Adherence with National Comprehensive Cancer Network posttreatment surveillance guidelines in patients with head and neck cancer.

BACKGROUND: Surveillance in head and neck cancer (HNC) is essential to detect recurrent or new lesions and to optimize function. This study describes drivers of surveillance adherence in patients with HNC and its effect on prognosis. METHODS: Adherence with surveillance of HNC patients was determined using the National Comprehensive Cancer Network HNC guidelines. Logistic regression and Cox proportional hazards models were used to determine predictors of adherence and overall survival (OS). RESULTS: Results showed that 110 of 221 patients (50.2%) were adherent with surveillance. Distance from the treatment center was the only significant association. Adherence was not associated with OS following multivariate adjustment (adjusted hazard ratio [aHR] = 0.68, 95% confidence interval [CI] = 0.43-1.09). However, 5-10 years after treatment completion, adherence was an independent predictor of survival (aHR = 0.24, 95% CI = 0.09-0.61). CONCLUSION: Adherence with surveillance is important in improving survival in patients with HNC, especially in the long term.

Utilization of rehabilitation services in patients with head and neck cancer in the United States: A SEER-Medicare analysis.

BACKGROUND: Head and neck cancer (HNC) and its treatment lead to functional impairments. Rehabilitation by speech-language pathology (SLP) and occupational/physical therapy (OT/PT) can decrease morbidity. METHODS: The Surveillance, Epidemiology and End Results-Medicare data for patients with HNC diagnosed between 2002 and 2011 was utilized to evaluate posttreatment rehabilitation. RESULTS: In 16 194 patients, the overall utilization rate was 20.7% for SLP and 26.2% for OT/PT services. Treatment modality was significantly associated rehabilitation utilization. Compared to patients treated with primary surgery, those treated with primary radiotherapy had significantly lower odds of OT/PT utilization. Patients treated with surgery plus adjuvant treatment and primary concurrent chemoradiation had higher odds of SLP utilization compared to patients treated with surgery alone. CONCLUSIONS: Rehabilitation services appeared to be underutilized by patients with HNC in the United States and vary with treatment modality. There is a need to improve integration of rehabilitation services into the HNC care continuum. SUMMARY: Rehabilitation services are underutilized by patients with HNC during posttreatment surveillance in the United States. Treatment modality significantly impacts rehabilitation utilization patterns.

Two-year prevalence of dysphagia and related outcomes in head and neck cancer survivors: An updated SEER-Medicare analysis.

BACKGROUND: The aim of the study was to examine prevalence of dysphagia at the population level in head and neck cancer (HNC) survivors. METHODS: Surveillance, Epidemiology, and End Results-Medicare claims among 16 194 patients with HNC (2002-2011) were analyzed to estimate 2-year prevalence of dysphagia, stricture, and aspiration pneumonia, and derive treatment- and site-specific estimates. RESULTS: Prevalence of dysphagia, stricture, pneumonia, and aspiration pneumonia was 45.3% (95% confidence interval [CI]: 44.5-46.1), 10.2% (95% CI: 9.7-10.7), 26.3% (95% CI: 25.6-26.9), and 8.6% (95% CI: 8.2-9.1), respectively. Dysphagia increased by 11.7% over the 10-year period (P < .001). Prevalence was highest after chemoradiation and multimodality therapy. CONCLUSION: Comparing to published rates using similar methodology the preceding decade (1992-1999), prevalence of dysphagia based on claims data was similar in 2002-2011 in this study. These results suggest persistence of dysphagia as a highly prevalent morbidity, even in the decade in which highly conformal radiotherapy and minimally invasive surgeries were popularized.

Improving patient outcomes through multidisciplinary treatment planning conference.

BACKGROUND: The purpose of this study was for us to determine National Comprehensive Cancer Network (NCCN) guideline-compliance of multidisciplinary conference (MDC) recommendations and actual treatment received, and to determine this impact on patient outcomes. METHODS: We conducted a retrospective review of patients presented at MDC between January 1, 2006, and December 31, 2006, with previously untreated incident cancers. RESULTS: We identified 232 patients, for whom MDC recommendations were NCCN guideline-compliant in 201 (86.6%). Actual treatment was NCCN guideline-compliant in 170 of 197 patients (86.3%). Adherence of MDC recommendations to NCCN guidelines was associated with superior overall survival (hazard ratio [HR] = 0.69; 95% confidence interval [CI] = 0.33-1.39; p = .3), as was guideline-compliance of actual treatment (HR = 0.6; 95% CI = 0.64-1.07; p = .07); congruence between MDC recommendations and actual treatment conferred a statistically significant overall survival benefit (HR = 0.49; 95% CI = 0.27-0.89; p = .02). CONCLUSION: Our findings argue for patient-centered application of NCCN guidelines. Prospective evaluation will enable more timely identification of systematic NCCN guideline deviations that quality improvement interventions may address. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1820-E1825, 2016.

Mortality among Soviet and Russian cosmonauts: 1960-2013.

INTRODUCTION: Though the mortality of U.S. astronauts has been studied repeatedly in the last 20 yr, little is known about the long-term mortality trends of Soviet and Russian cosmonauts. METHODS: Using data from 266 cosmonauts accepted into cosmonaut training from 1960 to 2013, we document the causes of death and crude death rates among cosmonauts. Using standardized mortality ratios (SMR), we compared cosmonauts to the general populations of Russia and Ukraine, and to 330 U.S. astronauts. RESULTS: Cosmonauts experienced significantly lower all-cause mortality risk compared to the general population. However, cosmonauts were at almost double the risk of all-cause mortality in comparison to U.S. astronauts (SMR = 190, 95% C.I. 154-239). Cosmonauts were also at greater risk of circulatory disease (SMR = 364, 95% C.I. 225-557) and cancer (SMR = 177, 95% C.I. 108-274) compared to U.S. astronauts. Though not statistically significant, cosmonauts experienced fewer fatal accidents (SMR = 88, 95% C.I. = 54-136) than their U.S. counterparts. DISCUSSION: Cosmonauts are at much lower risk of all-cause mortality than the general populations of Russia and Ukraine, yet are at greater risk for death by cardiovascular disease and cancer than are U.S. astronauts. This disparity may have common roots with decreases in life expectancy in Russia in recent decades. Further research is needed to understand these trends fully.

Utilization of lymph node dissection, race/ethnicity, and breast cancer outcomes.

OBJECTIVES: Although large differences by race/ethnicity in breast cancer survival are well established, it is unknown whether disparities in nodal surgery utilization explain the racial/ethnic disparities in survival among women with micrometastasis and macrometastasis in sentinel lymph nodes (SLNs). STUDY DESIGN: Retrospective cohort study. METHODS: Women with breast cancer who underwent sentinel lymph node biopsy (SLNB) and who were found to have nodal metastases were identified from the Surveillance, Epidemiology, and End Results database (1998-2005). Outcomes data were examined for patients who underwent SLNB alone versus SLNB with axillary lymph node dissection (ALND). RESULTS: Proportions of patients receiving SLNB alone or receiving SLNB with a complete ALND were not statistically different among women of different racial/ethnic backgrounds (P = .8). Patients of African American descent or Hispanic origin had reduced overall survival, whereas patients of Hispanic origin had reduced diseasespecific survival after adjusting for selected covariates. Adjusting for nodal surgery did not reduce racial/ethnic disparities in overall survival or disease-specific survival. CONCLUSIONS: The disparities in survival among African American and Hispanic women with breast cancer are not explained by nodal surgery utilization among women with micrometastasis and macrometastasis in SLNs.

Chemotherapy use and risk of bone marrow suppression in a large population-based cohort of older women with breast and ovarian cancer.

We studied 65,521 women with breast cancer and 7,420 women with ovarian cancer aged ≥ 65 identified from the 16 areas of the Surveillance, Epidemiology and End Results program linked with Medicare data during 1991-2002. Bone marrow toxicity associated with chemotherapy was defined using diagnosis codes from Medicare inpatient, outpatient and physician claims. The time to event Cox regression was utilized to estimate the risk of bone marrow toxicity. Use of anthracyclines, taxanes or platinums was associated with increased risks of short- (≤3 months) and long-term (>3 months) anemia and neutropenia in patients with breast cancer. Alkylating agents or antimetabolites were additional significant predictors of anemia in women with ovarian cancer. Patients who received chemotherapy (irrespective of regimens) were twice (breast cancer) or three times (ovarian cancer) as likely to develop thrombocytopenia compared to those not receiving chemotherapy. Among women with breast cancer, patients receiving cyclophosphamide, methotrexate and fluorouracil regimens (hazard ratio=19.0, 95% CI=11.2-32.5), platinum/taxane therapy (21.9, 11.9-40.4) or the cyclophosphamide, adriamycin and fluorouracil regimen (32.5, 19.6-53.9) were strongly associated with risk of aplastic anemia. There was a dose-response relationship between the use of taxane or platinum and the risk of bone marrow suppression, whereas the increased risk of bone marrow toxicity was consistently higher in those with use of alkylating agents or anthracycline-based regimens irrespective of the increasing number of cycles received. In conclusion, there was an association between chemotherapy use and clinical manifestations of bone marrow toxicities in a population-based setting.

Exposure to antibiotics in a United States-Mexico border birth cohort.

OBJECTIVE: The goal was to compare the frequency of children's antibiotic intake, emphasizing antibiotics with anti-Helicobacter pylori effects, in El Paso, Texas, and Juarez, Mexico. METHODS: Hispanic children were enrolled prenatally at mother-child clinics in El Paso, and Juarez, in 1998-2000, to identify determinants of H pylori infection. During follow-up examinations targeted every 6 months from 6 to 84 months of age, caretakers reported medication use during the preceding interval. Courses of any systemic and H pylori-effective antibiotics were compared for US and Mexican children. RESULTS: Antibiotic data were available for 602 children, from 2938 follow-up visits. Overall antibiotic intake was higher in Juarez, where 84% of children received > or = 1 course during the follow-up period (52% of visits), compared with El Paso, where 76% of children received > or = 1 course (40% of visits). In contrast, the intake of H pylori-effective antibiotics was higher in El Paso, where 65% of children received > or = 1 course during the follow-up period (27% of visits), compared with Juarez, where 44% of children received > or = 1 course (16% of visits). Of H pylori-effective courses, 94% contained amoxicillin and 2% each clarithromycin, metronidazole, and furazolidone; uses were primarily for throat and ear infections, diarrhea, and cold/flu. CONCLUSIONS: Pediatric antibiotic use was higher in Mexico than on the US side of the border. Apparent misuse of H pylori-effective antibiotics was more frequent in Juarez but also occurred in El Paso. Such misuse of antibiotics may lead to drug resistance and may impair the control of H pylori infection in this region.

Risk of chemotherapy-induced peripheral neuropathy in large population-based cohorts of elderly patients with breast, ovarian, and lung cancer.

There is little information on chemotherapy-induced peripheral neuropathy (PN) for community-dwelling patients with cancer. We studied 65,316 patients with breast cancer, 9242 with ovarian cancer, and 86,278 with non-small cell lung cancer from 1991 through 2002 identified from the 16 areas of Surveillance, Epidemiology and End Results. The incidence density of PN was 15.3, 21.5, and 18.3 per 1000 person-years for patients with breast, ovarian, and lung cancer who received platinum-taxane combination chemotherapy, respectively. Patients with breast, ovarian, and lung cancer receiving taxanes were more than twice as likely to develop PN compared with those not receiving chemotherapy (adjusted hazard ratio = 2.22, 95% confidence interval = 1.85-2.66 in patients with breast cancer), whereas patients who received platinum-taxane combination chemotherapy were more than 3 times as likely to develop PN compared with women who did not receive chemotherapy (adjusted hazard ratio = 3.33, 95% confidence interval = 2.05-5.05). In patients with ovarian or lung cancer receiving taxanes or platinum-taxane combination therapy, the risk of PN was increased with increasing number of chemotherapy cycles. These findings remained similar after adjusting for the history of preexisting PN or diabetes. Close monitoring for PN in patients receiving taxanes alone or in combination with platinum compounds may be warranted.

Risk of hospitalizations associated with adverse effects of chemotherapy in a large community-based cohort of elderly women with ovarian cancer.

PURPOSE: To determine the rates of hospitalization after receiving chemotherapy in patients who were diagnosed with ovarian cancer and to examine significant predictors for hospitalizations. METHODS: We studied 9361 women who were diagnosed with stages I to IV ovarian cancer at age 65 or older in 1991 to 2002, identified from the 16 areas of the Surveillance, Epidemiology, and End Results program linked with Medicare data. Hospitalization for adverse effects associated with chemotherapy was defined using primary and secondary diagnosis codes from the inpatient claims. Multivariate logistic regression was used to estimate the risk of being hospitalized for adverse effects in patients receiving chemotherapy compared with those who did not. RESULTS: A total of 1363 patients (14.6% of 9361) received platinum-based chemotherapy without taxane, 3094 patients (33.1%) received platinum-taxane combination chemotherapy, 1694 patients (18.1%) administered other (nonplatinum) chemotherapy, and 3210 patients (34.3%) did not receive chemotherapy. Compared with those receiving platinum-based chemotherapy, patients receiving nonplatinum chemotherapy had a higher risk of being hospitalized for infection (odds ratio [OR], 1.66; 95% confidence interval [95% CI], 1.19-2.31), whereas patients who did not receive chemotherapy (OR, 0.16; 95% CI, 0.10-0.28) or received platinum-taxane combination chemotherapy (OR, 0.54; 95% CI, 0.34-0.86) were significantly less likely to be hospitalized for hematologic toxicities. Although both comorbidity scores and age were significant predictors for hospitalization for infection and cardiovascular diseases, older age was not a significant predictor for gastrointestinal and hematologic toxicities. CONCLUSIONS: The nonplatinum chemotherapeutic regimens were associated with higher rates of hospitalizations for gastrointestinal and hematologic conditions or infections compared with platinum-based or platinum-taxane combination regimens. Comorbidity was a significant predictor for hospitalization for infections and gastrointestinal and cardiovascular diseases.

Racial disparities and survival for nonsmall-cell lung cancer in a large cohort of black and white elderly patients.

BACKGROUND: This study aimed to examine disparities in survival and associated factors for patients with nonsmall-cell lung cancer (NSCLC) and to determine whether racial disparities varied over time (1991-1995, 1996-1999, and 2000-2002). METHODS: The authors studied 70,901 patients aged>or=65 years with stage I-IV NSCLC identified from Surveillance, Epidemiology, and End Results/Medicare data. Multivariate time-to-event survival analyses were completed using Cox proportional regression modeling. RESULTS: The 5-year observed lung cancer-specific survival rates were 52.7% for whites and 47.5% for blacks with stage I-II disease, and 17.7% and 19.6% for whites and blacks, respectively at stages III-IV. After controlling for standard treatment, socioeconomic status (SES), and other factors, there were no significant differences in all-cause mortality, or lung cancer-specific mortality between black and white patients with stage I-II or III-IV lung cancer. However, blacks had an increased risk for overall all-cause mortality at stage I-IV (hazard ratio [HR], 1.24; 95% confidence interval, 1.13-1.35), and during 2000-2002 at stage III-IV for all-cause mortality (HR, 1.22; 95% CI, 1.02-1.47) and lung cancer-specific mortality (HR, 1.24; 95% CI,1.01-1.53). Standard treatment was significantly associated with increased survival, whereas poor SES was associated with increased mortality. CONCLUSIONS: There were no significant differences in survival between blacks and whites with NSCLC within stage stratifications after adjusting for covariates, except for black patients at overall stage for all-cause mortality and at stage III-IV diagnosed in 2000-2002. Receiving stage-specific evidence-based standard therapy was associated with significantly increased survival.

Gene expression in Barrett's esophagus: laser capture versus whole tissue.

OBJECTIVE: Diagnosis of Barrett's esophagus (BE) is typically done through morphologic analysis of esophageal tissue biopsy. Such samples contain several cell types. Laser capture microdissection (LCM) allows the isolation of specific cells from heterogeneous cell populations. The purpose of this study was to determine the degree of overlap of the two sample types and to define a set of genes that might serve as biochemical markers for BE. MATERIAL AND METHODS: Biopsies were obtained from regions of the glandular tissue of BE and normal esophagus from 9 subjects with BE. Samples from 5 subjects were examined as whole tissue (BE [whole]; E [whole]), and in 4 subjects the glandular epithelium of BE was isolated using LCM (BE [LCM]) and compared with the averaged values (E [LCM]) for both basal cell (B [LCM]) and squamous cell (S [LCM]) epithelium. RESULTS: Gene expression revealed 1797 probe sets between BE [whole] and E [whole] (fold change > 2.0; p<0.001). Most of these genes (74%) were also differentially expressed between BE [LCM] and E [LCM], showing that there was high concordance between the two sampling methods. LCM provided a great deal of additional information (2113 genes) about the alterations in gene expression that may represent the BE phenotype. CONCLUSIONS: There are differences in gene expression profiles depending on whether specimens are whole tissue biopsies or LCM dissected. Whole tissue biopsies should prove satisfactory for diagnostic purposes. Because the data from LCM samples delineated many more Barrett's-specific genes, this procedure might provide more information regarding pathogenesis than would whole tissue material.

Correspondence between Helicobacter pylori antibodies and urea breath test results in a US-Mexico birth cohort.

The uncertain accuracy of methods for detecting Helicobacter pylori infection in young children complicates research on this infection in early life. The aim of the present report was to describe the correspondence between positive serology and positive urea breath test (UBT) in children followed from age 0 to 24 months in the Pasitos Cohort Study, conducted along the US-Mexico border at El Paso and Juarez. Children were recruited before birth during 1998-2000 and examined at target ages of 6, 12, 18 and 24 months. H. pylori infection was detected using an enzyme immunoassay for serum immunoglobulin G antibodies and the (13)C-urea breath test corrected for age-dependent variation in CO(2) production. Of 472 children, 125 had one or more positive UBT results and 46 had one or more positive serology results. The prevalence of H. pylori infection at target ages of 6, 12, 18 and 24 months was 7%, 14%, 16% and 19%, respectively, by UBT and 8%, 2%, 3% and 3%, respectively, by serology. Few (<1%) of those tested on both tests were positive on both at any age. Among UBT-positive children, 6% were concurrently seropositive and 6% became seropositive later. Because UBT positivity cut points were selected to minimise false positives, these results suggest that H. pylori infection occurred frequently in this cohort, but rarely produced detectable antibodies. For clinical or epidemiological investigations, serology should not be used as the sole method for detecting H. pylori infection in children aged 2 years or less.

Genetic variants of glutathione S-transferase as possible risk factors for hepatocellular carcinoma: a HuGE systematic review and meta-analysis.

The authors performed a systematic review and meta-analysis to determine the effect of polymorphisms in genes encoding glutathione S-transferases (GSTs), phase II isoenzymes involved in cellular detoxification, on risk of hepatocellular carcinoma (HCC). Fifteen eligible studies were identified: 14 evaluated GSTM1; 13, GSTT1; three, GSTP1; and one each evaluated GSTM2, GSTM3, GSTA1, GSTA4, GSTO1, and GSTO2, respectively. All were case-control studies performed in populations with high (Asian, African) and medium (European) HCC incidence rates. Random-effects meta-analyses suggested a small excess risk of HCC with GSTT1 null (odds ratio (OR) = 1.19, 95% confidence interval (CI): 0.99, 1.44) and possibly GSTM1 null (OR = 1.16, 95% CI: 0.89, 1.53) genotypes. Cumulative meta-analyses demonstrated that both pooled estimators generally trended toward a small excess risk with publication of more recent studies. Results for GSTP1 A313G suggested no excess risk (OR = 0.75, 95% CI: 0.50, 1.15). A number of potentially interesting gene-gene and gene-environment interactions were reported, but these were too few and inconsistent to allow meta-analysis. The overall results suggest that there may be a small excess risk of HCC in individuals with GSTT1 null and possibly also with GSTM1 null genotypes. However, given the relatively limited total number of subjects examined and observed between-study heterogeneity, chance could not be excluded.

Epidemiology and transmission of hepatitis B and C viruses in Kazakhstan.

AIM: To investigate the epidemiology of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in the two major ethnic groups in Kazakhstan. METHODS: A cross-sectional prospective study of HBV and HCV seroprevalence was performed among individuals born in Kazakhstan with no history of chronic hepatitis or liver disease. RESULTS: There were 290 volunteers (140 Russians and 150 Kazakhs) aged 10 to 64 years, males accounted for 46%. Active HBV infection (HBsAg positive) was present in 3.8%, anti-HBc in 30%. The prevalence was similar in females and males (33% vs 25%) (P = 0.18). The prevalence of anti-HBc increased from 19% in 10-29 years old volunteers to 53% in 50-years and older volunteers. The prevalence of HBV infection was higher in married than in single adults (38% vs 26%, respectively) (P = 0.2) and more common in Kazakhs (35%) than in Russians (24%) (P = 0.07). HCV infection was present in 9 subjects (3.2%), 5 of them also were positive for anti-HBc in the absence of HBsAg. CONCLUSION: The frequency of active HBV infection (3.8%) coupled with a high prevalence of HBV exposure in those > 50 years of age increases with age, which suggests that horizontal transmission likely relates to the use of contaminated needles. The low prevalence of HCV infection suggests that HBV and HCV are acquired differently in this group of subjects.

The use of cytokeratin stain to distinguish Barrett's esophagus from contiguous tissues: a systematic review.

Our objective was to systematically review the existing literature regarding the use of cytokeratin (CK) stain in differentiating Barrett's esophagus (BE) from tissues of the gastric cardia, corpus, or antrum, with or without intestinal metaplasia (IM). Pubmed was searched for full publications in English (1983-2005) addressing the use of CK for differentiation of BE from contiguous tissues. Information was collected on the study sample, blinding, the methods used for CK staining, and for defining and applying the gold standard tests. Test characteristics were obtained or calculated. Sixteen studies (containing 46 comparisons) met the inclusion and exclusion criteria. Immunostaining for CK 7 and 20 was generally highly specific in distinguishing long-segment BE from antrum IM, fundus IM, or noncardiac gastric IM; 27 comparisons showed statistically significant differences. However, only 8 of 15 comparisons (6 of 12 studies) reported significant differences in CK staining patterns between BE and gastric cardia IM with a high sensitivity (89%-100%) and specificity (83%-100%) for long-segment BE and lower estimates for short-segment BE, while the other seven comparisons showed no significant differences and a very low sensitivity. Examination by a blinded pathologist was reported in five of six positive studies and in only one of six of the negative studies. In addition, variation in the patient populations, use of surgical resection versus endoscopic biopsies, and biopsy sampling technique in endoscopic studies may have accounted for these differences. Finally, two studies did not find significant differences in CK staining patterns between BE and normal cardiac mucosa. In conclusions, CK immunostaining has not performed well in differentiating BE, especially short-segment BE, from cardia IM. There seems to be a spectrum bias where the accuracy varies with different tested populations. CK immunostaining distinguished well between BE and IM in noncardiac segments of the stomach; however, these comparisons are not clinically relevant.

Point-of-care Helicobacter pylori urine antibody detection in a multi-ethnic adult population in the United States.

A need exists for accurate point-of-care tests for diagnosis of Helicobacter pylori (H. pylori) infection to evaluate a rapid urine-H. pylori antibody test device for detection of H. pylori infection in a point-of-care setting in the United States. A multi-center study in a multi-ethnic population compared the RAPIRUN urine antibody test with the (13)C-urea breath test (C-UBT) and a traditional serologic test, the high-molecular-weight cell-associated protein enzyme immunoassay (HM-CAP EIA). The primary comparator was with "definite positive" and "definite negative" patients defined as a concordance of combined results of the UBT and the HM-CAP IgG EIA. Overall, 188 eligible patients were enrolled (61 men, age range: 18-73 years, including 84 Hispanics, 73 Asian-Pacific Americans, 22 Black African-Americans, 6 non-Hispanic Caucasians, and 3 of "other" ethnicity). Compared with "definite positive" and "definite negative" results, the sensitivity and specificity of the urine antibody test were 0.9 and 1.0, respectively. The urine antibody test proved suitable for point-of-care rapid diagnosis of anti-H. pylori antibodies indicative of active or past H. pylori infection.

Is genomic evaluation feasible in endoscopic studies of Barrett's esophagus? A pilot study.

BACKGROUND: The global gene expression in Barrett's esophagus (BE) in comparison to adjacent or histologically similar tissues has not been extensively studied. OBJECTIVE: To test the feasibility of conducting gene arrays in endoscopically obtained mucosal specimens. DESIGN: Cross-sectional feasibility study. SETTING: The Houston Department of Veterans Affairs Medical Center. PATIENTS: We collected endoscopic biopsies from BE, normal esophagus, antrum, duodenum, and sigmoid colon from 5 patients with BE. RNA was extracted and subjected to cDNA microarrays and gene expression was compared between BE and control tissues. Reverse transcription-PCR was conducted to confirm some of the findings. MAIN OUTCOME MEASUREMENTS: Gene expression profiles in BE tissues and 4 control sites: squamous esophagus, antrum, duodenum, sigmoid colon. RESULTS: On average, 2 biopsies by disposable jumbo biopsy forceps provided approximately 5 microg required for microarrays. From the original number of 22,283 gene probes, 13,805 genes had a quality score of P < .05 and were subjected to further comparison. BE gene expression clustered most closely with that of antrum and least closely with squamous esophagus. Of the 587 genes that had significantly different expression between BE and duodenum, 246 were upregulated and 341 were downregulated in BE. The expression of genes involved in apoptosis, negative regulation of apoptosis, and inflammatory response was significantly lower in BE compared to squamous esophagus. None of the gene groups were significantly overexpressed in BE compared to squamous esophagus or antrum. The reverse transcription-PCR confirmed the results of microarrays. LIMITATIONS: Small sample size. CONCLUSIONS: Microarray-based studies are feasible in endoscopically obtained tissues. Differences in gene expression could identify potential markers and shed light on the pathogenesis of BE.

Problem of distinguishing false-positive tests from acute or transient Helicobacter pylori infections.

BACKGROUND: Reliable detection of acute Helicobacter pylori infections remains problematic. The high prevalence of false-positive non-invasive tests in low H. pylori prevalence populations makes identification of acute and transient infections difficult. METHODS: We explored the use of serum pepsinogens (PG) for diagnosis of acute infection in patients following H. pylori challenge such that the onset of the infection was known. We then compared those findings to a group of children with presumed acute infections defined as a positive urea breath test (UBT) and negative IgG serology. RESULTS: We examined the pattern and calculated cut-off values of PG levels in 18 adult volunteers with known acute H. pylori infection. We then compared the results with sera from nine symptomatic children with presumed acute H. pylori infection and a matched control group of nine children who did not meet criteria for acute H. pylori infection. In acute infection, both PGI and II levels increased following H. pylori infection reaching a peak by 2 weeks post-infection. The frequency of a positive test defined as a value > mean +2 SD was 17, 71, and 94% at week 1, 2, and 4 post-infection, respectively. Only one child with presumed acute H. pylori infection had an elevated serum PGI and one had an elevated PGII. Five of the children had follow-up UBTs and four were negative consistent with the diagnosis of false-positive UBT. H. pylori infection was confirmed in the child with an elevated PGI level. CONCLUSIONS: These data suggest that a single positive noninvasive test in populations of low prevalence is most likely a false-positive result. This suggests that a single positive test requires confirmation preferably using a test that measures a different parameter (e.g., UBT confirmed by stool antigen test). It appears that most "transient"H. pylori infections are diagnosed on the basis of false-positive tests. PG levels are possible candidates as the confirmatory test.

Noninvasive versus histologic detection of gastric atrophy in a Hispanic population in North America.

BACKGROUND & AIMS: Cancer risk is directly correlated with the severity and extent of mucosal atrophy, making identification of atrophy a goal in cancer prevention programs. The aim of this study was to compare targeted histology with noninvasive testing for the identification of antral and/or corpus atrophy in North America. METHODS: In a cross-sectional study of a random sample of households, 8 gastric biopsy specimens were obtained from defined locations in the antrum and corpus. Biopsies were scored for the presence of Helicobacter pylori and gastric atrophy (defined as loss of normal glandular components). Atrophy was scored by using the Sydney system and a system based on the number and location of corpus biopsies with atrophy. Patients' sera were examined for pepsinogen I, pepsinogen II, and gastrin-17 (fasting and stimulated). RESULTS: One hundred eighty volunteers, approximately 30 per age group and ranging in age from 18-82 years, participated. There were 76 men. The overall weighted prevalence of a corpus atrophy was 4.7% (95% confidence interval, 2.3-7.0). There was a significant inverse relationship between the grade of corpus atrophy and the pepsinogen I/pepsinogen II ratio (R = -0.31, P < .01). We failed to confirm the usefulness of the proposed algorithm by using gastrin-17, H. pylori serology, and serum pepsinogens to categorize the gastric histology. The Sydney system underestimated the prevalence of corpus atrophy by approximately 25%. CONCLUSION: Noninvasive testing is both possible and practical by using pepsinogen assays for the identification of the precancerous condition of moderate to severe corpus atrophy in North American Hispanic patients.