Human papillomavirus genotype attribution in invasive cervical cancer: a retrospective cross-sectional worldwide study.

BACKGROUND: Knowledge about the distribution of human papillomavirus (HPV) genotypes in invasive cervical cancer is crucial to guide the introduction of prophylactic vaccines. We aimed to provide novel and comprehensive data about the worldwide genotype distribution in patients with invasive cervical cancer. METHODS: Paraffin-embedded samples of histologically confirmed cases of invasive cervical cancer were collected from 38 countries in Europe, North America, central South America, Africa, Asia, and Oceania. Inclusion criteria were a pathological confirmation of a primary invasive cervical cancer of epithelial origin in the tissue sample selected for analysis of HPV DNA, and information about the year of diagnosis. HPV detection was done by use of PCR with SPF-10 broad-spectrum primers followed by DNA enzyme immunoassay and genotyping with a reverse hybridisation line probe assay. Sequence analysis was done to characterise HPV-positive samples with unknown HPV types. Data analyses included algorithms of multiple infections to estimate type-specific relative contributions. FINDINGS: 22,661 paraffin-embedded samples were obtained from 14,249 women. 10,575 cases of invasive cervical cancer were included in the study, and 8977 (85%) of these were positive for HPV DNA. The most common HPV types were 16, 18, 31, 33, 35, 45, 52, and 58 with a combined worldwide relative contribution of 8196 of 8977 (91%, 95% CI 90-92). HPV types 16 and 18 were detected in 6357 of 8977 of cases (71%, 70-72) of invasive cervical cancer. HPV types 16, 18, and 45 were detected in 443 of 470 cases (94%, 92-96) of cervical adenocarcinomas. Unknown HPV types that were identified with sequence analysis were 26, 30, 61, 67, 69, 82, and 91 in 103 (1%) of 8977 cases of invasive cervical cancer. Women with invasive cervical cancers related to HPV types 16, 18, or 45 presented at a younger mean age than did those with other HPV types (50·0 years [49·6-50·4], 48·2 years [47·3-49·2], 46·8 years [46·6-48·1], and 55·5 years [54·9-56·1], respectively). INTERPRETATION: To our knowledge, this study is the largest assessment of HPV genotypes to date. HPV types 16, 18, 31, 33, 35, 45, 52, and 58 should be given priority when the cross-protective effects of current vaccines are assessed, and for formulation of recommendations for the use of second-generation polyvalent HPV vaccines. Our results also suggest that type-specific high-risk HPV-DNA-based screening tests and protocols should focus on HPV types 16, 18, and 45.

Interstitial cells of Cajal in chagasic megaesophagus.

Chagasic visceromegalies are the most important digestive manifestations of Chagas disease and are characterized by motor disorders and dilation of organs such as esophagus and colon. One of the theories raised to explain the physiopathogenesis of chagasic megas is the plexus theory. Recent studies have shown a reduction of interstitial cells of Cajal (ICCs) in the colon of chagasic patients. These cells are present throughout the gastrointestinal tract and are considered to be pacemaker cells, that is, they are responsible for coordinating peristalsis and for mediating nerve impulses. In view of the lack of studies on these cells in megaesophagus and the previous observation of a reduction of ICCs in chagasic megacolons, we compared the distribution of ICCs in the esophagus of chagasic and nonchagasic patients to contribute to a better understanding of the physiopathogenesis of this esophageal disease. Esophageal biopsy samples from 10 chagasic and 5 nonchagasic patients were used. Cells were identified with the anti-CD117 antibody. The number of ICCs was quantified in longitudinal and circular muscle layers and myenteric plexus. The results were analyzed statistically by comparison of means. An intense reduction in the number of ICCs was observed in muscle layers and in the myenteric plexus of patients with megaesophagus. We conclude that there is an intense reduction of ICCs in the esophagus of chagasic patients when compared to nonchagasic patients, a finding supporting the important role of these cells in gastrointestinal tract motility. A deficiency in these cells might be implied in the genesis of megaesophagus.

[Alcoholization in the treatment of thyroid nodule in colloid goiter endemic region]. / Alcoolização de nódulo tiroidiano em região endêmica de bócio colóide.

Thyroid nodular disease is a common clinical disorder mainly in iodine lacking regions. This study has evaluated the effectiveness of percutaneous ethanol injection (PEI) in the treatment of single, multiple, solid, and cystic thyroid nodules of different sizes with or without glandular dysfunction, in goiter endemic region. Forty-two patients with diagnosis of colloid goiter or colloid nodular hyperplasia in fine-needle aspiration (FNA) were selected for analysis, after having been submitted to at least two PEI. Thyroid nodules were multiple (solid and or cystic) in 52.4% of the patients, single and solid or mixed in 35.7%, and single and cystic in 11.9%. The mean reduction of nodules after ethanol injection was of 58.2% in the single and of 60.8% in the cystic ones. The reduction of the whole thyroid lobe was evaluated in the multiple nodules and it reached 52.4%. The side-effects were registered only as a consequence of the application discomfort. This study points out that the percutaneous ethanol injection reaching volume mean reductions, varying from 49% to 60%, is a safe, effective, and simple method for the treatment of benign thyroid nodules.

Intestinal spirochetosis and colon diverticulosis.

A case of intestinal spirochetosis in a 62-year-old white male is reported. The condition was characterized by chronic flatulence and episodes of intestinal hemorrhage, in addition to the evidence of hypotonic diverticular disease, with a large number of slender organisms in the colon epithelium and cryptae. Spirochetes were demonstrated by Whartin-Starry stain. The serologic tests for syphilis and HIV were positive. Spirochetosis was treated with penicillin G, and the patient remains free of intestinal complaints 20 months later.

[Granulomatous nodule with Enterobius vermicularis in epiploon simulating metastasis of ovarian cancer]. / Nódulo granulomatoso com Enterobius vermicularis em epíploon simulando metástase de câncer de ovário.

The authors describe a case of peritoneal enterobiasis presenting as necrotizing granuloma, in a adolescent with tumor of the ovarian endodermic sinus. The diagnosis was established through biopsy of peritoneal nodule, during laparotomy for staging system of ovarian cancer. Granulomatous nodules due to parasites could simulate metastasis, and cause confusion in the staging system for cancer.

[Pulmonary schistosoma nodule simulating neoplasia: case report]. / Nódulo pulmonar esquistossomótico simulando neoplasia: relato de caso.

Healthy patient in which during ordinary examination a pulmonary schistosomotic nodule with an adult parasite, was detected 25 years far from endemic region and after specific treatment with oxamniquine. Clinically the nodule simulated neoplasia.

Potential impact of a 9-valent HPV vaccine in HPV-related cervical disease in 4 emerging countries (Brazil, Mexico, India and China).

BACKGROUND: We estimated the potential impact of an investigational 9-valent human papillomavirus (HPV) vaccine (HPVs 6/11/16/18/31/33/45/52/58) in HPV-related cervical disease in Brazil, Mexico, India and China, to help to formulate recommendations on cervical cancer prevention and control. METHODS: Estimations for invasive cervical cancer (ICC) were based on an international study including 1356 HPV-positive cases for the four countries altogether, and estimations for precancerous cervical lesions were extracted from a published meta-analysis including 6 025 HPV-positive women from the four mentioned countries. Globocan 2012 and 2012 World Population Prospects were used to estimate current and future projections of new ICC cases. RESULTS: Combined proportions of the 9 HPV types in ICC were 88.6% (95%CI: 85.2-91.3) in Brazil, 85.7% (82.3-88.8) in Mexico, 92.2% (87.9-95.3) in India and 97.3% (93.9-99.1) in China. The additional HPV 31/33/45/52/58 proportions were 18.8% (15.3-22.7) in Brazil, 17.6% (14.2-21.2) in Mexico, 11.3% (7.5-16.1) in India and 11.9% (7.5-17.2) in China. HPV6 and 11 single types were not identified in any of the samples. Proportion of the individual 7 high risk HPV types included in the vaccine varied by cytological and histological grades of HPV-positive precancerous cervical lesions. HPV 16 was the dominant type in all lesions, with contributions in low grade lesions ranging from 16.6%(14.3-19.2) in Mexico to 39.8% (30.0-50.2) in India, and contributions in high grade lesions ranging from 43.8% (36.3-51.4) in Mexico to 64.1% (60.6-67.5) in Brazil. After HPV 16, variations in other majors HPV types were observed by country, with an under representation of HPV 18 and 45 compared to ICC. CONCLUSION: The addition of HPVs 31/33/45/52/58 to HPV types included in current vaccines could increase the ICC preventable fraction in a range of 12 to 19% across the four countries, accounting the 9-types altogether 90% of ICC cases. Assuming the same degree of efficacy of current vaccines, the implementation of the 9-valent HPV vaccine in Brazil, Mexico, India and China would substantially impact on the reduction of the world cervical cancer burden.

Conservative treatment of uterine cervical adenocarcinoma in pregnancy.

Cancer of the cervix is the most common malignancy diagnosed during pregnancy, with an incidence of 1-10 cases per 10,000 pregnancies. The desire of patients to maintain pregnancy and subsequent fertility is a difficult target to be achieved and should be widely studied, since it depends on the stage of disease, gestational age at diagnosis, and the woman's desire to maintain pregnancy. We describe in this report the case of a pregnant woman with invasive cervical adenocarcinoma in stage IB1 (FIGO) initially treated with neoadjuvant chemotherapy, followed by radical surgery and cesarean section in the same surgical procedure.

Titanium pigment in tissues of drug addicts: report of 5 necropsied cases.

The aim of this report is to describe the anatomic-pathologic findings from necropsies of 5 drug addicts with titanium pigment in several organs after chronic intravenous injection of crushed propoxyphene hydrochloride tablets. Samples from liver, spleen, lungs, lymph nodes, and bone marrow were obtained, and after being grossly studied, they were submitted to evaluation using common light and polarized microscopy. In all 5 cases, a pigment with characteristics of titanium dioxide was found within tissue samples of the organs studied. Our findings suggest that research concerning titanium pigment within body tissues should be enhanced, considering the potential contribution of this morphologic data to forensic pathology.

Functional and histopathological study of the pancreas in hamsters (Mesocricetus auratus) infected and reinfected with Trypanosoma cruzi.

Histopathological and functional changes in the pancreas were studied in 94 hamsters infected and reinfected with Trypanosoma cruzi VIC strain and in 73 non-infected normal controls. Infection in each animal was verified by microhematocrit, hemoculture, specific peroxidase anti-peroxidase, polymerase chain reaction and seroagglutination. Blood glucose and insulin were determined. The number of islets per section and the number of islet cells marked with antibodies were counted. Insulitis, neuritis, fibrosis, atrophy and inflammatory infiltrates were evaluated. Experimental chagasic infection caused pancreatitis similar to human Chagas' disease, involving acini, islets and nerves, with atrophy and fibrosis, although without correlation to the number of reinfections. Erratic blood glucose levels and a tendency to hypoinsulinemia were observed in infected animals. During the acute phase, the number of somatostatin and pancreatic polipeptide producer islet cells was lower in infected hamsters, which was eventually related to changes in blood sugar levels and hypoinsulinemia. Our findings favor the hypothesis of the existence of an endocrine form of chronic chagasic infection.

Genitourinary changes in hamsters infected and reinfected with Trypanosoma cruzi.

Authors describe genitourinary changes in male hamsters infected and reinfected with Trypanosoma cruzi. Changes in genital organs have been described in human and in experimental chagasic infection. Genital dysfunctions in chronic chagasic patients affect ejaculation, libido and sexual potency, and testis biopsies may show arrested maturation of germ cells, oligozoospermia and azoospermia. Sixty-five male hamsters were inoculated and reinoculated with 2x10 trypomastigotes of T. cruzi VIC strain, and 22 non-infected animals constituted the control group. Animals were necropsied and fragments from testis, epididymis, seminal vesicle and bladder were collected and stained with hematoxylin-eosin. Peroxidase anti-peroxidase procedure was utilized to detect tissue parasitism. T. cruzi nests were found in testis, epididymis and seminal vesicle of these hamsters. Such parasitism plays a role in the origin of genital lesions observed in humans and laboratory animals during chronic chagasic infection.

Pancreatic hepatocytes in hamsters (Mesocricetus auratus) infected with Trypanosoma cruzi.

Hepatocytic metaplasia may be induced in hamsters by carcinogens, and associated with aging, diabetes or chronic pancreatitis. By means of histopathologic and immunohistochemic studies, we observed pancreatic hepatocytes in hamsters infected and reinfected with Trypanosoma cruzi. The change was seen in 18 (19%) out of 94 infected animals, and was not found among 53 controls, Normal islet cells were immunoreactive for neuron-specific enolase and not reactive for NCL-HAS. Metaplastic cells were immunoreactive for NCL-HAS and not reactive for islet hormones and enolase. No relationship was observed between number of inoculations and metaplasia; however, the intensity of the inflammatory process and sequels seems to favor the development of metaplastic cells. Hamsters infected with T. cruzi may be useful to study hepatocytic metaplasia, and contribute to clarify aspects of Chagas' disease and pancreatic changes. Our data indicate that aging, in addition to inflammation and atrophy, plays a role in this change.

C cells in the thyroid of pinealectomized rats.

PURPOSE: To study quantitatively C cells in the thyroids of non-isogenic rats to determine the possible effects of pinealectomy on the number of these cells, and consequently on the synthesis and secretion of calcitonin. METHODS: Twenty male rats of an outbred strain (200-300 g) were used in the present study. One group of 10 animals was pinealectomized 50 days prior to sacrifice. Thyroid tissue was stained for calcitonin (Dako Corporation) at a 1:1500 dilution. The number of C cells observed was expressed as number of cells/cm . Data were analyzed statistically by Mann-Whitney test. RESULTS: The number of C cells in pinealectomized and normal animals ranged from 489 to 2084 per cm and 227 to 1584 per cm , respectively, a difference that was statistically significant (P <0.05). CONCLUSIONS: These results showed consistent differences in the number of C cells after pinealectomy when compared to controls. We believe that pinealectomy increases the number of C cells in the rat thyroid.

Alcoolização de nódulo tiroidiano em região endêmica de bócio colóide / Alcoholization in the treatment of thyroid nodule in colloid goiter endemic region

A doença nodular tiroidiana é problema clínico comum, principalmente em regiões com carência de iodo. Esse estudo avaliou a eficácia da injeção percutânea de etanol (IPE) no tratamento de nódulos tiroidianos únicos, múltiplos, sólidos, císticos, de diferentes tamanhos com ou sem disfunção glandular, em região endêmica de bócio. Quarenta e dois pacientes com diagnóstico de bócio colóide ou hiperplasia nodular colóide, na punção biópsia aspirativa por agulha fina (PBAAF), foram selecionados para análise após terem sido submetidos a pelo menos duas IPEs. Os nódulos tiroidianos eram múltiplos (sólidos e ou císticos) em 52,4 por cento dos pacientes, únicos e sólidos ou mistos em 35,7 por cento e únicos e císticos em 11,9 por cento. A redução média dos nódulos após injeção de etanol foi de 58,2 por cento para os únicos e 60,8 por cento nos císticos. Nos nódulos múltiplos, avaliou-se a redução de todo o lobo tiroidiano, alcançando 52,4 por cento de redução. Os efeitos colaterais registrados foram decorrentes apenas do desconforto na aplicação. Este estudo indica que a injeção percutânea de etanol (IPE), alcançando reduções médias de volume que variam de 49 a 60 por cento, é método seguro, eficaz e simples para o tratamento de nódulos tiroidianos benignos.

Thyroid nodular disease is a common clinical disorder mainly in iodine lacking regions. This study has evaluated the effectiveness of percutaneous ethanol injection (PEI) in the treatment of single, multiple, solid, and cystic thyroid nodules of different sizes with or without glandular dysfunction, in goiter endemic region. Forty-two patients with diagnosis of colloid goiter or colloid nodular hyperplasia in fine-needle aspiration (FNA) were selected for analysis, after having been submitted to at least two PEI. Thyroid nodules were multiple (solid and or cystic) in 52.4 percent of the patients, single and solid or mixed in 35.7 percent, and single and cystic in 11.9 percent. The mean reduction of nodules after ethanol injection was of 58.2 percent in the single and of 60.8 percent in the cystic ones. The reduction of the whole thyroid lobe was evaluated in the multiple nodules and it reached 52.4 percent. The side-effects were registered only as a consequence of the application discomfort. This study points out that the percutaneous ethanol injection reaching volume mean reductions, varying from 49 percent to 60 percent, is a safe, effective, and simple method for the treatment of benign thyroid nodules.

Intestinal spirochetosis and colon diverticulosis

Um caso de espiroquetose intestinal é relatado em um homem branco de 62 anos. A condição foi caracterizada por flatulência crônica e episódios de hemorragia intestinal, além da evidência de doença diverticular hipotônica dos cólons, com numerosos organismos filamentosos no epitélio e nas criptas do cólon. Os espiroquetas foram demonstrados pela coloração de Whartin-Starry. Os testes sorológicos para sífilis e HIV foram positivos. A espiroquetose foi tratada com penicilina G e o paciente permanece sem queixas intestinais após 20 meses.

Titanium pigment in tissues of drug addicts: report of 5 necropsied cases

O objetivo deste relato é descrever os achados anatomopatológicos de cinco casos de toxicômanos com pigmento de titânio em vários órgãos, após injeção de comprimidos esmagados de cloridrato de propoxifeno. Foram obtidos fragmentos do fígado, baço, pulmões, linfonodos e medula óssea e, após a avaliação macroscópica, amostras foram submetidas à microscopia de luz comum e de luz polarizada. Em todos os cinco casos, foi encontrado um pigmento com características de dióxido de titânio nas amostras dos órgãos estudados. Nossos achados sugerem que a pesquisa sobre pigmento de titânio em tecidos corporais deva ser complementada, considerando-se a contribuição de dados morfológicos em Patologia Forense.

Nódulo granulomatoso com Enterobius vermicularis em epíploon simulando metástase de câncer de ovário / Granulomatous nodule with Enterobius vermicularis in epiploon simulating metastasis of ovarian cancer

Os autores descrevem caso de enterobíase peritoneal apresentando-se como granuloma necrosante, em adolescente com tumor do seio endodérmico do ovário. O diagnóstico foi estabelecido por biópsia de nódulo do epíploon, durante laparotomia para reestadiamento de câncer de ovário após tratamento clínico. Nódulos granulomatosos peritoneais causados por parasitas podem simular metástases, confundindo o estadiamento de neoplasias

Punçäo por agulha fina sem aspiraçäo (citopunçäo): aplicaçäo de nova técnica / Fine needle puncture without aspiration (cytopuncture): application of new technic

As vantagens e desvantagens de um método citológioco simplificado de punçäo por agulha fina sem aspiraçäo säo comparados com os da técnica de punçäo aspirativa clássica em uma série de 20 pacientes com punçöes em diferentes órgäos. Celularidade maior foi obtida pela técnica clássica e a mama foi o órgäo com maior número de material insuficiencia na técnica sem aspiraçäo. A qualidade do material obtido de gânglios linfáticos foi melhor com a nova técnica. O método da punçäo sem aspiraçäo (citopunçäo) é descrito e ilustrado e as implicaçöes para seu uso em diferentes órgäos säo discutidas. Em nosso conhecimento, este é o primeiro relato dessa técnica na literatura nacional

Genitourinary changes in hamsters infected and reinfected with Trypanosoma cruzi

Authors describe genitourinary changes in male hamsters infected and reinfected with Trypanosoma cruzi. Changes in genital organs have been described in human and in experimental chagasic infection. Genital dysfunctions in chronic chagasic patients affect ejaculation, libido and sexual potency, and testis biopsies may show arrested maturation of germ cells, oligozoospermia and azoospermia. Sixty-five male hamsters were inoculated and reinoculated with 2x10 trypomastigotes of T. cruzi VIC strain, and 22 non-infected animals constituted the control group. Animals were necropsied and fragments from testis, epididymis, seminal vesicle and bladder were collected and stained with hematoxylin-eosin. Peroxidase anti-peroxidase procedure was utilized to detect tissue parasitism. T. cruzi nests were found in testis, epididymis and seminal vesicle of these hamsters. Such parasitism plays a role in the origin of genital lesions observed in humans and laboratory animals during chronic chagasic infection

Hanseníase virchowiana em cardiopata chagásico: relato de necropsia / Generalized hanseniasis in Chagas' myocardiopathy: necropsy study

Relata-se caso de hanseníase virchowiana diagnosticada à necropsia, com alterações cardíacas causadas diretamente por micobactérias, em homem de 34 anos portador de miocardiopatia crônica chagásica. Enfatiza-se opossível papel de mediadores inflamatórios na gênese da disfunção miocárdica; bem como a possibilidade de que fatores associados à insuficiência cardíaca, como esplenomegalia congestiva e infartos esplênicos, possam causar imunodepressão, predispondo à infecção generalizada