[Apudoma of Vater's ampulla: case report and review of the literature]. / Apudoma dell'ampolla di Vater: caso clinico e revisione della letteratura.

The Authors report a case of Vater's ampulla apudoma and after having examined the characteristics of these neoplasms they discuss clinical presentation, diagnostic and treatment problems of islet cell adenomas. They review the literature and make some remarks.

Pancreatic endocrine tumors: recent advances.

Pancreatic endocrine tumors (PET's) can be divided on a clinical and pathologic basis into ten classes [insulinomas, gastrinomas (Zollinger-Ellison syndrome), VIPomas (Verner-Morrison syndrome, WDHA, pancreatic cholera), glucagonomas, somatostatinomas, ACTH-releasing tumors (ACTHomas), growth hormone-releasing factor secreting tumors (GRFomas), nonfunctioning or pancreatic polypeptide secreting tumors (non-functioning PET), PET's causing carcinoid syndrome and PET's causing hypercalcemia)]. Recent reports suggest calcitonin-secreting PET's also rarely occur but whether they cause a distinct clinical syndrome is unclear. PET's resemble carcinoid tumors histologically; in their ability to synthesize and frequently secrete multiple peptides such as neuroendocrine cell markers (chromogranins); their biologic behavior and their tumor growth patterns. Both groups of tumors are highly vascular, have high densities of somatostatin receptors and similar tumor localization studies including somatostatin receptor scintigraphy are used for both. PET's, similar to carcinoids causing the carcinoid syndrome, require two separate treatment options be considered: treatment directed against the hormone-excess state and treatment directed against the tumor per se because of their malignant nature. In the last few years there have been advances in tumor diagnosis, localization methods, treatment approaches particularly related to the use of synthetic somatostatin analogues, and the definition of the role of surgical procedures in these diseases. Important other advances include insights into the long-term natural history of PET's particularly from studies of gastrinomas, which allow prognostic factors to be identified and the timing of treatment options to better planned, as well as insights into the molecular basis of these disorders. The latter includes both a description of the molecular basis of the genetic inherited syndromes associated with PET's or carcinoid tumors, as well as an increased understanding of the molecular basis for sporadic PET's or carcinoid tumors. Each of these areas will be briefly highlighted in this presentation.

Gastrinomas and the change in their presentation and management in Northern Ireland, UK, from 1970 to 1996.

Thirty-five new cases of gastrinomas were diagnosed in N. Ireland between 1970 and 1996. Over this period, patient care has improved, with advances in imaging techniques and therapeutic regimens. Patients are now no longer presenting in the classical way with severe ulcer diathesis. Diarrhoea is often a major feature, occurring in 46% of patients. Thirty-one percent of patients presented with mixed amine precursor, uptake and decarboxylation (APUD) tumours. Survival has improved, most likely as a result of better detection of tumours, as well as treatment that is aimed at resection and removal of the gastrinoma. The advent of proton pump inhibitors has ensured symptom control in those for whom total tumour removal is impossible. Owing to improved survival, metastatic complications are often associated with patient mortality.

[Apudomas: nosographic and physiopathological aspects]. / Apudomi. Aspetti nosografici e fisiopatologici.

The authors intend to contribute to the knowledge of this complex and in part not fully defined subject of apudomas, in particular with regard to classification criteria and physiopathological aspects. After having examined the characteristics of these neoplasias (probably common embryonal origin, similar radioimmunological, immunohistochemical and ultrastructural characteristics, the capacity to convert amine precursors into amines), the authors focus on the most significant aspect of these carcinoids which, in the light of current knowledge, possess varying but undisputed degrees of biological aggressiveness. They also highlight the importance of the gastroenteric tract as an organ with an endocrine function and lastly affirm the value of the classification which, using the pancreas as the reference organ, distinguishes endocrine neoplasias in this tract into entopic and ectotopic examples.

Palliative treatment of neuroendocrine tumors.

Effective palliation of patients with incurable neuroendocrine tumors requires both control of hormonal overproduction symptoms as well as control of tumor growth. Several important advances have been made in recent years toward these two goals. Octreotide and omeprazole have both been extremely effective in ameliorating hormonal symptoms of carcinoids, islet cell tumors and medullary thyroid carcinoma. Newer cytotoxic chemotherapy regimens and interferon have increased response rates over traditional therapy. More aggressive surgical extirpation of metastatic disease has also been beneficial.

Transcatheter treatment of hepatic metastases.

After successful removal of a primary tumor, the exclusive or dominant site of metastatic spread is often the liver. Existing palliative treatments, particularly chemotherapy, have low success rates. Fortuitous physiologic circumstances allow the use of regional treatments, such as hepatic artery infusion therapy, for both primary and secondary malignant tumors in the liver. Despite encouraging results in early uncontrolled trials, subsequent randomized studies have failed to show survival benefit with regional infusion therapy via surgically implanted pumps in patients who have colorectal metastases, the most common tumor studied. Dissatisfaction with current treatments has led to a host of novel therapies, including embolization of liver tumors and the combined infusion of embolic particles and chemotherapeutic agents (i.e., chemoembolization).

[The diagnostic and therapeutic problems of endocrine tumors of the digestive system: our experience]. / Problematiche di diagnosi e terapia dei tumori endocrini dell'apparato digerente: la nostra esperienza.

The authors experience in the surgical treatment of endocrine tumours of the digestive tract is reported. Particularly, they emphasize that in spite of the several syndromes associated with these neoplasms, diagnostic and therapeutic concepts herein analyzed are similar.

Hepatic arterial chemoembolization in patients with liver metastases of endocrine tumors. A prospective phase II study in 24 patients.

BACKGROUND: Liver metastases of endocrine tumors are of major prognostic significance. The various therapeutic approaches have given disappointing results; however, locoregional treatment has allowed transient control of hepatic tumor growth. METHODS: Twenty-four patients with liver metastases of endocrine tumors (mainly carcinoid tumors [n = 18] and gastrinomas [n = 5]) were included in a Phase II study of hepatic arterial chemoembolization (CE). Metastases were bilateral in all patients and invaded more than 50% of the liver in 12. They were synchronous of the primary tumor in 62.5% of the patients. Seventeen patients had not responded to previous intravenous chemotherapy. CE courses were performed every 3 months using an emulsion of 10 ml of iodized oil and doxorubicin 50 mg/m2 injected into tumor vessels, followed by CE arterial occlusion with gelatin sponge particles. Seventy-one CE courses were performed in 23 patients; there was one technical failure. RESULTS: Among patients with carcinoid tumors, disappearance of diarrhea and/or flushing was observed in 8 of 11. Serotonin and/or its metabolite 5-hydroxyindoleacetic acid levels decreased by more than 50% in 57% of the patients. The size of liver metastases decreased by at least 50% in 6 of 18 patients, i.e., in 33% (range, 12-54%). Two had complete responses. The median duration of the responses was 14 months (range, 6-40). Among patients with noncarcinoid tumors, minor response or stabilization occurred in three of five patients. Major side effects were bleeding peptic ulcer (one patient) and oligoanuric renal failure (one patient). Abdominal pain, fever, and increases in hepatic enzyme levels were common and transient. CONCLUSIONS: These results suggest that CE is effective in patients with liver metastases of endocrine tumors, mainly in carcinoids. In the latter, CE allows control of the carcinoid syndrome and regression or stabilization of the liver tumors in 80% of patients.

Recombinant interferon alpha-2b in patients with metastatic apudomas: effect on tumours and tumour markers.

Malignant carcinoid tumours, islet cell tumours and medullary carcinomas of the thyroid are tumours with similar clinical features. In patients with unresectable or metastatic tumours leukocyte interferon (IFN) and recombinant human (rh) IFN have demonstrated efficacy. Twenty-four evaluable patients with progressive tumours were treated with 2.5 megaunits rh IFN alpha-2b, administered once daily subcutaneously, for a median duration of 7 months (range 0.5-37+). Two carcinoid patients demonstrated a response in tumour size, 80% showed stable disease (SD). Sixty percent of the carcinoid patients with elevated urinary 5-hydroxyindoleacetic (5-HIAA) levels reached a biochemical partial response of the urinary 5-HIAA levels (median duration 13.5 months). In the patients with an islet cell or medullary tumour and an elevated tumour marker, the marker did not further increase. Of the 12 carcinoid patients evaluable for a symptomatic response, ten (83%) experienced a relieve of symptoms. IFN alpha-2b dose reduction or discontinuation due to toxicity was necessary in three and ten patients, respectively. No neutralising IFN alpha-2b antibodies developed despite prolonged treatment. In conclusion, IFN alpha-2b had a beneficial effect in patients with progressive tumours, while long-term IFN alpha-2b treatment did not augment neutralising antibodies. In view of the IFN alpha-2b-related toxicity, administration of IFN alpha-2b on alternating days may be preferable.

APUDomas: acute complications and their medical management.

APUDomas are rare tumours originating from a variety of endocrine cells localized in different organs. Acute complications from APUDomas usually result from the increased biosynthesis and release of bioactive amines or polypeptide hormones by the tumour. Less frequently, bleeding or compression by the tumour can occur requiring emergency surgery. Increased gastrin production by gastrinomas is the cause of ZES (peptic ulceration and diarrhoea) by gastrin effects on gastric acid secretion. Volume depletion, hypokalaemia, severe bleeding, duodenal perforation, oesophageal stricture and pyloric stenosis are the most dramatic complications. Treatment of these complications and their prevention has been facilitated by the availability of antagonists to H2 receptors and H(+)-K+ proton pump. These medications should control acid output in every patient with ZES. Frequent manifestations of carcinoid tumours, VIPomas and medullary thyroid carcinomas are flushing and diarrhoea. Octreotide, a long-acting somatostatin analogue, has markedly changed the management of these patients, their symptoms decreasing in severity or disappearing in most cases. Octreotide has also been used with success in the prevention and treatment of the carcinoid crisis, a dreaded complication of carcinoid tumours. A better understanding of the pathophysiology of APUDomas has enabled new treatment designs which have considerably ameliorated the quality of life of patients affected by these tumours; efforts must be continued to affect their life expectancy.

Neuroendocrine (Merkel cell) carcinoma of the skin. Its natural history, diagnosis, and treatment.

Over 400 cases of neuroendocrine (Merkel cell) carcinoma of the skin (NCS) have been reported. This tumor continues to pose problems in diagnosis and effective treatment for physicians unfamiliar with its biological characteristics. Reported here are five additional cases of NCS and the literature for this rare neoplasm is comprehensively reviewed. An early and accurate diagnosis is made possible by combining clinical presentation with results of histologic study, immunoperoxidase staining for neuron-specific enolase (NSE), epithelial membrane antigen (EMA), cytokeratins, and electron microscopy. NCS is an aggressive tumor. Depending on the length of follow-up, up to 40% of tumors locally recur, 55% develop regional nodal metastases, and 36% undergo distant metastasis. Survival is sex, but not age, dependent, with an overall 2-year survival rate of 72% (males 58% vs. females 79%). No standard procedure for initial and/or follow-up treatment for NCS exists. The authors recommend that NCS be treated, whenever possible, using the same rationale as applied for the treatment of squamous cell carcinoma of the skin.

Carcinoid and other metabolically active tumors in the elderly.

This article reviews the clinical manifestations, diagnostic techniques, and therapy of carcinoid and other metabolically active tumors that occur in the elderly. These tumors secrete monoamine and polypeptide hormones into the vascular compartment. Because these hormones may produce symptoms early in the course of the illness and are amenable to measurement, physicians have the opportunity to make a prompt diagnosis.

Adenomatosis endocrina multiple tipo IIb / Endocrine multiple adenomatosis type IIb

Se revisa el sindrome de Adenomatosis Endocrina Multiple Tipo IIb, el cual esta constituido por carcinoma medular del tiroides, neuromas mucosos multiples, feocromocitoma y un habito marfanoide caracreristico. Este sindrome al igual que el Tipo I y el Tipo IIa son considerados actualmente como apudomas. El diagnostico se hace por las caracteristicas clinicas marfanoides descritas, por la dosificacion de calcitonina y por los hallazgos histopatologicos que muestran carcinoma medular, neuromas y feocromocitoma. El tratamiento es quirurgico y consiste en la tiroidectomia total y en la extirpacion de los feocromocitomas, cuando estos existen. El pronostico es sombrio y los pacientes invariablemente fallecen, considerandose el tratamiento quirurgico como de tipo paliativo; la radioterapia y la quimioterapia no evitan las metastasis ni las recurrencias. Se presenta un caso clinico con este curioso pero letal sindrome