Accuracy of combinations of visual inspection using acetic acid or lugol iodine to detect cervical precancer: a meta-analysis.

BACKGROUND: Visual inspection of the cervix with acetic acid (VIA) or with Lugol's iodine (VILI) have been evaluated for cervical cancer screening in developing countries. OBJECTIVES: To assess the diagnostic accuracy and clinical utility of visual methods to detect cervical intraepithelial neoplasia grade 2+ (CIN2+) using: (1) VIA alone; (2) VILI alone; (3) co-testing; and (4) VILI as a triage test of a positive VIA result. SEARCH STRATEGY: PubMed, EMBASE, and the Cochrane Library were searched up to May 2016. SELECTION CRITERIA: All reports on the accuracy of VIA and VILI, or combinations of VIA/VILI, to detect CIN2+ were identified. Histology and colposcopy when no biopsy was taken were used as the reference standard. DATA COLLECTION AND ANALYSIS: Selected studies were scored on methodological quality, and sensitivity and specificity were computed. Clinical utility was assessed from the positive predictive value (PPV) and the complement of the negative predictive value (cNPV). MAIN RESULTS: We included 23 studies comprising 101 273 women. The pooled sensitivity and specificity of VILI was 88 and 86%, respectively. VILI was more sensitive, but not less specific, compared with VIA (relative sensitivity = 1.11; 95% confidence interval, 95% CI, 1.06-1.16; relative specificity = 0.98; 95% CI 0.95-1.01). Co-testing was hardly more sensitive, but significantly less specific, than VILI alone. VILI to triage VIA-POSITIVE women was not less sensitive, but more specific, compared with VIA alone (relative sensitivity = 0.98, 95% CI 0.96-1.01; relative specificity = 1.04, 95% CI 1.02-1.05). The average PPVs were low (range 11-16%), whereas the cNPV varied between 0.3% (VILI, co-testing) and 0.6% (triage). CONCLUSIONS: Although imperfect, VILI alone appeared to be the most useful visual screening strategy. TWEETABLE ABSTRACT: VILI alone seems to be the most useful visual screening test for cervical cancer screening.

5'UTR +24T>C CR2 is not associated with nasopharyngeal carcinoma development in the North Region of Portugal.

OBJECTIVE: We have analysed the association of the +24T>C polymorphism (rs3813946) in CR2, the cellular receptor for Epstein-Barr virus (EBV), in the susceptibility for the development of nasopharyngeal carcinoma (NPC). METHODS: A retrospective case-control study was developed with peripheral blood samples from 111 individuals with NPC and 608 healthy individuals (controls) from the North region of Portugal. The genotyping analysis was performed by allelic discrimination real-time PCR using a TaqMan(®) SNP Genotyping Assay. RESULTS: The genotype distribution was 62.2% TT, 34.2% TC and 3.6% CC for NPC patients; and 65.0%, 30.6% and 4.4%, respectively, for controls. Our study showed no statistical association between the genotype distribution in controls and all types of NPC (P = 0.717); nevertheless, the analysis showed statistically significant differences (P = 0.038) regarding cases with well- or moderately differentiated types of NPC suggesting that +24CC/CT genotypes are associated with increased risk (OR = 4.16; 95% CI 1.28-15.7; P = 0.016). CONCLUSIONS: This is the first study in Western populations to characterize the association of the CR2 +24T>C polymorphism in NPC development, and our results suggest that more studies are required to clarify the impact on NPC susceptibility in different populations.

A randomized-controlled, double-blind study of the impact of selenium supplementation on thyroid autoimmunity and inflammation with focus on the GPx1 genotypes.

PURPOSE: To analyze the impact of selenium supplementation on serum antiTPO levels and thyroid echogenicity in patients with CAT, evaluating the response in subgroups with different GPx1 genotypes. METHODS: CAT patients (n = 55) with positive antiTPO were randomized to selenomethionine (SeMet) 200 µg daily (n = 28) or placebo (n = 27) for 3 months. Assessments included GPx1 genotyping at baseline and serum levels of plasma selenium, erythrocyte GPx1 activity, antiTPO and thyroid echogenicity at baseline, and 3 and 6 months. RESULTS: In the SeMet group, the increase in plasma levels of selenium and erythrocyte GPx1 activity was similar among patients with different GPx1 genotypes. In the overall cohort, patients randomized to SeMet showed a 5 % decrease in antiTPO levels at 3 months (p = non-significant) and 20 % at 6 months (p < 0.001 versus 3 months). In contrast, patients in the placebo group did not show significant changes in antiTPO levels at any time point. Subgroup analysis showed that patients with different GPx1 genotypes presented comparable responses in antiTPO levels and echogenicity index to SeMet. CONCLUSIONS: Selenium supplementation decreased serum antiTPO levels in CAT patients, with similar response among patients with different GPx1 genotypes.

Hyperbaric oxygen for radiation-induced cystitis: A long-term follow-up. / Oxígeno hiperbárico para la cistitis inducida por radioterapia: un seguimiento a largo plazo.

INTRODUCTION AND OBJECTIVES: Bladder complications may be seen in up to 12% of patients treated with pelvic irradiation. Hyperbaric oxygen therapy (HBOT) is an option for the management of radiation-induced hemorrhagic cystitis (RIHC). The aim of this study was to evaluate the efficacy of HBOT in radiation cystitis and to identify the predictive factors for a successful outcome. MATERIAL AND METHODS: We retrospectively reviewed 105 patients diagnosed with RIHC which were treated with HBOT between 2007 and 2016 in our institution. Patients received 100% oxygen in a multiplace hyperbaric chamber at 2.4atm for 80minutes. All patients fulfilled a questionnaire documenting symptom severity pre-HBOT and at the end of the follow-up period. RESULTS: After a median of 40 HBOT sessions, there was success rate of 92,4% in the control of hematuria. During our follow-up period (median of 63 months) 24,7% patients presented with recurrence of hematuria. The mean score of the questionnaire-assessed variables: dysuria, urinary frequency and hematuria, was significantly lower after the follow-up period (P<.05). Our data shows that the sooner HBOT is delivered after the first episode of hematuria, better response rates are achieved and lower recurrences concerning hematuria were registered (P<.05). No serious complications were observed. CONCLUSIONS: Our results support the safety and long-term benefits of HBOT on RIHC and other distressful bladder symptoms, which represents an expected improvement of quality of life in our patients.

Oncogenic virus-associated neoplasia: a role for cyclin D1 genotypes influencing the age of onset of disease?

Cyclin D1 (CCND1) is a key regulatory protein at the G1/S checkpoint of the cell cycle. The purpose of our study was to assess the role of CCND1 genotypes influencing the age of onset of oncogenic virus-associated neoplasia. We conducted a hospital-based case-control study of 581 individuals, including 247 controls and 334 cases (108 nasopharyngeal and 226 cervical cancer cases). The polymorphism analysis was performed in blood samples by PCR-RFLP methodology. Age-adjusted logistic regression analysis indicates that individuals carrying two G-alleles have an increased genetic susceptibility for the development of oncogenic virus-associated cancers (aOR=2.02, 95% CI 1.30-3.14, P=0.002). Moreover, our results indicate that the waiting time for onset of oncogenic virus-associated neoplasia in patients homozygous (GG) for CCND1 genotypes (52 years) was 12 years earlier in comparison with patients carrying AG or AA genotypes (60 years) (log-rank test: P=0.0003). Our results may be important in contributing to a more extensive knowledge of the mechanisms involved in oncogenic virus-associated carcinogenesis, as CCND1 may be an important target for the development of new strategies for cancer treatment and prevention.

Laminin concentration in ascites of patients with hepatic cirrhosis and peritoneal carcinomatosis.

Laminin levels in ascitic fluid have been proposed as a marker for neoplastic ascites. We compared the concentration of laminin in serum and in ascitic fluid from patients with hepatic cirrhosis and peritoneal carcinomatosis and assessed the diagnostic value of serum laminin levels in differentiating neoplastic from benign ascites. Laminin concentrations were determined by ELISA with antibodies against laminin extracted from the human placenta, in patients with ascites due to peritoneal carcinomatosis (N = 20) and hepatic cirrhosis (N = 33). Patients with infected or hemorrhagic ascites were excluded. The receiver operating characteristic curve was used to determine the sensitivity and specificity of serum laminin for the diagnosis of neoplastic ascites. When compared to the group with cirrhosis, the carcinomatosis group presented significantly higher mean laminin levels in serum (3.3 +/- 0.5 vs 2.1 +/- 0.4 microg/ml, mean +/- SD, P < 0.05) and ascites (2.8 +/- 0.5 vs 1.6 +/- 0.4 microg/ml, P < 0.05). Although laminin concentration was higher in serum than in ascites, the laminin serum/ascites ratio and serum-ascites gradient did not differ between the studied groups. A significant correlation (r = 0.93, P < 0.0001) was observed between the serum and ascites laminin values. Serum laminin levels >2.25 microg/ml showed 100% sensitivity and 73% specificity for the diagnosis of neoplastic ascites. Serum concentration seems to be the main determinant of laminin levels in ascitic fluid and its values can be used as a diagnostic parameter in the study of neoplastic ascites.

Estrogen and progesterone receptors in gastric and colorectal cancer.

BACKGROUND/AIMS: Estrogen (ER) and progesterone receptors (PR) have been evaluated in gastrointestinal cancer by several groups with conflicting results. The aim of the study is to examine the presence of these receptors in gastric and colon cancer. METHODOLOGY: Estrogen (ER) and progesterone (PR) receptors were assayed by the dextran-coated charcoal adsorption method from malignant and normal adjacent tissues in 16 patients with gastric adenocarcinomas and in 10 with colorectal adenocarcinomas. RESULTS: In gastric cancer, ER were detected in 62.5% and PR in 75% of the patients. In colorectal cancer, the ER and PR were detected in 60% of the patients. The binding activity ranged from 1.14-9.27 fmol/mg protein for estradiol and from 1.43-10.84 fmol/mg protein for progesterone. ER and PR were detected in normal gastric tissue in 62.5% and in 50%, respectively. In the normal colorectal tissue the ER and PR were detected in 30% and 50%. ER ranged from 1.20-16.63 fmol/mg protein for estradiol and from 1.44-9.94 fmol/mg protein for progesterone. There was no statistical difference in levels of ER and PR in both tissues. CONCLUSIONS: ER and PR were detected in normal and cancer tissues in low levels, suggesting a feature of the tissue rather than a consequence of a malignant process. Eventual role of ER or PR in these cancers remains to be elucidated.

The role of nt590 P21 gene polymorphism in the susceptibility to nasopharyngeal cancer.

AIM: The purpose of this study was to assess if the P21 nt590 polymorphism is associated with the susceptibility to nasopharyngeal cancer and with the age at diagnosis. MATERIALS AND METHODS: We analyzed the frequency of 3'UTR P21 polymorphisms in blood samples from 102 nasopharyngeal cancer patients and 191 controls, with no known oncologic disease, using PCR-RFLP. RESULTS: The polymorphism genotype frequencies were 93.2% (CC), 5.2% (CT) and 1.6% (TT) in the control group and 88.2% (CC), 10.8% (CT) and 1.0% (TT) in the cases group. We found no statistically significant association between the different P21 polymorphism genotypes and risk of nasopharyngeal cancer (p = 0.201). However, approximately a four-fold increased risk of undifferentiated nasopharyngeal carcinoma in early stages was observed for P21 T carriers (OR = 3.734; 95% IC 1.289-10.281; p = 0.01). Furthermore, our results indicate that the waiting time for onset of neoplasia in T carriers patients was 12.4 years earlier (56.5 years old), comparing with those carrying CC genotype (68.9 years old). CONCLUSIONS: Our findings suggest that the 3'UTR P21 polymorphism may play an important role in the pathogenesis and initiation, but not in the progression, of undifferentiated nasopharyngeal carcinoma. Moreover, the polymorphism seems to contribute to a significantly earlier age at diagnosis.

Cyclin D1 polymorphism in non-small cell lung cancer in a Portuguese population.

Cyclin D1 (CCND1) is a key regulatory protein of the cell cycle. The purpose of our study was to assess the role of CCND1 genetic variants influencing the genetic susceptibility of non-small cell lung cancer (NSCLC). We conducted a study of 1234 individuals, including 892 controls and 342 cases. Individuals carrying two G-alleles have a 2-fold increased risk for the development of NSCLC and the waiting time for onset of NSCLC in these patients was 2 years earlier in comparison with other individuals. Our results may be important in contributing to the knowledge of the mechanisms involved in lung carcinogenesis.

d-Amphetamine-induced hepatotoxicity: possible contribution of catecholamines and hyperthermia to the effect studied in isolated rat hepatocytes.

Amphetamines are indirect-acting sympathomimetic drugs widely abused due to their physical and psychostimulating effects. However, the use of these drugs has been associated with numerous reports of hepatotoxicity. While glutathione depletion induced by amphetamines contributes to the exposure of hepatocytes to oxidative damage, other indirect effects attributed to amphetamines may have a role in cell injury. To examine this possibility, Wistar rats were used for plasma measurements of d-amphetamine and catecholamines (noradrenaline, adrenaline and dopamine) (15 min) after i.p. injection of d-amphetamine (5, 20 and 80 mg/kg). Freshly isolated rat hepatocytes were put into contact for 2 h with concentrations of d-amphetamine and catecholamines similar to those found in vivo. Since hyperthermia is a common consequence of acute amphetamine intake, the study using isolated hepatocytes was conducted at 37 degrees C and also at 41 degrees C in order to simulate high temperature levels. We found that hyperthermia was an important cause of cell toxicity: in vitro, a rise in incubation temperature from 37 to 41 degrees C causes oxidative stress in freshly isolated rat hepatocytes, as shown by a depletion of reduced glutathione (GSH; 23%), an increase of oxidized glutathione (GSSG; 157%), the induction of lipid peroxidation with 77% increase of thiobarbituric acid substances TBARS) and the consequent loss of cell viability (< or = 44%). Single treatment of isolated hepatocytes with catecholamines at 37 degrees C induced lipid peroxidation (29% increase of TBARS) but had no effect on glutathione or cell viability. Conversely, a single treatment with d-amphetamine induced glutathione depletion (< or = 24% depletion of GSH) with no effect on lipid peroxidation or cell viability. Also, d-amphetamine potentiated the induction by catecholamines of lipid peroxidation at 37 degrees C (< or = 48% increase of TBARS), while concomitant treatment of d-amphetamine and catecholamines potentiated cell death at 41 degrees C (< or = 56% of cell death) although no effect on viability was seen at 37 degrees C. It is concluded that the aforementioned modifications induced by d-amphetamine in vivo are cytotoxic to freshly isolated rat hepatocytes.

Laminin concentration in ascites of patients with hepatic cirrhosis and peritoneal carcinomatosis

Laminin levels in ascitic fluid have been proposed as a marker for neoplastic ascites. We compared the concentration of laminin in serum and in ascitic fluid from patients with hepatic cirrhosis and peritoneal carcinomatosis and assessed the diagnostic value of serum laminin levels in differentiating neoplastic from benign ascites. Laminin concentrations were determined by ELISA with antibodies against laminin extracted from the human placenta, in patients with ascites due to peritoneal carcinomatosis (N = 20) and hepatic cirrhosis (N = 33). Patients with infected or hemorrhagic ascites were excluded. The receiver operating characteristic curve was used to determine the sensitivity and specificity of serum laminin for the diagnosis of neoplastic ascites. When compared to the group with cirrhosis, the carcinomatosis group presented significantly higher mean laminin levels in serum (3.3 ± 0.5 vs 2.1 ± 0.4 æg/ml, mean ± SD, P < 0.05) and ascites (2.8 ± 0.5 vs 1.6 ± 0.4 æg/ml, P < 0.05). Although laminin concentration was higher in serum than in ascites, the laminin serum/ascites ratio and serum-ascites gradient did not differ between the studied groups. A significant correlation (r = 0.93, P < 0.0001) was observed between the serum and ascites laminin values. Serum laminin levels >2.25 æg/ml showed 100 percent sensitivity and 73 percent specificity for the diagnosis of neoplastic ascites. Serum concentration seems to be the main determinant of laminin levels in ascitic fluid and its values can be used as a diagnostic parameter in the study of neoplastic ascites.