Implementation of prospective, surgeon-driven, risk-based pathway for pancreatoduodenectomy results in improved clinical outcomes and first year cost savings of $1 million.

BACKGROUND: Morbidity and costs after pancreatoduodenectomy remain increased, driven by postoperative pancreatic fistula (POPF). A risk-based pathway for pancreatoduodenectomy (RBP-PD) was implemented and the clinical and cost outcomes compared with that of our historic practice. METHODS: Prospective clinical and cost outcomes for our RBP-PD cohort treated from September 2014 to September 2015 were compared with a previously published cohort of pancreatoduodenectomies from January 2007 to February 2014. RESULTS: A total of 128 RBP-PD cases were compared with 808 historic controls. Apart from less blood loss, there were no significant clinical differences between the 2 groups. Overall POPF rate did not change. Average duration of stay decreased to 10 days from 12 (P < .001) despite similar readmission rates. Postsurgical interventional radiology procedures decreased to 18.0% from 26.4% (P = .048). Utilization of and duration of stay in monitored care decreased to 23.4% from 35.6% (P < .01) and to 1 day from 3 (P < .01). On multivariable analysis RBP-PD was independently associated with decreased odds of higher postoperative pancreatic fistula grade, monitored care, and prolonged duration of stay. Inpatient cost of care decreased $6,387 per patient (-11.1%, P = .016), and total 30-day costs decreased $8,565 per patient (-13.7%, P = .01), representing a total 30-day cost savings of $1.1 million. CONCLUSION: RBP-PD significantly improved patient outcomes, decreased costs of care, and likely has applicability for surgical care beyond pancreatoduodenectomy.

Surgical Treatment of Malignant Pheochromocytoma and Paraganglioma: Retrospective Case Series.

INTRODUCTION: Pheochromocytoma and paraganglioma (PPGL) are rare neoplasms; about 10% are malignant. Literature regarding possible benefit from resection is extremely limited. METHODS: A 20 year review of all patients undergoing surgery for malignant PPGL at the Mayo Clinic Rochester Campus between 1994 and June 2014 was performed. RESULTS: We identified 34 patients undergoing surgery for malignant PPGL. Median follow up was 6 and 5 years survival was 90% (median 11 years). Complete resection (R0) was achieved in 14 patients (41%). Median disease-free survival was 4.6 years for patients with R0 resection (up to 12 years). Only eight patients (23%) were disease-free on last follow up. Elevated preoperative fractionated metanephrines or catecholamines were documented in 23 patients (68%); these normalized in 13 of 23 patients (56%) postoperatively-with symptom relief in 15 of 18 preoperatively symptomatic patients (79%). Among 23 patients with hormone-producing tumors, significant reduction in number of antihypertensive medications was also noted postoperatively; 11 patients have remained off all antihypertensives, 6 required 1 medication, 1 required 2, while 5 required full blockade with phenoxybenzamine and a beta-adrenergic blocker. CONCLUSION: Surgery plays a significant role in the management of selected malignant PPGL. Resection can be effective in normalizing or significantly reducing levels of catecholamines and metanephrines, and can improve hormone-related symptoms and hypertension. Surgical resection, either complete or incomplete, is associated with durable survival despite a high rate of tumor recurrence.

Complications and Outcomes Associated With Surgical Management of Renal Cell Carcinoma Involving the Liver: A Matched Cohort Study.

OBJECTIVE: To assess the safety and utility of more aggressive surgical resection of renal cell carcinoma involving the liver at the time of nephrectomy. MATERIALS AND METHODS: We identified 34 cases at our institution where patients underwent simultaneous nephrectomy and hepatic resection for direct hepatic invasion (n = 17) or metastatic renal cell carcinoma (n = 21). Perioperative outcomes and complication rates were compared with a matched referent cohort (n = 68) undergoing simultaneous nephrectomy and resection of non-hepatic locally invasive or metastatic disease. RESULTS: Of the 34 cases, 17 (50%) patients underwent hepatic resection for pT4 liver involvement and 21 (62%) patients underwent simultaneous nephrectomy and hepatic metastasectomy. Deep vein thrombosis occurred more frequently following hepatic resection (15% vs 1%, P = .02); however, no significant differences were noted in Clavien grade 3-4 complications (12% vs 3%, P = .10) or perioperative mortality (3% vs 0%, P = .67). Two-year cancer-specific and overall survival for patients undergoing hepatic resection and non-hepatic resection were 40% and 29% (hazard ratio: 0.72, P = .2) and 40% and 28% (hazard ratio: 0.80, P = .30), respectively. CONCLUSION: In carefully selected patients, hepatic resection at the time of nephrectomy is associated with a higher risk of deep vein thrombosis and may be associated with a trend toward an increased risk of short-term Clavien IV complications; however, perioperative and overall mortality are comparable with those in matched patients undergoing surgical resection of locally advanced or metastatic disease involving non-hepatic organs.

A multicenter randomized controlled trial comparing pancreatic leaks after TissueLink versus SEAMGUARD after distal pancreatectomy (PLATS) NCT01051856.

BACKGROUND: Pancreatic leak is common after distal pancreatectomy. This trial sought to compare TissueLink closure of the pancreatic stump to that of SEAMGUARD. METHODS: A multicenter, prospective, trial of patients undergoing distal pancreatectomy randomized to either TissueLink or SEAMGUARD. RESULTS: Enrollment was closed early due to poor accrual. Overall, 67 patients were enrolled, 35 TissueLink and 32 SEAMGUARD. The two groups differed in American Society of Anesthesiologist class and diagnosis at baseline and were relatively balanced otherwise. Overall, 37 of 67 patients (55%) experienced a leak of any grade, 15 (46.9%) in the SEAMGUARD arm and 22 (62.9%) in the TissueLink arm (P = 0.19). The clinically significant leak rate was 17.9%; 22.9% for TissueLink and 12.5% for SEAMGUARD (P = 0.35). There were no statistically significant differences in major or any pancreatic fistula-related morbidity between the two groups. CONCLUSIONS: This is the first multicentered randomized trial evaluating leak rate after distal pancreatectomy between two common transection methods. Although a difference in leak rates was observed, it was not statistically significant and therefore does not provide evidence of the superiority of one technique over the other. Choice should remain based on surgeon comfort, experience, and pancreas characteristics.

Metabolic Syndrome is Associated with Increased Postoperative Morbidity and Hospital Resource Utilization in Patients Undergoing Elective Pancreatectomy.

PURPOSE: In patients undergoing elective partial pancreatectomy, our aim was to evaluate the effect of metabolic syndrome (MS) on postoperative mortality, morbidity, and utilization of hospital resources. Our hypothesis was that MS is associated with worse surgical outcomes after pancreatectomy. METHODS: Fifteen thousand eight hundred thirty-one patients undergoing elective pancreatectomy from 2005 to 2012 were identified in the Participant User File of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). Univariable and multivariable analyses were performed examining the association of MS (defined as body mass index ≥30 kg/m(2), hypertension requiring medications, and diabetes requiring medications and/or insulin) and risk of 30-day mortality, morbidity, and utilization of hospital resources (risk of blood transfusion in the first 72 h after pancreatectomy and prolonged hospital stay, defined as ≥13 days, which was the 75th percentile of this cohort). Multivariable logistic regression models controlled for age, sex, race, pancreatectomy type (distal versus proximal), smoking status, alcohol consumption, functional status, dyspnea, cardiovascular disease, hematocrit, INR, serum albumin, bilirubin, and creatinine. Stratified analyses were conducted by type of pancreatectomy and indication for pancreatectomy (benign versus malignant). RESULTS: On univariate analysis, 1070 (6.8%) patients had MS. MS was associated with increased postoperative morbidity, major morbidity, surgical site infection, septic shock, cardiac event, respiratory failure, pulmonary embolism, blood transfusion, and prolonged duration of hospital stay (P < 0.05 for all analyses). After controlling for potentially confounding variables, there was a 26% increased odds of postoperative morbidity (P < 0.001), 17% increased odds of major morbidity (P = 0.034), 32% increased odds of surgical site infection (P < 0.001), 34% increased odds of respiratory failure (P = 0.023), 68% increased odds of pulmonary embolism (P = 0.045), 26% increased odds of blood transfusion (P = 0.018), and 21% increased odds of prolonged hospital stay (P = 0.011) in patients with MS compared to patients without MS. MS was not associated with 30-day mortality after elective pancreatectomy (P = 0.465). When stratified by distal versus proximal pancreatectomy and benign versus malignant disease, the effect of MS on outcomes appears to be modified by type of pancreatectomy and indication with poorer outcomes observed for distal pancreatectomies and benign indications for resection. CONCLUSION: MS is an under-emphasized predictor of increased postoperative morbidity and utilization of hospital resources in patients undergoing elective pancreatectomy. The effect of MS on these postoperative outcomes appears to be more pronounced for patients with benign rather than malignant indications for pancreatectomy and in patients undergoing distal rather than proximal pancreatectomy. These results may inform patient selection, optimization of comorbidities prior to elective pancreatectomy, and strategies for postoperative management.

Spontaneous Hepatic Hemorrhage: A Single Institution's 16-Year Experience.

Spontaneous hemorrhage from hepatic tumors is an uncommon but serious complication. Recently, interventional radiologic (IR) techniques are being used increasingly in the management of these patients. We report our 16-year experience in managing spontaneous hemorrhage from liver tumors. Twenty-six consecutive patients were diagnosed with spontaneous liver hemorrhage between 1995 and 2011. Initial management was operative in eight, IR in six, and supportive in 12 patients. Of those managed operatively, five were segmentectomies; one hemihepatectomy; one wedge resection; and one packing who later died from coagulopathy. In the IR patients, seven had an angiographic embolization; two required reembolization; one underwent resection of a hepatic adenoma 21 days after angiographic embolization. The malignant lesions included hepatocellular carcinoma (n = 6), angiosarcoma (n = 1), metastatic squamous cell carcinoma (n = 1), metastatic leiomyosarcoma (n = 1), nonsquamous cell carcinoma (n = 1), or metastatic angiosarcoma (n = 1). Benign diseases included hepatic adenoma (n = 5), end-stage liver disease (n = 1), and polycystic liver (n = 1). Spontaneous hemorrhage from the liver occurs evenly from benign or malignant causes, one-third of which are primary liver disease. If the patients presents emergently, angiographic embolization may control the bleeding and allow for elective resection once the sequelae of bleeding have resolved.

Pancreatoduodenectomy for Chronic Pancreatitis-Results of a Pain Relief and Quality of Life Survey 15 Years Following Operation.

BACKGROUND: Over the last 30 years, numerous developments in the management of chronic pancreatitis have occurred, leading to multiple surgical and non-surgical options. PATIENTS AND METHODS: All patients who underwent pancreatoduodenectomy for chronic pancreatitis from January 1976 to July 2013 were reviewed. Surviving patients were contacted for a follow-up questionnaire and Short Form (SF)-12 Quality of Life Survey administration. RESULTS: A total of 166 patients were identified (cohort 1:1976-1997(N = 105) and cohort 2:1998-2013(N = 61)). Prior to pancreatoduodenectomy, a higher proportion of patients in cohort 2 had undergone endoscopic stenting, 67 vs 10 % (p < 0.001) and/or celiac plexus block 15 and 5 % (p = 0.026). Median follow-up for all survey respondents was 15 years. On the SF-12, mean physical component score was 43.8 ± 11.8 and mental component score was 54.3 ± 7.9. Patients were significantly lower on the physical component score (p < 0.001) and significantly better on the mental component score (p = 0.001) than the general US population. Mean pain score out of 10 was significantly lower after surgery 1.6 ± 2.6 than before surgery 7.9 ± 3.5 (p < 0.001). Diabetes developed in 28 % of patients who were not diabetic prior to surgery. CONCLUSION: Although practice has changed so that patients have a longer time from presentation until surgery as less-invasive techniques are attempted, pancreatoduodenectomy appears to provide effective long-term pain relief and acceptable quality of life in appropriately selected patients with chronic pancreatitis and intractable pain.

Laparoscopic pancreatoduodenectomy does not completely mitigate increased perioperative risks in elderly patients.

BACKGROUND: Elderly 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. METHODS: A 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. RESULTS: In elderly patients, the incidences of cardiac events (odds ratio [OR] 3.21, P < 0.001), respiratory events (OR 1.68, P = 0.04), delayed gastric emptying (DGE) (OR 1.73, P = 0.003), increased length of stay (LoS, 1 additional day) (P < 0.001), discharge disposition other than home (OR 8.14, P < 0.001) and blood transfusion (OR 1.48, P = 0.05) were greater than in non-elderly patients. Morbidity and mortality did not differ between the OPD and TLPD subgroups of elderly patients. In elderly patients, OPD was associated with increased DGE (OR 1.80, P = 0.03), LoS (1 additional day; P < 0.001) and blood transfusion (OR 2.89, P < 0.001) compared with TLPD. CONCLUSIONS: Elderly patients undergoing TLPD experience rates of mortality, morbidity and cardiorespiratory events similar to those in patients submitted to OPD. In elderly patients, TLPD offers benefits by decreasing DGE, LoS and blood transfusion requirements.

Clinical Risk Score to Predict Pancreatic Fistula after Pancreatoduodenectomy: Independent External Validation for Open and Laparoscopic Approaches.

BACKGROUND: A clinical risk score for pancreatic fistula (CRS-PF) was recently reported to predict postoperative pancreatic fistula (POPF) after pancreatoduodenectomy (PD). An independent external validation has not been performed. Our hypothesis was that CRS-PF predicts POPF after both laparoscopic and open PD. STUDY DESIGN: The CRS-PF was calculated from a retrospective review of patients undergoing PD from January 2007 to February 2014. Postoperative pancreatic fistula was graded using International Study Group of Pancreatic Fistula criteria. Grade B and C leaks were defined as clinically significant. Performance was measured based on sensitivity, specificity, positive and negative predictive value, accuracy, and R(2). RESULTS: There were 808 patients who met inclusion criteria; 539 (66.7%) had open and 269 (33.3%) had laparoscopic PD. The CRS-PF was high risk in 134 patients, intermediate in 492, low in 135, and negligible in 47. Postoperative pancreatic fistula occurred in 191 (23.6%) patients (grade A, 3.8%; B, 14.2%; and C, 5.6%), and it increased with risk category (R(2) = 0.935 all, 0.898 open, and 0.968 laparoscopic). High and intermediate risk categories were combined and classified as "test positive," and negligible and low risk categories were combined and classified "test negative," resulting in a CRS-PF with a sensitivity of 95% and a negative predictive value of 96% for predicting POPF. Contrary to previous studies, grade A POPF increased with increasing CRS-PF and POPF did not correlate with estimated blood loss (R(2) = 0.04). CONCLUSIONS: The CRS-PF was validated independently by predicting POPF for both laparoscopic and open PD. Predictive performance was at least as good for laparoscopic PD as for open PD. Lack of correlation with estimated blood loss suggests CRS-PF might be tailored for improved performance. The CRS-PF is a clinically useful tool for POPF risk stratification after PD and allows for targeted intra- and postoperative measures to address patients at increased risk.

Preoperative anemia is associated with increased use of hospital resources in patients undergoing elective hepatectomy.

BACKGROUND: In patients undergoing elective hepatectomy, we aimed to evaluate the effect of preoperative anemia on postoperative mortality, morbidity, readmission, risk of blood transfusion, and duration of hospital stay. METHODS: A total of 4,170 patients who underwent elective hepatectomy from 2010 to 2012 were identified in the American College of Surgeons National Surgical Quality Improvement Program. Univariate and multivariate analyses were performed by examination of the association of preoperative anemia (defined as hematocrit <5) and the risk of any perioperative blood transfusion (defined as ≥1 unit of blood within 72 hours of operation), mean duration of stay, prolonged duration of stay (defined as ≥9 days, which represented the 75th percentile of this cohort), 30-day readmission, major morbidity, and mortality. RESULTS: A total of 948 patients had preoperative anemia (22.7%). Preoperative anemia was associated with increased risk of any perioperative blood transfusion, prolonged duration of stay, major postoperative complication, and 30-day mortality (P < .05 for all analyses). After controlling for potentially confounding covariates, there was nearly a 3-fold greater risk of blood transfusion (adjusted OR = 2.79, P < .001) and 2-fold greater risk of prolonged duration of stay in anemic versus nonanemic patients (adjusted OR = 1.66, P < .001). Mean duration of stay was 10.0 days and 7.4 days for anemic and nonanemic patients, respectively (P < .001). CONCLUSION: Anemia is associated with an almost 3-fold increased risk of blood transfusion, 2-fold increased risk of prolonged duration of hospitalization, and hospital stays were 2.6 days greater in anemic patients. Anemia may significantly impact resource utilization for elective hepatectomy.

Pancreaticoduodenectomy with major vascular resection: a comparison of laparoscopic versus open approaches.

BACKGROUND: Major vascular resection when necessary for margin control during pancreaticoduodenectomy is relatively universal with perioperative and oncological outcomes that are similar to those of patients undergoing a PD without venous involvement. The present study compares total laparoscopic pancreaticoduodenectomy (TLPD) versus open pancreaticoduodenectomy (OPD) with major vascular resection. METHODS: We reviewed data for all patients undergoing TLPD or OPD with vascular resection at Mayo Clinic Rochester, between the dates of July 2007 and July 2013. RESULTS: A total of 31 patients undergoing TLPD and 58 patients undergoing OPD with major vascular resection were identified. Mean operative blood loss was significantly less in the laparoscopic (842 cc) compared to the open group (1,452 cc) (p < 0.001), as was median hospital stay, 6 (4-118) versus 9 (6-73) days, respectively (p = 0.006). There was no significant difference in the total number of complications (lap 35%, open 48%) (p = 0.24) or severe complications (≥III) (lap 6.4%, open 3.4%) (p = 0.51) in the two groups. In-hospital mortality or 30-day mortality was not statistically different between the laparoscopic and open groups, 3.2 and 3.4%, respectively (p = 0.96). Patency of the reconstructed vessels on postoperative imaging was not significantly different between the TLPD (93%) and OPD groups (91%) (p = 0.76). In patients with a diagnosis of adenocarcinoma, there was no significant difference in overall survival between the two groups (p = 0.22). CONCLUSION: The present study clearly demonstrates that not only is TLPD with major vascular resection feasible and safe but that it can achieve results that are similar in morbidity and mortality as well as oncologic outcome compared to patients undergoing OPD with major vascular resection.

Surgical resection of synchronously metastatic adrenocortical cancer.

INTRODUCTION: Metastatic adrenocortical carcinoma (ACC) is rapidly fatal, with few options for treatment. Patients with metachronous recurrence may benefit from surgical resection. The survival benefit in patients with hematogenous metastasis at initial presentation is unknown. METHODS: A review of all patients undergoing surgery (European Network for the Study of Adrenal Tumors) stage IV ACC between January 2000 and December 2012 from two referral centers was performed. Kaplan-Meier estimates were analyzed for disease-free and overall survival (OS). RESULTS: We identified 27 patients undergoing surgery for stage IV ACC. Metastases were present in the lung (19), liver (11), and brain (1). A complete resection (R0) was achieved in 11 patients. The median OS was improved in patients undergoing R0 versus R2 resection (860 vs. 390 days; p = 0.02). The 1- and 2-year OS was also improved in patients undergoing R0 versus R2 resection (69.9 %, 46.9 % vs. 53.0 %, 22.1 %; p = 0.02). Patients undergoing neoadjuvant therapy (eight patients) had a trend towards improved survival at 1, 2, and 5 years versus no neoadjuvant therapy (18 patients) [83.3 %, 62.5 %, 41.7 % vs. 56.8 %, 26.6 %, 8.9 %; p = 0.1]. Adjuvant therapy was associated with improved recurrence-free survival at 6 months and 1 year (67 %, 33 % vs. 40 %, 20 %; p = 0.04) but not improved OS (p = 0.63). Sex (p = 0.13), age (p = 0.95), and location of metastasis (lung, p = 0.51; liver, p = 0.67) did not correlate with OS after operative intervention. Symptoms of hormonal excess improved in 86 % of patients. CONCLUSION: Operative intervention, especially when an R0 resection can be achieved, following systemic therapy may improve outcomes, including OS, in select patients with stage IV ACC. Response to neoadjuvant chemotherapy may be of use in defining which patients may benefit from surgical intervention. Adjuvant therapy was associated with decreased recurrence but did not improve OS.

Model to predict survival after surgical resection of intrahepatic cholangiocarcinoma: the Mayo Clinic experience.

BACKGROUND: The 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. METHODS: A 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. RESULTS: A 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/m(2) (range: 17-46 kg/m(2) ). 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). CONCLUSIONS: The 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.

Metastasectomy of neuroendocrine tumors in patients with multiple endocrine neoplasia type 1.

BACKGROUND: Neuroendocrine (NE) tumors commonly afflict patients with multiple endocrine neoplasia type 1 (MEN1). It is thought that patients with MEN1 have improved survival compared with individuals with analogous lesions. The role of metastasectomy of NE tumors in MEN1 patients is not clearly defined. METHODS: A review of MEN1 patients undergoing surgery for NE tumors from 1994 to 2010 at a single tertiary care center was performed. Tumor function, the extent of metastasis, R0 resection, and survival were analyzed. RESULTS: We identified 30 patients who underwent resection including synchronous and metachronous metastasectomy. Synchronous metastases were identified in 19 patients (63%), whereas 11 (37%) had metachronous disease. R0 resection was achieved in 93% of patients. Estimated 10-year survival is 86.4% (95% confidence interval, 60% to 100%) with no factors predictive of overall survival. The disease-free interval at 1, 5, and 10 years was 89%, 50%, and 19%, respectively, with recurrence occurring at a median of 5.4 years (95% confidence interval, 77.7% to 100%). Synchronous metastasis (P = .0072; hazard ratio [HR], 3.4) and nonfunctioning tumors (P = .014; HR, 3.3) were more likely to recur, whereas age (P = .09; HR, 1.5), gender (P = .49; HR, 1.3), and the site of metastasis (P = .81; HR, 1.1) did not influence recurrence. DISCUSSION: Patients with MEN1 benefit from resection of metastatic NE disease. Despite a high recurrence rate, survival and disease-free interval is favorable vs patients without MEN1.

Total laparoscopic pancreaticoduodenectomy for pancreatic ductal adenocarcinoma: oncologic advantages over open approaches?

OBJECTIVE: To directly compare the oncologic outcomes of TLPD and OPD in the setting of pancreatic ductal adenocarcinoma. BACKGROUND: Total laparoscopic pancreaticoduodenectomy (TLPD) has been demonstrated to be feasible and may have several potential advantages over open pancreaticoduodenectomy (OPD), including lower blood loss and shorter hospital stay. Whether potential advantages could allow patients to recover in a timelier manner and pursue adjuvant treatment options remains to be answered. METHODS: We reviewed data for all patients undergoing TLPD (N = 108) or OPD (N = 214) for pancreatic ductal adenocarcinoma at our institution between January 2008 and July 2013. RESULTS: Neoadjuvant therapy, tumor size, node positivity, and margin-positive resection were not significantly different between the 2 groups. Median length of hospital stay was significantly longer in the OPD group (9 days; range, 5-73 days) than in the TLPD group (6 days; range, 4-118 days; P < 0.001). There was a significantly higher proportion of patients in the OPD group (12%) who had a delay of greater than 90 days or who did not receive adjuvant chemotherapy at all compared with that in the TLPD group (5%; P = 0.04). There was no significant difference in overall survival between the 2 groups (P = 0.22). A significantly longer progression-free survival was seen in the TLPD group than in the OPD group (P = 0.03). CONCLUSIONS: TLPD is not only feasible in the setting of pancreatic ductal adenocarcinoma but also has advantages such as shorter hospital stay and faster recovery, allowing patients to recover in a timelier manner and pursue adjuvant treatment options. This study also demonstrated a longer progression-free survival in patients undergoing TLPD than those undergoing OPD.

Effect of reversible intermittent intra-abdominal vagal nerve blockade on morbid obesity: the ReCharge randomized clinical trial.

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.

Adenomas of the ampulla of Vater: a comparison of outcomes of operative and endoscopic resections.

BACKGROUND: Data comparing operative and endoscopic resection of adenomas of the ampulla of Vater are limited. Our aims were to evaluate and compare the long-term results and outcomes of endoscopic and operative resections of benign tumors of the ampulla of Vater as well as to determine which features of benign periampullary neoplasms would predict recurrence or failure of endoscopic therapy and therefore need for operative treatment. METHODS: Retrospective review of all patients treated for adenomas of ampulla of Vater at our institution from 1994 to 2009. RESULTS: Over a 15-year span, 180 patients (mean age 59 years) were treated for benign adenomas of the ampulla of Vater with a mean follow-up of 4.4 years. Obstructive jaundice was more common in the operative resection group (p = 0.006). The adenomas were tubular in 83 patients (44%), tubulovillous in 77 (45%) and villous in 20 (11%). Endoscopic resection alone was performed in 130 patients (78%). Operative resection was performed in 50 patients (28%), with pancreatoduodenectomy in 40, transduodenal local resection in 9, and pancreas-sparing total duodenectomy in 1. Nine patients who underwent endoscopic resection initially were endoscopic treatment failures. Fifty-eight percent of endoscopically treated patients required one endoscopic resection, while 58 (42%) required two or more endoscopic resections (range 2-8). Patients who underwent operative resection had larger tumors with a mean size of 3.7 ± 2.8 versus 1.8 ± 1.5 cm in those treated by endoscopic resection (p < 0.001) or intraductal extension (p = 0.02). Intraductal extension and ulceration had no effect on recurrence if completely resected endoscopically (p = 0.41 and p = 0.98, respectively). Postoperative complications occurred in 58% of patients, and post-endoscopic complications in 29% (p < 0.001). Endoscopic resection was associated with a greater than fivefold risk of recurrence than operative resection (p = 0.006); 4% of recurrences had invasive carcinomas. When comparing patients who underwent local resections only (endoscopic and operative), there was no difference in the recurrence rate between endoscopic resection and operative transduodenal resection (32 versus 33%; p = 0.49). The need for two or more endoscopic resections for complete tumor removal was associated with 13-fold greater risk of recurrence (p < 0.001). CONCLUSION: There is no significant difference between endoscopic and local operative resections of benign adenomas of ampulla of Vater; recurrences are more common when two or more endoscopic resections are required for complete tumor removal. Appropriate adenomas for endoscopic resection included tumors <3.6 cm that do not extend far enough intraductally (on EUS) to preclude an endoscopic snare ampullectomy.

Portal venous thrombosis after distal pancreatectomy: clinical outcomes.

AIM: Outcomes of patients developing portal vein (PV) thrombosis (PVT) after distal pancreatectomy (DP) are unknown. The goal of this study was to identify risk factors for PVT and describe the long-term outcomes in these patients. METHODS: Patients undergoing DP without repair or reconstruction of the PV between 2001 and 2011 were included. Patients that showed evidence of PVT on pre-operative imaging were excluded from the study. Location and extent of thrombosis was determined by post-operative computed tomography or ultrasound imaging in all patients. Evidence of systemic thrombosis (if present) in addition to PVT was also documented. RESULTS: In the study period, 991 patients underwent DP and 21 (2.1%) patients were diagnosed with PVT. Pancreatic neoplasm was the most frequent indication for operation (n = 11). Thrombus occurred in the main PV in 15 and the right branch of the PV in 8 patients. Complete PV occlusion occurred in nine patients with a median time to diagnosis of 16 days (range 5-85 days). Seventeen patients were anticoagulated for a median duration of 6 months (range 3.3-36 months) after the diagnosis of PVT. Over a median follow-up of 22 months, resolution of PVT occurred in seven patients. Predictors of non-resolution of PVT included anesthesia time >180 min (p = 0.025), DM type II (p = 0.03), BMI >30 Kg/m(2) (p = 0.03), occlusive PVT (p < 0.001), or thrombus in a sectoral branch (p = 0.02). Anticoagulation therapy did not influence the frequency of thrombus resolution and was complicated by gastrointestinal hemorrhage in four patients. There was no mortality as a direct result of PVT or anticoagulation. CONCLUSION: PVT after distal pancreatectomy is a rare complication. Serious complications as a direct result of PVT in this setting are uncommon and are not dependent on thrombus resolution. Although anticoagulation does not appear to influence the rate of PVT resolution in this small retrospective series, we support the use of anticoagulation until larger, controlled studies define clear advantages or disadvantages.

Concurrent MCL1 and JUN amplification in pseudomyxoma peritonei: a comprehensive genetic profiling and survival analysis.

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. Ten patients were selected on the basis of availability of tissue and adequate follow-up. They were treated at our institution between September 2002 and August 2004. Using next-generation exomic sequencing, we tested for mutations in 236 cancer-related genes in formalin-fixed paraffin-embedded slides. MCL1 amplification was additionally tested with immunohistochemical staining. Detectable mutations were found in 8 patients (80%). Seven patients harbored a KRAS mutation, most commonly involving codon 12. 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 with immunohistochemistry, but MCL1 expression was also detected in some patients without amplification. To our knowledge, we are the first to report MCL1 and JUN coamplification in PMP. Expression of MCL1 may not be completely dependent on amplification. The prognostic and therapeutic implications of these recurrent mutational events are the subject of ongoing investigation.

Correlation of staging systems to survival in patients with resected hilar cholangiocarcinoma.

BACKGROUND: We aimed to identify staging parameters associated with survival in patients with hilar cholangiocarcinoma. METHODS: Clinicopathologic characteristics were obtained retrospectively for all resected patients with Bismuth-Corlette III cholangiocarcinoma between 1993 and 2011. Patients were stratified by the American Joint Commission on Cancer (AJCC) (7th edition) and Memorial Sloan-Kettering Cancer Center (MSKCC) staging systems. Survival analyses tested the effects of clinicopathologic factors and staging covariates on recurrence-free and overall survival. RESULTS: Eighty patients (mean age 63 ± 11 years, 63% male) underwent anatomic hepatectomy with bile duct resection/reconstruction for Bismuth-Corlette IIIa (53%) and IIIb (47%) cholangiocarcinoma. The median follow-up was 26 months (interquartile range = 12 to 50 months), and the median time to recurrence was 15 months (interquartile range = 6 to 38 months). Neither AJCC nor MSKCC staging systems were associated with recurrence-free survival (all P ≥ .059). MSKCC T-stage but not the AJCC staging system was associated with overall survival (P ≤ .026). CONCLUSIONS: MSKCC T-stage classification but not AJCC staging is independently associated with overall survival for patients after resection of hilar cholangiocarcinoma.