Predictors of dysplastic and neoplastic progression of Barrett's esophagus

Background: It is unknown why some cases of Barrett's esophagus progress to invasive malignant disease rapidly while others do so more slowly or not at all. The aim of this study was to identify demographic and endoscopic factors that predict dysplastic and neoplastic progression in patients with Barrett's esophagus. Methods: Patients with Barrett's esophagus who were assessed in 2000­2010 were assessed for inclusion in this retrospective study. Demographic and endoscopic variables were collected from an endoscopy database and the medical chart. Dysplastic and neoplastic progression was examined by time-to-event analysis. We used Cox proportional hazard regression modelling and generalized estimating equation methods to identify variables that were most predictive of neoplastic progression. Results: A total of 518 patients had Barrett's esophagus confirmed by endoscopy and pathology and at least 2 surveillance visits. Longer Barrett's esophagus segment (≥ 3 cm) (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.1­1.3) and increased age (≥ 60 yr) (OR 3.5, 95% CI 1.7­7.4) were independent predictors of progression from nondysplasia to dysplastic or neoplastic grades. Presence of mucosal irregularities (OR 8.6, 95% CI 2.4­30.4) and increased age (OR 5.1, 95% CI 1.6­16.6) were independent predictors of progression from nondysplasia to high-grade dysplasia or adenocarcinoma. Conclusion: Increased age, longer Barrett's segment and presence of mucosal irregularities were associated with increased risk of dysplastic and neoplastic progression. In addition to dysplasia, these factors may help stratify patients according to risk of neoplastic progression and be used to individualize surveillance. More prospective studies with larger samples are required to validate these results.

Contexte: On ignore pour quelle raison certains cas d'oesophage de Barrett évoluent rapidement vers une maladie maligne envahissante, tandis que d'autres progressent lentement ou se stabilisent. Le but de cette étude était d'identifier les facteurs démographiques et endoscopiques prédicteurs d'une progression dysplasique et néoplasique chez les patients porteurs d'un oesophage de Barrett. Méthodes: Des patients présentant un oesophage de Barrett ayant été examinés entre 2000 et 2010, ont été évalués en vue de leur participation à cette étude rétrospective. Les variables démographiques et endoscopiques ont été recueillies à partir d'une base de données endoscopiques et des dossiers médicaux. La progression dysplasique et néoplasique a été évaluée par analyse du délai de survenue de l'événement. Nous avons utilisé le modèle de la régression de Cox (risques proportionnels) et les équations d'estimation généralisée afin d'identifier les variables les plus prédictives d'une progression néoplasique. Résultats: En tout, 518 patients présentaient un oesophage de Barrett confirmé par examen endoscopique et anatomopathologique et comptaient au moins 2 visites de surveillance. La présence de segments d'oesophage de Barrett plus longs (≥ 3 cm) (rapport des cotes [RC] 1,2, intervalle de confiance à 95 % [IC] 1,1­1,3) et un âge avancé (≥ 60 ans) (RC 3,5, IC à 95 % 1,7­7,4) ont été des prédicteurs indépendants de progression d'un grade non dysplasique vers un grade dysplasique. La présence d'irrégularités muqueuses (RC 8,6, IC à 95 % 2,4­30,4) et l'âge avancé (RC 5,1, IC à 95 % 1,6­16,6) ont été des prédicteurs indépendants de progression de la non-dysplasie vers une dysplasie de haut grade ou l'adénocarcinome. Conclusion: L'âge avancé, des segments d'oesophage de Barrett plus longs et la présence d'irrégularités muqueuses ont été associés à un risque accru de progression dysplasique et néoplasique. En plus de la dysplasie, ces facteurs peuvent faciliter la stratification des patients selon le risque de progression néoplasique et servir à individualiser la surveillance. Il faudra procéder à d'autres études prospectives auprès d'échantillons de population plus volumineux pour valider ces résultats.

Laparoscopic Heller's myotomy versus pneumatic dilation in the treatment of idiopathic achalasia: a meta-analysis of randomized, controlled trials.

BACKGROUND: Pneumatic dilation (PD) and laparoscopic Heller's myotomy (LHM) are the mainstays of therapy in idiopathic achalasia. Equipoise exists in choosing the first-line therapy. OBJECTIVE: To assess comparative efficacies and adverse event rates of these methods. DESIGN: Intention-to-treat, fixed-model, Mantel-Haenszel meta-analysis of randomized, controlled trials comparing PD with LHM. SETTING: Randomized controlled trial comparing PD versus LHM. PATIENTS: Patients with newly diagnosed idiopathic achalasia. INTERVENTION: Comprehensive electronic and manual literature search from 1966 to March 2012 independently by two reviewers. MAIN OUTCOME MEASUREMENTS: Response rate, rate of different adverse events, and quality of life after each therapy. RESULTS: Three of 161 retrieved studies between 2007 and 2011, including 346 patients, were included. At 1 year, the cumulative response rate was significantly higher with LHM (86% vs 76%, odds ratio 1.98 (confidence interval 1.14-3.45); P = .02), with no significant heterogeneity (P = .39; I(2) 0%). Rates of major mucosal tears requiring subsequent intervention with LHM were significantly lower than those of esophageal perforation with PD requiring postprocedural medical or surgical therapy (0.6% and 4.8%, respectively; P = .04). Postprocedural rates of gastroesophageal reflux, lower esophageal sphincter pressures, and quality of life scores did not differ in trials with sufficient data. Data on longer follow-up were not available. LIMITATIONS: Lack of data on follow-ups over 1 year and a small number of included studies. CONCLUSION: This meta-analysis suggests that LHM may provide greater response rates as compared with graded PD in the treatment of newly diagnosed idiopathic achalasia, with lesser rates of major adverse events, in up to 1 year after treatment, although additional data are needed to confirm the validity of this conclusion in long-term follow-up.

The potential impact of contemporary developments in the management of patients with gastroesophageal reflux disease undergoing an initial gastroscopy.

BACKGROUND: Recent developments may alter the approach to patients presenting with gastroesophageal reflux disease (GERD)-like symptoms. A newly proposed Montreal consensus definition of Barrett's esophagus includes all types of esophageal columnar metaplasia, with or without intestinal-type metaplasia. There is also increasing recognition of eosinophilic esophagitis (EE) in patients with GERD-like symptoms. OBJECTIVE: To quantify the impact of these developments on a multiphysician general gastroenterology practice in a tertiary care medical centre. METHODS: Medical charts of all patients having an initial gastroscopy for GERD-like symptoms over a one-year period were reviewed retrospectively, and audits of their endoscopic images and esophageal biopsies were performed. RESULTS: Of the 353 study participants, typical symptoms of heartburn and acid reflux were present in 87.7% and 23.2%, respectively. Less commonly, patients presented with atypical symptoms (eg, dysphagia in 9.4%). At endoscopy, 26% were found to have erosive esophagitis and 12% had endoscopically suspected esophageal metaplasia. Histological evaluation was available for 65 patients. Ten of the 65 biopsied patients (15%) met traditional criteria for Barrett's esophagus (ie, exhibiting intestinal-type metaplasia), whereas 49 (75%) fulfilled the newly proposed consensus definition of Barrett's esophagus. Five patients (7.7%) met the study criteria for EE (more than 20 eosinophils per high-power field), four of whom had not been previously recognized. CONCLUSIONS: Among patients presenting with GERD-like symptoms, the prevalence of Barrett's esophagus may increase markedly if the Montreal definition is adopted. In addition, growing awareness of EE may lead to an increase in the prevalence of this diagnosis. Prospective studies of the management implications of these findings are warranted.

Cost-effectiveness of proton-pump inhibition before endoscopy in upper gastrointestinal bleeding.

BACKGROUND & AIMS: Randomized trials suggest high-dose proton-pump inhibitors (PPIs) administered before gastroscopy in suspected upper gastrointestinal bleeding downstage bleeding ulcer stigmata. We assessed the cost-effectiveness of this approach. METHODS: A decision model compared high-dose IVPPI initiated while awaiting endoscopy with IVPPI administration on the basis of endoscopic findings. IVPPIs were given to all patients undergoing endoscopic hemostasis for 72 hours thereafter. Once the IV regimen was completed or for patients with low-risk endoscopic lesions, an oral daily PPI was given for the remainder of the time horizon (30 days after endoscopy). The unit of effectiveness was the proportion of patients without rebleeding, representing the denominator of the cost-effectiveness ratio (cost per no rebleeding). Probabilities and costs were derived from the literature and national databases. RESULTS: IVPPIs before endoscopy were both slightly more costly and effective than after gastroscopy in the U.S. and Canadian settings, with cost-effectiveness ratios of US$5048 versus $4933 and CAN$6064 versus $6025 and incremental costs of US$45,673 and CAN$19,832 to prevent one additional rebleeding episode, respectively. Sensitivity analyses showed robust results in the US In Canada, intravenous proton-pump inhibitors (IVPPIs) before endoscopy became more effective and less costly (dominant strategy) when the uncomplicated stay for high-risk patients increased above 6 days or that of low-risk patients decreased below 3 days. CONCLUSIONS: With conservative estimates and high-quality data, IVPPIs given before endoscopy are slightly more effective and costly than no administration. In Canada, this approach becomes dominant as the duration of hospitalization for high-risk ulcer patients increases or that of low-risk ulcer patients decreases.

Comparison of patient-centered outcomes after laparoscopic Nissen fundoplication for gastroesophageal reflux disease or paraesophageal hernia.

BACKGROUND: Patients undergoing laparoscopic Nissen fundoplication (LNF) with paraesophageal hernias (PEH) are not only older and less healthy than those with gastroesophageal reflux disease (GERD), but in addition the repair is more complicated. We evaluated whether outcomes relating to GERD symptoms and quality of life (QOL) were impacted by the presence of PEH. METHODS: Prospectively entered data from 149 patients (109 GERD and 40 PEH) were evaluated prior to and one year after LNF with standardized and validated symptoms scores. Scores for heartburn, dysphagia, disease-specific QOL (GERD-HRQL), and general health-related QOL (SF-12 physical and mental component scores) were compared between patients undergoing LNF for PEH or for GERD alone, at baseline and one year after surgery. p < 0.05 was considered statistically significant. RESULTS: Preoperative data for GERD-HRQL, heartburn, and dysphagia were available for 134 patients, with 96% one-year follow-up. SF-12 data were collected for 98 patients with 100% follow-up. PEH patients were older and had greater comorbidity. Preoperative GERD-HRQL and heartburn were significantly worse in the GERD group. One year after surgery, both GERD and PEH patients showed significant improvement in GERD-HRQL, heartburn and dysphagia scores, with no difference in any of these disease or symptom measures between the two study groups. Postoperative PCS and MCS scores showed improvement in GERD patients, while PEH patient scores remained at or below the population mean. CONCLUSIONS: LNF is equally effective as an antireflux procedure in both GERD and PEH patients, prevents symptoms of reflux in PEH patients that have none preoperatively, and does not increase dysphagia in either group. Despite the increased complexity of the procedure, LNF provides an effective control of reflux symptoms in patients undergoing PEH repair.

The Stretta procedure versus proton pump inhibitors and laparoscopic Nissen fundoplication in the management of gastroesophageal reflux disease: a cost-effectiveness analysis.

BACKGROUND: The Stretta procedure is an endoscopic therapy for gastroesophageal reflux disease. OBJECTIVE: To evaluate the cost-effectiveness of the Stretta procedure and that of competing strategies in the long-term management of gastroesophageal reflux disease. METHODS: A Markov model was designed to estimate costs and health outcomes in Canadian patients with gastroesophageal reflux disease over five years, from a Ministry of Health perspective. Strategies included the use of daily proton pump inhibitors (PPIs), laparoscopic Nissen fundoplication (LNF) and the Stretta procedure. Probabilities and utilities were derived from the literature. Costs are expressed in 2006 Canadian dollars. Units of effectiveness were symptom-free months (SFMs) and quality-adjusted life years (QALYs), using a five-year time horizon. RESULTS: In the analysis that used SFMs, the strategy using PPIs exhibited the lowest costs ($40 per SFM) and the greatest number of SFMs, thus dominating both the LNF and Stretta systems. But the cost-effectiveness analysis using QALYs as the measure of effectiveness showed that PPIs presented the lowest cost-effectiveness ratio, while both the LNF and Stretta strategies were associated with very high incremental costs (approximately $353,000 and $393,000, respectively) to achieve an additional QALY. However, the PPI strategy did not dominate the two other strategies, which were associated with better effectiveness. CONCLUSIONS: If SFMs are used as the measure of effectiveness, PPIs dominate the Stretta and LNF strategies. However, if QALYs are used, the PPIs still present the lowest cost and LNF gives the best effectiveness. Regardless of the units of effectiveness or utility used in the present cost analysis, an approach of prescribing PPIs appears to be the preferred strategy.

The safety and usefulness of high-dose-rate endoluminal brachytherapy as a boost in the treatment of patients with esophageal cancer with external beam radiation with or without chemotherapy.

PURPOSE: This study reports the results of a single-institution experience with high-dose-rate brachytherapy (HDRBT) used as a boost in the treatment of esophageal cancer with external beam radiation therapy (ERT) with or without chemotherapy. METHODS AND MATERIALS: Patients without evidence of metastatic disease were identified. HDRBT was given before ERT with a dose of 20 Gy in 5 fractions. Patients with a Karnofsky performance of more than 70 received treatment with 50 Gy in 25 fractions and concurrent 5-fluorouracil and cis-platinum during Weeks 1 and 5, whereas patients with a Karnofsky performance of less than 70 were treated with radiation therapy alone with 35 Gy in 14 fractions. RESULTS: Fifty-three patients received HDRBT treatment with combined ERT and chemotherapy and 17 patients with ERT alone. The incidence of acute bone marrow toxicity was 55% Grade 2 and 15% Grade 3, and 85% of patients had Grade 2 esophagitis. With a median follow-up time of 26 months, the median survival was 21 months; the 2-year local recurrence was 25%, and the 5-year survival rate was 28%. CONCLUSION: HDRBT is safe and beneficial for local control in the radical treatment of patients with esophageal cancer.

Has the introduction of laparoscopic Heller myotomy altered the treatment paradigm of achalasia?

Although surgical myotomy is well established as the most effective and durable treatment for achalasia, wide acceptance of this procedure as a first-line treatment has been hampered by perceived invasiveness and morbidity. Laparoscopic myotomy has significantly reduced surgical trauma and morbidity while maintaining effectiveness. The effect of laparoscopic myotomy on the treatment pattern for achalasia is not currently known. All patients undergoing surgical myotomy in Quebec from 1997 to 2002 were identified from the Régie de l'assurance maladie du Québec billing database; previous endoscopic treatment was documented from 1990 to the time of surgery. Patients were divided into two groups (prelaparoscopy and postlaparoscopy) defined by the approximate date when laparoscopic myotomy became generally available in Quebec. A questionnaire examining treatment preference for achalasia was sent to all Quebec gastroenterologists. The number of myotomies performed in Quebec remained stable (prelaparoscopy = 28.7/year; postlaparoscopy = 33/year), but were performed on an older population. The rate of preoperative endoscopic treatment did not differ from prelaparoscopy (29.2%) to postlaparoscopy (23.3%). However, the time interval between the last endoscopy and myotomy diminished significantly. Questionnaire response rate was 41% (60 of 147). Although myotomy was recognized as the most effective treatment (54 of 60), only 22 of 60 gastroenterologists would refer a healthy patient for myotomy as initial treatment. Other choices included dilation (33 of 60), Botulinum toxin (two of 60) or calcium channel blockade (three of 60). Despite a decrease in time interval between endoscopic treatment and surgery, no decrease in the rate of existing endoscopic therapies occurred after laparoscopic myotomy became widely available. The benefits and minimal risks associated with laparoscopic myotomy need to be more effectively communicated by referring physicians.

Canadian Consensus Conference on the management of gastroesophageal reflux disease in adults - update 2004.

BACKGROUND: Gastroesophageal reflux disease (GERD) is the most prevalent acid-related disorder in Canada and is associated with significant impairment of health-related quality of life. Since the last Canadian Consensus Conference in 1996, GERD management has evolved substantially. OBJECTIVE: To develop up-to-date evidence-based recommendations relevant to the needs of Canadian health care providers for the management of the esophageal manifestations of GERD. CONSENSUS PROCESS: A multidisciplinary group of 23 voting participants developed recommendation statements using a Delphi approach; after presentation of relevant data at the meeting, the quality of the evidence, strength of recommendation and level of consensus were graded by participants according to accepted principles. OUTCOMES: GERD applies to individuals who reflux gastric contents into the esophagus causing symptoms sufficient to reduce quality of life, injury or both; endoscopy-negative reflux disease applies to individuals who have GERD and a normal endoscopy. Uninvestigated heartburn-dominant dyspepsia - characterised by heartburn or acid regurgitation - includes erosive esophagitis or endoscopy-negative reflux disease, and may be treated empirically as GERD without further investigation provided there are no alarm features. Lifestyle modifications are ineffective for frequent or severe GERD symptoms; over-the-counter antacids or histamine H2-receptor antagonists are effective for some patients with mild or infrequent GERD symptoms. Proton pump inhibitors are more effective for healing and symptom relief than histamine H2-receptor antagonists; their efficacy is proportional to their ability to reduce intragastric acidity. Response to initial therapy - a once-daily proton pump inhibitor unless symptoms are mild and infrequent (fewer than three times per week) - should be assessed at four to eight weeks. Maintenance medical therapy should be at the lowest dose and frequency necessary to maintain symptom relief; antireflux surgery is an alternative for a small proportion of selected patients. Routine testing for Helicobacter pylori infection is unnecessary before starting GERD therapy. GERD is associated with Barrett's epithelium and esophageal adenocarcinoma but the risk of malignancy is very low. Endoscopic screening for Barrett's epithelium may be considered in adults with GERD symptoms for more than 10 years; Barrett's epithelium and low-grade dysplasia generally warrant surveillance; endoscopic or surgical management should be considered for confirmed high-grade dysplasia or malignancy. CONCLUSION: Prospective studies are needed to investigate clinically relevant risk factors for the development of GERD and its complications; GERD progression, on and off therapy; optimal management strategies for typical GERD symptoms in primary care patients; and optimal management strategies for atypical GERD symptoms, Barrett's epithelium and esophageal adenocarcinoma.

Randomized controlled trial comparing outcomes of video capsule endoscopy with push enteroscopy in obscure gastrointestinal bleeding.

BACKGROUND: Optimal management of obscure gastrointestinal bleeding (OGIB) remains unclear. OBJECTIVE: To evaluate diagnostic yields and downstream clinical outcomes comparing video capsule endoscopy (VCE) with push enteroscopy (PE). METHODS: Patients with OGIB and negative esophagogastroduodenoscopies and colonoscopies were randomly assigned to VCE or PE and followed for 12 months. End points included diagnostic yield, acute or chronic bleeding, health resource utilization and crossovers. RESULTS: Data from 79 patients were analyzed (VCE n=40; PE n=39; 82.3% overt OGIB). VCE had greater diagnostic yield (72.5% versus 48.7%; P<0.05), especially in the distal small bowel (58% versus 13%; P<0.01). More VCE-identified lesions were rated possible or certain causes of bleeding (79.3% versus 35.0%; P<0.05). During follow-up, there were no differences in the rates of ongoing bleeding (acute [40.0% versus 38.5%; P not significant], chronic [32.5% versus 45.6%; P not significant]), nor in health resource utilization. Fewer VCE-first patients crossed over due to ongoing bleeding (22.5% versus 48.7%; P<0.05). CONCLUSIONS: A VCE-first approach had a significant diagnostic advantage over PE-first in patients with OGIB, especially with regard to detecting small bowel lesions, affecting clinical certainty and subsequent further small bowel investigations, with no subsequent differences in bleeding or resource utilization outcomes in follow-up. These findings question the clinical relevance of many of the discovered endoscopic lesions or the ability to treat most of these effectively over time. Improved prognostication of both patient characteristics and endoscopic lesion appearance with regard to bleeding behaviour, coupled with the impact of therapeutic deep enteroscopy, is now required using adapted, high-quality study methodologies.

Lower esophageal sphincter augmentation by endoscopic injection of dextranomer hyaluronic acid copolymer in a porcine gastroesophageal reflux disease model.

BACKGROUND: We previously demonstrated feasibility, safety, and a reproducible histologic bulking effect after injection of dextranomer hyaluronic acid copolymer (DxHA) into the gastroesophageal junction of rabbits. In the current study, we investigated the potential for DxHA to augment the lower esophageal sphincter (LES) in a porcine model of gastroesophageal reflux disease (GERD). METHODS: Twelve Yucatan miniature pigs underwent LES manometry and 24-hour ambulatory pH monitoring at baseline, after cardiomyectomy, and 6weeks after randomization to endoscopic injection of either DxHA or saline at the LES. After necropsy, the foregut, including injection sites, was histologically examined. RESULTS: Pigs in both groups had similar weight progression. Cardiomyectomy induced GERD in all animals, as measured by a rise in the median % of time pH <5 from 0.6 to 11.6 (p=0.02). Endoscopic injection of DxHA resulted in a higher median difference in LES length (1.8cm vs. 0.4cm, p=0.03). In comparison with saline injection, DxHA resulted in 120% increase in LES pressure, and 76% decrease in the mean duration of reflux episodes, but these results were not statistically significant. Injection of DxHA induced a foreign body reaction with fibroblasts and giant cells. CONCLUSIONS: Porcine cardiomyectomy is a reproducible animal GERD model. Injection of DxHA may augment the LES, offering a potential therapeutic effect in GERD.

The value of Botox-A in acute radiation proctitis: results from a phase I/II study using a three-dimensional scoring system.

PURPOSE: Acute radiation proctitis (ARP) is a common side effect of pelvic radiotherapy, and its management is challenging in daily practice. The present phase I/II study evaluates the safety and efficacy of the botulinum toxin A (BTX-A) in ARP treatment for rectal cancer patients undergoing neoadjuvant high-dose-rate endorectal brachytherapy (HDREBT). METHODS AND MATERIALS: Fifteen patients, treated with neoadjuvant HDREBT, 26-Gy in 4 fractions, received the study treatment that consisted of a single injection of BTX-A into the rectal wall. The injection was performed post-HDREBT and prior to the development of ARP. The control group, 20 such patients, did not receive the BTX-A injection. Both groups had access to standard treatment with hydrocortisone rectal aerosol foam (Cortifoam) and anti-inflammatory and narcotic medication. The ARP was clinically evaluated by self-administered daily questionnaires using visual analog scores to document frequency and urgency of bowel movements, rectal burning/tenesmus, and pain symptoms before and after HDREBT. RESULTS: At the time of this analysis, there was no observed systemic toxicity. Patient compliance with the self-administered questionnaire was 100% from week 1 to 4, 70% during week 5, and 40% during week 6. The maximum tolerated dose was established at the 100-U dose level, and noticeable mean differences were observed in bowel frequency (p = 0.016), urgency (p = 0.007), and pain (p = 0.078). CONCLUSIONS: This study confirms the feasibility and efficacy of BTX-A intervention at 100-U dose level for study patients compared to control patients. A phase III study with this dose level is planned to validate these results.

Pulmonary inflammatory myofibroblastic tumor invading the gastroesophageal junction.

Pulmonary inflammatory myofibroblastic tumors are rare neoplasms of intermediate malignant potential. Most patients are asymptomatic and present with incidental findings on imaging. Dysphagia due to direct invasion into the esophagus is an extremely rare presentation of this uncommon tumor. The diagnosis is difficult to make preoperatively. Complete surgical resection offers the best chance of cure. We describe a 27-year-old man who presented with progressive dysphagia and the diagnosis was only revealed after en bloc resection of the esophagus, cardia, and left lower lobe.

A new approach to analysis and modeling of esophageal manometry data in humans.

In this paper, we propose a new approach to the analysis and modeling of esophageal manometry (EGM) data to assist the diagnosis of esophageal motility disorders in humans. The proposed approach combines three techniques, namely, wavelet decomposition (WD), nonlinear pulse detection technique (NPDT), and statistical pulse modeling. Specifically, WD is applied to the filtering of the EGM data, which is contaminated with electrocardiography (ECG) artifacts. A new NPDT is applied to the denoised data leading to identification and extraction of diagnostically important information, i.e., esophageal pulses from the respiration artifacts. Such information is used to generate a statistical model that can classify the EGM patterns. The proposed approach is computationally effortless, thus making it suitable for real-time application. Experimental results using measured EGM data of 20 patients, including ten abnormal cases is presented. Comparison of our results with those from existing techniques illustrates the advantages of the proposed approach in terms of accuracy and efficiency.

Assessing clinical generalizability in sedation studies of upper GI endoscopy.

BACKGROUND: Prior endoscopic studies evaluating conscious sedation have recruited only a small proportion of the patients actually approached. The generalizability of such results to an unselected adult ambulatory care population is thus questionable. The objectives of this study were to determine the characteristics of patients who refused inclusion in a randomized controlled trial of sedation and to compare these characteristics to those of patients who agreed to participate. METHODS: Patients who refused participation in a randomized controlled trial of sedation completed standardized questionnaires addressing demographic data and possible confounding variables, and they also completed a validated anxiety questionnaire. Characteristics associated with refusal to participate in the randomized controlled trial were assessed by using uni- and multivariate analysis. Exploratory comparisons of outcomes between both groups included self-reported satisfaction with level of comfort and technical adequacy. RESULTS: Of 302 patients screened, 203 refused to participate in the randomized controlled trial. The most common reason for refusal was the request for no sedation (135/203). A total of 163 were enrolled in this synchronous study. Patients who refused to participate exhibited 3 distinguishing characteristics: prior treatment for an anxiety disorder (risk difference 9.4%: 95% CI[3%, 17%]), use of analgesic medication (risk difference 10.4%: 95% CI[2%, 19%]), and prior experience with EGD (risk difference 17.9: 95% CI[5%, 30%]). Only upper endoscopy experience was predictive of refusal to participate in the randomized controlled trial. No differences in outcomes existed between patients randomized to sedation and those refusing the randomized controlled trial who chose to receive sedative medication. Patients who refused participation in the randomized controlled trial and who underwent upper endoscopy without sedation were more satisfied than patients randomized to placebo (1.33 vs. 2.58; risk difference -1.25: 95% CI[-0.38, -2.1]). Moreover, the procedure in these patients was more adequate technically (4.86 vs. 4.18; risk difference 0.68: 95% CI[0.21, 1.13]). CONCLUSIONS: Characteristics of patients accepting and refusing randomization were highly similar, differing only with regard to upper endoscopy experience. An exploratory analysis of outcomes suggests that randomized controlled trial results may be biased in a direction that may underestimate the benefits of not administering sedative medication in a real-life setting.

Sedation versus no sedation in the performance of diagnostic upper gastrointestinal endoscopy: a Canadian randomized controlled cost-outcome study.

BACKGROUND: Sedation is not required to perform a technically adequate gastroscopy (EGDE), but does improve patient satisfaction, comfort, and willingness to repeat particularly in the elderly and those with decreased pharyngeal sensitivity. The comparative cost-efficacy of sedation versus no sedation remains poorly characterized. AIM: To compare the cost-efficacy of diagnostic EGDE with and without sedation in an adult ambulatory Canadian population. METHODS: A double-blind randomized controlled trial assigned patients to sedation versus placebo. "Successful endoscopy" was considered an EGDE rated 4/4 in technical adequacy (1 = inadequate to 4 = totally adequate), and 1-2/5 in patient self-reported comfort (1 = acceptable to 5 = unacceptable). Secondary outcomes included recovery room time, patient satisfaction alone, and willingness to repeat the procedure. Cost data were obtained using a published, institutional activity-based costing methodology. Analysis was intention to treat using standard univariate and multivariate methods. RESULTS: 419 patients (mean age 54.5, 48% male) were randomized (N = 210 active vs N = 209 placebo). Among patients randomized to active medication 76% of procedures were "successful" (placebo 46%), 79% were satisfied with their level of comfort (placebo 47%), and willingness to repeat was 81% (placebo 65%). We observed a 10% crossover rate from placebo to active medications. The use of sedation was the major determinant of successful endoscopy (OR = 3.8; 95% CI: 2.5-5.7), but contributed to an increased recovery room time (29 vs 15 min; p < 0.0001). The expected cost of an additional successful endoscopy using sedation was $90.06 (CDN). In a planned subgroup analysis, among the elderly (>75; N = 53) unsedated endoscopy became the dominant approach. Indeed, in this population, a trend was observed favoring the effectiveness of placebo (63%) versus active medication (57%) (OR = 0.75; 95% CI: 0.25-2.3) and was less costly resulting in $450 savings/unsedated EGDE. CONCLUSIONS: In the average Canadian ambulatory adult population, sedated diagnostic EGDE is more costly but remains an efficacious strategy by increasing the rate of successful endoscopies, patient satisfaction, and willingness to repeat. However, among the elderly (>75 yr), an unsedated strategy may be more cost-efficacious.

Predicting which patients can undergo upper endoscopy comfortably without conscious sedation.

BACKGROUND: Eliminating conscious sedation for diagnostic endoscopy may be advantageous for patient safety and cost containment. The aim of this study was to identify and validate independent predictors of a comfortable, technically adequate, unsedated diagnostic upper endoscopy in Canadian patients. METHODS: Patients were consecutively enrolled in a prospective fashion. Data collected on an initial cohort of 268 patients included demographics, a validated anxiety questionnaire, use of sedatives/analgesics, upper endoscopy experience, pharyngeal sensitivity, technical adequacy, and patient assessment of comfort after the procedure. The main outcome measure was "satisfactory upper endoscopy," a composite of optimal scores for patient comfort and technical adequacy. Univariate and multivariate analyses were performed to identify the optimal predictive model of a satisfactory unsedated diagnostic upper endoscopy. Once identified, 68 additional patients were enrolled in a similar fashion from an independent prospective sample for purposes of outcome validation. Multivariate analysis was then repeated with the total cohort (N = 336). These results were then compared for concordance with those obtained from the initial cohort. RESULTS: Among the initial 268 patients (54.3% women; mean age 51 +/- 17 years), 49% were anxious, 15% regularly used sedatives and analgesics, 28% experienced increased pharyngeal sensitivity, and 41% had previously undergone upper endoscopy. Endoscopy was completed in 94.7% of patients without sedation and was technically adequate in 97%, and 80.1% were willing to repeat the procedure under similar conditions. Satisfactory upper endoscopy was achieved in only 59% of the initial cohort. The only independent and significant predictors of a satisfactory upper endoscopy were advancing age (OR 1.2: 95% CI [1.1, 1.4]) and decreased pharyngeal sensitivity (OR 0.5: 95% CI [0.27, 0.93]). Concordance of results were noted after validation with the second cohort. Satisfactory endoscopy was achieved in only 59.5% of the total cohort (n = 336); only 61% reported a comfortable procedural experience. CONCLUSIONS: The proportion of patients who can comfortably undergo technically adequate unsedated upper endoscopy is modest. Unsedated upper endoscopy is most likely to be successful under these procedural conditions in patients of advancing age with decreased pharyngeal sensitivity. The generalizability of these findings to an American population requires further study and may assist in identifying a subgroup of patients in whom it is cost-effective to perform upper endoscopy comfortably without sedation.