Jonathan M. Wyse

Randomized, Double-Blind, Controlled Trial of Early Endoscopic Ultrasound–Guided Celiac Plexus Neurolysis to Prevent Pain Progression in Patients With Newly Diagnosed, Painful, Inoperable Pancreatic Cancer

PURPOSE Celiac plexus neurolysis (CPN) is currently used as salvage therapy for morphine-resistant pancreatic cancer pain. Endoscopic ultrasound-guided CPN (EUS-CPN) can be performed early, at the time of EUS. We hypothesized that early EUS-CPN would reduce pain and morphine consumption, increase quality of life (QOL), and prolong survival. PATIENTS AND METHODS Patients were eligible if referred for EUS for suspected pancreatic cancer with related pain. If EUS and EUS-guided fine-needle aspiration cytology confirmed inoperable adenocarcinoma, patients were randomly assigned to early EUS-CPN or conventional pain management. Pain scores (7-point Likert scale), morphine equivalent consumption, and QOL scores (Digestive Disease Questionnaire-15) were assessed at 1 and 3 months. RESULTS Five hundred eighty eligible patients were seen between April 2006 and December 2008. Ninety-six patients were randomly assigned (48 patients per study arm). Pain relief was greater in the EUS-CPN group at 1 month and significantly greater at 3 months (difference in mean percent change in pain score = -28.9 [95% CI, -67.0 to 2.8], P = .09, and -60.7 [95% CI, -86.6 to -25.5], P = .01, respectively). Morphine consumption was similar in both groups at 1 month (difference in mean change in morphine consumption = -1.0 [95% CI, -47.7 to 49.2], P = .99), but tended toward lower consumption at 3 months in the neurolysis group (difference in mean change in morphine consumption = -49.5 [95% CI, -127.5 to 7.0], P = .10). There was no effect on QOL or survival. CONCLUSION Early EUS-CPN reduces pain and may moderate morphine consumption in patients with painful, inoperable pancreatic adenocarcinoma. EUS-CPN can be considered in all such patients at the time of diagnostic and staging EUS.

Is routine second-look endoscopy effective after endoscopic hemostasis in acute peptic ulcer bleeding? A meta-analysis

BACKGROUND Routine second-look endoscopy in modern-era peptic ulcer bleeding (PUB) remains controversial. OBJECTIVE To assess the effectiveness of routine second-look endoscopy in patients with PUB exhibiting high-risk stigmata after standard medical care and endoscopic therapy. DESIGN Comprehensive literature searches (1990-2011) were performed, seeking randomized trials comparing a routine with an as-needed second endoscopy. MAIN OUTCOME MEASUREMENTS The main outcome was rebleeding. Secondary outcomes were surgery and mortality. Subanalyses assessed the influence of study quality, rebleeding definitions, endoscopic hemostasis modality, and proton pump inhibitor (PPI) therapies. Analyses were performed with Revman 5.1. Results are shown as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Only 4 published articles completely reporting studies and 4 abstracts (of 577 citations) were included (938 patients). Rebleeding was significantly decreased by a routine second-look endoscopy (OR 0.55; 95% CI, 0.37-0.81), as was surgery (OR 0.43; 95% CI, 0.19-0.96), but not mortality (OR 0.65; 95% CI, 0.26-1.62). Results remained robust with varying definitions of rebleeding, but not with varying endoscopic hemostasis modalities and PPI therapies; the only trial in which high-dose PPI was used did not show a benefit of a second-look endoscopy. When removing the 2 trials that included patients at highest risk of rebleeding, no significant benefit attributable to a second-look endoscopy was noted (OR 0.65; 95% CI, 0.42-1.00). LIMITATIONS The small number of trials and patients in each of these studies. CONCLUSIONS In the absence of high-dose PPI, especially in patients at very high risk (eg, active bleeding), routine second-look endoscopy appears effective in these selected patients with PUB. However, the generalizability of these results to the era of high-dose PPI and otherwise unselected patients with high-risk stigmata is unclear.

Fatalities Associated With Clozapine-Related Constipation and Bowel Obstruction: A Literature Review and Two Case Reports

BACKGROUND Constipation is an exceedingly common side effect of treatment with clozapine. In rare cases, this side effect has resulted in fatal complications. OBJECTIVE The authors review the literature on fatal complications of clozapine-related constipation and bowel obstruction. METHOD The authors provide two new case reports of patients who died of similar causes. RESULTS There were seven reports of deaths from clozapine-related bowel obstruction in the literature, with the most common mechanisms of death being severe impaction leading either to feculent vomiting or bowel necrosis. DISCUSSION The discussion outlines potential mechanisms and management of clozapine-related constipation.

Accuracy of administrative claims data for polypectomy

Background: The frequency of polypectomy is an important indicator of quality assurance for population-based colorectal cancer screening programs. Although administrative databases of physician claims provide population-level data on the performance of polypectomy, the accuracy of the procedure codes has not been examined. We determined the level of agreement between physician claims for polypectomy and documentation of the procedure in endoscopy reports. Methods: We conducted a retrospective cohort study involving patients aged 50–80 years who underwent colonoscopy at seven study sites in Montréal, Que., between January and March 2007. We obtained data on physician claims for polypectomy from the Régie de l’Assurance Maladie du Québec (RAMQ) database. We evaluated the accuracy of the RAMQ data against information in the endoscopy reports. Results: We collected data on 689 patients who underwent colonoscopy during the study period. The sensitivity of physician claims for polypectomy in the administrative database was 84.7% (95% confidence interval [CI] 78.6%–89.4%), the specificity was 99.0% (95% CI 97.5%–99.6%), concordance was 95.1% (95% CI 93.1%–96.5%), and the kappa value was 0.87 (95% CI 0.83–0.91). Interpretation: Despite providing a reasonably accurate estimate of the frequency of polypectomy, physician claims underestimated the number of procedures performed by more than 15%. Such differences could affect conclusions regarding quality assurance if used to evaluate population-based screening programs for colorectal cancer. Even when a high level of accuracy is anticipated, validating physician claims data from administrative databases is recommended.

Celiac plexus neurolysis in the management of unresectable pancreatic cancer: When and how?

Pancreatic cancer is the second most common abdominal cancer in North America with an estimated 20% resectability at diagnosis, and overall 5-year survival of 5%. Pain is common in pancreatic cancer patients with 70%-80% suffering substantial pain. Celiac plexus neurolysis (CPN) is a technique that can potentially improve pain control in pancreatic cancer while preventing further escalation of opioid consumption. CPN is performed by injecting absolute alcohol into the celiac plexus neural network of ganglia. This review sets out to explore the current status of CPN in non-resectable pancreatic cancer. We will examine: (1) the efficacy and safety of percutaneous-CPN and endoscopic ultrasound guided-CPN; (2) specific technique modifications including bilateral (vs central) injections and celiac ganglia neurolysis; and (3) the issue of CPN timing, early at pancreatic cancer diagnosis vs traditional late use as salvage therapy.

Occult dysplasia in a localized giant pseudopolyp in Crohn's colitis: A case report

Localized giant pseudopolyposis of the colon (pseudopolyp larger than 1.5 cm in size) is a rare complication of inflammatory bowel disease. There is one report of an occult carcinoma within such a lesion, and no reports of sole dysplasia. A case of a 42-year-old man with longstanding Crohns colitis who underwent a colonoscopy revealing a large, multilobulated mass at the splenic flexure that was not amenable to endoscopic removal, is described. Multiple biopsies showed no dysplasia and histology was consistent with an inflammatory pseudopolyp. Computed tomographic colonography demonstrated a mass resembling a large villous tumour. A decision for surgery was made. The surgical specimen was a complex anastomosing inflammatory pseudopolyp 5 cm x 4 cm x 3 cm in size, with a focus of low-grade dysplasia in an area free of inflammation. The present case is the first reported occult dysplasia in a giant pseudopolyp. Occult dysplasia without superficial dysplasia may exist in these lesions and further studies are needed to examine risk factors that make a giant pseudopolyp more likely to harbour dysplasia and/or carcinoma.

Can the presence of endoscopic high-risk stigmata be predicted before endoscopy? a multivariable analysis using the RUgBe database

BACKGROUND Many aspects in the management of acute upper gastrointestinal bleeding rely on pre-esophagogastroduodenoscopy (EGD) stratification of patients likely to exhibit high-risk stigmata (HRS); however, data predicting the presence of HRS are lacking. OBJECTIVE To determine clinical and laboratory predictors of HRS at the index EGD in patients presenting with acute upper gastrointestinal bleeding using retrospective data from a validated national database - the Canadian Registry in Upper Gastrointestinal Bleeding and Endoscopy registry. methods: Relevant clinical and laboratory parameters were evaluated. HRS was defined as spurting, oozing, nonbleeding visible vessel or adherent clot after vigorous irrigation. Multivariable modelling was used to identify predictors of HRS including age, sex, hematemesis, use of antiplatelet agents, American Society of Anesthesiologists (ASA) classification, nasogastric tube aspirate, hemoglobin level and elapsed time from the onset of bleeding to EGD. RESULTS Of the 1677 patients (mean [± SD] age 66.2 ± 16.8 years; 38.3% female), 28.7% had hematemesis, 57.8% had an ASA score of 3 to 5, and the mean hemoglobin level was 96.8 ± 27.3 g⁄L. The mean time from presentation to endoscopy was 22.2 ± 37.5 h. The best fitting multivariable model included the following significant predictors: ASA score 3 to 5 (OR 2.16 [95% CI 1.71 to 2.74]), a shorter time to endoscopy (OR 0.99 [95% CI 0.98 to 0.99]) and a lower initial hemoglobin level (OR 0.99 [95% CI 0.99 to 0.99]). CONCLUSION A higher ASA score, a shorter time to endoscopy and lower initial hemoglobin level all significantly predicted the presence of endoscopic HRS. These criteria could be used to improve the optimal selection of patients requiring more urgent endoscopy.

Practice guidelines for endoscopic ultrasound-guided celiac plexus neurolysis

Objectives: The objective of guideline was to provide clear and relevant consensus statements to form a practical guideline for clinicians on the indications, optimal technique, safety and efficacy of endoscopic ultrasound guided celiac plexus neurolysis (EUS-CPN). Methods: Six important clinical questions were determined regarding EUS-CPN. Following a detailed literature review, 6 statements were proposed attempting to answer those questions. A group of expert endosonographers convened in Chicago, United States (May 2016), where the statements were presented and feedback provided. Subsequently a consensus group of 35 expert endosonographers voted based on their individual level of agreement. A strong recommendation required 80% voter agreement. The modified GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria were used to rate the strength of recommendations and the quality of evidence. Results: Eighty percent agreement was reached on 5 of 6 consensus statements, 79.4% agreement was reached on the remaining one. Conclusions: EUS-CPN is efficacious, should be integrated into the management of pancreas cancer pain, and can be considered early at the time of diagnosis of inoperable disease. Techniques may still vary based on operator experience. Serious complications exist, but are rare.

Onsite evaluation of endoscopic ultrasound fine needle aspiration: the endosonographer, the cytotechnologist and the cytopathologist

Endoscopic ultrasound guided fine needle aspiration (EUS-FNA) has become an essential tool in the management of multiple diseases. Its accuracy is related to different aspects of the technique, one of the most important being the experience and interaction of the endosonographer and pathologist. Certain studies over the past years have highlighted the importance of having rapid on-site evaluation (ROSE) of samples obtained at the time of EUS-FNA. We have reviewed the role of ROSE, performed by the same endosonographer, a cytotechnologist and an expert cytopathologist. The available data suggest that ROSE (either by the endosonographer, the cytotechnologist, or the cytopathologist) improves sample adequacy and diagnostic yield, with the best option to have ROSE performed by an expert cytopathologist. However, if non-ROSE accuracy is already very high, any improvement is harder to achieve.