Endoscopist-Level and Procedure-Level Factors Associated With Increased Adenoma Detection With the Use of a Computer-Aided Detection Device.

INTRODUCTION: To investigate the impact of procedure-related and endoscopist-related factors on the effectiveness of a computer-aided detection (CADe) device in adenomas per colonoscopy (APC) detection. METHODS: The SKOUT clinical trial was conducted at 5 US sites. We present prespecified analyses of procedure-related and endoscopist-related factors, and association with APC across treatment and control cohorts. RESULTS: There were numeric increases in APC between SKOUT vs standard colonoscopy in community-based endoscopists, withdrawal time of ≥8 minutes, for endoscopists with >20 years of experience, and endoscopists with baseline adenoma detection rate <45%. DISCUSSION: The application of CADe devices in clinical practice should be carefully evaluated. Larger studies should explore differences in endoscopist-related factors for CADe.

A Case of Bouveret's Syndrome Treated With Holmium:Yttrium-Aluminum-Garnet Laser.

Bouveret's syndrome is a rare form of gallstone ileus described as a gastric outlet obstruction from a gallstone that travels from the gallbladder to the bowel through a bilioenteric fistula. Despite its rarity, the mortality rate of this condition is high. Endoscopic treatment is preferred over surgery due to the association with lower mortality rate. To date, there are limited data about the application of holmium:yttrium-aluminum-garnet (YAG) laser lithotripsy for fragmentation of gallstones in Bouveret's syndrome. We present the case of a 74-year-old man with multiple cardiac comorbidities who presented with periumbilical pain, decreased appetite, and vomiting. The patient had previously been admitted three months prior with acute cholecystitis, and a cholecystostomy tube was placed. He had leukocytosis and purulent discharge in his cholecystostomy bag. Computed tomography (CT) scan of the abdomen and pelvis showed a change in the position of a previously seen large gallstone from the neck of the gallbladder on the last admission, to the lumen of the duodenal bulb on this admission. This indicated the development of a cholecystoduodenal fistula, with the stone passing through this fistula into the duodenal bulb, causing the complete obstruction. Endoscopic treatment was recommended by the surgery team due to cardiac comorbidities and the significant friability of the tissue requiring laparotomy. Initial endoscopic evaluation showed complete obstruction of the duodenal bulb by a large smooth stone, not allowing passage of a guidewire beyond the stone. Therefore, holmium:YAG laser lithotripsy was used. After two sessions of laser therapy, four days apart, each breaking a pigmented and calcified stone, it eventually passed through the small bowel into the colon, relieving the obstruction. The patient had a favorable outcome and did not require surgery. This case report shows that holmium:YAG laser lithotripsy is capable of delivering favorable outcomes, as seen in a patient with a heavily calcified and pigmented stone, older age, and multiple comorbidities. Holmium:YAG laser could be considered for use with endoscopic equipment for future management of this condition, especially in patients who have medical comorbidities and heavily calcified gallstones.

"Evolving Trends in Pancreatic Cystic Tumors: A 3-Decade Single-Center Experience With 1290 Resections".

OBJECTIVE: The aim of this study was to describe our institutional experience with resected cystic tumors of the pancreas with emphasis on changes in clinical presentation and accuracy of preoperative diagnosis. SUMMARY BACKGROUND DATA: Incidental discovery of pancreatic cystic lesions has increased and has led to a rise in pancreatic resections. It is important to analyze surgical outcomes from these procedures, and the prevalence of malignancy, pre-malignancy and resections for purely benign lesions, some of which may be unintended. METHODS: Retrospective review of a prospective database spanning 3 decades. Presence of symptoms, incidental discovery, diagnostic studies, type of surgery, postoperative outcomes, and concordance between presumptive diagnosis and final histopathology were recorded. RESULTS: A total of 1290 patients were identified, 62% female with mean age of 60 years. Fifty-seven percent of tumors were incidentally discovered. Ninety-day operative mortality was 0.9% and major morbidity 14.4%. There were 23 different diagnosis, but IPMN, MCN, and serous cystadenoma comprised 80% of cases. Concordance between preoperative and final histopathological diagnosis increased by decade from 45%, to 68%, and is presently 80%, rising in parallel with the use of endoscopic ultrasound, cytology, and molecular analysis. The addition of molecular analysis improved accuracy to 91%. Of misdiagnosed cases, half were purely benign and taken to surgery with the presumption of malignancy or premalignancy. The majority of these were serous cystadenomas. CONCLUSIONS: Indications and diagnostic work-up of cystic tumors of the pancreas have changed over time. Surgical resection can be performed with very low mortality and acceptable morbidity and diagnostic accuracy is presently 80%. About 10% of patients are still undergoing surgery for purely benign lesions that were presumed to be malignant or premalignant. Further refinements in diagnostic tests are required to improve accuracy.

Pancreatic Cystic Neoplasms.

Early detection of high-risk pancreatic cystic lesions enables potentially curative surgical resection, and early detection of lesions without worrisome features may lead to appropriate surveillance. Regrettably, differentiating premalignant and malignant cysts from nonmalignant ones remains challenging. However, emerging additional diagnostic tools, including the needle biopsy with microforceps and needle-based confocal laser endomicroscopy, are of exciting potential along with cyst fluid analysis".

Computer-Aided Detection Improves Adenomas per Colonoscopy for Screening and Surveillance Colonoscopy: A Randomized Trial.

BACKGROUND & AIMS: Colonoscopy for colorectal cancer screening is endoscopist dependent, and colonoscopy quality improvement programs aim to improve efficacy. This study evaluated the clinical benefit and safety of using a computer-aided detection (CADe) device in colonoscopy procedures. METHODS: This randomized study prospectively evaluated the use of a CADe device at 5 academic and community centers by US board-certified gastroenterologists (n = 22). Participants aged ≥40 scheduled for screening or surveillance (≥3 years) colonoscopy were included; exclusion criteria included incomplete procedure, diagnostic indication, inflammatory bowel disease, and familial adenomatous polyposis. Patients were randomized by endoscopist to the standard or CADe colonoscopy arm using computer-generated, random-block method. The 2 primary endpoints were adenomas per colonoscopy (APC), the total number of adenomas resected divided by the total number of colonoscopies; and true histology rate (THR), the proportion of resections with clinically significant histology divided by the total number of polyp resections. The primary analysis used a modified intention-to-treat approach. RESULTS: Between January and September 2021, 1440 participants were enrolled to be randomized. After exclusion of participants who did not meet the eligibility criteria, 677 in the standard arm and 682 in the CADe arm were included in a modified intention-to-treat analysis. APC increased significantly with use of the CADe device (standard vs CADe: 0.83 vs 1.05, P = .002; total number of adenomas, 562 vs 719). There was no decrease in THR with use of the CADe device (standard vs CADe: 71.7% vs 67.4%, P for noninferiority < .001; total number of non-neoplastic lesions, 284 vs 375). Adenoma detection rate was 43.9% and 47.8% in the standard and CADe arms, respectively (P = .065). CONCLUSIONS: For experienced endoscopists performing screening and surveillance colonoscopies in the United States, the CADe device statistically improved overall adenoma detection (APC) without a concomitant increase in resection of non-neoplastic lesions (THR). CLINICALTRIALS: gov registration: NCT04754347.

Confocal endomicroscopy for evaluation of pancreatic cystic lesions: a systematic review and international Delphi consensus report.

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.

An international, multi-institution survey of the use of EUS in the diagnosis of pancreatic cystic lesions.

BACKGROUND AND OBJECTIVES: Currently, pancreatic cystic lesions (PCLs) are recognized with increasing frequency and have become a more common finding in clinical practice. EUS is challenging in the diagnosis of PCLs and evidence-based decisions are lacking in its application. This study aimed to develop strong recommendations for the use of EUS in the diagnosis of PCLs, based on the experience of experts in the field. METHODS: A survey regarding the practice of EUS in the evaluation of PCLs was drafted by the committee member of the International Society of EUS Task Force (ISEUS-TF). It was disseminated to experts of EUS who were also members of the ISEUS-TF. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized. RESULTS: Fifteen questions were extracted and disseminated among 60 experts for the survey. Fifty-three experts completed the survey within the specified time frame. The average volume of EUS cases at the experts' institutions is 988.5 cases per year. CONCLUSION: Despite the limitations of EUS alone in the morphologic diagnosis of PCLs, the results of the survey indicate that EUS-guided fine-needle aspiration is widely expected to become a more valuable method.

The underutilization of EUS-guided biliary drainage: Perception of endoscopists in the East and West.

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.

Moray micro forceps biopsy improves the diagnosis of specific pancreatic cysts.

BACKGROUND: Making a specific diagnosis of pancreatic cysts preoperatively is difficult. The new disposable Moray micro forceps biopsy (MFB) device allows tissue sampling from the pancreatic cyst wall/septum and aims to improve diagnosis. This study compares the diagnostic performance of the MFB with the current conventional analysis of pancreatic cyst fluid (PCF). METHODS: A total of 48 patients sampled with MFB were identified. Cysts were classified as mucinous on PCF based on extracellular mucin/mucinous epithelium, carcinoembryonic antigen (CEA) levels ≥192 ng/mL, or KRAS/GNAS mutation. A diagnosis of intraductal papillary mucinous neoplasm was supported by GNAS mutation; a diagnosis of serous cystadenoma was supported by Von Hippel-Lindau tumor suppressor (VHL) mutation. A diagnosis of mucinous cystic neoplasm required the presence of subepithelial ovarian-type stroma. A high-risk cyst was defined as a mucinous cyst with high-grade dysplasia or an adenocarcinoma. Comparisons in diagnostic performance between PCF and MFB were made. RESULTS: The mean age of the patients was 69.6 years (range, 27-90 years); 25 of 48 patients (52.1%) were female. Cysts were in the pancreatic head (13 patients), neck (2 patients), body (20 patients), and tail (13 patients), averaging 3.1 cm (range, 1.2-6.0 cm). There was concordance with mucinous versus nonmucinous classification (60.4% for PCF vs 58.3% for MFB; P = .949). Three high-risk cysts were detected by PCF and 2 were detected by MFB (P = .670). However, MFB diagnosed significantly more specific cysts compared with PCF (50.0% for MFB vs 18.8% for PCF; P<.001). CONCLUSIONS: PCF analysis and MFB have comparable performance in distinguishing between mucinous and nonmucinous cysts and for detecting high-risk cysts. However, MFB was found to be superior for diagnosing specific cyst subtypes, thus adding significant value to preoperative patient management. Cancer Cytopathol 2018;126:414-20. © 2018 American Cancer Society.

Feasibility and safety of microforceps biopsy in the diagnosis of pancreatic cysts.

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.

EMR is superior to rectal suction biopsy for analysis of enteric ganglia in constipation and dysmotility.

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 cm3 vs 0.26 cm3, 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.

Improved Detection of Circulating Epithelial Cells in Patients with Intraductal Papillary Mucinous Neoplasms.

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.

Ex vivo human bile duct radiofrequency ablation with a bipolar catheter.

BACKGROUND: Management of the primary and secondary tumors of the bile ducts still remains as a major clinical challenge. Radiofrequency (RF) ablation (RFA) of these tumors is feasible but the effect of RF energy on the human common bile duct (CBD) and surrounding tissues has not been investigated. This pilot study aimed to determine the relationship between RF energy and the depth of ablation in the normal human CBD. METHODS: The study was performed on fresh ex vivo human biliary-pancreatic tissue which had been resected for a pancreatic cyst or mass. The study was conducted within 15 min after resection. A bipolar Habib RFA catheter was placed into the middle of the intact CBD, and three different (5, 7, 10 W) power settings were applied over a 90-s period by an RF generator. Gross and histological examinations were performed. The depth of coagulation necrosis in CBD and the effect of RFA on CBD wall and surrounding pancreas tissue were determined by microscopic examination. RESULTS: The study included eight tissue samples. 5 W power was applied to three sites and RFA caused only focal epithelial necrosis limited to the CBD mucosa. 7 and 10 W were applied to five sites and coagulation necrosis occurred in all cases. Microscopically, necrosis was transmural, involved accessory bile duct glands, and extended to the surrounding pancreatic tissue in four of these cases. Macroscopically, RFA resulted in circumferential white-yellowish color change extending approximately 2 cm of the CBD. CONCLUSION: Bipolar RF energy application with 5 W resulted in limited ablation on CBD wall. However, 7 and 10 W generated tissue necrosis which extended through the CBD wall and into surrounding pancreas tissue. Endoscopic biliary RFA is an effective technique for local biliary tissue ablation but the use of high energy may injure surrounding tissue.

Endoscopic Ultrasound and Related Technologies for the Diagnosis and Treatment of Pancreatic Disease - Research Gaps and Opportunities: Summary of a National Institute of Diabetes and Digestive and Kidney Diseases Workshop.

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.

EUS and related technologies for the diagnosis and treatment of pancreatic disease: research gaps and opportunities-Summary of a National Institute of Diabetes and Digestive and Kidney Diseases workshop.

A workshop was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases to address the research gaps and opportunities in pancreatic 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.

Future Directions for Endoscopic Ultrasound: Where Are We Heading?

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.