Safety and efficacy of physician-administered balanced-sedation for the endoscopic mucosal resection of large non-pedunculated colorectal polyps.

Background and study aims Because of concerns about peri-procedural adverse events (AEs), guidelines recommend anesthetist-managed sedation (AMS) for long and complex endoscopic procedures. The safety and efficacy of physician-administered balanced sedation (PA-BS) for endoscopic mucosal resection (EMR) of large non-pedunculated colorectal polyps (LNPCPs) ≥20 mm is unknown. Patients and methods We compared PA-BS with AMS in a retrospective study of prospectively collected data from consecutive patients referred for management of LNPCPs (NCT01368289; NCT02000141). A per-patient propensity analysis was performed following a 1:2 nearest-neighbor (Greedy-type) match, based on age, gender, Charlson comorbidity index, and lesion size. The primary outcome was any peri-procedural AE, which included hypotension, hypertension, tachycardia, bradycardia, hypoxia, and new arrhythmia. Secondary outcomes were unplanned admissions, 28-day re-presentation, technical success, and recurrence. Results Between January 2016 and June 2020, 700 patients underwent EMR for LNPCPs, of whom 638 received PA-BS. Among them, the median age was 70 years (interquartile range [IQR] 62-76 years), size 35 mm (IQR 25-45 mm), and duration 35 minutes (IQR 25-60 minutes). Peri-procedural AEs occurred in 149 (23.4%), most commonly bradycardia (116; 18.2%). Only five (0.8%) required an unplanned sedation-related admission due to AEs (2 hypotension, 1 arrhythmia, 1 bradycardia, 1 hypoxia), with a median inpatient stay of 1 day (IQR 1-3 days). After propensity-score matching, there were no differences between PA-BS and AMS in peri-procedural AEs, unplanned admissions, 28-day re-presentation rates, technical success or recurrence. Conclusions Physician-administered balanced sedation for the EMR of LNPCPs is safe. Peri-procedural AEs are infrequent, transient, rarely require admission (<1%), and are experienced in similar frequencies to those receiving anesthetist-managed sedation.

Identifying the real-world challenges of dysplasia surveillance in inflammatory bowel disease: a retrospective cohort study in a tertiary health network.

BACKGROUND: Dysplasia surveillance in inflammatory bowel disease (IBD) is often suboptimal and deviates from guidelines. AIMS: To assess dysplasia surveillance behaviours and adherence to guidelines amongst a large tertiary teaching health network with a specialised IBD unit to identify areas where dysplasia surveillance could be improved. METHODS: A retrospective audit of IBD surveillance colonoscopy practice over an 18-month period was performed using the Provation Endoscopy Database and the hospital's primary sclerosing cholangitis database. RESULTS: The audit identified 115 dysplasia surveillance colonoscopies. A total of 37% of index dysplasia colonoscopies were outside recommended guidelines. A total of 10% had inadequate bowel preparation and only 40% had excellent bowel preparation. A total of 28% of patients underwent dye-based chromoendoscopy and 69% underwent high-definition white-light endoscopy. Dye chromoendoscopy was more likely to be used by IBD specialists than interventional endoscopists (P = 0.008) and other endoscopists (P = 0.004). Only IBD specialists and interventional endoscopists used dye chromoendoscopy. Dysplasia or colorectal cancer was detected in 3.4% of the colonoscopies. Overall, the several dysplasia examinations were lower than expected. CONCLUSIONS: Dysplasia surveillance in the IBD population remains an area of improvement given the current national guidelines. IBD specialists are more likely to perform dye chromoendoscopy than other endoscopists/gastroenterologists. Dysplasia rates in this real-world contemporary setting are less than expected in historical studies and may represent improvements in IBD management principles and medications.

Simple optical evaluation criteria reliably identify the post-endoscopic mucosal resection scar for benign large non-pedunculated colorectal polyps without tattoo placement.

BACKGROUND: Recognition of the post-endoscopic mucosal resection (EMR) scar is critical for large (≥ 20 mm) non-pedunculated colorectal polyp (LNPCP) management. The utility of intraluminal tattooing to facilitate scar identification is unknown. METHODS: We evaluated the ability of simple easy-to-use optical evaluation criteria to detect the post-EMR scar, with or without tattoo placement, in a prospective observational cohort of LNPCPs referred for endoscopic resection. The primary outcome was scar identification, further stratified by lesion size (20-39 mm, ≥ 40 mm) and histopathology (adenomatous, serrated). RESULTS: 1023 LNPCPs underwent both successful EMR and first surveillance colonoscopy (median size 35 mm, IQR 30-50 mm); 124 (12.1 %) had an existing tattoo or a tattoo placed at the index EMR. The post-EMR scar was identified in 1020 patients (99.7 %). The presence of a tattoo did not affect scar identification (100.0 % vs. 99.7 %; P > 0.99). There was no difference for LNPCPs 20-39 mm, LNPCPs ≥ 40 mm, adenomatous LNPCPs, and serrated LNPCPs (all P > 0.99). CONCLUSIONS: The post-EMR scar can be reliably identified with simple easy-to-use optical evaluation criteria, without the need for universal tattoo placement.

Effect of prophylactic endoscopic clip placement on clinically significant post-endoscopic mucosal resection bleeding in the right colon: a single-centre, randomised controlled trial.

BACKGROUND: Endoscopic mucosal resection (EMR) is a cornerstone in the management of large (≥20 mm) non-pedunculated colorectal polyps. Clinically significant post-EMR bleeding occurs in 7% of cases and is most frequently encountered in the right colon. We aimed to assess the use of prophylactic clip closure in preventing clinically significant post-EMR bleeding within the right colon. METHODS: We conducted a randomised controlled trial at a tertiary centre in Australia. Patients referred for the EMR of large non-pedunculated colorectal polyps in the right colon were eligible. Patients were randomly assigned (1:1) into the clip or control (no clip) group, using a computerised random-number generator. The primary endpoint was clinically significant post-EMR bleeding, defined as haematochezia necessitating emergency department presentation, hospitalisation, or re-intervention within 14 days post-EMR, which was analysed on the basis of intention-to-treat principles. The trial is registered with ClinicalTrials.gov, NCT02196649, and has been completed. FINDINGS: Between Feb 4, 2016, and Dec 15, 2020, 231 patients were randomly assigned: 118 to the clip group and 113 to the control group. In the intention-to-treat analysis, clinically significant post-EMR bleeding was less frequent in the clip group than in the control group (four [3·4%] of 118 patients vs 12 [10·6%] of 113; p=0·031; absolute risk reduction 7·2% [95% CI 0·7-13·8]; number needed to treat 13·9). There were no differences between groups in adverse events, including delayed perforation (one [<1%] in the clip group vs one [<1%] in the control group) and post-EMR pain (four [3%] vs six [5%]). No deaths were reported. INTERPRETATION: Prophylactic clip closure can be performed following the EMR of large non-pedunculated colorectal polyps of 20 mm or larger in the right colon to reduce the risk of clinically significant post-EMR bleeding. FUNDING: None.

Impact of technical innovations in EMR in the treatment of large nonpedunculated polyps involving the ileocecal valve (with video).

BACKGROUND AND AIMS: The endoscopic management of large nonpedunculated colorectal polyps involving the ileocecal valve (ICV-LNPCPs) remains challenging because of its unique anatomic features, with long-term outcomes inferior to LNPCPs not involving the ICV. We sought to evaluate the impact of technical innovations and advances in the EMR of ICV-LNPCPs. METHODS: The performance of EMR for ICV-LNPCPs was retrospectively evaluated in a prospective observational cohort of LNPCPs ≥20 mm. Efficacy was measured by clinical success (removal of all polypoid tissue during index EMR and avoidance of surgery) and recurrence at first surveillance colonoscopy. Accounting for the adoption of technical innovations, comparisons were made between an historical cohort (September 2008 to April 2016) and contemporary cohort (May 2016 to October 2020). Safety was evaluated by documenting the frequencies of intraprocedural bleeding, delayed bleeding, deep mural injury, and delayed perforation. RESULTS: Between September 2008 to October 2020, 142 ICV-LNPCPs were referred for EMR. Median ICV-LNPCP size was 35 mm (interquartile range, 25-50 mm). When comparing the contemporary (n = 66) and historical cohorts (n = 76) of ICV-LNPCPs, there were significant differences in clinical success (93.9% vs 77.6%, P = .006) and recurrence (4.6% vs 21.0%, P = .019). CONCLUSIONS: With technical advances, ICV-LNPCPs can be effectively and safely managed by EMR, independent of lesion complexity. Most patients experience excellent outcomes and avoid surgery.

Human papillomavirus infection in esophageal squamous cell carcinoma and esophageal adenocarcinoma: a concise review.

The causal link between high-risk human papillomavirus (hr-HPV) infection and cervical, anogenital, and some oropharyngeal malignancies has been established by both molecular and epidemiological data. The association between HPV and esophageal squamous cell carcinoma (ESCC) remains controversial, as is the true prevalence of HPV infection in ESCC. The wide range in reported rates reflects variability in the primary literature, with some larger scale case-control studies suggesting the infection rates range from 0% to 78%. Interactions between HPV and the Barrett's metaplasia-dysplasia-carcinoma sequence have been explored, and these studies have shown some conflicting data. Overall, systematic reviews have reported the prevalence of HPV-positive DNA in esophageal adenocarcinoma patients of between 13% and 35%. Postulated reasons for discrepancies in HPV prevalence rates in esophageal cancer include variations in testing methodology and assay sensitivities; technical issues, including the lack of a gold-standard primer; types of specimens utilized (fresh-frozen versus formalin-fixed tissue); geographical variation; cross-contamination; and small sample sizes. Thus, efforts must be undertaken to (1) standardize HPV testing, ideally in a central laboratory and utilizing tests that detect viral transcriptional activity; (2) avoid cross-contamination; and (3) recruit large numbers of patients to accurately ascertain HPV rates in esophageal malignancy.

Association of Biomarkers for Human Papillomavirus With Survival Among Adults With Barrett High-grade Dysplasia and Esophageal Adenocarcinoma.

Importance: The presence of high-risk human papillomavirus (HPV) has been associated with a favorable outcome in Barrett high-grade dysplasia (HGD) and esophageal adenocarcinoma (EAC). Nevertheless, the prognostic significance of other HPV-related biomarkers (ie, retinoblastoma protein [pRb], cyclin D1 [CD1], minichromosome maintenance protein [MCM2] and Ki-67) is unknown. Objective: To examine the association between HPV-related biomarkers and survival in adult patients with Barrett HGD and EAC. Design, Setting, and Participants: This retrospective case-control study examined the hypothesis that the HPV-related cell cycle markers (pRb, CD1, and Ki-67) and the viral surrogate marker (MCM2) may be associated with a favorable prognosis in Barrett HGD and EAC. Pretreatment biopsies were used for HPV DNA determination via polymerase chain reaction and immunohistochemistry for the HPV-related biomarkers. Recruitment of patients occurred in secondary and tertiary referral centers, with 151 patients assessed for eligibility. The study period was from December 1, 2002, to November 28, 2017, and the dates of analysis were from September 9, 2011, to November 28, 2017. Main Outcomes and Measures: Disease-free survival and overall survival. Results: Of 151 patients assessed for eligibility, 9 were excluded. Among the 142 patients with Barrett HGD or EAC (126 [88.7%] men; mean [SD] age, 66.0 [12.1] years; 142 [100%] white), 37 were HPV positive and 105 were HPV negative. No association with disease-free survival was noted for pRb, CD1, Ki-67, and MCM2. In regard to overall survival, only low expression of CD1 had a favorable prognosis (hazard ratio [HR], 0.53; 95% CI, 0.30-0.95; adjusted P = .03). All the biomarkers stratified by HPV status showed significant associations with survival. Patients with HPV-positive, low-expression pRb esophageal tumors were associated with a significantly improved disease-free survival compared with the HPV-negative, high-expression Rb tumors (HR, 0.33; 95% CI, 0.12-0.93; adjusted P = .04). Similarly, HPV-positive, low-expression CD1 was associated with a significantly favorable disease-free survival (HR, 0.26; 95% CI, 0.09-0.76; adjusted P = .01), as was HPV-positive, high-expression MCM2 (HR, 0.27; 95% CI, 0.09-0.78; adjusted P = .02). In regard to overall survival, HPV was significantly associated only with low CD1 (HR, 0.38; 95% CI, 0.15-0.94; adjusted P = .04). Conclusions and Relevance: This study's findings suggest that low expression of CD1 appears to be an independent prognostic marker in Barrett HGD and EAC. Human papillomavirus positivity in combination with pRb, CD1, MCM2, and Ki-67 was associated with a survival benefit in esophageal tumors. These findings suggest the possibility of personalization of therapy for Barrett HGD and EAC based on viral status.

Activity-induced weakness in recessive myotonia congenita with a novel (696+1G>A) mutation.

OBJECTIVE: To investigate the cause of the transient weakness that occurs in recessive myotonia congenita (RMC) following sustained muscle contraction. METHODS: Nerve excitability studies were performed on a 35-year-old male with RMC due to a novel 696+1G>A CLCN1 mutation. The median nerve was stimulated at the wrist and compound muscle action potentials (CMAPs) were recorded from abductor pollicis brevis (APB). Stimulus-response behaviour using two stimulus durations, threshold electrotonus to 100-ms polarizing currents, a current threshold relationship and the recovery of excitability following supramaximal stimulation were recorded at rest. Excitability parameters were also recorded before and after maximal voluntary contraction (MVC) of APB against resistance for 60s. Results were compared to data obtained from 12 normal controls. RESULTS: Baseline axonal excitability parameters were all normal, indicating that axonal function was normal at the point of stimulation. Following one minute of MVC, excitability parameters demonstrated a significant increase in threshold when compared to controls (RMC 54.9%; controls 15.5+/-3.1%). In the RMC patient, this increase in threshold was associated with a 39% reduction in the amplitude of the maximal CMAP, which remained unaffected in controls. CONCLUSIONS: The reduction in maximal CMAP is likely to represent muscle activation failure due to depolarization block, with the increase in threshold possibly reflecting a compensatory attempt by motor axons to overcome prolonged contraction-induced changes in the muscle membrane. SIGNIFICANCE: The prolonged recovery of excitability following sustained muscle contraction is likely to be a contributing factor to symptoms of weakness and fatigue experienced by RMC patients.