Management of Pathogenic CDH1 Variant Carriers Within the FREGAT Network: A Multicentric Retrospective Study.

OBJECTIVE: To describe the management of pathogenic CDH1 variant carriers (pCDH1vc) within the FREGAT (FRench Eso-GAsTric tumor) network. Primary objective focused on clinical outcomes and pathological findings, Secondary objective was to identify risk factor predicting postoperative morbidity (POM). BACKGROUND: Prophylactic total gastrectomy (PTG) remains the recommended option for gastric cancer risk management in pCDH1vc with, however, endoscopic surveillance as an alternative. METHODS: A retrospective observational multicenter study was carried out between 2003 and 2021. Data were reported as median (interquartile range) or as counts (proportion). Usual tests were used for univariate analysis. Risk factors of overall and severe POM (ie, Clavien-Dindo grade 3 or more) were identified with a binary logistic regression. RESULTS: A total of 99 patients including 14 index cases were reported from 11 centers. Median survival among index cases was 12.0 (7.6-16.4) months with most of them having peritoneal carcinomatosis at diagnosis (71.4%). Among the remaining 85 patients, 77 underwent a PTG [median age=34.6 (23.7-46.2), American Society of Anesthesiologists score 1: 75%] mostly via a minimally invasive approach (51.9%). POM rate was 37.7% including 20.8% of severe POM, with age 40 years and above and low-volume centers as predictors ( P =0.030 and 0.038). After PTG, the cancer rate on specimen was 54.5% (n=42, all pT1a) of which 59.5% had no cancer detected on preoperative endoscopy (n=25). CONCLUSIONS: Among pCDH1vc, index cases carry a dismal prognosis. The risk of cancer among patients undergoing PTG remained high and unpredictable and has to be balanced with the morbidity and functional consequence of PTG.

Management strategies of anastomotic ulcer after gastric bypass and risk factors of recurrence.

BACKGROUND: Marginal ulcers (MU) after gastric bypass are a challenging problem. The first-line treatment is a medical therapy with eviction of risk factors but is sometimes insufficient. The management strategies of intractable ulcers are still not clearly defined. The aim of our study was to analyse the risk factors for recurrence, the management strategies used and their efficiencies. METHODS: Based on a retrospective analysis of all MU managed in our tertiary care centre of bariatric surgery during the last 14 years, a descriptive analysis of the cohort, the management strategies and their efficiency were analysed. A logistic regression was done to identify the independent associated risk factors of intractable ulcer. RESULTS: Fifty-six patients matched inclusion criteria: 30 were referred to us (13 Roux-en-Y Gastric Bypass-RYGB and 17 One Anastomosis Gastric Bypass-OAGB), 26 were operated on in our institution (24 RYGB and 2 OAGB). 11 patients had a complicated inaugural MU requiring an interventional procedure in emergency: 7 perforations, 4 haemorrhages. The majority of MU were treated medically as a first-line therapy (n = 45; 80.4%). 32 MU recurred: 20 patients required surgery as a 2nd line therapy, 6 were operated on as a 3rd line therapy and 1 had a surgery as a 5th line therapy. The OAGB was the only risk factor of recurrence (p = 0.018). We found that the Surgical management was significantly more frequent for patients with a OAGB (84% versus 35% for RYGB, p = 0.001); the most performed surgical procedure was a conversion of OAGB to RYGB (n = 11, 37.9%). CONCLUSION: Surgery was required for a large number of MU especially in case of recurrence, but recurrence can still occur after the surgery. The OAGB was the only risk factor of recurrence identified and conversion to RYGB seemed to be effective for the healing.

L1 chimeric transcripts are expressed in healthy brain and their deregulation in glioma follows that of their host locus.

Besides the consequences of retrotransposition, long interspersed element 1 (L1) retrotransposons can affect the host genome through their antisense promoter. In addition to the sense promoter, the evolutionarily recent L1 retrotransposons, which are present in several thousand copies, also possess an anti-sense promoter that can produce L1 chimeric transcripts (LCT) composed of the L1 5' UTR followed by the adjacent genomic sequence. The full extent to which LCT expression occurs in a given tissue and whether disruption of the defense mechanisms that normally control L1 retrotransposons affects their expression and function in cancer cells, remain to be established. By using CLIFinder, a dedicated bioinformatics tool, we found that LCT expression was widespread in normal brain and aggressive glioma samples, and that approximately 17% of recent L1 retrotransposons, from the L1PA1 to L1PA7 subfamilies, were involved in their production. Importantly, the transcriptional activities of the L1 antisense promoters and of their host loci were coupled. Accordingly, we detected LCT-producing L1 retrotransposons mainly in transcriptionally active genes and genomic loci. Moreover, changes in the host genomic locus expression level in glioma were associated with a similar change in LCT expression level, regardless of the L1 promoter methylation status. Our findings support a model in which the host genomic locus transcriptional activity is the main driving force of LCT expression. We hypothesize that this model is more applicable when host gene and LCT are transcribed from the same strand.