Development of novel mucoadhesive gels containing nanoparticle for buccal administration of dexamethasone

Abstract This study aimed to develop promising and innovative mucoadhesive gel systems containing dexamethasone-loaded nanoparticle to increase the effectiveness of treatment for oral precancerous lesions and to reduce side effects. In this respect, a dexamethasone-loaded nanoparticle formulation was prepared by using emulsification/solvent evaporation method. The nanoparticle has high zeta potential (-10.3±0.5 mV), low particle size (218.42±2.1), low polydispersity index (0.070±0.014) and high encapsulation efficiency (95.018±2.982%). To improve the mucosal retention time, the dexamethasone-loaded nanoparticle was dispersed in mucoadhesive gel using gellan gum. The developed gels offered appropriate pH value, high drug content, suitable mechanical and mucoadhesive performance and appropriate viscosity for mucosal administration. All formulations exhibited plastic flow and typical gel-type mechanical spectra after the determined frequency value. The developed formulations exhibited extended drug release as intended for these systems. Cytotoxicity was tested by MTT assay in human epithelioid carcinoma cell (HeLa) in vitro. The MTT assay showed that the blank formulations were non-toxic to cells. It was observed that the bioactivity of the free dexamethasone was potentiated by mucoadhesive gels containing dexamethasone-loaded nanoparticle in HeLa cells. Results from this study indicate that mucoadhesive gels are effective for the local treatment of precancerous lesions. Our findings showed that the developed formulations were worthy of further studies.

Carcinoma del conducto salival: presentación de un caso / Salivary duct carcinoma: report of a case

El carcinoma de conductos salivales (CCS) es una neoplasia maligna primaria clínica y patológicamente distinta de las glándulas salivales. Debido a su rareza existe una falta de documentación exhaustiva en la literatura con respecto a sus características, manejo y resultados clínicos. En la presente publicación se presenta un caso de un paciente de sexo masculino de 74 años, que acudió al servicio de odontología del Hospital Interzonal General de Agudos Presidente Perón de Avellaneda. El resultado ecográfico arrojó a nivel submaxilar derecho una imagen nodular de aspecto solido que mide 25 x 24 mm Se le realizó la intervención quirúrgica y el resultado anatomopatológico confirmó el diagnóstico de carcinoma de conductos salivales, una de las neoplasias salivales más agresivas. En la actualidad, la muerte ocurre en 60 a 80% de los pacientes, por lo general dentro de los 5 años; alrededor del 33% desarrolla recidiva local y más del 50% metástasis a distancia, en sitios que incluyen pulmones, huesos, hígado, cerebro y piel (AU)

Salivary duct carcinoma (SDC) is a clinically and pathologically distinct primary malignant neoplasm of the salivary glands. Due to its rarity, there is a lack of exhaustive documentation in the literature regarding its characteristics, management, and clinical results. This publication presents a case of a 74-year-old male patient who attended the dentistry service of the Interzonal General Acute Hospital President Perón by Avellaneda. The ultrasound result revealed a nodular image at the right submaxillary level solid aspect measuring 25 x 24 mm. Surgical intervention was performed, and the pathological result confirmed the diagnosis of salivary duct carcinoma, one of the most aggressive salivary neoplasms. Currently, death occurs in 60% to 80% of patients, usually within 5 years; about 33% develop local recurrence and more than 50% distant metastases, at sites including the lungs, bones, liver, brain, and skin (AU)

Analyses of odontogenic tumours: the most recent classification proposed by the World Health Organization (2017)

BACKGROUND: The fourth edition of the “WHO Classification of Head and Neck Tumours” was published in January 2017 and includes a classification of odontogenic tumours. This review aims to examine the changes made in this new classification in comparison with the previous classification of 2005. MATERIAL AND METHODS: An electronic search was conducted in the PubMed, Scopus and Cochrane databases with the keywords “odontogenic tumor”, “WHO classification” and “update”. Studies published from January 2009 to April 2019 with a high level of scientific evidence were included, but studies not published in English, epidemiological studies and studies with a low level of evidence were excluded. RESULTS: The initial search found 457 articles and after eliminating duplicates, 8 studies were selected for full-text assessment. After excluding 3 epidemiological studies, 5 articles were finally included. These studies were stratified by their level of scientific evidence using SORT criteria (Strength of Recommendation Taxonomy). CONCLUSIONS: The new odontogenic tumour list has been simplified with the objective of improving its role as an international guide for diagnosis. Some changes have been possible thanks to the application of immunohisto-chemistry and molecular genetic techniques that allow better characterization of certain tumours. Further clinico-pathological and molecular studies are needed so that this new classification can be consolidated and/or amended

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Nova classificação da OMS para tumores odontogênicos: o que mudou? / Updated WHO classification for odontogenic tumors: what has changed?

Objetivo: apresentar e discutir as mais relevantes modificaçõesna quarta classificação de tumores de cabeçae pescoço da Organização Mundial de Saúde (OMS),no ano de 2017, especialmente para os tumores odontogênicos.Revisão de literatura: o trabalho baseia-seem uma revisão da literatura relacionada ao tema, emespecial no artigo publicado pelos professores John M.Wright e Marilena Vered no Head & Neck PathologyJournal, no ano de 2017, o qual apresenta as principaisatualizações desde as reuniões de 1992 e 2005. O quefoi excluído da terceira edição, o que foi retomado dasegunda edição, as novas descobertas e o porquê detais mudanças serão alguns pontos abordados. Consideraçõesfinais: observa-se que as atualizações foramorientadas pelos princípios de simplicidade, relevânciaclínica, validade científica e utilidade, no intuito defornecer uma classificação contemporânea e menoscomplexa, servindo como base para o clínico e o patologistaem termos de diagnóstico e condução dos casos. (AU)

Objective: this study aimed to present and discuss the most relevant updates in the 4th classification of head and neck tumors by the World Health Organization (WHO) in 2017, especially for odontogenic tumors. Literature review: the study is based on a literature review related to the topic, particularly on the article published by Professors John M. Wright and Marilena Vered in the Head & Neck Pathology Journal in 2017, which presents the main updates since the meetings of 1992 and 2005. What was excluded from the third edition and resumed from the second one, the new findings and the reason for such changes will be some of the points addressed. Final considerations: it is observed that the updates were guided by the principles of simplicity, clinical significance, and scientific validity and utility, in order to provide a contemporary and simpler classification that works as a basis for practitioners and pathologists in terms of diagnosis and management of cases. (AU)

Nueva clasificación de la OMS de los tumores tiroideos: una categorización pragmática de las neoplasias de la glándula tiroides / New WHO classification of thyroid tumors: a pragmatic categorization of thyroid gland neoplasms

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Cáncer sincrónico y metacrónico detectado con PET/CT en población oncológica / Multiple primary malignant neoplasms detected by PET/CT in cancer patients

Background Imaging with F18-fluorodeoxyglucose PET/CT is used to determine sites of abnormal glucose metabolism and can be used to characterize and localize many types of tumors. Aim To assess the prevalence of multiple primary malignant neoplasms (MPMN) detected by PET/CT in cancer patients. Material and Methods F18-fluorodeoxyglucose PET/CT scans performed to 800 patients with a newly diagnosed cancer or with already treated tumors were retrospectively reviewed. In patients whose examination described incidental findings not related to the primary tumor, a research was done about further laboratory, imaging or pathological studies. Results In 188 PET/CT scans (23%) an incidental finding was found. Of these, 66 (35%) were considered as MPMN, 12 as atypical metastases of a known primary tumor, 14 as false positive images (inflammatory or physiologic uptake) and 29 as benign or low grade tumors. In 67 cases (36% of all incidental tumors), the finding was not confirmed. Seven percent of patients with a newly diagnosed tumor had a synchronic MPMN detected by PET/CT. Nine percent of patients with treated tumors developed a metachronous MPMN during their follow up. The most common incidental tumors were thyroid cancer in 15 cases, kidney cancer in 13, lung cancer in 10, colorectal carcinoma in 9, breast cancer in 6, prostate cancer in 4, non-Hodgkin lymphoma in 3 and pancreatic cancer in 2. Conclusions A MPMN is detected by PET/CT in a significant number of cancer patients.

Cáncer colorrectal: prevención y tratamiento / Colorectal cancer: prevention and treatment

El cáncer colorrectal (CCR) es uno de los cánceres más comúnmente diagnosticados a nivel mundial, constituyendo el tercer tumor de mayor incidencia y la cuarta mayor causa de muerte. El CCR puede clasificarse como esporádico (90-95%) o hereditario y presenta una tasa de mortalidad de 19,6 por cada 100.000 habitantes y una tasa de incidencia de 46,4 por cada 100.000 habitantes. Son varios los factores de riesgo y protectores del CCR que se han descrito, algunos independientes del tipo de vida de los pacientes, sobre todo factores genéticos, y otros dependientes del mismo, como son la dieta, la obesidad, la actividad física, el consumo de tabaco y de alcohol. Las pruebas de cribado del CCR son una de las causas implicadas en la reducción de la mortalidad y de la incidencia del CCR, pues suponen una detección de CCR en estadios no avanzados que permiten afrontar la enfermedad en etapas tempranas proporcionando así mejores pronósticos. Tras el diagnóstico de CCR hay que conocer la estadificación del mismo para poder emplear el mejor esquema de quimioterapia posible. La quimioterapia adyuvante se emplea tras la intervención quirúrgica con carácter curativo, principalmente en pacientes con CCR en estadios II de alto riesgo y estadio III (tumores localmente avanzados). Los pacientes con tumores en estadio IV (tumor extendido a otros órganos) se benefician de la quimioterapia neoadyuvante, administrada previamente a la intervención quirúrgica con el fin de reducir el tumor. Estos esquemas de tratamiento se basan en combinaciones de quimioterapia y terapias dirigidas (AU)

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers in the world, it is the third most prevalent tumor and the fourth cause of death. CRC can be classified as sporadic (90-95 %) or hereditary and it has a mortality rate of 19.6 per 100,000 inhabitants and an incidence rate of 46.4 per 100,000 inhabitants. Several risk and protective factors have been described according CRC, some independent of the patients' life-style, especially genetic factors, and others dependent on it, such as diet, obesity, physical activity, tobacco and alcohol. CRC screening tests are one of the causes involved in the reduction of mortality and the incidence of CRC, because they involve CRC detection in non-advanced stages that allow the disease to be treated in the early stages, providing better predictions. After the diagnosis of CRC, it is necessary to know the staging of the tumor in order to be able to use the best possible chemotherapy regimen. Adjuvant chemotherapy is used after curative surgery, mainly in patients with CRC in stage II with high risk and stage III (locally advanced tumors). Patients with stage IV tumors (metastasic tumor) benefit from neoadjuvant chemotherapy, which is previously administered to the surgical intervention in order to reduce the tumor. These treatment regimens are based on combinations of chemotherapy and molecular targeted therapies (AU)

Presentación ecográfica no habitual de queratoacantoma subungueal con correlación clínica e histológica / Unusual Ultrasound Appearance of Subungual Keratoacanthoma With Clinical and Histological Correlation

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Leucoplasia verrucosa proliferativa e carcinoma verrucoso: semelhanças e diferenças histopatológicas e de proliferação celular por Ki67 / Proliferative verrucous leukoplakia and verrucous carcinoma: histopathological similarities and differences and cell proliferation by Ki67

Carcinoma verrucoso e leucoplasia verrucosa proliferativa, estão entre as lesões que apresentam difícil diagnóstico diferencial devido às semelhanças histopatológicas que ocorrem em determinada fase de evolução. Existe, para tanto, a necessidade de somar dados clínico-epidemiológicos ao histopatológico a fim de se estabelecer o diagnóstico final. A leucoplasia verrucosa proliferativa caracteriza-se por seu acometimento multifocal, grande potencial de recidiva e perfil progressivo que resulta em alto risco de transformação maligna. Por outro lado, o carcinoma verrucoso, variante de baixo grau do carcinoma epidermoide, é unifocal e dificilmente recidiva. A importância de novos estudos acerca das suas duas lesões mencionadas vem a agregar conhecimento de modo a facilitar um correto diagnóstico e, consequentemente, um apurado prognóstico. A leucoplasia verrucosa proliferativa, por se tratar de lesão com alto potencial de transformação maligna, pode evoluir para carcinoma epidermoide invasivo, menos diferenciado e mais agressivo com consequente prognostico obscuro, ao passo que, o carcinoma verrucoso não incorre em metástases e apresenta um prognóstico mais favorável. Isso posto, com o objetivo de aumentar a precisão diagnóstica, o presente trabalho propôs identificar e quantificar em porcentagem os critérios histopatológicos encontrados na leucoplasia verrucosa proliferativa e no carcinoma verrucoso visando diferenciar morfologicamente as lesões dos dois grupos.

Também buscamos comparar os dados epidemiológicos referentes aos casos inseridos no estudo, dentre eles vinte e dois casos de leucoplasia verrucosa proliferativa, dezoito casos de carcinoma verrucoso e dois casos apresentando tanto leucoplasia verrucosa proliferativa quanto carcinoma verrucoso, casos esses com diagnósticos estabelecidos previamente (baseando-se nos dados epidemiológicos somados ao histopatológico). A utilização de um marcador imuno-histoquímico da atividade proliferativa celular, o Ki67, também permitiu uma análise comparativa entre o comportamento biológico de ambas as lesões através de um ensaio quantitativo e qualitativo. A marcação mostrou-se escassa, mas evidente em células mitóticas da leucoplasia verrucosa proliferativa, mostrando, no entanto, maior número de células positivas no carcinoma verrucoso, estas visíveis nas camadas basal e parabasal. Os resultados do presente trabalho permitiram concluir então que o marcador Ki67 pode auxiliar no diagnóstico diferencial entre leucoplasia verrucosa proliferativa e carcinoma verrucoso. Foi possível depreender também que, histologicamente, o carcinoma verrucoso apresenta maior alteração em sua conformação epitelial, bem como maior número de atipias cito-arquiteturais quando comparado à leucoplasia verrucosa proliferativa, que, apesar de seu aspecto morfológico, evolui no sentido de uma potencial transformação maligna, apresentando, por sua vez, maior freqüência de projeções em gota.

Verrucous carcinoma and proliferative verrucous leukoplakia, are among the injuries presenting difficult differential diagnosis due to histopathological similarities that occur at some stage of evolution. There is a need to add clinical, epidemiological and histopathological data to achieve the final diagnosis. Proliferative verrucous leukoplakia is characterized by its multifocal involvement, great potential for relapse and progressive profile that results in malignant transformation high risk. On the other hand, the verrucous carcinoma, which is considered low-grade variant of squamous cell carcinoma, is unifocal and unlikely to return. The importance of new studies on its two mentioned lesions is to generate knowledge aiming at a correct diagnosis and prognosis. The proliferative verrucous leukoplakia, since it is a lesion with high potential for malignant transformation, can develop into less differentiated and more aggressive invasive squamous cell carcinoma with subsequent poor prognosis, whereas the verrucous carcinoma incurs no metastases and presents a more favorable prognosis. Thus, aimed to increase the diagnostic accuracy, the present work looked for to identify and quantify in percentage the histopathological criteria found on proliferative verrucous leukoplakia and verrucous carcinoma, aiming morphologically differentiate the lesions from both groups.

We also seek to compare the epidemiological data related to cases included in the study, including twenty-two cases of proliferative verrucous leukoplakia, eighteen cases of verrucous carcinoma and two cases showing both proliferative verrucous leukoplakia as verrucous carcinoma, cases with these diagnoses established previously (based on epidemiological data added to histopathology data). Using a cell proliferation immunohistochemical marker, Ki67, we made a comparative analysis between the biological behavior of both lesions by quantitative and qualitative assay. We saw a few strongly positive mitotic cells in samples of proliferative verrucous leukoplakia, and numerous positive cells observed in the basal and parabasal layers of verrucous carcinoma samples. This study results indicate, then, that the Ki67 marker may help in the differential diagnosis between proliferative verrucous leukoplakia and verrucous carcinoma. It was also possible to conclude that, histologically, the verrucous carcinoma shows greater change in its epithelial conformation and a higher number of cyto-architectural atypia when compared to proliferative verrucous leukoplakia, which, despite its morphological appearance, evolves towards a potential malignant transformation, presenting, in turn, higher drop-shaped rete ridges frequency.

Distribución fenotípica del carcinoma de mama en Venezuela / Phenotypic distribution of breast carcinoma in Venezuela

Objetivos. Determinar la distribución de los diferentes fenotipos tumorales del carcinoma mamario en pacientes venezolanas. Caracterizar las variables clinicopatológicas en cada subgrupo y establecer los patrones de supervivencia para cada fenotipo. Pacientes y métodos. Se evaluaron de forma retrospectiva los datos de 266 pacientes con diagnóstico de carcinoma de mama y estudio inmunohistoquímico de la biopsia inicial. Las pacientes fueron clasificadas en 3 grupos de fenotipos tumorales (receptor estrogénico positivo, HER2/neu sobreexpresado y triple negativo). Se determinaron y correlacionaron variables epidemiológicas, clínicas y patológicas.ResultadosLos grupos de fenotipos tumorales estuvieron distribuidos en receptor estrogénico positivo con un 60,9%, triple negativo con un 27,8% y HER2/neu sobreexpresado con un 11,3%. El 92% de las pacientes con fenotipo triple negativo eran de raza negra. La mejor supervivencia correspondió al fenotipo receptor estrogénico positivo, y la peor, al fenotipo triple negativo, aunque las diferencias no fueron significativas. ConclusionesLa distribución fenotípica del cáncer de mama en Venezuela es parecida a la de la literatura general. El subtipo triple negativo, que tuvo la peor supervivencia, aunque no de forma significativa, presentó una incidencia más elevada que la de otros grupos poblacionales. La mayoría de las pacientes en este subgrupo eran de raza negra (AU)

Objectives. To determine the distribution of the distinct breast carcinoma phenotypes in Venezuelan patients, characterize the clinicopathologic variables in each subgroup, and establish survival patterns for each phenotype. Patients and methods. We retrospectively evaluated data from 266 patients diagnosed with breast carcinoma and an immunohistochemical study of the initial biopsy. The patients were classified into 3 groups of tumor phenotypes (estrogen receptor-positive, HER2/neu overexpression and triple-negative). We determined and correlated epidemiological, clinical and pathological variables. ResultsT. he tumor phenotype groups were distributed as follows: estrogen receptor-positive in 60.9%, triple-negative in 27.8%, and HER2/neu overexpression in 11.3%. A total of 92% of the patients with triple-negative phenotype were African American. Survival was best with the estrogen receptor-positive phenotype and worst with the triple-negative phenotype, but these differences were not significant. Conclusions. The phenotypic distribution of breast carcinoma in Venezuela is similar to that reported in the general literature. The incidence of the triple-negative subtype, which showed the worst survival –although this result was not significant– was higher than in other populations. Most patients in this subgroup were African American (AU)

Achados de fibrobroncoscopia em pacientes com diagnóstico de neoplasia pulmonar / Fiberoptic bronchoscopy findings in patients diagnosed with lung cancer

OBJETIVO: Catalogar alterações encontradas em imagens obtidas por fibrobroncoscopia em pacientes com diagnóstico de neoplasia pulmonar e correlacionar esses achados com achados histopatológicos. MÉTODOS: Estudo retrospectivo envolvendo 212 pacientes com diagnóstico de câncer de pulmão confirmado por citologia obtida por lavado broncoalveolar e/ou histopatologia de biópsia endobrônquica ou transbrônquica. Os dados foram obtidos no Serviço de Endoscopia Respiratória do Hospital São Salvador (Goiânia-GO), entre 2005 e 2010. Os achados endoscópicos foram classificados como tumor endoscopicamente visível, tumor endoscopicamente não visível e lesão na mucosa, assim com quanto à pr sença/tipo de secreção. Os tumores visíveis também foram classificados de acordo com sua localização na árvore traqueobrônquica. RESULTADOS: O principal achado endoscópico foi a presença de massa endobrônquica (64%), seguido por infiltração da mucosa (35%). Quanto aos tipos histológicos (n = 199), os mais prevalentes foram carcinoma escamoso (39%), adenocarcinoma (21%), carcinoma de pequenas células (12%) e carcinoma de grandes células (1%). Mais de 45% dos tumores visíveis estavam localizados nos brônquios superiores. O carcinoma escamoso (n = 78) apresentou-se mais frequentemente como massa tumoral endobrônquica (74%), infiltração da mucosa (36%), estreitamento do lúmen (10%) e compressão extrínseca (6%). CONCLUSÕES: Nossos resultados indicam que a massa tumoral endobrônquica é o achado endoscópico que mais sugere malignidade. Proporcionalmente, infiltração da mucosa é mais comumente achada em carcinoma de pequenas células. Estreitamento do lúmen, compressão extrínseca, lesão na mucosa e secreção endobrônquica prevalecem no adenocarcinoma.

OBJECTIVE: To compile fiberoptic bronchoscopy findings in patients diagnosed with lung cancer and to correlate those with histopathological findings. METHODS: This was a retrospective study involving 212 patients with a confirmed diagnosis of lung cancer by cytological evaluation of BAL specimens or by histopathological evaluation of endobronchial or transbronchial biopsy specimens. The data were collected at the Respiratory Endoscopy Sector of Hospital São Salvador, located in the city of Goiânia, Brazil, between 2005 and 2010. The endoscopic findings were classified as endoscopically visible tumor, endoscopically invisible tumor, mucosal injury, as well as being classified by the presence/type of secretion. The visible tumors were also classified according to their location in the tracheobronchial tree. RESULTS: Endobronchial mass (64%) and mucosal infiltration (35%) were the main endoscopic findings. The histological type was determined in 199 cases, the most prevalent types being squamous carcinoma, in 78 (39%), adenocarcinoma, in 42 (21%) small cell carcinoma, in 24 (12%), and large cell carcinoma, in 2 (1%). More than 45% of the visible tumors were at the upper bronchi. Squamous carcinoma (n = 78) was most commonly visualized as an endobronchial mass (in 74%), mucosal infiltration (in 36%), luminal narrowing (in 10%), or external compression (in 6%). CONCLUSIONS: Our results show that the endobronchial mass is the most common bronchoscopic finding that is suggestive of malignancy. Proportionally, mucosal infiltration is the most common finding in small cell carcinoma. In adenocarcinoma, luminal narrowing, external compression, mucosal injury, and endobronchial secretion prevail.

Evaluation of ER-apha, ER-B1 and ER-B2 expression and correlation with clinicopathologic factors in invasive luminal subtype breast cancers

PURPOSE: Luminal subtype breast cancer is defined as oestrogen receptor (ER)- and/or progesterone receptor (PR)- positive breast cancer. We detected the expression of ER-alpha, ER-Β1 and ER-Β2 in the tissue samples of invasive luminal subtype breast cancer patients, evaluated the correlations between these ER statuses and prognosis, and tried to clarify whether the status of ER-alpha isoforms provides clinically useful information further to what is already provided by the traditional ER-alpha/PR assay. METHODS: The expression of ER-alpha, ER-Β1 and ER-Β2 in the paraffin-embedded sections of 162 invasive luminal subtype breast cancer patients was detected with an immunohistochemical staining method. With mid-long-term follow-up, the features of ER-alpha, ER-Β1 and ER-Β2 status and the correlations between clinical characteristics and the prognosis were analysed. RESULTS: ER-Β1-positive status was correlated with PR (rs=0.217, p<0.01). The median follow-up time was 92 months (range, 4-98 months). Univariate analysis suggested that ER-Β1 status was significantly correlated to diseasefree survival (DFS) time (log rank=3.98, p=0.046), especially in patients with positive lymph nodes (log rank=6.20, p=0.013). In patients with smaller tumour size (=20 mm), negative ER-Β2 status was significantly correlated to overall survival time (log rank=3.87, p=0.049). CONCLUSIONS: In invasive luminal subtype breast cancers, ER-Β1 is correlated with good prognosis and could be regarded as one of the factors for evaluating DFS time, especially in lymph node-positive patients. There may be some interactions between ER-Β1 and PR. In clinical practice, besides routine detection of ER-alpha and PR in invasive luminal subtype breast cancers, immunohistochemical staining of ER-Β1 and ER-Β2 should be considered in order to achieve more useful information. Further studies are needed to confirm our findings (AU)

Consenso de la Sociedad Española de Anatomía Patológica (SEAP) y de la Sociedad Española de Oncología Médica (SEOM) sobre la determinación de HER2 en el carcinoma gástrico / HER2 evaluation in gastric carcinoma: A consensus study by the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM)

La identificación de los carcinomas gástricos avanzados con alteraciones de HER2 es esencial en la práctica clínica diaria, ya que estas neoplasias requieren un tratamiento específico con trastuzumab. Por estos motivos, patólogos y oncólogos expertos en carcinoma gástrico y en la determinación de HER2, en representación de las sociedades respectivas (SEAP y SEOM), han trabajado para debatir y consensuar las recomendaciones nacionales de determinación de HER2 en los carcinomas gástricos. Estas recomendaciones se basan no sólo en la experiencia de los participantes en el consenso, sino también en la experiencia internacional publicada. En este consenso se muestran los requisitos mínimos que un laboratorio de anatomía patológica debe cumplir para garantizar la adecuada determinación de HER2 en la práctica diaria. Los laboratorios que carezcan de los estándares mínimos expuestos en esta guía deberían trabajar en alcanzarlo(AU)

The identification of HER2 alterations in advanced gastric carcinomas is critically important in daily clinical practice as such neoplasms require specific treatment with Trastuzumab. For this reason, expert pathologists and oncologists have agreed on national guidelines for HER2 testing in gastric carcinomas. The guidelines are based on the experience of the participants and pertinent recent international publications. They outline the minimum requirements for the Pathology Laboratory in order to guarantee satisfactory routine HER2 testing. The guidelines recommend that any laboratory not fulfilling such requirements make the adjustments necessary for compliance(AU)

Estrogen and progesterone receptor testing in breast carcinoma: concordance of results between local and reference laboratories in Brazil / Teste de receptores de estrógeno e progesterona em carcinoma de mama: concordância dos resultados entre laboratórios locais e de referência no Brasil

CONTEXT AND OBJECTIVE: Breast cancer accounts for approximately one quarter of all cancers in females. Estrogen and progesterone receptor testing has become an essential part of the clinical evaluation of breast carcinoma patients, and accurate results are critical in identifying patients who may benefit from hormone therapy. The present study had the aim of investigating the concordance of the results from hormone receptor tests between a reference laboratory and local (or community) laboratories in Brazil. DESIGN AND SETTING: Retrospective study at a reference pathology laboratory. METHODS: The concordance in the results from hormone receptor tests between a reference laboratory and 146 local laboratories in Brazil was compared in relation to 500 invasive breast carcinoma cases, using immunohistochemistry. RESULTS: There was concordance in 89.4 percent (447/500 cases) and 85.0 percent (425/500 cases) of the results from estrogen (κ = 0.744, P < 0.001) and progesterone (κ = 0.688, P < 0.001) receptor tests, respectively, between local and reference laboratories. This was similar to findings in other countries. The false negative rates from estrogen and progesterone receptor tests in local laboratories were 8.7 percent and 14.4 percent, respectively. The false positive rates from estrogen and progesterone receptor tests in local laboratories were 15.5 percent and 16.0 percent, respectively. CONCLUSION: Technical and result interpretation issues may explain most of the discordances in hormone receptor testing in local laboratories. Validation of estrogen and progesterone receptor tests at local laboratories, with rigorous quality control measures, is strongly recommended in order to avoid erroneous treatment of breast cancer patients.

CONTEXTO E OBJETIVO: O carcinoma de mama é responsável por cerca de um quarto de todos os cânceres em mulheres. O teste de receptores de estrógeno e progesterona se tornou parte essencial da avaliação clínica de pacientes com carcinoma de mama; assim, resultados precisos são fundamentais para identificação de pacientes que podem se beneficiar da terapia hormonal. O presente estudo tem por objetivo investigar a concordância nos resultados do teste de receptores hormonais entre um laboratório referência e laboratórios locais (ou comunitários) do Brasil. TIPO DE ESTUDO E LOCAL: Estudo retrospectivo em laboratório referência em patologia no Brasil. MÉTODOS: A concordância nos resultados dos testes de receptores hormonais entre um laboratório referência e 146 diferentes laboratórios locais brasileiros foi comparada em 500 casos de carcinoma invasivo de mama através da imunoistoquímica. RESULTADOS: Houve concordância de 89,4 por cento (447/500 casos) e 85,0 por cento (425/500 casos) nos resultados dos testes de receptores de estrógeno (κ = 0,744, P < 0,001) e progesterona (κ = 0,688, P < 0,001), respectivamente, entre laboratórios locais e referência, similar à descrita em outros países. A taxa de resultados falso-negativos nos testes de receptores de estrógeno e progesterona em laboratórios locais foi de 8,7 por cento e 14,4 por cento, respectivamente. A taxa de resultados falso-positivos nos testes de receptores de estrógeno e progesterona em laboratórios locais foi de 15,5 por cento e 16,0 por cento, respectivamente. CONCLUSÃO: Questões técnicas e de interpretação dos resultados podem explicar a maior parte das discordâncias nos testes de receptores hormonais em laboratórios locais. A validação dos testes de receptores de estrógeno e progesterona pelos laboratórios locais com medidas de controle de qualidade rigorosas é fortemente recomendada de modo a evitar o tratamento errôneo de pacientes com carcinoma de mama.

Breast cancer stem cell hypothesis: clinical relevance (answering breast cancer clinical features)

The cancer stem cells hypothesis arises from observation of normal tissue hierarchy and the demonstration of stem cells in normal tissues. Scientists continue to debate whether the putative cancer cells derive from the transformation of normal tissue stem cells or from more differentiated cells. The existence of a subpopulation of tumour cells with stem-cell-like characteristics, including very slow replication and resistance to standard chemotherapy, posses a novel therapeutic challenge. This review summarises the state of development of normal and cancer breast cells and the clinical and therapeutic relevance (AU)

Carcinoma diferenciado de tiroides (CDT) en niños y adolescentes: Evolución clínica y factores pronósticos / Differentiated thyroid carcinoma in children and adolescents: Clinial outcome and prognostic factors

Si bien la forma de presentación del CDT es más agresiva en la edad pediátrica que en los adultos, la tasa de sobrevida es superior al 90%.Objetivo: analizar retrospectivamente las características clínico-patológicas,la evolución y los factores pronósticos en pacientes prepuberales (PP) y puberales (P) con diagnostico de CDT controlados en nuestro servicio. Resultados se incluyeron 43 pacientes seguidos por un tiempo X (±DS) de 5.99 años(a) (3.57) a, rango 1 -14 a. El tratamiento consistió en tiroidectomía con vaciamiento ganglionar, Iodo131 y levotiroxina en dosis inhibitoria de TSH. Al diagnóstico: edad cronológica (EC) X (±DS)10.9 (3.84) a, rango: 4.7 -17a, relación femenino /masculino 2.9. Diecinueve PP y 24 P. El 53.5% (n:23) presentó nódulos confinados a la glándula con o sin extensión ganglionar y el 46.5% (n:20) tenia un estadío tumoral más avanzado con invasión local y metástasis (MTS) pulmonar. Treinta y ocho pacientes (88.4%) tenían MTS ganglionar cervical y 16(37.2%) MTS pulmonar. El grupo PP comparado con el P tenía EC significativamente menor X (±DS) 7.25 (2.03) a vs 13.83a (p <0.001), estadío tumoral más avanzado 84.2 vs16.8% (p<0.001) y mayor ocurrencia de MTS pulmonar 68.4 vs 12.5% (p<0.003). La sobrevida global fue de 92% y libre de enfermedad 78%.Las variables predictoras de persistencia de enfermedad más significativas fueron presencia de MTS pulmonar al diagnóstico y niveles séricos de tiroglobulina superiores a 8.5 ng/ml posterior al tratamiento inicial. Conclusión: el CDT pediátrico tiene una presentación agresiva especialmente en los pacientes prepuberales. El pediatra debería incorporar el examen clínico del cuello para realizar un diagnóstico y tratamiento precoz (AU)

Children-DTC has been found to behave differently than in adults. At diagnosis, children present in a more aggressive way. However the overall survival rates is greater than 90%. The aim of this study was to perform a retrospective analysis of clinicopathologycal features at diagnosis, evolution and prognostic factors for DTC in pre-pubertal (PP)and pubertal (P)children treated at our centre. Results: 43 CDT patients were included. Mean follow up was X (±DS) 5.99 (3.57) years (y) range: 1 -14 y. Treatment consisted on total thyroidectomy with lymph node dissection, radioiodine therapy, and TSH suppressive therapy with L-thyroxine. At diagnosis: chronological age (CA) was (±DS) :10.9 (3.84) y, range: 4.7 - 17y,sex: female/male ratio: 32/11,nineteen were PP and 24 P. Twentythree ( 53.5%) presented intrathyroidal nodes with or without lymph node MTS, Twenty patients (46.5%) had advanced disease, with adjacent tissue invasion and lung MTS. Thirty-eight patients (88.4%) had cervical lymph node MTS, 16 (37.2%) lung MTS.PP group had significant less CA X (±DS) 7.25 (2.03) y vs 13.83 (1.95)y (p <0.001),advanced tumor stage 84.2 vs16.8% (p<0.001) and more lung MTS occurrence 68.4 vs 12.5% (p<0.003). Global survival rate was 92% and disease free survival rate was 78%.Lung metastases (MTS) and serum thyroglobuline levels greater than 8.5 ng\ml post initial treatment were the most significant prognostic factor related to persistent disease. Conclusion: CDT had a more aggressive presentation in children; especially in PP children. Pediatricians should be aware of this in order to realize a precocious diagnosis and treatment (AU)

Carcinomas cutáneos: historia y clasificación / Cutaneous carcinomas: history and classification

Se efectua una apretada síntesis histórica desde los papiros egipcios hasta la actualidad. Luego se clasifica a los epiteliomas o carcinomas cutáneos en: 1- Carcinomas primitivos cutáneos. 2- Carcinomas intermediarios. 3- Carcinomas espinocelulares. 4- Carcinomas anexiales: sudoríparos, sebáceos, pilosos. 5- Carcinomas anexiales fundamentales. 6- Carcinomas "in situ" (intraepiteliales). Este sistema clasificatorio, basado en la histogénesis, ha demostrado ser de utilidad práctica a través del tiempo. Consideramos que se trata de un valioso trabajo de revisión y actualización producto de 5 décadas de experiencia. Se caracteriza por ser sintético, preciso y con criterio didáctico. Los conceptos están vertidos mediante 150 diapositivas demostrativas que expresan con certeza los caracteres clínicos e histológicos de las neoplasias cutáneas, salvo el melanoma. Uno de los autores (J.A) comienza el estudio en 1953 con su tesis de doctorado: "Epiteliomas cutáneos: ensayo de clasificación citogenética". Es un monumental ensayo ilustrado con numerosas microfotografías en blanco y negro, cuya consulta recomendamos en la Biblioteca de la Facultad de Ciencias Médicas de la UBA.

Clasificación de la OMS 2004 para los tumores vesicales: resumen y comentarios / The 2004 who classification of bladder tumors: a summary and commentary

Los puntos clave de la última clasificación de la OMS para los tumores uroteliales no invasivos son los siguientes: la descripción de las categorías ha aumentado para mejorar su reconocimiento: los tumores con particular buen pronóstico (neoplasia papilar urotelial de bajo potencial maligno) no deben ser etiquetados como 'cáncer'; esto evita el uso de una gradación ambigua tal como grado 1/2 o 2/3 (como se hacía en la clasificación de la OMS de 1973); el grupo de los tumores no invasivos de alto grado es bastante grande pues contiene todos los tumores con propiedades biológicas similares a las de los carcinomas invasivos, e igualmente un alto nivel de inestabilidad genética. Este esquema es el que se propone para sustituir a la clasificación de la OMS de 1973, pero no debe invalidarse definitivamente, y usarse conjuntamente con la nueva clasificación de 2004 hasta que esta última esté lo suficientemente validada

The Key points of the latest World Health Organization (WHO) classification of non-invasive urothelial tumors are the following: the description of the categories has been expanded to improve their recognition: a tumor with particularly good prognosis (papillary urothelial neoplasm of low malignant potential) no longer carries the label of 'cancer'; it avoids the use of ambiguous grading as grade 1/2 o 2/3 (as done in the 1973 WHO classification); the group of non-invasive high-grade carcinoma is large enough to virtually contain all those tumors having biological properties similar to those seen in invasive urothelial carcinoma, and a similarly high level of genetic instability. This scheme is meant to replace the 1973 WHO classification, but the use of both the 1973 and the latest WHO classification is recommended until the latter is sufficiently validated

Valoración de la 5ª edición de la clasificación TNM para el cáncer gástrico en nuestro medio / Appraisal of the fifth edition of the tumor-node-metastasis (TNM) classification for gastric cancer in our environment

Objetivo. Evaluar el número de casos de carcinoma gástrico que pueden ser estadificados con los criterios de la 5.a edición del sistema TNM y analizar qué factores pueden estar relacionados con la obtención de un número suficiente de ganglios. Pacientes y método. En 164 pacientes a los que se resecó un carcinoma gástrico, se estudiaron distintos factores que podían influir en el número de ganglios aislados, como el tamaño tumoral, el tipo de resección gástrica, el grado de diferenciación tumoral, el tipo histológico, la variabilidad entre patólogos que analizaron las piezas y la experiencia del cirujano. Resultados. La media de ganglios linfáticos analizados por los patólogos fue de 11,4 (intervalo de confianza del 95%, 10,12-12,66). Atendiendo a los criterios de la 5.a edición de la clasificación TNM, sólo se pudo clasificar correctamente al 31% de los pacientes. Encontramos una correlación positiva entre el tamaño tumoral y el número de ganglios aislados (p = 0,0018), así como un mayor número de ganglios analizados en las gastrectomías totales respecto de las subtotales (p = 0,034). No se observó una variación significativa en los ganglios analizados en relación con el patólogo que analizó la pieza ni con la experiencia del cirujano que efectuó la resección. Conclusiones. La 5.a edición del sistema TNM es fácilmente reproducible, aunque el número de ganglios necesarios para corroborar la afección ganglionar metastásica es difícil de conseguir en nuestro medio. Nuestros resultados sugieren que es necesario un esfuerzo conjunto por parte de cirujanos y patólogos para aumentar el número de pacientes estadificables con esta edición (AU)

Aim. To estimate the proportion of patients with gastric carcinoma that can be classified using the criteria of the fifth edition of the TNM system and to analyze which factors could be related to the finding of an adequate number of nodes. Patients and method. The influence of distinct factors that could influence the number of lymph nodes isolated was evaluated in 164 patients who underwent resection of gastric carcinoma. These factors included tumor size, surgical resection, grade, histological type, variability among the pathologists who analyzed the surgical specimens, and the surgeon's experience. Results. The mean number of lymph nodes examined by the pathologists was 11.4 (10.12-12.66). Applying the criteria of the fifth edition of the TNM classification, only 31% of the patients could be correctly classified. A positive correlation was found between tumor size and the number of resected nodes (p = 0.0018). In addition, a greater number of lymph nodes were found in total gastrectomies than in subtotal gastrectomies (p = 0.034). No significant association was found with the pathologist who analyzed the surgical specimen or with the experience of the surgeon who performed the resection. Conclusions. The fifth edition of the TNM system is easily reproducible, although the number of lymph nodes required to evaluate metastatic node involvement is difficult to obtain in our environment. Our results suggest that a combined effort between surgeons and pathologists is needed to increase the number of patients that can be reliably staged with this TNM edition (AU)