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

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

Muscle mitochondrial enzymatic activities according to hepatic fibrosis severity.

<p>Differences in mean mitochondrial enzymatic activities, citrate synthase (A), complex I (B), complex II (C), complex III (D) and complex IV (E) with fibrosis severity. Error bars: 95% CI. There was a trend to a progressive increase in complex I activity according to fibrosis stage.</p

Patients main features.

<p>NASH = non alcoholic steatohepatitis, BMI = body mass index, WTH = waist to hip, AST = aspartate aminotransferase, ALT = alanine aminotransferase, γ-GT = γ-glutamyl transpeptidase, ALP = alkaline phosphatase, NAS = NAFLD activity score.</p><p>P* = significance level in the comparison between NASH and non NASH.</p

Deltoid muscle histology.

<p>Slides showing intramyocellular fat accumulation highlighted in Oil red, (40×) (A) and inter fascicular fat, stained with hematoxylin & eosin (10×) (B).</p

Muscle morphology in morbidly obese patients with NAFLD and lean controls.

<p>NASH = non alcoholic steatohepatitis, T1F = type 1 fibers, Δ coefficient = variability coefficient, T2F = type 2 fibers, EMCL = extramyocellular lipids, EMCL = intramyocellular lipids, RRF = ragged red fibers presence, COX = presence of cytochrome oxidase negative fibers.</p><p>P* = significance level in the comparison between controls and obese patients;</p><p>P** = significance level in the comparison between NASH and non NASH.</p

Muscle mitochondrial enzymatic activities according to hepatic steatosis degree.

<p>Differences in mean mitochondrial enzymatic activities, citrate synthase (A), complex I (B), complex II (C), complex III (D) and complex IV (E) with steatosis severity. Error bars: 95% CI. Complex I activity progressively increased with hepatic steatosis severity.</p

Muscle mitochondrial respiratory chain enzymes activity in morbidly obese patients with NAFLD and lean controls.

<p>NASH = non alcoholic steatohepatitis. All enzymatic activities expressed in nmol/min/mg PNC.</p><p>P* = significance level in the comparison between controls and obese patients;</p><p>P** = significance level in the comparison between NASH and non NASH.</p

Insulin resistance according to liver histology.

<p>Differences in HOMA-IR according to the severity of steatosis (A), fibrosis stage (B) and lobular inflammatory grade (C). Error bars: 95% CI (not possible to calculate for fibrosis stage 3 or 4 or lobular inflammation grade 3, only one patient). HOMA-IR progressively increased with severity of hepatic steatosis, lobular inflammation and fibrosis.</p