Jennifer Chennat

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 Barretts eradication endoscopic mucosal resection (CBE-EMR) is the endoscopic removal of all Barretts 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 centers 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 Barretts esophagus (BE) with HGD/IMC who had been entered into our centers 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 Barretts epithelium on EMR specimens and/or treatment endoscopy biopsies. Overall, 1 of these 10 patients had Barretts 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.

Multisociety guideline on reprocessing flexible gastrointestinal endoscopes: 2011.

● The beneficial role of GI endoscopy for the prevention, diagnosis, and treatment of many digestive diseases and cancer is well established. Like many sophisticated medical devices, the endoscope is a complex, reusable instrument that requires reprocessing before being used on subsequent patients. The most commonly used methods for reprocessing endoscopes result in high-level disinfection. To date, all published occurrences of pathogen transmission related to GI endoscopy have been associated with failure to follow established cleaning and disinfection/ sterilization guidelines or use of defective equipment. Despite the strong published data regarding the safety of endoscope reprocessing, concern over the potential for pathogen transmission during endoscopy has raised questions about the best methods for disinfection or sterilization of these devices between patient uses. To this end, in 2003, the American Society for Gastrointestinal Endoscopy (ASGE) and the Society for Healthcare Epidemiology of America collaborated with multiple physician and nursing organizations, infection prevention and control organizations, federal and state agencies, and industry leaders to develop evidence-based guidelines for reprocessing GI endoscopes.1,2 Since that ime, high-level disinfectants, automated reprocessing mahines, endoscopes and endoscopic accessories have all volved.3-6 However, the efficacy of decontamination and high-level disinfection is unchanged and the principles guiding both remain valid.7 Additional outbreaks of infection related to suboptimal infection prevention practices during endoscopy or lapses in endoscope reprocessing have been well publicized. A cluster of hepatitis C cases was attributed to grossly inappropriate intravenous medication and sedation practices.8 In numerous other instances, risk of infection transission has been linked to less willful, but incorrect, eprocessing as a result of unfamiliarity with endoscope hannels, accessories, and the specific steps required for eprocessing of attachments.9 Recent on-site ambulatory urgery center surveys confirm widespread gaps in infecion prevention practices.10 Given the ongoing occurrences of endoscopy-associated infections attributed to

American Gastroenterological Association guidelines are inaccurate in detecting pancreatic cysts with advanced neoplasia: a clinicopathologic study of 225 patients with supporting molecular data

BACKGROUND AND AIMS The American Gastroenterological Association (AGA) recently reported evidence-based guidelines for the management of asymptomatic neoplastic pancreatic cysts. These guidelines advocate a higher threshold for surgical resection than prior guidelines and imaging surveillance for a considerable number of patients with pancreatic cysts. The aims of this study were to assess the accuracy of the AGA guidelines in detecting advanced neoplasia and present an alternative approach to pancreatic cysts. METHODS The study population consisted of 225 patients who underwent EUS-guided FNA for pancreatic cysts between January 2014 and May 2015. For each patient, clinical findings, EUS features, cytopathology results, carcinoembryonic antigen analysis, and molecular testing of pancreatic cyst fluid were reviewed. Molecular testing included the assessment of hotspot mutations and deletions for KRAS, GNAS, VHL, TP53, PIK3CA, and PTEN. RESULTS Diagnostic pathology results were available for 41 patients (18%), with 13 (6%) harboring advanced neoplasia. Among these cases, the AGA guidelines identified advanced neoplasia with 62% sensitivity, 79% specificity, 57% positive predictive value, and 82% negative predictive value. Moreover, the AGA guidelines missed 45% of intraductal papillary mucinous neoplasms with adenocarcinoma or high-grade dysplasia. For cases without confirmatory pathology, 27 of 184 patients (15%) with serous cystadenomas (SCAs) based on EUS findings and/or VHL alterations would continue magnetic resonance imaging (MRI) surveillance. In comparison, a novel algorithmic pathway using molecular testing of pancreatic cyst fluid detected advanced neoplasias with 100% sensitivity, 90% specificity, 79% positive predictive value, and 100% negative predictive value. CONCLUSIONS The AGA guidelines were inaccurate in detecting pancreatic cysts with advanced neoplasia. Furthermore, because the AGA guidelines manage all neoplastic cysts similarly, patients with SCAs will continue to undergo unnecessary MRI surveillance. The results of an alternative approach with integrative molecular testing are encouraging but require further validation.

Preoperative GNAS and KRAS Testing in the Diagnosis of Pancreatic Mucinous Cysts

Purpose: Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound–fine-needle aspiration (EUS–FNA) remains unclear. Experimental Design: GNAS and KRAS testing was performed on EUS–FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst. Results: Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83–1.00] but 65% sensitivity (95% CI, 0.52–0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86–1.00) and 84% sensitivity (95% CI, 0.70–0.92). Conclusions: The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms. Clin Cancer Res; 20(16); 4381–9. ©2014 AACR.

Integration of KRAS testing in the diagnosis of pancreatic cystic lesions: a clinical experience of 618 pancreatic cysts.

With improvements in abdominal imaging, detection of incidental pancreatic cysts are becoming increasingly common. Analysis of pancreatic cyst fluid from fine-needle aspiration is particularly important in identifying intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs), which have significant implications in clinical intervention and follow-up. Previous controlled studies have shown that KRAS mutations in cyst fluid are highly specific for mucinous differentiation in pancreatic cysts; however, this has not been examined in the clinical setting. Over a 6-year study period, 618 pancreatic cyst fluids obtained by fine-needle aspiration at the time of endoscopic ultrasound were tested for KRAS mutations as part of routine evaluation for a cystic neoplasm. Of the 618 specimens, 603 (98%) from 546 patients were satisfactory for molecular analysis. Patients ranged in age from 17 to 90 years (mean, 63.9 years) and were predominantly female (68%). Pancreatic cysts were relatively evenly distributed throughout the pancreas and ranged in size from 0.6 to 11.0 cm (mean, 2.3 cm). Mutations in KRAS were detected in 232 of 603 (38%) aspirates. Although sufficient for molecular analysis, 320 of 603 (53%) specimens were either less than optimal (38%) or unsatisfactory (15%) for cytopathologic diagnosis. Surgical follow-up information was available for 142 (26%) patients and consisted of 53 KRAS-mutated and 89 KRAS-wild-type cysts. Overall, KRAS mutations had a specificity of 100%, but a sensitivity of 54% for mucinous differentiation. When stratified by cyst type, KRAS had a sensitivity of 67% and 14% for IPMNs and MCNs, respectively. In summary, KRAS mutations were highly specific for mucinous differentiation, but were inadequate in identifying MCNs. Future molecular studies and the combination of other fluid markers are required to improve the detection and classification of pancreatic mucinous neoplasms by endoscopic ultrasound fine-needle aspiration.

Initial performance profile of a new 6F self-expanding metal stent for palliation of malignant hilar biliary obstruction.

BACKGROUND A 6F endoscopic biliary self-expanding metal stent (SEMS) has been newly introduced for intended simultaneous side-by-side bilateral deployment in hilar malignant obstruction. OBJECTIVE To report our initial experience with the Zilver 635 biliary SEMS. DESIGN Retrospective chart review. SETTING Tertiary referral medical center. PATIENTS Sixteen consecutive malignant hilar biliary obstruction patients. INTERVENTIONS Endoscopic palliative treatment of malignant biliary obstruction with the Zilver 635 SEMS from December 2008 to January 2010. MAIN OUTCOME MEASUREMENTS Technical/functional success rates, early complications (within 30 days of stent placement), early/late stent occlusion, and biliary reintervention rates. RESULTS A total of 49 Zilver SEMSs were placed in 16 patients (mean age 61 years, 6 men) for Bismuth type II (n = 4), III (n = 5), and IV (n = 7) lesions. Twelve had cholangiocarcinoma, 2 had metastatic colon cancer, 1 had lung cancer, and 1 had pancreatic cancer. The technical success rate was 100%. Side-by-side simultaneous bilateral stent deployment was required and was achieved successfully in 10 cases. Additional transpapillary stents were placed for potential future biliary access. The 30-day mortality rate was 0%. There were 1 early (6%) and 3 late (19%) stent occlusions. Successful overall biliary drainage was 75%. LIMITATIONS Small sample size, uncontrolled retrospective study. CONCLUSIONS Malignant hilar biliary obstruction endoscopic palliation with the Zilver 635 SEMS offers acceptable initial feasibility, safety, and efficacy profiles. The current design facilitates smaller bile duct negotiation and more precise intrahepatic placement. Expanding available lengths would allow transpapillary bridged bilateral SEMS placement for future reobstructed biliary access. Further long-term studies are required for comparative outcomes with other current SEMS technology.

Feasibility of a novel system for intraductal balloon-anchored direct peroral cholangioscopy and endotherapy with an ultraslim endoscope (with videos)

BACKGROUND Advantages of direct peroral cholangioscopy (DPOCS) by using an ultraslim endoscope include a single-operator platform, image quality equal to that of standard endoscopy, and separate water and air channels. However, DPOCS has significant limitations, including cumbersome biliary access, en-face position with the ampulla, and gastric looping of the endoscope. A newly designed anchoring balloon may overcome these challenges. OBJECTIVE To report the feasibility of DPOCS with the anchoring balloon. DESIGN Pilot study, porcine model. SETTING Animal resources center. INTERVENTION The anchoring balloon system developed by Cook Medical (Winston-Salem, NC) was used for DPOCS. MAIN OUTCOME MEASUREMENTS Primary: Feasibility of biliary access maintenance and intraductal mobility. Secondary: Feasibility of intraductal therapeutic procedures. RESULTS Four animal subjects underwent DPOCS with the anchoring balloon. Ductal access was achieved with sphincterotomy in 2 subjects and with a balloon sphincteroplasty in 2 subjects. Intraductal placement of the ultraslim endoscope was achieved in all biliary access attempts without balloon migration or deflation. Common bile duct, cystic duct, bifurcation, and main right and left duct direct visualization was achieved in all cases. Therapeutic interventions by DPOCS, including intraductal biopsy, balloon dilatation, and intraductal bilateral metal stent placement, were all completed successfully. Biliary perforation occurred in one case because of balloon overinflation and in a second case because of sphincterotomy. LIMITATIONS Prototype study in an animal model and small study size. CONCLUSION Our results show that the novel anchoring balloon system successfully and safely enables DPOCS for both diagnostic and therapeutic interventions. If corroborated in human trials, it could offer a new platform for biliary interventions.

Peripancreatic fat necrosis worsens acute pancreatitis independent of pancreatic necrosis via unsaturated fatty acids increased in human pancreatic necrosis collections

Background and aims Peripancreatic fat necrosis occurs frequently in necrotising pancreatitis. Distinguishing markers from mediators of severe acute pancreatitis (SAP) is important since targeting mediators may improve outcomes. We evaluated potential agents in human pancreatic necrotic collections (NCs), pseudocysts (PCs) and pancreatic cystic neoplasms and used pancreatic acini, peripheral blood mononuclear cells (PBMC) and an acute pancreatitis (AP) model to determine SAP mediators. Methods We measured acinar and PBMC injury induced by agents increased in NCs and PCs. Outcomes of caerulein pancreatitis were studied in lean rats coadministered interleukin (IL)-1β and keratinocyte chemoattractant/growth-regulated oncogene, triolein alone or with the lipase inhibitor orlistat. Results NCs had higher fatty acids, IL-8 and IL-1β versus other fluids. Lipolysis of unsaturated triglyceride and resulting unsaturated fatty acids (UFA) oleic and linoleic acids induced necro-apoptosis at less than half the concentration in NCs but other agents did not do so at more than two times these concentrations. Cytokine coadministration resulted in higher pancreatic and lung inflammation than caerulein alone, but only triolein coadministration caused peripancreatic fat stranding, higher cytokines, UFAs, multisystem organ failure (MSOF) and mortality in 97% animals, which were prevented by orlistat. Conclusions UFAs, IL-1β and IL-8 are elevated in NCs. However, UFAs generated via peripancreatic fat lipolysis causes worse inflammation and MSOF, converting mild AP to SAP.

Pancreatic Cystic Neoplasm

he increasing use of advanced radiographic and endoscopic techniques as led to more frequent detection of small, asymptomatic pancreatic ystic lesions. Most pancreatic cysts are nonneoplastic, occurring because f pancreatic injury, infection, or congenital anomalies. A smaller ercentage are neoplastic, and it is this group of pancreatic cystic lesions hat will be considered in this monograph. Pancreatic cystic neoplasms (PCN) may arise from the ductal epitheium (serous cystic neoplasms [SCNs], mucinous cystic neoplasms MCN], intraductal papillary mucinous neoplasms [IPMN], intraductal ubular neoplasms [ITN]), endocrine cells, pancreatic acinar cells (acinar ell cystadenoma, acinar cell cystadenocarcinoma), and mesenchymal lements. Solid-pseudopapillary tumors also appear cystic on imaging tudies, but in this group of tumors the cystic change is degenerative in tiology. The originating cell lineage of these tumors is as yet uncharacerized. Rarely, pancreatic neoplasms that are usually solid may appear ystic.

Hydrogen Peroxide-Assisted Endoscopic Necrosectomy for Walled-Off Pancreatic Necrosis: A Dual Center Pilot Experience

Pancreatic necrosis (PNec) is a serious local complication occurring in 10–15 % of patients with acute pancreatitis (AP). Necrotizing pancreatitis can organize into necrotic collections, termed walled-off necrosis (WON) [1, 2]. Symptomatic WON has traditionally been treated operatively [3]. In several recent trials, successful resolution of WON was achieved using endoscopic therapy, termed direct endoscopic necrosectomy (DEN) [4, 5]. A challenge to DEN is removal of all necrotic material from within the collection [6, 7]. Hydrogen peroxide (H2O2) is acknowledged as an effective means to achieve mechanical debridement of wounds [8–11]. In this case series, we describe a dual center experience with the use of H2O2 to facilitate removal of necrotic debris in patients undergoing DEN as the preliminary measure for management of WON.