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Diagnostic markers are desperately needed for the early detection of pancreatic ductal adenocarcinoma (PDA). We describe sets of markers expressed in temporal order in mouse models during pancreatitis, PDA initiation and progression. Cell type specificity and the differential expression of PDA markers were identified by screening single cell (sc) RNAseq from tumor samples of a mouse model for PDA (KIC) at early and late stages of PDA progression compared to that of a normal pancreas. Candidate genes were identified from three sources: (1) an unsupervised screening of the genes preferentially expressed in mouse PDA tumors; (2) signaling pathways that drive PDA, including the Ras pathway, calcium signaling, and known cancer genes, or genes encoding proteins that were identified by differential mass spectrometry (MS) of mouse tumors and conditioned media from human cancer cell lines; and (3) genes whose expression is associated with poor or better prognoses (PAAD, oncolnc.org). The developmental progression of PDA was detected in the temporal order of gene expression in the cancer cells of the KIC mice. The earliest diagnostic markers were expressed in epithelial cancer cells in early-stage, but not late-stage, PDA tumors. Other early markers were expressed in the epithelium of both early- and late-state PDA tumors. Markers that were expressed somewhat later were first elevated in the epithelial cancer cells of the late-stage tumors, then in both epithelial and mesenchymal cells, or only in mesenchymal cells. Stromal markers were differentially expressed in early- and/or late-stage PDA neoplasia in fibroblast and hematopoietic cells (lymphocytes and/or macrophages) or broadly expressed in cancer and many stromal cell types. Pancreatitis is a risk factor for PDA in humans. Mouse models of pancreatitis, including caerulein treatment and the acinar-specific homozygous deletion of differentiation transcription factors (dTFs), were screened for the early expression of all PDA markers identified in the KIC neoplasia. Prognostic markers associated with a more rapid decline were identified and showed differential and cell-type-specific expression in PDA, predominately in late-stage epithelial and/or mesenchymal cancer cells. Select markers were validated by immunohistochemistry in mouse and human samples of a normal pancreas and those with early- and late-stage PDA. In total, we present 2165 individual diagnostic and prognostic markers for disease progression to be tested in humans from pancreatitis to late-stage PDA.

Introduction: The anatomic location of the pancreas can result in involvement of major vasculature, which may act as a contraindication to resection. Several classification systems have been developed. We sought to discover the variations in the HPB community determining PDAC resectability., Methods: The multiple-choice survey was distributed to all full members of the IHPBA. Questions were asked regarding demographics and clinical scenarios regarding tumor resectability., Results: 164 responses were submitted. Most of the respondents were male and had been in practice for over 10 years. The median age range was 40-50 years old. Most practiced in either Asia (n = 57,35.9%), North America (n = 52,32.7%), or Europe (n = 32,20.1%). Classification systems used to determine resectability were: NCCN (n = 42,26.3%), JPS (n = 35,21.9%), International consensus (n = 33,20.6%), AHPBA/SSO (n = 23,14.4%), Alliance (n = 3,1.9%), and other/no-classification (n = 23,14.5%). There was significant variation in the frequency of the most common answer within the scenarios (84.7%-33.5%). Participant concordance with their stated classification system found a median rate of 62.5%. Participant decision of tumor resectability was not dependent on their adopted classification system., Conclusion: When classifying PDAC resectability, there is significant variation between surgeons as to how they would classify a specific tumour, independent of the classification system they use. In addition, surgeons do not show high concordance with the definitions within that classification system., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: The surgical decision making for pancreatic adenocarcinoma is complex. Although practice guidelines exist for many scenarios, these do not cover many common eventualities that may be encountered during these cases. We sought to identify the practice pattern variations amongst pancreatic surgeons in response to commonly experienced clinical scenarios., Methods: A multiple-choice questionnaire was distributed to all full members of the IHPBA. Participant demographics, training history, and clinical practice information were obtained. The survey provided various operative scenarios and participants were asked how they would likely proceed. Responses were collected and stored anonymously in a secure database. Statistical analysis was performed using Stata 16.0., Results: 164 responses were submitted. Most of the respondents were male and had been in practice for over 10 years. The median age range was 40-50 years old. When asked about staging laparoscopy, the majority performed it selectively. For most respondents a pathological aorto-caval nodes was a reason to abort the procedure but most would have continued in the setting of a positive hepatic artery node. When encountering a single Segment 2 liver metastasis, participants who practiced in Europe were significantly more likely to resect and proceed compared to those in Asia and North America. Participants who had undergone only a Surgical Oncology fellowship were most likely to abort. With respect to direct colonic invasion, most participants would resect the specimen en bloc. Respondents who participated in fewer that 20 PDAC operations/year were most likely to abort., Conclusions: Surgical decision making in PDAC surgery is complex and there is significant disagreement on the correct management. While formal guidelines cannot exist for all situations, this survey highlights the need for consensus on commonly encountered operative scenarios., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: We hypothesized that those patients with pancreatic neuroendocrine tumors (pNETs) ≤2 cm managed nonoperatively would have comparable disease progression to individuals undergoing an operation., Methods: Patients diagnosed with nonfunctional pNETs ≤ 2 cm who were evaluated at a single comprehensive cancer center from 2010 to 2017 were selected from a cancer registry database. Clinicopathologic variables were obtained via retrospective chart review. Primary outcomes were overall and disease specific survival. Variables were compared between the 2 groups using chi-square and independent t-test., Results: Fifty-two individuals had tumors ≤2 cm, of whom 75% had an operation, while 25% were observed. Each treatment arm had similar distributions of gender, race, and tumor location. The most common operation was distal pancreatectomy (n = 29) followed by pancreatoduodenectomy (n = 6). Nine patients had grade III postoperative complications and 4 had grade IV under Clavien-Dindo classification. The observation group was noted to have a mean disease progression interval of 80.9 months, while those who underwent an operation had a mean disease progression interval of 94.6 months ( P = .246)., Conclusions: Overall disease progression in patients with pNETs ≤ 2 cm without evidence of metastasis at the time of presentation is not different between those who underwent operation compared to those observed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Resection of pancreatic tissue is necessary for many pancreatic diseases. The most common form of cancer, pancreatic duct adenocarcinoma, manifests with early metastases and is thought to be resistant to other currently known treatment regimens. Such tumors present a complex and difficult management and handling challenge for a surgeon. Surgical resection affords a better prognosis with a median survival of 14-20 months following resection and up to 25% 5-year survival rates. In this study, data from 75 pancreatic resections for diverse malignant pancreatic lesions will be presented., Methods: At a teaching institute in Central India, this ongoing longitudinal study began in 2009 and was carried on till 2018. Only 75 of the 122 patients who underwent pancreatic resection were deemed appropriate for the current study. All patients were thoroughly examined after being admitted before being given the option of surgery. There were 22 female patients and 53 male patients. The age range for the group was 34-67 years. Results from a range of different malignancies and various pancreatic resection procedures are presented in this study., Results: One of the most aggressive cancers, pancreatic adenocarcinoma, responds to surgical treatment better than other alternative techniques. Out of 75 patients in our series, 32 had pancreatic head cancer, 28 had periampullary cancer, 2 had duodenal cancer, 8 had distal cholangiocarcinoma, and 1 had mucin-producing cystadenocarcinoma. Four patients had pancreatic cancer in both the body and tail. Fifty-three men and 22 women, ages 34-67 years, Whipple's operation and distal pancreatectomy were the most frequent procedures. In our series, survival ranged from 18 to 24 months, and the 5-year survival rate was 12%, which is primarily seen with periampullary carcinoma., Conclusion: The sole option for long-term survival or a cure for pancreatic cancer is surgery. Chemoradiation is ineffective as a first line of treatment. However, some reports contend that palliative chemotherapy actually improves the quality of life. The biology of the illness rules and determines the result; the kind of surgery performed had no bearing on survival, morbidity, or fatality., Context: The above study was taken up in the context of - pancreatic tumors and pathological types, how imaging helps in deciding the plan of surgical management without biopsy. Outcomes of pancreatic resections for pancreatic cancer., Settings and Design: In a suburban hospital which is a tertiary care center, this longitudinal prospective study was conducted from 2009 to 2018., Competing Interests: None

Introduction: Despite aggressive surgical care and systemic therapy, patients with pancreatic ductal adenocarcinoma (PDAC) have a poor prognosis. Recent studies show that racial disparities in outcome also exist. We sought to investigate the association lymph node (LN) metastases had with survival between Black and White patients with PDAC after resection., Methods: Retrospective analysis of 226 PDAC patients who underwent resection at a single institution from 2010 to 2018 was performed with attention to LN metastasis and patient race. The number of patients who received chemotherapy was also evaluated., Results: One Hundred Seventy Five (77.4%) PDAC patients were White and 51 (22.6%) were Black. 130 (59.3%) patients had LN metastasis (LN+). LN+ and LN- groups were similar in race (P = 0.93), sex (P = 0.10) and age at the time of diagnosis (P = 0.45). Patients with LN + disease were more likely to present with larger tumors (3.4 versus 2.8 cm, P = 0.02) and higher T status (P = 0.001). White and Black patients had similar rates of LN metastasis (59% versus 58.8%, P = 1.0). The median survival for LN- Black and White patients were similar (43.2 versus 30.2 mo, P = 0.82). LN + Black patients trended towards receiving more systemic therapy than White LN + patients (55% versus 42%, P = 0.10). The median survival for LN + Black patients was significantly less than LN + White patients (17.5 versus 24.6 mo, P = 0.04)., Conclusions: Black LN + PDAC patients have an inferior survival rate after resection when compared to their White counterparts. Our disparity in outcome cannot be solely explained by a difference in systemic treatment. Further investigation is warranted to determine racial differences in tumor biology or response to chemotherapy., (Copyright © 2022. Published by Elsevier Inc.)

A central challenge in biology is obtaining high-content, high-resolution information while analyzing tissue samples at volumes relevant to disease progression. We address this here with CODA, a method to reconstruct exceptionally large (up to multicentimeter cubed) tissues at subcellular resolution using serially sectioned hematoxylin and eosin-stained tissue sections. Here we demonstrate CODA's ability to reconstruct three-dimensional (3D) distinct microanatomical structures in pancreas, skin, lung and liver tissues. CODA allows creation of readily quantifiable tissue volumes amenable to biological research. As a testbed, we assess the microanatomy of the human pancreas during tumorigenesis within the branching pancreatic ductal system, labeling ten distinct structures to examine heterogeneity and structural transformation during neoplastic progression. We show that pancreatic precancerous lesions develop into distinct 3D morphological phenotypes and that pancreatic cancer tends to spread far from the bulk tumor along collagen fibers that are highly aligned to the 3D curves of ductal, lobular, vascular and neural structures. Thus, CODA establishes a means to transform broadly the structural study of human diseases through exploration of exhaustively labeled 3D microarchitecture., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Exocrine pancreatic insufficiency (EPI) is frequently seen in patients with pancreatic cancer (PDAC) and is thought to contribute to nutritional complications. While EPI can be pharmacologically temporized with pancreatic enzyme replacement therapy (PERT), there is lack of clear evidence informing its use in PDAC. Here we aim to survey pancreatic surgeons regarding their utilization of PERT in the management of EPI for PDAC., Methods: An online survey was distributed to the members of The Americas Hepato-Pancreato-Biliary Association (AHPBA) and The Pancreas Club., Results: 86.5% (180/208) of surgeons prescribe PERT for at least some resectable/borderline resectable PDAC cases. Only a minority of surgeons order investigations to confirm EPI before starting PERT (28.1%) or test for adequacy of therapy (28.3%). Few surgeons believe that PERT has an effect on overall survival (19.7%) or disease-free survival (6.25%) in PDAC., Conclusion: PERT is widely prescribed in patients with resectable/borderline resectable PDAC, but investigations establishing EPI and assessing PERT adequacy are underutilized. A substantial proportion of surgeons are unclear as to the effect of PERT on survival outcomes in PDAC. These data call for prospective studies to establish guidelines for optimal use of PERT and its effects on survival outcomes in PDAC., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: Systemic therapy is a key management component of pancreatic ductal adenocarcinoma(PDAC). Racial disparities exist in PDAC, often linked to socioeconomic variables. We investigated the impact of race in PDAC patients who had undergone systemic therapy and surgical resection., Methods: A retrospective analysis was performed for all patients who underwent surgical resection for PDAC from 2010 to 2018., Results: 234 patients (78.2% White; 21.8% Black) were included. Black patients presented at a younger age with larger tumors. White patients benefited from systemic therapy with longer overall survival (35vs20 months, p = 0.002). This survival advantage was not present in Black patients (21vs15 months, p = 0.15). Black patients receiving systemic therapy had similar survival as White patients who did not (p = 0.81)., Conclusion: Black PDAC patients present at younger ages and with larger initial tumors. In our population, White patients had a longer overall survival after both surgical and systemic therapy. These findings may indicate differences in tumor biology. Further prospective studies are needed., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: Pancreatic neuroendocrine tumor (PNET) survival outcomes differ by race. Current recommendations for surveillance of PNETs less than 2 cm in size are based on low malignant potential and low rates of lymph node metastases (LNM). We investigated whether these guidelines are universally applicable regardless of race., Study Design: A multi-institutional analysis of patients with resected, nonfunctional, sporadic PNETs was performed initially using the US Neuroendocrine Study Group dataset with the National Cancer Database as a validation dataset. Patients with distant metastatic disease were excluded from analysis., Results: A total of 453 (388 White and 65 Black) and 5,532 patients (4,772 White and 760 Black) were analyzed in the initial and validation datasets, respectively. White patients had a low incidence of LNM in tumors of less than 2 cm in both datasets (5% and 12%, respectively), which increased with tumor size. However, the incidence of LNM in Black patients was similar in the initial and validation datasets for tumors sized less than 2 cm (23% and 21%) and 2 to 3 cm (21% and 29%). Black patients had a significantly higher incidence of LNM in tumors less than 2 cm in size in the initial and validation datasets (p < 0.01) compared with White patients., Conclusions: The current recommendation for surveillance of PNETs of less than 2 cm in size is likely based on a low rate of LNM seen in a predominantly White population. The incidence of LNM in Black patients with tumors less than 2 cm in size is clinically relevant and concerning. Current guidelines may not be universally applicable, and a more aggressive approach to resection in Black patients with small PNETs may be warranted., (Copyright © 2022 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Many studies show significantly improved survival after R0 resection compared with R1 resection in pancreatic adenocarcinoma (PAC); however, the effect of neoadjuvant chemoradiation (NACRT) on this association is unknown., Objective: The aim of this study was to evaluate the prognostic significance of positive surgical margins (SMs) after NACRT compared with upfront surgery + adjuvant therapy in PAC., Methods: All cases of surgically resected PAC at a single institution were reviewed from 1996 to 2014; patients treated with palliative intent, metastatic disease, and biliary/ampullary tumors were excluded. The primary endpoint was overall survival (OS)., Results: Overall, 300 patients were included; 134 patients received NACRT with concurrent 5-fluorouracil or gemcitabine followed by surgery, and 166 patients received upfront surgery (+ adjuvant chemotherapy in 72% of patients and RT in 65%); 31% of both groups had a positive SM (+SM). The median OS for patients with a +SM or negative SM (-SM) was 26.6 and 31.6 months, respectively for NACRT, and 12.0 and 24.5 months, respectively, for upfront surgery. OS was significantly improved with -SM compared with +SM in both groups (p = 0.006). When resection yielded +SM, NACRT patients had improved OS compared with upfront surgery patients (p < 0.001). On multivariable analysis, +SM in the upfront surgery group (hazard ratio [HR] 2.94, 95% confidence interval [CI] 2.04-4.24; p < 0.001) and older age (HR 1.01, 95% CI 1.00-1.03, per year; p = 0.007) predicted worse OS. +SM in the NACRT group was not associated with worse OS (HR 1.09, 95% CI 0.72-1.65; p = 0.70)., Conclusion: Patients with a positive margin after NACRT and surgery had longer survival compared with patients with a positive margin after upfront surgery. NACRT should be strongly considered for patients at high risk of R1 resections., (© 2021. Society of Surgical Oncology.)

Objectives: Pancreatic cancer continues to be a major cause of cancer-related mortality. There has been a greater implementation of up-front chemotherapy for pancreatic adenocarcinoma patients. Although there are many theoretical benefits to neoadjuvant chemotherapy, its clinical impact is uncertain. We sought to understand the outcomes of patients with resectable and borderline-resectable pancreatic adenocarcinoma who underwent neoadjuvant chemotherapy., Methods: Patients were collected in a secure database from September 2018 to May 2020. Patients were excluded if they presented with locally advanced or metastatic disease, inability to complete chemotherapy, or if they were not a surgical candidate., Results: Sixty-six patients with resectable disease underwent chemotherapy. Folinic acid/5-fluorouracil/irinotecan/oxaliplatin was used in 41 patients (62.1%) and gemcitabine-based regimens in 28 patients (42.4%, greater than 100% as some patients underwent both regimens). After restaging, 47 patients (71.2%) were thought to have resectable disease. Of these patients, 36 have been successfully resected to date. Metastatic disease was found in 12 patients (18.2%) and 6 patients (9.1%) had locally advanced disease., Conclusions: Most patients with resectable pancreatic cancer are resected after neoadjuvant chemotherapy, but a subset will develop local or distant progression. Further studies will be needed to determine which patients will progress locally and may benefit from an up-front surgical approach., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background and Objectives: Pancreatic neuroendocrine tumors (PNETs) represent a rare form of pancreatic cancer. Racial/ethnic disparities have been documented in pancreatic ductal adenocarcinoma, but health disparities have not been well described in patients with PNETs., Methods: A retrospective review of patients with PNETs in the National Cancer Database was performed for 2004-2014. Approximately 16 605 patients with PNETs and available vital status were identified. Survival was compared by race/ethnicity and socioeconomic status using Kaplan-Meier methods and Cox regression., Results: There were no significant differences in survival between Non-Hispanic, White; Hispanic, White; or Non-Hispanic, Black patients on univariate analysis. Kaplan-Meier analysis showed that patients from communities with lower median household income and education level had worse survival (p < 0.001). Patients age less than 65 without insurance, similarly, had worse survival (p < 0.001). Multivariable modeling found no association between race/ethnicity and risk of mortality (p = 0.37). Lower median household income and lower education level were associated with increased mortality (p < 0.001)., Conclusions: Unlike most other malignancies, race/ethnicity is not associated with survival differences in patients with PNETs. Patients with lower socioeconomic status had worse survival. The presence of identifiable health disparities in patients with PNETs represents a target for intervention and opportunity to improve survival in patients with this malignancy., (© 2021 Wiley Periodicals LLC.)

Introduction: Margin accentuation (MA) using Irreversible electroporation (IRE) offers an unique opportunity to reduce the R1 resections in resectable pancreatic cancer (RPC). This study aims to assess the rate of margin positivity using IRE for MA during pancreaticoduodenectomy (PD) for resectable pancreatic head tumours., Materials and Methods: Following ethical approval, MA using IRE was carried out in 20 consecutive patients to posterior and superior mesenteric vein (SMV) margin, and the pancreatic neck, prior to the PD resection. The control group (non-IRE; n = 91) underwent PD without MA over the study period, March 2018 to March 2020., Results: There was no difference between the two groups in terms of patients' age, gender, pre-op biliary drainage, site of malignancy or pre-operative TNM stage. The overall margin positive rate for IRE group was lesser (35.0%) when compared to non-IRE group (51.6%; p = 0.177), with significantly less posterior pancreatic margin positivity (5.0% vs. 25.3%; p = 0.046). When only treated margins (SMA margin excluded) were compared, the IRE group had significantly lower margin positive rates (20.0% vs. 51.6%; p = 0.013). There was no difference between the two groups in terms of intra- or post-operative complications. With a median follow-up of 15.6 months, the median DFS and OS for IRE and non-IRE groups were 17 and 18 months (p = 0.306) and 19 and 22 months (p = 0.227) respectively., Conclusion: Our pilot study confirms the safety of MA using IRE for RPC, with reduction in margin positivity. These results as a proof of concept are promising and need further validation with a randomised controlled trial., Competing Interests: Declaration of competing interest The authors do not have any conflict of interest to declare., (Copyright © 2021 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Background: Pancreatic cancer is a leading cause of financial insolvency and cancer related deaths in the United States. The risk of catastrophic health expenditure (CHE) was calculated for patients undergoing pancreatic resection at an academic institution., Methods: Patients who underwent pancreatic resection between 2013 and 2017 were identified through an institutional cancer registry. A CHE was an out-of-pocket payment (OOP) > 10% of the estimated median household income., Results: 319 patients met inclusion criteria. Hospital median charge was $76,700. 99% of patients had insurance and hospital bill adjustments. As a result, 61% (n = 193) made no OOP. Only 3 patients risked CHE. For all tumors combined there were no differences in survival outcomes by OOP., Conclusion: This is the first study to use institutional financial data to calculate CHE risk for pancreatic resection patients. Insurance adjustments to hospital charges that accompany health insurance and voluntary hospital adjustments for the uninsured protect patients against CHE., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Pancreatic cancer is the fourth leading cause of cancer-related death among men and women in the United States. A major challenge in treatment remains patients' advanced disease at diagnosis. The NCCN Guidelines for Pancreatic Adenocarcinoma provides recommendations for the diagnosis, evaluation, treatment, and follow-up for patients with pancreatic cancer. Although survival rates remain relatively unchanged, newer modalities of treatment, including targeted therapies, provide hope for improving patient outcomes. Sections of the manuscript have been updated to be concordant with the most recent update to the guidelines. This manuscript focuses on the available systemic therapy approaches, specifically the treatment options for locally advanced and metastatic disease.

Objective: The incidence of pancreatic neuroendocrine tumors (PNETs) has increased over the last decade. Black patients have worse survival outcomes. This study investigates whether oncologic outcomes are racially disparate at a single institution., Methods: Retrospective analysis was performed on 151 patients with resected PNETs between 2010 and 2019., Results: More White males and Black females presented with PNETs (P = 0.02). White patients were older (65 years vs 60 years; P = 0.03), more likely to be married (P < 0.01), and had higher median estimated yearly incomes ($28,973 vs $17,767; P < 0.01) than Black patients. Overall and disease-free survival were not different. Black patients had larger median tumor sizes (30 mm vs 23 mm; P = 0.02). Tumor size was predictive of recurrence only for White patients (hazard ratio, 1.02; P = 0.01). Collectively, tumors greater than 20 mm in size were more likely to have recurrence (P = 0.048), but this cutoff was not predictive in either racial cohort independently., Conclusions: Black patients undergoing curative resection of PNETs at our institution presented with larger tumors, but that increased size is not predictive of disease-free survival in this population., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignancy and its mortality continues to rise globally. Because of its high heterogeneity and complex molecular landscapes, published gene signatures have demonstrated low specificity and robustness. Functional signatures containing a group of genes involved in similar biological functions may display a more robust performance., Methods: The present study was designed to excavate potential functional signatures for PDAC by analyzing maximal number of datasets extracted from available databases with a recently developed method of FAIME (Functional Analysis of Individual Microarray Expression) in a comprehensive and integrated way., Results: Eleven PDAC datasets were extracted from GEO, ICGC and TCGA databases. By systemically analyzing these datasets, we identified a robust functional signature of subpathway (path:00982&#95;1), which belongs to the drug metabolism-cytochrome P450 pathway. The signature has displayed a more powerful and robust capacity in predicting prognosis, drug response and chemotherapeutic efficacy for PDAC, particularly for the classical subtype, in comparison with published gene signatures and clinically used TNM staging system. This signature was verified by meta-analyses and validated in available cell line and clinical datasets with chemotherapeutic efficacy., Conclusion: The present study has identified a novel functional PDAC signature, which has the potential to improve the current systems for predicting the prognosis and monitoring drug response, and to serve a linkage to therapeutic options for combating PDAC. However, the involvement of path:00982&#95;1 subpathway in the metabolism of anti-PDAC chemotherapeutic drugs, particularly its biological interpretation, requires a further investigation. Video Abstract.

Background: Neoadjuvant therapy for pancreatic cancer is being employed more commonly. Most of these patients undergo biliary stenting which results in bacterial colonization and more surgical site infections (SSIs). However, the influence of neoadjuvant therapy on the biliary microbiome has not been studied., Methods: From 2007 to 2017, patients at our institution who underwent pancreatoduodenectomy (PD) and had operative bile cultures were studied. Patient demographics, stent placement, bile cultures, bacterial sensitivities, SSIs and clinically-relevant postoperative pancreatic fistulas (CR-POPF) were analyzed. Patients who underwent neoadjuvant therapy were compared to those who went directly to surgery. Standard statistical analyses were performed., Results: Eighty-three patients received neoadjuvant therapy while 89 underwent surgery alone. Patients who received neoadjuvant therapy were more likely to have enterococci (45 vs 22%, p < 0.01), and Klebsiella (37 vs 19%, p < 0.01) in their bile. Resistance to cephalosporins was more common in those who received neoadjuvant therapy (76 vs 60%, p < 0.05). Neoadjuvant therapy did not affect the incidence of SSIs or CR-POPFs., Conclusion: The biliary microbiome is altered in patients undergoing pancreatoduodenectomy (PD) after neoadjuvant therapy. Most patients undergoing PD with a biliary stent have microorganisms resistant to cephalosporins. Antibiotic prophylaxis in these patients should cover enterococci and gram-negative bacteria., (Copyright © 2019. Published by Elsevier Ltd.)

Background: The aim of this study was to evaluate health disparities in the outcomes of patients with resectable pancreatic adenocarcinoma., Methods: We retrospectively analyzed 280,935 patients from the National Cancer Data Base (NCDB), from 1998 to 2012 to compare the differences in patient characteristics, refusal of offered surgical treatment and overall survival after pancreatic adenocarcinoma resection between white vs. black patients., Results: Black patients did not undergo and refused offered surgical treatment more frequently. Race and insurance were the most important factors independently associated with not receiving the offered resection. Having private insurance, Hispanic ethnic background, geographic location, higher income, residing in urban/metropolitan area and systemic treatment were independently associated with improved survival. Race was associated with overall worse survival in an unadjusted model but not in multivariable analysis. The association between race and survival was removed when adjusting for facility location, income, education, tumor size, tumor stage or systemic treatment., Conclusion: Disparities exist at various levels in resectable pancreatic cancers. These findings help developing targeted interventions and quality improvement initiatives., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights discuss important updates to the 2019 version of the guidelines, focusing on postoperative adjuvant treatment of patients with pancreatic cancers.

Background: Symptomatic pancreaticojejunal anastomotic stricture (PJS) is a rare complication following pancreaticoduodenectomy. The incidence, presentation and management of this condition are infrequently reported in the literature. Revision surgery is thought to be an effective treatment. Recent literature shows some success from endoscopic management., Methods: The patients treated for symptomatic PJS from January 2005 to June 2014 were identified. Their clinical presentation and management was retrospectively reviewed. Patients were followed up in clinic or by telephonic interviews to assess their symptoms., Results: Three patients (two females and one male) had symptomatic PJS out of 314 who underwent pancreaticoduodenectomy (0.9%). Main presentating symptom was intermittent abdominal pain. The diagnosis was confirmed by computed tomography scan and/or magnetic resonance cholangiopancreatography. One patient underwent a failed endoscopic retrograde cholangiopancreatography attempt to dilate the stricture. A redo-pancreaticojejunostomy was performed in all patients. At a mean follow-up of 8 months, two patients had complete resolution of symptoms and one patient had partial benefit. Five out of seven case series in literature support surgical management., Conclusion: Symptomatic PJS can be successfully treated with redo-pancreaticojejunostomy, with good medium-term outcomes. Although endoscopic intervention has been described, review of the literature shows that success rates are low and the long-term results are unknown., (© 2017 Royal Australasian College of Surgeons.)

Background: We evaluated the role of lymph node (LN) retrieval in pancreatic adenocarcinoma (PA) patients undergoing pancreaticoduodenectomy (PD)., Methods: We utilized the National Cancer Data Base; Cox regression models and logistic regression models were used for statistical evaluation., Results: We evaluated 26,792 patients with PA who underwent PD. The mean LN retrieved in LN(-) patients was 10.8 vs 14.4 for LN(+) patients (P < 0.0001). Greater LN retrieval is an independent predictor of a negative microscopic margin and decreased length of stay. The median survival of LN(-) patients exceeded that of LN(+) patients (24.5 vs 15.1 months, P < 0.0001). Increasing LN retrieval is a significant predictor of survival in all patients, and in LN(-) patients. The relationship of increased LN retrieval and enhanced survival is a nearly linear trend., Conclusions: Rather than demonstrating an inflection point that defines the extent of adequate lymphadenectomy, this dataset demonstrates an incremental relationship between LN retrieval and survival., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Ductal adenocarcinoma and its variants account for most pancreatic malignancies. High-quality multiphase imaging can help to preoperatively distinguish between patients eligible for resection with curative intent and those with unresectable disease. Systemic therapy is used in the neoadjuvant or adjuvant pancreatic cancer setting, as well as in the management of locally advanced unresectable and metastatic disease. Clinical trials are critical for making progress in treatment of pancreatic cancer. The NCCN Guidelines for Pancreatic Adenocarcinoma focus on diagnosis and treatment with systemic therapy, radiation therapy, and surgical resection., (Copyright © 2017 by the National Comprehensive Cancer Network.)

Objective: Pancreatic adenocarcinoma is a rapidly progressive malignancy characterized by its tendency for early metastatic spread. MDCT is the primary diagnostic modality for the preoperative staging of patients with pancreatic cancer, with an accuracy established in multiple studies. However, for a variety of reasons, there is often a prolonged interval between staging MDCT and the surgical intervention. This study examines the relationship between the interval between imaging and surgery and the accuracy of MDCT in determining the presence or absence of metastatic disease at surgery in patients with pancreatic cancer., Materials and Methods: Patients were identified who had undergone surgery for pancreatic cancer at our institution with a dedicated preoperative pancreas-protocol MDCT performed in our department. Findings from the preoperative MDCT report were correlated with the operative findings, as well as the time between imaging and surgery., Results: Two hundred ninety-two MDCT scans were performed on 256 patients who underwent exploration for pancreatic adenocarcinoma. The patients had a median age of 67 years (range, 30-95 years), and 51.6% (132/256) were male. The median time between MDCT and surgical exploration was 15.5 days (range, 1-198 days). MDCT correctly predicted the absence of metastatic disease at surgery in 233 of 274 (85.0%) studies. MDCT was more accurate in predicting the absence of metastatic disease if the study was performed within 25 days of surgery than it was if the study was performed within more than 25 days of surgery (89.3% vs 77.0%; p = 0.0097). Furthermore, regression models showed that the negative predictive value of a given MDCT significantly decreased after approximately 4 weeks., Conclusion: MDCT is an accurate method to stage patients with pancreatic cancer, but its accuracy in excluding distant metastatic disease depreciates over time. Patients should undergo a repeat MDCT within 25 days of any planned definitive operative intervention for pancreatic cancer to avoid unexpectedly finding metastatic disease at surgery.

The NCCN Guidelines for Pancreatic Adenocarcinoma discuss the diagnosis and management of adenocarcinomas of the exocrine pancreas and are intended to assist with clinical decision-making. These NCCN Guidelines Insights summarize major discussion points from the 2014 NCCN Pancreatic Adenocarcinoma Panel meeting. The panel discussion focused mainly on the management of borderline resectable and locally advanced disease. In particular, the panel discussed the definition of borderline resectable disease, role of neoadjuvant therapy in borderline disease, role of chemoradiation in locally advanced disease, and potential role of newer, more active chemotherapy regimens in both settings., (Copyright © 2014 by the National Comprehensive Cancer Network.)

Purpose: This study aims to assess outcomes and characteristics associated with resection of metastatic renal cell carcinoma (mRCC) to the pancreas., Materials and Methods: From April 1989 to July 2012, a total of 42 patients underwent resection of pancreatic mRCC at our institution. We retrospectively reviewed records from a prospectively managed database and analyzed patient demographics, comorbidities, perioperative outcomes, and overall survival. Cox proportional hazards models were used to evaluate the association between patient-specific factors and overall survival., Results: The mean time from resection of the primary tumor to reoperation for pancreatic mRCC was 11.2 years (range, 0-28.0 years). In total, 17 patients underwent pancreaticoduodenectomy, 16 underwent distal pancreatectomy, and 9 underwent total pancreatectomy. Perioperative complications occurred in 18 (42.9%) patients; there were two (4.8%) perioperative mortalities. After pancreatic resection, the median follow-up was 7.0 years (0.1-23.2 years), and median survival was 5.5 years (range, 0.4-21.9). The overall 5-year survival was 51.8%. On univariate analysis, vascular invasion (hazard ratio, 5.15; p = 0.005) was significantly associated with increased risk of death., Conclusions: Pancreatic resection of mRCC can be safely achieved in the majority of cases and is associated with long-term survival. Specific pathological factors may predict which patients will benefit most from resection.

Identifying key mediators of cancer cell invasion and metastasis is critical to the development of more effective cancer therapies. We previously identified Filamin A interacting protein 1-like (FILIP1L) as an important inhibitor of cell migration and invasion in ovarian cancer. FILIP1L expression was inversely correlated with the invasive potential of ovarian cancer cell lines and ovarian cancer specimens. We also demonstrated that DNA methylation in the FILIP1L promoter was a mechanism by which FILIP1L was down-regulated in ovarian cancer. In our present study, we tested this observation in other cancer histologies: breast, colon, lung and pancreatic cancers. Both mRNA and protein expression of FILIP1L were down-regulated in these cancer cells compared with their normal epithelial cells. As in ovarian cancer, DNA methylation is a mechanism by which FILIP1L is down-regulated in these cancer histologies. Methylation status of the FILIP1L promoter was inversely correlated with FILIP1L expression. Reduced methylation in the FILIP1L promoter following treatment with a DNA demethylating agent was associated with restoration of FILIP1L expression in these cancer cells. Further, FILIP1L expression was inversely correlated with the invasive potential of these cancer cells. Re-expression of FILIP1L in FILIP1L-low expressing, highly-invasive cancer cell lines resulted in inhibition of cell invasion. Correspondingly, knockdown of FILIP1L in FILIP1L-high expressing, low-invasive cancer cell lines resulted in increase of cell invasion. Overall, these findings suggest that down-regulation of FILIP1L associated with DNA methylation is related with the invasive phenotype in various cancers. Thus, modulation of FILIP1L expression has the potential to be a target for cancer therapy.

Objective: To identify pathologic features that may account for the favorable survival after resection of invasive pancreatic adenocarcinoma arising in the setting of intraductal papillary mucinous neoplasm (IPMN) compared with standard pancreatic ductal adenocarcinoma (PDA) in the absence of IPMN., Summary Background Data: The 5-year survival after resection of IPMN-associated invasive adenocarcinoma is reported to be between 40% and 60%, which is superior to the 10-25%, typically cited after resection of standard PDA. It remains unclear whether this represents distinct biology or simply a tendency for earlier presentation of IPMN-associated invasive adenocarcinoma., Methods: A single institution's prospective pancreatic resection database was retrospectively reviewed to identify patients with invasive pancreatic adenocarcinoma who underwent pancreatectomy with curative intent. Log rank and Cox regression analysis were used to identify factors associated with survival., Results: From 1995 to 2006, 1260 consecutive patients were identified, 132 (10%) with IPMN-associated invasive adenocarcinoma and 1128 (90%) with standard PDA. Actuarial 5-year survival was 42% after resection for IPMN-associated versus 19% for standard PDA (P < 0.001). However, compared with standard PDA, invasive adenocarcinoma arising within an IPMN was associated with a lower incidence of (1) advanced T stage (T2-T4, 96% vs. 73%, P < 0.001); (2) regional lymph node metastasis (78% vs. 51%, P < 0.001); (3) poor tumor differentiation (44% vs. 26%, P < 0.001); (4) vascular invasion (54% vs. 33%, P < 0.001); (5) perineural invasion (92% vs. 63%, P < 0.001); and (6) microscopic margin involvement (28% vs. 14%, P < 0.001). Specifically, in the presence of any one of the aforementioned adverse pathologic characteristics, outcomes after resection for IPMN-associated and standard PDA were not significantly different., Conclusion: The favorable biologic behavior of IPMN-associated compared with standard PDA is based on its lower rate of advanced T stage, lymph node metastasis, high tumor grade, positive resection margin, perineural, and vascular invasion. In the presence of any one of the aforementioned adverse pathologic characteristics, however, survival outcomes after resection of IPMN-associated and after resection of standard pancreatic adenocarcinoma are similar.

Purpose: Surgery followed by chemotherapy and radiation (CRT) offers patients with pancreatic adenocarcinoma a chance for extended survival. In some patients, however, resection is difficult because of vascular involvement by the carcinoma, necessitating resection and grafting of the mesenterico-portal vessels. The purpose of this study was to compare outcomes between pancreaticoduodenectomy (PD) with and without mesenterico-portal vein resection (VR) in patients receiving adjuvant CRT for pancreatic adenocarcinoma., Methods and Materials: Between 1993 and 2005, 160 patients underwent PD with 5-FU-based adjuvant CRT followed by maintenance chemotherapy at the Johns Hopkins Hospital; 20 (12.5%) of the 160 underwent VR. Clinical outcomes, including median survival, overall survival, and complication rates were assessed for both groups., Results: Patients who underwent VR had significantly longer operative times (p = 0.009), greater intraoperative blood loss (p = 0.01), and longer postoperative lengths of stay (p = 0.03). However, postoperative morbidity, median survival, and overall survival rates were similar between the two groups. Most patients (70%) from both groups were able to complete CRT, and a subgroup analysis demonstrated no appreciable differences in terms of complications. None of the VR patients who received adjuvant CRT developed veno-oclusive disease or graft failure/leakage., Conclusion: In a cohort of patients treated with adjuvant 5-FU-based CRT at the Johns Hopkins Hospital, having a VR at the time of PD resulted in similar complication rates and survival. These data support the feasibility and safety of adjuvant CRT in patients undergoing VR at the time of PD.

Objective: To analyze relative perioperative and long-term outcomes of patients undergoing total pancreatectomy versus pancreaticoduodenectomy., Background: The role of total pancreatectomy has historically been limited due to concerns over increased morbidity, mortality, and perceived worse long-term outcome., Methods: Between 1970 and 2007, patients who underwent total pancreatectomy (n = 100) or pancreaticoduodenectomy (n = 1286) for adenocarcinoma were identified. Clinicopathologic, morbidity, and survival data were collected and analyzed., Results: Total pancreatectomy patients had larger median tumor size (4 cm vs. 3 cm; P < 0.001) but similar rates of vascular (50.0% vs. 54.7%) and perineural invasion (90.7% vs. 91.8%) (total pancreatectomy vs. pancreaticoduodenectomy, respectively, both P > 0.05). A similar proportion of total pancreatectomy (74.7%) and pancreaticoduodenectomy (78.3%) patients had N1 disease (P = 0.45). Total pancreatectomy patients had more lymph nodes harvested (27 vs. 16) and were less likely to have positive resection margins (22.2% vs. 43.7%) (total pancreatectomy vs. pancreaticoduodenectomy, respectively, both P < 0.0001). Total pancreatectomy was increasingly used over time (1970-1989, n = 10, 1990-1999, n = 37, 2000-2007, n = 53). Total pancreatectomy was associated with higher 30-day mortality compared with pancreaticoduodenectomy (8.0% vs. 1.5%, respectively; P = 0.0007). However, total pancreatectomy operative mortality decreased over time (1970-1989, 40%; 1990-1999, 8%; 2000-2007, 2%; P = 0.0002). While operative morbidity was higher following total pancreatectomy (69.0% vs. 38.6% for pancreaticoduodenectomy; P < 0.0001), most complications were minor (Clavien Grade 1-2) (59%). Total pancreatectomy and pancreaticoduodenectomy patients had comparable 5-year survival (18.9% vs. 18.5%, respectively, P = 0.32)., Conclusions: Total pancreatectomy perioperative mortality dramatically decreased over time. Long-term survival following total pancreatectomy versus pancreaticoduodenectomy was equivalent. Total pancreatectomy should be performed when oncologically appropriate.

Background: Solid-pseudopapillary neoplasms (SPNs) are rare pancreatic tumors with malignant potential. Clinicopathologic characteristics and outcomes of patients with SPN were reviewed., Study Design: Longterm outcomes were evaluated in patients with an SPN who were followed from 1970 to 2008., Results: Thirty-seven patients were identified with an SPN. Thirty-three (89%) were women, and median age at diagnosis was 32 years. Most patients were symptomatic; the most common symptom was abdominal pain (81%). Thirty-six patients underwent resection; one patient with distant metastases was not operated on. There were no 30-day mortalities. Median tumor size was 4.5 cm. Thirty-four patients underwent an R0 resection, 1 had an R1 resection, and 1 had an R2 resection. Two patients had lymph node metastases, and one patient had perineural invasion. After resection, 34 (94%) patients remain alive. One patient died of unknown causes 9.4 years after resection, and another died of unrelated causes 25.6 years after operation. The patient with widespread disease who didn't have resection died 11 months after diagnosis. Thirty-five of the 36 patients having resection remained disease free, including those who died of unrelated causes (median followup, 4.8 years). One patient developed a recurrence 7.7 years after complete resection. She was treated with gemcitabine and remains alive 13.6 months after recurrence., Conclusions: SPNs are rare neoplasms with malignant potential found primarily in young women. Formal surgical resection may be performed safely and is associated with longterm survival.

Metastasectomy with curative intent has become standard practice for the management of some malignancies. Resection of isolated metastatic colorectal cancer, gastrointestinal stromal tumours, neuroendocrine cancers, renal-cell cancer and sarcoma is associated with longer survival or even cure. The strongest evidence in favour of metastasectomy exists for colorectal cancer, in which resection of limited metastatic disease in some patients is associated with 5-year survival rates of more than 50%.(1-3) High incidence of the disease, predictable tumour biology, and development of successful chemotherapies have encouraged metastasectomy. Furthermore, improved safety of complex surgeries over the past several decades has lowered the threshold for more aggressive surgical intervention. Most literature on metastasectomy pertains to the resection of disease involving the liver, lung, and brain. However, metastasectomy has been described for almost every organ system, including the pancreas. In this Review, we discuss resection of isolated cancer metastases to the pancreas. Pancreatic metastasectomy is most often done through a formal pancreatic resection such as pancreaticoduodenectomy or distal pancreatectomy. Less often, pancreatic metastasectomy is done by enucleation or a pancreas sparing operation such as a central pancreatectomy.

There is emerging evidence that the oncogenic potential of hdm2 (human and/or murine double minute-2 protein) stems not only from its ability to counteract tumor suppressor p53 but also from its less understood p53-independent functions. Surprisingly, little is known about the role and regulation of hdm2 in pancreatic tumors, a large proportion (50-75%) of which contain mutant p53. In this study, we determined that hdm2 was expressed in a Ras-signaling-dependent manner in various pancreatic cancer cell lines. As p53 was mutated and inactive in these cells, the expression of hdm2 was seemingly redundant. Indeed, the proliferation and survival of cell lines such as Panc-1 and Panc-28 could be inhibited by PRIMA-1 (mutant p53 activator) but not by Nutlin-3 (inhibitor of the hdm2-p53 interaction). Unexpectedly, however, the proliferation of both cell lines was strongly inhibited by hdm2-specific RNAi. Our data also revealed cyclin D1, c-Jun and c-Myc to be novel targets of hdm2 and suggested that they might mediate hdm2's role in cellular proliferation and/or survival. We conclude from our results that hdm2 is expressed in pancreatic cancer cells as a result of activated Ras signaling, and that it regulates cellular proliferation and the expression of three novel target genes by p53-independent mechanisms.

SPN is a rare neoplasm that affects mainly young women. Despite this feature, SPN have been seen in both genders, multiple races, and at a wide range of ages. The genetic mechanism behind the development of SPN is distinct from the more lethal ductal carcinoma of the pancreas. This difference is reflected in the favorable outcome for patients with SPN. Surgery is typically curative in patents with localized disease and possibly in patients with limited metastasis or local extension. No consensus exists on an effective systemic therapy. There are no reliable predictors for disease-specific mortality or recurrence in the minority of patients who develop aggressive disease.

Background: The goal of this study is to report the safety and efficacy of pancreatic resection for isolated metastatic cancers from nonpancreatic primary disease., Methods: We retrospectively identified patients from a single institution's prospectively gathered pancreaticobiliary database from 1970 to 2007 who underwent a pancreatic resection for metastatic disease., Results: Forty-nine patients were identified with metastatic lesions to the pancreas. Pancreaticoduodenectomy, distal pancreatectomy, and total pancreatectomy were performed in 31, 14, and 4 patients, respectively. Pathology distribution was as follows: 21 renal cell carcinoma (RCC), 6 gallbladder cancer, 4 lung cancer, 4 ovarian cancer, 4 sarcoma, 3 melanoma, 2 colon cancer, 1 breast cancer, 1 hepatocellular carcinoma, 1 seminoma, 1 Langerhans cell histiocytosis, and 1 nonpancreatic endocrine cancer. Postoperative morbidity was 48%. There were no perioperative deaths. A statistically significant difference in survival was found between cancer types (P = .007) with median survivals ranging from 4.8 years for RCC to .9 years for melanoma. Univariate analysis demonstrated a survival disadvantage for patients with perineural (hazard ratio [HR] = 5.4, P = .004) and vascular invasion (HR = 4.4, P = .002). The most commonly resected metastatic lesion of the pancreas was RCC. Eighteen of the 23 patients with RCC had a metachronous lesion with a median length between initial operation and pancreatic resection of 9.3 years. Metachronous lesions had a survival similar to that of synchronous lesions (HR = 1.0, P = .98). Vascular invasion (HR = 2.4, P = .007) and lymph node metastases (HR = 24.1, P = .01) were associated with greater mortality., Conclusion: Long-term survival can be achieved in patients undergoing resection of isolated metastases to the pancreas.

The goal of this article is to describe the different types of benign pancreatic neoplasms, methods to distinguish between them, and treatment options. Pancreatic adenocarcinoma is associated with specific neoplastic lesions that are similar in radiographic appearance to some benign lesions. The correct differentiation of these malignant and premalignant lesions from their benign counterpart is paramount to their proper management.

Objective: To describe the occurrence of metastatic malignant insulinoma in a patient with preexisting type 2 diabetes mellitus., Methods: We present a detailed case report, with clinical, biochemical, and imaging findings, and summarize the data from 21 similar cases in the literature., Results: The occurrence of malignant insulinoma in a patient with preexisting diabetes is very rare and thus can be a diagnostic challenge. In our patient with type 2 diabetes, endogenous hyperinsulinism was confirmed by demonstrating elevated insulin and C-peptide levels during hypoglycemic episodes in the absence of sulfonylurea on a blood screen. Abdominal computed tomographic scan and magnetic resonance imaging revealed a pancreatic mass as well as metastatic lesions in the liver. The pancreatic mass was removed and confirmed to be a malignant insulinoma. This procedure was followed by disappearance of the hypoglycemic episodes as well as the diabetes for a few months. On follow-up, however, more metastatic lesions appeared in conjunction with a protracted course of hypoglycemia that necessitated treatment with antihypoglycemic agents and, 3 years after the initial surgical intervention, culminated in the death of the patient., Conclusion: Our patient is one of the few subjects known to have a malignant insulinoma in conjunction with preexisting diabetes. A high degree of suspicion for the presence of an insulinoma should be maintained when unexplained hypoglycemic episodes occur in a patient with previously stable diabetes.

Pancreatic cancer is, indisputably, one of the most malignant gastrointestinal tumors. Although the etiology of this disease is unknown, it is clearly linked to alterations in the biologic activities of various signaling molecules. Aberrant signaling activities of growth factors and their receptors, transcription factors, and proteins that control the cell cycle have been increasingly implicated in the pathogenesis and dissemination of pancreatic tumors. It is indeed possible that several of these molecules are, in fact, part of a signaling network that has gone awry. This review summarizes some recent advances in an attempt to generate a working model for future investigations.

We report herein a case of histologically identified peliosis of pancreatic islets in the surgically removed portion of the pancreas of a 30-year-old woman with multiple endocrine neoplasm, type 1 (MEN-1) syndrome. In addition to microscopic peliosis, the pancreas contained multiple endocrine tumors producing insulin, glucagon, somatostatin, and growth hormone-releasing factor and showed evidence of widespread nesidioblastosis. It is uncertain whether peliosis of pancreatic islets and MEN-1 syndrome were coincidental or whether the two diseases were causally related. Since hormonal factors can result in hepatic peliosis, it is tempting to speculate that the endocrine imbalance secondary to MEN-1 syndrome might have played a role in the genesis of peliosis in this case. Although no direct proof of vascular damage was encountered, it is conceivable that escape of red blood cells from the circulation and their accumulation in tissue spaces was due to abnormal islet blood flow and increased capillary permeability.