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Background and objectives Weight loss is the mainstay of management for women with polycystic ovarian syndrome (PCOS). However, lifestyle and dietary modifications, and gastric banding have generally poor long-term efficacy. We aimed to investigate whether gastric bypass is equally efficacious in women with or without PCOS. Methods We performed a matched case–control study of primary Roux-en-Y gastric bypass surgery in women with PCOS (cases, n = 30) compared to women without PCOS (controls, n = 60) matched for baseline age, body mass index (BMI) and presence or absence of type 2 diabetes (T2D). Data shown represent mean values. Results At 24 months after surgery the 90 participants (age 36.1 years) experienced significant reductions in BMI (53.4 vs. 34.9 kg/m2, p Conclusion In women with PCOS with morbid obesity, gastric bypass resulted in significant weight loss and metabolic outcomes similar to women without PCOS.

Background Emerging evidence suggests an association between impaired high-density lipoprotein (HDL) functionality and cardiovascular disease (CVD). HDL is essential for reverse cholesterol transport (RCT) and reduces inflammation and oxidative stress principally via paraoxonase-1 (PON1). RCT depends on HDL’s capacity to accept cholesterol (cholesterol efflux capacity [CEC]) and active transport through ATP-binding cassette (ABC) A1, G1, and scavenger receptor-B1 (SR-B1). We have studied the impact of Roux-en-Y gastric bypass (RYGB) in morbidly obese subjects on RCT and HDL functionality. Methods Biomarkers associated with increased CVD risk including tumour necrosis factor-α (TNF-α), high-sensitivity C-reactive protein (hsCRP), myeloperoxidase mass (MPO), PON1 activity, and CEC in vitro were measured in 44 patients before and 6 and 12 months after RYGB. Overweight but otherwise healthy (mean body mass index [BMI] 28 kg/m2) subjects acted as controls. Twelve participants also underwent gluteal subcutaneous adipose tissue biopsies before and 6 months after RYGB for targeted gene expression (ABCA1, ABCG1, SR-B1, TNF-α) and histological analysis (adipocyte size, macrophage density, TNF-α immunostaining). Results Significant (P Conclusion RYGB enhances HDL functionality in association with a reduction in adipose tissue and systemic inflammation.

The causal relationship between LDL cholesterol (LDL-C) and the pathogenesis of atherosclerosis is well established. Previous studies have shown that modifications, glycation and oxidation of LDL enhance its atherogenic potential. Glycation of LDL occurs in it is main protein component, apolipoprotein B100 (ApoB). Our aim was to assess the effect of bariatric surgery on circulating glycApoB levels and understand the factors influencing changes in its circulating levels.We measured glycApoB in 49 individuals before, 6 and 12 months after bariatric surgery. We also assessed clinical parameters, lipoproteins, markers of inflammation and glycaemia. Correlation analysis was done to understand associations between changes in variables from baseline to 12 months after surgery.Reductions in glycApoB post-bariatric surgery were significant regardless of whether the patients suffered from type 2 diabetes (T2DM) or took lipid-lowering therapy. There were no significant differences in glycApoB levels at baseline and follow-up between participants with T2DM and those without. GlycApoB declined from baseline in non-diabetics at 6 months and significantly at 12 months (1.09 mg/l vs 0.63 mg/l vs 0.49 mg/l, p 0.05), and in those with T2DM at 6 months and significantly at 12 months (1.77 mg/l vs 1.03 mg/l vs 0.68 mg/l, p 0.05). The percentage change in glycApoB correlated (p 0.05) with changes in glucose (ρ = 0.40), insulin (ρ = 0.41) and HOMA-IR (%) (ρ = 0.43). There were no significant associations between changes in glycApoB and changes in total serum ApoB, LDL-C, high sensitivity C-reactive protein, weight, or BMI.Bariatric surgery reduces levels of glycApoB; this reduction is associated with decreased insulin resistance postoperatively. This potentially reflects the potent influence of obesity-related insulin resistance on lipoprotein glycation. Our observations are of potential importance in explaining the effectiveness of bariatric surgery in decreasing cardiovascular disease (CVD) risk in both T2DM and obese individuals without T2DM, as glycation of ApoB is known to be associated with increased atherogenesis.

Abigail E Derbyshire,1 Michelle L MacKintosh,1 Christina M Pritchard,1 Arya Pontula,2 Basil J Ammori,3,4 Akheel A Syed,4,5 Rebecca J Beeken,6 Emma J Crosbie1,2 1Department of Obstetrics and Gynaecology, Manchester University NHS Foundation Trust, Manchester, UK; 2Division of Cancer Sciences, University of Manchester, Manchester, UK; 3Department of Surgery, Salford Royal NHS Foundation Trust, Salford, UK; 4Division of Diabetes, Endocrinology and Gastroenterology, University of Manchester, Manchester, UK; 5Department of Obesity Medicine, Diabetes & Endocrinology, Salford Royal NHS Foundation Trust, Salford, UK; 6Leeds Institute of Health Sciences, University of Leeds, Leeds, UKCorrespondence: Emma J CrosbieDivision of Cancer Sciences, University of Manchester, Manchester, UK, Tel +44 161 701 6942, Email emma.crosbie@manchester.ac.ukIntroduction: Endometrial cancer rates are rising in parallel with the global obesity epidemic. Our aim was to assess the willingness of women at greatest risk of obesity-related endometrial cancer to engage with risk-reducing strategies and establish perceived barriers that may preclude their participation in a randomized controlled trial of primary endometrial cancer prevention.Materials and Methods: Women attending gynecology, obesity and sleep apnea clinics in Manchester Academic Health Sciences Centre-affiliated hospitals with obesity classes II (BMI 35– 39.9kg/m2) and III (BMI ≥ 40kg/m2) were invited to participate in a cross-sectional survey. We asked women about their perceived risk, knowledge of risk factors and willingness to engage with endometrial cancer risk-reducing interventions.Results: Seventy-four women with a median age of 51 years (range 22– 73) and BMI of 47kg/m2 (range 34– 81) took part in the study. Two-thirds (65.6%) knew that obesity was a risk factor for endometrial cancer but few were able to recall other major risk factors. Just over half (53.5%) perceived their risk of developing endometrial cancer to be higher than average. Women were prepared to lose weight (94%), eat healthily (91%), exercise more (87%), take a pill every day (74%) or receive an intra-uterine device (49%) for primary endometrial cancer prevention. Perceived barriers included cost, forgetting, willpower, finding time, physical fitness, social anxiety, possible side effects and previous bad experiences.Conclusion: Women at highest risk of obesity-related endometrial cancer may not always appreciate their susceptibility. However, willingness to engage in risk-reducing strategies suggests recruitment to a randomized controlled trial for primary endometrial cancer prevention could be feasible.Keywords: endometrial cancer, obesity, risk reducing interventions, weight loss, exercise, chemoprevention, levonorgestrel-releasing intrauterine system, metformin

Intrauterine progestin is a treatment option for women with atypical hyperplasia or low-risk endometrial cancer who wish to preserve their fertility, or whose poor surgical fitness precludes safe hysterectomy. We hypothesized that in such women with obesity, weight loss during progestin treatment may improve oncological outcomes. We conducted a prospective nonrandomized study of women with obesity and atypical hyperplasia or low-grade stage 1a endometrial cancer undergoing progestin treatment. Women with a body mass index (BMI) ≥ 35 kg/m2 were offered bariatric surgery; those who declined and those with a BMI of 30 to 34.9 kg/m2 were encouraged to lose weight by low-calorie diet. We assessed uptake of bariatric surgery; weight lost during progestin treatment; and the impact of more than 10% total body weight loss on progestin treatment response at 12 months. 71 women [median age 58 years (interquartile range; IQR 35–65); mean BMI 48 kg/m2 (SD 9.3)] completed the study. Twenty-three women (32%) had bariatric surgery, on average 5 months (IQR 3–8) after progestin treatment commenced. Weight change during progestin treatment was −33.4 kg [95% confidence interval (CI) −42.1, −24.7] and −4.6 kg (95% CI −7.8, −1.4) in women receiving bariatric surgery and low-calorie diet, respectively (P < 0.001). Forty-three women (61%) responded to progestin, while 23 (32%) showed stabilized and 5 (7%) progressive disease. Response at 12 months was not predicted by age or baseline BMI, but women who lost more than 10% of their total body weight were more likely to respond to progestin than those who did not (adjusted odds ratio 3.95; 95% CI 1.3, 12.5; P = 0.02). Thus weight loss may improve oncological outcomes in women with obesity-associated endometrial neoplastic abnormalities treated with progestin. Prevention Relevance: This study found that weight loss improves response rates in women with obesity and atypical hyperplasia or low-risk endometrial cancer undergoing conservative management with intrauterine progestin. Given the additional benefits of weight loss for fertility, cardiovascular health and quality of life, future research should focus on how best to accomplish it.

Background Revisional bariatric surgery is unavoidable in a proportion of patients. Despite its need, the development of this speciality has been hampered by its complexity and preferred delivery in institutional set ups. Although primary bariatric surgery can be delivered in the private sector; safety and feasibility of revisional bariatric surgery remains unexplored in this setting. Materials and methods Patients undergoing revisional bariatric surgery following previous Laparoscopic Adjustable Gastric Band (LAGB) between 2008 and 2019 at a single private bariatric unit with a minimum follow up of at least 6 months were included. The primary aim was safety outcomes and 30-day morbidity. Results 178 patients with BMI of 45.6 ± 8.2 kg/m2 underwent revisional bariatric surgery. One stage conversion was performed for 86.5% of the cases. At 9.5 ± 5.3 months follow up, BMI and percentage excess BMI loss were 31.8 ± 6.2 kg/m2 and 62.6 ± 40% respectively. There was no mortality, and the major complication rate was 2.8%. There was no statistically significant difference in the incidence of complications based on one-stage vs. two-stage conversion (p = 0.52). There were no differences in weight loss outcomes post-revisional surgery according to the indication for revision (p = 0.446) or weight loss following primary surgery (p = 0.12). Conclusion Revisional bariatric surgery can be delivered safely in the private sector with good outcomes. One-stage conversions are feasible and do not detrimentally affect the morbidity of the procedure or the weight loss outcomes. More importantly, success following revisional surgery is independent of the indication for revision and weight loss outcomes following primary surgery.

Weight loss of 5%-10% is advised in medical weight management (MWM) programmes prior to bariatric surgery but it remains to be established whether it influences postoperative weight loss outcomes. We studied postoperative percent total weight loss (%TWL) in 168 patients categorized by preoperative referral weight loss

Background Obesity is associated with adverse cardiovascular outcomes and this is improved following bariatric surgery. Oxidised phospholipids (OxPL) are thought to reflect the pro-inflammatory effects of lipoprotein(a) [Lp(a)], and both are independent predictors of cardiovascular disease. Objective Our study sought to determine the impact of bariatric surgery on OxPL, biomarkers of oxidised LDL (OxLDL) and Lp(a). Methods This is a prospective, observational study of 59 patients with severe obesity undergoing bariatric surgery. Blood samples were obtained prior to surgery and at 6 and 12 months after. Sixteen patients attending the tertiary medical weight management clinic at the same centre were also recruited for comparison. Lipid and metabolic blood parameters, OxLDL, OxPL on apolipoprotein B-100 (OxPL-apoB), IgG and IgM autoantibodies to MDA-LDL, IgG and IgM apoB-immune complexes and Lp(a) were measured. Results Reduction in body mass index (BMI) was significant following bariatric surgery, from median 48 kg/m2 at baseline to 37 kg/m2 at 6 months and 33 kg/m2 at 12 months. OxPL-apoB levels decreased significantly at 12 months following surgery [5.0 (3.2–7.4) to 3.8 (3.0–5.5) nM, p = 0.001], while contrastingly, Lp(a) increased significantly [10.2 (3.8–31.9) to 16.9 (4.9–38.6) mg/dl, p = 0.002]. There were significant post-surgical decreases in IgG and IgM biomarkers, particularly at 12 months, while OxLDL remained unchanged. Conclusions Bariatric surgery results in a significant increase in Lp(a) but reductions in OxPL-apoB and other biomarkers of oxidised lipoproteins, suggesting increased synthetic capacity and reduced oxidative stress. These biomarkers might be clinically useful to monitor physiological effects of weight loss interventions.

INTRODUCTION Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage. METHODS Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI: 26.8 ± 4.2, HbA1c: 39.1 ± 2.6) underwent detailed assessment of neuropathy at baseline and 12 months after bariatric surgery. RESULTS Obese subjects had normal peroneal (45.9 ± 5.5 vs. 48.1 ± 4.5, P = 0.1) and sural (46.9 ± 7.6 vs. 47.9 ± 10.6, P = 0.1) nerve conduction velocity, but a significantly higher neuropathy symptom profile (NSP) (4.3 ± 5.7 vs. 0.3 ± 0.6, P = 0.001), vibration perception threshold (VPT) (V) (10.2 ± 6.8 vs. 4.8 ± 2.7, P

BACKGROUND The laparoscopic approach to pancreaticoduodenectomy (LPD) is technically demanding, but may offer benefits over open surgery [open pancreaticoduodenectomy (OPD)]. The aim of this study was to compare the outcomes of these 2 approaches at a tertiary cancer center from the Middle East. MATERIALS AND METHODS Fifty consecutive patients who underwent LPD (n=12) and OPD (n=38) between 2015 and 2018 were considered. One surgeon performed LPD for "all comers," while 3 other surgeons performed open surgery. Patients were randomly matched on a 1:2 basis for pathology (benign vs. malignant), malignancy size (±1 cm), and whether the pancreatic duct was dilated (>3 mm). RESULTS Six patients were excluded, leaving 44 patients, of whom 33 were matched (LPD n=11, OPD n=22). The groups were comparable for age (57 vs. 63 y, P=0.123) and sex distribution (female; 55% vs. 45%, P=0.721), tumor size (3 cm in each group), frequency of pancreatic duct dilatation (45% in each group), and malignant pathology (82% in each group). There were no conversions to open surgery. Although the operating time for LPD was significantly longer (680 vs. 313 min, P

Background Colon cancer rarely presents with a gastrocolic fistula and resection, if feasible, is usually carried out by open surgery. The authors present the first literature case report of laparoscopic multivisceral resection for gastrocolic fistula secondary to locally advanced colon cancer. Materials and methods A 54-year-old man presented with feculant vomiting, cachexia, and severe iron deficiency anemia. Investigations confirmed a large nonmetastatic splenic flexure colon cancer with fistulation into the stomach. After 10 weeks of nutritional support and laparoscopic defunctioning proximal transverse loop colostomy, we proceeded to laparoscopic extended left hemicolectomy with en bloc sleeve gastrectomy and partial splenectomy. Result The procedure was completed laparoscopically (operating time, 400 min; blood loss, 150 mL). He was discharged on the 6th postoperative day after an uneventful recovery. Histology showed an R0 resection of a pT4N1a (1/45 lymph nodes involved) colon cancer with gastrocolic fistula. Conclusion Laparoscopic multivisceral en bloc R0 resection of locally advanced colon cancer with gastrocolic fistula can be accomplished safely in experienced hands.

We conducted a narrative review of the medical and surgical management of people with obesity and diabetes. Results of this review showed that a 5-10% loss in body weight can be achieved with a change in lifestyle, diet and behaviour and with approved pharmacological therapies in people with obesity and diabetes. New targeted therapies are now available for patients with previously untreatable genetic causes of obesity. Compared to medical treatment, metabolic and bariatric surgery is associated with significantly higher rates of remission from type 2 diabetes and lower rates of incident macrovascular and microvascular complications and mortality. The National Institute for Health and Care Excellence and the American Diabetes Association endorse metabolic and bariatric surgery in obese adults with type 2 diabetes and there may also be a role for this in obese individuals with type 1 diabetes. The paediatric committee of the American Society for Metabolic and Bariatric Surgery have recommended metabolic and bariatric surgery in obese adolescents with type 2 diabetes. Earlier and more aggressive treatment with metabolic and bariatric surgery in obese or overweight people with diabetes can improve morbidity and mortality.

Background: It has been suggested that patients with a Body Mass Index (BMI) of > 60 kg/m2 should be offered expedited Bariatric Surgery (BS) during the Coronavirus Disease-2019 (COVID-19) pandemic. The main objective of this study was to assess the safety of this approach. Methods: We conducted a global study of patients who underwent BS between 1/05/2020 and 31/10/2020. Patients were divided into three groups according to their preoperative BMI - Group I (BMI60 kg/m2). The effect of preoperative BMI on 30-day morbidity and mortality, procedure choice, COVID-19 specific safety protocols, and comorbidities was assessed. Results: This study included 7084 patients (5197;73.4 % females). The mean preoperative weight and BMI were 119.49 ± 24.4 Kgs and 43.03 ± 6.9 Kg/m2, respectively. Group I included 6024 (85 %) patients, whereas Groups II and III included 905 (13 %) and 155 (2 %) patients, respectively. The 30-day mortality rate was higher in Group III (p = 0.001). The complication rate and COVID-19 infection were not different. Comorbidities were significantly more likely in Group III (p = 70 kg/m2 had a 30-day mortality of 7.7 % (2/26). None of these patients underwent a Roux-en-Y Gastric Bypass. Conclusion: The 30-day mortality rate was significantly higher in patients with BMI > 60 kg/m2. There was, however, no significant difference in complications rates in different BMI groups, probably due to differences in procedure selection.

Purpose Autoantibodies against apolipoprotein A-1 have been associated with cardiovascular disease, poorer CV outcomes and all-cause mortality in obese individuals. The impact of bariatric surgery (BS) on the presence of circulating anti-apoA-1 IgG antibodies is unknown. This study aimed to determine the effect of bariatric surgery on auto-antibodies titres against Apolipoprotein A-1 (anti-apoA-1 IgG), looking for changes associated with lipid parameters, insulin resistance, inflammatory profile and percentage of excess body mass index loss (%EBMIL). Materials and Methods We assessed 55 patients (40 women) before, 6 and 12 months post-operatively. Baseline and post-operative clinical history and measurements of body mass index (BMI), serum cholesterol, triglycerides, high- and low-density lipoprotein cholesterol (HDL-C and LDL-C), apoA-1, highly sensitive C-reactive protein (hsCRP), fasting glucose (FG), glycated haemoglobin (HbA1c) and HOMA-IR were taken at each point. Human anti-apoA-1 IgG were measured by ELISA. Results The mean age of participants was 50 years. BS significantly improved BMI, %EBMIL triglycerides, HDL-C, apoA-1, hsCRP, HBA1c, FG and HOMA-IR. Baseline anti-apoA-1 IgG seropositivity was 25% and was associated with lower apoA-1 and higher hsCRP levels. One year after BS, anti-apoA-1 IgG seropositivity decreased to 15% (p = 0.007) and median anti-apoA-1 IgG values decreased from 0.70 (0.56–0.84) to 0.47 (0.37–0.61) AU (p Conclusion Bariatric surgery results in significant reduction in anti-apoA-1 IgG levels, which may adversely influence weight loss. The exact mechanisms underpinning these results are elusive and require further study before defining any clinical recommendations. Graphical abstract

Background Age ≥ 65 years is regarded as a relative contraindication for bariatric surgery. Advanced age is also a recognised risk factor for adverse outcomes with Coronavirus Disease-2019 (COVID-19) which continues to wreak havoc on global populations. This study aimed to assess the safety of bariatric surgery (BS) in this particular age group during the COVID-19 pandemic in comparison with the younger cohort. Methods We conducted a prospective international study of patients who underwent BS between 1/05/2020 and 31/10/2020. Patients were divided into two groups — patients ≥ 65-years-old (Group I) and patients < 65-years-old (Group II). The two groups were compared for 30-day morbidity and mortality. Results There were 149 patients in Group 1 and 6923 patients in Group II. The mean age, preoperative weight, and BMI were 67.6 ± 2.5 years, 119.5 ± 24.5 kg, and 43 ± 7 in Group I and 39.8 ± 11.3 years, 117.7±20.4 kg, and 43.7 ± 7 in Group II, respectively. Approximately, 95% of patients in Group 1 had at least one co-morbidity compared to 68% of patients in Group 2 (p = < 0.001). The 30-day morbidity was significantly higher in Group I (11.4%) compared to Group II (6.6%) (p = 0.022). However, the 30-day mortality and COVID-19 infection rates were not significantly different between the two groups. Conclusions Bariatric surgery during the COVID-19 pandemic is associated with a higher complication rate in those ≥ 65 years of age compared to those < 65 years old. However, the mortality and postoperative COVID-19 infection rates are not significantly different between the two groups. Graphical abstract

Background: We have previously shown that subjects with obesity have elevated vibration and thermal perception thresholds and central corneal nerve loss and patients with diabetic neuropathy have greater corneal nerve loss at the inferior whorl compared to the central cornea. In the current study, we assessed whether there is evidence for a dying-back neuropathy in subjects with obesity with and without diabetes. Methods: 57 obese subjects, with and without diabetes (DM+, n=30; DM-, n=27 respectively) and age- and sex‑matched controls (n=21) underwent venous blood sampling and assessment of the neuropathy symptom profile (NSP), neuropathy disability score (NDS), vibration, cold and warm threshold testing, cardiac autonomic function, and corneal confocal microscopy (CCM).Results: NSP and NDS were significantly elevated in obese DM+ (p- (p+ (p=0.001), but not in DM- (p=0.06), compared to controls, whilst cold (p = 0.87) and warm (p = 0.52) perception thresholds did not differ between groups. Deep breathing heart rate variability was significantly lower in DM+ (p=0.01), but not DM- (p=0.9) subjects compared to controls. Corneal nerve fibre density [26.8 ±6.22 vs 26.8 ±6.01 vs 35.3 ±7.41, p+ (47.3% vs 25.5%) and DM- (49.3% vs 34.1%).Conclusion: We demonstrate evidence of peripheral neuropathy characterised by neuropathic symptoms, neurological deficits, elevated vibration perception and autonomic dysfunction with a dying-back neuropathy affecting the corneal nerves in obese subjects with and without type 2 diabetes.

Background Bariatric surgery for severe obesity can lead to micronutrient/vitamin deficiencies. Aims To study baseline and post-surgical prevalence of vitamin D deficiency in patients undergoing bariatric surgery. Participants and Setting Patients undergoing bariatric surgery in a university teaching hospital in North West England. Methods We performed an observational cohort analysis of longitudinal data on vitamin D and related parameters in patients who underwent bariatric surgery. Patients were routinely recommended daily combined calcium and vitamin D supplementation post-surgery. Results We studied 460 patients who had completed at least 12 months post-operatively; mean (standard deviation) age was 48.0 (10.5) years, weight 144.7 (27.3) kg and body mass index 50.0 (7.6) kg/m2; 292 (63.5%) underwent gastric bypass and 168 (36.5%) sleeve gastrectomy. Vitamin D level was 33.1 (23.9) nmol/L at baseline, rising to 57.1 (23.1) nmol/L at 12 months post-surgery. Whereas 43.2% had vitamin D deficiency and 34.7% insufficiency preoperatively, 8.9% and 26.7% had deficiency and insufficiency, respectively, at 12 months with similar trends up to 4 years of follow-up. There were no significant differences between procedures or sexes in vitamin D levels or sufficiency rates. Conclusion Vitamin D deficiency and insufficiency were prevalent pre-surgery and reduced significantly with routine supplementation post-surgery.

Obesity and associated dyslipidemia may contribute to increased cardiovascular disease. Obesity has also been associated with neuropathy. We have investigated presence of peripheral nerve damage in patients with severe obesity without type 2 diabetes and the status of metabolic syndrome and lipoprotein abnormalities. 47participants with severe obesity and 30 age-matched healthy controls underwent detailed phenotyping of neuropathy and an assessment of lipoproteins and HDL-functionality. Participants with severe obesity had a higher neuropathy symptom profile, lower sural and peroneal nerve amplitudes, abnormal thermal thresholds, heart rate variability with deep breathing and corneal nerve parameters compared to healthy controls. Circulating apolipoprotein A1 (P = 0.009), HDL cholesterol (HDL-C) (P P = 0.002) and paroxonase-1 (PON-1) activity (P P P = 0.02), lower PON-1 activity (P = 0.002) and higher prevalence of metabolic syndrome (58% vs. 23%, P = 0.02) compared to those without. However, HDL-C (P = 0.8), cholesterol efflux (P = 0.08), apoA1 (P = 0.8) and SAA (P = 0.8) did not differ significantly between obese participants with and without small nerve fibre damage. Small nerve fibre damage occurs in people with severe obesity. Patients with obesity have deranged lipoproteins and compromised HDL functionality compared to controls. Obese patients with evidence of small nerve fibre damage, compared to those without, had significantly higher serum triglycerides, lower PON-1 activity and a higher prevalence of metabolic syndrome.

The incidence of endometrial cancer is rising in parallel with the obesity epidemic. Obesity increases endometrial cancer risk and weight loss is protective, but the underlying mechanisms are incompletely understood. We hypothesise that the immune microenvironment may influence susceptibility to malignant transformation in the endometrium. The aim of this study was to measure the impact of obesity and weight loss on the immunological landscape of the endometrium.We conducted a prospective cohort study of women with class III obesity (body mass index, BMI ≥ 40 kg/mForty-three women with matched serum and tissue samples at all three time points were included in the analysis. Their median age and BMI were 44 years and 52 kg/mWeight loss is associated with reduced systemic inflammation and a recruitment of protective immune cell types to the endometrium, supporting the concept that immune surveillance may play a role in endometrial cancer prevention.

BACKGROUND Patients with head and neck cancers may require feeding tube gastrostomy (FTG) during their treatment. Surgical gastrostomy is indicated in patients who fail or unsuitable for endoscopic or radiologic FTG insertion. OBJECTIVE The aim of this study was to compare the outcomes of a novel laparoscopic technique to the insertion of feeding tube gastrostomy (FTG) in patients with head and neck cancer vs conventional open surgery. METHODS Patients were randomly matched on a 1:1 basis according to whether the procedure was therapeutic or prophylactic and whether a concomitant less major surgical procedure was required. RESULTS The groups (17 patients in each group) were comparable for age, sex distribution, ASA score, body mass index, serum albumin levels and the frequencies of previous upper abdominal surgery, hypoalbuminaemia and prior chemoradiotherapy and/or cancer surgery. There were no conversions to open surgery. No significant differences were detected between the groups with regard to the operating time (median, 40 vs 60 minutes, P = .053) and 30-day clinically significant morbidity (17.6% vs 23.5%, P = .180) or mortality (11.8% in each group). However, laparoscopy was associated with significantly shorter hospital stay (0 vs 2.8 days, P

Roux-en-Y gastric bypass (RYGB) is one of the most commonly performed weight-loss procedures, but how severe obesity and RYGB affect circulating HDL-associated microRNAs (miRNAs) remains unclear. Here, we aim to investigate how HDL-associated miRNAs are regulated in severe obesity and how weight loss after RYGB surgery affects HDL-miRNAs. Plasma HDLs were isolated from patients with severe obesity (n = 53) before and 6 and 12 months after RYGB by immunoprecipitation using goat anti-human apoA-I microbeads. HDLs were also isolated from 18 healthy participants. miRNAs were extracted from isolated HDL and levels of miR-24, miR-126, miR-222, and miR-223 were determined by TaqMan miRNA assays. We found that HDL-associated miR-126, miR-222, and miR-223 levels, but not miR-24 levels, were significantly higher in patients with severe obesity when compared with healthy controls. There were significant increases in HDL-associated miR-24, miR-222, and miR-223 at 12 months after RYGB. Additionally, cholesterol efflux capacity and paraoxonase activity were increased and intercellular adhesion molecule-1 (ICAM-1) levels decreased. The increases in HDL-associated miR-24 and miR-223 were positively correlated with an increase in cholesterol efflux capacity (r = 0.326, P = 0.027 and r = 0.349, P = 0.017, respectively). An inverse correlation was observed between HDL-associated miR-223 and ICAM-1 at baseline. Together, these findings show that HDL-associated miRNAs are differentially regulated in healthy participants versus patients with severe obesity and are altered after RYGB. These findings provide insights into how miRNAs are regulated in obesity before and after weight reduction and may lead to the development of novel treatment strategies for obesity and related metabolic disorders.

Background Postoperative pancreatic fistula (POPF) remains a common complication after distal pancreatectomy and is a major source of operative morbidity. Although various mechanical, biological, and synthetic aids have been used to reduce the risk of POPF, none have a proven benefit. Materials and methods The authors describe (and present a video, Supplemental Digital Content 1, http://links.lww.com/SLE/A256) a novel technique in which the autologous falciform ligament was harvested, wrapped around the pancreas at the site of proposed pancreatic transection, and secured with sutures to buttress the pancreatic transection staple line. The pancreas was then transected with a triple-row stapler. Results Two male patients aged 40 and 57 years each with a 4.3 and 4.2 cm solid mass in the body of the pancreas respectively underwent laparoscopic anterior radical antegrade modular pancreaticosplenectomy, the former patient underwent an en block transverse colectomy for suspected malignancy. Both patients had soft pancreata. They experienced no POPF, made an uneventful recovery, and were discharged from the hospital on the second and fourth postoperative days, respectively. No pancreatic complications were encountered at 5 and 6 months follow-up, respectively. Conclusions The use of the falciform ligament to buttress the staple line at the time of pancreatic transection is a novel technique. Its potential benefit in reducing the risk of POPF warrants further assessment.

Purpose Bariatric surgery is associated with deficiencies of vitamins and minerals, and patients are routinely advised supplements postoperatively. We studied prevalence of vitamin B12, folate and iron deficiencies and anaemia before and after bariatric surgery over 4 years of follow-up. Materials and Methods We performed a retrospective cohort analysis of 353 people with obesity, including 257 (72.8%) women, who underwent gastric bypass (252, 71.4%) or sleeve gastrectomy (101, 28.6%) at our National Health Service bariatric centre in Northwest England. Results At baseline, mean (standard error) age was 46.0 (0.6) years, body mass index 53.1 (0.4) kg/m2, serum vitamin B12 400.2 (16.4) pg/L, folate 7.7 (0.2) μg/L, iron 12.0 (0.3) μmol/L, ferritin 118.3 (8.4) μg/L and haemoglobin 137.9 (0.8) g/L. Frequency of low vitamin B12 levels reduced from 7.5% preoperatively to 2.3% at 48 months (P P P P P Conclusion There were notable rates of haematinic insufficiencies in bariatric surgical candidates preoperatively. Our study lends further support to regular supplementation with vitamin B12, folic acid, and iron in people undergoing bariatric surgery.

Purpose of review Bariatric surgery is an effective therapy for morbid obesity that also improves weight-related metabolic parameters and reduces morbidity and mortality. The purpose of this review is to consolidate our current understanding of metabolic, macrovascular and microvascular benefits of bariatric surgery and to provide an update. Recent findings Early resolution of insulin resistance and type 2 diabetes mellitus (T2DM) varies by type of bariatric surgery and appears to be mediated by changes in secretion of gut hormones, metabolism of bile acids, expression of glucose transporters and the gut microbiome. Dyslipidaemia, atherosclerosis, microvascular complications of obesity and diabetes, systemic and tissue-level inflammation show evidence of regression and hypertension improves significantly after bariatric surgery. Summary Bariatric surgery leads to improvements in obesity-related metabolic comorbidities such as dyslipidaemia, HDL functionality, hypertension, T2DM, insulin resistance and inflammation. It slows the atherosclerotic process and reduces cardiovascular and all-cause mortality. Recent data have demonstrated regression of the microvascular complications of obesity and diabetes including the regeneration of small nerve fibres. The magnitude of change in short-term metabolic effects depends on the surgical procedure whilst longer term effects are related to the amount of sustained excess weight loss.

Obesity is associated with an increased risk of several cancers including adenocarcinomas of the esophagus and gastric cardia but not with distal gastric cancer (GC). Laparoscopic sleeve gastrectomy (LSG) is a popular bariatric procedure. We report the fifth case in the medical literature of non-cardia gastric adenocarcinoma 63 months after LSG in a 26-year-old woman with no known recognizable risk factors. Among these five cases, the median (range) age at time of diagnosis of GC was 47 (26-64) years, the body mass index (BMI) prior to LSG was 47 (35.3-65.1) kg/m2 , the BMI at time of cancer diagnosis was 32 (29.3-47.0) kg/m2 , and the interval between LSG and diagnosis was 54 (9-63) months. Nonetheless, the link between LSG and the risk of GC remains skeptical and is discussed.

Subjects with obesity have metabolic risk factors for nerve fibre damage. Because bariatric surgery improves these risk factors we have assessed whether this can ameliorate nerve fibre damage.Twenty-six obese subjects without diabetes (age: 46.23 ± 8.6, BMI: 48.7 ± 1.5, HbA1c: 38.0 ± 4.5) and 20 controls (age: 48.3 ± 6.2, BMI: 26.8 ± 4.2, HbA1c: 39.1 ± 2.6) underwent detailed assessment of neuropathy at baseline and 12 months after bariatric surgery.Obese subjects had normal peroneal (45.9 ± 5.5 vs. 48.1 ± 4.5, P = 0.1) and sural (46.9 ± 7.6 vs. 47.9 ± 10.6, P = 0.1) nerve conduction velocity, but a significantly higher neuropathy symptom profile (NSP) (4.3 ± 5.7 vs. 0.3 ± 0.6, P = 0.001), vibration perception threshold (VPT) (V) (10.2 ± 6.8 vs. 4.8 ± 2.7, P 0.0001), warm threshold (C°) (40.4 ± 3.5 vs. 37.2 ± 1.8, P = 0.003) and lower peroneal (3.8 ± 2.2 vs. 4.9 ± 2.2, P = 0.02) and sural (8.9 ± 5.8 vs. 15.2 ± 8.5, P 0.0001) nerve amplitude, deep breathing-heart rate variability (DB-HRV) (beats/min) (21.7 ± 4.1 vs. 30.1 ± 14, P = 0.001), corneal nerve fibre density (CNFD) (n/mmObese subjects have evidence of neuropathy, and bariatric surgery leads to an improvement in weight, HbA1c, lipids, neuropathic symptoms and deficits and small nerve fibre regeneration without a change in quantitative sensory testing, autonomic function or neurophysiology.

Background: The role of the laparoscopic approach to D2 gastrectomy for gastric cancer remains controversial. The aim of this study was to compare the operative and short-term oncologic outcomes of...

BACKGROUND The open approach to right hemicolectomy remains the most widely adopted, whereas laparoscopic surgery is technically more demanding with possible loss of benefit for lengthy procedures compared with open surgery. The aim of this study is to compare the outcomes of the laparoscopic versus open surgery for right colon cancer resections. MATERIALS AND METHODS Patients who underwent an elective and potentially curative right colectomy for colon cancer between 2015 and 2019 were included and those who underwent emergency surgery, palliative resection, or cytoreductive surgery were excluded. Patients were randomly matched on 1:2 basis for age, disease stage, neoadjuvant chemotherapy, and extent of colectomy (right vs. extended right hemicolectomy, and additional major resection). The analysis was conducted on an intention-to-treat basis. The outcomes were reported as median (range) or percent as appropriate. RESULTS Among 160 patients, 18 were excluded. The final matching included 69 patients. The were no significant differences between the groups regarding patients' age and sex distribution, tumor size, and preoperative serum albumin and hemoglobin. There were 2 conversions (8.7%) to open surgery. Although the operating time for laparoscopic surgery was longer (200 vs. 140 min, P

Colon cancer rarely presents with a gastrocolic fistula and resection, if feasible, is usually carried out by open surgery. The authors present the first literature case report of laparoscopic multivisceral resection for gastrocolic fistula secondary to locally advanced colon cancer.A 54-year-old man presented with feculant vomiting, cachexia, and severe iron deficiency anemia. Investigations confirmed a large nonmetastatic splenic flexure colon cancer with fistulation into the stomach. After 10 weeks of nutritional support and laparoscopic defunctioning proximal transverse loop colostomy, we proceeded to laparoscopic extended left hemicolectomy with en bloc sleeve gastrectomy and partial splenectomy.The procedure was completed laparoscopically (operating time, 400 min; blood loss, 150 mL). He was discharged on the 6th postoperative day after an uneventful recovery. Histology showed an R0 resection of a pT4N1a (1/45 lymph nodes involved) colon cancer with gastrocolic fistula.Laparoscopic multivisceral en bloc R0 resection of locally advanced colon cancer with gastrocolic fistula can be accomplished safely in experienced hands.

Obesity is the strongest risk factor for endometrial cancer (EC). To inform targeted screening and prevention strategies, we assessed the impact of obesity and subsequent bariatric surgery‐induced weight loss on endometrial morphology and molecular pathways implicated in endometrial carcinogenesis. Blood and endometrial tissue were obtained from women with class III–IV obesity (body mass index ≥40 and ≥50 kg/m2, respectively) immediately prior to gastric bypass or sleeve gastrectomy, and at two and 12 months’ follow up. The endometrium underwent pathological examination and immunohistochemistry was used to quantify proliferation (Ki‐67), oncogenic signaling (PTEN, pAKT, pERK) and hormone receptor (ER, PR) expression status. Circulating biomarkers of insulin resistance, reproductive function and inflammation were also measured at each time point. Seventy‐two women underwent bariatric surgery. At 12 months, the mean change in total and excess body weight was −32.7 and −62.8%, respectively. Baseline endometrial biopsies revealed neoplastic change in 10 women (14%): four had EC, six had atypical hyperplasia (AH). After bariatric surgery, most cases of AH resolved (5/6) without intervention (3/6) or with intrauterine progestin (2/6). Biomarkers of endometrial proliferation (Ki‐67), oncogenic signaling (pAKT) and hormone receptor status (ER, PR) were significantly reduced, with restoration of glandular PTEN expression, at 2 and 12 months. There were reductions in circulating biomarkers of insulin resistance (HbA1c, HOMA‐IR) and inflammation (hsCRP, IL‐6), and increases in reproductive biomarkers (LH, FSH, SHBG). We found an unexpectedly high prevalence of occult neoplastic changes in the endometrium of women undergoing bariatric surgery. Their spontaneous reversal and accompanying down‐regulation of PI3K‐AKT–mTOR signaling with weight loss may have implications for screening, prevention and treatment of this disease., What's new? Obesity is a major risk factor for endometrial cancer (EC). In this study, the authors found that, in obese women, bariatric surgery‐induced weight loss resulted in significant, beneficial changes in circulating biomarkers of insulin resistance, inflammation, and reproductive hormones, in endometrial morphology, and in molecular pathways that are implicated in endometrial carcinogenesis. The latter included changes in Ki‐67 expression and activation of the PI3K‐AKT‐mTOR oncogenic signaling pathway, including PTEN and pAKT. These results may have important implications for screening, prevention and treatment of EC.

Preservation of all or part the spleen is desired whenever oncologically acceptable and technically possible. Although a number of techniques for partial splenectomy have been described, the ideal approach remains elusive. We describe a novel technique in which the autologous falciform ligament was harvested, wrapped around the proposed splenic transection site, and secured with sutures to act as a buttress to a splenic transection staple line during a laparoscopic multivisceral resection for gastrocolic fistula secondary to locally advanced colon cancer. The spleen transection staple line was bloodless and the patient's recovery was uneventful. Our novel application of the falciform ligament to buttress the staple line at the time of spleen transection during partial splenectomy appears safe and warrants further assessment.

CONTEXT:Multiple factors contribute to sexual dysfunction in men with obesity. Sex hormone levels are commonly abnormal in men with obesity and this abnormality is often the focus of management in clinical practice. The role of small fibre neuropathy in obesity-related sexual dysfunction is not well established.OBJECTIVE:We aimed to investigate the relationship between sexual function, sex hormone levels and small nerve fibre morphology in men with severe obesity.MATERIALS AND METHODS:A prospective study of 29 men with severe obesity was undertaken. Sexual function was assessed using the European Male Ageing Study Sexual Function Questionnaire. Small nerve fibre morphology was quantified using corneal confocal microscopy. Sex hormone levels were measured by mass spectrophotometry.RESULTS:Erectile dysfunction was present in 72% of the cohort with a higher prevalence of diabetes among the symptomatic group (88% vs 38%, p = 0.006). Corneal nerve fibre length (CNFL) and corneal nerve fibre density (CNFD) were both significantly lower in participants with erectile dysfunction compared to those without (p = 0.039 and p = 0.048 respectively). The erectile function score correlated with CNFL (r = -0.418, p = 0.034) and CNFD (r = -0.411, p = 0.037). Total testosterone and calculated free testosterone levels did not differ significantly between men with or without erectile dysfunction (median 8.8 nmol/L vs 9.0 nmol/L, p = 0.914; and median 176 pmol/L vs 179 pmol/L, p = 0.351 respectively), infrequent sexual thoughts (median 8.1 nmol/L vs 9.2 nmol/L, p = 0.650; and median 184 pmol/L, vs 176 pmol/L, p = 0.619 respectively) and decreased morning erections (median 9.0 nmol/L vs 8.8 nmol/L, p = 0.655; and median 170 pmol/L vs 193 pmol/L, p = 0.278 respectively).CONCLUSION:Sexual dysfunction is highly prevalent in men with severe obesity. We found an association between small fibre neuropathy with erectile dysfunction with presence of diabetes a likely a significant contributing factor. We found no associations between testosterone levels with sexual symptoms (including frequency of sexual thoughts). The influence of small nerve fibre neuropathy on response to therapeutic interventions and whether interventions that improve small fibre neuropathy can improve erectile function in this population merits further study.

Background:Reaven originally described the clustering of insulin resistance/hyperinsulinaemia, obesity (particularly visceral), altered cytokine levels, glucose intolerance, hypertriglyceridaemia and low high-density lipoprotein cholesterol. Subsequently, a potentially highly atherogenic small, dense low-density lipoprotein was also reported. We have studied the effect of bariatric surgery on this and other risk factors for atherosclerosis.Methods:Forty patients (20 with type 2 diabetes mellitus) undergoing bariatric surgery were studied before and 1 year after bariatric surgery.Results:Twelve months after bariatric surgery, median body mass index had decreased from 49.5 to 36.5 kg/m2, fasting insulin from 21.3 to 7.8 mU/L and insulin resistance (homeostatic model assessment of insulin resistance) from 5.9 to 1.8 (all p Conclusion:The association between marked weight loss and change in insulin resistance and hyperinsulinaemia with the change in small, dense low-density lipoprotein and interleukin-6 warrants further investigation. Bariatric surgery provides a model for investigating the mechanisms linking insulin resistance/hyperinsulinaemia to atherosclerosis.

A Correction to this paper has been published: 10.1007/s11695-020-04943-0

// May Abd Al Samid 1, 2, * , Belal Chaudhary 1, * , Yazan S. Khaled 3 , Basil J. Ammori 3 , Eyad Elkord 1, 2, 3 1 Biomedical Research Centre, School of Environment and Life Sciences, University of Salford, Manchester, United Kingdom 2 College of Medicine and Health Sciences, United Arab Emirates University, Al Ain, United Arab Emirates 3 Institute of Cancer Sciences, University of Manchester, Manchester, United Kingdom * These authors contributed equally to this work Correspondence to: Eyad Elkord, e-mail: eelkord@uaeu.ac.ae , e.elkord@salford.ac.uk and eyad.elkord@manchester.ac.uk Keywords: regulatory T cells, markers, GARP/LAP, FoxP3, Helios Received: December 09, 2015 Accepted: January 29, 2016 Published: February 11, 2016 ABSTRACT Regulatory T cells (Tregs) comprise numerous heterogeneous subsets with distinct phenotypic and functional features. Identifying Treg markers is critical to investigate the role and clinical impact of various Treg subsets in pathological settings, and also for developing more effective immunotherapies. We have recently shown that non-activated FoxP3 – Helios + and activated FoxP3 +/– Helios + CD4 + T cells express GARP/LAP immunosuppressive markers in healthy donors. In this study we report similar observations in the peripheral blood of patients with pancreatic cancer (PC) and liver metastases from colorectal cancer (LICRC). Comparing levels of different Treg subpopulations in cancer patients and controls, we report that in PC patients, and unlike LICRC patients, there was no increase in Treg levels as defined by FoxP3 and Helios. However, defining Tregs based on GARP/LAP expression showed that FoxP3 – LAP + Tregs in non-activated and activated settings, and FoxP3 + Helios + GARP + LAP + activated Tregs were significantly increased in both groups of patients, compared with controls. This work implies that a combination of Treg-specific markers could be used to more accurately determine expanded Treg subsets and to understand their contribution in cancer settings. Additionally, GARP –/+ LAP + CD4 + T cells made IL-10, and not IFN-γ, and levels of IL-10-secreting CD4 + T cells were elevated in LICRC patients, especially with higher tumor staging. Taken together, our results indicate that investigations of Treg levels in different cancers should consider diverse Treg-related markers such as GARP, LAP, Helios, and others and not only FoxP3 as a sole Treg-specific marker.

Highlights • Duplication of the gallbladder is a very rare surgical encounter. • We report a patient with symptomatic gallstones incidentally found to have abnormal biliary anatomy. • Intraoperative cholangiography enables diagnosis and avoids repeat cholecystectomy., Introduction Duplication of the gallbladder (GB) is a very rare surgical encounter affecting 1 in 4000–5000 population that often eludes detection on preoperative ultrasonography, and might increase operative difficulty and risk. The H-type anomaly is the most common whereby each GB drains into the common bile duct via a separate cystic duct. Presentation of case We report a young female patient with symptomatic gallstones who was incidentally found to have abnormal biliary anatomy on a CT colonography and an H-type duplication of the GB on MRCP. A challenging laparoscopic double cholecystectomy was performed uneventfully. Discussion Gallbladder duplication can be classified as a type-I anomaly (partiality split primordial gallbladder), a type-II anomaly (two separate gallbladders, each with their own cystic duct) or a rare type-III anomaly (triple gallbladders draining by 1–3 separate cystic ducts). Such anatomical variations are associated with increased operative difficulty and risks, including conversion to open cholecystectomy and common bile duct injury. Conclusion A young female patient was pre-operatively diagnosed with a Harlaftis’s type-II GB anomaly. Each gallbladder was drained by a distinct cystic duct (H-type anomaly). A laparoscopic cholecystectomy was performed with no complications afterwards. Awareness of this rare anomaly might require intraoperative cholangiography when initially suspected during a cholecystectomy to facilitate anatomical recognition and avoid missing a symptomatic pathologic GB and the need for a repeat cholecystectomy.

Background: The laparoscopic approach in distal pancreatectomy is associated with higher rates of splenic preservation compared to open surgery. Although favorable postoperative short-term outcomes have been reported in open spleen-preserving distal pancreatectomy when compared to distal pancreatectomy with splenectomy, it is unclear whether this observation applies to the laparoscopic approach. The aim of this study is to compare laparoscopic spleen-preserving distal pancreatectomy (LSPDP) with laparoscopic distal pancreatectomy with splenectomy (LDPS). Study design: This is a UK wide, propensity score-matched study, including patients who underwent LSPDP or LDPS between 2006 and 2016. Short-term outcomes were compared between LSPDP and LDPS according to intention to treat. Additionally, risk factors for unplanned splenectomy were explored. Results: A total of 456 patients were included from eleven centers (229 LSPDP and 227 LDPS). We were able to match 173 LSPDP cases to 173 LDPS cases, according to intention to treat. No differences were seen in postoperative morbidity between the groups. The only identified risk factor for unplanned splenectomy was tumor size ≥ 30 mm. Conclusions: Preserving the spleen during laparoscopic distal pancreatectomy is not associated with a lower postoperative morbidity compared to sacrificing the spleen. Tumor size is a risk factor for unplanned splenectomy.

Splenic cysts are a rare entity in the Western population and are either true cysts (primary, 25%) or pseudocysts (secondary, 75%) complicating trauma, haemorrhage or infarction. Congenital or simple splenic cysts are the commonest primary cysts and surgery is recommended for cysts larger than 5 cm as these are prone to infection, bleeding or rupture and for symptomatic or complicated cysts. Splenic preservation techniques using the laparoscopic approach are the most prevalent. We present a case of a giant painful simple splenic cyst treated with laparoscopic de-capsulation with application of a new technique for achieving vascular control, whereby control of the splenic pedicle was achieved using a Nylon tape. This approach was safe and well tolerated with a total splenic ischaemia time of 30 min and a successful result. The patient was discharged with no antecedent complications and no recurrence of the cyst at 6 months follow up ultrasound scan.

Obesity has become a worldwide epidemic that is accompanied by a rise in Type 2 diabetes mellitus. Management of obesity is paramount to prevent the associated mortality and morbidity. Several randomized control trials show that bariatric surgery is an effective method for the treatment of obesity and remission of Type 2 diabetes in the short term. Long-term observational studies have further validated the improvements in weight and Type 2 diabetes as well as cardiovascular events and overall mortality. There is an improvement in microvascular outcomes, in particular retinopathy and nephropathy show promising results but further studies are needed to evaluate hard-end points for neuropathy. Bariatric surgery is cost effective with the cost of surgery being offset by future cost benefits.