Prognostic Factors in Patients with Malignant Salivary Gland Neoplasms in a Brazilian Population

Due to the difficulty of follow-up for long periods, information about the survival rates of malignant salivary gland tumors is deficient in the global scientific literature. This study was aimed at investigating the epidemiological profile and prognostic factors that might affect survival in patients with primary malignant salivary gland tumors in Brazil. Patients were investigated regarding histopathological subtypes, age, gender, anatomic localization, smoking and alcohol intake, tumor size, clinical stage, histological grade, recurrence, metastasis, and treatment on clinicopathological outcomes. Survival curves were generated using the Kaplan-Meier method, and both univariate and multivariate analyses were performed using the log rank test and Cox regression, respectively. A total of 63 cases were analyzed, females beingslightly predominant (50.8%), with ages ranging from 13 to 87 years. The most common diagnosis was adenoid cystic carcinoma and the most affected anatomical location was the parotid. Tumors were predominantly classified as stage I and high-grade at the diagnosis. The 5- and 10-year overall survival rates were 84.6% and 74.7%, respectively. Disease-free survival (DFS) rates were 71.6% (5 years) and 56.6% (10 years). Univariate analysis showed significant effects of tumor size and clinical stage on the DFS (P < 0.0001 for both), and Cox regression analysis confirmed clinical stage as an independent prognostic factor (P = 0.035). Our results highlight the relevance of clinical stage as an independent prognostic parameter for malignant salivary gland tumors.

Vascular endothelial growth factor and beta-human chorionic gonadotropin are associated with trophoblastic invasion into the tubal wall in ectopic pregnancy

Objective: To assess the association between the depth of trophoblastic penetration into the tubal wall with serum concentrations of vascular endothelial growth factor (VEGF) and beta-hCG and to assess its predictive value. Design: Prospective study. Setting: Tertiary care university hospital. Patient(s): Thirty patients with ampullary pregnancy undergoing salpingectomy were analyzed. Intervention(s): Trophoblastic invasion was histologically classified as stage I when limited to the tubal mucosa, stage II when extending to the muscle layer, and stage III in the case of complete tubal wall infiltration. Main Outcome Measure(s): The relation between depth of trophoblastic infiltration into the tubal wall with VEGF and beta-hCG serum concentrations on the day of surgery. Result(s): An association between the depth of trophoblastic invasion and maternal serum concentrations of VEGF and beta-hCG was observed. VEGF levels of 297.2 pg/mL showed 100.0% sensitivity and 90.0% specificity for stage I, and levels of 440.1 pg/mL showed 81.8% sensitivity and 88.8% specificity for stage III. Beta-hCG levels of 2590.0 mIU/mL showed 88.9% sensitivity and 80.0% specificity for stage I, and levels of 10,827.0 mUI/mL showed 72.7% sensitivity and 88.9% specificity for stage III. Conclusion(s): Maternal serum VEGF and beta-hCG concentrations are associated with depth of trophoblastic penetration into the tubal wall. (Fertil Steril (R) 2010;94:1595-600. (C) 2010 by American Society for Reproductive Medicine.)

Dietary habits, ethanol and tobacco consumption as predictive factors in the development of esophageal carcinoma in patients with head and neck neoplasms

Patients with primary head and neck cancers have a higher risk of developing esophageal cancer. The aim of this study was to investigate esophageal cancer prevalence, its risk factors (ethanol and tobacco consumption) and dietary habits in patients with head and neck cancer. Three hundred and twenty-six adults with primary head and neck cancer were followed by a retrospective observational study in a general university hospital in Sao Paulo, Brazil. Flexible videoendoscopy with lugol chromoscopy was the method used to investigate esophageal cancer prevalence. All subjects were interviewed face-to-face, revealing detailed information about their tobacco and alcohol use, as well as their dietary habits. Thirty-six patients with esophageal cancer were diagnosed and the overall prevalence rate was 11.04%. Patients who developed second esophageal tumors had the following characteristics: earlier age of initial ethanol consumption (P < 0.05), longer duration period of ethanol consumption (P < 0.05) and higher weekly consumption rate (P < 0.05). There was an increased risk of esophageal carcinoma in those patients who both smoked and drank (P < 0.05). There was no association between carcinoma of the esophagus and dietary habits in patients who developed esophageal neoplasms, compared with those who did not. Prevalence rate of esophageal neoplasms was 11.04% in patients with head and neck carcinoma, whose ethanol consumption was associated with esophageal cancer. There was an increased risk between ethanol and tobacco consumption and esophageal carcinoma development. On the other hand, there was no association regarding dietary habits between patients who developed esophageal cancer and those who did not.

Arginase-1 A New Immunohistochemical Marker of Hepatocytes and Hepatocellular Neoplasms

The distinction of hepatocellular carcinoma (HCC) from metastatic tumor in the liver often presents a diagnostic challenge that carries significant impact on prognostication and therapy. The number of diagnostically useful immunohistochemical markers of hepatocytes is limited to hepatocyte paraffin antigen (HepPar-1), polyclonal carcinoembryonic antigen, and CD10, with alpha-fetoprotein and glypican-3 labeling HCCs. Arginase-1 (Arg-1) is a binuclear manganese metalloenzyme that catalyzes the hydrolysis of arginine to ornithine and urea. We used immunohistochemistry to compare the sensitivity of Arg-1 to that of HepPar-1 in 151 HCCs. We found that the overall sensitivities of Arg-1 and HepPar-1 are 96.0% and 84.1%, respectively. The sensitivities of Arg-1 in well, moderately, and poorly differentiated HCCs are 100%, 96.2%, and 85.7%, respectively, whereas, in comparison, HepPar-1 demonstrated sensitivities of 100%, 83.0%, and 46.4% for well, moderately, and poorly differentiated tumors, respectively. There were no HCCs in our study that were reactive for HepPar-1 but nonreactive for Arg-1. We also examined Arg-1 expression in nonhepatocellular tumors, including many that are potential mimics of HCC (renal cell carcinomas, neuroendocrine tumors, melanomas, gastric adenocarcinomas, and adrenocortical carcinomas) and found that only 2 non-HCC tumors were reactive for Arg-1. Arg-1 represents a sensitive and specific marker of benign and malignant hepatocytes that may ultimately prove to be a useful diagnostic tool in routine surgical pathology practice.

Sonographic appearance of gestational trophoblastic disease evolving into epithelioid trophoblastic tumor

Epithelioid trophoblastic tumor is a distinctive but rare trophoblastic tumor. It derives from intermediate trophoblastic cells of the chorion laeve and is usually associated with a previous gestational event. We report the case of a patient who had undergone dilatation and curettage for a missed miscarriage. Three months later gestational trophoblastic disease was suspected because of persistent vaginal bleeding and high levels of beta-human chorionic gonadotropin (beta-hCG). Transvaginal ultrasound revealed irregular echolucent lacunae within the myometrium, some of them filled with low-resistance, turbulent blood flow on Doppler examination, emphasizing the diagnosis of gestational trophoblastic disease. The patient was treated with 12 courses of multiagent chemotherapy. After a 2-year remission, a low rise in serum beta-hCG was observed. Transvaginal ultrasound revealed a well-circumscribed echogenic lesion with a diameter of 1.8 cm in the uterine fundus, with no detectable blood flow on Doppler imaging. A diagnosis of tumor of intermediate trophoblastic cells was suspected and total hysterectomy was performed. On pathological examination, the histological and immunohistochemical features were characteristic of epithelioid trophoblastic tumor. Most reported cases of epithelioid trophoblastic tumor have solitary nodules with sharp margins, which is consistent with our ultrasound findings. Ultrasound may be helpful in differentiating epithelioid trophoblastic tumor from placental-site trophoblastic tumor, another tumor of intermediate trophoblastic cells, which shows infiltrative growth insinuating between muscle fibers. Copyright (C) 2010 ISUOG. Published by John Wiley & Sons, Ltd.

Association between ultrasound findings and extent of trophoblastic invasion into the tubal wall in ampullary pregnancy

Objective Predictive factors of damage to the Fallopian tube may guide the treatment of Patients with tubal pregnancy. The aim of the present study was to investigate the association between the depth of trophoblastic invasion into the tubal wall, assessed on postoperative histological examination, with the findings obtained on transvaginal sonograpby (TVS) in women with ampullary Methods Women with ampullary pregnancy undergoing salpingectomy were enrolled into the study. Only women with a finding of either an embryo with cardiac activity or a tubal ring on TVS were included in the analysis, a total of 8.5 patients. Trophoblastic invasion was assessed postoperatively and was histologically classified as Stage I when limited to the tubal mucosa, Stage II when extending to the muscle layer and Stage III in the case of complete tubal wall infiltration. The association between findings on TVS and the stage of trophoblastic invasion was evaluated. Results There was a significant association between the findings on TVS and the depth of trophoblastic invasion (P < 0.001). All patients in whom an embryo with cardiac activity bad been identified were found to have Stage II (17.9%) or Stage III (82.1%) invasion, whereas in those patients who showed a tubal ring on TVS, Stage I invasion was the most frequent finding (41.3%). Conclusions In ampullary pregnancy, the finding on TVS of an embryo with cardiac activity is associated with deeper penetration of trophoblastic tissue into the tubal wall than is the finding of a tubal ring. Copyright (C) 2009 ISUOG, Published by John Wiley & Sons, Ltd.

Treatment for low-risk gestational trophoblastic disease: Comparison of single-agent methotrexate, dactinomycin and combination regimens

Objectives. To compare the efficacy of three different standard chemotherapy regimens for low-risk gestational trophoblastic disease according to the FIGO staging system in a single-institute setting. Methods. From 1980 until 2002, we retrospectively reviewed 108 cases with low-risk persistent gestational trophoblastic disease who were treated with first-line chemotherapy. Patients were divided in three groups according to chemotherapy regimen: patients treated with methotrexate (MTX group; n=42), patients treated with dactinomycin (ACT group; n=42) and patients treated with methotrexate and dactinomycin in combination (MACT group; n=24). We compared the number of chemotherapy courses for achieving remission, the duration of treatment, the adverse side effects, the efficacy of the treatment and the need for performing a hysterectomy among the groups Results. The complete remission rates were 69%, 61.4% and 79.1% for methotrexate (MTX), dactinomycin (ACT) and the combination regimen (MACT) treated groups, respectively (p=0.7). The duration of the treatment and the number of chemotherapy courses were similar among the groups (p = 0.2 and p = 0.4, respectively). Adverse side effects rate was reported to be 62.5% in the MACT group, 28.6% in the MTX group and 19.1% in the ACT group (p=0.0003). Second-line chemotherapy was indicated for 30 patients. Hysterectomy was performed in 21 patients overall, and there was no difference among the groups (P=0.6). Conclusion. Our analysis indicates that single-agent chemotherapy regimens are as effective as combination chemotherapy for low-risk gestational trophoblastic disease. Dactinomycin is a less toxic drug and might offer the best cost-effective treatment option. Methotrexate must be considered as the regimen of choice for low resource areas because of the feasibility of its administration. (c) 2007 Elsevier Inc. All rights reserved.

Angioleiomioma de cavidade nasal: relato de um caso e revisão de literatura

Leiomioma de cavidade nasal e seios paranasais é raro. Ele constitui menos de 1% de todos os leiomiomas do corpo humano. Isto se deve à escassez de células musculares no nariz. Estas neoplasias podem ser classificadas em três grupos: leiomioma, angiomioma e leiomioma epitelióide. Somente 15 casos de angiomioma foram encontrados na literatura. O tratamento de escolha é a excisão cirúrgica. Um novo caso e a revisão da literatura são apresentados.

Imunofenótipo e evolução de câncer de mama: comparação entre mulheres muito jovens e mulheres na pós-menopausa

OBJETIVO: avaliar características clínicas, patológicas e moleculares de carcinomas mamários em mulheres muito jovens em comparação a tumores de mulheres na pós-menopausa. MÉTODOS: foram selecionados 106 casos de câncer de mama de mulheres jovens e 130 casos de mulheres pós-menopausa. Foram analisados dados clínicos (idade ao diagnóstico, estadiamento, ocorrência de metástases, tempo de sobrevida global e livre de doença), anátomo-patológicos (tamanho do tumor, tipo e grau histológico do tumor primário) e marcadores moleculares (receptores de estrógeno e progesterona, HER2, p53, p63, citoqueratinas 5 e 14 e EGFR) com uso da imunoistoquímica empregando microarranjo de tecido. Foi analisada a relação entre as características clínico-patológicas, imunoistoquímicas e de sobrevidas global e livre de doença. RESULTADOS: as pacientes muito jovens apresentaram maior frequência de nuliparidade (p=0,03), maior diâmetro dos tumores (p<0,000), estadiamento clínico mais avançado (p=0,01), maior número de linfonodos positivos (p=0,001) e tumores pouco diferenciados (p=0,004). A maioria das pacientes jovens recebeu tratamento com quimioterapia (90,8%) e radioterapia (85,2%) e em menor proporção com tamoxifeno (31,5%), comparado às mulheres na pós-menopausa. Observamos baixa positividade para o receptor de estrógeno (49,1%; p=0,01) e alta positividade para a proteína HER2 (28,7%; p=0,03) nas mulheres jovens. O fenótipo triplo-negativo foi observado em 29,6% no grupo jovem e em 20% nas mulheres na pós-menopausa. Os tumores de fenótipo basal foram mais frequentes nas mulheres jovens (50%). As metástases sistêmicas ocorreram em 55,3% dos casos nas jovens e em 39,2% nas idosas. As sobrevidas global e livre de doença em cinco anos foram, respectivamente, 63 e 39% para as mulheres jovens e 75 e 67% para o grupo de mulheres na pós-menopausa. CONCLUSÕES: carcinomas mamários de mulheres muito jovens têm características clínicas, patológicas e moleculares mais agressivas quando comparadas às mulheres acima de 50 anos.

Carcinomas mamários de tipo basal: perfil clínico-patológico e evolutivo

OBJETIVO: Investigar a frequência de carcinomas mamários de fenótipo basal em uma série de tumores triplo-negativos (TTN), definidos pela negatividade para receptores de estrógeno (RE), de progesterona (RP) e HER2. MÉTODOS: Selecionamos 140 TTN, obtendo-se características clínico-patológicas e sobrevida. Microarranjo de tecido (2 cilindros de cada tumor) foi construído e submetido à imunoistoquímica para RE, RP, HER2, citoqueratinas (Cks) 5 e 14, EGFR, p63 e p53. Consideramos carcinomas de fenótipo basal os tumores negativos para RE, RP e HER2, e positivos para CK5. RESULTADOS: Encontramos 105 carcinomas de fenótipo basal entre 140 TTN (frequência=75%). A idade média das pacientes foi de 54,8 anos, sendo que 34,3% estavam na pré-menopausa. A maioria dos tumores foi classificada como carcinoma ductal invasor de alto grau. Os TTN exibiram positividade para CK5 (75,0%), CK14 (29%), EGFR (36,4%), p63 (28,6%) e p53 (67,1%). Estadiamento avançado da doença foi observado em 52 pacientes (50%), com diâmetro tumoral maior que 5 cm em 41 casos (39%) e metástases axilares em 61 casos (59,2%). Seguimento clínico foi obtido em 89 pacientes (média=51 meses). Destas, 45 pacientes (50,5%) evoluíram sem doença; 6 (6,7%) estavam vivas com doença e 38 (42,6%) morreram pelo câncer. Recidiva sistêmica ocorreu em 42 pacientes (47,1%), sendo pulmões, cérebro e ossos os principais sítios de metástases. As médias das sobrevidas global e livre de doença foram de 36 e 28 meses, respectivamente. CONCLUSÕES: Nosso estudo confirma comportamento clínico agressivo e elevada frequência dos carcinomas de fenótipo basal entre os TTN, semelhante ao descrito em casuísticas norte-americanas e europeias.

Immunohistochemical expression of p53, p16 and hTERT in oral squamous cell carcinoma and potentially malignant disorders

Oral carcinogenesis is a multi-step process. One possible step is the development of potentially malignant disorders known as leukoplakia and erytroplakia. The objective of this study was to use immunohistochemistry to analyze the patterns of expression of the cell-cycle regulatory proteins p53 and p16INK4a in potentially malignant disorders (PMD) of the oral mucosa (with varying degrees of dysplasia) and in oral squamous cell carcinomas (OSCC) to correlate them with the expression of telomerase (hTERT). Fifteen PMD and 30 OSCC tissue samples were analyzed. Additionally, 5 cases of oral epithelial hyperplasia (OEH) were added to analyze clinically altered mucosa presenting as histological hyperplasia without dysplasia. p53 positivity was observed in 93.3% of PMD, in 63.3% of OSCC and in 80% of OEH. Although there was no correlation between p53 expression and the grade of dysplasia, all cases with severe dysplasia presented p53 suprabasal immunoexpression. p16INK4a expression was observed in 26.7% of PMD, in 43.3% of OSCC and in 2 cases of OEH. The p16INK4a expression in OEH, PMD and OSCC was unable to differentiate non-dysplastic from dysplastic oral epithelium. hTERT positivity was observed in all samples of OEH and PMD and in 90% of OSCC. The high hTERT immunoexpression in all three lesions indicates that telomerase is present in clinically altered oral mucosa but does not differentiate hyperplastic from dysplastic oral epithelium. In PMD of the oral mucosa, the p53 immunoexpression changes according to the degree of dysplasia by mechanisms independent of p16INK4a and hTERT.

Expressão da proteína erbB-2 e dos receptores de hormônios na transição das regiões in situ para invasora de tumores da mama

OBJETIVOS: avaliar a expressão de erbB-2 e dos receptores hormonais para estrógeno e progesterona (RE/RP) nas regiões de transição entre as frações in situ e invasoras de neoplasias ductais da mama (CDIS e CDI, respectivamente). MÉTODOS: oitenta e cinco casos de neoplasias mamárias, contendo regiões contíguas de CDIS e CDI, foram selecionados. Espécimes histológicos das áreas de CDIS e de CDI foram obtidos através da técnica de tissue microarray (TMA). As expressões da erbB-2 e dos RE/RP foram avaliadas por meio de imunoistoquímica convencional. A comparação da expressão da erbB-2 e dos RE/RP nas frações in situ e invasoras da mama foi realizada com emprego do teste de McNemar. Os intervalos de confiança foram determinados em 5% (p=0,05). Foram calculados coeficientes de correlação intraclasse (ICC) para avaliar a concordância na tabulação cruzada da expressão de erbB-2 e RE/RP nas frações de CDIS e CDI. RESULTADOS: a expressão da erbB-2 não diferiu entre as áreas de CDIS e CDI (p=0,38). Comparando caso a caso suas áreas de CDIS e CDI, houve boa concordância na expressão da erbB-2 (coeficiente de correlação intraclasse, ICC=0,64), dos RP (ICC = 0,71) e dos RE (ICC = 0,64). Considerando apenas tumores cujo componente in situ apresentasse áreas de necrose (comedo), o ICC para erbB-2 foi de 0,4, comparado a 0,6 no conjunto completo de casos. Os ICC não diferiram substancialmente daqueles obtidos com o conjunto completo de espécimes em relação aos RE/RP: para RE, ICC=0,7 (versus 0,7 no conjunto completo), e para RP, ICC=0,7 (versus 0,6 no conjunto completo). CONCLUSÕES: nossos achados sugerem que as expressões de erbB-2 e RE/RP não diferem nos componentes contíguos in situ e invasivo em tumores ductais da mama.

Survival and quality of life of patients with oral and oropharyngeal cancer at 1-year follow-up of tumor resection

OBJECTIVE: This study aimed to assess the survival and life quality evolution of patients subjected to surgical excision of oral and oropharyngeal squamous cell carcinoma. MATERIAL AND METHODS: Forty-seven patients treated at a Brazilian healthcare unit specialized in head and neck surgery between 2006 and 2007 were enrolled in the study. The gathering of data comprised reviewing hospital files and applying the University of Washington Quality of Life (UW-QOL) questionnaire previously and 1 year after the surgery. Comparative analysis used Poisson regression to assess factors associated with survival and a paired t-test to compare preoperative and 1-year postoperative QOL ratings. RESULTS: 1 year after surgery, 7 patients were not found (dropout of the cohort); 15 had died and 25 fulfilled the UW-QOL again. The risk of death was associated with having regional metastasis previously to surgery (relative risk=2.18; 95% confidence interval=1.09-5.17) and tumor size T3 or T4 (RR=2.30; 95%CI=1.05-5.04). Survivors presented significantly (p<0.05) poorer overall and domain-specific ratings of quality of life. Chewing presented the largest reduction: from 74.0 before surgery to 34.0 one year later. Anxiety was the only domain whose average rating increased (from 36.0 to 70.7). CONCLUSIONS: The prospective assessment of survival and quality of life may contribute to anticipate interventions aimed at reducing the incidence of functional limitations in patients with oral and oropharyngeal cancer.

Evolução dos doentes com citologia oncótica alterada e colposcopia anal normal

A citologia anal vem sendo usada para rastreamento do carcinoma anal e suas lesões precursoras nas populações de risco. Quando o raspado do canal anal mostra alterações citológicas está indicada o exame com colposcópio e ácido acético para identificar e realizar biópsia para confirmar o achado. Poucos estudos mostram o seguimento dos doentes tratados de condilomas acuminados perianais. Temos usado os métodos em associação e encontrado lesões subclínicas em metade dos doentes, cujo exame proctológico não revelava doença HPV induzida. Essas lesões são tratadas com tópicos. Entretanto, algumas citologias estavam alteradas e a colposcopia anal não revelou doença HPV induzida. O objetivo deste estudo foi observar o comportamento dessas lesões no seguimento semestral, durante 12 meses, e avaliar se a periodicidade da reavaliação foi suficiente para evitar o aparecimento das lesões de alto grau ou superior. Encontramos 58 (21%) entre 273 doentes nessas condições. As reavaliações de 22 deles após um ano mostraram que as colposcopias permaneceram normais em 17 (74%), sendo que em cinco (22%) a citologia voltou aos padrões normais e 12 (52%) persistiram com alterações. Os outros seis (26%) desenvolveram lesões clínicas ou subclínicas provocadas pelo HPV. As contagens de linfócitos T CD4 dos doentes HIV-positivos foram inferiores nos doentes cujas lesões progrediram. Os resultados permitiram concluir que as alterações podem progredir ou regredir neste grupo distinto de doentes, sendo relacionada à imunidade, e que o intervalo de seis meses é suficiente para cada reavaliação.