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OBJECTIVE To evaluate the association between glucagon-like peptide 1 (GLP-1) secretion and the long-term (>2 years) outcome of type 2 diabetes mellitus (T2DM) after Roux-en-Y gastric bypass (RYGBP). METHODS Cross-sectional study in 18 T2DM morbidly obese subjects who underwent RYGBP but differed in the long-term outcome of T2DM (remission: G1, n = 6; relapse: G2, n = 6; lack of remission: G3: n = 6). Groups were matched for their sex, age, and body mass index. The GLP-1, glucose, C-peptide, and glucagon responses to a standardized test meal (STM) were evaluated. Insulin secretion and insulin sensitivity were estimated from the STM and by frequently sampling intravenous glucose tolerance test (FSIVGTT). Dual-energy X-ray absorptiometry was used to assess body composition. RESULTS Patients in G1 presented a lower area under the curve (AUC0-120) of glucose in response to the STM as compared with G2, and G3 (P < 0.01). In contrast, the AUC0-120 of GLP-1 (P = 0.884) and glucagon (P = 0.630) did not differ significantly among the 3 groups. Indices of insulin secretion adjusted by the prevailing insulin sensitivity derived from STM and FSIVGTT, demonstrated larger β-cell function in subjects in G1 as compared with G2 or G3 (Disposition Index-STM, P = 0.005; DI-FSIVGTT, P = 0.006). Body composition and inflammatory markers did not differ significantly among the 3 study groups. CONCLUSIONS Our data show that in subjects with T2DM an enhanced GLP-1 response to meal intake is not sufficient to maintain normal glucose tolerance in the long term after RYGBP. Our data suggest that β-cell function is a key determinant of the long-term remission of T2DM after this bariatric surgery technique.

Metabolic and inflammatory disturbances associated with obesity are considered important trigger factors for venous thromboembolism (VTE). Identification of clinical markers indicating a hypercoagulability state could define a group of high-risk patients in the surgical setting. This study aimed to identify these markers using rotational thrombelastometry (ROTEM) analysis, an established method for hemostasis testing that can detect hyperfunctional stages of the clotting process. From June to December 2010, this study investigated 109 consecutive obese patients (28 women and 22 men, mean age 46 years, body mass index 46.6 ± 7 kg/m2) with no history of VTE who were candidates for bariatric surgery. Preoperative clinical and metabolic characteristics and ROTEM analysis were recorded. Hypercoagulable risk was defined when patients showed a clot strength (G) of ≥11 dynes/cm2. Of the 109 patients, 20 (18 %) were hypercoagulable according to ROTEM analysis. Metabolic/inflammatory biomarkers such as leptin, C-reactive protein, fibrinogen levels, and platelet count were significantly higher in the high-risk patients. In the multivariate analysis, fibrinogen was an independent predictor of G ≥ 11 dynes/cm2 [odds ratio (OR) 2.92, 95 % confidence interval (CI) 1.80–5.21, p = 0.023]. After adjustment to other data, only waist circumference affected the prediction [OR 4.42, 95 % CI 2.27–6.71, p = 0.009]. Receiver operating characteristic curve analysis showed that 3.95 g/l was the best cutoff point for fibrinogen predictability (sensitivity 100 %, specificity 41 %). A hypercoagulability state in obese patients is associated with central obesity and high fibrinogen levels, which should be considered clinical hallmarks of this state. More aggressive perioperative prophylaxis for VTE should be recommended when these hallmarks are present in obese patients.

The authors examined the impact of the laparoscopic approach on the early outcome of resected colon carcinomas. The role of laparoscopic techniques in the treatment of colon carcinomas is questionable. Previous studies have suggested technical feasibility of surgical resections of these cancers by laparoscopic means and have implied a benefit to laparoscopic technique for patients undergoing colorectal resections. A prospective, randomized study was conducted comparing laparoscopic assisted colectomy (LAC) open colectomy (OC) for colon cancer. We present the preliminary results in relation to the short-term outcome and judge the feasibility of the laparoscopic procedure to as a way of performing accurate oncologic resection and staging. Benefit has been demonstrated with LAC in this setting. Passing flatus, oral intake, and discharge from hospital occurred earlier in LAC- than OC-treated patients. The mean operative time was significantly longer in the LAC group than in the OC group. The overall morbidity was significantly lower in the LAC group. No significant differences were observed between both groups in the number of lymph nodes removed or the pathological stage following the Astler-Coller modification of the Dukes classification. The laparoscopic approach improves the short-term outcome of segmental colectomies for colon cancer. However, the further follow-up of these patients will allow us to answer in the near future whether or not the LAC may influence the long-term outcome.

Data on long-term dietary changes and nutritional deficiencies after sleeve gastrectomy (SG) in grade 3 obese patients are scarce.To prospectively compare dietary changes and nutritional deficiencies in grade 3 obese patients 5 years after SG and Roux-en-y gastric bypass (GBP).Three hundred and fifty-five patients who had SG (n=61) or GBP (n=294) (May 2001-December 2006) at a Spanish university hospital.Longitudinal, prospective, observational study. PRIMARY OUTCOMES/STATISTICAL ANALYSES: Changes in energy, macronutrient, and micronutrient intake, and weight loss were analyzed using mixed models for repeated measurements.At the 5-year follow-up visit, the percentage of excess weight loss (P=0.420) and daily energy intake (P=0.826), as well as the proportion of energy from carbohydrates (P=0.303), protein (P=0.600), and fat (P=0.541) did not differ between surgical groups. Energy intake (P=0.004), baseline weight (P0.001), and time period (P0.001), but not the proportion of different macronutrients or the type of surgery, independently predicted the percentage excess weight loss over time. After SG or GBP, the mean daily dietary intake of calcium, magnesium, phosphorus, and iron was less than the current recommendations. Despite universal supplementation, the prevalence of nutritional deficiencies was comparable after SG or GBP, with 25-hydroxyvitamin D being the most commonly observed deficiency (SG, 93.3% to 100%; GBP, 90.9% to 85.7%, P=not significant). In an adjusted multivariate regression model, energy intake and lipid intake independently predicted plasma 25(OH)-vitamin D levels.Data show that SG and GBP are associated with similar long-term weight loss with no differences in terms of dietary intake. Furthermore, data demonstrate that both types of surgeries carry comparable nutritional consequences.

To analyse the causes for claims due to alleged malpractice in bariatric surgery and the results of the legal process.A review was carried out on the case files of claims for damages as a result of bariatric surgery presented to the Professional Liability Department of the Catalonian Medical Colleges Council from 1992 to 2009. The claims rate was calculated using a survey of bariatric surgeons.A total of 49 cases were analysed, which represented 0.6% of the patients operated on. The patient died in 23 (47%) of the cases, 14% were left with serious after effects, 18% had mild after effects, and 21% made a complete recovery. The most frequent causes of death were peritonitis due to suture dehiscence (48%), and respiratory complications (17.4%). Retrospectively, malpractice was considered to have occurred in 10 (20%) of the sued cases due to lack of an adequate informed consent document, delay in recognising a complication, or an error in interpretation, or treatment of the complication. The doctor sued was convicted in 10 of the cases, 3 in a criminal court, and 7 in a civil court. There was acquittal in 19 cases, an out-of court settlement with payment of compensation in 4, withdrawal of the claim in 4, and judgement or sentence is still pending in 12 cases.The study showed a relatively low rate of claims for complications associated with bariatric surgery. The number of convictions was relatively high. The early detection of surgical complications is essential in order to reduce legal claims associated with bariatric surgery.

Sleeve gastrectomy is gaining relevance in the surgical armamentarium against obesity. The transumbilical single port has proved to be an attractive and safe alternative for a variety of minimally invasive abdominal surgeries. The purpose of this study is to evaluate the initial results of a group of patients operated by single-port sleeve gastrectomy compared with a group operated by conventional laparoscopic technique. We present a prospective cohort study of two groups of consecutive patients with body mass index (BMI) between 35 and 55 kg/m2, with an indication of sleeve gastrectomy. In 20 patients, we used a transumbilical single-port (TUSP) technique; in 22 patients, we used the conventional laparoscopic (CL) technique. All surgeries were performed between June and December 2009 in the Gastrointestinal Surgery Department of Hospital Clinic, Barcelona. The same medical team, in a standardized fashion, carried out all surgeries. There were no differences between groups in body mass index (BMI), age, sex, number and type of comorbidities, or history of previous abdominal surgery. Operative time (79.2 min) was significantly higher in the TUSP group (p = 0.002) than in the CL group (54.1 min). There were no conversions to open surgery in any of the patients operated upon via CL, but one conversion to laparoscopic surgery, requiring the addition of three trocars, in the TUSP group. There were no significant differences in morbidity or hospital stay between the groups. Percentage excess weight loss and excess BMI loss at 3 and 6 months, as indexes for improvement and resolution of comorbidities associated with obesity, showed that there were no significant differences between the groups. Transumbilical single-port sleeve gastrectomy has proved to be safe, technically feasible, and reproducible, with results that are similar to those obtained with conventional laparoscopic surgery.

This is an open-access article distributed under the terms of the Creative Commons Attribution License.-- et al., [Background]: Probiotics appear to be beneficial in inflammatory bowel disease, but their mechanism of action is incompletely understood. We investigated whether probiotic-derived sphingomyelinase mediates this beneficial effect. [Methodology/Principal Findings]: Neutral sphingomyelinase (NSMase) activity was measured in sonicates of the probiotic L. brevis (LB) and S. thermophilus (ST) and the non-probiotic E. coli (EC) and E. faecalis (EF). Lamina propria mononuclear cells (LPMC) were obtained from patients with Crohn's disease (CD) and Ulcerative Colitis (UC), and peripheral blood mononuclear cells (PBMC) from healthy volunteers, analysing LPMC and PBMC apoptosis susceptibility, reactive oxygen species (ROS) generation and JNK activation. In some experiments, sonicates were preincubated with GSH or GW4869, a specific NSMase inhibitor. NSMase activity of LB and ST was 10-fold that of EC and EF sonicates. LB and ST sonicates induced significantly more apoptosis of CD and UC than control LPMC, whereas EC and EF sonicates failed to induce apoptosis. Pre-stimulation with anti-CD3/CD28 induced a significant and time-dependent increase in LB-induced apoptosis of LPMC and PBMC. Exposure to LB sonicates resulted in JNK activation and ROS production by LPMC. NSMase activity of LB sonicates was completely abrogated by GW4869, causing a dose-dependent reduction of LB-induced apoptosis. LB and ST selectively induced immune cell apoptosis, an effect dependent on the degree of cell activation and mediated by bacterial NSMase. [Conclusions]: These results suggest that induction of immune cell apoptosis is a mechanism of action of some probiotics, and that NSMase-mediated ceramide generation contributes to the therapeutic effects of probiotics., The funding sources included grants from Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Ministerio de Ciencia e Innovación (SAF2005-00280 and SAF2008-03676 to MS, FIS2009-00056 to AM, SAF2009-11417 to JCF), Fundación Ramón Areces (to MS), the National Institutes of Health (DK30399 and DK50984 to CF) and the Research Center for Liver and Pancreatic Diseases funded by the United States National Institute for Alcohol Abuse and Alcoholism (P50 AA 11999 to JCF).

Many patients who undergo bariatric surgery develop postoperative gastrointestinal complications that can require upper gastrointestinal endoscopy.To prospectively describe the gastrointestinal complications diagnosed by endoscopy after bariatric surgery.We followed up patients undergoing laparoscopic bariatric surgery between January 1998 and December 2006. The following data were recorded: age, sex, body mass index, comorbidity, type and duration of bariatric surgery, clinical presentation of complications, time of presentation, endoscopic treatment and follow-up.A total of 474 patients underwent surgery (74% women, 26% men) with a mean age of 44±11 years (range, 15-66) and a mean BMI of 47±7 (range, 33-82). The most frequent surgical procedure was Roux-en-Y gastric bypass (90%). We identified 68 complications (14%) requiring upper gastrointestinal endoscopy: anastomotic stenosis (21 cases, 5%), upper gastrointestinal hemorrhage (16 cases, 3.6%), epigastric pain (12 cases, 2.5%), vomiting (7 cases, 1.5%), heartburn (6 cases, 1.3%) and other (6 cases, 1.3%). No prognostic factor for the development of complications requiring postsurgical endoscopy was identified.Anastomotic stenosis is the most common complication requiring endoscopic treatment after bariatric surgery. Upper gastrointestinal bleeding in the immediate and late postoperative period can be safely and effectively treated with endoscopic techniques.

Background: Excessive fibroblast expansion and extracellular matrix (ECM) deposition are key events for the development of bowel stenosis in Crohn's disease (CD) patients. Tocotrienols are vitamin E compounds with proven in vitro antifibrogenic effects on rat pancreatic fibroblasts. We aimed at investigating the effects of tocotrienols on human intestinal fibroblast (HIF) proliferation, apoptosis, autophagy, and synthesis of ECM. Methods: HIF isolated from CD, ulcerative colitis (UC), and normal intestine were treated with tocotrienol-rich fraction (TRF) from palm oil. HIF proliferation was quantified by 3H-thymidine incorporation, apoptosis was studied by DNA fragmentation, propidium iodide staining, caspase activation, and poly(ADP-ribose) polymerase cleavage, autophagy was analyzed by quantification of LC3 protein and identification of autophagic vesicles by immunofluorescence and production of ECM components was measured by Western blot. Results: TRF significantly reduced HIF proliferation and prevented basic fibroblast growth factor-induced proliferation in CD and UC, but not control HIF. TRF enhanced HIF death by promoting apoptosis and autophagy. HIF apoptosis, but not autophagy, was prevented by the pan-caspase inhibitor zVAD-fmk, whereas both types of cell death were prevented when the mitochondrial permeability transition pore was blocked by cyclosporin A, demonstrating a key role of the mitochondria in these processes. TRF diminished procollagen type I and laminin γ-1 production by HIF. Conclusions: Tocotrienols exert multiple effects on HIF, reducing cell proliferation, enhancing programmed cell death through apoptosis and autophagy, and decreasing ECM production. Considering their in vitro antifibrogenic properties, tocotrienols could be useful to treat or prevent bowel fibrosis in CD patients. (Inflamm Bowel Dis 2011)

The feasibility and safety of Natural Orifice Translumenal Endoscopic Surgery (NOTES) transanal endoscopic rectosigmoid resection using transanal endoscopic microsurgery (TEM) was previously demonstrated in human cadavers and a porcine survival model. We report the first clinical case of a NOTES transanal resection for rectal cancer using TEM and laparoscopic assistance, performed by a team of surgeons from Barcelona and Boston with extensive experience with NOTES and minimally invasive approaches to colorectal diseases. Transanal endoscopic rectal resection with total mesorectal excision using the TEM platform was performed in a 76-year-old woman with a T2N2 rectal cancer treated with preoperative chemoradiation. Laparoscopic visualization and assistance with retraction and exposure during rectosigmoid mobilization was provided through one 5-mm port, which was later used as the stoma site, and 2-mm needle ports, one of which was used as a drain site. The specimen was transected transanally followed by handsewn coloanal anastomosis. The procedure was completed successfully with an operative time of 4 hours and 30 minutes. Mesorectal excision was complete. The postoperative course was uneventful, and the patient was discharged on the fourth postoperative day. The final pathology demonstrated pT1N0 with 23 negative lymph nodes and negative proximal, distal, and radial margins. NOTES transanal endoscopic rectosigmoid resection using TEM and laparoscopic assistance is feasible and safe. Careful patient selection and improvement in NOTES instrumentation are critical to optimize this approach before widespread clinical application.

Standard sleeve gastrectomy for the morbidly obese is feasible and safe using the hybrid transvaginal minilaparoscopic-assisted natural orifice surgery (MA-NOS) with available laparoscopic/endoscopic instruments and technology as illustrated by this technical report on a female patient.The intervention was a transvaginal sleeve gastrectomy in a 67-year-old woman who was hypertensive, noninsulin-dependent with diabetes with morbid obesity (BMI, 37). Operative field view was maintained at all times with a gastroscope introduced through a transvaginal trocar. The surgeon positioned himself at the right side of the patient using a 2-mm needle port/mini-grasper placed in the left upper quadrant for traction of the greater curvature of the stomach. A 12-mm umbilical trocar was used as the port for insertion of the LigaSure device used for division of the short gastric vessels and the Endo-GIA stapler for creation of the gastric tube. The first assistant used a second mini-grasper for liver retraction and stomach positioning. The resected stomach was retrieved through the vagina. There were no intraoperative complications. The operative time was 150 minutes.The advantages of minimally invasive surgery seemed to be enhanced with this hybrid laparoscopic approach. Postoperative course was uneventful. All component steps of a laparoscopic sleeve gastrectomy (LSG) were reproduced. The patient was discharged on the third postoperative day.Transvaginal hybrid MA-NOS sleeve gastrectomy is both feasible and safe. The hybrid technique ensured safety during the performance of the procedure. MA-NOS is a potential option to avoid abdominal incisions and related complications for the laparoscopic resection of large intra-abdominal organs. Combined hybrid laparoscopic NOS for humans is currently a safe and reliable approach for major surgery through the NOS approach in female patients. Hybrid surgery allows controlled implementation of NOS techniques in clinical practice, providing a stepwise progression to the pure NOS approach once the appropriate technology has been developed. Additionally, it is the best way to stimulate the active development and evaluation of the underpinning technologies and instruments for these novel endoscopic surgical approaches. Appropriate clinical indications for these new procedures are yet to be defined. LSG is associated with short-term excess weight loss and resolution of comorbidities comparable to those obtained with other restrictive procedures. The performance of sleeve gastrectomy is an option in selected patients undergoing bariatric surgical treatment, particularly in the super obese and those who are considered high risk because of comorbid disease.

Natural orifice transluminal endoscopic surgery (NOTES) is the paradigm of the evolution of minimally invasive surgery. The laparoscopicrevolutionhas introduced new ideas in general surgery, one of them being that modern surgery is the work of multidisciplinary teams. A clear example of this is provided by NOTES. The aim of this type of surgery is to perform conventional laparoscopic procedures without incision, using flexible endoscopic technology usually employed in the diagnosis and treatment of intraluminal lesions and reaching the inside of the abdominal cavity through natural orifices (mouth, anus, vagina and even urethra). This type of access opens a highly interesting field for certain types of patients, such as those with high surgical risk, the morbidly obese, and those with multiple prior abdominal interventions or surgical wound infections. Animal models have shown that a wide variety of interventions (cholecystectomy, appendicectomy, splenectomy, hysterectomy, tubal ligations, gastroenteroanastomosis, peritoneoscopy, liver biopsy and herniorrhaphy, among others) can be performed. However, before use in humans, this new technique must be shown to be safe and to provide real advantages for patients. To do this, a series of issues, including safe methods for closure of the gastric incision and the avoidance of infections, among others, must be solved. Another critical element for the development of this new type of surgery is the creation of appropriate instrumentation, requiring input not only from medical professionals but also from engineers and industry. The present article describes the major advances made in NOTES since this technique was first described and analyzes the risks and potential benefits associated with this novel procedure.

The aim of this study was to compare the long-term outcome of laparoscopy-assisted colectomy (LAC) and open colectomy (OC) for nonmetastatic colon cancer.From November 1993 to July 1998 all patients with adenocarcinoma of the colon were assessed for entry in this single center, clinically randomized trial. Adjuvant therapy and postoperative follow-up were similar in both groups. The primary endpoint was cancer-related survival and secondary endpoints were probability of overall survival and probability of being free of recurrence. Data were analyzed according the intention-to-treat principle.Two hundred and nineteen patients entered the study (111 LAC group and 108 OC group). The median follow-up was 95 months (range, 77-133). There was a tendency of higher cancer-related survival (P = 0.07, NS) and overall survival (P = 0.06, NS) for the LAC group. Probability of cancer-related survival was higher in the LAC group (P = 0.02) when compared with OC. The regression analysis showed that LAC was independently associated with a reduced risk of tumor relapse (hazard ratio 0.47, 95% CI 0.23-0.94), death from a cancer-related cause (0.44, 0.21-0.92) and death from any cause (0.59, 0.35-0.98).LAC is more effective than OC in the treatment of colon cancer.

With available laparoscopic and endoscopic instruments/technology a standard radical sigmoid resection is feasible and safe using transvaginal minilaparoscopic-assisted natural orifice surgery (MA-NOS). The intervention was a transvaginal MA-NOS sigmoidectomy in a 78-year-old woman with a sigmoid adenocarcinoma. Maintaining triangulation the surgeon positioned himself at the right side of the patient and used the transvaginal trocar for dissection and stapling of both the inferior mesenteric vessels and the upper rectum. The colonic resection was performed extracorporeally in the conventional fashion and was followed by an intra-abdominal endoscopically assisted stapled anastomosis. Advantages of minimally invasive surgery seemed to be enhanced with this hybrid laparoscopic approach. Postoperative course was uneventful. All oncological principles governing resection and management were accomplished and the pathology examination confirmed a T3N1 lesion. The patient was discharged on the fourth postoperative day. Transvaginal MA-NOS radical sigmoidectomy is a feasible and oncologically safe procedure. MA-NOS is a realistic option for avoiding the need of assisting incisions and related morbidity in the laparoscopic resection of large intra-abdominal lesions. Combined hybrid laparoscopic NOS in humans (MA-NOS) currently provides a safe and reliable way of defining future clinical applications and advantages of NOS and NOTES. Additionally, it stimulates the active development and evaluation of the underpinning technologies and instrumentation.

Data on the effectiveness of sleeve gastrectomy in improving or resolving type 2 diabetes mellitus (T2DM) and the metabolic syndrome (MS) are scarce.A twelve-month prospective study on the changes in glucose homeostasis and the MS in 91 severely obese T2DM subjects undergoing laparoscopic SG (SG; n = 39) or laparoscopic Roux-en-Y gastric bypass (GBP; n = 52), matched for DM duration, type of DM treatment, and glycemic control was conducted.At 12 months after surgery, subjects undergoing SG and GBP lost a similar amount of weight (%EBL: SG: 63.00 +/- 2.89%, BPG: 66.06 +/- 2.34%; p = 0.413). On that evaluation, T2DM had resolved, respectively, in 33 out of 39 (84.6%) and 44 out of 52 (84.6%) subjects after SG and GBP (p = 0.618). The rate of resolution of the MS (SG: 62.2%, BPG: 67.3%; p = 0.392) was also comparable. A shorter DM duration (p0.05), a DM treatment not including pharmacological agents (p0.05), and a better glycemic control (p0.05), were significantly associated with T2DM resolution in both surgical groups. Weight loss was not associated with T2DM resolution after SG or GBP, but was associated with resolution of the MS following the two surgical procedures (p0.05).Our data show that at 12 months after surgery, SG is as effective as GBP in inducing remission of T2DM and the MS. Furthermore, our data suggest that SG and GBP represent a successful an integrated strategy for the management of the different cardiovascular risk components of the MS in subjects with T2DM.

To prospectively assess the relationship between circulating peptide YY (PYY), body weight, and glucose tolerance in severely obese subjects undergoing Roux-en-Y gastric bypass (RYGBP).The mechanisms accounting for the beneficial effects of RYGBP on body weight and glucose homeostasis are not well understood.Prospective study on the response of PYY to a standardized test meal (STM) and its relationship with weight loss and glucose homeostasis (fasting plasma glucose, HbA1c, HOMA-IR, HOMA-B) in nondiabetic (n = 25) and diabetic (n = 10) severely obese subjects evaluated before, and at 6 and 52 weeks after RYGBP.The PYY response to a STM significantly increased (P0.001) already at 6 weeks at a time when subjects despite presenting a significant weight loss (-14.6% +/- 1.2%) were still markedly obese. Despite massive weight loss (-43.0% +/- 2.3%), no further increase in the area under the curve of PYY was observed at 52 weeks after surgery (P = 0.44). The PYY response to a STM at 6 weeks after surgery significantly correlated (r = 0.489, P0.05) with the percent excess weight loss at 32.5 +/- 1.1 months after surgery. In contrast, no significant correlation was found between PYY and glucose homeostasis parameters in nondiabetic and diabetic patients.Our data support the hypothesis that an increased PYY response after meal ingestion is involved in the sustained weight loss observed after RYGBP. In contrast, our data does not support PYY being relevant in the changes in glucose homeostasis occurring after this type of bariatric surgery.

Background Early upper GI hemorrhage (UGH) is a potential complication after laparoscopic Roux-en-Y gastric bypass (RYGBP), and early reoperative intervention is the most accepted treatment. Experience with endoscopic treatment is limited. Objective Our purpose was to describe the role of endoscopy and injection therapy in the management of early UGH after laparoscopic RYGBP. Design Case series study. Setting Endoscopy Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain. Patients We describe the endoscopic treatment of 6 patients with early UGH within 24 hours after a RYGBP. Instrumentation Upper endoscopy was performed in all 6 cases. The origin of the bleeding was identified at the staple line in all cases, and epinephrine alone or combined with polidocanol was successfully injected in 5 of 6 patients. Results Endoscopic therapy arrested active bleeding without any complications in all cases without the need for further surgery or endoscopic treatments. Limitation Our experience is limited to 6 cases. Conclusion Early postoperative UGH after RYGBP may be adequately controlled with endoscopic treatment and may obviate the need for surgery. Further data are necessary to evaluate the safety and the efficacy of this approach.

Background: It has been proposed, that the dramatic amelioration of type 2 diabetes following Roux-en-Y gastric bypass (RYGBP) could by accounted for, at least in part, by changes in glucagon-like peptide-1 (GLP-1) secretion. However, human data supporting this hypothesis is scarce. Methods: A 12-month prospective study on the changes in glucose homeostasis, and active GLP-1 in response to a standard test meal (STM) was conducted in 34 obese subjects (BMI 49.1±1.0 kg/m2) who had different degrees of glucose tolerance: normal glucose tolerance (NGT, n=12), impaired glucose tolerance (IGT, n=12), and type 2 diabetes (n=10). Results: At 6 weeks after RYGBP, despite the subjects still being markedly obese (BMI 43.5±0.9 kg/m2), fasting plasma glucose and HbA1c decreased in the 3 study groups (P

Corrigendum: Characterization of Inflammation and Fibrosis in Crohn’s Disease Lesions by Magnetic Resonance Imaging

Background: The effects of adiponectin on glucose and lipid metabolism are mediated by the adiponectin receptors, adipoR1 and adipoR2, which are mainly in liver and muscle. We investigated the presence of adiponectin receptors in intra-abdominal adipose tissue (IAAT) in obesity and diabetes and their association with adiponectin expression and components of the metabolic syndrome and/or other metabolic factors associated with atherosclerotic cardiovascular disease (ASCVD). Methods: AdipoR1 and adipoR2 gene expression was measured by quantitative real time reverse transcription polymerase chain reaction in IAAT from lean and obese patients with or without diabetes type 2. Correlation between metabolic characteristics of obese patients and expression of these receptors was studied. Results: Neither obesity nor diabetes were associated with changes in IAAT-adipoR1 expression. In contrast, IAAT-adipoR2 was decreased by 39.5% in obese non-diabetics and by 52.7% in obese diabetics when compared to lean subjects. AdipoR1 and adiponectin expression was associated in lean (r=0.943, P

Despite the advances in our understanding of Crohn's disease (CD), the course of the disease in a particular patient remains unpredictable. Surgery is frequently needed, and a large number of patients require more than 1 operation.1,2 Several articles have attempted to define predictive factors for requirement of initial surgery1,3–5 or reoperation1,5–16 based on the analysis of clinical variables. However, the results of these studies have been inconsistent. This may be attributable to differences in study design concerning patient population, clinical classification used, criteria for variables definition, ethnicity, or duration of CD. Besides, it is important to note that clinical characteristics of CD may change over time;17 therefore, classification of CD patients may significantly benefit from associated stable genetic factors. Three variants of Nod2/CARD15 gene (R702W, G908R, L1007fsinsC), present in 30% to 50% of CD white patients, are implicated in the susceptibility to CD.18–21 Since a number of genotype-phenotype studies have suggested that Nod2/CARD15 variants are associated with ileal disease and development of intestinal strictures,21–26 it is conceivable that variants of this gene may be also accurate predictors of surgery requirement. A few studies have assessed surgery requirement in relation to Nod2/CARD15 genotype. In 2 recent reports Nod2/CARD15 gene variants were more frequent in patients requiring bowel surgery,25,27 whereas another study found an association only with surgery indicated for the treatment of stricturing lesions.24 However, in none of these studies were the Nod2/CARD15 gene variants independent predictors of surgery requirement. In the only study that evaluated the need of a second surgery, an association with the Nod2/CARD15 gene variants was not found.24 If Nod2/CARD15 genotype were a good predictor of surgery requirement, this genetic factor would allow identification of patients who might benefit from preventive and/or early therapeutic interventions. Therefore, the aim of our study was to ascertain whether the Nod2/CARD15 gene variants are independent predictive factors for both initial surgery and the need of subsequent surgical procedures in patients with CD.

Laparoscopic excision of a gastric lipoma is reported here. The diagnosis was done preoperatively be computed tomography, which gave evidence of fat tissue due to its low attenuation. The patient undergoes a complete submucosal excision enjoying the benefit of the laparoscopic approach with rapid postoperative recovery. This procedure offers a good alternative to open laparotomy in the treatment of benign gastric tumours.

The applicability of laparoscopic surgery in the treatment of colorectal diseases is still controversial. Early reports on laparoscopic-assisted colectomy in patients with colon cancer suggested that it minimizes surgical trauma, decreases perioperative complications, and leads to a more rapid recovery. To our knowledge, no previous studies have compared the laparoscopic vs the open approach in rectal cancer. The aim of this paper was to assess the results of laparoscopic techniques in patients with rectal cancer. From March 1998 to February 2003, all patients admitted to our unit with adenocarcinoma of the rectum were evaluated for surgery by the laparoscopic approach. A total of 220 patients with a mean age of 67.3 years were included in the study. One hundred thirty patients (59%) were treated with neoadjuvant chemoradiotherapy. In >75% of the patients, a surgical procedure with sphincter preservation was perfomed. The rate of conversion to the open approach was 20%. Ten patients had intraoperative complications. Fifty-eight patients (26.3%) developed postoperative complications. The length of hospital stay was 6.8 days. The distribution of tumor stages was as follows: stage I, 16.81%; stage II, 33.6%; stage III, 26.36%; stage IV, 19.09%. The mean number of lymph nodes was 13.8. The incidence of local relapse was 5.3%, with a follow-up of 18 months. Laparoscopic surgery can be safely performed in patients with adenocarcinoma of the rectum with good short-term results. Randomized controlled trials are needed to confirm these results.

Summary Background Although early reports on laparoscopy-assisted colectomy (LAC) in patients with colon cancer suggested that it reduces perioperative morbidity, its influence on long-term results is unknown. Our study aimed to compare efficacy of LAC and open colectomy (OC) for treatment of non-metastatic colon cancer in terms of tumour recurrence and survival. Methods From November, 1993, to July, 1998, all patients with adenocarcinoma of the colon were assessed for entry in this randomised trial. Adjuvant therapy and postoperative follow-up were the same in both groups. The main endpoint was cancer-related survival. Data were analysed according to the intention-to-treat principle. Findings 219 patients took part in the study (111 LAC group, 108 OC group). Patients in the LAC group recovered faster than those in the OC group, with shorter peristalsis-detection (p=0·001) and oral-intake times (p=0·001), and shorter hospital stays (p=0·005). Morbidity was lower in the LAC group (p=0·001), although LAC did not influence perioperative mortality. Probability of cancer-related survival was higher in the LAC group (p=0·02). The Cox model showed that LAC was independently associated with reduced risk of tumour relapse (hazard ratio 0·39, 95% CI 0·19–0·82), death from any cause (0·48, 0·23–1·01), and death from a cancer-related cause (0·38, 0·16–0·91) compared with OC. This superiority of LAC was due to differences in patients with stage III tumours (p=0·04, p=0·02, and p=0·006, respectively). Interpretation LAC is more effective than OC for treatment of colon cancer in terms of morbidity, hospital stay, tumour recurrence, and cancer-related survival.

Elevated intraabdominal pressure due to gas insufflation for laparoscopic surgery may result in regional blood flow changes. Impairments of hepatic, splanchnic, and renal blood flow during peritoneal insufflation have been reported. Therefore we set out to investigate the effects of peritoneal insufflation with helium (He) and carbon dioxide (CO2) on hepatic blood flow in a porcine model.Twelve pigs were anesthetized and mechanically ventilated with a fixed tidal volume after the stabilization period. Peritoneal cavity was insufflated with CO2 (n = 6) or He (n = 6) to a maximum intraabdominal pressure of 15 mmHg. Hemodynamic parameters, gas exchange, and oxygen content were studied at baseline, 90 mm and 150 min after pneumoperitoneum, and 30 min after desufflation. Determination of hepatic blood flow with indocyanine green was made at all measured points by a one-compartment method using hepatic vein catheterization.A similar decrease in cardiac output was observed during insufflation with both gases. Hepatic vein oxygen content decreased with respect to the baseline during He pneumoperitoneum (p0.05), but it did not change during CO2 insufflation. Hepatic blood flow was significantly reduced in both the He and CO2 pneumoperitoneums at 90 min following insufflation (63% and 24% decrease with respect to the baseline; p0.001 and p0.05, respectively) being this decrease marker in the He group (p = 0.02).These findings suggest that helium intraperitoneal insufflation results in a greater impairment on hepatic blood flow than CO2 insufflation.

Background: This study was performed to prospectively assess the impact of the laparoscopic approach to the patterns of port site metastases (PSM) and recurrence rate (RR) of resected colon carcinomas as compared with conventional colectomies. Methods: All patients were included in a prospective randomized trial comparing laparoscopic-assisted colectomy (LAC) versus open colectomy (OC) for colon cancer. The randomization was stratified for localization of the lesion. Patients with metastasic disease at the time of the surgery were excluded. Follow-up in the outpatient clinic was done every 3 months for a minimum of 12 months. Endpoints for the study were metastasis at port site and laparotomy incision as well as recurrence rate. Results: Of 91 segmental colectomies performed from November 1993 to January 1996, there were 44 LAC and 47 OC. Patient data were similar in both groups (age, sex, Dukes stage, type of operation). Mean follow-up was 21.4 months, with a range of 13 to 41 months. There were no wounds or PSM in those series. RR was similar for both groups. For LAC, it was five of 31 (16.1%); for OC, it was six of 40 (15%). Conclusions: The laparoscopic approach has a recurrence rate similar to that for open procedures for colon cancer. However, additional follow-up of these patients is needed before we can determine whether or not the laparoscopic approach influences overall survival.

Background: This study was performed to prospectively assess the complications of 118 consecutive patients who underwent laparoscopic assisted colorectal resections. Methods: The variables included were: indication for surgery, type of resection, duration of operation, duration of postoperative ileus, length of hospital stay, port-site recurrence, and complications in relation to the laparoscopic technique. Results: 118 Laparoscopic-assisted procedures were performed between July 1992 and October 1995. Surgical indications were: 106 patients for colonic malignancy, six for diverticulitis, two for Crohn's disease, two for benign polyps, one for endometriosis, and one for ischemic colitis. Fifteen patients required conversion to open techniques for completion of the operations (12.7%). The mean operating time was 168.8 min. The amount of operative blood loss was 98 ml. The mean time for passing flatus was 36 ± 16 h. Mean postoperative stay was 5.4 (range 3–13) days. Eight patients (6.8%) sustained complications: four unrelated to laparoscopy (three wound infection, one anastomotic leak); and four complications related to the laparoscopic approach: one small-bowel obstruction, one trocar injury, one rotation of the anastomosis, and one misdiagnosed synchronous adenocarcinoma. Conclusions: We suggest that with the development of improved technical devices and more experience, the indications for laparoscopic colectomy should continue to expand. The low incidence of infectious complications suggests an important role for the laparoscopic approach to colorectal surgery.

3536 Background: Neoadjuvant chemo-radiotherapy (CRT) is the standard of care for patients (pts) with u>T3 by endoscopic ultrasound (EUS) rectal cancer. Although pts with complete pathological response (ypT0N0) fare well in multiple series, there is uncertainty of whether it’s due to the induction (CRT), due to the adjuvant chemotherapy (ACT) or due to the combination of both therapies. We have evaluated long-term outcomes in CRT-treated pts. Those with ypT0N0, were not treated with ACT. Methods: Pts with u>T3 rectal cancer, received neoadjuvant chemotherapy (225mg/m2/day 5-fluorouracil (FU)) in continuous infusion (CI) per 5 weeks (wks) and concomitant radiotherapy (45 Gy). Laparoscopic surgery (LAP) was planned after an interval of 5-8 wks. Pts achieving ypT0N0 were no treated with ACT. Pts with ypT>1 or N1 were treated with 3 gr/m2 FU in 48 hour CI and LV 200 mg/m2 every 2 wks x 6 cycles. Results: From November 2000 to November 2008, a cohort of 173 pts were treated with induction CRT and 167 pts underwent total mesorectal excision (LAP, n=158, open surgery n=9). Complete pathological response was achieved in 26/167 pts (15.5%). After a median follow-up of 58.3 months, pts with ypT0N0 have a 5-year disease-free survival and overall survival rate of 96% (95% CI 76 to 99%) and 100% (95% CI not estimable) respectively. Conclusions: Using these results, a clinical trial comparing observation versus adjuvant therapy in ypT0N0 after standard CRT, would need to enroll 3088 pts to show a HR of 0.75 in favor of ACT after 5 years of follow-up (alpha=.05, beta=.2). In case that the true DFS lied in the lower bound of the 95% CI, 636 patients would be needed under the same assumptions. These results do not support the administration of ACT to ypT0N0 patients.

3586 Background: Retrospective data suggest that RT might not be needed in all patients with stage II/III RC. Modern systemic therapy might have local efficacy similar to chemoradiation (CRT). Methods: A multicenter phase II trial was undertaken to evaluate safety and efficacy of neoadjuvant CAPOX-B in patients with T3 middle third rectal adenocarcinoma. Eligible patients (pts) had measurable disease at the baseline and candidate for R0 total mesorectal escision (TME) with intermediate-risk defined by pelvic MR a) T3 with distal border of tumor > 5 cm from the anal verge and below the sacral promontory. b) tumor ≥2 mm from the mesorectal fascia. Pts received 4 cycles of Cap 2000 mg/m2 (d1-14), Ox 130 mg/m2 (d1) and B 7.5 mg/kg (d1) every 3 weeks (last cycle without B). Pts undergo re-staging with MR. One radiologist reviewed all pre- and post-treatment MR scans independently. Pts without progression proceed to TME 4-6 weeks from the last cycle. If progression, pts were to be referred for pre-op cap/RT followed by TME. 1º Endpoint: Tumor Response (RECIST). Design: Simon 2-stage; 28 pts 1st stage and 46 pts 2nd stage. We report data on the planned analysis of pts included for 1st stage. Results: 28 eligible pts (10F/18M) were enrolled from 7/09-5/11. Tumor response, compliance and toxicity details are shown in table below. Two pN2 pts received postop Cap/RT. Conclusions: Neoadjuvant CAPOX-B is active and safe. Early parameters of efficacy are encouraging and seem similar to those observed with CRT. [Table: see text]

3634 Background: QRTP and subsequent TME is the standard treatment in patients with stage II-III RC. Laparoscopic surgery in RC is not a standard treatment. We present long-term outcomes in patient...

14556 Background: To establish the feasibility and efficacy of capecitabine with weekly irinotecan (CAPIRI) and concurrent radiotherapy (RT) in patients with locally advanced and resectable metastatic rectal cancer, followed by LAME. Methods: Eligible criteria included adenocarcinoma of the rectum staged by endoscopic ultrasonography (us), spiral abdominal and pelvic CT and chest X-ray. Patients received weekly irinotecan 50 mg/m2 (days 1,8,15,22,29) and two doses of capecitabine (days 1 through 5 for 5 weeks); dose level; (DL) I 250 mg/m2 bid; DL II 375 mg/m2 bid; DL III 500 mg/m2 bid, according to phase I methodology. Conformal radiotherapy was administered up to a total dose of 45 Gy/1.8 Gy per fraction. LAME was planned 5–7 weeks after CRT. Results: From January 2003 to March 2006, 22 patients (three with potentially resectable metastatic disease) were included. Median age was 62 (range 48 to 78). 6 pts were usT3N0 and 16 pts usT3–4N1. Seven patients were treated at DL I, six at DL II and nine at DL III. Grade 3 or 4 adverse events were observed in all levels; DL I asthenia (1p); DL II diarrhea (2p) and DL III asthenia and neutropenia (1p), diarrhea (1p) and hyperbilirrubinaemia (1p). All patients except one who refused treatment after 1 week therapy (DL I), completed CRT and underwent surgical resection (R0 81%, R2 19%). Abdominoperineal resection was done in two cases (9%). Conversion rate to open surgery was 5%. Median hospital stay was 7.9 days. The overall postoperative morbidity was 4.7%. Median excised nodes were 11 (range 4–21). Pathological complete response was observed in two patients (9%), both of them in DL III. With a median follow-up of 25 months (range 9–46), disease free survival and overall survival was 67% and 95% respectively. Conclusions: Preoperative CRT with CAPIRI is feasible, but severe adverse events were found in all levels despite the use of lower dose of capecitabine than previously published. LAME after CAPIRI had short oncologic outcomes comparable with open mesorectal excision. No significant financial relationships to disclose.

To perform a meta-analysis of trials randomizing patients with colon cancer to laparoscopically assisted or open colectomy to enhance the power in determining whether laparoscopic colectomy for cancer is oncologically safe.The databases of the Barcelona, Clinical Outcomes of Surgical Therapy (COST), Colon Cancer Laparoscopic or Open Resection (COLOR), and Conventional vs Laparoscopic-Assisted Surgery in Patients With Colorectal Cancer (CLASICC) trials were the data sources for the study.Patients who had at least 3 years of complete follow-up data were selected.Patients who had undergone curative surgery before March 1, 2000, were studied. Three-year disease-free survival and overall survival were the primary outcomes of this analysis.Of 1765 patients, 229 were excluded, leaving 796 patients in the laparoscopically assisted arm and 740 patients in the open arm for analysis. Three-year disease-free survival rates in the laparoscopically assisted and open arms were 75.8% and 75.3%, respectively (95% confidence interval [CI] of the difference, -5% to 4%). The associated common hazard ratio (laparoscopically assisted vs open surgery with adjustment for sex, age, and stage) was 0.99 (95% CI, 0.80-1.22; P = .92). The 3-year overall survival rate after laparoscopic surgery was 82.2% and after open surgery was 83.5% (95% CI of the difference, -3% to 5%). The associated hazard ratio was 1.07 (95% CI, 0.83-1.37; P = .61). Disease-free and overall survival rates for stages I, II, and III evaluated separately did not differ between the 2 treatments.Laparoscopically assisted colectomy for cancer is oncologically safe.

The authors report a case of complete rotation of the left colon after laparoscopic sigmoidectomy. Such an uncommon complication in open colectomies has not been previously described with the laparoscopic approach. During the performance of laparoscopic-assisted colectomies the proximal segment of the colon can be rotated when removing the specimen through a small incision. Therefore we recommend inspecting the position of the colon before the stapler is fired.

AIM: To evaluate the long-term results of conventional chemoradiotherapy and laparoscopic mesorectal excision in rectal adenocarcinoma patients without adjuvant therapy. METHODS: Patients with biopsy-proven adenocarcinoma of the rectum staged cT3-T4 by endoscopic ultrasound or magnetic resonance imaging received neoadjuvant continuous infusion of 5-fluorouracil for five weeks and concomitant radiotherapy. Laparoscopic surgery was planned after 5-8 wk. Patients diagnosed with ypT0N0 stage cancer were not treated with adjuvant therapy according to the protocol. Patients with ypT1-2N0 or ypT3-4 or N+ were offered 5-fluorouracil-based adjuvant treatment on an individual basis. An external cohort was used as a reference for the findings. RESULTS: One hundred and seventy six patients were treated with induction chemoradiotherapy and 170 underwent total mesorectal excision. Cancer staging of ypT0N0 was achieved in 26/170 (15.3%) patients. After a median follow-up of 58.3 mo, patients with ypT0N0 had five-year disease-free and overall survival rates of 96% (95%CI: 77-99) and 100%, respectively. We provide evidence about the natural history of patients with localized rectal cancer achieving a complete response after preoperative chemoradiation. The inherent good prognosis of these patients will have implications for clinical trial design and care of patients. CONCLUSION: Withholding adjuvant chemotherapy after complete response following standard neoadjuvant chemoradiotherapy and laparoscopic mesorectal excision might be safe within an experienced multidisciplinary team.