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OBJECTIVE The virtual interview season has challenged general surgery residency programs to recruit applicants through the loss of visiting clerkships, tours, and time with residents. Webinars, increased informal resident and faculty sessions, and live-narrated video tours are potential solutions. This study aimed to assess the effectiveness of these elements in virtually showcasing a residency program during the virtual interview season. DESIGN/SETTING Prospective applicants to one general surgery residency program (Mayo Clinic in Rochester, Minnesota) were invited to attend six webinars: Program Overview, Simulation Education, Diversity, Resident Life, Mingle with Residents, and Last-Minute Q&A. An anonymous survey was sent to all registered participants of the webinars. Interviewees participated in a preinterview social hour with resident and faculty and a live-narrated video tour of our facilities during their interview. A second anonymous survey was sent to all interviewees. PARTICIPANTS Webinars – 33% of 159 unique registrants surveyed participated. Interviews – 46% of 109 interviewees surveyed participated. RESULTS Average satisfaction with the webinars was 9.4/10. Overall, 98% of attendees felt that the webinars gave them a “feel” for the program. Attendees found the Last-Minute Q&A webinar and Program Overview to be most useful. For resident-led webinars, 100% of attendees felt that themed break-out rooms were effective. Average satisfaction with the interviews was 4.4/5. Interviewees rated access to faculty and residents highly (4.4/5 and 4.5/5, respectively). 98% of interviewees found the live-narrated video tour helpful. CONCLUSIONS A webinar curriculum can be effective in virtual residency recruitment, as prospective applicants developed a good understanding of the resident program after participating. Further, live-narrated video tours and purposefully incorporating several avenues for informal conversations with residents and faculty can successfully address applicant concerns about virtual interviews.

BackgroundElderly patients undergoing open pancreatoduodenectomy (OPD) are at increased risk for surgical morbidity and mortality. Whether totally laparoscopic pancreatoduodenectomy (TLPD) mitigates these risks has not been evaluated.MethodsA retrospective review of outcomes in patients submitted to pancreatoduodenectomy during 2007–2014 was conducted (n = 860). Outcomes in elderly patients (aged ≥70 years) were compared with those in non elderly patients with respect to risk adjusted postoperative morbidity and mortality. Differences in outcomes between patients submitted to OPD and TLPD, respectively, were evaluated in the elderly subgroup.ResultsIn elderly patients, the incidences of cardiac events (odds ratio [OR] 3.21, P

Background A delayed post pancreatoduodenectomy haemorrhage is associated with a significant increase in peri operative mortality. Endovascular techniques are frequently used for a delayed haemorrhage. However, limited data exists on the short and long term outcomes of this approach. A retrospective review over a 10 year period at a quaternary referral pancreatic centre was performed. Methods Between 2002–2012, 1430 pancreatoduodenectomies were performed, and 32 patients had a delayed haemorrhage (occurring >24 h post operatively) managed by endovascular techniques. The clinicopathological variables related to a haemorrhage were investigated. Results A total of 42 endovascular procedures were performed at a median of 25 days, with the majority of delayed haemorrhages occurring after 7 days. There were four deaths (13%) with three occurring in patients with a grade C haemorrhage. Seven patients (22%) experienced rebleeding, and two patients developed hepatic abscesses. Conclusion A delayed haemorrhage post pancreaticoduodenectomy can be managed by endovascular techniques with acceptable morbidity and mortality. Rebleeding and hepatic abscesses may occur and can be managed non operatively in most cases. The association of a delayed haemorrhage with a pancreatic fistula makes this a challenging clinical problem.

BackgroundThe 7th edition of the American Joint Committee on Cancer (AJCC) staging system has recently been validated and shown to predict survival in patients with intrahepatic cholangiocarcinoma (ICC). The present study attempted to investigate the validity of these findings.MethodsA single‐centre, retrospective cohort study was conducted. Histopathological restaging of disease subsequent to primary surgical resection was carried out in all consecutive ICC patients. Overall survival was compared using Kaplan–Meier estimates and log‐rank tests.ResultsA total of 150 patients underwent surgery, 126 (84%) of whom met the present study's inclusion criteria. Of these 126 patients, 68 (54%) were female. The median length of follow‐up was 4.5 years. The median patient age was 58 years (range: 24–79 years). Median body mass index was 27 kg/m2 (range: 17–46 kg/m2). Staging according to the AJCC 7th edition categorized 33 (26%) patients with stage I disease, 27 (21%) with stage II disease, five (4%) with stage III disease, and 61 (48%) with stage IVa disease. The AJCC 7th edition failed to accurately stratify survival in the current cohort; analysis revealed significantly worse survival in those with microvascular invasion, tumour size of >5 cm, grade 4 disease, multiple tumours and positive lymph nodes (P < 0.001). A negative resection margin was associated with improved survival (P < 0.001).ConclusionsThe AJCC 7th edition did not accurately predict survival in patients with ICC. A multivariable model including tumour size and differentiation in addition to the criteria used in the AJCC 7th edition may offer a more accurate method of predicting survival in patients with ICC.

BackgroundNew‐onset diabetes mellitus after a pancreaticoduodenectomy (PD) remains poorly defined. The aim of this study was to define the incidence and predictive factors of immediate post‐resection diabetes mellitus (iPRDM).MethodsRetrospective review of patients undergoing PD from January 2004 through to July 2010. Immediate post‐resection diabetes mellitus was defined as diabetes requiring pharmacological treatment within 30 days post‐operatively. Logistic regression was conducted to identify factors predictive of iPRDM.ResultsOf 778 patients undergoing PD, 214 were excluded owing to pre‐operative diabetes (n= 192), declined research authorization (n= 14) or death prior to hospital discharge (n= 8); the remaining 564 patients comprised the study population. iPRDM occurred in 22 patients (4%) who were more likely to be male, have pre‐operative glucose intolerance, or an increased creatinine, body mass index (BMI), pre‐operative glucose, operative time, tumour size or specimen length compared with patients without iPRDM (P < 0.05). On multivariate analysis, pre‐operative impaired glucose intolerance (P < 0.001), pre‐operative glucose ≥ 126 (P < 0.001) and specimen length (P= 0.002) were independent predictors of iPRDM. A predictive model using these three factors demonstrated a c‐index of 0.842.DiscussionNew‐onset, post‐resection diabetes occurs in 4% of patients undergoing PD. Factors predictive of iPRDM include pre‐operative glucose intolerance, elevated pre‐operative glucose and increased specimen length. These data are important for patient education and predicting outcomes after PD.

BackgroundPrimary gastrointestinal stromal tumours (GISTs) of the duodenum are rare. The aim of this study was to review the surgical management of GISTs in this anatomically complex region.MethodsRetrospective review from January 1999 to August 2011 of patients with primary GISTs of the duodenum.ResultsForty-one patients underwent resection of duodenal GISTs. All operations were performed with intent to cure with negative margins of resection. The most common location of origin was the second portion of the duodenum. Local excision (n= 19), segmental resection with primary anastomosis (n= 11) and a pancreatoduodenectomy (n= 11) were performed. Two patients underwent an ampullectomy with local excision. Peri-operative mortality and overall morbidity were 0 and 12, respectively. Patients with high-risk GISTs (P= 0.008) and those who underwent a pancreatoduodenectomy (P= 0.021) were at a greater risk for morbidity. The median follow-up was 18 months. Eight patients developed recurrence. High-risk GISTs and neoplasms with ulceration had the greatest risk for recurrence (P= 0.017, P= 0.029 respectively). The actuarial 3- and 5-year survivals were 85% and 74%, respectively.ConclusionThe choice and type of resection depends on the proximity to the ampulla of Vater, involvement of adjacent organs and the ability to obtain negative margins. The morbidity depends on the type of procedure for GIST.

To evaluate the role of neoadjuvant chemoradiation therapy and rescue surgery in the management of unresectable or recurrent duodenal adenocarcinoma.Retrospective review of all adults treated with neoadjuvant therapy and rescue surgery for locally unresectable or locally recurrent duodenal adenocarcinoma from 1994 to 2010.Ten patients received various forms of neoadjuvant therapy prior to operative exploration for potential resection. Six patients presented with locally unresectable disease, while four had local recurrences. Six patients had vascular encasement, three had retroperitoneal extension with vascular invasion, and one had invasion of surrounding organs. Of the six patients with locally advanced disease, preoperative therapy consisted of chemotherapy alone (3) or chemoradiotherapy (3). Of the four patients with local recurrences, preoperative therapy consisted of chemotherapy alone (1), chemoradiotherapy alone (1), chemoradiotherapy after chemotherapy (1), and chemoradiotherapy followed by combination chemotherapy (1). Nine of ten patients became resectable after neoadjuvant therapy. Clinically, two patients had complete responses, and four had partial responses. Histopathology revealed complete pathologic response in two patients and near-complete pathologic response in one (1 mm of residual disease). Currently, five patients are alive (range 18-83 months postoperatively). All have no evidence of disease.Neoadjuvant therapy may convert locally unresectable duodenal adenocarcinoma to resectable disease with subsequent prolonged survival.

Diacylglycerol acyltransferase (DGAT) could be a rate limiting step in triglyceride (TG) synthesis as it is the final step in this pathway. As such, between depot differences in DGAT activity could influence regional fat storage. DGAT activity and in vitro rates of direct free fatty acid (FFA) storage were measured in abdominal subcutaneous and omental adipose tissue samples from 12 non-obese (BMI < 30kg/m2) and 23 obese men and women (BMI > 30kg/m2) undergoing elective surgery. DGAT activity was greater in omental than in abdominal subcutaneous adipose tissue from non-obese patients (2.0 ± 0.9 vs. 0.9 ± 0.3 pmol/min/mg lipid, respectively, P = 0.003), but not from obese patients (1.4 ± 0.6 vs. 1.7 ± 0.7 pmol/min/mg lipid, respectively, P = 0.10). DGAT activity per unit adipose weight was negatively correlated with adipocyte size (p

The basis of hepatocellular injury and progressive fibrosis in a subset of patients with nonalcoholic fatty liver disease (NAFLD) is poorly understood. We sought to identify hepatic proteins that are differentially abundant across the histologic spectrum of NAFLD. Hepatic protein abundance was measured in liver samples from four groups (n = 10 each) of obese (body mass index >30 kg/m2) patients: (1) obese normal group (normal liver histology), (2) simple steatosis (SS), (3) nonalcoholic steatohepatitis (NASH)-mild (steatohepatitis with fibrosis stage 0-1), and (4) NASH-progressive (steatohepatitis with fibrosis stage 2-4). Hepatic peptides were analyzed on an API Qstar XL quadrupole time-of-flight mass spectrometer using Analyst QS software. Linear trends tests were performed and used to screen for differential abundance. Nine known proteins were expressed with differential abundance between study groups. For seven proteins differential abundance is likely to have been on the basis increased hepatic lipid content and/or inflammation. Lumican, a 40-kDa keratin sulfate proteoglycan that regulates collagen fibril assembly and activates transforming growth factor-beta and smooth muscle actin, was expressed similarly in obese normal and SS but was overexpressed in a progressive manner in NASH-mild versus SS (124%, P < 0.001), NASH-progressive versus NASH-mild (156%, P < 0.001) and NASH-progressive versus obese normal (178%, P < 0.001). Fatty acid binding protein-1 (FABP-1), which is protective against the detergent effects of excess free fatty acids, facilitates intracellular free fatty acid transport and is an important ligand for peroxisome proliferator-activated receptor–mediated transcription, was overexpressed in SS when compared to the obese normal group (128%, P < 0.001), but was paradoxically underexpressed in NASH-mild versus SS (73%, P < 0.001), NASH-progressive versus NASH-mild (81%, P < 0.001), and NASH-progressive versus obese normal (59%, P < 0.001). Conclusion: Histologically progressive NAFLD is associated with overexpression of lumican, an important mediator of fibrosis in nonhepatic tissues, whereas FABP-1 is paradoxically underexpressed in NASH, suggesting a new potential mechanism of lipotoxicity in NAFLD. Further studies are needed to determine the biologic basis of lumican and/or FABP-1 dysregulation in NAFLD. (HEPATOLOGY 2009;49:1375–1384.)

Intraductal mucinous papillary neoplasm (IPMN) is being recognized with increasing frequency around the world. The true incidence, however, remains unknown. Our goal was to determine the incidence of IPMN in a population study.We used the records-linkage system of the Rochester Epidemiology Project to ascertain age- and sex-adjusted incidence rates of IPMN in Olmsted County, Minn, from January 1, 1984, to December 31, 2005. We also evaluated the number of prevalent cases as of December 31, 2005.We identified 28 incident cases of IPMN. The age- and sex-adjusted cumulative incidence for IPMN in Olmsted County is 2.04 cases per 100,000 persons (95% confidence interval [CI], 1.28-2.80) from 1984 to 2005. Point prevalence on December 31, 2005, was 25.96 cases per 100,000 persons (95% CI, 14.53-37.38 cases) or 1 per 3852. Restricting to county residents 60 years and older, the point prevalence is 99.10 cases per 100,000 persons (95% CI, 54.40-143.79 cases) or one per 1009 persons. Thirty-two percent of patients were treated surgically. The 5-year survival rate after diagnosis was 59.6%.The incidence of IPMN in Olmsted County is low but increasing. Most patients do not die of complications related to the disease.

performed using techniques of enucleation and renorraphy previously described. Renal function outcomes were stratified based on CKD stages I, II and III. Statistical analysis was performed using pairedsamples T-Test. RESULTS: The distribution of CKD stages is presented in Table 1. Patients with CKD I and II pre-operatively showed no statistically significant increase in creatinine (Cr) or decrease in estimated glomerular filtration (eGFR) was observed post-operatively or at 3 month follow-up (p1⁄40.42 and p1⁄40.36 respectively). For patients with a pre-operative eGFR

Background. Historically, the operative mortality associated with hepatic abscess was >50%. More recently, patients have been treated with percutaneous drainage; however, those failing conservative management are treated operatively. Our aim was to evaluate the outcome of operation for hepatic abscess in those failing conservative treatment or in those presenting as a surgical emergency. Patients and methods. This was a retrospective review of patients undergoing operation for hepatic abscess at the Mayo Clinic, Rochester, Minnesota from 1990 to 2003. Results. Of 288 patients diagnosed with hepatic abscesses, 32 required operation. Percutaneous drainage was the initial treatment in 15 (47%). The remaining 17 were initially managed with operation. Operative indication was septic shock (41%), failed nonoperative management (31%), and failure to make a diagnosis (28%). Operation was drainage (62%) or resection (38%). The morbidity and mortality rates were 41% and 15.6%, respectively. Factors associated with increased operative mortality were shock (p=0.04), INR > 1.5 (p=0.03), WBC >15 000 (p=0.04), AST > 150 U/L (p=0.01), alkaline phosphatase >500 U/L (p=0.03), positive blood cultures (p=0.03), total bilirubin >2.0 mg/dl (p0.10), peritonitis (p>0.10), intensive care admission (p>0.10), polymicrobial infection (p>0.10), and blood transfusion (p>0.10). Conclusion. Operative intervention is avoided in 89% of patients with hepatic abscess. Septic shock is the most common reason for operation. Patients with septic shock, INR > 1.5, WBC > 15 000, AST > 150 U/L, total bilirubin >2.0 mg/dl, positive blood cultures, or alkaline phosphatase >500 U/L have increased mortality when undergoing operation for hepatic abscess.

Importance Although conventional bariatric surgery results in weight loss, it does so with potential short-term and long-term morbidity. Objective To evaluate the effectiveness and safety of intermittent, reversible vagal nerve blockade therapy for obesity treatment. Design, Setting, and Participants A randomized, double-blind, sham-controlled clinical trial involving 239 participants who had a body mass index of 40 to 45 or 35 to 40 and 1 or more obesity-related condition was conducted at 10 sites in the United States and Australia between May and December 2011. The 12-month blinded portion of the 5-year study was completed in January 2013. Interventions One hundred sixty-two patients received an active vagal nerve block device and 77 received a sham device. All participants received weight management education. Main Outcomes and Measures The coprimary efficacy objectives were to determine whether the vagal nerve block was superior in mean percentage excess weight loss to sham by a 10-point margin with at least 55% of patients in the vagal block group achieving a 20% loss and 45% achieving a 25% loss. The primary safety objective was to determine whether the rate of serious adverse events related to device, procedure, or therapy in the vagal block group was less than 15%. Results In the intent-to-treat analysis, the vagal nerve block group had a mean 24.4% excess weight loss (9.2% of their initial body weight loss) vs 15.9% excess weight loss (6.0% initial body weight loss) in the sham group. The mean difference in the percentage of the excess weight loss between groups was 8.5 percentage points (95% CI, 3.1-13.9), which did not meet the 10-point target ( P = .71), although weight loss was statistically greater in the vagal nerve block group ( P = .002 for treatment difference in a post hoc analysis). At 12 months, 52% of patients in the vagal nerve block group achieved 20% or more excess weight loss and 38% achieved 25% or more excess weight loss vs 32% in the sham group who achieved 20% or more loss and 23% who achieved 25% or more loss. The device, procedure, or therapy–related serious adverse event rate in the vagal nerve block group was 3.7% (95% CI, 1.4%-7.9%), significantly lower than the 15% goal. The adverse events more frequent in the vagal nerve block group were heartburn or dyspepsia and abdominal pain attributed to therapy; all were reported as mild or moderate in severity. Conclusion and Relevance Among patients with morbid obesity, the use of vagal nerve block therapy compared with a sham control device did not meet either of the prespecified coprimary efficacy objectives, although weight loss in the vagal block group was statistically greater than in the sham device group. The treatment was well tolerated, having met the primary safety objective. Trial Registration clinicaltrials.gov Identifier:NCT01327976

Objective To determine prospectively the results of Roux-en-Y gastric bypass (RYGB) used as the primary weight-reducing operation in patients with medically complicated ("morbid") obesity. The RYGB procedure combines the advantages of a restrictive physiology (pouch of 10 mL) and a "dumping physiology" for high-energy liquids without requiring an externally reinforced (banded) stoma. Patients and Methods Between April 1987 and December 1998, a total of 191 consecutive patients with morbid obesity (median weight, 138 kg [range, 91–240 kg]; median body mass index, 49 kg/m 2 [range, 36–74 kg/m 2 ]), all of whom had directly weight-related morbidity, underwent RYGB and prospective follow-up. Results Hospital mortality was 0.5% (1/191), and hospital morbidity occurred in 10.5% (20/191). Good longterm weight loss was achieved, and patients adapted well to the required new eating habits. The mean ± SD weight loss at 1 year after operation (113 patients) was 52±1 kg or 68% ±2% of initial excess body weight. By 3 years postoperatively (74 patients), weight loss was still 66% ±2% of excess body weight. Overall, 53 (72%) of 74 patients had achieved and maintained a weight loss of 50% or more of their preoperative excess body weight 3 years after the operation. In addition, only 1 (1%) of 98 patients had persistent postoperative vomiting 1 or more times per week. Conclusion We believe that RYGB is a safe, effective procedure for most patients with morbid obesity and thus may be the current procedure of choice in patients requiring bariatric surgery for morbid obesity.

Background: Hemosuccus pancreaticus, a rare form of upper gastrointestinal bleeding, may complicate chronic pancreatitis and pose a significant diagnostic and therapeutic dilemma. Aim: To present our experience with this potentially life-threatening complication of chronic pancreatitis. Methods: We reviewed our experience with management (both operative as well as angiographic embolization) of patients with hemosuccus pancreaticus complicating histologically documented chronic pancreatitis between 1976 and 1997. Diagnosis of hemosuccus pancreaticus was based on clinical presentation, preoperative endoscopic and radiographic imaging, operative findings, and pathologic evaluation. Results: During the period, we managed eight patients with hemosuccus pancreaticus (1.5% of all patients with chronic pancreatitis treated surgically). Gastrointestinal bleeding presented as hematemesis in three and hematochezia in three, but all had recent melena and were anemic; three of these patients were hemodynamically unstable. Abdominal pain was present in six. When performed, angiography (n=6) was diagnostic of a pseudoaneurysm; computed tomography (n=7) showed a pseudoaneurysm in two and a pseudocyst in five. Endoscopy (n=8) revealed blood issuing from the ampullary papilla in two patients. Operative management (n=6) involved distal pancreatectomy, pancreatoduodenectomy, or total pancreatectomy in two patients each. Angiographic embolization was successful in one patient, but the other died from uncontrollable hemorrhage. Conclusions: Hemosuccus pancreaticus is rare, but should be considered in patients with chronic pancreatitis and gastrointestinal bleeding. In the absence of pancreatitis-related indications for surgery, angiographic embolization can be definitive treatment. If there are pancreatitis-related indications for operation, angiographic embolization may allow an elective operative procedure based on structural changes of the pancreas. If embolization fails, pancreatic resection is usually required, often on an emergent basis.

Cholangiocarcinoma is a highly-malignant adenocarcinoma originating from cholangiocytes. Current concepts support escape from immune surveillance using aberrant expression of Fas ligand (FasL) and dysregulation of receptor (FasR) signaling as a potential mechanism for tumor progression. Our aims were to determine if altered expression of FasR and FasL or changes in expression of FLICE inhibitor (I-FLICE) allow cholangiocarcinoma cells to escape immune surveillance. Human cholangiocarcinoma cell lines were evaluated for the functional expression of FasR and FasL by (1) quantitating apoptosis after incubation of cells with agonistic antibodies and (2) an in vitro cell death assay involving coculture of cholangiocarcinoma cells with Fas-sensitive thymocytes. I-FLICE antisense treatment was performed by stable transfection with complementary DNA (cDNA) for I-FLICE in the reverse orientation. We found that normal cholangiocytes in vivo express FasL. Human cholangiocarcinoma cell lines express both FasL and FasR and I-FLICE. FasL expressed by cholangiocarcinomas in vitro induced lymphocyte cell death (70% after 24 hours). Despite the expression of FasR, exposure of the cells to agonistic antibodies (500 ng/mL) induced only minimal apoptosis in the Jurkat cells. Antisense treatment of cholangiocarcinomas in vitro with I-FLICE reduced protein expression of I-FLICE by 90% to 95% and increased Fas-mediated apoptosis 2-fold. We concluded that cholangiocarcinomas escape immune surveillance either by disabling FasR signaling through the expression of I-FLICE and/or increased FasL expression to induce apoptosis of invading T cells. Reduction of I-FLICE expression in cholangiocarcinoma cells restored Fas-mediated apoptosis. Therapeutic maneuvers to inhibit expression of I-FLICE may aid in the treatment of cholangiocarcinoma.

Background Resection of liver metastases from neuroendocrine cancer (NEC) prolongs survival and provides durable symptom relief. Not all hepatic lesions are amenable to resection, particularly when there is multifocal involvement. In this study, it was hypothesized that ablation of concomitant non‐resectable NEC liver metastases is safe and salvages patients who would not have been selected for cytoreductive surgery. Methods Patients who underwent adjuvant ablation of NEC liver metastases between 1995 and 2008 were reviewed. NEC was classified by patient and tumour characteristics. Regression and Kaplan–Meier models were used to compare variables and generate survival curves. Results Ninety‐four patients underwent hepatic resection and intra‐operative ablation of metastatic NEC. The median number of lesions ablated was 3, and median size was 1.4 cm. One abscess occurred at an ablation site. Local recurrence was detected in four patients (3.8%). Overall survival was 80% and 59% at 5 and 10 years. Age, gender, tumour type, grade, primary site and need for repeat ablation had no significant association with survival. The Ki67 proliferative index was a significant predictor of decreased survival. Symptom‐free survival was 34% at 3 years and 16% at 5 years, independent of the tumour grade. Conclusion Concurrent ablation of NEC metastases to the liver not amenable to resection is safe and increases the candidacy of patients for cytoreductive surgery. Ablation performed intra‐operatively and repeated post‐operatively as needed provides significant symptom control regardless of the tumour grade.

Hepatic resection is the only treatment for patients with colorectal cancer metastatic to the liver that has resulted in long-term survival. This apparent efficacy of hepatectomy has prompted efforts to expand the surgical approach for disease progression within the liver. A review of personal experience and of the literature was performed in an attempt to define the role of surgery for disease progression. Twenty-one patients who underwent hepatic resection between 1983 and 1991 for isolated disease progression in the liver were retrospectively reviewed. The median follow-up of patients still alive was 1·7 years (range 4 months to 4·5 years). The median survival from the date of repeat hepatic resection was 3·4 years with an estimated actuarial survival rate of 43 per cent at 4 years. These patients experienced no significant morbidity and the mortality rate was 5 per cent. Hepatic resection of metastatic colorectal carcinoma can produce long-term survival without prohibitive risk. These findings support an aggressive surgical approach for metastatic progression in the liver from colorectal carcinoma.

Although the increased risk of developing pancreatic cancer (PC) in families with a strong history of the disease is well known, characteristics and outcomes of patients with familial PC is not described well.This study aims to evaluate outcomes following resection in patients with familial PC.We studied 208 patients who underwent resection of PC from 2000 to 2007 and had prospectively completed family history questionnaires for the Biospecimen Resource for Pancreas Research at our institution. We compared clinical characteristics and outcomes of familial and sporadic PC patients.Familial (N = 15) and sporadic PC patients (N = 193) did not have significantly different demographics, pre-operative CA19-9, pre-operative weight loss, R0 status, or T-staging (all p ≥ 0.05). Familial PC patients had lower pre-operative total serum bilirubin concentrations (p = 0.03) and lesions outside of the pancreatic head more frequently (p = 0.02) than sporadic PC patients. There was no difference in survival at 2 years between familial and sporadic PC patients (p = 0.52).Familial PC patients appear to develop tumors outside of the pancreatic head more frequently than sporadic PC patients. This difference in tumor distribution may be due to a broader area of cancer susceptibility within the pancreas for familial PC patients.

Background Outcomes for patients with hepatocellular carcinoma (HCC) without cirrhosis and factors associated with disease progression remain unclear. The goals of this single-institution study were to define the outcomes for such patients, and to determine factors associated with survival and disease progression. Methods This was a retrospective review of consecutive patients with HCC without cirrhosis who underwent hepatic resection between 1985 and 2003. Survival was estimated by the Kaplan–Meier method and risk factors were identified by Cox proportional hazards models. Results A total of 143 patients were enrolled, of whom 29·4 per cent had identifiable risk factors for chronic liver disease. Major resection (at least three segments) was undertaken in 63·6 per cent of patients. The operative mortality rate was 3·5 per cent. Median disease-free survival was 2·4 years. Multivariable analysis revealed presence of multiple tumours as the only independent predictor of tumour recurrence. Median overall survival was 3·3 years. Factors independently associated with decreased overall survival were multiple tumours, high histological grade, perioperative transfusion, male sex and age at least 66 years. Conclusion Patients with HCC but without cirrhosis have acceptable outcomes after resection. Specific risk factors for the development of HCC in these patients have yet to be defined.

BackgroundHepatic epithelioid haemangioendothelioma (HEH) is a rare vascular neoplasm with unpredictable clinical behaviour.AimTo compare overall survival (OS) and disease-free survival (DFS) between liver resection (LR) and orthotopic liver transplantation (OLT) for the treatment of HEH.MethodsRetrospective review of 30 patients with HEH treated at Mayo Clinic during 1984 and 2007.ResultsMedian age was 46 years with a female predominance of 2:1. Treatment included LR (n= 11), OLT (n= 11), chemotherapy (n= 5) and no treatment (n= 3). LR was associated with a 1-, 3- and 5-year OS of 100%, 86% and 86% and a DFS of 78%, 62% and 62%, respectively. OLT was associated with a 1-, 3- and 5-year OS of 91%, 73% and 73% and a DFS 64%, 46% and 46%, respectively. Metastases were present in 37% of patients but did not significantly affect OS. Important predictors of a favourable OS and DFS were largest tumour ≤ 10cm and multifocal disease with ≤10 nodules.ConclusionLR and OLT achieve comparable results in the treatment of HEH. LR is appropriate for patients with resectable disease and favourable prognostic factors. OLT is appropriate for patients with unresectable disease and possibly those with unfavourable prognostic factors. Metastases may not be a contraindication to surgical treatment.

Laparoscopic distal pancreatectomy (LDP) provides outcome advantages compared with open distal pancreatectomy (ODP).Single-institutional, retrospective review from January 1, 2004, to May 1, 2009.Tertiary referral center.Patients undergoing LDP (n = 100) were matched by age, pathologic diagnosis, and pancreatic specimen length to a cohort undergoing ODP (n = 100).Perioperative outcomes and overall 30-day morbidity and mortality. Univariate and multivariate analyses were performed using logistic or linear regression as appropriate.Patients in the LDP group did not differ from those in the ODP group in age (mean, 59.0 vs 58.6 years; P = .85), sex (60% vs 50% female; P = .16), body mass index (calculated as weight in kilograms divided by height in meters squared) (mean, 27.4 vs 27.9; P = .44), or American Society of Anesthesiologists score of 3 or higher (58% vs 52%; P = .39). Tumor size was greater in the ODP group than in the LDP group (mean, 4.0 vs 3.3 cm; P = .02). The LDP group as compared with the ODP group demonstrated decreased blood loss (mean, 171 vs 519 mL; P.001) and shorter duration of hospital stay (mean, 6.1 vs 8.6 days; P.001). There were no differences between the LDP and ODP groups in operative time (mean, 214 vs 208 minutes; P = .50), pancreatic leak rate (17% vs 17%; P.99), overall 30-day morbidity (34% vs 29%; P = .45), and 30-day mortality (3% vs 1%; P = .62).The laparoscopic approach to distal pancreatectomy appears to provide advantages of reduced blood loss and length of hospital stay in selected patients compared with the open approach. Overall complication rates appear similar. Patient selection bias and limits of a retrospective analysis warrant prospective validation.

To determine if neoadjuvant FOLFOX/FOLFIRI is associated with improved disease-free survival (DFS) or overall survival (OS) in patients with colorectal metastases (CRM) to the liver. Ninety-nine patients (from 457 eligible) with CRM that underwent hepatic resection during 2000 to 2005 were included. Group 1 (n = 44) patients received neoadjuvant FOLFOX/FOLFIRI, and Group 2 (n = 55) did not receive neoadjuvant therapy. There were 58% men. The median age for Group 1 was 58 and Group 2, 64 (p = 0.03). OS for Group 1 at 1, 3, and 5 years was 93%, 62%, and 51%, respectively, with a median OS of 5.8 years. In Group 2 survival at 1l, 3, and 5 years was 90%, 63%, and 45%, respectively, with a median OS of 3.7 years (HR 1.06, p = 0.87). The DFS for Group 1 at 1, 3, and 5 years was 51%, 20%, and 20%, with a median DFS of 1.1 years and Group 2 at 1, 3, and 5 years was 58%, 32%, and 32% (median DFS—1.2 years; HR = 1.24, p = 0.45). Neoadjuvant FOLFOX/FOLFIRI was employed more frequently in younger patients with CRM; however, neoadjuvant chemotherapy for CRM was not significantly associated with an increase in OS or DFS, despite additional adjuvant therapy.

Introduction: Predictors of outcome in patients with metastatic colorectal cancer remain inconsistent. We aimed to identify predictors of outcome in these patients, to develop a prognostic scoring system, and to assess the general applicability of the current major risk scoring systems. Materials and Methods: Following IRB approval, medical records of 662 consecutive patients undergoing resection of colorectal metastases to the liver during 1960 to 1995 were reviewed. Clinicopathologic and outcome data were assessed from records and mailed questionnaire. Clinicopathologic variables were tested using univariate and multivariate analyses; best-fit models were then generated to study the effect of each independent risk factor on outcome. To validate existing scoring models, our independent data set was applied to those scores. The relative concordance probability estimates were calculated for these models and compared with that of the proposed Mayo model. Results: The overall and disease-specific 5-year survival rates were 37% and 42%, respectively. The probability of recurrence at any site was 65% at 5 years. Perioperative blood transfusion and positive hepatoduodenal nodes were the major determinants of survival and recurrence. To assess the general applicability of the proposed risk scoring systems, we imported the data from our patient population into 3 other scoring systems. Neither survival nor recurrence among our patients was stratified discretely by any of the scoring systems. Based on probability estimates, all models were only marginally better than chance alone in predicting outcome. Conclusion: Broad application of risk scoring systems for patients with metastatic colorectal cancer has limited clinical value and refinement and external validation should be undertaken before utilization.

The epidemic of obesity in developed countries has resulted in patients with extreme (class III) obesity undergoing the full breadth of medical and surgical procedures. The popularity of bariatric surgery in the treatment of extreme obesity has raised awareness of the unique considerations in the care of this patient population. Minimizing the risk of perioperative complications that contribute to morbidity and mortality requires input from several clinical disciplines and begins with the preoperative assessment of the patient. Airway management, intravenous fluid administration, physiologic responses to pneumoperitoneum during laparoscopic procedures, and the risk of thrombotic complications and peripheral nerve injuries in extremely obese patients are among the factors that present special intraoperative challenges that affect postoperative recovery of the bariatric patient. Early recognition of perioperative complications and education of the patient regarding postoperative issues, including nutrition and vitamin supplementation therapy, can improve patient outcomes. A suitable physical environment and appropriate nursing and dietetic support provide a safe and dignified hospital experience. This article reviews the multidisciplinary management of extremely obese patients who undergo bariatric surgery at the Mayo Clinic.

Hypothesis Major hepatectomy, bile duct resection, and regional lymphadenectomy for hilar cholangiocarcinoma are associated with actual long-term (>5 years) survival. Design Retrospective outcome study. Setting Single tertiary referral institution. Patients Between 1979 and 1997, 46 consecutive patients had resection of hilar cholangiocarcinoma by major hepatectomy, bile duct resection, and regional lymphadenectomy. Main Outcome Measures Overall survival and tumor recurrence were correlated to clinicopathological factors, operative morbidity, and mortality. Results Twenty-five patients underwent left hepatectomy, 17 underwent right hepatectomy, and 4 had extended right hepatectomy. Eighteen patients underwent resection of segment 1. Negative (R0) resection margins were achieved in 37 patients (80%). The operative mortality rate was 9%, and the surgical morbidity rate was 52%. Actual 1-year, 3-year, and 5-year survival rates were 80%, 39%, and 26%, respectively. Factors adversely associated with patient survival rates included: male sex, lymph node metastases, tumor grade 3 or 4, elevated direct serum bilirubin level at diagnosis, elevated preoperative activated partial thromboplastin time, and more than 4 U of red blood cells transfused perioperatively. Tumor size and R0 resection approached significance for survival. Factors associated with tumor recurrence included: male sex, tumor grade 3 or 4, a low hemoglobin level both at diagnosis and preoperatively, and a low preoperative prothrombin time and low alkaline phosphatase level at diagnosis and preoperatively. Median time to recurrence was 3.6 years. Tumor recurrence was predominantly local and regional. Conclusions The actual 5-year survival rate of 26% justifies major partial hepatectomy, bile duct resection, and regional lymphadenectomy for hilar cholangiocarcinoma. The high frequency of local and regional recurrence warrants investigation of adjuvant therapy.

UNLABELLED: Octreotide may be a life-saving treatment in the case of an acute carcinoid crisis, but when given as an i.v. bolus in larger doses, it may cause significant effects on the cardiac conduction system. We describe cardiac conduction impairment observed during octreotide administration in a patient undergoing carcinoid tumor surgery. In this patient, i.v. boluses of 100 microg of octreotide resulted in symptomatic bradycardia, Mobitz type II atrioventricular block, and complete heart block. Perioperative physicians especially need to be aware of these potential effects because they may be more likely to occur during surgery because of the larger doses and boluses that are used to treat acute symptoms secondary to tumor manipulation. IMPLICATIONS: In some susceptible patients, i.v. bolus administration of octreotide may cause significant bradycardia and cardiac conduction defects. Therefore, when octreotide is administered as a bolus, it may be advisable to give it slowly while monitoring the electrocardiogram.

Gastrointestinal neuroendocrine cancers are of significant interest to clinicians and basic scientists. Although accuracy of diagnosis has improved with advances in radioimmune and hormonal assays and in the diagnosis of earlier disease by computed tomography (CT) and magnetic resonance imaging (MRI), many patients still present with hepatic metastases. In contrast to most metastatic gastrointestinal cancers, which have rapid clinical progression with a general decrease in performance status or symptoms related to visceral obstruction and pain, the progression of gastrointestinal neuroendocrine cancers is often slow and associated with clinical endocrinopathies from overproduction of gut hormones. This small subgroup of patients with metastatic neuroendocrine malignancies to the liver has become the focus of intensive multimodality therapy.

for relevant studies (Search date Sept 2013). Case control studies with gastrectomy for benign diseases were included. Gastrectomy for malignant conditions was excluded. Standardized forms were used to extract data. Data was extracted by two reviewers independently. Odds ratio was calculated using comprehensive Meta-analysis software. Newcastle-Ottawa Scale (NOS) was used to assess the quality of study. Heterogeneity was also assessed. Random effects model was used for pooling the data. Results: Eleven case-control studies were included in this study (3951 cases/9609 control). Studies were reported from USA (6), Europe (4) and Taiwan (1). Seven studies included hospital based controls and 4 included population based controls. The sample sized ranged from 142 to 720 (cases) and 180 to 2098 (control). The age of the patients ranged from 20 79 yrs. The risk of pancreatic cancer was not increased in patients with prior history of gastrectomy (OR 1.39; 95% CI, 0.95 -2.03, p= 0.09). Subgroup analysis based on the geographical location revealed the risk was not increased in the USA (OR 1.65; 95% CI, 0.96-2.82, p=0.068) or Europe (OR 1.13; 95% CI 0.61-2.08, p=0.07). Subgroup analysis for Asia was not performed as there was only one study. Subgroup analysis based on the design of the study (population based control or hospital based controls) showed no significant difference. As per NewcastleOttawa Scale, nine studies were of high quality (7 or more NOS points) and two were of low quality (6 NOS points). Subgroup analysis based on quality did not show any significant difference. Moderate heterogeneity was present (I square =56%) and thus random effects model was used for analysis. Conclusion: A prior history of gastrectomy for benign gastric disorders is not associated with an increased risk for pancreatic cancer.

Cholangiocytes are the target of a group of liver diseases termed the cholangiopathies that include conditions characterized by periductal inflammation and cholangiocyte apoptosis. Because inflammation is associated with oxidative stress, we developed the hypothesis that cholangiocytes exposed to oxidative stress will be depleted of endogenous cytoprotective molecules, leading to cholangiocyte apoptosis. To begin to test this hypothesis, we explored the relationships among glutathione (GSH) depletion, expression of Bcl-2 (a protooncogene that inhibits apoptosis), and apoptosis in a nonmalignant human cholangiocyte cell line. Monolayers of human bile duct epithelial cells, derived from normal liver and immortalized by SV40 transformation, were depleted of GSH using buthionine sulfoximine (BSO). Bcl-2 expression was assessed by quantitative immunoblot analysis, and apoptosis quantified by fluorescence microscopy using the DNA binding dye 4′,6′-diamidino-2-phenylindole. Bcl-2 message was assessed by RNase protection assay, and Bcl-2 protein synthesis and half-life by pulse-chase analysis. Exposure of human cholangiocytes in culture to BSO reduced GSH levels by 93 ± 3% ( P < 0.01). In addition, treatment of cholangiocytes with BSO reduced Bcl-2 levels by 87 ± 2% ( P < 0.01) and was associated with a time-dependent increase in the number of cells undergoing apoptosis; ∼11 ± 1% of cultured cells demonstrated morphological changes of apoptosis by 72 h compared with 1.5 ± 0.1% in untreated cholangiocytes ( P < 0.01). Maintenance of GSH levels by addition of glutathione ethyl ester in the presence of BSO blocked the BSO-associated increase in apoptosis in BSO-treated cholangiocytes and also prevented the decrease in Bcl-2 protein. BSO treatment of cholangiocytes did not change steady-state levels of bcl-2 mRNA or Bcl-2 protein synthesis. However, Bcl-2 protein half-life decreased 57% in BSO-treated vs. untreated cells. Our results using a human cholangiocyte cell line demonstrate that reduction in the cellular levels of an antioxidant such as GSH results in increased degradation of Bcl-2 protein and an increase in apoptosis. These data provide a mechanistic link between the consequences of oxidative stress and cholangiocyte apoptosis, an observation that may be important in the pathogenesis of the inflammatory cholangiopathies.

Background: Pseudomyxoma peritonei (PMP) is a rare abdominal malignancy. We hypothesized that next generation exomic sequencing would identify recurrent mutations that may have prognostic or therapeutic implications. Methods and Materials: Ten patients were selected based on availability of tissue and adequate follow-up. Mutations were tested for in 236 cancer-related genes in formalin-fixed paraffin-embedded (FFPE) slides using next-generation exomic sequencing (Foundation Medicine, Cambridge, MA). Immunohistochemistry (IHC) was used to detect MCL1 expression. Results: Detectable mutations were found in 80% of patients. Seventy percent harbored a KRAS mutation, most commonly involving codon 12 (G12D in four cases, and one case each of G12V, G12A and A59T). Four GNAS mutations (R201H/R201C substitutions) were also detected. MCL1 and JUN were concurrently amplified in three patients. One patient with MCL1 and JUN amplification had concurrent amplification of MYC and NFKBIA. ZNF703 was amplified in one patient. Patients with MCL1 amplification were also found to express MCL1 by IHC, but MCL1 expression was also detected in some patients without amplification. Conclusions: We are first to report MCL1 and JUN co-amplification in PMP. Expression of MCL1 may not be completely dependent upon amplification. The prognostic and therapeutic implications of these recurrent mutational events are the subject of ongoing investigation. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A135. Citation Format: Aaron S. Mansfield, Terence Sio, Travis E. Grotz, Rondell P. Graham, Julian R. Molina, Florencia G. Que, Robert C. Miller. Concurrent MCL1 and JUN amplification in pseudomyxoma peritonei. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr A135.

S A T A b st ra ct s differentiated carcinoma (P = 0.006), positive lymph node metastases, (P = 0.006), the need for blood transfusions at hepatectomy (P = 0.02), major hepatectomy (P = 0.017) and major posthepatectomy complications (P = 0.001) were associated with worse overall survival after liver resection. Independent risk factors for shorter overall survival identified in multivariate analysis included poorly differentiated carcinoma (hazard ratio [HR] = 3.1, 95% confidence interval [CI] = 1.17-8.15, P = 0.022), major hepatectomy (HR = 3.0, 95% CI = 1.22-7.39, P = 0.017) and major posthepatectomy complications (HR = 4.1, 95% CI = 1.31-12.57, P = 0.015). Conclusions: liver resection should be considered in selected patients with GELM. Patients with poor differentiated tumor and those who require major hepatectomy because of more advanced disease derive the least benefit from this approach.

We have reviewed in a conceptual manner with appropriate scientific detail the role apoptosis plays in diseases of the gastrointestinal tract. This information should help the clinician and clinician investigator to better understand and treat gastrointestinal diseases. Future investigations in apoptosis probably will provide further insight into the cell-signaling cascades regulating apoptosis, the mechanism(s) by which Bcl-2 inhibits apoptosis, and the precise role of apoptosis in cancer initiation, promotion, and progression. We anticipate that in the future, the practicing gastroenterologist will have therapeutic strategies available to inhibit apoptosis for various gastrointestinal diseases associated with cell death and to induce apoptosis for the treatment of gastrointestinal neoplasia. (Gastroenterology 1996 Apr;110(4):1238-43)

Background/Aims: There is limited information on treatment options for massive, highly symptomatic polycystic liver disease. The aim of the study was to analyze the immediate and long-term outcome of combined liver resection and fenestration. Methods: Information was abstracted from medical records. Follow-up was obtained by mailed questionnaire. Liver volume was quantified by computed tomography. Results: Thirty-one patients underwent liver resection and fenestration between July 1985 and June 1993. Mean liver volume was 9357 mL before and 3567 mL after surgery. There was one death from postoperative intracerebral bleed. Eighteen patients experienced complications, usually transient pleural effusions or transient ascites. Twenty-eight of 29 surviving patients with adequate follow-up have experienced immediate and sustained relief of symptoms and improvement in quality of life. After median follow-up of 2.4 years (range, 0.2 to 7.9 years), most patients have not had clinically significant enlargement of the liver. Sequential computed tomography scans before and after surgery suggest that hepatic enlargement in the age range of the patients in the study mainly resulted from the expansion of existing cysts rather than from the development of new cysts. Conclusions: Selected patients with severe symptomatic polycystic liver disease and favorable anatomy benefit from liver resection and fenestration with acceptable morbidity and mortality. The extent of hepatic resection and fenestration is important for the long-term effectiveness of this procedure.

Objective To evaluate the efficacy of transanastomotic pancreatic duct internal stenting in the reduction of postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy. Design Retrospective study. Setting Mayo Clinic. Patients Between January 1, 1999, and September 30, 2010, 553 patients underwent pancreaticoduodenectomy by a single surgeon. Main Outcome Measures Rates of POPF, morbidity, and mortality between stent and no-stent groups. Results The clinically relevant POPF (International Study Group on Pancreatic Fistula definition grade B or C) rates in the stent and no-stent groups were similar (9.6% [43 of 449 patients] and 12.5% [13 of 104 patients], respectively; P = .38). Postoperative outcomes and morbidity were also similar between the 2 groups. Mortality was 0.7% (3 of 449 patients) for the stent group and 1.0% (1 of 104 patients) for the no-stent group. Four patients (0.9%) required endoscopic retrieval of the anastomotic stent. In subset analysis, the clinically relevant POPF rates in patients with a small pancreatic duct (≤3 mm; n = 167) were similar in the stent and no-stent groups (17.7% [23 of 130 patients] and 24.3% [9 of 37 patients], respectively; P = .38). In patients with a soft pancreatic gland (n = 64), rates of clinically relevant pancreatic fistulae were also similar in the stent and no-stent groups (31.7% [13 of 41 patients] and 17.4% [4 of 23 patients], respectively; P = .20). Conclusions Internal transanastomotic pancreatic duct stenting does not decrease the frequency or severity of POPF. The effect of stenting on long-term anastomotic patency warrants further investigation.

Background: Diabetes is a known, but poorly understood sequela of pancreatic resection in a subset of patients. Our aim was to define the incidence and risk factors of postresection diabetes (PRD) after distal pancreatectomy (DP). Methods: A retrospective review of all consecutive patients undergoing DP at our institution from January 2004 through July 2010. Data was obtained from medical records, pathology reports, and postoperative imaging. Postoperative CT scans were evaluated to determine extent of resection, defined by site of transection as limited (adrenal or left), standard (superior mesenteric artery or left to adrenal), extended (neck), subtotal (into head). Comparisons between patients with and without PRD were evaluated using chi-square, Fisher's exact, and Wilcoxon rank sum tests. Univariate and multivariable associations with PRD were evaluated using logistic regression models and summarized with odds ratios and 95% confidence intervals. Results: Of 583 patients undergoing DP, 90 patients with pre-existing type I (n=24) or type II (n=66) diabetes were excluded. The remaining 493 patients represent the study population with a mean age of 57 years and BMI (kg/m2) of 27.4. Operative indications included benign lesions in 253 patients (51%) and malignancy in 240 (49%). Extent of pancreatic resection was limited in 141 patients (37%), standard in 87 (23%), extended in 128 (33%), and subtotal in 30 (8%). Postoperatively, 179 patients (36%) required no postoperative treatment, 269 (55%) required perioperative hyperglycemic control, and 45 (9%) developed diabetes including 34 requiring insulin, and 11 oral hypoglycemic medication. Patients developing PRD had higher mean preoperative glucose levels (98.2 vs. 112.1, p