Search

Background: Pancreatic surgery is associated with considerable morbidity and, consequently, offers a large and complex field for research. To prioritize relevant future scientific projects, it is of utmost importance to identify existing evidence and uncover research gaps. Thus, the aim of this project was to create a systematic and living Evidence Map of Pancreatic Surgery., Methods: PubMed, the Cochrane Central Register of Controlled Trials, and Web of Science were systematically searched for all randomized controlled trials and systematic reviews on pancreatic surgery. Outcomes from every existing randomized controlled trial were extracted, and trial quality was assessed. Systematic reviews were used to identify an absence of randomized controlled trials. Randomized controlled trials and systematic reviews on identical subjects were grouped according to research topics. A web-based evidence map modeled after a mind map was created to visualize existing evidence. Meta-analyses of specific outcomes of pancreatic surgery were performed for all research topics with more than 3 randomized controlled trials. For partial pancreatoduodenectomy and distal pancreatectomy, pooled benchmarks for outcomes were calculated with a 99% confidence interval. The evidence map undergoes regular updates., Results: Out of 30,860 articles reviewed, 328 randomized controlled trials on 35,600 patients and 332 systematic reviews were included and grouped into 76 research topics. Most randomized controlled trials were from Europe (46%) and most systematic reviews were from Asia (51%). A living meta-analysis of 21 out of 76 research topics (28%) was performed and included in the web-based evidence map. Evidence gaps were identified in 11 out of 76 research topics (14%). The benchmark for mortality was 2% (99% confidence interval: 1%-2%) for partial pancreatoduodenectomy and <1% (99% confidence interval: 0%-1%) for distal pancreatectomy. The benchmark for overall complications was 53% (99%confidence interval: 46%-61%) for partial pancreatoduodenectomy and 59% (99% confidence interval: 44%-80%) for distal pancreatectomy., Conclusion: The International Study Group of Pancreatic Surgery Evidence Map of Pancreatic Surgery, which is freely accessible via www.evidencemap.surgery and as a mobile phone app, provides a regularly updated overview of the available literature displayed in an intuitive fashion. Clinical decision making and evidence-based patient information are supported by the primary data provided, as well as by living meta-analyses. Researchers can use the systematic literature search and processed data for their own projects, and funding bodies can base their research priorities on evidence gaps that the map uncovers., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to critically analyze the surgical experience of managing autoimmune pancreatitis (AIP) in an era of modern diagnostics and compare these patients with those who were managed conservatively., Methods: Two prospectively maintained databases were used to retrospectively identify patients with AIP who were either managed conservatively or underwent pancreatectomy., Results: Eighty-eight patients were included in the study, of which 56 (63.6%) underwent resection and 32 (36.4%) were managed conservatively. Patients who underwent resection were more likely to present with jaundice (64.3% vs 18.1%, P < 0.001) and weight loss (53.6% vs 15.6%, P = 0.005). The cohort who underwent resection had a significantly higher median carbohydrate antigen 19-9 (40.0 vs 18.6 U/mL, P = 0.034) and was less likely to have elevated immunoglobulin G4 (26.1% vs 50.0%, P < 0.001). The most frequent initial diagnosis in the cohort who underwent resection was ductal adenocarcinoma (82.1%). Nine patients (28.1%) in the conservatively managed cohort experienced AIP relapse compared with 6 patients (10.7%) in the cohort who underwent resection., Conclusions: The most frequent reason for surgical resection of AIP is concern for malignancy. Carbohydrate antigen 19-9 elevations were more common than immunoglobulin G4 in our cohort, suggesting that this laboratory profile is suboptimal for this population., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Pancreatic cystic neoplasms (PCN) are a heterogeneous group of pancreatic cysts that include intraductal papillary mucinous neoplasms, mucinous cystic neoplasms, serous cystic neoplasms and other rare cystic lesions, all with different biological behaviours and variable risk of progression to malignancy. As more pancreatic cysts are incidentally discovered on routine cross-sectional imaging, optimal surveillance for patients with PCN is becoming an increasingly common clinical problem, highlighting the need to balance cancer prevention with the risk of (surgical) overtreatment. This Review summarizes the latest developments in the diagnosis and management of PCN, including the quality of available evidence. Also discussed are the most important differences between the PCN guidelines from the American Gastroenterological Association, the International Association of Pancreatology and the European Study Group on Cystic Tumours of the Pancreas, including diagnostic and follow-up strategies and indications for surgery. Finally, new developments in the management of patients with PCN are addressed.

Visualizing pathologies in three dimensions can provide unique insights into the biology of human diseases. A rapid and easy-to-implement dibenzyl ether-based technique was used to clear thick sections of surgically resected human pancreatic parenchyma. Protocols were applicable to both fresh and formalin-fixed, paraffin-embedded tissue. The penetration of antibodies into dense pancreatic parenchyma was optimized using both gradually increasing antibody concentrations and centrifugal flow. Immunolabeling with antibodies against cytokeratin 19 was visualized using both light sheet and confocal laser scanning microscopy. The technique was applied successfully to 26 sections of pancreas, providing three-dimensional (3D) images of normal pancreatic tissue, pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasms, and infiltrating pancreatic ductal adenocarcinomas. 3D visualization highlighted processes that are hard to conceptualize in two dimensions, such as invasive carcinoma growing into what appeared to be pre-existing pancreatic ducts and within venules, and the tracking of long cords of neoplastic cells parallel to blood vessels. Expanding this technique to formalin-fixed, paraffin-embedded tissue opens pathology archives to 3D visualization of unique biosamples and rare diseases. The application of immunolabeling and clearing to human pancreatic parenchyma provides detailed visualization of normal pancreatic anatomy, and can be used to characterize the 3D architecture of diseases including pancreatic intraepithelial neoplasia, intraductal papillary mucinous neoplasm, and pancreatic ductal adenocarcinomas., (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

Background & Aims: The management of pancreatic cysts poses challenges to both patients and their physicians. We investigated whether a combination of molecular markers and clinical information could improve the classification of pancreatic cysts and management of patients., Methods: We performed a multi-center, retrospective study of 130 patients with resected pancreatic cystic neoplasms (12 serous cystadenomas, 10 solid pseudopapillary neoplasms, 12 mucinous cystic neoplasms, and 96 intraductal papillary mucinous neoplasms). Cyst fluid was analyzed to identify subtle mutations in genes known to be mutated in pancreatic cysts (BRAF, CDKN2A, CTNNB1, GNAS, KRAS, NRAS, PIK3CA, RNF43, SMAD4, TP53, and VHL); to identify loss of heterozygozity at CDKN2A, RNF43, SMAD4, TP53, and VHL tumor suppressor loci; and to identify aneuploidy. The analyses were performed using specialized technologies for implementing and interpreting massively parallel sequencing data acquisition. An algorithm was used to select markers that could classify cyst type and grade. The accuracy of the molecular markers was compared with that of clinical markers and a combination of molecular and clinical markers., Results: We identified molecular markers and clinical features that classified cyst type with 90%-100% sensitivity and 92%-98% specificity. The molecular marker panel correctly identified 67 of the 74 patients who did not require surgery and could, therefore, reduce the number of unnecessary operations by 91%., Conclusions: We identified a panel of molecular markers and clinical features that show promise for the accurate classification of cystic neoplasms of the pancreas and identification of cysts that require surgery., (Copyright © 2015 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Purpose: We investigated the incremental diagnostic yield of S-MRCP in a population with high prevalence of small pancreatic cysts., Methods: Standard MRCP protocol was performed with and without secretin using 1.5 T units in subjects undergoing pancreatic screening because of a strong family history of pancreatic cancer as part of the multicenter Cancer of the Pancreas Screening-3 trial (CAPS 3). All studies were reviewed prospectively by two independent readers who recorded the presence and number of pancreatic cysts, the presence of visualized ductal communication before and after secretin, and the degree of confidence in the diagnoses., Result: Of 202 individuals enrolled (mean age 56 years, 46% males), 93 (46%) had pancreatic cysts detected by MRCP, and 64 of the 93 had pre-and post-secretin MRCP images available for comparison. Data from the 128 readings show that 6 (6/128=4.7%) had ductal communication visualized only on the secretin studies compared to pre-secretin studies (odds ratio 1.28, p=0.04). In addition, there was a statistically significant increase in confidence in reporting ductal communication after secretin compared to before secretin (p<0.0005)., Conclusion: At 1.5 T MRI, the use of secretin can improve the visualization of ductal communication of cystic pancreatic lesions., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: The use of minimally invasive surgery (MIS) techniques for pancreatic and liver operations remains ill defined. We sought to compare inpatient outcomes among patients undergoing open versus MIS pancreas and liver operations using a nationally representative cohort., Methods: We queried the Nationwide Inpatient Sample database for all major pancreatic and hepatic resections performed between 2000 and 2011. Appropriate International Classification of Diseases, 9th Revision (ICD-9) coding modifiers for laparoscopy and robotic assist were used to categorize procedures as MIS. Demographics, comorbidities, and inpatient outcomes were compared between the open and MIS groups., Results: A total of 65,033 resections were identified (pancreas, n = 36,195 [55.7%]; liver, n = 28,035 [43.1%]; combined pancreas and liver, n = 803 [1.2%]). The overwhelming majority of operations were performed open (n = 62,192, 95.6%), whereas 4.4% (n = 2,841) were MIS. The overall use of MIS increased from 2.3% in 2000 to 7.5% in 2011. Compared with patients undergoing an open operation, MIS patients were older and had a greater incidence of multiple comorbid conditions. After operation, the incidence of complications for MIS (pancreas, 35.4%; liver, 29.5%) was lower than for open (pancreas, 41.6%; liver, 33%) procedures (all P < .05) resulting in a shorter median length of stay (8 vs 7 days; P = .001) as well as a lower in-hospital mortality (5.1% vs 2.8%; P = .001)., Conclusion: During the last decade, the number of MIS pancreatic and hepatic operations has increased, with nearly 1 in 13 HPB cases now being performed via an MIS approach. Despite MIS patients tending to have more preoperative medical comorbidities, postoperative morbidity, mortality, and duration of stay compared favorably with open surgery., (Copyright © 2014 Mosby, Inc. All rights reserved.)

Pancreatic cancer is the deadliest of all solid malignancies. Early detection offers the best hope for a cure, but characteristics of this disease, such as the lack of early clinical symptoms, make the early detection difficult. Recent genetic mapping of the molecular evolution of pancreatic cancer suggests that a large window of opportunity exists for the early detection of pancreatic neoplasia, and developments in cancer genetics offer new, potentially highly specific approaches for screening of curable pancreatic neoplasia. We review the challenges of screening for early pancreatic neoplasia, as well as opportunities presented by incorporating molecular genetics into these efforts., (©2014 American Association for Cancer Research.)

Although patients with surgically resected noninvasive mucinous cystic neoplasms (MCNs) of the pancreas are cured, the behavior of surgically resected minimally invasive adenocarcinomas arising in MCN has not been well established. We report 16 surgically resected MCNs with minimal invasion defined as unifocal or multifocal microscopic invasive adenocarcinoma confined to the ovarian stroma of the MCN without capsular or pancreatic parenchymal invasion. Pathologic findings were correlated with patient demographics, type of surgery, and long-term follow-up. Our study included 15 women and 1 man ranging in age from 25 to 66 years. The patients were followed up for a mean of 48.6 months (range, 12 to 148 mo). The MCNs ranged in size from 3.5 to 25 cm and were all located in the body/tail of the gland. Lymphovascular invasion was not identified in any of the cases, and all lymph nodes were negative for tumor. Ten neoplasms had unifocal invasion, whereas 6 had multifocal invasion. Twelve of the neoplasms were partially submitted for microscopic examination, whereas 4 were submitted entirely. Only 1 of the 16 minimally invasive MCNs recurred, and that tumor had been lighlty sampled pathologically. Our study demonstrates that the majority of patients with minimally invasive adenocarcinoma arising in MCNs are cured by surgery, particularly if the neoplasms are completely examined histologically.

Objective: Autoimmune pancreatitis (AIP) is an inflammatory, IgG4-associated condition that often overlaps clinically and radiographically with pancreatic ductal adenocarcinoma. We reviewed our institutional experience with fine needle aspiration (FNA) cytology in patients subsequently diagnosed with AIP., Study Design: A retrospective review was conducted of FNA results correlating to all surgical pancreatic specimens diagnosed as AIP or lymphoplasmacytic sclerosing pancreatitis from 1984 to 2011., Results: AIP was diagnosed in 15 cases by surgical resection and in 2 by combined clinical findings and nondiagnostic biopsies. Of 20 aspirates from 17 patients, 1 was diagnosed as malignant, 1 as neoplasm (mucinous), 10 as atypical, 5 as benign, and 3 as scant or nondiagnostic. Of the 10 aspirates diagnosed as atypical, 1 was suspicious for malignancy, 1 could not exclude neuroendocrine neoplasm, 1 was markedly atypical, and 7 demonstrated scattered ductal atypia. Common morphologic features included hypocellularity, focal-to-marked ductal epithelial atypia, fibrous tissue fragments, and a smear background lacking red blood cells., Conclusion: On FNA, AIP most often leads to an 'atypical' cytopathologic interpretation and rarely may be diagnosed as adenocarcinoma. Thus, caution is warranted to avoid overdiagnosis on FNA when a mass lesion is reported in a patient with clinical or radiographic suspicion of AIP., (Copyright © 2012 S. Karger AG, Basel.)

Background and Aims: Early diagnosis of cancer in pancreatic cysts is important for timely referral to surgery. The aim of this study was to develop a predictive model for pancreatic cyst malignancy to improve patient selection for surgical resection., Methods: We performed retrospective analyses of endoscopic ultrasound (EUS) and pathology databases identifying pancreatic cysts with available final pathological diagnoses. Main-duct intraductal papillary mucinous neoplasms (IPMNs) were excluded due to the clear indication for surgery. Patient demographics and symptoms, cyst morphology, and cyst fluid characteristics were studied as candidate risk factors for malignancy., Results: 270 patients with pancreatic cysts were identified and analyzed (41% men, mean age 61.8 years). Final pathological diagnoses were branch-duct IPMN (n = 118, 50% malignant), serous cystadenoma (n = 71), pseudocyst (n = 37), mucinous cyst adenoma/adenocarcinoma (n = 36), islet cell tumor (n = 4), simple cyst (n = 3), and ductal adenocarcinoma with cystic degeneration (n = 1). Optimal cut-off points for surgical resection were cyst fluid carcinoembryonic antigen (CEA) > or =3,594 ng/ml, age >50, and cyst size >1.5 cm. Cyst malignancy was independently associated with white race (OR = 4.1, p = 0.002), weight loss (OR = 3.9, p = 0.001), cyst size >1.5 cm (OR = 2.4, p = 0.012), and high CEA > or =3,594 (OR = 5.3, p = 0.04). In white patients >50 years old presenting with weight loss and cyst size >1.5 cm, the likelihood of malignancy was nearly sixfold greater than in those patients who had none of these factors (OR = 5.8, 95% CI = 2.1-16.1, p = 0.004)., Conclusions: Risk factors other than cyst size are important for determination of malignancy in pancreatic cysts. Exceptionally high cyst fluid CEA levels and certain patient-related factors may help to better predict cyst malignancy and the need for surgical treatment., (Copyright 2009 S. Karger AG, Basel.)

The aim of this study was to determine the role of site-specific metastatic patterns over time and assess factors associated with extended survival in metastatic PDAC. Half of all patients with pancreatic ductal adenocarcinoma (PDAC) present with metastatic disease. The site of metastasis plays a crucial role in clinical decision making due to its prognostic value. We examined 56,757 stage-IV PDAC patients from the National Cancer Database (2016–2019), categorizing them by metastatic site: multiple, liver, lung, brain, bone, carcinomatosis, or other. The site-specific prognostic value was assessed using log-rank tests while time-varying effects were assessed by Aalen's linear hazards model. Factors associated with extended survival (>3years) were assessed with logistic regression. Median overall survival (mOS) in patients with distant lymph node-only metastases (9.0 months) and lung-only metastases (8.1 months) was significantly longer than in patients with liver-only metastases (4.6 months, p < 0.001). However, after six months, the metastatic site lost prognostic value. Logistic regression identified extended survivors (3.6 %) as more likely to be younger, Hispanic, privately insured, Charlson-index <2, having received chemotherapy, or having undergone primary or distant site surgery (all p < 0.001). While synchronous liver metastases are associated with worse outcomes than lung-only and lymph node-only metastases, this predictive value is diminished after six months. Therefore, treatment decisions beyond this time should not primarily depend on the metastatic site. Extended survival is possible in a small subset of patients with favorable tumor biology and good conditional status, who are more likely to undergo aggressive therapies. [ABSTRACT FROM AUTHOR]

Simple Summary: Surgical candidacy in the treatment of pancreatic cancer is complex. There are multiple factors influencing if a patient is a good candidate for surgery with or without preceding treatment with chemotherapy. This review summarizes the importance of both anatomical (tumor size and its relation to important blood vessels to the liver and bowel) and biological (aggressiveness of the tumor) considerations. Pancreatic ductal adenocarcinoma (PDAC) remains associated with poor outcomes with a 5-year survival of 12% across all stages of the disease. These poor outcomes are driven by a delay in diagnosis and an early propensity for systemic dissemination of the disease. Recently, aggressive surgical approaches involving complex vascular resections and reconstructions have become more common, thus allowing more locally advanced tumors to be resected. Unfortunately, however, even after the completion of surgery and systemic therapy, approximately 40% of patients experience early recurrence of disease. To determine resectability, many institutions utilize anatomical staging systems based on the presence and extent of vascular involvement of major abdominal vessels around the pancreas. However, these classification systems are based on anatomical considerations only and do not factor in the burden of systemic disease. By integrating the biological criteria, we possibly could avoid futile resections often associated with significant morbidity. Especially patients with anatomically resectable disease who have a heavy burden of radiologically undetected systemic disease most likely do not derive a survival benefit from resection. On the contrary, we could offer complex resections to those who have locally advanced or oligometastatic disease but have favorable systemic biology and are most likely to benefit from resection. This review summarizes the current literature on defining anatomical and biological resectability in patients with pancreatic cancer. [ABSTRACT FROM AUTHOR]

Supplemental Digital Content is available in the text Objective: To evaluate the influence of consensus guidelines on the management of intraductal papillary mucinous neoplasms (IPMN) and the subsequent changes in pathologic outcomes. Background: Over time, multiple guidelines have been developed to identify high-risk IPMN. We hypothesized that the development and implementation of guidelines should have increased the percentage of resected IPMN with high-risk disease. Methods: Memorial Sloan-Kettering (MSK), Johns Hopkins (JH), and Massachusetts General Hospital (MGH) databases were queried for resected IPMN (2000–2015). Patients were categorized into main-duct (MD-IPMN) versus branch-duct (BD-IPMN). Guideline-specific radiographic/endoscopic features were recorded. High-risk disease was defined as high-grade dysplasia/carcinoma. Fisher's exact test was used to detect differences between institutions. Logistic regression evaluated differences between time-points [preguidelines (pre-GL, before 2006), Sendai (SCG, 2006–2012), Fukuoka (FCG, after 2012)]. Results: The study included 1210 patients. The percentage of BD-IPMN with ≥1 high-risk radiographic feature differed between centers (MSK 69%, JH 60%, MGH 45%; P < 0.001). In MD-IPMN cohort, the presence of radiographic features such as solid component and main pancreatic duct diameter ≥10 mm also differed (solid component: MSK 38%, JH 30%, MGH 18%; P < 0.001; duct ≥10 mm: MSK 49%, JH 32%, MGH 44%; P < 0.001). The percentage of high-risk disease on pathology, however, was similar between institutions (BD-IPMN: P = 0.36, MD-IPMN: P = 0.48). During the study period, the percentage of BD-IPMN resected with ≥1 high-risk feature increased (52% pre-GL vs 67% FCG; P = 0.005), whereas the percentage of high-risk disease decreased (pre-GL vs FCG: 30% vs 20%). For MD-IPMN, there was not a clear trend towards guideline adherence, and the rate of high-risk disease was similar over the time (pre-GL vs FCG: 69% vs 67%; P = 0.63). Conclusion: Surgical management of IPMN based on radiographic criteria is variable between institutions, with similar percentages of high-risk disease. Over the 15-year study period, the rate of BD-IPMN resected with high-risk radiographic features increased; however, the rate of high-risk disease decreased. Better predictors are needed. [ABSTRACT FROM AUTHOR]

Introduction: Improvement in imaging has resulted in frequent diagnosis of benign and premalignant pancreatic tumors. Pancreatic nerve sheath (PNS) tumors are one of the rarest pancreatic tumors. Literature on PNS is limited and their biology is poorly understood. Here, we report the largest series of PNS tumors to date and review the literature to evaluate the current data available on PNS tumors.Methods: An institutional database was used to identify patients who underwent resection for PNS tumors. Clinicopathological characteristics and outcomes of these patients were reported. Furthermore, a review of literature was performed.Results: From January 1994 through December 2016, seven patients underwent resection for PNS tumors. The median age was 57.7 years (IQR, 44.9-61.9) and the sex was approximately equally distributed (male = 4; 57.1%). Three (42.9%) patients were diagnosed incidentally and six (85.7%) were misdiagnosed as having other pancreatic tumors. The median tumor size was 2.1 (IQR 1.8-3.0) cm and six (85.7%) had no nodal disease. At a median follow-up of 15.5 (IQR 13.7-49.3) months, six patients were alive without evidence of disease and one patient was lost to follow-up. The literature review identified 49 studies reporting 54 patients with PNS tumors. Forty-six were misdiagnosed as having other pancreatic tumors. The median tumor size was 3.6 (range 1-20) cm, nodal disease was present in six patients (22.2%), and no patient had distant metastatic disease. At the time of last follow-up, all patients were free of disease.Conclusion: This is the largest single institution series on PNS tumors reported to date. These tumors are rare and are often misdiagnosed, given their radiological characteristics. PNS tumors have a benign course of disease and surgical resection results in favorable long-term outcomes. [ABSTRACT FROM AUTHOR]

Background: The new T1 pancreatic cancer by the eighth edition of the AJCC staging system discards the concept of "extension beyond the pancreas" and focuses on size only. Furthermore, the new T1 is divided into T1a, T1b, and T1c based on size. The evidence pertaining to these changes has not been evaluated. This is to evaluate the feasibility of the new T1 definition in the pancreas head cancer cohort.Methods: Data from 540 patients with T1 pancreatic ductal adenocarcinoma as defined by the eighth edition were collected from Korea, Japan, and the USA. Invasive IPMNs were excluded. Survival analyses were performed.Results: Of the 540 patients, 181 patients were T1 according to the seventh edition and 359 were down-staged to T1 from the former T3 because the concept of "extension beyond the pancreas" was discarded. The 5-year survival rate and the median survival of T1 patients were 30.6% and 27 months, respectively. Comparing tumors that extend beyond the pancreas (new T1) and those confined within the pancreas (original T1), the latter showed significantly longer median survival (43 vs. 24 months, p < 0.001). In terms of T1a/b/c, there were no significant differences in survival. Using MaxStat, subdividing into two groups using 1.1 cm as the cut-off value, yielded significantly discrete prognostic groups (p < 0.001).Conclusion: The new T1 definition may be more practical, but the implications of the concept of "extension beyond the pancreas" should be re-investigated. Further, the subcategorization of T1a/b/c may not be adequate and may require revision or deletion. [ABSTRACT FROM AUTHOR]

Background & Aims Many patients with pancreatic adenocarcinoma carry germline mutations associated with increased risk of cancer. It is not clear whether patients with intraductal papillary mucinous neoplasms (IPMNs), which are precursors to some pancreatic cancers, also carry these mutations. We assessed the prevalence of germline mutations associated with cancer risk in patients with histologically confirmed IPMN. Methods We obtained nontumor tissue samples from 315 patients with surgically resected IPMNs from 1997 through 2017, and we sequenced 94 genes with variants associated with cancer risk. Mutations associated with increased risk of cancer were identified and compared with individuals from the Exome Aggregation Consortium. Results We identified 23 patients with a germline mutation associated with cancer risk (7.3%; 95% confidence interval, 4.9–10.8). Nine patients had a germline mutation associated with pancreatic cancer susceptibility (2.9%; 95% confidence interval, 1.4–5.4). More patients with IPMNs carried germline mutations in ATM (P <.0001), PTCH1 (P <.0001), and SUFU (P <.0001) compared with controls. Patients with IPMNs and germline mutations associated with pancreatic cancer were more like to have concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations (P <.0320). Conclusions In sequence analyses of 315 patients with surgically resected IPMNs, we found that almost 3% to carry mutations associated with pancreatic cancer risk. More patients with IPMNs and germline mutations associated with pancreatic cancer had concurrent invasive pancreatic carcinoma compared with patients with IPMNs without these mutations. Genetic analysis of patients with IPMNs might identify those at greatest risk for cancer. [ABSTRACT FROM AUTHOR]

Objective: Previous nomogram models for patients undergoing resection of intraductal papillary mucinous neoplasms (IPMNs) have been relatively small single-institutional series. Our objective was to improve upon these studies by developing and independently validating a new model using a large multiinstitutional dataset. Summary Background Data: IPMNs represent the most common radiographically identifiable precursor lesions of pancreatic cancer. They are a heterogenous group of neoplasms in which more accurate markers of highgrade dysplasia or early invasive carcinoma could help avoid unnecessary surgery in 1 case and support potentially curative intervention (resection) in another. Methods: Prospectively maintained databases from 3 institutions were queried for patients who had undergone resection of IPMNs between 2005 and 2015. Patients were separated into main duct [main and mixed-type (MD)] and branch duct (BD) types based on preoperative imaging. Logistic regression modeling was used on a training subset to develop 2 independent nomograms (MD and BD) to predict low-risk (low- or intermediate-grade dysplasia) or high-risk (high-grade dysplasia or invasive carcinoma) disease. Model performance was then evaluated using an independent validation set. Results: We identified 1028 patients who underwent resection for IPMNs [MD: n = 454 (44%), BD: n = 574 (56%)] during the 10-year study period. High-risk disease was present in 487 patients (47%). Patients with high-risk disease comprised 71% and 29% of MD and BD groups, respectively (P <0.0001). MD and BD nomograms were developed on the training set [70% of total (n = 720); MD: n = 318, BD: n = 402] and validated on the test set [30% (n = 308); MD: n = 136, BD: n = 172]. The presence of jaundice was almost exclusively associated with high-risk disease (57 of 58 patients, 98%). Cyst size >3.0 cm, solid component/mural nodule, pain symptoms, and weight loss were significantly associated with high-risk disease. C-indices were 0.82 and 0.81 on training and independent validation sets, respectively; Brier scores were 0.173 and 0.175, respectively. Conclusions: For patients with suspected IPMNs, we present an independently validated model for the prediction of high-risk disease. [ABSTRACT FROM AUTHOR]

Background: There are no established guidelines for pathologic diagnosis/ reporting of intraductal papillary mucinous neoplasms (IPMNs). Design: An international multidisciplinary group, brought together by the Verona Pancreas Group in Italy-2013, was tasked to devise recommendations. Results: (1) Crucial to rule out invasive carcinoma with extensive (if not complete) sampling. (2) Invasive component is to be documented in a full synoptic report including its size, type, grade, and stage. (3) The term "minimally invasive" should be avoided; instead, invasion size with stage and substaging of T1 (1a, b, c;⩽0.5, >0.5-⩽1, >1 cm) is to be documented. (4) Largest diameter of the invasion, not the distance from the nearest duct, is to be used. (5) A category of "indeterminate/(suspicious) for invasion" is acceptable for rare cases. (6) The term "malignant" IPMN should be avoided. (7) The highest grade of dysplasia in the non-invasive component is to be documented separately. (8) Lesion size is to be correlated with imaging findings in cysts with rupture. (9) The main duct diameter and, if possible, its involvement are to be documented; however, it is not required to provide main versus branch duct classification in the resected tumor. (10) Subtyping as gastric/intestinal/pancreatobiliary/oncocytic/mixed is of value. (11) Frozen section is to be performed highly selectively, with appreciation of its shortcomings. (12) These principles also apply to other similar tumoral intraepithelial neoplasms (mucinous cystic neoplasms, intra-ampullary, and intrabiliary/ cholecystic). Conclusions: These recommendations will ensure proper communication of salient tumor characteristics to the management teams, accurate comparison of data between analyses, and development of more effective management algorithms. [ABSTRACT FROM AUTHOR]

Pancreatic carcinomas with acinar differentiation, including acinar cell carcinoma, pancreatoblastoma and carcinomas with mixed differentiation, are distinct pancreatic neoplasms with poor prognosis. Although recent whole-exome sequencing analyses have defined the somatic mutations that characterize the other major neoplasms of the pancreas, the molecular alterations underlying pancreatic carcinomas with acinar differentiation remain largely unknown. In the current study, we sequenced the exomes of 23 surgically resected pancreatic carcinomas with acinar differentiation. These analyses revealed a relatively large number of genetic alterations at both the individual base pair and chromosomal levels. There was an average of 119 somatic mutations/carcinoma. When three outliers were excluded, there was an average of 64 somatic mutations/tumour (range 12-189). The mean fractional allelic loss ( FAL) was 0.27 (range 0-0.89) and heterogeneity at the chromosome level was confirmed in selected cases using fluorescence in situ hybridization ( FISH). No gene was mutated in >30% of the cancers. Genes altered in other neoplasms of the pancreas were occasionally targeted in carcinomas with acinar differentiation; SMAD4 was mutated in six tumours (26%), TP53 in three (13%), GNAS in two (9%), RNF43 in one (4%) and MEN1 in one (4%). Somatic mutations were identified in genes in which constitutional alterations are associated with familial pancreatic ductal adenocarcinoma, such as ATM, BRCA2 and PALB2 (one tumour each), as well as in genes altered in extra-pancreatic neoplasms, such as JAK1 in four tumours (17%), BRAF in three (13%), RB1 in three (13%), APC in two (9%), PTEN in two (9%), ARID1A in two (9%), MLL3 in two (9%) and BAP1 in one (4%). Perhaps most importantly, we found that more than one-third of these carcinomas have potentially targetable genetic alterations, including mutations in BRCA2, PALB2, ATM, BAP1, BRAF and JAK1. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Summary: Pancreatic neuroendocrine tumors with prominent stromal fibrosis are often clinically, radiographically, and grossly indistinguishable from ductal adenocarcinoma. We recently described a small series of fibrotic pancreatic neuroendocrine tumors that express serotonin. To understand better the relationship between histopathologic patterns and serotonin expression, we reviewed 361 pancreatic neuroendocrine tumors to identify those with prominent stromal fibrosis exceeding 30% of total tumor area. We identified 52 cases and immunolabeled these neoplasms with antibodies to serotonin and Ki-67. Two predominant histologic subtypes were identified: 14 (26.9%) of 52 had a trabecular or trabecular-glandular cellular pattern with interspersed fibrosis, whereas 38 (73.1%) of 52 had solid architecture. Of the 52, 14 (26.9%) pancreatic neuroendocrine tumors showed at least focal serotonin immunoreactivity. Tumors with predominantly trabecular architecture were significantly more likely to express serotonin than those with solid architecture (P < .01). Only 2 of 34 pancreatic neuroendocrine tumors with fibrosis less than 30% of total tumor area expressed serotonin. The 14 serotonin-expressing tumors were less likely to have lymph node metastases (P = .016) and more likely to involve large pancreatic ducts (P < .01) than were the 38 serotonin-negative tumors. The serotonin-expressing tumors were also found in a younger patient population (P < .01). There was no significant association of serotonin immunoreactivity with Ki-67 proliferation index, tumor size, or distant metastases. Our data demonstrate a strong correlation between trabecular architecture and serotonin immunoreactivity in pancreatic neuroendocrine tumors with stromal fibrosis. Serotonin-expressing tumors are also less likely to have lymph node metastases and more likely to involve large pancreatic ducts. [ABSTRACT FROM AUTHOR]

IPMN consensus guidelines make implicit judgments on what cancer risk level should prompt surgery. We used decision modeling to estimate this cancer risk threshold (CRT) for BD-IPMN patients. We created a decision model to compare quality-adjusted life years (QALYs) following surgery or surveillance for BD-IPMNs. We simulated treatment decisions for hypothetical patients, varying age, comorbidities and lesion location (pancreatic head/tail). The base case was a 60-year-old patient with mild comorbidities and pancreatic head IPMN. Probabilities, life expectancies, and utilities were incorporated from literature/public datasets. CRT was defined as the level of cancer risk at which the expected value of QALYs for surgery first exceeded that of surveillance. In the base case, surgery was preferred over surveillance, yielding 21.90 vs. 21.88 QALYs. The optimal CRT for a BD-IPMN patient depended on age, comorbidities, and location. CRT in the base case was 20 % and 3 % for an IPMN in the head and tail of the pancreas, respectively. Other drivers of preferred treatment were age and likelihood of postoperative mortality. For BD-IPMNs, the optimal CRT varies depending on patient age and risk of surgical complications. Personalized risk threshold values could guide treatment decisions and inform future treatment consensus guidelines. [ABSTRACT FROM AUTHOR]

Lymph node (LN) metastasis is associated with decreased survival following resection for pancreatic ductal adenocarcinoma (PDAC). In N0 disease, increasing total evaluated LN (ELN) correlates with improved outcomes suggesting patients may be understaged when LNs are undersampled. We aim to assess the optimal number of examined lymph nodes (ELN) following pancreatectomy. Data from 1837 patients undergoing surgery were prospectively collected. The binomial probability law was utilized to analyze the minimum number of examined LNs (minELN) and accurately characterize each histopathologic stage. LN ratio (LNR) was compared to American Joint Committee on Cancer (AJCC) guidelines. As ELN total increased, the likelihood of finding node positive disease increased. An evaluation based upon the binomial probability law suggested an optimal minELN of 12 for accurate AJCC N staging. As the number of ELNs increased, the discriminatory capacity of alternative strategies to characterize LN disease exceeded that offered by AJCC N stage. This is the first study dedicated to optimizing histopathologic staging in PDAC using models of minELN informed by the binomial probability law. This study highlights two separate cutoffs for ELNs depending upon prognostic goal and validates that 12 LNs are adequate to determine AJCC N stage for the majority of patients. [ABSTRACT FROM AUTHOR]

Abstract: Solid-pseudopapillary neoplasms of the pancreas are uncommon and usually occur in young women. They are generally large, encapsulated masses with mixture of solid, cystic, and hemorrhagic components. Some cases have atypical features; for example, they can form a small predominantly solid mass and produce dilatation of the main pancreatic duct. In this article we discuss and illustrate the spectrum of the appearances of this distinctive neoplasm on multidetector CT. [ABSTRACT FROM AUTHOR]