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Some epithelial neoplasms of the appendix, including low-grade appendiceal mucinous neoplasm and adenocarcinoma, can result in pseudomyxoma peritonei (PMP). Little is known about the mutational spectra of these tumor types and whether mutations may be of clinical significance with respect to therapeutic selection. In this study, we identified somatic mutations using the Ion Torrent AmpliSeq Cancer Hotspot Panel v2. Specimens consisted of 3 nonneoplastic retention cysts/mucocele, 15 low-grade mucinous neoplasms (LAMNs), 8 low-grade/well-differentiated mucinous adenocarcinomas with pseudomyxoma peritonei, and 12 adenocarcinomas with/without goblet cell/signet ring cell features. Barcoded libraries were prepared from up to 10 ng of extracted DNA and multiplexed on single 318 chips for sequencing. Data analysis was performed using Golden Helix SVS. Variants that remained after the analysis pipeline were individually interrogated using the Integrative Genomics Viewer. A single Janus kinase 3 (JAK3) mutation was detected in the mucocele group. Eight mutations were identified in the V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) and GNAS complex locus (GNAS) genes among LAMN samples. Additional gene mutations were identified in the AKT1 (v-akt murine thymoma viral oncogene homolog 1), APC (adenomatous polyposis coli), JAK3, MET (met proto-oncogene), phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA), RB1 (retinoblastoma 1), STK11 (serine/threonine kinase 11), and tumor protein p53 (TP53) genes. Among the PMPs, 6 mutations were detected in the KRAS gene and also in the GNAS, TP53, and RB1 genes. Appendiceal cancers showed mutations in the APC, ATM (ataxia telangiectasia mutated), KRAS, IDH1 [isocitrate dehydrogenase 1 (NADP+)], NRAS [neuroblastoma RAS viral (v-ras) oncogene homolog], PIK3CA, SMAD4 (SMAD family member 4), and TP53 genes. Our results suggest molecular heterogeneity among epithelial tumors of the appendix. Next generation sequencing efforts have identified mutational spectra in several subtypes of these tumors that may suggest a phenotypic heterogeneity showing mutations that are relevant for targeted therapies.

In this sham-controlled, randomized trial involving patients with dysplastic Barrett's esophagus, patients who were treated with radiofrequency ablation were more likely to have complete eradication of dysplasia and intestinal metaplasia and less likely to progress to more severe dysplasia or cancer. Adverse events included chest pain and esophageal stricture. Patients with dysplastic Barrett's esophagus who were treated with radiofrequency ablation were more likely to have complete eradication of dysplasia and intestinal metaplasia and less likely to progress to more severe dysplasia or cancer. Barrett's esophagus is defined as metaplasia of the esophageal epithelium, with normal squamous epithelium replaced by columnar epithelium containing goblet cells, also known as intestinal metaplasia (Figure 1A). 1 This change is associated with gastroesophageal reflux disease. 2 Approximately 10% of patients with chronic reflux have Barrett's esophagus, 3 , 4 and the prevalence of the condition in a recent population study was 1.6%. 5 The condition is associated with an increased risk of esophageal adenocarcinoma. 6 , 7 The incidence of this once rare cancer has increased by more than 500% since the 1970s. 8 The cancer remains highly lethal, with a 5-year survival rate of less . . .

BackgroundComplications of endoscopic mucosal resection (EMR) of large colorectal polyps remain a concern.ObjectiveWe aimed to compare safety and efficacy of cold EMR (without electrocautery) to hot EMR (with electrocautery) of large colorectal polyps.DesignIn this multicentre randomised trial, patients with any large (≥20 mm) non-pedunculated colon polyp were assigned to cold or hot EMR (primary intervention), and to submucosal injection with a viscous or non-viscous solution (secondary intervention) following a 2×2 design. The primary outcome was the rate of severe adverse events (SAEs). The secondary outcome was polyp recurrence. In this study, we report results of the primary intervention.Results660 patients were randomised and analysed. An SAE was observed in 2.1% of patients in the cold EMR group and in 4.3% in the hot EMR group (p=0.10) (per protocol analysis 1.4 vs 5.0%, p=0.017) with fewer perforations following cold EMR (0%) compared with hot EMR (1.6%, p=0.028). Postprocedure bleeding did not differ (1.5% vs 2.2%, p=0.57). The effect of cold resection was independent of the type of submucosal injection solution, polyp size or antithrombotic medications. Recurrence was detected in 27.6% and 13.6% in the cold and hot EMR groups, respectively (p<0.001). Recurrence was not significantly different for 20–29 mm polyps (18.6% vs 13.4%, p=0.24) and for sessile serrated polyps (14.1% vs 8.5%, p=0.33).ConclusionUniversal application of cold EMR did not significantly lower SAEs (unless cold EMR could be completed) and doubled the recurrence rate compared with hot EMR.Trial registration detailsClinicalTrials.gov, number: NCT03865537.

INTRODUCTION:Forceps-assisted cannulation has been reported to facilitate difficult papillary cannulation during endoscopic retrograde cholangiopancreatography (ERCP), especially in the context of abnormal papillary anatomy or associated papillary diverticula. We performed a randomized, controlled trial to evaluate if forceps-assisted cannulation improves cannulation success rates, reduces the incidence of difficult cannulations, and decreases the risk of post-ERCP pancreatitis.METHODS:One hundred fifty-two patients with difficult papillary cannulation during ERCP were randomized to cannulation with or without forceps. Difficult cannulation was defined as follows: papilla in/on the rim of a diverticulum, difficult cannulation (defined as 5 or more attempts, 5 or more minutes, or 2 or more unintended pancreatic duct wire passages), redundant tissue overlaying the papilla, or a type 2, 3, or 4 papilla. The primary clinical outcome was rate of successful cannulation.RESULTS:In total, 70 patients underwent forceps-assisted cannulation and 81 did not use forceps. Forceps patients were younger (62 vs 68 years P = 0.009), but otherwise baseline demographics, ERCP indication, trainee involvement, and papilla classification were similar with failed initial cannulation the most common reason for enrollment. One hundred percent of patients in the forceps-assisted group vs 83.9% in the no forceps group (P < 0.001) underwent successful cannulation. All patients in the no forceps group who crossed over to the forceps group had successful cannulation. Although not statistically significant, the difficult cannulation rate (57.1 vs 69.1, P = 0.132) was higher in the no forceps group and the post-ERCP pancreatitis rate was low in both groups (5.7 vs 3.7, P = 0.705).DISCUSSION:Using forceps-assisted technique to overcome difficult cannulation improves ERCP cannulation success rates.

The presence of a pancreatic cyst often prompts concern, although the rate of malignant transformation to mucin-producing adenocarcinoma is not known. We aimed to determine the prevalence rate of mucin-producing adenocarcinoma in US adults with pancreatic cysts. This retrospective, population-based cross-sectional study calculated the annual number of mucin-producing adenocarcinomas using the Surveillance Epidemiology and End Results (SEER 18) database and the 2010 US census. The overall prevalence rate of cysts in the population was found using data from large cross-sectional imaging studies of incidental cyst prevalence. Prevalence rates were then calculated by dividing the annual number of mucin-producing adenocarcinomas by the cyst prevalence rate. Between 2005 and 2009, 1,137 mucin-producing adenocarcinomas were estimated to be found annually in a US adult population of 137,154,960. The total number of pancreas cysts, given a cyst prevalence rate of 2.5%, was 3,428,874. Therefore, the prevalence rate of mucin-producing adenocarcinoma arising in patients with pancreatic cysts was 33.2 per 100,000 (95% confidence interval (CI): 21.9-44.5). The prevalence rate was 32.8 per 100,000 (95% CI: 21.6-44.0) in women and 33.5 per 100,000 (95% CI: 22.2-44.8) in men. As expected, the rate of malignant transformation increased linearly with advancing age (highest 38.6 per 100,000 in 80- to 84-year-old men). Malignant transformation of pancreatic cysts into mucin-producing adenocarcinoma in US adults is a very rare event. Current clinical guidelines and resource allocation for pancreatic cyst disease should be reconsidered given these findings.

This corrects the article DOI: 10.1038/ajg.2016.368.

Introduction Endoscopic radiofrequency ablation (ERFA) is being evaluated as definitive treatment for patients with Barrett’s esophagus (BE). Guidelines have yet to be developed for the application of this technology to patients with ultralong-segment BE (ULBE, ≥8 cm). This study reports a single institution’s experience with ERFA of ULBE. Methods A retrospective review of patients with ULBE undergoing ERFA from August 2005 to February 2009 was conducted. The entire segment of intestinal metaplasia (IM) was treated at each session using balloon- and/or plate-based devices (BARRX Medical, Inc., Sunnyvale, CA). Retreatments, endoscopic mucosal resection (EMR), dilations, and biopsies were performed based on endoscopic findings. Surveillance was conducted according to standard guidelines. Results Twenty-five patients (22 male) with a median age of 66 years [interquartile range (IQR) 57–74 years] were included. The length of BE treated was 10 cm (median; IQR 8–12 cm). Intramucosal carcinoma (IMC) was present in 3 patients, 15 had high-grade dysplasia (HGD), 6 had low-grade dysplasia (LGD), and 1 had IM without dysplasia. Complications for all 25 patients included hemorrhage ( n  = 1), stricture ( n  = 2), and nausea and vomiting ( n  = 2). Time from the initial procedure was such that 15 patients had postablation biopsies at least once. One patient with biopsies elected to undergo esophagectomy. Of these patients, 78.5% (11/14) had complete response (CR; no residual IM), two patients regressed from HGD to IM, and one patient with IMC had residual HGD and was treated with repeat EMR. The number of ablations in this group was 2.5 (median, IQR 2–3) during a median follow-up time of 20.3 months (IQR 10.4–29.2 months). Conclusion ERFA is safe and feasible in patients with ULBE and can be applied to the entire length of IM during one session. Eradication of BE can be achieved with few repeat ablations and continued, vigilant surveillance.

Aim: To compare the quality between 2 commonly used sedation practices for upper endoscopic ultrasound (EUS) by using expert observational analysis of the sedation practice. Methods: After institutional review board approval, 50 adults undergoing EUS had videotape observation of the procedural sedation: 25 received benzodiazepine/opiate administered by the endoscopy team as per the standard protocol at our institution, and 25 received propofol administered by a dedicated anesthesiologist. Quantitative analysis of the video was performed using the Dartmouth Operative Conditions Scale (DOCS). The DOCS is a tool previously developed to quantify the adequacy of procedural sedation through an objective measurement of the patient state during the sedation process. In this study, the DOCS was used in a novel way to compare the quality of sedation provided by different sedation protocols. Data were collected on patient demographics, patient and provider satisfaction, efficiency, side effects, and safety measures. Results: Videotape analysis using the DOCS revealed that 52% (13/25) of the standard group exhibited an uncontrolled patient state (significant undersedation and/or oversedation) on 1 or more occasion during their EUS procedure compared with 28% (7/25) of the propofol group. Patients in the standard group spent 7.1% of the procedure in an uncontrolled patient state, whereas patients in the propofol group experienced an uncontrolled state approximately 1.0% of the procedure time. Overall efficiency as measured by time in both the procedure room and in recovery was superior in the propofol group. These patients spent 12 less minutes on average in the procedure room and were ready for discharge in about half the time (56 minutes versus 109 minutes). The propofol group experienced significantly less in-hospital and at-home nausea and vomiting and felt back to baseline status more quickly. Finally, patient satisfaction was improved in the propofol group: 60% felt the procedure was better than anticipated versus 21% in the standard group. Conclusions: Expert videotape analysis of the patient state during procedural sedation allows direct comparison of sedation methodologies using small numbers of patients. In our institution, endoscopist-directed sedation using a midazolam/narcotic combination for EUS proved inferior to sedation using propofol given by an anesthesiologist. Specifically, a midazolam/narcotic combination provided less effective intraprocedural conditions, was less efficient both before and after the procedure, and was less satisfactory to patients as compared with propofol. Results of this type of analysis can be used to drive appropriate system redesign and improve patient care.