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Jarrod P Meadows1,2, James A Tumlin3, Mark G Clemens4, Iain H McKillop1,4, Susan Evans1,21Department of Surgery; 2FH “Sammy” Ross Jr Trauma Center, Carolinas Medical Center, Charlotte, NC, USA; 3Department of Medicine, Division of Nephrology, University of Tennessee College of Medicine at Chattanooga, Chattanooga, TN, USA; 4Department of Biology, University of North Carolina at Charlotte, Charlotte, NC, USABackground: Neutrophils are implicated in initiating perioperative inflammation and postoperative outcome, particularly in patients with acute renal failure. The aim of the current study was to assess the role of neutrophil function in patients following cardiovascular surgery with mild preoperative renal dysfunction (PRD).Materials and methods: Patients scheduled for cardiovascular operations were screened for renal function, and divided into those with glomerular filtration rate (GFR) < 60 mL/minute (PRD, n = 9), and GFR > 60 mL/minute (normal controls; [C] n = 7). Neutrophils were isolated from plasma preoperatively, and 2, 24, and 48 hours postoperatively. Neutrophil activity (respiratory burst; RB) and apoptosis were then determined.Results: In the whole population, neutrophil apoptosis decreased from 67% preoperatively, to 42% postoperatively, with no significant difference between the groups (C = 64.8%–41.2%, PRD = 68.2%–42.6%). RB increased by 70% postoperatively in the whole population, with no significant difference between the groups (C = 68.1%, PRD = 72.9%, P = 0.86).Conclusion: Collectively these data demonstrate that, in addition to decreasing neutrophil apoptosis, cardiovascular surgery leads to increased neutrophil RB, thus contributing to postoperative systemic oxidative stress. This can lead to clinically significant complications and tissue damage. Our data also suggest that differences in postoperative inflammation between patients with and without PRD, do not exist, at least in the setting of mild preoperative renal insufficiency.Keywords: neutrophil, renal function, apoptosis, respiratory burst, glomerular filtration rate

Irreversible electroporation (IRE) is a minimally thermal tissue ablation modality used to treat solid tumors adjacent to critical structures. Widespread clinical adoption of IRE has been limited due to complicated anesthetic management requirements and technical demands associated with placing multiple needle electrodes in anatomically challenging environments. High-frequency irreversible electroporation (H-FIRE) delivered using a novel single-insertion bipolar probe system could potentially overcome these limitations, but ablation volumes have remained small using this approach. While H-FIRE is minimally thermal in mode of action, high voltages or multiple pulse trains can lead to unwanted Joule heating. In this work, we improve the H-FIRE waveform design to increase the safe operating voltage using a single-insertion bipolar probe before electrical arcing occurs. By uniformly increasing interphase ( d 1 ) and interpulse ( d 2 ) delays, we achieved higher maximum operating voltages for all pulse lengths. Additionally, increasing pulse length led to higher operating voltages up to a certain delay length (  ∼ 25 μs), after which shorter pulses enabled higher voltages. We then delivered novel H-FIRE waveforms via an actively cooled single-insertion bipolar probe in swine liver in vivo to determine the upper limits to ablation volume possible using a single-needle H-FIRE device. Ablations up to 4.62 ± 0.12cm x 1.83 ± 0.05cm were generated in 5 minutes without a requirement for cardiac synchronization during treatment. Ablations were minimally thermal, easily visualized with ultrasound, and stimulated an immune response 24 hours post H-FIRE delivery. These data suggest H-FIRE can rapidly produce clinically relevant, minimally thermal ablations with a more user-friendly electrode design.

Background: Colorectal cancer (CRC) is the third most common cause of cancer mortality worldwide. Of these, approximately 25% will have liver metastasis. We performed 394 microwave ablations (MWAs) and analyzed outcomes for survival and ablation failure., Study Design: We conducted a retrospective review of patients who underwent a surgical MWA at a single-center high-volume institution from October 2006 to September 2022 using a prospectively maintained database. The primary outcome was overall survival., Results: A total of 394 operations were performed on 328 patients with 842 tumors undergoing MWA. Median tumor size was 1.5 cm (range 0.4 to 7.0 cm), with the median number of tumors ablated per operation being 1 (range 1 to 11). A laparoscopic approach was used 77.9% of the time. Concomitant procedures were performed 63% of the time, most commonly hepatectomy (22.3%), cholecystectomy (17.5%), and colectomy (6.6%). Clavien-Dindo grade III or IV complication occurred in 12 patients (3.6%), and all of these patients had undergone concomitant procedures. Mortality within 30 days occurred in 4 patients (1.2%). The rate of incomplete ablation was 1.5% per tumor. Local recurrence occurred at a rate of 6.3% per tumor. Black patients were found to have a higher incidence of incomplete ablation and local recurrence. One-year survival probability was 91% (95% CI 87.9 to 94.3), with a mean overall survival of 57.6 months (95% CI 49.9 to 65.4 months)., Conclusions: Surgical MWA offers a low-morbidity approach to treatment of colorectal liver metastasis, with low rate of failure. This large series reviews the outcomes of MWA as definitive treatment for colorectal liver metastasis., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Microwave ablation is becoming increasingly common for the treatment of liver tumors. Despite numerous studies aimed at identifying risk factors for local recurrence after microwave ablation, a consensus on modifiable risk factors for failure remains elusive, partly because of the limited statistical power of these studies. This study investigated the incidence of technical failure after microwave ablation, encompassing both incomplete ablation and local recurrence, and aimed to identify modifiable factors that reduce technical failure., Methods: This retrospective review included patients who underwent surgical microwave ablation at a high-volume institution between October 2006 and March 2023. Univariate analysis, multivariate analysis, and propensity score matching were performed to identify risk factors for technical failure., Results: A total of 1,613 surgical microwave ablations were performed on 3,035 tumors, with 226 instances (14% per procedure, 7.4% per tumor) of technical failure. Incomplete ablation occurred at a rate of 1.7% per tumor, whereas local recurrence was identified in 6.5% of ablations in per-tumor analysis. Body mass index >25 was significant for failure (odds ratio, 1.50; 95% confidence interval, 1.07-2.11; P < .05), suggesting that more difficult targeting may lead to increased technical failure rates. African American race (odds ratio, 1.62; 95% confidence interval, 1.16-2.27; P < .05), pre-microwave ablation transarterial chemoembolization (odds ratio, 1.54; 95% confidence interval, 1.08-2.21; P < .05), and previous ablation (odds ratio, 1.58; 95% confidence interval, 1.09-2.29; P < .05) were found to be statistically significant., Conclusion: On the basis of the largest microwave ablation database available to date, this study identified novel modifiable and nonmodifiable risk factors of microwave ablation failure. These results can lead to decreasing technical failure rates after microwave ablation., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The incidence of obesity in African Americans (AAs) is higher than in non-AA in the USA. Previous studies using large national databases report that AA patients have worse outcomes than non-AA patients., Objectives: To assess perioperative outcomes among AA patients after MBS at a center of excellence (COE) that serves a large, diverse patient population., Setting: University Hospital METHODS: A retrospective analysis was performed on patients undergoing MBS between 2010 and 2020 at our two accredited MBSAQIP (Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program) COEs where the AA population makes up over 35% of the population. Preoperative variables were compared using unpaired t-test or chi-squared test where appropriate. Thirty-day outcomes were compared following propensity score matching (exact algorithm) of demographics and comorbidities., Results: Overall, 5742 patients (AA = 2058, 36%) had Roux-en-Y gastric bypass (AA = 1028, 26%) or sleeve gastrectomy (AA = 1030, 27%). AA patients were more often female (90.2% vs. 80.2%, p < 0.001) and had higher rates of hypertension (56.3% vs. 47.8%, p < 0.001), while non-AA patients had higher rates of hyperlipidemia (27.3% vs. 20.7%, p < 0.001) and obstructive sleep apnea (41.2% vs. 37.1%, p = 0.0024). Matched data showed that AA patients had higher rates of pulmonary embolism (PE) (0.3% vs. 0.1%, p = 0.020) and more emergency department visits (7.0% vs. 5.1%, p = 0.012) but no differences in mortality, readmission, reintervention, or reoperation rates., Conclusions: In a diverse area, AA patients who underwent MBS had similar perioperative outcomes compared to non-AA patients except that they experienced higher rates of PE. They also experienced higher rates of emergency department visits but had similar readmission rates., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Alcohol-associated liver disease (ALD) is a substantial cause of morbidity and mortality worldwide and represents a spectrum of liver injury beginning with hepatic steatosis (fatty liver) progressing to inflammation and culminating in cirrhosis. Multiple factors contribute to ALD progression and disease severity. Here, we overview several crucial mechanisms related to ALD end-stage outcome development, such as epigenetic changes, cell death, hemolysis, hepatic stellate cells activation, and hepatic fatty acid binding protein 4. Additionally, in this review, we also present two clinically relevant models using human precision-cut liver slices and hepatic organoids to examine ALD pathogenesis and progression.

This study introduces a new method of targeting acidosis (low pH) within the tumor microenvironment (TME) through the use of cathodic electrochemical reactions (CER). Low pH is oncogenic by supporting immunosuppression. Electrochemical reactions create local pH effects when a current passes through an electrolytic substrate such as biological tissue. Electrolysis has been used with electroporation (destabilization of the lipid bilayer via an applied electric potential) to increase cell death areas. However, the regulated increase of pH through only the cathode electrode has been ignored as a possible method to alleviate TME acidosis, which could provide substantial immunotherapeutic benefits. Here, we show through ex vivo modeling that CERs can intentionally elevate pH to an anti-tumor level and that increased alkalinity promotes activation of naïve macrophages. This study shows the potential of CERs to improve acidity within the TME and that it has the potential to be paired with existing electric field-based cancer therapies or as a stand-alone therapy., (© 2023. The Author(s) under exclusive licence to Biomedical Engineering Society.)

Introduction: Acetaminophen (APAP) toxicity remains a significant cause of adult and pediatric liver failure in North America and Europe. Previous research has evaluated the impaired mitochondrial function associated with APAP toxicity. The primary aim of this study was to evaluate the effects of APAP toxicity on platelet mitochondrial function using platelet oxygen consumption in a murine model in vivo. Our secondary objectives were to determine the effect of 4-MP on platelet mitochondrial function and hepatic toxicity in the setting of APAP overdose, and to correlate platelet mitochondrial function with other markers of APAP toxicity., Methods: Male C57Bl/6 mice were randomized to receive APAP (300 or 500 mg/kg) or vehicle followed 90 minutes later by either 4-MP (50 mg/kg) or vehicle via intraperitoneal injection. Mice were euthanized 0, 12, or 24 hours later and platelets isolated from cardiac blood and counted. Platelet oxygen consumption (POC) was determined using a closed-system respirometer. Liver injury was assessed by measuring alanine transferase (ALT) and histological evaluation., Results: Injection of 500 mg/kg APAP led to increased POC versus pair-matched control (vehicle) (p < 0.001). Administration of 4-MP did not affect POC in control or 300 mg/kg APAP mice. In mice receiving 500 mg/kg APAP and 4-MP, POC decreased significantly compared to mice receiving 500 mg/kg APAP alone (p < 0.01). Serum and histological analysis confirmed APAP-induced hepatic damage in mice receiving 500 mg/kg APAP and these effects blunted by treatment with 4-MP., Conclusions: Platelet oxygen consumption as a measure of mitochondrial function may be useful as a biomarker of hepatic APAP toxicity in the setting of moderate to severe overdose. Treatment with 4-MP decreases hepatic necrosis and may mitigate the harmful effects of APAP on platelet mitochondrial function detected via POC., (© 2023. American College of Medical Toxicology.)

Background: A significant number of patients with advanced pancreatic cancer are unable to undergo resection due to vascular involvement. Irreversible electroporation (IRE) has shown promise in improving survival. This study sought to assess a novel IRE application whereby IRE was performed pre-resection to alter tissue plasticity and assist tumor removal from underlying vasculature when surgical excision was otherwise precluded., Methods: After multidisciplinary evaluation appropriate patients were consented for IRE therapy. All IRE cases were tracked prospectively using an institutional review board-approved database that was retrospectively queried for patients undergoing IRE-assisted resection (IRE-AR) for pancreatic adenocarcinoma located in the head/uncinate process. Patients who underwent other IRE therapy or had disease location elsewhere were excluded., Results: 5 patients met the study inclusion criteria with a mean tumor size of 3.2 cm (range 2.4-4.1 cm). Using IRE-AR median recurrence free survival was 10.6 months, with 21.6 month overall survival. The average comprehensive complication index score was 23.23. One patient had grade 3 [or higher] complications and there were no 90 day mortalities., Discussion: Employing a high-starting voltage for ablation along resection margins allows for resection when margins are anticipated to be positive. Patients with locally advanced pancreatic adenocarcinoma who underwent IRE-AR had promising outcomes., Conclusion: This study reports IRE-AR as a novel approach for resecting locally advanced pancreatic adenocarcinoma. A prospective trial of IRE-AR for inoperable pancreatic adenocarcinoma will provide additional data for the long-term application of this approach.

Surgical revision of biliary enteric anastomoses (BEA) can be a challenging undertaking and a robotic platform may provide advantages that address many of the technical obstacles. We present our technical approach and outcomes for patients undergoing robotic revision of BEA for benign strictures. A retrospective review was performed for robot-assisted benign BEA revision at our institution. Operative details, perioperative metrics, and outcomes are reported. Four patients underwent anastomotic revision following previously failed non-operative management. There were no intraoperative complications, mean length of stay was 4-days, and all patients experienced resolution of presenting clinical signs and symptoms. No patients required reoperation and there was no mortality. Postoperative outcomes were consistent with findings reported for other interventional modalities. Based on our experience we conclude robotic intervention in this context is safe and improves the technical feasibility of this complex procedure.

Background: Obesity rates in Hispanics and African Americans (AAs) are higher than in Caucasians in the USA, yet the rate of metabolic and bariatric surgery (MBS) for weight loss remains lower for both Hispanics and AAs., Methods: Patient demographics and outcomes of adult AA and Hispanic patients undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) procedures were analyzed using the MBSAQIP dataset [2015-2018] using unmatched and propensity-matched data., Results: In total, 173,157 patients were included, of whom 98,185 were AA [56.7%] [21,163-RYGB; 77,022-SG] and 74,972 were Hispanic [43.3%] [20,282-RYGB; 54,690-SG]). Preoperatively, the AA cohort was older, had more females, and higher BMIs with higher rates of all tracked obesity-related medical conditions except for diabetes, venous stasis, and prior foregut surgery. Intra- and postoperatively, AAs were more likely to experience major complications including unplanned ICU admission, 30-day readmission/reintervention, and mortality. After propensity matching, the differences in ED visits, treatment for dehydration, 30-day readmission, 30-day intervention, and pulmonary embolism remained for both SG and RYGB cohorts. Progressive renal insufficiency and ventilator use lost statistical significance in both cohorts. Conversely, 30-day reoperation, postoperative ventilator requirement, unplanned intubation, unplanned ICU admission, and mortality lost significance in the RYGB cohort, but not SG patients., Conclusion: Outcomes for AA patients were worse than for Hispanic patients, even after propensity matching. After matching, differences in major complications and mortality lost significance for RYGB, but not SG. These data suggest that outcomes for RYGB may be driven by the presence and severity of pre-existing patient-related factors., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Donated platelets are critical components of hemostasis management. Extending platelet storage beyond the recommended guidelines (5 days, 22 °C) is of clinical significance. Platelet coagulation function can be prolonged with resveratrol (Res) or cytochrome c (Cyt c) at 4 °C. We hypothesized that storage under these conditions is associated with maintained aggregation function, decreased reactive oxygen species (ROS) production, increased mitochondrial respiratory function, and preserved morphology. Donated platelets were stored at 22 °C or 4 °C supplemented with 50 μM Res or 100 μM Cyt c and assayed on days 0 (baseline), 5, 7 and 10 for platelet aggregation, morphology, intracellular ROS, and mitochondrial function. Declining platelet function and increased intracellular ROS were maintained by Res and Cyt c. Platelet respiratory control ratio declined during storage using complex I + II (CI + CII) or CIV substrates. No temperature-dependent differences (4 °C versus 22 °C) in respiratory function were observed. Altered platelet morphology was observed after 7 days at 22 °C, effects that were blunted at 4 °C independent of exposure to Res or Cyt c. Storage of platelets at 4 °C with Res and Cyt c modulates ROS generation and platelet structural integrity.

Fatty acid binding protein-4 ( FABP4 ) is not normally expressed in the liver but is induced in alcohol-dependent liver disease (ALD)). This study sought to identify mechanisms whereby ethanol (EtOH) metabolism alters triglyceride accumulation and FABP4 production. Human hepatoma cells which were stably transfected to express alcohol dehydrogenase (ADH) or cytochrome P4502E1 (CYP2E1) were exposed to EtOH in the absence/presence of inhibitors of ADH (4-methylpyrazole) or CYP2E1 (chlormethiazole). Cells were analyzed for free fatty acid (FFA) content and FABP4 mRNA, then culture medium assayed for FABP4 levels. Cell lysates were analyzed for AMP-activated protein kinase-α (AMPKα), Acetyl-CoA carboxylase (ACC), sterol regulatory element binding protein-1c (SREBP-1c), and Lipin-1β activity and localization in the absence/presence of EtOH and pharmacological inhibitors. CYP2E1-EtOH metabolism led to increased FABP4 mRNA/protein expression and FFA accumulation. Analysis of signaling pathway activity revealed decreased AMPKα activation and increased nuclear-SREBP-1c localization following CYP2E1-EtOH metabolism. The role of AMPKα-SREBP-1c in regulating CYP2E1-EtOH-dependent FFA accumulation and increased FABP4 was confirmed using pharmacological inhibitors and over-expression of AMPKα. Inhibition of ACC or Lipin-1β failed to prevent FFA accumulation or changes in FABP4 mRNA expression or protein secretion. These data suggest that CYP2E1-EtOH metabolism inhibits AMPKα phosphorylation to stimulate FFA accumulation and FABP4 protein secretion via an SREBP-1c dependent mechanism.

Introduction: The interaction between activated hepatic stellate cells (aHSCs) and macrophages is central to liver fibrosis development. The cargo contained within aHSC exosomes (aHSC-EXOs) and how aHSC-EXOs affect macrophage function is poorly understood., Methods: RNA from aHSC-EXOs was separated into small (<200-basepairs) and large (≥200-basepairs) RNA species, transfected into macrophages, and macrophage IL-6 and TNFα mRNA expression and protein secretion measured. Next generation sequencing was performed on EXOs from rat quiescent and aHSCs and human aHSCs. aHSCs were transfected with siRNA against ectodysplasin-A (EDA), EXOs collected, and their effect on macrophage function analyzed. Human cirrhotic liver was analyzed for EDA mRNA expression and compared to non-tumor liver (NTL)., Results: Transfection with large RNA from aHSC-EXOs stimulated macrophage IL-6 and TNFα mRNA expression and protein secretion. EDA mRNA was highly expressed in aHSCs and transfection of aHSCs with EDA-siRNA decreased aHSC-EXO EDA mRNA and blunted the effect of aHSC-EXOs on macrophage function (IL-6/TNFα expression and macrophage migration). Human cirrhotic liver exhibited high EDA mRNA compared to NTL., Conclusions: HSC activation leads to altered EXO mRNA/miRNA profiles with aHSC-EXOs mRNAs exerting a dominant role in altering macrophage function. Ectodysplasin-A mRNA is an important component in aHSC-EXOs in regulating macrophage function., Competing Interests: Declaration of competing interest The authors have no disclosures to report., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: This study investigated how the association between metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) diagnosis varies between non-Hispanic African American and white patients. Methods: A retrospective cohort study was performed using electronic medical records from an integrated health care system (2010-2018). Adults with records for all MetS measurements (body mass index, lipids, blood pressure, and blood glucose) in 2011, who did not have a NAFLD diagnosis before their last MetS measurement, were included. Results: The study cohort consisted of 139,336 patients (age 56.1 ± 15.2 years, 57.9% female, 79.4% non-Hispanic white). The rate of NAFLD diagnosis was higher in MetS patients compared with non-MetS patients [adjusted hazards ratio (AHR) = 1.99, 95% CI = 1.91-2.09] with a significant interaction by race (AHR = 2.05, 95% CI = 1.95-2.15 in non-Hispanic whites vs. AHR = 1.76, 95% CI = 1.58-1.96 non-Hispanic African Americans, P  = 0.017). Secondary analyses revealed that the relative NAFLD diagnosis rate was higher in non-Hispanic whites with MetS compared with non-Hispanic African Americans with MetS among females and patients 18-39 years of age and 40-59 years, but not among males and those ≥60 years of age. Conclusions: Non-Hispanic white patients with MetS, particularly females and those <60 years of age, may be at increased risk of NAFLD compared with non-Hispanic African American MetS patients and may benefit from extra attention regarding NAFLD screening.

Background: Hepatic steatosis is an early pathology of alcohol-associated liver disease (ALD). Fatty acid-binding protein-4 (FABP4, a FABP not normally produced in the liver) is secreted by hepatocytes in ALD and stimulates hepatoma proliferation and migration. This study sought to investigate the mechanism[s] by which hepatic ethanol metabolism regulates FABP4 and steatosis., Methods: Human hepatoma cells (HepG2/HuH7) and cells stably transfected to express cytochrome P450 2E1 (CYP2E1), were exposed to ethanol in the absence or presence of chlormethiazole (a CYP2E1-inhibitor; CMZ) and/or EX-527 (a sirtuin-1 [SIRT1] inhibitor). The culture medium was analyzed for ethanol metabolism and FABP4 protein abundance. Cells were analyzed for FABP4 mRNA expression, SIRT1 protein abundance, and neutral lipid accumulation. In parallel, cells were analyzed for forkhead box O1 [FOXO1], β-catenin, peroxisome proliferator-activated receptor-α [PPARα], and lipin-1α protein abundance in the absence or presence of ethanol and pharmacological inhibitors of the respective target proteins., Results: CYP2E1-dependent ethanol metabolism inhibited the amount of SIRT1 protein detected, concomitant with increased FABP4 mRNA expression, FABP4 protein secretion, and neutral lipid accumulation, effects abolished by CMZ. Analysis of pathways associated with lipid oxidation revealed increased FOXO1 nuclear localization and decreased β-catenin, PPARα, and lipin-1α protein levels in CYP2E1-expressing cells in the presence of ethanol. Pharmacological inhibition of SIRT1 mimicked the effects of ethanol, while inhibition of FOXO1 abrogated the effect of ethanol on FABP4 mRNA expression, FABP4 protein secretion, and neutral lipid accumulation in CYP2E1-expressing cells. Pharmacological inhibition of β-catenin, PPARα, or lipin-1α failed to alter the effects of ethanol on FABP4 or neutral lipid accumulation., Conclusion: CYP2E1-dependent ethanol metabolism inhibits SIRT1-FOXO1 signaling, which leads to increased FABP4 mRNA expression, FABP4 protein secretion, and neutral lipid accumulation. These data suggest that FABP4 released from steatotic hepatocytes could play a role in promoting tumor cell expansion in the setting of ALD and represents a potential target for therapeutic intervention., (© 2022 by the Research Society on Alcoholism.)

Introduction: For patients with super obesity (BMI > 50 kg/m 2 ), biliopancreatic diversion/duodenal switch (BPD/DS) can be an effective bariatric operation. Technical challenges and patient safety concerns, however, have limited its use as a primary procedure. This study sought to assess the safety of primary versus revisional BPD/DS., Materials and Methods: The MBSAQIP database was queried for primary and revisional BPD/DS (2015-2018). Inclusion criteria were patients ≥ 18 years of age, BMI > 50 kg/m 2 , and with no concurrent procedures. Preoperative variables were compared using a chi-square test or Wilcoxon two-sample tests. Multivariate logistic or robust linear regression models were used to compare outcomes., Results: There were 3,378 primary BPD/DS and 487 revisional BPD/DS patients. Primary BPD/DS patients had higher BMI (56.5 [IQR4.4] versus 54.8 [IQR4] kg/m 2 , p < 0.0001) and had more diabetes mellitus type II (29.1% versus 17.2%, p < 0.0001). Intraoperatively, revisional BPD/DS had longer operative time (165 [IQR47] min versus 139 [IQR100] min, p < 0.0001). After adjusting for preoperative characteristics, there was no difference in 30-day readmission or ED visits (primary 12.9% versus revisional 14.6%), reoperation or reintervention (primary 5.7% versus revisional 7.8%), or mortality (primary 0.4% versus revisional 0.6%). In contrast, the revisional BPD/DS patients had higher odds of major morbidity (primary 3.4% versus revisional 5.3%, OR 1.9, CI 1.1-3.2, p = 0.019)., Conclusions: Revisional BPD/DS is associated with higher morbidity than primary BPD/DS in patients with super obesity. These patients should thus be counselled appropriately when choosing a primary or revisional bariatric procedure., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Roux-en-Y gastric bypass (RYGB) is an established surgical treatment for obesity. Variations in limb length during RYGB procedures have been investigated for optimizing weight loss while minimizing nutritional deficiencies. The role of the total alimentary limb length (TALL; Roux limb plus common channel [CC]), however, is poorly defined., Objective: Compare TALL in RYGB procedures for weight loss outcomes and malnutrition., Setting: Systematic review., Methods: Ovid Medline and PubMed databases were searched for entries between 1993 and 2020. Search terms included "gastric bypass" and "TALL." Two independent reviewers screened the results., Results: A total of 21 studies measured TALL in RYGB. Of these, 4 of 6 reported a relationship between TALL and weight loss. Additionally, 11 studies reported that when TALL was ≤400 cm and CC <200 cm, 3.4% to 63.6% of patients required limb lengthening for protein malnutrition., Conclusions: The majority of studies on RYGB do not report TALL length. There is some evidence that weight loss is affected by shortening TALL, while a TALL ≤400 cm with CC<200 should be avoided due to severe protein malnutrition. More studies on the effect of TALL are needed., (Copyright © 2021 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Purpose: Marginal ulceration (MU) is a common long-term complication following Roux-en-Y gastric bypass (RYGB). The causes of MU after RYGB are multifactorial and include surgical technique of constructing the gastrojejunal anastomosis (GJA). The purpose of this study is to evaluate the relationship between gastric pouch size in RYGB and MU using CT volumetrics., Material and Methods: Patients were retrospectively identified who underwent esophagogastroduodenoscopy (EGD) following RYGB at a tertiary care teaching hospital. Measurement of gastric pouch size was performed using 3-D CT software. Standard statistical methods were used, a univariate comparison was performed between MU and non-MU patients followed by a propensity-matched comparison to control for factors known to affect MU, and a propensity-matched subgroup analysis was also performed., Results: In total, 122 patients met criteria, 57 of which had MU on EGD and 65 who did not. The MU group had more smokers and patients with PPI use than the non-MU group, and the mean time from operation to CT scan was 26.6 months (range: 0-108 months). The MU group had a larger gastric pouch size than the non-MU group (34.1 ± 11.8 versus 20.1 ± 6.8 cm 3 ). When analyzed for matched patient cohorts, this difference remained for the MU group that included smokers and PPI use. When stratified for pouch size, for each 5 cm 3 increase in pouch size, patients had 2.4 times odds increase of MU formation., Conclusions: CT volumetric analysis demonstrated that a larger gastric pouch size was associated with MU following RYGB., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Irreversible electroporation (IRE) is a non-thermal tumor ablation technology employed to treat solid tumors not amenable to resection or thermal ablation. The IRE systems currently in clinical use deliver electrical pulses via multiple monopolar electrodes. This approach can present significant technical challenges due to the requirement for accurate placement of multiple electrodes and maintenance of parallel electrode alignment during pulse delivery. In this study, we sought to evaluate a novel IRE electrode configuration consisting of a single bipolar electrode with deployable tines. Using commercial finite element software predicted ablation outcomes, thermal damage, ablation sphericity, and energy delivery were calculated for existing monopolar and bipolar electrodes, and bipolar electrodes with either 4 or 8 deployable tines. The bipolar electrodes with tines generated larger predicted ablations compared to existing monopolar (>100%) and bipolar (>10%) arrangements, and the ablation shape using bipolar electrodes with tines were more spherical than those modeled for bipolar electrodes. Thermal damage modeled for bipolar electrodes and bipolar electrodes with tines was less than that of monopolar electrodes (using identical pulse parameters), and bipolar electrodes with tines delivered less energy than monopolar or bipolar electrodes. These studies using a single point of device insertion suggest the potential for developing alternative IRE delivery techniques, and may simplify clinical use and increase the predicted ablation shape/volume., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: Patients undergoing laparoscopic Roux-en-Y gastric bypass (RYGB) are at risk of developing strictures of the gastrojejunal anastomosis (GJA). Several variables can affect this, one of which may be the method of anastomosis. Between 2010 and 2014, our institution utilized three different anastomotic techniques for creating the GJA (25 mm end-to-end circular-stapled (CS), linear-stapled (LS), and robotic hand sewn (HS)). Our objectives were to compare the method of GJA relative to the subsequent development of anastomotic stricture., Methods: We queried our electronic health record for all patients who underwent an upper endoscopy (EGD) after RYGB (2010-2014). Patient charts were retrospectively reviewed for type of GJA, weight loss, complications, interventions, and revisions of the GJA., Results: In total, 1112 RYGB were performed at our institute, and 17.4% of patients (194/1112) had an upper endoscopy (EGD). Overall, 3.1% (34/1112) were found to have a stricture of the GJA. Patients undergoing a CS, LS, and HS anastomosis had GJA stricture rates of 4.9%, 0.5%, and 1.2% respectively (CS to LS (p < 0.05), p = NS among CS vs. HS, and LS vs. HS). The rate of GJA revision was 1.5%, 0.5%, and 0.1% (p = NS). In patients who had an EGD, excess BMI loss was 57.4%, 64.6%, and 59.2% (p = NS). In patients symptomatic from strictures, excess BMI loss was 69.4%, 83%, and 63.5% respectively (p = NS)., Conclusion: The anastomotic technique for creating of the GJA may impact the formation of strictures. Based on our experience, gastrojejunostomies created with a 2-mm EEA-stapling technique are at higher risk of strictures., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Hepatic stellate cell (HSC) differentiation/activation is central to liver fibrosis and is innately linked to the immune response to liver injury. Exosomes (EXOs) are important means of communication between cell populations. This study sought to characterize EXO release from HSCs and the effect of HSC-EXOs on macrophage cytokine release/function., Methods: Liver from a rat fibrosis model was analyzed for EXO expression and localization. Quiescent and culture-activated rat and mouse HSCs and activated human HSCs were analyzed for microRNA expression. Mouse, rat, and human HSCs were culture-activated and EXOs purified from culture medium prior to addition to macrophages, and interleukin-6 (IL-6) and tumor necrosis factor-α (TNFα) mRNA and protein measured. The effect of activated HSC-EXOs on macrophage migration was assayed., Results: Activation of rat HSCs led to increased EXO production in vivo, an effect mirrored by in vitro rat HSC culture-activation. Culture activation of mouse and rat HSCs led to altered EXO microRNA profiles, with a similar microRNA profile detected in activated human HSCs. Addition of activated HSC-EXOs to macrophages stimulated IL-6 and TNFα mRNA expression and protein secretion in mouse and human macrophages, but not for rat HSC-EXO-macrophages. Addition of human EXOs to macrophages stimulated migration, effects mirrored by the direct addition of rhIL-6 and rhTNFα., Conclusions: HSC-EXOs associate with macrophages and stimulate cytokine synthesis-release and macrophage migration. Constructing a comprehensive understanding of EXO interactions between liver cell populations in the setting of inflammation/fibrosis increases the potential for developing new diagnostic/therapeutic approaches., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Jejunojejunal intussusception (JI) is a serious but rare complication that may occur following Roux-en-Y gastric bypass (RYGB) surgery. Causes of JI and best management strategy are not clearly defined., Methods: Electronic health records were queried for ICD 9/10 codes for intussusception after RYGB surgery (2009-2019), and charts retrospectively reviewed. Patient demographics, operative technique, presentation, radiology, and JI management were analyzed., Results: Of the 2,327 RYGB patients identified at our institute, 34 (1.5%) were treated for JI. The mean age was 45.0 ± 8.6 years, mean BMI (RYGB surgery) was 43.1 ± 8.2 kg/m 2 , mean BMI at JI was 28.3 ± 5.8 kg/m 2 , and 30/34 were female, The mean time between RYGB and JI was 5.5 ± 4.3 years (range 1-17 years). Of the JI patients identified, 9 had operative notes that did not include jejunojejunostomy linear stapler length (JJ-LSL). Of the remaining 25 JI patients, 9 had a 60-mm JJ-LSL and 16 had a 120-mm JJ-LSL. Rate of intussusception was higher in the 120-mm versus 60-mm JJ-LSL group (p < 0.05). Acute abdominal pain was present in all JI patients and 32/34 had radiologic findings (CT scan) that corroborated for JI. The majority of JI patients were managed operatively (26/34) with 22/26 using laparoscopy (2/22 were converted to open). Intraoperative findings included intussusception (15/26), and 9/26 had other pathologies (internal hernia (2/26), cholecystitis (4/26), marginal ulcer (3/26)). Operative management of JI was either reduction and enteropexy (7/15), reduction only (5/15), or JJ revision (3/15). Recurrence of JI occurred in 7/23 patients, of who 4/7 were managed operatively., Conclusions: In our experience, JI appears to be a relatively rare complication after RYGB surgery. However, for patients developing JI, the majority had a JJ length ≥ 120 mm, and most patients required operative management which was associated with a higher rate of conversion to open and risk of JI recurrence. Reduction only technique had the highest risk of JI recurrence and therefore is not recommended.

Background and Purpose: Operative microwave ablation (MWA) is a safe modality for treating hepatic tumors. The aim of this study is to present our 10-year, single-center experience of operative MWA for neuroendocrine liver metastases (NLM). Methods: A single-institution retrospective review of patients who underwent operative MWA for NLM was performed (2008-2018). Demographics, primary tumor site, operative approach, combined surgical operations, and carcinoid symptoms were recorded. Clinical outcomes for major complications, readmission, and mortality were analyzed 30 days postoperatively. Postablation imaging was evaluated for incomplete ablation/missed lesions, and surveillance imaging reviewed for local, regional, and metastatic recurrence. Results: Of the 50 patients (166 targeted lesions) who received MWA for NLM, 41 (82%) were treated with a minimally invasive approach, and 22 (44%) underwent MWA concomitant with hepatectomy and/or primary tumor resection. Within the study cohort 70% of patients were treated with curative intent with a 77% (27/35) success rate. Carcinoid symptoms were reported in 40% (20/50) of patients preoperatively, and MWA treatment improved symptoms in 19/20 patients. Incomplete ablation occurred in 1/166 treated lesions. Recurrence-free survival at 1 and 5 years was 86% and 28%, respectively. Overall survival at 1 and 5 years was 94% and 70%, respectively (median follow-up 32 months, range 0-116 months). Conclusion: Operative MWA is a versatile modality, which can be safe and effectively performed alone or combined with hepatectomy for NLM, preferably using a minimally invasive approach, to achieve symptom control and possibly improve survival.

Background: Marginal ulceration (MU) and bleeding are possible complications following laparoscopic Roux-en-Y gastric bypass (RYGB). Our institution utilizes three techniques for performing the gastrojejunal anastomosis (GJA), providing a means to compare postoperative MU and bleeding as it relates to GJA technique., Objectives: We sought to analyze the incidence of MU and bleeding between the 25-mm end-to-end anastomosis (EEA) stapler, linear stapler (LS), and robotic hand-sewn (RHS) GJA techniques., Methods: Electronic health records for all patients who had an upper endoscopy (EGD) after RYGB were queried (2010-2014). Charts were retrospectively reviewed for type of GJA, complications, endoscopic interventions, and smoking and NSAID use., Results: Out of 1112 RYGBs, the GJA was created using an EEA, LS, or RHS approach in 58.6%, 33.6%, and 7.7% of patients, respectively. 17.4% had an EGD (19.9% EEA, 13.9% LS, and 14.0% RHS). Incidence of MU was 7.3% (9.3% EEA, 4.8% LS, and 5.8% RHS). Rates of EGD and MU were significantly higher after EEA vs. LS GJA (p<0.05). The bleeding rate was 1.5%, [1.1% EEA, 2.1% LS, and 2.3% RHS (p=NS)]. MU within 90 days of RYGB occurred in 4.1%, 0.8%, and 4.7%, respectively (p<0.05 for EEA vs LS only). NSAID and cigarette use were identified in 29.3%, 38.9%, and 60% and 17.2%, 22.2%, and 20%, respectively, for the EEA, LS, and RHS GJA (p=NS)., Conclusion: The method of GJA has an impact on rate of MU formation. A GJA fashioned with a 25-mm EEA stapler tends to have higher rates of EGD and MU.

Background: Complex abdominal wall reconstruction using biologic mesh can lead to increased recurrence rates, nonincorporation, and high perioperative costs. We developed a novel decellularization method and applied it to porcine muscle fascia to mirror target-tissue architecture. The aims of this study were to analyze mechanical strength and tissue-graft incorporation., Methods: After serial decellularization, muscle-fascia mesh was created and tested for mechanical strength and DNA content. The muscle-fascia mesh was implanted subcutaneously in rats (n = 4/group) and the cohorts killed 1 to 4 weeks later. Explants were examined histologically or immunohistochemically., Results: Mechanical testing demonstrated equivalent strength compared with a commercially available biological mesh (AlloDerm), with mechanical strength attributable to the fascia component. Grafts were successfully implanted with no observable adverse events. Gross necroscopy revealed excellent subdermal scaffold engraftment. Microscopic evaluation identified progressive collagen deposition within the graft, neoangiogenesis, and presence of CD34 positive cells, in the absence of discernable graft rejection., Conclusion: This study confirms a decellularization process can successfully create a DNA-free composite abdominal wall (muscle-fascia) scaffold that can be implanted intraspecies without rejection. Expanding this approach may allow exploitation of the angiogenic capacities of decellularized muscle, concomitant with the inherent strength of decellularized fascia, to perform preclinical analyses of graft strength in animal models in vivo., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Ruptured, or bleeding, hepatocellular carcinoma (rHCC) is a relatively rare disease presentation associated with high acute mortality rates. This study sought to evaluate outcomes following laparoscopic microwave ablation (MWA) and washout in rHCC., Methods: A retrospective single-center review was performed to identify patients with rHCC (2008-2018). The treatment algorithm consisted of transarterial embolization (TAE) or trans-arterial chemoembolization (TACE) followed by laparoscopic MWA and washout., Results: Fifteen patients with rHCC were identified (n = 5 single lesion, n = 5 multifocal disease, n = 5 extrahepatic metastatic disease). Median tumor size was 83 mm (range 5-228 mm), and 10 of 15 underwent TAE or TACE followed by laparoscopic MWA/washout. One patient required additional treatment for bleeding after MWA with repeat TAE. Thirty-day mortality was 6/15. For those patients discharged (n = 9), additional treatments included chemotherapy (n = 5), TACE (n = 3), and/or partial lobectomy (n = 2). Median follow-up was 18.2 months and median survival was 431 days (range 103-832) (one-year survival n = 7; two-year survival n = 4; three-year survival n = 3). Six patients had post-operative imaging from which one patient demonstrated recurrence., Conclusion: Using laparoscopic MWA with washout may offer advantage in the treatment of ruptured HCC. It not only achieves hemostasis but also could have oncologic benefit by targeting local tumor and decreasing peritoneal carcinomatosis risk., (Copyright © 2020. Published by Elsevier Ltd.)

Fatty liver disease (hepatosteatosis) is a common early pathology in alcohol-dependent and obese patients. Fatty acid binding protein-4 (FABP4) is normally expressed in adipocytes and macrophages and functions as a regulator of intracellular lipid movement/storage. This study sought to investigate hepatic FABP4 expression and function in alcoholic liver disease (ALD) and hepatocellular carcinoma (HCC). Using chronic ethanol fed mouse models and patient samples FABP4 expression was analyzed. Human HCC cells, and HCC cells transfected to express CYP2E1, were exposed to ethanol and analyzed for FABP4 expression, or exposed to rhFABP4 (in the absence/presence of ERK, p38-MAPK or JNK1/2 inhibitors) and cell proliferation and migration measured. Hepatosteatotic-ALD mouse models exhibited increased hepatic FABP4 mRNA and protein levels, with FABP4 expression confirmed in hepatocytes. In HCC cells, CYP2E1-dependent ethanol metabolism induced FABP4 expression in vitro and exogenous rhFABP4 stimulated proliferation and migration, effects abrogated by ERK and JNK1/2 inhibition. Increased FABP4 was also detected in ALD/ALD-HCC patients, but not patients with viral hepatitis/HCC. Collectively these data demonstrate ethanol metabolism induces hepatic FABP4 expression and FABP4 promotes hepatoma cell proliferation/migration. These data suggest liver-derived FABP4 may be an important paracrine-endocrine factor during hepatic foci expansion and/or hepatoma progression in the underlying setting of ALD., Competing Interests: Declaration of Competing Interest None of the authors have any conflicts of interest to declare., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Correlating patient outcomes with length of stay (LoS) is an important consideration in metabolic and bariatric surgery. At present, conflicting data exists regarding patient safety for ambulatory (AMB) metabolic and bariatric surgery., Objective: Outcomes for AMB-metabolic and bariatric surgery patients (LoS <1 d) undergoing laparoscopic Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) were compared with matched patients with LoS ≥1 day (non-AMB) using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) registry., Setting: MBSAQIP national database., Methods: The MBSAQIP registry was queried for patients undergoing SG or RYGB (2015-2017) and patients grouped as AMB/non-AMB. Exclusion criteria included LoS >4 days, age <18 or >75 years, revision surgery, gastric banding, body mass index <35 kg/m 2 , and day of surgery mortality. Variables were combined into major/minor complications and 30-day mortality. Analysis was performed using univariate and multivariate logistic regression and propensity matching., Results: After exclusions were applied 408,895 patients remained (9973 AMB). Overall, 111,279 patients underwent RYGB (1032 AMB) and 297,616 underwent SG (8941 AMB), with similar demographic characteristics and co-morbidities between groups. For AMB patients, there was no increase in 30-day mortality, reoperation, or readmission, and fewer drains were placed versus matched non-AMB patients. In AMB-SG patients more surgical site infections were reported versus non-AMB-SG, although AMB-SG patients had fewer intensive care unit admissions. For AMB-RYGB, no differences in complications were detected versus non-AMB-RYGB., Conclusion: Based on our analysis of the MBSAQIP database, patients undergoing laparoscopic RYGB or SG procedures can be safely discharged on the day of their procedure without increased incidence of mortality, reoperation, or readmission., (Published by Elsevier Inc.)

Background: The incidence of obesity is disproportionally high in African Americans (AA) in the United States. This study compared outcomes for AA patients undergoing Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) with non-AA patients., Methods: The MBSAQIP database was reviewed for RYGB and SG patients (2015-2017). Patients were identified as AA or non-AA and grouped to RYGB or SG. Combined and univariate analyses were performed on unmatched/propensity matched populations to assess outcomes., Results: After applying exclusion criteria, 75,409 AA and 354,305 non-AA patients remained. Univariate analysis identified AA-RYGB and AA-SG patients were heavier and younger than non-AA patients. Overall, AA patients tended to have fewer preoperative comorbidities than non-AA patients with the majority of AA comorbidities related to hypertension and renal disease. Analysis of propensity matched data confirmed AA bariatric surgery patients had increased cardiovascular-related disease incidence compared with non-AA patients. Perioperatively, AA-RYGB patients had longer operative times, increased rates of major complications/ICU admission, and increased incidence of 30-day readmission, re-intervention, and reoperation, concomitant with lower rates of minor complications/superficial surgical site infection (SSI) compared with non-AA patients. For SG, AA patients had longer operative times and higher rates of major complications and 30-day readmission, re-intervention, and mortality, coupled with fewer minor complications, superficial/organ space SSI, and leak., Conclusion: African American patients undergoing bariatric surgery are younger and heavier than non-AA patients and present with different comorbidity profiles. Overall, AAs exhibit worse outcomes following RYGB or SG than non-AA patients, including increased mortality rates in AA-SG patients.

Background: The obesity rate for the Hispanic population is significantly higher than that of white, non-Hispanic people in the United States, yet Hispanic people undergo disproportionately fewer metabolic and bariatric surgery procedures. This study used the Metabolic Bariatric Surgery Accreditation and Quality Improvement Program data registry to examine potential differences in preoperative co-morbidities and postoperative outcomes in Hispanic adults undergoing sleeve gastrectomy or Roux-en-Y gastric bypass procedures in the United States., Objectives: To study the presence of the Hispanic paradox in metabolic and bariatric surgery utilizing the MBSAQIP registry., Setting: Academic Teaching Institution., Methods: Participant User Files from the Metabolic Bariatric Surgery Accreditation and Quality Improvement Program were reviewed for patients undergoing sleeve gastrectomy or Roux-en-Y gastric bypass (2015-2017). Patients were grouped by race (Hispanic versus all other races) and primary procedure performed. Variables for major and minor postoperative complications were combined. A univariate analysis was performed on unmatched and propensity-matched cohorts., Results: After applying exclusions, 53,353 (13.7%) Hispanic patients and 335,299 non-Hispanic patients remained. A univariate analysis demonstrated Hispanic patients had the lowest preoperative co-morbidity profile compared with all other races and decreased rates of major and minor postoperative complications. Using matched-cohort data, when complications were assessed and grouped as major/minor complications, rates of major and minor complications in Hispanic patients were lower in the Roux-en-Y gastric bypass group, despite Hispanic patients having higher leak rates. Similarly, there were no differences between Hispanic/non-Hispanic sleeve gastrectomy patients in overall major/minor complication rates despite Hispanic patients exhibiting higher venous thromboembolism and lower bleeding compared with non-Hispanic patients., Conclusion: Hispanic patients undergo disproportionately low rates of metabolic and bariatric surgery procedures and present with lower incidence of preoperative co-morbidities. Additionally, Hispanic patients have the same or decreased incidence of postoperative complications compared with non-Hispanic patients, thereby corroborating the Hispanic paradox., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Obesity in the United States is increasingly prevalent in adolescents. Metabolic and bariatric surgery is offered at select sites to adolescents (<18 yr). Controversy exists regarding the safety of performing metabolic and bariatric surgery in adolescents., Objectives: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program registry was employed to compare outcomes of adolescents with adults (18-40 yr) undergoing sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB)., Setting: Academic Teaching Institution., Methods: The Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program Participant User Files were reviewed for patients undergoing SG or RYGB (2015-2018). Patients were stratified by age and outcomes for adolescents versus adults compared. A bivariate analysis was performed on propensity-matched data., Results: After exclusion criteria were applied, 227,671 patients <40 years remained, of whom 1005 were adolescents. For those undergoing RYGB (13.8% adolescents, 25.3% adults), demographic characteristics were similar. Adolescent SG patients were more likely to be male and Hispanic, but less likely to be smokers or have preoperative co-morbidities. There were no differences in infection rates, mortality, major complications, reoperation, readmission, or other interventions for RYGB and SG groups. For both adult SG and adolescent SG, patients' operative times were less than adult and adolescent RYGB, respectively. However, operative times were shorter for adolescent RYGB versus adult RYGB patients, yet longer for adolescent SG patients versus adult SG patients., Conclusions: Metabolic and bariatric surgery is as safe for adolescents undergoing an SG or RYGB as adults. Currently, SG is more commonly performed in adolescents than RYGB, and adolescent SG patients have similar outcomes and shorter operating room times compared with adolescent RYGB patients., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Underutilization of operative management of early stage pancreatic cancer is associated with sociodemographic variables, including age, race, facility type, insurance, and education. It is currently unclear how these variables are associated with survival in patients who undergo surgery. Methods: Patients with clinical stage I pancreatic adenocarcinoma were identified within the National Cancer Database (2010-2016). Utilization of surgery and nonoperative management was determined. Nonclinical factors associated with nonoperative management were identified by multivariable analysis. The association between nonclinical factors and survival was assessed in patients who received operative management. Results: A total of 17,833 patients with clinical stage I pancreatic cancer were identified, and 41.2% underwent operative intervention. Approximately 46% of nonoperatively managed patients lacked a contraindication. Operatively managed patients had longer overall survival (OS) than those who were nonoperatively managed or untreated (25.1 months vs. 11.1 months vs. 5.1 months, p  < 0.0001). Factors associated with nonoperative management included age, black/Hispanic race, nonacademic facilities, nonprivate health insurance, lower education level, and lower income. In operatively managed patients, nonclinical factors associated with lower OS included Medicaid (hazard ratio [HR] 1.27) and treatment at nonacademic facilities (HR 1.20-1.22). Patients on Medicaid received less adjuvant therapy and had higher 30- and 90-day mortality rates. Patients treated at nonacademic facilities received less neoadjuvant therapy, had worse pathologic outcomes, and had higher 30- and 90-day mortality rates. Conclusions: Surgical management is underutilized in clinical stage I pancreatic cancer. Primary insurance payor and facility type appear to be associated with OS in patients who undergo operative management., Competing Interests: No competing financial interests exist., (© Michael D. Watson et al., 2020; Published by Mary Ann Liebert, Inc.)

Background: Bariatric surgery is the most effective modality to treat obesity and obesity-related comorbidities. This study sought to utilize the MBASQIP® Data Registry to analyze the impact of age at time of surgery on outcomes following sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) procedures., Methods: The MBSAQIP® Data Registry for patients undergoing SG or RYGB procedures between 2015 and 2016 was reviewed. Patients were divided into 4 age groups [18-44; 45-54; 55-64; > 65 years]. Minimal exclusions for revisional and/or emergency surgery were selected and combination variables created to classify complications as major or minor. A comorbidity index was constructed to include diabetes, gastroesophageal reflux disease (GERD), obstructive sleep apnea (OSA), and prior cardiac surgery. Univariate and multivariate logistic regression analyses were performed to compare age stratifications to the young adult (18-45 years) cohort., Results: Of 301,605 cases, 279,419 cases (71.2% SG) remained after applying exclusion criteria (79.2% female, mean BMI 45.5 ± 8.1 kg/m 2 , 8.9% insulin-dependent diabetics). Mean age was 44.7 ± 12.0 years (51.3% 18-44 years; 26.9% 45-54 years; 16.3% 55-64 years; 5.5% > 65 years). A univariate analysis demonstrated preoperative differences of lower BMI with increasing age concomitant with increasing frequency of RYGB and a higher comorbidity index (p < 0.0001 vs. 18-45 years). At age > 45 years, major complications and 30-day mortality increased independent of procedure type (p < 0.0001). A multivariate analysis controlling for comorbidity indices demonstrated increasing age (> 45 years) increased risk for major complications and mortality., Conclusion: Overall, bariatric surgery (SG or RYGB) remains a low mortality risk procedure for all age groups. However, all age group classifications > 45 years had higher incidence of major complications and mortality compared to patients 18-45 years (despite older individuals having lower preoperative BMI) indicating delaying surgery is detrimental.

Background: Male patients undergoing bariatric surgery have (historically) been considered higher risk than females. The aim of this study was to examine the disparity between genders undergoing laparoscopic sleeve gastrectomy (SG) and laparoscopic Roux-en-Y gastric bypass (RYGB) procedures and assess gender as an independent risk factor., Methods: The MBSAQIP® Data Registry Participant User Files for 2015-2017 was reviewed for patients having primary SG and RYGB. Patients were divided into groups based on gender and procedure. Variables for major complications were grouped together, including but not limited to PE, stroke, and MI. Univariate and propensity matching analyses were performed., Results: Of 429,664 cases, 20.58% were male. Univariate analysis demonstrated males were older (46.48 ± 11.96 vs. 43.71 ± 11.89 years, p < 0.0001), had higher BMI (46.58 ± 8.46 vs. 45.05 ± 7.75 kg/m 2 , p < 0.0001), and had higher incidence of comorbidities. Males had higher rates of major complications (1.72 vs. 1.05%; p < 0.0001) and 30-day mortality (0.18 vs. 0.07%, p < 0.0001). Significance was maintained after subgroup analysis of SG and RYGB. Propensity matched analysis demonstrated male gender was an independent risk factor for RYGB and SG, major complications [2.21 vs. 1.7%, p < 0.0001 (RYGB), 1.12 vs. 0.89%, p < 0.0001 (SG)], and mortality [0.23 vs. 0.12%, p < 0.0001 (RYGB), 0.10 vs. 0.05%; p < 0.0001 (SG)]., Conclusion: Males continue to represent a disproportionately small percentage of bariatric surgery patients despite having no difference in obesity rates compared to females. Male gender is an independent risk factor for major post-operative complications and 30-day mortality, even after controlling for comorbidities.

Objective: To demonstrate the feasibility of a single electrode and grounding pad approach for delivering high frequency irreversible electroporation treatments (H-FIRE) in in-vivo hepatic tissue., Methods: Ablations were created in porcine liver under surgical anesthesia by adminstereing high frequency bursts of 0.5-5.0 μs pulses with amplitudes between 1.1-1.7 kV in the absence of cardiac synchronization or intraoperative paralytics. Finite element simulations were used to determine the electric field strength associated with the ablation margins (E Lethal ) and predict the ablations feasible with next generation electronics., Results: All animals survived the procedures for the protocol duration without adverse events. E Lethal of 2550, 1650, and 875 V/cm were found for treatments consisting of 100x bursts containing 0.5 μs pulses and 25, 50, and 75 μs of energized-time per burst, respectively. Treatments with 1 μs pulses consisting of 100 bursts with 100 μs energized-time per burst resulted in E Lethal of 650 V/cm., Conclusion: A single electrode and grounding pad approach was successfully used to create ablations in hepatic tissue. This technique has the potential to reduce challenges associated with placing multiple electrodes in anatomically challenging environments., Significance: H-FIRE is an in situ tumor ablation approach in which electrodes are placed within or around a targeted region to deliver high voltage electrical pulses. Electric fields generated around the electrodes induce irrecoverable cell membrane damage leading to predictable cell death in the relative absence of thermal damage. The sparing of architectural integrity means H-FIRE offers potential advantages compared to thermal ablation modalities for ablating tumors near critical structures.

Background: Previous reports of bariatric surgery outcomes when cases are assisted by residents and/or fellows have been inconclusive., Objective: To compare bariatric surgery outcomes for cases with surgical trainees (ST; residents and fellows) versus nonsurgical trainees (nST; all other assistants) using the Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program (MBSAQIP) Registry., Setting: Academic teaching., Methods: The MBSAQIP Registry was reviewed (2015-2017) for Roux-en-Y gastric bypass, sleeve gastrectomy, and revision surgery based on ST and nST status. Univariate, multivariate logistic regression, and propensity matching analyses were performed., Results: Of 477,670 cases, 26.8% were performed with ST. For ST patients 79.9% were female (versus 80.3% nST) and mean body mass index was 45.2 ± 8 kg/m 2 (versus 45.0 ± 8.1 kg/m 2 nST). Overall, 31.7% of patients underwent Roux-en-Y gastric bypass (versus 25.7% nST), 65.9% underwent sleeve gastrectomy (versus 71.6% nST), and 2.4% of patients had revision surgery (versus 2.7% nST). After matching, no difference in 30-day mortality was observed between groups. However, ST patients had higher incidence of deep vein thrombosis (P = .004), pulmonary embolism (P = .005), superficial surgical site infection (P < .0001), postoperative sepsis (P = .005), blood transfusions (P = .0307), nonoperative interventions (P = .004), 30-day readmission rates (P < .0001), and longer operative times (P < .0001), but lower 30-day reoperation rates (P = .0001)., Conclusion: Overall, there was no difference observed in 30-day mortality between the ST and nST groups. However, despite lower 30-day reoperation rates, ST patients exhibited higher rates of postoperative deep vein thrombosis, pulmonary embolism, superficial surgical site infection, postoperative sepsis, blood transfusions, 30-day readmission rates, and longer operative times than nST patients., (Copyright © 2020 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Chronic alcohol consumption is a leading risk factor for the development of hepatocellular carcinoma (HCC), which is associated with a marked increase in hepatic expression of pro-inflammatory IL-17A and its receptor IL-17RA., Methods: Genetic deletion and pharmacological blocking were used to characterize the role of IL-17A/IL-17RA signaling in the pathogenesis of HCC in mouse models and human specimens., Results: We demonstrate that the global deletion of the Il-17ra gene suppressed HCC in alcohol-fed diethylnitrosamine-challenged Il-17ra -/- and major urinary protein-urokinase-type plasminogen activator/Il-17ra -/- mice compared with wild-type mice. When the cell-specific role of IL-17RA signaling was examined, the development of HCC was decreased in both alcohol-fed Il-17ra ΔMΦ and Il-17ra ΔHep mice devoid of IL-17RA in myeloid cells and hepatocytes, but not in Il-17ra ΔHSC mice (deficient in IL-17RA in hepatic stellate cells). Deletion of Il-17ra in myeloid cells ameliorated tumorigenesis via suppression of pro-tumorigenic/inflammatory and pro-fibrogenic responses in alcohol-fed Il-17ra ΔMΦ mice. Remarkably, despite a normal inflammatory response, alcohol-fed Il-17ra ΔHep mice developed the fewest tumors (compared with Il-17ra ΔMΦ mice), with reduced steatosis and fibrosis. Steatotic IL-17RA-deficient hepatocytes downregulated the expression of Cxcl1 and other chemokines, exhibited a striking defect in tumor necrosis factor (TNF)/TNF receptor 1-dependent caspase-2-SREBP1/2-DHCR7-mediated cholesterol synthesis, and upregulated the production of antioxidant vitamin D 3 . The pharmacological blocking of IL-17A/Th-17 cells using anti-IL-12/IL-23 antibodies suppressed the progression of HCC (by 70%) in alcohol-fed mice, indicating that targeting IL-17 signaling might provide novel strategies for the treatment of alcohol-induced HCC., Conclusions: Overall, IL-17A is a tumor-promoting cytokine, which critically regulates alcohol-induced hepatic steatosis, inflammation, fibrosis, and HCC., Lay Summary: IL-17A is a tumor-promoting cytokine, which critically regulates inflammatory responses in macrophages (Kupffer cells and bone-marrow-derived monocytes) and cholesterol synthesis in steatotic hepatocytes in an experimental model of alcohol-induced HCC. Therefore, IL-17A may be a potential therapeutic target for patients with alcohol-induced HCC., Competing Interests: Conflict of interest The authors declare they have no conflicts of interest. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2020 European Association for the Study of the Liver. All rights reserved.)

Hepatic resection presents unique surgical challenges to reduce blood loss during parenchymal division. The development of saline-coupled bipolar devices, in which hemostasis is achieved at lower temperatures than electrocautery or other bipolar sealing devices, have been employed for open hepatic resection. Saline-coupled bipolar devices have now become available for minimally invasive use. The goals of this study were to evaluate the feasibility and safety of a laparoscopic saline-coupled bipolar device for minimally invasive hepatectomy. Seventeen patients (median age 66 years, range 36-81) were consented for inclusion and enrolled. Patient demographics, intraoperative data, and surgeon feedback were collected. Seven robot-assisted partial hepatectomies, 9 laparoscopic partial hepatectomies, and 1 laparoscopic cholecystectomy with liver abscess resection were performed. Average operating time was 222 ± 33 minutes (median 188 minutes; range 61-564 minutes) with no difference between robotic versus laparoscopic time. Successful seals were achieved in all cases following application of 150 to 200 J energy (average 179 ± 3 J, average time to achieve a successful seal 9.3 ± 2.7 minutes). Estimated blood loss was 362 ± 74 mL (median 300 mL, range 5-1200 mL) and 3/17 patients received intraoperative blood transfusion. No bile leaks were detected in any of the patients. Median length of stay was 5 days (range 1-20 days), and there were no readmissions within 30 days. Postoperative morbidity occurred in 5/17 patients, all of which were Clavien Grade 1. There was no mortality within 90 days or complications requiring a return to the operating room, and there were no liver-specific morbidities. These data suggest the laparoscopic Aquamantys device represents a useful device for use in minimally invasive liver resection.

Fatty acid binding proteins (FABPs) are small, water soluble proteins that bind long chain fatty acids and other biologically active ligands to facilitate intracellular localization. Twelve FABP family members have been identified to date, with 10 isoforms expressed in humans. Functionally, FABPs are important in fatty acid metabolism and transport, with distinct family members having the capacity to influence gene transcription. Expression of FABPs is usually cell/tissue specific to one predominant FABP family member. Dysregulation of FABP expression can occur through genetic mutation and/or environmental-lifestyle influences. In addition to intracellular function, exogenous, circulating FABP expression can occur and is associated with specific disease states such as insulin resistance. A role for FABPs is increasingly being reported in tumor biology with elevated exogenous FABP expression being associated with tumor progression and invasiveness. However, a less clear role has been appreciated for dysregulated FABP expression during cell transformation and early expansion., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Purpose: To investigate the feasibility of single-needle high-frequency irreversible electroporation (SN-HFIRE) to create reproducible tissue ablations in an in vivo pancreatic swine model., Materials and Methods: SN-HFIRE was performed in swine pancreas in vivo in the absence of intraoperative paralytics or cardiac synchronization using 3 different voltage waveforms (1-5-1, 2-5-2, and 5-5-5 [on-off-on times (μs)], n = 6/setting) with a total energized time of 100 μs per burst. At necropsy, ablation size/shape was determined. Immunohistochemistry was performed to quantify apoptosis using an anticleaved caspase-3 antibody. A numerical model was developed to determine lethal thresholds for each waveform in pancreas., Results: Mean tissue ablation time was 5.0 ± 0.2 minutes, and no cardiac abnormalities or muscle twitch was detected. Mean ablation area significantly increased with increasing pulse width (41.0 ± 5.1 mm 2 [range 32-66 mm 2 ] vs 44 ± 2.1 mm 2 [range 38-56 mm 2 ] vs 85.0 ± 7.0 mm 2 [range 63-155 mm 2 ]; 1-5-1, 2-5-2, 5-5-5, respectively; p < 0.0002 5-5-5 vs 1-5-1 and 2-5-2). The majority of the ablation zone did not stain positive for cleaved caspase-3 (6.1 ± 2.8% [range 1.8-9.1%], 8.8 ± 1.3% [range 5.5-14.0%], and 11.0 ± 1.4% [range 7.1-14.2%] cleaved caspase-3 positive 1-5-1, 2-5-2, 5-5-5, respectively), with significantly more positive staining at the 5-5-5 pulse setting compared with 1-5-1 (p < 0.03). Numerical modeling determined a lethal threshold of 1114 ± 123 V/cm (1-5-1 waveform), 1039 ± 103 V/cm (2-5-2 waveform), and 693 ± 81 V/cm (5-5-5 waveform)., Conclusions: SN-HFIRE induces rapid, predictable ablations in pancreatic tissue in vivo without the need for intraoperative paralytics or cardiac synchronization., (Copyright © 2019 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Limited availability and use of whole blood (WB) following trauma is driven by perceptions that hemostatic function is limited by platelet dysfunction within 5 days storage. We sought to define the hemostatic function of WB stored at 4°C for up to 25 days, elucidate changes in metabolic parameters and mitochondrial dysfunction in platelets in WB, and the effect of supplementation using resveratrol (Res) or cytochrome c (Cyt c)., Methods: Whole blood was collected, aliquoted, and stored at 4°C without agitation. Resveratrol or Cyt c was supplemented before storage, or 10 days post-storage. Serial samples were collected and analyzed for hemostatic function by platelet mapping thromboelastography. Platelets isolated from WB were counted and mitochondrial function assessed by oxygen consumption, mitochondrial membrane potential, and biochemical parameters., Results: Platelet function of WB was maintained up to 15 days at 4°C before a significant decrease was observed at 25 days. Resveratrol or Cyt c improved WB aggregation potential when supplemented 10 days post-storage. Platelet oxygen consumption was maintained until 10-day storage but significantly decreased thereafter in the absence of change in platelet count. Cytochrome c increased oxygen consumption on Day 15 and platelet mitochondrial membrane potential steadily decreased over time, an effect attenuated by Res or Cyt c supplementation 10 days post-storage. Potassium and lactate levels increased during storage, while pH levels decreased, with no observed effect following Res or Cyt c supplementation., Conclusion: Storing cold WB with Res or Cyt c supplementation enhances ex vivo aggregation by improving platelet function, thereby extending overall storage life. These findings have potential significance for improving WB availability in immediate trauma situations, including treatment in a battlefield trauma setting., Level of Evidence: Translational study, diagnostic test or criteria, level II.

Fibrotic liver injury is a significant healthcare burden in the United States. It represents a major cause of morbidity and mortality for which there are no effective Food and Drug Administration-approved treatment strategies. Fibrosis is considered a disruption of the normal wound healing responses mediated by fibroblastic cells, which are triggered and sustained by pro-fibrotic cytokines such as transforming growth factor beta 1 (TGF-β1). TGF-β1-mediated trans-differentiation of hepatic stellate cells (HSCs) from quiescent to activated myofibroblasts is a pivotal event in the development of fibrosis. Activation is accompanied by global changes in microRNA (miR) expression. It has been previously reported that miR19b is decreased in activated HSCs and contributes to increased expression of TGF-β receptor II and connective tissue growth factor, both confirmed targets of miR19b. An adeno-associated virus serotype 2 vector (AAV2) with a miR19b transgene downstream of enhanced green fluorescent protein under the murine collage alpha 1(I) promoter was developed specifically to target HSCs. Male Sprague Dawley rats (250 g) underwent sham or bile-duct ligation (BDL) surgery. Directly after BDL, rats received AAV2-miR19b, AAV2-control, or vehicle normal saline (NS) by portal-vein injection. After 2 weeks, the animals were euthanized, and blood was collected for alanine and aspartate aminotransferase, total and direct bilirubin, and alkaline phosphatase. Tissue was collected for RNA and protein extraction and histology. Fibrosis and measures of hepatic injury were significantly reduced in AAV2-miR19b-treated rats in combination with significant improvements in total and direct bilirubin. Histological analysis of collagen by PicroSirius Red staining revealed a ∼50% reduction compared to AAV2-control or NS-injected animals. Pro-fibrotic markers, smooth-muscle alpha-actin, TGF-β receptor II, and collagen alpha 2(I) mRNA and protein were significantly decreased compared to AAV2-control and NS groups. AAV2-mediated reintroduction of miR-19b, specifically expressed in HSCs, improved liver function, inhibited fibrosis, and improved measures of hepatic injury in a BDL model.

Background and Aims: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related mortality. Risk factors for developing HCC include viral hepatitis, alcohol and obesity. Fatty acid-binding proteins (FABPs) bind long-chain free fatty acids (FFAs) and are expressed in a tissue-specific pattern; FABP1 being the predominant hepatic form, and FABP4 the predominant adipocyte form. The aims of this study were to investigate the expression and function of FABPs1-9 in human and animal models of obesity-related HCC., Methods: FABP1-9 expression was determined in a mouse model of obesity-promoted HCC. Based on these data, expression and function of FABP4 was determined in human HCC cells (HepG2 and HuH7) in vitro. Serum from patients with different underlying hepatic pathologies was analysed for circulating FABP4 levels., Results: Livers from obese mice, independent of tumour status, exhibited increased FABP4 mRNA and protein expression concomitant with elevated serum FABP4. In vitro, FABP4 expression was induced in human HCC cells by FFA treatment, and led to FABP4 release into culture medium. Treatment of HCC cells with exogenous FABP4 significantly increased proliferation and migration of human HCC cells. Patient serum analysis demonstrated significantly increased FABP4 in those with underlying liver disease, particularly non-alcoholic fatty liver disease (NAFLD) and HCC., Conclusions: These data suggest FABP4, an FABP not normally expressed in the liver, can be synthesized and secreted by hepatocytes and HCC cells, and that FABP4 may play a role in regulating tumour progression in the underlying setting of obesity., (© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Conditions of systemic stress can lead to increased reactive oxygen species production, mitochondrial dysfunction, systemic inflammation, and multiorgan dysfunction. Triphenylphosphonium (TPP+) is a lipophilic cation used to target therapeutics to mitochondria. We sought to determine the effects of TPP+ on mitochondrial integrity. Male rats were anesthetized and TPP+ (5 mg/kg) or vehicle (saline) was administered intravenously 30-minutes after anesthesia initiation and intraperitoneally (20 mg/kg) 60-minutes later. Rats were exsanguinated 2-hours postinjection. Cardiac, pulmonary, hepatic, splenic, and renal tissues were analyzed for inflammation, lipid peroxidation, endogenous antioxidant activity, cytokine expression, and mitochondrial function. In vitro modeling was performed using freshly isolated hepatocytes subjected to 8-hours hypoxia/30-minutes reoxygenation in the absence or presence of TPP+. TPP+ increased lipid peroxidation in the liver, lung, and kidney as well as antioxidant activity in the liver, kidney, and spleen. Conversely, antioxidant activity decreased in the lung with TPP+. In addition, TPP+ altered hepatic inflammatory mediators. In vitro, TPP+ attenuated oxygen consumption and, when combined with hypoxic injury, depolarized mitochondrial membranes in hepatocytes. TPP+ induces systemic responses associated with oxidative stress and worsening pathologies in animals. Caution should be exercised when employing TPP+ for therapeutics.