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Background: The optimal nutritional therapy in the field of pancreatic surgery is still debated., Methods: An international panel of recognized pancreatic surgeons and pancreatologists decided that the topic of nutritional support was of importance in pancreatic surgery. Thus, they reviewed the best contemporary literature and worked to develop a position paper to provide evidence supporting the integration of appropriate nutritional support into the overall management of patients undergoing pancreatic resection. Strength of recommendation and quality of evidence were based on the approach of the grading of recommendations assessment, development and evaluation Working Group., Results: The measurement of nutritional status should be part of routine preoperative assessment because malnutrition is a recognized risk factor for surgery-related complications. In addition to patient's weight loss and body mass index, measurement of sarcopenia and sarcopenic obesity should be considered in the preoperative evaluation because they are strong predictors of poor short-term and long-term outcomes. The available data do not show any definitive nutritional advantages for one specific type of gastrointestinal reconstruction technique after pancreatoduodenectomy over the others. Postoperative early resumption of oral intake is safe and should be encouraged within enhanced recovery protocols, but in the case of severe postoperative complications or poor tolerance of oral food after the operation, supplementary artificial nutrition should be started at once. At present, there is not enough evidence to show the benefit of avoiding oral intake in clinically stable patients who are complicated by a clinically irrelevant postoperative pancreatic fistula (a so-called biochemical leak), while special caution should be given to feeding patients with clinically relevant postoperative pancreatic fistula orally. When an artificial nutritional support is needed, enteral nutrition is preferred whenever possible over parenteral nutrition. After the operation, regardless of the type of pancreatic resection or technique of reconstruction, patients should be monitored carefully to assess for the presence of endocrine and exocrine pancreatic insufficiency. Although fecal elastase-1 is the most readily available clinical test for detection of pancreatic exocrine insufficiency, its sensitivity and specificity are low. Pancreatic enzyme replacement therapy should be initiated routinely after pancreatoduodenectomy and in patients with locally advanced disease and continued for at least 6 months after surgery, because untreated pancreatic exocrine insufficiency may result in severe nutritional derangement., Conclusion: The importance of this position paper is the consensus reached on the topic. Concentrating on nutritional support and therapy is of utmost value in pancreatic surgery for both short- and long-term outcomes., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Recent literature suggests that chyle leak may complicate up to 10% of pancreatic resections. Treatment depends on its severity, which may include chylous ascites. No international consensus definition or grading system of chyle leak currently is available., Methods: The International Study Group on Pancreatic Surgery, an international panel of pancreatic surgeons working in well-known, high-volume centers, reviewed the literature and worked together to establish a consensus on the definition and classification of chyle leak after pancreatic operation., Results: Chyle leak was defined as output of milky-colored fluid from a drain, drain site, or wound on or after postoperative day 3, with a triglyceride content ≥110 mg/dL (≥1.2 mmol/L). Three different grades of severity were defined according to the management needed: grade A, no specific intervention other than oral dietary restrictions; grade B, prolongation of hospital stay, nasoenteral nutrition with dietary restriction, total parenteral nutrition, octreotide, maintenance of surgical drains, or placement of new percutaneous drains; and grade C, need for other more invasive in-hospital treatment, intensive care unit admission, or mortality., Conclusion: This classification and grading system for chyle leak after pancreatic resection allows for comparison of outcomes between series. As with the other the International Study Group on Pancreatic Surgery consensus statements, this classification should facilitate communication and evaluation of different approaches to the prevention and treatment of this complication., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Purpose: This prospective, multicenter, randomized clinical trial was performed to compare the effectiveness of the bioprosthesis Surgisis Gold (Cook Biotech, Inc, West Lafayette, IN) to suture closure alone in reinforcing the abdominal wall after open Roux-en-Y gastric bypass (RYGB)., Methods: A total of 402 adult patients (body mass index ≥35 kg/m(2)) scheduled to undergo open RYGB procedures were randomized to receive either Surgisis Gold placed as a sublay directly under and opposed to the posterior rectus fascia without intervening preperitoneal fat or suture closure alone. Peri- and postoperative complications were tracked. Incisional hernia formation in each group was examined at 6 weeks, 3, 6, and 9 months, and 1 and 2 years after RYGB., Results: A total of 380 (78 male; 302 female) patients with a mean age of 45 years (range 18-69) and a mean BMI of 48 (range 35-79) underwent RYGB. There were no differences in patient demographics or comorbidities between groups. Placement of the Surgisis Gold increased operating time by an average of 14 minutes. Complications were more common in the Surgisis Gold group with significantly more wound events and seroma formation compared with the suture closure alone group. At final follow-up, 32 of 185 (17%) of patients in the reinforced arm and 38 of 195 (20%) in the suture alone arm developed an incisional hernia (P = .6)., Conclusion: In this challenging patient population, the use of Surgisis Gold for reinforcing the abdominal wall after open RYGB was not shown to be greatly different from a primary suture repair., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Major trauma is an independent risk factor for developing venous thromboembolism. While increases in thrombin generation and/or procoagulant microparticles have been detected in other patient groups at greater risk for venous thromboembolism, such as cancer or coronary artery disease, this association has yet to be documented in trauma patients. This pilot study was designed to characterize and quantify thrombin generation and plasma microparticles in individuals early after traumatic injury., Methods: Blood was collected in the trauma bay from 52 blunt injured patients (cases) and 19 uninjured outpatients (controls) and processed to platelet poor plasma to allow for (1) isolation of microparticles for identification and quantification by flow cytometry, and (2) in vitro thrombin generation as measured by calibrated automatic thrombography. Data collected are expressed as either mean ± standard deviation or median with interquartile range., Results: Among the cases, which included 39 men and 13 women (age, 40 ± 17 years), the injury severity score was 13 ± 11, the international normalized ratio was 1.0 ± 0.1, the thromboplastin time was 25 ± 3 seconds, and platelet count was 238 ± 62 (thousands). The numbers of total (cell type not specified) procoagulant microparticles, as measured by Annexin V staining, were increased compared to nontrauma controls (541 ± 139/μL and 155 ± 148/μL, respectively; P < .001). There was no significant difference in the amount of thrombin generated in trauma patients compared to controls; however, peak thrombin was correlated to injury severity (Spearman correlation coefficient R, 0.35; P = .02)., Conclusion: Patients with blunt trauma have greater numbers of circulating procoagulant microparticles and increased in vitro thrombin generation. Future studies to characterize the cell-specific profiles of microparticles and changes in thrombin generation kinetics after traumatic injury will determine whether microparticles contribute to the hypercoagulable state observed after injury., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: GLUT2 is translocated to the apical membrane of enterocytes exposed to glucose concentrations >∼50 mM. Mechanisms of GLUT2-mediated glucose uptake in cell culture models of enterocytes have not been studied., Aim: To explore mechanism(s) of glucose uptake in 3 enterocyte-like cell lines., Methods: Glucose uptake was measured in Caco-2, RIE-1, and IEC-6 cell lines using varying concentrations of glucose (0.5-50 mM). Effects of phlorizin (SGLT1 inhibitor), phloretin (GLUT2 inhibitor), nocodazole and cytochalasin B (disrupters of cytoskeleton), calphostin C and chelerythrine (PKC inhibitors), and phorbol 12-myristate 13-acetate (PKC activator) were evaluated., Results: Phlorizin inhibited glucose uptake in all 3 cell lines. Phloretin inhibited glucose uptake in Caco-2 and RIE-1 cells. Starving cells decreased glucose uptake in Caco-2 and RIE-1 cells. Glucose uptake was saturated at >10 mM glucose in all 3 cell lines when exposed briefly (<1 min) to glucose. After exposure for >5 min in Caco-2 and RIE-1 cells, glucose uptake did not saturate and K(m) and V(max) increased. This increase in glucose uptake was inhibited by phloretin, nocodazole, cytochalasin B, calphostin C, and chelerythrine. PMA enhanced glucose uptake by 20%. Inhibitors and PMA had little or no effect in the IEC-6 cells., Conclusion: Constitutive expression of GLUT2 in the apical membrane along with additional translocation of cytoplasmic GLUT2 to the apical membrane via an intact cytoskeleton and activated PKC appears responsible for enhanced carrier-mediated glucose uptake at greater glucose concentrations (>20 mM) in Caco-2 and RIE-1 cells. IEC-6 cells do not appear to express functional GLUT2., (Copyright © 2012 Mosby, Inc. All rights reserved.)

Background: Hyperoxaluria and increased calcium oxalate stone formation occur after Roux-en-Y gastric bypass (RYGB) surgery for morbid obesity. The etiology of this hyperoxaluria is unknown. We hypothesized that after bariatric surgery, intestinal hyperabsorption of oxalate contributes to increases in plasma oxalate and urinary calcium oxalate supersaturation., Methods: We prospectively examined oxalate metabolism in 11 morbidly obese subjects before and 6 and 12 months after RYGB (n = 9) and biliopancreatic diversion-duodenal switch (BPD-DS) (n = 2). We measured 24-hour urinary supersaturations for calcium oxalate, apatite, brushite, uric acid, and sodium urate; fasting plasma oxalate; 72-hour fecal fat; and increases in urine oxalate following an oral oxalate load., Results: Six and 12 months after RYGB, plasma oxalate and urine calcium oxalate supersaturation increased significantly compared with similar measurements obtained before surgery (all P ≤ .02). Fecal fat excretion at 6 and 12 months was increased (P = .026 and .055, 0 vs 6 and 12 months). An increase in urine oxalate excretion after an oral dose of oxalate was observed at 6 and 12 months (all P ≤ .02). Therefore, after bariatric surgery, increases in fecal fat excretion, urinary oxalate excretion after an oral oxalate load, plasma oxalate, and urinary calcium oxalate supersaturation values were observed., Conclusion: Enteric hyperoxaluria is often present in patients after the operations of RYGB and BPD-DS that utilize an element of intestinal malabsorption as a mechanism for weight loss., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Esophagogastroduodenoscopy (EGD) is commonly used in the diagnosis and treatment of gastrointestinal (GI) disorders. Our aim was to define the risk of perforation associated with EGD and identify patients who required operative intervention., Methods: We retrospectively reviewed 72 patients from our institution plus 5 transferred patients who sustained EGD-associated perforations from January 1996 through July 2008. Percutaneous endoscopic gastrostomy, endoscopic ultrasonography, endoscopic retrograde cholangiopancreatography, transthoracic echocardiography, and concurrent colonoscopy procedures were excluded., Results: Perforations in 72 of 217,507 EGD procedures were identified (incidence, 0.033%); 124,844 EGDs included an interventional procedure and 92,663 were examination only. The incidence of perforation was similar whether an interventional procedure was performed or not (0.040% vs 0.029%; P = .181). The esophagus was injured most commonly (51%), followed by the duodenum (32%), jejunum (6%), stomach (3%), and common bile duct (3%). Overall mortality after perforation was 17% with a morbidity rate of 40%. Thirty-eight patients (49%) were initially treated nonoperatively, 7 of whom (18%) failed nonoperative management. The only factors we could determine that were associated with failure were free fluid or contrast extravasation on computed tomography (75% vs 23% [P < .005] and 33% vs 0% [P = .047], respectively). The morbidity of failures was equivalent to those who underwent initial operative management (63% vs 61%; P = .917), with mortality seeming to be greater (43% vs 21%; P = .09)., Conclusion: EGD is safe in the majority of patients; however, iatrogenic perforation is associated with considerable morbidity and mortality. Nonoperative management of GI perforation can be successful if there is no evidence of contrast extravasation or free fluid on radiographic studies. If nonoperative management fails, the outcomes may be worse than those treated initially with operative repair., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Background: To date, there is no uniform and standardized manner of defining pancreatic anastomoses after pancreatic resection., Methods: A systematic search was performed to determine the various factors, either related to the pancreatic remnant after pancreatic resection or to types of pancreatoenteric anastomoses that have been shown to influence failure rates of pancreatic anastomoses., Results: Based on the data obtained, we formulated a new classification that incorporates factors related to the pancreatic remnant, such as pancreatic duct size, length of mobilization, and gland texture, as well as factors related to the pancreatoenteric anastomosis, such as the use of pancreatojejunostomy/pancreatogastrostomy; duct-to-mucosa anastomosis; invagination (dunking) of the remnant into the jejunum or stomach; and the use of a stent (internal or external) across the anastomosis., Conclusion: By creating a standardized classification for recording and reporting of the pancreatoenterostomy, future publications would allow a more objective comparison of outcomes after pancreatic surgery. In addition, use of such a classification might encourage studies evaluating outcomes after specific types of anastomoses in certain clinical situations that could lead to the formulation of best practice guidelines of anastomotic techniques for a particular combination of findings in the pancreatic remnant., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Background: The role of neural regulation in expression and function of intestinal hexose transporters is unknown. The aim of this study is to determine the role of intestinal innervation in gene expression and function of the membrane hexose transporters, SGLT1, GLUT2, and GLUT5 in the enterocyte. We hypothesize that denervation of the small intestine decreases expression of hexose transporters, which leads to decreased glucose absorption., Methods: Six groups of Lewis rats were studied (n = 6 each) as follows: control, 1 week after sham laparotomy, 1 and 8 weeks after syngeneic (no immune rejection) orthotopic small-bowel transplantation (SBT) (SBT1 and SBT8) to induce complete extrinsic denervation, and 1 and 8 weeks after selective disruption of intrinsic neural continuity to jejunoileum by gut transection and reanastomosis (T/A1 and T/A8). All tissue was harvested between 8 AM and 10 AM. In duodenum, jejunum, and ileum, mucosal messenger RNA (mRNA) levels were quantitated by real-time polymerase chain reaction (PCR), protein by Western blotting, and transporter-mediated glucose absorption using the everted sleeve technique., Results: Across the 6 groups, the relative gene expression of hexose transporter mRNA and protein levels were unchanged, and no difference in transporter-mediated glucose uptake was evident in any region. The glucose transporter affinity (K(m)) and functional transporter levels (V(max)) calculated for duodenum and jejunum showed no difference among the 6 groups., Conclusion: Baseline regulation of hexose transporter function is not mediated tonically by intrinsic or extrinsic neural continuity to the jejunoileum.

Background: Hexose transporter mRNA and protein levels follow a diurnal rhythm in rat jejunum. Their coordinated expression and resultant function throughout the small bowel is not well understood. We hypothesized that hexose transporter levels and glucose absorption follow a coordinated, site-specific diurnal rhythm in rat duodenum and jejunum, but not in ileum., Methods: Sprague-Dawley rats were housed in a strictly maintained, 12-h, light/dark room [light 6 am to 6 pm] with free access to water and chow. Mucosa was harvested from duodenum, jejunum, and ileum at 3 am, 9 am, 3 pm, and 9 pm, and full thickness 1-cm segments were harvested at 9 am, and 9 pm (n = 6 for each segment at each time point). mRNA levels were determined by reverse-transcription, real-time polymerase chain reaction (n > or = 5), protein levels by semiquantitative Western blotting (n > or = 5), and transporter-mediated glucose uptake by everted sleeve technique (n = 6)., Results: mRNA levels of SGLT1 and GLUT5 followed a temporally coordinated, diurnal rhythm in all 3 segments (P < .01), while mRNA for GLUT2 and protein levels for SGLT1 and GLUT2 varied diurnally only in duodenum and jejunum (P > .05) but not in ileum (P > .10). SGLT1 and GLUT5 mRNA induction decreased aborally. Baseline SGLT1 and GLUT5 mRNA levels and SLGT1 and GLUT2 protein levels did not vary aborally (P > .05 for all). GLUT2 mRNA baseline levels were decreased in ileum (P < .01). Glucose uptake varied diurnally in duodenum and jejunum with no difference in ileum. Transporter-mediated glucose uptake was greater in duodenum and jejunum compared with ileum., Conclusion: Regulation of hexose absorption in rat small bowel seems to be site-specific and mediated by multiple mechanisms.

Background: Delayed gastric emptying (DGE) is one of the most common complications after pancreatic resection. In the literature, the reported incidence of DGE after pancreatic surgery varies considerably between different surgical centers, primarily because an internationally accepted consensus definition of DGE is not available. Several surgical centers use a different definition of DGE. Hence, a valid comparison of different study reports and operative techniques is not possible., Methods: After a literature review on DGE after pancreatic resection, the International Study Group of Pancreatic Surgery (ISGPS) developed an objective and generally applicable definition with grades of DGE based primarily on severity and clinical impact., Results: DGE represents the inability to return to a standard diet by the end of the first postoperative week and includes prolonged nasogastric intubation of the patient. Three different grades (A, B, and C) were defined based on the impact on the clinical course and on postoperative management., Conclusion: The proposed definition, which includes a clinical grading of DGE, should allow objective and accurate comparison of the results of future clinical trials and will facilitate the objective evaluation of novel interventions and surgical modalities in the field of pancreatic surgery.

Background: Postoperative hemorrhage is one of the most severe complications after pancreatic surgery. Due to the lack of an internationally accepted, universal definition of postpancreatectomy hemorrhage (PPH), the incidences reported in the literature vary considerably, even in reports from randomized controlled trials. Because of these variations in the definition of what constitutes a PPH, the incidences of its occurrence are not comparable., Methods: The International Study Group of Pancreatic Surgery (ISGPS) developed an objective, generally applicable definition of PPH based on a literature review and consensus clinical experience., Results: Postpancreatectomy hemorrhage is defined by 3 parameters: onset, location, and severity. The onset is either early (< or =24 hours after the end of the index operation) or late (>24 hours). The location is either intraluminal or extraluminal. The severity of bleeding may be either mild or severe. Three different grades of PPH (grades A, B, and C) are defined according to the time of onset, site of bleeding, severity, and clinical impact., Conclusions: An objective, universally accepted definition and clinical grading of PPH is important for the appropriate management and use of interventions in PPH. Such a definition also would allow comparisons of results from future clinical trials. Such standardized definitions are necessary to compare, in a nonpartisan manner, the outcomes of studies and the evaluation of novel operative treatment modalities in pancreatic surgery.

Hypothesis: Solid tumor cells bind to ICAM-1 on endothelial surfaces via MUC-1. Tumor binding to ICAM-1 auto-upregulates tumor ICAM-1 at the leading edge of the tumor and promotes release of chemoattractants for circulating macrophages, and circulating macrophages bind to tumor-expressed ICAM-1, invoking propagation of further chemokines and cytokines that recruit neutrophils. Tight adherence between cell surface ligands on neutrophils and tumor-expressed ICAM-1 activates neutrophils to degranulate, releasing elastases, which break down endovascular and endolymphatic barriers permitting transendothelial tumor cell migration. Consequently, tumor cell ICAM-1 expression dictates metastatic potential and metastatic potential determines cancer lethality.

Background: For the past 11 years, we have used a malabsorptive form of Roux-en-Y gastric bypass (RYGB), the "very, very long limb" RYGB, for selected patients with BMIs >50 kg/m(2) and in highly selected patients with BMI <50 kg/m(2). This modified distal gastric bypass establishes a 100-cm common channel (for digestion and absorption) and a "very, very" long Roux limb of 400 to 500 cm., Methods: To determine long-term efficacy and complications, we followed prospectively 257 consecutive patients; 188 (73%) participated in a postoperative survey., Results: Of the patients, 60% were female; overall age (x +/- SD) was 45 +/- 11 years, and BMI was 61 +/- 11 kg/m(2). Operative mortality was 1% with substantive postoperative morbidity occurring in 13%. Eighty-two percent of patients returning the survey an average of 48 months postoperatively (range, 12 to 148 months) lost >50% of excess body weight; BMI at follow-up was 37 +/- 9 kg/m(2). Resolution of comorbidities included diabetes mellitus (94%), hypertension (65%), sleep apnea (48%), and asthma (30%). Side effects included mild food intolerance (82%), occasional loose or watery stools (71%), nephrolithiasis (16%), and symptomatic steatorrhea (5%). Nine patients (4%) who developed or were developing impending protein/calorie malnutrition required proximal relocation of the enteroenterostomy with symptom resolution., Conclusions: Overall, 90% were satisfied with the operation, and 93% would recommend it to a friend. The very, very long limb RYGB is relatively safe and effective and has acceptable side effects in the treatment of selected patients with super obesity (BMI >50). Because of the possibility of malabsorptive sequelae, patients should be selected based on degree of medical sophistication, insight, and compliance.

Background: Protein and messenger RNA (mRNA) levels of the hexose transporters sodium-dependent glucose transporter-1, glucose transporter 2, and glucose transporter 5 follow a (daily) diurnal rhythm in rat jejunum. Because vagal innervation mediates the diurnal activity of other proteins in the rat small bowel, we hypothesized that the diurnal variation of mRNA and protein levels of these hexose transport proteins are mediated by vagal innervation., Methods: Forty-eight rats kept in a strictly maintained, alternating 12-hour light-dark room underwent either sham laparotomy (n = 24) or bilateral total abdominal vagotomy (n = 24). Four weeks postoperatively, jejunal mucosa was harvested from 6 rats in each group at 3 am, 9 am, 3 pm and 9 pm; mRNA levels were determined by reverse transcription real-time polymerase chain reaction and protein levels by semiquantitative Western blot analysis. Transporter mRNA and protein levels were expressed as a ratio to the corresponding mRNA and protein levels of the stably expressed housekeeping gene glyceraldehyde-6-phosphate dehydrogenase., Results: mRNA and protein levels for all 3 hexose transporters showed diurnal variation in sham controls (P < or = .01 for all). After vagotomy, although mRNA levels of all 3 transporters showed diurnal variation (each P < .01), diurnal variation in all 3 hexose transporter protein levels was abolished (P > .10 for all)., Conclusions: Vagal innervation appears to differentially mediate the diurnal changes in hexose transporter mRNA and protein expression in the rat jejunum by posttranscriptional, and/or posttranslational processes.

Background: Small bowel transplantation (SBT) is complicated by changes in graft motility, especially in the early postoperative period. This dysmotility may be related in part to the extrinsic denervation necessitated by the procedure, but specific neurotransmitter response to SBT is incompletely understood. The aim of this study was to evaluate the role of nitric oxide and nonadrenergic, noncholinergic (NANC) enteric neural input in the nonimmunologic etiology of the dysmotility seen after SBT., Methods: A technique of jejunoileal extrinsic denervation (without disruption of mesenteric vascular supply) was used as a model of canine jejunoileal autotransplantation to avoid potential confounding factors such as ischemia-reperfusion and postallotransplant immunologic effects. Longitudinal smooth muscle strips from ileum and jejunum were studied with in vitro tissue chamber methodology at 0, 2, and 8 weeks after this experimental model to explore early and late effects of denervation. Effects of exogenous nitric oxide (NO) and electric field stimulation (EFS), which releases native, endogenous enteric neurotransmitters) were evaluated in neurally intact control dogs and those undergoing extrinsic denervation., Results: Exogenous NO caused a dose-dependent inhibition of spontaneous contractile activity and in some muscle strips a decrease in basal tone in both groups of dogs. These effects were unchanged by neural blockade with tetrodotoxin and preserved after extrinsic denervation. EFS produced inhibition of spontaneous contractile activity in ileum and a complex, inconsistent response in jejunum. The response to EFS in both ileum and jejunum was unchanged after extrinsic denervation., Conclusions: Nitric oxide inhibits contractile activity in canine longitudinal muscle of small bowel. Motility changes seen after this large animal model of extrinsic denervation are not caused by changes in NO or NANC neural function. The variability observed between different segments of intestine is important to consider in the context of SBT.