Login to MyKarger

New to MyKarger? Click here to sign up.



Login with Facebook

Forgot your password?

Authors, Editors, Reviewers

For Manuscript Submission, Check or Review Login please go to Submission Websites List.

Submission Websites List

Institutional Login
(Shibboleth or Open Athens)

For the academic login, please select your country in the dropdown list. You will be redirected to verify your credentials.

Original Paper

Advanced Release (accepted, unedited manuscript)

Prognostic Factors for Survival among Patients with Small Bowel Neuroendocrine Tumours Associated with Mesenteric Desmoplasia

Laskaratos F.M.a · Diamantopoulos L.a · Walker M.b · Walton H.c · Khalifa M.c · El-Khouly F.a · Koffas A.a · Demetriou G.a · Caplin M.a · Toumpanakis C.a · Mandair D.a

Author affiliations

aNeuroendocrine Tumour Unit, Centre for Gastroenterology, ENETS Centre of Excellence, Royal Free London NHS Foundation Trust, London, United Kingdom
bDepartment of Infectious Disease Epidemiology, School of Public Health, Imperial College London, London, United Kingdom
cRadiology Department, Royal Free London NHS Foundation Trust, London, United Kingdom

Related Articles for ""

Do you have an account?

Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



Login Information





Contact Information











I have read the Karger Terms and Conditions and agree.



To view the fulltext, please log in

To view the pdf, please log in

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!

If you would like to redeem your KAB credit, please log in.


Save over 20% compared to the individual article price.
Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply

Rental: USD 8.50
Cloud: USD 20.00


Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates


Select

* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: July 31, 2017
Accepted: December 05, 2017
Published online: January 10, 2018

Number of Print Pages: 15
Number of Figures: 4
Number of Tables: 5

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

Abstract

Background: Small intestinal neuroendocrine tumours (SI NETs) represent 30–50% of small bowel neoplasms and are often associated with diverse fibrotic complications. Mesenteric fibrosis is a hallmark of SI NETs which may cause substantial morbidity and is considered an adverse feature. However, survival analyses in this group of patients are lacking. Methods: The aim of this retrospective study was to determine the overall survival (OS) and factors affecting prognosis in a large cohort of 147 patients with SI NETs and radiological evidence of mesenteric desmoplasia from our centre. The severity of desmoplasia was graded radiologically and its effect on OS and long-term complications was assessed. The median follow-up period was 82 months. Results: The median OS was 8.7 years (95% CI 6.8–9.9) with an overall 5-year survival of 71%. The univariate analysis demonstrated that an age >65 years, a liver tumour burden >50% of the hepatic parenchyma, carcinoid heart disease, chromogranin A levels >10 times the upper limit of normal, and urinary 5-hydroxyindoleacetic acid (5-HIAA) levels >5 times the upper limit of normal were poor prognosticators, while primary resection was associated with a longer OS. However, only an age >65 years and urinary 5-HIAA levels >10 times the upper limit of normal remained statistically significant after multivariate analysis. The severity of mesenteric desmoplasia did not seem to demonstrate a statistically significant relationship to OS or long-term outcomes. Conclusion: This study is the first comprehensive survival analysis of patients with SI NETs associated with mesenteric desmoplasia and has provided important and clinically relevant epidemiological data for this group of patients.

© 2018 S. Karger AG, Basel


References

  1. Niederle B, Pape UF, Costa F, Gross D, Kelestimur F, Knigge U, Öberg K, Pavel M, Perren A, Toumpanakis C, O’Connor J, O’Toole D, Krenning E, Reed N, Kianmanesh R: ENETS Consensus Guidelines update for neuroendocrine neoplasms of the jejunum and ileum. Neuroendocrinology 2016; 103: 125–138.
  2. Grozinsky-Glasberg S, Grossman AB, Gross DJ: Carcinoid heart disease: from pathophysiology to treatment – “something in the way it moves.” Neuroendocrinology 2015; 101: 263–273.
  3. Pantongrag-Brown L, Buetow PC, Carr NJ, Lichtenstein JE, Buck JL: Calcification and fibrosis in mesenteric carcinoid tumor: CT findings and pathologic correlation. AJR Am J Roentgenol 1995; 164: 387–391.
  4. Druce MR, Bharwani N, Akker SA, Drake WM, Rockall A, Grossman AB: Intra-abdominal fibrosis in a recent cohort of patients with neuroendocrine (“carcinoid”) tumours of the small bowel. QJM 2010; 103: 177–185.
  5. Daskalakis K, Karakatsanis A, Stålberg P, Norlén O, Hellman P: Clinical signs of fibrosis in small intestinal neuroendocrine tumours. Br J Surg 2017; 104: 69–75.
  6. Norlén O, Stålberg P, Öberg K, Eriksson J, Hedberg J, Hessman O, Janson ET, Hellman P, Åkerström G: Long-term results of surgery for small intestinal neuroendocrine tumors at a tertiary referral center. World J Surg 2012; 36: 1419–1431.
  7. Rodríguez Laval V, Pavel M, Steffen IG, Baur AD, Dilz LM, Fischer C, Detjen K, Prasad V, Pascher A, Geisel D, Denecke T: Mesenteric fibrosis in midgut neuroendocrine tumors: functionality and radiological features. Neuroendocrinology 2017, Epub ahead of print.
  8. Bosman FT, Carneiro F, Hruban RH, Theise ND: WHO Classification of Tumours of the Digestive System, ed 4. Lyon, IARC, 2010.
  9. Rindi G, Klöppel G, Couvelard A, Komminoth P, Körner M, Lopes J, McNicol A, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B: TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Arch 2007; 451: 757–762.
  10. Collett D: Modelling Survival Data in Medical Research. London, Chapman & Hall, 2003.
  11. McCullagh P, Nelder, JA: Generalized Linear Models. London, Chapman & Hall, 1989.
  12. Modlin IM, Lye KD, Kidd M: A 5-decade analysis of 13,715 carcinoid tumors. Cancer 2003; 97: 934–959.
  13. Toumpanakis C, Vlachou E, Ramakrishnan S, Phillips E, Wilkins D, Tuck A, Gertner J, Garcia-Hernandez J, Theocharidou E, Caplin M: Predictive factors for survival in patients with advanced small bowel neuroendocrine tumours. Gastroenterology 2016; 150(suppl 1): S207.
  14. Zar N, Garmo H, Holmberg L, Rastad J, Hellman P: Long-term survival of patients with small intestinal carcinoid tumors. World J Surg 2004; 28: 1163–1168.
  15. Strosberg J, Gardner N, Kvols L: Survival and prognostic factor analysis of 146 metastatic neuroendocrine tumors of the mid-gut. Neuroendocrinology 2009; 89: 471–476.
  16. Söreide JA, van Heerden JA, Thompson GB, Schleck C, Ilstrup DM, Churchward M: Gastrointestinal carcinoid tumors: long-term prognosis for surgically treated patients. World J Surg 2000; 24: 1431–1436.
  17. Bergestuen DS, Aabakken L, Holm K, Vatn M, Thiis-Evensen E: Small intestinal neuroendocrine tumors: prognostic factors and survival. Scand J Gastroenterol 2009; 44: 1084–1091.
  18. Landry CS, Brock G, Scoggins CR, McMasters KM, Martin RC 2nd: A proposed staging system for small bowel carcinoid tumors based on an analysis of 6,380 patients. Am J Surg 2008; 196: 896–903.
  19. Curran T, Tulin-Silver S, Patel K, Ward S, Schneiderman M, Harpaz N, Schwartz M, Itzkowitz S, Warner RR, Kim MK: Prognostic clinicopathologic factors in longitudinally followed patients with metastatic small bowel carcinoid tumors. Pancreas 2011; 40: 1253–1257.
  20. van der Horst-Schrivers AN, Post WJ, Kema IP, Links TP, Willemse PH, Wymenga AN, de Vries EG: Persistent low urinary excretion of 5-HIAA is a marker for favourable survival during follow-up in patients with disseminated midgut carcinoid tumours. Eur J Cancer 2007; 43: 2651–2657.
  21. Ahmed A, Turner G, King B, Jones L, Culliford D, McCance D, Ardill J, Johnston BT, Poston G, Rees M, Buxton-Thomas M, Caplin M, Ramage JK: Midgut neuroendocrine tumours with liver metastases: results of the UKINETS study. Endocr Relat Cancer 2009; 16: 885–894.
  22. Turner GB, Johnston BT, McCance DR, McGinty A, Watson RG, Patterson CC, Ardill JE: Circulating markers of prognosis and response to treatment in patients with midgut carcinoid tumours. Gut 2006; 55: 1586–1591.
  23. Westberg G, Wängberg B, Ahlman H, Bergh CH, Beckman-Suurküla M, Caidahl K: Prediction of prognosis by echocardiography in patients with midgut carcinoid syndrome. Br J Surg 2001; 88: 865–872.
  24. Tomassetti P, Campana D, Piscitelli L, Casadei R, Nori F, Brocchi E, Santini D, Pezzilli R, Corinaldesi R: Endocrine tumors of the ileum: factors correlated with survival. Neuroendocrinology 2006; 83: 380–386.
  25. Burke AP, Thomas RM, Elsayed AM, Sobin LH: Carcinoids of the jejunum and ileum: an immunohistochemical and clinicopathologic study of 167 cases. Cancer 1997; 79: 1086–1093.
  26. Janson ET, Holmberg L, Stridsberg M, Eriksson B, Theodorsson E, Wilander E, Öberg K: Carcinoid tumors: analysis of prognostic factors and survival in 301 patients from a referral center. Ann Oncol 1997; 8: 685–690.
  27. Hellman P, Lundström T, Öhrvall U, Eriksson B, Skogseid B, Öberg K, Tiensuu Janson E, Åkerström G: Effect of surgery on the outcome of midgut carcinoid disease with lymph node and liver metastases. World J Surg 2002; 26: 991–997.
  28. Nykjaer KM, Grønbaek H, Nielsen DT, Christiansen P, Astrup LB: Description of patients with midgut carcinoid tumours: clinical database from a Danish centre. In Vivo 2007; 21: 679–684.
  29. Landerholm K, Zar N, Andersson RE, Falkmer SE, Järhult J: Survival and prognostic factors in patients with small bowel carcinoid tumour. Br J Surg 2011; 98: 1617–1624.
  30. Khan MS, Kirkwood A, Tsigani T, Garcia-Hernandez J, Hartley JA, Caplin ME, Meyer T: Circulating tumor cells as prognostic markers in neuroendocrine tumors. J Clin Oncol 2013; 31: 365–372.
  31. Khan MS, Luong TV, Watkins J, Toumpanakis C, Caplin ME, Meyer T: A comparison of Ki-67 and mitotic count as prognostic markers for metastatic pancreatic and midgut neuroendocrine neoplasms. Br J Cancer 2013; 108: 1838–1845.
  32. Cadden I, Johnston BT, Turner G, McCance D, Ardill J, McGinty A: An evaluation of cyclooxygenase-2 as a prognostic biomarker in mid-gut carcinoid tumours. Neuroendocrinology 2007; 86: 104–111.
  33. Cunningham JL, Grimelius L, Sundin A, Agarwal S, Janson ET: Malignant ileocaecal serotonin-producing carcinoid tumours: the presence of a solid growth pattern and/or Ki67 index above 1% identifies patients with a poorer prognosis. Acta Oncol 2007; 46: 747–756.
  34. Jann H, Roll S, Couvelard A, Hentic O, Pavel M, Müller-Nordhorn J, Koch M, Röcken C, Rindi G, Ruszniewski P, Wiedenmann B, Pape UF: Neuroendocrine tumors of midgut and hindgut origin: tumor-node-metastasis classification determines clinical outcome. Cancer 2011; 117: 3332–3341.
  35. Woltering EA, Voros BA, Beyer DT, Wang YZ, Thiagarajan R, Ryan P, Wright A, Ramirez RA, Ricks MJ, Boudreaux JP: Aggressive surgical approach to the management of neuroendocrine tumors: a report of 1,000 surgical cytoreductions by a single institution. J Am Coll Surg 2017; 224: 434–447.
  36. Landry CS, Lin HY, Phan A, Charnsangavej C, Abdalla EK, Aloia T, Nicolas Vauthey J, Katz MH, Yao JC, Fleming JB: Resection of at-risk mesenteric lymph nodes is associated with improved survival in patients with small bowel neuroendocrine tumors. World J Surg 2013; 37: 1695–1700.
  37. Modlin IM, Gustafsson BI, Pavel M, Svejda B, Lawrence B, Kidd M: A nomogram to assess small-intestinal neuroendocrine tumor (“carcinoid”) survival. Neuroendocrinology 2010; 92: 143–157.
  38. Clift AK, Faiz O, Goldin R, Martin J, Wasan H, Liedke MO, Schloericke E, Malczewska A, Rindi G, Kidd M, Modlin IM, Frilling A: Predicting the survival of patients with small bowel neuroendocrine tumours: comparison of 3 systems. Endocr Connect 2017; 6: 71–81.
  39. Gustafsson BI, Hauso O, Drozdov I, Kidd M, Modlin IM: Carcinoid heart disease. Int J Cardiol 2008; 129: 318–324.
  40. Makridis C, Ekbom A, Bring J, Rastad J, Juhlin C, Öberg K, Åkerström G: Survival and daily physical activity in patients treated for advanced midgut carcinoid tumors. Surgery 1997; 122: 1075–1082.
  41. Dumoulein M, Verslype C, van Cutsem E, Meuris B, Herijgers P, Flameng W, Herregods MC: Carcinoid heart disease: case and literature review. Acta Cardiol 2010; 65: 261–264.
  42. Korse CM, Taal BG, de Groot CA, Bakker RH, Bonfrer JM: Chromogranin-A and N-terminal pro-brain natriuretic peptide: an excellent pair of biomarkers for diagnostics in patients with neuroendocrine tumor. J Clin Oncol 2009; 27: 4293–4299.
  43. Møller JE, Pellikka PA, Bernheim AM, Schaff HV, Rubin J, Connolly HM: Prognosis of carcinoid heart disease: analysis of 200 cases over two decades. Circulation 2005; 112: 3320–3327.
  44. Modlin IM, Shapiro MD, Kidd M: Carcinoid tumors and fibrosis: an association with no explanation. Am J Gastroenterol 2004; 99: 2466–2478.
  45. Laskaratos FM, Rombouts K, Caplin M, Toumpanakis C, Thirlwell C, Mandair D: Neuroendocrine tumors and fibrosis: an unsolved mystery? Cancer 2017; 123: 4770–4790.
  46. Svejda B, Kidd M, Giovinazzo F, Eltawil K, Gustafsson BI, Pfragner R, Modlin IM: The 5-HT2B receptor plays a key regulatory role in both neuroendocrine tumor cell proliferation and the modulation of the fibroblast component of the neoplastic microenvironment. Cancer 2010; 116: 2902–2912.
  47. Kidd M, Modlin I, Shapiro M, Camp R, Mane S, Usinger W, Murren J: CTGF, intestinal stellate cells and carcinoid fibrogenesis. World J Gastroenterol 2007; 13: 5208–5216.

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: July 31, 2017
Accepted: December 05, 2017
Published online: January 10, 2018

Number of Print Pages: 15
Number of Figures: 4
Number of Tables: 5

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN


Copyright / Drug Dosage / Disclaimer

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.