The c.386A>C p.(Asn129Thr) variant in SMAD4 is likely to be pathogenic, causing Juvenile Polyposis Syndrome. A case report of a mosaic variant.

BACKGROUND: Juvenile Polyposis Syndrome (JPS) is a rare autosomal dominant hereditary disorder characterized by the development of multiple hamartomatous gastrointestinal polyps. Here, we present a case of JPS with a mosaic variant in SMAD4. METHODS: Exome sequencing TRIO analysis, using germline DNA from the biological mother and father along with the index case (IC). RESULTS: A 46-year-old male with no family history of cancer presented with chronic iron deficiency anemia and was diagnosed with massive gastric polyposis (≥100 polyps). At the age of 59, he underwent a total gastrectomy, revealing numerous polyps occupying the entire gastric mucosa, including a 5 cm gastric hyperplastic polyp with high-grade dysplasia and focal adenocarcinoma. TRIO analysis identified the c.386A>C p.(Asn129Thr) variant in the SMAD4 gene at an allele frequency (AF) of 22%, suggesting its mosaic origin. Subsequently, the variant was found in heterozygosity in the IC's son, who exhibited two subcentimeter polyps in the colon and seven inflammatory gastric polyps with gastric inflammatory areas and hyperplasia, suggesting that the c.386A>C p.(Asn129Thr) variant in SMAD4 segregated with the phenotype. CONCLUSION: Our study provides evidence supporting the classification of the c.386A>C p.(Asn129Thr) variant in SMAD4 as a likely pathogenic variant. This finding contributes to improved accuracy in the diagnosis and genetic counseling of JPS.

A novel lumen-apposing metal stent for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a prospective cohort study.

BACKGROUND AND STUDY AIMS: A novel large-diameter, lumen-apposing, self-expanding metal stent with bilateral flanges was recently developed for endoscopic ultrasound (EUS)-guided transmural drainage of symptomatic pancreatic fluid collections (PFCs). The aim of this study was to evaluate the efficacy and safety of this stent in a large cohort. PATIENTS AND METHODS: Patients with a PFC undergoing EUS-guided drainage with this novel stent were prospectively enrolled in this multicenter cohort study. RESULTS: There were 61 patients: 46 patients (75 %) with walled-off necrosis (WON) and 15 (25 %) with a pancreatic pseudocyst. Stent placement was technically successful in 60 patients (98 %, 95 %CI 95 % - 100 %). Clinical success, defined as resolution of clinical symptoms in combination with a decrease in the PFC size to ≤ 2 cm on imaging, was achieved in 93 % of patients with a pancreatic pseudocyst (95 %CI 77 % - 100 %) and in 81 % of patients with WON (95 %CI 69 % - 94 %). Treatment failure occurred in nine patients (16 %, 95 %CI 6 % - 26 %), including four patients who required surgical intervention. Stent removal was performed in 82 % of patients after a median of 32 days (range 2 - 178) and was rated as easy in all but one patient. In 10 patients, endoscopic stent removal was not performed because of stent migration (n = 3), stent dislodgement during necrosectomy (n = 3), stent removal during surgery (n = 2), or refusal by the patient (n = 2). In total, five major complications were reported (9 %, 95 %CI 2 % - 16 %), including PFC infection (n = 4) and perforation (n = 1). CONCLUSION: EUS-guided drainage using this novel stent is feasible and the clinical results obtained are promising with a low major complication rate.

Complete Barrett's eradication endoscopic mucosal resection: an effective treatment modality for high-grade dysplasia and intramucosal carcinoma--an American single-center experience.

OBJECTIVES: Complete Barrett's eradication endoscopic mucosal resection (CBE-EMR) is the endoscopic removal of all Barrett's epithelium with the curative intent of eliminating high-grade dysplasia (HGD)/intramucosal carcinoma (IMC) and reducing the risk of metachronous lesion development. We report our single tertiary referral center's long-term clinical experience using this modality in HGD/IMC management. METHODS: In this study, we retrospectively reviewed all patients who had CBE-EMR for Barrett's esophagus (BE) with HGD/IMC who had been entered into our center's prospectively collected database. High-definition white-light and narrow-band imaging examinations were used according to the protocol. Staging endoscopic ultrasound was done before CBE-EMR to exclude invasive disease or suspicious lymphadenopathy. High-dose proton pump inhibition was instituted after initial treatment, and Seattle-type surveillance biopsies were performed on follow-up every 6 months once the CBE-EMR procedure was completed. RESULTS: A total of 49 patients (mean age 67 years, median 65, s.d. 11; 75% men) with histologically confirmed BE and HGD (33), IMC (16), underwent CBE-EMR from August 2003 to August 2008. The mean BE segment length was 3.2 cm (median 2, s.d. 2.2); 26 patients had short-segment BE, and 30 had visible lesions. A total of 106 EMR procedures were performed. On initial EMR, two patients had superficial submucosal carcinoma invasion (sm1) and two had IMC with lymphatic channel invasion. All four patients were referred for esophagectomy, but one opted for continued endoscopic management, without evidence of residual or recurrent carcinoma. A total of 14 patients await completion of EMR (9) or first follow-up endoscopy (5). CBE-EMR therapy was completed in 32 patients by an average of 2.1 sessions (median 2, s.d. 0.9). Surveillance biopsies showed normal squamous epithelium in 31 of 32 (96.9%) patients (mean remission time 22.9 months, median 17, s.d. 16.7, interquartile range 11-38). In all, 10 of 46 patients who continued in the endoscopic protocol had subsquamous Barrett's epithelium on EMR specimens and/or treatment endoscopy biopsies. Overall, 1 of these 10 patients had Barrett's underneath squamous mucosa on most recent surveillance biopsies. CBE-EMR upstaged pre-EMR pathology results in 7 of 49 (14%) of patients and downstaged pathology in 15 of 49 (31%) patients. In all, 18 of 49 (37%) patients developed symptomatic esophageal stenosis after a mean of 24.4 days (median 13.5, s.d. 27.8); all were successfully managed by endoscopic treatment. No perforations or uncontrollable bleeding occurred. CONCLUSIONS: To our knowledge, this is the largest American single-center experience demonstrating that CBE-EMR with close endoscopic surveillance is an effective treatment modality for BE with HGD/IMC. Although the rate of stenosis development is significant, it is easily treated by endoscopic dilation. Patients considering endoscopic ablation should be counseled appropriately. The role of CBE-EMR in patients with lymphatic invasion or superficial submucosal invasion remains to be defined.

Helicobacter pylori infection in patients with erosive esophagitis is associated with rapid heartburn relief and lack of relapse after treatment with pantoprazole.

Previous studies have shown an increased effect of proton pump inhibitors on intragastric pH in Helicobacter pylori (HP)-infected patients suffering from gastroesophageal reflux disease (GERD). We evaluated the effect of HP infection on healing and symptom relief in GERD patients with erosive esophagitis treated with pantoprazole. Two hundred twenty-seven patients with endoscopically proven reflux esophagitis were treated for 8 weeks with pantoprazole, 40 mg daily. Patients achieving endoscopic healing at that time were treated for 16 weeks more with pantoprazole, 20 mg daily. Healing and symptom relief rates for HP infection were compared. We found complete relief of heartburn in 72.3% of the HP-positive versus 58.8% of the HP-negative group (P < 0.05). Overall prevalence of heartburn at 8 weeks was higher in the HP-negative group (40.3 vs. 25.8%; P < 0.05), with no significant differences in endoscopic healing (overall 80.4%). At 24 weeks of treatment, the symptomatic relapse rate was higher in the HP-negative group (25.9 vs. 10.2%; P < 0.020). At 8 weeks, patients with erosive esophagitis and HP infection exhibited a significantly better response to pantoprazole through complete heartburn relief, with no differences in endoscopic healing rates between the groups. After 24 weeks, the relapse rate was significantly higher in the HP-negative group.