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General Information About Carcinoid And Related Neuroendocrine Tumors

This section contains links to websites with full-text or abstract versions of published papers that focus on general information (reviews) of diagnosis, treatment and current research in the field of carcinoid and neuroendocrine tumors.

Reviews,Research, Book Resources and Miscellaneous Information

    NEW Population-based study of islet cell carcinoma (Full Text)
    Online Full Text
    Yao JC, Eisner MP, Leary C, Dagohoy C, Phan A, Rashid A, Hassan M, Evans DB. Department of Gastrointestinal Medical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA. jyao@mdanderson.org
    Ann Surg Oncol. 2007 Dec;14(12):3492-500. Epub 2007 Sep 26.

    CONCLUSION: Patients with malignant pancreatic neuroendocrine tumors commonly present with advanced disease. Although, curative resection is not frequent, survival benefit may be obtainable with aggressive surgical management even in the face of metastatic disease.

    Note: Acknowledgments Supported by gifts from Raymond Sackler, the J. Stuart Foundation, and the Carcinoid Cancer Foundation.

  • Chemoembolization and Bland Embolization of
    Neuroendocrine Tumor Metastases to the Liver
    (Full text)
    J Vasc Interv Radiol. 2007 Jul;18(7):847-55
    Ruutiainen AT, Soulen MC, Tuite CM, Clark TW, Mondschein JI, Stavropoulos SW, Trerotola SO.
    Division of Interventional Radiology, University of Pennsylvania, 1 Silverstein, Philadelphia, PA 19104, USA.
    (Abstract)
    CONCLUSIONS: Chemoembolization was not associated with a higher degree of toxicity than bland embolization. Chemoembolization demonstrated trends toward improvement in TTP, symptom control, and survival. Based on these results, a multicenter prospective randomized trial is warrante
  • Valproic Acid activates Notch-1 Signaling and Regulates the Neuroendocrine Phenotype in Carcinoid Cancer Cells   (full text)
    Oncologist. 2007 Aug;12(8):942-51
    Greenblatt DY, Vaccaro AM, Jaskula-Sztul R, Ning L, Haymart M, Kunnimalaiyaan M, Chen H
    F.A.C.S., H4/750 Clinical Science Center, 600 Highland Avenue, Madison, Wisconsin 53792, USA.

    Carcinoid tumors are neuroendocrine malignancies that frequently metastasize and secrete hormones that cause debilitating symptoms in patients. In this study we report the effects of valproic acid (VPA), a drug long used for the treatment of epilepsy, on the growth and neuroendocrine phenotype of human carcinoid cancer cells. VPA treatment of gastrointestinal and pulmonary carcinoid cells resulted in a dose-dependent inhibition of cancer cell growth. Western blot analysis revealed degradation of cyclin D1 and an increase in cyclin-dependent kinases p21 and p27 with VPA treatment. Flow cytometry confirmed that the mechanism of VPA-induced growth inhibition is G(1) phase cell cycle arrest. Furthermore, VPA suppressed expression of the neuroendocrine tumor marker chromogranin A. In addition to these effects, VPA also increased levels of full-length Notch-1 and the active Notch-1 intracellular domain. Luciferase reporter assays incorporating the centromere-binding factor 1 (CBF-1) binding site and the achaete-scute complex-like 1 (ASCL-1) promoter confirmed the functional activity of VPA-induced Notch-1. Transfection of Notch-1 small-interfering RNA into carcinoid tumor cells blocked the effects of VPA on Notch-1 activation, ASCL-1 suppression, p21 induction, and cell growth inhibition. VPA also suppressed growth of carcinoid tumors in vivo in a mouse tumor xenograft experiment. These findings confirm the important role of Notch-1 in regulating the growth and neuroendocrine phenotype of carcinoid tumor cells. On the basis of this study, a clinical trial of VPA for patients with advanced carcinoid cancer will be conducted.

  • Tumor Suppressor Role of Notch-1 Signaling in Neuroendocrine Tumors
    (full text)
    Muthusamy Kunnimalayaan, Herbert Chen
    Endocrine Surgery Research Laboratories, Department of Surgery, The University of Wisconsin, and the University of Wisconsin Comprehensive Cancer Center, Madison, Wisconsin, USA
    The Oncologist 2007;12:535–542

    ABSTRACT
    A growing body of literature is demonstrating that Notch signaling is a more complex process than originally thought. Contradictory findings of notch-1 acting as an oncogene or a tumor suppressor revealed that its role is very specific to the cellular context. In this review we focus on the tumor suppressor role of Notch-1 signaling in neuroendocrine tumors (NETs) such as carcinoid and medullary thyroid cancers. NETs secrete various bioactive hormones that can cause debilitating symptoms. Surgery is the only potential curative treatment for the patients with NETs. Notch-1 signaling is absent in these tumors and activation of Notch-1 significantly
    reduces tumor growth in vitro. Therefore, identification
    of compound(s) that activate the Notch-1 pathway in NETs could be a potential strategy to treat patients with NETs.

  • ENETS 2007 Consensus Guidelines for the Management pf Patients with Digestive Neuroendocrine tumors. Part1 Stomach, Duodenum and Pancreas
  • Liver metastases of neuroendocrine tumors; early reduction of tumour load lead to improved life expectancy
    .(for full text CLICK HERE)
    Liesbeth M Veenendaal1, Inne HM Borel Rinkes1, Cornelis JM Lips2 and Richard van Hillegersberg, Netherlands.
    Published: 26 June 2006 World Journal of Surgical Oncology 2006, 4:35
    Review
    Abstract : Background: Neuroendocrine tumours frequently metastasize to the liver. Although generally slowly progressing, hepatic metastases are the major cause of carcinoid syndrome and ultimately lead to liver dysfunction, cardiac insufficiency and finally death.
    Conclusion: Treatment for patients with neuroendocrine hepatic metastases must be tailored for each individual patient. When local ablative therapies are used early in the course of the disease, the occurrence of carcinoid syndrome with end stage hepatic disease can be postponed or prevented.

  • Goblet cell carcinoid of the appendix
    Payam S Pahlavan1  and Rani Kanthan2 
    1Department of Physiology and Pathophysiology, University of Heidelberg, Heidelberg, Germany
    2Department of Pathology, University of Saskatchewan, Saskatoon, Canada
    World Journal of Surgical Oncology 2005, 3:36
  • Over expression of the Notch1 intracellular domain (NICD) inhibits cellular proliferation and alters the neuroendocrine phenotype of medullary thyroid cancer cells
    Muthusamy Kunnimalaiyaan, Abram M. Vaccaro, Mary A. Ndiaye, and Herbert Chen
    Surgery, University of Wisconsin, Madison, WI 53792
    Papers In Press, published online ahead of print November 7, 2006
    J. Biol. Chem, 10.1074/jbc.M603578200
    Accepted on November 7, 2006
    Full Text

    Other papers published by Muthusamy Kunnimalaiyaan in Pub Med

  • Human Tumor Assay
    Editor Larry Weisenthal, MD, Phd
    What is Cell culture drug resistance testing (CCDRT)?
    Also known as "chemotherapy sensitivity and resistance assays" or ("CSRAs")

    This journal describes the use of CCDR and its use to identify the best forms of chemotherapy for cancer patients on an individual basis.
  • Information on Carcinoid and Related Neuroendocrine Tumors (HTML page)
    This website, created by Endotext.org. provides comprehensive, authoritative, and updated full text information on endocrine disease directed to physicians around the world caring for patients with these problems. All material may be freely downloaded for personal use and is a textbook format.

    Topics covered on these webpages included:
    • Introduction-Development and Anatomy, by Aaron Vinik, M.D. , Ph.D.
    • Carcinoid Tumors, by Aaron Vinik M.D.
    • Gastrinoma Syndrome, by Roger R Perry, M.D. , FACS
    • Insulinomas, by Roger R Perry M.D.
    • MEN I and MEN I, by Roger R Perry M.D.
    • VIPomas, by Aaron Vinik M.D.
    • Glucagonoma, by Aaron Vinik M.D.
    • Somatostatinoma, by Aaron Vinik M.D.
    • Pancreatic Polypeptide-oma, by Aaron Vinik M.D.
    • Neurotensinoma, by Aaron Vinik M.D.
    • Ghrelinoma, by Aaron Vinik M.D.
    • Management of Neuroendocrine Tumors of the GI Tract, by Aaron Vinik M.D.
    • Chemotherapy for Islet Cell Carcinomas, by Aaron Vinik M.D.
  • Gastroenteropancreatic Neuroendocrine Tumor Disease: Molecular and Cell Biological Aspects
    This link is to an abstract. Full text of this volume is available to subscribers of the Annals of the New York Academy of Sciences or by per-article payment. Nonmembers may browse the table of content and abstracts by following the link above.
    Volume 1014 published Apr 2004
    Edited by Bertram Wiedenmann; Gerhard M. Christofori; Michael Hoecker

  • Diagnosis and Management of Neuroendocrine Tumors (Full text)
    by Rudolph Arnold, M.D., FRCP
    8th United European Gastroenterology Week
    Reference provided by Medscape
  • Considerations Concerning a Tailored, Individualized Therapeutic Management of Patients with (neuro)Endocrine Tumors of the Gastrointestinal Tract and Pancreas (Full text PDF)
    W W de Herder, E P Krenning, C H J van Eijck 2 and S W J Lamberts
    Endocrine-Related Cancer (2004) 11 19–34
  • Diagnosis and Treatment of Carcinoid Tumors (Full text PDF)
    By Oberg Kjell
    Department of Endocrine Oncology, University Hospital,
    Uppsala, Sweden. kjell.oberg@medicin.uu.se
    Expert Rev Anticancer Ther. 2003 Dec;3(6):863-77.
  • Carcinoid Tumors: Molecular genetics, tumor biology, and update of diagnosis and treatment
    This link is to an abstract. Full text of this volume is available to subscribers of the Current Opinion on Oncology or by per-article payment.
    Article by Oberg Kjell M.D.
    Department of Medical Sciences, Uppsala University Hospital,
    Uppsala, Sweden.
    Current Opinion Oncology 2002 Jan;14(1):38-45

    "Chromogranin A is an important general tumor marker for all types of carcinoid tumors. Somatostatin receptor scintigraphy is a cornerstone in staging and localization of carcinoid tumors, but newer techniques such as positron emission tomography will challenge its position in the future. Although surgical cure is not obtainable, a more aggressive surgery has emerged during the last decade. Debulking and other cytoreductive procedures are quite common today. Somatostatin analogues have been the treatment of choice in symptomatic patients with carcinoid tumors, but more recent studies have indicated a cytostatic effect of somatostatin analogues. Tumor-targeted radioactive treatment based on somatostatin analogues is now under clinical evaluation. Preliminary data indicate interesting clinical potentials"
  • Carcinoid Tumour
    This link is to an abstract only.
    Article by McStay MK, Caplin ME.
    Department of Gastroenterology, Royal Free Hospital,
    London, UK.
    Minerva Med 2002 Oct;93(5):389-401

    "We conclude that with the increasing number of investigative procedures and therapeutic options available to diagnose and treat carcinoid tumors, a multidisciplinary approach is needed. Furthermore, additional scientific research and controlled clinical trials are needed to determine the efficacy of the many treatment options, which for these rare tumors can only be achieved by collaboration"
  • Gastrointestinal Carcinoid Tumors (PDQ®): Treatment for Health Professionals (HTML page)
    From the National Cancer Institute

Incidence/Statistics

  • A 5-Decade Analysis of 13,715 Carcinoid Tumors (Full text PDF)
    By Irving M. Modlin, M.D., Kevin D. Lys, M.D., Mark Kidd, Ph.D.
    Cancer 2003 Feb 15;97(4):934-59

    CONCLUSIONS: Carcinoids appear to have increased in overall incidence over the past 30 years; for some sites, this trend has been evident for nearly half a century. Recent marked increases in gastric and rectal carcinoids and a concomitant decrease in appendiceal carcinoid incidence may be due in part to varying rules of registration among the compiled databases examined in this report or to improvements in diagnostic technology; increased awareness of and about carcinoid tumors also may play a significant role. In 12.9% of all patients with carcinoid, distant metastases already were evident at the time of diagnosis; the overall 5-year survival rate for all carcinoid tumors, regardless of site, was 67.2%. These findings bring into question the widely promulgated relative benignity of carcinoid disease. Certain carcinoid tumors, such as those of the rectum, appear to be over-represented among the black and Asian populations within the United States, suggesting the role of genetics in the development of this intriguing disease.
  • Updated Population-Based Review of Carcinoid Tumors (Full text PDF)
    By Maggard MA, O'Connell JB, Ko CY.
    Ann Surg. 2004 Jul;240(1):117-22

Carcinoid Heart Disease

  • NEW Early and Late Results of Valvular Surgery for Carcinoid Heart Disease
    Javier G. Castillo, Farzan Filsoufi, Parwis B. Rahmanian, Anelechi Anyanwu, Jerome S. Zacks, Richard R.P. Warner, David H. Adam
    Journal of the American College of Cardiology
    Volume 51, Issue 15, 15 April 2008, Pages 1507-1509
    Pages 1507-1509
    Full Text
  • Carcinoid heart disease: The role of urinary 5-hydroxyindoleacetic acid excretion and plasma levels of atrial natriuretic peptide, transforming growth factor-beta and fibroblast growth factor (Full text PDF)
    Zuetenhorst JM, Bonfrer JM, Korse CM, Bakker R, Van Tinteren H, Taal BG.
    Cancer 2003;97:1609-1615
  • Carcinoid heart disease: presentation, diagnosis, and management
    Fox and Khattar
    Heart, 90 (10), p. 1224
  • Carcinoid Heart Disease
    By Zuetenhorst JM, Taal BG.
    N Engl J Med. 2003 Jun 5;348(23):2359-61

    CONCLUSIONS: High levels of 5-HIAA excretion and ANP were found to be associated with CHD.
    " ...there was an even stronger relationship between carcinoid heart disease and the serotonin load over time."
    " Even in the absence of severe symptoms of the carcinoid syndrome, it is highly recommended that serotonin levels be reduced." "Which can be realized by combination of different treatment modalities such as octreotide analogues,......" and other treatment modalities.
  • Carcinoid heart disease : presentation, diagnoaias, and managemente
    This link is to an abstract. Full text is available at www.heartjnl.com to subscribers of Heart or by per-article payment
    .Fox DJ, Khattar RS.
    .Heart. 2004 Oct;90(10):1224-8
    Review:
    Tricuspid and pulmonary valve regurgitation usually occurs as a secondary phenomenon caused by dilatation of the valve ring secondary to right ventricular failure or pulmonary hypertension, respectively. Primary diseases of the tricuspid or pulmonary valves are uncommon, but the more likely causes might include congenital abnormalities, rheumatic heart disease, or infective endocarditis. Carcinoid heart disease is a rare, but interesting and important cause of intrinsic tricuspid and pulmonary valve disease leading to significant morbidity and mortality caused by right heart failure. When treated medically, and in appropriate cases surgically, significant benefits in overall quality of life and long term survival can be achieved. We review the current literature regarding the pathophysiological basis of the disease, the cardiovascular complications, and the currently available treatment strategie.

Clinical trials

  • Now recruiting
    University of California, San Francisco (UCSF) Comprehensive Cancer Center - Clinical Trial
    Chemotherapy drugs like 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX) work in different ways to cause tumor cells to stop growing or die. Bevacizumab is a monoclonal antibody that may inhibit cancer growth by blocking blood flow to tumors. Adding bevacizumab to combination chemotherapy may be a better way to block tumor growth than giving either type of therapy alone. The FOLFOX plus bevacizumab combination is being studied in patients with neuroendocrine tumors because FOLFOX appears to inhibit the growth of a variety of different tumor types but has not yet been tested in this disease. In addition, neuroendocrine tumors appear to depend on blood vessels for growth suggesting that they may respond to a treatment like bevacizumab. This clinical trial is for patients who have not responded to other treatments to see if the FOLFOX/bevacizumab combination is safe and if it can inhibit the growth of metastatic neuroendocrine tumors.

    LOCATION AND CONTACT INFORMATION
    Mary O’Rourke, R.N.
    Clinical Trials Recruitment Nurse
    UCSF Comprehensive Cancer Center
    Clinical Research Support Services
    1600 Divisadero Street
    San Francisco, CA 94115
    Tel: (415) 353-9612
    Fax: (415) 353-9738
    Email:
    morourke@cc.ucsf.edu
  • Results from Clinical Trials of Systemic treatment with Y90, LU-177 and 111-In
    Overview of Results of Peptide Receptor Radionuclide Therapy with 3 Radiolabeled Somatostatin Analogs (Full Text)
    Kwekkeboom DJ, Mueller-Brand J, Paganelli G, Anthony LB, Pauwels S, Kvols LK, O'dorisio TM, Valkema R, Bodei L, Chinol M, Maecke HR, Krenning EP.
    J Nucl Med. 2005 Jan;46 Suppl 1:62S-6S
    .
    Conclusion:The results obtained with [(90)Y-DOTA(0),Tyr(3)]octreotide and [(177)Lu-DOTA(0),Tyr(3)]octreotate are very encouraging in terms of tumor regression. Also, if kidney protective agents are used, the side effects of this therapy are few and mild, and the duration of the therapy response for both radiopharmaceuticals is more than 2 y. These data compare favorably with those for the limited number of alternative treatment approaches.

Other Topics of Interest

PEDIATRIC CARCINOID BRONCHIAL / LUNG / CARINOID
  • NEW  Bronchopulmonary Carcinoid: Phenotype and Long-term Outcome in
    a Single-Institution Series of Italian Patients (Full Text PDF)

    Massimo Rugge, Matteo Fassan, Roberto Clemente4, Giovanna Rizzardi,
    Luciano Giacomelli, Gianmaria Pennelli, Claudia Mescoli1, Daniela Segat, and Federico Rea
    Clinical Cancer Research 14, 149-154, January 1,
    2008. doi: 10.1158/1078-0432.CCR-07-1631
  • Bronchial Carcinoid (Full text PDF)
    By Dan Granberg M.D. : Bronchial Carcinoids.
    Uppsala, 2001. - 75p.
    Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine,
    ISSN 0282-7476 ; 1006
    ISBN 91-554-4957-3
  • Additional references regarding treatment of patients with bronchial carcinoids
    Provided by
    Dan Granberg, MD, PhD, Consultant, Assistant Head of Department
    Department of Endocrine Oncology
    University Hospital
    SE-751 85 Uppsala
    Sweden


    Lung and t
    hymic neuroendocrine tumors.
    Granberg D, Skogseid B.
    In: Doherty G, Skogseid B, eds. Surgical Endocrinology. Philadelphia. Lippincott Williams & Wilkins. 2001:413-430

    Granberg D, Eriksson B, Wilander E, Grimfjärd P, Fjällskog M-L, Öberg K, Skogseid B. Experience in treatment of metastatic pulmonary carcinoid tumors. Ann Oncol 2001;12(10):1383-1391
    2008-04-01 kl. 14.18 skrev Monica Warner:

    Temozolomide as monotherapy is effective in treatment of advanced malignant neuroendocrine tumors.
    Ekeblad S, Eriksson B, Sundin A, Welin S, Granberg D, Kindmark H, Dunder K, Kozlovacki G, Örlefors H, Sigurd M, Öberg K, Janson ET, Skogseid B
    Clin Cancer Res 2007;13(10):2986-2991

    Outcome of patients with pulmonary carcinoid tumors receiving chemotherapy or chemoradiotherapy. Lung Cancer 2004;44:213-20.

    Peptide receptor radionuclide therapy with (177)Lu-octreotate in patients with foregut carcinoid tumours of bronchial, gastric and thymic origin
    Wirth LJ, Carter MR, Jänne PA, Johnson BE.
    .van Essen, M et al. Eur J Nucl Med Mol Imaging 2007;34(8):1219-1227

    Response of atypical pulmonary carcinid tumors to chemotherapy. Aretrospective study of 37 patients.
    Guigay J.
    Poster presented at the12th World Conference on Lung Cancer, Seoul, Korea, September 2007.

    Lung and Thymic Neuroendocrine Tumors.
    Granberg D, Öberg K.
    In: Hay I, Turner H, Wass J, eds. Clinical Endocrine Oncology, 2nd edition. Oxford. Blackwell Publishing Ltd. In press, to be published on April 15th.
  • A list of proceedings from the UK-NET/ENET meeting in London, May 2003
    This page also includes links to full text versions of the presentations.
  • ENETS (European Neuroendocrine Tumor Network Society
    The European Neuroendocrine Tumor Society is an international professional association composed of physicians and researchers, whose main area of study is related to neuroendocrine tumors. Society members, currently numbering around 200, bring a variety of expertise to ENETS, such as oncology, pathology, endocrinology, surgery and gastroenterology. ENETS is supported via membership dues, as well as through educational grants from the pharmaceutical community. It is administratively-based in Berlin, Germany.
    European Neuroendocrine Tumor Network (ENETS)
    Budapest, Hungary, March 25 – 27, 2004.(PHOTOS)

Genetics

 

Additional Medical References


Last Modified: Saturday, 19-Apr-2008 14:36:53 EDT