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Importance: Combining immune checkpoint blockade (ICB) with chemotherapy improves outcomes in patients with metastatic gastric and gastroesophageal junction (G/GEJ) adenocarcinoma; however, whether this combination has activity in the perioperative setting remains unknown., Objective: To evaluate the safety and preliminary activity of perioperative chemotherapy and ICB followed by maintenance ICB in resectable G/GEJ adenocarcinoma., Design, Setting, and Participants: This investigator-initiated, multicenter, open-label, single-stage, phase 2 nonrandomized controlled trial screened 49 patients and enrolled 36 patients with resectable G/GEJ adenocarcinoma from February 10, 2017, to June 17, 2021, with a median (range) follow-up of 35.2 (17.4-73.0) months. Thirty-four patients were deemed evaluable for efficacy analysis, with 28 (82.4%) undergoing curative resection. This study was performed at 4 referral institutions in the US., Interventions: Patients received 3 cycles of capecitabine, 625 mg/m2, orally twice daily for 21 days; oxaliplatin, 130 mg/m2, intravenously and pembrolizumab, 200 mg, intravenously with optional epirubicin, 50 mg/m2, every 3 weeks before and after surgery with an additional cycle of pembrolizumab before surgery. Patients received 14 additional doses of maintenance pembrolizumab., Main Outcomes and Measures: The primary end point was pathologic complete response (pCR) rate. Secondary end points included overall response rate, disease-free survival (DFS), overall survival (OS), and safety., Results: A total of 34 patients (median [range] age, 65.5 [25-90] years; 23 [67.6%] male) were evaluable for efficacy. Of these patients, 28 (82.4%) underwent curative resection, 7 (20.6%; 95% CI, 10.1%-100%) achieved pCR, and 6 (17.6%) achieved a pathologic near-complete response. Of the 28 patients who underwent resection, 4 (14.3%) experienced disease recurrence. The median DFS and OS were not reached. The 2-year DFS was 67.8% (95% CI, 0.53%-0.87%) and the OS was 80.6% (95% CI, 0.68%-0.96%). Treatment-related grade 3 or higher adverse events for evaluable patients occurred in 20 patients (57.1%), and 12 (34.3%) experienced immune-related grade 3 or higher adverse events., Conclusion and Relevance: In this trial of unselected patients with resectable G/GEJ adenocarcinoma, capecitabine, oxaliplatin, and pembrolizumab resulted in a pCR rate of 20.6% and was well tolerated. This trial met its primary end point and supports the development of checkpoint inhibition in combination with perioperative chemotherapy in locally advanced G/GEJ adenocarcinoma., Trial Registration: ClinicalTrials.gov Identifier: NCT02918162.

Patients with pancreatic ductal adenocarcinoma (PDAC) have a grim prognosis despite complete surgical resection and intense systemic therapies. While immunotherapies have been beneficial with many different types of solid tumors, they have almost uniformly failed in the treatment of PDAC. Understanding how therapies affect the tumor immune microenvironment (TIME) can provide insights for the development of strategies to treat PDAC. We used quantitative multiplexed immunofluorescence (qmIF) quantitative spatial analysis (qSA), and immunogenomic (IG) analysis to analyze formalin-fixed paraffin embedded (FFPE) primary tumor specimens from 44 patients with PDAC including 18 treated with neoadjuvant chemoradiation (CRT) and 26 patients receiving no treatment (NT) and compared them with tissues from 40 treatment-naïve melanoma patients. We find that relative to NT tumors, CD3 + T cell infiltration was increased in CRT treated tumors (p = .0006), including increases in CD3 + CD8 + cytotoxic T cells (CTLs, p = .0079), CD3 + CD4 + FOXP3 - T helper cells (T h , p = .0010), and CD3 + CD4 + FOXP3 + regulatory T cells (Tregs, p = .0089) with no difference in CD68 + macrophages. IG analysis from micro-dissected tissues indicated overexpression of genes involved in antigen presentation, T cell activation, and inflammation in CRT treated tumors. Among treated patients, a higher ratio of Tregs to total T cells was associated with shorter survival time (p = .0121). Despite comparable levels of infiltrating T cells in CRT PDACs to melanoma, PDACs displayed distinct spatial profiles with less T cell clustering as defined by nearest neighbor analysis (p < .001). These findings demonstrate that, while CRT can achieve high T cell densities in PDAC compared to melanoma, phenotype and spatial organization of T cells may limit benefit of T cell infiltration in this immunotherapy-resistant tumor., Competing Interests: YMS has recieved funding from Regeneron. BTF has financial interests in both Regeneron and Thermo Fisher Scientific. GAM is a consultant for CEND Biopharma and Synthekine, and has recieved funding from MERCK, Roche, BioLine, and Regeneron. None of the disclosures listed are related to this work., (© 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.)

Background: Total gastrectomy with Roux-en-Y esophagojejunostomy is a life-extending procedure for patients with nonmetastatic proximal gastric and gastroesophageal junction adenocarcinoma, yet it can be a life-altering procedure with negative impact on quality of life. 1 Perioperative recovery often involves the need for supplemental nutrition (either enteral or parenteral). Furthermore, long-term effects of early satiety, dysphagia, sustained weight loss, and difficulty in maintaining a healthy weight, dumping syndrome, and intestinal overgrowth are not unusual. Although the alternative of untreated cancer is clearly unacceptable, these lifestyle consequences are not benign., Methods: A retrospective review of patients who had undergone laparoscopic total and proximal gastrectomy for gastric adenocarcinoma was conducted. Patient demographic data, pathologic parameters, and short-term and long-term clinical data were compared between total gastrectomy and proximal gastrectomy cohorts., Results: Seventeen patients were included in the study: 13 had undergone laparoscopic total gastrectomy (LTG) and 4 had undergone laparoscopic proximal gastrectomy (LPG). Patients who had LPG, given the nature of the procedure, were confined to early stage (up to T2) tumors in the gastric cardia or GE junction. Patients who had LTG tended to be larger, later stage tumors (but not exclusively). The mean operative time was greater for LTG than for LPG (247 ± 54 versus 181 ± 49 min, respectively, P  = .036). Length of hospital stay (9.0 ± 3.2 versus 5.0 ± 0.8 days, P  < .001) and readmission for postoperative complication (38.5 versus 0%, P  = .009) were also higher in the LTG group. There was no significant difference in terms of mean estimated blood loss or blood transfusion rates, overall complications, or anastomotic stricture requiring endoscopic dilation between the patients who underwent LTG and those who underwent LPG., Conclusion: In early stage tumors (T1b or T2), proximal gastrectomy (PG) should be considered to mitigate diminished quality of life. PG with esophagogastrostomy, which can easily be performed minimally invasively, can be more tolerable for the patient, with no anatomic basis for dumping syndrome or small intestinal bacterial overgrowth (SIBO), and a greater reservoir for more normal meal habits when compared to total gastrectomy (TG) with Roux-en-Y reconstruction., Competing Interests: Conflicts of interest: The authors declare no conflict of interest., (© 2021 by SLS, Society of Laparoscopic & Robotic Surgeons.)

Patients with chronic pancreatitis have benefited from total pancreatectomy and autologous islet cell transplantation (TPAIT) since the 1970s. Over the past few decades, improvements have been made in surgical technique and perioperative management that have led to improved success of islet cell function, insulin independence and patient survival. This article focuses on recent updates and advances for the TPAIT procedure that continue to expand and innovate the impact on patients with debilitating disease.

Context: The prevalence of obesity is burgeoning among African American and Latina women; however, few studies investigating the skeletal effects of bariatric surgery have focused on these groups., Objective: To investigate long-term skeletal changes following Roux-en-Y gastric bypass (RYGB) in African American and Latina women., Design: Four-year prospective cohort study., Patients: African American and Latina women presenting for RYGB (n = 17, mean age 44, body mass index 44 kg/m2) were followed annually for 4 years postoperatively., Main Outcome Measures: Dual-energy x-ray absorptiometry (DXA) measured areal bone mineral density (aBMD) at the spine, hip, and forearm, and body composition. High-resolution peripheral quantitative computed tomography measured volumetric bone mineral density (vBMD) and microarchitecture. Individual trabecula segmentation-based morphological analysis assessed trabecular morphology and connectivity., Results: Baseline DXA Z-Scores were normal. Weight decreased ~30% at Year 1, then stabilized. Parathyroid hormone (PTH) increased by 50% and 25-hydroxyvitamin D was stable. By Year 4, aBMD had declined at all sites, most substantially in the hip. There was significant, progressive loss of cortical and trabecular vBMD, deterioration of microarchitecture, and increased cortical porosity at both the radius and tibia over 4 years. There was loss of trabecular plates, loss of axially aligned trabeculae, and decreased trabecular connectivity. Whole bone stiffness and failure load declined. Risk factors for bone loss included greater weight loss, rise in PTH, and older age., Conclusions: African American and Latina women had substantial and progressive bone loss, deterioration of microarchitecture, and trabecular morphology following RYGB. Further studies are critical to understand the long-term skeletal consequences of bariatric surgery in this population., (© The Author(s) 2020. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Fibrinolysis is initiated by tissue-type plasminogen activator (tPA) and inhibited by plasminogen activator inhibitor 1 (PAI-1). In obese humans, plasma PAI-1 and tPA proteins are increased, but PAI-1 dominates, leading to reduced fibrinolysis and thrombosis. To understand tPA-PAI-1 regulation in obesity, we focused on hepatocytes, a functionally important source of tPA and PAI-1 that sense obesity-induced metabolic stress. We showed that obese mice, like humans, had reduced fibrinolysis and increased plasma PAI-1 and tPA, due largely to their increased hepatocyte expression. A decrease in the PAI-1 (SERPINE1) gene corepressor Rev-Erbα increased PAI-1, which then increased the tPA gene PLAT via a PAI-1/LRP1/PKA/p-CREB1 pathway. This pathway was partially counterbalanced by increased DACH1, a PLAT-negative regulator. We focused on the PAI-1/PLAT pathway, which mitigates the reduction in fibrinolysis in obesity. Thus, silencing hepatocyte PAI-1, CREB1, or tPA in obese mice lowered plasma tPA and further impaired fibrinolysis. The PAI-1/PLAT pathway was present in primary human hepatocytes, and associations among PAI-1, tPA, and PLAT in livers from obese and lean humans were consistent with these findings. Knowledge of PAI-1 and tPA regulation in hepatocytes in obesity may suggest therapeutic strategies for improving fibrinolysis and lowering the risk of thrombosis in this setting.

Background & Aims: Carriers of pathogenic variants in CDH1 have a high risk of hereditary diffuse gastric cancer (HDGC). Guidelines recommend prophylactic total gastrectomy (PTG) at age 20-30 years, although there is controversy over the optimal age. We developed a simulation model to analyze the effects of PTG at different ages on quality-adjusted life-years (QALYs), cancer mortality, and life expectancy., Methods: We used a Markov model of HDGC progression associated with pathogenic variants in CDH1 to simulate outcomes of hypothetical cohorts with different ages at time of PTG (ages 20-79 years). Model inputs including health state transition probabilities, mortality and complication rates, quality of life utility values, and endoscopic surveillance sensitivity were derived from publications. The primary outcome, used to determine the optimal strategy, was age at which PTG yielded the highest QALYs. Secondary outcomes were cancer mortality and unadjusted life-years., Results: Our model found that for men, the optimal age for PTG is 39 years, resulting in 32.01 incremental QALYs, 58.81 life-years (biologic age, 72.81 years), and lifetime cancer mortality of 8.5%. Incorporating endoscopic surveillance prior to PTG decreased cancer mortality to 6.7%, but had lower QALYs (31.59). PTG at age 30 reduced cancer mortality to 3.2%, with 31.45 incremental QALYs. For women, the optimal age for PTG was calculated to be 30 years, with 33.09 incremental QALYs, 66.17 life-years (biologic age, 80.17 years), and lifetime cancer mortality of 1.6%. Addition of endoscopic surveillance did not decrease the risk of HDGC mortality in women., Conclusions: Using a Markov model of HDGC progression associated with pathogenic variants in CDH1 to simulate outcomes, we found the optimal ages for PTG to be 39 years for men and 30 years for women, when QALYs are the primary endpoint. These ages for PTG are older than those of current recommendations., (Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background & Aims: In the West, early gastric cancer is increasingly managed with endoscopic resection (ER). This is, however, based on the assumption that the low prevalence and risk of lymph node metastases observed in Asian patients is applicable to patients in the United States. We sought to evaluate the frequency of and factors associated with metastasis of early gastric cancers to lymph nodes, and whether the Japanese ER criteria are applicable to patients in the US., Methods: We performed a retrospective study of 176 patients (mean age 68.5 years; 59.1% male; 58.5% white) who underwent surgical resection with lymph node dissection of T1 and Tis gastric adenocarcinomas, staged by pathologists, at 7 tertiary care centers in the US from January 1, 1999, through December 31, 2016. The frequency of lymph node metastases and associated risk factors were determined., Results: The mean size of gastric adenocarcinomas was 23.0 ± 16.6 mm-most were located in the lower-third of the stomach (67.0%), invading the submucosa (55.1%), and moderately differentiated (31.3%). Lymphovascular invasion was observed in 18.2% of lesions. Overall, 20.5% of patients had lymph node metastases. Submucosal invasion (odds ratio, 3.9; 95% CI, 1.4-10.7) and lymphovascular invasion (odds ratio, 4.6; 95% CI, 1.8-12.0) were independently associated with increased risk of metastasis to lymph nodes. The frequency of lymph node metastases among patients fulfilling standard and expanded Japanese criteria for ER were 0 and 7.5%, respectively., Conclusions: The frequency of lymph node metastases among patients with early gastric cancer in a US population is higher than that of published Asian series. However, early gastric cancer lesions that meet the Japanese standard criteria for ER are associated with negligible risk of metastasis to lymph nodes, so ER can be recommended for definitive therapy. Expanded criteria cancers appear to have a higher risk of metastasis to lymph nodes, so ER may be considered for select cases., (Copyright © 2019 AGA Institute. Published by Elsevier Inc. All rights reserved.)

First described in the early 1980s, total pancreatectomy with autologous islet cell transplantation for the treatment of chronic pancreatitis is still only offered in select centers worldwide. Indications, process details including surgery as well as islet isolation, and results are reviewed. In addition, areas for further research to optimize results are identified., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Asymptomatic pancreatic cysts are a common clinical problem but only a minority of these cases progress to cancer. Our aim was to compare the accuracy to detect malignancy of the 2015 American Gastroenterological Association (AGA), the 2012 International Consensus/Fukuoka (Fukuoka guidelines [FG]), and the 2010 American College of Radiology (ACR) guidelines.We conducted a retrospective study at 3 referral centers for all patients who underwent resection for an asymptomatic pancreatic cyst between January 2008 and December 2013. We compared the accuracy of 3 guidelines in predicting high-grade dysplasia (HGD) or cancer in resected cysts. We performed logistic regression analyses to examine the association between cyst features and risk of HGD or cancer.A total of 269 patients met inclusion criteria. A total of 228 (84.8%) had a benign diagnosis or low-grade dysplasia on surgical pathology, and 41 patients (15.2%) had either HGD (n = 14) or invasive cancer (n = 27). Of the 41 patients with HGD or cancer on resection, only 3 patients would have met the AGA guideline's indications for resection based on the preoperative cyst characteristics, whereas 30/41 patients would have met the FG criteria for resection and 22/41 patients met the ACR criteria. The sensitivity, specificity, positive predictive value, negative predictive value of HGD, and/or cancer of the AGA guidelines were 7.3%, 88.2%, 10%, and 84.1%, compared to 73.2%, 45.6%, 19.5%, and 90.4% for the FG and 53.7%, 61%, 19.8%, and 88% for the ACR guidelines. In multivariable analysis, cyst size >3 cm, compared to ≤3 cm, (odds ratio [OR] = 2.08, 95% confidence interval [CI] = 1.11, 4.2) and each year increase in age (OR = 1.07, 95% CI = 1.03, 1.11) were positively associated with risk of HGD or cancer on resection.In patients with asymptomatic branch duct-intraductal papillary mucinous neoplasms or mucinous cystic neoplasms who underwent resection, the prevalence rate of HGD or cancer was 15.2%. Using the 2015 AGA criteria for resection would have missed 92.6% of patients with HGD or cancer. The more "inclusive" FG and ACR had a higher sensitivity for HGD or cancer but lower specificity. Given the current deficiencies of these guidelines, it will be important to determine the acceptable rate of false-positives in order to prevent a single true-positive.

Although vitamin D deficiency is prevalent among obese individuals, its cause is poorly understood. Few studies have measured vitamin D concentrations in adipose of obese (OB) subjects, and none have included normal weight controls (C). The goal of this study was to investigate whether the relationship between body composition, serum 25-hydroxyvitamin D (25OHD), vitamin D in subcutaneous (SQ) and omental (OM) adipose, and total adipose stores of vitamin D differ among OB and C. Obese women undergoing bariatric surgery and normal-weight women undergoing abdominal surgery for benign gynecologic conditions were enrolled. Subjects had measurements of serum 25OHD by high-performance liquid chromatography (HPLC) and body composition by dual-energy X-ray absorptiometry (DXA). Vitamin D concentrations in SQ and OM adipose were measured by mass spectroscopy. Thirty-six women were enrolled. Serum 25OHD was similar between groups (OB 27 ± 2 versus C 26 ± 2 ng/mL; p = 0.71). Adipose vitamin D concentrations were not significantly different in either SQ (OB 34 ± 9 versus C 26 ± 12 ng/g; p = 0.63) or OM compartments (OB 51 ± 13 versus C 30 ± 18 ng/g; p = 0.37). The distribution of vitamin D between SQ and OM compartments was similar between groups. Serum 25OHD was directly related to adipose vitamin D in both groups. Total body vitamin D stores were significantly greater in OB than in C (2.3 ± 0.6 versus 0.4 ± 0.8 mg, respectively; p < 0.01). In summary, although OB had significantly greater total vitamin D stores than C, the relationship between serum 25OHD and fat vitamin D and the overall pattern of distribution of vitamin D between the OM and SQ fat compartments was similar. Our data demonstrate that obese subjects have greater adipose stores of vitamin D. They support the hypotheses that the enlarged adipose mass in obese individuals serves as a reservoir for vitamin D and that the increased amount of vitamin D required to saturate this depot may predispose obese individuals to inadequate serum 25OHD. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

Defective insulin signaling in hepatocytes is a key factor in type 2 diabetes. In obesity, activation of calcium/calmodulin-dependent protein kinase II (CaMKII) in hepatocytes suppresses ATF6, which triggers a PERK-ATF4-TRB3 pathway that disrupts insulin signaling. Elucidating how CaMKII suppresses ATF6 is therefore essential to understanding this insulin resistance pathway. We show that CaMKII phosphorylates and blocks nuclear translocation of histone deacetylase 4 (HDAC4). As a result, HDAC4-mediated SUMOylation of the corepressor DACH1 is decreased, which protects DACH1 from proteasomal degradation. DACH1, together with nuclear receptor corepressor (NCOR), represses Atf6 transcription, leading to activation of the PERK-TRB3 pathway and defective insulin signaling. DACH1 is increased in the livers of obese mice and humans, and treatment of obese mice with liver-targeted constitutively nuclear HDAC4 or DACH1 small hairpin RNA (shRNA) increases ATF6, improves hepatocyte insulin signaling, and protects against hyperglycemia and hyperinsulinemia. Thus, DACH1-mediated corepression in hepatocytes emerges as an important link between obesity and insulin resistance., (Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This study examined whether changes in adipocyte long chain fatty acid (LCFA) uptake kinetics explain the weight regain increasingly observed following bariatric surgery., Methods: Three groups (10 patients each) were studied: patients without obesity (NO: BMI 24.2 ± 2.3 kg m(-2) ); patients with obesity (O: BMI 49.8 ± 11.9); and patients classified as super-obese (SO: BMI 62.6 ± 2.8). NO patients underwent omental and subcutaneous fat biopsies during clinically indicated abdominal surgeries; O were biopsied during bariatric surgery, and SO during both a sleeve gastrectomy and at another bariatric operation 16 ± 2 months later, after losing 113 ± 13 lbs. Adipocyte sizes and [(3) H]-LCFA uptake kinetics were determined in all biopsies., Results: Vmax for facilitated LCFA uptake by omental adipocytes increased exponentially from 5.1 ± 0.95 to 21.3 ± 3.20 to 68.7 ± 9.45 pmol/sec/50,000 cells in NO, O, and SO patients, respectively, correlating with BMI (r = 0.99, P < 0.001). Subcutaneous results were virtually identical. By the second operation, the mean BMI (SO patients) fell significantly (P < 0.01) to 44.4 ± 2.4 kg m(-2) , similar to the O group. However, Vmax (40.6 ± 11.5) in this weight-reduced group remained ~2X that predicted from the BMI:Vmax regression among NO, O, and SO patients., Conclusions: Facilitated adipocyte LCFA uptake remains significantly upregulated ≥1 year after bariatric surgery, possibly contributing to weight regain., (© 2015 The Obesity Society.)

Objective: To examine changes in depressive symptoms and treatment in the first 3 years following bariatric surgery., Methods: The longitudinal assessment of bariatric surgery-2 (LABS-2) is an observational cohort study of adults (n = 2,458) who underwent a bariatric surgical procedure at 1 of 10 US hospitals between 2006 and 2009. This study includes 2,148 participants who completed the Beck depression inventory (BDI) at baseline and ≥ one follow-up visit in years 1-3., Results: At baseline, 40.4% self-reported treatment for depression. At least mild depressive symptoms (BDI score ≥ 10) were reported by 28.3%; moderate (BDI score 19-29) and severe (BDI score ≥30) symptoms were uncommon (4.2 and 0.5%, respectively). Mild-to-severe depressive symptoms independently increased the odds (OR = 1.75; P = 0.03) of a major adverse event within 30 days of surgery. Compared with baseline, symptom severity was significantly lower at all follow-up time points (e.g., mild-to-severe symptomatology was 8.9%, 6 months; 8.4%, 1year; 12.2%, 2 years; 15.6%, 3 years; ps < 0.001), but increased between 1 and 3 years postoperatively (P < 0.01). Change in depressive symptoms was significantly related to change in body mass index (r = 0.42; P < 0001)., Conclusion: Bariatric surgery has a positive impact on depressive features. However, data suggest some deterioration in improvement after the first postoperative year. LABS-2, #NCT00465829, http://www.clinicaltrials.gov/ct2/show/NCT00465829., (Copyright © 2014 The Obesity Society.)

Background: Large centralized databases are used with increasing frequency for reporting hospital-specific and nationwide trends and outcomes after various surgical procedures in order to improve quality of surgical care. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) is a risk-adjusted, case-weighted complication tracking initiative that reports 30-day outcomes from more than 400 academic and community institutions in the US. However, the accuracy of event reporting specific to pancreatic surgery has never been examined in depth., Methods: We retrospectively reviewed medical records of patients, the information on whose postoperative course was originally reported through ACS-NSQIP between 2006 and 2010. Preoperative characteristics, operative data, and postoperative events were recorded after review of electronic medical records including physician and nursing notes, operative room records and anesthesiologist reports. Fidelity of reported clinical events was assessed. Accuracy, sensitivity, and specificity were calculated for each variable of interest., Results: Two hundred and forty-nine pancreatectomies were reviewed, including 145 (58.2 %) Whipple procedures, 19 (7.6 %) total pancreatectomies, 65 (26.1 %) distal pancreatectomies, and 15 (6.0 %) central or partial resections. Median age was 65.7, males comprised 41.5 % of the group, and 74.3 % of patients were Caucasian. The overall rate of complications reported by NSQIP was 44.0 %, compared with 45.0 % in our review, however discordance was observed in 27.3 % of the time, including 34 cases of reporting a complication where there was not one, and 34 cases of missed complication. The most frequently reported event was postoperative bleeding requiring transfusion, however this was also the event most commonly misclassified. Additionally, three procedures unrelated to the index operation were recorded as reoperation events. While a pancreas-specific module does not yet exist, ACS-NSQIP reports a 7.6 % rate of organ-space surgical site infections; when compared with our institutional rate of Grades B and C postoperative fistula (10.4 %), we observed discordance 4.4 % of the time. Delayed gastric emptying, a common post-pancreatectomy morbidity, was not captured at all. Additionally, there were significant inaccuracies in reporting urinary tract infections, postoperative pneumonia, wound complications, and postoperative sepsis, with discordance rates of 4.4, 3.2, 3.6, and 6.8 %, respectively., Conclusions: ACS-NSQIP data are an important and valuable tool for evaluating quality of surgical care, however pancreatectomy-specific postoperative events are often misclassified, underscoring the need for a hepatopancreatobiliary-specific module to better capture key outcomes in this complex and unique patient population.

Background: Metabolic syndrome is associated with higher risk for cardiovascular disease, sleep apnea, and nonalcoholic steatohepatitis, all common conditions in patients referred for bariatric surgery, and it may predict early postoperative complications. The objective of this study was to determine the prevalence of metabolic syndrome, defined using updated National Cholesterol Education Program criteria, in adults undergoing bariatric surgery and compare the prevalence of baseline co-morbid conditions and select operative and 30-day postoperative outcomes by metabolic syndrome status., Methods: Complete metabolic syndrome data were available for 2275 of 2458 participants enrolled in the Longitudinal Assessment of Bariatric Surgery-2 (LABS-2), an observational cohort study designed to evaluate long-term safety and efficacy of bariatric surgery in obese adults., Results: The prevalence of metabolic syndrome was 79.9%. Compared to those without metabolic syndrome, those with metabolic syndrome were significantly more likely to be men, to have a higher prevalence of diabetes and prior cardiac events, to have enlarged livers and higher median levels of liver enzymes, a history of sleep apnea, and a longer length of stay after surgery following laparoscopic Roux-en-Y gastric bypass (RYGB) and gastric sleeves but not open RYGB or laparoscopic adjustable gastric banding. Metabolic syndrome status was not significantly related to duration of surgery or rates of composite end points of intraoperative events and 30-day major adverse surgical outcomes., Conclusions: Nearly four in five participants undergoing bariatric surgery presented with metabolic syndrome. Establishing a diagnosis of metabolic syndrome in bariatric surgery patients may identify a high-risk patient profile, but does not in itself confer a higher risk for short-term adverse postsurgery outcomes.

Background: Quality of life after total pancreatectomy (TP) is perceived to be poor secondary to insulin-dependent diabetes and pancreatic insufficiency. As a result, surgeons may be reluctant to offer TP for benign and premalignant pancreatic diseases., Methods: We retrospectively reviewed presenting features, operative characteristics, and postoperative outcomes of all patients who underwent TP at our institution. Quality of life was assessed using institutional questionnaires and validated general, pancreatic disease-related, and diabetes-related instruments (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30 and module EORTC-PAN26], Audit of Diabetes Dependent Quality of Life), and compared with frequency-matched controls, patients after a pancreaticoduodenectomy (PD). Continuous variables were compared using Student t-test or analysis of variance. Categorical variables were compared using χ(2) or Fisher exact test., Results: Between 1994 and 2011, 77 TPs were performed. Overall morbidity was 49%, but only 15.8% patients experienced a major complication. Perioperative mortality was 2.6%. Comparing 17 TP and 14 PD patients who returned surveys, there were no statistically significant differences in quality of life in global health, functional status, or symptom domains of EORTC QLQ-C30 or in pancreatic disease-specific EORTC-PAN26. TP patients had slightly but not significantly higher incidence of hypoglycemic events as compared with PD patients with postoperative diabetes. A negative impact of diabetes assessed by Audit of Diabetes Dependent Quality of Life did not differ between TP and PD. Life domains most negatively impacted by diabetes involved travel and physical activity, whereas self-confidence, friendships and personal relationships, motivation, and feelings about the future remained unaffected., Conclusions: Although TP-induced diabetes negatively impacts select activities and functions, overall quality of life is comparable with that of patients who undergo a partial pancreatic resection., (Copyright © 2014. Published by Elsevier Inc.)

Background: Although it is recognized that a standardized approach to reporting weight change is essential to meaningful comparisons among cohorts and across studies, consensus is lacking. This study aimed to propose a method of reporting weight change that would allow meaningful comparisons among studies of patients who underwent bariatric surgery and to demonstrate its utility using an example from the Longitudinal Assessment of Bariatric Surgery (LABS)., Methods: Relationships among several measures of weight change are described. Results from an observational, longitudinal cohort study of adults undergoing bariatric surgery and from simulation studies are used to illustrate the proposed method., Results: Baseline weight is a critical parameter when assessing weight change. Men undergoing a bariatric procedure other than gastric bypass or adjustable band tended to have greater weight loss 12 months after surgery than men undergoing gastric bypass when not accounting for baseline weight, but the opposite was found when results were adjusted for baseline weight. Simulation results show that with relatively modest sample sizes, the adjusted weight loss was significantly different between the 2 groups of men., Conclusion: A consistent metric for reporting weight loss after bariatric surgery is essential to interpret outcomes across studies and among subgroups. The baseline weight adjusted percent of weight loss (A%WL) uses a standard population (e.g., the LABS cohort) to account for differences between cohorts with respect to baseline weight, and its use can change the interpretation of results compared with an unadjusted measure., (Copyright © 2013 American Society for Metabolic and Bariatric Surgery. All rights reserved.)

Purpose: We evaluated the efficacy and safety of capecitabine and temozolomide (CAPTEM) in patients with metastatic neuroendocrine tumors (NETs) to the liver. This regimen was based on our studies with carcinoid cell lines that showed synergistic cytotoxicity with sequence-specific dosing of 5-fluorouracil preceding temozolomide (TMZ)., Methods: A retrospective review was conducted of 18 patients with NETs metastatic to the liver who had failed 60 mg/month of Sandostatin LAR™ (100%), chemotherapy (61%), and hepatic chemoembolization (50%). Patients received capecitabine at 600 mg/m(2) orally twice daily on days 1-14 (maximum 1,000 mg orally twice daily) and TMZ 150-200 mg/m(2) divided into two doses daily on days 10-14 of a 28-day cycle. Imaging was performed every 2 cycles, and serum tumor markers were measured every cycle., Results: Using RECIST parameters, 1 patient (5.5%) with midgut carcinoid achieved a surgically proven complete pathological response (CR), 10 patients (55.5%) achieved a partial response (PR), and 4 patients (22.2%) had stable disease (SD). Total response rate was 61%, and clinical benefit (responders and SD) was 83.2%. Of four carcinoid cases treated with CAPTEM, there was 1 CR, 1 PR, 1 SD, and 1 progressive disease. Median progression-free survival was 14.0 months (11.3-18.0 months). Median overall survival from diagnosis of liver metastases was 83 months (28-140 months). The only grade 3 toxicity was thrombocytopenia (11%). There were no grade 4 toxicities, hospitalizations, opportunistic infections, febrile neutropenias, or deaths., Conclusions: CAPTEM is highly active, well tolerated and may prolong survival in patients with well-differentiated, metastatic NET who have progressed on previous therapies.

Background: Bariatric surgery results in bone loss at weight-bearing sites, the mechanism of which is unknown., Methods: Twenty-two women (mean body mass index 44 kg/m(2); aged 45 years) who underwent Roux-en-Y gastric bypass (n = 14) and restrictive procedures (n = 8) had measurements of areal bone mineral density by dual-energy x-ray absorptiometry at the lumbar spine, total hip (TH), femoral neck (FN), and one third radius and trabecular and cortical volumetric bone mineral density and microstructure at the distal radius and tibia by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline and 12 months postoperatively., Results: Mean weight loss was 28 ± 3 kg (P < .0001). PTH rose 23% (P < .02) and 25-hydroxyvitamin D was stable. C-telopeptide increased by 144% (P < .001). Bone-specific alkaline phosphatase did not change. Areal bone mineral density declined at TH (-5.2%; P < .005) and FN (-4.5%; P < .005). By HR-pQCT, trabecular parameters were stable, whereas cortical bone deteriorated, particularly at the tibia: cortical area (-2.7%; P < .01); cortical thickness (-2.1%; P < .01); total density (-1.3%; P = .059); cortical density (-1.7%; P < .01). In multivariate regression, bone loss at the TH and FN were predicted by weight loss. In contrast, only PTH increase predicted cortical deterioration at the tibia. Roux-en-Y gastric bypass patients lost more weight, had more bone loss by dual-energy x-ray absorptiometry and HR-pQCT than those with restrictive procedures, and had declines in cortical load share estimated by finite element analysis., Conclusions: After bariatric surgery, hip bone loss reflects skeletal unloading and cortical bone loss reflects secondary hyperparathyroidism. This study highlights deterioration of cortical bone loss as a novel mechanism for bone loss after bariatric surgery.

Background: Mortality following bariatric surgery is a rare event in contemporary series, making it difficult for any single center to draw meaningful conclusions as to cause of death. Nevertheless, much of the published mortality data come from single-center case series and reviews of administrative databases. These sources tend to produce lower mortality estimates than those obtained from controlled clinical trials. Furthermore, information about the causes of death and how they were determined is not always available. The aim of the present report is to describe in detail all deaths occurring within 30 days of surgery in the Longitudinal Assessment of Bariatric Surgery (LABS)., Methods: LABS is a ten-center observational cohort study of bariatric surgical outcomes. Data were collected prospectively for bariatric surgeries performed between March 2005 and April 2009. All deaths occurring within 30-days of surgery were identified, and cause of death assigned by an independent Adjudication Subcommittee, blinded to operating surgeon and site., Results: Six thousand one hundred eighteen patients underwent primary bariatric surgery. Eighteen deaths (0.3%) occurred within 30-days of surgery. The most common cause of death was sepsis (33% of deaths), followed by cardiac causes (28%), and pulmonary embolism (17%). For one patient cause of death could not be determined despite examination of all available information., Conclusions: This study confirms the low 30-day mortality rate following bariatric surgery. The recognized complications of anastomotic leak, cardiac events, and pulmonary emboli accounted for the majority of 30-day deaths.

Objective: To describe the reproductive health history and characteristics of women having bariatric surgery and to determine whether this differs by age of onset of obesity., Design: Retrospective and cross-sectional analyses of self-reported survey data., Setting: Six sites of the Longitudinal Assessment of Bariatric Surgery-2 study., Patient(s): The study included 1,538 females having bariatric surgery., Intervention(s): None., Main Outcome Measure(s): Reported polycystic ovary syndrome (PCOS), pregnancy and fertility history, contraceptive use, and plans for pregnancies., Result(s): Mean age was 44.8 years (range, 18-78 years); mean body mass index was 47.2 kg/m2 (range, 33.8-87.3 kg/m2). PCOS had been diagnosed by a health care provider in 13.1% of subjects. Of women who had tried to conceive, 41.9% experienced infertility and 61.4% had a live birth after experiencing infertility. In the whole group, prior live birth was reported by 72.5%. Women who were obese by 18 years old were more likely to report PCOS and infertility and less likely to have ever been pregnant, compared with women who became obese later in life. Future pregnancy was important to 30.3% of women younger than 45 years, whereas 48.6% did not plan to become pregnant in the future. In the year before surgery, 51.8% used contraception., Conclusion(s): Self-reporting of obesity by age 18 appears to be related to reproductive morbidity. Women undergoing bariatric surgery have important reproductive health care needs, including reliable contraception and counseling about plans for postoperative pregnancy., (Copyright (c) 2010 American Society for Reproductive Medicine. All rights reserved.)

Background: The current National Institutes of Health guidelines have recommended bariatric surgery for patients with a body mass index (BMI) >40 kg/m(2) or BMI >35 kg/m(2) with significant co-morbidities. However, some preliminary studies have shown that patients with a BMI that does not meet these criteria could also experience similar weight loss and the benefits associated with it., Methods: An institutional review board-approved protocol was obtained to study the effectiveness of laparoscopic adjustable gastric banding in patients with a low BMI. A total of 66 patients with a BMI of 30-35 kg/m(2) and co-morbidities (n = 22) or a BMI of 35-40 kg/m(2) without co-morbidities (n = 44) underwent laparoscopic adjustable gastric banding. These patients were compared with 438 standard patients who had undergone laparoscopic adjustable gastric banding who met the National Institutes of Health criteria for bariatric surgery. The excess weight loss at 3, 6, 12, and 18 months and the status of their co-morbidities were compared between the 2 groups., Results: The average BMI for the study group was 36.1 +/- 2.6 kg/m(2) compared with 46.0 +/- 7.3 kg/m(2) for the control group. Both groups had significant co-morbidities, including hypertension, diabetes, hyperlipidemia, arthritis, gastroesophageal reflux disease, stress incontinence, and obstructive sleep apnea. The mean percentage of excess weight loss was 20.3% +/- 9.0%, 28.5% +/- 14.0%, 44.7% +/- 19.3%, and 42.2% +/- 33.7% at 3, 6, 12, and 18 months, respectively. This was not significantly different from the excess weight loss in the control group, except for at 12 months. Both groups showed similar improvement of most co-morbidities., Conclusion: Moderately obese patients whose BMI is less than the current guidelines for bariatric surgery will have similar weight loss and associated benefits. Laparoscopic adjustable gastric banding is a safe and effective treatment for patients with a BMI of 30-35 kg/m(2)., (Copyright 2010 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Studies have shown that type 2 diabetes (T2DM) improves or resolves shortly after Roux-en-Y gastric bypass (RYGB). Few data are available on T2DM recurrence or the effect of weight regain on T2DM status., Methods: A review of 42 RYGB patients with T2DM and >or=3 years of follow-up and laboratory data was performed. Postoperative weight loss and T2DM status was assessed. Recurrence or worsening was defined as hemoglobin A1c >6.0% and fasting glucose >124 mg/dL and/or medication required after remission or improvement. Patients whose T2DM recurred or worsened were compared with those whose did not, and patients whose T2DM improved were compared with those whose T2DM resolved., Results: T2DM had either resolved or improved in all patients (64% and 36%, respectively); 24% (10) recurred or worsened. The patients with recurrence or worsening had had a lower preoperative body mass index than those without recurrence or worsening (47.9 versus 52.9 kg/m2; P = .05), regained a greater percentage of their lost weight (37.7% versus 15.4%; P = .002), had a greater weight loss failure rate (63% versus 14%; P = .03), and had greater postoperative glucose levels (138 versus 102 mg/dL; P = .0002). Patients who required insulin or oral medication before RYGB were more likely to experience improvement rather than resolution (92% versus 8%, P

Background: Although gastric bypass is the most common bariatric procedure in the United States, it is has been associated with a failure rate of 15% (range 5-40%). The addition of an adjustable gastric band to Roux-en-Y gastric bypass has been reported to be a useful revision strategy in a small series of patients with inadequate weight loss after proximal gastric bypass., Methods: We report on 22 patients who presented with inadequate weight loss or significant weight regain after proximal gastric bypass. All patients underwent revision with the placement of an adjustable silicone gastric band around the proximal gastric pouch. The bands were adjusted at 6 weeks postoperatively and beyond, as needed. Complications and weight loss at the most recent follow-up visit were evaluated., Results: The mean age and body mass index at revision was 41.27 years (range 25-58) and 44.8 +/- 6.34 kg/m(2), respectively. Patients had experienced a loss of 19%, 27%, 47.3%, 42.3%, 43%, and 47% of their excess weight at 6, 12, 24, 36, 48, and 60 months after the revisional procedure, respectively. Three major complications occurred requiring reoperation. No band erosions have been documented., Conclusion: The results from this larger series of patients have also indicated that the addition of the adjustable silicone gastric band causes significant weight loss in patients with poor weight loss outcomes after gastric bypass. That no anastomosis or change in absorption is required makes this an attractive revisional strategy. As with all revisional procedures, the complication rates appear to be increased compared with a similar primary operation., (2010 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Several studies have suggested that morbid obesity is associated with vitamin D deficiency and elevated parathyroid hormone (PTH). Studies have also suggested that there is an increase in vitamin D deficiency, bone resorption, and elevated PTH after gastric bypass surgery. Few studies have evaluated markers of bone and calcium metabolism after laparoscopic adjustable gastric banding or compared these results to those after gastric bypass., Methods: Data on all patients undergoing primary gastric bypass (GBP; n = 979) and laparoscopic adjustable gastric banding (LAGB; n = 269) procedures at a tertiary-referral center from June 1996 through March 2005 were reviewed from a prospective database. Only patients with 25OH vitamin D levels available were included in this study (n = 534; GBP = 403, LAGB = 131). All patients were advised to take at least 1,200 mg calcium and 800-1,200 IU of vitamin D daily before and subsequent to their operation. Markers for bone metabolism [25OH Vitamin D, corrected serum calcium, alkaline phosphatase (AP), and PTH] were evaluated preoperatively and 3, 6, 12, and 24 months postoperatively. An analysis of variance and chi-square were performed to determine differences between the operative groups. Linear regression analysis was performed to evaluate the relationship between preoperative body mass index (BMI) and 25OH vitamin D and PTH levels and between percent excess weight loss and 25OH vitamin D and PTH after surgery., Results: Sixty-four percent of all patients presented with vitamin D deficiency (<20 ng/ml) and 14% presented with elevated PTH preoperatively. Mean 25OH vitamin D levels and AP levels increased significantly after GBP surgery (vitamin D, 17 to 25 ng/ml 12 months post-op; AP, 80 to 90 IU/L 24 months post-op). Corrected calcium levels remained within normal limits and showed no change over time after both procedures. AP levels significantly increased from 76 IU/l preoperatively to 82 IU/l 6 months after LAGB surgery and then decreased to 59 IU/l 24 months after LAGB surgery. Linear regression analysis of preoperative vitamin D, PTH, and BMI values showed a significant positive relationship between initial BMI and PTH (r = 0.29) and a significant negative relationship between vitamin D and initial BMI (r = -0.19). A significant positive linear relationship between vitamin D and percent excess weight loss was evident 12 and 24 months after GBP surgery (r = 0.39 and 0.57, respectively). A negative relationship was evident between PTH and vitamin D 6 months after GBP surgery (r = -0.35) and 12 months after LAGB surgery (r = -0.61)., Conclusions: These findings suggest that morbid obesity is associated with vitamin D deficiency, and elevated PTH and with adequate supplementation, GBP, and particularly LAGB, patients can improve their bone metabolism abnormalities related to obesity. Furthermore, adequate supplementation for GBP patients may attenuate the increased risk for bone loss associated with malabsorption from the bypass.