflected time survived after resection, as investigated for other malignancies. The aim of the present study was to understand how survival estimates change after pancreatic resection for cancer based on time already survived (conditional survival)., Methods: Pancreatectomies performed for pancreatic ductal adenocarcinoma (PDAC) between 2001 and 2010 were reviewed. Clinicopathological variables were evaluated to identify predictors of survival. Expected survival according to a validated nomogram for pancreatic cancer as well as conditional survival estimates and actual survival were calculated., Results: In all, 186 patients underwent pancreatic resection for PDAC [154 (82.8%) Whipple, 26 (14.0%) distal and 6 (3.2%) total]. Median (range) survival was 22 (3.4-107.3) months. Predictors of overall survival were: absence of nodal disease [odds ratio (OR) 8.8], age <67 years (OR 8.4) and lower stage (OR 4.3). Expected survival according to the nomogram was 70% (1 year), 39.5% (2 years) and 24% (3 years). As time passed, and overall and expected survival decreased, conditional survival increased., Discussion: The available prognostic system for PDAC underestimated survival compared with actual survival in the present study. Conditional survival estimates, based on accrued lifespan, were better than either predicted or actual survival, suggesting that survival is a dynamic, rather than static, concept. Conditional survival may, therefore, be a useful tool to allow patients and clinicians to project subsequent survival based on time accrued since resection., (© 2011 International Hepato-Pancreato-Biliary Association.)

Introduction: Obstruction of the pancreatico-biliary (PB) drainage limb following major PB operations creates unique diagnostic and management dilemmas. We describe the etiology and prevalence, as well as diagnostic and therapeutic approaches for this challenging problem., Methods: Individuals with PB limb obstruction were identified from a cohort of 477 patients undergoing major PB resections or bypasses for benign and malignant (N = 265) diseases from September 2000 to January 2010. Their presentation, management, short-term outcomes, and survival were analyzed., Results: Thirteen patients developed eventual PB limb obstruction with a mean time to presentation of 18.4 months (range 0.5-41.9), representing an overall adjusted incidence of 4%. Presenting symptoms were reflective of limb obstruction (elevated LFTs, jaundice, cholangitis, and pancreatitis). CT scans demonstrated dilation of the PB drainage limb in all 13 patients and evidence of intrahepatic biliary dilation in eight. Endoscopy was not valuable for either diagnostic or therapeutic purposes in the five patients evaluated in this manner. Percutaneous transhepatic biliary drainage (PTC) was pursued in six patients and provided definitive palliation in two, while three were temporized by this modality prior to a definitive operation, and it was employed postoperatively in another. Operative management occurred in 11 of 13 patients. Causative lesions were not accurately predicted by preoperative imaging and included adhesions, limb volvulus, abscess, malignant local recurrence, solitary metastatic disease, and carcinomatosis. Surgical interventions varied (five enteric bypasses, three adhesiolyses, two explorations, and one external limb venting). There were two perioperative mortalities, but limited morbidity otherwise (one myocardial infarction, one wound dehiscence, and one empyema from PTC placement). The median duration of postoperative hospital stay was 9 days, and no patient required readmission for further surgical management. No patients suffered subsequent recurrence of PB obstruction. In follow-up, nine of the remaining 11 patients are deceased with a median survival of 2.3 months (0.6-9.4 months). The other two are alive at a mean follow-up of 48 months., Conclusion: Although infrequent, PB limb obstruction occurs for a variety of reasons and most commonly in the setting of an original malignancy. Since numerous therapeutic modalities are available, an improved understanding of the condition is important in managing these complex patients. Decisive operative intervention accurately assesses the cause and extent of the problem and, for most presentations, provides definitive palliation with limited morbidity for this near-terminal event.

Objective: To evaluate pancreatic surgery as a model for high-acuity surgery in elderly patients for immediate and long-term outcomes, predictors of adverse outcomes, and hospital costs., Design: Retrospective case series., Setting: University tertiary care referral center., Patients: Four hundred twelve consecutive patients who underwent pancreatic resection from October 1, 2001, through March 31, 2008, for benign and malignant periampullary conditions., Main Outcome Measures: Clinical outcomes were compared for elderly (> or = 75 years) and nonelderly patient cohorts. Quality assessment analyses were performed to show the differential impact of complications and resource utilization between the groups., Results: The elderly cohort constituted one-fifth of all patients. Benchmark standards of quality were achieved in this group, including low operative mortality (1%). Despite higher patient acuity, clinical outcomes were comparable to those of nonelderly patients at a marginal cost increase (median, $2202 per case). Cost modeling analysis showed further that minor and moderate complications were more frequent but no more debilitating for elderly patients. Major complications, however, were far more threatening to older patients. In these cases, duration of hospital stay doubled, and invasive interventions were more commonly deployed., Conclusions: Quality standards for pancreatic resection in the elderly can--and should--mirror those for younger patients. Age-related care, including geriatric consultation, supplemental enteral nutrition, and early rehabilitation placement planning, can be designed to mitigate the impact of complications in the elderly and guarantee quality.

Background: Pancreatic fistula is traditionally suspected on the basis of increased drain amylase activity. However, some patients have a low amylase level but later manifest clinical evidence of a fistula. This study investigated the prevalence and significance of these presentations., Methods: Severity of fistula was determined according to the International Study Group on Pancreatic Fistula criteria for 405 consecutive pancreatic resections. Latent fistulas, initially lacking amylase-rich effluent but ultimately clinically relevant (grades B or C), were examined to determine their impact and significance., Results: Fistula of any extent occurred in 107 patients (26.4 per cent). Latent fistulas occurred in 20 patients (4.9 per cent of all resections, 18.7 per cent of all fistulas and 36 per cent of all clinically relevant fistulas). Initial amylase activity was consistently low (range 3-235 units/l), but these fistulas subsequently manifested clinical relevance (abdominal pain, radiographic evidence, fever, sinister effluent, wound infection). Latent presentations had twice the infection rate of evident fistulas, required more aggressive interventions, resulted in longer hospitalizations and incurred greater hospital costs., Conclusion: A considerable proportion of patients with pancreatic fistula do not initially demonstrate an amylase-rich effluent. These patients have significantly worse outcomes. In fistula definition, the clinical course is important as well as biochemical parameters., ((c) 2009 British Journal of Surgery Society Ltd.)

Introduction: Although asymptomatic pancreatic lesions (APLs) are being discovered incidentally with increasing frequency, their true significance remains uncertain. Treatment decisions pivot off concerns for malignancy but at times might be excessive. To understand better the role of surgery, we scrutinized a spectrum of APLs as they presented to our surgical practice over defined periods., Methods: All incidentally identified APLs that were operated upon during the past 5 years were clinically and pathologically annotated. Among features evaluated were method/reason for detection, location, morphology, interventions, and pathology. For the past 2 years, since our adoption of the Sendai guidelines for cystic lesions, we scrutinized our approach to all patients presenting with APLs, operated upon or not., Results: Over 5 years, APLs were identified most frequently during evaluation of: genitourinary/renal (16%), asymptomatic rise in liver function tests (LFTs; 13%), screening/surveillance (7%), and chest pain (6%). APLs occurred throughout the pancreas (body/tail 63%; head/uncinate 37%) with 48% being solid. One hundred ten operations were performed with no operative mortality including 89 resections (distal 57; Whipple 32) and 21 other procedures. Morbidity was equivalent or better than those cases performed for symptomatic lesions during the same time frame. During these 5 years, APLs accounted for 23% of all pancreatic resections we performed. In all, 22 different diagnoses emerged including non-malignant intraductal papillary mucinous neoplasm (IPMN; 17%), serous cystadenoma (14%), and neuroendocrine tumors (13%), while 6% of patients had >1 distinct pathology and 12% had no actual pancreatic lesion at all. Invasive malignancy was present 17% of the time, while carcinoma in situ or metastases was identified in an additional eight patients. Thus, the overall malignancy rate for APLs equals 24% and these patients were substantially older (68 vs 58 years; p = 0.003). An asymptomatic rise in LFTs correlated significantly (p = 0.009) with malignancy. Furthermore, premalignant pathology was found an additional 47% of the time. Seven patients ultimately chose an operation over continued observation for radiographic changes (mean 2.6 years), but none had cancer. In the last 2 years, we have evaluated 132 new patients with APLs, representing 47% of total referrals for pancreatic conditions. Nearly half were operated upon, with a 3:2 ratio of solid to cystic lesions. This differs significantly (p = 0.037) from the previous 3 years (2:3 ratio), reflecting tolerance for cysts <3 cm and side-branch IPMN. Surgery was undertaken more often when a solid APL was encountered (74%) than for cysts (32%). Some solid APLs were actually unresectable cancers. Due to anxiety, two patients requested an operation over continued observation, and neither had cancer., Conclusion: APLs occur commonly, are often solid, and reflect a spectrum of diagnoses. Sendai guidelines are not transferable to solid masses but have safely refined management of cysts. An asymptomatic rise in LFTs cannot be overlooked nor should a patient or doctor's anxiety, given the prevalence of cancer in APLs.

Pancreatic cancer is the fifth most common cause of cancer-related death in the USA. However, the antepartum diagnosis of pancreatic adenocarcinoma in the pregnant patient is exceedingly rare, with only six cases previously reported in the literature. Optimizing both maternal and fetal health outcomes is particularly challenging when surgical procedures are necessary for staging and/or therapeutic purposes--as these interventions often pose significant risks to both the mother and the developing fetus. In this article, we report a case of pancreatic adenocarcinoma diagnosed during pregnancy and review the literature on the management issues confronted in this unique clinical situation.

Pancreatic cancer is lethal because of its invasiveness, rapid progression, and profound resistance to chemotherapy and radiation therapy. To identify the molecular mechanisms underlying this, we have examined the expression and potency of three major death receptors: tumor necrosis factor receptor (TNF-R), TNF-related apoptosis-inducing ligand receptor (TRAIL-R), and Fas in mediating cytotoxicity in four invasive pancreatic cancer cell lines. We have analyzed the expression of major antiapoptotic factors, cell cycle regulators and death receptor decoys (DcR) in comparison with normal pancreas tissues and five other human malignant tumor cell lines. We have found that different pancreatic cancer cell lines coexpress high-level TRAIL-R, Fas, and TNF-R1 but are strongly resistant to apoptosis triggered by the death receptors. DcR2 and DcR3 overexpression may partly contribute to the resistance of pancreatic cancer cells to TRAIL-R- and Fas-mediated cytotoxicity. Bcl-XL and Bcl-2 are predominantly overexpressed in pancreatic cancer cell lines, respectively. Bcl-XL is also predominantly overexpressed in prostate, colorectal, and intestinal cancer cells. The knockdown of the predominant Bcl-XL overexpression significantly reduces the viability of pancreatic cancer cells to TNFalpha- and TRAIL-mediated apoptosis by sublethal-dose single and combined antitumor drugs, including geldanamycin, PS-341, Trichostatin A, and doxorubicine. Geldanamyin and PS-341 synergistically block NFkappaB activation, suppress Akt/PKB pathway, and down-regulate Bcl-XL, Bcl-2, cIAP-1, and cyclin D1 expression. This combined regimen dramatically enhances TRAIL cytotoxic effects and breaks through chemoresistance. Bcl-XL plays a vital role in pancreatic cancer chemoresistance. Geldanamycin, PS-341, and TRAIL triple combination may be a novel therapeutic strategy for pancreatic cancer.