Injectable, Drug-Eluting Nanocrystals Prevent Fibrosis and Stricture Formation In Vivo.

BACKGROUND & AIMS: Tissue fibrosis results from uncontrolled healing responses leading to excessive mesenchymal cell activation and collagen and other extracellular matrix deposition. In the gastrointestinal tract, fibrosis leads to narrowing of the lumen and stricture formation. A drug treatment to prevent fibrosis and strictures in the gastrointestinal tract would be transformational for patient care. We aimed to develop a stricture treatment with the following characteristics and components: a small molecule with strong antifibrotic effects that is delivered locally at the site of the stricture to ensure correct lesional targeting while protecting the systemic circulation, and that is formulated with sustained-release properties to act throughout the wound healing processes. METHODS: A high-throughput drug screening was performed to identify small molecules with antifibrotic properties. Next, we formulated an antifibrotic small molecule for sustained release and tested its antifibrotic potential in 3 animal models of fibrosis. RESULTS: Sulconazole, a US Food and Drug Administration-approved drug for fungal infections, was found to have strong antifibrotic properties. Sulconazole was formulated as sulconazole nanocrystals for sustained release. We found that sulconazole nanocrystals provided superior or equivalent fibrosis prevention with less frequent dosing in mouse models of skin and intestinal tissue fibrosis. In a patient-like swine model of bowel stricture, a single injection of sulconazole nanocrystals prevented stricture formation. CONCLUSIONS: The current data lay the foundation for further studies to improve the management of a range of diseases and conditions characterized by tissue fibrosis.

Novel through-the-scope suture closure of colonic EMR defects (with video).

BACKGROUND AND AIMS: Large colon polyps removed by EMR can be complicated by delayed bleeding. Prophylactic defect clip closure can reduce post-EMR bleeding. Larger defects can be challenging to close using through-the-scope clips (TTSCs), and proximal defects are difficult to reach using over-the-scope techniques. A novel, through-the-scope suturing (TTSS) device allows direct closure of mucosal defects without scope withdrawal. The goal of this study was to evaluate the rate of delayed bleeding after the closure of large colon polyp EMR sites with TTSS. METHODS: A multicenter retrospective cohort study was performed involving 13 centers. All defect closure by TTSS after EMR of colon polyps ≥2 cm from January 2021 to February 2022 were included. The primary outcome was rate of delayed bleeding. RESULTS: A total of 94 patients (52% female; mean age, 65 years) underwent EMR of predominantly right-sided (n = 62 [66%]) colon polyps (median size, 35 mm; interquartile range, 30-40 mm) followed by defect closure with TTSS during the study period. All defects were successfully closed with TTSS alone (n = 62 [66%]) or with TTSS and TTSCs (n = 32 [34%]), using a median of 1 (interquartile range, 1-1) TTSS system. Delayed bleeding occurred in 3 patients (3.2%), with 2 requiring repeated endoscopic evaluation/treatment (moderate). CONCLUSION: TTSS alone or with TTSCs was effective in achieving complete closure of all post-EMR defects, despite a large lesion size. After TTSS closure with or without adjunctive devices, delayed bleeding was seen in 3.2% of cases. Further prospective studies are needed to validate these findings before wider adoption of TTSS for large polypectomy closure.

Through-the-scope suture closure of nonampullary duodenal endoscopic mucosal resection defects: a retrospective multicenter cohort study.

BACKGROUND: Delayed bleeding is among the most common adverse events associated with endoscopic mucosal resection (EMR) of nonampullary duodenal polyps. We evaluated the rate of delayed bleeding and complete defect closure using a novel through-the-scope (TTS) suturing system for the closure of duodenal EMR defects. METHODS: We reviewed the electronic medical records of patients who underwent EMR for nonampullary duodenal polyps of ≥ 10 mm and prophylactic defect closure with TTS suturing between March 2021 and May 2022 at centers in the USA. We evaluated the rates of delayed bleeding and complete defect closure. RESULTS: 36 nonconsecutive patients (61 % women; mean [SD] age, 65 [12] years) underwent EMR of ≥ 10-mm duodenal polyps followed by attempted defect closure with TTS suturing. The mean (SD) lesion size was 29 (19) mm, defect size was 37 (25) mm; eight polyps (22 %) involved > 50 % of the lumen circumference. Complete closure was achieved in all cases (78 % with TTS suturing alone), using a median of one TTS suturing kit. There were no cases of delayed bleeding and no adverse events attributed to application of the TTS suturing device. CONCLUSION: Prophylactic closure of nonampullary duodenal EMR defects using TTS suturing resulted in a high rate of complete closure and no delayed bleeding events.

In vivo endomicroscopy improves detection of Barrett's esophagus-related neoplasia: a multicenter international randomized controlled trial (with video).

BACKGROUND: Confocal laser endomicroscopy (CLE) enables in vivo microscopic imaging of the GI tract mucosa. However, there are limited data on endoscope-based CLE (eCLE) for imaging Barrett's esophagus (BE). OBJECTIVE: To compare high-definition white-light endoscopy (HDWLE) alone with random biopsy (RB) and HDWLE + eCLE and targeted biopsy (TB) for diagnosis of BE neoplasia. DESIGN: Multicenter, randomized, controlled trial. SETTING: Academic medical centers. PATIENTS: Adult patients with BE undergoing routine surveillance or referred for early neoplasia. INTERVENTION: Patients were randomized to HDWLE + RB (group 1) or HDWLE + eCLE + TB (group 2). Real-time diagnoses and management plans were recorded after HDWLE in both groups and after eCLE in group 2. Blinded expert pathology diagnosis was the reference standard. MAIN OUTCOME MEASUREMENTS: Diagnostic yield, performance characteristics, clinical impact. RESULTS: A total of 192 patients with BE were studied. HDWLE + eCLE + TB led to a lower number of mucosal biopsies and higher diagnostic yield for neoplasia (34% vs 7%; P < .0001), compared with HDWLE + RB but with comparable accuracy. HDWLE + eCLE + TB tripled the diagnostic yield for neoplasia (22% vs 6%; P = .002) and would have obviated the need for any biopsy in 65% of patients. The addition of eCLE to HDWLE increased the sensitivity for neoplasia detection to 96% from 40% (P < .0001) without significant reduction in specificity. In vivo CLE changed the treatment plan in 36% of patients. LIMITATIONS: Tertiary-care referral centers and expert endoscopists limit generalizability. CONCLUSION: Real-time eCLE and TB after HDWLE can improve the diagnostic yield and accuracy for neoplasia and significantly impact in vivo decision making by altering the diagnosis and guiding therapy. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01124214.).

Through-the-scope suturing for closure of contained leak after cricopharyngeal peroral endoscopic myotomy.

Video 1.

Primary anastomosis closure after endoscopic ultrasound-directed transgastric intervention.

Background and study aims Endoscopic ultrasound-directed transgastric intervention (EDGI) is a technique that creates an anastomosis between the gastric pouch or jejunum to the excluded stomach in Roux-en-Y gastric bypass (RYGB) anatomy to allow access to the pancreaticobiliary system. Thus far, management of anastomosis closure at the time of lumen-apposing metal stent (LAMS) removal has varied widely. This study aimed to assess the efficacy of primary closure at the time of LAMS removal using a through-the-scope (TTS) tack-based suture system.  Patients and methods This was a two-center retrospective study of RYGB patients who underwent single-stage EDGI using a 20-mm LAMS and subsequent primary anastomosis closure with the X-tack system at the time of stent removal. Patient demographics, procedure details, clinical outcomes, and imaging findings are reported. Results Nineteen patients (median age 63 years, 84% female) underwent single-stage EDGI with a median follow-up of 31.5 months. Adverse events occurred in two patients (11%) who had abdominal pain requiring hospitalization. The median LAMS dwell time was 32 days (range 16-86). All patients (100%) who underwent follow-up studies after LAMS removal had confirmed anastomosis closure (n = 18). Most patients had documented weight loss at the time of LAMS removal and at last follow-up (68%, n = 13). Conclusions Single-stage EDGI is an effective approach to managing RYGB patients with pancreaticobiliary pathology. Thus far, endoscopic TTS tack-based suturing appears to have a high success rate in anastomosis closure after LAMS removal and should be considered as a primary method for preventing chronic fistulae.

Endoscopic removal of a retained esophageal stent using the stent-in-stent technique.

Video 1Stent-in-stent technique for removal of retained esophageal self-expanding metal stent.

Higher Levels of Fibrosis in a Cohort of Veterans with Chronic Viral Hepatitis are Associated with Extrahepatic Cancers.

BACKGROUND AND AIMS: An estimated 2.4 million Americans, including more than 150,000 veterans, are chronically infected with hepatitis C virus (HCV). HCV is estimated to cause roughly 25% of all hepatocellular carcinoma. Although its mechanism is unknown, developing evidence suggests that chronic HCV infection is also associated with the development of extrahepatic cancers (EHCs). This paper aims to assess the relationship of hepatic fibrosis and chronic HCV with the risk of developing EHC. METHODS: We conducted a single-center retrospective chart review of 1541 patients linked to the hepatitis clinic at the Veterans Affairs (VA) Maryland Health Care System who underwent transient elastography for evaluation and management of liver disease from 2014 to 2018. Liver fibrosis was measured using ultrasound and transient elastography. Extrahepatic cancer and site was identified by a retrospective chart review. RESULTS: In adjusted analysis of EHCs, advanced age (OR: 1.97, 95% CI: 1.30-3.04), and higher measured stiffness (OR 2.19, 95% CI: 1.32-3.64) were associated with an increased likelihood of developing EHC, controlling for HBV infection, HCV exposure, heavy alcohol use, and body mass index. CONCLUSIONS: We observed a significant association between increasing age and increasing levels of liver fibrosis with increased risk of EHC, notably prostate, head and neck squamous cell, lung, and hematologic cancers.