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Objective Prospective evaluation of 2 clinical-molecular models in patients with unknown pathology who underwent endoscopic ultrasound with fine-needle aspiration (EUS-FNA) for a cystic lesion of the pancreas. Summary of background data Preoperative prediction of histologic subtype (mucinous vs nonmucinous) and grade of dysplasia in patients with pancreatic cystic neoplasms is challenging. Our group has previously published 2 clinical-molecular nomograms for intraductal papillary mucinous neoplasms (IPMN) that incorporated both clinical/radiographic features and cyst fluid protein markers (sFASL, CA72-4, MMP9, IL-4). Methods This multiinstitutional study enrolled patients who underwent EUS-FNA for a cystic lesion of the pancreas. Treatment recommendations regarding resection were based on standard clinical, radiographic, and endoscopic features. Predicted probabilities of high-risk IPMN (high-grade dysplasia/invasive cancer) were calculated using the previously developed clinical-molecular nomograms. Results Cyst fluid was obtained from 100 patients who underwent diagnostic EUS-FNA. Within this group there were 35 patients who underwent resection, and 65 were monitored radiographically. Within the group that underwent resection, 26 had low-risk IPMN or benign non-IPMN lesions, and 9 had high-risk IPMN. Within the surveillance group, no patient progressed to resection or developed cancer after a median follow-up of 12 months (range: 0.5-38). Using the clinical/radiographic nomogram alone, 2 out of 9 patients with high-risk IPMN had a predicted probability >0.5. In the clinical-molecular models, 6 of 9 patients in model 1, and 6 of 9 in model 2, had scores >0.5. Conclusions This prospective study of patients with unknown cyst pathology further demonstrates the importance of cyst fluid protein analysis in the preoperative identification of patients with high-risk IPMN. Longer follow-up is necessary to determine if this model will be useful in clinical practice.

Background and study aims The aim of thi systematic review and consensus report is to standardize the practice of endoscopic ultrasound (EUS-guided needle-based confocal laser endomicroscopy (nCLE) for pancreatic cystic lesion (PCL) evaluation. Methods We performed an international, systematic, evidence-based review of the applications, outcomes, procedural processes, indications, training, and credentialing of EUS-nCLE in management of PCLs. Based on available clinical evidence, preliminary nCLE consensus statements (nCLE-CS) were developed by an international panel of 15 experts in pancreatic diseases. These statements were then voted and edited by using a modified Delphi approach. An a priori threshold of 80 % agreement was used to establish consensus for each statement. Results Sixteen nCLE-CS were discussed. Thirteen (81 %) nCLE-CS reached consensus addressing indications (non-communication PCL meeting criteria for EUS-FNA or with prior non-diagnostic EUS-FNA), diagnostic outcomes (improved accuracy for mucinous PCLs and serous cystadenomas with substantial interobserver agreement of image patterns), low incidence of adverse events (fluorescein-associated and pancreatitis), procedural processes (nCLE duration, manipulation of needle with probe), and training (physician knowledge and competence). Conclusion Based on a high level of agreement pertaining to expert consensus statements, this report standardizes the practice of EUS-nCLE. EUS-nCLE should be systematically considered when EUS-FNA is indicated for PCL evaluation.

Introduction Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is the standard diagnostic procedure for many intrathoracic and intra-abdominal lesions. Next-generation fine-needle biopsies (FNBs) can increase diagnostic yield by procuring tissue suitable for histological processing. We evaluate the diagnostic yield and operating characteristics of the SharkCore (SC; Medtronic Corp., Minneapolis, MN) FNB in a tertiary referral facility. Materials and methods We performed a single-center retrospective review of SC-FNB–acquired tissue between January 2014 and March 2018. Patient demographic data, endoscopic features, and pathology data were obtained from the electronic medical record. Diagnostic yield was assessed by the ability to obtain a definitive diagnosis, defined as malignant or benign interpretations. Operating characteristics were also calculated. Results A total of 179 lesions were sampled with the SC-FNB in 157 patients (mean age: 63 years, 57% male). Of these, 31 lesions were concomitantly sampled with a conventional FNA needle. Most lesions were pancreatic (49%). Diagnostic yield was 86%, which was independent of lesion location, lesion size and needle gauge. Diagnostic accuracy was highest when both histology and cytology specimens were analyzed concurrently (96.5%). In patients with a history of chronic pancreatitis, accuracy, sensitivity, and negative predictive value were reduced (71.4%, 20.0%, and 69.2%, respectively). Rapid onsite evaluation (ROSE) occurred in 64.8% of cases and was more likely to be diagnostic at the time of rapid evaluation if SC-acquired tissue was utilized versus FNA-acquired tissue (P = 0.03); however, final diagnostic yield did not differ between needles (P = 0.13). Conclusions SC-FNB shows high diagnostic yield and accuracy and provides diagnostic tissue for ROSE. SC-FNB is an effective alternative to conventional FNA.

Background and Objectives: EUS-guided biliary drainage (EUS-BD) is increasingly utilized to manage unresectable malignant biliary obstruction after a failed ERCP. However, there is no data on how endoscopists perceive EUS-BD. The aim of this study was to investigate the perception of endoscopists on EUS-BD. Patients and Methods: A survey questionnaire of six topics with 22 survey statements was developed. A total of 17 pancreatobiliary endoscopists (10 from East and 7 from West) were invited to survey. The participants were asked to answer the multiple choice questionnaire and give comments. The opinions of the participants for individual survey statements were assessed using 5-point Likert scale. Results: All participants completed the survey. The endoscopists had a trend to perceive EUS-BD as a procedure indicated after a failed ERCP. Various EUS-BD methods were regarded as having different efficacy and safety. The superiority of EUS-BD over percutaneous transhepatic BD (PTBD) with regard to efficacy, procedure-related adverse events, and unscheduled re-intervention was not in agreement. Conclusions: EUS-BD was not yet perceived as the initial procedure to relieve the unresectable malignant biliary obstruction. Various EUS-BD methods were regarded as having different efficacy and safety. The superiority of EUS-BD over PTBD was not in agreement. Refining the procedure, developing dedicated devices, and gaining expertise in the procedure are necessary to popularize EUS-BD.

Background and study aims Detecting colorectal neoplasia is the goal of high-quality screening and surveillance colonoscopy, as reflected by high adenoma detection rate (ADR) and adenomas per colonoscopy (APC). The aim of our study was to evaluate the performance of a novel artificial intelligence (AI)-aided polyp detection device, Skout, with the primary endpoints of ADR and APC in routine colonoscopy. Patients and methods We compared ADR and APC in a cohort of outpatients undergoing routine high-resolution colonoscopy with and without the use of a real-time, AI-aided polyp detection device. Patients undergoing colonoscopy with Skout were enrolled in a single-arm, unblinded, prospective trial and the results were compared with a historical cohort. All resected polyps were examined histologically. Results Eighty-three patients undergoing screening and surveillance colonoscopy at an outpatient endoscopy center were enrolled and outcomes compared with 283 historical control patients. Overall, ADR with and without Skout was 54.2 % and 40.6 % respectively (P = 0.028) and 53.6 % and 30.8 %, respectively, in screening exams (P = 0.024). Overall, APC rate with and without Skout was 1.46 and 1.01, respectively, (P = 0.104) and 1.18 and 0.50, respectively, in screening exams (P = 0.002). Overall, true histology rate (THR) with and without Skout was 73.8 % and 78.4 %, respectively, (P = 0.463) and 75.0 % and 71.0 %, respectively, in screening exams (P = 0.731). Conclusion We have demonstrated that our novel AI-aided polyp detection device increased the ADR in a cohort of patients undergoing screening and surveillance colonoscopy without a significant concomitant increase in hyperplastic polyp resection. AI-aided colonoscopy has the potential for improving the outcomes of patients undergoing colonoscopy.

A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to address the research gaps and opportunities in pancreatic endoscopic ultrasound (EUS). The event occurred on July 26, 2017 in 4 sessions: (1) benign pancreatic diseases, (2) high-risk pancreatic diseases, (3) diagnostic and therapeutics, and (4) new technologies. The current state of knowledge was reviewed, with identification of numerous gaps in knowledge and research needs. Common themes included the need for large multicenter consortia of various pancreatic diseases to facilitate meaningful research of these entities; to standardize EUS features of different pancreatic disorders, the technique of sampling pancreatic lesions, and the performance of various therapeutic EUS procedures; and to identify high-risk disease early at the cellular level before macroscopic disease develops. The need for specialized tools and accessories to enable the safe and effective performance of therapeutic EUS procedures also was discussed.

Endoscopic ultrasound (EUS) plays an important role as a diagnostic and therapeutic modality in gastroenterology. New developments have emerged, especially in the last decade, and are being introduced to endoscopists. The ability to readily visualize and access organs in the gastrointestinal tract has allowed endoscopists to perform new interventional procedures. EUS procedures have taken the place of conventional approaches for the treatment of various gastrointestinal diseases, including pancreatic cystic lesions. This article focuses on the advances and future of diagnostic and therapeutic EUS.

Endoscopic ultrasonography (EUS) has become an interventional procedure for the diagnosis and treatment of various gastrointestinal and pancreatic tumors. Because of the unique anatomical location of the pancreas, EUS-guided therapies offer substantial promise for the delivery of targeted treatments. This article reviews the recent EUS-guided various therapeutic methods for pancreatic cyst and tumor ablation, especially focusing on cystic neoplasms.

Early detection strategies for pancreatic ductal adenocarcinoma are needed. This article describes a high‐sensitivity platform for detection of epithelial cells shed from preneoplastic lesions at a high risk of becoming malignant and a combination of technologies that could be used for early detection of disease in high‐risk patients., Background. Recent work has demonstrated early shedding of circulating epithelial cells (CECs) from premalignant intraductal papillary mucinous neoplasms (IPMNs). However, the potential use of CECs as a “liquid biopsy” for patients with IPMNs has been limited by antigen dependence of CEC isolation devices and the lack of robust detection biomarkers across CEC phenotypes. Materials and Methods. We utilized a negative depletion microfluidic platform to purify CECs from contaminating leukocytes and coupled this platform with immunofluorescence, RNA in situ hybridization, and RNA sequencing (RNA‐seq) detection and enumeration. Results. Using established protein (EpCAM, cytokeratins) and novel noncoding RNA (HSATII, cytokeratins) biomarkers, we detected CECs in 88% of patients bearing IPMN lesions. RNA‐seq analysis for MUC genes confirm the likely origin of these CECs from pancreatic lesions. Conclusion. Our findings increase the sensitivity of detection of these cells and therefore could have clinical implications for cancer risk stratification. Implications for Practice. This work describes a high‐sensitivity platform for detection of epithelial cells shed from preneoplastic lesions at high risk of malignant transformation. Further research efforts are underway to define the transcriptional programs that might allow discrimination between circulating cells released from tumors that will become malignant and cells released from tumors that will not. After further refinement, this combination of technologies could be deployed for monitoring and early detection of patients at high risk for developing new or recurrent pancreatic malignancies.

Background and Objectives: Pancreatic cysts are evaluated by endoscopic ultrasound and fine needle aspiration (EUS). The only accepted treatment is pancreatectomy, which is associated with morbidity and mortality. This study evaluated the optimal thermal dosimetry of a novel radiofrequency ablation device using a standard electrosurgical unit in ex vivo cyst models. Methods: A modified EUS 22-gauge monopolar needle prototype with a tip electrode connected to a standard electrosurgical unit (Erbe USA, Marietta, GA, USA) was used to induce a subboiling point temperature. A cyst model was created using 2-cm sections of porcine small intestine ligated and filled with saline. After ablation, the cyst models were prepared for pathological evaluation. The epithelial layers were measured in at least two different sites with a micrometer and compared with the corresponding control sample. Results: Thirty-two cyst models were ablated with maximum temperatures of 50°C, 60°C, 90°C, and 97°C in 8, 11, 11, and 2 cysts, respectively. Longer ablation times were required to induce higher temperatures. A trend in the reduction in thickness of the measured layers was observed after exposure to higher temperatures. A temperature over 50°C was required for the ablation of the muscularis, submucosa, and villi, and over 60°C was required to ablate the mucosal crypts. Conclusions: In a preclinical model, a novel radiofrequency EUS-capable needle connected to a standard electrosurgical unit using standard low-voltage coagulation provided ablation in a temperature-dependent fashion with a threshold of at least 60°C and a safe cyst margin below 97°C. This potentially will allow low-cost, convenient cyst ablation.

BACKGROUND Mucinous cystic neoplasms (MCNs) of the pancreas present a management conundrum. The majority are benign but all are resected due to their malignant potential. Recent studies have recommended nonsurgical management. In the current study, the authors analyzed the preoperative imaging, cytology, and cyst fluid characteristics of 136 histologically confirmed MCNs to assess predictors of a high-risk (HR) cyst for surgical triage. METHODS MCNs resected at the Massachusetts General Hospital between 1990 and 2014 formed the study cohort. Patient demographics, cyst size, and mural nodules (MNs) by endoscopic ultrasound, cytology, and cyst fluid carcinoembryonic antigen and amylase levels were correlated with histological grade. A HR cyst was defined as high-grade dysplasia or invasive carcinoma on histology. Performance characteristics were assessed for each parameter, with a cyst size ≥3 cm or a MN on imaging and malignant cytology considered to be “true-positive” results for predicting malignancy. RESULTS Only 15 of the 136 cysts had HR histology (11%). On average, patients with HR cysts were older than those with low-risk cysts (55 years vs 49 years, respectively). High-grade cytology was the most accurate predictor of malignancy (95%) followed by MN and cyst size together (88%) and MN alone (83%). The average carcinoembryonic antigen level (in ng/mL) increased with the grade of dysplasia but the ranges overlapped between low risk and HR cysts. CONCLUSIONS To the authors' knowledge, the current study is the largest series to date analyzing the cytological features of histologically confirmed MCN. Cytology is insensitive but very specific for detecting a HR MCN and outperformed imaging for the detection of HR MCN. Endoscopic ultrasound-guided fine-needle aspiration and cytology should be performed on any clinically suspected MCN that is being considered for conservative management. Cancer Cytopathol 2017;125:169–177. © 2016 American Cancer Society.

Background & Aims Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas occur mostly in older individuals. Individual life expectancy and risk of death from other factors must be carefully considered in analyzing the risks that IPMNs pose. We investigated whether there is a subset of patients with IPMNs and a high risk of dying from other causes who would not benefit from pancreatic surgery. Methods We collected data from 725 patients at Massachusetts General Hospital who underwent resection or have been under observation for IPMNs from 1992 through 2012. Comorbidities were classified according to the age-adjusted Charlson comorbidity index (CACI). Causes of death were recorded, and survival data were analyzed by the Kaplan-Meier method. Results The patients' median CACI score was 3; 10% of patients had CACI of 7 or more. Of the entire cohort, 55% underwent resection, and the remaining 45% have been under observation. After a median follow-up period of 5 years, 177 patients died (24%, 55% of deaths within 5 years of diagnosis); 78% of deaths were not related to IPMNs. The median survival time for all patients with CACI score of 7 or more was 43 months. Multivariate regression analysis revealed that the chance of non-IPMN−related death within 3 years of diagnosis is 11-fold higher for patients with CACI score of 7 or more than for patients with lower scores. Conclusions The CACI can be used to identify patients with a high risk of death from factors other than IPMNs within a few years after diagnosis. These patients are therefore not likely to benefit from further IPMN observation or pancreatic resection.

Background and study aims: Current guidelines recommend using endoscopic ultrasound (EUS), carcinoembryonic antigen (CEA) testing and cytology to manage incidental pancreatic cystic neoplasms (PCN); however, studies suggest a strategy including integrated molecular pathology (IMP) of cyst fluid may further aid in predicting risk of malignancy. Here, we evaluate several strategies for diagnosing and managing asymptomatic PCN using healthcare economic modeling. Patients and methods: A third-party-payer perspective Markov decision model examined four management strategies in a hypothetical cohort of 1000 asymptomatic patients incidentally found to have a 3 cm solitary pancreatic cystic lesion. Strategy I used cross-sectional imaging, recommended surgery only if symptoms or risk factors emerged. Strategy II considered patients for resection without initial EUS. Strategy III (EUS + CEA + Cytology) referred only those with mucinous cysts (CEA > 192 ng/mL) for resection. Strategy IV implemented IMP; a commercially available panel provided a “Benign,” “Mucinous,” or “Aggressive” classification based on the level of mutational change in cyst fluid. “Benign” and “Mucinous” patients were followed with surveillance; “Aggressive” patients were referred for resection. Quality-adjusted life-years (QALY), relative risk with 95 %CI, Number Needed to Treat (NNT), and incremental cost-effectiveness ratios were calculated. Results: Strategy IV provided the greatest increase in QALY at nearly identical cost to the cheapest approach, Strategy I. Relative risk of malignancy compared to the current standard of care and nearest competing strategy, Strategy III, was 0.18 (95 %CI 0.06 – 0.53) with an NNT of 56 (95 %CI 34 – 120). Conclusions: Use of IMP was the most cost-effective strategy, supporting its routine clinical use.

Background and Aims The tissue acquisition and diagnostic yield of cyst fluid cytology is low-to-moderate and rarely provides a specific diagnosis. The aim of this study was to compare the tissue acquisition and diagnostic tissue yield of microforceps biopsy (MFB) with cyst fluid cytology. Methods In this multicenter study, data of 42 patients who had cysts both aspirated by EUS-guided FNA (EUS-FNA) and biopsy specimens were then obtained with an MFB device, were collected. Cytology analysis of cyst fluid and histologic analysis of biopsy specimens were done. Acquisition yield was defined as percentage of patients with tissue present in the aspirate or biopsy. Diagnostic tissue yield was evaluated at 3 levels: the ability of differentiation between mucinous and/or nonmucinous cysts, detection of high risk for malignancy, and specific cyst type diagnosis. Results The mean patient age was 69 years. Sixteen pancreatic cysts (38.1%) were located in the head, 17 (40.5%) in the body, and 9 (21.4%) in the tail. The mean cyst size was 28.2 mm (12-60 mm); 25 of 42 (60%) were septated. The EUS-FNA tissue (fluid) acquisition yield was 88.1% (37/42). The MFB tissue acquisition yield was 90.4% (38/42). The diagnostic cytology yield to differentiate between mucinous and/or nonmucinous cysts was 47.6% (20/42), and the MFB histologic yield to differentiate between mucinous and/or nonmucinous cysts was 61.9% (26/42) ( P = .188). The percentage of cysts at high risk for malignancy by cytology was 54.7% (23/42), and MFB was 71.5% (30/42) ( P = .113). However, the ability of MFB to provide a specific cyst type diagnosis was 35.7% (15/42), and that for cytology was 4.8% (2/42) ( P = .001). Surgical histology was concordant with that of MFB in 6 of 7 patients (85%), and with that of cytology in 1 of 7 patients (15%). Conclusion The cyst tissue acquisition yield for MFBs was 90%. Although cytology of cyst fluid and MFB were comparable in distinguishing mucinous and nonmucinous cysts and detecting cysts at high risk for malignancy, MFB was far superior to cytology for providing a specific cyst diagnosis.

Background and Aims Patients with chronic constipation or motility disorders may be referred for rectal suction biopsy (RSB) to rule out Hirschsprung's disease (HD). RSB may not be successful beyond infancy because of the increased thickness of the rectal mucosa. EMR could improve the diagnostic yield for HD when compared with traditional RSB because larger and deeper samples are acquired for analysis. Methods In this prospective, single-center study, patients referred for RSB were offered enrollment for concurrent EMR. Specimens were analyzed pathologically for size, submucosal ganglionic tissue, and acetylcholinesterase or calretinin staining. Biopsy results were compared with transit studies, anorectal manometry, and constipation severity through validated questionnaires. Results Seventeen patients (2 male, 15 female; mean age, 35.8 years; range, 22-61 years) were enrolled in the study from 2008 to 2014. All patients underwent anorectal manometry (88% with anorectal dysfunction, 68% with outlet obstruction) and transit studies (41% with delayed transit). There were no reports of adverse events from the RSB and EMR procedures. The RSB sample volumes were significantly lower than the EMR sample volumes (0.023 cm 3 vs 0.26 cm 3 , P = .001). There was diagnostic tissue for submucosal visualization by RSB in 53% (9/17) of cases compared with 100% (17/17) with EMR ( P = .003). No cases of HD were diagnosed by RSB; one patient had rare ganglions observed by EMR. Conclusions EMR provides greater tissue volume and can improve the characterization of ganglion cells in rectal tissue compared with RSB in patients with moderate to severe constipation with suspected HD.

Little is known about the development of branch duct intraductal papillary mucinous neoplasms (BD-IPMNs). We evaluated long-term outcomes of a large cohort of patients with BD-IPMNs to determine risk of malignancy and define a subset of low-risk BD-IPMNs.We performed a retrospective analysis of data from 577 patients with suspected or presumed BD-IPMN under surveillance at the Massachusetts General Hospital. Patients underwent cross-sectional imaging analysis at 3 months or later after their initial diagnosis. The diagnosis of BD-IPMN was based on the presence of unilocular or multilocular cysts of the pancreas and a non-dilated main pancreatic duct (5 mm). We collected demographic, clinical, and pathology data. Cysts were characterized at the time of diagnosis and during the follow-up period. Follow-up duration was time between initial cyst diagnosis and date of last visit or death for patients without development of pancreatic cancer, date of surgery for patients with histologically confirmed malignancy, or date of first discovery of malignancy by imaging analysis for patients with unresectable tumors or who underwent neoadjuvant treatment before surgery. The primary outcome was risk of malignancy, with a focus on patients followed for 5 years or more, compared with that of the US population, based on standardized incidence ratio.Of the 577 patients studied, 479 (83%) were asymptomatic at diagnosis and 363 (63%) underwent endoscopic ultrasound at least once. The median follow-up time was 82 months (range, 6-329 months) for the entire study cohort; 363 patients (63%) underwent surveillance for more than 5 years, and 121 (21%) for more than 10 years. Malignancies (high-grade dysplasia or invasive neoplasm) developed after 5 years in 20 of 363 patients (5.5%), and invasive cancer developed in 16 of 363 patients (4.4%). The standardized incidence ratio for patients with BD-IPMNs without worrisome features of malignancy at 5 years was 18.8 (95% confidence interval, 9.7-32.8; P.001). One hundred and eight patients had cysts ≤1.5 cm for more than 5 years of follow-up; only 1 of these patients (0.9%) developed a distinct ductal adenocarcinoma. By contrast, among the 255 patients with cysts1.5 cm, 19 (7.5%) developed malignancy (P = .01).In a retrospective analysis of patients with BD-IPMNs under surveillance, their overall risk of malignancy, almost 8%, lasted for 10 years or more, supporting continued surveillance after 5 years. Cysts that remain ≤1.5 cm for more than 5 years might be considered low-risk for progression to malignancy.

BACKGROUND Cystic pancreatic neuroendocrine tumors (cPanNETs) account for 13% to 17% of PanNETs. Although the value of endoscopic ultrasound (EUS) imaging and cyst fluid analysis (CFA) in their preoperative diagnosis has been well described, limited information is available about the diagnostic role of cytology samples obtained from fine-needle aspiration (FNA). METHODS Cytopathology records between 1992 and 2013 were searched for all reports of cysts interpreted as PanNET. Patient demographics, clinical and radiologic information, CFA, histopathology, and cytopathology findings were recorded. Performance characteristics of cytology and EUS for the accurate diagnosis of cPanNET were calculated. RESULTS In total, 35 FNAs from 33 patients with cPanNETs were identified, and 34 EUS were performed. Cytology made a specific diagnosis of a cPanNET in 71% of the biopsies compared with a specific diagnosis by EUS in 38% of cases. An interpretation of suspicious for cPanNET was given in 77% of cases by cytology and in 47% by EUS. Cytology identified 86% of the lesions as high-risk pancreatic cysts compared with 56% by EUS. Diagnostic morphology was present on both cytology and cell block preparations in 60% of aspirates, on cytology only in 20%, and on cell block only in 20%. CFA was performed on 51% cyst fluids. All cysts but 1 revealed low carcinoembryonic antigen levels (range, 0.2 to >500 ng/mL; mean, 29.5 ng/mL), and amylase levels were

The accurate diagnosis of cystic neoplasms of the pancreas (CNP) with current diagnostic methods is limited. Endoscopic ultrasound (EUS)-guided needle-based confocal laser endomicroscopy (nCLE) is a new technique which can obtain images from the cyst wall during EUS-fine needle aspiration (EUS-FNA). The aim of this study was to assess the safety, feasibility, and diagnostic value of nCLE for CNP. Patients who underwent EUS-FNA to evaluate a CNP larger than 2 cm were enrolled. The cyst was punctured with 19-G FNA needle preloaded with an nCLE probe. The images from different areas of the cyst wall were recorded. Using the final diagnosis defined by surgery or EUS-FNA cyst fluid analysis, the accuracy of the confocal images was defined. The procedure and image acquisition was successful in 18 of the 20 patients. Predefined typical structures for mucinous cysts were visualized in 8 of 12 (66%) cysts but none of the non-mucinous cysts. The superficial vascular network which is a typical finding of serous cysts was observed in 2 of 3 patients. The sensitivity, specificity, and diagnostic accuracy of the findings of epithelial structures by nCLE were 66, 100, and 80%, respectively, for a mucinous cyst diagnosis. All patients tolerated the procedure well, and no adverse effects were determined. nCLE was found to be safe and feasible with high technical success, in this pilot study. With an overall accuracy of 80%, it has the potential to contribute to the diagnosis of CNP with specific imaging.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors arising from the gastrointestinal tract. GISTs can occur in any segment of the gastrointestinal tract from the distal esophagus to the anus, but they are most common in the stomach. The presence of c-KIT staining is a strong and universal marker of GISTs. Approximately 70 % patients with GISTs have some clinical symptoms, including gastrointestinal bleeding, manifested as melena, hematemesis, or bright red blood per rectum. Most GISTs are incidentally detected during endoscopic examinations. Endoscopic features are usually insufficient for the diagnosis of GISTs. Endoscopic ultrasonography (EUS) has become an important diagnostic tool for the evaluation of subepithelial lesions such as GISTs. EUS-guided sampling of GISTs is the preferred technique for histological diagnosis. The capability of endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) for biopsy of GISTs is better than any other well-accepted method. The EUS-guided Tru-cut core biopsy technique provides a grossly visible sample of tissue, but it has some technical disadvantages. The curative treatment of GISTs is still complete surgical resection. However, optimal endoscopic treatment along with imatinib remains controversial. Advanced resection techniques by endoscopic devices, including endoscopic submucosal resection, endoscopic submucosal tunnel dissection, and endoscopic-laparoscopic combined approach, have been used in the treatment of GISTs.

Bournet et al. have questioned the role of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) plus KRAS and GNAS mutations in malignant intraductal papillary mucinous neoplasms (IPMNs) of the pancreas in this issue of Endoscopy International Open 1 . Bournet et al. claimed that testing for KRAS mutations in cystic fluid improved the accuracy of results for cytopathologic diagnosis of malignancy whereas GNAS mutation testing did not improve the results. How should clinicians interpret these outcomes and do these results help to detect and treat an IPMN before it progresses to a pancreatic adenocarcinoma?

BACKGROUND Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic cysts obtains cyst fluid for cytologic and biochemical analysis, which may determine whether the cyst is mucinous and malignant, contributing to patient management. Despite this added value, EUS-FNA remains controversial in the preoperative assessment of pancreatic cysts. The objective of this study was to assess the utility of EUS-FNA in a cohort of small pancreatic cysts that were benign on imaging studies. METHODS All pancreatic cysts that underwent initial EUS-FNA in 2006 and 2007 were retrospectively analyzed. Ninety-two patients with pancreatic cysts met the inclusion criteria. Patients who had high-risk or worrisome features on imaging studies were excluded. Cytology, histology, and cyst fluid analysis data were collected. The main outcome measurements were radiologic and clinical follow-up as well as cytopathologic and histologic results. RESULTS EUS-FNA supported a diagnosis of a mucinous cyst in 38 of 92 patients (41%) by carcinoembryonic antigen (CEA) measurement and/or cytology. Cytology demonstrated an absence of high-grade atypia (HGA) in 89 of 92 patients (97%). The mean follow-up was 4.4 years (range, 0-7.7 years), during which 6 cysts were surgically resected and 16 cysts were resampled by at least 1 subsequent EUS-FNA. The overall negative predictive value of cytologic examination for HGA was 99%. CONCLUSIONS EUS-FNA is a screening test that contributes to a triple-negative test for pancreatic cysts—no high-risk stigmata, no worrisome features, and no HGA on cytology—providing a negative predictive value of 99% for conservative management. Cancer (Cancer Cytopathol) 2014;122:412–419. © 2013 American Cancer Society.

Background Pancreatic neuroendocrine tumours are uncommon neoplasms which may rarely be cystic. Differentiation from other more common cystic neoplasms may be difficult. Aims To describe the morphologic, cytologic, and cyst fluid characteristics of cystic pancreatic neuroendocrine tumours. Methods Retrospective analysis of consecutive patients referred for endosonographic evaluation of pancreatic cysts at four centres. Results 27 patients (12 males) with cystic pancreatic neuroendocrine tumours were identified. Prior to endosonography, this tumour was suspected in only 2 patients based on presenting symptoms (7.4%). The median cyst size was 35 mm (range 8–80 mm). Wall thickening was identified in 13 cases. The median carcinoembryonic antigen level was 1.25 (range 0.6–500). Fine needle aspiration cytology in 17 of 24 patients confirmed neuroendocrine tumour (71%). In 8 of 9 patients who had needle targeting of the cyst wall, cytology was consistent with neuroendocrine tumour (88.9%). 18 patients underwent surgical resection. Conclusions Cystic pancreatic neuroendocrine tumour was rarely suspected, including by cross-sectional imaging. Wall thickening was identified in approximately half of cases on endosonography. Cyst fluid was typically non-viscous with very low carcinoembryonic antigen levels. Targeting the wall during fine needle aspiration had a high diagnostic yield and should be performed.

PURPOSE OF REVIEW The purpose of this review is to examine the recent developments in the use of endoscopic retrograde cholangio-pancreatography (ERCP) and endoscopic ultrasound (EUS) in the management of patients with pancreatic-biliary disease. RECENT FINDINGS The use of ERCP to guide selective placement of pancreatic sphincterotomes, stone extraction balloons, and stents enables clinicians to treat pancreatic sphincteric and ductal disorders. Pancreatic stones are a remediable cause of recurrent pancreatitis and small calculi can be easily removed. The gold standard for the diagnosis of pancreas divisum remains ERCP and sphincterotomy is highly effective in the treatment of relapsing pancreatitis. Intraductal papillary mucinous neoplasms are the most common pancreatic malignancy and ERCP, as well as EUS can identify and sample the solid and cystic lesions. Mural nodules can be detected and sampled effectively by EUS-fine needle aspiration (FNA). The sensitivity of EUS-FNA for pancreatic adenocarcinoma is excellent (more than 85%). Although cyst fluid carcinoembryonic antigen is a very good marker for the presence of a mucinous cystic lesion, it is not an indicator of malignancy. SUMMARY In summary, ERCP and EUS are important tools for the management of benign and malignant lesions of the pancreas.

BACKGROUND The recognition of epithelial cells with high-grade atypia (HGA) in the cyst fluid of an intraductal papillary mucinous neoplasm (IPMN) identifies a cyst at high risk of invasive carcinoma. To the best of the authors' knowledge, the cytological features of HGA have not been systematically analyzed to define diagnostic criteria. METHODS Cell groups from patients with histologically confirmed branch-duct IPMNs were evaluated by 2 cytopathologists with expertise in pancreatic cytology. A consensus interpretation categorized the cell groups as having either low-grade (LG) or high-grade (HG) morphology. Characteristics regarding cell size and architecture, nuclear and cytoplasmic features, and background necrosis were analyzed. Performance characteristics were assessed using the Fisher exact test at 95% confidence intervals. RESULTS Sixty cell groups yielded 27 LG and 25 HG morphological groups. No consensus was reached for 8 groups, which were excluded from statistical analysis. Five features that were found to be significantly different between the LG and HG groups included: 1) cell size

Differentiating between malignant and benign bile duct strictures is often challenging. Endoscopic retrograde cholangiopancreatography with brush cytology and/or endobiliary forceps biopsy is routinely performed. Advanced cytologic methods such as fluorescence in situ hybridization or digital image analysis increases the sensitivity of cytology. Endoscopic ultrasonography enables detailed examination of tissues surrounding the bile duct stricture and offers the advantage of fine-needle aspiration. Intraductal ultrasonography enables detailed evaluation of bile duct wall layers, and cholangioscopy offers direct visualization of the bile duct lesions. Novel techniques of probe-based confocal laser endomicroscopy and optical coherence tomography have introduced the era of in vivo histology.

Background and study aims: Limited data are available on the endoscopic ultrasound (EUS) and fine-needle aspiration (FNA) characteristics of cystic pancreatic neuroendocrine tumors (CPanNets). The aims of this study were to describe the EUS and FNA characteristics of pathologically confirmed CPanNets and to compare these characteristics with mucinous cysts from matched patients. Patients and methods: From an EUS – FNA database (between 1999 and 2011), 19 patients with a pathologically confirmed CPanNet were identified. Patient characteristics, cyst fluid carcinoembryonic antigen (CEA) levels, pathology, and EUS findings were analyzed. For comparison, age- and sex-matched patients with mucinous cysts were randomly chosen from the same database. Results: Of the 19 patients, two had multiple endocrine neoplasia type 1 and two had metastases. The median diameter of the lesions was 24 mm. EUS revealed unilocular lesions in 7 patients, thinly septated lesions with thin walls in 1, and mixed solid-cystic lesions in 11. EUS – FNA cytology confirmed neoplasm in 12 of the 19 patients (63.2 %). The median cyst fluid CEA level (n = 15) was 1.1 ng/mL (range 0.3 – 500 ng/mL). Compared with matched patients with mucinous cysts, the median cyst fluid CEA was lower (1.1 ng/mL vs. 400 ng/mL), thick walls were more common (66.7 % vs. 13.3 %), and diagnostic cytology was more likely (73.3 % vs. 20.0 %). Conclusions: Analysis of EUS and FNA results showed that the cyst fluid from CPanNets had a lower CEA concentration, a higher frequency of thick walls on EUS, and higher diagnostic cytology compared with mucinous cysts. These findings may aid in the diagnosis of CPanNets.

Background and Aims EUS-guided needle-based confocal laser endomicroscopy (nCLE) characteristics of common types of pancreatic cystic lesions (PCLs) have been identified; however, surgical histopathology was available in a minority of cases. We sought to assess the performance characteristics of EUS nCLE for differentiating mucinous from non-mucinous PCLs in a larger series of patients with a definitive diagnosis. Methods Six endosonographers (nCLE experience >30 cases each) blinded to all clinical data, reviewed nCLE images of PCLs from 29 patients with surgical (n = 23) or clinical (n = 6) correlation. After 2 weeks, the assessors reviewed the same images in a different sequence. A tutorial on available and novel nCLE image patterns was provided before each review. The performance characteristics of nCLE and the κ statistic for interobserver agreement (IOA, 95% confidence interval [CI]), and intraobserver reliability (IOR, mean ± standard deviation [SD]) for identification of nCLE image patterns were calculated. Landis and Koch interpretation of κ values was used. Results A total of 29 (16 mucinous PCLs, 13 non-mucinous PCLs) nCLE patient videos were reviewed. The overall sensitivity, specificity, and accuracy for the diagnosis of mucinous PCLs were 95%, 94%, and 95%, respectively. The IOA and IOR (mean ± SD) were κ = 0.81 (almost perfect); 95% CI, 0.71-0.90; and κ = 0.86 ± 0.11 (almost perfect), respectively. The overall specificity, sensitivity, and accuracy for the diagnosis of serous cystadenomas (SCAs) were 99%, 98%, and 98%, respectively. The IOA and IOR (mean ± SD) for recognizing the characteristic image pattern of SCA were κ = 0.83 (almost perfect); 95% CI, 0.73-0.92; and κ = 0.85 ± 0.11 (almost perfect), respectively. Conclusions EUS-guided nCLE can provide virtual histology of PCLs with a high degree of accuracy and inter- and intraobserver agreement in differentiating mucinous versus non-mucinous PCLs. These preliminary results support larger multicenter studies to evaluate EUS nCLE. (Clinical trial registration number: NCT02516488.)

Background and study aim: Obstruction of biliary self-expandable metal stents (SEMSs) is seen frequently. Radiofrequency ablation (RFA) causes tissue necrosis. This study aimed to assess the efficacy of RFA for management of occluded SEMS. Patients and methods: Patients with biliary malignancy and treated for an occluded SEMS were retrospectively reviewed. The study group comprised patients treated with RFA using an Habib endoprobe inside the SEMS. The control group comprised patients treated only with insertion of a plastic stent into an occluded SEMS. The end points were; 90-day stent patency rate, time to stent reocclusion, 30-day mortality, and 3 – and 6-month survival rates. Results: During the 5-year study period 25 patients with an occluded SEMS underwent RFA and 25 patients underwent a plastic stent placement only. Both groups were matched for age and diagnosis. Immediate biliary drainage was restored in all patients. In the RFA group, the stenosis was ablated successfully in 14 patients (56 %); ablation failed in 11 and a plastic stent was then inserted into the SEMS for these. The control group had only placement of a plastic stent across the stenosis. Stent patency rate at 90 days was 56 % and 24 % in the RFA and control groups, respectively (P = 0.04). The mean stent patency time was significantly longer in the RFA group compared to the control group (119.5 vs. 65.3 days, P = 0.03). Conclusion: The application of RFA for occluded SEMS improves stent patency. RFA is an alternative treatment of tissue ingrowth in malignant biliary obstruction.

Pancreatic cystic lesions (PCLs) have been detected more frequently as a result of the increasing use of high-resolution cross-sectional imaging and the growth of the aging population in recent years. Among the common types of PCLs, the mucinous cystic neoplasms and the intraductal papillary mucinous neoplasms are well known with their malignant potential. Therefore, their differentiation from nonmucinous cysts is very important to help guide further management and prevention of invasive cancers. Cross-sectional imaging is very helpful for screening and detection of PCLs, but their value to differentiate types of cysts is limited. Endoscopic ultrasound (EUS) allows for high-frequency imaging of the pancreas and provides morphologic characteristics of cystic lesions. However, its capability to differentiate benign and malignant cysts or mucinous and nonmucinous lesions is still limited. Besides, it is an operator-dependent technique and interobserver agreement is not high. EUS-guided fine-needle aspiration (FNA) provides cyst fluid for further analysis and improves significantly the differentiation of benign/malignant and mucinous/nonmucinous PCLs. Gross appearance of fluid, cytological examination, fluid amylase, and CEA levels are helpful in certain lesions for differential diagnosis. Molecular analysis of KRAS and GNAS mutations have been proposed in recent years to further improve the mucinous/nonmucinous discrimination. New tests and methods are still under investigation to improve the diagnostic yield of EUS-FNA. In this chapter, the key issues of EUS-FNA in the differential diagnosis of PCLs are reviewed based on the recent literature.

BACKGROUND: Pancreatic cysts are aspirated to assess whether a cyst is mucinous on one hand and malignant on the other. The authors' retrospective data have indicated that high-grade atypical epithelial cells (AECs) identified on cytology are a high-risk feature and a better threshold than “positive” for detecting malignancy. The objective of the current study was to assess the accuracy of AECs in predicting malignancy in pancreatic cysts. METHODS: Cysts aspirated by endoscopic ultrasound (EUS)-guided fine-needle aspiration (EUS-FNAs) obtained between January 2006 and June 2011 were evaluated. Cytologic, histologic, imaging, and cyst fluid analysis data were recorded. AECs were defined as cells that had an increased nuclear-to-cytoplasmic ratio and nuclear hyperchromasia with or without membrane abnormalities and with or without cytoplasmic vacuoles, but of insufficient quality and quantity for a “positive” interpretation. Malignancy included mucinous cysts with high-grade dysplasia and invasive carcinoma. Performance characteristics of cytology with AECs or worse (high-grade atypia [HGA]) for predicting malignancy were assessed. RESULTS: There were 70 FNAs that had histologic confirmation from 404 EUS-FNAs in 352 patients. Excluding 4 nondiagnostic FNAs, the study cohort consisted of 66 FNAs for analysis. There were 24 malignant cysts with 20 true-positive, 4 false-negative, 36 true-negative, and 6 false-positive results. For the detection of malignancy, HGA had 83% sensitivity, 86% specificity, a positive predictive value of 77%, a negative predictive value of 90%, and 85% overall accuracy. The lower threshold for malignancy with AECs resulted in a 12% increase in the detection of malignancy. CONCLUSIONS: A finding of AECs on cytology is a high-risk feature for malignancy and is an accurate triage threshold for resection. Cancer (Cancer Cytopathol) 2013;121:29–36 © 2012 American Cancer Society.

Pancreatic cystic lesions are being detected with an increasing frequency. Endoscopic ultrasound (EUS) provides both diagnostic and therapeutic means for pancreatic cystic lesions. Detailed imaging and EUS-guided fine-needle aspiration provide additional information on pancreatic cystic lesions. EUS-guided pseudocyst drainage has advantages over conventional drainage modalities. EUS-guided cyst ablation is a promising therapeutic modality.

We demonstrate for the first time that optical coherence tomography (OCT) imaging can reliably distinguish between morphologic features of low risk pancreatic cysts (i.e., pseudocysts and serous cystadenomas) and high risk pancreatic cysts (i.e., mucinous cystic neoplasms and intraductal papillary mucinous neoplasms). In our study fresh pancreatectomy specimens (66) from patients with cystic lesions undergoing surgery were acquired and examined with OCT. A training set of 20 pathology-OCT correlated tissue specimens were used to develop criteria for differentiating between low and high risk cystic lesions. A separate (validation) set of 46 specimens were used to test the OCT criteria by three clinicians, blinded to histopathology findings. Histology was finally used as a ‘gold’ standard for testing OCT findings. OCT was able to reveal specific morphologic features of pancreatic cysts and thus to differentiate between low-risk and high-risk cysts with over 95% sensitivity and specificity. This pilot study suggests that OCT could be used by clinicians in the future to more reliably differentiate between benign and potentially malignant pancreatic cysts. However, in vivo use of OCT requires a probe that has to fit the bore of the pancreas biopsy needle. Therefore, we have developed such probes and planned to start an in vivo pilot study within the very near future.

Background Secure esophagotomy closure methods are a critical element in the advancement of transesophageal natural orifice transluminal endoscopic surgery (NOTES) procedures. Objective To compare the clinical outcomes in swine receiving an esophageal stent or no stent after a submucosal tunnel NOTES access procedure. Design Prospective, randomized, controlled trial in 10 Yorkshire swine. Setting Academic center. Intervention An endoscopic mucosectomy device was used to create an esophageal mucosal defect. An endoscope was advanced through a submucosal tunnel into the mediastinum and thorax, and diagnostic mediastinoscopy and thoracoscopy were performed. Ten animals were randomized to no stenting (n = 5) or stenting (n = 5) with a prototype small-intestine submucosa–covered stent. Main Outcome Measurements Gross and histologic appearance of the mucosectomy and esophagotomy sites as well as clinical outcomes. Results There was a significant difference in the overall procedure time between the animals that received a stent (35.0 min, range 27-46.0 min) and those with no closure (19.0 min, range 17-32 min) (P value = .018). The unstented group achieved endoscopic and histologic evidence of complete re-epithelialization and healing (100%) at the mucosectomy site compared with the stented group (20%, P = .048). Stent migration into the stomach occurred in two swine. Both groups had complete closure of the submucosal tunnel and well-healed esophagotomy sites. Limitations Animal study, small number of subjects. Conclusion The placement of a covered esophageal stent significantly interferes with mucosectomy site healing.

Background The criterion standard for sampling mediastinal lymph nodes is cervical mediastinoscopy. Current methods that require transthoracic or cervical incisions can result in significant postoperative pain. Objective To determine the feasibility of a novel, transesophageal endoscopic technique for mediastinal lymph node dissection and en bloc resection. Design Nonsurvival and survival animal study. Setting Animal trial at a tertiary-care academic center. Subjects This study involved 12 Yorkshire swine. Intervention An endoscopic cap band mucosectomy device was used to create an esophageal mucosal defect. By using the tip of the endoscope and biopsy forceps, a submucosal tunnel was fashioned, and, within the submucosal space, a hook-knife incised the muscular esophageal wall. The endoscope was then advanced into the mediastinum and chest. Mediastinoscopy and thoracoscopy were performed to identify lymph node stations. Prototype endoscopic devices permitted lymph node dissection prior to removal with an electrocautery snare. A covered prototype stent was placed over the mucosectomy site. Main Outcome Measurements Feasibility of endoscopic transesophageal lymphadenectomy. Results Three lymph nodes (1 para-aortic and 2 right paratracheal) were removed in the 3 nonsurvival swine. Nine swine were survived for 14 days (range 13-14 days) and had a total of 7 lymph nodes (2 para-aortic and 5 paratracheal) removed. Two swine had no endoscopically visible lymph nodes in the mediastinum or chest. Lymph node dissection and resection was successful in all cases where lymph nodes were identified. Lymphadenectomy was completed in a median time of 20.0 minutes (range 8-60 minutes); median total procedure time was 70.0 minutes (range 28-105 minutes). Median lymph node size was 1.1 cm (range 0.6-1.4 cm). Limitations Animal study. Conclusion An endoscopic transesophageal approach can accomplish mediastinal lymph node dissection and en bloc resection and provides architecturally intact lymph node specimens for histologic examination.

Safe esophageal closure remains a challenge in transesophageal Natural Orifice Transluminal Endoscopic Surgery (NOTES). Previously described methods, such as suturing devices, clips, or submucosal tunneling, all have weaknesses. In this survival animal series, we demonstrate safe esophageal closure with a prototype retrievable, antimigration stent.Nine Yorkshire swine underwent thoracic NOTES procedures. A double-channel gastroscope equipped with a mucosectomy device was used to create an esophageal mucosal defect. A 5-cm submucosal tunnel was created and the muscular esophageal wall was incised with a needle-knife. Mediastinoscopy and thoracoscopy were performed in all swine; lymphadenectomy was performed in seven swine. A prototype small intestinal submucosal (SurgiSIS(®)) covered stent was deployed over the mucosectomy site and tunnel. Three versions of the prototype stent were developed. Prenecropsy endoscopy confirmed stent location and permitted stent retrieval. Explanted esophagi were sent to pathology.Esophageal stenting was successful in all animals. Stent placement took 15.8 ± 4.8 minuted and no stent migration occurred. Prenecropsy endoscopy revealed proximal ingrowth of esophageal mucosa and erosion with Stent A. Mucosal inflammation and erosion was observed proximally with Stent B. No esophageal erosion or pressure damage from proximal radial forces was seen with Stent C. On necropsy, swine 5 had a 0.5-cm periesophageal abscess. Histology revealed a localized inflammatory lesion at the esophageal exit site in swine 1, 3, and 9. The mucosectomy site was partially healed in three swine and poorly healed in six. All swine thrived clinically, except for a brief period of mild lethargy in swine 9 who improved with short-term antibiotic therapy. The submucosal tunnels were completely healed and no esophageal bleeding or stricture formation was observed. All swine survived 13.8 ± 0.4 days and gained weight in the postoperative period.Esophageal stenting provides safe closure for NOTES thoracic procedures but may impede healing of the mucosectomy site.

Background Gastric leak testing after natural orifice transluminal endoscopic surgery (NOTES) gastrotomy closure may help reduce the risk of leaks after transgastric procedures. Objective To develop a novel endoscopy-based system to determine the presence of a leak after NOTES gastrotomy and to compare this system prospectively with radiographic leak testing. Design Prospective, randomized, controlled trial. Setting Academic Medical Center laboratory. Subjects Fifty swine. Intervention During the pretrial phase, an endoscopic system for the measurement of intragastric pressure was developed. In the trial phase, swine with a NOTES gastrotomy were randomized to endoscopic versus radiographic leak testing. If a leak was demonstrated, the gastrotomy was reclosed by using a second-generation prototype T-anchor system. The primary outcome was leak detection after gastrotomy closure. The secondary outcome variables included necropsy findings, peritoneal fluid analysis, histologic examination, and clinical outcome. Results Fourteen swine were included in the pretrial phase and 36 in the randomized trial. Swine were survived for a mean of 9 days postoperatively. Endoscopic pressure monitoring demonstrated a reproducible change in intragastric pressure with insufflation; r = 0.735, P = .001 and r = 0.769, P ≤ .000 for the total and maximum pressures, respectively. Post-peritoneoscopy, there was a detectable and significant decrease in the mean total and mean maximum pressures versus baseline ( P = .006 and P = .009). There was no significant difference between the radiologic and endoscopic arms in leak detection rate (4/18 vs 3/18, respectively, P = .500). Clinical outcomes and mean weight gain were equivalent. There was 1 operative abdominal wall injury and no deaths. Limitations Animal study. Conclusion Endoscopic pressure monitoring was reproducible, demonstrated the presence of gastric leak, and was as reliable as contrast-based radiographic leak testing.

The feasibility of transanal rectosigmoid resection with transanal endoscopic microsurgery (TEM) was previously demonstrated in a swine nonsurvival model in which transgastric endoscopic assistance also was shown to extend the length of colon mobilized transanally. A 2-week survival study evaluating transanal endoscopic rectosigmoid resection with stapled colorectal anastomosis was conducted with swine using the transanal approach alone (TEM group, n = 10) or a transanal approach combined with transgastric endoscopic assistance (TEM + TG group, n = 10). Gastrotomies were created using a needleknife and balloon dilation, then closed using prototype T-tags. Outcomes were evaluated and compared between the groups using Student’s t-test and Fisher’s exact test. Relative to the TEM group, the average length of rectosigmoid mobilized in the TEM + TG group was 15.6 versus 10.5 cm (p

Background Thoracoscopic sympathectomy is the preferred surgical treatment for patients with disabling palmar hyperhidrosis. Current methods require a transthoracic approach to permit ablation of the thoracic sympathetic chain. Objective To develop a minimally invasive, transesophageal endoscopic technique for a sympathectomy in a swine model. Design Nonsurvival animal study. Setting Animal trial at a tertiary care academic center. Subjects This study involved 8 healthy Yorkshire swine. Interventions After insertion of a double-channel gastroscope, a Duette Band mucosectomy device was used to create a small esophageal mucosal defect. A short, 5-cm submucosal tunnel was created by using the tip of the endoscope and biopsy forceps. Within the submucosal space, a needle-knife was used to incise the muscular esophageal wall and permit entry into the mediastinum and chest. The sympathetic chain was identified at the desired thoracic level and was ablated or transected. The animals were killed at the completion of the procedure. Main Outcome Measurements Feasibility of endoscopic transesophageal thoracic sympathectomy. Results The sympathetic chain was successfully ablated in 7 of 8 swine, as confirmed by gross surgical pathology and histology. In 1 swine, muscle fibers were inadvertently transected. On average, the procedure took 61.4±24.5minutes to gain access to the chest, whereas the sympathectomy was performed in less than 3minutes in all cases. One animal was killed immediately after sympathectomy, before the completion of the observation period, because of hemodynamic instability. Limitations Nonsurvival series, animal study. Conclusions Endoscopic transesophageal thoracic sympathectomy is technically feasible, simple, and can be performed in a porcine model.

To evaluate the role of computed tomography (CT) perfusion in detection of pancreatic necrosis and pancreatitis after endoscopic ultrasound-guided ethanol ablation of porcine pancreas and to correlate the evaluation with histopathology.Under endoscopic ultrasound guidance, 0.9% saline (control) and ethanol at 60%, 80%, and 100% concentrations were injected into the pancreatic tails of 4 pigs. On day 4, dynamic perfusion CT of the pancreas was performed. Perfusion analysis and evaluation of enhancement characteristics were done and correlated with histopathology.Ethanol injections at 80% and 100% concentrations resulted in focal necrosis surrounded by focal pancreatitis, whereas 60% ethanol injection caused severe focal pancreatitis with microscopic necrosis. The necrotic area revealed reduced blood flow, blood volume, permeability-surface area product, and increased mean transit time compared with pancreatitis and normal tissue (Por = 0.001). In the control pig, no pancreatitis or necrosis was observed on perfusion images and histopathology.Pancreatic necrosis and pancreatitis after ethanol injection reduced the tissue perfusion on CT in comparison to normal tissue, with the changes being more substantial in necrosis than pancreatitis. These findings have possible implications in the accurate detection of pancreatic necrosis in patients with severe pancreatitis.

Background Natural orifice transluminal endoscopic surgery (NOTES) research has primarily involved case series reports of low-risk procedures. Distal pancreatectomy has significant postoperative morbidity and would permit rigorous examination in a controlled trial setting. Objective To compare endoscopic transgastric distal pancreatectomy (ETDP) and laparoscopic distal pancreatectomy (LDP). Design Prospective, randomized, controlled trial. Setting Academic hospital. Subjects Forty-one swine, 28 block randomized. Interventions LDP was performed with 3 trocars and stapled transection of the pancreas. ETDP was performed via a gastrotomy, with 1 trocar for visualization, by using endoloop placement, snare transection, and purse-string gastrotomy closure. Main Outcome Measurements Clinical examination, CT, serum chemistries, necropsy, peritoneal fluid analysis, and histologic examination. Results Swine were survived for 8 days. The procedure time for ETDP was significantly greater than for LDP (1:52 vs 0:33 [hours:minutes]; P = .00). Pancreatic specimen weight was similar (4.1 g vs 5.5 g; P = .108). Postoperatively, 26 of 28 animals thrived. In the LDP group, 1 death caused by pancreatic leak and renal failure occurred on day 1. In the ETDP group, 1 death caused by pneumothorax occurred intraoperatively. The necropsy, CT, and histologic examinations revealed focal resection-margin necrosis in 3 to 7 swine in the ETDP group with no proximal necrosis or pancreatitis. The groups were equivalent clinically, by survival, and by serum and peritoneal fluid analysis. The gastrotomy closure was associated with small serosal adhesions, but no gross abscess or necrosis. Limitation Animal study. Conclusions In the largest controlled trial of NOTES orifice surgery to date, there was no clinical or survival difference between NOTES and laparoscopic approaches.

Background EUS-guided FNA has been well documented to aid in the diagnosis of subepithelial lesions by providing cytologic material. Studies to date evaluating the sensitivity of EUS-FNA for the diagnosis of GI stromal cell tumors (GIST) have been small, and few have relied on surgical histologic diagnosis as the reference standard. Objective Our purpose was to determine the diagnostic yield and sensitivity of EUS-FNA for the diagnosis of GIST and to identify EUS features of GIST that are predictive of the ability to obtain adequate tissue by EUS-FNA. Design All patients with histologically confirmed, c-kit –positive GIST who underwent EUS-FNA from 1998 to 2006 were reviewed. EUS images were examined for mass size, shape, location, wall layer, heterogeneity, echogenicity, cystic spaces, lobulation, ulceration, and central umbilication. Needle gauge, number of needle passes, and presence of a cytologist during the EUS-FNA were recorded. Results A total of 37 patients (29 with diagnostic FNA cytology; 8 with nondiagnostic cytology) met the inclusion criteria. The diagnostic yield and sensitivity of EUS-FNA cytology for the diagnosis of GIST was 78.4% (29/37). The sensitivity was 84.4% (27/32) for GISTs located in the stomach, but poor for lesions located in the duodenum because none of these tumors yielded diagnostic cytology (n = 3). An increase in size up to 10 cm, round/oval shape, and identification of the origin of GIST within a specific sonographic wall layer were statistically significant in their ability to predict adequate tissue yield. Conclusions The sensitivity of EUS-FNA cytology for the diagnosis of GIST is 78.4% and is influenced by size, location, shape, and layer of origin.

BACKGROUND: The management of patients with pancreatic cysts is based on the preoperative distinction of nonmucinous and mucinous cysts in general and of benign and malignant cysts in particular. An accurate diagnosis is challenging, because endoscopic ultrasound (EUS) and cyst fluid analysis for carcinoembryonic antigen (CEA) and cytology have low sensitivity and specificity. Currently, molecular analysis is a commercially available test that promises an accurate diagnosis. The objective of the current study was to correlate a commercially provided molecular diagnosis (MDx) with a clinical consensus diagnosis (CCD) in the general categories of malignant, benign mucinous, and benign nonmucinous pancreatic cysts. METHODS: Pancreatic cysts that had aspirated fluid submitted for a commercially available molecular test (PathFinderTG) were reviewed. The CCD, defined by histology, malignant cytology, or 2 concordant tests (such as EUS, cytology, or CEA � 192 ng/mL for mucinous cysts), was categorized as malignant, benign mucinous, or benign nonmucinous cyst in 35 patients. Their MDx, based on the PathFinderTG report, including analysis of k-ras mutation, loss of heterozygosity, and quantity/quality of DNA, also was classified as malignant, benign mucinous, or benign nonmucinous cyst. These 2 diagnoses were compared and correlated. RESULTS: The concordance between CCD and MDx was 5 of 6 (83%), 13 of 15 (87%), and 13 of 14 (93%), respectively, for malignant, benign mucinous, and benign nonmucinous cysts, with an overall Cohen kappa statistic of 0.816. The sensitivity, specificity, and positive predictive value of the MDx were 83%, 100%, and 100%, respectively, for a malignant cyst and 86%, 93%, and 95%, respectively for a benign mucinous cyst. CONCLUSIONS: Molecular analysis of pancreatic cyst fluid adds diagnostic value to the preoperative diagnosis with high sensitivity, specificity, and positive predictive value for the diagnosis of malignant and benign mucinous pancreatic cysts. Cancer (Cancer Cytopathol) 2009;117:217–27. V C 2009 American Cancer

The objective of this study was to evaluate the efficacy of EUS-guided CPN for pain relief in patients with chronic pancreatitis and pancreatic cancer. An initial search identified 1,439 reference articles, of which 130 relevant articles were selected and reviewed. Data was extracted from 8 studies (N = 283) for EUS-guided CPN for pain due to pancreatic cancer and nine studies for chronic pancreatitis (N = 376) which met the inclusion criteria. With EUS-guided CPN, the pooled proportion of patients with pancreatic cancer that showed pain relief was 80.12% (95% CI = 74.47-85.22). In patients with pain due to chronic pancreatitis, EUS-guided CPN provided pain relief in 59.45% (95% CI = 54.51-64.30). In conclusion, EUS-guided CPN offers a safe alternative technique for pain relief in patients with chronic pancreatitis or pancreatic cancer. In patients with pain due to chronic pancreatitis, better techniques or injected materials are needed to improve the response.

Background— It is common practice to empirically limit the radiofrequency (RF) power when ablating the posterior left atrium during atrial fibrillation ablation to avoid thermal injury to the esophagus. The objective of this study was to determine whether RF energy delivery limited by luminal esophageal temperature (LET) monitoring is associated with a reduction in esophageal injury compared with a strategy of RF power limitation alone. Methods and Results— Eighty-one consecutive patients who underwent atrial fibrillation ablation followed by esophageal endoscopy were included in this observational study. All patients underwent extraostial electric pulmonary vein isolation by using an electroanatomic mapping system and irrigated RF ablation. All RF applications on the posterior left atrium were limited to 35 W. A commercially available, single-thermocouple esophageal probe was used to monitor LET in a subset of patients (n=67). In these cases, applications were promptly interrupted when LET was ≥38.5�C; further applications were performed at reduced power to obtain a LET P Conclusions— These data suggest that LET monitoring may be associated with a reduction in esophageal injury compared with power limitation alone.

Transesophageal endoscopic mediastinoscopy (MX) and thoracoscopy (TX) could reduce pain, eliminate intercostal neuralgia, provide better access to the posterior mediastinal compartment and pulmonary hilum, and improve cosmesis. The purpose of this study was to demonstrate the feasibility of transesophageal natural orifice translumenal endoscopic surgery (NOTES) and to determine the complications that might be seen in surviving animals. Using cap endoscopic mucosal resection and blunt dissection, a 15–20 cm submucosal tunnel was created in the esophagus and an endoscope passed through the tunnel into the mediastinum. One swine underwent MX; three swine underwent both MX and TX. The mediastinal compartment, hilar lymph nodes, pleura, lung, and esophagus were identified. Esophageal closure was obtained via submucosal tunnel flap-valve alone (two swine) or reinforcement with mucosal clips (two swine). The esophagus, mediastinum, and thorax were examined at necropsy. The esophagus was excised and sent for pathological examination. NOTES MX and TX provided excellent visualization of mediastinal and thoracic structures. Pleural biopsy was easily accomplished. All animals survived the procedure, ate well, and showed no ill effects. Swine were sacrificed at either 8 or 12 days postoperatively. At necropsy, mild atelectasis was noted in each animal. One animal (mucosal clip closure) developed a fluid collection in the submucosal tunnel. There was no evidence of mediastinitis or thoracic contamination in any animals. Transesophageal endoscopic mediastinoscopy and thoracoscopy provide excellent visualization of mediastinal and intrathoracic structures. Pleural biopsy can be easily obtained under direct visualization. Structures that are difficult to visualize via traditional cervical mediastinoscopy and thoracoscopy are seen well with this approach. The submucosal tunnel creates a flap-valve that, alone, may be sufficient for preventing esophageal leak. These procedures can be performed safely in swine with short-term survival. Further study with a larger sample size and longer survival is warranted.

Pancreatic adenocarcinoma is one of the leading causes of cancer death in the West, with a poor overall 5-year survival rate of only 4%. Late clinical presentation with an advanced disease results in a low rate of surgical intervention. Tumor serum marker CA 19-9 is sensitive, although not specific for the diagnosis of adenocarcinomas of the pancreas. The treatment approach is based on whether the tumor is resectable or non-resectable at presentation. Therefore, imaging plays a crucial role in the management of this disease. Many modalities are available to image the pancreas. They include non-invasive techniques, like ultrasound, contrast-enhanced multidetector computed tomography, magnetic resonance imaging and integrated positron emission tomography/computed tomography, and invasive techniques, like endoscopic retrograde cholangiopancreatography and endoscopic ultrasound. Each of these modalities has its peculiar strengths and weaknesses.