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Background & Aims: Patients receiving oncological esophagectomy or gastrectomy are known to be at high risk for vitamin and micronutrient deficiency before, during and after surgery. However, there are no clear guidelines for these cancer patients regarding postoperative vitamin supplementation., Methods: We conducted a metanalysis consisting of 10 studies regarding vitamin and micronutrient deficiencies after oncological gastric or esophageal resection. 5 databases were searched., Results: Data was sufficient regarding Vitamins B12 and 25-OH D3 as well as calcium. We were able to show deficiencies in 25-OH Vitamin D3 levels (p < 0.001) and lower levels of Vitamin B12 and calcium (bit p < 0.001) when compared to the healthy population., Conclusions: Patients from these groups are at risk for vitamin deficiencies. A guideline on postoperative supplementation is needed., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Oesophageal cancer (EC) and gastric cancer (GC) are among the top 10 cancers worldwide. Both diseases impact the nutritional status of patients and their Quality of Life (QoL). Preoperative malnutrition is reported in 42%-80%. However, studies investigating postoperative nutritional status are limited, and postoperative identification and treatment of micronutrient and macronutrient deficiencies are currently lacking in (inter-)national guidelines. The aim of this study is to identify and target micronutrient deficiencies after surgery for oesophagogastric neoplasms., Methods: This is a single-centre prospective intervention trial performed in Zuyderland Medical Centre. 248 patients who underwent oesophagectomy (n=124) or (sub)total gastrectomy (n=124) from 2011 until 2022 will be included. Both groups will receive Calcium Soft Chew D3 and a multivitamin supplement (MVS) specifically developed according to the type of operation patients underwent; the oesophagectomy group will receive Multi-E and the gastrectomy group will receive Multi-G. The MVSs will be taken once daily and Calcium Soft Chew D3 two times per day. Supplementation will start after baseline measurements. At baseline (T0), blood withdrawal for micronutrient analysis and faecal elastase-1 analysis for exocrine pancreatic insufficiency (EPI) will be performed. Additionally, patients will receive questionnaires regarding QoL and dietary behaviour. After 180 days of supplementation (T1), baseline measurements will be repeated, and the supplement tolerance questionnaire will be completed. Measurements will also be conducted after 360 days (T2) and after 720 days (T3) of supplementation. The main study parameter is micronutrient deficiency (yes/no) for all measurements. Secondary parameters include occurrence of EPI (n, %), diarrhoea (n, %), steatorrhoea (n, %) or bloating (n, %), time between surgery and start of supplementation (mean in months), and QoL at all time points., Ethics and Dissemination: The study was approved by the Zuyderland Medical Centre Ethics Committee, Heerlen, the Netherlands. The findings will be disseminated through scientific congresses and in peer-reviewed journals., Trial Registration Number: NCT05281380., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/objectives: 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., Subjects/methods: 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., Results: 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)., Conclusions: Our study shows that higher levels of thyroid hormone are associated with a higher level of cold-activated BAT., Trial Registration: ClinicalTrials.gov NCT02499471.

Introduction: Mild cold acclimation is known to increase brown adipose tissue (BAT) activity and cold-induced thermogenesis (CIT) in humans. We here tested the effect of a lifestyle with frequent exposure to extreme cold on BAT and CIT in a Dutch man known as 'the Iceman', who has multiple world records in withstanding extreme cold challenges. Furthermore, his monozygotic twin brother who has a 'normal' sedentary lifestyle without extreme cold exposures was measured., Methods: The Iceman (subject A) and his brother (subject B) were studied during mild cold (13°C) and thermoneutral conditions (31°C). Measurements included BAT activity and respiratory muscle activity by [18F]FDG-PET/CT imaging and energy expenditure through indirect calorimetry. In addition, body temperatures, cardiovascular parameters, skin perfusion, and thermal sensation and comfort were measured. Finally, we determined polymorphisms for uncoupling protein-1 and β3-adrenergic receptor., Results: Subjects had comparable BAT activity (A: 1144 SUVtotal and B: 1325 SUVtotal), within the range previously observed in young adult men. They were genotyped with the polymorphism for uncoupling protein-1 (G/G). CIT was relatively high (A: 40.1% and B: 41.9%), but unlike during our previous cold exposure tests in young adult men, here both subjects practiced a g-Tummo like breathing technique, which involves vigorous respiratory muscle activity. This was confirmed by high [18F]FDG-uptake in respiratory muscle., Conclusion: No significant differences were found between the two subjects, indicating that a lifestyle with frequent exposures to extreme cold does not seem to affect BAT activity and CIT. In both subjects, BAT was not higher compared to earlier observations, whereas CIT was very high, suggesting that g-Tummo like breathing during cold exposure may cause additional heat production by vigorous isometric respiratory muscle contraction. The results must be interpreted with caution given the low subject number and the fact that both participants practised the g-Tummo like breathing technique.

Background: Obesity and type 2 diabetes are associated with impaired skeletal muscle mitochondrial metabolism. As an intrinsic characteristic of an individual, skeletal muscle mitochondrial dysfunction could be a risk factor for weight gain and obesity-associated co-morbidities, such as type 2 diabetes. On the other hand, impaired skeletal muscle metabolism could be a consequence of obesity. We hypothesize that marked weight loss after bariatric surgery recovers skeletal muscle mitochondrial function., Methods: Skeletal muscle mitochondrial function as assessed by high-resolution respirometry was measured in 8 morbidly obese patients (body mass index [BMI], 41.3±4.7 kg/m(2); body fat, 48.3%±5.2%) before and 1 year after bariatric surgery (mean weight loss: 35.0±8.6 kg). The results were compared with a lean (BMI 22.8±1.1 kg/m(2); body fat, 15.6%±4.7%) and obese (BMI 33.5±4.2 kg/m(2); body fat, 34.1%±6.3%) control group., Results: Before surgery, adenosine diphosphate (ADP)-stimulated (state 3) respiration on glutamate/succinate was decreased compared with lean patients (9.5±2.4 versus 15.6±4.4 O2 flux/mtDNA; P<.05). One year after surgery, mitochondrial function was comparable to that of lean controls (after weight loss, 12.3±5.5; lean, 15.6±4.4 O2 flux/mtDNA). In addition, we observed an increased state 3 respiration on a lipid substrate after weight loss (10.0±3.2 versus 14.0±6.6 O2 flux/mtDNA; P< .05)., Conclusion: We conclude that impaired skeletal muscle mitochondrial function is a consequence of obesity that recovers after marked weight loss., (Copyright © 2013 American Society for Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

Background: 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., Methods and Findings: 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)., Conclusions: 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., Trial Registration: The study was registered in the Clinical Trial Register under the ClinicalTrials.gov Identifier NCT01491282.

In recent years, it has been shown that humans have active brown adipose tissue (BAT) depots, raising the question of whether activation and recruitment of BAT can be a target to counterbalance the current obesity pandemic. Here, we show that a 10-day cold acclimation protocol in humans increases BAT activity in parallel with an increase in nonshivering thermogenesis (NST). No sex differences in BAT presence and activity were found either before or after cold acclimation. Respiration measurements in permeabilized fibers and isolated mitochondria revealed no significant contribution of skeletal muscle mitochondrial uncoupling to the increased NST. Based on cell-specific markers and on uncoupling protein-1 (characteristic of both BAT and beige/brite cells), this study did not show "browning" of abdominal subcutaneous white adipose tissue upon cold acclimation. The observed physiological acclimation is in line with the subjective changes in temperature sensation; upon cold acclimation, the subjects judged the environment warmer, felt more comfortable in the cold, and reported less shivering. The combined results suggest that a variable indoor environment with frequent cold exposures might be an acceptable and economic manner to increase energy expenditure and may contribute to counteracting the current obesity epidemic.

Context: Since the discovery of functional brown adipose tissue (BAT) in adult humans, there has been a renewed interest in the physiology of human BAT. Imaging studies from our laboratory and others have shown increased glucose uptake in adipose tissue regions assumed to be BAT in humans. We have also shown that human BAT from the supraclavicular (SCV) region is positive for uncoupling protein-1. To date, however, the oxidative capacity of this adipose tissue (AT) depot has not been characterized in humans., Objective: We hypothesize that oxidative capacity is increased in the AT of the SCV region known to contain human BAT., Design: This was an observational prospective cohort study., Setting: The study was conducted at a referral center., Patients: Participants were 13 patients for whom thyroid gland surgery was indicated., Main Outcome Measure: Basal cellular oxygen consumption in human AT biopsy samples from the SCV region, known to be [¹⁸F]fluorodeoxyglucose positron emission tomography-computed tomography-positive, was compared with the cellular oxygen consumption in subcutaneous white adipose tissue (WAT) from the same region of the same subject., Results: We show for the first time that AT from the human BAT region displays increased oxygen consumption (P < .05), on average 300% higher, than subcutaneous WAT of the same individual. The contribution of the proton leak to maximal respiration increased with age in the WAT but not in the AT from the BAT region., Conclusions: These results suggest that human adipose tissue from the BAT region can be distinguished from subcutaneous WAT by a higher basal oxidative capacity. Additional studies are warranted to further elucidate the metabolic and bioenergetic characteristics of this AT depot in humans.

Background: After Roux-en-Y gastric bypass (RYGB), a substantial number of patients do not achieve successful long-term weight loss. In cases of loss of restriction, the application of an adjustable gastric band ("salvage banding") over the gastric pouch, or gastrojejunostomy, could prevent weight regain or increase weight loss. The objective of this literature review is to provide an overview of the studies that report the effect of salvage banding after failed RYGB., Methods: A systemic literature search was conducted in PubMed, Google Scholar, Medline, the Cochrane Library, and the online websites of specific bariatric surgery journals to identify all relevant studies describing salvage banding after failed RYGB., Results: Seven studies, with a total of 94 patients, were included for a systemic literature review. Inclusion criteria for salvage banding varied from unsuccessful weight loss to technical pouch failure. After salvage banding, all studies reported further weight loss, varying from 55.9%-94.2% excess body mass index loss (EBMIL) after 12-42 months of follow-up. In the included study group, 18% (17/94) of the patients developed long-term complications requiring a re-revision in 17% (16/94) of the cases., Conclusion: The results of all 9 studies that were included in this review report a further increase in weight loss after salvage banding for failed RYGB. In case of insufficient weight loss or technical pouch failure after RYGB, all reports suggest that salvage banding is a safe and feasible revisional procedure. Prospective studies are necessary to determine to the success of direct application of an adjustable gastric band in primary RYGB., (Copyright © 2012 American Society for Metabolic and Bariatric Surgery. Published by Elsevier Inc. All rights reserved.)

A hibernoma is a benign tumour of brown adipose tissue (BAT). BAT is also present in physiological depots, previously considered residual. However, in 2009 functional BAT in adults was reported. Metabolically active BAT is suggested to significantly influence the energy balance and increasing BAT activity could possibly treat obesity. This strongly increased the interest in BAT in man and currently more research is conducted. We describe the case of an intramuscular hibernoma and illustrate the pathophysiology of the observed hibernoma in relation to recent insights on physiological BAT. Immunofluorescence staining of the hibernoma showed the presence of uncoupling-protein-1, a protein specific for active BAT. This suggests that this hibernoma contains BAT that could possibly contribute to the human energy balance.

Context: Stimulation of thermogenesis in brown adipose tissue (BAT) is a potential target to treat obesity. We earlier demonstrated that BAT activity is relatively low in obese subjects. It is unknown whether BAT can be recruited in adult humans., Objective: To study the dynamics of BAT, we observed BAT activity in morbidly obese subjects before and after weight loss induced by bariatric surgery., Design: This was an observational prospective cohort study., Setting: The study was conducted at a referral center., Patients: Ten morbidly obese subjects eligible for laparoscopic adjustable gastric banding surgery were studied before and 1 yr after bariatric surgery., Main Outcome Measure: The main outcome measure was BAT activity, as determined after acute cold stimulation using (18)F-fluorodeoxyglucose positron emission tomography and computed tomography., Results: Before surgery, only two of 10 subjects showed active BAT. One year after surgery, the number of subjects with active BAT was increased to five. After weight loss, BAT-positive subjects had significantly higher nonshivering thermogenesis compared with BAT-negative subjects (P < 0.05)., Conclusions: The results show that in humans BAT can be recruited in the regions in which it was also reported in lean subjects before. These results for the first time show recruitment of BAT in humans and may open the door for BAT-targeted treatments of obesity.

Background: Laparoscopic adjustable gastric banding (LAGB) is a safe and frequently performed bariatric procedure. Unfortunately, re-operations are often necessary. Reports on the success of revisional procedures are scarce and show variable results, either supporting or declining the idea of revising LAGB. This study describes a large cohort of re-operations after failed LAGB to determine the success of revision., Methods: By use of a prospective cohort, all LAGB revisions performed between 1996 and 2008 were identified. From 301 primary LAGB procedures in our centre, 43 patients (14.3%) required a band revision. In addition, 51 patients were referred from other centres. Our analysis included in total 94 patients with a mean follow-up period of 38 months after revision., Results: Revision was mainly necessary due to anterior slippage (46%) and symmetrical pouch dilatation (36%), which could be resolved by replacing (70%) or refixating the band (27%). Weight loss significantly increased after revision (excess BMI loss (EBMIL), 37.2 ± 36.3% versus 47.5 ± 30.4%, P < 0.05). After revision, 23 patients (24%) needed a second re-operation. Patients converted to other procedures (16%) during the second re-operation showed larger weight loss than the revised group (EBMIL, 64.3 ± 28.1% versus 44.3 ± 28.7%, P < 0.05)., Conclusions: We report on a large cohort of LAGB revisions with 38 months of follow-up. Revision of failed LAGB by either refixation or replacement of the band is successful and further increases weight loss.

Background: 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., Methods and Findings: 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., Conclusions: 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.

Hypothesis: The prevalence of and risk factors for incisional hernias among temporary stoma wounds have implications for clinical practice., Design: Retrospective cohort study., Setting: University tertiary care hospital., Patients: All adult patients with a stoma closed between January 1, 2000, and August 1, 2004. Of 150 living patients, 111 (74.0%) were included for analysis after follow-up at the outpatient clinic., Main Outcome Measures: The main outcome was incisional hernia in a temporary stoma wound, defined as a defect within the musculature and fascia detected by ultrasonographic examination. Risk factors for incisional hernias and the diagnostic validity of clinical symptoms and palpation during the Valsalva maneuver were determined., Results: After a median follow-up of 35 months (range, 5-77 months), hernia prevalence was 32.4%. Among patients with a body mass index (calculated as weight in kilograms divided by height in meters squared) of less than 30, hernia prevalence was 25.8%; among patients with a body mass index of 30 or higher, hernia prevalence was 59.1%. Palpation demonstrated the highest sensitivity (58.3%). One in 6 patients had discomfort at the temporary stoma site and no palpable defect but showed an incisional hernia on ultrasonographic examination. Obesity was the sole significant risk factor identified in this study (odds ratio, 5.53; 95% confidence interval, 1.72-17.80). The presence of a stoma in situ for less than 6 months showed a trend toward being a risk factor (odds ratio, 2.38; 95% confidence interval, 0.96-5.99)., Conclusion: Incisional hernias occur in 1 of 3 temporary stoma wounds, and a body mass index of 30 or higher is a risk factor.