Interleukin-1 beta single-nucleotide polymorphism's C allele is associated with elevated risk of gastric cancer in Helicobacter pylori-infected Peruvians.

Particular alleles of the interleukin-1B (IL-1B) gene have been correlated with increased risk of atrophic gastritis and gastric cancer in the populations of East Asia and Europe. No such data exist from Peru, a developing country with a population genotypically different from others studied and with a high prevalence of Helicobacter pylori infection and gastric cancer. We conducted a case-control study comparing 334 hospitalized patients with atrophic gastritis or gastric cancer with 158 nonatrophic gastritis patients (controls). Conditional logistic regression analysis revealed that an increased risk of atrophic gastritis (odds ratio, 5.60) and gastric cancer (odds ratio, 2.36) was associated with the IL-1B-511 C allele. Our study is the first to establish this allele as a risk for these conditions. Given the high prevalence of H. pylori and recurrence rate after treatment, IL-1B-511 single-nucleotide polymorphism analysis may identify those individuals who would benefit most from robust H. pylori eradication efforts in Peru.

Susceptibility-guided vs. empiric retreatment of Helicobacter pylori infection after treatment failure.

Successful eradication of Helicobacter pylori after failure of standard triple therapy is difficult because of the higher resistance to metronidazole and clarithromycin. We evaluated the efficacy of susceptibility-guided vs. empiric retreatment for H. pylori after at least one treatment failure and determined the prevalence of posttreatment antibiotic resistance. Forty-nine patients in whom at least one treatment regimen for H. pylori eradication had failed underwent gastric biopsy and culture and were retreated according to the in vitro susceptibility results. Findings were compared with those for 49 control patients referred to our center for a (13)C-urea breath test. H. pylori eradication was assessed by urea breath test at least 6 weeks after retreatment in both groups. Susceptibility-guided retreatment was associated with better eradication rates than empiric treatment. The difference remained significant in stratified and multivariate analysis. Susceptibility-guided retreatment appears to be significantly more effective than empiric retreatment in eradicating H. pylori after at least one previous treatment failure.

Validity of serum pepsinogen levels and quininium resin test combined for gastric cancer screening.

BACKGROUND: To investigate the feasibility of combining several serum markers into a valid serum screening tool for gastric cancer, we performed a study evaluating the association between gastric cancer and precancerous conditions and a blood test for gastric acidity (the blood quininium resin test [QRT]) combined with serum pepsinogen levels. METHODS: We performed immunoradiometric assays of serum pepsinogen I (PG I), II (PG II) levels, and QRT's in 10 endoscopically normal subjects, in 20 patients with chronic atrophic gastritis, and in 13 patients with biopsy-confirmed gastric adenocarcinoma. RESULTS: Serum PG I, II levels, I/II ratio were significantly different among normal, gastritis, and cancer patients. Serum PG I/II ratios were much lower in cancer patients. Serum quinine levels by QRT were correlated with PG I/II ratio (rs=0.39, p<0.01). Age was negatively correlated both with PG I/II ratio (rs=-0.58, p<0.01) and serum quinine level (rs=-0.45, p<0.01). The screening using serum PG levels was more valid (sensitivity of 69%, specificity of 77%) than that using QRT alone. The combination of serum PG levels and QRT increased specificity for detecting gastric cancer to 87% without altering sensitivity. CONCLUSION: Although blood QRT is a useful addition to other serum screening tests for gastric cancer, these tests alone are not sufficiently accurate as screening tools for gastric cancer.

Outcome after negative colposcopy among human immunodeficiency virus-infected women with borderline cytologic abnormalities.

OBJECTIVE: To estimate the risk of and risk factors for progression among human immunodeficiency virus (HIV)-seropositive women with abnormal cervical cytology but negative colposcopy. METHODS: In a prospective cohort study, 391 HIV-seropositive and 103 seronegative women with cervical cytology read as atypical squamous cells (ASC) or low-grade squamous intraepithelial lesion (LSIL) but negative colposcopy were followed up for a mean of 4.0 years with cytology at 6-month intervals. Colposcopy was prescribed for any epithelial abnormality. RESULTS: Progression to CIN2, CIN3, high-grade SIL/severe dysplasia, or cancer occurred in 47 (12%) HIV-seropositive women and 4 (4%) HIV-seronegative women (P = .02). Progression to CIN1 was seen in an additional 12 HIV-seropositive women and 1 seronegative woman. In multivariate analysis, high-risk but not low-risk HPV detection (hazard ratio [HR] 2.46-95% confidence interval [CI] 1.18-5.12, P = .02 for high risk, HR 1.41, 95% CI 0.62-3.21, P = .42 for low risk), satisfactory colposcopy (HR 2.01, 95% CI 1.11-3.65, P = .02), and non-Hispanic African-American ethnicity (HR 5.08, 95% CI 1.72-14.98, P = .003) were the only factors associated with progression, while HIV serostatus was marginally significant (HR 2.53, 95% CI 0.85-7.50, P = .09). CONCLUSION: Human immunodeficiency virus-seropositive women with negative colposcopy after borderline cytology face a higher risk of progression than seronegative women, but the absolute risk is low and becomes nonsignificant after controlling for HPV risk type, ethnicity, and colposcopic findings. Observation is appropriate. LEVEL OF EVIDENCE: II-2.

Natural history of grade 1 cervical intraepithelial neoplasia in women with human immunodeficiency virus.

OBJECTIVE: We sought to estimate rates of progression and regression of grade 1 cervical intraepithelial neoplasia (CIN 1) among women with human immunodeficiency virus (HIV). METHODS: In a multicenter prospective cohort study, HIV-seropositive and HIV-seronegative women were evaluated colposcopically after receiving an abnormal cytology test result between November 1994 and September 2002. Women with CIN 1 were included, except those who had undergone hysterectomy, cervical therapy, or had CIN 2-3 or cervical cancer. Those women who were included were followed cytologically twice yearly, with colposcopy repeated for atypia or worse. RESULTS: We followed 223 women with CIN 1 (202 HIV seropositive and 21 HIV seronegative) for a mean of 3.3 person-years. Progression occurred in 8 HIV-seropositive women (incidence density, 1.2/100 person-years; 95% confidence interval [CI] 0.5-2.4/100 person-years) and in no HIV seronegative women. Regression occurred in 66 (33%) HIV-seropositive women (13/100 person-years, 95% CI 10-16/100 person-years) versus 14 (67%) seronegative women (32/100 person-years, relative risk 0.40, 95% CI 0.25-0.66; P < .001). In multivariate analysis, regression was associated with human papillomavirus (HPV) detection (hazard ratio [HR] for low risk 0.28, 95% CI 0.13-0.61, P = .001; and for high-risk 0.34, 95% CI 0.20-0.55, P < .001 versus no HPV detected) and Hispanic ethnicity (HR 0.48, 95% CI 0.230.98; P = .04); HIV serostatus was only marginally linked to regression (HR 0.52, 95% CI 0.27-1.03; P = .06), but seropositive women were less likely to regress when analysis was limited to 146 women with HPV detected at CIN 1 diagnosis (HR 0.18, 95% CI 0.05-0.62; P = .006). CONCLUSION: Grade 1 cervical intraepithelial neoplasia infrequently progresses in women with HIV. Thus, observation appears safe absent other indications for treatment. LEVEL OF EVIDENCE: II-1.

Helicobacter pylori: consensus and controversy.

Helicobacter pylori is uniquely adapted to colonize the human stomach. Infection leads to a range of subclinical and clinical outcomes that depend on properties of the infecting strain, the host, and the environment. Eradication therapy is indicated for infected persons who develop peptic ulcer disease or gastric lymphoma or who are beginning long-term treatment with nonsteroidal anti-inflammatory drugs. However, treatment may worsen gastroesophageal reflux disease and increase the risk of esophageal cancer. H. pylori infections can be diagnosed noninvasively and can be eradicated with approximately 85% success by a variety of multidrug, 7-14-day regimens. Unfortunately, antibiotic resistance is affecting treatment effectiveness in the United States and abroad. A more complete understanding of the variation in H. pylori pathogenesis should lead to clearer recommendations about treatment for infected persons who have neither peptic ulcer disease nor gastric lymphoma.