Laparotomy and intraoperative enteroscopy for obscure gastrointestinal bleeding before and after the era of video capsule endoscopy and deep enteroscopy: A tertiary center experience.

BACKGROUND: To evaluate roles of intraoperative endoscopy (IOE) in management of severe obscure GI bleeding (OGIB) before vs. after introduction of video capsule endoscopy (VCE) and deep enteroscopy (DE). METHODS: We retrospectively reviewed prospectively collected data of patients undergoing IOE for severe OGIB in a tertiary referral center. RESULTS: 52 patients had laparotomy/IOE for OGIB, 11 pre and 41 post VCE/DE eras. In the pre VCE/DE era, 36.4% (4/11) had preoperative presumptive diagnoses while in the post VCE/DE era presumptive diagnoses were made in 48.8% (20/41) (p = 0.18). Preoperative evaluation led to correct diagnoses in 18.2% (2/11) in the pre and 51.2% (21/41) in the post VCE/DE era (p = 0.09). Vascular lesions and ulcers were the most common diagnoses, but rebleeding was common. No rebleeding was found among patients with tumors, Meckel's diverticulum, and aortoenteric fistula. CONCLUSIONS: Presumptive diagnoses in the post VCE/DE era were usually accurate. If VCE or DE are negative, the probability of negative IOE is high. Patients with tumors and Meckel's diverticulum were the best candidates for IOE.

Doppler Endoscopic Probe Monitoring of Blood Flow Improves Risk Stratification and Outcomes of Patients With Severe Nonvariceal Upper Gastrointestinal Hemorrhage.

BACKGROUND & AIMS: For 4 decades, stigmata of recent hemorrhage in patients with nonvariceal lesions have been used for risk stratification and endoscopic hemostasis. The arterial blood flow that underlies the stigmata rarely is monitored, but can be used to determine risk for rebleeding. We performed a randomized controlled trial to determine whether Doppler endoscopic probe monitoring of blood flow improves risk stratification and outcomes in patients with severe nonvariceal upper gastrointestinal hemorrhage. METHODS: In a single-blind study performed at 2 referral centers we assigned 148 patients with severe nonvariceal upper gastrointestinal bleeding (125 with ulcers, 19 with Dieulafoy's lesions, and 4 with Mallory Weiss tears) to groups that underwent standard, visually guided endoscopic hemostasis (control, n = 76), or endoscopic hemostasis assisted by Doppler monitoring of blood flow under the stigmata (n = 72). The primary outcome was the rate of rebleeding after 30 days; secondary outcomes were complications, death, and need for transfusions, surgery, or angiography. RESULTS: There was a significant difference in the rates of lesion rebleeding within 30 days of endoscopic hemostasis in the control group (26.3%) vs the Doppler group (11.1%) (P = .0214). The odds ratio for rebleeding with Doppler monitoring was 0.35 (95% confidence interval, 0.143-0.8565) and the number needed to treat was 7. CONCLUSIONS: In a randomized controlled trial of patients with severe upper gastrointestinal hemorrhage from ulcers or other lesions, Doppler probe guided endoscopic hemostasis significantly reduced 30-day rates of rebleeding compared with standard, visually guided hemostasis. Guidelines for nonvariceal gastrointestinal bleeding should incorporate these results. ClinicalTrials.gov no: NCT00732212 (CLIN-013-07F).

Origin, Clinical Characteristics and 30-Day Outcomes of Severe Hematochezia in Cirrhotics and Non-cirrhotics.

BACKGROUND: The sites of origin, causes and outcomes of severe hematochezia have not been compared between cirrhotics and non-cirrhotics. In cirrhotics versus non-cirrhotics presenting with severe hematochezia, we aimed at (1) identifying the site and etiology of gastro-intestinal bleeding and independent predictors of bleeding from the upper gastrointestinal tract versus small bowel or the colon, (2) comparing 30-day clinical outcomes, and (3) proposing an algorithm for management of severe hematochezia. METHODS: In this cohort study from two university-based medical centers, 860 consecutive patients with severe hematochezia admitted from 1995 to 2011 were prospectively enrolled with 160 (18.6 %) cirrhotics. We studied (a) general clinical and laboratory characteristics of cirrhotics versus non-cirrhotics, (b) predictors of bleeding sites in each patient group by multiple variable regression analysis, and compared (c) 30-day outcomes, including rebleeding, surgery and deaths. RESULTS: Cirrhosis independently predicted an upper gastrointestinal source of bleeding (OR 3.47; 95 % CI 2.01-5.96) as well as history of hematemesis, melena in the past 30 days, positive nasogastric aspirate, prior upper gastrointestinal bleeding or use of aspirin or non-steroidal anti-inflammatory. The most prevalent diagnoses were esophageal varices (20 %) in cirrhotics and colon diverticular bleeding (27.1 %) in non-cirrhotics. Thirty-day rates of rebleeding, surgical interventions and deaths were 23.1 versus 15 % (P = 0.01), 14.4 versus 6.4 % (P < 0.001), and 17.5 versus 4.1 % (P < 0.001), in cirrhotics versus non-cirrhotics, respectively. CONCLUSIONS: Cirrhosis predicted an upper gastrointestinal site of bleeding in patients presenting with severe hematochezia. The 30-day rates of rebleeding, surgery, and death were significantly higher in cirrhotics than in non-cirrhotics.

Doppler endoscopic probe as a guide to risk stratification and definitive hemostasis of peptic ulcer bleeding.

BACKGROUND AND AIMS: For more than 4 decades endoscopists have relied on ulcer stigmata for risk stratification and as a guide to hemostasis. None used arterial blood flow underneath stigmata to predict outcomes. For patients with severe peptic ulcer bleeding (PUB), we used a Doppler endoscopic probe (DEP) for (1) detection of blood flow underlying stigmata of recent hemorrhage (SRH), (2) quantitating rates of residual arterial blood flow under SRH after visually directed standard endoscopic treatment, and (3) comparing risks of rebleeding and actual 30-day rebleed rates for spurting arterial bleeding (Forrest [F] IA) and oozing bleeding (F IB). METHODS: Prospective cohort study of 163 consecutive patients with severe PUB and different SRH. RESULTS: All blood flow detected by the DEP was arterial. Detection rates were 87.4% in major SRH-spurting arterial bleeding (F IA), non-bleeding visible vessel (F IIA), clot (F IIB)-and were significantly lower at 42.3% (P < .0001) for an intermediate group of oozing bleeding (F IB) or flat spot (F IIC). For spurting bleeding (F IA) versus oozing (F IB), baseline DEP arterial flow was 100% versus 46.7%, residual blood flow detected after endoscopic hemostasis was 35.7% versus 0%, and 30-day rebleed rates were 28.6% versus 0% (all P < .05). CONCLUSIONS: (1) For major SRH versus oozing or spot, the arterial blood flow detection rate by the DEP was significantly higher, indicating a higher rebleed risk. (2) Before and after endoscopic treatment, spurting (F IA) PUB had significantly higher rates of blood flow detection than oozing (F IB) PUB and a significantly higher 30-day rebleed rate. (3) The DEP is recommended as a new endoscopic guide with SRH to improve risk stratification and potentially definitive hemostasis for PUB.

Comparison of Three Risk Scores to Predict Outcomes of Severe Lower Gastrointestinal Bleeding.

BACKGROUND AND AIMS: Improved medical decisions by using a score at the initial patient triage level may lead to improvements in patient management, outcomes, and resource utilization. There is no validated score for management of lower gastrointestinal bleeding (LGIB) unlike for upper gastrointestinal bleeding. The aim of our study was to compare the accuracies of 3 different prognostic scores [Center for Ulcer Research and Education Hemostasis prognosis score, Charlson index, and American Society of Anesthesiologists (ASA) score] for the prediction of 30-day rebleeding, surgery, and death in severe LGIB. METHODS: Data on consecutive patients hospitalized with severe gastrointestinal bleeding from January 2006 to October 2011 in our 2 tertiary academic referral centers were prospectively collected. Sensitivities, specificities, accuracies, and area under the receiver operator characteristic curve were computed for 3 scores for predictions of rebleeding, surgery, and mortality at 30 days. RESULTS: Two hundred thirty-five consecutive patients with LGIB were included between 2006 and 2011. Twenty-three percent of patients rebled, 6% had surgery, and 7.7% of patients died. The accuracies of each score never reached 70% for predicting rebleeding or surgery in either. The ASA score had a highest accuracy for predicting mortality within 30 days (83.5%), whereas the Center for Ulcer Research and Education Hemostasis prognosis score and the Charlson index both had accuracies <75% for the prediction of death within 30 days. CONCLUSIONS: ASA score could be useful to predict death within 30 days. However, a new score is still warranted to predict all 30 days outcomes (rebleeding, surgery, and death) in LGIB.

Natural history of definitive diverticular hemorrhage based on stigmata of recent hemorrhage and colonoscopic Doppler blood flow monitoring for risk stratification and definitive hemostasis.

BACKGROUND AND AIMS: Few prospective reports describe the short-term natural history of colon diverticular hemorrhage based on stigmata of recent hemorrhage, and none include blood flow detection for risk stratification or as a guide to definitive hemostasis. Our purposes were to report the 30-day natural history of definitive diverticular hemorrhage based on stigmata and to describe Doppler probe blood flow detection as a guide to definitive hemostasis. METHODS: Different cohorts of patients with severe diverticular bleeding and stigmata on urgent colonoscopy are reported. For 30-day natural history, patients were treated medically. If severe rebleeding occurred, they had surgical or angiographic treatment. We report natural history with major stigmata (active bleeding, visible vessel, or adherent clot) and no stigmata or flat spots after clots were washed away. We also report Doppler probe detection of arterial blood flow underneath stigmata before and after hemostasis in a recent cohort. RESULTS: For natural history, patients with major stigmata treated medically had 65.8% (25/38) rebleeding rates, and 44.7% (17/38) had intervention for hemostasis. Patients with spots or clean bases had no rebleeding. A Doppler probe detected arterial blood flow in 92% of major stigmata--none after hemostasis--and there was no rebleeding. CONCLUSIONS: (1) Patients with major stigmata treated medically had high rates of rebleeding and intervention for hemostasis. (2) Patients with clean diverticula or only flat spots had no rebleeding. (3) High rates of arterial blood flow were detected under major stigmata with a Doppler probe, but with obliteration by hemostasis no rebleeding occurred.

Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage.

AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). METHODS: This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. RESULTS: A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. CONCLUSION: Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT.

Esomeprazole versus other proton pump inhibitors in erosive esophagitis: a meta-analysis of randomized clinical trials.

BACKGROUND & AIMS: There are limited data comparing the effectiveness of available proton pump inhibitors (PPIs) in erosive esophagitis (EE). We performed a meta-analysis to calculate the pooled effect of esomeprazole on healing rates, symptom relief, and adverse events versus competing PPIs in EE. METHODS: We performed a structured electronic search of MEDLINE and EMBASE and reviewed published abstracts to identify English-language, randomized clinical trials from 1995-2005, comparing rates of endoscopic healing, symptom relief, and adverse events with esomeprazole versus alternative PPIs in the treatment of gastroesophageal reflux disease (GERD)/EE. We then performed meta-analysis to compare the relative risk (RR) of EE healing, symptom relief, and adverse events between study arms and calculated the absolute risk reduction and number needed to treat (NNT) for each outcome. RESULTS: Meta-analysis was performed on 10 studies (n=15,316). At 8 weeks, there was a 5% (RR, 1.05; 95% confidence interval, 1.02-1.08) relative increase in the probability of healing of EE with esomeprazole, yielding an absolute risk reduction of 4% and NNT of 25. The calculated NNTs by Los Angeles grade of EE (grades A-D) were 50, 33, 14, and 8, respectively. Last, esomeprazole conferred an 8% (RR, 1.08; 95% confidence interval, 1.05-1.11) relative increase in the probability of GERD symptom relief at 4 weeks. CONCLUSIONS: As compared with other PPIs, esomeprazole confers a statistically significant improvement, yet, clinically, only a modest overall benefit in 8-week healing and symptom relief in all-comers with EE. The clinical benefit of esomeprazole appears negligible in less severe erosive disease but might be important in more severe disease.

Treatment alternatives for hepatitis B cirrhosis: a cost-effectiveness analysis.

BACKGROUND: Hepatitis B virus (HBV) patients with cirrhosis are at risk for developing costly, morbid, or mortal events, and therefore need highly effective therapies. Lamivudine is effective but is limited by viral resistance. In contrast, adefovir and entecavir have lower viral resistance, but are more expensive. The most cost-effective approach is uncertain. METHODS: We evaluated the cost-effectiveness of six strategies in HBV cirrhosis: (1) No HBV treatment ("do nothing"), (2) lamivudine monotherapy, (3) adefovir monotherapy, (4) lamivudine with crossover to adefovir on resistance ("adefovir salvage"), (5) entecavir monotherapy, or (6) lamivudine with crossover to entecavir on resistance ("entecavir salvage"). The primary outcome was the incremental cost per quality-adjusted life-year (QALY) gained. RESULTS: The "do nothing" strategy was least effective yet least expensive. Compared with "do nothing," using adefovir cost an incremental US dollars 19,731. Entecavir was more effective yet more expensive than adefovir, and cost an incremental US dollars 25,626 per QALY gained versus adefovir. Selecting between entecavir versus adefovir was highly dependent on the third-party payer's "willingess-to-pay" (e.g., 45% and 60% of patients fall within budget if willing-to-pay US dollars 10K and US dollars 50K per QALY gained for entecavir, respectively). Both lamivudine monotherapy and the "salvage" strategies were not cost-effective. However, between the two salvage strategies, "adefovir salvage" was more effective and less expensive than "entecavir salvage." CONCLUSION: Both entecavir and adefovir are cost-effective in patients with HBV cirrhosis. Choosing between adefovir and entecavir is highly dependent on available budgets. In patients with HBV cirrhosis with previous lamivudine resistance, "adefovir salvage" appears more effective and less expensive than "entecavir salvage."

The cost-effectiveness and budget impact of intravenous versus oral proton pump inhibitors in peptic ulcer hemorrhage.

BACKGROUND & AIMS: The most cost-effective route of administering proton pump inhibitor (PPI) therapy in peptic ulcer hemorrhage remains uncertain. Oral (PO) PPI therapy may be less effective than intravenous (IV) PPI therapy, but is less expensive and does not mandate a 72-hour posthemostasis hospital stay to complete a full therapeutic course. Because there are currently no published head-to-head clinical trials comparing IV vs PO PPIs, we used decision analysis with budget impact modeling to measure the clinical and economic outcomes of these competing modes of administration. METHODS: We compared 3 postendoscopic strategies for high-risk peptic ulcer hemorrhage: (1) PO PPI therapy, (2) IV PPI therapy, and (3) IV histamine(2) receptor antagonist therapy. The primary outcomes were cost per quality-adjusted life-year gained, and per-member per-month cost in a hypothetical managed care organization with 1,000,000 covered lives. RESULTS: Compared with the PPI strategies, the histamine(2) receptor antagonist strategy was more expensive and less effective. Of the 2 PPI strategies, using IV instead of PO PPI cost an incremental 708,735 US dollars per year to gain 1 additional quality-adjusted life-year. Substituting IV in lieu of PO PPI cost each member 2.86 US dollars per month to subsidize. The IV PPI strategy became dominant when the rebleed rate with PO PPIs exceeded 24% (base case = 13%), and when the hospital stay on IV PPIs decreased to less than 72 hours. CONCLUSIONS: The higher effectiveness of IV PPI therapy may not offset its increased costs vs PO PPI therapy in ulcer hemorrhage. The managed care budget impact of IV PPIs exceeds most benchmarks.

Comparing rates of dyspepsia with Coxibs vs NSAID+PPI: a meta-analysis.

PURPOSE: Because dyspeptic symptoms are far more prevalent than ulcer complications in users of nonsteroidal anti-inflammatory drugs (NSAIDs), economic models indicate that dyspepsia rates (not ulcer complications) are the major determinant of cost-effectiveness in treating arthritis. We performed a meta-analysis to compare rates of dyspepsia for two common therapies in high-risk patients with arthritis: cyclooxygenase-2 inhibitor (Coxib) alone and combination therapy with a nonselective NSAID and a proton pump inhibitor (PPI) (NSAID+PPI). METHODS: We performed a systematic review to identify trials comparing either a Coxib versus NSAID or NSAID+PPI versus NSAID in chronic arthritis. We selected studies that report incident dyspepsia, defined a priori as "epigastric pain," "dyspepsia," and "nausea." We then performed meta-analysis to compare the relative risk reduction and absolute risk reduction of dyspepsia for Coxib versus NSAID and NSAID+PPI versus NSAID. RESULTS: Meta-analysis of 26 studies comparing dyspepsia between Coxibs and NSAIDs revealed a 12% relative risk reduction for Coxibs with an absolute risk reduction of 3.7%. Meta-analysis of four studies comparing dyspepsia between the NSAID+PPI combination and NSAIDs alone revealed a 66% relative risk reduction for NSAID+PPI with an absolute risk reduction of 9%. Compared with the NSAID strategy, the number needed to treat to prevent dyspepsia was 27 for Coxibs and 11 for NSAID+PPI. CONCLUSION: NSAID+PPI affords greater risk reduction for dyspepsia than Coxibs when compared with the common baseline of NSAIDs. Because there are limited head-to-head data comparing Coxibs versus NSAID+PPI, these data provide the best indirect evidence that NSAID+PPI may be superior to Coxibs in minimizing incident dyspepsia.

Treatment of watermelon stomach.

Watermelon stomach (WMS), or gastric antral vascular ectasia, is an uncommon but clinically important cause of chronic occult or overt gastrointestinal (GI) blood loss. Patients typically present with symptomatic anemia and hemoccult positive stools. Although the diagnosis is based primarily on the typical endoscopic appearance, the lesion may be overlooked on initial evaluation or interpreted as "gastritis." Gastric biopsy may be helpful in confirming the diagnosis by showing vascular ectasia, typically without inflammation. WMS is idiopathic but is often associated with autoimmune diseases or cirrhosis of the liver. The majority of patients with classic WMS are elderly and female. In contrast, there is no gender predominance with the diffuse pattern associated with cirrhosis. General supportive care includes transfusion of blood products as necessary to control symptomatic anemia and coagulopathy, iron replacement therapy by oral or parenteral routes, identification and treatment of iatrogenic (eg, warfarin) or hereditary (eg, von Willebrand's disease) coagulopathy, and avoidance of substances that might cause gastric mucosal damage and/or bleeding (eg, aspirin, NSAIDs, alcohol). The goals of therapy are to eliminate or decrease the need for blood transfusions, hospitalization, office visits, and endoscopic therapy sessions aimed at cessation of GI blood loss and resolution of symptomatic anemia. Multipolar electrocoagulation is our preferred technique for endoscopic ablation of WMS. A 10-Fr probe (3.2 mm in diameter) is used at a generator setting of 12 to 16 W. Pulse duration can be as short as 1 to 2 seconds if a pinpoint coagulation technique is used, or continuous if a paint-stroke technique is used to coagulate all vascular stripes in the classic WMS pattern or as many small lesions as possible in the diffuse type. Other techniques we currently use are argon plasma coagulation (APC) or heater probe. In the past, lasers (neodymium: yttrium-aluminum-garnet , KTP, or argon) were successfully used for such treatments. An initial treatment interval of 4 to 8 weeks should allow for interim healing of iatrogenic ulcers. Patients are routinely given standard doses of available proton-pump inhibitors (PPIs) to facilitate healing of iatrogenic ulcers and to prevent secondary bleeding. The treatment interval can be gradually lengthened as the long-term goals of obliteration of angiomata and resolution of anemia are reached. Side effects may include iatrogenic ulceration at the site of treatment, bleeding, and transient abdominal pain. Antral scarring (after APC or Nd:YAG laser) and hyperplastic polyps have also been reported after endoscopic treatment of classic WMS. Surgical antrectomy is very effective in the prevention of bleeding but has substantial (5% to 10%) mortality in older patients with comorbidity and is now reserved for endoscopic failures.

Is a negative colonoscopy associated with reassurance or improved health-related quality of life in irritable bowel syndrome?

BACKGROUND: Although colonoscopy is rarely of clinical use in irritable bowel syndrome (IBS), it is, nonetheless, frequently performed in IBS. Proponents contend that a normal colonoscopy provides reassurance and improves health-related quality of life (HRQOL). However, no previous data have measured these effects. We sought to measure the association of a normal colonoscopy with reassurance and HRQOL in patients with IBS aged <50 years. METHODS: We retrospectively evaluated 458 patients with IBS, aged 18 to 49 years. Subjects completed a symptom questionnaire, the Symptom Checklist 90 (SCL-90) psychometric checklist, and the Short Form 36 (SF-36) Health Survey. The main outcomes were HRQOL as measured by the mental component score (MCS) and the physical component score (PCS) of the SF-36 and reassurance as operationalized by a negative response to the question: "Do you think there is something seriously wrong with your body?" The independent variable was presence or absence of a previous normal colonoscopy. We performed regression analysis to control for potential confounders, including timing of colonoscopy. RESULTS: The unadjusted mean SF-36 PCS was 42 +/- 10 (0-100 scale: 0, worst) in patients with recent colonoscopy (<12 months), 45 +/- 11 in patients with distant colonoscopy (>12 months), and 45 +/- 10 in patients without colonoscopy (p = 0.78). The mean SF-36 MCS in the 3 groups were 42 +/- 13, 44 +/- 11, and 43 +/- 11 (p = 0.57). Colonoscopy did not impact the proportion reassured (69.3%, 67.2%, 66.6%; p = 0.85). There were no significant differences between groups for any outcomes when adjusting for potential confounders. CONCLUSIONS: We found no independent association between a negative colonoscopy and reassurance or improved HRQOL in IBS patients aged <50 years. These results suggest that the role of colonoscopy in IBS may be limited but require confirmation in prospective trials.

Impact of chronic viral hepatitis on health-related quality of life in HIV: results from a nationally representative sample.

BACKGROUND: Little is known about the health burden of chronic viral hepatitis in HIV-infected patients. We compared health-related quality of life (HRQOL) of patients with HIV and hepatitis C virus (HCV) or HIV and hepatitis B virus (HBV) coinfection to those with HIV monoinfection. METHODS: Using a nationally representative sample of 1,874 adults with HIV who completed a baseline and two follow-up interviews, we identified those with HIV monoinfection (n = 1,493), HIV-HCV coinfection (n = 279), and HIV-HBV coinfection (n = 122). We measured baseline and change over time scores for physical and mental health (PHS, MHS), overall quality of life (QOL), overall health, and disability days. To identify the independent effect of coinfection, we adjusted for demographic and clinical predictors of HRQOL using multivariable regression. RESULTS: Despite significant differences in socio-demographic characteristics between groups, there were no differences in the baseline scores for PHS, MHS, overall QOL, overall health, or disability days between groups. The HRQOL did not decline significantly over time for the HIV patients with or without HCV or HBV coinfection. All groups reported similar longitudinal changes in the HRQOL scores for all measures. CONCLUSIONS: We found no significant differences in disease burden as assessed by a generic HRQOL instrument between patients with HIV monoinfection and HIV-HCV or HIV-HBV coinfection. These data are relevant in counseling coinfected patients regarding the impact of coinfection on HRQOL, and are important in designing clinical trials and conducting cost-effectiveness analyses including this vulnerable cohort.

Treatment alternatives for chronic hepatitis B virus infection: a cost-effectiveness analysis.

BACKGROUND: Treatment options for chronic hepatitis B virus (HBV) infection have disparate risks and benefits. Interferon has clinically significant side effects, and lamivudine is associated with viral resistance. In contrast, adefovir is safe and has lower viral resistance but is more expensive. The most cost-effective approach is uncertain. OBJECTIVE: To determine whether and under what circumstances the improved efficacy of adefovir offsets its increased cost compared with lamivudine or interferon. DESIGN: Cost-utility analysis stratified by hepatitis B e antigen (HBeAg) status. DATA SOURCES: Systematic review of MEDLINE from 1970 to 2005. TARGET POPULATION: Patients with chronic HBV infection, elevated aminotransferase levels, and no cirrhosis. TIME HORIZON: Lifetime. PERSPECTIVE: Third-party payer. INTERVENTIONS: 1) No HBV treatment ("do nothing" strategy), 2) interferon monotherapy, 3) lamivudine monotherapy, 4) adefovir monotherapy, or 5) lamivudine with crossover to adefovir upon resistance ("adefovir salvage" strategy). OUTCOME MEASURE: Incremental cost per quality-adjusted life-year (QALY) gained. RESULTS OF BASE-CASE ANALYSIS: The "do nothing" strategy was least effective yet least expensive. Compared with the "do nothing" strategy, using interferon cost an incremental 6337 dollars to gain 1 additional QALY. Compared with interferon, the adefovir salvage strategy cost an incremental 8446 dollars per QALY gained. Both the lamivudine and adefovir monotherapy strategies were more expensive yet less effective than the alternative strategies and were therefore dominated. RESULTS OF SENSITIVITY ANALYSIS: In sensitivity analysis, interferon was most cost-effective in health care systems with tight budgetary constraints and a high prevalence of HBeAg-negative patients. LIMITATIONS: These results apply only to patients with chronic HBV infection, elevated aminotransferase levels, and no clinical or histologic evidence of cirrhosis. They do not apply to alternative populations. CONCLUSIONS: Neither lamivudine nor adefovir monotherapy is cost-effective in chronic HBV infection. However, a hybrid salvage strategy reserving adefovir only for lamivudine-associated viral resistance may be highly cost-effective across most health care settings. Interferon therapy may still be preferred in health care systems with limited resources, especially in those serving populations with a high prevalence of HBeAg-negative HBV.

Dysplasia and risk of further neoplastic progression in a regional Veterans Administration Barrett's cohort.

OBJECTIVES: No published data are available on the risk of further neoplastic progression in Barrett's patients stratified by baseline dysplasia status. Our aims were to estimate and compare the risk of progression to high-grade dysplasia or cancer in groups of Barrett's patients stratified by baseline dysplasia status. METHODS: Consecutive Barrett's cases from 1988-2002 were identified via pathology databases in a regional VA health-care system and medical record data were abstracted. The risk of progression to high-grade dysplasia or cancer was measured and compared in cases with versus without low-grade dysplasia within 1 yr of index endoscopy using survival analysis. RESULTS: A total of 575 Barrett's cases had 2,775 patient-years of follow-up. There were 13 incident cases of high-grade dysplasia and two of cancer. The crude rate of high-grade dysplasia or cancer was 1 of 78 patient-years for those with baseline dysplasia versus 1 of 278 patient-years for those without (p= 0.001). One case of high-grade dysplasia in each group underwent successful therapy. One incident cancer case underwent successful resection and the other was unresectable. Two cases with high-grade dysplasia later developed cancer, one died postoperatively, the other was unresectable. When these two cases were included (total of four cancers), the crude rate of cancer was 1 of 274 patient-years for those with baseline dysplasia versus 1 of 1,114 patient-years for those without. CONCLUSIONS: In a large cohort study of Barrett's, incident malignancy was uncommon. The rate of progression to high-grade dysplasia or cancer was significantly higher in those with baseline low-grade dysplasia. These data may warrant reevaluation of current Barrett's surveillance strategies.

Effect of a new diagnosis of Barrett's esophagus on insurance status.

BACKGROUND: Barrett's esophagus (BE) is associated with an increased risk of adenocarcinoma of the esophagus. Despite this increased risk, most cohort studies demonstrate that the mean life expectancy of subjects with BE is no different than age-matched controls. The indirect costs associated with a diagnosis of BE are unclear. AIM: To assess the effect of a diagnosis of BE on insurance premiums. METHODS: We assessed twenty national life insurance companies (10 in southern California, 10 in North Carolina) to determine the effect of a diagnosis of BE on life insurance premiums. Our base case in Los Angeles was a 36-yr-old female nonsmoker, and in North Carolina, a 43-yr-old Caucasian male nonsmoker, both in excellent health except for a diagnosis of prevalent BE with no dysplasia. The policy requested was a 20-yr guaranteed term life insurance in the amount of $1,000,000. Companies were asked for their best price exclusive of the BE, and also their best price when considering BE as a preexisting condition. For those companies not offering the "preferred" rates, the insurance representative was subsequently sent a physician's letter explaining BE and providing data substantiating a normal life expectancy in the condition. Companies were also asked for health insurance quotes, including premiums and deductibles, inclusive and exclusive of the diagnosis of BE. RESULTS: Twenty national insurance companies were contacted. For the 43-yr-old man with no BE, the yearly "preferred" premium for life insurance averaged $1,255. The mean cost of the policies offered to the same individual with BE as a preexisting condition was $2,731 (p < 0.001). For the 36-yr-old female the base rate exclusive of BE was $517, with a range of $472-$551. After inclusion of the diagnosis of BE, the mean rate rose by 177%, to $1,434, with a range of $1,144-$1,896. Companies either refused to provide health insurance to the individual with BE or would not provide a quote without review of the medical record. None of the insurance companies changed their quoted rates after receiving the letter written by the physician on behalf of the individual. CONCLUSIONS: Despite the preponderance of data demonstrating a normal life expectancy associated with the condition, a diagnosis of BE more than doubles life insurance premiums, and impacts the availability of health insurance. Further steps to educate insurance companies about the risks associated with BE are warranted, and patients should understand this additional "risk" of endoscopic screening for BE. There are significant indirect costs associated with a diagnosis of BE.

Randomized trial of argon plasma coagulation vs. multipolar electrocoagulation for ablation of Barrett's esophagus.

BACKGROUND: Endoscopic ablation of Barrett's esophagus has been described in which various thermocoagulation modalities are used in combination with a high dose of a proton pump inhibitor. No randomized comparison of ablation strategies has been published. METHODS: Referred patients were screened to identify those with Barrett's esophagus 2 to 7 cm in length, without high-grade dysplasia or cancer. Included patients received pantoprazole (40 mg twice a day), followed by randomization to treatment with argon plasma coagulation (APC) or multipolar electrocoagulation (MPEC). The primary outcome measure was the number of treatment sessions required for endoscopic ablation. RESULTS: Of 235 patients screened, 52 were randomized. The mean length of Barrett's esophagus was 3.1 cm in the MPEC group vs. 4.0 cm in the APC group (p = 0.03). Otherwise, the treatment groups were similar with regard to baseline characteristics. The mean number of treatment sessions required for endoscopic ablation was 2.9 for MPEC vs. 3.8 for APC (p = 0.04) in an intention-to-treat analysis (p = 0.249, after adjustment for the difference in length of Barrett's esophagus). The proportion of patients in which ablation was endoscopically achieved proximal to the gastroesophageal junction was 88% for the MPEC group vs. 81% for the APC group (p = 0.68) and histologically achieved in 81% for MPEC vs. 65% for APC (p = 0.21). The mean time required for the first treatment session was 6 minutes with MPEC vs. 10 minutes with APC (p = 0.01) in per protocol analysis. There was no serious adverse event, but transient moderate to severe upper-GI symptoms occurred after MPEC in 8% vs. 13% after APC (p = 0.64). Conclusions Although there were no statistically significant differences, ablation of Barrett's esophagus with pantoprazole and MPEC required numerically fewer treatment sessions, and endoscopic and histologic ablation was achieved in a greater proportion of patients compared with treatment with pantoprazole and APC.

Colonic stent vs. emergency surgery for management of acute left-sided malignant colonic obstruction: a decision analysis.

BACKGROUND: Acute colonic obstruction because of malignancy is often a surgical emergency. Surgical decompression with colostomy with or without resection and eventual re-anastomosis is the traditional treatment of choice. Endoscopic colonic stent insertion effectively decompresses the obstructed colon, allowing for surgery to be performed electively. This study sought to determine the cost-effectiveness of colonic stent vs. surgery for emergent management of acute malignant colonic obstruction. METHODS: Decision analysis was used to calculate the cost-effectiveness of two competing strategies in a hypothetical patient presenting with acute, complete, malignant colonic obstruction: (1) emergent colonic stent followed by elective surgical resection and re-anastomosis; (2) emergent surgical resection followed by diversion (Hartmann's procedure) or primary anastomosis. Cost estimates were obtained from a third-party payer perspective. Primary outcome measures were mortality, stoma requirement, and total number of operative procedures. RESULTS: Colonic stent resulted in 23% fewer operative procedures per patient (1.01 vs. 1.32 operations per patient), an 83% reduction in stoma requirement (7% vs. 43%), and lower procedure-related mortality (5% vs. 11%). Colonic stent was associated with a lower mean cost per patient ($45,709 vs. $49,941). CONCLUSIONS: Colonic stent insertion followed by elective surgery appears more effective and less costly than emergency surgery under base-case conditions. This finding remains robust over a wide range of assumptions for clinical inputs in sensitivity analysis. Our findings suggest that colonic stent insertion should be offered, whenever feasible, as a bridge to elective surgery in patients presenting with malignant colonic obstruction.