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Venezuela

Cancer Statistics
Population in 2008: 28.1m
People newly diagnosed with cancer (excluding NMSC) / yr: 37,000
Age-standardised rate, incidence per 100,000 people/yr: 152.6
Risk of getting cancer before age 75:15.6%
People dying from cancer /yr: 21,200
Data from IARC GlobalCan (2008)
Venezuela: Cancer Organisations and Resources
Latest Research Publications from Venezuela

Venezuela: Cancer Organisations and Resources (5 links)


Latest Research Publications from Venezuela

Puche ML, Kay-Valero S, Michelli P, et al.
Genetic diversity of hepatitis B virus and mutations associated to hepatocellular carcinoma in patients from Venezuela, with different stages of liver disease.
Invest Clin. 2016; 57(1):38-46 [PubMed] Related Publications
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.

Lou H, Villagran G, Boland JF, et al.
Genome Analysis of Latin American Cervical Cancer: Frequent Activation of the PIK3CA Pathway.
Clin Cancer Res. 2015; 21(23):5360-70 [PubMed] Free Access to Full Article Related Publications
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.

Labrador L, Torres K, Camargo M, et al.
Association of common variants on chromosome 8q24 with gastric cancer in Venezuelan patients.
Gene. 2015; 566(1):120-4 [PubMed] Related Publications
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.

Núñez-Troconis J, Tulliani E, Gabriela Martínez M, Fernández N
Knowledge and attitudes as predictors of cervical cancer screening among women in a Venezuelan urban area.
Invest Clin. 2013; 54(1):20-33 [PubMed] Related Publications
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.

Lara K, Consigliere N, Pérez J, Porco A
BRCA1 and BRCA2 mutations in breast cancer patients from Venezuela.
Biol Res. 2012; 45(2):117-30 [PubMed] Related Publications
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.

Sánchez-Lander J, Cortiñas P, Loureiro CL, et al.
Human papillomavirus in invasive cervical cancer and cervical intraepithelial neoplasia 2 and 3 in Venezuela: a cross-sectional study.
Cancer Epidemiol. 2012; 36(5):e284-7 [PubMed] Related Publications
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.

Osada T, Berglund P, Morse MA, et al.
Co-delivery of antigen and IL-12 by Venezuelan equine encephalitis virus replicon particles enhances antigen-specific immune responses and antitumor effects.
Cancer Immunol Immunother. 2012; 61(11):1941-51 [PubMed] Free Access to Full Article Related Publications
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.

Selinski S, Lehmann ML, Blaszkewicz M, et al.
Urinary bladder cancer risk in relation to a single nucleotide polymorphism (rs2854744) in the insulin-like growth factor-binding protein-3 (IGFBP3) gene.
Arch Toxicol. 2012; 86(2):195-203 [PubMed] Related Publications
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.

Marquez ME, Deglesne PA, Lopez JL, et al.
Unexpectedly high frequency of European parentage in Venezuelan patients with chronic lymphocytic leukemia.
Leuk Lymphoma. 2012; 53(2):235-41 [PubMed] Related Publications
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.

Correnti M, Medina F, Cavazza ME, et al.
Human papillomavirus (HPV) type distribution in cervical carcinoma, low-grade, and high-grade squamous intraepithelial lesions in Venezuelan women.
Gynecol Oncol. 2011; 121(3):527-31 [PubMed] Related Publications
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.

Lehmann ML, Selinski S, Blaszkewicz M, et al.
Rs710521[A] on chromosome 3q28 close to TP63 is associated with increased urinary bladder cancer risk.
Arch Toxicol. 2010; 84(12):967-78 [PubMed] Related Publications
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.

Correnti M, González X, Avila M, et al.
Human papillomavirus and Epstein Barr virus in oral hairy leukoplakia among HIV positive Venezuelan patients.
Acta Odontol Latinoam. 2010; 23(2):117-23 [PubMed] Related Publications
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.

Correnti M, Cavazza ME, Herrera O, Rodríguez A
Presence of human papillomavirus infection determined by hybrid capture assay in cervical lesions in a Venezuelan population.
Invest Clin. 2010; 51(1):27-35 [PubMed] Related Publications
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.

González X, Correnti M, Rivera H, Perrone M
Epstein Barr Virus detection and latent membrane protein 1 in oral hairy leukoplakia in HIV+ Venezuelan patients.
Med Oral Patol Oral Cir Bucal. 2010; 15(2):e297-302 [PubMed] Related Publications
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.

Orellana ME, Fernandes BF, Arean C, et al.
Clinical pathologic study of a cohort of patients with retinoblastoma from a developing country.
J Pediatr Ophthalmol Strabismus. 2009 Sep-Oct; 46(5):294-9 [PubMed] Related Publications
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.

Rivera H, Nikitakis NG, Correnti M, et al.
Oral and oropharyngeal cancer in a Venezuelan population.
Acta Odontol Latinoam. 2008; 21(2):175-80 [PubMed] Related Publications
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.

Núñez-Troconis J, Velásquez J, Mindiola R, Munroe D
Educational level and cervical cancer screening programs in a Venezuelan urban area.
Invest Clin. 2008; 49(3):331-9 [PubMed] Related Publications
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.

Canzian F, Franceschi S, Plummer M, et al.
Genetic polymorphisms in mediators of inflammation and gastric precancerous lesions.
Eur J Cancer Prev. 2008; 17(2):178-83 [PubMed] Related Publications
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.

Plummer M, Vivas J, Lopez G, et al.
Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population.
J Natl Cancer Inst. 2007; 99(2):137-46 [PubMed] Related Publications
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.

Hernàndez DE, Hernàndez AE
Human immunodeficiency virus-associated diffuse non-Hodgkin's lymphoma in Venezuelan patients: treatment with full-dose cyclophosphamide-doxorubicin-vincristine-prednisone without routine use of granulocyte-colony stimulating factor.
Eur J Cancer Care (Engl). 2006; 15(5):493-6 [PubMed] Related Publications
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.

Kato I, Canzian F, Plummer M, et al.
Polymorphisms in genes related to bacterial lipopolysaccharide/peptidoglycan signaling and gastric precancerous lesions in a population at high risk for gastric cancer.
Dig Dis Sci. 2007; 52(1):254-61 [PubMed] Related Publications
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.

Cortés-Charry R, Figueira LM, García-Barriola V, et al.
Gestational trophoblastic neoplasia: clinical trends in 8 years at Hospital Universitario de Caracas.
J Reprod Med. 2006; 51(11):888-91 [PubMed] Related Publications
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.

Cortés-Charry R, Figueira LM, García-Barriola V, et al.
Gestational trophoblastic disease in ectopic pregnancy: A case series.
J Reprod Med. 2006; 51(10):760-3 [PubMed] Related Publications
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.

Dorfman S, Cavazza M, Cardozo J
Penile cancer associated with so-called low-risk human papilloma virus. Report of five cases from rural Venezuela.
Trop Doct. 2006; 36(4):232-3 [PubMed] Related Publications
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.

Kato I, Canzian F, Franceschi S, et al.
Genetic polymorphisms in anti-inflammatory cytokine signaling and the prevalence of gastric precancerous lesions in Venezuela.
Cancer Causes Control. 2006; 17(9):1183-91 [PubMed] Related Publications
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.

Martínez RG
"What's wrong with me?": cervical cancer in Venezuela--living in the borderlands of health, disease, and illness.
Soc Sci Med. 2005; 61(4):797-808 [PubMed] Related Publications
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.

Dao DD, Sierra-Torres CH, Robazetti SC, et al.
HLA-DQB1 and cervical cancer in Venezuelan women.
Gynecol Oncol. 2005; 96(2):349-54 [PubMed] Related Publications
BACKGROUND: Cervical cancer represents a major health problem in Venezuela as well as in other Latin American countries. High-risk human papillomavirus (HR-HPV) infection is known as the major risk factor of cervical cancer. However, whether or not a HR-HPV-infected woman progresses to cervical cancer may depend on the immune system effectors induced by viral antigens presented by her specific human leukocyte antigens (HLA) alleles. The role of the HLA system in presenting peptides to antigen-specific T-cells may be critical for genetic susceptibility and genetic resistance to cervical carcinoma.
OBJECTIVE: We aimed to investigate the relationship between HLA-DQB1, HPV infection, and cervical cancer in Venezuelan women.
METHODS: Blood samples and cervical swabs were obtained from 36 patients and 79 healthy controls; additional cervical biopsies were obtained from all the patients. HPV DNA was detected by PCR and HLA-DQB1 genotyping was performed using a PCR-SSP protocol. RESULTS.: A positive association with cervical cancer was observed for HLA-DQB1*0201-0202 and *0402 alleles, however after Bonferroni correction only HLA-DQB1*0402 remained statistically significant (P value = 0.004, RR = 5.067).
CONCLUSION: This is the first report of HLA-DQB1 alleles associated with cervical carcinoma in Venezuelan women. Larger studies are needed to assess whether these HLA-DQB1*0201-0202 and *0402 alleles have a direct effect on disease susceptibility.

Baillargeon JP, Jakubowicz DJ, Iuorno MJ, et al.
Effects of metformin and rosiglitazone, alone and in combination, in nonobese women with polycystic ovary syndrome and normal indices of insulin sensitivity.
Fertil Steril. 2004; 82(4):893-902 [PubMed] Related Publications
OBJECTIVE: To determine whether insulin-sensitizing drugs would improve ovulation and T levels in women with polycystic ovary syndrome (PCOS), without clinical or biochemical criteria indicating insulin resistance and whether the combination of two distinct insulin-sensitizing drugs would be of any benefit over either drug alone.
DESIGN: Randomized controlled double-blind trial.
SETTING: A referral center in Caracas, Venezuela.
PATIENT(S): One hundred twenty-eight nonobese PCOS women with normal indices of insulin sensitivity-that is, normal glucose tolerance, fasting insulin, peak insulin during an oral glucose tolerance test (OGTT), and fasting glucose-to-insulin ratio. Twenty-eight women were lost to follow-up initially and did not receive any intervention.
INTERVENTION(S): One hundred women received twice daily one of the following for 6 months: metformin (850 mg), rosiglitazone (4 mg), combination of both drugs, or at least one placebo.
MAIN OUTCOME MEASURE(S): Frequencies of ovulation and serum free T after 6 months.
RESULT(S): Frequencies of ovulation were higher after treatment with an insulin-sensitizing drug (ovulations per subject in 6 months: metformin, 3.3; rosiglitazone, 2.4; and combination, 3.4) than with placebo (0.4). Ovulatory frequencies increased significantly more with metformin than rosiglitazone, and the combination was not more potent. After treatment, serum free-T levels were comparable among all active treatment groups (metformin: 2.34 pg/mL, rosiglitazone: 3.06 pg/mL, and combination: 2.39 pg/mL) and were significantly lower than in the placebo group (7.26 pg/mL). Compared with placebo, fasting insulin levels, area under the insulin curve during OGTT, the homeostatic model assessment of insulin sensitivity, and OGTT-derived insulin sensitivity index improved significantly after metformin or combination therapies but not after rosiglitazone.
CONCLUSION(S): These findings suggest that insulin-sensitizing drugs increase ovulatory frequency and ameliorate hyperandrogenemia, even in nonobese women with PCOS who appear to have normal insulin sensitivity.

Acquatella G, Insausti CL, García R, et al.
Outcome of children with B cell lymphoma in Venezuela with the LMB-89 protocol.
Pediatr Blood Cancer. 2004; 43(5):580-6 [PubMed] Related Publications
BACKGROUND: We analyzed the results of the LMB-89 protocol performed in seven centers in Venezuela in 96 children having B-cell non-Hodgkin lymphoma treated from 1995 to 2002.
PROCEDURE: Mean age was 7.1 years with 71 (74%) been male. Eighty-two patients (85%) had diffuse small cell lymphoma Burkitt and Burkitt-like, and 14 (15%) had diffuse large B-cell lymphoma. Initial disease sites included the abdomen in 67%, peripheral nodes in 8%, and mediastinal in 4%. Treatment was directed to risk groups as described for LMB-89 protocol. Group A: seven patients (7%), group B: 80 patients (83%), and group C: nine patients (9%).
RESULTS: Mean follow-up was 35 +/- 31 months. Complete remission (CR) occurred in 70 patients (73%); four patients (6%) had relapse during the first year and ten patients (10%) had progressive disease. Overall survival (OS) and event free survival (EFS) were 85 and 80% at 1 year, and 82 and 75% at 2 years, respectively. The EFS by therapeutic groups at 3 years was A: 100%; B: 76%, and C: 56%.
TOXICITY: neutropenia in 75%, thrombocytopenia in 63%, febrile neutropenia in 39%. Viral infections: hepatitis B in 20%, hepatitis C in 2%, and Herpes zoster in 3%. Tumor lysis syndrome (TLS) occurred in 9% during induction phase with a high mortality of 44% (urate-oxidase was available only at the end of the study).
CONCLUSIONS: The high mortality rate during induction phase prohibited a better EFS. Prophylactic use of xantine-oxidase may improve future results. The high incidence of hepatitis B requires a vaccination program.

Núñez JT, Delgado M, Girón H, Pino G
Prostitution and other cofactors in preinvasive and invasive lesions of the cervix.
Aust N Z J Obstet Gynaecol. 2004; 44(3):239-43 [PubMed] Related Publications
OBJECTIVE: To examine risk factors for preinvasive and invasive lesions of the cervix in Venezuelan female sex workers (FSW).
METHODS: A total of 438 FSW were analysed. Each FSW had their clinical history recorded, a gynaecological examination, a Pap smear and a colposcopic examination of the cervix. A cervical biopsy was taken under colposcopic guidance when there was an abnormal epithelium. The statistical methods used were Student's t-test, chi(2) test and logistic regression.
RESULTS: The sex workers' mean age was 32.1 +/- 7.9 years old (mean +/- standard deviation). The age of the first sexual intercourse activity for the FSW was 15.9 +/- 2.1 years. Sixty-four of the 84 women (76.2%) who had cervical biopsies had preinvasive and invasive lesions; 41 (9.4%) had cervical intra-epithelial neoplasia (CIN) 1, 12 (2.7%) had CIN 2, eight (1.8%) had CIN 3, two (0.5%) had microinvasive carcinoma, and one (0.2%) had invasive carcinoma. Forty of these 64 women (62.5%) with preinvasive or invasive lesions had a concurrent histological diagnosis of human papilloma virus (HPV) infection (P < 0.0001). The FSW with cervical pathology were younger (P < 0.05) and had their first sexual intercourse earlier (P < 0.02) than FSW with no pathology. Two hundred and seventy-six (63%) of the FSW were current smokers, and 47 of these women (17.6%) had cervical pathology (P < 0.03).
CONCLUSIONS: First sexual experience before 20 years of age, cigarette smoking and HPV infection were high-risk factors for preinvasive and invasive lesions of the cervix in Venezuelan FSW.

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