Faculty Bibliography

Introduction: The gastrojejunostomy (GJ) during Roux-en-Y gastric bypass (RYGB) can be performed by stapled or hand-sewn techniques, and is at risk for anastomotic stricture, reported in the literature at rates from 0 to 33%. This study reviews a single center's experience with anastomotic stricture and intervention required. Methods and Procedures: A retrospective chart review was performed of 904 patients who underwent RYGB as primary or revisional surgery at a single institution from October 2000 through September 2017. There were 182 patients excluded for follow up duration of less than 1 year, 5 for an esophagojejunostomy rather than GJ, and 1 for gastroparesis as the surgical indication rather than morbid obesity. This left 716 patients to be included in the study. Demographic and operative data were collected including technique for GJ, postoperative follow up, and complications, with a focus on GJ stricture and subsequent interventions.
Result(s): Gastrojejunostomy (GJ) was performed with a 25 CEEA stapler in 674 (94.1%) patients, with a linear stapler in 25 (3.5%), was hand-sewn in 7 (1.3%), and the technique was unknown in the remaining 8 (1.1%). Roux-en-Y gastric bypass was performed as a primary surgery in 522 (72.9%) patients and as a revisional surgery in 194 (27.1%). Stricture of the GJ was diagnosed in 29 (4.1%) patients. The average time to diagnosis of early strictures occurring prior to 3 months was 40.3 days, and for late strictures was 871 days. By technique, stricture was diagnosed in 26 (3.9%) patients in the 25CEEAgroup, 1 (4%) in the linear stapler group, and 2 (22.2%) in the hand-sewn anastomosis group. In primaryRYGBpatients stricture was diagnosed in 20 (3.8%) patients, and in revisionalRYGB in 9 (4.6%) patients (p = 0.626). Esophagogastroduodenoscopy (EGD) with dilation was performed at least once (1-9 times) in 26 patients, 2 with concomitant stenting, 2 required operative intervention, and 1 patient awaits operative intervention. Both patients who required surgery also had marginal ulcers, and possible gastro-gastric fistula at time of surgery.
Conclusion(s): The results of this study show that the 25 CEEA circular stapler is a reasonable technique for performance of the GJ anastomosis in RYGB, with a stricture rate of 3.9%. There is also a slightly increased stricture rate in revisional surgical patients, though not statistically significant

BACKGROUND:When administered as a continuous infusion, ketamine is known to be a potent analgesic and general anaesthetic. Recent studies suggest that a single low-dose administration of ketamine can provide a long-lasting effect on mood, but its effects when given in the postoperative period have not been studied. OBJECTIVE:We hypothesised that a single low-dose administration of ketamine after bariatric surgery can improve pain and mood scores in the immediate postoperative period. DESIGN/METHODS:We performed a randomised, double-blind, placebo-controlled study to compare a single subanaesthetic dose of ketamine (0.4 mg kg) with a normal saline placebo in the postanaesthesia care unit after laparoscopic gastric bypass and gastrectomy. SETTING/METHODS:Single-centre, tertiary care hospital, October 2014 to January 2018. PATIENTS/METHODS:A total of 100 patients were randomised into the ketamine and saline groups. INTERVENTION/METHODS:Patients in the ketamine group received a single dose of ketamine infusion (0.4 mg kg) in the postanaesthesia care unit. Patients in the placebo groups received 0.9% saline. OUTCOME MEASURES/METHODS:The primary outcome was the visual analogue pain score. A secondary outcome was performance on the short-form McGill's Pain Questionnaire (SF-MPQ). RESULTS:There were no significant differences in visual analogue pain scores between groups (group-by-time interaction P = 0.966; marginal group effect P = 0.137). However, scores on the affective scale of SF-MPQ (secondary outcome) significantly decreased in the ketamine group as early as postoperative day (POD) 2 [mean difference = -2.2 (95% bootstrap CI -2.9 to 1.6), Bonferroni adjusted P < 0.001], compared with placebo group in which the scores decreased only by POD 7. Scores on the total scale of SF-MPQ for the ketamine group were smaller compared with the placebo group (P = 0.034). CONCLUSION/CONCLUSIONS:Although there was no significant difference between ketamine and placebo for the primary outcome measure, patients who received ketamine experienced statistically and clinically significant improvement in their comprehensive evaluation of pain, particularly the affective component of pain, on POD 2. However, future studies are needed to confirm the enduring effects of ketamine on the affective response to postoperative pain. CLINICAL TRIAL REGISTRATION/BACKGROUND:NCT02452060.

Introduction: We aimed to create a morbidity prediction score for patients undergoing RYGB using MBSA-QIP data. Methods and Procedures: We retrospectively analyzed all RYGB cases in MBSA-QIP during 2015, and identified factors associated with 30-day complications using chi-squared analysis. Multiple logistic regression identified pre-operative factors independently associated with 30-day complication to develop a prediction score, verified using a Cochran Armitage trend test. Results: For 42,849 procedures, there were 3034 (7.1%) with any 30-day complication. Preoperative patient characteristics independently associated with increased risk of morbidity are shown in Table 1. A scoring algorithm was formulated by assigning points based on strength of the odds ratio (Table 1), with the final score a summation of points accrued. The rate of any 30-day complication was evaluated across the range of scores (Table 2). Higher scores were associated with a higher rate of morbidity (p<0.0001 for each). [Figure Presented] Conclusion: We created and verified a morbidity prediction score for patients undergoing RYGB based on MBSA-QIP data

Aims: Laparoscopic adjustable gastric banding (LAGB) has gained popularity as a safe, reversible surgical treatment for morbid obesity. However, there are few studies and no consensus on revisional bariatric surgery for those patients in whom banding has failed. We analyzed results of conversion from LAGB to Roux-en-Y gastric bypass or biliopancreatic diversion in one high-volume center. Methods: A single-institution retrospective review was conducted on patients who had undergone conversion of LGB to a revisional bypass procedure during the time period January 2003 through November 2011. Data on patient demographics, surgical technique, pre- and post-operative complications, and weight loss (body mass index [BMI] and percent excess weight loss [%EWL]) were collected and analyzed. Results: We identified 76 patients at our institution who underwent conversion from LAGB to Roux-en-Y gastric bypass (RYGB; n = 62), biliopancreatic diversion (BPD; n = 12), or biliopancreatic diversion with duodenal switch (BPD/DS; n = 2). 69 of the 76 conversions (90.8%) were completed laparoscopically. 29/76 (38.2%) had required additional surgery prior to conversion for band-related complications including slippage, erosion, port migration, hiatal hernia, bowel obstruction, or leakage; all occurred at >;30 days. After conversion, the rate of complications requiring hospitalization was 27.6% (21/76); 14.5% (11/76) occurred at<30 days. There was one mortality. Mean time from band placement to conversion was 1439 +/- 661.4 days (range 245-3140). At time of conversion, mean BMI was 44.4 +/- 6.6 kg/ m², and mean %EWL was 12.21 +/- 20.7 (range 67-75). Following conversion, mean BMI and %EWL at 12 months, respectively, were 31.6 +/- 4.2 kg/m² and 55.2 +/- 24.7, at 24 months 33.6 +/- 5.6 kg/m² and 45.3 +/- 20.1, and at 36 months 33.0 +/- 7.5 kg/m² and 46.0 +/- 18.2. Conclusions: There is an increasing need for proven corrective solutions to failed LAGB. Our results show that con!

The transition of chronic pancreatic fibroinflammatory disease to neoplasia is a primary example of the paradigm linking inflammation to carcinogenesis. However, the cellular and molecular mediators bridging these entities are not well understood. Because TLR4 ligation can exacerbate pancreatic inflammation, we postulated that TLR4 activation drives pancreatic carcinogenesis. In this study, we show that lipopolysaccharide accelerates pancreatic tumorigenesis, whereas TLR4 inhibition is protective. Furthermore, blockade of the MyD88-independent TRIF pathway is protective against pancreatic cancer, whereas blockade of the MyD88-dependent pathway surprisingly exacerbates pancreatic inflammation and malignant progression. The protumorigenic and fibroinflammatory effects of MyD88 inhibition are mediated by dendritic cells (DCs), which induce pancreatic antigen-restricted Th2-deviated CD4(+) T cells and promote the transition from pancreatitis to carcinoma. Our data implicate a primary role for DCs in pancreatic carcinogenesis and illustrate divergent pathways in which blockade of TLR4 signaling via TRIF is protective against pancreatic cancer and, conversely, MyD88 inhibition exacerbates pancreatic inflammation and neoplastic transformation by augmenting the DC-Th2 axis.

Introduction: Chronic pancreatitis (CP) is characterized by fibro-inflammatory transformation of the pancreatic parenchyma. the precise cellular mediators in CP are incompletely understood. Dendritic cells (DC) have recently emerged as initiators of organ-specific inflammation. Pancreatic stellate cells (PSC) become potently pro-inflammatory in CP and are primarily responsible for deposition of extracellular matrix proteins and fibrillar collagen. We postulated that an intimate relationship between DC and PSC mediate the dramatic fibro-inflammatory changes in CP. Methods: DC were isolated from bone marrow aspirates and cultured for 8 days in complete RPMI supplemented with murine GMCSF. PSC were isolated aftermechanical and chemical digestion of pancreas, followed by density centrifugation and plastic adherence. DC-PSC co-culture was accomplished by culturing equal number of DC and PSC for 24 to 48 hours before washing off the non-adherent DC. Cell culture supernatant was assayed using cytometric bead or ELISA. for in vivo experiments, a three week caerulein model of chronic pancreatitis was employed in C57BL/6micewith selectmice receiving i. p. adoptive transfer of DC (1x106 thrice weekly). in vivo PSC activation was measured using monoclonal antibodies directed against Desmin and a-SMA. Results: in vitroDC-PSCco-culture resulted in activation ofPSCsurface phenotype and the production ofhigher levels ofPDGF,as well as numerous chemokines and cytokines byPSC(Table). Effectswere contingent on direct cellular interaction betweenDCand PSC as well as DCexpression of ICAM-1 and MyD88. in vivo i. p. adoptive transfer of DC in murine caerulein-induced chronic pancreatitis resulted in markedly increased fibro- inflammatory changes in the pancreas as well as 4-fold increase in percent desmin-positive acini, and approximately 80% a-SMA-positive acini (Figure). However, whereasDCinduced PSC to become pro-inflammatory, DC inhibited PSC proliferation, failed to stimulate PSC migration, and did not induce PSC to express higher levels of extra-cellular matrix proteins or Collagen I in co-culture experiments. Furthermore, our experimental data suggest bi-directional cross-talk asPSCprevented DCmaturation but acted as a potentDCchemoattractant. Conclusions: DCand PSC induce robust bidirectional crosstalk that affects CP. DCinduce PSC to become pro-inflammatory, but do cannot cause PSC to adopt fully mature myofibroblast-like properties. (Figure presented)

BACKGROUND & AIMS: The cellular mediators of acute pancreatitis are incompletely understood. Dendritic cells (DCs) can promote or suppress inflammation, depending on their subtype and context. We investigated the roles of DC in development of acute pancreatitis. METHODS: Acute pancreatitis was induced in CD11c.DTR mice using caerulein or L-arginine; DCs were depleted by administration of diphtheria toxin. Survival was analyzed using Kaplan-Meier method. RESULTS: Numbers of major histocompatibility complex II(+)CD11c(+) DCs increased 100-fold in pancreata of mice with acute pancreatitis to account for nearly 15% of intrapancreatic leukocytes. Intrapancreatic DCs acquired a distinct immune phenotype in mice with acute pancreatitis; they expressed higher levels of major histocompatibility complex II and CD86 and increased production of interleukin-6, membrane cofactor protein-1, and tumor necrosis factor-alpha. However, rather than inducing an organ-destructive inflammatory process, DCs were required for pancreatic viability; the exocrine pancreas died in mice that were depleted of DCs and challenged with caerulein or L-arginine. All mice with pancreatitis that were depleted of DCs died from acinar cell death within 4 days. Depletion of DCs from mice with pancreatitis resulted in neutrophil infiltration and increased levels of systemic markers of inflammation. However, the organ necrosis associated with depletion of DCs did not require infiltrating neutrophils, activation of nuclear factor-kappaB, or signaling by mitogen-activated protein kinase or tumor necrosis factor-alpha. CONCLUSIONS: DCs are required for pancreatic viability in mice with acute pancreatitis and might protect organs against cell stress

Acetaminophen (APAP) overdose is one of the most frequent causes of acute liver failure in the United States and is primarily mediated by toxic metabolites that accumulate in the liver upon depletion of glutathione stores. However, cells of the innate immune system, including natural killer (NK) cells, neutrophils, and Kupffer cells, have also been implicated in the centrilobular liver necrosis associated with APAP. We have recently shown that dendritic cells (DCs) regulate intrahepatic inflammation in chronic liver disease and, therefore, postulated that DC may also modulate the hepatotoxic effects of APAP. We found that DC immune-phenotype was markedly altered after APAP challenge. In particular, liver DC expressed higher MHC II, costimulatory molecules, and Toll-like receptors, and produced higher interleukin (IL)-6, macrophage chemoattractant protein-1 (MCP-1), and tumor necrosis factor alpha (TNF-alpha). Conversely, spleen DC were unaltered. However, APAP-induced centrilobular necrosis, and its associated mortality, was markedly exacerbated upon DC depletion. Conversely, endogenous DC expansion using FMS-like tyrosine kinase 3 ligand (Flt3L) protected mice from APAP injury. Our mechanistic studies showed that APAP liver DC had the particular capacity to prevent NK cell activation and induced neutrophil apoptosis. Nevertheless, the exacerbated hepatic injury in DC-depleted mice challenged with APAP was independent of NK cells and neutrophils or numerous immune modulatory cytokines and chemokines. Conclusion: Taken together, these data indicate that liver DC protect against APAP toxicity, whereas their depletion is associated with exacerbated hepatotoxicity. (HEPATOLOGY 2011;)

INTRODUCTION: Tolerance is the hallmark of hepatic immune function and dendritic cells (DC) are critical to this phenomenon. Lipid accumulation causes DC dysfunction in cancer.We postulated that liver DC are conspicuously lipid-rich and therefore mediate tolerance. METHODS: Immune cells from C57BL/6 livers were isolated using FACS. Cytokines were measured using a bead array. CTL lysis was measured using Cr51. NK and iNKT cells were tested in DC cocultures. EG7 was employed in tumor experiments. RESULTS: We discovered two distinct liver DC populations, high lipid containing (HL-DC) and low lipid containing (LL-DC). HL-DC exhibited an activated phenotype, produced robust levels of cytokines, activated CD4+ T, NK and iNKT cells, induced CTL responses and prevented tumor growth after adoptive transfer immunization. Conversely, LL-DC induced Tregs, anergy to cancer, and mediated tolerance to oral antigen. (Table Presented) CONCLUSIONS: Endogenous lipid content in hepatic DC subsets defines their immunogenic potential. Contrary to our hypothesis, HL-DC are potently immunogenic while LL-DC maintain tolerance. Manipulation of the HL-Dc: LL-DC ratio may be an attractive strategy for experimental therapeutics to modulate hepatic immunity and tolerance