Appendiceal Neuroendocrine Tumours - Experience of One Service / Tumores neuroendócrinos do apêndice - Experiência de um serviço

Abstract Tumours of the appendix are rare and tend to be diagnosed incidentally, in cases of acute appendicitis. For some authors, appendiceal neuroendocrine tumours (ANETs) are the most frequent neoplasm of the appendix, observed in 0.3% to 0.9% of cases acute appendicitis. The present is a unicentric retrospective study conducted between January 2005 and March 2017. Out of a total of 3,007 surgeries for appendiceal pathologies performed in the adult population at the hospital where the present study was conducted, there were 70 (2.33%) malignant cases, 20 (28.6%) of which were ANETs. The patients had a median age of 44 years (range: 18 to 85 years), and were predominantly women (there were 1.9 times more women than men). In 16 cases (80%), a simple appendicectomy was performed (1 patient was submitted to a right hemicolectomy later). The cases of ANETs had a good prognosis in our series: 85% of the patients are either alive today or were alive after 5 years of follow-up. Despite the fact that ANETs are described as the most frequent tumor of the appendix, this was not confirmed in our series, in which they only represented 28.6% of the cases; adenocarcinoma was the most frequent tumor (65.7%) among our sample.

Resumo Tumores do apêndice são raros, e tendem a ser diagnosticados de forma incidental, em casos de apendicite aguda. Para alguns autores, tumores neuroendócrinos do apêndice (TNEAs) são as neoplasias mais frequentes do apêndice, e são observados em 0,3 a 0,9% de todos os casos agudos de apendicite. Este é um estudo monocêntrico e retrospectivo realizado entre janeiro de 2005 e março de 2017. Entre umtotal de 3.007 cirurgias para patologias do apêndice realizadas na população adulta no hospital em que o estudo foi conduzido, houve 70 (2,33%) casos de malignidade, 20 (28,6%) dos quais eram TNEAs. Os pacientes tinham uma idade média de 44 anos (gama: 18-85 anos), e eram predominantemente mulheres (havia 1,9 vezes mais mulheres do que homens). Em 16 casos (80%), realizou-se uma simples apendicectomia (1 paciente foi submetido a uma hemicolectomia direita mais tarde). Os casos de TNEAs tiveram um bom prognóstico em nossa série: 85% dos pacientes estão vivos hoje, ou estavam após um seguimento de 5 anos. Apesar de os TNEAs serem descritos como os tumores mais frequentes do apêndice, isso não foi confirmado nesta série, na qual eles representaram apenas 28,6% dos casos; adenocarcinoma foi o tumor mais frequente (65,7%) emnossa amostra.

Appendiceal neuroendocrine tumors: approach and treatment / Tumores neuroendócrinos do apêndice: abordagem e tratamento

ABSTRACT The incidence of tumors in the appendix has increased over the years, and they are mainly found in the anatomical and pathological examination of appendices operated due to acute appendicitis. The annual incidence of neuroendocrine tumors of the appendix, also called carcinoid tumors, is 0.15-0.16 per 100,000 people. In absolute terms, the incidence of these tumors has increased in the last decade by 70-133%. Appendiceal carcinoid tumors occur more often in women, and are found in 0.3-0.9% of the appendices removed in appendectomies. They appear in the subepithelial neuroendocrine cells and have an indolent course, with the symptoms being indistinguishable from an acute appendicitis. There are two classifications, one presented by the European Neuroendocrine Tumor Society and the other by the American Joint Committee on Cancer. Both classifications use tumor size as a predictor of tumor burden. The classification used by European Neuroendocrine Tumor Society also uses the invasion of the mesoappendix to select the best surgical treatment. However, these classifications require the inclusion of more criteria to define the selection of surgical treatment of tumors between 1 and 2 cm. Thus, along with the size of the tumor and the invasion of the mesoappendix, other factors such as vascular invasion, ki67 index, mitotic index and tumor location should be considered at the time of classification, for a better selection of the treatment and prognostic evaluation.

RESUMO A incidência de tumores no apêndice tem aumentado ao longo dos anos, principalmente encontrados no exame anatomopatológico dos apêndices operados por apendicite aguda. A incidência anual de tumores neuroendócrinos do apêndice, também designados por tumores carcinoides é de 0,15 a 0,16 por 100.000 pessoas. Em termos absolutos, a incidência destes tumores tem aumentado na última década em 70% a 133%. Os tumores carcinoides do apêndice ocorrem mais em mulheres e são encontrados em 0,3%‒0,9% dos apêndices removidos em apendicectomias. Têm origem nas células neuroendócrinas subepiteliais e apresentam um curso indolente, sendo os sintomas indistinguíveis de uma apendicite aguda. Existem duas classificações, a apresentada pela ENETS (European Neuroendocrin Tumor Society) e da AJCC (American Joint Committee on Cancer). Ambas as classificações utilizam o tamanho do tumor como preditor de carga tumoral. A classificação utilizada pela ENETS recorre ainda à invasão do mesoapêndice para selecionar o melhor tratamento cirúrgico. Contudo, estas classificações necessitam incluir mais critérios para definir a escolha do tratamento cirúrgico de tumores entre 1‒2 cm. Assim, para além do tamanho do tumor e da invasão do mesoapêndice, outros fatores como a invasão vascular, o ki67, o índice mitótico e a localização do tumor devem ser considerados no momento da classificação, para uma melhor seleção do tratamento e avaliação prognóstica.

Tumores neuroendocrinos primarios de colon y recto / Primary neuroendocrine tumors of the colon and rectum

Resumen Introducción La clasificación y el manejo de los tumores neuroendocrinos (TNEs) han cambiado drásticamente en la última década. Se realiza un análisis crítico del manejo de los TENs colorrectales primarios intervenidos en nuestro centro a la luz de la nueva clasificación. Material y Método Análisis retrospectivo de los resultados del tratamiento quirúrgico radical de este tipo de lesiones en un período de 15 años. Resultados Se trata de 10 pacientes, con un promedio de 56 años (extremos 48-76), 6 ubicados cercanos a la válvula ileocecal (VIC) que se presentaron con un cuadro de obstrucción intestinal incompleto y tres en el recto (2 pólipos) y un pólipo en colon sigmoides. La cirugía efectuada incluye cuatro resecciones anteriores y seis colectomías derechas (con resección de una metástasis hepática en 1 caso). La mediana de seguimiento fue de 78,3 meses (extremos 8-180), durante el cual dos pacientes fallecen por metástasis a distancia. Conclusión Los TNEs ubicados en el colon habitualmente se presentaron como grandes masas tumorales cercanos a la VIC, lo que proporcionalmente no ocurre con las lesiones del rectosigmoides que son diagnosticados más precozmente como pólipos o lesiones submucosas. Algunos tumores de bajo grado muestran un compromiso avanzado en la pared y/o los linfonodos regionales lo que justifica la resección radical y/o la quimioterapia adyuvante. A la luz de esta experiencia, es necesario complementar el grado del tumor OMS 2010 (Ki-67 y número de mitosis) con el estadio TNM para caracterizar adecuadamente los TNEs, lo que influye en el manejo multidisciplinario.

Background The nomenclature and staging classification of neuroendocrine tumors (NETs) has changed drastically in the past decade. Objective To do a critical analysis of management of colorectal NETs in our institution in the light of the new classification. Methods We retrospectively reviewed the records of consecutive patients operated on with radical intention due to a colorectal NET in the last 15 years. Results There were 10 patients, median age was 56 years (range 48-76), six of them located near the ileocecal valve, three in the rectum (2 of them polyps) and one polyp in the sigmoid colon. Surgical procedure included four anterior resections and six right colectomy (one with hepatic resection). The median follow up was 78.3 months (range 8-180). Two patients died due to metastatic disease. Conclusion NETs located near de ileocecal valve were diagnosed usually as a big tumor with obstructing symptoms, while NETs of the rectum and sigmoid colon more frequently were detected as polyps or submucosal lesions. Some low grade TENs may invade the colonic wall and/or have metastasis in the regional lymph nodes and those cases need radical resection and/or adjuvant therapy. Combine the grade (Ki-67 and number and/or number of mitosis) of 2010 WHO classification with TNM showed prognostic value for classification and staging colorectal NETs with important therapeutic implications.

Síndrome de Cushing ectópico: revisión de la literatura / Ectopic Cushing Syndrome: A literature review

El síndrome de Cushing es una enfermedad muy rara pero asociada a una morbimortalidad significativa. Se clasifica como dependiente de la hormona adrenocorticotrópica (ACTH: tumores hipofisiarios y ectópicos) o independiente de ACTH (lesiones de origen adrenal). En la mayoría de los casos, las lesiones responsables del síndrome corresponden a tumores hipofisiarios, seguida de lesiones adrenales y por último de tumores ectópicos (5-15% de todos los casos). En este artículo se hará una revisión de los aspectos epidemiológicos, clínicos, diagnósticos y terapéuticos más importantes de los tumores ectópicos causantes del síndrome de Cushing.

Cushing's syndrome is a very rare disease associated with significant morbidity and mortality. It is classified as adrenocorticotropic hormone (ACTH) dependent (Pituitary and ectopic tumors) or ACTH independent (lesions of adrenal origin). In most cases, pituitary tumors are responsible for the Cushing's syndrome, followed by adrenal lesions and finally by ectopic tumors (5-15% of all cases). This article describes the most important epidemiological, clinical, diagnostic and therapeutic aspects of ectopic tumors causing Cushing's syndrome.

Tumores carcinoides pulmonares tratados quirúrgicamente valor pronóstico de la 7ª estadificación TNM

Con el objetivo de evaluar el valor pronóstico de la 7a estadificación TNM se analizaron 43 mujeres (61%) y 28 hombres (39%) con diagnóstico de tumor carcinoide tratados quirúrgicamente desde enero/1975 hasta diciembre/2011. Mediana de edad: 38 años (13-67). Presentaron carcinoide típico (CT) 63 (89%) pacientes y 8 (11%) carcinoide atípico (CA). Mediana de seguimiento: 4 años (1 - 24 años). Los estadios correspondientes a CT fueron: IA = 33 (52%), IB = 10 (16%), IIA = 2 (3%), IIB = 2 (3%), IIIA = 12 (19%) y IIIB = 2 (3%); para los CA fueron: IA = 1 (12.5%), IIB = 1 (12.5%), IIIA = 2 (25%) y IIIB = 4 (50%). No hubo diferencia estadísticamente significativa en la supervivencia global a cinco años en el análisis estratificando por estadios (p = 0.689), ni analizando separadamente cada tipo histológico (CT p = 0.547; CA p = 0.592). El intervalo libre de enfermedad fue significativamente menor (CT: 3 años vs CA: 2 años, p = 0.000) y las recaídas más frecuentes en el grupo de carcinoides atípicos (CA: 50% vs CT: 2%, p = 0.000). Los pacientes con CT presentaron buena evolución aun en estadios avanzados, mientras que los que tuvieron CA presentaron menor tiempo de supervivencia e intervalo libre de enfermedad, y mayor frecuencia de recurrencia. El subtipo histológico resultó un factor significativo de pronóstico, mientras que la 7ª estadificación TNM no contribuyó en predecir la supervivencia en los tumores carcinoides.

We analyzed 43 women (61%) and 28 men (39%) surgically treated for carcinoid tumors from Jan/1975 to Dec/2011. Median age: 38 years (13-67). Typical carcinoid (TC) appeared in 63 (89%) patients, 8 (11%) suffered from atypical carcinoid (AC). Median follow-up: 4 years (1-24). TC stages were: IA = 33 (52%), IB = 10 (16%), IIA = 2 (3%), IIB = 2 (3%), IIIA = 12 (19%) and IIIB = 2 (3%); AC stages were: IA = 1 (12.5%), IIB = 1 (12.5%), IIIA = 2 (25%) and IIIB = 4 (50%). TNM classification did not show significant differences on 5-years survival period by stage (p = 0.689), even according to histological type (TC: p = 0.547; AC: p = 0.592). The disease-free survival rate was significantly lower (TC: 3 years vs. AC: 2 years, p = 0.000) and relapses were more frequent in AC (AC: 50% vs. TC: 2%, p = 0.000). The 7th TNM staging was not influential in estimating survival from carcinoid tumours in our population. The histological subtype was a better prognostic factor.

Caso inusual de síndrome de cushing

Objetivo: discutir las dificultades en el diagnóstico y manejo terapéutico de un caso poco frecuente de Síndrome de Cushing (SC). Caso Clínico: se reporta el caso de un paciente femenino, de 24 años, con hipercortisolismo y patrón bioquímico sugestivo de SC dependiente de corticotropina (ACTH). Estudios imagenológicos mostraron agrandamiento de la glándula hipófisis, extensión supraselar y una lesión lateral izquierda, sugestiva de microadenoma. Sometida a cirugía transesfenoidal en dos oportunidades, sin obtenerse la remisión del cuadro. Tomografía computarizada (TC) de tórax demostró la presencia de nódulo pulmonar único izquierdo, hipercaptante en el gammagrama con octreotido. Fue removido quirúrgicamente en forma satisfactoria produciéndose un abrupto descenso en los niveles de ACTH y cortisol pero nuevamente se incrementaron 24 horas después, permaneciendo elevados desde entonces. La inmunohistoquímica fue positiva para ACTH y cromogranina; el estudio anatomapatológico reportó tumor carcinoide típico sin invasión a ganglios linfáticos; sin embargo, la evolución clínica sugirió enfermedad residual. Se inició tratamiento con análogos de somatostatina (octreotido), el cual se ha mantenido por once meses, obteniéndose mejoría significativa del cuadro clínico y control parcial del hipercortisolismo. TC de tórax y gammagrama con octreotido recientemente practicados, revelaron pequeño foco, el cual correspondió a adenopatía mediastinal derecha. Se plantea la hipótesis de que el tumor producía simultáneamente ACTH y hormona liberadora de corticotropina (CRH, por sus siglas en inglés), explicándose de esta manera la hiperplasia hipofisaria. Conclusión: En pacientes con SC dependiente de ACTH hay que tener presente la existencia de incidentalomas que pueden confundir el diagnóstico. Considerar que la hiperplasia hipofisaria puede ser secundaria a una fuente ectópica productora de CRH y aunque en este caso no pudo realizarse inmunohistoquímica para CRH en las células tumorales, es posible suponer que dichas células secretaban conjuntamente CRH y ACTH lo cual explica la hiperplasia hipofisaria.

Objective: to discuss the diagnostic and therapeutic difficulties of a rare case of Cushing´s syndrome. Case Report: we describe a case of a 24-year-old female patient who developed symptoms compatible with hypercortisolism; the biochemical pattern was suggestive of ACTH dependent Cushin´s Syndrome. Imaging studies showed pituitary enlargement with suprasellar extension and a lesion suggestive microadenoma on the left side. Transsphenoidal surgery was performed in two occasions without remission. Subsequent explorations showed the presence of a single left lung nodule, positive to octreoscan. It was successfully operated and, a sharp decline on ACTH and cortisol levels was seen immediately after operation, increasing again 24 hours later and, remained elevated since then. Inmunohistochemestry studies were positive for ACTH and chromogranin and although the pathology was compatible with typical carcinoid, and no lymph node invasion was seen, the clinical evolution suggested the presence of residual disease. Treatment with somatostatin analogues (Octreotide) was started and has being maintained for eleven months, up to the present. A significant improvement of the clinical picture and partial control of the hypercortisolism has being obtained. Chest CT and octreoscan recently performed, revealed small focus, which corresponded to a right mediastinal adenopathy. We hypothesize that the tumor was simulta-neously producing ACTH and CRH, explaining in this way the pituitary hyperplasia. Conclusion: In patients with ACTH dependent Cushing the existence of incidentalomas could confuse the diagnosis and should be ruled out. Pituitary hyperplasia might be secondary to an ectopic CRH source. Although in our case immunohistochemostry for CRH was not performed, we assume that tumor cells secreted both, CRH and ACTH, explaining the pituitary hyperplasia.

Quantificação do ácido 5-hidroxi-indolacético urinário por técnica caseira do nitrosonaftol comparada com ensaio de nitrosonaftol em microcoluna de cromatografia e imunoensaio enzimático / Quantification of urinary 5-hydroxyindoleacetic acid by in-house nitrosonaphthol reaction compared with nitrosonaphthol micro column chromatography and enzyme-linked immunosorbent assay

The aim of this study was to compare the colorimetric "kit" and enzyme-linked immunosorbent assay (ELISA) methods to quantify urinary 5-hydroxyindoleacetic acid through the Goldenberg's technique, exploring the potential of replacing it. 24-hour urine samples were tested by Goldenberg's assay and compared with kits. The agreement was almost perfect for the comparison of Goldenberg's assay with both colorimetric kit, and with ELISA kit, considering ≤ 7.5 mg/24h normal cutoff value. Therefore, both "kits" would be good alternatives to Goldenberg's technique due to practicality and agreement between values...

O objetivo deste estudo foi comparar métodos por kit colorimétrico e por ensaio imunossorvente ligado à enzima (ELISA) para quantificar o ácido 5-hidroxi-indolacético urinário com a técnica de Goldenberg, explorando o potencial de substituí-la. Amostras de urina de 24 horas foram testadas pela técnica de Goldenberg e com os kits. A concordância foi quase perfeita, tanto para a comparação do ensaio de Goldenberg com o kit colorimétrico quanto para com o kit ELISA, considerando normal o valor de corte de ≤ 7.5 mg/24h. Portanto, ambos os kits seriam boa alternativa para a técnica de Goldenberg devido à praticidade e à concordância entre os valores...

Tumores carcinoides gastrointestinales, experiencia en Médica Sur: Gastrointestinal carcinoid tumors, experience in ''Médica Sur''

Objetivo: Evaluación de los casos de tumores carcinoides gastrointestinales en el Hospital y Fundación Clínica Médica Sur y confrontarlos con la literatura. Sede: Hospital y Fundación Clínica Médica Sur (centro de atención de tercer nivel). Diseño: Estudio retrospectivo, transversal, descriptivo, observacional. Análisis estadístico: Porcentaje como medida de resumen para variables cualitativas. Material y métodos: Se revisaron 19 casos de muestras de patología del Hospital y Fundación Clínica Médica Sur. Resultados: En este trabajo presentamos 19 casos de pacientes diagnosticados con tumores carcinoides gastrointestinales encontrados en toma de biopsias por endoscopia o piezas postquirúrgicas. Histológicamente se observaron células tumorales similares, con escaso citoplasma granular eosinófilo o núcleo redondeado moteado. Las variaciones de tamaño nuclear y celular fueron mínimas y las mitosis raras. El crecimiento celular fue predominantemente submucoso con extensión a capa muscular y serosa en algunos casos. Doce correspondieron al sexo femenino y siete, al masculino. El promedio de edad fue de 47 años. El órgano con más frecuencia de aparición fue el estómago y el apéndice cecal y los de menor frecuencia fueron el duodeno y el hígado. Conclusión: El sexo femenino predominó, constituyendo el 63% de los casos, la edad media para las mujeres fue de 49 años, coincidiendo con lo revisado en la literatura. Se encontró una incidencia aumentada en tumores de estómago y apéndice.

Objective: To evaluate the cases of gastrointestinal carcinoid tumors in the Hospital y Fundación Clínica Médica Sur, and to compare them with reports in the literature. Setting: Hospital y Fundación Clínica Médica Sur (third level health care center). Design: Retrospective, cross-sectional, descriptive, observational study. Statistical analysis: Percentage as summary measure for qualitative variables. Material and methods: We reviewed 19 cases of pathology samples from the Hospital y Fundación Clínica Médica Sur. Results: In this report we present 19 cases of patients diagnosed with gastrointestinal carcinoid tumors found in endoscopically taken biopsy samples or in postsurgical pieces. Histologically, similar tumor cells were observed with scarce granular eosinophilic cytoplasm or rounded spotted nucleus. Variations in nuclear and cellular size were minimal and mitoses were rare. Cell growth was predominantly submucous extending to the muscular and serosa layer in some cases. Twelve corresponded to women and seven to men. Average age was of 47 years. The organs most frequently affected were the stomach and the cecal appendix, the least frequent ones were the duodenum and the liver. Conclusion: Women predominated, constituting 63% of cases, mean age of women was of 49 years, coinciding with the literature. We found an increased incidence of tumors in the stomach and appendix.

Apudomas pancreáticos: um desafio para clínicos e cirurgiões / Pancreatic apudomas: a challenge for surgeons and physicians

OBJETIVO: O propósito do presente estudo é analisar as dificuldades quanto ao diagnóstico, avaliação prognóstica e conduta em sete pacientes portadores de tumores neuroendócrinos do pâncreas (apudomas), estudados na última década, comparando os resultados com aqueles discutidos na literatura. MÉTODO: A idade dos pacientes variou de 15 a 66 anos, com média de 38,4 anos. Todos foram submetidos a alguma forma de ressecção pancreática por tumores neuroendócrinos. Os exames histológicos foram feitos pelas técnicas tradicionais e por imuno-histoquímica. RESULTADOS: Três pacientes tiveram um diagnóstico inespecífico de tumor neuroendócrino; dois de vipoma e dois de gastrinoma. As síndromes não se manifestaram claramente, ainda que cada caso tenha tido um rótulo diagnóstico. Os exames por imuno-histoquímica demonstraram a presença de múltiplos hormônios, mas por falta de sintomas clínicos, as correlações ficaram prejudicadas na maioria dos casos, havendo correlação somente em caso de gastrinoma. Um paciente faleceu no pós-operatório; um sobreviveu sete anos e cinco estão vivos, com sobrevida variando entre três e cinco anos. CONCLUSÕES: Não houve uma manifestação sindrômica evidente, porém a sobrevida dos pacientes tem sido compatível com os dados de literatura.

BACKGROUND: The purpose of the present study is to analyze the difficulties concerning diagnostic, prognostic and clinical conduct of seven patients with pancreatic neuroendocrine tumors (APUDomas), evaluated over the past decade. METHODS: Patients varied in age from 15 to 66 years old, with a mean age of 38.4 years. All patients underwent some type of pancreatic resection as treatment of the neuroendocrine tumor. The histological sections were submitted to traditional and imunohistochemical examination. RESULTS: Three patients were diagnosed with unspecific neuroendocrine tumor, two with VIPoma and two with Gastrinoma. Syndromes were not clearly manifested, although every case had a differential diagnosis. Imunohistochemistry showed the presence of multiple hormones, but due to the lack of clinical symptoms, correlation was harmed in most cases, however one Gastrinoma showed typical clinical symptoms. One patient died in the post-operative period, one survived for 7 years and five are still alive, with a life expectancy varying from 3 to 5 years. CONCLUSIONS: We observed a lack of typical clinical syndromes for most cases, but life expectancy was compatible with the one described in the literature.