Influence of ApoE and FABP2 polymorphisms and environmental factors in the susceptibility to gallstone disease.

BACKGROUND: Gallstone disease (GSD) is a common chronic disease in the Western hemisphere, yet environmental and genetic factors may be responsible for the variations in the prevalence of GSD among populations. AIM: To analyze the relationship of the ApoE and FABP2 polymorphisms with diet, physical activity and emotional health in patients with GSD from West Mexico. MATERIAL AND METHODS: A total of 120 patients with GSD and 370 healthy subjects were enrolled. Anthropometric, biochemical, nutritional, clinical and physical activity parameters were measured. ApoE and FABP2 genotypes were assesed by PCR-RFLPs assays. RESULTS: ApoE E3/E4 genotype and the ApoE E4 allele was highly prevalent among the GSD patients compared to the controls (32% vs. 12.0% and 22% vs. 8.4% respectively p < 0.01). Patients with the Apo E4 allele showed an upward trend of cholesterol levels compared to non-Apo E4 allele carriers (E4 186 ± 30 mg/dL; E3 143 ± 37 mg/dL; E2 129 ± 34 mg/dL). High triglyceride levels were associated with patients that were FABP2 Thr54 allele carriers (p < 0.05) but lacked association with GSD. This may be due to changes in dietary fats after GSD diagnosis, masking the clinical course of the disease. Sedentary lifestyle and negative emotions were detected in 83% and 63% of patients, respectively. CONCLUSION: These data suggest that the Apo E4 allele could confer genetic susceptibility for the development of GSD among the Mexican population. The Ala54Thr polymorphism of FABP2 was associated with high triglycerides levels, but not to GSD; suggesting that environmental factors modulate such susceptibility.

Correlating routine cytology, quantitative nuclear morphometry by digital image analysis, and genetic alterations by fluorescence in situ hybridization to assess the sensitivity of cytology for detecting pancreatobiliary tract malignancy.

Routine cytologic (RC), fluorescence in situ hybridization (FISH), digital image analysis (DIA), and quantifiable morphometric results from 284 pancreatobiliary stricture brushings were compared. We chose specific DIA nuclear features assessed by pathologists in evaluating RC specimens, such as area and shape. A visual nuclear morphometric score (VNMS) was calculated. There was a difference (P < .001) in the mean VNMS when RC results were classified as negative (11.5), atypical (12.5), suspicious (13.8), and positive (16.5). The mean VNMS of specimens diagnosed as disomy (11.3), trisomy 7 (12.1), and polysomy (14.7) by FISH was also different (P < .001). There was no difference in the VNMS of false-negative and true-negative cytologic specimens (P = .225). Our findings substantiate the relationship between cell nuclear visual alterations and genetic FISH abnormalities. The low sensitivity of cytologic examination for pancreatobiliary carcinoma is due to an absence of tumor cells or the presence of well-differentiated tumor lacking recognizable nuclear atypia.

Clinical and pathologic factors associated with survival in young adult patients with fibrolamellar hepatocarcinoma.

BACKGROUND: Fibrolamellar Carcinoma (FLC), a subtype of hepatocellular carcinoma (HCC), is a rare primary hepatic malignancy. Several aspects of the clinic features and epidemiology of FLC remain unclear because most of the literature on FLC consists of case reports and small cases series with limited information on factors that affect survival. METHODS: We did a retrospective analysis of the clinical and histological characteristics of FLC. We also determined the rate of cellular proliferation in biopsies of these tumors. We assessed whether these variables were associated with survival. RESULTS: We found 15 patients with FLC out of 174 patients with HCC (8.6%). Between patients with these neoplasms, we found statistically significant survival, age at onset, level of alpha fetoprotein, and an earlier stage of the disease. The 1, 3 and 5 year survival in patients with FLC was of 66, 40 and 26% respectively. The factors associated with a higher survival in patients with FLC were age more than 23 years, feasibility of surgical resection, free surgical borders, absence of thrombosis or invasion to hepatic vessels and the absence of alterations in liver enzymes. The size of the tumor, gender, cellular proliferation and atypia did not affect the prognosis. CONCLUSION: We concluded that FLC patients diagnosed before 23 years of age have worse prognosis than those diagnosed after age 23. Other factors associated with worse prognosis in this study are: lack of surgical treatment, presence of positive surgical margins, vascular invasion, and altered hepatic enzymes.

Efficacy and safety of transarterial radioembolization versus chemoembolization in patients with hepatocellular carcinoma.

PURPOSE: Intermediate-stage hepatocellular carcinoma (HCC) is usually treated with locoregional therapy using transarterial chemoembolization (TACE). Transarterial radioembolization (TARE) using ß-emitting yttrium-90 integral to the glass matrix of the microspheres is an alternative to TACE. This retrospective case-control study compared the outcomes and safety of TARE versus TACE in patients with unresectable HCC. MATERIALS AND METHODS: Patients with unresectable HCC without portal vein thrombosis treated with TARE between 2005 and 2008 (n = 61) were retrospectively frequency-matched by age, sex, and liver dysfunction with TACE-treated patients (n = 55) in the Mayo Clinic Hepatobiliary Neoplasia Registry. Imaging studies were reviewed, and clinical and safety outcomes were abstracted from the medical records. RESULTS: Complete tumor response was more common after TARE (12 %) than after TACE (4 %) (p = 0.17). When complete response was combined with partial response and stable disease, there was no difference between TARE and TACE. Median survival did not differ between the two groups (15.0 months for TARE and 14.4 months for TACE; p = 0.47). Two-year survival rates were 30 % for TARE and 24 % for TACE. TARE patients received fewer treatments (p < 0.001). Fifty-nine (97 %) TARE patients received outpatient treatment. In contrast, 53 (98 %) TACE patients were hospitalized for ≥1 day (p < 0.001). Compared with TACE, TARE was more likely to induce fatigue (p = 0.003) but less likely to cause fever (p = 0.02). CONCLUSION: There was no significant difference in efficacy between TARE and TACE. TARE patients reported more fatigue but had less fever than TACE patients. Treatment with TARE required less hospitalization than treatment with TACE. These findings require confirmation in randomized trials.

Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures.

BACKGROUND & AIMS: Two advanced cytologic techniques for detecting aneuploidy-digital image analysis (DIA) and fluorescence in situ hybridization (FISH)-have recently been developed to help identify malignant pancreatobiliary strictures. The aim of this study was to assess the clinical utility of cytology, DIA, and FISH for the identification of malignant pancreatobiliary strictures. METHODS: Brush cytologic specimens from 233 consecutive patients undergoing endoscopic retrograde cholangiopancreatography for pancreatobiliary strictures were examined by all 3 (cytology, DIA, and FISH) techniques. Strictures were stratified as proximal (n = 33) or distal (n = 114) based on whether they occurred above or below the cystic duct, respectively. Strictures in patients with primary sclerosing cholangitis (n = 86) were analyzed separately. RESULTS: Despite the stratification, the performances of the tests were similar. Conventional cytology has a low sensitivity (4%-20%) but 100% specificity. Because of the high specificity for cytology, we assessed the performance of the other tests when conventional cytology was negative. In this clinical context, FISH had an increased sensitivity (35%-60%) when assessing for chromosomal gains (polysomy) while preserving the specificity of cytology. The sensitivity and specificity of DIA was intermediate as compared with routine cytology and FISH but was additive to FISH values demonstrating only trisomy of chromosome 7 or chromosome 3. CONCLUSIONS: These findings suggest that FISH and DIA increase the sensitivity for the diagnosis of malignant pancreatobiliary tract strictures over that obtained by conventional cytology while maintaining an acceptable specificity.