Clinical outcomes of patients with pancreatic tumors discussed in Tumor Board.

OBJECTIVE: the recommendations of the decisions made by the Tumor Board (TB) should be followed to identify barriers that may interfere with the execution of the previously decided, best care for the patient. The aim of this study is to assess whether the TB conduct decision was performed in patients with pancreatic tumors, their life status 90 days after the TB decision, and to analyze the reasons why the conduct was not performed. METHODS: we conducted a retrospective study with patients with pancreas tumors, evaluated between 2017 and 2019. We collected data on epidemiological status, whether the TB procedure was performed, the reason for not performing it, life status 90 days after the TB decision, and how many times each patient was discussed at a meeting. We compared categorical variables using the chi square test, numerical variables were presented as means and standard deviation. RESULTS: we studied 111 session cases, in 95 patients, 86 (90.5%) diagnosed with cancer. After 90 days of TB, 83 patients (87.37%) remained alive, 9 had (9.47%) died, and 3 (3.16%) were lost to follow-up. The TB decision was not observed in 12 (10.8%) cases and the reasons were: 25% (3) for loss of follow-up, 8.33% (1) for patient refusal, and 66.67% (8) due to clinical worsening. The cases of patients with metastases had a lower rate of TB conduct compliance (p=0.006). CONCLUSIONS: the TB conduct was performed in most cases and the most evident reason for non-compliance with the conducts is the patient's clinical worsening.

Clinical outcomes of patients with pancreatic tumors discussed in Tumor Board / Desfechos clínicos dos pacientes com tumores de pâncreas discutidos em Tumor Board

ABSTRACT Objective: the recommendations of the decisions made by the Tumor Board (TB) should be followed to identify barriers that may interfere with the execution of the previously decided, best care for the patient. The aim of this study is to assess whether the TB conduct decision was performed in patients with pancreatic tumors, their life status 90 days after the TB decision, and to analyze the reasons why the conduct was not performed. Methods: we conducted a retrospective study with patients with pancreas tumors, evaluated between 2017 and 2019. We collected data on epidemiological status, whether the TB procedure was performed, the reason for not performing it, life status 90 days after the TB decision, and how many times each patient was discussed at a meeting. We compared categorical variables using the chi square test, numerical variables were presented as means and standard deviation. Results: we studied 111 session cases, in 95 patients, 86 (90.5%) diagnosed with cancer. After 90 days of TB, 83 patients (87.37%) remained alive, 9 had (9.47%) died, and 3 (3.16%) were lost to follow-up. The TB decision was not observed in 12 (10.8%) cases and the reasons were: 25% (3) for loss of follow-up, 8.33% (1) for patient refusal, and 66.67% (8) due to clinical worsening. The cases of patients with metastases had a lower rate of TB conduct compliance (p=0.006). Conclusions: the TB conduct was performed in most cases and the most evident reason for non-compliance with the conducts is the patient's clinical worsening.

RESUMO Objetivo: as recomendações das decisões em Tumor Board (TB) deveriam ser acompanhadas para identificar barreiras que possam interferir na execução do melhor cuidado para o paciente decidido previamente. O objetivo do estudo é avaliar se a decisão de conduta em TB foi realizada em pacientes com tumores pancreáticos, o status de vida 90 dias após TB e analisar os motivos pelos quais a conduta não foi realizada. Métodos: estudo retrospectivo com pacientes com tumores de pâncreas, avaliados entre 2017 a 2019. Dados epidemiológicos, se a conduta de TB foi realizada, o motivo da não realização, o status de vida em 90 dias após decisão de TB e quantas vezes cada paciente foi discutido em reunião foram coletados. As variáveis categóricas foram comparadas pelo teste de qui-quadrado; variáveis numéricas foram apresentadas como médias e desvio padrão. Resultados: 111 casos, 95 pacientes, 86 (90,5%) com diagnóstico de câncer. Após 90 dias de TB, 83 pacientes (87,37%) permaneceram vivos, 9 pacientes (9,47%) faleceram e 3 (3,16%) perderam o seguimento. A conduta do TB não foi realizada em 12 (10,8%) dos casos e os motivos foram: 25% (3) por perda de seguimento, 8,33% (1) por recusa do paciente e 66,67% (8) devido à piora clínica. Os casos de pacientes com metástases tiveram menor execução de conduta de TB (p=0,006). Conclusões: a conduta do TB é realizada na maior parte dos casos e o motivo mais evidente para o não cumprimento das condutas é a piora clínica do paciente.

Rational design and validation of an anti-protein kinase C active-state specific antibody based on conformational changes.

Protein kinase C (PKC) plays a regulatory role in key pathways in cancer. However, since phosphorylation is a step for classical PKC (cPKC) maturation and does not correlate with activation, there is a lack of tools to detect active PKC in tissue samples. Here, a structure-based rational approach was used to select a peptide to generate an antibody that distinguishes active from inactive cPKC. A peptide conserved in all cPKCs, C2Cat, was chosen since modeling studies based on a crystal structure of PKCß showed that it is localized at the interface between the C2 and catalytic domains of cPKCs in an inactive kinase. Anti-C2Cat recognizes active cPKCs at least two-fold better than inactive kinase in ELISA and immunoprecipitation assays, and detects the temporal dynamics of cPKC activation upon receptor or phorbol stimulation. Furthermore, the antibody is able to detect active PKC in human tissue. Higher levels of active cPKC were observed in the more aggressive triple negative breast cancer tumors as compared to the less aggressive estrogen receptor positive tumors. Thus, this antibody represents a reliable, hitherto unavailable and a valuable tool to study PKC activation in cells and tissues. Similar structure-based rational design strategies can be broadly applied to obtain active-state specific antibodies for other signal transduction molecules.

Accuracy of typing and grading invasive mammary carcinomas on core needle biopsy compared with the excisional specimen.

INTRODUCTION: Breast core needle biopsy (CNB) allows evaluation of histological, prognostic, and predictive factors in invasive mammary carcinomas (IMC). We tested the CNB accuracy on typing and grading of invasive breast carcinomas. MATERIALS AND METHODS: A histological review of 120 CNBs and their related surgical specimens was carried out in a double-blind fashion. Tumor type and grade were assigned according to the World Health Organization classification and the Nottingham grading system. RESULTS: The sum of CNB fragment lengths varied from 4 mm to 38 mm (mean 16.7 mm), and tumor sample size varied from 1 mm to 26 mm (mean 11.1 mm). Histological type matched surgical specimen evaluation in 80 of 120 cases (66.6%). Of the cases, 17 (14.2%) were changed to a different prognostic category. Histological grade comparison was accurate in 56 of 95 cases (59.0%, kappa=0.35). Histological grade components (tubule formation, nuclear grade, and mitotic index) agreed, respectively, in 54.7%, 58.9%, and 62.1% (kappa index 0.30, 0.36, and 0.28). DISCUSSION: Typing IMC on CNB can be routinely assessed based on good correlation with surgical specimens, especially considering prognostic categories for IMC. Grading IMC based on CNB is not as accurate, and its evaluation should be delayed until the surgical specimen examination. Tumor heterogeneity seems to be the most important factor for disagreement.

[Importance of parathyroid SPECT and 99mTc scintigraphy, and of clinical, laboratorial, ultrasonographic and citologic correlation in the pre-operative localization of the parathyroid adenoma - pictorial assay]. / Importância da complementação com SPECT e 99mTc na cintilografia das paratiroides e da correlação clínica, laboratorial, ultrassonográfica e citológica na localização pré-operatória do adenoma de paratiroide - ensaio pictórico.

OBJECTIVE: In patients with primary hyperparathyroidism, candidates for surgical intervention, the parathyroid pre-operative localization is of fundamental importance in planning the appropriate surgical approach. MATERIALS AND METHODS: The additional acquisition of SPECT and Technetium-99m images, during parathyroid scintigraphy with Sestamibi, is not common practice. Usually, only planar image acquisition, 15 minutes prior and 2 hours after radiopharmaceutical administration, is performed. RESULTS: In our experience, the complete protocol in parathyroid scintigraphy increases the accuracy of pre-operative parathyroid localization. CONCLUSION: The complete utilization of all available nuclear medicine methods (SPECT e 99mTc) and image interpretation in a multidisciplinary context can improve the accuracy of parathyroid scintigraphy.

Keratoacanthoma of the lower lip: still a matter of diagnosis / Ceratoacancoma do lábio inferior: ainda um problema de diagnóstico

Introduction: Keratoacanthoma is a lesion that may mimic squamous cells carcinoma clinically and histologically and the distinction between both lesions has been a matter of discussion. Typical lesions consist of a firm dome-shaped nodule, 1 to 2 centimeters in diameter, with a horn-filled crater in its center. Objectives: To present it was selected an atypical case of a 43-year-old woman who had a solitary keratoacanthoma (KA) of the lower lip with a history of two years of evolution and mistreatment and to discuss the difficulties of the diagnosis process. Conclusion: Because of the rarity of the lesion and its similarity with squamous cells carcinoma the general dentist must explain to the patient that the clinical aspects are not conclusive of the diagnosis and a correct acquisition of the surgical specimen is crucial to an accurate histopathological interpretation and conclusive diagnosis.

Introdução: O ceratoacantoma é uma lesão que pode mimetizar clínica e histologicamente o carcinoma espinocelular, sendo discutível a distinção entre as duas lesões. As lesões típicas consistem em um nódulo firme, em forma de cúpula, com 1 a 2 centímetros de diâmetro e uma cratera central preenchida com queratina. Objetivo: Apresentar um caso atípico de uma mulher de 43 anos que apresentava uma lesão solitária de queratoacantoma no lábio inferior, com uma história de dois anos de evolução e erros de tratamento e discutir a dificuldade no processo de diagnóstico. Conclusão: Devido à raridade da lesão e sua semelhança com o carcinoma, o clínico geral deve explicar ao paciente que os aspectos clínicos não são conclusivos do diagnóstico e que a aquisição correta do espécime cirúrgico são cruciais para a análise histopatológica correta e para o diagnóstico conclusivo.

Importância da complementação com SPECT e 99mTc na cintilografia das paratiroides e da correlação clínica, laboratorial, ultrassonográfica e citológica na localização pré-operatória do adenoma de paratiroide - ensaio pictórico / Importance of parathyroid SPECT and 99mTc scintigraphy, and of clinical, laboratorial, ultrasonographic and citologic correlation in the pre-operative localization of the parathyroid adenoma - pictorial assay

OBJETIVO: Diante de um paciente portador de hiperparatiroidismo primário com indicação de tratamento cirúrgico, a localização pré-operatória da paratiroide é de fundamental importância para definir a melhor abordagem cirúrgica. MATERIAIS E MÉTODOS: A realização adicional de imagens SPECT e da cintilografia com 99mTc durante a cintilografia das paratiroides com Setamibi não é rotina em nosso meio, sendo comum a aquisição apenas das imagens planas − precoce (15 minutos) e tardia (2 horas). RESULTADOS: Na nossa experiência, tem-se percebido que a realização do protocolo completo contribui de maneira decisiva na sensibilidade da localização pré-operatória da paratiroide. CONCLUSÃO: A aplicação completa de todos os métodos cintilográficos disponíveis (SPECT e 99mTc) e a análise cuidadosa das imagens em um contexto multidisciplinar podem aumentar a acurácia da cintilografia das paratiroides.

OBJECTIVE: In patients with primary hyperparathyroidism, candidates for surgical intervention, the parathyroid pre-operative localization is of fundamental importance in planning the appropriate surgical approach. MATERIALS AND METHODS: The additional acquisition of SPECT and Technetium-99m images, during parathyroid scintigraphy with Sestamibi, is not common practice. Usually, only planar image acquisition, 15 minutes prior and 2 hours after radiopharmaceutical administration, is performed. RESULTS: In our experience, the complete protocol in parathyroid scintigraphy increases the accuracy of pre-operative parathyroid localization. CONCLUSION: The complete utilization of all available nuclear medicine methods (SPECT e 99mTc) and image interpretation in a multidisciplinary context can improve the accuracy of parathyroid scintigraphy.

Imunofenótipo e evolução de câncer de mama: comparação entre mulheres muito jovens e mulheres na pós-menopausa / Immunophenotype and evolution of breast carcinomas: a comparison between very young and postmenopausal women

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...

PURPOSE: the objective of this study was to evaluate the clinical, pathological and molecular characteristics in very young women and postmenopausal women with breast cancer. METHODS: we selected 106 cases of breast cancer of very young women (≤35 years) and 130 cases of postmenopausal women. We evaluated clinical characteristics of patients (age at diagnosis, ethnic group, family history of breast cancer, staging, presence of distant metastases, overall and disease-free survival), pathological characteristics of tumors (tumor size, histological type and grade, axillary lymph nodes status) and expression of molecular markers (hormone receptors, HER2, p53, p63, cytokeratins 5 and 14, and EGFR), using immunohistochemistry and tissue microarray. RESULTS: when comparing clinicopathologic variables between the age groups, younger women demonstrated greater frequency of nulliparity (p=0.03), larger tumors (p≤0.000), higher stage disease (p=0.01), lymph node positivity (p=0.001), and higher grade tumors (p=0.004). Most of the young patients received chemotherapy (90.8%) and radiotherapy (85.2%) and less tamoxifen therapy (31.5%) comparing with postmenopausal women. Lower estrogen receptor positivity 49.1% (p=0.01) and higher HER2 overexpression 28.7% (p=0.03) were observed in young women. In 32 young patients (29.6%) and in 20% of the posmenopausal women, the breast carcinomas were of the triple-negative phenotype (p=0.034). In 16 young women (50%) and in 10 postmenopausal women (7.7%), the tumors expressed positivity for cytokeratin 5 and/or 14, basal phenotype (p=0.064). Systemic metastases were detected in 55.3% of the young women and in 39.2% of the postmenopausal women. Breast cancer overall survival and disease-free survival in five years were, respectively, 63 and 39% for young women and 75 and 67% for postmenopausal women. CONCLUSIONS: breast cancer arising in very young women showed negative clinicobiological characteristics and more aggressive tumors.

Intracystic papillary carcinoma of the breast: risks in diagnostic, staging and treatment

Intracystic papillary carcinoma (IPC) of the breast is a rare form of breast in situ carcinoma that comprises 0.5-2% of all breast tumors. IPC of the breast occurs in women around the sixth decade of life and presents an injury of great dimensions, more frequently retroareolar. Clinical and radiological findings can be confused with advanced-staged invading carcinomas (T2 or T3), leading to unnecessarily aggressive treatment. The correlation of clinical, radiological and anatomopathological findings is necessary for a correct diagnosis. We present two cases of IPC and discuss diagnostic characteristics.

O arranjo em matriz de amostras teciduais (tissue microarray): larga escala e baixo custo ao alcance do patologista / Tissue microarrays: high throughput and low cost avaiable for pathologists

O arranjo em matriz de amostras teciduais, ou tissue microarray (TMA), é uma técnica descrita em 1998 por Kononen et al. com ampla aceitação pela literatura mundial. Com um conceito extremamente simples, trata-se de agrupar um grande número de amostras teciduais em um único bloco de parafina, permitindo o estudo de expressão de marcadores moleculares em larga escala com grande aproveitamento do material arquivado, do tempo e dos custos. Discutimos as vantagens e limitações do método, as estratégias e técnica de construção, as aplicações e dificuldades encontradas para a patologia investigativa nos últimos cinco anos de uso no Hospital do Câncer A. C. Camargo.

Tissue microarrays (TMA) is a worldwide well accepted technique described in 1998 by Kononen et al. It uses an extremely simple concept of ordering hundreds of samples in just one paraffin block to evaluate protein expression in large cohorts with great advantages on costs, time and sample saving. We discuss the technique, its advantages and limitations, strategies to construct the receptor block, its usefulness and difficulties experienced in the last five years at Hospital do Cancer A.C. Camargo.

Estudo de fatores moleculares prognósticos e preditivos do linfoma não-Hodgkin difuso de grandes células B através de tissue microarrays / Predictive and prognostic factors in difuse large B-cell lymphoma using Tissue Microarrays

Os linfomas difusos de grandes células B (LDGCB) compõem um grupo heterogêneo do ponto de vista clínico, morfológico, molecular e de resposta ao tratamento. O Índice Prognóstico Internacional (IPI) é o fator prognóstico mais importante mas os avanços no conhecimento molecular permitiu a identificação de subgrupos baseados no perfil ontogenético do linfócito B (“centro germinativo” vs. “linfócito ativado”) com diferenças prognósticas independente do IPI. Avaliamos a expressão protéica por tissue microarrays de proteínas relacionadas ao ciclo celular, apoptose, diferenciação do linfócito e resposta a citocinas/metabolismo oxidativo em 109 pacientes adultos com LDGCB nodal diagnosticados e tratados com esquema baseado em antraciclina no Hospital do Câncer AC Camargo. RESULTADOS: As variáveis estágio clínico, remissão completa, IPI, p53, OCT2, ciclina G1 e B1 e NF-kappaB mostraram significância estatística (p< 0,05) para a sobrevida câncer-especifíca em 5 anos na análise univariada. A classificação ontogenética (CD10/BCL6/MUM1) foi possível mas não mostrou relevância clínica (p=0,348). O modelo de regressão Cox incluiu apenas IPI e remissão completa. O grupo IPI de baixo risco esteve associado a positividade para STAT1 (p=0,017) e cJUN (p=0,041). Pacientes com IPI de baixo risco e evolução desfavorável associaram-se a positividade para BCL2 (p=0,029). Um algoritmo elaborado a partir da expressão de OCT2 e p53 foi capaz de identificar três grupos com diferentes curvas de sobrevida (p=0,02) CONCLUSAO: A melhor maneira de usar o conhecimento molecular nos LDGCB ainda não está clara. Um modelo de classificação multi-função parece ser mais racional do que aquele baseado apenas na diferenciação do linfócito...(AU)

Genetic profiling has confirmed Diffuse Large B-cell Lymphoma (DLBCL) subtypes with distinct clinical outcomes named "germinal center" (GC) and "activated B-cell" (ABC). Apoptosis and cell cycle pathways are also of clinical importance. We evaluated protein expression in 109 specimens from adult patients with nodal DLBCL. METHODS: Forty-four antigens covering cell cycle, apoptosis, lymphoid differentiation markers and cytokines response/oxidative metabolism were studied using tissue microarray technology. RESULTS: No statistic difference on cancer specific survival was noted between GC and ABC profiles (p=0.348). International Prognostic Index (IPI), complete remission, clinical stage, p53, OCT2, cyclin G1 and B1 and NF-kappaB were considered statistically significant by univariate analysis (p<0.05). Cox regression model identified complete remission and IPI as predictive variables. Low-risk IPI was associated to positive STAT1 (p=0,017) and cJUN (p=0,041). Patients with low-risk IPI but poor outcome were associated with positive BCL2 (p=0,029). Grouping OCT2 and p53 results identified three subgroups with distinct survival curves (p=0,02). CONCLUSION: A multi-pathway approach seems to be more rational for molecular profiling of DLBCL (AU)