Biliary complications after adult-to-adult living-donor liver transplantation: An international multicenter study of 3633 cases.

In living-donor liver transplantation, biliary complications including bile leaks and biliary anastomotic strictures remain significant challenges, with incidences varying across different centers. This multicentric retrospective study (2016-2020) included 3633 adult patients from 18 centers and aimed to identify risk factors for these biliary complications and their impact on patient survival. Incidences of bile leaks and biliary strictures were 11.4% and 20.6%, respectively. Key risk factors for bile leaks included multiple bile duct anastomoses (odds ratio, [OR] 1.8), Roux-en-Y hepaticojejunostomy (OR, 1.4), and a history of major abdominal surgery (OR, 1.4). For biliary anastomotic strictures, risk factors were ABO incompatibility (OR, 1.4), blood loss >1 L (OR, 1.4), and previous abdominal surgery (OR, 1.7). Patients experiencing biliary complications had extended hospital stays, increased incidence of major complications, and higher comprehensive complication index scores. The impact on graft survival became evident after accounting for immortal time bias using time-dependent covariate survival analysis. Bile leaks and biliary anastomotic strictures were associated with adjusted hazard ratios of 1.7 and 1.8 for graft survival, respectively. The study underscores the importance of minimizing these risks through careful donor selection and preoperative planning, as biliary complications significantly affect graft survival, despite the availability of effective treatments.

Novel Benchmark for Adult-to-Adult Living-donor Liver Transplantation: Integrating Eastern and Western Experiences.

OBJECTIVE: To define benchmark values for adult-to-adult living-donor liver transplantation (LDLT). BACKGROUND: LDLT utilizes living-donor hemiliver grafts to expand the donor pool and reduce waitlist mortality. Although references have been established for donor hepatectomy, no such information exists for recipients to enable conclusive quality and comparative assessments. METHODS: Patients undergoing LDLT were analyzed in 15 high-volume centers (≥10 cases/year) from 3 continents over 5 years (2016-2020), with a minimum follow-up of 1 year. Benchmark criteria included a Model for End-stage Liver Disease ≤20, no portal vein thrombosis, no previous major abdominal surgery, no renal replacement therapy, no acute liver failure, and no intensive care unit admission. Benchmark cutoffs were derived from the 75th percentile of all centers' medians. RESULTS: Of 3636 patients, 1864 (51%) qualified as benchmark cases. Benchmark cutoffs, including posttransplant dialysis (≤4%), primary nonfunction (≤0.9%), nonanastomotic strictures (≤0.2%), graft loss (≤7.7%), and redo-liver transplantation (LT) (≤3.6%), at 1-year were below the deceased donor LT benchmarks. Bile leak (≤12.4%), hepatic artery thrombosis (≤5.1%), and Comprehensive Complication Index (CCI ® ) (≤56) were above the deceased donor LT benchmarks, whereas mortality (≤9.1%) was comparable. The right hemiliver graft, compared with the left, was associated with a lower CCI ® score (34 vs 21, P < 0.001). Preservation of the middle hepatic vein with the right hemiliver graft had no impact neither on the recipient nor on the donor outcome. Asian centers outperformed other centers with CCI ® score (21 vs 47, P < 0.001), graft loss (3.0% vs 6.5%, P = 0.002), and redo-LT rates (1.0% vs 2.5%, P = 0.029). In contrast, non-benchmark low-volume centers displayed inferior outcomes, such as bile leak (15.2%), hepatic artery thrombosis (15.2%), or redo-LT (6.5%). CONCLUSIONS: Benchmark LDLT offers a valuable alternative to reduce waitlist mortality. Exchange of expertise, public awareness, and centralization policy are, however, mandatory to achieve benchmark outcomes worldwide.

Combined heart and liver transplantation in a patient supported by left ventricular assist device (LVAD) with propionic acidemia.

Propionic acidemia (PA) is a rare inherited metabolic disease due to inborn errors of metabolism. PA results in the accumulation of abnormal organic acid metabolites in multiple systems, mainly the central nervous system and the heart. Cardiac complications include dilated cardiomyopathy (DCM) and carry a 40-50% increased mortality risk. Liver transplantation (LT) is required in PA patients when medical treatment fails and may prevent or slow down the cardiomyopathy progression. However, severe heart disease may be a serious contraindication to LT. We present a complicated case of a PA patient, supported with a Left Ventricular Assist Device, who underwent a heart and Liver transplant. PA patients are at increased risk for metabolic acidosis during surgery, with increased anion gap and hyperammonemia. A strict multi-disciplinary approach is needed to prevent and treat metabolic decompensation. The patient had a successful heart and liver transplant after a strict treatment protocol in the pre, intra, and post-operative periods. His case highlights the complexity of PA patients and the increased risk for metabolic decompensation during surgery and provides an insight into how to manage such complicated patients.

Ex Vivo Liver Resection and Autotransplantation: Should It be Used More Frequently?

OBJECTIVE: We herein advocate for more extensive utilization of ex vivo resection techniques for otherwise unresectable liver tumors by presenting the largest collective American experience. BACKGROUND: Advanced in situ resection and vascular reconstruction techniques have made R0 resection possible for otherwise unresectable liver tumors. Ex vivo liver resection may further expand the limits of resectability but remains underutilized due to concerns about technical complexity and vascular thrombosis. However, we believe that the skillset required for ex vivo liver resection is more widespread and the complications less severe than widely assumed, making ex vivo resection a more attractive option in selected case. METHODS: We retrospectively analyzed 35 cases performed by surgical teams experienced with ex vivo liver resections (at least 4 cases) between 1997 and 2021. RESULTS: We categorized malignancies as highly aggressive (n=18), moderately aggressive (n=14), and low grade (n=3). All patients underwent total hepatectomy, vascular reconstruction and resection in hypothermia on the backtable, and partial liver autotransplantation. Overall survival was 67%/39%/28%, at 1/3/5 years, respectively, with a median survival of 710 days (range: 22-4824). Patient survival for highly aggressive, moderately aggressive, and low-grade tumors was 61%/33%/23%, 67%/40%/22%, and 100%/100%/100% at 1/3/5 years, respectively, with median survival 577 days (range: 22-3873), 444 days (range: 22-4824), and 1825 days (range: 868-3549). CONCLUSIONS: Ex vivo resection utilizes techniques commonly practiced in partial liver transplantation, and we demonstrate relatively favorable outcomes in our large collective experience. Therefore, we propose that more liberal use of this technique may benefit selected patients in centers experienced with partial liver transplantation.

Ex Vivo Resection and Autotransplantation for Conventionally Unresectable Tumors - An 11-year Single Center Experience.

BACKGROUND AND AIMS: Ex vivo surgery may provide a chance at R0 resection for conventionally unresectable tumors. However, long-term outcomes have not been well documented. In this study, we analyze our 11-year outcomes to define its role. STUDY DESIGN: We retrospectively analyzed 46 consecutive patients who underwent ex vivo surgery at our institution 2008-2019. RESULTS: The types of tumors were: carcinoma (n = 20), sarcoma (n = 20) and benign to low grade tumor (n = 6). The type of ex vivo surgery was chosen based on tumor location and vascular involvement. The most commonly performed procedure was ex vivo hepatectomy (n = 18), followed by ex vivo resection and intestinal autotransplantation (n = 12), ex vivo Whipple procedure and liver autotransplantation (n = 8) and multivisceral ex vivo procedure (n = 7). Twenty-three patients (50%) are currently alive with median follow-up of 4.0-years (11 months-11.8 years). The overall survival was 70%/59%/52%, at 1-/3-/5-years, respectively. Patient survival for benign to low grade tumors, sarcoma, and carcinoma was 100%/100%/100%, 65%/60%/50%, and 65%/45%/40%, at 1-/3-/5-years, respectively. Ninety-one percent patients had R0 resection, and 57% had no recurrence to date with median follow-up of 3.1-years. Two patients (4.3%) died within 30 days due to sepsis and gastroduodenal artety (GDA) stump blowout. Two additional patients died between 30 and 90 days due to sepsis. Perioperative mortality in the last 23 consecutive cases was limited to 1 patient who died of sepsis between 30 and 90 days. CONCLUSIONS: For a selected group of patients with conventionally unresectable tumors, ex vivo surgery can offer effective surgical removal with a reasonably low perioperative mortality at experienced centers.

Bariatric surgery prior to living donor nephrectomy: a solution to expand the living donor kidney pool - a retrospective study.

Most transplant centers decline morbidly obese people for living kidney donation. Their inclusion in the living donor pool after weight loss and reversal of comorbidities by bariatric surgery could reverse the downward living donation trend. We investigated whether bariatric surgery in the morbidly obese altered their candidacy for donation, complicated their subsequent donor nephrectomy, and impacted their early postoperative outcomes in a series of 22 donors who had bariatric surgery 0.7-22 years prior to laparoscopic living donor nephrectomy. Eighteen would have been excluded from donation prior to bariatric surgery based on a body mass index (BMI) > 40. Seventeen reached a BMI < 35 after bariatric surgery. One had hypertension that resolved after bariatric surgery. Prior bariatric surgery did not influence port placement and laterality of donor nephrectomy. None required open conversion or blood transfusion. In an exploratory comparison with 37 donors with a BMI 35-40, length of stay and warm ischemic time were shorter, blood loss and postoperative complications were similar, and operative time was longer. We therefore advocate the consideration of bariatric surgery in preparation for donation in morbidly obese people since it positively alters their candidacy without major impact on the subsequent living donor nephrectomy and early outcomes.

Synthesis and evaluation of antimicrobial, antitubercular and anticancer activities of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamides.

BACKGROUND: The study describes the synthesis, characterization, in vitro antimicrobial and anticancer evaluation of a series of 2-(1-benzoyl-1H-benzo[d]imidazol-2-ylthio)-N-substituted acetamide derivatives. The synthesized derivatives were also assessed for in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The compounds found active in in vitro study were assessed for their in vivo antitubercular activity in mice models and for their inhibitory action on vital mycobacterial enzymes viz, isocitrate lyase, pantothenate synthetase and chorismate mutase. RESULTS: Compounds 8, 9 and 11 emerged out as excellent antimicrobial agents in antimicrobial assays when compared to standard antibacterial and antifungal drugs. The results of anticancer activity displayed that majority of the derivatives were less cytotoxic than standard drugs (tamoxifen and 5-fluorouracil) towards MCF7 and HCT116 cell lines. However, compound 2 (IC50 = 0.0047 µM/ml) and compound 10 (IC50 = 0.0058 µM/ml) showed highest cytotoxicity against MCF7 and HCT116 cell lines, respectively. The results of in vivo antitubercular activity revealed that a dose of 1.34 mg/kg was found to be safe for the synthesized compounds. The toxic dose of the compounds was 5.67 mg/kg while lethal dose varied from 1.81 to 3.17 mg/kg body weight of the mice. Compound 18 inhibited all the three mycobacterial enzymes to the highest level in comparison to the other synthesized derivatives but showed lesser inhibition as compared to streptomycin sulphate. CONCLUSIONS: A further research on most active synthesized compounds as lead molecules may result in discovery of novel anticancer and antitubercular agents.

Increasing body mass index portends abbreviated survival following pancreatoduodenectomy for pancreatic adenocarcinoma.

BACKGROUND: Body mass index (BMI), a common surrogate marker for grading obesity, does not differentiate between metabolically active visceral fat and the relatively inert subcutaneous fat. We aim to determine the utility of BMI as a prognostic marker for the impact of obesity on outcomes and survival following pancreatoduodenectomy for pancreatic adenocarcinoma. METHODS: From a database of over 1,000 patients who had undergone pancreatoduodenectomy, 228 patients with a diagnosis of pancreatic adenocarcinoma were identified. Demographic data including BMI and perioperative parameters-operative time, estimated blood loss, length of stay, survival, nodal status, and American Joint Committee on Cancer stage-were obtained. Data are presented as median. RESULTS: One hundred ninety-two patients had a BMI less than or equal to 29 and 36 patients had a BMI greater than or equal to 30 (24 vs. 34, P < .001). Median age was 70 and the majority of the patients (52%) were male and the 2 groups of patients did not differ in this regard. A significantly greater number of obese patients had positive nodes (69% vs. 62%, P < .05) and this was associated with a worse survival (14 vs. 18 months, P < .05). CONCLUSIONS: For patients with pancreatic adenocarcinoma undergoing pancreatoduodenectomy, obesity does not impact operative complexity or length of stay but results in a shortened survival. Therefore, we conclude that BMI is an important prognostic marker that portends an abbreviated survival following pancreatoduodenectomy for pancreatic adenocarcinoma.

Margin status impacts survival after pancreaticoduodenectomy but negative margins should not be pursued.

Negative margins are the goal with pancreaticoduodenectomy for pancreatic adenocarcinoma. Thereby, margins are assessed intraoperatively with frozen section analysis and negative margins are pursued. This study was undertaken to determine the impact of margin status with pancreaticoduodenectomy for pancreatic adenocarcinoma and the value of extending resections to achieve negative margins. The intraoperative frozen section analysis and final margins for 448 patients undergoing pancreaticoduodenectomy for pancreatic adenocarcinoma were assessed and their impact on survival was determined. Median data are presented. Two hundred ninety-eight (67%) patients had negative margins (R0), an additional 110 (25%) patients had microscopically positive and macroscopically negative margins (R1), and an additional 40 (9%) patients had initially positive microscopic margins, which became negative with further resection (R1 → R0). R0 resections were more likely to have smaller tumors, earlier T grade, earlier N grade, lower American Joint Committee on Cancer stage, and less frequent extrapancreatic extension (P ≤ 0.03 for each). Survival was better with R0 resections than R1 resections (20 vs 12 months, P < 0.001); extending resections to achieve negative margins (i.e., R1 → R0) did not improve survival beyond R1 resections (14 vs 12 months, P = 0.19). Survival after pancreaticoduodenectomy is disappointing. Patients with initial negative margins do best. Positive microscopic margins reflect more aggressive tumor-specific factors and lead to abbreviated survival even with extended resections to achieve negative margins (i.e., R1 → R0). With an initial positive margin, pursuing negative margins does not improve survival and, thereby, negative margins should not be "chased."

Transduodenal ampullectomy for ampullary adenomas: a safe and effective procedure with long-term salutary outcomes.

With widespread use of endoscopy, ampullary adenomas are more frequently identified, many of which are not amenable to endoscopic resection. Pancreatoduodenctomy is curative for these lesions but carries high morbidity. The purpose of this study was to determine the safety and efficacy of transduodenal ampullectomy for these lesions. Data were collected on 32 patients who underwent transduodenal ampullectomy from 2002 to 2010. The median age of patients was 64 years. Adenomas were found because of abdominal pain in 34 per cent, jaundice in 22 per cent, and incidentally on endoscopic screening in 16 per cent and on computed tomography scan of the abdomen in 9 per cent. All patients had a preoperative diagnosis of premalignant disease; 6 per cent required intraoperative conversion to pancreaticoduodenectomy after frozen section evaluation documented carcinoma. Of ampullectomies, 97 per cent had clear margins. Follow-up was 28 months. Four (13%) patients developed recurrent disease at 4 years, 2 years, 1.5 years, and 4 months; all had clear margins at ampullectomy and underwent subsequent pancreaticoduodenectomy with invasive malignancy in a single patient. After preoperative biopsy documenting premalignant disease, malignancy at ampullectomy is unusual. Recurrence is uncommon but occurs even with clear margins necessitating diligent follow-up; even with diligent follow-up, recurrence can be malignant.

Obesity portends increased morbidity and earlier recurrence following liver transplantation for hepatocellular carcinoma.

BACKGROUND: Obesity has been associated with poor oncologic outcomes following pancreatoduodenectomy for pancreatic cancer. However, there is a paucity of evidence on the impact of obesity on postoperative complications, oncologic outcome and survival in patients with hepatocellular carcinoma (HCC) undergoing orthotopic liver transplantation (OLT). METHODS: From a database of over 1000 patients who underwent OLT during 1996-2008, 159 patients with a diagnosis of HCC were identified. Demographic data, body mass index (BMI), perioperative parameters, recurrence and survival were obtained. Complications were grouped according to Clavien-Dindo grading (Grades I-V). RESULTS: There were increased incidences of life-threatening complications in overweight (58%) and obese (70%) patients compared with the non-obese patient group (41%) (P < 0.05). Furthermore, the incidence of recurrence of HCC was doubled in the presence of overweight (15%) and obesity (15%) compared with non-obesity (7%) (P < 0.05). Time to recurrence also decreased significantly. Differences in mean ± standard deviation survival in the overweight (45 ± 3 months) and obese (41 ± 4 months) groups compared with the non-obese group (58 ± 6 months) did not reach statistical significance. CONCLUSIONS: These findings indicate that BMI is an important surrogate marker for obesity and portends an increased risk for complications and a poorer oncologic outcome following OLT for HCC.

The perforated appendiceal carcinoid in children: a surgical dilemma.

The decision for aggressive reoperation after discovery of an appendiceal carcinoid is generally based upon criteria such as size, grade, degree of involvement of the mesoappendix or the appendiceal base, lymphovascular invasion, and the presence of goblet cell or adenocarcinoid features. No guidelines currently exist for the management of perforated appendiceal carcinoids. We present a case of perforated appendiceal carcinoid that was subsequently treated with right hemicolectomy, and we review the pertinent literature.

Preoperative computed tomography measurements of pancreatic steatosis and visceral fat: prognostic markers for dissemination and lethality of pancreatic adenocarcinoma.

BACKGROUND: Increased visceral fat and pancreatic steatosis promote lymphatic metastases and decreased survival in patients with pancreatic adenocarcinoma after pancreatoduodenectomy (PD). OBJECTIVES: We aim to determine the utility of preoperative computed tomography (CT) measurements of pancreatic steatosis and visceral fat as prognostic indicators in patients with pancreatic adenocarcinoma. METHODS: High-resolution CT scans of 42 patients undergoing PD for pancreatic adenocarcinoma were reviewed. Attenuation in CT of the pancreas, liver and spleen were measured in Hounsfield units and scored by two blinded investigators. Perirenal adipose tissue was measured in mm. RESULTS: Lymphatic metastases were present in 57% of patients. Age, gender, tumour size and margin status were similar in patients with and without nodal metastases. Node-positive patients had increased visceral but not subcutaneous fat pads compared with node-negative patients and decreased CT attenuation of the pancreatic body and tail and liver. Node-positive patients stratified by visceral adiposity (≥10 mm vs. <10 mm) demonstrated poorer survival (7 ± 1 months vs. 16 ± 2 months; P < 0.01). CONCLUSIONS: In resected pancreatic adenocarcinoma, increased pancreatic steatosis and increased visceral fat stores are associated with lymphatic metastases. Furthermore, increased visceral fat is associated with abbreviated survival in patients with lymphatic metastases. Hence, increased visceral fat may be a causative factor of abbreviated survival and serves a prognostic role in patients with pancreatic malignancies.

Obesity potentiates the growth and dissemination of pancreatic cancer.

BACKGROUND: Obesity is an independent risk factor for pancreatic cancer development and progression, although the mechanisms underlying this association are completely unknown. The aim of the current study was to investigate the influence of obesity on pancreatic cancer growth using a novel in vivo model. METHODS: Lean (C57BL/6 J) and obese (Lep(Db) and Lep(Ob)) mice were inoculated with murine pancreatic cancer cells (PAN02), and studied after 5 weeks of tumor growth. Tumor histology was evaluated by hematoxylin and eosin staining, cellular proliferation was assessed by 5-bromodeoxyuridine, and apoptosis was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay. Serum adiponectin, leptin, and insulin levels were assayed. RESULTS: Obese mice developed larger tumors, and a significantly greater number of mice developed metastases; mortality was also greater in obese mice. Tumor apoptosis did not differ among strains, but tumors from both obese strains had greater proliferation relative to those growing in lean animals. Serum adiponectin concentration correlated negatively and serum insulin concentration correlated positively with tumor proliferation. Intratumoral adipocyte mass in tumors from both obese strains was significantly greater than that in tumors of lean mice. CONCLUSION: Data from this novel in vivo model suggest that the altered adipokine milieu and insulin resistance observed in obesity may lead directly to changes in tumor microenvironment, thereby promoting pancreatic cancer growth and dissemination.

Pancreatic steatosis promotes dissemination and lethality of pancreatic cancer.

BACKGROUND: Obesity is a worldwide epidemic. Clinical and basic studies have shown obesity to be associated with an increased incidence and progression of pancreatic cancer. The precise role that pancreatic fat plays in this process has remained undefined. We tested the hypothesis that pancreatic steatosis would be associated with increased dissemination and reduced survival in patients with resected pancreatic cancer. STUDY DESIGN: A case-control analysis was conducted in patients who had undergone resection for pancreatic adenocarcinoma. Twenty lymph node-positive patients and 20 node-negative patients were matched for age (59 versus 63 years), gender (70% male versus 60% male), body mass index (24.5 versus 25.6), medical comorbidities (hypertension, diabetes, hyperlipidemia), tumor size (2.8 versus 2.6 cm), and resection status (Ro 80% versus 85%). Pancreatic neck margins were reviewed in a blinded fashion by two trained investigators. Pancreatic fat (number of cells/5 high power field) and degree of fibrosis (0 to 4+) were recorded. RESULTS: Node-positive patients had significantly more fat cells in the pancreas compared with node-negative patients (46.4 +/- 8.7 versus 21.4 +/- 4.8; p < 0.02). Node-positive patients also demonstrated decreased fibrosis compared with node-negative patients (1.7 +/- 0.3 versus 2.7 +/- 0.3; p < 0.02). Mean survival was reduced in node-positive patients (18.9 +/- 2.7 versus 30.8 +/- 4.8 months; p < 0.04). CONCLUSIONS: These data show that increased pancreatic fat promotes dissemination and lethality of pancreatic cancer. We conclude that pancreatic steatosis alters the tumor microenvironment, enhances tumor spread, and contributes to the early demise of patients with pancreatic adenocarcinoma.

Nuclear magnetic resonance spectroscopy-based metabolomics of the fatty pancreas: implicating fat in pancreatic pathology.

BACKGROUND: Obesity is a worldwide epidemic and a significant risk factor for pancreatic diseases including pancreatitis and pancreatic cancer; the mechanisms underlying this association are unknown. Metabolomics is a powerful new analytical approach for describing the metabolome (compliment of small molecules) of cells, tissue or biofluids at any given time. Our aim was to analyze pancreatic fat content in lean and congenitally obese mice using both metabolomic analysis and conventional chromatography. METHODS: The pancreatic fat content of 12 lean (C57BL/6J), 12 obese leptin-deficient (Lep(ob)) and 12 obese hyperleptinemic (Lep(db)) mice was evaluated by metabolomic analysis, thin-layer and gas chromatography. RESULTS: Pancreata of congenitally obese mice had significantly more total pancreatic fat, triglycerides and free fatty acids, but significantly less phospholipids and cholesterol than those of lean mice. Metabolomic analysis showed excellent correlation with thin-layer and gas chromatography in measuring total fat, triglycerides and phospholipids. CONCLUSIONS: Differences in pancreatic fat content and character may have important implications when considering the local pancreatic proinflammatory milieu in obesity. Metabolomic analysis is a valid, powerful tool with which to further define the mechanisms by which fat impacts pancreatic disease.

Cannabinoid receptor-1 blockade attenuates acute pancreatitis in obesity by an adiponectin mediated mechanism.

BACKGROUND: Obesity is a risk factor for increased severity of acute pancreatitis. Adipocytes produce adiponectin, an anti-inflammatory molecule that is paradoxically decreased in the setting of obesity. We have shown that adiponectin concentration inversely mirrors the severity of pancreatitis in obese mice. Cannabinoid receptor CB-1 blockade increases circulating adiponectin concentration. We, therefore, hypothesize that blockade of CB-1 would increase adiponectin and attenuate pancreatitis severity. METHODS: Forty lean (C57BL/6J) and 40 obese (Lep(Db)) mice were studied. Half of the mice in each strain received intraperitoneal injection of the CB-1 antagonist rimonabant (10 mg/kg daily for 7 days); the others received vehicle. Pancreatitis was induced by intraperitoneal injection of cerulein (50 microg/g hourly x 6). Pancreatitis severity was determined by histology. Pancreatic chemokine and proinflammatory cytokine concentrations were measured by ELISA. RESULTS: Rimonabant treatment significantly increased circulating adiponectin concentration in obese mice (p < 0.03 vs. vehicle). After induction of pancreatitis, obese mice treated with rimonabant had significantly decreased histologic pancreatitis (p < 0.001), significantly lower pancreatic tissue levels of monocyte chemoattractant protein-1 (p = 0.03), tumor necrosis factor-alpha (p < 0.001), interleukin-6 (p < 0.001), and myeloperoxidase (p = 0.006) relative to vehicle-treated animals. CONCLUSIONS: In obese mice, cannabinoid receptor CB-1 blockade with rimonabant attenuates the severity of acute pancreatitis by an adiponectin-mediated mechanism.

Steatocholecystitis: the influence of obesity and dietary carbohydrates.

INTRODUCTION: We have recently demonstrated that obese and lean mice fed a high fat diet have increased gallbladder wall fat and decreased gallbladder contractility, cholecystosteatosis. Animal and human data also suggest that diets high in refined carbohydrates lead to gallstone formation. However, no data are available on the role of dietary carbohydrates on gallbladder wall fat and inflammation. Therefore, we tested the hypothesis that both obesity and dietary carbohydrates would increase gallbladder fat and cytokines, steatocholecystitis. METHODS: At 8 wk of age, 47 lean and 22 obese female mice were fed a 45% carbohydrate (CHO) diet while an equal number of lean and obese mice were fed a 75% CHO diet for 4 wk. All mice underwent cholecystectomy, and the gallbladders were snap-frozen. Individual and total lipids were measured by gas chromatography. Interleukin (IL)-1beta, tumor necrosis factor (TNF)-alpha, and IL-6 were measured by enzyme-linked immunosorbent assay. Data were analyzed by analysis of variance and Tukey test. RESULTS: Gallbladder total fat, triglycerides, and cholesterol were maximum (P < 0.001) in obese mice on the 75% CHO diet. Gallbladder TNF-alpha and IL-1beta as well as serum cholesterol levels showed a similar pattern (P < 0.001). Gallbladder saturated free fatty acids and IL-6 levels were highest (P < 0.001) in obese mice on the 45% CHO diet. CONCLUSIONS: These data suggest that (1) both obesity and dietary carbohydrates increase gallbladder total fat, triglycerides, cholesterol, TNF-alpha, and IL-1beta and (2) obesity also increases gallbladder free fatty acids and IL-6. Therefore, we conclude that obesity is associated with steatocholecystitis and that a high carbohydrate diet exacerbates this phenomenon.

Fatty pancreas: a factor in postoperative pancreatic fistula.

OBJECTIVE: To determine whether patients who develop a pancreatic fistula after pancreatoduodenectomy are more likely to have pancreatic fat than matched controls. BACKGROUND: Pancreatic fistula continues to be a major cause of postoperative morbidity and increased length of stay after pancreatoduodenectomy. Factors associated with postoperative pancreatic fistula include a soft pancreas, a small pancreatic duct, the underlying pancreatic pathology, the regional blood supply, and surgeon's experience. Fatty pancreas previously has not been considered as a contributing factor in the development of postoperative pancreatic fistula. METHODS: Forty patients with and without a pancreatic fistula were identified from an Indiana University database of over 1000 patients undergoing pancreatoduodenectomy and matched for multiple parameters including age, gender, pancreatic pathology, surgeon, and type of operation. Surgical pathology specimens from the pancreatic neck were reviewed blindly for fat, fibrosis, vessel density, and inflammation. These parameters were scored (0-4+). RESULTS: The pancreatic fistula patients were less likely (P < 0.05) to have diabetes but had significantly more intralobular (P < 0.001), interlobular (P < 0.05), and total pancreatic fat (P < 0.001). Fistula patients were more likely to have high pancreatic fat scores (50% vs. 13%, P < 0.001). Pancreatic fibrosis, vessel density, and duct size were lower (P < 0.001) in the fistula patients and negative correlations (P < 0.001) existed between fat and fibrosis (R = -0.40) and blood vessel density (R = -0.15). CONCLUSIONS: These data suggest that patients with postoperative pancreatic fistula have (1) increased pancreatic fat and (2) decreased pancreatic fibrosis, blood vessel density, and duct size. Therefore, we conclude that fatty pancreas is a risk factor for postoperative pancreatic fistula.