Person:

Forcione, David

Endoscopic mucosal resection (EMR) is being advocated as a diagnostic, staging, and therapeutic technique for the management of Barrett esophagus (BE)-related neoplasia. With the emergence of new endoluminal therapy including EMR for the treatment of BE-related superficial adenocarcinomas, accurate staging has become crucial to select patients for different treatment arms. Intramucosal adenocarcinomas can be successfully treated by endoluminal techniques, whereas submucosal invasive tumors with a greater risk of lymph node metastasis are likely candidates for esophagectomy. Endoscopic ultrasound (EUS) is used to stage superficial BE-related neoplasms, yet endoscopic staging can be incongruent to that obtained after pathologic examination. In this study, we sought to determine morphologic factors, which may influence EUS staging in 35 cases with intramucosal adenocarcinoma diagnosed by subsequent EMR, focusing on tumor characteristics and structural changes associated with BE. Among the latter duplication of the muscularis mucosae, either fragmented or well-organized, was seen in 64% of 11 cases that were overstaged as having submucosal invasion by EUS, compared with 38% of those accurately staged. A greater vertical thickness of the tumor was also associated with overstaging by EUS (1.61+/-0.75 mm in the discordant vs. 1.16+/-0.67 mm in the concordant groups, P=0.028). The results illustrate how morphologic factors may affect EUS staging of superficial esophageal adenocarcinomas. EUS alone is not sufficient for staging these neoplasms precisely, and to accurately stratify patients into different treatment arms, EMR should play a role as a complementary staging modality.

Abstract Background: In patients with inoperable malignant biliary strictures, endoscopic retrograde cholangiopancreatography (ERCP) guided biliary stenting fails in 5% to 10% patients due to difficult anatomy/inability to cannulate the papilla. Recently, endoscopic ultrasound guided biliary drainage (EUS-BD) has been described. Primary outcomes were to evaluate the biliary drainage success rates with EUS and compare it to percutaneous transhepatic biliary drainage (PTBD). Secondary outcomes were to evaluate overall procedure related complications. Methods: Study selection criteria: Studies evaluating the efficacy of EUS-BD and comparing EUS-BD versus PTBD in inoperable malignant biliary stricture patients with a failed ERCP were included in this analysis. Data collection and extraction: Articles were searched in Medline, PubMed, and Ovid journals. Two authors independently searched and extracted data. The study design was written in accordance to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Subgroup analyses of prospective studies and EUS-BD versus PTBD were performed. Statistical method: Pooled proportions were calculated using fixed and random effects model. I2 statistic was used to assess heterogeneity among studies. Results: Initial search identified 846 reference articles, of which 124 were selected and reviewed. Sixteen studies (N = 528) that met the inclusion criteria were included in this analysis. In the pooled patient population, the percentage of patients that had a successful biliary drainage with EUS was 90.91% (95% CI = 88.10–93.38). The proportion of patients that had overall procedure related complications with EUS-PD was 16.46% (95% CI = 13.20–20.01). The pooled odds ratio for successful biliary drainage in EUS-PD versus PTBD group was 3.06 (95% CI = 1.11–8.43). The risk difference for overall procedure related complications in EUS-PD versus PTBD group was −0.21 (95% CI = −0.35 to −0.06). Relative risk for infectious complications and bile leak in EUS-BD versus PTBD was 0.25 (95% CI = 0.07–0.94) and 0.33 (95% CI = 0.12–0.87), respectively. Conclusions: In patients with inoperable malignant biliary strictures who failed an ERCP guided biliary stenting, EUS-BD seems to be an excellent management option and superior to PTBD with higher successful biliary drainage rates and relatively fewer complications.

Background and aims: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. Patients and methods: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. Results: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100 % and 93.2 %), but low sensitivity (48.3 % and 56.3 %) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8 %) and AUC (0.84) significantly compared to KRAS (65.3 % and 0.74) or CEA (65.8 % and 0.74) alone, but only in the clinical cohort (P < 0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73 % vs. 37 %, P = 0.001). The negative predictive value of KRAS mutation was 77.6 % in differentiating non-malignant cysts. Conclusions: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use.

Background: Patients with acute cholecystitis are treated with early cholecystectomy. A subset of patients are unfit for surgery due to comorbidities and late presentation. Prompt gall bladder drainage (GBD) with percutaneous or endoscopic approach remains a viable therapeutic option for nonoperative candidates. Endoscopic ultrasound (EUS) guided transluminal gall bladder drainage (EUS-GBD) continues to evolve as an alternative approach to percutaneous drainage. With continued refinement in stent technology, lumen apposing self-expandable metal stent (LAMS) offers several advantages. We performed a pooled analysis on the efficacy and safety of EUS-GBD with LAMS in nonoperative candidates with acute cholecystitis. Methods Extensive English language literature search was performed in Medline, Embase, Cochrane Central, and Google Scholar using keywords “endoscopic ultrasound”, “stent”, “gallbladder”, “acute cholecystitis”, and “cholecystostomy” from Jan 2000 to Dec 2016. Fixed and random effects models were used to calculate the pooled proportions. Results Data was extracted from 13 studies that met the inclusion criteria (n = 233). Pooled proportion of technical success was 93.86% (95% CI = 90.56 to 96.49) and clinical success was 92.48% (95% CI = 88.9 to 95.42). Overall complication rate was 18.31% (95% CI = 13.49 to 23.68) and stent related complication rate was 8.16% (95% CI = 4.03 to 14.96) in the pooled percentage of patients. Pooled proportion for perforation was 6.71% (95% CI 3.65 to 10.6) and recurrent cholangitis/cholecystitis was noted in 4.05% (95% CI = 1.64 to 7.48). Publication bias calculated using Harbord-Egger bias indicator gave a value of −0.61 (95% CI = −1.39 to 0.16, p = 0.11). The Begg-Mazumdar indicator for bias gave Kendall's tau b value of −0.42 (p ≥ 0.05). Conclusions EUS-GBD with LAMS is a safe and alternative treatment modality for patients needing gallbladder drainage, with acceptable intraprocedural and postprocedural complications. However, due to the limited data and lack of direct comparison with other methods, further controlled trials are necessary to estimate the overall efficacy and safety and the role of EUS-GBD with LAMS in management of nonoperative patients with acute cholecystitis.

IgG4-related disease is a newly recognized fibro-inflammatory condition characterized by several features: a tendency to form tumefactive lesions in multiple sites; a characteristic histopathological appearance; and—often but not always—elevated serum IgG4 concentrations. An international symposium on IgG4-related disease was held in Boston, MA, on 4–7 October 2011. The organizing committee comprising 35 IgG4-related disease experts from Japan, Korea, Hong Kong, the United Kingdom, Germany, Italy, Holland, Canada, and the United States, including the clinicians, pathologists, radiologists, and basic scientists. This group represents broad subspecialty expertise in pathology, rheumatology, gastroenterology, allergy, immunology, nephrology, pulmonary medicine, oncology, ophthalmology, and surgery. The histopathology of IgG4-related disease was a specific focus of the international symposium. The primary purpose of this statement is to provide practicing pathologists with a set of guidelines for the diagnosis of IgG4-related disease. The diagnosis of IgG4-related disease rests on the combined presence of the characteristic histopathological appearance and increased numbers of IgG4+ plasma cells. The critical histopathological features are a dense lymphoplasmacytic infiltrate, a storiform pattern of fibrosis, and obliterative phlebitis. We propose a terminology scheme for the diagnosis of IgG4-related disease that is based primarily on the morphological appearance on biopsy. Tissue IgG4 counts and IgG4:IgG ratios are secondary in importance. The guidelines proposed in this statement do not supplant careful clinicopathological correlation and sound clinical judgment. As the spectrum of this disease continues to expand, we advocate the use of strict criteria for accepting newly proposed entities or sites as components of the IgG4-related disease spectrum.