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Purpose Gastric staple line leakage (GL) is a serious complication of laparoscopic sleeve gastrectomy (LSG), with a specific mortality ranging from 0.2 to 3.7%. The current treatment of choice is stent insertion. However, it is unclear whether the type of stent which is inserted affects treatment outcome. Therefore, we aimed not only to determine the effectiveness of stent treatment for GL but also to specifically clarify whether treatment outcome was dependent on the type of stent (small- (SS) or megastent (MS)) which was used. Patients and Methods A single-centre retrospective study of 23 consecutive patients was conducted to compare the outcomes of SS (n = 12) and MS (n = 11) for the treatment of GL following LSG. The primary outcome measure was the success rate of stenting, defined as complete healing of the GL without changing the treatment strategy. Treatment change or death were both coded as failure. Results The success rate of MS was 91% (10/11) compared to only 50% (6/12) for SS (p = 0.006). An average of 2.3 ± 0.5 and 6.8 ± 3.7 endoscopies were required to achieve healing in the MS and SS groups respectively (p < 0.001). The average time to resumption of oral nutrition was shorter in the MS group (1.4 ± 1.1 days vs. 23.1 ± 33.1 days, p = 0.003). Conclusions Stent therapy is only effective and safe for the treatment of GL after LSG if a MS is used. Treatment with a MS may not only increase treatment success rates but may also facilitate earlier resumption of oral nutrition and shorten the duration of hospitalization. Graphical Abstract

Liver resident CD8 T cells have an essential role in immunopathology in a mouse model of nonalcoholic steatohepatitis, by becoming auto-aggressive following sequential transcriptional and metabolic activation steps . Nonalcoholic steatohepatitis (NASH) is a manifestation of systemic metabolic disease related to obesity, and causes liver disease and cancer(1,2). The accumulation of metabolites leads to cell stress and inflammation in the liver(3), but mechanistic understandings of liver damage in NASH are incomplete. Here, using a preclinical mouse model that displays key features of human NASH (hereafter, NASH mice), we found an indispensable role for T cells in liver immunopathology. We detected the hepatic accumulation of CD8 T cells with phenotypes that combined tissue residency (CXCR6) with effector (granzyme) and exhaustion (PD1) characteristics. Liver CXCR6(+) CD8 T cells were characterized by low activity of the FOXO1 transcription factor, and were abundant in NASH mice and in patients with NASH. Mechanistically, IL-15 induced FOXO1 downregulation and CXCR6 upregulation, which together rendered liver-resident CXCR6(+) CD8 T cells susceptible to metabolic stimuli (including acetate and extracellular ATP) and collectively triggered auto-aggression. CXCR6(+) CD8 T cells from the livers of NASH mice or of patients with NASH had similar transcriptional signatures, and showed auto-aggressive killing of cells in an MHC-class-I-independent fashion after signalling through P2X7 purinergic receptors. This killing by auto-aggressive CD8 T cells fundamentally differed from that by antigen-specific cells, which mechanistically distinguishes auto-aggressive and protective T cell immunity.

ZusammenfassungDie Prävalenzen von Adipositas und metabolischen Erkrankungen wie Diabetes mellitus Typ 2 (DM2), Nicht-alkoholischer Fettlebererkrankung (NAFLD), arterieller Hypertonie (aHT) oder Obstruktiver Schlafapnoe (OSAS) steigen. Die Adipositas-Chirurgie ist nicht nur hinsichtlich des Gewichtsverlustes der konservativen Therapie überlegen, sondern zeigt ebenfalls positive Effekte auf metabolische Erkrankungen. Die meisten Daten finden sich für den DM2, hier kommt es unabhängig vom Gewichtsverlust zu einer besseren glykämischen Kontrolle, Verbesserung mikro- und makrovaskulärer Komplikationen wie der diabetischen Nephropathie oder Polyneuropathie und Reduktion der Mortalität. Bei Patienten mit NAFLD zeigen sich sowohl laborchemisch als auch histologisch Befundverbesserungen bis hin zur Regredienz fibrotischer Veränderungen. Die antihypertensive Medikation kann nach metabolischem Eingriff nachhaltig reduziert oder gar sistiert werden, gleiches gilt für die medikamentöse Therapie der Dyslipidämie. Patienten mit diabetischer Nephropathie oder auch Adipositas-assoziierter Albuminurie profitieren von einer Erholung der Nierenfunktion und Reduktion der Dialysepflichtigkeit. Auch das OSAS, eine häufige Erkrankung adipöser Patienten mit Erhöhung des kardiovaskulären Risikos, zeigt postoperativ eine Befundverbesserung. Diese beginnt sogar schon bevor es zu einem relevanten Gewichtsverlust kommt, welcher zusätzlich die Atemmechanik erleichtert.Interessanterweise zeigen sich die beschriebenen Effekte nicht nur bei adipösen, sondern auch bei normalgewichtigen Patienten. Der DM2 stellt daher bereits in bestimmten Fällen beim normalgewichtigen Patienten eine Indikation zur metabolischen Chirurgie dar. Eine Anpassung der Leitlinien hinsichtlich anderer metabolischer Erkrankungen steht trotz zunehmender hochklassiger Evidenz diesbezüglich noch aus.

BackgroundPatient-related risk factors such as diabetes mellitus and obesity are increasing in western countries. At the same time the indications for liver resection in both benign and malignant diseases have been significantly extended in recent years. Major liver resection is performed more frequently in a patient population of old age, comorbidity and high rates of neoadjuvant chemotherapy. The aim of this study was to evaluate whether diabetes mellitus, obesity and overweight are risk factors for the short-term post-operative outcome after major liver resection.MethodsFour hundred seventeen major liver resections (≥ 3 segments) were selected from a prospective database. Exclusion criteria were prior liver resection in patient’s history and synchronous major intra-abdominal procedures. Overweight was defined as BMI ≥ 25 kg/m2and 2and obesity as BMI ≥ 30 kg/m2. Primary end point was 90-day mortality and logistic regression was used for multivariate analysis. Secondary end points included morbidity, complications according to Clavien–Dindo classification, unplanned readmission, bile leakage, and liver failure. Morbidity was defined as occurrence of a post-operative complication during hospital stay or within 90 days postoperatively.ResultsFifty-nine patients had diabetes mellitus (14.1%), 48 were obese (11.6%) and 147 were overweight (35.5%). There were no statistically significant differences in mortality rates between the groups. In the multivariate analysis, diabetes was an independent predictor of morbidity (OR = 2.44, p = 0.02), Clavien–Dindo grade IV complications (OR = 3.6, p = 0.004), unplanned readmission (OR = 2.44, p = 0.04) and bile leakage (OR = 2.06, p = 0.046). Obese and overweight patients did not have an impaired post-operative outcome compared patients with normal weight.ConclusionsDiabetes has direct influence on the short-term postoperative outcome with an increased risk of morbidity but not mortality. Preoperative identification of high-risk patients will potentially decrease complication rates and allow for individual patient counseling as part of a shared decision-making process. For obese and overweight patients, major liver resection is a safe procedure.

Background The incidence of colorectal cancer (CRC) among patients, The incidence of colorectal cancer (CRC) among patients

Die Adipositaschirurgie nimmt in Deutschland und weltweit immer weiter zu. Die Patienten haben per se ein erhohtes Operationsrisiko im Vergleich zu nichtadiposen Patienten. Umso wichtiger ist es, die praoperative Abklarung der Patienten sorgfaltig durchzufuhren, um damit das Operationsrisiko so weit wie moglich zu reduzieren. Die Indikationsstellung fur die Operation geht zunehmend weg von einem bestimmten Body-Mass-Index (BMI) hin zur adipositasassoziierten Begleiterkrankung als Entscheidungsgrundlage. Die 2018 erschienene S3-Leitlinie legte verschiedene Kriterien fest, die als Wegweiser fur eine Operationsindikation zur Hand genommen werden konnen. Die Indikation sollte im interdisziplinaren Team von Chirurgen, Diabetologen, Internisten, Ernahrungsmedizinern und Psychologen gestellt werden. Eine Aufklarung der Patienten uber realistische Ziele und Moglichkeiten der Operation sollte durch den behandelnden Chirurgen erfolgen, ebenso die Beratung bezuglich der verschiedenen Operationsvarianten. Auserdem sollten die Patienten durch einen Diabetologen oder Internisten endokrinologisch im Hinblick auf relevante Komorbiditaten abgeklart werden. Diese sollten so weit wie moglich praoperativ therapiert oder es sollen bereits vorhandene Medikamente angepasst werden. Die psychologische Freigabe fur die Operation kann erfolgen, wenn die Patienten konservativ therapeutisch oder medikamentos gut betreut und eingestellt sind bzw. ihre psychische Erkrankung kompensiert ist. Durch eine kurzzeitige praoperative kohlenhydratarme und eiweisreiche Flussigernahrung kann das Risiko fur postoperative Komplikationen reduziert werden, vor allem bei Patienten mit hohem BMI. Eine praoperative Gewichtsabnahme im Sinne einer verpflichtenden Abnahme eines festgelegten Anteils des Korpergewichts ist nicht sinnvoll.

Background Insufflation pressures of or in excess of 25 mm Hg CO2 are routinely used during posterior retroperitoneoscopic adrenalectomy (PRA) in most centres. A critical analysis of the surgical literature provides limited evidence to support this strategy. Objective To determine whether high pressure (≥ 25 mm Hg) compared with lower pressure ( Methods A multi-centre retrospective cohort study was performed using data collected over a period of almost one decade (1st November 2008 until 1st February 2018) from surgical centres in Germany. A total of 1032 patients with benign adrenal tumours were identified. We compared patients undergoing PRA with insufflation pressures of Results The baseline patient characteristics were similar in both groups, with the exception of tumour size, BMI and surgeon's experience in PRA. After propensity score matching, perioperative outcomes, especially perioperative complications (3.7% vs. 5.5% in G20 and G25, respectively; p = 0.335) and operation duration (47 min vs. 45 min in G20 and G25, respectively; p = 0.673), did not significantly differ between the groups. Conclusion Neither patient safety nor operative success was compromised when PRA was performed with insufflation pressures below 25 mm Hg. Prospective studies are required to determine whether an optimal insufflation pressure exists that maximizes patient safety and minimizes the risks of post-surgical complications. Nevertheless, our results call for a careful re-evaluation of the routine use of high insufflation pressures during PRA. In the absence of prospective data, commencing PRA with lower insufflation pressures, with the option of increasing insufflation pressures to counter intraoperative bleeding or exposition difficulties, may represent a reasonable strategy.

To systematically review the problem of appetite loss after major abdominal surgery.Appetite loss is a common problem after major abdominal surgery. Understanding of etiology and treatment options is limited.We searched Medline, Cochrane Central Register of Controlled Trials, and Web of Science for studies describing postoperative appetite loss. Data were extracted to clarify definition, etiology, measurement, surgical influence, pharmacological, and nonpharmacological treatment. PROSPERO registration ID: CRD42021224489.Out of 6144 articles, we included 165 studies, 121 of which were also analyzed quantitatively. A total of 19.8% were randomized, controlled trials (n = 24) and 80.2% were nonrandomized studies (n = 97). The studies included 20,506 patients undergoing the following surgeries: esophageal (n = 33 studies), gastric (n = 48), small bowel (n = 6), colon (n = 27), rectal (n = 20), hepatobiliary (n = 6), and pancreatic (n = 13). Appetite was mostly measured with the Quality of Life Questionnaire of the European Organization for Research and Treatment of Cancer (EORTC QLQ C30, n = 54). In a meta-analysis of 4 randomized controlled trials gum chewing reduced time to first hunger by 21.2 hours among patients who had bowel surgery. Other reported treatment options with positive effects on appetite but lower levels of evidence include, among others, intravenous ghrelin administration, the oral Japanese herbal medicine Rikkunshito, oral mosapride citrate, multidisciplin-ary-counseling, and watching cooking shows. No studies investigated the effect of well-known appetite stimulants such as cannabinoids, steroids, or megestrol acetate on surgical patients.Appetite loss after major abdominal surgery is common and associated with increased morbidity and reduced quality of life. Recent studies demonstrate the influence of reduced gastric volume and ghrelin secretion, and increased satiety hormone secretion. There are various treatment options available including level IA evidence for postoperative gum chewing. In the future, surgical trials should include the assessment of appetite loss as a relevant outcome measure.

Background: Obesity and metabolic disorders as type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD) or better called metabolic dysfunction fatty liver disease (MAFLD), arterial hypertension (AHT), and obstructive sleep apnea syndrome (OSAS) show a rising prevalence. The increased cardiovascular risk is one of the main causes for death of obese, metabolic ill patients. Sustainable and efficient therapeutic options are needed. Summary: Metabolic surgery not only permits a substantial and lasting weight loss but also ameliorates metabolic co-morbidities and reduces cardiovascular risk and mortality of obese patients. Most existing data focused on T2D, but evidence for other metabolic co-morbidities such as NAFLD, AHT, and OSAS increase constantly. After metabolic surgery, glycemic control of diabetic patients is superior compared to conservative treatment. Also, diabetes related micro- and macrovascular complications are reduced after surgery, and the median life expectancy is over 9 years longer. In patients with MAFLD, metabolic surgery leads to reduction of steatosis and fibrosis while the risk to develop a hepatocellular carcinoma is reduced significantly. Patients with OSAS have an improved lung function and continuous pressure airway treatment during the night is unnecessary in many patients. Patients with AHT need significantly less or even no antihypertensive medication after surgery and the hazard ratio of death is reduced by 49.2%. Therefore, the focus in treating obese and metabolic ill patients is no longer on pure weight loss but on improvement of co-morbidities and reduction of mortality. This is reflected by the updated S3-guidelines of 2018 that provide nationally established consistent guidelines with clear indications for metabolic surgery no longer focusing on body mass index (BMI) only. This article aims to give an overview over the existing literature concerning surgical treatment options for metabolic syndrome. Key Messages: Metabolic co-morbidities impact life-quality and life expectancy of obese patients. Metabolic surgery offers the chance to treat those metabolic co-morbidities independently of the preoperative BMI and should be considered early as a treatment option for obese patients.

Obesity is a major health burden worldwide and is associated with nonalcoholic fatty liver disease, which can lead to cirrhosis. Bariatric surgery is increasingly being used to treat obesity, and the number of patients with obesity and cirrhosis undergoing bariatric surgery is also rising. However, the safety and feasibility of bariatric surgery in patients with obesity and cirrhosis are controversial.In this meta-analysis, we compared postoperative complications, mortality, and weight loss between patients with and without cirrhosis undergoing bariatric surgery.An electronic search of Medline, Web of Science, and Cochrane Central Register of Controlled Trials (CENTRAL).Patient morbidity and mortality odds ratios (ORs) and mean differences (MDs) with 95% confidence intervals (CIs) were assessed. Intraoperative and overall complications, length of hospital stay, in-hospital mortality, long-term mortality, and total weight loss were recorded.The literature search yielded 2977 articles. Eight studies were included in the analysis. Meta-analysis showed that the overall complications (OR: 2.1; 95% CI: 1.47-3.00; P.0001), postoperative bleeding (OR: 2.22; 95% CI: 1.95-2.54; P.00001), length of hospital stay (MD: .68; 95% CI: .14-1.19; P = .01), and in-hospital/90-day mortality (OR: 3.59; 95% CI: 2.84-4.54; P.00001) were significantly higher in patients with compensated cirrhosis than in patients without cirrhosis. Intraoperative complications, operation time, major complications, and long-term mortality were similar between the groups. Total weight loss was also not significantly different between the groups.Bariatric surgery can be considered only in highly selected patients with obesity and compensated cirrhosis.

Metabolic dysfunction-associated fatty liver disease (MAFLD) reflects the multifactorial pathogenesis of fatty liver disease in metabolically sick patients. The effects of metabolic surgery on MAFLD have not been investigated. This study assesses the impact of Roux-en-Y gastric bypass (RYGB) on MAFLD in a prototypical cohort outside the guidelines for obesity surgery.Twenty patients were enrolled in this prospective, single-arm trial investigating the effects of RYGB on advanced metabolic disease (DRKS00004605). Inclusion criteria were an insulin-dependent type 2 diabetes, body mass index of 25 to 35 kg/m 2 , glucagon-stimulated C-peptide of1.5 ng/mL, glycated hemoglobin7%, and age 18 to 70 years. A RYGB with intraoperative liver biopsies and follow-up liver biopsies 3 years later was performed. Steatohepatitis was assessed by expert liver pathologists. Data were analyzed using the Wilcoxon rank sum test and a P value0.05 was defined as significant.MAFLD completely resolved in all patients 3 years after RYGB while fibrosis improved as well. Fifty-five percent were off insulin therapy with a significant reduction in glycated hemoglobin (8.45±0.27% to 7.09±0.26%, P =0.0014). RYGB reduced systemic and hepatic nitrotyrosine levels likely through upregulation of NRF1 and its dependent antioxidative and mitochondrial genes. In addition, central metabolic regulators such as SIRT1 and FOXO1 were upregulated while de novo lipogenesis was reduced and β-oxidation was improved in line with an improvement of insulin resistance. Lastly, gastrointestinal hormones and adipokines secretion were changed favorably.RYGB is a promising therapy for MAFLD even in low-body mass index patients with insulin-treated type 2 diabetes with complete histologic resolution. RYGB restores the oxidative balance, adipose tissue function, and gastrointestinal hormones.

Background Delayed gastric emptying (DGE) occurs in up to 40% of patients after esophageal resection and prolongs recovery and hospital stay. Surgically pyloroplasty does not effectively prevent DGE. Recently published methods include injection of botulinum toxin (botox) in the pylorus and mechanical interventions as preoperative endoscopic dilatation of the pylorus. The aim of this study was to investigate the efficacy of those methods with respect to the newly published Consensus definition of DGE. Methods A systematic literature search using CENTRAL, Medline, and Web of Science was performed to identify studies that described pre- or intraoperative botox injection or mechanical stretching methods of the pylorus in patients undergoing esophageal resection. Frequency of DGE, anastomotic leakage rates, and length of hospital stay were analyzed. Outcome data were pooled as odd’s ratio (OR) or mean difference using a random-effects model. Risk of bias was assessed using the Robins-I tool for non-randomized trials. Results Out of 391 articles seven retrospective studies described patients that underwent preventive botulinum toxin injection and four studies described preventive mechanical stretching of the pylorus. DGE was not affected by injection of botox (OR 0.87, 95% confidence interval [CI] 0.37–2.03, P = 0.75), whereas mechanical stretching resulted in significant reduction of DGE (OR 0.26, 95% CI 0.14–0.5, P Conclusion Mechanical stretching of the pylorus, but not injection of botox reduces DGE after esophageal cancer resection. A newly developed consensus definition should be used before the conduction of a large-scale randomized-controlled trial.

ObjectiveTo optimize anastomotic technique and gastric conduit perfusion with hyperspectral imaging (HSI) for total minimally invasive esophagectomy (MIE) with linear stapled anastomosis.Summary Background DataEsophagectomy is the mainstay of esophageal cancer treatment but anastomotic insufficiency related morbidity and mortality remain challenging for patient outcome.MethodsA live porcine model (n=50) for MIE was used with gastric conduit formation and linear stapled side-to-side esophagogastrostomy. Four main experimental groups differed in stapling length (3 vs. 6 cm) and anastomotic position on the conduit (cranial vs. caudal). Tissue oxygenation around the anastomotic site was evaluated using HSI and was validated with histopathology.ResultsThe tissue oxygenation (ΔStO2) after the anastomosis remained constant only for the short stapler in caudal position (−0.4± 4.4%, n.s.) while it dropped markedly in the other groups (short-cranial: -15.6± 11.5%, p=0.0002; long-cranial: -20.4± 7.6%, p=0.0126; long-caudal: -16.1± 9.4%, pConclusionsTissue oxygenation at the anastomotic site of the gastric conduit during MIE is influenced by stapling technique. Optimal oxygenation was achieved with a short stapler (3 cm) and sufficient distance of the anastomosis to the cranial end of the gastric conduit. HSI tissue deoxygenation corresponded to histopathologic necrotic tissue changes. These findings allow for optimization of gastric conduit perfusion and anastomotic technique in MIE.Level of EvidenceNot applicable. Translational animal science. Original article.

Minimally invasive oesophagectomy (MIO) for oesophageal cancer may reduce surgical complications compared with open oesophagectomy. MIO is, however, technically challenging and may impair optimal oncological resection. The aim of the present study was to assess if MIO for cancer is beneficial.A systematic literature search in MEDLINE, Web of Science and CENTRAL was performed and randomized controlled trials (RCTs) comparing MIO with open oesophagectomy were included in a meta-analysis. Survival was analysed using individual patient data. Random-effects model was used for pooled estimates of perioperative effects.Among 3219 articles, six RCTs were identified including 822 patients. Three-year overall survival (56 (95 per cent c.i. 49 to 62) per cent for MIO versus 52 (95 per cent c.i. 44 to 60) per cent for open; P = 0.54) and disease-free survival (54 (95 per cent c.i. 47 to 61) per cent versus 50 (95 per cent c.i. 42 to 58) per cent; P = 0.38) were comparable. Overall complication rate was lower for MIO (odds ratio 0.33 (95 per cent c.i. 0.20 to 0.53); P 0.010) mainly due to fewer pulmonary complications (OR 0.44 (95 per cent c.i. 0.27 to 0.72); P 0.010), including pneumonia (OR 0.41 (95 per cent c.i. 0.22 to 0.77); P 0.010).MIO for cancer is associated with a lower risk of postoperative complications compared with open resection. Overall and disease-free survival are comparable for the two techniques.Oesophagectomy for cancer is associated with a high risk of complications. A minimally invasive approach might be less traumatic, leading to fewer complications and may also improve oncological outcome. A meta-analysis of randomized controlled trials comparing minimally invasive to open oesophagectomy was performed. The analysis showed that the minimally invasive approach led to fewer postoperative complications, in particular, fewer pulmonary complications. Survival after surgery was comparable for the two techniques.Oesophagectomy for cancer is associated with a high risk of complications. A minimally invasive approach might be less traumatic, leading to fewer complications and may also improve oncological outcome. A meta-analysis of randomized controlled trials comparing minimally invasive to open oesophagectomy was performed. The analysis showed that the minimally invasive approach led to fewer postoperative complications, in particular, fewer pulmonary complications. Survival after surgery was comparable for the two techniques.

Introduction: Nonalcoholic fatty liver disease covers a broad spectrum. Simple steatosis has usually a benign course while nonalcoholic steatohepatitis (NASH) can progress into hepatocellular carcinoma, and cirrhosis. Therefore, differentiating patients with benign steatosis and NASH is crucial. Liver biopsy, the usual gold standard for NASH diagnosis, cannot be used as a screening method due to its associated risks. This is especially problematic for obese patients with a prevalence of nonalcoholic fatty liver disease (NAFLD) in >80% of patients. The aim of this study was therefore to develop and validate a noninvasive NASH screening test in a cohort of high-risk, morbidly obese patients. Methods: This prospective study examined diagnostic accuracy in accordance with STARD guidelines. 112 liver biopsies were consecutively assigned to either a training or validation cohort. Using the Bedossa histological scoring system, the cohorts were subdivided into NASH versus NAFLD/No NAFLD. Predictors of NASH were evaluated with receiver operating characteristic (ROC) curves. A model was then constructed using a backward stepwise logistic regression and evaluated in an independent validation cohort. Results: 53.5% of the patients had NASH and 4 patients had cirrhosis. Mean body mass index (BMI) was 49.8 ± 7.5 kg/m2. Backward stepwise logistic regression identified 4 parameters associated with the presence of NASH: alanin-aminotransferase, albumin, BMI, and triglycerides. The noninvasive NASH detection score (NI-NASH-DS) had an ROC of 0.851 and 0.727 in the training and validation cohorts, respectively. Sensitivity and specificity were 77.1% and 88% in the training cohort and 88% and 48% in the validation cohort which was much better than the established noninvasive scores. Discussion/Conclusion: The NI-NASH-DS is easy-to-use, inexpensive, and noninvasive and can reliably detect NASH in patients with morbid obesity. Due to its simplicity, it can be used frequently and repeatedly.

Background Little is known about the long-term outcomes of patients with end-stage organ failure (ESOF) undergoing obesity surgery. Objective To investigate the perioperative and mid-term outcomes of patients with ESOF undergoing obesity surgery. Setting University hospital, Germany Methods 1,094 patients undergoing obesity surgery from 2006-2019 were screened. Inclusion criteria were ejection fraction Results Twenty-seven ESOF patients (56% female, age 50.3±8.6, BMI 53.8±8.7kg/m2) were identified. Eighty-five percent had a sleeve gastrectomy. Mid-term total weight loss was 26.6%±9.0% in the ESOF patients vs. 17.8%±11.1% in MS patients (p=0.181). Long-term improvement of type 2 diabetes was comparable (ESOF-HbA1c 8.79±2.06% to 6.25±1.17%, p=0.047; MS-HbA1c: 7.94±2.02% to 7.2±1.28%; p=0.343). Depression scores (PHQ-9) among ESOF patients improved from 13.0±6.3 to 6.1±5.8 (p=0.004) but without significant change in MS patients (9.4±7.3 to 4.3±5.7; p=0.082). Lung function improved in all patients (although only 15% were off oxygen therapy) and treatment goals were achieved in >50% of the other groups. Major complications occurred in 11% (ESOF) vs. 4% (MS) of patients (p=0.299) with one death in the ESOF group (4%). Conclusion Both groups had similar outcomes regarding weight loss and comorbidity improvement. Depression only improved significantly in the ESOF group. Patients with ESOF should not be precluded from obesity surgery. Further investigation is needed to define optimized selection criteria.

This study sought to use a newly developed intracellular ATP delivery to enhance incisional wound healing to reduce surgical wound dehiscence and to explore possible mechanism for this effect. Thirty-five adult New Zealand white rabbits were used. Skin incisions were made on the back and closed. ATP-vesicles were mixed with a neutral cream for one side of the wounds while the neutral cream alone was used on the other side of the wounds. Laser speckle contrast imaging (LSCI), biomechanical, histological, and immunohistochemical analyses were performed 7 and 14 days after surgery, and macrophage culture was used to test the enhanced collagen production ability. Among them, 10 were used for wound perfusion study and 25 were used for wound biomechanical and histological/immunohistochemical studies. Wound tissue perfusion was reduced after surgery especially in early days. Wound tissue tensile strength, breaking stress, and elasticity were all much higher in the ATP-vesicle treated group than in the cream treated group at days 7 and 14. The healing was complemented by earlier macrophage accumulation, in situ proliferation, followed by direct collagen production. The results were further confirmed by human macrophage culture. It was concluded that intracellular ATP delivery enhanced healing strength of incisional wounds via multiple mechanisms.

Background Early diagnosis of kidney disease in obese patients and in such patients with type 2 diabetes (T2D) can significantly improve treatment outcome. Serum uromodulin (sUMOD) may be a sensitive parameter for early detection of nephropathy. Objectives To analyze sUMOD and traditional markers of kidney function in a cohort study of patients with and without obesity or T2D undergoing metabolic surgery compared with blood donors. Setting University of Heidelberg, Germany. Methods Patients with obesity (body mass index >35 kg/m2) without T2D (n = 10) and T2D (n = 10) and patients with nonsevere obesity (body mass index, 25–35 kg/m2) and insulin-dependent T2D (n = 16) undergoing Roux-en-Y gastric bypass (RYGB) were enrolled. The control group consisted of 190 blood donors. sUMOD was compared with established renal markers. Results Using sUMOD, impaired kidney function at baseline was present in both groups with T2D and in none of the patients with obesity without T2D. This impairment was not detectable through traditional markers. Significant improvement of sUMOD was shown in patients with obesity and T2D 12 months postoperatively (from 130.0 ± 77.5 to 239.5 ± 179.0 ng/mL; P = .004) and in patients with nonsevere obesity and T2D 6 months after RYGB (from 140.6 ± 78.0 to 298.7 ± 154.0 ng/mL; P = .017). In patients with obesity without T2D, sUMOD remained stable (P = .375). Conclusions sUMOD may serve as a tissue-specific biomarker in incipient diabetic nephropathy. Improvement of sUMOD after RYGB seems to profoundly restore the structural integrity of nephrons in these patients at risk for diabetic nephropathy.

Background Metabolic surgery is the most effective therapy for patients with type 2 diabetes (T2D), also improving diabetic kidney disease. Whether these effects depend on weight loss is currently unknown. Objectives To assess the correlation between weight loss and improvement of diabetic kidney disease in patients with T2D undergoing metabolic surgery. Setting University of Heidelberg, Germany. Methods A systematic literature search was performed in December 2018 using the MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases without language restrictions or time limit. Studies reporting exact data on change in urinary albumin-creatinine ratio (uACR) or albuminuria as well as change in body mass index in patients with T2D undergoing metabolic surgery were included. Out of 2145 potentially eligible hits, 15 studies were included. Study quality was assessed using the Downs and Black score. Data were pooled using a random-effects model, and a Spearman’s rank correlation was performed. Results No correlation was found between improved renal injury (change in uACR or albuminuria) and weight loss (change in body mass index) (rs = -.306, P = 0.504, and rs = -.086, P = .872), and no significant correlation was found between improved renal injury (change in uACR or albuminuria) and improved glycemic control (change in A1C) (rs = .378, P = .403, and rs = .500, P = .391. Conclusion Metabolic surgery can improve diabetic kidney disease independent of weight loss and glycemic control. Other mechanisms, including modified adipokine balance, signaling pathways of fat tissue and gut hormones, or reduced systemic inflammation, contribute to improved renal injury, while weight loss seems to play a lesser role than expected.

Hepatocellular carcinoma (HCC) can have viral or non-viral causes1–5. Non-alcoholic steatohepatitis (NASH) is an important driver of HCC. Immunotherapy has been approved for treating HCC, but biomarker-based stratification of patients for optimal response to therapy is an unmet need6,7. Here we report the progressive accumulation of exhausted, unconventionally activated CD8+PD1+ T cells in NASH-affected livers. In preclinical models of NASH-induced HCC, therapeutic immunotherapy targeted at programmed death-1 (PD1) expanded activated CD8+PD1+ T cells within tumours but did not lead to tumour regression, which indicates that tumour immune surveillance was impaired. When given prophylactically, anti-PD1 treatment led to an increase in the incidence of NASH–HCC and in the number and size of tumour nodules, which correlated with increased hepatic CD8+PD1+CXCR6+, TOX+, and TNF+ T cells. The increase in HCC triggered by anti-PD1 treatment was prevented by depletion of CD8+ T cells or TNF neutralization, suggesting that CD8+ T cells help to induce NASH–HCC, rather than invigorating or executing immune surveillance. We found similar phenotypic and functional profiles in hepatic CD8+PD1+ T cells from humans with NAFLD or NASH. A meta-analysis of three randomized phase III clinical trials that tested inhibitors of PDL1 (programmed death-ligand 1) or PD1 in more than 1,600 patients with advanced HCC revealed that immune therapy did not improve survival in patients with non-viral HCC. In two additional cohorts, patients with NASH-driven HCC who received anti-PD1 or anti-PDL1 treatment showed reduced overall survival compared to patients with other aetiologies. Collectively, these data show that non-viral HCC, and particularly NASH–HCC, might be less responsive to immunotherapy, probably owing to NASH-related aberrant T cell activation causing tissue damage that leads to impaired immune surveillance. Our data provide a rationale for stratification of patients with HCC according to underlying aetiology in studies of immunotherapy as a primary or adjuvant treatment., In hepatocellular carcinoma driven by non-alcoholic steatohepatitis, aberrant T cell activation and impaired immune surveillance seem to make hepatocellular carcinoma less responsive to anti-PD1 or anti-PDL1 immunotherapy.

We aimed to evaluate the medium-term efficacy of sleeve gastrectomy (SG)We identified severely obese patients [body mass index (BMI)35 kg/mNinety-six patients were investigated; 44 (45.8%) were women. The mean pre-operative BMI was 45.2 kg/mBariatric 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.

Non-alcoholic steatohepatitis (NASH) comprises a major healthcare problem affecting up to 30% of patients with obesity and the associated risk for cardiovascular and liver-related mortality. Several new drugs for NASH-treatment are currently investigated. No study thus far directly compared surgical and non-surgical therapies for NASH. This network meta-analysis compares for the first time the effectiveness of different therapies for NASH using a novel statistical approach.The study was conducted according to the PRISMA guidelines for network meta-analysis. PubMed, CENTRAL and Web of Science were searched without restriction of time or language using a validated search strategy. Studies investigating therapies for NASH in adults with liver biopsies at baseline and after at least 12 months were selected. Patients with liver cirrhosis were excluded. Risk of bias was assessed with ROB-2 and ROBINS-I-tools. A novel method for population-adjusted indirect comparison to include and compare single-arm trials was applied. Main outcomes were NASH-resolution and improvement of fibrosis.Out of 7,913 studies, twelve randomized non-surgical studies and twelve non-randomized surgical trials were included. NASH-resolution after non-surgical intervention was 29% [95% confidence interval (CI): 23-40%] and 79% (95% CI: 72-88%) after surgery. The network meta-analysis showed that surgery had a higher chance of NASH-resolution than medication [odds ratio (OR) =2.68; 95% CI: 1.44-4.97] while drug treatment was superior to placebo (OR =2.24; 95% CI: 1.55-3.24). Surgery (OR =2.18; 95% CI: 1.34-3.56) and medication (OR =1.79; 95% CI: 1.39-2.31) were equally effective to treat fibrosis compared to placebo without difference between them. The results did not change when only new drugs specifically developed for the treatment of NASH were included.Metabolic surgery has a higher effectiveness for NASH-therapy than medical therapy while both were equally effective regarding improvement of fibrosis. Trials directly comparing surgery with medication must be urgently conducted. Patients with NASH should be informed about surgical treatment options.

This study sought to use a newly developed intracellular ATP delivery to enhance incisional wound healing to reduce surgical wound dehiscence and to explore possible mechanism for this effect. Thirty-five adult New Zealand white rabbits were used. Skin incisions were made on the back and closed. ATP-vesicles were mixed with a neutral cream for one side of the wounds while the neutral cream alone was used on the other side of the wounds. Laser speckle contrast imaging (LSCI), biomechanical, histological, and immunohistochemical analyses were performed 7 and 14 days after surgery, and macrophage culture was used to test the enhanced collagen production ability. Among them, 10 were used for wound perfusion study and 25 were used for wound biomechanical and histological/immunohistochemical studies. Wound tissue perfusion was reduced after surgery especially in early days. Wound tissue tensile strength, breaking stress, and elasticity were all much higher in the ATP-vesicle treated group than in the cream treated group at days 7 and 14. The healing was complemented by earlier macrophage accumulation, in situ proliferation, followed by direct collagen production. The results were further confirmed by human macrophage culture. It was concluded that intracellular ATP delivery enhanced healing strength of incisional wounds via multiple mechanisms.

Primary hyperaldosteronism is a recognized risk factor for myocardial infarction, stroke, and atrial fibrillation. Minimally invasive adrenalectomy is the first-line treatment for localized primary hyperaldosteronism. Whether minimally invasive adrenalectomy should be performed using a cortex-sparing technique (partial minimally invasive adrenalectomy) or not (total minimally invasive adrenalectomy) remains a subject of debate. The aim of our study was to evaluate the clinical and biochemical efficacy of both procedures and to examine the morbidity associated with partial minimally invasive adrenalectomy versus total minimally invasive adrenalectomy in a multicenter study.Using a retrospective study design, we determined the efficacy, morbidity, and mortality of partial minimally invasive adrenalectomy and total minimally invasive adrenalectomy. The Primary Aldosteronism Surgical Outcome Study classification was used to explore clinical and biochemical success. Matched-pair analysis was used in order to address possible bias.We evaluated 234 matched patients with unilateral primary hyperaldosteronism: 78 (33.3%) underwent partial minimally invasive adrenalectomy, and 156 (66.7%) were treated with total minimally invasive adrenalectomy. Complete clinical success was achieved in 40.6%, and partial clinical success in an additional 52.6% of patients in the entire cohort. Complete biochemical success was seen in 94.0% of patients. Success rates and the incidence of perioperative complications were comparable between groups. Both postoperative hypocortisolism (11.5% vs 25.0% after partial minimally invasive adrenalectomy and total minimally invasive adrenalectomy, respectively; P.001) and postoperative hypoglycemia (2.6% vs 7.1% after partial minimally invasive adrenalectomy and total minimally invasive adrenalectomy; P = .039) occurred more frequently after total minimally invasive adrenalectomy.Our study provides evidence that patients with unilateral primary hyperaldosteronism are good surgical candidates for partial minimally invasive adrenalectomy. Not only is the surgical outcome comparable to that of total minimally invasive adrenalectomy, but also postsurgical morbidity, particularly in terms of hypocortisolism and hypoglycemia, may be reduced.

Obesity is becoming more and more prevalent especially in Western industrial nations. The understanding of adipose tissue as an endocrine organ as well as the detection of adipocytokines – hormones that are secreted from the adipose tissue – gave reason to examine the interactions between adipose tissue and target organs. These efforts have been intensified especially in the context of bariatric surgery as promising weight loss therapy. Interactions between the lung and adipose tissue have rarely been investigated and are not well understood. There are obvious mechanical effects of obesity on lung function explaining the associations between obesity and lung diseases, in particular obesity hypoventilation syndrome, obstructive sleep apnea syndrome, asthma, and chronic obstructive pulmonary disease. The rise in the prevalence of obesity affects the epidemiology of pulmonary diseases as well. The aim of this review is to summarize the current knowledge on interactions, associations, and consequences of obesity and weight loss on lung function and lung diseases. Based on these data, areas for future research are identified.

Gastroesophageal reflux disease (GERD), a prevalent problem among obese individuals, is strongly associated with obesity and weight loss. Hence, bariatric surgery effectively improves GERD for many patients. Depending on the type of bariatric procedure, however, surgery can also worsen or even cause a new onset of GERD. As a consequence, GERD remains a relevant problem for many bariatric patients, and especially those who have undergone sleeve gastrectomy (SG). Affected patients report not only a decrease in physical functioning but also suffer from mental and emotional problems, resulting in poorer social functioning. The pathomechanism of GERD after SG is most likely multifactorial and triggered by the interaction of anatomical, physiological, and physical factors. Contributing factors include the shape of the sleeve, the extent of injury to the lower esophageal sphincter, and the presence of hiatal hernia. In order to successfully treat post-sleeve gastrectomy GERD, the cause of the problem must first be identified. Therapeutic approaches include lifestyle changes, medication, interventional treatment, and/or revisional surgery.

Background Non-alcoholic steatohepatitis (NASH) associated hepatocellular carcinomas (NASH-HCC) are increasing. NASH-HCC often develops in the fibrotic liver. Several analyses report conflicting results regarding the outcome of non-cirrhotic NASH-HCC. Furthermore, type 2 diabetes (T2D) is considered a risk factor for poor survival. The aim of this study was to investigate oncological outcomes of non-cirrhotic NASH-HCC and the impact of T2D. Methods Patients with non-cirrhotic NASH-HCC with T2D as determined by an expert pathologist conducting histological slide review were matched for risks factors for poor outcome (age, gender, body mass index) with patients with NASH-HCC without T2D. These patients were then matched 1:1 with HCCs of other underlying liver diseases with and without T2D. Oncological outcomes were assessed using Kaplan-Meier curves. Results Out of 365 HCCs resected between 2001 and 2017, 34 patients with non-cirrhotic NASH-HCC were selected (17 with T2D, 17 without T2D) and matched with 26 patients with hepatitis-HCC and 28 patients with alcohol-related HCC. Oncological risk factors such as tumor size, resection margin, and vessel invasion were comparable. There was no difference in overall survival (5-year survival 71.3% for NASH-HCC, 60.4% for hepatitis-HCC, 79.9% for alcohol-HCC). NASH-HCC was associated with longer disease-specific survival than hepatitis-HCC (5-year 87.5% vs. 63.7%, p = 0.048), while recurrence-free survival was identical. T2D had no impact on oncological outcomes in either liver disease. Conclusion Non-cirrhotic NASH-HCC has outcomes comparable with other underling etiologies. Despite a lack of cirrhosis, patients with non-cirrhotic NASH-HCC have the same risks of HCC recurrence as patients with cirrhotic liver disease of other etiologies.

Background This study aimed to examine the effect of metabolic surgery on pre-existing and future microvascular complications in patients with type 2 diabetes mellitus (T2DM) in comparison with medical treatment. Although metabolic surgery is the most effective treatment for obese patients with T2DM regarding glycaemic control, it is unclear whether the incidence or severity of microvascular complications is reduced. Methods A systematic literature search was performed in MEDLINE, Embase, Web of Science and the Cochrane Central Register of Controlled Trials (CENTRAL) with no language restrictions, looking for RCTs, case–control trials and cohort studies that assessed the effect of metabolic surgery on the incidence of microvascular diabetic complications compared with medical treatment as control. The study was registered in the International prospective register of systematic reviews (CRD42016042994). Results The literature search yielded 1559 articles. Ten studies (3 RCTs, 7 controlled clinical trials) investigating 17 532 patients were included. Metabolic surgery reduced the incidence of microvascular complications (odds ratio 0·26, 95 per cent c.i. 0·16 to 0·42; P < 0·001) compared with medical treatment. Pre-existing diabetic nephropathy was strongly improved by metabolic surgery versus medical treatment (odds ratio 15·41, 1·28 to 185·46; P = 0·03). Conclusion In patients with T2DM, metabolic surgery prevented the development of microvascular complications better than medical treatment. Metabolic surgery improved pre-existing diabetic nephropathy compared with medical treatment.

The underlying causes of type 2 diabetes (T2DM) remain poorly understood. Adipose tissue dysfunction with high leptin, inflammation, and increased oxidative stress may play a pivotal role in T2DM development in obese patients. Little is known about the changes in the adipose tissue after Roux-Y gastric bypass (RYGB) in non-severely obese patients (BMI

Hintergrund Die Adipositas stellt eine medizinische und wirtschaftliche Herausforderung dar. Der Weg eines Patienten mit Operationsindikation von der Erstvorstellung bis zum Zeitpunkt der Operation ist mit einem erheblichen Ressourceneinsatz verbunden.

Zusammenfassung Hintergrund Die onkologische Ösophagektomie ist mit hoher Morbidität verbunden. Mit minimal invasiven Operationsverfahren ist verschiedentlich versucht worden, diese zu reduzieren. Hauptproblem ist dabei die intrathorakale Anastomose. Es existieren verschiedene Techniken, mit dem Problem umzugehen, wie die Anlage einer funktionell problematischen zervikalen Anastomose, die offene Anlage der thorakalen Anastomose (Hybrid-Technik) oder die robotergestützte Anlage der technisch sehr anspruchsvollen Zirkularstapleranastomose. Als minimal invasiv auch ohne Roboterassistenz relativ einfach machbare Alternative zeigen wir die intrathorakale Seit-zu-Seit Ösophagogastrostomie in Linearstapler-Technik. Operationstechnik Der abdominelle Teil erfolgt in French-Lagerung. Nach Dissektion des Omentum majus entlang der gastroepiploischen Arkade und des Milzhilus sowie Trennung des Omentum minus 6 cm präpylorisch wird ein 4,5 cm breiter Magenschlauch in Linearstaplertechnik gebildet. Dann erfolgt die systematische abdominale und transmediastinale Lymphadenekotmie. Nach Umlagerung des Patienten in Links-Seitenlage wird die Lymphadenektomie thorakal komplettiert und das Präparat entfernt. Die Seit-zu-Seit Ösophagogastrostomie beginnt mit der Inzision des Ösophagusstumpfes. Dann wird der Magenschlauch mesonah 5 cm vom oralen Absetzungsrand inzidiert und ein Linearstapler über 3 cm in die beiden Inzisionen eingebracht und abgefeuert. Die verbleibende Öffnung wird mit einer fortlaufenden Naht modifiziert zweireihig quer verschlossen. Diskussion Die Seit-zu-Seit Ösophagogastrostomie in Linearstapler-Technik scheint eine einfache und sichere Alternative für die Rekonstruktion nach minimal invasiver Ösophagektomie zu sein. Die Methode wird aktuell in einer randomisiert kontrollierten Studie untersucht.

This study aimed to evaluate changes in body tissue composition with obesity surgery regarding visceral fat, subcutaneous fat, and skeletal muscle. Prospective non-randomized single-center cohort study Whole-body magnetic resonance imaging (MRI) measured volumes of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), and skeletal muscle (SM) in 31 patients with laparoscopic sleeve gastrectomy (LSG, 20) or Roux-en-Y gastric bypass (RYGB, 11) preoperatively, at three- and 12-months follow-up. Body mass index (BMI) went down from 45.2 ± 6.5 preoperatively to 37.2 ± 5.6 (p

Objective: Extracellular matrix remodeling is required for adipose expansion under increased caloric intake. In turn, inhibited expandability due to aberrant collagen deposition promotes insulin resistance and progression towards the metabolic syndrome. An emerging role for the small leucine-rich proteoglycan Lumican in metabolically driven nonalcoholic fatty liver disease sparks an interest in further understanding its role in diet-induced obesity and metabolic complications.Methods: Whole body ablation of Lumican (Lum(-/-)) gene and adeno-associated virus-mediated over-expression were used in combination with control or high fat diet to assess energy balance, glucose homeostasis as well as adipose tissue health and remodeling.Results: Lumican was found to be particularly enriched in the stromal cells isolated from murine gonadal white adipose tissue. Likewise murine and human visceral fat showed a robust increase in Lumican as compared to fat from the subcutaneous depot. Lumican null female mice exhibited moderately increased fat mass, decreased insulin sensitivity and increased liver triglycerides in a diet-dependent manner. These changes coincided with inflammation in adipose tissue and no overt effects in adipose expandability, i.e. adipocyte formation and hypertrophy. Lumican over-expression in visceral fat and liver resulted in improved insulin sensitivity and glucose clearance.Conclusions: These data indicate that Lumican may represent a functional link between the extracellular matrix, glucose homeostasis, and features of the metabolic syndrome. (C) 2018 The Authors. Published by Elsevier GmbH.