Fistula Recurrence: A Clinical Reality after Successful Endoscopic Closure of Laparoscopic Sleeve Gastrectomy Fistulas.

BACKGROUND AND AIMS: Laparoscopic sleeve gastrectomy (LSG)-related fistulas are important and potentially fatal complications. We aimed at determining the incidence, predictive factors, and management of recurrence of post-LSG fistulas. METHODS: This is a retrospective cohort study of 12 consecutive patients with LSG fistulas managed endoscopically between 2008 and 2013. We analyzed factors associated with recurrence of post-LSG fistulas and the efficacy of a primarily endoscopic approach to manage fistula recurrence. RESULTS: The average age at fistula detection after LSG was 43.3 ± 10.9 years, and 10 (83%) patients were female. The median interval between surgery and initial fistula detection was 14 (4-145) days. Fistulas were located at the gastric cardia in 9/12 patients. A median of 4 (1-10) endoscopies were performed per patient until all fistulas were successfully closed. The median follow-up was 30.5 (15-72) months. Fistula recurrence was detected in 3 (25%) female patients with an average age of 31.7 ± 7.9 years after a median of 119 (50-205) days of the initial fistula closure. Fistulas in all 3 patients recurred at the gastric cardia and were successfully managed endoscopically. There was a second recurrence in 1 patient after 6 months, and she was re-operated with anastomosis of a jejunal loop at the site of the fistula orifice at the gastric cardia. We did not find any factors at initial fistula detection that were significantly associated with fistula recurrence. There were no deaths related to initial fistula after LSG and fistula recurrence. CONCLUSIONS: A primarily endoscopic approach is an effective and safe method for the management of fistulas after LSG. Fistula recurrence occurred in 25% of patients and was managed endoscopically. KEY MESSAGES: Although we could not define predictive factors of post-LSG fistula recurrence, it is a clinical reality and can be managed endoscopically.

OBJECTIVOS: As fistulas pós-gastrectomia vertical (sleeve) laparoscópica (LSG) são complicações importantes e potencialmente fatais. O objectivo do estudo foi determinar a incidência, factores preditivos e manejo da recorrência de fistulas pós LSG. MÉTODOS: Estudo retrospectivo de 12 doentes com fistulas pós LSG manejados endoscopicamente entre 2008 e 2013. Analisámos factores associados à recorrência de fistulas pós LSG e a eficácia da abordagem endoscópica. RESULTADOS: Idade média na detecção das fistulas pós LSG foi de 43.3 ± 10.9 anos e 10 (83%) doentes eram mulheres. O intervalo mediano entre a cirurgia e a detecção da fistula inicial foi de 14 (4­145) dias. As fistulas localizaram-se no cárdia em 9/12 doentes. Foram realizadas em mediana 4 (1­10) endoscopias por doente até ao encerramento eficaz das fistulas. O tempo mediano de seguimento foi de 30.5 (15­72) meses. A recorrência das fistulas foi detectada em 3 (25%) doentes, todas mulheres, com idade média de 31.7 ± 7.9 anos, após um tempo mediano de 119 (50­205) dias após encerramento da fistula inicial. As recorrências das fistulas nas três doentes ocorreram no cárdia e foram manejados endoscopicamente.Houve uma segunda recorrência de fistula numa doente após 6 meses que foi reoperada com anastomose de ansa jejunal no local do orifício de fistula no cárdia. Não conseguimos determinar factores na altura da detecção da fistula inicial pós LSG significativamente associados com recorrência de fistulas. Não houve mortalidade associada às fistulas pós LSG (inicial ou recorrência). CONCLUSÕES: A abordagem primariamente endoscópica das fistulas pós LSG é um método eficaz e seguro. A recorrência de fistulas ocorreu em 25% dos doentes. As recorrências de fistulas pós LSG são manejáveis endoscopicamente. MENSAGENS CHAVE: Embora não tenhamos conseguido definir factores preditivos de recorrência de fistulas pós LSG, a recorrência de fistulas é uma realidade clínica e é manejável endoscopicamente.

How adiponectin, leptin, and ghrelin orchestrate together and correlate with the severity of nonalcoholic fatty liver disease.

BACKGROUND: Adipose tissue contributes to nonalcoholic fatty liver disease (NAFLD), being a source of fatty acids and cytokines such as leptin and adiponectin, and regulating ghrelin production. Their role in NAFLD pathogenesis remains controversial. We aimed to study the influence of those cytokines on the severity of NAFLD. METHODS: Morbidly obese individuals with biopsy-proven NAFLD were recruited. The NAFLD activity score was applied to liver histology. Serum concentrations of adiponectin, leptin, and ghrelin were determined. RESULTS: Eighty-two patients were included, 13% with nonalcoholic steatohepatitis (NASH). Hypertriglyceridemia (P=0.018) and metabolic syndrome (P=0.040) were independent factors associated with NASH. Leptin associated positively and ghrelin associated negatively with BMI; adiponectin associated negatively with the waist to hip ratio. Adiponectin associated negatively with insulin resistance, hypertension, and metabolic syndrome; ghrelin associated positively with diabetes mellitus. Adiponectin below 23 ng/ml associated with NASH (odds ratio 12.95, P<0.001). Leptin increased progressively (P=0.032) and adiponectin decreased (P=0.004) with increasing severity of steatosis. Also, leptin increased progressively with more severe fibrosis (P=0.053). A formula incorporating the three cytokines yielded an AUROC of 0.789 (P=0.002), a sensitivity of 81.8%, and a specificity of 76.1% for NASH. CONCLUSION: An imbalance in adiponectin, leptin, and ghrelin seems to be associated with more severe NAFLD. A formula combining the three cytokines showed good accuracy for NASH.

Liver and muscle in morbid obesity: the interplay of fatty liver and insulin resistance.

INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) can be seen as a manifestation of overnutrition. The muscle is a central player in the adaptation to energy overload, and there is an association between fatty-muscle and -liver. We aimed to correlate muscle morphology, mitochondrial function and insulin signaling with NAFLD severity in morbid obese patients. METHODS: Liver and deltoid muscle biopsies were collected during bariatric surgery in NAFLD patients. NAFLD Activity Score and Younossi's classification for nonalcoholic steatohepatitis (NASH) were applied to liver histology. Muscle evaluation included morphology studies, respiratory chain complex I to IV enzyme assays, and analysis of the insulin signaling cascade. A healthy lean control group was included for muscle morphology and mitochondrial function analyses. RESULTS: Fifty one NAFLD patients were included of whom 43% had NASH. Intramyocellular lipids (IMCL) were associated with the presence of NASH (OR 12.5, p<0.001), progressive hepatic inflammation (p = 0.029) and fibrosis severity (p = 0.010). There was a trend to an association between IMCL and decreased Akt phosphorylation (p = 0.059), despite no association with insulin resistance. In turn, hepatic steatosis (p = 0.015) and inflammation (p = 0.013) were associated with decreased Akt phosphoryation. Citrate synthase activity was lower in obese patients (p = 0.047) whereas complex I (p = 0.040) and III (p = 0.036) activities were higher, compared with controls. Finally, in obese patients, complex I activity increased with progressive steatosis (p = 0.049) and with a trend with fibrosis severity (p = 0.056). CONCLUSIONS: In morbid obese patients, presence of IMCL associates with NASH and advanced fibrosis. Muscle mitochondrial dysfunction does not appear to be a major driving force contributing to muscle fat accumulation, insulin resistance or liver disease. Importantly, insulin resistance in muscle might occur at a late point in the insulin signaling cascade and be associated with IMCL and NAFLD severity.

Impaired renal function in morbid obese patients with nonalcoholic fatty liver disease.

INTRODUCTION AND AIMS: Obesity is a common risk factor for nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). NAFLD and CKD have been associated in many epidemiological studies. We hypothesize that more severe liver disease, namely nonalcoholic steatohepatitis (NASH), is related with further renal impairment. We aimed to evaluate if changes in renal function were present in morbid obese patients with NAFLD. METHODS: Prospective and consecutive recruitment of morbid obese patients with biopsy proven NAFLD obtained during bariatric surgery. Renal function was evaluated with CKD-Epidemiology Collaboration estimated glomerular filtration rate (eGFR). Plasmatic adiponectin, leptin and active ghrelin concentrations were determined. RESULTS: One hundred and forty-eight patients were included of whom 25% had NASH and 75% simple steatosis. NASH patients were older, with higher body mass index and had more frequently metabolic syndrome and lower eGFR (97 ± 22 vs 106 ± 16 ml/min/1.73(2), P = 0.035). NASH conferred an odds ratio (OR) 3.0 (1.3-7.0) for eGFR < 90 and OR 9.7 (1.0-96.4) for eGFR < 60 ml/min/1.73(2). eGFR < 90 ml/min/1.73(2) associated with aspartate aminotransferase [OR 2.9 (1.1-7.6)] and γ-glutamyl transpeptidase elevation [OR 3.0 (1.3-7.2)], NASH [OR 3.0 (1.3-7.0)], any lobular inflammatory activity [OR 3.0 (1.3-7.0)] and severe fibrosis [OR 3.4 (1.1-10.8)]. Neither eGFR nor liver histology was associated with adipokines levels. CONCLUSIONS: In morbid obese patients, NASH, particularly lobular inflammation and advanced fibrosis, associates with mild decreases in eGFR, suggesting a common inflammatory link between liver and renal lesion.