Genomic profile concordance between pancreatic cyst fluid and neoplastic tissue

BACKGROUND DNA mutational analysis of pancreatic cystic fluid (CF) is a useful adjunct to the evaluation of pancreatic cysts. KRAS/GNAS or RAF/PTPRD/CTNNB1/RNF43 mutations are highly specific to precancerous or advanced neoplasia. Several studies recently demonstrated the ability of next-generation sequencing (NGS)analysis to detect DNA mutations in pancreatic CF, but few studies have performed a systematic comparative analysis between pancreatic CF and neoplastic surgical tissue (NT). The value of CF-NGS analysis indicators for determining surgical resection necessitates evaluation. AIM To confirm whether CF genomic profiles are a reliable malignancy predictor by comparing NGS mutational analyses of CF and NT. METHODS Patients requiring surgery for high-risk pancreatic cysts were included in a multicenter prospective pilot study. DNA from CF (collected by endoscopic ultrasound-guided fine needle aspiration (known as EUS-FNA)) and NT (collected by surgery) were analyzed by NGS. The primary objective was to compare the mutation profiles of paired DNA samples. The secondary objective was to correlate the presence of specific mutations (KRAS/GNAS, RAF/ PTPRD/CTNNB1/RNF43/POLD1/TP53) with a final cancer diagnosis. Sensitivity and specificity were also evaluated. RESULTS Between December 2016 and October 2017, 20 patients were included in this pilot study. Surgery was delayed for 3 patients. Concordant CF-NT genotypes were found in 15/17 paired DNA, with a higher proportion of mutated alleles in CF than in NT. NGS was possible for all pancreatic CF collected by EUS-FNA. In 2 cases, the presence of a KRAS/GNAS mutation was discordant between CF and NT. No mutations were found in 3 patients with NT or pancreatic cysts with high-grade dysplasia. The sensitivity and specificity of KRAS/GNAS mutations in CF to predict an appropriate indication for surgical resection were 0.78 and 0.62, respectively. The sensitivity and specificity of RAF/PTPRD/CTNNB1 /RNF43/POLD1/TP53 mutations in CF were 0.55 and 1.0, respectively. CONCLUSION Mutational analyses of CF and NT were highly concordant, confirming the value of NGS analysis of CF in the preoperative malignancy assessment. However, these results need to be confirmed on a larger scale.

Management of recto-vaginal fistulas after prosthetic reinforcement treatment for pelvic organ prolapse

AIM: To communicate our findings on successful treat-ment of recto-vaginal fistulas (RVFs) after prosthetic reinforcement surgery of pelvic organ prolapse (POP). METHODS: A retrospective single center study between 1998 and 2008 was performed. A total of 80 patients with RVF were identified, of which five patients (6%), with a mean age of 65 years (range: 52-73), had undergone previous surgery for POP with pros-thetic reinforcement. RESULTS: All patients complained about ongoing vaginal infections and febrile episodes. These symptomswere reported after a mean period of 18 mo after POP repair. As a first intervention, three patients underwent ablation of the prosthetic material (PM). As a second intervention, open proctectomy with a primary anas-tomosis, an omental patch, and a protective ileostomy were performed in two patients. One patient required a terminal colostomy due to complete destruction of the anal sphincters. In two other patients, ablation of the PM and proctectomy was performed as a one-step procedure. The postoperative course in all patients was uneventful, with a mean length of hospitalization of 20 d (range: 15-30). Closure of the ileostomy was achieved in all four patients within four months. After a mean period of 35 mo (range: 4-60) of follow-up, no recurrence was observed with normal continence in four patients.CONCLUSION: In our experience, the definitive treat-ment of high RVFs after PM repair for POP necessitates ablation of the PM, proctectomy with a primary colo-rectal anastomosis, an omental patch interposition, and a temporary ileostomy.