Costs associated with Barrett's esophagus screening in the community: an economic analysis of a prospective randomized controlled trial of sedated versus hospital unsedated versus mobile community unsedated endoscopy.

BACKGROUND AND AIMS: Data on the economic impact associated with screening for Barrett's esophagus (BE) are limited. As part of a comparative effectiveness randomized trial of unsedated transnasal endoscopy (uTNE) and sedated EGD (sEGD), we assessed costs associated with BE screening. METHODS: Patients were randomly allocated to 3 techniques: sEGD or uTNE in a hospital setting (huTNE) versus uTNE in a mobile research van (muTNE). Patients were called 1 and 30 days after screening to assess loss of work (because of the screening procedure) and medical care sought after procedure. Direct medical costs were extracted from billing claims databases. Indirect costs (loss of work for subject and caregiver) were estimated using patient reported data. Statistical analyses including multivariable analysis accounting for comorbidities were conducted to compare costs. RESULTS: Two hundred nine patients were screened (61 sEGD, 72 huTNE, and 76 muTNE). Thirty-day direct medical costs and indirect costs were significantly higher in the sEGD than the huTNE and muTNE groups. Total costs (direct medical + indirect costs) were also significantly higher in the sEGD than in the uTNE group. The muTNE group had significantly lower costs than the huTNE group. Adjustment for age, sex, and comorbidities on multivariable analysis did not change this conclusion. CONCLUSIONS: Short-term direct, indirect, and total costs of screening are significantly lower with uTNE compared with sEGD. Mobile uTNE costs were lower than huTNE costs, raising the possibility of mobile screening as a novel method of screening for BE and esophageal adenocarcinoma.

Prevalence and Predictors of Gastroesophageal Reflux Complications in Community Subjects.

BACKGROUND: Predictors of erosive esophagitis (EE) and Barrett's esophagus (BE) and the influence of number of risk factors in the community are not well defined. METHODS: Rates of BE and EE among community residents identified in a randomized screening trial were defined. The risk of EE and BE associated with single and multiple risk factors (gender, age, GERD, Caucasian ethnicity, ever tobacco use, excess alcohol use, family history of BE or EAC, and central obesity) was analyzed. RESULTS: Sixty-eight (33 %) of 205 subjects had EE and/or BE. BE prevalence was 7.8 % with dysplasia present in 1.5 %. Rates were comparable between subjects with and without GERD. Male sex and central obesity were independent risk factors. The odds of EE or BE were 3.7 times higher in subjects with three or four risk factors and 5.7 times higher in subjects with five or more risk factors compared with those with two or less factors. CONCLUSIONS: EE and BE are prevalent in the community regardless of the presence of GERD. Risk appeared to be additive, increasing substantially with three or more risk factors.

A randomized comparative effectiveness trial of novel endoscopic techniques and approaches for Barrett's esophagus screening in the community.

OBJECTIVES: The objective of this study was to compare participation rates and clinical effectiveness of sedated esophagogastroduodenoscopy (sEGD) and unsedated transnasal endoscopy (uTNE) for esophageal assessment and Barrett's esophagus (BE) screening in a population-based cohort. METHODS: This was a prospective, randomized, controlled trial in a community population. Subjects ≥50 years of age who previously completed validated gastrointestinal symptom questionnaires were randomized (stratified by age, sex, and reflux symptoms) to one of three screening techniques (either sEGD or uTNE in a mobile research van (muTNE) or uTNE in a hospital outpatient endoscopy suite (huTNE)) and invited to participate. RESULTS: Of the 459 subjects, 209 (46%) agreed to participate (muTNE n=76, huTNE n=72, and sEGD n=61). Participation rates were numerically higher in the unsedated arms of muTNE (47.5%) and huTNE (45.7%) compared with the sEGD arm (40.7%), but were not statistically different (P=0.27). Complete evaluation of the esophagus was similar using muTNE (99%), huTNE (96%), and sEGD (100%) techniques (P=0.08). Mean recovery times (min) were longer for sEGD (67.3) compared with muTNE (15.5) and huTNE (18.5) (P<0.001). Approximately 80% of uTNE subjects were willing to undergo the procedure again in future. Respectively, 29% and 7.8% of participating subjects had esophagitis and BE. CONCLUSIONS: Mobile van and clinic uTNE screening had comparable clinical effectiveness with similar participation rates and safety profile to sEGD. Evaluation time with uTNE was significantly shorter. Prevalence of BE and esophagitis in community subjects ≥50 years of age was substantial. Mobile and outpatient unsedated techniques may provide an effective alternative strategy to sEGD for esophageal assessment and BE screening.

Endoscopic and surgical treatment of mucosal (T1a) esophageal adenocarcinoma in Barrett's esophagus.

BACKGROUND & AIMS: Endoscopic therapy is emerging as an alternative to surgical therapy in patients with mucosal (T1a) esophageal adenocarcinoma (EAC) given the low likelihood of lymph node metastases. Long-term outcomes of patients treated endoscopically and surgically for mucosal EAC are unknown. We compared long-term outcomes of patients with mucosal EAC treated endoscopically and surgically. METHODS: Patients treated for mucosal EAC between 1998 and 2007 were included. Patients were divided into an endoscopically treated group (ENDO group) and a surgically treated group (SURG group). Vital status information was queried using an institutionally approved internet research and location service. Statistical analysis was performed using Kaplan-Meier curves and Cox proportional hazard ratios. RESULTS: A total of 178 patients were included, of whom 132 (74%) were in the ENDO group and 46 (26%) were in the SURG group. The mean follow-up period was 64 months (standard error of the mean, 4.8 mo) in the SURG group and 43 months (standard error of the mean, 2.8 mo) in the ENDO group. Cumulative mortality in the ENDO group (17%) was comparable with the SURG group (20%) (P = .75). Overall survival also was comparable using the Kaplan-Meier method. Treatment modality was not a significant predictor of survival on multivariable analysis. Recurrent carcinoma was detected in 12% of patients in the ENDO group, all successfully re-treated without impact on overall survival. CONCLUSIONS: Overall survival in patients with mucosal EAC when treated endoscopically appears to be comparable with that of patients treated surgically. Recurrent carcinoma occurs in a limited proportion of patients, but can be managed endoscopically.

Utility of biomarkers in prediction of response to ablative therapy in Barrett's esophagus.

BACKGROUND & AIMS: Photodynamic therapy (PDT) has been shown to be effective in the treatment of high-grade dysplasia (HGD)/mucosal carcinoma in Barrett's esophagus (BE). Substantial proportions of patients do not respond to PDT or progress to carcinoma despite PDT. The role of biomarkers in predicting response to PDT is unknown. We aimed to determine if biomarkers known to be associated with neoplasia in BE can predict loss of dysplasia in patients treated with ablative therapy for HGD/intramucosal cancer. METHODS: Patients with BE and HGD/intramucosal cancer were studied prospectively from 2002 to 2006. Biomarkers were assessed using fluorescence in situ hybridization performed on cytology specimens, for region-specific and centromeric probes. Patients were treated with PDT using cylindric diffusing fibers (wavelength, 630 nm; energy, 200 J/cm fiber). Univariate and multiple variable logistic regression was performed to determine predictors of response to PDT. RESULTS: A total of 126 consecutive patients (71 who underwent PDT and 55 patients who did not undergo PDT and were under surveillance, to adjust for the natural history of HGD), were included in this study. Fifty (40%) patients were responders (no dysplasia or carcinoma) at 3 months after PDT. On multiple variable analysis, P16 allelic loss (odds ratio [OR], 0.32; 95% confidence interval [CI], 0.10-0.96) predicted decreased response to PDT. BE segment length (OR, 0.71; 95% CI, 0.59-0.85), and performance of PDT (OR, 7.17; 95% CI, 2.50-20.53) were other independent predictors of loss of dysplasia. CONCLUSIONS: p16 loss detected by fluorescence in situ hybridization can help predict loss of dysplasia in patients with BE and HGD/mucosal cancer. Biomarkers may help in the selection of appropriate therapy for patients and improve treatment outcomes.

Correlation of histology with biomarker status after photodynamic therapy in Barrett esophagus.

BACKGROUND: Currently, histology is used as the endpoint to define success with photodynamic therapy (PDT) in patients with high-grade dysplasia (HGD). Recurrences despite 'successful' ablation are common. The role of biomarkers in assessing response to PDT remains undefined. The objectives of the current study were 1) to assess biomarkers in a prospective cohort of patients with HGD/mucosal cancer before and after PDT and 2) to correlate biomarker status after PDT with histology. METHODS: Patients who underwent PDT for HGD/mucosal cancer were studied prospectively. All patients underwent esophagogastroduodenoscopy, 4-quadrant biopsies every centimeter, endoscopic mucosal resection of visible nodules, and endoscopic ultrasound. Cytology samples were obtained by using standard cytology brushes. Biomarkers were assessed by using fluorescence in situ hybridization (FISH). The biomarkers that were assessed included loss of 9p21 (site of the p16 gene) and 17p13.1 (site of the p53 gene) loci; gains of the 8q24(c-myc), 17q (HER2-neu), and 20q13 loci; and multiple gains. Patients received PDT 48 hours after the administration of sodium porfimer. Demographic and clinical variables were collected prospectively. Patients were followed with endoscopy and repeat cytology for biomarkers. The McNemar test was used to compare biomarker proportions before and after PDT. RESULTS: Thirty-one patients were studied. The median patient age was 66 years (interquartile range [IQR], 56-73 years), and 28 patients (88%) were men. The mean Barrett segment length was 5 cm (standard error of the mean, 0.5 cm). Post-PDT biomarkers were obtained after a median duration of 9 months (IQR, 3-12 months). There was a statistically significant decrease in the proportion of several biomarkers assessed after PDT. Six patients without HGD after PDT still had positive FISH results for 1 or more biomarkers: of these, 2 patients (33%) developed recurrent HGD. CONCLUSIONS: In this initial study, histologic downgrading of dysplasia after PDT was associated with the loss of biomarkers that have been associated with progression of neoplasia in Barrett esophagus. Patients with persistently positive biomarkers appeared to be at a higher risk of recurrent HGD. These findings should be confirmed in a larger study.

Predictors of recurrent esophageal food impaction: a case-control study.

BACKGROUND: Esophageal food impaction (FI) is a distressing condition requiring urgent endoscopic intervention, with a reported recurrence rate between 10% and 20%. Knowledge of factors predisposing to recurrent FI may enable preventive measures to minimize the risk of recurrence. OBJECTIVE: To identify risk factors associated with recurrent FI. DESIGN: Retrospective case-control study. SETTING: Tertiary referral center. PATIENTS: A prospectively maintained database and medical records of all patients undergoing emergent endoscopy for FI from 1989 to 2000 were reviewed. Cases were defined as those presenting with more than 1 episode of FI, whereas controls were defined as those without recurrence within 5 years of the index episode. Several demographic, clinical, endoscopic, and follow-up variables were extracted. Statistical analysis included chi2 tests and t tests for univariate analysis, and stepwise logistic regression for multivariate analysis. INTERVENTIONS: NA. MAIN OUTCOME MEASUREMENTS: Predictors of recurrent FI. RESULTS: A total of 52 cases and 124 controls were identified (recurrence rate 30%). Presence of a diaphragmatic hernia [odds ratio (OR) 2.65; confidence interval (CI) 1.19-5.89], disimpaction by piecemeal extraction (OR 2.32; CI 1.09-4.97), and acquisition of esophageal biopsies (OR 3.69; CI 1.42-9.66) increased odds for recurrent FI. Physician follow-up after FI decreased the odds for recurrent FI (OR 0.38; CI 0.18-0.80). LIMITATIONS: Retrospective study. CONCLUSIONS: The presence of a diaphragmatic hernia, complexity of endoscopic disimpaction technique, and lack of follow-up increased risk for recurrent FI. Collection of esophageal biopsies as a risk factor suggests a visibly more severe esophageal disorder as a potential cause for recurrent FI.

Factors associated with increased survival after photodynamic therapy for cholangiocarcinoma.

BACKGROUND & AIMS: Recent studies have shown a survival advantage using photodynamic therapy (PDT) in patients with unresectable cholangiocarcinoma. Factors associated with increased survival after PDT are unknown. METHODS: Twenty-five patients with cholangiocarcinoma who were treated with PDT at the Mayo Clinic Rochester from 1991 to 2004 were studied. Porfimer sodium (2 mg/kg) was administered intravenously to patients with Bismuth type I (3 patients), type III a/b (13 patients), and type IV (9 patients) tumors. Forty-eight hours later, PDT was administered using a 1.5- to 2.5-cm diffusing fiber that was advanced across the tumor by either retrograde (20 patients) or percutaneous (5 patients) cholangiography. Laser light was applied for a total energy of 180 J/cm2 in 1-3 applications. Patients received PDT treatments every 3 months. Plastic biliary stents (10-11.5 F) were inserted to decompress the biliary system after PDT. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Patients were 64 (standard error of the mean, +/-2.6) years of age; 20 (80%) were men. The median overall survival period was 344 days. The median survival period after PDT was 214 days. The 1-year survival rate was 30%. On multivariate analysis, the presence of a visible mass on imaging studies (hazard ratio, 3.55; 95% confidence interval, 1.21-10.38), and increasing time between diagnosis and PDT (hazard ratio, 1.13; 95% confidence interval, 1.02-1.25) predicted a poorer survival rate after PDT. A higher serum albumin level (hazard ratio, 0.16; 95% confidence interval, 0.04-0.59) predicted a lower mortality rate after PDT. CONCLUSIONS: Patients with unresectable cholangiocarcinoma without a visible mass may benefit from earlier treatment with PDT.

Long-term survival following endoscopic and surgical treatment of high-grade dysplasia in Barrett's esophagus.

BACKGROUND & AIMS: Photodynamic therapy (PDT) for high-grade dysplasia (HGD) in Barrett's esophagus is a Food and Drug Administration-approved alternative to esophagectomy. Critical information regarding overall survival of patients followed up long-term after these therapies is lacking. Our aim was to compare the long-term survival of patients treated with PDT with patients treated with esophagectomy. METHODS: We reviewed records of patients with HGD seen at our institution between 1994 and 2004. PDT was performed 48 hours following the intravenous administration of a photosensitizer using light at 630 nm. Esophagectomy was performed by either transhiatal or transthoracic approaches by experienced surgeons. We excluded all patients with evidence of cancer on biopsy specimens. Vital status and death date information was queried using an institutionally approved Internet research and location service. Statistical analysis was performed using Kaplan-Meier curves and Cox proportional hazards ratios. RESULTS: A total of 199 patients were identified. A total of 129 patients (65%) were treated with PDT and 70 (35%) with esophagectomy. Overall mortality in the PDT group was 9% (11/129) and in the surgery group was 8.5% (6/70) over a median follow-up period of 59 +/- 2.7 months for the PDT group and 61 +/- 5.8 months for the surgery group. Overall survival was similar between the 2 groups (Wilcoxon test = 0.0924; P = .76). Treatment modality was not a significant predictor of mortality on multivariate analysis. CONCLUSIONS: Overall mortality and long-term survival in patients with HGD treated with PDT appears to be comparable to that of patients treated with esophagectomy.

Predictors of stricture formation after photodynamic therapy for high-grade dysplasia in Barrett's esophagus.

BACKGROUND: Stricture formation is the leading cause of long-term morbidity after photodynamic therapy (PDT). Risk factors for stricture formation have not been studied. OBJECTIVE: To assess risk factors for stricture formation in patients undergoing PDT for Barrett's esophagus with high-grade dysplasia (HGD). DESIGN: Retrospective cohort study. SETTING: Barrett's Unit, Mayo Clinic, Rochester, Minnesota. METHODS: Records of patients undergoing PDT for HGD were reviewed. Patients underwent PDT by using either bare cylindrical diffusing fibers (2.5-5.0 cm in length) or balloon diffusers with 5- to 7-cm windows. Univariate and multivariate logistic regression analyses were performed to assess risk factors for stricture formation. MAIN OUTCOME MEASUREMENT: Esophageal stricture formation. RESULTS: Thirty-five of 131 patients (27%) developed strictures. On multivariate analysis, statistically significant predictors of stricture formation were the following: EMR before PDT was odds ratio (OR) 2.7, 95% confidence interval (CI) 1.13-6.59; a prior history of esophageal stricture was OR 2.7, 95% CI 1.15-6.47; and the number of PDT applications was OR 2.2, 95% CI 1.22-4.12. The OR for stricture formation in patients when centering balloons were used was 0.41, 95% CI 0.11-1.46, P = .168, indicating that centering balloons did not significantly decrease the risk of stricture formation. LIMITATIONS: Retrospective single-center study; small proportion of patients treated with centering balloons. CONCLUSIONS: Risk factors for development of strictures after PDT included history of a prior esophageal stricture, performance of EMR before PDT, and more than 1 PDT application in 1 treatment session. The use of centering balloons was not associated with a statistically significant reduction in the risk of stricture formation.

Combined endoscopic mucosal resection and photodynamic therapy versus esophagectomy for management of early adenocarcinoma in Barrett's esophagus.

BACKGROUND & AIMS: Although esophagectomy is the standard of care for treating early adenocarcinoma in Barrett's esophagus, the procedure is associated with significant morbidity and mortality. For these patients, the multimodal approach of endoscopic mucosal resection and photodynamic therapy (EMR/PDT) may be a viable, less invasive option. METHODS: A retrospective review (1996-2001) of all patients undergoing either combined EMR/PDT group or esophagectomy (SURG) for early-stage Barrett's adenocarcinoma was performed. Data were collected on patient demographics, tumor staging, procedure-related morbidity and mortality, persistence or recurrence of cancer, and cancer-related deaths after therapy. Differences in outcomes between the 2 groups were assessed. RESULTS: Twenty-four patients were identified in the EMR/PDT group and 64 in the SURG group. The SURG group was found to have a significantly higher procedure-related complication rate compared with the EMR/PDT group (31 vs. 4; P < 0.01). There were no procedure-related deaths in the EMR/PDT group, whereas one death occurred in the SURG group as a result of complications. Eighty-three percent of patients (20 of 24) in the EMR/PDT group and all patients in the SURG group remained free of cancer over a follow-up of 12 +/- 2 and 19 +/- 3 months, respectively. Four patients in the EMR/PDT group failed to respond to therapy; 2 of them underwent alternate therapies and are free of disease, whereas the other 2 died of unrelated causes. CONCLUSIONS: The combination of EMR/PDT seems to be a viable and less morbid alternative to standard esophagectomy in patients presenting with early Barrett's esophageal adenocarcinoma. A prospective randomized, controlled trial of EMR/PDT compared with esophagectomy for managing early adenocarcinoma in Barrett's esophagus may be warranted.