BACKGROUND: Cervical cancer (CC) and genital warts (GW) are a significant public health issue in Venezuela. Our objective was to assess the cost-effectiveness of the two available vaccines, bivalent and quadrivalent, against Human Papillomavirus (HPV) in Venezuelan girls in order to inform decision-makers.
METHODS: A previously published Markov cohort model, informed by the best available evidence, was adapted to the Venezuelan context to evaluate the effects of vaccination on health and healthcare costs from the perspective of the healthcare payer in an 11-year-old girls cohort of 264,489. Costs and quality-adjusted life years (QALYs) were discounted at 5%. Eight scenarios were analyzed to depict the cost-effectiveness under alternative vaccine prices, exchange rates and dosing schemes. Deterministic and probabilistic sensitivity analyses were performed.
RESULTS: Compared to screening only, the bivalent and quadrivalent vaccines were cost-saving in all scenarios, avoiding 2,310 and 2,143 deaths, 4,781 and 4,431 CCs up to 18,459 GW for the quadrivalent vaccine and gaining 4,486 and 4,395 discounted QALYs respectively. For both vaccines, the main determinants of variations in the incremental costs-effectiveness ratio after running deterministic and probabilistic sensitivity analyses were transition probabilities, vaccine and cancer-treatment costs and HPV 16 and 18 distribution in CC cases. When comparing vaccines, none of them was consistently more cost-effective than the other. In sensitivity analyses, for these comparisons, the main determinants were GW incidence, the level of cross-protection and, for some scenarios, vaccines costs.
CONCLUSIONS: Immunization with the bivalent or quadrivalent HPV vaccines showed to be cost-saving or cost-effective in Venezuela, falling below the threshold of one Gross Domestic Product (GDP) per capita (104,404 VEF) per QALY gained. Deterministic and probabilistic sensitivity analyses confirmed the robustness of these results.

AIM: To explore the association between TCF7L2 rs12255372 and rs7903146 single nucleotide polymorphisms (SNPs) and gastric cancer risk in Venezuelan patients.
METHODS: We performed a case-control study including 122 paraffin-embedded archived intestinal-type gastric cancer samples and 129 biopsies obtained by superior endoscopy from chronic gastritis patients. Gastric cancer samples were classified according the degree of carcinoma differentiation. Genomic DNA was extracted from tissues, and the two SNPs of TCF7L2 gene (rs12255372 and rs7903146) were genotyped by polymerase chain reaction-restriction fragment length polymorphism reactions. Multiple regression analysis with adjustments for age and gender were performed and best-fitting models of inheritance were determined. Statistic powers were post-hoc calculated.
RESULTS: After adjusting for age and sex the TCF7L2 rs7903146 TT genotype was associated with gastric cancer risk under the recessive genetic model (OR = 3.11, 95%CI: 1.22-7.92, P = 0.017). We further investigated the distribution of rs12255372 and rs7903146 genotypes according gastric cancer stratified by degree of differentiation, and we observed that carriers of rs7903146 T allele (CT + TT vs CC) had a significantly increased risk of moderate/well differentiated gastric cancer (dominant model, OR = 2.55, 95%CI: 1.35-4.80, P = 0.004), whereas the rs7903146 TT genotype was associated with poorly differentiated gastric cancer in the recessive model (OR = 3.65, 95%CI: 1.25-10.62, P = 0.018). We did not find association between rs12255372 SNP and the susceptibility of developing gastric cancer.
CONCLUSION: TCF7L2 rs7903146 polymorphism is associated with gastric cancer risk in the Venezuelan population, and could be related to determine the degree of differentiation of tumor cells.

BACKGROUND: The recent increase of breast cancer mortality has put on alert to most countries in the region. However it has taken some time before breast cancer could be considered as a relevant problem. Only in recent years breast cancer has been considered a priority in some Latin American countries and resources have been mobilized to confront the problem at the institutional level. The article analyzes the efforts made in five Latin American countries (Argentina, Brazil, Colombia, Mexico and Venezuela) in the last 15 years to design and implement policies to address the growing incidence of breast cancer.
METHODS: Data was collected between July and December 2010 from both primary and secondary sources. Semi-structured interviews were conducted with key informants from governmental and non-governmental organizations. Secondary data was obtained from publications in journals, government reports and official statistics in each country. Analysis combines information from both types of sources.
RESULTS: Countries have followed different paths and are in different stages of policy implementation. In all cases early detection is a key strategy. Through the design of programs and guidelines, the allocation of financial resources to treat patients, as well as a formally structured information system, Brazil and Mexico have been able to set up comprehensive national policies. Argentina, Colombia and Venezuela have made important advancements but not yet capable of coordinating comprehensive national policies.
CONCLUSION: Breast cancer is being considered a priority in all five countries but there are different stages in the rolling out of comprehensive national policies due to differences in their capacity to allocate resources, implement operational strategies and encourage the participation of relevant stakeholders.

Globally, about 50% of liver cancer originates as a result of long term infection with hepatitis B virus (HBV), and some genotypes and mutations have been associated with an increased severity of infection. The aim of this study was to evaluate the genetic diversity of HBV in patients from Venezuela, with chronic infection, cirrhosis and hepatocellular carcinoma (HCC) and to compare the occurrence of mutations in all patient groups. Samples from patients with different pathologies of the liver, associated with HBV infection, were collected. The HBV S region was analyzed for genotype determination and, when available, the whole genome sequence was examined for mutations analysis. Genotype F was the most common genotype (87%). While the HBV subgenotype F3 was the most frequent genotype in the whole group of samples (44%), the subgenotype F2 predominated in HCC patients (56%). Mutations were more common in HCC and cirrhosis cases (p=0.01). The A1762T mutation was significantly associated with the advanced stage of liver disease (p=0.008). Additionally, mutations were more common in early stages of liver disease in HBV subgenotype F2-infected patients, and a significant association between this subgenotype and the emergence of T 1753C, A1762T, A1762T/G1764A (p=0.04) and C1773T (p=0.001) mutations in chronic patients was found, when compared to the HBV subgenotype F3. By comparing F2 with all other HBV subgenotypes, a positive association for the three basal core promoter (BCP) mutants (A1762T, A1762T/G1764A p=0.01, G1764A p=0.04) was found. These results suggest that the HBV subgenotype F2 might be associated to more severe forms of liver disease in comparison with the HBV subgenotype F3.

PURPOSE: Cervical cancer is one of the most common causes of cancer mortality for women living in poverty, causing more than 28,000 deaths annually in Latin America and 266,000 worldwide. To better understand the molecular basis of the disease, we ascertained blood and tumor samples from Guatemala and Venezuela and performed genomic characterization.
EXPERIMENTAL DESIGN: We performed human papillomavirus (HPV) typing and identified somatically mutated genes using exome and ultra-deep targeted sequencing with confirmation in samples from Mexico. Copy number changes were also assessed in the exome sequence.
RESULTS: Cervical cancer cases in Guatemala and Venezuela have an average age of diagnosis of 50 years and 5.6 children. Analysis of 675 tumors revealed activation of PIK3CA and other PI3K/AKT pathway genes in 31% of squamous carcinomas and 24% of adeno- and adenosquamous tumors, predominantly at two sites (E542K, E545K) in the helical domain of the PIK3CA gene. This distribution of PIK3CA mutations is distinct from most other cancer types and does not result in the in vitro phosphorylation of AKT. Somatic mutations were more frequent in squamous carcinomas diagnosed after the age of 50 years. Frequent gain of chromosome 3q was found, and low PIK3CA mutation fractions in many tumors suggest that PI3K mutation can be a late event in tumor progression.
CONCLUSIONS: PI3K pathway mutation is important to cervical carcinogenesis in Latin America. Therapeutic agents that directly target PI3K could play a role in the therapy of this common malignancy.

Gastric cancer remains one of the leading causes of death in the world, being Central and South America among the regions showing the highest incidence and mortality rates worldwide. Although several single nucleotide polymorphisms (SNPs) identified in the chromosomal region 8q24 by genome-wide association studies have been related with the risk of different kinds of cancers, their role in the susceptibility of gastric cancer in Latin American populations has not been evaluated yet. Hereby, we performed a case-control study to explore the associations between three SNPs at 8q24 and gastric cancer risk in Venezuelan patients. We analyzed rs1447295, rs4733616 and rs6983267 SNPs in 122 paraffin-embedded tumor samples from archival bank and 129 samples with chronic gastritis (obtained by upper endoscopy during the study) from the Central Hospital of Barquisimeto (Lara, Venezuela). Genotypes were determined by PCR-RFLP reactions designed in this study for efficient genotyping of formalin-fixed/paraffin-embedded tissues. No significant differences in genotype frequencies between case and control groups were found. However, carriers of the homozygous TT genotype of SNP rs4733616 had an increased risk of developing poorly differentiated gastric cancer according to the codominant (OR=3.59, P=0.035) and the recessive models (OR=4.32, P=0.014, best-fitting model of inheritance), adjusted by age and gender. Our study suggests that the SNP rs4733616 is associated with susceptibility to poorly differentiated gastric cancer in Venezuelans. Additional studies are needed to further interrogate the prognostic value of the rs4733616 marker in this high-risk population for gastric cancer.

OBJECTIVE: Radical prostatectomy (RP) is the standard treatment for cancer control in the long term. The rise of minimally invasive surgery and new technologies have yielded better results and enabled us to pursue more ambitious objectives. The main works still use the trifecta as classic presentation, but this does not cover all aspects of surgery. Pentafecta is a new and more comprehensive methodology to report outcomes after RP, including complications and surgical margin status with the three major outcomes classically reported. The purpose of this study is to report our experience with robot-assisted laparoscopic radical prostatectomy (RALRP) by applying the concept of pentafecta.
MATERIAL AND METHOD: Describe the experience in this institution from March 2009 to December 2012 of RALRP by pentafecta.
RESULTS: We performed 101 interventions and obtained the following results: Average age 60.89 ± 7.32 years (40-77), total PSA 8.5 ± 5.57 ng/dl (0.2-29); D'Amico classification: Low 29 (28.71%), Medium 65 (64.36%), High 7 (6.93%); Operative time 253.44 ± 51.51 min (90-540), Complications 12.9% (Clavien I-II 10.89% and Clavien IIIa 1.98%); Positive surgical margins 20.83%; Biochemistry recurrence 12.5% follow-up (6-44 months); and Continence 87.5% per year and Potency 59.52%.
CONCLUSIONS: RALRP is a safe and reproducible procedure with excellent results in terms of pentafecta, inclusive during the initial experience at a low volumen center for prostate cancer. A longer follow-up study and experience with higher volume of patients are required to obtain better results and data to be compared with excellence centers.

The purpose of this research was to investigate how the knowledge and attitudes have influence in Cervical Cancer (CC) screening among Venezuelan women, by realizing a cross-sectional descriptive study based on a structured non disguised questionnaire with closed ended questions: yes/no questions and multiple choices. The survey was performed on 691 volunteers, of which 595 were analyzed. Each patient was asked to fill in the questionnaire. Four hundred ninety three of 522 (94.4%) answered that they knew that Pap smear is for screening CC. Knowledge of Pap smear was statistically significant when it was compared to high educational level (p < 0.0001) although 185 (76%) of 244 low educational level interviewees answered that they had the knowledge that the Pap smear is used for screening of CC. Four hundred four of 504 (84.7%; p < 0.001) mentioned that they had a Pap smear at least once. One hundred ninety two (38.1%) of 504 women were adherent to an annual Pap smear test and more than half of the women (n = 337, 67%) had the last Pap smear in the last 1-3 years. Women with a high educational level showed higher adherence to the annual Pap smear screening (68.2%). Two hundred fifty seven (87.4%) of 294 said that they remembered when they got the information about Pap smear. The conclusions of this investigation were that our women were aware about Pap smear, had a good attitude to have a Pap smear and to be adherent to a regularly performed screening.

A sample of 58 familial breast cancer patients from Venezuela were screened for germline mutations in the coding sequences and exon-intron boundaries of BRCA1 (MIM no. 113705) and BRCA2 (MIM no. 600185) genes by using conformation-sensitive gel electrophoresis. Ashkenazi Jewish founder mutations were not found in any of the samples. We identified 6 (10.3%) and 4 (6.9%) patients carrying germline mutations in BRCA1 and BRCA2, respectively. Four pathogenic mutations were found in BRCA1, one is a novel mutation (c.951_952insA), while the other three had been previously reported (c.1129_1135insA, c.4603G>T and IVS20+1G>A). We also found 4 pathogenic mutations in BRCA2, two novel mutations (c.2732_2733insA and c.3870_3873delG) and two that have been already reported (c.3036_3039delACAA and c.6024_6025_delTA). In addition, 17 variants of unknown significance (6 BRCA1 variants and 11 BRCA2 variants), 5 BRCA2 variants with no clinical importance and 22 polymorphisms (12 in BRCA1 and 10 in BRCA2) were also identified. This is the first genetic study on BRCA gene mutations conducted in breast cancer patients from Venezuela. The ethnicity of our population, as well as the heterogeneous and broad spectrum of BRCA genes mutations, must be considered to optimize genetic counseling and disease prevention in affected families.

BACKGROUND: This study investigated the distribution of human papillomavirus (HPV) types in invasive cervical cancer (ICC), cervical intraepithelial neoplasia 2 (CIN2) and cervical intraepithelial neoplasia 3 (CIN3) in Venezuela.
METHODS: Paraffin-embedded samples from 329 women from 29 medical centers of the 24 states of Venezuela were analyzed to determine the distribution of HPV types for ICC, CIN2, and CIN3, the prevalence of single and multiple infection, and the association of HPV types with severity of lesion, comparing CIN2 versus CIN3+ (CIN3 and ICC). The samples were analyzed with the polymerase chain reaction (PCR) followed by reverse hybridization for the identification of HPV types.
RESULTS: HPV was identified in 95/96 ICC specimens (98.9%), in 142/149 CIN3 (95.3%) and in 78/84 CIN2 samples (92.8%). The most common types for ICC and CIN3 were: HPV16, 18, 31, and 33, and for CIN2 were HPV16, 31, 51, 52, and 18. HPV single infection was found in 82.1% of ICC cases, in 79.4% of CIN2 cases, and in 77.4% of CIN3 cases. HPV16 was identified as a single infection more frequently in women with CIN3+ than in those with CIN2 (68.6% versus 46.7%, P=0.002), and HPV16 or HPV18 types were more prevalent in CIN3+ than in CIN2 (73.4% versus 50%, P=0.0006).
CONCLUSION: this is the first study of the distribution of HPV types in ICC, CIN2, and CIN3 conducted throughout the territory of Venezuela. HPV16 and HPV18 were the most frequent HPV types identified in single and multiple infections in both ICC and CIN3 groups, and are associated with severity of lesion. The knowledge of the distribution of HPV types would allow organization of an HPV-DNA-based screening test, and consideration of the implementation of prophylactic vaccination in Venezuela.

We recently demonstrated that Venezuelan equine encephalitis virus-based replicon particle (VRPs) encoding tumor antigens could break tolerance in the immunomodulatory environment of advanced cancer. We hypothesized that local injection of VRP-expressing interleukin-12 (IL-12) at the site of injections of VRP-based cancer vaccines would enhance the tumor-antigen-specific T cell and antibody responses and antitumor efficacy. Mice were immunized with VRP encoding the human tumor-associated antigen, carcinoembryonic antigen (CEA) (VRP-CEA(6D)), and VRP-IL-12 was also administered at the same site or at a distant location. CEA-specific T cell and antibody responses were measured. To determine antitumor activity, mice were implanted with MC38-CEA-2 cells and immunized with VRP-CEA with and without VRP-IL-12, and tumor growth and mouse survival were measured. VRP-IL-12 greatly enhanced CEA-specific T cell and antibody responses when combined with VRP-CEA(6D) vaccination. VRP-IL-12 was superior to IL-12 protein at enhancing immune responses. Vaccination with VRP-CEA(6D) plus VRP-IL-12 was superior to VRP-CEA(6D) or VRP-IL-12 alone in inducing antitumor activity and prolonging survival in tumor-bearing mice. Importantly, local injection of VRP-IL-12 at the VRP-CEA(6D) injection site provided more potent activation of CEA-specific immune responses than that of VRP-IL-12 injected at a distant site from the VRP-CEA injections. Together, this study shows that VRP-IL-12 enhances vaccination with VRP-CEA(6D) and was more effective at activating CEA-specific T cell responses when locally expressed at the vaccine site. Clinical trials evaluating the adjuvant effect of VRP-IL-12 at enhancing the immunogenicity of cancer vaccines are warranted.

Currently, twelve validated genetic variants have been identified that are associated with urinary bladder cancer (UBC) risk. However, those validated variants explain only 5-10% of the overall inherited risk. In addition, there are more than 100 published polymorphisms still awaiting validation or disproval. A particularly promising of the latter unconfirmed polymorphisms is rs2854744 that recently has been published to be associated with UBC risk. The [A] allele of rs2854744 has been reported to be associated with a higher promoter activity of the insulin-like growth factor-binding protein-3 (IGFBP3) gene, which may lead to increased IGFBP-3 plasma levels and cancer risk. Therefore, we investigated the association of rs2854744 with UBC in the IfADo case-control series consisting of 1,450 cases and 1,725 controls from Germany, Hungary, Venezuela and Pakistan. No significant association of rs2854744 with UBC risk was obtained (all study groups combined: unadjusted P = 0.4446; adjusted for age, gender and smoking habits P = 0.6510), besides a small effect of the [A] allele in the Pakistani study group opposed to the original findings (unadjusted P = 0.0508, odds ratio (OR) = 1.43 for the multiplicative model) that diminished after adjustment for age, gender and smoking habits (P = 0.7871; OR = 0.93). Associations of rs2854744 with occupational exposure to urinary bladder carcinogens and smoking habits were also not present. A meta-analysis of all available case-control series including the original discovery study resulted in an OR of 1.00 (P = 0.9562). In conclusion, we could not confirm the recently published hypothesis that rs2854744 in the IGFBP3 gene is associated with UBC risk.

There is insufficient information on the characteristics of chronic lymphocytic leukemia (CLL) in Latin American patients. Immunoglobulin variable-region heavy-chain (IGVH) gene usage and mutation status and prognostic factors were investigated in patients resident in Venezuela. The most frequently used IGVH family genes were: VH3 > VH1 > VH4 > VH5, with a high incidence of IGVH1.69 and IGVH3.21 genes, and 55.2% of IGVH genes were mutated. Analysis of HCDR3 (third complementarity-determining region of the heavy chain) revealed that 24% of Venezuelan HCDR3s belonged to a CLL stereotyped HCDR3. Results for prognostic factors were similar to those reported previously for Caucasian populations. Interestingly, we found an over-representation of people of European extraction among Venezuelan patients with CLL, suggesting the possibility of a higher frequency of susceptibility genes for CLL in Europeans in comparison with Latin American mestizos.

OBJECTIVE: Cervical cancer is an important cause of mortality among women in developing countries, especially in the Latin America and Caribbean (LAC) region. Infection with high-risk (HR) human papillomavirus (HPV) has been identified as the primary cause of cervical cancer. The aim of this study was to determine the frequency of HR-HPV genotypes in low-grade and high-grade squamous intraepithelial lesions (LSIL, HSIL) and cervical carcinoma (CC) among Venezuelan women.
MATERIALS AND METHODS: Subjects with histopathological diagnosis of LSIL, HSIL, and CC (LSIL=200; HSIL=100; CC=150) were enrolled in the study after obtaining informed consent. Biopsy samples of these subjects were analyzed to determine the lesion type. HPV detection and typing was done using polymerase chain reaction (PCR) and reverse hybridization. HPV type specific prevalence was determined in subjects with single and multiple infections.
RESULTS: HPV DNA was detected in 68%, 95%, and 98.7% of LSIL, HSIL, and CC cases, respectively. HR-HPV and low-risk oncogenic HPV (LR-HPV) was observed in 66.9%/11.8% of LSIL cases, 87.3%/3.2% of HSIL cases, and 91.2%/0.7% of CC cases. HPV types -16/-18 (65%) were the most common high-risk HPV types observed, followed by types -52, -33, -45, and -31.
CONCLUSION: Cervical cancer burden in Venezuelan women is substantial. HPV types -16/-18 were the most common types prevalent among Venezuelan women followed by types -52, -33, -45, and -31 (prevalence, ~90.1%). The results of this study provide baseline information on the HPV type distribution, which may facilitate the development of a cervical cancer prevention and control program in Venezuela.

Single nucleotide polymorphism (SNP) rs710521[A], located near TP63 on chromosome 3q28, was identified to be significantly associated with increased bladder cancer risk. To investigate the association of rs710521[A] and bladder cancer by new data and by meta-analysis including all published data, rs710521 was studied in 1,425 bladder cancer cases and 1,740 controls that had not been included in previous studies. Blood samples were collected from 1995 to 2010 in Germany (n = 948/1,258), Hungary (n = 262/65), Venezuela (n = 112/190) and Pakistan (n = 103/227) supplemented by a meta-analysis of 5,695 cases and 40,187 controls. Detection of a A/G substitution (rs710521) on chromosome 3q28, position 191128627 was done via fast real-time polymerase chain reaction (rt-PCR). Rs710521[A] is associated with increased risk in the unadjusted analysis (OR = 1.21; 95% Cl = 1.04-1.40; P = 0.011) and in the recessive model adjusted for age, gender, smoking habits and ethnicity (OR = 1.23; 95% Cl = 1.05-1.44; P = 0.010). No difference between individuals occupationally exposed versus not occupationally exposed to urinary bladder carcinogens was observed concerning the relevance of rs710521[A]. Similarly, rs710521[A] did not confer different susceptibility in smokers and non-smokers. Performing a meta-analysis of 5,695 cases and 40,187 controls including all published studies on rs710521, a convincing association with bladder cancer risk was obtained (OR = 1.18; 95% Cl = 1.12-1.25; P < 0.0001). However, the odds ratio is relatively small.

Oral hairy leukoplakia (OHL) is commonly found in individuals infected with HIV and represents the most frequent oral manifestation. The purpose of this study was to detect the presence of Human Papillomavirus (HPV) and Epstein Barr Virus (EBV) in OHL of HIV+ Venezuelan patients. We evaluated 21 HIV+ adult patients with clinically present OHL lesions: 11 under antiretroviral therapy, 10 without therapy, and 10 oral mucosal samples as controls. Nested-PCR was used to detect EBV and HPV infection. The INNO-LiPA HPV Genotyping v2 was applied to determine the HPV genotype. The EBV genome was found in 16/21 (76%) of the HIV+ patients with OHL. No difference was observed in EBV+ and EBV- patients related to antiretroviral therapy viral load and CD4+ Tcell coant. HPV-DNA was observed in 7/21 HIV positive cases (33%). The HPV genotypes detected were: 6, 11, 31, 33, 52, and 56/74. The most frequently HPV found was genotype 6 in 7/7, while two cases were HPV-11 and two HPV-52. Of the positive cases, 5/7 (71%) presented co-infection with more than one HPV genotype and 4/7 (57%) had HPV coinfection with high and low risk types. No case was EBV or HPV positive in the control group. In this study, a higher EBV prevalence was observed in OHL-HIV+ patients, confirming the etiologic role in this entity. A considerable number of cases were positive for HPV infection, and many patients presented coinfection with more than one HPV genotype as well as the presence of high oncogenic risk HPV in OHL.

The aim of this study was to establish the presence of HPV infection in cervical lesions in a Venezuelan population, by Hybrid Capture Assay II (HCA II), and its association with cytological diagnosis. The study included 1483 cervical samples analysed at Laboratorios CITOMED, Caracas, Venezuela, from 2005 to 2007. The woman age range was between 20 and 58 years, and the mean age was 28.8. HPV infection was determined using HCA II. The cytological diagnosis of the smears showed LSIL in 1120/1483 samples (75.5%), HSIL in 354/1483 (23.9%) and ASC-US, in 9/1483 (0.6%). The positivity of HPV DNA detected by HCA II was 54.6% (811/1483). Of the positives cases, 138/811 (17%) presented HPV DNA of low oncogenic risk and 673/811 (82.9%) had high-risk HPV. There were significant differences in the low and high oncogenic HPV type frequencies of the evaluated samples (p > 0.0001). Low risk HPV types were detected in 127 cases of LSIL, 9 of HSIL and 2 of ASC-US. High-risk HPV was detected in most of the cases: 361 LSIL, 308 HSIL and 4 ASC-US. Our study showed a high presence of cervical infection by human papillomavirus of a high risk genotype. Our results contribute to the epidemiological data that report diversity in the prevalence rates in different countries.

PURPOSE: To determine the prevalence of Epstein Barr virus (EBV) in oral hairy leukoplakia lesions (OHL) in HIV+ Venezuelan patients.
MATERIAL AND METHOD: In this case study, we evaluated 21 HIV+ adult patients with clinically present OHL lesions, 11 who were undergoing antiretroviral therapy, 10 who were not undergoing therapy and 10 HIV-negative adult patients with hyperkeratotic oral mucosal lesions. All of the subjects were assessed at the Infectious Disease Center, Faculty of Dentistry, Central University of Venezuela, and were clinically examined to detect oral mucosal lesions with the confirmed histopathologic diagnosis. Nested-PCR was used to determine the EBV infection and the latent membrane protein-1 (LMP-1) expression by immunohistochemistry.
RESULTS: Of the subjects, 16/21 (76%) of the HIV+/AIDS patients tested positive for EBV, whereas 5/10 (50%) of the HIV-negative subjects tested positive for EBV.
CONCLUSIONS: In the present study, a higher EBV prevalence was observed in HIV-positive patients when compared to HIV-negative patients without oral hairy leukoplakia, confirming the etiologic role in this entity. The LMP-1 in OHL patients who were both HIV+ and EBV+ was highly expressed (60%) at the epithelial basal cells. No association between the alcohol and tobacco consumption was observed among the EBV-positive cases.

PURPOSE: To describe the histopathologic characteristics of all retinoblastoma biopsy specimens received at one institution.
METHODS: All retinoblastoma biopsy specimens received between January 2000 and December 2005 were evaluated and a total of 109 eyes from 101 patients were studied.
RESULTS: There were 9 (8.3%) well differentiated, 25 (23.0%) moderately differentiated, and 66 (60.5%) poorly differentiated retinoblastomas. The most common growth pattern was mixed, comprising 81 (74.4%) cases. Vitreous seeding, invasion of the anterior chamber, and invasion of the optic nerve beyond the lamina cribrosa, was present in 79 (72.5%), 24 (22.0%), and 44 (40.4%) eyes, respectively. The tumor was confined to the retina in only 26 (23.9%) cases, whereas 16 (14.8%) had minimal choroidal invasion, 45 (41.3%) had massive choroidal involvement, 10 (9.2%) had scleral invasion, and 11 (10.1%) had extraocular extension.
CONCLUSION: In this study, the percentage of patients with choroidal and optic nerve invasion, reflecting a poor prognosis, was much higher than in previously reported North American series. However, similar findings have been described in other developing countries, where late diagnosis is common. This study emphasized the need for early diagnosis and treatment.

The aim of this work was to analyze diagnosed cases of Oral Cancer (OC) and Oropharyngeal Cancer (OPC) in a Venezuelan population. We clinically evaluated 130 patients with OC and OPC and a histopathologic diagnosis of squamous cell carcinoma. The patients were analyzed according to gender age, and use of alcohol and tobacco and the tumors were classIfied based on anatomic location, staging parameters, and degree of difFerentiation. Ninety one patients (70%) were male and 39 (30%) were female. Patients' age ranged from 26 to 86 years old. Use of smoking tobacco, alcohol or both was reported by 84.3%, 49.1% and 45.4% of patients, respectively, and was more frequent in males. The most common oropharyngeal anatomic location was the base of the tongue (22.3%), followed by the tonsils (13.9%), while the most frequently affected oral location was the oral tongue (19.2%) followed by the gingiva and alveolar mucosa (10.8%), and the floor of mouth (7.7%). The majority of tumors (77.7%) were diagnosed at an advanced stage (Stage III or IV); metastasis to the regional lymph nodes occurred in 53.1% of cases. According to degree of diferentiation, well, moderately and poorly difFerentiated tumors accounted for 45.4%, 46.1% and 8.5% of cases, respectively. Well differentiated tumors accounted for 56.7% of OC cases, while the majority of OPC cases were classified as moderately or poorly differentiated (72.3%) (p < or = 0.002). Also, non-metastatic cases (NO) showed a predominance of well-diferentiated tumors (61.2%), while metastatic tumors (N+) were classified as moderately or poorly differentiated in 89.8% of cases (p < or = 0.0001). Our study population was characterized by a predominance of smokers and/or drinkers and a predilection for male patients. Most tumors were diagnosed at an advanced stage with a high incidence of metastatic spread to the regional lymph nodes, indicating possible delays in diagnosis. Less differentiated tumors were more frequently encountered among OPC cases and accounted for the vast majority of metastatic cases, supporting the prognostic value of assessing the degree of difFerentiation.

The purpose of this study was to investigate, in a group of Venezuelan women, the knowledge and understanding of the purpose of the Pap smear and the correlation of this knowledge with their educational level. Women were recruited for a cervical cancer screening program and answered a questionnaire concerning what a Pap smear is used for. Three hundred one women were included in the study. Two hundred eighty six women (95%) answered that they knew about Pap smear. Two hundred sixty eight patients (89%) knew that the Pap smear is used for cervical cancer screening. One hundred sixteen women (38.5%) had a low educational level. One hundred and four of them (89.7%) knew that Pap smear is used to screen cervical cancer. Ninety two percent of women who did not complete elementary school had the knowledge of the purpose of vaginal cytology. Two hundred eighty one patients (93%) mentioned that they had at least one Pap smear. One hundred sixty four patients (58.3%) reported to have > or = 4 Pap smears in their life time. Two hundred fifty seven women (91.5%) remembered when the first Pap smear was taken. Twenty one patients (7%) had a Pap smear for the first time. The conclusions are: 1) low educational level in an urban area is not a limitation for knowing about and having a cervical cytology test taken; 2) high percentage of Venezuelan women in an urban area know what the Pap smear is used for.

Chronic inflammation induced by Helicobacter pylori is a key process in gastric carcinogenesis. We hypothesized that genetic polymorphisms in important mediators of H. pylori-induced inflammation may influence the risk of developing various grades of precancerous lesions. We studied the associations between single nucleotide polymorphisms (SNPs) in cyclooxygenase 1 and 2 (PTGS1 and PTGS2), inducible nitric oxide synthase (NOS2A), interferon gamma (IFNG) and its receptor (IFNGR1), and risk of gastric precancerous lesions in a Venezuelan population characterized by high rates of H. pylori infection. We found no association of precancerous lesions with SNPs in PTGS1 and in IFNG. A nonsynonymous SNP of NOS2A (Ser608Leu) and an SNP located in the promoter of IFNGR1 (C-56T) were associated with higher risk of atrophic gastritis [odds ratio (OR)=1.37, 95% confidence interval (CI)=1.01-1.86, and OR=1.49, 95% CI=1.01-2.19, respectively]. Two SNPs of PTGS2 were associated with risk of dysplasia (OR=1.60, 95% CI=1.01-2.54, and OR=0.66, 95% CI=0.43-0.99). We conclude that genetic variability in the genes we studied does not play a major role in the early stages of gastric carcinogenesis.

BACKGROUND: Gastric cancer is one of the most common malignancies worldwide. Histopathologic studies have identified a sequence of changes in the gastric mucosa that mark the slow progression from normal tissue to carcinoma. Epidemiologic evidence suggests that a diet rich in fresh fruit and vegetables could be a protective factor against this disease. This effect may be mediated through antioxidant vitamins.
METHODS: A randomized, double-blind chemoprevention trial was conducted among 1980 subjects in Tachira State, Venezuela (whose population is at high risk for gastric cancer), to determine the effect of dietary supplementation with vitamin C, vitamin E, and beta-carotene on the progression and regression of precancerous gastric lesions. Subjects were randomly assigned to receive either a combination of vitamin C (750 mg/day), vitamin E (600 mg/day), and beta-carotene (18 mg/day) or placebo for 3 years. Changes in the gastric mucosa were determined by histologic diagnosis based on five biopsies taken from prespecified areas of the stomach at baseline and annually for 3 years. All biopsies were reviewed by a single expert pathologist. Progression rates (and regression rates) were calculated by comparing the first and last available gastroscopies for each subject and dividing the number of subjects whose diagnoses increased (decreased) in severity by the total follow-up time. Overall rate ratios were calculated by Poisson regression, controlling for baseline diagnosis. All statistical tests were two-sided.
RESULTS: Median plasma vitamin levels were increased in the treatment group between baseline and 1 year after randomization from 0.43 micromol/L (interquartile range [IQR] = 0.26-0.69) to 2.89 micromol/L (IQR = 1.76-4.22) for beta-carotene, from 26.7 micromol/L (IQR = 23.1-31.2) to 54.9 micromol/L (IQR = 42.8-67.6) for alpha-tocopherol, and from 47.70 micromol/L (IQR = 36.9-58.5) to 61.9 micromol/L (IQR = 52.2-72.7) for vitamin C. Overall progression rates per 100 person-years were 74.3 in the placebo group and 67.8 in the group randomly assigned to vitamins. Overall regression rates were 109.4 in the placebo group and 116.5 in the group randomly assigned to vitamins. There was no statistically significant difference in progression rate (rate ratio = 0.92, 95% confidence interval [CI] = 0.74 to 1.15) or regression rate (rate ratio = 1.09, 95% CI = 0.90 to 1.33) between vitamin and placebo groups.
CONCLUSION: Supplementation with antioxidant micronutrients is not an effective tool for gastric cancer control in this high-risk population. The results of this trial are consistent with previous findings on the lack of effect of nutritional supplementation on precancerous gastric lesions.

The routine use of granulocyte-colony stimulating factor (G-CSF) for 10 days during full-dose cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP) chemotherapy in HIV-associated diffuse non-Hodgkin's lymphoma (NHL) patients is very expensive in developing countries. We treated 22 HIV-associated diffuse NHL patients with standard-dose CHOP and used G-CSF after an episode of febrile neutropenia until neutrophil count reached 1000/mm3. The clinical response was: complete response (36%), partial response (32%), stable disease (14%) and progression (18%). There were no toxicity-related deaths. Grade 3 or 4 neutropenia was observed in 16% of cycles, but only 8% were complicated with febrile neutropenia. Seventeen patients died (median survival 15 months; range 2-70). There are five patients alive (median survival 24+ months; range 17-36+). Our experience showed that we can treat HIV-related NHL patients with full-dose CHOP, achieve good responses and have an acceptable toxicity profile, with the use of G-CSF as needed.

As Helicobacter pylori (HP) is a Gram-negative bacterium, we investigated the associations between several functional polymorphisms in genes involved in lipopolysaccharide (LPS) signaling and the prevalence of various stages of gastric premalignant lesions in a Venezuelan population. The two NOD2 polymorphisms, del3020insC and Gly908Arg, were too infrequent to study their associations with gastric lesions. The risk of intestinal metaplasia (IM) was significantly increased among subjects with the CD14 T-260 allele compared to those without this allele. A similar, but nonsignificant increase in risk for dysplasia was observed among homozygotes of this allele. There was no association between TLR4 Asp299Gly polymorphism and any type of lesions, except for a slight nonsignificant increase in risk of IM associated with the AA genotype among subjects with a higher histological HP score. These results suggest that genetic polymorphisms in HP LPS signaling may be implicated in the development of intermediate stages of gastric premalignant lesions.

OBJECTIVE: To analyze the clinical trends of gestational trophoblastic neoplasia (GTN) at the Department of Obstetrics and Gynecology, Hospital Universitario de Caracas (HUC).
STUDY DESIGN: A medical record review was performed of epidemiologic, clinical and diagnostic features of 25 cases of GTN at HUC from 1997 to 2004.
RESULTS: During the study period, 35,300 deliveries occurred, and 25 patients were diagnosed with GTN; the prevalence was 0.70:1,000 deliveries. The mean age was 29.2 years. Fifty-six percent were posthydatidiform mole (HM), 36% postchoriocarcinoma (CC), 4% postinvasive mole and 4% postabortion with abundant intermediate trophoblast. Vaginal bleeding was the main symptom in patients with CC. Two cases resembled ectopic pregnancy, and another resembled a vaginal endometrioma. Fifty-two percent of cases were at stage Ib; 76% received single-agent chemotherapy. Hysterectomy was performed in 6 cases. Twenty-one patients achieved remission, 2 showed regression and 2 died.
CONCLUSION: GTN had a high prevalence because HUC is a reference center. The most common presentation was post-HM GTN. Vaginal bleeding is frequent in CC and can mimic other gynecologic diseases. Chemotherapy is helpful, and hysterectomy can be performed in selected cases at early stages or with severe vaginal bleed-with a good ing. GTN has a good prognosis, and early diagnosis is possible.

OBJECTIVE: To describe 6 cases of gestational trophoblastic disease (GTD) in ectopic pregnancy admitted to Hospital Universitario de Caracas (HUC).
STUDY DESIGN: Medical records of 6 patients admitted to the Obstetrics and Gynecology Department, HUC, from 1996 to 2004 were reviewed. They underwent surgery with a diagnosis of ectopic pregnancy, and histologic analysis revealed GTD. Clinical trends were analyzed.
RESULTS: The prevalence of GTD in ectopic pregnancy was 0.16:1,000 deliveries. The mean patient age was 29 years. The preceding gestation was a term delivery in 4 and abortion in 2. The mean gestational age at admission was 8 weeks. All patients complained of abdominal pain, and 3 of them also had vaginal bleeding. Ultrasound revealed an adnexal tumor in 5 cases; this tumor and hemoperitoneum (6 cases) were the most frequent surgical findings. Histopathologic diagnosis was partial mole in 5 and choriocarcinoma in 1. Four patients were lost to follow-up.
CONCLUSION: In this series the prevalence of ectopic GTD was high. The condition can mimic the usual symptoms of ectopic pregnancy, especially when a hemoperitoneum is present. It is important to apply strict histologic criteria for GTD when a sample of ectopic pregnancy is analyzed and to monitor those patients with careful human chorionic gonadotropin follow-up.

Penile cancer is uncommon in western countries. It has been related to human papilloma virus (HPV) types 16 and 18. We describe five cases of carcinoma of the penis in men from a rural Venezuelan town that were related to HPV types 6, 11, 53, which represent a rather low risk for cancer.

OBJECTIVES: The aim of the study was to assess the effects of genetic polymorphisms in anti-inflammatory mediators, i.e., IL10, IL4 and IL4R on the prevalence of gastric precancerous lesions and their interactions with other environmental factors.
METHODS: The study population consisted of 2,033 Venezuelan subjects known to have extremely high Helicobacter Pylori (HP) infection rates. The odds ratios (OR) and 95% confidence intervals (CI) associated with these polymorphisms were estimated by multinominal logistic regression models for gastric precursor lesions.
RESULTS: We found a 60% increase in risk of intestinal metaplasia (IM) and dysplasia combined (OR 1.62, 95% CI: 1.10-2.38) among the carriers of the IL10-1082 low activity allele. This increased risk was more pronounced for dysplasia than for IM. On the other hand, homozygotes with the low activity allele of the A398G polymorphism in the IL4R gene had a modest increase in risk of atrophic gastritis (OR = 1.52, 95% CI: 1.05-2.21), compared with homozygotes of the high activity allele. There were no statistically significant synergetic interactions between these polymorphisms and environmental risk factors (low fruit intake, high starchy vegetable intake and cigarette smoking) for these lesions.
CONCLUSION: While the results of the present study suggest roles of genetic variability in these anti-inflammatory mediators in different stages of gastric carcinogenesis, there is high likelihood that they were chance findings due to multiple comparisons.

Social scientists concerned with studying the social and cultural meaning of illness problematize the relationship between disease and illness, noting that illness can exist without disease-abnormal physical changes in the body. What has received less attention is the existence of disease-made visible through technological advances-in the absence of illness. Cervical cancer (or the more ambiguous cervical abnormalities) is an example of a disease that is largely symptomless in its early stages and can occur in the absence of illness. In this paper I explore how women seek to understand and negotiate cervical cancer in the context of their everyday lives, as they are confronted with seemingly disparate and contradictory physical and psychological states of well-being, sickness, and disease. This experience is what I call living on the borderlands of health, disease, and illness, where all of these states are experienced concurrently and boundaries between them blur. Through observations of patient-doctor interactions, ethnographic interviews with doctors and women seeking treatment for cervical cancer and pre-cancerous abnormalities, I analyze how women try to understand their medical experience. And they do so with the added challenge of little information being shared with them by the doctors who treat them. While patients do not ask many questions of their doctors, this does not mean that women are disinterested in their health. In fact, they develop strategies for eliciting clinical information about their medical conditions and actively seek to make sense of their experiences. By problematizing the concepts of health, disease, and illness, and avoiding the tendency to see these as distinct and contradictory phenomenon, we can gain a better understanding of their interrelatedness, and how people negotiate this borderland.