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      Ablative Therapies for Liver Metastases of Gastroenteropancreatic Endocrine Tumors

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          Abstract

          Hepatic metastases are frequent in patients with gastroenteropancreatic (GEP) endocrine tumors. The presence of hepatic metastases affects overall prognosis and quality of life especially in the presence of debilitating functional syndromes. Surgery, although the method of choice for hepatic metastases, is usually impossible due to disease extent. Results of systemic chemotherapy are also disappointing especially in patients with metastases from midgut GEP tumors. These latter patients usually have carcinoid syndrome which can be controlled by somatostatin analogues. Other therapeutic options in the treatment of highly vascular liver metastases from GEP tumors are locoregional strategies by inducing vascular occlusion resulting in ischemia and necrosis of tumoral tissue. Surgical ligation of the hepatic artery or transient hepatic ischemia has been replaced by transcatheter arterial chemoembolization (TACE). TACE has proven effective in controlling symptoms and gives objective tumor response in about half of patients. Other regional destructive methods, used either alone or in combination with surgery, include radiofrequency ablation and cryotherapy. The latter strategies are poorly evaluated to date and are usually adjuncts to surgery and reserved for limited disease.

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          Most cited references 21

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          Carcinoid TumorsAn analysis of 2837 cases

           J Godwin (1975)
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            Hepatic arterial chemoembolization in patients with liver metastases of endocrine tumors. A prospective phase II study in 24 patients.

            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. 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. 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. 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.
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              Prognostic factors in patients with endocrine tumours of the duodenopancreatic area.

              The development of endocrine tumours of the duodenopancreatic area (ETDP) is thought to be slow, but their natural history is not well known. The aim of this study was to determine the factors that influence survival of patients with ETDP. Eighty two patients with ETDP (44 non-functioning tumours, 23 gastrinomas, seven calcitonin-secreting tumours, four glucagonomas, three insulinomas, one somatostatinoma) followed from October 1991 to June 1997 were included in the study. The following factors were investigated: primary tumour size, hormonal clinical syndrome, liver metastases, lymph node metastases, extranodular/extrahepatic metastases, progression of liver metastases, local invasion, complete resection of the primary tumour, and degree of tumoral differentiation. The prognostic significance of these factors was investigated by uni- and multi-variate analysis. Twenty eight patients (34%) died within a median of 17 months (range 1-110) from diagnosis. Liver metastases (p = 0.001), lymph node metastases (p = 0.001), progression of liver metastases (p or = 3 cm (p = 0.001), non-functioning tumours (p = 0.02), and poor tumoral differentiation (p = 0.006) were associated with an unfavourable outcome by univariate analysis. Multivariate analysis identified only liver metastases (risk ratio (RR) = 8.3; p < 0.0001), poor tumoral cell differentiation (RR = 8.1; p = 0.0001), and lack of complete resection of the primary tumour (RR = 4.8; p = 0.0007) as independent risk factors. Five year survival rates were 40 and 100% in patients with and without liver metastases, 85 and 42% in patients with and without complete resection of primary tumour, and 17 and 71% in patients with poor and good tumour cell differentiation respectively. Liver metastases are a major prognostic factor in patients with ETDP. Progression of liver metastases is also an important factor which must be taken into account when deciding on the therapeutic approach. The only other independent prognostic factors are tumoral cell differentiation and complete resection of the primary tumour.
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                Author and article information

                Journal
                NEN
                Neuroendocrinology
                10.1159/issn.0028-3835
                Neuroendocrinology
                S. Karger AG
                978-3-8055-7848-6
                978-3-318-01162-3
                0028-3835
                1423-0194
                2004
                October 2004
                15 October 2004
                : 80
                : Suppl 1
                : 74-78
                Affiliations
                Medical-Surgical Federation of Hepato-Gastroenterology, Hôpital Beaujon and University of Paris VII, Clichy, France
                Article
                80746 Neuroendocrinology 2004;80(suppl 1):74–78
                10.1159/000080746
                15477722
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Tables: 2, References: 42, Pages: 5
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