Distribution of transient receptor potential vanilloid-1 channels in gastrointestinal tract of patients with morbid obesity

BACKGROUND Transient receptor potential vanilloid-1(TRPV1),a nonselective cation channel,is activated by capsaicin,a pungent ingredient of hot pepper.Previous studies have suggested a link between obesity and capsaicin-associated pathways,and activation of TRPV1 may provide an alternative approach for obesity treatment.However,data on the TRPV1 distribution in human gastric mucosa are limited,and the degree of TRPV1 distribution in the gastric and duodenal mucosal cells of obese people in comparison with normal-weight individuals is unknown.AIM To clarify gastric and duodenal mucosal expression of TRPV1 in humans and compare TRPV1 expression in obese and healthy individuals.METHODS Forty-six patients with a body mass index(BMI)of>40 kg/m^(2) and 20 patients with a BMI between 18-25 kg/m^(2) were included.Simultaneous biopsies from the fundus,antrum,and duodenum tissues were obtained from subjects between the ages of 18 and 65 who underwent esophagogastroduodenoscopy.Age,sex,history of alcohol and cigarette consumption,and past medical history regarding chronic diseases and medications were accessed from patient charts and were analyzed accordingly.Evaluation with anti-TRPV1 antibody was performed separately according to cell types in the fundus,antrum,and duodenum tissues using an immunoreactivity score.Data were analyzed using SPSS 17.0.RESULTS TRPV1 expression was higher in the stomach than in the duodenum and was predominantly found in parietal and chief cells of the fundus and mucous and foveolar cells of the antrum.Unlike foveolar cells in the antrum,TRPV1 was relatively low in foveolar cells in the fundus(4.92±0.49 vs 0.48±0.16,P<0.01,Mann-Whitney U test).Additionally,the mucous cells in the duodenum also had low levels of TRPV1 compared to mucous cells in the antrum(1.33±0.31 vs 2.95±0.46,P<0.01,Mann-Whitney U test).TRPV1 expression levels of different cell types in the fundus,antrum,and duodenum tissues of the morbidly obese group were similar to those of the control group.Staining with TRPV1 in fundus chief cells and antrum and duodenum mucous cells was higher in patients aged≥45 years than in patients<45 years(3.03±0.42,4.37±0.76,2.28±0.55 vs 1.9±0.46,1.58±0.44,0.37±0.18,P=0.03,P<0.01,P<0.01,respectively,Mann-Whitney U test).The mean staining levels of TRPV1 in duodenal mucous cells in patients with diabetes and hypertension were higher than those in patients without diabetes and hypertension(diabetes:2.11±0.67 vs 1.02±0.34,P=0.04;hypertension:2.42±0.75 vs 1.02±0.33,P<0.01 Mann-Whitney U test).CONCLUSION The expression of TRPV1 is unchanged in the gastroduodenal mucosa of morbidly obese patients demonstrating that drugs targeting TRPV1 may be effective in these patients.

Apolipoprotein E in diet-induced obesity:a paradigm shift from conventional perception

Apolipoprotein E（APOE） is a major protein component of peripheral and brain lipoprotein transport systems.APOE in peripheral circulation does not cross the blood brain barrier or blood cerebrospinal fluid barrier. As a result,peripheral APOE expression does not affect brain APOE levels and vice versa. Numerous epidemiological studies suggest a key role of peripherally expressed APOE in the development and progression of coronary heart disease while brain APOE has been associated with dementia and Alzheimer＇s disease. More recent studies, mainly in experimental mice, suggested a link between Apoe and morbid obesity. According to the latest findings, expression of human apolipoprotein E3（APOE3） isoform in the brain of mice is associated with a potent inhibition of visceral white adipose tissue（WAT） mitochondrial oxidative phosphorylation leading to significantly reduced substrate oxidation,increased fat accumulation and obesity. In contrast, hepatically expressed APOE3 is associated with a notable shift of substrate oxidation towards non-shivering thermogenesis in visceral WAT mitochondria, leading to resistance to obesity. These novel findings constitute a major paradigm shift from the widely accepted perception that APOE promotes obesity via receptor-mediated postprandial lipid delivery to WAT. Here, we provide a critical review of the latest facts on the role of APOE in morbid obesity.

Sugammadex is associated with better respiratory recovery than neostigmine following reversal of anaesthesia-associated neuromuscular blockade in the morbidly obese patients following elective laparoscopic surgery

Complete and reliable neuromuscular reversal is important to successful anaesthetic recovery in the morbidly obese patient undergoing laparoscopic surgery.Our goal was to determine whether sugammadex,a selective reversal agent is associated with better respiratory recovery than neostigmine following the reversal of anaesthesia-associated neuromuscular blockade by rocuronium in the morbidly obese.Peak Expiratory Flow Rate a surrogate marker for respiratory function,was the primary outcome measured and secondary outcome measures included post-operative nausea and vomiting,pain and head lifting.We found that patients reversed with sugammadex had a significantly higher post-operative PEFR as compared to those reversed with neostigmine and glycopyrrolate group.

Laparoscopic Sleeve Gastrectomy following Pylorus-Preserving Pancreaticoduodenectomy

Background: A 35-year-old married female (68 kg, 150 cm, BMI: 30.2) with pancreatic divisum complicated chronic pancreatitis and underwent pylorus-preserving pancreaticoduodenectomy in 2010. After that, her condition was well. However, body weight gained progressively to 76 kg (BMI: 33.7) and hypertension developed. During these two years, tried exercise and medication control for hypertension, but in vain. She received a laparoscopic sleeve gastrectomy in October 2013. The post-operative course was uneventful. Methods: We applied three ports for laparoscopic operation, including two 12 mm and one 5 mm trocars. The liver was not needed to be elevated due to adhesion. The operative time was 75 minutes. Results: The patient’s body weight was 10 kg reduced in the first two months and reduced to 59 kg 6 months later. Conclusions: We report a case that received laparoscopic sleeve gastrectomy following pylorus-preserving pancreaticoduodenectomy due to pancreatic divisum. This case encourages us to extend the indication of laparoscopic sleeve gastrectomy.

Two case reports of acute upper gastrointestinal bleeding from duodenal ulcers after Roux-en-Y gastric bypass surgery: Endoscopic diagnosis and therapy by single balloon or push enteroscopy after missed diagnosis by standard esophagogastroduodenoscopy

The diagnosis and opportunity for endoscopic therapy of gastric or duodenal lesions may be missed at esophagogastroduodenoscopy(EGD) because of technical difficulty in intubating at EGD the postoperatively excluded stomach and proximal duodenum in patients status post Roux-en-Y gastric bypass(RYGB). Two cases are reported of acute upper gastrointestinal bleeding 10 or 11 years status postRYGB, performed for morbid obesity, in which the EGD was non-diagnostic due to failure to intubate the excluded stomach and proximal duodenum, whereas subsequent push enteroscopy or single balloon enteroscopy were diagnostic and revealed 4-cm-wide or 5-mm-wide bulbar ulcers and even permitted application of endoscopic therapy. These case reports suggest consideration of push enteroscopy, or single balloon enteroscopy, where available, in the endoscopic evaluation of acute UGI bleeding in patients status post RYGB surgery when the EGD was non-diagnostic because of failure to intubate these excluded segments.

Management of gallstones and gallbladder disease in patients undergoing gastric bypass

The appropriate management of gallstones and gallbladder disease in patients undergoing gastric bypass remains unknown.Several therapeutic modalities are used and include performing cholecystectomy on all patients at the time of gastric bypass,performing concomitant cholecystectomy only when patients have gallstones and performing cholecystectomy only in the presence of both symptoms and gallstones.Some groups administer ursodeoxycholic acid for gallstone prevention in the postoperative period.All treatment modalities are analyzed and their results and rationality are discussed.

Surgical outcome of laparoscopic sleeve gastrectomy and Roux-en-Y gastric bypass for resolution of type 2 diabetes mellitus:A systematic review and meta-analysis

BACKGROUND Bariatric procedures are considered superior to medical therapies in managing type 2 diabetes mellitus(T2DM).Laparoscopic Roux-en-Y gastric bypass(LRYGB)and laparoscopic sleeve gastrectomy(LSG)are the most commonly used procedures for weight loss and comorbidity resolution worldwide.However,it is not yet known whether the degree of T2DM is influenced by the choice of bariatric procedure.AIM To quantitatively compare T2DM resolution over 1-5 years follow-up by LRYGB and LSG in morbidly obese patients.METHODS We searched the selected databases for full-text English language clinical studies that compared the effectiveness of LRYGB and LSG for T2DM resolution.Review manager 5.3 was used for data analysis,and the overall effect summary was represented in a forest plot.RESULTS From 1,650 titles retrieved by an initial search,we selected nine studies for this research.We found insignificant differences for T2DM resolution by LRYGB and LSG,with an odds ratio of 0.93(95%CI:0.64-1.35,Z statistics=0.38,P=0.71).Additionally,subset analyses for T2DM resolution showed insignificant differences after 24 mo(χ^2=1.24,df=4,P=0.87,overall Z effect=0.23),36 mo(χ^2=0.41,df=2,P=0.81,overall Z effect=0.51),and 60 mo(χ^2=4.75,df=3,P=0.19,overall Z effect=1.20)by LRYGB and LSG.This study reports a T2DM remission rate of 82.3%by LRYGB and 80.7%by LSG.CONCLUSION This study reports similar T2DM resolution rates by both LRYGB and LSG during 1-5 years of follow-up.However,long-term follow-up of 10 years is needed to further substantiate these findings.

Endoscopic therapy of weight regain after bariatric surgery

Weight regain following primary bariatric surgery occurs in a significant proportion of patients and is attributed to epidemiological,anatomical and metabolic factors.Surgical revision of these patients has significant risks and limited benefits.Endoscopic revisions that reduce gastric pouch size and diameter of the gastrojejunal anastomosis may offer an effective,safe,less invasive and even reproducible treatment.We herein discuss the indication,selection and feasibility of different endoscopic techniques that could be used in the management of weight regain following primary bariatric surgery.Future research could optimize a personalized approach not only in the endoscopic management but also in combination with other therapeutic modalities for weight regain after bariatric surgery.

Laparoscopic Sleeve Gastrectomy Outcomes

Introduction: Sleeve gastrectomy was first defined in 1990 as a part of the duodenal switch procedure with the formation of a narrow stomach tube along the small curvature of the stomach. Later, researchers proposed that Laparoscopic leave gastrectomy (LSG) reduced the risk profile of the duodenal switch procedure in high risk patients. Additionally, LSG was accepted as a rapid single bariatric surgical procedure due to its simplicity and efficacy. The aim of this study was to describe the outcomes of LSG at a single bariatric unit in King Salman North West Armed Forced Hospital (KSAFH), Tabuk, Saudi Arabia. Objective: To compare outcomes of primary LSG regarding pre and post operative sleep apnea, diabetes mellitus (DM), arterial hypertension (HTN), bronchial asthma, female urinary incontinence, infertility, and gastroesophageal reflux (GERD). We will assess our complications according to the Clavein-Dindo classification. We reviewed the medical records of patients who underwent LSG in King Salman Armed Forces Hospital from 1/1/2015 till 31/6/2017. Methods: This retrospective comparative study is performed in the Department of Surgery, KSAFH. All patients are instructed for follow-up at 1 week and 1, 3, 6, 12, 18, 24 months postoperatively. Laboratory tests are requested every 6 months post op. Improvement of Comorbidities assessed post-operatively. Surgical Complications reported according to the Clavein-Dindo classification. Our results were compared with international studies. Inclusion criteria (more than 14 years, morbid obese with BMI > 40 and obese class 11 with comorbidities). Exclusion criteria (less than 14 years, BMI < 35 and BMI < 40 with no medical illness, revisional cases). Results: A total of 127 patients underwent LSG at King Salman Armed Forces Hospital from 1/1/2015 till 31/5/2017. Of these, 40 were male (31.5%) and 87 were female (68.5%). The mean age was 35 years. Comorbidities included diabetes 31 (24.4%),

Anhedonia and functional dyspepsia in obese patients:Relationship with binge eating behaviour

BACKGROUND Obese patients(Ob)with a binge eating disorders(BED)behavior pattern have a higher prevalence of postprandial distress syndrome(PDS)compared to Ob without a BED behavior pattern,while an increase of PDS has been described in Ob after sleeve gastrectomy(SG).Hedonic response to a meal is dissociable from satiation in healthy subjects.Anhedonia is the lowered ability to experience pleasure.There are no studies investigating the presence of anhedonia in Ob with and without SG and its relationship to PDS symptoms.AIM To assess the relationship among anhedonia,BED and upper gastrointestinal symptoms in two group of morbidly Ob with and without SG.METHODS Eighty-one Ob without SG,45 Ob with SG and 55 healthy controls(HC)were studied.All subjects fulfilled the binge eating scale(BES)to investigate BED,the validated 14 items Snaith-Hamilton pleasure scale(SHAPS)to assess Anhedonia as well as the Beck Depression Inventory-II(BDI II)and State Trait Anxiety Inventory(STAI)questionnaires to screen for depression and anxiety.All patients underwent a standardized questionnaire investigating the intensity-frequency scores(0-6)of upper gastrointestinal symptoms and were diagnosed for the presence of functional dyspepsia(FD)and its subtypes according to ROME IV criteria.RESULTS Ob without SG who were positive for BED had a 4.7 higher risk of FD compared to Ob without SG who were negative for BED(OR:4.7;95.0%CI 1.23-18.24;P=0.02).STAI-Y2 scores were significantly higher in Ob without SG positive for BED(42.2±1.5 vs Ob negative for BED:39.6±1.0,P=0.04),while SHAPS scores and BDI II did not differ in the two groups(1.16±1.30 vs 0.89±1.02,P=0.49).A lower prevalence of BED(BES>17:11.4%vs 40.7%,P=0.001)and BDI-II(6.8±1.2 vs 13.8±1.9,P=0.005)was reported in Ob with SG than Ob without SG,on the contrary total mean scores of STAI-Y1 and STAI-Y2 were significantly higher in Ob with SG than Ob without SG.Thirty-five percent of Ob with SG fulfilled the diagnosis of FD.SHAPS mean scores and the prevalence of anhedonia did not differ among the two groups(18.2 vs 8.1%,P=0.2).Fifty-four percent of Ob with SG achieved surgical success excess weight loss>50%.Excess weight loss was negatively related to SHAPS total mean scores[adjusted B:-7.099(95%CI:-13.91 to-0.29),P=0.04].CONCLUSION Ob without SG showed a higher prevalence of PDS,mood disorders and anxiety when positive for BE behavior compared to those negative for BE behavior,whereas no differences were found in SHAPS score.Ob with SG showed a higher prevalence of PDS compared to Ob without SG.Concerning psychological aspect,BED and depression are less frequent in the Ob with SG,while both state and trait anxiety are significantly higher.Moreover,the more an Ob with SG is anhedonic,less surgical success was achieved.

Range of adiposity and cardiorenal syndrome

Obesity and obesity-related co-morbidities,diabetes mellitus,and hypertension are among the fastest-growing risk factors of heart failure and kidney disease worldwide.Obesity,which is not a unitary concept,or a static process,ranges from alterations in distribution to the amount of adiposity.Visceral adiposity,which includes intraabdominal visceral fat mass and ectopic fat deposition such as hepatic,cardiac,or renal,was robustly associated with a greater risk for cardiorenal morbidity than subcutaneous adiposity.In addition,morbid obesity has also demonstrated a negative effect on cardiac and renal functioning.The mechanisms by which adipose tissue is linked with the cardiorenal syndrome(CRS)are hemodynamic and mechanical changes,as well neurohumoral pathways such as insulin resistance,endothelial dysfunction,nitric oxide bioavailability,renin-angiotensin-aldosterone,oxidative stress,sympathetic nervous systems,natriuretic peptides,adipokines and inflammation.Adiposity and other associated co-morbidities induce adverse cardiac remodeling and interstitial fibrosis.Heart failure with preserved ejection fraction has been associated with obesity-related functional and structural abnormalities.Obesity might also impair kidney function through hyperfiltration,increased glomerular capillary wall tension,and podocyte dysfunction,which leads to tubulointerstitial fibrosis and loss of nephrons and,finally,chronic kidney disease.The development of new treatments with renal and cardiac effects in the context of type 2 diabetes,which improves mortality outcome,has highlighted the importance of CRS and its prevalence.Increased body fat triggers cellular,neurohumoral and metabolic pathways,which create a phenotype of the CRS with specific cellular and biochemical biomarkers.Obesity has become a single cardiorenal umbrella or type of cardiorenal metabolic syndrome.This review article provides a clinical overview of the available data on the relationship between a range of adiposity and CRS,the support for obesity as a single cardiorenal umbrella,and the most relevant studies on the recent therapeutic approaches.

Portomesenteric Venous Thrombosis in Patients after Laparoscopic Bariatric Surgery

Objective: Obesity has become a worldwide epidemic that is directly related to chronic tissue inflammation and impaired fibrinolysis, both of which lead to an increased risk of thrombosis. The management of complications after bariatric surgery is still a challenge. The study aims to report the incidence of portomesenteric venous thrombosis (PMVT) in patients undergoing bariatric surgery. Introduction: Bariatric surgery is the procedure of choice for the treatment of obesity type III. Despite the safe technique, the surgeon must be aware of the risks linked to laparoscopy such as the PMVT. Computed tomography (CT) with intravenous contrast was the imaging method of choice for diagnosis. Materials and Methods: We performed a retrospective analysis of 4790 patients from August 1999 to June 2020 was observed the incidence of PMVT in this group. Of all patients, 72.8% were female and 27.2% male. The mean age was 46.3 years (34 - 72) and the mean BMI before bariatric surgery was 41.4 kg/m2. Results: The study showed an incidence of PMVT of 0.12% (N = 6), portal vein thrombosis was of 0.10% (n = 5) and 0.03% of MVT (n = 1). Of these, 72.5% (n = 3473 patients) underwent laparoscopic gastric bypass, 23.6% (n = 1131 patients) were submitted to the laparoscopic sleeve gastrectomy and 3.8% (n = 186 patients) to other procedures. The mean postoperative hospital stay for bariatric surgery was 3.3 days. The average time of hospital stay of patients complicated with PMVT range from 5 to 14 days. No patient died of complications related to PMVT. Conclusion: Portomesenteric vein thrombosis is a rare presentation after laparoscopic bariatric surgery. However, it is a serious complication that has a high index of suspicion for making its diagnosis. Conservative treatment using anticoagulants and thrombolytics is effective, it should always be considered the main treatment option. However, these patients must be followed up in the long term, as late complications can occur in high numbers of patients.

Excessive Weight Loss Following Laparoscopic Gastric Mini Bypass or Roux-En-Y Gastric Bypass Surgery

Background: More than 90 percent of obesity surgery is done using a laparoscope. This method is superior to open surgery and lead to fewer complications, shorter hospital stay and faster recovery. This study compared course of weight loss following laparoscopic Gastric Mini Bypass or Roux-En-Y Gastric Bypass surgery, after one year of follow up. Materials and Methods: This randomized clinical trial was conducted among obese patients admitted to Rasoul Akram Hospital Obesity Clinic, Half underwent laparoscopic Roux-En-Y Gastric Bypass and the rest were undergoing laparoscopic Mini Gastric Bypass. The amount of weight loss during the first year after surgery will be discussed. Results: In this study, 75 obese patients were studied. Most of the participants were female (82.7%). Participants aged between 18 and 59 years old (average = 36.8 ± 9.8 y/o). Before the surgery, there was no significant difference in weight between the two groups. Excessive weight loss after one month, six months nine months and one year between the two groups was significant and was more in Mini Gastric Bypass (p < 0.05). Conclusion: Respecting the benefits of Mini Gastric Bypass compared to the Roux-En-Y Gastric Bypass technique, it is suggested for patients with morbid obesity.

Combined non-alcoholic fatty liver disease and type 2 diabetes in severely obese patients-medium term effects of sleeve gastrectomy versus Roux-en-Y-gastric bypass on disease markers

Background:We aimed to evaluate the medium-term efficacy of sleeve gastrectomy(SG)vs.Roux-en-Y gastric bypass(RYGB)on remission of non-alcoholic fatty liver disease(NAFLD)in patients with type 2 diabetes mellitus(T2DM).Methods:We identified severely obese patients[body mass index(BMI)>35 kg/m^(2)]with NAFLD(as defined by the Longitudinal Assessment of Bariatric Surgery Study)and T2DM(as defined by the American Association of Clinical Endocrinologists and the American College of Endocrinology)who underwent SG or RYGB in a single university surgical centre.The cohorts were match-paired and data were analysed after at least 3 years of follow up.The key outcomes measured were:(I)the improvement of liver function tests and NAFLD markers;(II)glycemic control and insulin resistance.Results:Ninety-six patients were investigated;44(45.8%)were women.The mean pre-operative BMI was 45.2 kg/m2 in the SG and 42.0 kg/m^(2) in the RYGB group.SG and RYGB both significantly reduced serum liver enzyme concentrations.NAFLD markers resolved 2 years after SG in all patients.In contrast,only 78%and 80%of patients achieved remission of NAFLD 2 and 3 years after RYBG respectively.Both procedures resulted in comparable rates of remission of T2DM.Conclusions:Bariatric surgery with SG may be preferable to RYGB for obese patients with NAFLD and T2DM based on the rates of remission of markers of these co-morbidities.However,our results need to be confirmed in prospective trials.Understanding the metabolic effects of specific bariatric surgical procedures may facilitate the development of a personalised approach to weight-loss surgery.