Trends in gastroenteropancreatic neuroendocrine tumors

Carcinoids were first reported approximately 100 years ago and proposed to be neuroendocrine tumors of hormonal origin some 50 years later. The first edition of the WHO classification included neuroendocrine tumors of the digestive organs and pancreas, but thereafter it was pointed that neuroendocrine cells are distributed throughout the body and thus that carcinoids occur in various other organs. The most recent edition of the WHO classification takes into account the occurrence of neuroendocrine tumors throughout the body. In addition, carcinoids were originally thought to be variants of a benign tumor type with a low malignancy rate, but thereafter metastases were observed. The term "neuroendocrine tumors" is now preferred instead of "carcinoids," and the malignant potential of such tumors is recognized. This paper reviews the classification and treatment of gastroenteropancreatic neuroendocrine tumors.     

Neuroendocrine tumors of the pancreas

Neuroendocrine tumours are rare and often include insulinoma, gastrinoma and other low frequency tumours that secrete gastrointestinal hormones. Their preoperative localization, despite continuous medical advances, is extremely difficult but helpful in guiding the surgeon towards a proper form of treatment. After presenting their cases, the authors conclude that the treatment of choice for these tumours is surgery due to their anatomopathological features (benign, scarcely malign or invasive, slow growth). On the other hand, medical therapy plays an important role in either preparing the surgical intervention or alleviating symptoms when the patient is inoperable.     

Neuroendocrine tumors of the thymus

Neuroendocrine tumors of the thymus (NETTs) are unusual thymic neoplasms that were misdiagnosed as thymomas until the 1970s, when they eventually acquired a distinct identity. No collective large series have been published so far, and information about clinical presentation, diagnosis, histology, and treatment is derived from analysis of the case series and case reports published over a long period. NETTs are more aggressive than their pulmonary and abdominal counterparts, presenting at a more advanced stage, often with distant metastases, and are associated with poor long-term survival. Most patients are symptomatic at presentation as a result of the local invasion. Twenty percent to 30% of the cases are associated with endocrine disorders, mostly Cushing syndrome and multiple endocrine neoplasia syndrome. There is no official staging system for these tumors and investigators rely on the Masaoka staging system used for thymomas. Histologically, 2 classification are used: the World Health Organization and the Armed Forces Institute of Pathology classifications. Histologically, most tumors show moderately to poorly differentiated histologic features, reflecting their aggressive clinical behavior. Surgery is the most effective treatment option, although the aggressiveness of the tumor often requires extensive resection. Chemotherapy and radiotherapy may be used either preoperatively or postoperatively, although the small number of patients does not allow the design of standard guidelines about optimal schedules and doses. Survival depends on stage at presentation, histologic degree of differentiation, associated endocrine syndromes, and resectability rate. Recurrences are frequent after surgery and may be locoregional or distant. Surgery is recommended when feasible in the treatment of locoregional recurrences.     

Neuroendocrine tumors of the pancreas

Background: The benefits of associating magnetic resonance imaging (MRI) and laparoscopy for localizing and treating neuroendocrine pancreatic tumors (NEPTs) have been poorly documented. Methods: In a retrospective study, eight patients with a mean age of 48 years were operated on for a NEPT. MRI was used to localize the lesions. In all patients a laparoscopic resection was carried out. Laparoscopic ultrasonography (LUS) was used during most operations. Results: The tumor was clearly localized by MRI in seven patients, and LUS showed the lesion in another patient whose preoperative MRI had been unsuitable. Three enucleations, three spleen-preserving caudal pancreatectomies, and two caudal pancreatectomies with splenectomy were carried out. There were no conversions and the mean operating time was 260 min, with a mean blood loss of 180 ml. The mean hospital stay was 7 days. There were no minor nor major complications during the hospitalization period. However, a pancreatic abscess was diagnosed in one patient 1 month later, requiring an urgent laparotomy. Conclusion: MRI as well as LUS are indeed suitable techniques to localize NEPTs. Moreover, the minimally invasive approach ensured an adequate treatment with a more comfortable and short postoperative recovery.     

Neuroendocrine tumors of the gut

Of 75 patients with neuroendocrine tumors of the gut, 50 had functioning lesions, causing endocrine syndromes. These included 16 insulinomas, 13 gastrinomas, 5 vipomas (4 pancreatic, 1 adrenal), 4 corticotrophinomas, and 1 renal enteroglucagonoma. Three patients had mixed endocrine syndromes. Eight or 9 patients with pancreatic lesions had multiple endocrine adenopathy (MEA I), including 3 of 4 patients with multiple insulinomas and all 3 patients with malignant gastrinomas. Localization of the pancreatic insulinomas, vipomas, and mixed tumors by arteriography was excellent, but few gastrinomas were detected before operation. Eight patients developed the malignant carcinoid syndrome with metastases from primary tumors in the ileum (6 patients), bronchus, and stomach. Hepatic artery embolization provided palliative relief for several with this and some other syndromes. Twenty-five patients had tumors that caused nonspecific features only. These included 18 appendicular carcinoids, 5 islet cell carcinomas, and 2 other apudomas (1 hepatic and 1 whose primary site is unknown). The importance of the latter is that they are more responsive to therapy and have a better prognosis than the more common acinar tumors. Over 40% of the patients had lesions that were cured surgically and over 80% obtained some benefit from treatment.

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Resumen La serie incluye todos los pacientes con tumores neuroendocrinos intestinales, o lesiones relacionadas, que fueron referidos a cirujanos del Hospital Hammersmith para consulta o manejo, entre 1937 y 1983. De 75 pacientes con tumores neuroendocrinos intestinales, 50 presentaron lesiones funcionales causantes de síndromes endocrinos. Estos incluyeron 16 insulinomas, 13 gastrinomas, 5 vipomas (4 pancreáticos, 1 adrenal), 4 corticotrofinomas y 1 enteroglucagonoma renal. Tres pacientes presentaron síndromes endocrinos mixtos. Ocho o nueve pacientes con lesiones pancreáticas exhibieron el síndrome de adenomas endocrinos múltiples tipo I (AEM I), incluyendo 3 de 4 pacientes con insulinomas múltiples y la totalidad de los 3 pacientes con gastrinomas malignos. La localización de los insulinomas pancreáticos, vipomas y tumores mixtos por medio de la arteriografía fué excelente, pero sólo unos pocos de los gastrinomas pudieron ser detectados antes de la operación. Ocho pacientes desarrollaron el síndrome carcinoide maligno con metástasis del tumor primario ubicado en el íleon (6), bronquio y estómago. La embolización de la arteria hepática significó mejoría paliativa para varios pacientes con éste y otros síndromes. Veinticinco pacientes presentaron tumores que sólo causaban manifestaciones no específicas. Estos incluyeron 18 carcinoides apendiculares, 5 carcinomas de células insulares y otros 2 apudomas (1 hepático y 1 cuya ubicación primaria permaneció desconocida). La importancia de estos últimos radica en que exhiben mayor capacidad de respuesta a la terapia y que poseen un mejor pronóstico que los mas comunes tumores acinares. Más del 40% de los pacientes presentaron lesiones que fueron curadas quirúrgicamente y más de 80% obtuvieron algún beneficio del tratamiento.

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Résumé Chez 75 sujets porteurs de tumeurs neuroendocriniennes du tube digestif 50 présentaient des lésions fonctionnelles se manifestant par des syndromes endocriniens. Parmi ces derniers, on comptait 16 insulinomes, 13 gastrinomes, 5 vipomes (4 pancréatique, 1 rénal), 4 corticotrophinomes et 1 entéroglucagonome. Trois malades présentaient des syndromes endocriniens mixtes. Huit ou neuf malades porteurs de lésions pancréatiques présentaient un syndrome MEA I comprenant 3 malades avec des insulinomes multiples sur 4 et 3 sujets avec des gastrinomes malins. La localisation des insulinomes pancréatiques, des vipomes et des tumeurs mixtes par l'artériographie fut excellente alors que peu des gastrinomes furent découverts avant l'intervention. Huit sujets présentèrent un syndrome carcinoide malin avec des métastases hépatiques alors que la lésion primitive siègeait au niveau de l'iléon, des bronches ou de l'estomac. L'embolisation de l'artère hépatique permis plusieurs fois d'obtenir une rémission de l'affection. Sur les 75 sujets observés, 25 ne présentaient pas de troubles fonctionnels spécifiques: les lésions répondant à 18 carcinoides appendiculaires, 5 carcinomes langheransiens et 2 apudomes (1 hépatique et 1 de siège inconnu). Ces formes sont plus sensibles au traitement et présentent un meilleur pronostic que les tumeurs acineuses plus fréquentes. Plus de 40% des malades furent guéris chirugicalement et au total 80% bénéficierent du traitement.

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The Hammersmith Surgical Series, presented at the International Association of Endocrine Surgeons at Hamburg, September, 1983.     

Neuroendocrine tumors of the bronchopulmonary tract: a reappraisal of their classification after 20 years

This article is an overview of the classification of pulmonary neuroendocrine neoplasms, their presentation, their pathologic appearance, and their clinical management. In addition, the original classification, based on histologic features, is reassessed in the light of newer areas in study, including neurosecretory products, neuroendocrine markers, ultrastructural studies, ploidy analysis, cell adhesion markers, apoptosis, oncogene mutation analysis, and genetic alterations. The histologic classification proposed in 1983 remains the single most valuable factor in establishing the diagnosis and, together with the TNM status, the prognosis of this group of interesting neoplasms.     

Neuroendocrine tumors of the larynx.

A review of the international literature has revealed 68 paragangliomas, 42 large cell, and 74 small cell tumors of the larynx. Paragangliomas are usually benign, although malignant cases have been reported. Large cell tumors are malignancies associated with a high incidence of early cervical metastasis. Small cell tumors are aggressive cancers characterized by early, diffuse metastatic disease. All three neoplasms demonstrate a propensity for the supraglottic larynx. While surgery remains the treatment of choice for paragangliomas and large cell cancers, small cell cancers are best treated by radiotherapy and chemotherapy. The determinate 5-year survival for patients with paragangliomas, large cell, and small cell cancers is 60%, 34%, and 14%, respectively. While representing distinct clinical entities, these neoplasms demonstrate similar ultrastructural and histochemical features and should be classified as neuroendocrine tumors of the larynx (NETL). A comprehensive analysis of these laryngeal tumors is presented herein. Their clinical behavior and management options are reviewed and a scheme for their nomenclature and classification is proposed.     

The diversity and commonalities of gastroenteropancreatic neuroendocrine tumors

Background  

Recent data demonstrate that the incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) has increased exponentially (overall ~500%) over the last three decades, thus refuting the erroneous concept of rarity. GEP-NETs comprise 2% of all malignancies and in terms of prevalence, are the second commonest gastrointestinal malignancy after colorectal cancer. Diagnosis is usually late since there is no biochemical screening test and symptoms are protean and overlooked. As a consequence, 60–80% exhibit metastases with a consequent suboptimal outcome.     

Our experience regarding biologically inactive gastroenteropancreatic neuroendocrine tumors

The Authors present 9 cases of gastro-enteropancreatic neuro-endocrine biologically inactive tumors. In 5 cases the tumor site was appendicular. In 4 patients an appendectomy was performed, in one patient a right hemicolectomy and the patients after a period of 3-9 years are well and disease free. In a patient with a gastric carcinoid and a single hepatic metastasis a total gastrectomy with an hepatic metastasectomy were performed but the patient died 16 months thereafter. In a case localized to the right colon with a single hepatic metastasis a right hemicolectomy was performed with a metastasectomy but the patient died after 12 months. In a case localized to an ileal loop a segmental resection was performed followed by a medical therapy with octreotide and the patient is well and disease free after 3 years. In a case localized to the pancreas with widespread lymphatic metastasis it was performed a simple biliary diversion (coledocho-duodenostomy) followed by medical therapy with octreotide. Surprisingly after 4 years the patient is alive and a TC control shows a decrease of the pancreatic tumor and of the lympho glandular tumefactions.     

Neuroendocrine "silent" tumors of the pancreas

Neuroendocrine tumors are the rare pathology. They are characterized by slow growth and favorable prognosis for life. From 1985 to 2000 fifty-two patients with "silent" neuroendocrine tumors were treated. Clinical symptoms in 60% patients were associated with squeezing of the surrounding organs and tissues (gastroduodenal obstruction or cholestasis), in 20% patients tumors were diagnosed within the framework of syndrome of multiple endocrine metaplasia and in 16% cases tumors were revealed accidentally. Fifty-two percent of the tumors located in the head of the pancreas, 23 and 25% - in the corpus and tail of the pancreas respectively. All the patients underwent surgery. Neuroendocrine nature of the tumors was verified during morphologic study. Five-year survival was 51.8, 41.6 and 54.5% when tumor located in the head, corpus and tail of the pancreas, respectively.