Submucosal injection fluid and tattoo agents.

BACKGROUND AND AIMS: EMR and endoscopic submucosal dissection (ESD) are minimally invasive endoscopic techniques, developed for the removal of benign and early malignant lesions throughout the GI tract. Submucosal injection of a marking agent can help to identify lesions during surgery. Endoscopic resection frequently involves "lifting" of the lesions by injection of a substance within the submucosal space to create a cushion for safe resection. This review summarizes the current techniques and agents available for endoscopic marking and lifting of GI tract lesions. METHODS: The MEDLINE database was searched through April 2023 for relevant articles related to the lifting and marking aspect of EMR by using key words such as "endoscopy" or "endoscopic" combined with "marking," "tattoo," and "lifting." The report was drafted, reviewed, and edited by the American Society for Gastrointestinal Endoscopy Technology Committee and approved by the Governing Board of the American Society for Gastrointestinal Endoscopy. RESULTS: This technology review describes the techniques for endoscopic tattoo placement and submucosal lifting, along with currently available agents, safety, and costs. CONCLUSIONS: Endoscopists performing EMR and ESD have several choices in submucosal injection materials for lifting and marking agents for tattoos. These may be commercially prepared agents or off-the-shelf materials with or without additives to facilitate visualization. A thorough understanding of the indications, techniques, properties of various agents, costs, and adverse events is necessary in choosing the appropriate materials and technique to optimize lesion resection in EMR and ESD.

Utilization of an artificial intelligence-enhanced, web-based application to review bile duct brushing cytologic specimens: A pilot study.

BACKGROUND: The authors previously developed an artificial intelligence (AI) to assist cytologists in the evaluation of digital whole-slide images (WSIs) generated from bile duct brushing specimens. The aim of this trial was to assess the efficiency and accuracy of cytologists using a novel application with this AI tool. METHODS: Consecutive bile duct brushing WSIs from indeterminate strictures were obtained. A multidisciplinary panel reviewed all relevant information and provided a central interpretation for each WSI as being "positive," "negative," or "indeterminate." The WSIs were then uploaded to the AI application. The AI scored each WSI as positive or negative for malignancy (i.e., computer-aided diagnosis [CADx]). For each WSI, the AI prioritized cytologic tiles by the likelihood that malignant material was present in the tile. Via the AI, blinded cytologists reviewed all WSIs and provided interpretations (i.e., computer-aided detection [CADe]). The diagnostic accuracies of the WSI evaluation via CADx, CADe, and the original clinical cytologic interpretation (official cytologic interpretation [OCI]) were compared. RESULTS: Of the 84 WSIs, 15 were positive, 42 were negative, and 27 were indeterminate after central review. The WSIs generated on average 141,950 tiles each. Cytologists using the AI evaluated 10.5 tiles per WSI before making an interpretation. Additionally, cytologists required an average of 84.1 s of total WSI evaluation. WSI interpretation accuracies for CADx (0.754; 95% CI, 0.622-0.859), CADe (0.807; 95% CI, 0.750-0.856), and OCI (0.807; 95% CI, 0.671-0.900) were similar. CONCLUSIONS: This trial demonstrates that an AI application allows cytologists to perform a triaged review of WSIs while maintaining accuracy.

Utility of methylated DNA markers for the diagnosis of malignant biliary strictures.

BACKGROUND AND AIMS: Early identification of malignant biliary strictures (MBSs) is challenging, with up to 20% classified as indeterminants after preliminary testing and tissue sampling with endoscopic retrograde cholangiopancreatography. We aimed to evaluate the use of methylated DNA markers (MDMs) from biliary brushings to enhance MBS detection in a prospective cohort. APPROACH: Candidate MDMs were evaluated for their utility in MBS diagnosis through a series of discovery and validation phases. DNA was extracted from biliary brushing samples, quantified, bisulfite-converted, and then subjected to methylation-specific droplet digital polymerase chain reaction.  Patients were considered to have no malignancy if the sampling was negative and there was no evidence of malignancy after 1 year or definitive negative surgical histopathology. RESULTS: Fourteen candidate MDMs were evaluated in the discovery phase, with top-performing and new markers evaluated in the technical validation phase. The top 4 MDMs were TWIST1, HOXA1, VSTM2B, and CLEC11A, which individually achieved AUC values of 0.82, 0.81, 0.83, and 0.78, respectively, with sensitivities of 59.4%, 53.1%, 62.5%, and 50.0%, respectively, at high specificities for malignancy of 95.2%-95.3% for the final biologic validation phase. When combined as a panel, the AUC was 0.86, achieving 73.4% sensitivity and 92.9% specificity, which outperformed cytology and fluorescence in situ hybridization (FISH). CONCLUSIONS: The selected MDMs demonstrated improved performance characteristics for the detection of MBS compared to cytology and FISH. Therefore, MDMs should be considered viable candidates for inclusion in diagnostic testing algorithms.

Valuing innovative endoscopic techniques: hemostatic powder for the treatment of GI tumor bleeding.

BACKGROUND AND AIMS: Access to new endoscopic treatment modalities often depends on price. To resolve this gap and therefore help to ensure that care delivery can occur on a clinical basis, we aimed to establish the value to insurers of novel hemostatic powder to treat GI tumor bleeding. METHODS: A decision-analytic model developed to assess the impact of endoscopic intervention on the risk of 30-day readmission for GI bleeding from an insurer perspective was adapted to assess GI tumor bleeding with hemostatic powder or standard endoscopic therapy. Costs were derived from Medicare populations. Outcomes were derived from a recent multicenter randomized clinical trial. RESULTS: Costs ranged from $651 to $1613 to treat upper GI tumor bleeding and from $531 to $1014 to treat lower GI tumor bleeding based on risk reduction in 30-day hospital readmission for recurrent bleeding. These valuations should represent medical device and incremental facility costs in addition to incremental physician and staff time. CONCLUSIONS: Coverage for novel endoscopic hemostatic powder therapy seems cost-saving to insurers.

Development and initial validation of a video-based peroral endoscopic myotomy assessment tool.

BACKGROUND AND AIMS: Video analysis has emerged as a potential strategy for performance assessment and improvement. We aimed to develop a video-based skill assessment tool for peroral endoscopic myotomy (POEM). METHODS: POEM was deconstructed into basic procedural components through video analysis by an expert panel. A modified Delphi approach and 2 validation exercises were conducted to refine the POEM assessment tool (POEMAT). Twelve assessors used the final POEMAT version to grade 10 videos. Fully crossed generalizability (G) studies investigated the contributions of assessors, endoscopists' performance, and technical elements to reliability. G coefficients below .5 were considered unreliable, between .5 and .7 as modestly reliable, and above .7 as indicative of satisfactory reliability. RESULTS: After task deconstruction, discussions, and the modified Delphi process, the final POEMAT comprised 9 technical elements. G analysis showed low variance for endoscopist performance (.8%-24.9%) and high interrater variability (range, 63.2%-90.1%). The G score was moderately reliable (≥.60) for "submucosal tunneling" and "myotomy" and satisfactorily reliable (≥.70) for "active hemostasis" and "mucosal closure." CONCLUSIONS: We developed and established initial content and response process validity evidence for the POEMAT. Future steps include appraisal of the tool using a wider range of POEM videos to establish and improve the discriminative validity of this tool.

Endoscopic retrograde cholangiopancreatography (ERCP) approach for patients with Roux-en-Y gastric bypass: a comparative study between four ERCP techniques with proposed management algorithm.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is technically challenging in patients with Roux-en-Y gastric bypass (RYGB) due to altered anatomy. OBJECTIVE: To compare the procedural and clinical outcomes of 4 different ERCP techniques in RYGB patients. SETTING: Academic tertiary referral center in the United States. METHODS: A retrospective cohort study including patients with RYGB anatomy who underwent an ERCP between January 2015 and September 2020. We compared procedural success and adverse events (AEs) rates of balloon-assisted enteroscopy (BAE), gastrostomy-assisted ERCP (GAE), endoscopic ultrasound (EUS)-directed transgastric ERCP (EDGE), and rendezvous guidewire-assisted ERCP (RGA). RESULTS: Seventy-eight RYGB patients underwent a total of 132 ERCPs. The mean age was 60 ± 11.8 years, with female predominance (85.7%). The ERCP procedures performed were BAE (n = 64; 48.5%), GAE (n = 18; 13.7%), EDGE (n = 25; 18.9%), and RGA (n = 25; 18.9%), with overall procedure success rates of 64.1%, 100%, 89.5%, and 91.7%, respectively. All approaches were superior to BAE (GAE versus BAE, P = .003; EDGE versus BAE, P = .034; RGA versus BAE, P = .011). The overall AE rates were 10.9%, 11.1%, 15.8 %, and 25.0%, respectively. There was no statistical difference in AEs. There were also no differences in bleeding, post-ERCP pancreatitis, and perforation rates between the 4 approaches. CONCLUSION: Procedure success was similar between GAE, RGA, and EDGE, but superior to BAE. AE rates were similar between approaches.

Tips and tricks for endoscopic transpapillary gallbladder drainage.

Background and Aims: Percutaneous gallbladder drainage has traditionally been the reference standard treatment for cholecystitis in patients deemed unfit for surgery. Endoscopic transpapillary gallbladder drainage has emerged as a reliable alternative that offers an internal, incisionless option in nonsurgical patients. The aim of this study was to describe techniques for successful selective cystic duct cannulation and gallbladder drainage during ERCP. Methods: A series of endoscopic transpapillary gallbladder procedures is shown, including endoscopic and fluoroscopic video and images. Each case highlights best practices, devices, and techniques to aid with successful completion of challenging cases. Results: Standard cystic duct cannulation and gallbladder access is described using a standard catheter and a 0.035-inch angled guidewire. Challenges to selective cystic duct cannulation are overcome using various approaches, including using a rotatable catheter system, downsizing to a smaller guidewire, occluding the proximal common hepatic duct with an occlusion balloon, and directly intubating the cystic duct using peroral cholangioscopy. Dilation of the cystic duct is performed using standard devices designed for biliary intervention, but smaller, percutaneous angioplasty balloons are used for small ducts and severe strictures. After dilation, a plastic, double-pigtail stent is deployed across the papilla, and access is reobtained in a similar fashion to place a second, parallel stent. To eliminate the need to re-access the gallbladder after initial stent deployment, a cytology brush catheter is repurposed to obtain dual-wire access within the gallbladder before initial stent deployment. Conclusions: When the fundamentals of ERCP and the techniques described here are used, endoscopic transpapillary gallbladder drainage can be performed safely and effectively to treat cholecystitis in patients who are not surgical candidates.

KRT17High/CXCL8+ tumor cells display both classical and basal features and regulate myeloid infiltration in the pancreatic cancer microenvironment.

PURPOSE: Pancreatic ductal adenocarcinoma (PDAC) is generally divided in two subtypes, classical and basal. Recently, single cell RNA sequencing has uncovered the co-existence of basal and classical cancer cells, as well as intermediary cancer cells, in individual tumors. The latter remains poorly understood; here, we sought to characterize them using a multimodal approach. EXPERIMENTAL DESIGN: We performed subtyping on a single cell RNA sequencing dataset containing 18 human PDAC samples to identify multiple intermediary subtypes. We generated patient-derived PDAC organoids for functional studies. We compared single cell profiling of matched blood and tumor samples to measure changes in the local and systemic immune microenvironment. We then leveraged longitudinally patient-matched blood to follow individual patients over the course of chemotherapy. RESULTS: We identified a cluster of KRT17-high intermediary cancer cells that uniquely express high levels of CXCL8 and other cytokines. The proportion of KRT17High/CXCL8+ cells in patient tumors correlated with intra-tumoral myeloid abundance, and, interestingly, high pro-tumor peripheral blood granulocytes, implicating local and systemic roles. Patient-derived organoids maintained KRT17High/CXCL8+cells and induced myeloid cell migration in an CXCL8-dependent manner. In our longitudinal studies, plasma CXCL8 decreased following chemotherapy in responsive patients, while CXCL8 persistence portended worse prognosis. CONCLUSIONS: Through single cell analysis of PDAC samples we identified KRT17High/CXCL8+ cancer cells as an intermediary subtype, marked by a unique cytokine profile and capable of influencing myeloid cells in the tumor microenvironment and systemically. The abundance of this cell population should be considered for patient stratification in precision immunotherapy.

Risk of post-sphincterotomy bleeding in patients with thrombocytopenia.

Background: Reports suggest that the rate of adverse events (AEs) post-endoscopic sphincterotomy (ES) to be as high as 10%, with gastrointestinal bleeding being most common after post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. Objective: The aim of this study was to characterize the incidence of bleeding in patients with thrombocytopenia following ES. Design: Retrospective observational cohort study. Methods: Patients with thrombocytopenia (defined as <150,000 platelets/µL) who underwent ES between May 2017 and December 2020 were identified at a tertiary care medical center. The incidence of immediate (intraprocedural oozing >5 min or requiring intervention) or delayed (clinical bleeding with associated hemoglobin drop within 14 days) post-ES bleeding was determined via manual chart review. Results: A total of 221 patients with a mean platelet count of 108,000 ± 13,000 platelets/µL underwent ERCP with ES. Immediate bleeding occurred in 11 (5%) patients with no significant drop in hemoglobin or transfusion requirement. Two patients (0.9%), both of whom were noted to have immediate bleeding, also developed delayed bleeding. Presence of malignancy was associated with an increased risk of bleeding (36.4% versus 11.4%, p = 0.037) while platelet count was not. Conclusion: In a cohort of patients with thrombocytopenia, rates of immediate and delayed bleeding are similar to previously reported AE rates of ES in the general patient population. Careful attention should be given to patients with a history of active malignancy as well as those who develop immediate bleeding as they appear to be at increased risk for bleeding complications.

Risk of bleeding in patients with low platelet counts after sphincterotomy during endoscopic retrograde cholangiopancreatography procedures The sphincter that controls the flow of bile into the small bowel is often cut for a variety of clinical indications (sphincterotomy) during a procedure called endoscopic retrograde cholangiopancreatography (ERCP). One of the complications of this maneuver is bleeding. The physiology of bleeding is complex, and the risk of bleeding cannot be well captured by a single condition or laboratory test. It was presumed that low platelet counts would increase a patient's risk of bleeding during a procedure, but emerging data suggests that many endoscopic procedures are safer than previously understood in these patients. However, there is limited data for sphincterotomy and ERCP. This study from a single, academic center evaluates the outcomes of all patients who underwent sphincterotomy with platelets that were below the normal threshold. Overall, the data shows that sphincterotomy appears to be as safe in patients with low platelets as the general population. Patients with active cancer may be at slightly higher risk for bleeding. Additional precautions may be needed in this group, however further studies are needed to confirm this finding.

Third and Fourth Vaccine Doses Broaden and Prolong Immunity to SARS-CoV-2 in Adult Patients with Immune-Mediated Inflammatory Diseases.

Previous studies have reported impaired humoral responses after SARS-CoV-2 mRNA vaccination in patients with immune-mediated inflammatory diseases (IMIDs), particularly those treated with anti-TNF biologics. We previously reported that IMID patients diagnosed with inflammatory bowel disease, psoriasis, psoriatic arthritis, ankylosing spondylitis, or rheumatoid arthritis exhibited greater waning of Ab and T cell responses than healthy control subjects after SARS-CoV-2 vaccine dose 2. Fewer data are available on the effects of third and fourth doses. This observational cohort study collected plasma and PBMCs from healthy control subjects and untreated or treated patients with IMIDs prevaccination and after one to four doses of SARS-CoV-2 mRNA vaccine (BNT162b2 or mRNA-1273). SARS-CoV-2-specific Ab levels, neutralization, and T cell cytokine release were measured against wild-type and Omicron BA.1 and BA.5 variants of concern. Third vaccine doses substantially restored and prolonged Ab and T cell responses in patients with IMIDs and broadened responses against variants of concern. Fourth-dose effects were subtle but also prolonged Ab responses. However, patients with IMIDs treated with anti-TNF, especially patients with inflammatory bowel disease, exhibited lower Ab responses even after the fourth dose. Although T cell IFN-γ responses were maximal after one dose, IL-2 and IL-4 production increased with successive doses, and early production of these cytokines was predictive of neutralization responses at 3-4 mo postvaccination. Our study demonstrates that third and fourth doses of the SARS-CoV-2 mRNA vaccines sustain and broaden immune responses to SARS-CoV-2, supporting the recommendation for three- and four-dose vaccination regimens in patients with IMIDs.

Endoscopic ultrasound-guided versus percutaneous drainage for the management of post-operative fluid collections after distal pancreatectomy.

BACKGROUND: Post-operative pancreatic fluid collections (POPFCs) can be drained using percutaneous or endoscopic approaches. The primary aim of this study was to compare rates of clinical success between endoscopic ultrasound-guided drainage (EUSD) with percutaneous drainage (PTD) in the management of symptomatic POPFCs after distal pancreatectomy. Secondary outcomes included technical success, total number of interventions, time to resolution, rates of adverse events (AEs), and POPFC recurrence. METHODS: Adults who underwent distal pancreatectomy from January 2012 to August 2021 and developed symptomatic POPFC in the resection bed were retrospectively identified from a single academic center database. Demographic data, procedural data, and clinical outcomes were abstracted. Clinical success was defined as symptomatic improvement and radiographic resolution without requiring an alternate drainage modality. Quantitative variables were compared using a two-tailed t-test and categorical data were compared using Chi-squared or Fisher's exact tests. RESULTS: Of 1046 patients that underwent distal pancreatectomy, 217 met study inclusion criteria (median age 60 years, 51.2% female), of whom 106 underwent EUSD and 111 PTD. There were no significant differences in baseline pathology and POPFC size. PTD was generally performed earlier after surgery (10 vs. 27 days; p < 0.001) and more commonly in the inpatient setting (82.9% vs. 49.1%; p < 0.001). EUSD was associated with a significantly higher rate of clinical success (92.5% vs. 76.6%; p = 0.001), fewer median number of interventions (2 vs. 4; p < 0.001), and lower rate of POPFC recurrence (7.6% vs. 20.7%; p = 0.007). AEs were similar between EUSD (10.4%) and PTD (6.3%, p = 0.28), with approximately one-third of EUSD AEs due to stent migration. CONCLUSION: In patients with POPFCs after distal pancreatectomy, delayed drainage with EUSD was associated with higher rates of clinical success, fewer interventions, and lower rates of recurrence than earlier drainage with PTD.

Uncovered versus fully covered self-expandable metal stents for the management of distal malignant biliary obstruction.

BACKGROUND AND AIM: Self-expandable metal stents (SEMSs) are widely used for palliation of distal malignant biliary obstruction (dMBO). However, previous studies comparing the outcomes between uncovered SEMSs (UCSEMSs) and fully covered SEMSs (FCSEMSs) report conflicting results. This large cohort study aimed to compare the clinical outcomes between UCSEMSs and FCSEMSs for dMBO. METHODS: A retrospective cohort study was performed in patients with dMBO who underwent either UCSEMS or FCSEMS placement between May 2017 and May 2021. Primary outcomes were rates of clinical success, adverse events (AEs), and unplanned endoscopic reintervention. Secondary outcomes were types of AEs, intervention-free stent patency, and management and outcomes of stent occlusion. RESULTS: The cohort included 454 patients (364 in the UCSEMS group and 90 in the FCSEMS group). Median follow-up duration was 9.6 months and was similar between the 2 groups. Use of UCSEMSs and FCSEMSs had comparable clinical success (P = .250). However, use of UCSEMSs had significantly higher rates of AEs (33.5% vs 21.1%; P = .023) and unplanned endoscopic reintervention (27.0% vs 11.1%; P = .002). UCSEMSs had a higher rate of stent occlusion (26.9% vs 8.9%; P < .001) and shorter median time to stent occlusion (4.4 months vs 10.7 months; P = .002). Stent reintervention-free survival was higher in the FCSEMS group. FCSEMSs had a significantly higher rate of stent migration (7.8% vs 1.1%; P < .001), but patients in the FCSEMS group had similar rates of cholecystitis (.3% vs 1.1%; P = .872) and post-ERCP pancreatitis (6.3% vs 6.6%; P = .90). When UCSEMSs did occlude, placement of a coaxial plastic stent had a higher rate of stent reocclusion compared with coaxial SEMS placement (46.7% vs 19.7%; P = .007). CONCLUSION: FCSEMSs should be considered for the palliation of dMBO because of lower rates of AEs, longer patency rates, and lower rates of unplanned endoscopic intervention.

Identification of patients with malignant biliary strictures using a cholangioscopy-based deep learning artificial intelligence (with video).

BACKGROUND AND AIMS: Accurately diagnosing malignant biliary strictures (MBSs) as benign or malignant remains challenging. It has been suggested that direct visualization and interpretation of cholangioscopy images provide greater accuracy for stricture classification than current sampling techniques (ie, brush cytology and forceps biopsy sampling) using ERCP. We aimed to develop a convolutional neural network (CNN) model capable of accurate stricture classification and real-time evaluation based solely on cholangioscopy image analysis. METHODS: Consecutive patients with cholangioscopy examinations from 2012 to 2021 were reviewed. A CNN was developed and tested using cholangioscopy images with direct expert annotations. The CNN was then applied to a multicenter, reserved test set of cholangioscopy videos. CNN performance was then directly compared with that of ERCP sampling techniques. Occlusion block heatmap analyses were used to evaluate and rank cholangioscopy features associated with MBSs. RESULTS: One hundred fifty-four patients with available cholangioscopy examinations were included in the study. The final image database comprised 2,388,439 still images. The CNN demonstrated good performance when tasked with mimicking expert annotations of high-quality malignant images (area under the receiver-operating characteristic curve, .941). Overall accuracy of CNN-based video analysis (.906) was significantly greater than that of brush cytology (.625, P = .04) or forceps biopsy sampling (.609, P = .03). Occlusion block heatmap analysis demonstrated that the most frequent image feature for an MBS was the presence of frond-like mucosa/papillary projections. CONCLUSIONS: This study demonstrates that a CNN developed using cholangioscopy data alone has greater accuracy for biliary stricture classification than traditional ERCP-based sampling techniques.

Endoscopic Ultrasound-Guided Gastrojejunostomy for Superior Mesenteric Artery Syndrome Secondary to Rapid Weight Loss.

A 19-year-old man diagnosed with diffuse large B-cell lymphoma undergoing chemotherapy presented for recurrent emesis and weight loss. Imaging studies of the abdomen demonstrated features of superior mesenteric artery syndrome. The patient deferred conservative treatment options and was deemed not to be a surgical candidate. Endoscopic ultrasound-guided gastroenterostomy using a lumen-apposing metal stent was performed to bypass the obstruction. Subsequently, the patient's oral intake and weight significantly improved. The stent was removed 6 months after placement with resolution of superior mesenteric artery syndrome symptoms.

Histological assessment of new cholangioscopy-guided forceps in ERCP biliary stricture sampling: a blinded comparative study.

Background and study aims Obtaining quality tissue during ERCP biliary stricture sampling is of paramount importance for a timely diagnosis. While single-operator cholangioscopy (SOC)-guided biopsies have been suggested to be the superior biliary tissue acquisition modality given direct tissue visualization, less is known about the specimen histological quality. We aimed to analyze the specimen quality of SOC biopsies and compare the new generation forceps with prior "legacy" forceps. Patients and methods Patients who underwent SOC from January 2017-August 2021 for biliary sampling were reviewed. In February 2020, the SOC-guided biopsy forceps were changed from legacy SpyBite to the SpyBite Max forceps (max). Specimens were assessed by blinded pathologists for crush artifact (none, mild, or severe) and gross size (greatest dimension in mm). Crush artifact and gross size were compared between the two groups. The diagnostic performance characteristics for cholangiocarcinoma (CCA), were assessed in an exploratory fashion. Results Eighty-one patients (max = 27, legacy = 54) with similar baseline characteristics were included in this study. On blinded pathological assessment, 58 % had crush artifact, without significant differences between the two groups (Max 63 % vs. Legacy 56 %; P  = 0.64). A similar mean specimen size was found (max 3 mm vs. legacy 3.2 mm; P  = 0.24). The overall prevalence of CCA was 40 %. The sensitivity, specificity, positive predictive value, and negative predictive value of the entire cohort using a combination of cytology, fluorescence in situ hybridization, and SOC-guided biopsies were 78.1 %, 91.8 %, 86.2 %, and 86.5 %, respectively. No difference between legacy or max groups was found. Conclusions A high rate of crush artifact was found in SOC-guided biopsy specimens. Further investigation regarding proper biopsy technique and handling is necessary to increase the diagnostic yield with SOC-guided biopsies.