Carcinoma primário do pulmão

Em um período de 23 anos, de 1919 a 1941, observaram-se 25 casos de carcinoma primário do pulmão entre o total de 6.458 necrópsias, registadas na Secção de Anatomia Patológica do Instituto Osvaldo Cruz e realizadas nos vários hospitais do Rio de Janeiro. Os indivíduos eram de procedência variada, não só de diferentes regiões do Brasil, como também de alguns países estrangeiros. A incidência do carcinoma primário do pulmão, considerado como causa mortis, entre o total das necrópsias e de 0,38 % e, entre os casos de cancer, 4,5 %. Em referência ao sexo, 21 casos eram de indivíduos masculinos (84 %) e 4 femininos (16 %), fornecendo a relação de 5:1. Dos 25 casos, 13 (52 %) eram de nacionalidade estrangeira e 12 (48 %) brasileira; 18, em indivíduos de cor branca, 6 pretos e 1 pardo. Em relação à idade, a maior incidência ocorreu entre 41 e 70 anos, com o máximo entre 51 a 60, existindo casos extremos de 21 e 93 anos. A forma anatômica mais freqüente, no mesmo material, e a infiltrante hilar, 16 casos (64 %), seguindo-se a nodular, com 7 casos (28 %) e a difusa, 2 casos (8) . O carcinoma de células indiferenciadas é o tipo histológico mais comum, existindo em 13 casos (52 %), seguindo-se o tipo de células cilíndricas, em 8 casos (32 %) e o de células pavimentosas em 4 casos (16 %). A incidência das metastases foi observada em 22 casos (88 %), sendo, para o carcinoma de células indiferenciadas, de 76,9 %, e, tanto para o carcinoma de células cilíndricas como para o de células pavimentosas, de l00%. Em três casos (12 %), não foram observadas metástases. Entre os orgãos sede frequente das metástases, foi observada a seguinte relação: gênglios linfáticos, 72 %; fígado, 56 %; pleura, 12 %; peritônio, pericárdio, rins e suprarrenal, 8 %; cérebro e osso, 4 %. Nos últimos 10 anos (1932 a 1941), ocorreram 16 casos (64 % do total dos 25 encontrados), demostrando senão o aumento do cancer pulmonar, certamente o maior número de diagnostico positivos.

Carcinoma metastatico do baço

Among the material of the archives of the Pathological Section of the Oswaldo Cruz Institue (Rio de Janeiro, Brasil) we found 9 cases of cancer metastasis in the spleen. Four of them were macroscopically apparent, but five had only been diagnosed microscopically. Of these cases of tumors, 3 are adenocarcinoma originated from the pancreas (cases 1, 3, 5,); 3 are primary carcinoma of stomach (cases 7,8 and 9); 1 adenocarcinoma of gall-bladder (case 2); 1 originated form the mammary gland (case 4) and finally 1 form the colon. (case 6.). The incidence of the metastasis observed in the spleen among the total of 6.400 studied autopsies is of 0,14%; The same incidence among those of epithelial blastomata is of 1,8%.

Carcinoma primário do pâncreas

O estudo anatomopatológico baseado em uma coleção de 6823 necrópsias, constantes do arquivo da Seção de Anatomia Patológica do Instituto Oswaldo Cruz, Rio de Janeiro, Brasil, realizadas durante os anos de 1919 a 1944, revelou a existência de 28 casos de carcinoma primário do pâncreas. A incidência deste tipo de tumor entre o total das necropsias examinadas atinge a 0,40% e, entre os casos de câncer observados na referida série de necrópsias, a 4,08%. O tumor localizou-se na cabeça do pâncreas em 20 casos (71,4%); na cauda, em um caso (3,5%); difuso, em cinco casos (17,8%) e sem localização precisada, em dois casos (7,1%). O tipo histológico predominante foi o adenocarcinoma, reconhecido em 2 casos (78,57%); e em seguida o carcinoma acinoso, em seis casos (21,43%). Geralmente se observa o tipo cirrótico e, em alguns casos, era pronunciada a formação de mucina. A incidência das metástases, em relação aos casos de adenocarcinoma, foi de 95,45% (21 vêzes em 22 casos) e, em relação ao carcinoma acinoso, de 100% (6 vêzes em 6 casos). Entre os órgãos atingidos pelas metástases citam-se em ordem decrescente: o fígado e os gânglios linfáticos (70,3%) o peritônio (25,9%), o pulmão (22,2%), a suprarrenal (18,5%), a pleura bago e rim (7,4%), os intestinos, tiróide, pericárdio, epiploon, estomago, ovário e seio venoso longitudinal superior (3,7%).Em um só caso, não houve produção de metástase (3,57%). Em relação às metástases no peritônio, é interessante acentuar a sua maior freqüência nos casos de adenocarcinoma (7 vêzes em 22 casos). A distribuição do tumor, segundo o sexo, foi de 19 casos em indivíduos do sexo masculino (67,8%) e nove casos, para os do sexo feminino (32,1%), fornecendo a relação de cêrca de 2:1. Segundo a nacionalidade, observaram-se 21 casos (75%) em brasileiros e sete casos (25%) em estrangeiros. Segundo a côr, em 15 casos (53,5%) eram indivíduos de côr branca, em oito casos, (28,5%) de côr preta e, em cinco casos (17,8%), de côr parda. O maior número de casos, em referência à idade, ocorreu em indivíduos de 41 a 50 anos, quando a incidência foi de 11 casos ou 39,3% do total dos casos observados. Em referência a ocorrência anual, verifica-se o maior número (22 casos ou 78,9%) nos últimos dez anos, isto e, de 1935 a 1944.

Inhibitory effect of cyclophosphamide on the biosynthesis of a perchloro-soluble protein fraction of ehrlich ascites carcinoma cells

The perchloro-soluble mucroptotein fraction was determined in the cells of Ehrlich ascites carcinoma on the 10th and 12th days post-inoculation of the tumor. After 3 days of a single subcutaneous dose of cyclophosphamide (200 mg/kg) the mucoprotein levels were found considerable lower. This difference was highly significant statistically.

Human papillomavirus detection in genital lesions by in situ hybridization and ultrastructural observations

Detection of papillomavirus DNA in sity hybridization technique was perfomed in 29 symptomatic patients (6 males and 23 females) during the period of 1989-1991 at the Clinic for Sexually Transmitted Diseases, Universidade Federal Fluminense, State of rio de Janeiro. All the male patients had condyloma acuminata. Only HPV 6/11 were found in these lesions. Clinical features inthe female patients included vulvar condyloma acuminata, bowenoid populosis, flat cervical condyloma, cervical condyloma acuminatum and cervical intraepithelialneoplasia grade II (CIN II). We also found cases of condyloma acuminata associated to vulvar intraepithelial neoplasia grade III (VIN III), as well as to vaginal invasive carcinoma. HPV 6/11 and 16/18 were found in vulvar condyloma acuminata. Mixed infection by 6/11-16/18 HPV were also seen in these lesions as well as in the patient who had cervical condyloma acuminatum. HPV 16/18 were found in the condyloma acuminatum plus VIN III and in the CIN II lesions. We have found HPV31/33/51 in the specimen of condyloma acuminatum plus invasive carcinoma. In order to investigate the ultrastructural aspects of HPV infection in genital tissue, the biopsies of three female patients were observed under electron microscope.Mature virus particles were found in the cells of a condyloma acuminatum as wellas in the condyloma acuminatum plus invasive carcinoma case. In another sample, chromosome breakages were found in the nuclei of the infected cells although no viral particles were observed.

Prevalence of human papillomavirus types in women with pre-neoplastic and neoplastic cervical lesions in the Federal District of Brazil

As a contribution to the public health authorities in planning prophylactic and therapeutic vaccine strategies, we describe the prevalence of human papillomavirus (HPV) types in women presenting abnormal cytological results in Pap smear screening tests in the Federal District, Central Brazil. We studied 129 cervical scraping samples from women whose cytological tests showed either pre-neoplastic or neoplastic lesions. Amplification of HPV DNA was performed by polymerase chain reaction using consensus primers MY09 and MY11 followed by identification of isolates by restriction fragment length polymorphism. We detected HPV DNA in 62% of the samples, including HPV-16 in 43.8%, HPV-58 in 12.5%, HPV-31 in 10%, HPV-53 in 6.3%, each of HPV-18 and HPV-33 in 3.8% of the isolates. Other types (HPV-35, -52, -66, -CP8304, -6, -11, and -CP8061) were less frequent (= or < 2.5% each). The prevalence of HPV-58 was relatively higher in this population than in data in South America, but similar to results obtained in other studies in Latin America, Europe, and Eastern Asia. Case-control studies need to be carried out to establish the association between the prevalence of HPV types specially the less frequent high-risk types and cervical cancer.

Immunoblotting for the serodiagnosis of Helicobacter pylori infection in Brazilian patients with and without gastric carcinoma

We evaluated the performance of a commercial immunoblotting in the serodiagnosis of Helicobacter pylori infection in Brazilian patients. The presence of anti-H. pylori antibodies was also investigated in a group of 20 duodenal ulcer patients after successful treatment. One hundred and ninety one patients were studied. Among the 164 infected patients, 46 had gastric carcinoma. The duodenal ulcer patients were treated with antimicrobial drugs and the eradication of the microorganism was confirmed in all of them one month after the end of the treatment by the 13C-urea breath test. Sera were assayed for H. pylori antibodies using the Helicoblot 2.0 (Genelabs Diagnostics, Singapore). The sensitivity, specificity, positive, and negative predictive values of the test were 93.9%, 92.6%, 98.7%, and 71.4%, respectively. The sensitivity of the test was similar in patients with (93.5%) and without (95.7%) gastric carcinoma. Twenty-four months after the end of the treatment, the band of 116 kDa was still detected in one of the patients. In conclusion, the Helicoblot 2.0 is an accurate test to diagnose H. pylori infection and although it can not be employed to monitor the bacterium eradication, it may be useful for diagnosing past infection, especially in gastric carcinoma patients.

Prevalence of human papillomavirus type 16 variants in the Federal District, Central Brazil

We report the prevalence of human papillomavirus type 16 (HPV-16) variants in women with cervical lesions from the Federal District, Central Brazil. We analyzed 34 HPV-16 samples, identifying the sequence variations of E6 and L1 genes and correlating variant frequency with disease status. The most prevalent HPV-16 variant was the European (50%), followed by Asian-American (41.2%), African-1 (5.9%), and African-2 (2.9%). European and non-European variants appeared in equal frequencies among the cytological types of lesions - atypical squamous or glandular cells of undetermined significance, cytological alterations suggesting HPV infection, cervical intraepithelial neoplasias, squamous cell carcinoma, and adenocarcinoma.

Immune response in cervical dysplasia induced by human papillomavirus: the influence of human immunodeficiency virus-1 co-infection - review

Human immunodeficiency virus (HIV-1) has become an important risk factor for human papillomavirus (HPV) infection and the development of HPV associated lesions in the female genital tract. HIV-1 may also increase the oncogenicity of high risk HPV types and the activation of low risk types. The Center for Disease Control and Prevention declared invasive cervical cancer an acquired immunodeficience virus (AIDS) defining illness in HIV positive women. Furthermore, cervical cancer happens to be the second most common female cancer worldwide. The host's local immune response plays a critical factor in controlling these conditions, as well as in changes in the number of professional antigen-presenting cells, cytokine, and MHC molecules expression. Also, the production of cytokines may determine which arm of the immune response will be stimulated and may influence the magnitude of immune protection. Although there are many studies describing the inflammatory response in HPV infection, few data are available to demonstrate the influence of the HIV infection and several questions regarding the cervical immune response are still unknown. In this review we present a brief account of the current understanding of HIV/HPV co-infection, emphasizing cervical immune response.

HPV vaccination: the beginning of the end of cervical cancer? - A Review

Human papillomavirus (HPV) is responsible for all cases of cervical cancer, as well as a great percentage of other anogenital tumors and oropharyngeal tumors. Since the main etiologic factor for these diseases is a virus, prophylactic measures are the best way to reduce the burden caused by the infection and associated disease. This review brings up to date information on the two commercially available prophylactic HPV vaccines against HPV, as well as presenting the ongoing research on HPV peptide, protein and dendritic cell based therapeutic vaccines.

High prevalence and low E6 genetic variability of human papillomavirus 58 in women with cervical cancer and precursor lesions in Southeast Mexico

Infection with some genotypes of human papillomavirus (HPV) is the most important risk factor associated with cervical cancer (CC). Throughout the world, HPV type 58 prevalence varies from one region to another; it is higher in women from certain countries in Asia and Latin America, such as China and Mexico. Although intratypic variants have been reported on a few occasions, our knowledge about HPV 58 genetic variation remains limited. Therefore, this work aims to (i) determine the prevalence of HPV type 58 amongst Mexican women with invasive CC or precursor lesions and (ii) identify HPV 58 sequence variants. One hundred and forty five colposcopy clinic patients were studied. Genotyping of HPV 16, 18 and 58 was determined by specific nested PCR and HPV 58 variants were detected by direct sequencing. The general prevalence of HPV was 51.7% (75/145). HPV 16 was found in 30.6% (23/75) and HPV 58 in 24% (18/75) of the patients. HPV 18 was not identified in patients with cervical intraepithelial neoplasia (CIN) grade I; it was only found in those with CIN II, with a prevalence of 6.8% (3/44). In patients with CC, the prevalence of HPV 16 and 58 was 78.9%. Regarding HPV 58 variants, 94.4% of the HPV 58 sequences were identical to the prototype strain, whereas one sample showed changes at a single nucleotide. This study demonstrates a high prevalence of HPV 58 and a low genetic variability of E6 sequences amongst Mexican colposcopy patients.

Correlation between koilocytes and human papillomavirus detection by PCR in oral and oropharynx squamous cell carcinoma biopsies

The purpose of this study was to compare the histopathological analysis with polymerase chain reaction (PCR) methods to predict the presence of human papillomavirus (HPV) infection in oral squamous cell carcinoma biopsies. Eighty-three paraffin-embedded tissue specimens from patients with oropharynx and mouth floor squamous cell carcinoma were submitted to histopathological analysis under light microscopy, specifically for the determination of the presence of koilocytes. Subsequently, DNA was purified from the same paraffin-embedded specimens and submitted to PCR. Fisher's exact test showed no statistically significant correlation between the two methods. The results suggest that the presence of koilocytes is unreliable for the detection of HPV presence in oral and oropharynx squamous cell carcinoma.

An evaluation of p16INK4a expression in cervical intraepithelial neoplasia specimens, including women with HIV-1

Although several studies have evaluated the role of p16INK4a as a diagnostic marker of cervical intraepithelial neoplasia (CIN) and its association with disease progression, studies regarding the role of p16INK4a in human immunodeficiency virus (HIV)-infected patients remain scarce. The present study was designed to determine the potential utility of p16INK4a as a diagnostic marker for CIN and invasive cervical cancer in HIV-positive and negative cervical specimens. An immunohistochemical analysis of p16INK4a was performed in 326 cervical tissue microarray specimens. Performance indicators were calculated and compared using receiving operating characteristics curve (ROC)/area under the curve. In HIV-1-negative women, the percentage of cells that was positive for p16INK4a expression was significantly correlated with the severity of CIN (p < 0.0001). A ROC curve with a cut-off value of 55.28% resulted in a sensitivity of 89%, a specificity of 81%, a positive predictive value of 91% and a negative predictive value of 78%. HIV-seropositive women exhibited decreased expression of p16INK4a in CIN2-3 specimens compared with HIV-negative specimens (p = 0.031). The ROC data underscore the potential utility of p16INK4a under defined conditions as a diagnostic marker for CIN 2-3 staging and invasive cervical cancer. HIV-1 infection, however, is associated with relatively reduced p16INK4a expression in CIN 2-3.

Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil

Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4+ lymphocyte count < 200/mm3 (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

CCR2 and CCR5 genes polymorphisms in women with cervical lesions from Pernambuco, Northeast Region of Brazil: a case-control study

Polymorphisms in chemokine receptors play an important role in the progression of cervical intraepithelial neoplasia (CIN) to cervical cancer (CC). Our study examined the association of CCR2-64I (rs1799864) andCCR5-Δ32 (rs333) polymorphisms with susceptibility to develop cervical lesion (CIN and CC) in a Brazilian population. The genotyping of 139 women with cervical lesions and 151 women without cervical lesions for the CCR2-64I and CCR5-Δ32 polymorphisms were performed using polymerase chain reaction-restriction fragment length polymorphism. The individuals carrying heterozygous or homozygous genotypes (GA+AA) for CCR2-64I polymorphisms seem to be at lower risk for cervical lesion [odds ratio (OR) = 0.37, p = 0.0008)]. The same was observed for the A allele (OR = 0.39, p = 0.0002), while no association was detected (p > 0.05) with CCR5-Δ32 polymorphism. Regarding the human papillomavirus (HPV) type, patients carrying the CCR2-64Ipolymorphism were protected against infection by HPV type 16 (OR = 0.35, p = 0.0184). In summary, our study showed a protective effect ofCCR2-64I rs1799864 polymorphism against the development of cervical lesions (CIN and CC) and in the susceptibility of HPV 16 infection.