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Introduction: Pancreatic intraductal papillary mucinous neoplasms (IPMN) are now identified with increasing frequency. The detection of carcinoma in IPMN is difficult and suffers from high false-positive and false-negative rates, often resulting in inappropriate treatment decisions. Improved detection of malignancy using novel biomarkers may therefore improve diagnostic accuracy. One such promising novel biomarker is Plectin-1 (Plec-1).Methods: Using immunohistochemistry, Plec-1 expression was assayed in benign (low and moderate dysplasia, n = 6) as well as malignant IPMN (high-grade dysplasia and invasive carcinoma, n = 31) and lymph node metastases from carcinoma arising in IPMN (n = 12). Furthermore, cyst fluids from benign (n = 3) and malignant IPMN (n = 4) were evaluated for Plec-1 expression.Results and Discussion: Twenty-six of 31 malignant IPMN and all 12 lymph node metastases were Plec-1 positive. In contrast, only one of six benign IPMN expressed Plec-1. The specificity of Plec-1 in distinguishing malignant IPMN from benign IPMN was 83% and its sensitivity 84%. Furthermore, all (four out of four) cyst fluids from malignant IPMN, but none of the three benign IPMN, were Plec-1 positive. These data support Plec-1 as an excellent biomarker for the early detection of carcinoma arising in IPMN. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether pathological staging is significant prognostically and can inform the delivery of adjuvant therapy after pancreatectomy preceded by neoadjuvant therapy. Methods: This multicentre retrospective study included patients who underwent pancreatectomy for pancreatic ductal adenocarcinoma after neoadjuvant treatment at two Italian centres between 2013 and 2017. T and N status were assigned in accordance with the seventh and eighth editions of the AJCC staging system, as well as according to a modified system with T status definition combining extrapancreatic invasion and tumour size. Patients were then stratified by receipt of adjuvant therapy. Survival analysis and multivariable interaction analysis of adjuvant therapy with pathological parameters were performed. The results were validated in an external cohort from the USA. Results: The developmental set consisted of 389 patients, with a median survival of 34.6 months. The modified staging system displayed the best prognostic stratification and the highest discrimination (C-index 0.763; 1-, 2- and 3-year time-dependent area under the curve (AUC) 0.746, 0.722, and 0.705; Uno's AUC 0.710). Overall, 67.0 per cent of patients received adjuvant therapy. There was no survival difference by receipt of adjuvant therapy (35.0 versus 36.0 months; P = 0.772). After multivariable adjustment, interaction analysis suggested a benefit of adjuvant therapy for patients with nodal metastases or with tumours larger than 2 cm with extrapancreatic extension, regardless of nodal status. These results were confirmed in the external cohort of 216 patients. Conclusion: Modified staging with a T status definition combining extrapancreatic invasion and tumour size is associated with better prognostic segregation after postneoadjuvant pancreatectomy. This system allows identification of patients who might benefit from adjuvant therapy. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Dutch Pancreatitis Study Group. Endoscopic transgastric vs surgical necrosectomy for infected necrotizing pancreatitis: a randomized trial," in the 2012 issue of the journal and a response by the authors is also presented.

Abstract: State-of-the-art pancreatic surgery is the result of multiple innovations in imaging, pharmacology, endoscopy, and surgical technology, but the initial driving force that brought this discipline to its current level was the boldness and creativity of a group of surgical pioneers. From the many individuals who participated in this process, a group of 11 surgeons was selected, and brief descriptions of their contributions are given. [Copyright &y& Elsevier]

The article discusses the highlights of the Pancreas Club's 40th Annual Meeting held at the University of California in Los Angeles (UCLA) on May 21, 2006. It says that the symposium focused on the topic middle pancreatectomy. Claudio Bassi from Italy and Howard Reber, host at UCLA, were the event's speakers. Accordingly, a discussion from the audience has also been conducted.

Background: The 2017 revised International Association of Pancreatology guidelines for management of intraductal papillary mucinous neoplasm (IPMN) describe worrisome features (WF) and high-risk stigmata (HRS), recommending resection in the latter and further work-up and close surveillance for patients with WF. The effect of multiple WF on the likelihood of malignancy has not been evaluated.Study Design: Eight hundred ten patients who underwent pancreatic resection for IPMN in 2 tertiary referral centers were identified from prospective institutional databases. Patients were retrospectively categorized into subgroups according to the number of WF or HRS and presence of malignancy, defined as high-grade dysplasia (HGD) or invasive cancer on final pathology.Results: Three hundred seventy-nine (47%) patients had HRS, 370 (46%) had 1 or more WF, and 61 patients (7%) had neither. Malignancy was present in 70% (n = 267) of patients with HRS and in 30% (n = 127) of those with WF. Only 3 of 61 patients without WF/HRS had malignancy, and all only in the form of HGD. The risk of malignancy increased in a stepwise fashion with the number of WF, to 22%, 34%, and 59% with 1, 2, and 3 WF, respectively (p = 0.001), and reached 100% in patients with 4 or more WF. Although the relative risks differed for particular WF, the areas under the curve were not statistically different.Conclusion: We confirm that presence of HRS in IPMN is associated with a very high likelihood of malignancy. The presence of a single WF has a malignancy risk of 22%, and additional WF increase this risk significantly. When 3 or more WF are present, the risk is similar to that of HRS. [ABSTRACT FROM AUTHOR]

Background and study aims: There have been concerns about peritoneal seeding after endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of mucinous pancreatic cystic lesions. The aims of this study were to determine the frequency of postoperative peritoneal seeding in patients with intraductal papillary mucinous neoplasm (IPMN) who had undergone pre-operative EUS-FNA and to compare it with that of patients with IPMN who had surgery with no pre-operative tissue sampling. Patients and methods: A total of 175 patients who had undergone resection of IPMNs with pre-operative EUS-FNA (EUS-FNA group) were analyzed and compared with 68 patients who had undergone resection with no pre-operative tissue sampling (No Sampling group). Patient characteristics, pathology, and frequency of peritoneal seeding after surgery were analyzed and compared. Peritoneal seeding was diagnosed based on pathology or image findings. Results: The two groups were comparable with respect to sex, age, follow-up duration, involvement of the pancreatic head, involvement of the main duct, grade of dysplasia, and size of histologically proven branch-duct IPMNs. Four patients (2.3 %) with invasive IPMN developed peritoneal seeding in the EUS-FNA group, whereas three (4.4 %, two with invasive IPMN and one with high-grade dysplasia) developed peritoneal seeding in the No Sampling group (P =0.403). No peritoneal seeding was noted during surgery in these cases. Except for one patient in the EUS-FNA group, no spillage occurred during resection in these patients. Conclusions: In this cohort of patients undergoing resection of IPMN, the difference in the frequency of peritoneal seeding in the EUS-FNA group and the No Sampling group was not significant. [ABSTRACT FROM AUTHOR]

Background: Cystic pancreatic endocrine neoplasms (CPENs) are considered rare, and their behavior is thought to be similar to that of solid pancreatic endocrine neoplasms (PENs). This study aims to describe the characteristics of CPENs in a large patient cohort. Study Design: We performed a retrospective review of 170 patients who underwent resections for PENs at Massachusetts General Hospital from 1977 to 2006. Twenty-nine patients (51% men, mean age 53) with CPENs were compared with 141 patients with solid PENs. Differences in clinical presentation, pathologic and radiographic features, and survival were described. Results: CPENs comprised 17% of all PENs (29 of 170) and 5.4% of all resected cystic pancreatic neoplasms(29 of 535). Ten (34%) were purely cystic and 19 (66%) were partially cystic. Compared with solid PENs, CPENs were larger (49 mm versus 23.5 mm, p < 0.05), more likely symptomatic (73% versus 45%, p < 0.05), and more likely nonfunctional (80% versus 50%, p < 0.05). They expressed synaptophysin (100%), chromogranin (82%), and cytokeratin (CK)-19 (24%). Multiple endocrine neoplasia type 1 (MEN-1) was 3.5 times more common in CPENs than in solid tumors (21% versus 6%, p < 0.05). No significant difference was found in location, propensity for metastasis, invasion, or 5-year survival (87% versus 77%, p=0.38). Conclusions: This series, the largest report of CPENs in the literature, shows that CPENs are more common than previously thought, so they should be included in the differential of the cystic lesions of the pancreas. CPENs are larger and more likely to be symptomatic then solid PENs. They are also more likely to be associated with MEN-1 and to be nonfunctional, suggesting they may be a distinct tumor type. [ABSTRACT FROM AUTHOR]

In pancreatic cancer patients, survival and palliation of symptoms should be balanced with social and functional impairment, and for this reason, health-related quality of life measurements could play an important role in the decision-making process. The aim of this work was to evaluate the quality of life and survival in 92 patients with different stages of pancreatic adenocarcinoma who underwent surgical and/or medical interventions. Patients were evaluated with the Functional Assessment of Cancer Therapy questionnaires at diagnosis and follow-up (3 and 6 months). At diagnosis, 28 patients (30.5%) had localized disease (group 1) and underwent surgical resection, 34 (37%) had locally advanced (group 2), and 30 (32.5%) metastatic disease (Group 3). Improvement in quality of life was found in group 1, while in group 3, it decreased at follow-up (p=0.03). No changes in quality of life in group 2 were found. Chemotherapy/chemoradiation seems not to significantly modify quality of life in groups 2 and 3. Median survival time for the entire cohort was 9.8 months (range, 1-24). One-year survival was 74%, 30%, and 16% for groups 1, 2, and 3 respectively (p=0.001). Pancreatic cancer prognosis is still dismal. In addition to long-term survival benefits, surgery impacts favorably quality of life. [ABSTRACT FROM AUTHOR]

Background: Dynamic survival data based on time already survived are lacking for resected borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC) patients who received total neoadjuvant therapy (TNT) with FOLFIRINOX followed by chemoradiation. Conditional survival, i.e., the probability of surviving an additional length of time after having already survived an amount of time, offers such information. We aimed to determine actuarial and conditional overall (OS, COS) and disease-free survival (DFS, CDFS) among this cohort. Methods: Clinicopathologic data were retrospectively collected for resected BR/LA PDAC patients who received TNT (2011–2019). COS and CDFS rates were calculated for patients being event (death/recurrence)-free at multiple intervals and by recurrence status. Results: After a median follow-up of 32.1 months, the 183 patients had a median OS and DFS of 39.1 months and 16.8 months, respectively. COS and CDFS increased as a function of time already survived. The probability of surviving an additional 24 months if a patient survived 2 years post-operatively was 70%, whereas the 4-year actuarial OS was 47%. Similarly, the probability of surviving disease-free an additional 24 months after 2 years was 66%, while actuarial 48-month DFS was 27%. COS for disease-free patients increased further over time. For patients remaining disease-free 12 months post-operatively, BR vs. LA status at diagnosis, tumor ≤ 4 cm at diagnosis, and R0 resection were independent predictors of favorable additional OS and DFS. Conclusions: For resected TNT-treated BR/LA PDAC patients, the probability of surviving an additional length of time increases as a function of survival already accrued. Dynamic survival estimates may allow personalized follow-up and counseling. [ABSTRACT FROM AUTHOR]

Several inhibitors of angiogenesis have been identified in bovine and shark cartilage. One of them is troponin I, which is the molecule responsible for the inhibition of the actomyosin ATPase during muscle contraction. In this study we sought to investigate if the active site of troponin I (peptide Glu94-Leu123; pTnI) is also the one responsible for the antiangiogenic properties of this protein. The effects of pTnI on endothelial cell tube formation and endothelial cell division were investigated using human umbilical vein endothelial cells, Matrigel, light microscopy, carboxyfluorescein diacetate, succinimidyl esterlabeling, and flow cytometry. Its effects on induction of ICAM-1 and production of vascular endothelial growth factor by pancreatic cancer cells (CAPAN-1) were also investigated, as was its efficacy in a mouse model of pancreatic cancer metastases. Our results show that concentrations as low as 1 pg/ml of pTnI significantly inhibit endothelial cell tube formation, and that endothelial cell division was inhibited at 96 hours by 3 μg/ml pTnI (P = 0.0001). No effects were seen using troponin peptide 124-181 as a control. pTnI-treated supernatant from the pancreatic cancer cell line CAPAN-1 downregulated ICAM-1 expression on human umbilical vein endothelial cells up to 10 ng/ml pTnI, and a significant reduction in vascular endothelial growth factor production was seen by treating CAPAN-1 cells with up to 1 μg/ml pTnI. After intrasplenic injection of CAPAN-1 cells, mice treated with pTnI had fewer liver metastases compared to control mice (liver/body weight 5.5 vs. 11.1; P = 0.03). The active region of troponin I is the one responsible for its antiangiogenic effect. The mechanism of action of this peptide is probably multifactorial. [Copyright &y& Elsevier]

: BackgroundPancreatic fistula complicates up to 15% to 25% of pancreatic resections, especially with soft, normal pancreas, and is most common after distal pancreatectomy. A new synthetic, absorbable hydrogel sealant has recently been developed and tested for sealing of human aorta, bronchi, and dura; it is FDA approved as a lung sealant in humans. Our objective was to test the efficacy of the sealant in preventing pancreatic leaks in a dog model of distal pancreatectomy.: Study designTen dogs underwent bilateral distal pancreatectomy under general anesthesia. Animals were randomized to receive application of the sealant to the pancreatic stumps (n = 5) or no treatment (n = 5). The transected pancreatic duct was not ligated, and the end of the pancreas was neither oversewn nor stapled; closed-suction drains were placed in proximity to the pancreatic stumps before abdominal closure. All animals received normal chow starting on the second postoperative day. Drainage was collected for volume and amylase determination twice daily for 14 days, after which the animals were sacrificed. Pancreatic tissue was collected from the area of transection and was formalin fixed for histopathology.: ResultsThere was no perioperative mortality. Fluid recovered from closed-suction drains in all animals was uniformly amylase-rich. Over the 14-day study period, daily volume of pancreatic drainage was significantly different between control animals and animals treated with sealant (p < 0.001). By postoperative day 6, the total mean pancreatic drainage in dogs treated with sealant was 25 ± 5 mL/drain (versus 91 ± 26 mL/drain in untreated dogs; p < 0.05). This is the point at which we remove the drains in our clinical practice. Examination at 14 days revealed intact sealant at the pancreatic stumps in the treatment group, and histopathology showed a characteristic benign histiocyte reaction to the sealant but no other qualitative differences in the degree of inflammation between control and treatment animals. There were no undrained collections or abscesses.: ConclusionsA new synthetic hydrogel sealant prevents the formation of significant pancreatic fistulae after distal pancreatectomy in the dog and may be suitable for clinical application. [Copyright &y& Elsevier]

Aims: Pancreatic ductal adenocarcinomas (PDACs) are increasingly being treated with neoadjuvant therapy. However, the American Joint Committee on Cancer (AJCC) 8th edition T staging based on tumour size does not reflect treatment effect, which often results in multiple, small foci of residual tumour in a background of mass‐forming fibrosis. Thus, we evaluated the performance of AJCC 8th edition T staging in predicting patient outcomes by the use of a microscopic tumour size measurement method. Methods and results: One hundred and six post‐neoadjuvant therapy pancreatectomies were reviewed, and all individual tumour foci were measured. T stages based on gross size with microscopic adjustment (GS) and the largest single microscopic focus size (MFS) were examined in association with clinicopathological variables and patient outcomes. Sixty‐three of 106 (59%) were locally advanced; 78% received FOLFIRINOX treatment. The average GS and MFS were 25 mm and 11 mm, respectively; nine cases each were classified as T0, 35 and 85 cases as T1, 42 and 12 cases as T2, and 20 and 0 cases as T3, based on the GS and the MFS, respectively. Higher GS‐based and MFS‐based T stages were significantly associated with higher tumour regression grade, lymphovascular and perineural invasion, and higher N stage. Furthermore, higher MFS‐based T stage was significantly associated with shorter disease‐free survival (DFS) (P < 0.001) and shorter overall survival (OS) (P = 0.002). GS was significantly associated with OS (P = 0.046), but not with DFS. Conclusions: In post‐neoadjuvant therapy PDAC resections, MFS‐based T staging is superior to GS‐based T staging for predicting patient outcomes, suggesting that microscopic measurements have clinical utility beyond the conventional use of GS measurements alone. [ABSTRACT FROM AUTHOR]

Background: A minimally invasive step-up (MIS) approach has been associated with reduced morbidity compared with open surgical necrosectomy (OSN) for treatment of necrotizing pancreatitis. We sought to determine whether transitioning from an OSN to an MIS-based approach would result in reduced mortality. MIS interventions included percutaneous drainage, endoscopic transgastric necrosectomy, video-assisted retroperitoneal debridement, sinus tract endoscopic necrosectomy, or a combination of techniques, with selective use of OSN.Study Design: We conducted an observational cohort study with retrospective comparison at a single tertiary referral center (2006 through 2019). Eighty-eight patients were treated with OSN and 91 were treated with an MIS-based approach. Baseline characteristics and clinical outcomes were compared between groups. The primary end point was 90-day mortality.Results: There was no difference in baseline characteristics. Ninety-day mortality was 2% with MIS compared with 10% with OSN (p = 0.03). One-year mortality was 3% with MIS compared with 15% with OSN (p = 0.012). The rate of organ failure was lower with MIS (30% vs 45%; p = 0.029), but there was a higher bleeding rate (19% vs 9%; p = 0.064). In the MIS group, 9% were treated with percutaneous drainage, 32% with endoscopic transgastric necrosectomy, 8% with video-assisted retroperitoneal debridement, 15% with sinus tract endoscopic necrosectomy, and 27% with a combination of techniques.Conclusions: Adoption of a multidisciplinary MIS-based approach to necrotizing pancreatitis resulted in a 5-fold decrease in mortality compared with OSN. [ABSTRACT FROM AUTHOR]

Aim: The aim of this paper is to describe the characteristics of intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in young patients.Methods: We evaluated 1693 patients from the Pancreatic Surgery Consortium who underwent resection for IPMN and classified them as younger or older than 50 years of age at the time of surgery. We assessed the relationship of age with clinical, radiological, pathological, and prognostic features.Results: We identified 90 (5%) young patients. Age was not associated with differences in main pancreatic duct size (P = 0.323), presence of solid components (P = 0.805), or cyst size (P = 0.135). IPMNs from young patients were less likely to be of gastric type (37 vs. 57%, P = 0.005), and more likely to be of oncocytic (15 vs. 4%, P = 0.003) and intestinal types (44 vs. 26%, P = 0.004). Invasive carcinomas arising from IPMN were less common in young patients (17 vs. 27%, P = 0.044), and when present they were commonly of colloid type (47 vs. 31% in older patients, P = 0.261) and had better overall survival than older patients (5-year, 71 vs. 37%, log-rank P = 0.031).Conclusion: Resection for IPMN is infrequent in young patients, but when they are resected, IPMNs from young patients demonstrate different epithelial subtypes from those in older patients and more favorable prognosis. [ABSTRACT FROM AUTHOR]

Patient-derived xenograft (PDX) tumors are powerful tools to study cancer biology. However, the ability of PDX tumors to model the biological and histological diversity of pancreatic ductal adenocarcinoma (PDAC) is not well known. In this study, we subcutaneously implanted 133 primary and metastatic PDAC tumors into immunodeficient mice. Fifty-seven tumors were successfully engrafted and even after extensive passaging, the histology of poorly-, moderately-, and well-differentiated tumors was maintained in the PDX models. Moreover, the fibroblast and collagen contents in the stroma of patient tumors were recapitulated in the corresponding PDX models. Analysis of the clinicopathological features of patients revealed xenograft tumor engraftment was associated with lymphovascular invasion (P = 0.001) and worse recurrence-free (median, 7 vs. 16 months, log-rank P = 0.047) and overall survival (median, 13 vs. 21 months, log-rank P = 0.038). Among successful engraftments, median time of growth required for reimplantation into new mice was 151 days. Reflective of the inherent biological diversity between PDX tumors with rapid (<151 days) and slow growth, differences in their growth were maintained during extensive passaging. Rapid growth was additionally associated with lymph node metastasis (P = 0.022). The association of lymphovascular invasion and lymph node metastasis with PDX formation and rapid growth may reflect an underlying biological mechanism that allows these tumors to adapt and grow in a new environment. While the ability of PDX tumors to mimic the cellular and non-cellular features of the parental tumor stroma provides a valuable model to study the interaction of PDAC cells with the tumor microenvironment, the association of successful engraftment with adverse clinicopathological features suggests PDX models over represent more aggressive forms of this disease. [ABSTRACT FROM AUTHOR]

Background The different epithelial phenotypes of intraductal papillary mucinous neoplasms (IPMNs) are predictors of tumor biology and post-surgical outcomes. Oncocytic-type IPMN (O-IPMN) seems to have a unique natural history, but not much information is available because of its rarity. We sought to describe the characteristics of a cohort of patients resected for O-IPMNs, focusing on their long-term outcomes after surgery. Study Design We conducted a retrospective review of the demographics, clinical presentation, pathology, and survival of a cohort of patients resected for IPMN between 1990 and 2013, comparing O-IPMN with other IPMN subtypes. Results Eighteen of 400 patients (4.5%) who underwent resection for IPMN had the oncocytic subtype. Compared with other IPMN patients, those with O-IPMNs were more likely to be male (72% vs 45%; p = 0.02) and to have main pancreatic duct involvement (72% vs 42%; p = 0.01). Oncocytic IPMNs occurred in asymptomatic individuals in 67% of cases. They had either invasive carcinoma (61%) or high-grade dysplasia (39%), and the proportions in other epithelial subtypes were 19% and 21%, respectively (p < 0.001). After resection, the 10-year recurrence rate for O-IPMNs was 46%. Recurrences occurred up to 11 years after the initial resection and a completion total pancreatectomy was performed in 4 patients. At a median follow-up of 7 years, no patients with O-IPMN had died from the disease. Conclusions Oncocytic IPMN is a unique tumor subtype that occurs mostly in the main pancreatic duct and is malignant. Recurrences after resection are not uncommon and can occur more than 10 years after the initial resection. Reoperations for recurrent O-IPMN are often feasible and have excellent results in terms of survival. [ABSTRACT FROM AUTHOR]

Introduction: Despite the decreasing mortality of pancreaticoduodenectomy (PD), it continues to be associated with prolonged length of postoperative hospital stay (LOS). This study aimed to determine factors that could predict short LOS after PD. Additionally, as preliminary data of minimally invasive PD emerges, we sought to determine the average LOS after open PD at a high-volume center to set a standard to which minimally invasive PD can be compared. Methods: A total of 634 consecutive patients who underwent open PD between January 2007 and December 2012 at the Massachusetts General Hospital comprised the study cohort. 'High performers' were defined as patients with postoperative LOS ≤5 days. Results: Median LOS was 7 days. A total of 61 patients (9.6 %) had LOS ≤5 days and were deemed 'high performing.' In multivariate logistic regression analysis, male gender ( p = 0.032), neoadjuvant chemoradiation ( p = 0.001), epidural success ( p = 0.019), epidural duration ≤3 days ( p = 0.001), lack of complications ( p < 0.001), surgery on Thursday or Friday ( p = 0.001), and discharge on Monday through Wednesday ( p < 0.001) were independently associated with LOS ≤5 days. Readmission rate, time to readmission, and mortality were not different between the two groups. The proportion of patients with pancreatic ductal adenocarcinoma who went on to receive adjuvant therapy was no different if LOS was ≤5 or >5 days, but high performance was predictive of beginning therapy <8 weeks after surgery ( p = 0.010). Conclusion: In our experience, median LOS was 7 days, and early discharge (≤5 days) after open PD is safe and feasible in about 10 % of patients. These high performers are more likely to be male, have received neoadjuvant therapy, and had successful epidural analgesia. High performers with cancer are more likely to start chemotherapy <8 weeks after surgery. Minimally invasive PD should be compared to this high standard for median LOS, among other quality metrics, to justify its increased cost, operative duration, and learning curve. [ABSTRACT FROM AUTHOR]

Introduction: The morbidity and mortality of pancreaticoduodenectomy (PD) have significantly decreased over the past decades to the point that they are no longer the sole indicators of quality and safety. In recent times, hospital readmission is increasingly used as a quality metric for surgical performance and has direct implications on health-care costs. We sought to delineate the natural history and predictive factors of readmissions after PD.Methods: The clinicopathologic and long-term follow-up data of 1,173 consecutive patients who underwent PD between August 2002 and August 2012 at the Massachusetts General Hospital were reviewed. The NSQIP database was linked with our clinical database to supplement perioperative data. Readmissions unrelated to the index admission were omitted.Results: We identified 173 (15 %) patients who required readmission after PD within the study period. The readmission rate was higher in the second half of the decade when compared to the first half (18.6 vs 12.3 %, p = 0.003), despite a stable 7-day median length of stay. Readmitted patients were analyzed against those without readmissions after PD. The demographics and tumor pathology of both groups did not differ significantly. In the multivariate logistic regression analysis, pancreatic fistula (18.5 vs 11.3 %, OR 1.86, p = 0.004), multivisceral resection at time of PD (3.5 vs 0.6 %, OR 4.02, p = 0.02), length of initial hospital stay >7 days (59.5 vs 42.5 %, OR 1.57, p = 0.01), and ICU admissions (11.6 vs 3.4 %, OR 2.90, p = 0.0005) were independently associated with readmissions. There were no postoperative biochemical variables that were predictive of readmissions. Fifty percent (n = 87) of the readmissions occurred within 7 days from initial operative discharge. The reasons for immediate (≤7 days) and nonimmediate (>7 days) readmissions differed; ileus, delayed gastric emptying, and pneumonia were more common in early readmissions, whereas wound infection, failure to thrive, and intra-abdominal hemorrhage were associated with late readmissions. The incidences of readmissions due to pancreatic fistulas and intra-abdominal abscesses were equally distributed between both time frames. The frequency of readmission after PD is 15 % and has been on the uptrend over the last decade.Conclusion: The complexity of initial resection and pancreatic fistula were independently associated with hospital readmissions after PD. Further efforts should be centered on preventing early readmissions, which constitute half of all readmissions. [ABSTRACT FROM AUTHOR]

Introduction: The morbidity and mortality of pancreaticoduodenectomy (PD) have significantly decreased over the past decades to the point that they are no longer the sole indicators of quality and safety. In recent times, hospital readmission is increasingly used as a quality metric for surgical performance and has direct implications on health-care costs. We sought to delineate the natural history and predictive factors of readmissions after PD. Methods: The clinicopathologic and long-term follow-up data of 1,173 consecutive patients who underwent PD between August 2002 and August 2012 at the Massachusetts General Hospital were reviewed. The NSQIP database was linked with our clinical database to supplement perioperative data. Readmissions unrelated to the index admission were omitted. Results: We identified 173 (15 %) patients who required readmission after PD within the study period. The readmission rate was higher in the second half of the decade when compared to the first half (18.6 vs 12.3 %, p = 0.003), despite a stable 7-day median length of stay. Readmitted patients were analyzed against those without readmissions after PD. The demographics and tumor pathology of both groups did not differ significantly. In the multivariate logistic regression analysis, pancreatic fistula (18.5 vs 11.3 %, OR 1.86, p = 0.004), multivisceral resection at time of PD (3.5 vs 0.6 %, OR 4.02, p = 0.02), length of initial hospital stay >7 days (59.5 vs 42.5 %, OR 1.57, p = 0.01), and ICU admissions (11.6 vs 3.4 %, OR 2.90, p = 0.0005) were independently associated with readmissions. There were no postoperative biochemical variables that were predictive of readmissions. Fifty percent ( n = 87) of the readmissions occurred within 7 days from initial operative discharge. The reasons for immediate (≤7 days) and nonimmediate (>7 days) readmissions differed; ileus, delayed gastric emptying, and pneumonia were more common in early readmissions, whereas wound infection, failure to thrive, and intra-abdominal hemorrhage were associated with late readmissions. The incidences of readmissions due to pancreatic fistulas and intra-abdominal abscesses were equally distributed between both time frames. The frequency of readmission after PD is 15 % and has been on the uptrend over the last decade. Conclusion: The complexity of initial resection and pancreatic fistula were independently associated with hospital readmissions after PD. Further efforts should be centered on preventing early readmissions, which constitute half of all readmissions. [ABSTRACT FROM AUTHOR]

Background: Autoimmune pancreatitis (AIP) is a rare subtype of chronic pancreatitis that may mimic adenocarcinoma of the pancreas. The aim of this study was to evaluate the short-term and long-term outcomes of pancreatectomy for patients with AIP. Methods: In this multi-institutional study, we identified all patients who underwent pancreatectomy for AIP from 1986 to 2011. AIP was confirmed by pathology review. Clinical presentation, operative details, and postoperative outcomes were analyzed. Results: Seventy-four patients (median age, 60 years; 69 % male) with AIP underwent pancreatectomy. The main indication for operation was concern for malignancy ( n = 59, 80 %). No patients were found to have pancreatic adenocarcinoma on final pathology. Major complications occurred in ten (14 %) patients, with one perioperative death (1 %). Clinically relevant (grade B/C) pancreatic fistulae occurred in two patients. No patients required reoperation for AIP and 11 (17 %) patients developed recurrent AIP. Conclusion: Although we do not advocate pancreatectomy for AIP, strong suspicion of malignancy may require an operation in selected patients. For patients with AIP, pancreatectomy resulted in few pancreatic fistulae, a low rate of re-intervention, and a 17 % recurrence rate. [ABSTRACT FROM AUTHOR]

Introduction: We evaluated the prognostic accuracy of LN variables (N0/N1), numbers of positive lymph nodes (PLN), and lymph node ratio (LNR) in the context of the total number of examined lymph nodes (ELN). Methods: Patients from SEER and a single institution (MGH) were reviewed and survival analyses performed in subgroups based on numbers of ELN to calculate excess risk of death (hazard ratio, HR). Results: In SEER and MGH, higher numbers of ELN improved the overall survival for N0 patients. The prognostic significance (N0/N1) and PLN were too variable as the importance of a single PLN depended on the total number of LN dissected. LNR consistently correlated with survival once a certain number of lymph nodes were dissected (≥13 in SEER and ≥17 in the MGH dataset). Conclusions: Better survival for N0 patients with increasing ELN likely represents improved staging. PLN have some predictive value but the ELN strongly influence their impact on survival, suggesting the need for a ratio-based classification. LNR strongly correlates with outcome provided that a certain number of lymph nodes is evaluated, suggesting that the prognostic accuracy of any LN variable depends on the total number of ELN. [ABSTRACT FROM AUTHOR]

High platelet counts are associated with an adverse effect on survival in various neoplastic entities. The prognostic relevance of preoperative platelet count in pancreatic cancer has not been clarified. We performed a retrospective review of 205 patients with ductal adenocarcinoma who underwent surgical resection between 1990 and 2003. Demographic, surgical, and clinicopathologic variables were collected. A cutoff of 300,000/μl was used to define high platelet count. Of the 205 patients, 56 (27.4%) had a high platelet count, whereas 149 patients (72.6%) comprised the low platelet group. The overall median survival was 17 (2–178) months. The median survival of the high platelet group was 18 (2–137) months, and that of the low platelet group was 15 (2–178) months ( p = 0.7). On multivariate analysis, lymph node metastasis, vascular invasion, positive margins, and CA 19–9 > 200 U/ml were all significantly associated with poor survival. There is no evidence to support preoperative platelet count as either an adverse or favorable prognostic factor in pancreatic ductal adenocarcinoma. Use of 5-year actual survival data confirms that lymph node metastases, positive margins, vascular invasion, and CA 19–9 are predictors of poor survival in resected pancreatic cancer. [ABSTRACT FROM AUTHOR]

Acute mesenteric ischemia, a frequently lethal disease, requires prompt diagnosis and intervention for favorable clinical outcomes. This goal remains elusive due, in part, to lack of a noninvasive and accurate imaging study. Traditional angiography is the diagnostic gold standard but is invasive and costly. Computed tomography (CT) is readily available and noninvasive but has shown variable success in diagnosing this disease. The faster scanning time of multidetector row CT (M.D.CT) greatly facilitates the use of CT angiography (CTA) in the clinical setting. We sought to determine whether M.D.CT-CTA could accurately demonstrate vascular anatomy and capture the earliest stages of mesenteric ischemia in a porcine model. Pigs underwent embolization of branches of the superior mesenteric artery, then imaging by M.D.CT-CTA with three-dimensional reconstruction protocols. After scanning, diseased bowel segments were surgically resected and pathologically examined. Multidetector row CT and CT angiography reliably defined normal and occluded mesenteric vessels in the pig. It detected early changes of ischemia including poor arterial enhancement and venous dilatation, which were seen in all ischemic animals. The radiographic findings—compared with pathologic diagnoses— predicted ischemia, with a positive predictive value of 92%. These results indicate that M.D.CT-CTA holds great promise for the early detection necessary for successful treatment of acute mesenteric ischemia. [Copyright &y& Elsevier]

Hedgehog signalling-an essential pathway during embryonic pancreatic development, the misregulation of which has been implicated in several forms of cancer-may also be an important mediator in human pancreatic carcinoma. Here we report that sonic hedgehog, a secreted hedgehog ligand, is abnormally expressed in pancreatic adenocarcinoma and its precursor lesions: pancreatic intraepithelial neoplasia (PanIN). Pancreata of Pdx-Shh mice (in which Shh is misexpressed in the pancreatic endoderm) develop abnormal tubular structures, a phenocopy of human PanIN-1 and -2. Moreover, these PanIN-like lesions also contain mutations in K-ras and overexpress HER-2/neu, which are genetic mutations found early in the progression of human pancreatic cancer. Furthermore, hedgehog signalling remains active in cell lines established from primary and metastatic pancreatic adenocarcinomas. Notably, inhibition of hedgehog signalling by cyclopamine induced apoptosis and blocked proliferation in a subset of the pancreatic cancer cell lines both in vitro and in vivo. These data suggest that this pathway may have an early and critical role in the genesis of this cancer, and that maintenance of hedgehog signalling is important for aberrant proliferation and tumorigenesis. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinases (MMPs) catalyze the degradation of collagen and extracellular matrix. They play a role in pathologic states including malignancy, in which they facilitate invasion and metastasis. MMP inhibition has been shown to block neoplastic invasion and improve survival in animal models of malignancy. Concern about the effects of MMP inhibitors on wound and anastomotic healing may limit their potential use in the perioperative period to prevent local and systemic showering of cancer cells from surgical manipulation. We sought to assess the safety of perioperative administration of an MMP inhibitor (BB-94) with respect to skin and bowel healing in a rat model. Absorption of BB-94 was confirmed through high-pressure liquid chromatography and mass spectroscopy of sera from treated animals. Bowel bursting pressure in all animals increased almost 10-fold between 4 and 14 days. Two-way analysis of variance showed no significant difference in bowel bursting pressure between control and treatment animals over time. There was a significant increase in the collagen content of skin specimens of all animals combined between 4 and 28 days. Similarly, all animals showed an increase in bowel collagen between 4 and 28 days. There was no significant difference in skin or bowel collagen concentrations between control and treatment animals over time. Perioperative treatment with MMP inhibition does not impair wound or enteric healing in a rat model of laparotomy and small bowel resection. MMP inhibitors are safe for use as adjuvant therapy after resection for cancer. ( J Gastrointest Surg 2002;6:488–495.) [ABSTRACT FROM AUTHOR]