Discovery proteomics reveals potential protein signature associated with malignant phenotype acquisition in pleomorphic adenoma.

OBJECTIVE: To analyze the proteomic profile of salivary pleomorphic adenoma (PA) and carcinoma ex pleomorphic adenoma (CXPA) samples and correlate them with the malignant transformation of the PA. MATERIALS AND METHODS: Thirty samples (10 PA, 16 CXPA, and 4 residual PA) were microdissected and submitted to liquid chromatography-tandem mass spectrometry (LC-MS/MS). The proteomic data and protein identification were analyzed through LC-MS/MS spectra using the MaxQuant software. RESULTS: The proteomic analysis identified and quantified a total of 240 proteins in which 135 were found in PA, residual PA, and CXPA. The shared proteins were divided into six subgroups, and the proteins that showed statistically significant differences (p > 0.05) and fold-change > or <2.5 in one subgroup to another subgroup were included. Seven proteins (Apolipoprotein A-I-APOA1, haptoglobin-HP, protein of the synaptonemal complex 1-SYCP1, anion transport protein of band 3-SLC4A1, subunit µ1 of AP-1 complex-AP1M1, beta subunit of hemoglobin-HBB, and dermcidin-DCD) were classified as potential protein signatures, being HP, AP1M1, and HBB with higher abundance for PA to residual PA, APOA1 with higher abundance for PA to CXPA, SLC4A1 with lower abundance in the PA to CXPA, SYCP1with lower abundance for residual PA to CXPA, and DCD with higher abundance in the CXPA with epithelial differentiation to myoepithelial differentiation. CONCLUSIONS: In this work, we demonstrated the comparative proteomic profiling of PA, residual PA, and CXPA, and seven were proposed as protein signatures, some of which may be associated with the malignant phenotype acquisition.

Pattern of Intraoperative Parathyroid Hormone and Calcium in the Treatment of Tertiary Hyperparathyroidism.

OBJECTIVE: Tertiary hyperparathyroidism, an autonomous hyperproduction of parathyroid hormone (PTH), has a challenge in its treatment. This study asked whether the intraoperative PTH and calcium drop can confirm the resection of all parathyroid tissues. STUDY DESIGN: Case series with planned data collection. SETTING: Tertiary referral medical center. SUBJECTS AND METHODS: The study assessed patients with tertiary hyperparathyroidism who were treated at the Hospital of the State University of Campinas from 2007 to 2015. All patients underwent total parathyroidectomy with autotransplantation of parathyroid fragments. PTH and calcium were collected during the preoperative period; at 10, 20, and 240 minutes after resection of the glands; and at 1 year after the procedure. Data were analyzed by analysis of variance and logistic regression analysis with statistical values of P < .05. RESULTS: Thirty-five patients were assessed: 17 women (48.57%) and 18 men (51.43%). The percentage of PTH drop was statistically significant at all times, unlike the calcium analysis, but only PTH collected at 20 minutes was able to confirm the removal of all parathyroid tissues (P = .029). Based on the receiver operating characteristic curve, the 71.2% drop obtained high sensitivity and specificity (P = .028). CONCLUSIONS: Treatment success can be predicted by analyzing the decrease of intraoperative PTH and not by calcium. The 71.2% PTH drop at 20 minutes after parathyroidectomy had high sensitivity and specificity to predict surgical cure.

Carcinoma ex-pleomorphic adenoma derived from recurrent pleomorphic adenoma shows important difference by array CGH compared to recurrent pleomorphic adenoma without malignant transformation / Carcinoma ex-adenoma pleomórfico derivado de adenoma pleomórfico recorrente mostra diferença importante por array CGH em comparação com adenoma pleomórfico recorrente sem transformação maligna

Abstract Introduction: A key step of cancer development is the progressive accumulation of genomic changes resulting in disruption of several biological mechanisms. Carcinoma ex-pleomorphic adenoma (CXPA) is an aggressive neoplasm that arises from a pleomorphic adenoma. CXPA derived from a recurrent PA (RPA) has been rarely reported, and the genomic changes associated with these tumors have not yet been studied. Objective: We analyzed CXPA from RPAs and RPAs without malignant transformation using array-comparative genomic hybridization (array-CGH) to identify somatic copy number alterations and affected genes. Methods: DNA samples extracted from FFPE tumors were submitted to array-CGH investigation, and data was analyzed by Nexus Copy Number Discovery Edition v.7. Results: No somatic copy number alterations were found in RPAs without malignant transformation. As for CXPA from RPA, although genomic profiles were unique for each case, we detected some chromosomal regions that appear to be preferentially affected by copy number alterations. The first case of CXPA-RPA (frankly invasive myoepithelial carcinoma) showed copy number alterations affecting 1p36.33p13, 5p and chromosomes 3 and 8. The second case of CXPA-RPA (frankly invasive epithelial-myoepithelial carcinoma) showed several alterations at chromosomes 3, 8, and 16, with two amplifications at 8p12p11.21 and 12q14.3q21.2. The third case of CXPA-RPA (minimally invasive epithelial-myoepithelial carcinoma) exhibited amplifications at 12q13.3q14.1, 12q14.3, and 12q15. Conclusion: The occurrence of gains at chromosomes 3 and 8 and genomic amplifications at 8p and 12q, mainly those encompassing the HMGA2, MDM2, WIF1, WHSC1L1, LIRG3, CDK4 in CXAP from RPA can be a significant promotional factor in malignant transformation.

Resumo Introdução: Uma etapa fundamental do desenvolvimento do câncer é o acúmulo progressivo de alterações genômicas, resultando na ruptura de vários mecanismos biológicos. Carcinoma ex-adenoma pleomórfico (CXAP) é uma neoplasia agressiva que surge a partir de um adenoma pleomórfico. O CXAP derivado de um AP recorrente (APR) foi raramente relatado e, até o momento, as alterações genômicas associadas a esses tumores não foram estudados. Objetivo: Avaliar as diferenças entre os CXAPs decorrentes de APRs e os APRs sem transformações malignas usando hibridização genômica comparativa em microarrays (array Comparative Genomic Hibridization - aCGH) a fim de identificar alterações no número de cópias somáticas e os genes afetados. Método: Amostras de DNA extraídas de tumores provenientes de tecido emblocado em parafina foram submetidos à investigação com a técnica aCGH, e os dados foram analisados com o Nexus Copy Number Discovery Edition v.7. Resultados: Não observamos alterações no numero de cópias somáticas nos APRs sem transformação maligna. Quanto ao CXAP de APR, embora os perfis genômicos sejam exclusivos para cada caso, detectamos algumas regiões cromossômicas que pareciam ser preferencialmente afetadas por alterações no número de cópias. O primeiro caso de CXAP-APR (carcinoma mioepitelial francamente invasivo) apresentou alterações no numero de cópias afetando 1p36.33p13, 5p e cromossomos 3 e 8. O segundo caso de CXAP-APR (carcinoma epitelialmioepitelial francamente invasivo) apresentou várias alterações nos cromossomos 3, 8 e 16, com duas amplificações em 8p12p11.21 e 12q14.3q21.2. O terceiro caso de CXAP-APR (carcinoma epitelial-mioepitelial minimamente invasivo) apresentou amplificações em 12q13.3q14.1, 12q14.3, e 12q15. Conclusão: A ocorrência de ganhos de cromossomos 3 e 8, e as amplificações genômicas em 8p e 12q, principalmente aquelas que englobam os HMGA2, MDM2, WIF1, WHSC1L1, RG3, CDK4 no CXAP decorrente de APR podem ser fatores promocionais significativos para a transformação maligna.

Loss of expression of Plag1 in malignant transformation from pleomorphic adenoma to carcinoma ex pleomorphic adenoma.

PLAG1 (pleomorphic adenoma gene 1) is frequently activated in pleomorphic adenoma (PA). Carcinoma ex pleomorphic adenoma (CXPA) arises in PA, and PLAG1 expression is believed to be maintained from PA to CXPA, as it can contribute to the carcinogenesis process. To evaluate if PLAG1 is a good marker of malignant transformation from PA to CXPA as well as to evaluate if PLAG1 expression is associated with progression and histopathologic subtype of CXPA. Forty PAs, 21 residual PAs (without malignant transformation), and 40 CXPAs were analyzed by immunohistochemistry with PLAG1 antibody. The proportion of positive neoplastic cells was assessed according to a 2-tiered scale: >10% to 50%, and >50% positive cells. The CXPA group was classified according to histopathologic subtype and invasiveness degree. Thirty-seven PAs (92.5%), 15 residual PAs (71%), and 14 CXPAs (35%) were positive for PLAG1. In relation to the CXPA group, among the intracapsular cases, myoepithelial carcinoma and epithelial-myoepithelial carcinoma showed the highest level of PLAG1 expression. PLAG1 expression is lost when PA undergoes malignant transformation, possibly due to other pathway activation and different clone cells. In addition, PLAG1 expression seems to be present mainly in low-grade carcinomas and in cases with early phase of invasion, due to its regulation of oncogene-induced cell senescence. In CXPA, PLAG1 expression was most associated with myoepithelial differentiation. This way, loss of PLAG1 expression can be considered a hallmark of CXPA carcinogenesis, mainly when there is only epithelial differentiation.

Carcinoma ex-pleomorphic adenoma derived from recurrent pleomorphic adenoma shows important difference by array CGH compared to recurrent pleomorphic adenoma without malignant transformation.

INTRODUCTION: A key step of cancer development is the progressive accumulation of genomic changes resulting in disruption of several biological mechanisms. Carcinoma ex-pleomorphic adenoma (CXPA) is an aggressive neoplasm that arises from a pleomorphic adenoma. CXPA derived from a recurrent PA (RPA) has been rarely reported, and the genomic changes associated with these tumors have not yet been studied. OBJECTIVE: We analyzed CXPA from RPAs and RPAs without malignant transformation using array-comparative genomic hybridization (array-CGH) to identify somatic copy number alterations and affected genes. METHODS: DNA samples extracted from FFPE tumors were submitted to array-CGH investigation, and data was analyzed by Nexus Copy Number Discovery Edition v.7. RESULTS: No somatic copy number alterations were found in RPAs without malignant transformation. As for CXPA from RPA, although genomic profiles were unique for each case, we detected some chromosomal regions that appear to be preferentially affected by copy number alterations. The first case of CXPA-RPA (frankly invasive myoepithelial carcinoma) showed copy number alterations affecting 1p36.33p13, 5p and chromosomes 3 and 8. The second case of CXPA-RPA (frankly invasive epithelial-myoepithelial carcinoma) showed several alterations at chromosomes 3, 8, and 16, with two amplifications at 8p12p11.21 and 12q14.3q21.2. The third case of CXPA-RPA (minimally invasive epithelial-myoepithelial carcinoma) exhibited amplifications at 12q13.3q14.1, 12q14.3, and 12q15. CONCLUSION: The occurrence of gains at chromosomes 3 and 8 and genomic amplifications at 8p and 12q, mainly those encompassing the HMGA2, MDM2, WIF1, WHSC1L1, LIRG3, CDK4 in CXAP from RPA can be a significant promotional factor in malignant transformation.

Cellular Proliferation Index between Carcinoma Ex-Pleomorphic Adenoma and Pleomorphic Adenoma.

Carcinoma ex pleomorphic adenoma (CXPA) has been considered an interesting model of carcinogenesis, presenting various histological subtypes and invasiveness phase. The objective was to determine the proliferative index of CXPA and comparing to pleomorphic adenoma (PA). Thirty six cases of CXPA (36 PA) and 22 areas of PA in CXPA (residual PA) were studied by Ki-67 expression. All CXPA cases were classified according to invasiveness phase (intracapsular, minimally and frankly invasive) and histopathological subtypes. Data was statistically analyzed by Wilcoxon, Mann-Whitney and Kruskal-Wallis tests. CXPA included 5 intracapsular, 9 minimally invasive and 22 frankly invasive cases. Fifteen cases corresponded to salivary duct carcinoma, 7 to adenocarcinoma NOS, 7 myoepithelial, 5 epithelial-myoepithelial, one case of squamous cell and one case of sarcomatoid carcinoma. The Ki-67 index of PA and residual PA were significantly lower than CXPA. Intracapsular and minimally invasive showed smaller proliferative index than frankly invasive. Considering the subtypes of CXPA, there was not a statistic difference among them. Ki-67 is a useful marker in the differential diagnosis of PA and CXPA, even when in the early invasive phase.

Preservation of the external jugular vein in bilateral radical neck dissections: technique in two cases and review of the literature.

Context. The possibility of cephalic venous hypertension with the resultant facial edema and elevated cerebrospinal fluid pressure continues to challenge head and neck surgeons who perform bilateral radical neck dissections during simultaneous or staged procedures. Case Report. The staged procedure in patients who require bilateral neck dissections allows collateral venous drainage to develop, mainly through the internal and external vertebral plexuses, thereby minimizing the risks of deleterious consequences. Nevertheless, this procedure has disadvantages, such as a delay in definitive therapy, the need for a second hospitalization and anesthesia, and the risk of cutting lymphatic vessels and spreading viable cancer cells. In this paper, we discuss the rationale and feasibility of preserving the external jugular vein. Considering the limited number of similar reports in the literature, two cases in which this procedure was accomplished are described. The relevant anatomy and technique are reviewed and the patients' outcomes are discussed. Conclusion. Preservation of the EJV during bilateral neck dissections is technically feasible, fast, and safe, with clinically and radiologically demonstrated patency.

Tobacco experimental model to induce urinary bladder neoplasms.

OBJECTIVE: to develop an experimental model of exposure to tobacco burning (cigarette) products to assess the effects of its chronic use in relation to cancers of the bladder. METHODS: the animals were chronically exposed to the burning tobacco products in a semi-open chamber to simulate smoking. Thirty young Wistar rats were divided into two groups: one with 20 animals simulating smoking for six months, and ten not exposed control animals for the same period. After exposure by inhalation of cigarette smoke, animals were euthanized and subjected to histopathological study of the bladder wall. RESULTS: no tumor was found but mild and non significant alterations. The studies of hemo-oximetry (carboxyhemoglobin and methemoglobin) and the concentration of carbon dioxide (CO2) confirm that the animals were exposed to high concentrations of tobacco smoke and its derivatives. CONCLUSION: no bladder mucosal neoplasia was found in the pathological study of animals. The developed experimental models were highly efficient, practical and easy to use and can be used in other similar studies to determine the harmful effects caused by smoking.

Carotid body tumor: retrospective analysis on 22 patients.

CONTEXT AND OBJECTIVE: Carotid body tumors, or chemodectomas, are the most common head and neck paragangliomas, accounting for 80% of the cases. They may present minor symptoms; however, they deserve special attention in order to achieve accurate diagnosis and adequate treatment. The objectives of this study were to show the approach towards chemodectomas and evaluate the complications of the patients treated surgically without previous embolization. DESIGN AND SETTING: Retrospective study on chemodectomas followed up at the Head and Neck Surgery Service, Department of Surgery, Unicamp. METHODS: Twenty-two patients were evaluated between 1983 and 2009. The diagnosis was based on clinical findings and imaging methods. The epidemiological characteristics, lesion characteristics, diagnostic methods, treatment and complications were analyzed. RESULTS: The paragangliomas were classified as Shamblin I (9%), II (68.1%) and III (22.7%). Angiography, magnetic resonance imaging and computed tomography confirmed the diagnosis in 20 patients (90.9%). Five (22.7%) had significant bleeding during the surgery, while four (18.1%) had minor bleeding. Four patients (18.1%) developed neurological sequelae. Seven (31.8%) needed ligatures of the external carotid artery. Three patients (13.6%) underwent carotid bulb resection. The postoperative follow-up ranged from 3 months to 14 years without recurrences or mortality. CONCLUSIONS: In our experience and in accordance with the literature, significant bleeding and neurological sequelae may occur in chemodectoma cases, particularly in Shamblin III patients. The complications from treatment without previous embolization were similar to data in the literature data, from cases in which this procedure was applied prior to surgery.

Carotid body tumor: retrospective analysis on 22 patients / Tumor de corpo carotídeo: análise retrospectiva de 22 pacientes

CONTEXT AND OBJECTIVE: Carotid body tumors, or chemodectomas, are the most common head and neck paragangliomas, accounting for 80% of the cases. They may present minor symptoms; however, they deserve special attention in order to achieve accurate diagnosis and adequate treatment. The objectives of this study were to show the approach towards chemodectomas and evaluate the complications of the patients treated surgically without previous embolization. DESIGN AND SETTING: Retrospective study on chemodectomas followed up at the Head and Neck Surgery Service, Department of Surgery, Unicamp. METHODS: Twenty-two patients were evaluated between 1983 and 2009. The diagnosis was based on clinical findings and imaging methods. The epidemiological characteristics, lesion characteristics, diagnostic methods, treatment and complications were analyzed. RESULTS: The paragangliomas were classified as Shamblin I (9%), II (68.1%) and III (22.7%). Angiography, magnetic resonance imaging and computed tomography confirmed the diagnosis in 20 patients (90.9%). Five (22.7%) had significant bleeding during the surgery, while four (18.1%) had minor bleeding. Four patients (18.1%) developed neurological sequelae. Seven (31.8%) needed ligatures of the external carotid artery. Three patients (13.6%) underwent carotid bulb resection. The postoperative follow-up ranged from 3 months to 14 years without recurrences or mortality. CONCLUSIONS: In our experience and in accordance with the literature, significant bleeding and neurological sequelae may occur in chemodectoma cases, particularly in Shamblin III patients. The complications from treatment without previous embolization were similar to data in the literature data, from cases in which this procedure was applied prior to surgery. .

CONTEXTO E OBJETIVO: O tumor de corpo carotídeo, ou quimiodectoma, é o paraganglioma mais comum em cabeça e pescoço, com aproximadamente 80% dos casos. Pode apresentar poucos sintomas; no entanto, necessita atenção especial para o diagnóstico e tratamento adequado. Os objetivos deste estudo são mostrar a abordagem do quimiodectoma e avaliar as complicações nos pacientes tratados cirurgicamente sem embolização prévia. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo de quimiodectomas acompanhados pelo Serviço de Cirurgia de Cabeça e Pescoço, Departamento de Cirurgia, Unicamp. MÉTODOS: Vinte e dois pacientes foram avaliados entre 1983 e 2009. O diagnóstico foi baseado em achados clínicos e métodos de imagens. Foram analisados aspectos epidemiológicos, características das lesões, métodos diagnósticos, tratamento e complicações. RESULTADOS: Os paragangliomas foram classificados em Shamblin I (9%), II (68,1%) e III (22,7%). Angiografia, ressonância nuclear magnética e tomografia computadorizada confirmaram o diagnóstico em 20 pacientes (90,9%). Cinco (22,7%) tiveram sangramento significativo durante a cirurgia, enquanto quatro (18,1%) tiveram sangramento mínimo. Quatro pacientes (18,1%) tiveram sequelas neurológicas. Sete (31,8%) necessitaram de ligadura da artéria carótida externa. Três (13,6%) foram submetidos a ressecção do bulbo carotídeo. O acompanhamento variou de 3 meses a 14 anos, sem recorrências ou óbitos. CONCLUSÕES: Em nossa experiência e de acordo com a literatura, sangramentos significativos e sequelas neurológicas podem ocorrer nos quimiodectomas principalmente em pacientes Shamblin III. As complicações do tratamento sem embolização prévia foram similares aos relatos observados ...

Tobacco experimental model to induce urinary bladder neoplasms / Modelo experimental de tabagismo para indução de neoplasia da bexiga urinária

OBJECTIVE: to develop an experimental model of exposure to tobacco burning (cigarette) products to assess the effects of its chronic use in relation to cancers of the bladder. METHODS: the animals were chronically exposed to the burning tobacco products in a semi-open chamber to simulate smoking. Thirty young Wistar rats were divided into two groups: one with 20 animals simulating smoking for six months, and ten not exposed control animals for the same period. After exposure by inhalation of cigarette smoke, animals were euthanized and subjected to histopathological study of the bladder wall. RESULTS: no tumor was found but mild and non significant alterations. The studies of hemo-oximetry (carboxyhemoglobin and methemoglobin) and the concentration of carbon dioxide (CO2) confirm that the animals were exposed to high concentrations of tobacco smoke and its derivatives. CONCLUSION: no bladder mucosal neoplasia was found in the pathological study of animals. The developed experimental models were highly efficient, practical and easy to use and can be used in other similar studies to determine the harmful effects caused by smoking. .

OBJETIVO: desenvolver modelo experimental de exposição aos produtos da queima do tabaco (cigarro) para avaliar os efeitos do seu uso crônico em relação às neoplasias de bexiga. MÉTODOS: Os animais foram expostos cronicamente aos produtos da queima do tabaco em câmara semi-aberta para simular o tabagismo. Trinta ratos jovens da raça Wistar foram distribuídos em dois grupos: um com 20 animais simulando o tabagismo por período de seis meses, e um com dez animais controle sem exposição por igual período. Após exposição por inalação da fumaça do cigarro, os animais foram eutanasiados e submetidos a estudo histopatológico da parede da bexiga. RESULTADOS: Não foi encontrada neoplasia e sim alterações leves e não significativas. Os estudos da hemo-oximetria (carboxiemoglobina e metemoglobina) e da concentração de dióxido de carbono (CO2) confirmam que os animais foram expostos a altas concentrações da fumaça do tabaco e de seus derivados. CONCLUSÃO: No estudo anatomopatológico dos animais não foi encontrada neoplasia na mucosa da bexiga. Os modelos experimentais desenvolvidos foram altamente eficientes, práticos e fáceis de usar podendo ser empregados em outros estudos semelhantes para determinar os efeitos nocivos causados pelo tabagismo. .

Retalhos miocutâneos para reconstrução em cirurgia de cabeça e pescoço: Experiência da UNICAMP / Myocutaneous flaps for reconstruction in head and neck surgery: UNICAMP experience

Introdução: Retalhos miocutâneos pediculados sãoreconhecidos como importante método para reconstrução emcirurgia de cabeça e pescoço. São amplamente utilizados apósressecções oncológicas extensas que resultam em grandesdefeitos cirúrgicos. Apesar de atualmente os retalhos livresrealizados com técnicas microvasculares serem largamenteutilizados e considerados a melhor opção em grandes centros, ouso de retalhos pediculados é técnica frequentemente empregadaem muitos serviços. Objetivo: Avaliar a taxa de sucesso e ascomplicações encontradas com o uso de retalhos miocutâneospediculados em pacientes submetidos a ablações cirúrgicasoncológicas extensas no serviço de Cirurgia de Cabeça e Pescoçoda UNICAMP. Método: Entre fevereiro de 1990 e janeiro de 2010,foram avaliados retrospectivamente os dados de 138 pacientessubmetidos à ressecção oncológica em cabeça e pescoço, o tipode retalho utilizado para reconstrução, a taxa de sucesso e ascomplicações observadas. Resultados: A taxa global de sucessofoi de 92,7%. Para o retalho de músculo peitoral maior a taxa desucesso foi de 93,6%; para o retalho infra-hioideo, 85,9%; parao retalho de grande dorsal, 100%. Conclusão: Os resultadosencontrados fundamentam o uso dos retalhos miocutâneospediculados na cirurgia de reconstrução em cabeça e pescoço,pois apresentam altas taxas de sucesso e podem ser realizadosem centros que não disponham de equipe especializada emcirurgia microvascular.

Experimental model of smoking and simulation of reflux with acid and pepsin in rats.

PURPOSE: To develop experimental models to evaluate the effects of hydrochloric acid associated with the pepsin instilled in the mucosa of the upper esophagus and the esophagogastric junction of young male rats Wistar, simulating injury caused by gastroesophageal reflux on the mucosa of aero-digestive tract in humans as well as the action of the risk exposure of mucosa to cigarette smoke. METHODS: Fifty young male Wistar rats divided in 5 groups with 10 animals each one, respectively simulating pharyngo-laryngeal reflux and gastroesophageal reflux, pharyngo-laryngeal reflux and smoking, smoking only, gastroesophageal reflux and control group. RESULTS: The histopathologic studies no recorded neoplasias, only mild changes and no significant alterations. The hemo-oximetry (carboxyhemoglobin and methemoglobim) and CO2 concentration confirm that the animals were submitted to high intensity of exposure to carcinogens in tobacco and its derivatives. CONCLUSION: The experimental models were highly efficient, practical, easy to use and economical and can be employed in other similar studies to determine the harmful effects by smoking and reflux.

Caracterização imuno-histoquímica do infiltrado linfocitário em biópsia de carcinoma espinocelular da língua e soalho oral e sua implicação prognóstica / Character description by immuno-histochemmical technique in lymphocytic inflammatory infiltration in epidermoid carcinomas biopsies of the tongue and floor of t he mouth

Introdução: O infiltrado inflamatório tem sido considerado comoum possível fator prognóstico em neoplasias malignas. O objetivodo presente estudo é caracterizar pela técnica imuno-histoquímica,o infiltrado inflamatório linfocitário em biópsias de carcinomaespino celular (CEC) da língua e soalho de boca, analisando seuvalor prognóstico por correlação dos achados, com os dadosdo estadiamento TNM e com a probabilidade de sobrevida dosdoentes. Método: Foram analisadas 46 biópsias de pacientes nãotratados com CEC de língua e soalho da boca, nas quais foramavaliadas as seguintes características do infiltrado inflamatório:intensidade do infiltrado inflamatório geral, intensidade relativa doinfiltrado de linfócitos T (CD45R0+) e B (CD20+) em relação aoinfiltrado geral nas regiões intra e peritumorais, epitélio displásicoe epitélio normal; quantidade de linfócitos CD4+, quantidade delinfócitos CD8+ e razão CD4/CD8 nas regiões intra e peritumorais.Resultados: Tanto o infiltrado inflamatório geral, como o infiltradode linfócitos T e B eram mais intensos na área peritumoral doque na intratumoral. Em ambas, os linfócitos T foram encontradosem maior quantidade do que os linfócitos B, a proporção CD4/CD8 não mostrou diferença significativa entre as áreas intra eperitumorais. Foi observado correlação inversa significativa entrea intensidade do infiltrado inflamatório geral intratumoral e apresença de metástases cervicais e estádio da doença. Houve,também, correlação inversa significativa entre intensidade deinfiltrado de linfócitos B intratumoral e presença de metástasescervicais. Não foi encontrado qualquer correlação entre sobrevidae infiltrado inflamatório relacionado ao CEC na amostra estudada.Conclusão: Concluiu-se que, a análise do infiltrado inflamatórioem biópsias pode contribuir para a avaliação do prognóstico dosdoentes com CEC de cavidade oral.

Introduction: Inflammatory infiltration has been considered asa likely prognostic factor in malign neoplasms. The aim of thiswork is to characterize, by immuno-histochemical technique, thelymphocytic inflammatory infiltration in epidermoid carcinomasbiopsies of the tongue and floor of the mouth. Analyse itsprognostic value by correlating the results with the data of TNMstaging system and with the probability of survival. Method: Itwas studied 46 biopsies of non-treated patients with epidermoidcarcinoma of the tongue and floor of the mouth in wich wasanalysed the following inflammatory infiltration parameters:general inflammatory infiltration intensity, T and B lymphocytesinfiltration intensity in relation to the general inflammatoryinfiltration in tumor parenchyma, stroma region, displasia andnormal epithelium, amount of CD4+ lymphocytes, amount ofCD8+ lymphocytes and CD4/CD8 ratio in tumor parenchyma andstroma. Results: Both the general inflammatory infiltration and Tand B lymphocytes infiltration were more intense in the stromalthan in the parenchymal tumor. In both sites the T lymphocyteswere found more frequently than the B lymphocytes. The CD4/CD8 ratio didn?t show expressive difference between stroma andparenchyma tumor. It was seen a significant inverse correlationbetween parenchymal inflammatory infiltration intensity andpresence of neck metastases and also with TNM staging. Therewas significant correlation between lack in B lymphocytes infiltrationof the parenchyma tumor and presence of neck metastases.Conclusion: It wasn?t found any correlation between survivaland inflammatory infiltration parameters related to epidermoidcarcinomas in this study. It was concluded that the analysis ofinflammatory infiltration found in biopsies could aid information tothe prognostic evaluation in patients with epidermoid carcinomasof the mouth.

Experimental carcinogenesis on the oropharyngeal mucosa of rats with hydrochloric acid, sodium nitrate and pepsin / Carcinogênese experimental na mucosa orofaríngea de ratos com ácido clorídrico, nitrato de sódio e pepsina

PURPOSE: To investigate the carcinogenic action of hydrochloric acid, pepsin and sodium nitrate on the oropharyngeal mucosa of rats, simulating the reflux of gastric contents. METHODS: Eighty-two Wistar rats were divided in seven groups and submitted to 2 or 3 weekly applications of hydrochloric acid, pepsin and sodium nitrate on the pharyngeal mucosa during six months. Study groups comprised 12 animals each. Rats in groups I and II were submitted to 2 (GI) or 3 (GII) weekly applications of 0.1N hydrochloric acid. Groups III and IV were submitted to 2 (GIII) or 3 (GIV) weekly applications of 0.1N hydrochloric acid solution with pepsin. Groups V and VI were submitted to 2 (GV) or 3 (GVI) weekly applications of 0.1N hydrochloric acid and treated with daily nitrate diluted in water. Group VII consisted of 10 animals submitted to 2 weekly applications of filtered water. RESULTS: No dysplasia, intra-epithelial neoplasia or invasive carcinomas were detected. Inflammatory changes were observed in varying degrees and mast cells were more common in Groups V and VI (p=0.006). CONCLUSION: The data of the current study could not corroborate the hypothesis that gastroesophageal and pharyngolaryngeal refluxes are carcinogenic factors to the laryngopharyngeal mucosa, and more studies are necessary in the future.

OBJETIVO: Investigar a ação carcinogênica do ácido clorídrico, pepsina e nitrato de sódio na mucosa orofaríngea de ratos, simulando o refluxo do conteúdo gástrico à mucosa do faringo-laringea. MÉTODOS: Oitenta e dois ratos Wistar foram divididos em 7 grupos e submetidos a 2 ou 3 aplicações semanais de ácido clorídrico, pepsina e nitrato de sódio na mucosa orofaríngea durante 6 meses. Os grupos de estudo envolveram 12 animais cada. Os ratos nos grupos I e II foram submetidos à 2 (GI) ou 3 (GII) aplicações semanais de ácido clorídrico 0,1N. Nos grupos III e IV foram 2 (GIII) ou 3 (GIV) aplicações semanais de ácido clorídrico e pepsina. Nos grupos V e VI foram 2 (GV) ou 3 (GVI) aplicações semanais de ácido clorídrico além da oferta de nitrato diluído em água diariamente. Grupo VII era composto por 10 animais submetidos a 2 aplicações semanais de água filtrada. RESULTADOS: Não se observou displasia, neoplasia intra-epitelial ou neoplasia invasora. Alterações inflamatórias em graus variados foram observadas, com infiltrado mastocitário mais intenso nos grupos V e VI. (p=0,006). CONCLUSÃO: Os dados do presente estudo não confirmam a hipótese que o refluxo gastro-esofágico e faringo-laringeo são fatores carcinogênicos para a mucosa laringo-faringea e mais estudos são necessários no futuro.

Experimental carcinogenesis on the oropharyngeal mucosa of rats with hydrochloric acid, sodium nitrate and pepsin.

PURPOSE: To investigate the carcinogenic action of hydrochloric acid, pepsin and sodium nitrate on the oropharyngeal mucosa of rats, simulating the reflux of gastric contents. METHODS: Eighty-two Wistar rats were divided in seven groups and submitted to 2 or 3 weekly applications of hydrochloric acid, pepsin and sodium nitrate on the pharyngeal mucosa during six months. Study groups comprised 12 animals each. Rats in groups I and II were submitted to 2 (GI) or 3 (GII) weekly applications of 0.1N hydrochloric acid. Groups III and IV were submitted to 2 (GIII) or 3 (GIV) weekly applications of 0.1N hydrochloric acid solution with pepsin. Groups V and VI were submitted to 2 (GV) or 3 (GVI) weekly applications of 0.1N hydrochloric acid and treated with daily nitrate diluted in water. Group VII consisted of 10 animals submitted to 2 weekly applications of filtered water. RESULTS: No dysplasia, intra-epithelial neoplasia or invasive carcinomas were detected. Inflammatory changes were observed in varying degrees and mast cells were more common in Groups V and VI (p=0.006). CONCLUSION: The data of the current study could not corroborate the hypothesis that gastroesophageal and pharyngolaryngeal refluxes are carcinogenic factors to the laryngopharyngeal mucosa, and more studies are necessary in the future.

Laryngeal adenoid cystic carcinoma: case report.

CONTEXT: Adenoid cystic carcinomas are malignant tumors that occur in both the major and the minor salivary glands. A laryngeal location is rare because of the paucity of accessory salivary glands in this area. Adenoid cystic carcinomas account for less than 1% of all malignant tumors in the larynx, and only about 120 cases have been reported in the literature. These tumors have a slight female predisposition, and their peak incidence is in the fifth and sixth decades of life. In this article, we describe a case of laryngeal adenoid cystic carcinoma and discuss its clinical characteristics and treatment. CASE REPORT: We report on a case of laryngeal adenoid cystic carcinoma in a 55 year-old female patient who presented with dyspnea and hoarseness. Features of the diagnostic and therapeutic evaluation are described and the clinical management of such cases is outlined. The clinical course, definitive treatment strategy and surgical procedure, and also adjuvant treatment with irradiation are discussed. Although the tumor is radiosensitive, it is not radiocurable.

Associação entre CEC de laringofaringe e doença do refluxo gastroesofágico / Pharyngolaryngeal squamous cell carcinoma and gastroesophageal reflux disease

Introdução: o carcinoma espinocelular (CEC) de laringe e hipofaringe tem como seus principais fatores etiológicos o tabagismo e o etilismo. Muitos autores sugerem uma ação co-carcinogênica da inflamação crônica na mucosa escamosa do epitélio laringo-faríngeo devido ao refluxo do conteúdo gástrico em pacientes portadores de doença do refluxo gastroesofágico (DRGE). Objetivo: avaliar a presença de refluxo laringo-faríngeo em pacientes portadores de CEC de laringe e hipofaringe, as características do tumor, tratamento realizado, sintomas de DRGE e evolução clínica dos doentes. Pacientes e Método: análise retrospectiva, entre 1998 e 2005, de 21 pacientes tratados cirurgicamente de CEC de laringe e hipofaringe no serviço de Cirurgia de Cabeça e Pescoço da UNICAMP. Resultados: vinte pacientes (95%) eram do gênero masculino. Dezessete tumores (81%) acometiam a laringe; dos quatro tumores (19%) que acometiam a hipofaringe, todos eram de recesso piriforme. Entre os portadores de CEC laríngeo, 10 (58,8%) apresentavam sintomas clínicos pré-operatórios típicos de DRGE; entre os portadores de CEC de hipofaringe apenas um (25%) apresentava sintomas. Conclusão: a DRGE e o refluxo laringo-faríngeo estão presentes em número significativo de pacientes portadores de CEC de laringe e hipofaringe.

Introduction: the laryngeal and hypopharyngeal squamous cell carcinoma (SCC) occurs due to the association of tobacco and alcohol abuse. Many authors suggest an association between chronic inflammation in the pharyngolaryngeal squamous epithelium due to reflux of the gastric contents to the laryngopharynx and the development of SCC. Objective: to evaluate the presence of pharyngolaryngeal reflux in patients with SCC in the larynx and hypopharynx, the tumor characteristics, treatment, reflux symptoms and clinical behavior of the patients. Methods: retrospective study between 1998 and 2005 of 21 patients treated surgically for laryngeal or hypopharyngeal SCC in the Head and Neck Department of UNICAMP. Results: twenty patients (95%) were men. Seventeen tumors (81%) occurred in the larynx; four tumors occurred in the hypopharynx (19%), all in the piriform sinus. Among the patients with laryngeal SCC, 10 (58,8%) showed preoperative symptoms of gastroesophageal reflux disease; among hypopharyngeal tumors, only one patient had symptoms (25%). Conclusion: pharyngolaryngeal reflux occurs in a significant number of patients with laryngeal or hypopharyngeal SCC.