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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

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.

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.

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.

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.

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.

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

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.

Morbidly obese patients have lower quality of life (QOL) when compared to the general population. So far, no studies have compared gender and procedural differences in gastrointestinal QOL after sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB). Patients before and after bariatric surgery completed the gastrointestinal quality of life index (GIQLI), a 36-item questionnaire with five subscores. Differences between SG and RYGB were analyzed, as were gender differences. Some 186 patients completed the questionnaire, 75 before surgery, 56 within 6 months, and 55 within 24 months after surgery. Total GIQLI score and all subscores were significantly better within 24 months after surgery (80.9 ± 19.2 vs. 109.2 ± 17.7, p

Background: Obesity surgery has proven successful for weight loss and the resolution of comorbidities. There is, however, little evidence on its success and the risk of complications when considering age of onset of obesity (AOO), years of obesity (YOO), preoperative body mass index (BMI), Edmonton obesity staging system (EOSS) score, and age as possible predictors of weight loss, the resolution of comorbidities, and the risk of complications. Methods: Patients who underwent Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) from a prospective database were analyzed. Multiple regression analyses were used to predict comorbidities and their resolution, percentage excess weight loss (%EWL) and total weight loss (%TWL) 12 months after surgery, and the risk of complications using the predictors AOO, YOO, age, EOSS, and BMI. Results: 180 patients aged 46.8 ± 11.1 years with a preoperative BMI 49.5 ± 7.5 were included. The number of preoperative comorbidities was higher with older age (β = 0.054; p = 0.023) and a greater BMI (β = 0.040; p = 0.036) but was not related to AOO and YOO. Patients with AOO as a child or adolescent were more likely to have an EOSS score of ≥2. Greater preoperative BMI was negatively associated with %EWL (β = –1.236; p < 0.001) and older age was negatively associated with %TWL (β = –0.344; p = 0.020). Postoperative complications were positively associated with EOSS score (odds ratio [OR] 1.147; p = 0.042) and BMI (OR 1.010; p = 0.020), but not with age. AOO and YOO were not related to postoperative outcome. Conclusion: Greater BMI was associated with a lower %EWL and age was associated with a low %TWL. YOO and AOO did not influence outcome. Age, BMI, and EOSS score were the most important predictors for risk and success after obesity surgery. Surgery should be performed early enough for optimal outcomes.

Although research has shown that metabolic surgery is superior to medical therapy in terms of glycemic control and other cardiovascular risk factors, it remains unclear whether these beneficial effects ultimately result in a reduced incidence of macrovascular complications or mortality in patients with type 2 diabetes.This meta-analysis assesses the impact of metabolic surgery versus medical therapy on mortality and macrovascular complications in patients with type 2 diabetes.Academic centers in the United States, Europe, and Asia.An unrestricted systematic literature search of MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials was performed. Randomized controlled trials (RCTs), case-control trials, and cohort studies comparing the effect of metabolic surgery on mortality and the incidence of diabetes-associated macrovascular complications to a medically treated control group were identified. The last search was performed on June 15, 2018.The literature search yielded 3721 potentially eligible articles. Nineteen studies (6 RCTs, 13 nonrandomized studies) were ultimately included. Metabolic surgery was found to be associated with reduced mortality (odds ratio .34, 95% confidence interval [.25-.46], P.00001) and macrovascular complication rates (odds ratio .38, 95% confidence interval [.22-.67], P = .0008).Because metabolic surgery is associated with lower mortality and macrovascular complication rates than medical therapy, it seems to be the superior treatment choice for patients with type 2 diabetes. Additional, high-quality RCTs with adequate follow-up comparing state of the art surgical and medical therapies including glifozins and liraglutide are nevertheless needed to identify which patients would benefit most from metabolic surgery.

Most antidiabetic drugs treat disease symptoms rather than adipose tissue dysfunction as a key pathogenic cause in the metabolic syndrome and type 2 diabetes. Pharmacological targeting of adipose tissue through the nuclear receptor PPARg, as exemplified by glitazone treatments, mediates efficacious insulin sensitization. However, a better understanding of the context‐specific PPARg responses is required for the development of novel approaches with reduced side effects. Here, we identified the transcriptional cofactor Cited4 as a target and mediator of rosiglitazone in human and murine adipocyte progenitor cells, where it promoted specific sets of the rosiglitazone‐dependent transcriptional program. In mice, Cited4 was required for the proper induction of thermogenic expression by Rosi specifically in subcutaneous fat. This phenotype had high penetrance in females only and was not evident in beta‐adrenergically stimulated browning. Intriguingly, this specific defect was associated with reduced capacity for systemic thermogenesis and compromised insulin sensitization upon therapeutic rosiglitazone treatment in female but not male mice. Our findings on Cited4 function reveal novel unexpected aspects of the pharmacological targeting of PPARg.

The transient activation of inflammatory networks is required for adipose tissue remodeling including the “browning” of white fat in response to stimuli such as β3-adrenergic receptor activation. In this process, white adipose tissue acquires thermogenic characteristics through the recruitment of so-called beige adipocytes. We investigated the downstream signaling pathways impinging on adipocyte progenitors that promote de novo formation of adipocytes. We showed that the Jak family of kinases controlled TGFβ signaling in the adipose tissue microenvironment through Stat3 and thereby adipogenic commitment, a function that was required for beige adipocyte differentiation of murine and human progenitors. Jak/Stat3 inhibited TGFβ signaling to the transcription factors Srf and Smad3 by repressing local Tgfb3 and Tgfb1 expression before the core transcriptional adipogenic cascade was activated. This pathway cross-talk was triggered in stromal cells by ATGL-dependent adipocyte lipolysis and a transient wave of IL-6 family cytokines at the onset of adipose tissue remodeling induced by β3-adrenergic receptor stimulation. Our results provide insight into the activation of adipocyte progenitors and are relevant for the therapeutic targeting of adipose tissue inflammatory pathways.

Hypothermia is a well-known risk factor for postoperative complications because it prolongs the monocyte inflammatory response. The purpose of this study was to investigate whether temperature-activated ion channels (transient receptor protein channels [TRP] A1 and V1) mediate the effects of temperature on monocytes.Primary human monocytes were isolated and stimulated with lipopolysaccharide at 32°C or 39°C. RNA was isolated for analysis of microRNA (miR)-155 expression, and cytokines in the supernatant were measured with an enzyme-linked immunosorbent assay. Specific inhibitors of TRPA1 (HC- 030031) and a specific activator of TRPV1 (capsaicin) were used to block or activate TRPA1 and TRPV1, respectively. Statistical analysis was performed using the Wilcoxon signed-rank test.TRPM8 mRNA was not expressed in primary human monocytes, whereas TRPA1 and TRPV1 were expressed. TRPV1 mRNA expression was suppressed at 32°C but not at 39°C. TRPA1 was induced strongly at 32°C and 39°C. Immunofluorescence microscopy confirmed that monocytes express TRPA1 and TRPV1 on their cell surface. Interleukin-10 secretion was increased by blocking TRPA1 (77.8 ± 3 2.8 pg/mL) and activating TRPA1 (79.4 ± 16.1 pg/mL) after 24 hours at 32°C (control 37.4 ± 17.1 pg/mL, P .05). At 36 hours, tumor necrosis factor secretion was decreased after TRPA1 blockade (2,321 ± 439 pg/mL) and TRPV1 activation (2,137 ± 411 pg/mL) compared with control (2,567 ± 495 pg/mL, P .05). Furthermore, miR-155 expression also was suppressed at 24 hours by TRPA1 blockade and TRPV1 activation (both P .05). Silencing of TRPA1 normalized monocyte IL-10 secretion at 32°C.These results demonstrate that hypothermia mediates its effects on monocytes through TRPA1. Blockade of TRPA1 or activation of TRPV1 may be used to modify the effects of hypothermia on the monocyte inflammatory response.

The learning curve to achieve competency in laparoscopic donor nephrectomy (LDN) is poorly outlined. Online databases were searched for training in LDN. Abstracts and manuscripts were excluded if they did not address introduction of a laparoscopic technique for donor nephrectomy. Relevant manuscripts were reviewed for surgical technique, use of animal models, co-surgeons, surgeon specialty and training, institution type/volume, and assessment of training method. Forty-four met inclusion criteria, with 75% describing the evolution from open to LDN. Eighty-two percent were from academic centers, and 36% were from centers performing

Background Diabetic neuropathy is common in type 2 diabetic patients (T2DM) but tight glycemic control does not improve the symptoms. In contrast, Roux-Y gastric bypass (RYGB) has a positive effect on active neuropathic symptoms, independent from glycemic control. The purpose of the present study was to identify potential mechanisms of improved diabetic neuropathic symptoms after RYGB. Methods A prospective cohort of 20 patients with insulin-dependent T2DM and BMI 2 were treated with RYGB. Nineteen patients had complete follow-up. Fasting glucose, HbA1c (glycated hemoglobin), markers for nitrosative, carbonyl, and oxidative stress (nitrotyrosine, carboxylated-lysine (CML), methylglyoxal, oxidized low-density-lipoprotein (oxLDL)) as well as Neuropeptid Y and Neurokinin A were investigated over 12 months. Neuropathy was assessed using the Neuropathy Deficit Score (NDS). Results The preoperative NDS improved within twelve months (5.1±0.6 to 2.6±0.4, P = .010). Fasting glucose and HbA1c also improved compared to preoperative values (201.1±16.6 mg/dL to 128±8.7 mg/dL, P = .004 and 8.5±0.3% (53±3.3 mmol/mol) to 7±0.3% (67±3.3 mmol/mol), P = .001, respectively). Nitrotyrosine, CML, and methylglyoxal all 3 decreased postoperatively (1067.3±266.9 nM to 355.8±36.4 nM, P = .003; 257.1±10.2 ng/ml to 215.3±18.3 ng/ml, P = .039; 402.3±3.9 nM to 163.4±10.3 nM, P = .002). OxLDL remained unchanged. Fasting glucose and HbA1c did not correlate with improved neuropathy. The decrease in nitrotyrosine correlated with improvement in the NDS after 6 and twelve months (r = .9 , P P = .03). The decrease in methylglyoxal after 6 months correlated with decrease in NDS after twelve months (r = 0.897, P = .003). Conclusion RYGB seems to improve oxidative, nitrosative and carbonyl stress, known to have a causal role in diabetic neuropathy.

To compare surgical versus medical treatment of type 2 diabetes mellitus (T2DM) remission and comorbidities in patients with a body mass index (BMI) less than 35 kg/m2.Obesity surgery can achieve remission of T2DM and its comorbidities. Metabolic surgery has been proposed as a treatment option for diabetic patients with BMI less than 35 kg/m2 but the efficacy of metabolic surgery has not been conclusively determined.A systematic literature search identified randomized (RCT) and nonrandomized comparative observational clinical studies (OCS) evaluating surgical versus medical T2DM treatment in patients with BMI less than 35 kg/m2. The primary outcome was T2DM remission. Additional analyses comprised glycemic control, BMI, HbA1c level, remission of comorbidities, and safety. Random effects meta-analyses were calculated and presented as weighted odds ratio (OR) or mean difference (MD) with 95% confidence intervals (95% CI).Five RCTs and 6 OCSs (706 total T2DM patients) were included. Follow-up ranged from 12 to 36 months. Metabolic surgery was associated with a higher T2DM remission rate (OR: 14.1, 95% CI: 6.7-29.9, P0.001), higher rate of glycemic control (OR: 8.0, 95% CI: 4.2-15.2, P0.001) and lower HbA1c level (MD: -1.4%, 95% CI -1.9% to -0.9%, P0.001) than medical treatment.-5.5 kg/m2, 95% CI: -6.7 to -4.3 kg/m2, P0.001), rate of arterial hypertension (OR: 0.25, 95% CI: 0.12-0.50, P0.001) and dyslipidemia (OR: 0.21, 95% CI: 0.10-0.44, P0.001) were lower after surgery.Metabolic surgery is superior to medical treatment for short-term remission of T2DM and comorbidities. Further RCTs should address the long-term effects on T2DM complications and mortality.

Bariatric surgery gains attention as a potential treatment for non-alcoholic fatty liver disease (NAFLD). The present study aimed to evaluate improvement of NAFLD after the two most common bariatric procedures with validated non-invasive instruments. N = 100 patients scheduled for laparoscopic sleeve gastrectomy (LSG) or Roux-en-Y gastric bypass (RYGB) were included. NAFLD was evaluated preoperatively and postoperatively with liver stiffness measurement by transient elastography and laboratory-based fibrosis scores. Clinical data included body mass index (BMI), total weight loss (%TWL), excess weight loss (%EWL), age, gender, comorbidities, and the Edmonton obesity staging system (EOSS). There were significant improvements of BMI, %TWL, %EWL, and EOSS after bariatric surgery. Liver stiffness was significantly improved from pre- to postoperative (12.9 ± 10.4 vs. 7.1 ± 3.7 kPa, p

Squamous cell cancer (SCC) is a rare histological subtype of rectal cancer. It is unclear whether SCC should be treated by multimodal therapy, including surgery, or by chemoradiation alone. The objective of the study was to define an optimal treatment strategy. Patients with rectal cancer and SCC histology were identified in the Surveillance Epidemiology and End Results Database between 1990 and 2013. According to treatment, three groups were defined: radiotherapy and surgery (RT/SX), radiotherapy (RT), and surgery (SX). Overall survival (OS) and disease-specific survival (DSS) for localized, regional, and distant disease were assessed using a multivariable Cox regression model. Out of 856,435 colorectal cancer patients, 1747 with SCC of the rectum were eligible. Four hundred and fifty-five were treated with RT/SX, 994 with RT, and 298 with SX. Adjusted hazard ratios (HR) did not differ for OS and DSS in localized disease. In regional disease, OS and DSS were improved for RT/SX compared to RT (HR 0.751, 95% CI 0.566–0.997, P = 0.048 and HR 0.679, 95% CI 0.478–0.966, P = 0.031). In distant disease, OS and DSS were not different. Multimodal therapy including surgery improved OS and DSS compared to receiving a treatment without surgery for regional disease in rectal SCC. No difference was observed in localized and distant disease. The findings contradict with recent reports favoring definitive chemoradiation.

BACKGROUND The organ procurement network recommends a surgeon record 15 cases as surgeon or assistant for laparoscopic donor nephrectomies (LDN) prior to independent practice. The literature suggests that the learning curve for improved perioperative and patient outcomes is closer to 35 cases. In this article, we describe our development of a model utilizing fresh tissue and objective, quantifiable endpoints to document surgical progress, and efficiency in each of the major steps involved in LDN. MATERIALS AND METHODS Phase I of model development focused on the modifications necessary to maintain visualization for laparoscopic surgery in a human cadaver. Phase II tested proposed learner-based metrics of procedural competency for multiport LDN by timing procedural steps of LDN in a novice learner. RESULTS Phases I and II required 12 and nine cadavers, with a total of 35 kidneys utilized. The following metrics improved with trial number for multiport LDN: time taken for dissection of the gonadal vein, ureter, renal hilum, adrenal and lumbrical veins, simulated warm ischemic time (WIT), and operative time. CONCLUSION Human cadavers can be used for training in LDN as evidenced by improvements in timed learner-based metrics. This simulation-based model fills a gap in available training options for surgeons.

The effects of bariatric surgery on excess weight loss (EWL) and comorbidities are proven. Still, a significant number of patients prefer conservative therapy (ConsP). The goal of this study was to examine why ConsP and patients awaiting bariatric surgery (SurgP) choose which therapy, and to define the differences in their expectations. Prospective study, 1 university hospital, 1 general hospital, Germany. ConsP and SurgP were asked to complete a questionnaire. Statistical analysis including all patients and a BMI-matched cohort was performed using the chi-square and Wilcoxon rank-sum test. Overall, 151 patients participated in this study (50 ConsP, 101 SurgP, 69.4% females). The mean age was 41.1 years (SD ± 12.2 years). ConsP had a significant lower body mass index (BMI, 44.7 kg/m2 vs. 49.3 kg/m2, p

We have reported a new phenomenon in acute wound healing following the use of intracellular ATP delivery—extremely rapid tissue regeneration, which starts less than 24 h after surgery, and is accompanied by massive macrophage trafficking, in situ proliferation, and direct collagen production. This unusual process bypasses the formation of the traditional provisional extracellular matrix and significantly shortens the wound healing process. Although macrophages/monocytes are known to play a critical role in the initiation and progression of wound healing, their in situ proliferation and direct collagen production in wound healing have never been reported previously. We have explored these two very specific pathways during wound healing, while excluding confounding factors in the in vivo environment by analyzing wound samples and performing in vitro studies. The use of immunohistochemical studies enabled the detection of in situ macrophage proliferation in ATP-vesicle treated wounds. Primary human macrophages and Raw 264.7 cells were used for an in vitro study involving treatment with ATP vesicles, free Mg-ATP alone, lipid vesicles alone, Regranex, or culture medium. Collagen type 1α 1, MCP-1, IL-6, and IL-10 levels were determined by ELISA of the culture supernatant. The intracellular collagen type 1α1 localization was determined with immunocytochemistry. ATP-vesicle treated wounds showed high immunoreactivity towards BrdU and PCNA antigens, indicating in situ proliferation. Most of the cultured macrophages treated with ATP-vesicles maintained their classic phenotype and expressed high levels of collagen type 1α1 for a longer duration than was observed with cells treated with Regranex. These studies provide the first clear evidence of in situ macrophage proliferation and direct collagen production during wound healing. These findings provide part of the explanation for the extremely rapid tissue regeneration, and this treatment may hold promise for acute and chronic wound care.

Hypothermia occurs in as many as 7% of elective colorectal operations and is an underestimated risk factor for complications and death. Rewarming of hypothermic patients alone is not sufficient to prevent such adverse events. We investigated the outcomes of patients who became hypothermic (35°C) after elective operations and compared them with closely matched, nonhypothermic operative patients to better define the impact of hypothermia on surgical outcomes, as well as to identify independent risk factors for hypothermia.We queried the University HealthSystem Consortium (UHC) database for elective operative patients who became unintentionally hypothermic from October 2008 to March 2012, and identified 707 patients. Exclusion criteria were deliberate hypothermia, age18 years, or death on day of admission. Separately, to validate the accuracy of hypothermia coding, we reviewed the hospital charts of all University of Louisville Hospital patients with hypothermia whose data were submitted to UHC.All patients from UHC with a code for hypothermia were indeed unintentionally hypothermic. Hypothermic patients undergoing elective operations experienced a 4-fold increase in mortality (17.0% vs 4.0%; P.001) and a doubled complication rate (26.3% vs 13.9%; P.001), in which sepsis and stroke increased the most. Several independent risk factors for hypothermia were amenable to preoperative improvement: anemia, chronic renal impairment, and unintended weight loss. Severity of illness on admission, age65 years, male sex, and neurologic disorders also were risk factors.Hypothermia is associated with an increased rate of mortality and complications. Preventive treatment of these risk factors before operation and aggressive warming measures in the "at risk" population may decrease hypothermia-related morbidity and mortality in elective operations. Randomized-controlled trials should be conducted to evaluate the impact of aggressive warming measures in the at-risk population.

Stops at nontrauma centers for severely injured patients are thought to increase deaths and costs, potentially because of unnecessary imaging and indecisive/delayed care of traumatic brain injuries (TBIs).We studied 754 consecutive blunt trauma patients with an Injury Severity Score greater than 20 with an emphasis on 212 patients who received care at other sites en route to our level 1 trauma center.Referred patients were older, more often women, and had more severe TBI (all P.05). After correction for age, sex, and injury pattern, there was no difference in the type of TBI, Glasgow Coma Scale (GCS) upon arrival at the trauma center, or overall mortality between referred and directly admitted patients. GCS at the outside institution did not influence promptness of transfer.Interhospital transfer does not affect the outcome of blunt trauma patients. However, the unnecessarily prolonged stay of low GCS patients in hospitals lacking neurosurgical care is inappropriate.

Objective This article reviews the current understanding of transient receptor potential ion channels (TRP channels) in health and disease. Background Transient receptor potential ion channels are a group of 27 channels that are expressed in all tissues. These channels play important roles in surgically important problems, such as chronic pain, susceptibility to infection, hypothermia, and some cancers. Methods A literature search was performed. This review focuses on the role of TRP channels in a few surgically important disease processes, such as pain, inflammation, airway diseases, and malignant melanomas. In addition, we discuss some of the structural properties that are important for the activation of TRP channels. Results TRPA1 and TRPV1 are expressed on pain fibers and play an important role in the development of chronic pain, such as chemotherapy-related neuropathic pain. Deletion of TRPA1 and TRPV1 suppresses the development of chronic pain, and blockers of TRPA1 and TRPV1 show promise as a new class of painkillers. Furthermore, several TRP channels are expressed on immune cells. Macrophages express at least 3 different TRP channels, and the properly balanced activation of all these channels together allows normal macrophage function. Deletion of any of these channels results in impaired macrophage function and increased susceptibility to infection. Because several of these TRP channels on macrophages are temperature sensitive, they may comprise the link for hypothermia-related infectious complications in trauma, and to a lesser degree, in elective surgical patients. Conclusions Transient receptor potential ion channels are involved in several surgically important disease processes. Activation or blockade of these channels offers new therapeutic opportunities. Pharmacologic activation or blockade of TRP channels may offer new treatment options in surgical patients for the management of pain and infections.

Trauma patients frequently have serious chest injuries. Retained hemothoraces and persistent pneumothoraces are among the most frequent complications of chest injuries which may lead to major, long-term morbidity and mortality if these complications are not recognized and treated appropriately. Video-assisted thoracoscopy (VATS) is a well-established technique in surgical practice. The usefulness of VATS for treatment of complications after chest trauma has been demonstrated by several authors. However, there is an ongoing debate about the optimal timing of VATS. A computerized search was conducted which yielded 450 studies reporting on the use of VATS for thoracic trauma. Eighteen of these studies were deemed relevant for this review. The quality of these studies was assessed using a check-list and the PRISMA guidelines. Outcome parameters were successful evacuation of the retained hemothorax or treatment of other complications as well as reduction of empyema rate, length of hospital stay, and hospital costs. There was only one randomized trial and two prospective studies. Most studies report case series of institutional experiences. VATS was found to be very successful in evacuation of retained hemothoraces and seems to reduce the empyema rate subsequently. Furthermore, the length of hospital stay and costs can be drastically reduced with the early use of VATS. Early VATS is an effective treatment for retained hemothoraces or other complications of chest trauma. We propose a clinical pathway, in which VATS is used as an early intervention in order to prevent serious complications such as empyemas or trapped lung.

Background The objective of this study was to evaluate the potential benefits of immunonutrition in major abdominal surgery with special regard to subgroups and influence of bias. Methods A systematic literature search from January 1985 to July 2015 was performed in MEDLINE, Embase and CENTRAL. Only RCTs investigating immunonutrition in major abdominal surgery were included. Outcomes evaluated were mortality, overall complications, infectious complications and length of hospital stay. The influence of different domains of bias was evaluated in sensitivity analyses. Evidence was rated according to the GRADE Working Group grading of evidence. Results A total of 83 RCTs with 7116 patients were included. Mortality was not altered by immunonutrition. Taking all trials into account, immunonutrition reduced overall complications (odds ratio (OR) 0·79, 95 per cent c.i. 0·66 to 0·94; P = 0·01), infectious complications (OR 0·58, 0·51 to 0·66; P < 0·001) and shortened hospital stay (mean difference –1·79 (95 per cent c.i. –2·39 to –1·19) days; P < 0·001) compared with control groups. However, these effects vanished after excluding trials at high and unclear risk of bias. Publication bias seemed to be present for infectious complications (P = 0·002). Non-industry-funded trials reported no positive effects for overall complications (OR 1·13, 0·88 to 1·46; P = 0·34), whereas those funded by industry reported large effects (OR 0·66, 0·48 to 0·91; P = 0·01). Conclusion Immunonutrition after major abdominal surgery did not seem to alter mortality (GRADE: high quality of evidence). Immunonutrition reduced overall complications, infectious complications and shortened hospital stay (GRADE: low to moderate). The existence of bias lowers confidence in the evidence (GRADE approach).

Unintentional hypothermia is a well-described risk factor for death and complications after elective and emergency surgery. The molecular mechanisms by which hypothermia exerts its detrimental effects are not well understood. Differences in cytokine production and the overall cell function have been reported under hypothermic conditions. We investigated the effect of a range of clinically relevant temperatures on cytokine production and microRNA (miRNA) expression in a whole-blood model. We found that there was a wide variation in tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and IL-10 production among different subjects, ranging from low to high TNF-α producers. The intersubject variation can also be found on the transcriptional level: high producers had higher upregulation of TNF-α messenger RNA than intermediate and low producers. This variation in TNF-α was reproducible in each individual. Temperature seems to modulate TNF-α production among these different groups. miRNA expression was modulated by temperature. miRNA-181a might control, or be a part of the mechanism which controls, TNF-α production. However, an analysis of whole-leukocyte RNA does not allow the investigation of mechanisms in a specific leukocyte subpopulation such as monocytes, because these changes may be concealed by miRNA expression changes in the other leukocyte subsets. In conclusion, TNF-α, IL-6, and IL-10 production is highly variable among different persons, but temperature affects the expression of miRNAs, which may consequently alter the production of TNF-α.

Lung cancer is the most lethal cancer due to late detection in advanced stages; early diagnosis of lung cancer allows surgical treatment and improves the outcome. The prevalence of gastroesophageal reflux-related adenocarcinomas of the esophagus is increasing; repetitive surveillance endoscopies are necessary to detect development of cancer. A blood-based biomarker would simplify the diagnosis and treatment of both diseases. MicroRNAs (miRNAs) are short RNA strands that interfere with protein production. miRNAs play pivotal roles in cell homeostasis, and dysregulation of miRNAs can lead to the development of cancer. miRNAs can be found in all body fluids and have been proposed to serve as messengers between closely localized cells but also distant organs. Cancer cells actively secrete miRNAs, and these miRNA profiles can be found in blood. We outline, here, how these miRNAs may aid in diagnosis and treatment of lung and esophageal cancers, as well as their apparent limitations.

MICRORNAS ARE VERY SMALL RNA molecules that are approximately 22 nucleotides in length. These microRNAs do not encode proteins; therefore, they are part of the family of noncoding RNA molecules. Because of their short length, they have been ignored for some time, despite being first described in 1993. MicroRNAs have started to gain interest after the discovery by Fire and Mello that these short, double-stranded RNAs, known as silencing RNA (siRNA), would inhibit quite strongly the protein translation after injection into cells of Caenorhabditis elegans. For this contribution, they received The Nobel Prize in Physiology or Medicine 2006. All of a sudden, these earlier described (but so far not understood) small RNA molecules seemed to have a profound impact on cell function by inhibiting protein translation. Indeed, microRNAs exist in all animals and plants, and their effect on the inhibition of protein translation has been demonstrated in all cells investigated to date. In addition to the classic regulation of protein production via upregulation ofmessenger RNA (mRNA) transcription, there exists an additional system regulating protein production by microRNAs. Subsequent research revealed the profound impact of microRNAs on cell development and cell function in health and disease. This short review provides a concise overview of the function ofmicroRNAs with an emphasis on clinical application for diagnosis, prognosis determination and, hopefully soon, therapeutic applications. Because of the huge amount of newly

Although all bariatric procedures improve non-alcoholic fatty liver disease (NAFLD) in metabolically sick obese patients, it remains unclear whether different procedures achieve similar effects. Sleeve gastrectomy (SG) and Roux-Y-gastric bypass (RYGB) were compared for their effects on liver function tests (LFT) and glycemic control in a highly selected group of metabolically sick obese patients with both elevated alanine aminotransferase (ALT), a common marker for NAFLD and type 2 diabetes mellitus (T2DM). Thirty-four obese patients with a body mass index (BMI) >35 kg/m2, ALT > 35 U/L, and T2DM were well-matched from a prospective database and retrospectively analyzed. Seventeen patients each underwent RYGB and SG, respectively. The effects on LFT and glycemic control were evaluated over 12 months. Both procedures significantly lowered ALT and aspartate aminotransferase (AST) after 12 months, but SG improved both LFT significantly better than RYGB (ALT 17.8 ± 8.8 vs. 31.1 ± 11.2 U/L, p = 0.003; AST 17.0 ± 8.8 vs. 24.3 ± 7.5 U/L, p = 0.004). In contrast to RYGB, SG normalized elevated ALT levels completely (41 vs. 0 %, p = 0.007). Both SG and RYGB improved insulin resistance, glycemic control, and reduced the need of insulin significantly without any difference between the procedures. SG appears to improve LFT better than RYGB in well-matched obese patients with both elevated ALT and T2DM. This suggests that SG may have a better effect on NAFLD than RYGB with similar effects on glycemic control. The present findings should be verified in randomized controlled trials to obtain further evidence for the decision-making on the most appropriate bariatric procedure for metabolically sick patients.

Due to its reliable effects on type 2 diabetes mellitus (T2DM) remission, Roux-en-Y gastric bypass (RYGB) has recently been investigated as a treatment option for nonseverely obese patients with T2DM (body mass index (BMI)35 kg/m(2)). The purpose of this study was to investigate whether RGYB induces malnutrition of macro- and micronutrients within 24 months in these patients.A prospective cohort of 20 patients with longstanding, insulin-dependent T2DM and a BMI of 25-35 kg/m(2) were treated with RYGB. The patients were supplemented with over-the-counter, multivitamin, and micronutrient supplements. Serum concentrations of albumin, vitamins, and trace elements, hemoglobin, and bone density were measured preoperatively and over a 24-month period (DRKS00004605).RYGB did not result in underweight or protein malnutrition. No new onset of deficiencies of water- or fat-soluble vitamins developed over the study period. However, serum selenium, zinc, and ferritin decreased significantly (selenium, 1.17 ± 0.13 to 0.89 ± 0.11 μmol/l, p = 0.018; zinc, 13.9 ± 0.5 to 10.8 ± 0.5 μmol/l, p = 0.012; ferritin, 171.7 ± 26.9 to 31.8 ± 11.2 μg/l, p = 0.018). Hemoglobin remained stable. Vitamin D (13.7 ± 1.8 to 19.1 ± 1.1 ng/ml, p = 0.017) and osteocalcin (15.3 ± 1.7 to 25.4 ± 2.7 ng/ml, p = 0.025) rose significantly, whereas the parathyroid hormone remained stable. Despite increased bone formation, bone density decreased (T score hip, 0.15 ± 0.25 to -0.71 ± 0.34, p = 0.005) resulting in a significant increase in osteopenia rates (18 to 50 %, p = 0.046).This is the first prospective cohort to investigate malnutrition after RYGB in nonseverely obese patients. These patients are at risk of developing iron, selenium, and zinc deficiencies within 24 months, as well as osteopenia despite an increase in bone formation.

Current guidelines advocate that all rectal cancer patients with American Joint Committee on Cancer (AJCC) stages II and III disease should be subjected to neoadjuvant therapy. However, improvements in surgical technique have resulted in single-digit local recurrence rates with surgery only. Operative, postoperative, and oncological outcomes of patients with and without neoadjuvant therapy were compared between January 2002 and December 2013. For this purpose, all patients resected with low anterior rectal resection (LAR) and total mesorectal excision (TME) who had or had not been irradiated were identified from the authors’ prospectively maintained database. Patients who were excluded were those with high rectal cancer or AJCC stage IV disease; in the surgery-only group, patients with AJCC stage I disease or with pT4Nx rectal cancer; and in the irradiated patients, patients with ypT4Nx or cT4Nx rectal cancer. Overall, 454 consecutive patients were included. A total of 342 (75 %) patients were irradiated and 112 (25 %) were not irradiated. Median follow-up for all patients was 48 months. Among patients with and without irradiation, pathological circumferential resection margin positivity rates (2.9 vs. 1.8 %, p = 0.5) were not different. At 5 years, in irradiated patients compared with surgery-only patients, the incidence of local recurrence was decreased (4.5 vs. 3.8 %, p = 0.5); however, systemic recurrences occurred more frequently (10 vs. 17.8 %, p = 0.2). Irradiation did not affect overall or disease-free survival (neoadjuvant treatment vs. surgery-only: 84.9 vs. 88.2 %, p = 0.9; 76 vs. 79.1 %, p = 0.8). The current study adds to the growing evidence that suggests a selective rather than generalized indication for neoadjuvant treatment in stages II and III rectal cancer.

Objective To investigate whether warming to normal body temperature or to febrile range temperature (39°C) is able to reverse the detrimental effects of hypothermia. Background Unintentional intraoperative hypothermia is a well-described risk factor for surgical site infections but also sepsis. We have previously shown that hypothermia prolongs the proinflammatory response whereas normothermia and especially febrile range temperature enhance the anti-inflammatory response. Methods Primary human monocytes were isolated from healthy volunteers. After stimulation with LPS (Lipopolysaccharide), the monocytes were exposed to 32°C for 3 hours or 6 hours and then warmed at either 37°C or 39°C for the remaining 33 hours or 36 hours, respectively. Tumor necrosis factor α, interleukin 10, and the expression of miR-155 and miR-101 were assessed at 24 hours and 36 hours. Results Warming to 37°C does not normalize monocyte cytokine secretion within 36 hours, whereas warming to 39°C partially reverses the effects of hypothermia on monocyte function. Both miR-155 and miR-101 were suppressed after the warming episode. However, 39°C had a stronger suppressive effect than 37°C. The duration of hypothermia and the warming temperature seem to be critical for a full reversibility of the effects of hypothermia. Conclusion Warming to normal body temperature (37°C) does not restore normal monocyte function in vitro. These data suggest that hypothermic patients should be warmed to febrile range temperatures. Furthermore, febrile range temperatures should be investigated as a means to modulate the inflammatory response in patients with systemic infections.