Giant Terahertz Birefringence in an Ultrathin Anisotropic Semimetal.

Manipulating the polarization of light at the nanoscale is key to the development of next-generation optoelectronic devices. This is typically done via waveplates using optically anisotropic crystals, with thicknesses on the order of the wavelength. Here, using a novel ultrafast electron-beam-based technique sensitive to transient near fields at THz frequencies, we observe a giant anisotropy in the linear optical response in the semimetal WTe2 and demonstrate that one can tune the THz polarization using a 50 nm thick film, acting as a broadband wave plate with thickness 3 orders of magnitude smaller than the wavelength. The observed circular deflections of the electron beam are consistent with simulations tracking the trajectory of the electron beam in the near field of the THz pulse. This finding offers a promising approach to enable atomically thin THz polarization control using anisotropic semimetals and defines new approaches for characterizing THz near-field optical response at far-subwavelength length scales.

LOAd703, an oncolytic virus-based immunostimulatory gene therapy, combined with chemotherapy for unresectable or metastatic pancreatic cancer (LOKON001): results from arm 1 of a non-randomised, single-centre, phase 1/2 study.

BACKGROUND: Pancreatic ductal adenocarcinoma is characterised by low immunogenicity and an immunosuppressive tumour microenvironment. LOAd703, an oncolytic adenovirus with transgenes encoding TMZ-CD40L and 4-1BBL, lyses cancer cells selectively, activates cytotoxic T cells, and induces tumour regression in preclinical models. The aim of this study was to evaluate the safety and feasibility of combining LOAd703 with chemotherapy for advanced pancreatic ductal adenocarcinoma. METHODS: LOKON001 was a non-randomised, phase 1/2 study conducted at the Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine, Houston, TX, USA, and consisted of two arms conducted sequentially; the results of arm 1 are presented here. In arm 1, patients 18 years or older with previously treated or treatment-naive unresectable or metastatic pancreatic ductal adenocarcinoma were treated with standard 28-day cycles of intravenous nab-paclitaxel 125 mg/m2 plus gemcitabine 1000 mg/m2 (up to 12 cycles) and intratumoural injections of LOAd703 every 2 weeks. Patients were assigned using Bayesian optimal interval design to receive 500 µL of LOAd703 at 5 × 1010 (dose 1), 1 × 1011 (dose 2), or 5 × 1011 (dose 3) viral particles per injection, injected endoscopically or percutaneously into the pancreatic tumour or a metastasis for six injections. The primary endpoints were safety and treatment-emergent immune response in patients who received at least one dose of LOAd703, and antitumour activity was a secondary endpoint. This study was registered with ClinicalTrials.gov, NCT02705196, arm 2 is ongoing and open to new participants. FINDINGS: Between Dec 2, 2016, and Oct 17, 2019, 23 patients were assessed for eligibility, leading to 22 patients being enrolled. One patient withdrew consent, resulting in 21 patients (13 [62%] men and eight [38%] women) assigned to a dose group (three to dose 1, four to dose 2, and 14 to dose 3). 21 patients were evaluable for safety. Median follow-up time was 6 months (IQR 4-10), and data cutoff was Jan 5, 2023. The most common treatment-emergent adverse events overall were anaemia (96 [8%] of 1237 events), lymphopenia (86 [7%] events), hyperglycaemia (70 [6%] events), leukopenia (63 [5%] events), hypertension (62 [5%] events), and hypoalbuminaemia (61 [5%] events). The most common adverse events attributed to LOAd703 were fever (14 [67%] of 21 patients), fatigue (eight [38%]), chills (seven [33%]), and elevated liver enzymes (alanine aminotransferase in five [24%], alkaline phosphatase in four [19%], and aspartate aminotransferase in four [19%]), all of which were grade 1-2, except for a transient grade 3 aminotransferase elevation occurring at dose 3. A maximum tolerated dose was not reached, thereby establishing dose 3 as the highest-evaluated safe dose when combined with nab-paclitaxel plus gemcitabine. Proportions of CD8+ effector memory cells and adenovirus-specific T cells increased after LOAd703 injections in 15 (94%) of 16 patients for whom T-cell assays could be performed. Eight (44%, 95% CI 25-66) of 18 patients evaluable for activity had an objective response. INTERPRETATION: Combining LOAd703 with nab-paclitaxel plus gemcitabine in patients with advanced pancreatic ductal adenocarcinoma was feasible and safe. To build upon this novel chemoimmunotherapeutic approach, arm 2 of LOKON001, which combines LOAd703, nab-paclitaxel plus gemcitabine, and atezolizumab, is ongoing. FUNDING: Lokon Pharma, the Swedish Cancer Society, and the Swedish Research Council.

Ambulatory Endoscopic Submucosal Dissection for Gastrointestinal Neoplasms: Trends and Associated Factors in the United States.

Endoscopic submucosal dissection (ESD) is a minimally invasive treatment for superficial gastrointestinal (GI) cancers.1,2 ESD practice is expanding significantly in the United States and Western countries. This is attributed to a shorter hospital stay, better quality of life, and fewer adverse events compared with surgery. In the United States, ESD usually is performed and managed in an outpatient setting (ambulatory ESD) or with an overnight hospital stay. This practice is in contrast to Eastern Asian countries, where 3 to 5 days of hospital stay is a routine process for observation after ESD. A Swedish study showed that patients with well-selected colorectal neoplasms (median tumor size, 37 mm) could be managed safely in an outpatient setting after ESD.3 A North American multicenter ESD study also reported that ambulatory ESD was safe and feasible in selected cases (noninvasive cancers, no adverse events, high-volume endoscopists with short procedure time).4 However, procedural and technical aspects that enable safe outpatient management of patients after ESD need to be investigated.

Hybrid Versus Conventional Colorectal Endoscopic Submucosal Dissection: A Multicenter Randomized Controlled Trial (Short-Endoscopic Submucosal Dissection).

INTRODUCTION: Hybrid endoscopic submucosal dissection (H-ESD), which utilizes ESD knife along with snare-based resection, has been developed to overcome the technical complexity of conventional ESD (C-ESD). The aim of this study was to compare the therapeutic outcomes of H-ESD vs C-ESD for nonpedunculated colorectal lesions ≥20 mm in size. METHODS: We conducted a multicenter randomized controlled trial to compare H-ESD and C-ESD (Short-ESD trial). Patients with colorectal lesions between 20 and 50 mm in size were randomly assigned (1:1) to H-ESD or C-ESD. Primary outcome was procedure time/speed. Secondary outcomes were en bloc and complete (R0) resection rates and adverse event rates. RESULTS: A total of 89 patients (median age 63 years; 49.3% women) with the median polyp size of 30 mm underwent H-ESD (n = 40) and C-ESD (n = 49). The mean procedure time of H-ESD was significantly shorter than that of C-ESD (41.1 ± 16.3 vs 54.3 ± 28.2 minutes; P = 0.007). The en bloc and R0 resection rates trended lower in the H-ESD vs C-ESD groups (77.5% vs 87.8%; P = 0.26% and 72.5% vs 79.6%; P = 0.46) without reaching statistical significance. Adverse event rate was similar between H-ESD and C-ESD (10% vs 8.2%; P = 1.00). DISCUSSION: Both H-ESD and C-ESD were safe and effective for resection of large colorectal lesions. H-ESD was associated with a shorter procedure time. H-ESD may represent a viable alternative to C-ESD, with the main advantage being easy applicability of a snare-based technique for colorectal lesions. Future studies are needed to further define the most suitable lesions for H-ESD, as to optimize efficiency and safety without compromising resection outcomes. ClinicaTrials.gov NCT NCT05347446.

Development of clinical screening tool for exocrine pancreatic insufficiency in patients with definite chronic pancreatitis.

BACKGROUND/OBJECTIVES: No simple, accurate diagnostic tests exist for exocrine pancreatic insufficiency (EPI), and EPI remains underdiagnosed in chronic pancreatitis (CP). We sought to develop a digital screening tool to assist clinicians to predict EPI in patients with definite CP. METHODS: This was a retrospective case-control study of patients with definite CP with/without EPI. Overall, 49 candidate predictor variables were utilized to train a Classification and Regression Tree (CART) model to rank all predictors and select a parsimonious set of predictors for EPI status. Five-fold cross-validation was used to assess generalizability, and the full CART model was compared with 4 additional predictive models. EPI misclassification rate (mRate) served as primary endpoint metric. RESULTS: 274 patients with definite CP from 6 pancreatitis centers across the United States were included, of which 58 % had EPI based on predetermined criteria. The optimal CART decision tree included 10 variables. The mRate without/with 5-fold cross-validation of the CART was 0.153 (training error) and 0.314 (prediction error), and the area under the receiver operating characteristic curve was 0.889 and 0.682, respectively. Sensitivity and specificity without/with 5-fold cross-validation was 0.888/0.789 and 0.794/0.535, respectively. A trained second CART without pancreas imaging variables (n = 6), yielded 8 variables. Training error/prediction error was 0.190/0.351; sensitivity was 0.869/0.650, and specificity was 0.728/0.649, each without/with 5-fold cross-validation. CONCLUSION: We developed two CART models that were integrated into one digital screening tool to assess for EPI in patients with definite CP and with two to six input variables needed for predicting EPI status.

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).

The use of a self-assembling peptide gel for stricture prevention in the esophagus after endoscopic submucosal dissection: a U.S. multicenter prospective study (with video).

BACKGROUND AND AIMS: Postoperative stricture is a serious common adverse event after extensive endoscopic submucosal dissection (ESD) in the esophagus. Self-assembling peptide (SAP) gel has been shown to promote tissue healing and re-epithelialization. The aim of this study was to evaluate the effect of the SAP gel for esophageal stricture prevention after ESD. METHODS: This was a multicenter prospective study of patients who underwent esophageal ESD followed by SAP gel application between March 2022 and December 2023. Patients were included if the ESD mucosal defect involved ≥50% of the circumference of the esophagus. High-risk cases were defined as mucosal defects ≥75% of the circumference. Stricture was defined as the inability to pass an endoscope ≥8.9 mm in diameter or a narrow-caliber lumen in a patient with symptoms. RESULTS: A total of 43 patients (median age, 71 years; 81.4% male) underwent ESD (median resected specimen size, 50 mm) during the study period. SAP gel (median, 3 mL) was successfully applied in all cases (median time, 4 minutes). In aggregate, stricture occurred in 20.9% (9 of 43) of the cases. Stricture developed in 30.8% of the high-risk cases: 80% (4 of 5) after circumferential ESD and 19% (4 of 21) in those with defects ≥75% but <100% of the circumference. All cases of stricture resolved with endoscopic treatment. Three cases (6.9%) of postoperative bleeding occurred and were adequately managed endoscopically. CONCLUSIONS: We show that SAP gel application was easy, quick, and associated with a relatively low stricture rate comparable to other prophylactic methods. Additional comparative studies are needed to corroborate these preliminary findings.

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.

Low delayed bleeding and high complete closure rate of mucosal defects with the novel through-the-scope dual-action tissue clip after endoscopic resection of large nonpedunculated colorectal lesions (with video).

BACKGROUND AND AIMS: Complete closure after endoscopic resection of large nonpedunculated colorectal lesions (LNPCLs) can reduce delayed bleeding but is challenging with conventional through-the-scope (TTS) clips alone. The novel dual-action tissue (DAT) clip has clip arms that open and close independently of each other, facilitating tissue approximation. We aimed to evaluate the rate of complete closure and delayed bleeding with the DAT clip after endoscopic resection of LNPCLs. METHODS: This was a multicenter prospective cohort study of all patients who underwent defect closure with the DAT clip after EMR or endoscopic submucosal dissection (ESD) of LNPCLs ≥20 mm from July 2022 to May 2023. Delayed bleeding was defined as a bleeding event requiring hospitalization, blood transfusion, or any intervention within 30 days after the procedure. Complete closure was defined as apposition of mucosal defect margins without visible submucosal areas <3 mm along the closure line. RESULTS: One hundred seven patients (median age, 64 years; 42.5% women) underwent EMR (n = 63) or ESD (n = 44) of LNPCLs (median size, 40 mm; 74.8% right-sided colon) followed by defect closure. Complete closure was achieved in 96.3% (n = 103) with a mean of 1.4 ± .6 DAT clips and 2.9 ± 1.8 TTS clips. Delayed bleeding occurred in 1 patient (.9%) without requiring additional interventions. CONCLUSIONS: The use of the DAT clip in conjunction with TTS clips achieved high complete defect closure after endoscopic resection of large LNPCLs and was associated with a .9% delayed bleeding rate. Future comparative trials and formal cost-analyses are needed to validate these findings. (Clinical trial registration number: NCT05852457.).

Peroral endoscopic myotomy for spastic esophageal dysmotility among opioid users: a multicenter propensity score matching study.

BACKGROUND AND AIMS: Opioid-induced esophageal dysfunction (OIED) often presents as spastic esophageal disorders (SEDs) and esophagogastric junction outflow obstruction (EGJOO). The aim of this study was to evaluate and compare clinical outcomes of peroral endoscopic myotomy (POEM) for SEDs and EGJOO among opioid users and nonusers. METHODS: This propensity score (PS) matching study included consecutive opioid users and nonusers who underwent POEM for SEDs and EGJOO between January 2018 and September 2022. The following covariates were used for the PS calculation: age, sex, duration of symptoms, Eckardt score, type of motility disorder, and length of myotomy during POEM. Clinical response was defined as a post-POEM Eckardt score ≤3. RESULTS: A total of 277 consecutive patients underwent POEM during the study period. PS matching resulted in the selection of 64 pairs of patients strictly matched 1:1 (n = 128) with no statistically significant differences in demographic, baseline, or procedural characteristics or in the parameters considered for the PS between the 2 groups. Clinical response to POEM was significantly lower among opioid users (51 of 64 [79.7%]) versus nonusers (60 of 64 [93.8%]) (P = .03) at a median follow-up of 18 months. Among opioid users, higher opioid dose (>60 morphine milligram equivalents per day) was associated with a higher likelihood of failure to respond to POEM (odds ratio, 4.59; 95% confidence interval, 1.31-3.98; P = .02). CONCLUSIONS: Clinical response to POEM for SEDs and EGJOO is significantly lower among opioid users versus nonusers. There was a dose-relationship between opioids and response to POEM, with higher daily opioid usage associated with a higher likelihood of treatment failure.

Prospective feasibility study of a novel rigidizing stabilizing overtube in the resection of complex gastrointestinal polyps.

BACKGROUND: A novel rigidizing overtube (ROT) was developed to facilitate endoscopic removal of complex gastrointestinal polyps. We aimed to prospectively evaluate the efficacy and safety of the device in the management of large gastrointestinal polyps. METHODS: A prospective, single-center study, conducted between May 2021 and April 2023, enrolled patients undergoing endoscopic resection of colon/duodenal polyps ≥25 mm. Primary outcomes were safety, technical success, and clinical success defined as the ability of ROT to facilitate endoscopic polyp removal without changing the initial resection method. RESULTS: 97 patients (98 polyps), with a mean polyp size of 33.2 mm (median 31.1), were evaluated. Technical and clinical success rates were 100% and 84%, respectively. Ileocecal valve location was the only predictor of clinical failure (P = 0.02). The mean time to reach the lesion was 7.2 minutes (95%CI 5-8), with overall resection and procedure times of 53.6 minutes (95%CI 48-61) and 88.9 minutes (95%CI 79-95), respectively. No device-related adverse events occurred. Lower technical (67%) and clinical (67%) success rates were seen for duodenal polyps (n = 6). CONCLUSION: The novel ROT was safe, with high technical and clinical success during resection of complex colon polyps. Future studies will determine timing of implementation during routine endoscopic resection.

Applicability of Child-Turcotte-Pugh Score in Anticipating Post-ERCP Adverse Events in Patients With Cirrhosis: A Systematic Review and Meta-analysis.

Limited objective data exist on the comparison of post-endoscopic retrograde cholangiopancreatography (ERCP) complications in patients with cirrhosis based on the severity of the disease. We evaluated the effectiveness of the Child-Turcotte-Pugh (CTP) score system in anticipating the risk of post-ERCP complications in patients with cirrhosis. The PubMed, Scopus, Embase, and Cochrane databases were searched from inception through September 2022 to identify studies comparing post-ERCP complications in patients with cirrhosis based on CTP score. Odds ratios (ORs) and their associated 95% CIs were pooled using a random-effect model to calculate effect size. The reference group for analysis was the CTP class C patient group. Seven studies comprising 821 patients who underwent 1068 ERCP procedures were included. The CTP class C patient population exhibited a higher risk of overall post-ERCP adverse events compared with those with class A or B (OR: 2.87, 95% CI: 1.77-4.65, P = 0.00 and OR: 2.02, 95% CI: 1.17-3.51, P = 0.01, respectively). Moreover, CTP class B patients had a significantly higher complication rate than CTP class A patients (OR: 1.62, 95% CI: 1.04-2.53, P = 0.03). However, no statistically significant differences were found in the occurrence of specific types of complications, including bleeding, pancreatitis, cholangitis, perforation, or mortality across the three CTP groups. We demonstrated that the CTP classification system is a reliable predictor of ERCP complications in patients with cirrhosis. Consequently, caution should be exercised when performing ERCP in patients classified as CTP class C.

Blockade of L-Type Ca2+ Channel Activity Alleviates Oligodendrocyte Pathology following Brain Injury in Male Rats.

A growing body of studies suggests that Ca2+ signaling controls a variety of biological processes in brain elements. Activation of L-type voltage-operated Ca2+ channels (VOCCs) plays a role in the development of oligodendrocyte (OL) lineage loss, and indicates that the blocking of these channels may be an effective way to inhibit OL lineage cell loss. For this study, 10.5-day-old male Sprague-Dawley rats were used to generate cerebellar tissue slices. The slice tissues were cultured and randomly allocated to one of four groups (six each) and treated as follows: Group I, (sham control); Group II, 0.1% dimethyl sulfoxide (DMSO) only (vehicle control); Group III, injury (INJ); Group IV, (INJ and treatment with NIF). The injury was simulated by exposing the slice tissues to 20 min of oxygen-glucose deprivation (OGD). At 3 days post-treatment, the survival, apoptosis, and proliferation of the OL lineages were measured and compared. Results: In the INJ group, there was a decrease in mature myelin basic protein+ OLs (MBP+ OLs) and their precursors, NG2+ OPCs (Nerve-glia antigen 2+ oligodendrocyte precursor cell), compared with controls. A significant elevation was observed in the NG2+ OPCs and apoptotic MBP+ OLs as confirmed by a TUNEL assay. However, the cell proliferation rate was decreased in NG2+ OPCs. NIF increased OL survival as measured by apoptosis rate in both OL lineages and preserved the rate of proliferation in the NG2+ OPCs. Conclusions: Activation of L-type VOCCs may contribute to OL pathology in association with reduced mitosis of OPCs following brain injury as a strategy to treat demyelinating diseases.

Association of Chronic Pancreatitis Pain Features With Physical, Mental, and Social Health.

BACKGROUND AND AIMS: Pain is a cardinal symptom of chronic pancreatitis (CP). Using Patient-Reported Outcomes Measurement Information System (PROMIS) measures, we characterized physical and mental health and symptom profiles of a well-defined cohort of individuals with CP and compared them with control subjects. Among patients with CP, we also examined associations between pain (intensity, temporal nature) and PROMIS symptom profiles and the prevalence of clinically significant psychological comorbidities. METHODS: We analyzed baseline data in 488 CP patients and 254 control subjects enrolled in PROCEED (Prospective Evaluation of Chronic Pancreatitis for Epidemiologic and Translational Studies), an ongoing longitudinal cohort study. Participants completed the PROMIS-Global Health, which captures global physical and mental health, and the PROMIS-29 profile, which captures 7 symptom domains. Self-reported pain was categorized by severity (none, mild-moderate, severe) and temporal nature (none, intermittent, constant). Demographic and clinical data were obtained from the PROCEED database. RESULTS: Pain was significantly associated with impairments in physical and mental health. Compared with participants with no pain, CP participants with severe pain (but not mild-moderate pain) had more decrements in each PROMIS domain in multivariable models (effect sizes, 2.54-7.03) and had a higher prevalence of clinically significant depression, anxiety, sleep disturbance, and physical disability (odds ratios, 2.11-4.74). Similar results were noted for constant pain (but not intermittent pain) for PROMIS domains (effect sizes, 4.08-10.37) and clinically significant depression, anxiety, sleep disturbance and physical disability (odds ratios, 2.80-5.38). CONCLUSIONS: Severe and constant pain are major drivers for poor psychological and physical health in CP. Systematic evaluation and management of psychiatric comorbidities and sleep disturbance should be incorporated into routine management of patients with CP. (ClinicalTrials.gov, Number: NCT03099850).

Validation of a pre-endoscopy risk score for predicting the presence of gastric intestinal metaplasia in a U.S. population.

BACKGROUND AND AIMS: Surveillance of gastric intestinal metaplasia (GIM) may lead to early gastric cancer detection. Our purpose was to externally validate a predictive model for endoscopic GIM previously developed in a veteran population in a second U.S. METHODS: We previously developed a pre-endoscopy risk model for detection of GIM using 423 GIM cases and 1796 control subjects from the Houston Veterans Affairs Hospital. The model included sex, age, race/ethnicity, smoking, and Helicobacter pylori infection with an area under the receiver-operating characteristic curve (AUROC) of .73 for GIM and .82 for extensive GIM. We validated this model in a second cohort of patients from 6 Catholic Health Initiative (CHI)-St Luke's hospitals (Houston, Tex, USA) from January to December 2017. Cases were defined as having GIM on any gastric biopsy sample and extensive GIM as involving both the antrum and corpus. We further optimized the model by pooling both cohorts and assessing discrimination using AUROC. RESULTS: The risk model was validated in 215 GIM cases (55 with extensive GIM) and 2469 control subjects. Cases were older than control subjects (59.8 vs 54.7 years) with more nonwhites (59.1% vs 42.0%) and H pylori infections (23.7% vs 10.9%). The model applied to the CHI-St Luke's cohort had an AUROC of .62 (95% confidence interval [CI], .57-.66) for predicting GIM and of .71 (95% CI, .63-.79) for predicting extensive GIM. When the Veterans Affairs and CHI-St Luke's cohorts were pooled, discrimination of both models improved (GIM vs extensive GIM AUROC: .74 vs .82). CONCLUSIONS: A pre-endoscopy risk prediction model was validated and updated using a second U.S. cohort with robust discrimination for endoscopic GIM. This model should be evaluated in other U.S. populations to risk-stratify patients for endoscopic GIM screening.

Safety and efficacy of a novel suturing device for closure of large defects after endoscopic submucosal dissection (with video).

BACKGROUND AND AIMS: Endoscopic suturing enables full closure of large defects after endoscopic submucosal dissection (ESD). However, its use is limited by the need for a double-channel endoscope. A novel closure system, the OverStitch Sx (Apollo Endosurgery, Austin, Tex, USA), compatible with any single-channel endoscope, was introduced to address these shortcomings. The aim of this study was to assess the safety and feasibility of OverStitch Sx for the closure of large defects after ESD. METHODS: This is a prospective single-center feasibility study of patients who underwent closure of large defects after ESD using the OverStitch Sx system. Main outcomes of the study are technical and clinical success, same-day discharge rate, and adverse event rate. RESULTS: Thirty-three patients were enrolled. The mean diameter of included lesions was 5.38 ± 2.52 cm. The defect occupied ≥50% of the lumen circumference in 70% of the cases. En-bloc resection, R0 resection, and curative resection were achieved in 97%, 87.5%, and 78.8% of patients, respectively. Technical success and clinical success were seen in 93.9% and 90.9% of the cases, respectively. Same-day hospital discharge was achieved in 77.4% of patients. Total adverse event rate was 35.7%, including delayed bleeding in 1 patient after rectal ESD that was managed conservatively, self-resolving rectal pain in 7 patients, rectal stricture requiring dilation in 1 patient, and temporary dysphagia in 1 patient. No immediate or delayed perforation was reported. CONCLUSIONS: OverStitch Sx enabled safe and effective closure of large defects after ESD. Future trials are needed to determine its superiority over OverStitch for the closure of defects in challenging locations. (Clinical trial registration number: NCT04361227.).

Safety and feasibility of same-day discharge after endoscopic submucosal dissection: a Western multicenter prospective cohort study.

BACKGROUND AND AIMS: Recent Western studies support the safety and efficacy of endoscopic submucosal dissection (ESD) for lesions throughout the GI tract. Although admission for observation after ESD is standard in Asia, a more selective approach may optimize resource utilization. We aimed to evaluate the safety and feasibility of same-day discharge (SDD) after ESD and factors associated with admission. METHODS: This was a post hoc analysis of a multicenter, prospective cohort of patients undergoing ESD (2016-2021). The primary end points were safety of SDD and factors associated with post-ESD admission. RESULTS: Of 831 patients (median age, 67 years; 57% male) undergoing 831 ESDs (240 performed in the esophagus, 126 in the stomach, and 465 in the colorectum; median lesion size, 44 mm), 588 (71%) were SDD versus 243 (29%) admissions. Delayed bleeding and perforation occurred in 12 (2%) and 4 (.7%) of SDD patients, respectively; only 1 (.2%) required surgery. Of the 243 admissions, 223 (92%) were discharged after ≤24 hours of observation. Interestingly, larger lesion size (>44 mm) was not associated with higher admission rate (odds ratio [OR], .5; 95% confidence interval [CI], .3-.8; P = .001). Lesions in the upper GI tract versus colon (OR, 1.7; 95% CI, 1.1-2.6; P = .01), invasive cancer (OR, 1.9; 95% CI, 1.2-3.1; P = .01), and adverse events (OR, 2.7; 95% CI, 1.5-4.8; P = .001) were independent factors for admission. Admissions were more likely performed by endoscopists with ESD volume <50 cases (OR, 2.1; 95% CI, 1.3-3.3; P = .001) with procedure time >75 minutes (OR, 13.5; 95% CI, 8.5-21.3; P < .0001). CONCLUSIONS: SDD after ESD can be safe and feasible. Patients with invasive cancer, lesions in the upper GI tract, longer procedure times, or procedures performed by low-volume ESD endoscopists are more likely to be admitted postprocedure. Risk stratification of patients for SDD after ESD should help optimize resource utilization and enhance ESD uptake in the West. (Clinical trial registration number: NCT02989818.).

American Society for Gastrointestinal Endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers: methodology and review of evidence.

This document from the American Society for Gastrointestinal Endoscopy (ASGE) provides a full description of the methodology used in the review of the evidence used to inform the final guidance outlined in the accompanying Summary and Recommendations document regarding the role of endoscopic submucosal dissection (ESD) in the management of early esophageal and gastric cancers. This guideline used the Grading of Recommendations, Assessment, Development and Evaluation framework and specifically addresses the role of ESD versus EMR and/or surgery, where applicable, for the management of early esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric adenocarcinoma (GAC) and their corresponding precursor lesions. For ESCC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >15 mm, whereas in patients with similar lesions ≤15 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for such patients with ESCC, whenever possible. For EAC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >20 mm, whereas in patients with similar lesions measuring ≤20 mm, the ASGE suggests either ESD or EMR. For GAC, the ASGE suggests ESD over EMR for patients with early-stage, well or moderately differentiated, nonulcerated intestinal type cancer measuring 20 to 30 mm, whereas for patients with similar lesions <20 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for patients with such lesions measuring ≤30 mm, whereas for lesions that are poorly differentiated, regardless of size, the ASGE suggests surgical evaluation over endosic approaches.

American Society for Gastrointestinal Endoscopy guideline on endoscopic submucosal dissection for the management of early esophageal and gastric cancers: summary and recommendations.

This clinical practice guideline from the American Society for Gastrointestinal Endoscopy (ASGE) provides an evidence-based summary and recommendations regarding the role of endoscopic submucosal dissection (ESD) in the management of early esophageal and gastric cancers. It is accompanied by the document subtitled "Methodology and Review of Evidence," which provides a detailed account of the methodology used for the evidence review. This guideline was developed using the Grading of Recommendations, Assessment, Development and Evaluation framework and specifically addresses the role of ESD versus EMR and/or surgery, where applicable, for the management of early esophageal squamous cell carcinoma (ESCC), esophageal adenocarcinoma (EAC), and gastric adenocarcinoma (GAC) and their corresponding precursor lesions. For ESCC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >15 mm, whereas in patients with similar lesions ≤15 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for such patients with ESCC, whenever possible. For EAC, the ASGE suggests ESD over EMR for patients with early-stage, well-differentiated, nonulcerated cancer >20 mm, whereas in patients with similar lesions measuring ≤20 mm, the ASGE suggests either ESD or EMR. For GAC, the ASGE suggests ESD over EMR for patients with early-stage, well- or moderately differentiated, nonulcerated intestinal type cancer measuring 20 to 30 mm, whereas for patients with similar lesions <20 mm, the ASGE suggests either ESD or EMR. The ASGE suggests against surgery for patients with such lesions measuring ≤30 mm, whereas for lesions that are poorly differentiated, regardless of size, we suggest surgical evaluation over endoscopic approaches.

A novel through-the-scope helix tack-and-suture device for mucosal defect closure following colorectal endoscopic submucosal dissection: a multicenter study.

BACKGROUND: Complete closure of large mucosal defects following colorectal endoscopic submucosal dissection (ESD) with through-the-scope (TTS) clips is oftentimes not possible. We aimed to report our early experience of using a novel TTS suturing system for the closure of large mucosal defects after colorectal ESD. METHODS: We performed a retrospective multicenter cohort study of consecutive patients who underwent attempted prophylactic defect closure using the TTS suturing system after colorectal ESD. The primary outcome was technical success in achieving complete defect closure, defined as a < 5 mm residual mucosal defect in the closure line using TTS suturing, with or without adjuvant TTS clips. RESULTS: 82 patients with a median defect size of 30 (interquartile range 25-40) mm were included. Technical success was achieved in 92.7 % (n = 76): TTS suturing only in 44 patients (53.7 %) and a combination of TTS suturing to approximate the widest segment followed by complete closure with TTS clips in 32 (39.0 %). Incomplete/partial closure, failure of appropriate TTS suture deployment, and the need for over-the-scope salvage closure methods were observed in 7.3 % (n = 6). One intraprocedural bleed, one delayed bleed, and three intraprocedural perforations were observed. There were no adverse events related to placement of the TTS suture. CONCLUSION: The TTS suture system is an effective and safe tool for the closure of large mucosal defects after colorectal ESD and is an alternative when complete closure with TTS clips alone is not possible.