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.

Ectopic Cushing syndrome in Colombia

ABSTRACT Objective The aim was to describe the clinical features of patients with ectopic Cushing syndrome (ECS) from Colombia and compare these findings with other series to provide the best management for these patients. Materials and methods Records of patients with ECS from 1986 to 2017 were retrospectively reviewed; patients with a diagnosis of adrenal or pituitary Cushing syndrome (CS) were excluded. Results Fourteen patients with ECS were analyzed in this study. The mean age was 54.4 (SD 17.1) years, and the female to male ratio was 1.33:1. Regarding the etiology of ECS, four patients had lung carcinoids (28.6%), three had small-cell lung carcinoma (21.4%), three had pancreatic neuroendocrine tumors (21.4%), one had medullary thyroid cancer (7.1%), one had non-metastatic pheochromocytoma (7.1%), one had metastatic thymoma (7.1%) and one patient had an occult source of ACTH (7.1%). The most common clinical features at presentation were moon-face, muscle weakness, diabetes mellitus and hypertension. Hyperpigmentation was present in 36% of patients, and 12 patients had hypokalemia with a mean value of 2.3 mEq/L (SD 0.71). The median basal cortisol, 24-hour urinary free cortisol (UFC) and ACTH were 30.5 ug/dL (IQR 21-59 ug/dL), 2,600 ug/24 h (IQR 253-6,487 ug/24 h) and 91 pg/mL (IQR 31.9-141.9), respectively. Thirteen patients (92.8%) had the site of the primary lesion identified. Six patients had undergone a surgical intervention to address the primary tumor. Resection was curative in 28.5% of patients. Death occurred in 57.1% of patients, and the median overall survival was 27 months. Intrathoracic tumors had the most aggressive behavior. Conclusions ECS is a rare disease; however, it is associated with high morbidity and mortality. A rapid intervention supported by an interdisciplinary group is required to improve overall survival and quality of life

Tumor neuroendocrino Tipo 1: reporte de un caso y revisión de la literatura / Localized neuroendocrine tumor of the stomach: a case report and literature review

Resumen Introducción: Los tumores neuroendocrinos (TNE), son tumores compuestos por células productoras de péptidos y aminas. Los TNE gástricos, representan el 1% de todas las neoplasias, sin embargo su incidencia ha ido en aumento. Son generalmente asintomáticos y no funcionantes. El tratamiento es generalmente la resección local. Caso Clínico: paciente de 48 años con sospecha de cáncer gástrico; su estudio demuestra un TNE gástrico bien diferenciado tipo 1. Se realiza etapificación y se define en comité oncológico la vigilancia endoscópica. El hallazgo de un TNE, en el estudio de cáncer gástrico, es un hallazgo poco frecuente. Debido al aumento progresivo en la realización de endoscopías digestivas altas, secundario a la alta prevalencia de cáncer gástrico en nuestro país, se espera que aumenten hallazgos como un TNE. Es por esto que realizamos una revisión de la literatura y planteamos algunas conclusiones al respecto.

Introduction: Neuroendocrine tumors (NETs) are composed of cells that produce peptides and amines. Gastric NETs represent 1% of all neoplasms; however their incidence has been increasing. They are usually asymptomatic and non-functioning. The treatment is usually local resection. Case Report: We present the case of a 48-year-old patient who was suspected of gastric cancer; her study shows a well-differentiated type 1 gastric NET. Staging is performed and endoscopic surveillance is defined in the oncology board. The finding of a NET, in the study of gastric cancer, is a rare finding. Due to the progressive increase in the performance of upper gastrointestinal endoscopies, secondary to the high prevalence of gastric cancer in our country, it is expected to increase findings as a NET. That is why we conducted a review of the literature and made some conclusions about it.

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.

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.

Radiolabeled somatostatin analogs for radionuclide imaging and therapy in patients with gastroenteropancreatic neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine tumours (GEP-NETs) are a rare type of cancer that can arise from the diffused endocrine system, located in the gastrointestinal (GI) tract (carcinoids) and in the pancreas (insular tumors). Approximately 2% of all malignant tumours of the gastrointestinal system are GEP-NETs which can express somatostatin receptors. 111In-pentetreotide (octreoscan) and 68Ga-DOTA NOC (68Ga-labelled [1,4,7,10- tetraazacyclododecane-1,4,7,10-tetraacetic acid]-1-Nal3-Octreotide) are the commonly used radiopharmaceuticals for imaging. Once localized using 68Ga DOTA NOC or octreoscan, these tumours can be successfully targeted with radiolabelled somatostatin analogues. This review focuses on common nuclear medicine procedures used in both imaging and treatment of these tumors.

Acute perforated appendicitis: An analysis of risk factors to guide surgical decision making.

Introduction: Acute perforated appendicitis is associated with increased post-operative morbidity and mortality. Avoiding delays in surgery in these patients may play a role in reducing observed morbidity. Objective: To analyze the clinico-pathological profile and outcomes in a cohort of patients undergoing emergency appendicectomies for suspected acute appendicitis and to determine factors influencing the risk of perforated appendicitis in order to aid better identification of such patients and develop protocols for improved management of this subset of patients. Materials and Methods: A retrospective analysis of patients undergoing emergency appendicectomies following presentation with acute appendicitis to the Modbury hospital, South Australia from March 2007 to April 2011 was conducted. Statistical analyses were performed in SAS 9.2. Results and Discussion: 506 patients underwent emergency appendectomy for acute appendicitis which included equal number of male and female patients with a median age of 25 years. Perforated appendicitis was found in 102 (20%) patients. Post-operative morbidity was significantly higher in patients with perforated appendicitis (28.4% vs 4.7%; P<0.0001). Male sex, patients older than 60 years, along with raised neutrophil counts and C-reactive protein levels were found to be significantly associated with the risk of perforation (P<0.05). Conclusions: Acute perforated appendicitis is associated with high morbidity. The increased risk of perforation in males and elderly patients appears unrelated to delays in presentation, diagnosis, or surgery. Patients with clinically diagnosed acute appendicitis and an elevation in neutrophil count and CRP level must be considered candidates for early surgery as they are likely to have an appendicular perforation.

Role of (68)Ga-DOTATOC PET/CT in the Evaluation of Primary Pulmonary Carcinoids

BACKGROUND/AIMS: Although carcinoid tumors usually have good prognosis, early and specific diagnosis is important. Computed tomography and magnetic resonance imaging do not provide findings that are specific for carcinoids, and somatostatin receptor scintigraphy suffers from low spatial resolution. 18-Fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) has limited sensitivity for carcinoids due to low uptake of the marker. A PET/CT system that uses the somatostatin receptor-based PET tracer 1,4,7,10-tetraazacyclododecane-N(I),N(II),N(III),N(IIII)-tetraacetic acid (D)-Phe(1)-thy(3)-octreotide ((68)Ga-DOTATOC) has also been used in the evaluation of carcinoids, although information regarding its use for the detection of primary pulmonary carcinoids is limited. Thus, we investigated the value of (68)Ga-DOTATOC PET/CT for the diagnosis of primary pulmonary carcinoid tumors. METHODS: This was a retrospective analysis of patients with primary pulmonary tumors who underwent (68)Ga-DOTATOC PET/CT. All the patients had a histopathologic diagnosis of carcinoid. The rate of detection of primary pulmonary carcinoid tumors using (68)Ga-DOTATOC PET/CT was assessed. RESULTS: Twenty patients were diagnosed as having carcinoid, and 19 tumors showed significant uptake on (68)Ga-DOTATOC (detection rate, 95%). The maximal standardized uptake value (SUV(max)) ranged from 1.1 to 66, with a median value of 21.6. In one patient, (68)Ga-DOTATOC PET/CT revealed additional lesions. CONCLUSIONS: Our results demonstrate that (68)Ga-DOTATOC PET/CT is useful in the evaluation of primary pulmonary carcinoids and should be included in the diagnostic work-up of these patients.

Goblet cell carcinoid of the appendix: a clinicopathological analysis of 3 cases / 肿瘤研究与临床

Objective To investigate the histogenesis,clinicopathological features and biological behavior of goblet cell carcinoid (GCC) of the appendix. Methods 3 cases of GCC of the appendix were studied by light microscopy and immunohistochemistry. Results 3 cases all occured in men. Microscopically: the tumor was composed of goblet cells containing mucin-filled with basal round to crescentic nuclei without atypia.These tumor cells were arranged in single forms,nests or acinus with no central lumen. 1 case was composed of simple goblet cells and typical carcinoid cells were seen in other 2 cases arranged in trabeculae and tubule.There was transition between goblet cells with tubelar and crypt epithelium.Immunohistochemical staining revealed that goblet cells were positively reacted with CgA, Syn, CEA, CK and p53 in 1 case. Conclusions Goblet cell carcinoid of the appendix arise from a pluripotent cell with divergent neuroendocrine and mucinous differentiation .It is a subtype of carcinoids of the appendix.The diagnosis mainly bases on its morphologic changes and immunohistochemical findings. The unpredictable behavior of this tumor is probably related to its component and the degree of infiltration.

Tumor carcinoide del ileon: descripción de caso y revisión bibliográfica / Ileal Carcinoid tumor: case report and bibliographical review

Los carcinoides gastrointestinales son tumores neuroendócrinos. Cerca del 75% se localizan en tracto digestivo y son capaces de producir varios péptidos. Su curso clínico es a menudo indoloro, pero pueden ser agresivos y resistentes a la terapia. La incidencia de estos tumores es aproximadamente de 2,5 por 100000 personas al año. La clasificación antigua de carcinoides del intestino anterior, medio y posterior, aún se sigue usando.La determinación de la histopatología de este tumor es de importancia y comprende el uso de inmunohistoquímica para cromogranina A, sinaptofisina, serotonina y gastrina. Los procedimientos para su localización incluyen la TAC, ultrasonido, resonancia magnética, cintigrafía del receptor de somatostatina y tomografía de emisión de positrones. La cirugía se mantiene como el procedimiento ideal con capacidad curativa. Procedimientos citorreductivos incluyen la ablación por radiofrecuencia, tratamiento por láser y quimioembolización. Nuevas terapias, como los análogos de somatostatina de larga duración, junto con tratamientos dirigidos al tumor, se usarán en un futuro cercano.Describimos un caso de obstrucción intestinal asociada con tumor carcinoide del íleon en paciente de 78 años, que presentó dolor abdominal, vómito y una masa tumoral en cuadrante inferior derecho.

Gastrointestinal (GI) carcinoids are neuroendocrine tumors. About 75% of such tumors are located within the gastrointestinal tract and are capable of producing various peptides. Their clinical course is often indolent but can also be aggressive and resistant to therapy. The incidence of these tumors is approximately 2.5 in 100,000 people per year. The former classification system of foregut, midgut and hindgut tumors is still used.Determination of the histopathology of these tumors is of great importance and involves specific immunohistochemical staining for chromogranin A, synaptophysin, serotonine and gastrine. Localization procedures include computerized tomography, ultrasound, magnetic resonance imaging, somatostatin receptor scintigraphy and positron emission tomography scan.Surgery remains the cornerstone of treatment and provides the only chance of a cure. Other cytoreductive procedures include radiofrequency ablation, laser treatment and chemoembolization. New therapies, such as long-acting somatostatine analogs, together with further development of tumor-targeted treatments, will come into clinical use in the near future.We describe a case of small bowel obstruction associated with an ileal carcinoid tumor in a 78 year old man who presented with abdominal pain, vomiting, and a mass in right lower quadrant.

Surgically Removed Malignant Duodenal Carcinoids

Carcinoid tumors are slow growing neoplasms that arise from enterochromaffin cells, with malignant potential, and those of the duodenum are rare neoplasms, with an incidence of 2.0~8.9% of all gastrointestinal carcinoid tumors. Duodenal carcinoid tumors rarely manifest gastrointestinal symptoms and carcinoid syndrome. A healthy 43 year old woman was admitted due to an incidentally detected duodenal mass during regular health screening. An abdominal CT scan and UGI series showed a polypoid mass at the second portion of the duodenum without bowel dilatation. The duodenoscopic finding was a carcinoid tumor, which was proven by immunohistochemical staining. A pylorus- preserving pancreatoduodenectomy was performed and a 2.5x2.2 cm sized submucosal tumor found at the second portion of the duodenum, with two periduodenal lymph node enlargements. Immunohistochemical staining showed that the tumor cells to have positive reaction for NSE, chromogranin and synaptophysin. Herein, our experience of a malignant duodenal carcinoid tumor is reported.

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.