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Cold-stimulated adaptive thermogenesis in brown adipose tissue (BAT) to increase energy expenditure is suggested as a possible therapeutic target for the treatment of obesity. We have recently shown high prevalence of BAT in adult humans, which was inversely related to body mass index (BMI) and body fat percentage (BF%), suggesting that obesity is associated with lower BAT activity. Here, we examined BAT activity in morbidly obese subjects and its role in cold-induced thermogenesis (CIT) after applying a personalized cooling protocol. We hypothesize that morbidly obese subjects show reduced BAT activity upon cold exposure. After applying a personalized cooling protocol for maximal non-shivering conditions, BAT activity was determined using positron-emission tomography and computed tomography (PET-CT). Cold-induced BAT activity was detected in three out of 15 morbidly obese subjects. Combined with results from lean to morbidly obese subjects (n = 39) from previous study, the collective data show a highly significant correlation between BAT activity and body composition (P<0.001), respectively explaining 64% and 60% of the variance in BMI (r = 0.8; P<0.001) and BF% (r = 0.75; P<0.001). Obese individuals demonstrate a blunted CIT combined with low BAT activity. Only in BAT-positive subjects (n = 26) mean energy expenditure was increased significantly upon cold exposure (51.5±6.7 J/s versus 44.0±5.1 J/s, P = 0.001), and the increase was significantly higher compared to BAT-negative subjects (+15.5±8.9% versus +3.6±8.9%, P = 0.001), indicating a role for BAT in CIT in humans. This study shows that in an extremely large range of body compositions, BAT activity is highly correlated with BMI and BF%. BAT-positive subjects showed higher CIT, indicating that BAT is also in humans involved in adaptive thermogenesis. Increasing BAT activity could be a therapeutic target in (morbid) obesity.

Background Single-incision laparoscopic cholecystectomy (SILC) might maximize the advantages of laparoscopic cholecystectomy (LC) by reducing postoperative pain and improving cosmesis. However, the safety and feasibility of SILC has not yet been established. This study assesses safety, patient reported outcome measures and feasibility of SILC versus conventional LC. Methods Literature search for RCT’s comparing SILC with conventional LC in gallstone-related disease was performed in PubMed and Embase. The conventional LC was defined as two 10-mm and two 5-mm ports. Study selection was done according to predefined criteria. Two reviewers assessed the risk of bias. Pooled outcomes were calculated for adverse events, pain, cosmesis, quality of life and feasibility using fixed-effect and random-effects models. Results Nine RCT’s were included with total of 860 patients. No mortality was observed. More mild adverse events (RR 1.55; 95% CI 0.99–2.42) and significantly more serious adverse events (RR 3.00; 95% CI 1.05–8.58) occurred in the SILC group. Postoperative pain (MD -0.46; 95% CI -0.74 to -0.18) and cosmesis (SMD 2.38; 95% CI 1.50–3.26) showed significantly better results for the SILC group, but no differences were observed in quality of life. Operating time (MD 23.12; 95% CI 11.59–34.65) and the need for additional ports (RR 11.43; 95% CI 3.48–37.50) were significantly higher in the SILC group. No difference was observed in conversion to open cholecystectomy or hospital stay longer than 24 h. Conclusions SILC does not provide any clear advantages over conventional LC except for less postoperative pain and improved cosmesis. It is questionable whether these advantages outweigh the higher occurrence of adverse events and shortcomings in feasibility. Considering considerable heterogeneity and low methodological quality of the studies it is advisable to perform well-designed RCT’s in the future to address the safety and clinical benefits of SILC.

Adhesions, that form in 60-80% of all abdominal operations, can cause complications such as chronic abdominal pain, small-bowel obstruction, female infertility, and the need for adhesiolysis in future surgeries. Our 2010 Adhesion Awareness survey demonstrated that despite the huge clinical impact of adhesions; adhesion-related complications were seldom mentioned in the informed consent. Six years later, a follow-up survey was conducted to assess the progress on awareness on adhesion-related complications in the Netherlands. The 2010 Adhesion Awareness survey was repeated after a literature update. The knowledge regarding adhesions; the use of anti-adhesive agents and involvement in the informed consent process were assessed. Surgeons and surgical trainees were contacted by e-mail. The data was analysed using a Chi-square or Mann-Whitney U test and corrected for multiple testing. The response rate was 32.6%, similar to the survey in 2010 (34.4%). 88.1% agreed with the clinical relevance of adhesions, comparable to 2010 (89.8%). The score on the knowledge test was 38.8% (2010: 37.2%). Involvement of adhesion-related complications in the informed consent process increased, although 32.5% almost never mentions adhesions. In 2016, 42.4% reported a correct occurrence of bowel lesions during adhesiolysis, higher than in 2010 (P<0.001). The adhesion awareness did not increase in six years, despite the efforts made. However, an increased awareness regarding adhesiolysis related complications was detected. Improvement of knowledge and behavior is essential to narrowing the gap between the impact of adhesions as a major complication of abdominal surgery and the limited adhesion awareness.

BackgroundThough often only briefly described in the literature, there are clearly factors that have an influence on the fluorescence intensity, and thereby the usefulness of the technique. This article aims to provide an overview of the factors influencing the fluorescence intensity of fluorescence imaging with Indocyanine green, primarily focussed on NIRF guided cholangiography.MethodsA systematic search was conducted to gain an overview of currently used methods in NIRF imaging in laparoscopic cholecystectomies. Relevant literature was searched to gain advice on what methods to use. Ex vivo experiments were performed to assess various factors that influence fluorescence intensity and whether the found clinical advices can be confirmed.ResultsICG is currently the most widely applied fluorescent dye. Optimal ICG concentration lies between 0.00195 and 0.025 mg/ml, and this dose should be given as early as achievable—but maximum 24 h—before surgery. When holding the laparoscope closer and perpendicular to the dye, the signal is most intense. In patients with a higher BMI and/or cholecystitis, fluorescence intensity is lower, but NIRF seems to be more helpful. There are differences between various marketed fluorescence systems. Also, no uniform method to assess fluorescence intensity is available yet.ConclusionsThis study identified and discussed several factors that influence the signal of fluorescence cholangiography. These factors should be taken into account when using NIRF cholangiography. Also, surgeons should be aware of new dyes and clinical systems, in order to benefit most from the potential of NIRF imaging.

Human brown adipose tissue (BAT) activity is inversely related to obesity and positively related to energy expenditure. BAT is highly innervated and it is suggested the vagus nerve mediates peripheral signals to the central nervous system, there connecting to sympathetic nerves that innervate BAT. Vagus nerve stimulation (VNS) is used for refractory epilepsy, but is also reported to generate weight loss. We hypothesize VNS increases energy expenditure by activating BAT. Fifteen patients with stable vns therapy (age: 45 ± 10 yrs; body mass index; 25.2 ± 3.5 kg/m(2)) were included between January 2011 and June 2012. Ten subjects were measured twice, once with active and once with inactivated VNS. Five other subjects were measured twice, once with active VNS at room temperature and once with active VNS under cold exposure in order to determine maximal cold-induced BAT activity. BAT activity was assessed by 18-Fluoro-Deoxy-Glucose-Positron-Emission-Tomography-and-Computed-Tomography. Basal metabolic rate (BMR) was significantly higher when VNS was turned on (mean change; +2.2%). Mean BAT activity was not significantly different between active VNS and inactive VNS (BAT SUV(Mean); 0.55 ± 0.25 versus 0.67 ± 0.46, P = 0.619). However, the change in energy expenditure upon VNS intervention (On-Off) was significantly correlated to the change in BAT activity (r = 0.935, P<0.001). VNS significantly increases energy expenditure. The observed change in energy expenditure was significantly related to the change in BAT activity. This suggests a role for BAT in the VNS increase in energy expenditure. Chronic VNS may have a beneficial effect on the human energy balance that has potential application for weight management therapy. The study was registered in the Clinical Trial Register under the ClinicalTrials.gov Identifier NCT01491282.

Analysis of volatile organic compounds (VOCs) in exhaled breath has the potential to serve as an accurate diagnostic tool for gastro-intestinal diseases. Animal studies could be instrumental as a preclinical base and subsequent clinical translation to humans, as they are easier to standardize and better equipped to relate specific VOCs to metabolic and pathological processes. This review provides an overview of the study design, characteristics and methodological quality of previously published animal studies on analysis of exhaled breath in gastrointestinal and hepatic diseases. Guidelines are provided for standardization in study design and breath collection methods to improve comparability, avoid duplication of research and reduce discomfort of animals in future studies. PubMed and Embase database were searched for animal studies using exhaled breath analysis to detect gastro-intestinal diseases. Risk of bias was assessed using the SYRCLE's risk of bias tool for animal studies. Information on study design, standardization methods, animal models, breath collection methods and identified VOCs were extracted from the included studies. 10 studies were included (acute liver failure n = 1, non-alcoholic steatohepatitis n = 1, hepatic ischemia n = 2, mesenteric ischemia n = 2, sepsis and peritonitis n = 3, colitis n = 1). Rats were used in most of the studies. Exhaled breath was mostly collected using invasive procedures as tracheal cannulation or tracheostomy. Poor reporting on standardization, breath collection methods, analytical techniques, as well as heterogeneity of the studies, complicate comparison of the different studies. Poor reporting of essential methodological details impaired comprehensive summarizing the various studies on exhaled breath in gastrointestinal and hepatic diseases. Potential pitfalls in study design, and suggestions for improvement of study design are discussed which, when applied, lead to consistent and generalizable results and a reduction in the use of laboratory animals. Refining the methodological quality of animal studies has the potential to improve subsequent clinical trial design.

The authors of this study measured putative brown-adipose-tissue activity in relation to body composition and energy metabolism, using a standard protocol and integrated positron-emission tomography and computed tomography. Twenty-three of 24 healthy men had detectable levels of activity after cold exposure but not under thermoneutral conditions. Brown-adipose-tissue activity was positively related to resting metabolic rate and was significantly lower in overweight or obese subjects than in lean subjects. The authors measured putative brown-adipose-tissue activity in relation to body composition and energy metabolism. Brown-adipose-tissue activity was positively related to resting metabolic rate and was significantly lower in overweight or obese subjects than in lean subjects. There is evidence that stimulating adaptive thermogenesis, defined as the facultative heat produced in response to cold and diet, might serve as a means of preventing or treating obesity 1 ; thus, it is of interest to understand the mechanisms underlying adaptive thermogenesis. We previously reported that cold-induced thermogenesis in the absence of shivering accounts for an average of 11.8% of the resting metabolic rate, with high individual variation. 2 Individual differences in energy expenditure can have large, long-term effects on body weight. 3 Several prospective studies have shown that a relatively low energy expenditure predicts a gain in body weight. 4 , 5 Hence, . . .

Adhesions are the most common driver of long-term morbidity after abdominal surgery. Although laparoscopy can reduce adhesion formation, the effect of minimally invasive surgery on long-term adhesion-related morbidity remains unknown. We aimed to assess the impact of laparoscopy on adhesion-related readmissions in a population-based cohort. We did a retrospective cohort study of patients of any age who had abdominal or pelvic surgery done using laparoscopic or open approaches between June 1, 2009, and June 30, 2011, using validated population data from the Scottish National Health Service. All patients who had surgery were followed up until Dec 31, 2017. The primary outcome measure was the incidence of hospital readmissions directly related to adhesions in the laparoscopic and open surgery cohorts at 5 years. Readmissions were categorised as directly related to adhesions, possibly related to adhesions, and readmissions for an operation that was potentially complicated by adhesions. We did subgroup analyses of readmissions by anatomical site of surgery and used Kaplan-Meier analyses to assess differences in survival across subgroups. We used multivariable Cox-regression analysis to determine whether surgical approach was an independent and significant risk factor for adhesion-related readmissions. Between June 1, 2009, and June 30, 2011, 72 270 patients had an index abdominal or pelvic surgery, of whom 21 519 (29·8%) had laparoscopic index surgery and 50 751 (70·2%) had open surgery. Of the 72 270 patients who had surgery, 2527 patients (3·5%) were readmitted within 5 years of surgery for disorders directly related to adhesions, 12 687 (17·6%) for disorders possibly related to adhesions, and 9436 (13·1%) for operations potentially complicated by adhesions. Of the 21 519 patients who had laparoscopic surgery, 359 (1·7% [95% CI 1·5–1·9]) were readmitted for disorders directly related to adhesions compared with 2168 (4·3% [4·1–4·5]) of 50 751 patients in the open surgery cohort (p<0·0001). 3443 (16·0% [15·6–16·4]) of 21 519 patients in the laparoscopic surgery cohort were readmitted for disorders possibly related to adhesions compared with 9244 (18·2% [17·8–18·6]) of 50 751 patients in the open surgery cohort (p<0·005). In multivariate analyses, laparoscopy reduced the risk of directly related readmissions by 32% (hazard ratio [HR] 0·68, 95% CI 0·60–0·77), and of possibly related readmissions by 11% (HR 0·89, 0·85–0·94) compared with open surgery. Procedure type, malignancy, sex, and age were also independently associated with risk of adhesion-related readmissions. Laparoscopic surgery reduces the incidence of adhesion-related readmissions. However, the overall burden of readmissions associated with adhesions remains high. With further increases in the use of laparoscopic surgery expected in the future, the effect at the population level might become larger. Further steps remain necessary to reduce the incidence of adhesion-related postsurgical complications. Dutch Adhesion Group and Nordic Pharma.

Objective To estimate the disease burden of the most important complications of postoperative abdominal adhesions: small bowel obstruction, difficulties at reoperation, infertility, and chronic pain. Design Systematic review and meta-analyses. Data sources Searches of PubMed, Embase, and Central, from January 1990 to December 2012, without restrictions to publication status or language. Study selection All types of studies reporting on the incidence of adhesion related complications were considered. Data extraction and analysis The primary outcome was the incidence of adhesive small bowel obstruction in patients with a history of abdominal surgery. Secondary outcomes were the incidence of small bowel obstruction by any cause, difference in operative time, enterotomy during adhesiolysis, and pregnancy rate after abdominal surgery. Subgroup and sensitivity analyses were done to study the robustness of the results. A random effects model was used to account for heterogeneity between studies. Results We identified 196 eligible papers. Heterogeneity was considerable for almost all meta-analyses. The origin of heterogeneity could not be explained by study design, study quality, publication date, anatomical site of operation, or operative technique. The incidence of small bowel obstruction by any cause after abdominal surgery was 9% (95% confidence interval 7% to 10%; I2=99%). the incidence of adhesive small bowel obstruction was 2% (2% to 3%; I2=93%); presence of adhesions was generally confirmed by emergent reoperation. In patients with a known cause of small bowel obstruction, adhesions were the single most common cause (56%, 49% to 64%; I2=96%). Operative time was prolonged by 15 minutes (95% confidence interval 9.3 to 21.1 minutes; I2=85%) in patients with previous surgery. Use of adhesiolysis resulted in a 6% (4% to 8%; I2=89%) incidence of iatrogenic bowel injury. The pregnancy rate after colorectal surgery in patients with inflammatory bowel disease was 50% (37% to 63%; I2=94%), which was significantly lower than the pregnancy rate in medically treated patients (82%, 70% to 94%; I2=97%). Conclusions This review provides detailed and systematically analysed knowledge of the disease burden of adhesions. Complications of postoperative adhesion formation are frequent, have a large negative effect on patients’ health, and increase workload in clinical practice. The quantitative effects should be interpreted with caution owing to large heterogeneity. Registration The review protocol was registered through PROSPERO (CRD42012003180).

Thyroid hormone receptors are present on brown adipose tissue (BAT), indicating a role for thyroid hormone in the regulation of BAT activation. The objective of this study was to examine the effect of thyroid hormone withdrawal followed by thyroid hormone in TSH-suppressive dosages, on energy expenditure and brown adipose tissue activity. This study was a longitudinal study in an academic center, with a follow-up period of 6 months. Ten patients with well-differentiated thyroid carcinoma eligible for surgical treatment and subsequent radioactive iodine ablation therapy were studied in a hypothyroid state after thyroidectomy and in a subclinical hyperthyroid state (TSH-suppression according to treatment protocol). Paired two-tailed t-tests and linear regression analyses were used. Basal metabolic rate (BMR) was significantly higher after treatment with synthetic thyroid hormone (levothyroxine) than in the hypothyroid state (BMR 3.8 ± 0.5 kJ/min versus 4.4 ± 0.6 kJ/min, P = 0.012), and non-shivering thermogenesis (NST) significantly increased from 15 ± 10% to 25 ± 6% (P = 0.009). Mean BAT activity was significantly higher in the subclinical hyperthyroid state than in the hypothyroid state (BAT standard uptake value (SUVMean) 4.0 ± 2.9 versus 2.4 ± 1.8, P = 0.039). Our study shows that higher levels of thyroid hormone are associated with a higher level of cold-activated BAT. ClinicalTrials.gov NCT02499471.