Impact on sleeve gastrectomy in patients with esophageal motor disorder.

BACKGROUND: Gastroesophageal reflux disease (GERD) and esophageal motor disorders (EMD) are frequent conditions among patients with obesity. The effects of sleeve gastrectomy (SG) on esophageal function can worsen GERD, but little is known about its effects on EMD and the consequences of preexisting EMD on GERD after SG. OBJECTIVES: To study the postoperative outcomes of SG in a population of patients displaying preexisting EMD. SETTING: University Hospital, France. METHODS: Patients with EMD confirmed by high-resolution manometry who underwent a laparoscopic SG between 2010 and 2019 were retrospectively included in this monocenter study. GERD symptoms and high-resolution manometry results were recorded before surgery and during follow-up. Conversion to gastric bypass were also recorded. RESULTS: Thirty-seven patients were included. Mean age was 52.6 ± 12.9 years. Most patients were female (70%). EMD were achalasia (19% of patients), hypercontractile (22%), hypocontractile (30%) and nutcracker esophagus (22%), and ineffective esophageal motility (8%). GERD symptoms were present in 10 patients (27%) preoperatively and 18 (49%) postoperatively. Achalasia was not resolved after SG and was constantly associated with disabling food blockage or GERD symptoms after surgery, and 3 of 4 patients with nutcracker esophagus had postoperative GERD symptoms and underwent gastric bypass. CONCLUSIONS: This study is the largest to describe the course of GERD and EMD after SG in patients displaying preoperative EMD. Achalasia and nutcracker esophagus are associated with poorer postoperative outcomes, and another procedure such as a gastric bypass should be performed.

Hepatic FNDC5 is a potential local protective factor against Non-Alcoholic Fatty Liver.

The proteolytic cleavage of Fibronectin type III domain-containing 5 (FNDC5) generates soluble irisin. Initially described as being mainly produced in muscle during physical exercise, irisin mediates adipose tissue thermogenesis and also regulates carbohydrate and lipid metabolism. The aim of this study was to evaluate the hepatic expression of FNDC5 and its role in hepatocytes in Non-Alcoholic Fatty Liver (NAFL). Here we report that hepatic expression of FNDC5 increased with hepatic steatosis and liver injury without impacting the systemic level of irisin in mouse models of NAFLD (HFD and MCDD) and in obese patients. The increased Fndc5 expression in fatty liver resulted from its upregulation in hepatocytes and non-parenchymal cells in mice. The local production of Fndc5 in hepatocytes was influenced by genotoxic stress and p53-dependent pathways. The down-regulation of FNDC5 in human HepG2 cells and in primary mouse hepatocytes increased the expression of PEPCK, a key enzyme involved in gluconeogenesis associated with a decrease in the expression of master genes involved in the VLDL synthesis (CIDEB and APOB). These alterations in FNDC5-silenced cells resulted to increased steatosis and insulin resistance in response to oleic acid and N-acetyl glucosamine, respectively. The downregulation of Fndc5 also sensitized primary hepatocytes to apoptosis in response to TNFα, which has been associated with decreased hepatoprotective autophagic flux. In conclusion, our human and experimental data strongly suggest that the hepatic expression of FNDC5 increased with hepatic steatosis and its upregulation in hepatocytes could dampen the development of NAFLD by negatively regulating steatogenesis and hepatocyte death.

The Differential Expression of Cide Family Members is Associated with Nafld Progression from Steatosis to Steatohepatitis.

Improved understanding of the molecular mechanisms responsible for the progression from a "non-pathogenic" steatotic state to Non-Alcoholic Steatohepatitis is an important clinical requirement. The cell death-inducing DFF45 like effector (CIDE) family members (A, B and FSP27) regulate hepatic lipid homeostasis by controlling lipid droplet growth and/or VLDL production. However, CIDE proteins, particularly FSP27, have a dual role in that they also regulate cell death. We here report that the hepatic expression of CIDEA and FSP27 (α/ß) was similarly upregulated in a dietary mouse model of obesity-mediated hepatic steatosis. In contrast, CIDEA expression decreased, but FSP27-ß expression strongly increased in a dietary mouse model of steatohepatitis. The inverse expression pattern of CIDEA and FSP27ß was amplified with the increasing severity of the liver inflammation and injury. In obese patients, the hepatic CIDEC2 (human homologue of mouse FSP27ß) expression strongly correlated with the NAFLD activity score and liver injury. The hepatic expression of CIDEA tended to increase with obesity, but decreased with NAFLD severity. In hepatic cell lines, the downregulation of FSP27ß resulted in the fractionation of lipid droplets, whereas its overexpression decreased the expression of the anti-apoptotic BCL2 marker. This, in turn, sensitized cells to apoptosis in response to TNF α and saturated fatty acid. Considered together, our animal, human and in vitro studies indicate that differential expression of FSP27ß/CIDEC2 and CIDEA is related to NAFLD progression and liver injury.

Brain metastases from colorectal cancer: characteristics and management.

BACKGROUND: Brain metastases (BMs) are the most common intracranial neoplasms in adults, but they rarely arise from colorectal cancer (CRC). The objective of this study was to report an overview of the characteristics and current management of CRC BMs. METHODS: A systematic review on CRC BMs was performed using Medline database from 1983 to 2015. The search was limited to studies published in English. Review articles, not relevant case report or studies or studies relating to animal and in vitro experiments were excluded. RESULTS: BMs occurred in 0.06-4% of patients with CRC. Most BMs were metachronous and were associated with lung (27-92%) and liver (12-80%) metastases. Treatment options depended on the number of BMs, the general conditions of the patient and the presence of other metastases. Most frequent treatment was whole-brain radiotherapy (WBRT) alone (36%), with median overall survival comprised between 2 and 9 months. Median overall survival was better after surgery alone (from 3 to 16.2 months), or combined with WBRT (from 7.6 to 14 months). After stereotactic radiosurgery alone, overall survival could reach 9.5 months. Many favourable prognostic factors were identified, such as high Karnofsky performance status, low recursive partitioning analysis classes, lack of extracranial disease, low number of BMs and possibility to perform surgical treatment. CONCLUSION: BMs from CRC are rare. In the presence of favourable prognostic factors, an aggressive management including surgical resection with or without WBRT or stereotactic radiosurgery can improve the overall survival.

Temporary successful results of ventral rectopexy for enterocele surgical correction, about 138 patients.

PURPOSE: This work aimed to analyse short- and long-term results of enterocele surgical treatment by ventral rectopexy. METHODS: All females who underwent ventral rectopexy for enterocele in our department were included. All patients underwent standardized preoperative evaluation. Data was retrospectively collected, after examination of patients or by telephone survey. Postoperative evaluation was performed by an independent observer. RESULTS: One hundred thirty-eight females (median age = 63 years [21-86 years]) were included. They were postmenopausal and multiparous in 94 and 70% of cases, respectively. Pelvic pressure, vaginal prolapse, or the both were observed in 28, 16 or 56% of the patients, respectively. The most frequent associated symptoms were dyschezia (63%) and faecal incontinence (30%). On preoperative workup, enterocele was isolated in two cases. Rectocele, internal rectal prolapse and cervicocystoptosis were the most frequently associated pelvic floor disorders. Ventral rectopexy was performed through laparoscopy in 128 patients (93%). In the short term, all pelvic symptoms were significantly improved, except urinary incontinence. At the end of follow-up (56 months [7-125]), specific symptoms and dyschezia were still significantly improved. Secondary failure was reported in 31% of patients. By multivariate analysis, two predictive factors for long-term failure were found: diagnosis of rectocele on preoperative MRI (odd ratio = 15; 95% CI 1.4-163; p = 0.03) and conversion into open surgery (odd ratio = 8; 95% CI 1.4-43; p = 0.02). CONCLUSION: This study suggests that ventral rectopexy is an effective treatment of enterocele, but secondary failure can be observed. Patients should be informed of the potential risk of long-term degradation.

Baseline Anthropometric and Metabolic Parameters Correlate with Weight Loss in Women 1-Year After Laparoscopic Roux-En-Y Gastric Bypass.

BACKGROUND: In this study, we explored in a prospective cohort of morbidly obese women undergoing laparoscopic Roux-en-Y gastric bypass (LRYGP) correlations between baseline anthropometrics, metabolic parameters, resting energy expenditure (REE), body composition, and 1-year % excess body mass index loss (%EBMIL). We also investigated risk factors for insufficient %EBMIL. METHODS: One hundred three consecutive women were prospectively evaluated at baseline (age 40.6 ± 11.2, weight 113.9 kg ± 15.3, BMI 43.3 ± 4.9 kg/m2) and 1 year after LRYGP. Weight, excess weight, brachial circumference, waist circumference, fat mass (FM) and fat-free mass (FFM) (measured with bioelectrical impedance analysis), REE, inflammation, insulin resistance, and lipid disturbances were determined before and 1 year after LRYGP. RESULTS: At 1 year, mean weight loss was 39.8 kg ± 11.7 and mean EBMIL was 15.2 kg/m2 ± 4.2. Mean %EBMIL was 86% ± 21% (range 30-146%). Baseline brachial circumference, waist circumference and triceps skinfold thickness decreased significantly at 1 year (P < 0.001). Blood glucose and insulin levels, HDL cholesterol, LDL cholesterol, triglycerides, and CRP also decreased significantly (P < 0.001). The mean loss of initial FFM and FM was 9.1 kg ± 8.2 (15%) and 30.7 kg ± 11.8 (53%), respectively. REE on body weight ratio (REE/BW) increased from 15.3 kcal/kg ± 2.8 to 18.4 kcal/kg ± 2.5 (p < 0.0001) and REE on FFM ratio decreased from 31.2 to 28.7 kcal/day/kg (p < 0.001). Preoperative waist circumference (r = -0.3; P < 0.001), blood glucose level (r = -0.37; P < 0.001), and CRP (r = -0.28; P = 0.004) were negatively correlated with EBMIL% 1 year after surgery. Among baseline body composition parameters, only preoperative FM was negatively correlated with %EBMIL (r = -0.23; p = 0.02). One year after surgery FM change was negatively correlated with EBMIL% (r = -0.49; P < 0.001) while FFM/BW ratio was positively correlated with %EBMIL (r = 0.71; P < 0.001). Increase in REE/BW at 1 year was positively correlated with %EBMIL (r = 0.47; p < 0.001). On multivariate analysis, baseline blood glucose level (OR = 1.77; CI 95%: [1.3-2.4]) was the only predictive factor of EBMIL <60% at 1 year. CONCLUSION: LRYGB has beneficial effects on clinical, biological parameters, and body composition. Increasing the proportion of FFM on total BW and REE/BW is associated with better results in terms of weight loss. Baseline glucose level may be helpful in identifying poor responders to LRYGBP. TRIAL REGISTRATION: NCT02820285y ( https://clinicaltrials.gov/ct2/show/NCT02820285?term=Characterization+of+Immune+Semaphorin+in+Non-Alcoholic+Fatty+Liver+Disease+and+NASH&rank=1 ).

Roux-En Y Gastric Bypass Results in Long-Term Remission of Hepatocyte Apoptosis and Hepatic Histological Features of Non-alcoholic Steatohepatitis.

The long-term effects of bariatric surgery on non-alcoholic steatohepatitis (NASH), focusing on liver injury and hepatocyte apoptosis, are not well-established. We here performed a longitudinal study with paired liver biopsies of nine morbidly obese women (median BMI: 42 [38.7; 45.1] kg/m(2)) with NASH with a median follow-up of 55 [44; 75] months after laparoscopic Roux-en-Y gastric bypass (LRYGB) surgery. LRYGB surgery was associated with significant weight loss (median BMI loss -13.7 [-16.4; -9.5] kg/m(2)), improved hepatic steatosis in all patients (55.5% with total resolution), and resolution of hepatic inflammation and hepatocyte ballooning in 100 and 88.8% of cases, respectively. Alanine aminotransferase levels dropped to normal values while hepatic activated cleaved caspase-3 levels strongly decreased after a median follow-up of 55 months. Hepatocyte apoptosis, as evaluated by serum caspase-generated keratin-18 fragment, improved within the first year following LRYGB and these improvements persisted for at least 55 months. LRYGB in morbidly obese patients with NASH is thus associated with a long-lasting beneficial impact on hepatic steatohepatitis and hepatocyte death.