Risk of gastric cancer, gastrointestinal cancers and other cancers: a comparison of treatment with pantoprazole and other proton pump inhibitors.

BACKGROUND: Proton pump inhibitors (PPIs) have been shown to be carcinogenic in rodent studies. AIM: As part of a long-term post-marketing surveillance study requested by the US Food and Drug Administration, to compare incidence rates of gastric and other cancers after sustained exposures to pantoprazole, a long-acting PPI, compared with other shorter acting PPIs. METHODS: We conducted a cohort study within the membership of the Kaiser Permanente Northern California healthcare system and compared rates of gastric and other cancers among pantoprazole users and users of other PPI medications. The Cox proportional hazards model was used to adjust for potential confounders such as sex, age, receipt of treatment for Helicobacter pylori, cumulative PPI dose, total years PPI treatment and year of index date. The study was developed in consultation with, and approved by, the FDA. RESULTS: A total of 61 684 persons with at least a 240-day supply of medication (34 178 pantoprazole and 27 686 other PPIs) were followed up for a total of 547 020 person-years (274 700 vs. 272 321 person-years, respectively). The primary analyses demonstrated comparable risks between the pantoprazole and other PPI groups for gastric cancer [hazard ratio (HR) = 0.68, 95% CI 0.24-1.93); colorectal, liver, pancreatic, or small bowel cancers (HR = 0.95, 95% CI 0.65-1.40) or any cancer (HR = 1.06, 95% CI 0.93-1.21). CONCLUSIONS: We found no evidence that pantoprazole, a longer acting PPI, compared with shorter-acting agents, conferred an excess risk of gastric cancer, other gastrointestinal cancers or all cancers for pantoprazole compared with other shorter-acting PPIs.

Diabetes, hypertension and hyperlipidemia: prevalence over time and impact on long-term survival after liver transplantation.

With increasing short-term survival, the transplant community has turned its focus to delineating the impact of medical comorbidities on long-term outcomes. Unfortunately, conditions such as diabetes, hypertension and hyperlipidemia are difficult to track and often managed outside of the transplant center by primary care providers. We collaborated with Kaiser Permanente Northern California to create a database of 598 liver transplant recipients, which incorporates diagnostic codes along with laboratory and pharmacy data. Specifically, we determined the prevalence of diabetes, hypertension and hyperlipidemia both before and after transplant and evaluated the influence of disease duration as a time-dependent covariate on posttransplant survival. The prevalence of these comorbidities increased steadily from the time of transplant to 7 years after transplant. The estimated risk for all-cause mortality (hazard ratio = 1.07 per year increment, 95% CI 1.01-1.13, p < 0.02) and mortality secondary to cardiovascular events, infection/multisystem organ failure and allograft failure (hazard ratio = 1.08 per year increment, 95% CI 1.00-1.16, p = 0.05) increased for each additional year of diabetes. No associations were found for duration of hypertension and hyperlipidemia. Greater attention to management of diabetes may mitigate its negative impact on long-term survival in liver transplant recipients.

Race, ethnicity, sex and temporal differences in Barrett's oesophagus diagnosis: a large community-based study, 1994-2006.

OBJECTIVE: To evaluate the demographics and incidence of Barrett's oesophagus diagnosis using community-based data. DESIGN: Observational study. SETTING: Kaiser Permanente, Northern California healthcare membership, 1994-2006. PATIENTS: Members with an electronic diagnosis of Barrett's oesophagus. MAIN OUTCOME MEASURES: Incidence and prevalence of a new Barrett's oesophagus diagnosis by race, sex, age and calendar year. RESULTS: 4205 persons met the study definition for a diagnosis of Barrett's oesophagus. The annual incidence in 2006 was highest among non-Hispanic whites (39/100,000 race-specific member-years, 95% confidence interval (95% CI) 35 to 43), with lower rates among Hispanics (22/100,000, 95% CI 16 to 29), Asians (16/100,000, 95% CI 11 to 22), and blacks (6/100,000, 95% CI 2 to 12). The annual incidence was higher among men than women (31 vs 17/100,000, respectively, year 2006; p<0.01). The incidence increased with age from 2 per 100,000 for persons aged 21-30 years, to a peak of 31 per 100,000 member-years for persons aged 61-70 years (year 2006). There was no increase in the incidence of new diagnoses until the last two observation years, which coincided with changes in data collection methods and may be due to bias. The overall prevalence among active members increased almost linearly to 131/100,000 member-years by 2006. CONCLUSIONS: The demographic distributions of Barrett's oesophagus differ markedly by race, age and sex and were comparable to those for oesophageal adenocarcinoma. Thus, demographic disparities in oesophageal adenocarcinoma risk may arise partly from the risk of having Barrett's oesophagus, rather than from differing risks of progression from Barrett's oesophagus to cancer. There has been an almost linear increase in the prevalence of diagnosed disease.

Helicobacter pylori infection and the risk of Barrett's oesophagus: a community-based study.

OBJECTIVE: Gastric colonisation with the Helicobacter pylori bacterium is a proposed protective factor against oesophageal adenocarcinoma, but its point of action is unknown. Its associations with Barrett's oesophagus, a metaplastic change that is a probable early event in the carcinogenesis of oesophageal adenocarcinoma, were evaluated METHODS: A case-control study was carried out in the Kaiser Permanente Northern California population, a large health services delivery organisation. Persons with a new Barrett's oesophagus diagnosis (cases) were matched to subjects with gastro-oesophageal reflux disease (GORD) without Barrett's oesophagus and to population controls. Subjects completed direct in-person interviews and antibody testing for H pylori and its CagA (cytotoxin-associated gene product A) protein. RESULTS: Serological data were available on 318 Barrett's oesophagus cases, 312 GORD patients and 299 population controls. Patients with Barrett's oesophagus were substantially less likely to have antibodies for H pylori (OR = 0.42, 95% CI 0.26 to 0.70) than population controls; this inverse association was stronger among those with lower body mass indexes (BMIs < 25, OR = 0.03, 95% CI 0.00 to 0.20) and those with CagA+ strains (OR = 0.08, 95% CI 0.02 to 0.35). The associations were diminished after adjustment for GORD symptoms. The H pylori status was not an independent risk factor for Barrett's oesophagus compared with the GORD controls. CONCLUSIONS: Helicobacter pylori infection and CagA+ status were inversely associated with a new diagnosis of Barrett's oesophagus. The findings are consistent with the hypothesis that H pylori colonisation protects against Barrett's oesophagus and that the association may be at least partially mediated through GORD.

Controlling charge injection in organic field-effect transistors using self-assembled monolayers.

We have studied charge injection across the metal/organic semiconductor interface in bottom-contact poly(3-hexylthiophene) (P3HT) field-effect transistors, with Au source and drain electrodes modified by self-assembled monolayers (SAMs) prior to active polymer deposition. By using the SAM to engineer the effective Au work function, we markedly affect the charge injection process. We systematically examine the contact resistivity and intrinsic channel mobility and show that chemically increasing the injecting electrode work function significantly improves hole injection relative to untreated Au electrodes.

Octreotide for acute esophageal variceal bleeding: a meta-analysis.

BACKGROUND & AIMS: Studies of octreotide have not demonstrated a consistent benefit in efficacy or safety compared with conventional therapies. This study statistically pooled existing trials to evaluate the safety and efficacy of octreotide for esophageal variceal hemorrhage. METHODS: We identified randomized trials of octreotide for variceal hemorrhage from computerized databases, scientific meeting abstracts, and the manufacturer of octreotide. Blinded reviewers abstracted the data, and a meta-analysis was performed. RESULTS: Octreotide improved control of esophageal variceal hemorrhage compared with all alternative therapies combined (relative risk [RR], 0.63; 95% confidence interval [CI], 0.51-0.77); vasopressin/terlipressin (RR, 0.58; 95% CI, 0.42-0.81); or no additional intervention/placebo (among patients that received initial sclerotherapy/banding before randomization) (RR, 0.46; 95% CI, 0.32-0.67). Octreotide had comparable efficacy to immediate sclerotherapy for control of bleeding (RR, 0.94; 95% CI, 0.55-1.62), fewer major complications than vasopressin/terlipessin (RR, 0.31; 95% CI, 0.11-0.87), and a complication profile comparable to no intervention/placebo (RR, 1.06; 95% CI, 0.72-1.55). No specific alternative therapy demonstrated a mortality benefit. CONCLUSIONS: These results favor octreotide over vasopressin/terlipressin in the control of esophageal variceal bleeding and suggest it is a safe and effective adjunctive therapy after variceal obliteration techniques. Trials are needed to determine the optimal dose, route, and duration of octreotide treatment.

Oesophageal and gastric cardia adenocarcinomas: analysis of regional variation using the Cancer Incidence in Five Continents database.

BACKGROUND: Adenocarcinomas of the oesophagus and proximal stomach are the most rapidly increasing malignancies in some countries; however, there are no comparative studies on global disease incidence, and the relationships between these two malignancies are undefined. METHODS: We evaluated the cumulative rates and age-specific incidence rates per 100 000 population for adenocarcinomas of the oesophagus and proximal stomach for all countries in the Cancer Incidence in Five Continents database, and compared them with rates for oesophageal squamous cell carcinoma. RESULTS: Substantial variations in cumulative cancer rates were found between genders, between countries, between different ethnicities within the same country, and within the same ethnicity residing in different countries. Cumulative rates (ages 0-74 years) for oesophageal adenocarcinoma varied from 0 (e.g. Thailand) to 0.6 (Scotland, males, 95% CI : 0.56, 0.64); for proximal stomach cancer from 0 (Singapore, Malay females, 95% CI : -0.01, 0.11) to 0.52 (The Netherlands, males, 95% CI : 0.49, 0.55); and for oesophageal squamous cell carcinomas from 0 (non-Jews in Israel, females) to 1.84 (Brazil, Porto Alegre, males, 95% CI : 1.42, 2.26). There was a continuous increase in age-specific incidence rates with advancing age for oesophageal/proximal stomach adenocarcinomas, but a decrease in age-specific incidence rates for oesophageal squamous cell carcinoma after age 75 years. The cumulative rate trends for adenocarcinomas of the oesophagus and proximal stomach were often dissimilar, and varied by country, gender, and ethnicity. CONCLUSIONS: These results suggest that different risk factors may be associated with adenocarcinomas of the oesophagus versus the proximal stomach; the marked rate variation implies a substantial environmental component to the recent incidence changes.

Accuracy of endoscopic databases for assessing patient symptoms: comparison with self-reported questionnaires in patients infected with the human immunodeficiency virus.

BACKGROUND: Endoscopic databases are increasingly used for clinical research, but their validity as research instruments has not been assessed. We compared the accuracy of endoscopic indications recorded in an endoscopic database with patient symptom questionnaires. METHODS: All patients infected with the human immunodeficiency virus referred to the outpatient gastroenterology practice were prospectively evaluated using recognized symptom questionnaires. For patients undergoing esophagogastroduodenoscopy, the procedure indications recorded in the endoscopic database and the patient's self-reported symptom scores were compared. RESULTS: Ninety-three patients were evaluated. The symptoms of nausea/vomiting, diarrhea, and anorexia were highly predictive for the presence of these symptoms on the patient questionnaires. The symptoms of dyspepsia/abdominal pain did not predict well the presence of these symptoms on the questionnaire. Patients reported frequent and severe symptoms that were not recorded as indications for the procedures. The overall agreement (kappa statistic) was highly variable, from slight (kappa = 0.07 for anorexia) to moderate (kappa = 0.44 for diarrhea). CONCLUSIONS: Endoscopic indications are variably associated with self-reported symptom scores. These findings raise concerns about using some endoscopic database indications as accurate representations of patients' symptoms. Until performance characteristics of a given database are known, symptom-oriented research should use validated questionnaires whenever possible.

Evaluation of upper gastrointestinal tract symptoms in patients infected with HIV.

OBJECTIVE: Upper gastrointestinal tract (UGI) symptoms are frequent in patients infected with the human immunodeficiency virus (HIV), but little published information exists about their characteristics or methods of evaluation. We evaluated the prevalence of nonesophageal UGI symptoms in a referral population, the utility of esophagogastroduodenoscopy (EGD) for diagnosis, and clinical predictors of abnormal endoscopic findings in patients infected with HIV. METHODS: All HIV-infected patients referred to.the outpatient gastroenterology clinics were prospectively evaluated using recognized symptom questionnaires. EGD indications, results, and the patients' self-reported symptom scores were compared. HIV-infected patients undergoing EGD were compared with HIV-infected patients not receiving an EGD and with symptomatic non-HIV-infected patients undergoing EGD. RESULTS: A total of 201 patients completed 280 questionnaires. Among 93 patients who underwent endoscopy, severe symptoms occurring at least several times per week included: anorexia (70%), upper abdominal pain (34%), vomiting (32%), or a recent weight loss of approximately 15 lb (31%). Patients undergoing EGD had more frequent/severe symptoms, but did not have differences in overall well-being or mean GI symptom score. The frequency of substantial and treatable endoscopic findings among patients infected with HIV was comparable to that found in the non-HIV-infected control group. There were no independent symptoms predicting substantial or treatable disease on EGD. CONCLUSIONS: We conclude that: 1) upper gastrointestinal symptoms are common in HIV-infected patients referred for GI consultation; 2) symptomatic HIV patients have a high prevalence of both treatable and untreatable upper GI pathologies; 3) and physicians use symptom frequency and severity to select patients for EGD, but these factors correlate poorly with abnormalities on EGD. Given this discrepancy, longitudinal study is needed to determine whether treating endoscopic abnormalities improves UGI symptoms.

Early indicators of prognosis in upper gastrointestinal hemorrhage.

OBJECTIVE: Endoscopy allows accurate risk stratification of patients presenting with gastrointestinal bleeding; frequently, however, it is not immediately available. Initial management and triage of patients thus depends on nonendoscopic information. We sought to risk stratify patients with upper gastrointestinal bleeding using variables available on initial presentation (ie., before endoscopy). METHODS: A retrospective observational study was performed using data from 335 admissions with an initial diagnosis of upper gastrointestinal hemorrhage. All patients underwent endoscopy and were evaluated for an adverse outcome during their hospitalization. An adverse outcome was defined as death, the need for any operation, recurrent hematemesis, recurrent melena after initial clearing, or a hematocrit falling despite transfusion. RESULTS: Univariate analysis identified 17 distinct variables associated (p < 0.05) with an adverse outcome. A stepwise logistic regression identified five variables as independent predictors (p < 0.05) of an adverse outcome: an initial hematocrit <30%, initial systolic blood pressure < 100 mm Hg, red blood in the nasogastric lavage, history of cirrhosis or ascites on exam, and a history of vomiting red blood. We derived a decision rule based on patients having 0-5 of these independent predictors. This decision rule allowed identification of a large patient population with a <10% chance of an adverse outcome. CONCLUSION: Risk stratification is possible from information available at the time of initial presentation. If confirmed in other populations, these predictors can be used to identify patients who require a less intensive level of care.