Gastrobronchial Fistula: A Serious Complication of Sleeve Gastrectomy. Results of a French Multicentric Study.

BACKGROUND: Gastrobronchial fistula (GBF) is a complication of esophageal, splenic, or antireflux surgeries and was recently described as a complication of bariatric surgery. Our aim was to study all cases of GBF after laparoscopic sleeve gastrectomy (LSG) managed in five French university bariatric centers in order to establish the incidence and to evaluate the different treatments of this complication. METHODS: We retrospectively studied 13 patients which developed GBF after LSG performed between March 2007 and August 2012. Patients were separated into two groups: patients who had early gastric fistula which has evolved into a GBF (group 1) and patients who had a late gastric fistula, either directly GBF or a late gastric fistula evolved in GBF (group 2). RESULTS: Group 1 consisted of five patients and group 2 of eight patients. All patients were undernourished at diagnosis. Management of GBF was a combined thoraco-abdominal surgery with gastrojejunal anastomosis (n = 5) or total gastrectomy (n = 1), multiple endoscopic treatment and thoracic surgery (n = 3), an endobronchial valve (n = 1), total gastrectomy and thoracic drainage (n = 1), and transorificial intubation with thoracic surgery or drainage (n = 2). There was no mortality. All GBF healed. CONCLUSIONS: GBF after LSG is a serious complication which is not anecdotal. Most of the early gastric fistulas occuring after LSG become chronic and can evolve into a GBF. Surgical approach is an effective treatment. Endobronchial valve is a novel alternative.

Mitochondrial localization of the forkhead box class O transcription factor FOXO3a in brain.

FOXO3a is member of the Forkhead box class O transcription factors, which functions in diverse pathways to regulate cellular metabolism, differentiation, and apoptosis. FOXO3a shuttles between the cytoplasm and nucleus and may be activated in neurons by stressors, including seizures. A subset of nuclear transcription factors may localize to mitochondria, but whether FOXO3a is present within brain mitochondria is unknown. Here, we report that purified mitochondrial fractions from rat, mouse, and human hippocampus, as well as HT22 hippocampal cells, contain FOXO3a protein. Immunogold electron microscopy supported the presence of FOXO3a within brain mitochondria, and chromatin immunoprecipitation analysis suggested FOXO3a was associated with mitochondrial DNA. Over-expression of a mitochondrially targeted FOXO3a fusion protein in HT22 cells, but not primary hippocampal neurons, conferred superior protection against glutamate toxicity than FOXO3a alone. Mitochondrial FOXO3a levels were reduced in the damaged region of the mouse hippocampus after status epilepticus, while mitochondrial fractions from the hippocampus of patients with temporal lobe epilepsy displayed higher levels of FOXO3a than controls. These results support mitochondria as a site of FOXO3a localization, which may contribute to the overall physiological and pathophysiological functions of this transcription factor.

BH3-only protein Bid is dispensable for seizure-induced neuronal death and the associated nuclear accumulation of apoptosis-inducing factor.

Prolonged seizures activate members of the Bcl-2 homology domain 3-only sub-group of the Bcl-2 protein family, which are essential for initiation of apoptosis signaling. Bid is a potent pro-apoptotic Bcl-2 homology domain 3-only protein, which upon proteolytic activation translocates to mitochondria to promote activation of the Bax/Bak sub-group of the pro-apoptotic Bcl-2 family and thereby contributes to release of apoptogenic molecules, such as cytochrome c and possibly apoptosis-inducing factor (AIF). Bid-deficient mice have been reported to show reduced lesion volumes after ischemia and trauma in vivo but a causal role for Bid in the setting of seizure-induced neuronal death has not been investigated. In this study, we studied Bid activation following status epilepticus in mice and compared hippocampal damage between wild-type and Bid-deficient animals. Full-length Bid was detected in normal mouse hippocampus and the cleaved (activated) p15 fragment of Bid was detected shortly after status epilepticus. Bid-deficient mice underwent equivalent electrographic seizure responses during status epilepticus as wild-type animals. Hippocampal counts of degenerating neurons and surviving neuron-specific nuclear protein-positive cells were not significantly different between wild-type and Bid-deficient mice. Additionally, nuclear translocation of AIF was not reduced in Bid-deficient compared with wild-type animals subjected to status epilepticus. The present study demonstrates that AIF is not dependent on Bid for mitochondrial release and nuclear import in this model and that while Bid is cleaved during seizure-induced neuronal death, it may be functionally redundant or even not essential.