Early postoperative systemic inflammatory response as predictor of anastomotic leakage after esophagectomy: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Postesophagectomy anastomotic leakage occurs in up to 16% of patients and is the main cause of morbidity and mortality. The leak severity is determined by the extent of contamination and the degree of sepsis, both of which are related to the time from onset to treatment. Early prediction based on inflammatory biomarkers such as C-reactive protein (CRP) levels, white blood cell counts, albumin levels, and combined Noble-Underwood (NUn) scores can guide early management. This review aimed to determine the diagnostic accuracy of these biomarkers. METHODS: This study was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and registered in the PROSPERO (International Prospective Register of Systematic Reviews) database. Two reviewers independently conducted searches across PubMed, MEDLINE, Web of Science, and Embase. Sources of bias were assessed, and a meta-analysis was performed. RESULTS: Data from 5348 patients were analyzed, and 13% experienced leakage. The diagnostic accuracy of the serum biomarkers was analyzed, and pooled cutoff values were identified. CRP levels were found to have good diagnostic accuracy on days 2 to 5. The best discrimination was identified on day 2 for a cutoff value < 222 mg/L (area under the curve = 0.824, sensitivity = 81%, specificity = 88%, positive predictive value = 38.6%, and negative predictive value = 98%). A NUn score of >10 on day 4 correlated with poor diagnostic accuracy. CONCLUSION: The NUn score failed to achieve adequate accuracy. CRP seems to be the only valuable biomarker and is a negative predictor of postesophagectomy leakage. Patients with a CRP concentration of <222 mg/L on day 2 are unlikely to develop a leak, and patients can safely proceed through their enhanced recovery after surgery protocol. Patients with a CRP concentration of <127 mg/L on day 5 can be safely discharged when clinically possible.

Bariatric surgery post-Liver Transplantation: A Belgian nationwide study.

BACKGROUND: Weight gain poses a rising concern post-liver transplantation (LT), and metabolic dysfunction-associated steatotic liver disease (MASLD) might impair graft health. The timing is crucial when considering bariatric surgery (BS) in a population with liver disease or transplantation. BS can be considered for post-LT weight gain, although the evidence is limited and the long-term outcome still uncertain. METHODS: We conducted a national retrospective analysis in 5 Belgian transplant centres and included 25 patients with a liver transplantation followed by a bariatric procedure. 187 LT patients without BS were included for comparison. Clinical, biochemical and outcome data were retrospectively retrieved. RESULTS: In our nationwide cohort, 25 patients had undergone BS post-LT, at a median 3.5 years after LT. Twenty-one (84.0%) patients received a sleeve gastrectomy (SG). Patients were predominantly male (72.0%), with a lower age at time of transplantation compared to non-BS population (54.5 vs. 60.6, p<0.001). Weight loss was significant and sustained, with a decrease in BMI from 41.0±4.5 pre-BS to 32.6±5.8 1-3 years post-BS (p<0.001) and 31.1±5.8 3-5 years post-BS (p<0.001). Post-LT pre-BS three (12.0%) patients presented with recurrent and one (4.0%) de novo MASLD, with 100% resolution post-BS (p=0.016). Notable reductions were observed in ALT levels (40.5±28.5 U/L to 27.1±25.1 U/L post-BS, p=0.05) and HbA1c levels (6.9±1.6 to 6.0±1.4 post-BS, p<0.001). Three patients were re-transplanted, and eight patients died, of which five (20.0%) due to a non-hepatic malignancy and one (4.0%) due to liver failure. CONCLUSIONS: SG is the favored BS post-LT and has proven to be safe and feasible in a post-LT setting with favorable metabolic consequences. SG post-LT is a valid treatment for de novo and recurrent MASLD post-LT. Although we report on the largest cohort to date, there is still a need for larger cohorts to examine the effect of BS on patient and graft survival.

Systemic Inflammatory Response and the Noble and Underwood (NUn) Score as Early Predictors of Anastomotic Leakage after Esophageal Reconstructive Surgery.

Anastomotic leakage (AL) remains the main cause of post-esophagectomy morbidity and mortality. Early detection can avoid sepsis and reduce morbidity and mortality. This study evaluates the diagnostic accuracy of the Nun score and its components as early detectors of AL. This single-center observational cohort study included all esophagectomies from 2010 to 2020. C-reactive protein (CRP), albumin (Alb), and white cell count (WCC) were analyzed and NUn scores were calculated. The area under the curve statistic (AUC) was used to assess their predictive accuracy. A total of 74 of the 668 patients (11%) developed an AL. CRP and the NUn-score proved to be good diagnostic accuracy tests on postoperative day (POD) 2 (CRP AUC: 0.859; NUn score AUC: 0.869) and POD 4 (CRP AUC: 0.924; NUn score AUC: 0.948). A 182 mg/L CRP cut-off on POD 4 yielded a 87% sensitivity, 88% specificity, a negative predictive value (NPV) of 98%, and a positive predictive value (PPV) of 47.7%. A NUn score cut-off > 10 resulted in 92% sensitivity, 95% specificity, 99% NPV, and 68% PPV. Albumin and WCC have limited value in the detection of post-esophagectomy AL. Elevated CRP and a high NUn score on POD 4 provide high accuracy in predicting AL after esophageal cancer surgery. Their high negative predictive value allows to select patients who can safely proceed with enhanced recovery protocols.

Patients hospitalized with alcohol-related liver disease and prior bariatric surgery are more prone to develop acute-on-chronic liver failure.

BACKGROUND & AIMS: Patients with a history of bariatric surgery (BS) are susceptible to developing alcohol use disorder. We and others have previously shown that these patients can develop severe alcohol-related liver disease (ARLD). Our aim was to describe the demographics, co-morbidities and mortality of a hospitalized population diagnosed with alcohol-related liver disease, in relation to BS. METHODS: We included 299 patients hospitalized with ARLD at the Ghent University Hospital between 1 January 2018 and 31 December 2022. Clinical, biochemical and outcome data were retrospectively retrieved from the most recent hospitalization. Statistical analysis was performed using the t test, Mann-Whitney U and χ2 tests. RESULTS: Thirteen per cent (39/299) of patients admitted with ARLD had a history of bariatric surgery, of whom 25 (64.1%) had undergone Roux-en-Y gastric bypass. Patients with a history of BS were predominantly female (76.9%), in contrast to the non-BS population (29.2%) (p < .0001), and despite being significantly younger (p < .0001) and had a similar survival (61.5% vs. 58.1%). Bariatric surgery and older age at diagnosis were both significantly associated with poorer transplant-free survival. The cause of death was acute-on-chronic liver failure in 73.3% of BS patients, compared to only 19.2% of those without a history of BS (p < .0001). The weekly amount of alcohol consumed (p = .012) and duration of use (p < .0001) were significantly lower/shorter in the BS population. CONCLUSIONS: BS patients hospitalized with ARLD are predominantly younger women with a lower cumulative alcohol consumption compared to those without prior BS. BS impacted transplant-free survival, with ACLF as the predominant cause of death in these patients.

Intervention pathways for low anterior resection syndrome after sphincter-saving rectal cancer surgery: A systematic scoping review.

AIM: Low anterior resection syndrome (LARS) has a large impact on patients' quality of life. Several heterogeneous intervention pathways are suggested in the literature. The steps and timing of the different steps in the pathways are unclear. This systematic scoping review aims to map the range of intervention pathways for LARS after sphincter-saving rectal cancer surgery. METHODS: A search was undertaken on four databases (CINAHL, EMBASE, PubMed, and Web of Science). Any type of paper describing intervention pathways for patients with LARS following sphincter-saving surgery was included. Excluded were patients with a stoma, no full paper, no intervention pathway and not being written in English or Dutch. The review was registered with Open Science Framework (10.17605/OSF.IO/JB5H8). Narrative synthesis of the results was performed by charting and summarising key results. RESULTS: A total of 373 records were screened and 12 papers were included. There was a high variability among the intervention pathways, including which patients should be included. The number of pathway steps ranged from 2-6. Most intervention pathways were treatment-led. Intervention options ranged from conservative measures to a permanent stoma. Pathway flow was highly variable and sometimes not well described, with different or no timings provided for the start, progression, or end of the pathways. Three studies discussed the use of a nurse to coordinate the pathway. CONCLUSION: This systematic scoping review shows that despite similarities in treatment options there are variations in which treatments are included, when treatments should be instigated, and even which patients should be treated.

Information and counselling needs of patients with major low anterior resection syndrome: A qualitative study.

AIMS AND OBJECTIVES: The aim was to explore the information and counselling needs of rectal cancer survivors confronted with major low anterior resection syndrome. BACKGROUND: Rectal cancer survivors are often confronted with bowel problems after surgery. This is called low anterior resection syndrome. Patients are unsure what to expect after treatment and healthcare professionals often underestimate the impact of low anterior resection syndrome on patients' lives. DESIGN: A qualitative study with a grounded theory approach was conducted. METHODS: Patients were recruited between 2017 and 2019 in three hospitals, and a call was distributed in two patients' organisations. Semi-structured interviews with patients confronted with major low anterior resection syndrome were performed. An iterative process between data collection and data analysis was used. Data analysis was done using the constant comparative method, and investigators' triangulation was applied. Qualitative data were reported following COREQ guidelines. The study was registered at Clinicaltrials.gov NCT04896879. RESULTS: A total of 28 patients were interviewed until theoretical data saturation. Before surgery patients' need for information varied according to their individual coping mechanisms. Some patients required information before surgery, while others considered this too overwhelming. When confronted with LARS, patients desired that healthcare professionals recognised its impact and clarified its expected evolution. A proactive counselling with an easy accessible and approachable healthcare professional was beneficial. CONCLUSION: Patients expressed several needs regarding the information before rectal cancer surgery and counselling of low anterior resection syndrome after surgery. RELEVANCE TO CLINICAL PRACTICE: Better knowledge and understanding of major low anterior resection syndrome and its challenges by healthcare professionals are crucial. Especially the impact on quality of life is significant for patients and underestimated by healthcare professionals. Information before surgery and counselling when confronted with major low anterior resection syndrome should be optimised and tailored to patients' needs.

A rare complication of laparoscopic Roux-en-Y gastric bypass: case report of gastric remnant necrosis.

Gastric remnant necrosis is a very rare, but potential life-threatening complication after laparoscopic Roux-en-Y gastric bypass (LRYGB). We report a case of gastric remnant necrosis that was complicated by peritonitis and resulted in septic shock in a 49-year-old woman who had undergone a LRYGB three months prior to admission. An emergent laparoscopy with subtotal gastrectomy was performed. The patient was treated for septic shock and could leave the hospital in a good condition. Potential etiological factors for gastric remnant necrosis were elaborated.

Barriers and Enablers of Second-Order Problem-Solving Behavior: How Nurses Can Break Away From the Workaround Culture.

BACKGROUND AND OBJECTIVES: Nurses are challenged by numerous day-to-day unexpected problems due to poorly performing work systems that hinder patient care. These operational failures persist in hospitals, partly because nurses tend to prefer quick fixes or workarounds over real improvements that prevent recurrence. The aim of this review is to shed light on the barriers to and enablers of nurses' second-order problem-solving behavior and their consequences, so that hospitals can learn from failure and improve organizational outcomes. METHODS: We conducted a systematic review, with quantitative, qualitative, and mixed-method articles, searching 6 databases (PubMed, Embase, Web of Science, CINAHL, and Google Scholar) following the Preferred Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Quality assessment for inclusion was performed by 2 independent authors using the Mixed Methods Appraisal Tool (MMAT). A descriptive synthesis was used for analysis. RESULTS: This study reveals the barriers and enablers for second-order problem-solving behavior, and synthesizes improvement proposals within 3 perspectives, namely the "empowerment" perspective, the "process improvement" perspective, and the "time" perspective. Furthermore, we found that limited attention is given to the patient's perspective, and the existence of a no-action behavior. CONCLUSION: Although operational failures have several important consequences for hospital staff and organizations, there has been hardly any research into the barriers and enablers that initiate second-order problem-solving behavior; stemming this nursing behavior has thus rarely appeared as a suggestion for improvement.

Interprofessional perspectives on care for patients with low anterior resection syndrome: A qualitative study.

AIM: Many patients are confronted with low anterior resection syndrome after rectal surgery. The perspectives of both healthcare professionals and patients on the impact of bowel problems may differ. This study aimed to explore experiences of healthcare professionals on how to provide, organise and optimise care for patients with low anterior resection syndrome from an interprofessional perspective. METHODS: An explorative qualitative design was used. Healthcare professionals were recruited in October 2018 in one general teaching hospital and one university hospital. Twenty one healthcare professionals from different professions caring for patients with low anterior resection syndrome were included in three focus group interviews. RESULTS: Healthcare professionals confirmed a lack of focus on patients who are confronted with low anterior resection syndrome and stated a need for a standardised approach of care. Additionally, three levels for care optimization emerged from the data: information before surgery with strong emphasis on the timing of informing, counselling of patients when confronted with low anterior resection syndrome and organisation of care. CONCLUSIONS: Healthcare professionals find it important to adopt the moment and amount of information to the coping mechanism and timing of the trajectory. Counselling and follow-up of patients with LARS should be organised proactively and should not remain restricted to pharmacological and nutritional advice. A possible strategy is to develop and implement late effects nurse-led clinics coordinated by the clinical nurse specialist.

Clinical utility of near-infrared perfusion assessment of the gastric tube during Ivor Lewis esophagectomy.

BACKGROUND: Anastomotic leakage (AL) after Ivor Lewis esophagectomy with intrathoracic anastomosis carries a significant morbidity. Adequate perfusion of the gastric tube (GT) is an important predictor of anastomotic integrity. Recently, near infrared fluorescent (NIRF) imaging using indocyanine green (ICG) was introduced in clinical practice to evaluate tissue perfusion. We evaluated the feasibility and efficacy of GT indocyanine green angiography (ICGA) after Ivor Lewis esophagectomy. METHODS: This retrospective analysis used data from a prospectively kept database of consecutive patients who underwent Ivor Lewis (IL) esophagectomy with GT construction for cancer between January 2016 and December 2020. Relevant outcomes were feasibility, ICGA complications and the impact of ICGA on AL. RESULTS: 266 consecutive IL patients were identified who matched the inclusion criteria. The 115 patients operated with perioperative ICGA were compared to a control group in whom surgery was performed according to the standard of care. ICGA perfusion assessment was feasible and safe in all 115 procedures and suggested a poorly perfused tip in 56/115 (48.7%) cases, for which additional resection was performed. The overall AL rate was 16% (43/266), with 12% (33/266) needing an endoscopic our surgical intervention and 6% (17/266) needing ICU support. In univariable and multivariable analyses, ICGA was not correlated with the risk of AL (ICGA:14.8% vs non-ICGA:17.2%, p = 0.62). However, poor ICGA perfusion of the GT predicted a higher AL rate, despite additional resection of the tip (ICGA poorly perfused: 19.6% vs ICG well perfused: 10.2%, p = 0.19). CONCLUSIONS: ICGA is safe and feasible, but did not result in a reduction of AL. The interpretation and necessary action in case of perioperative presence of ischemia on ICGA have yet to be determined. Prospective randomized trials are warranted to analyze its benefit on AL in esophageal surgery. Trial registration Ethical approval for a prospective esophageal surgery database was granted by the Ethical committee of the Ghent University Hospital. Belgian registration number: B670201111232. Ethical approval for this retrospective data analysis was granted by our institutional EC. REGISTRATION NUMBER: BC-09216.

Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches.

The liver is the largest solid organ in the body, yet it remains incompletely characterized. Here we present a spatial proteogenomic atlas of the healthy and obese human and murine liver combining single-cell CITE-seq, single-nuclei sequencing, spatial transcriptomics, and spatial proteomics. By integrating these multi-omic datasets, we provide validated strategies to reliably discriminate and localize all hepatic cells, including a population of lipid-associated macrophages (LAMs) at the bile ducts. We then align this atlas across seven species, revealing the conserved program of bona fide Kupffer cells and LAMs. We also uncover the respective spatially resolved cellular niches of these macrophages and the microenvironmental circuits driving their unique transcriptomic identities. We demonstrate that LAMs are induced by local lipid exposure, leading to their induction in steatotic regions of the murine and human liver, while Kupffer cell development crucially depends on their cross-talk with hepatic stellate cells via the evolutionarily conserved ALK1-BMP9/10 axis.

A SIMPLE Performance Assessment of Bariatric Procedures and Post-operative Weight Regain.

BACKGROUND: When assessing and reporting the performance of bariatric procedures, longitudinal total weight loss % (TWL%) is the preferred method of choice. This averages out significant individual weight regains. Due to no assessment of individual weight trajectories, numerous patients with weight recidivism are missed in the overall assessment of the applied procedures. MATERIALS AND METHODS: The SIMPLE acronym (Survival analysis of Interpolated weight trajectories in a Markov chain, assessing Predictors, Longitudinal TWL% and individual procedure success and relapse Events) provides a framework to assess the performance of bariatric procedures in everyday practice, identifying a procedures' overall performance both in terms of longitudinal total weight loss % and individual events of weight regain. The SIMPLE approach is demonstrated on a cohort of 907 bariatric patients collected over 7 years. Six hundred eighteen patients received a primary RYGB, 81 a primary SG, while 208 were conversions to either a RYGB (n = 198) or SG (n = 10). Successful surgery was defined as 20% TWL; a weight regain as a 15% increase from the lowest individually attained weight post-surgery. RESULTS: The longitudinal TWL% performance at 5 years was 34.5%, 21.3%, and 22.9% for the primary RYGB, primary sleeve gastrectomy, and conversion operation, respectively. However, nearly 20% of the conversion operations never reached success, while 33.5% registered a relapse event within 5 years. CONCLUSION: The combined approach of the SIMPLE assessment clearly showed that a non-trivial amount of individuals did not achieve success or regained significant weight after surgery. This indicates that a combined approach to reporting bariatric performance is preferred.

Patient-reported outcomes after pelvic exenteration for colorectal cancer: A systematic review.

AIM: Pelvic exenteration (PE) carries high morbidity. Our aim was to analyse the use of patient-reported outcome measures (PROMs) in PE patients. METHOD: Search strategies were protocolized and registered in PROSPERO. PubMed, Embase, Cochrane Library, Google Scholar, Web of Science and ClinicalTrials.gov were searched with the terms 'patient reported outcomes', 'pelvic exenteration' and 'colorectal cancer'. Studies published after 1980 reporting on PROMs for at least 10 PE patients were considered. Study selection, data extraction, rating of certainty of evidence (GRADE) and risk of bias (ROBINS-I) were performed independently by two reviewers. RESULTS: Nineteen of 173 studies were included (13 retrospective, six prospective). All studies were low to very low quality, with an overall moderate/serious risk of bias. Studies included data on 878 patients with locally advanced rectal cancer (n = 344), recurrent rectal cancer (n = 411) or cancer of unknown type (n = 123). Thirteen studies used validated questionnaires, four used non-validated measures and two used both. Questionnaires included the Functional Assessment of Cancer Therapy-Colorectal questionnaire (n = 6), Short Form Health Survey (n = 6), European Organization for Research and Treatment for Cancer (EORTC) Quality of Life Questionnaire C30 (n = 6), EORTC-CR38 (n = 4), EORTC-BLM30 (n = 1), Brief Pain Inventory (n = 2), Short Form 12 (n = 1), Assessment of Quality of Life (n = 1), Short Form Six-Dimension (n = 1), the Memorial Sloan Kettering Cancer Center Sphincter Function Scale (n = 1), the Cleveland Global Quality of Life (n = 1) or other (n = 4). Timing varied between studies. CONCLUSIONS: Whilst the use of validated questionnaires increased over time, this study shows that there is a need for uniform use and timing of PROMs to enable multicentre studies.

First Inventory of Access and Quality of Metabolic Surgery Across Europe.

INTRODUCTION: Europe consists of 51 independent countries. Variation in healthcare regulations results in differing challenges faced by patients and professionals. This study aimed to gain more insight into the accessibility, patient pathway and quality indicators of metabolic and body contouring surgery. METHODS AND MATERIALS: Expert representatives in the metabolic field from all 51 countries were sent an electronic self-administered online questionnaire on their data and experiences from the previous year exploring accessibility to and quality indicators for metabolic surgery and plastic surgery after weight loss. RESULTS: Forty-five responses were collected. Sixty-eight percent of countries had eligibility criteria for metabolic surgery; 59% adhered to the guidelines. Forty-six percent had reimbursement criteria for metabolic surgery. Forty-one percent had eligibility criteria for plastic surgery and 31% reimbursement criteria. Average tariffs for a metabolic procedure varied € 800 to 16,000. MDTs were mandated in 78%, with team members varying significantly. Referral practices differed. In 45%, metabolic surgery is performed by pure metabolic surgeons, whilst re-operations were performed by a metabolic surgeon in 28%. A metabolic training programme was available in 23%. Access to metabolic surgery was rated poor to very poor in 33%. Thirty-five percent had a bariatric registry. Procedure numbers and numbers of hospitals performing metabolic surgery varied significantly. Twenty-four percent of countries required a minimum procedure number for metabolic centres, which varied from 25 to 200 procedures. CONCLUSION: There are myriad differences between European countries in terms of accessibility to and quality indicators of metabolic surgery. Lack of funding, education and structure fuels this disparity. Criteria should be standardised across Europe with clear guidelines.

Bariatric surgery and the liver-Mechanisms, benefits, and risks.

The prevalence of obesity and metabolic diseases such as type 2 diabetes and nonalcoholic fatty liver disease (NAFLD) has risen dramatically over the past decades. At present, bariatric surgery is the most effective treatment for this global health problem, through effects on food intake, gut hormone secretion, metabolic signaling pathways, and adipose tissue dysfunction. The liver occupies a central role in carbohydrate, protein, and lipid metabolism. Notably, a reduction in hepatic fat content and an improvement in hepatic insulin resistance are among the earliest beneficial effects of bariatric surgery, which has therefore emerged as an attractive treatment option for NAFLD. However, as the scope and popularity of weight loss surgery have expanded, new questions have arisen regarding its safety in patients with liver cirrhosis, the outcome of liver transplantation in patients with a history of bariatric surgery, and over incidental reports of liver failure following surgery. Studies in humans and rodents have also linked bariatric surgery to an increased risk of developing alcohol use disorder, a major risk factor for liver disease. This review integrates data from clinical and translational research to delineate both the beneficial impact of bariatric surgery on the liver and the potential risks involved.

Divergent dynamics in systemic and tissue-specific metabolic and inflammatory responses during weight loss in subjects with obesity.

AIM: Dysfunction of adipose and muscle tissue associates with obesity-related co-morbidities such as insulin resistance (IR) and inflammation. This study investigates changes in systemic and tissue-specific markers of IR and inflammation after gastric bypass surgery (GBS) in subjects with obesity. METHODS: Prospective study, twenty subjects with obesity (50 ± 10 years, 14 men). Prior to, and six months and one year after GBS, subcutaneous abdominal adipose tissue (SAT), skeletal muscle and fasting serum samples were collected. Serum levels of C-reactive protein (CRP), glucose and insulin were determined using standard laboratory assays and serum IL-6, IL-10 and TNF-α levels were determined using ELISA. Tissue mRNA expression of inflammation and insulin/glucose metabolism markers were analyzed using qPCR. RESULTS: After GBS, HOMA-IR, CRP and IL-6 serum levels decreased. In SAT, expression of bone morphogenetic protein 4 (BMP4), IL-6, IL-10 and MCP1 decreased and GLUT4 increased (all p < 0.05). In muscle, expression of BMP4, GLUT4 and IL-6 decreased and of MCP1 and IRS-1 increased (all p < 0.05). CONCLUSION: Systemic improvements in inflammation and IR after GBS are only partially mirrored by corresponding changes in adipokine and myokine expression patterns. As changes in expression of other markers of inflammation and insulin/glucose metabolism appear less consistent and even divergent between tissues, the inflammatory and IR status at systemic level cannot be extrapolated to the situation in metabolically active tissues.

Metabolism of testosterone during weight loss in men with obesity.

OBJECTIVE: Men with obesity often have low total and, with increasing adiposity, also low free testosterone (T) levels, which can partially restore during weight loss. Although this is partly explained by lower sex hormone binding globulin (SHBG) production and hypothalamic-pituitary downregulation, it is still not unravelled whether changes in androgen metabolism contribute to this phenomenon. Therefore, early changes in urinary excretion of T and its metabolites, during weight loss, in men with obesity are investigated. DESIGN: Longitudinal study. METHODS: Fourteen men with obesity (age 52(45-60)years, BMI 42.6(41.8-44.8)kg/m²) underwent gastric bypass surgery (GBS). Before surgery and 3 weeks, 6 weeks, 6 months and 1 year thereafter, 24 h urine and fasting serum samples were collected. Serum T and estradiol (E2) levels were analyzed using LC-MS/MS and urinary metabolites of T with GC-MS/MS. RESULTS: Already three weeks after GBS, serum SHBG and total T levels increased and remained increased as compared to baseline (all,p < 0.0125). Gonadotropins and (free) E2 levels were unchanged, serum E2/T ratio decreased (p < 0.0125). Total amount of urinary T increased non-significantly with mean increases of 53 % one year after GBS (p = 0.026). Urinary E2/T, estrone/T, 3α-androstanediol/T and androsterone/T ratios decreased after GBS (p < 0.0125). CONCLUSIONS: Restoration of circulating T levels during weight loss in this population is not only brought about by normalization of circulating SHBG levels, but increased production of and alterations in T metabolism also contribute. More specifically, relative decreases in aromatization and lower 5α-reductase activity might also be involved in restoring T levels in men with obesity.

Physiological Disturbance in Fatty Liver Energy Metabolism Converges on IGFBP2 Abundance and Regulation in Mice and Men.

Fatty liver occurs from simple steatosis with accumulated hepatic lipids and hepatic insulin resistance to severe steatohepatitis, with aggravated lipid accumulation and systemic insulin resistance, but this progression is still poorly understood. Analyses of hepatic gene expression patterns from alb-SREBP-1c mice with moderate, or aP2-SREBP-1c mice with aggravated, hepatic lipid accumulation revealed IGFBP2 as key nodal molecule differing between moderate and aggravated fatty liver. Reduced IGFBP2 expression in aggravated fatty liver was paralleled with promoter hypermethylation, reduced hepatic IGFBP2 secretion and IGFBP2 circulating in plasma. Physiologically, the decrease of IGFBP2 was accompanied with reduced fatty acid oxidation and increased de novo lipogenesis potentially mediated by IGF1 in primary hepatocytes. Furthermore, methyltransferase and sirtuin activities were enhanced. In humans, IGFBP2 serum concentration was lower in obese men with non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) compared to non-obese controls, and liver fat reduction by weight-loss intervention correlated with an increase of IGFBP2 serum levels. In conclusion, hepatic IGFBP2 abundance correlates to its circulating level and is related to hepatic energy metabolism and de novo lipogenesis. This designates IGFBP2 as non-invasive biomarker for fatty liver disease progression and might further provide an additional variable for risk prediction for pathogenesis of fatty liver in diabetes subtype clusters.

Bariatric Surgery Patients Are at Risk for Alcoholic Liver Disease with Need for Liver Transplantation.

Recent studies have indicated that patients with prior bariatric surgery (BS) are at risk for developing alcohol use disorder. We explored patient demographics and impact on liver disease severity in 11 patients with prior BS listed for transplantation due to alcoholic liver disease, and compared these with 177 patients without BS. BS patients were younger with a female predominance and presented with more severe decompensation. The timeframe between diagnosis, listing, and transplantation was significantly shorter in patients with prior BS. The incidence of post-transplant complications and 3-year survival rate was comparable. In conclusion, alcoholic liver disease with rapid decompensation may develop after BS, warranting rapid identification with referral to a transplant center. Attention should be paid to pre-surgery screening for alcohol overuse risk factors.