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New Peer Review Articles

• NEW New Study First to Confirm Sandostatin LAR(R) Depot Controls Tumor Growth in Patients With Rare Gastrointestinal Tumors
  (full Text)
  "In recent years, a growing body of evidence has suggested that Sandostatin LAR provides antitumor effects, but these are the first data to confirm this effect from a well-designed, prospective, placebo-controlled study," said David Epstein,President & CEO of Novartis Oncology.
  
  EAST HANOVER, N.J., Jan. 13 /PRNewswire/ -- Sandostatin LAR(R) Depot (octreotide acetate suspension for injection) demonstrated antitumor benefit in patients with metastatic neuroendocrine tumors (NETs) of the midgut,according to interim data presented today at the 2009 Gastrointestinal Cancer Symposium of the American Society of Clinical Oncology.
  - Data show significant 66% reduction in risk of disease progression versus placebo
  - Sandostatin LAR more than doubled time without tumor growth for a median of 14 months compared to six months on
  placebo
  - Results support Sandostatin LAR as first treatment after surgery in certain patients with newly diagnosed
  neuroendocrine tumors (NETs)
• NCI Carcinoid/NET Summit 2007; Main Conclusions (full text)
  
  Priorities for Improving the Management of
  Gastroenteropancreatic Neuroendocrine Tumors
  Irvin M . Modlin , Steven F . Moss , Daniel C . Chung , Robert T . Jensen , Elizabeth Snyderwine
  Published by: J Natl Cancer Inst 2008;100: 1282 – 1289 Vol. 100, Issue 18 | September 17, 2008
  
  ABSTRACT:A National Cancer Institute summit meeting on gastroenteropancreatic neuroendocrine and carcinoid tumors was held in September 2007 to present the currently accepted standards of care for patients with these tumors and to identify areas requiring investigation and development. These tumors are clinically and pathologically heterogeneous, present commonly with obscure symptoms that lead to delays in diagnosis of years, and have an incidence in the United States of 2.5 to 5 cases per 100 000. The 5-year survival rates range between 15% and 95%, depending on the site and extent of disease. This report delineates the main conclusions of the meeting, including the best practice diagnosis and treatment strategies for gastropancreatic neuroendocrine tumors, and the identification of clinical and scientific areas that are most in need of attention. The most pressing needs were public and physician education,identification of molecular markers for early diagnosis and therapeutic monitoring, improved imaging modalities and molecular prognostication, development of a standardized pathological classification system, and creation of regional centers of expertise with tumor and laboratory data banks. In addition, adequately validated neuroendocrine tumor models and cell lines should be established to investigate the molecular mechanisms involved in the control of their growth and secretion, and to facilitate the development of specific therapies that should be examined in well-designed multicenter studies of defined patient groups.
  
• Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases.(full text)
  King J, Quinn R, Glenn DM, Janssen J, Tong D, Liaw W, Morris DL.
  Department of Surgery, University of New South Wales, St. George Hospital, Sydney, New South Wales, Australia.
  Cancer. 2008 Sep 1;113(5):921-9.
  CONCLUSIONS.: In this open study of 34 patients, the results demonstrated that radioembolization with (90)Y resin microspheres can achieve relatively long-term responses in some patients with nonresectable NETLMs.
  
• NEW  Radioembolization for Unresectable Neuroedocrine Hepatic Metastases Using Resin ⁹⁰Y-Microspheres: Early Results in 148 Patients (full text)
  Kennedy AS, Dezarn WA, McNeillie P, Coldwell D, Nutting C, Carter D, Murthy R, Rose S, Warner RR, Liu D, Palmedo H, Overton C, Jones B, Salem R.
  American Journal of Clinical Oncology. Volume 31. Number 3, June 2008
  Abstract:
  CONCLUSION: Radioembolization with ⁹⁰Y-Microspheres to the whole liver, or lobe with single or multiple fractions are safe and produce high response rates, even with extensive tumor replacement of normal liver and/or heavy pretreatment. The acute and delayed toxicity was very low without a treatment related grade 4 acute event or radiation induced liver disease in this modest-sized cohort. The significant objective response suggests that further investigation of this approach is warranted
• 90Y Radioembolization for metastatic neuroendocrine liver tumors: preliminary results from a multi-institutional experience.(Abstract)
  Rhee TK, Lewandowski RJ, Liu DM, Mulcahy MF, Takahashi G, Hansen PD, Benson AB 3rd, Kennedy AS, Omary RA, Salem .
  Ann Surg. 2008 Jun;247(6):1029-35
  CONCLUSION: Yttrium-90 (Y) radioembolization of metastatic NET is a viable therapy with acceptable toxicity. Further investigation is warranted.
• Clinical Value of monitoring Plasma Octreotide Levels During Chronic OctreotideLong-Acting Repeateble Threapy in Carcinoid Patients
  (PDF full text)
  Woltering EA, Salvo VA, O'Dorisio TM, Lyons J 3rd, Li G, Zhou Y, Seward JR, Go VL, Vinik AI, Mamikunian P, Mamikunian G.
  Department of Surgery, Louisiana State University Health Sciences Center, New Orleans, LA, USA. ewolte@lsuhsc.edu
  Pancreas. 2008 Jul;37(1):94-100.
  Abstract
  CONCLUSIONS: Current plasma octreotide values are significantly lower than previously reported for 30-, 60-, and 120-mg/mo LAR doses. Serial plasma octreotide value measurements should be used to determine if increasing symptoms or tumor growth are associated with suboptimal drug dosing.
• IMPROVING WORLDWIDE CANCER CARE AND
  PREVENTION AWARENESS
  Oncology by OncologyStat
  Elsevier’s Oncologystat.com recently upgraded its website.
  OncologySTAT's mission is to improve worldwide cancer care and prevention by providing healthcare professionals with immediate integrated access to the most authoritative evidence-based information available. OncologySTAT’s commitment to international health ensures that news, research, education, and analysis from all regions of the world are covered in a publisher, society, and sponsor-neutral online environment.
  TIP: for example, type"carcinoid tumors all sites" (or other cancers) in the advanced search window and you will receive a comprehensive list of up-to-date peer-review articles of carcinoid tumors from over 100 Elsevier cancer-related journals, including The Lancet Oncology, The Breast, Lung Cancer, The American Journal of Medicine, Cancer Letters, etc. Many articles are full text.
  
• Webcasts from NANETS Conference 2008, Southampton Bermuda "New Horizons in NET Management" are now available from their website http://nanets.net/joomla/
  Direct link to webcasts click here
  
  
ABOUT NANETS :
NANETS ( North American NeuroEndocrine Tumor Society) was established in September 2006. The purpose of this professional organization is to improve neuroendocrine tumor (NET) disease management through increased research and educational opportunities.
• Long-term survival after pancreatoduodenectomy for pancreatic adenocarcinoma: is cure possible? (Abstract)
  
  Schnelldorfer T, Ware AL, Sarr MG, Smyrk TC, Zhang L, Qin R, Gullerud RE, Donohue JH, Nagorney DM, Farnell MB.
  
  Ann Surg. 2008 Mar;247(3):456-62Division of Gastroenterologic and General Surgery; Mayo Clinic, Rochester, MN 55905, USA.
  

  CONCLUSION: Pancreatoduodenectomy for adenocarcinoma in the head of pancreas can provide long-term survival in a subset of patients, particularly in the absence of lymph node metastasis. One of 8 patients can achieve 10-year survival with a potential for cure.
  PMID: 18376190 [PubMed - indexed for MEDLINE]

• 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
  
• 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
• The European Neuroendocrine Tumor Society  ENETS held their
  FIFTH annual conference in Paris on March 6-8 2008 in Paris.
  The program  included the following topics; Test TNM cases; modeling MEN X; minimal requirements for work-up and diagnosis; pitfalls in NET diagnosis and treatment; and, inherited tumors
  The Paris meeting included two abstract sessions, one for basic science, the other for clinical research. Please continue to visit the ENETS website for more information.
  
• ENETS Consensus Guidelines for the Diagnosis and Treatment of Neuroendocrine Gastrointestinal Tumors
  Part 2 - Midgut and Hindgut Tumors
  Published in Neuroendocrinology Special Issue: 2008, Vol. 87, No. 1
  Editor(s):  de Herder, W.W. (Rotterdam);   O'Toole, D. (Dublin);   Rindi, G. (Parma);   Wiedenmann, B. (Berlin) Click on each Editors name and get additional neuroendocrine related articles.
  
  Readers will be able to find answers to debated questions for specific tumors, such as the diagnostic procedure for midgut classic carcinoids, follow-up for appendix carcinoids, or the algorithm for liver metastasis treatment of patients with extrahepatic spread from gut neuroendocrine carcinomas.
  Table of Content
  For full text articles contact CCF at   carcinoid@optonline.net
  
• 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.
• Bronchopulmonary Carcinoid: Phenotype and Long-term Outcome in a Single-Institution Series of Italian Patients
  Massimo Rugge1,4,5, Matteo Fassan1, Roberto Clemente4, Giovanna Rizzardi2, Luciano Giacomelli5, Gianmaria Pennelli1,4, Claudia Mescoli1, Daniela Segat3 and Federico Rea2
  Clinical Cancer Research 14, 149-154, January 1, 2008. doi: 10.1158/1078-0432.CCR-07-1631
  

  Requests for reprints: Massimo Rugge, Cattedra di Anatomia Patologica, Università degli Studi di Padova, Istituto Oncologico Veneto-IRCCS, Via Aristide Gabelli, 61, 35121 Padua, Italy. Phone: 39-0498-272-252; E-mail: massimo.rugge@unipd.it .

  Purpose: The histologic distinction between low-grade typical and intermediate-grade atypical bronchopulmonary carcinoids basically lies on cellular differentiation, mitotic activity, and presence of "neoplastic" necrosis; at single patient level, however, none of these features enables a reliable prediction of the clinicopathologic outcome.

  Conclusions: Mib1 and Bcl2 significantly discriminate between recurrent versus nonrecurrent tumors, producing a biologically plausible, diagnostically suitable immunohistochemical pattern.

• Neuroendocrine Tumor Cell Growth Inhibition by ZM336372 through alterations in multiple signaling pathways
  (Surgery 2007;142:959-64.)
  Kunnimalaiyaan M, Ndiaye M, Chen H. Endocrine Surgery Research Laboratories, Section of Endocrine Surgery, Department of Surgery, Madison, Wisconsin, USA. kunni@surgery.wisc.edu
  
  BACKGROUND: We have shown previously that activation of the Raf-1/mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK)1/2 signaling pathway by ZM336372 inhibits carcinoid cells growth. In the present study, we further characterize the molecular details of the growth inhibition by the signaling-based compound ZM336372 in neuroendocrine neoplasms (NENs). METHODS: NEN cells were treated with ZM336372 (20 to 100 mumol/L) or carrier (DMSO). Western Blot was used to determine the activation of the Raf-1/MEK/ERK, other pathways activation, and cellular bioactive hormone production.
  
  CONCLUSION: This is the first description of a novel compound ZM336372 that regulates multiple pathways in NEN cells.
  
• Neuroendocrine Tumors
  RADIOEMBOLIZATION FOR NEUROENDOCRINE HEPATIC METASTASES (Abstract)
  

  Andrew S. Kennedy; Richard Warner, Patrick McNeillie,

  William A. Dezarnl, Doug Coldwell, Charles Nutting , Dennis

  Carter , Ravi Murthy, Steven Rose, David Liu, Carroll

  Overton, Riad Salem
  

  Cancer Investigation, 25(S 1):55-56,2007

  ISSN: 0735-7907 print/ 1532-4192 online

  
  
• Surgery in malignant pancreatic neuroendocrine tumors.(Full text)
  Abstract
  J Surg Oncol. 2007 Oct 1;96(5):397-403
  Nguyen SQ, Angel LP, Divino CM, Schluender S, Warner RR.
  Department of Surgery, Division of General Surgery, The Mount Sinai School of Medicine, New York, New York 10029-6574, USA. scott.nguyen@mountsinai.org
  
  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.
• 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 warranted
• ENETS held its 4th Annual Conference in Barcelona, Spain, 15-17 March 2007. The conference covered topics such as the application of the ENETS Guidelines to clinical practice; rare hereditary diseases and endocrine tumors; NET imaging and surgery; and new therapies and clinical trials. A summary of this conference can be viewed in their latest NEWS LETTER.
  ENETS 2007 Consensus Guidelines for the Management pf Patients with Digestive Neuroendocrine tumors. Part1 Stomach, Duodenum and Pancreas
  For access to full text of these guidelines please contact CCF at carcinoid@carcinoid.org . Please specify which article you are interested in
• Recommendations for radioembolization of hepatic malignancies using Yttrium-90 microsphere brachytherapy.
  A consensus panel report from the radioembolization brachytherapy oncology consortium
  Int. J. Radiation Oncology Biol. Phys., Vol. 68, No. 1, pp. 13–23, 2007
  Full Text
  PURPOSE: To standardize the indications, techniques, multimodality treatment approaches, and dosimetry to be used for yttrium-90 (Y90) microsphere hepatic brachytherapy.
  METHODS AND MATERIALS: Members of the Radioembolization Brachytherapy Oncology Consortium met as an independent group of experts in interventional radiology, radiation oncology, nuclear medicine, medical oncology, and surgical oncology to identify areas of consensus and controversy and to issue clinical guidelines for Y90 microsphere brachytherapy.therapies.
  CONCLUSIONS: Yttrium-90 microsphere therapy is a complex procedure that requires multidisciplinary management for safety and success. Practitioners and cooperative groups are encouraged to use these guidelines to formulate their treatment and dose-reporting policies.
  

  

• 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.
• An aggressive approach leads to long-term survival in patients with pancreatic endocrine tumors (Abstract) for full text Click here
  Fendrich V, Langer P, Celik I, Bartsch DK, Zielke A, Ramaswamy A,
  Rothmund M
  Department of Surgery, Philipps-University Marburg, Marburg, Germany. fendrich@med.uni-marburg.de
  Ann Surg. 2006 Dec;244(6):845-51; discussion 852-3.
  OBJECTIVE: To evaluate the outcome of reoperations in patients with duodenopancreatic neuroendocrine tumors (PETs) in a tertiary referral center.
  CONCLUSIONS: We show that an aggressive surgical approach leads to long-term survival in patients with malignant PETs. Although long-term cure can only be achieved in a proportion of patients with malignant PETs, significant long-term palliation can be achieved.
•  Management of Goblet Cell Carcinoid (Full text)
  Journal of Surgical Oncology
  Volume 94, Issue 5, Date: 1 October 2006, Pages: 396-402
  John C. Byrn, Ju-Lin Wang, Celia M. Divino, Scott Q. Nguyen, Richard R.P. Warner
  
  Background and Objectives: Goblet cell carcinoid, a rare tumor of intermediate malignant potential, is known to account for a significant minority of appendiceal neoplasms. Sixteen new cases of gastrointestinal goblet cell carcinoid were reviewed to describe their presentation, treatment, and outcome.
  Conclusions: Goblet cell carcinoid is a rare malignant tumor largely affecting the appendix. In patients presenting with appendicitis, our series does not support the recommendation of right hemicolectomy based on pathologic diagnosis alone and surgical intervention must be customized to the individual patient.
  
• Liver metastases of neuroendocrine tumors; early reduction of tumour load lead to improved life expectancy.(for full text Click here) (Technical)
  Liesbeth M Veenendaal1, Inne HM Borel Rinkes1, Cornelis JM Lips2 and Richard van Hillegersberg*1 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.
  Conclusions: 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.
  



• 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 CCDRT and its use to identify the best forms of chemotherapy for cancer patients on an individual basis.
  
  

• Therapeutic Options for Gastrointestinal Carcinoids (abstract)
  Irvin M. Modlin, Igor Latich, Mark Kidd, Michelle Zikusoka, and Geeta Eick.
  Department of Surgery, Yale University School of Medicine, New Haven, Connecticut 06520-8062, USA. imodlin@optonline.net
  Clin Gastroenterol Hepatol. 2006 May;4(5):526-47.
  Full text
  Review
  
  “Sapiens nihil affirmat quod non probat
  A wise man states as true nothing he does not prove”