A multicenter, retrospective study of a through-the-needle injection-capable electrosurgical knife for endoscopic submucosal dissection.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) is a technically challenging resection technique for en-bloc removal of dysplastic and early cancerous gastrointestinal (GI) lesions. We conducted a single-arm retrospective study evaluating the safety and efficacy of a new through-the-needle injection-capable electrosurgical knife used in upper and lower ESD procedures performed at 6 US academic centers. METHODS: Data were retrospectively collected on consecutive cases in which the new ESD knife was used. The primary efficacy endpoint was successful ESD (en bloc resection with negative margins). Secondary efficacy endpoints included en-bloc resection rate, curative resection rate, median ESD time, and median dissection speed. The safety endpoint was device- or procedure-related serious adverse events (SAEs). RESULTS: ESD of 581 lesions in 579 patients were reviewed, including 187 (32.2%) upper GI and 394 (67.8%) lower GI lesions. Prior treatment was reported in 283 (48.9%) patients. Successful ESD was achieved in 477 (82.1% of 581) lesions ‒ lower for patients with versus without submucosal fibrosis (73.6% versus 87.0%, respectively, P < 0.001), but similar for those with versus without previous treatment (81.7% versus 82.3%, respectively, P = 0.848). Four hundred and forty-three (76.2% of 581) lesions met criteria for curative resection. Median ESD time was 1.0 (range 0.1-4.5) hour. Median dissection speed was 17.1 (IQR 5.3-29.8) cm2/hour. Related SAEs were reported in 15 (2.6%) patients, including delayed hemorrhage (1.9%), perforation (0.5%), or postpolypectomy syndrome (0.2%). CONCLUSION: A newly developed through-the-needle injection-capable ESD knife showed a good success rate and excellent safety at US centers. (ClinicalTrials.gov number, NCT04580940).

Establishment of Standards for the Referral of Large Non-Pedunculated Colorectal Polyps: An International Expert Consensus Using a Modified Delphi Process.

BACKGROUND AND AIMS: Resection of colorectal polyps has been shown to decrease the incidence and mortality of colorectal cancer. Large non-pedunculated colorectal polyps are often referred to expert centres for endoscopic resection, which requires relevant information to be conveyed to the therapeutic endoscopist to allow for triage and planning of resection technique. The primary objective of our study was to establish minimum expected standards for the referral of LNPCP for potential ER. METHODS: A Delphi methodology was employed to establish consensus on minimum expected standards for the referral of large colorectal polyps among a panel of international endoscopy experts. The expert panel was recruited through purposive sampling, and three rounds of surveys were conducted to achieve consensus, with quantitative and qualitative data analysed for each round. RESULTS: A total of 24 international experts from diverse continents participated in the Delphi study, resulting in consensus on 19 statements related to the referral of large colorectal polyps. The identified factors, including patient demographics, relevant medications, lesion factors, photodocumentation and the presence of a tattoo, were deemed important for conveying the necessary information to therapeutic endoscopists. The mean scores for the statements ranged from 7.04 to 9.29 out of 10, with high percentages of experts considering most statements as a very high priority. Subgroup analysis by continent revealed some variations in consensus rates among experts from different regions. CONCLUSION: The identified consensus statements can aid in improving the triage and planning of resection techniques for large colorectal polyps, ultimately contributing to the reduction of colorectal cancer incidence and mortality.

Delays in definitive endoscopic resection of previously manipulated colorectal polyps as a risk factor for inferior resection outcomes.

BACKGROUND AND AIMS: Manipulation of colorectal polyps by biopsy, incomplete resection, or tattoo placement under the lesion has been shown to cause submucosal fibrosis and associated inferior outcomes. The effect of delays between index manipulation and definitive resection on the incidence of fibrosis is unknown. METHODS: Patients undergoing EMR of previously manipulated colorectal polyps ≥10 mm from 2016 to 2021 at a tertiary referral center were included. Time from index manipulation to definitive resection and the presence of fibrosis were noted. The effects of fibrosis on EMR outcomes were assessed. RESULTS: Among 221 previously manipulated lesions (180 biopsy, 23 incomplete/failed resection, 1 tattoo under lesion, 17 multiple types of manipulation), 51 (23%) demonstrated fibrosis. Fibrotic lesions were found to have been resected significantly later than nonfibrotic lesions (76 vs 61 days; P = .014). In a multivariate analysis controlling for other predictors of fibrosis, each 2-week delay was associated with a 14% increase in the odds of fibrosis. Fibrotic lesions had inferior outcomes with a lower en-bloc resection rate (8% vs 24%; P = .014) and longer procedure time (71 vs 52 minutes; P < .001). Adverse event and recurrence rates were similar between groups. CONCLUSIONS: Delays in definitive resection of previously manipulated polyps are associated with an increased incidence of fibrosis with time and associated inferior outcomes. Manipulation should be discouraged, and if it occurs, prompt referral and scheduling for definitive resection should be prioritized.

Endoscopic Resection Techniques for Duodenal and Ampullary Adenomas.

Background and Aims: Duodenal polyps have a reported incidence of 0.3% to 4.6%. Sporadic, nonampullary duodenal adenomas (SNDAs) comprise less than 10% of all duodenal polyps, and ampullary adenomas are even less common. Nonetheless, the incidence continues to rise because of widespread endoscopy use. Duodenal polyps with villous features or those that are larger than 10 mm may raise concern for malignancy and require removal. We demonstrate endoscopic resection of SNDAs and ampullary adenomas using some of our preferred techniques. Methods: The duodenum has several components that can make EMR of duodenal polyps technically challenging. Not only does the duodenum have a thin muscle layer, but it is also highly mobile and vascular, which may explain higher rates of perforation and bleeding of duodenal EMR reported in the literature compared with colon EMR. A standard adult gastroscope with a distal cap is commonly used for duodenal EMRs. Based on the location, however, side-viewing duodenoscopes or pediatric colonoscopes may be used. To prepare for EMR, a submucosal injection is performed for an adequate lift. The polyp is then resected via stiff monofilament snares and subsequently closed with hemostatic clips if feasible. The ampullectomy technique differs slightly from duodenal EMRs and carries the additional risk of pancreatitis. Submucosal injection in the ampulla may not lift well; thus, its utility is debatable. Biliary sphincterotomy should be performed, and based on endoscopist preference, the pancreatic duct (PD) guidewire can be left during resection to maintain access. After resection, a PD stent is placed to minimize pancreatitis risk. Results: The video shows the aforementioned duodenal EMR techniques. Two clips of ampullectomy are also shown in the video. Conclusions: A few common techniques used to perform duodenal EMR and ampullectomy are highlighted in the video. It is important to understand and manage adverse events associated with these procedures and to have established surveillance plans.

Global prospective case series of ERCPs using a single-use duodenoscope.

BACKGROUND: The first commercialized single-use duodenoscope was cleared by the US Food and Drug Administration in December 2019. Data regarding endoscopic retrograde cholangiopancreatography (ERCP) using a single-use duodenoscope are needed on a broader range of cases conducted by endoscopists with varying levels of experience in a wide range of geographic areas. METHODS: 61 endoscopists at 22 academic centers in 11 countries performed ERCP procedures in adult patients aged ≥ 18. Outcomes included ERCP completion for the intended indication, rate of crossover to a reusable endoscope, device performance ratings, and serious adverse events (SAEs). RESULTS: Among 551 patients, 236 (42.8 %) were aged > 65, 281 (51.0 %) were men, and 256 (46.5 %) had their procedure as an inpatient. ERCPs included 196 (35.6 %) with American Society for Gastrointestinal Endoscopy complexity of grades 3-4. A total of 529 ERCPs (96.0 %) were completed: 503 (91.3 %) using only the single-use duodenoscope, and 26 (4.7 %) with crossover to a reusable endoscope. There were 22 ERCPs (4.0 %) that were not completed, of which 11 (2.0 %) included a crossover and 11 (2.0 %) were aborted cases (no crossover). Median ERCP completion time was 24.0 minutes. Median overall satisfaction with the single-use duodenoscope was 8.0 (scale of 1 to 10 [best]). SAEs were reported in 43 patients (7.8 %), including 17 (3.1 %) who developed post-ERCP pancreatitis. CONCLUSIONS: In academic medical centers over a wide geographic distribution, endoscopists with varying levels of experience using the first marketed single-use duodenoscope had good ERCP procedural success and reported high performance ratings for this device.

Endoscopic biliary treatment of unresectable cholangiocarcinoma: A meta-analysis of survival outcomes and systematic review.

BACKGROUND: Endoscopic radiofrequency ablation (ERFA), percutaneous radiofrequency ablation (PRFA), and photodynamic therapy (PDT), when used in conjunction with conventional biliary stenting, have demonstrated a survival benefit in patients with unresectable cholangiocarcinoma. AIM: To compare pooled survival outcomes, adverse event rates, and mean stent patency for those undergoing these procedures. METHODS: A comprehensive literature review of published studies and abstracts from January 2011 to December 2020 was performed comparing survival outcomes in patients undergoing ERFA with stenting, biliary stenting alone, PRFA with stenting, and PDT with stenting for unresectable cholangiocarcinoma (CCA). RESULTS: Data from four studies demonstrated a pooled mean survival favoring ERFA as compared to biliary stenting alone (12.0 ± 0.9 mo vs 6.8 ± 0.3 mo, P < 0.001) as well as statistically improved median survival time (13 mo vs 8 mo, P < 0.001). Both ERFA with stenting and PRFA with stenting groups demonstrated statistical superiority to biliary stenting alone (P < 0.001 and P = 0.004, respectively). However, when comparing ERFA to PRFA, pooled data demonstrated overall higher mean survival in the ERFA with stenting cohort as compared to PRFA with stent cohort (12.0 + 0.9 mo vs 8.1 + 2.1 mo, P < 0.0001). Data from two studies demonstrated a pooled median survival favoring ERFA with stenting as compared to PDT with stenting (11.3 mo vs 8.5 mo, P = 0.02). CONCLUSION: While further prospective, randomized studies are needed to assess efficacy of ERFA, our meta-analysis demonstrated that this technique offers endoscopists a reasonable palliative method by which to treat patients with unresectable CCA that results in longer survival as compared to biliary stenting alone, percutaneous radiofrequency ablation with biliary stenting, and PDT with biliary stenting as well as an acceptable adverse event profile based on available published data.

AGA Clinical Practice Update on Role of EUS-Guided Gallbladder Drainage in Acute Cholecystitis: Commentary.

DESCRIPTION: Endoscopic gallbladder drainage is a feasible and efficacious alternative to percutaneous drainage in the management of acute cholecystitis for high-risk surgical candidates. Endoscopic ultrasound-guided gallbladder drainage and per-oral cholecystoscopy is facilitated by the use of lumen-apposing metal stents. Endoscopic ultrasound-guided gallbladder drainage should be performed by those expert in advanced therapeutic endoscopic ultrasound. Multidisciplinary collaboration between interventional radiology and surgery is paramount in the care of these patients. Choosing the optimal drainage method is dependent on individual patient characteristics. METHODS: This commentary was drawn from a review of the literature to provide practical advice. Because this was not a systematic review, we did not perform any formal rating of the quality of evidence or strength of the presented considerations. This expert commentary was commissioned and approved by the American Gastroenterological Association (AGA) Institute Clinical Practice Updates Committee and the AGA Governing Board to provide timely guidance on a topic of high clinical importance to the AGA membership, and underwent internal peer-review by the Clinical Practice Updates Committee and external peer-review through standard procedures of Clinical Gastroenterology and Hepatology.

Endoscopic Ultrasound Predicts Risk of Occult Intra-Abdominal Metastases in Localized Gastric Cancer: A Validation Study.

Background: In gastric cancer (GC) patients without imaging evidence of distant metastasis, diagnostic staging laparoscopy (DSL) is recommended to detect radiographically occult peritoneal metastasis (M1). DSL carries a risk for morbidity and its cost-effectiveness is unclear. Use of endoscopic ultrasound (EUS) to improve patient selection for DSL has been proposed but not validated. We aimed to validate an EUS-based risk classification system predicting risk for M1 disease. Methods: We retrospectively identified all GC patients without positron emission tomography (PET)/computed tomography (CT) evidence of distant metastasis who underwent staging EUS followed by DSL between 2010 and 2020. T1-2, N0 disease was EUS "low-risk"; T3-4 and/or N+ disease was "high-risk". Results: A total of 68 patients met inclusion criteria. DSL identified radiographically occult M1 disease in 17 patients (25%). Most patients had EUS T3 tumors (n = 59, 87%) and 48 (71%) patients were node-positive (N+). Five (7%) patients were classified EUS "low-risk" and 63 (93%) were classified "high-risk". Of 63 "high-risk" patients, 17 (27%) had M1 disease. The ability of "low-risk" EUS to predict M0 disease at laparoscopy was 100% and DSL would have been avoided in five patients (7%). This stratification algorithm showed a sensitivity of 100% (95% confidence interval (CI): 80.5-100%) and a specificity of 9.8% (95% CI: 3.3-21.4%). Conclusions: Use of an EUS-based risk classification system in GC patients without imaging evidence of metastasis helps identify a subset of patients at low-risk for laparoscopic M1 disease who may avoid DSL and proceed directly to neoadjuvant chemotherapy or resection with curative intent. Larger, prospective studies are needed to validate these findings.

Nontunneling Full Thickness Techniques for Neoplasia.

Colorectal cancer is the third most common cancer worldwide and the fourth leading cause of cancer-related deaths in the world, second in the United States. Although most lesions are managed surgically especially when they have already invaded into the submucosal layer, endoscopic full-thickness resection (EFTR) has become an emerging technique that can serve as a safe and effective alternative management for locally invasive gastrointestinal cancers. This article discusses the indications and various techniques and limitations of nontunneled EFTRs of gastrointestinal cancer and reviews the current literature on the outcomes of EFTR.

Endoscopic submucosal dissection for colorectal lesions: outcomes from a United States experience.

BACKGROUND AND STUDY AIMS: Endoscopic submucosal dissection (ESD) is commonly used in Asia for resection of large non-pedunculated colorectal polyps (LNPCPs) and early (T1) colorectal cancers. It allows for en bloc removal and is often curative. We describe outcomes of colorectal ESD from a United States (US) academic medical center and compare this to international experiences. METHODS: Retrospective review was performed of colonic lesions referred to the University of Chicago Medical Center for ESD from 2012 to 2020. Clinical and procedural data were collected. RESULTS: The study included 78 lesions with mean size of 29.7 mm (range 10-100 mm). The overall en bloc resection rate was 73.1% (n = 57). Between the first and second half of the study, it improved from 61.5 to 84.6% (p = 0.02). Histology showed adenocarcinoma in fifteen lesions (19.2%). Of all neoplastic lesions (n = 68), resection with negative margins (R0) was achieved in 54 cases (79.4%). Adverse events occurred in 9 cases (11.5%), but most (n = 6, 66.7%) were successfully treated endoscopically. Follow-up endoscopy was performed in 46 patients (59.0%) at a mean interval of 6.8 months (SD ± 5.0 months) with two case of recurrent lesion (4.3%). CONCLUSIONS: This study shows successful colorectal ESD outcomes at a US tertiary center. The en bloc resection rate was lower than other cohorts, but a learning curve was demonstrated. The R0 resection, lesion recurrence, and adverse event rates were similar to other non-Asian experiences, but not as favorable as in Asia [Fuccio et al. in Gastrointest Endosc 86:74-86.e17, 2017]. Increased ESD training in the US can help optimize utilization and outcomes.

Standardization of EUS imaging and reporting in high-risk individuals of pancreatic adenocarcinoma: consensus statement of the Pancreatic Cancer Early Detection Consortium.

BACKGROUND AND AIMS: Pancreatic ductal adenocarcinoma is an aggressive disease most often diagnosed after local progression or metastatic dissemination, precluding resection and resulting in a high mortality rate. For individuals with elevated personal risk of the development of pancreatic cancer, EUS is a frequently used advanced imaging and diagnostic modality. However, variability in the expertise and definition of EUS findings exists among gastroenterologists, as well as a lack of standardized reporting of relevant findings at the time of examination. Adoption of standardized EUS reporting, using a universally accepted and agreed on terminology, is needed. METHODS: A consensus statement designed to create a standardized reporting template was authored by a multidisciplinary group of experts in pancreatic diseases that includes gastroenterologists, radiologists, surgeons, oncologists, and geneticists. This statement was developed using a modified Delphi process as part of the Pancreatic Cancer Early Detection Consortium, and >75% agreement was required to reach consensus. RESULTS: We identified reporting elements and present standardized reporting templates for EUS indications, procedural data, EUS image capture, and descriptors of findings, tissue sampling, and postprocedural assessment of adequacy. CONCLUSIONS: Adoption of this standardized EUS reporting template should improve consistency in clinical decision-making for individuals with elevated risk of pancreatic cancer by providing complete and accurate reporting of pancreatic abnormalities. Standardization will also help to facilitate research and clinical trial design by using clearly defined and consistent imaging descriptions, thus allowing for comparison of results across different centers.

Endoscopic resection is more effective than biopsy or EUS to detect residual rectal neuroendocrine tumor.

Background and study aims Rectal neuroendocrine tumors (NETs) are often discovered incidentally and may be misidentified as adenomatous polyps. This can result in a partial resection at the index procedure, and lesions are often referred for staging or evaluation for residual disease at the resection site. The aim of this study was to identify the ideal method to confirm complete excision of small rectal NETs. Patients and methods Data from patients with a previously resected rectal NET referred for follow-up endoscopy or endoscopic ultrasound (EUS) were retrospectively reviewed. Univariate analysis was performed on categorical data using the Chi-squared test. Results Forty-nine patients with rectal NETs were identified by pathology specimens. Of those, 39 underwent follow-up endoscopy or EUS and were included. Baseline characteristics included gender (71 % F, 29 % M), age (57.2 ±â€Š13.4 yrs) lesion size (7.3 ±â€Š4.2 mm) and location. The prior resection site was identified in 37/39 patients who underwent tissue sampling. Residual NET was found histologically in 14/37 lesions. All residual disease was found during salvage endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) and 43 % had a normal-appearing scar. Every patient undergoing EUS had an unremarkable exam. Initial cold biopsy polypectomy ( P  = 0.006), visible lesions ( P  = 0.001) and EMR/ESD of the prior resection site ( P  = 0.01) correlated with residual NET. Conclusions Localized rectal NETs may be incompletely removed with standard polypectomy. If an advanced resection is not performed initially, repeat endoscopy with salvage EMR or ESD of the scar should be considered. For small rectal NETs, biopsy may miss residual disease when there is no visible lesion and EUS appears to have no benefit.

Personalized Antibodies for Gastroesophageal Adenocarcinoma (PANGEA): A Phase II Study Evaluating an Individualized Treatment Strategy for Metastatic Disease.

The one-year and median overall survival (mOS) rates of advanced gastroesophageal adenocarcinomas (GEA) are ∼50% and <12 months, respectively. Baseline spatial and temporal molecular heterogeneity of targetable alterations may be a cause of failure of targeted/immunooncologic therapies. This heterogeneity, coupled with infrequent incidence of some biomarkers, has resulted in stalled therapeutic progress. We hypothesized that a personalized treatment strategy, applied at first diagnosis then serially over up to three treatment lines using monoclonal antibodies combined with optimally sequenced chemotherapy, could contend with these hurdles. This was tested using a novel clinical expansion-platform type II design with a survival primary endpoint. Of 68 patients by intention-to-treat, the one-year survival rate was 66% and mOS was 15.7 months, meeting the primary efficacy endpoint (one-sided P = 0.0024). First-line response rate (74%), disease control rate (99%), and median progression-free survival (8.2 months) were superior to historical controls. The PANGEA strategy led to improved outcomes warranting a larger randomized study. SIGNIFICANCE: This study highlights excellent outcomes achieved by individually optimizing chemotherapy, biomarker profiling, and matching of targeted therapies at baseline and over time for GEA. Testing a predefined treatment strategy resulted in improved outcomes versus historical controls. Therapeutic resistance observed in correlative analyses suggests that dual targeted inhibition may be beneficial.This article is highlighted in the In This Issue feature, p. 211.

Histologic changes caused by injection of a novel submucosal lifting agent for endoscopic resection in GI lesions.

BACKGROUND AND AIMS: ORISE Gel is a recently introduced, U.S. Food and Drug Administration-approved submucosal lifting agent used in endoscopic resection of GI lesions. Histologically evident gel deposits in resected specimens may pose a potential diagnostic pitfall. To aid in recognition of this procedure-related artifact, we report the largest histologic series of ORISE Gel in endoscopic and surgical resection specimens to date. METHODS: Fifty-eight EMR/endoscopic submucosal dissection (ESD) specimens with ORISE Gel injection and 5 interval surgical resection specimens with previous ORISE Gel injection were included. Patient demographics and endoscopy reports were obtained. Histologic slides from all cases were reviewed. Histochemical stains were performed on select cases. RESULTS: Fifty-one EMR and 7 ESD specimens were identified. In 51 of 58 (88%) endoscopic resection specimens, amorphous, pale blue-gray, finely granular material was evident in the submucosa, as well as focally within the mucosa in 4 cases. Most cases showed homogeneous near-complete filling of the submucosa with this material, whereas a few demonstrated areas of condensation and retraction. Mucicarmine and periodic acid-Schiff stains were negative for mucin. Interval surgical resection specimens revealed extensive deposition of dense, eosinophilic material with associated multinucleated giant cells in the submucosa in all cases, with transmural extension in 3 cases. CONCLUSION: ORISE Gel injection during endoscopic resection of GI lesions results in deposition of amorphous, blue-gray material seen in histologic sections, whereas interval surgical resection specimens demonstrate dense, eosinophilic material with an associated giant cell reaction. Awareness of these artifacts will help avoid misinterpretation of their presence as pathologic findings.

Endoscopic ultrasound acquired portal venous circulating tumor cells predict progression free survival and overall survival in patients with pancreaticobiliary cancers.

BACKGROUND AND AIMS: Despite recent advances, patients with pancreaticobiliary cancers have a poor prognosis. We previously demonstrated the efficacy of endoscopic ultrasound (EUS) guided acquisition of portal vein (PV) blood for enumeration of circulating tumor cells (CTCs). The aim of this study was to assess PV-CTCs as potential biomarkers for the assessment of progression-free (PFS) and overall survival (OS) in patients with pancreaticobiliary cancers. METHODS: 17 patients with biopsy-proven pancreaticobiliary malignancy were enrolled. CTCs were enumerated from both peripheral and PV blood. All patients were followed until death. PFS and OS were evaluated with the log-rank test and summarized with the use of Kaplan-Meier methods. Unadjusted and adjusted Cox-proportional hazards models were fitted to study the relationship between PV-CTCs and PFS and OS. RESULTS: After 3.5 years of follow-up, all patients had expired. PV-CTCs were detected in all patients (median PV-CTCs 62.0/7.5 mL (interquartile range [IQR] 17-132). The mean PFS in patients with PV-CTCs <185/7.5 mL was significantly longer than patients with PV-CTCs ≥185/7.5 mL (43.3 weeks vs. 12.8 weeks, log-rank p = 0.002). The mean OS in patients with PV-CTCs <185/7.5 mL was significantly longer than patients with PV-CTCs ≥185/7.5 mL (75.8 weeks vs. 29.5 weeks, log-rank p = 0.021). In an adjusted Cox-proportional hazards model, PV-CTCs were significant predictors of both PFS and OS (HR 1.004, p = 0.037; HR 1.004, p = 0.044 respectively). CONCLUSION: In this pilot and feasibility study, EUS-acquired PV-CTCs predicted PFS and OS. Our findings suggest that PV-CTCs can help provide important prognostic data for both providers and patients.