Seltene Tumoren des Gastrointestinaltraktes beim alten und geriatrischen Patienten (NET, GIST)

  • Michael Rassner
  • Harald Lahner
  • Nikolas von Bubnoff
  • Frank Lammert
Chapter
Part of the Springer Reference Medizin book series (SRM)

Zusammenfassung

Die häufigsten mesenchymalen Tumoren des Gastrointestinaltrakts bei geriatrischen Patienten sind gastrointestinale Stromatumoren (GIST) und Leiomyome. Die Behandlung erfolgt individualisiert, wobei Imatinib wie bei jüngeren Patienten eine wichtige Option in der postoperativen und palliativen Therapie darstellt. Zu beachten sind insbesondere Komorbiditäten sowie unerwünschte Arzneimittelwirkungen und -interaktionen. Submuköse Tumoren (Lipome, Leiomyome, Granularzelltumoren) werden in Abhängigkeit von der Histologie beobachtet oder endoskopisch bzw. chirurgisch therapiert. Die neuroendokrine Tumoren (NET) können aufgrund ihrer hormoneller Aktivität und eines Karzinoid-Syndroms symptomatisch werden. Das Therapiekonzept besteht führend aus der chirurgischen Resektion und dem Einsatz von Somatostatin-Analoga bei Somatostatinrezeptor-positiven Tumoren. Bei fortgeschrittenen Tumoren werden auch bei älteren Patienten neue Substanzen wie Everolimus oder Multikinaseinhibitoren eingesetzt.

Literatur

  1. Abraham SC, Krasinskas AM, Hofstetter WL, Swisher SG, Wu T-T (2007) „Seedling“ mesenchymal tumors (gastrointestinal stromal tumors and leiomyomas) are common incidental tumors of the esophagogastric junction. Am J Surg Pathol 31:1629–1635PubMedCrossRefGoogle Scholar
  2. Abrikossoff AI (1926) Über Myome, ausgehend von der quergestreiften willkürlichen Muskulatur. Virchows Arch Pathol Anat 260:214–233CrossRefGoogle Scholar
  3. Aggarwal G, Sharma S, Zheng M, Reid MD, Crosby JH, Chamberlain SM, Nayak-Kapoor A, Lee JR (2012) Primary leiomyosarcomas of the gastrointestinal tract in the post-gastrointestinal stromal tumor era. Ann Diagn Pathol 16:532–540PubMedCrossRefGoogle Scholar
  4. Akahoshi K, Oya M, Koga T, Koga H, Motomura Y, Kubokawa M, Gibo J, Nakamura K (2014) Clinical usefulness of endoscopic ultrasound-guided fine needle aspiration for gastric subepithelial lesions smaller than 2 cm. J Gastrointest Liver Dis JGLD 23:405–412Google Scholar
  5. American Gastroenterological Association (AGA) (2006) Medical position statement on the management of gastric subepithelial masses. Gastroenterology 130(7):2215–2216CrossRefGoogle Scholar
  6. Attila T, Faigel DO (2011) Endoscopic ultrasound in patients over 80 years old. Dig Dis Sci 56:3065–3071PubMedCrossRefGoogle Scholar
  7. Bainbridge HE, Larbi E, Middleton G (2015) Symptomatic control of neuroendocrine tumours with everolimus. Horm Cancer 6:254–259PubMedCrossRefGoogle Scholar
  8. Barajas-Gamboa JS, Acosta G, Savides TJ, Sicklick JK, Fehmi SMA, Coker AM, Green S, Broderick R, Nino DF, Harnsberger CR, Berducci MA, Sandler BJ, Talamini MA, Jacobsen GR, Horgan S (2015) Laparo-endoscopic transgastric resection of gastric submucosal tumors. Surg Endosc 29:2149–2157PubMedCrossRefGoogle Scholar
  9. Begum N, Maasberg S, Plöckinger U, Anlauf M, Rinke A, Pöpperl G, Lehnert H, Izbicki JR, Krausch M, Vashist YK, Raffel A, Bürk CG, Hoffmann J, Goretzki P, Pape UF, Weitere Vertreter des deutschen NET-Registers (2014) Neuroendokrine Tumoren des Verdauungstrakts – Daten des deutschen NET-Registers. Zentralbl Chir 139(3):276–283PubMedGoogle Scholar
  10. Bettini R et al (2011) Tumor size correlates with malignancy in nonfunctioning pancreatic endocrine tumor. Surgery 150(1):75–82PubMedCrossRefGoogle Scholar
  11. Bilimoria KY, Bentrem DJ, Wayne JD, Ko CY, Bennett CL, Talamonti MS (2009) Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years. Ann Surg 249:63–71PubMedCrossRefGoogle Scholar
  12. Boden RA, Clark MA, Neuhaus SJ, A’hern JR, Thomas JM, Hayes AJ (2006) Surgical management of soft tissue sarcoma in patients over 80 years. Eur J Surg Oncol 32(10):1154–1158PubMedCrossRefGoogle Scholar
  13. Borch K, Ahrén B, Ahlman H, Falkmer S, Granérus G, Grimelius L (2005) Gastric carcinoids: biologic behavior and prognosis after differentiated treatment in relation to type. Ann Surg 242(1):64–73PubMedPubMedCentralCrossRefGoogle Scholar
  14. Bosman FT, World Health Organization, International Agency for Research on Cancer (2010) WHO classification of tumours of the digestive system, 4. Aufl, World Health Organization classification of tumours. International Agency for Research on Cancer, Lyon, 417 pGoogle Scholar
  15. Brämswig K, Ploner F, Martel A, Bauernhofer T, Hilbe W, Kühr T, Leitgeb C, Mlineritsch B, Petzer A, Seebacher V, Stöger H, Girschikofsky M, Hochreiner G, Ressler S, Romeder F, Wöll E, Brodowicz T (2014) Sorafenib in advanced, heavily pretreated patients with soft tissue sarcomas. Anticancer Drugs 25:848–853PubMedCrossRefGoogle Scholar
  16. Brudvik KW, Patel SH, Roland CL, Conrad C, Torres KE, Hunt KK, Cormier JN, Feig BW, Aloia TA, Vauthey J-N (2015) Survival after resection of gastrointestinal stromal tumor and sarcoma liver metastases in 146 patients. J Gastrointest Surg Off J Soc Surg Aliment Tract 19:1476–1483CrossRefGoogle Scholar
  17. Bushnell DL, O’Dorisio TM, O’Dorisio MS, Menda Y, Hicks RJ, Van Cutsem E, Baulieu J-L, Borson-Chazot F, Anthony L, Benson AB, Oberg K, Grossman AB, Connolly M, Bouterfa H, Li Y, Kacena KA, LaFrance N, Pauwels SA (2010) 90Y-edotreotide for metastatic carcinoid refractory to octreotide. J Clin Oncol Off J Am Soc Clin Oncol 28:1652–1659CrossRefGoogle Scholar
  18. Caplin ME, Pavel M, Ćwikła JB, Phan AT, Raderer M, Sedláčková E, Cadiot G, Wolin EM, Capdevila J, Wall L, Rindi G, Langley A, Martinez S, Blumberg J, Ruszniewski P (2014) Lanreotide in metastatic enteropancreatic neuroendocrine tumors. N Engl J Med 371:224–233PubMedCrossRefGoogle Scholar
  19. Chen T, Yao L-Q, Xu M-D, Zhang Y-Q, Chen W-F, Shi Q, Cai S-L, Chen Y-Y, Xie Y-H, Ji Y, Chen S-Y, Zhou P-H, Zhong Y-S (2016) Efficacy and safety of endoscopic submucosal dissection for colorectal carcinoids. Clin Gastroenterol Hepatol Off Clin Pract J Am Gastroenterol Assoc 14:575–581Google Scholar
  20. Cheslyn-Curtis S, Sitaram V, Williamson RC (1993) Management of non-functioning neuroendocrine tumours of the pancreas. Br J Surg 80(5):625–627PubMedCrossRefGoogle Scholar
  21. Chou FF, Eng HL, Sheen-Chen SM (1996) Smooth muscle tumors of the gastrointestinal tract: analysis of prognostic factors. Surgery 119:171–177PubMedCrossRefGoogle Scholar
  22. Chu QD et al (2002) Predictive factors associated with long-term survival in patients with neuroendocrine tumors of the pancreas. Ann Surg Oncol 9(9):855–862PubMedCrossRefGoogle Scholar
  23. Cohen MJ, Bloom AI, Barak O, Klimov A, Nesher T, Shouval D, Levi I, Shibolet O (2013) Trans-arterial chemo-embolization is safe and effective for very elderly patients with hepatocellular carcinoma. World J Gastroenterol 19:2521–2528PubMedPubMedCentralCrossRefGoogle Scholar
  24. Crippa S et al (2014) Incidental diagnosis as prognostic factor in different tumor stages of nonfunctioning pancreatic endocrine tumors. Surgery 155(1):145–153PubMedCrossRefGoogle Scholar
  25. De Herder WW, Rehfeld JF, Kidd M, Modlin IM (2016) A short history of neuroendocrine tumours and their peptide hormones. Best Pract Res Clin Endocrinol Metab 30:3–17PubMedCrossRefGoogle Scholar
  26. Dematteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF (2000) Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 231(1):51–58PubMedPubMedCentralCrossRefGoogle Scholar
  27. Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, Demetri GD, Blackstein ME, Blanke CD, von Mehren M, Brennan MF, Patel S, McCarter MD, Polikoff JA, Tan BR, Owzar K, American College of Surgeons Oncology Group (ACOSOG) Intergroup Adjuvant GIST Study Team (2009) Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 373(9669):1097–1104PubMedPubMedCentralCrossRefGoogle Scholar
  28. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M, Fletcher JA, Silverman SG, Silberman SL, Capdeville R, Kiese B, Peng B, Dimitrijevic S, Druker BJ, Corless C, Fletcher CD, Joensuu H (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347(7):472–480PubMedCrossRefGoogle Scholar
  29. Demetri GD, von Mehren M, Jones RL, Hensley ML, Schuetze S, Staddon AP, Milhem MM, Elias AD, Ganjoo KN, Tawbi HA-H, Van Tine BA, Spira AI, Dean AP, Khokhar NZ, Park YC, Knoblauch RE, Parekh TV, Maki RG, Patel S (2015) A randomized phase III study of trabectedin (T) or dacarbazine (D) for the treatment of patients (pts) with advanced liposarcoma (LPS) or leiomyosarcoma (LMS). J Clin Oncol 33(15 Suppl)Google Scholar
  30. Deshpande A, Nelson D, Corless CL, Deshpande V, O’Brien MJ (2014) Leiomyoma of the gastrointestinal tract with interstitial cells of cajal: a mimic of gastrointestinal stromal tumor. Am J Surg Pathol 38:72–77PubMedCrossRefGoogle Scholar
  31. Edris B, Espinosa I, Mühlenberg T, Mikels A, Lee C-H, Steigen SE, Zhu S, Montgomery KD, Lazar AJF, Lev D, Fletcher JA, Beck AH, West RB, Nusse R, van de Rijn M (2012) ROR2 is a novel prognostic biomarker and a potential therapeutic target in leiomyosarcoma and gastrointestinal stromal tumour. J Pathol 227:223–233PubMedPubMedCentralCrossRefGoogle Scholar
  32. Ellis L, Shale MJ, Coleman MP (2010) Carcinoid tumors of the gastrointestinal tract: trends in incidence in England since 1971. Am J Gastroenterol 105(12):2563–2569PubMedCrossRefGoogle Scholar
  33. Eriksson B et al (2008) Consensus guidelines for the management of patients with digestive neuroendocrine tumors – well-differentiated jejunal-ileal tumor/carcinoma. Neuroendocrinology 87(1):8–19PubMedCrossRefGoogle Scholar
  34. ESMO/European Sarcoma Network Working Group (2014) Gastrointestinal stromal tumours: ESMO clinical practice guidelines. Ann Oncol 25(Suppl 3):iii21–iii26CrossRefGoogle Scholar
  35. Faiss S, Pape U-F, Böhmig M, Dörffel Y, Mansmann U, Golder W, Riecken EO, Wiedenmann B, International Lanreotide and Interferon Alfa Study Group (2003) Prospective, randomized, multicenter trial on the antiproliferative effect of lanreotide, interferon alfa, and their combination for therapy of metastatic neuroendocrine gastroenteropancreatic tumors – the International Lanreotide and Interferon Alfa Study Group. J Clin Oncol Off J Am Soc Clin Oncol 21:2689–2696CrossRefGoogle Scholar
  36. Falconi M et al (2006) Well-differentiated pancreatic nonfunctioning tumors/carcinoma. Neuroendocrinology 84(3):196–211PubMedCrossRefGoogle Scholar
  37. Falconi M et al (2016) Consensus Guidelines Update for the Management of Functional p-NETs (F-p-NETs) and Non-Functional p-NETs (NF-p-NETs). NeuroendocrinologyGoogle Scholar
  38. Fjallskog ML et al (2008) Treatment with combined streptozotocin and liposomal doxorubicin in metastatic endocrine pancreatic tumors. Neuroendocrinology 88(1):53–58PubMedCrossRefGoogle Scholar
  39. Garbay D, Maki RG, Blay JY, Isambert N, Piperno Neumann S, Blay C, Zanardi E, Boudou-Rouquette P, Bozec L, Duffaud F, Bertucci F, Italiano A (2013) Advanced soft-tissue sarcoma in elderly patients: patterns of care and survival. Ann Oncol 24(7):1924–1930PubMedCrossRefGoogle Scholar
  40. Grozinsky-Glasberg S, Thomas D, Strosberg JR, Pape UF, Felder S, Tsolakis AV, Alexandraki KI, Fraenkel M, Saiegh L, Reissman P, Kaltsas G, Gross DJ (2013) Metastatic type 1 gastric carcinoid: a real threat or just a myth? World J Gastroenterol 19(46):8687–8695PubMedPubMedCentralCrossRefGoogle Scholar
  41. Halfdanarson TR et al (2008) Pancreatic neuroendocrine tumors (PNETs): incidence, prognosis and recent trend toward improved survival. Ann Oncol 19(10):1727–1733PubMedPubMedCentralCrossRefGoogle Scholar
  42. Hamada T, Yasunaga H, Nakai Y, Isayama H, Horiguchi H, Matsuda S, Fushimi K, Koike K (2013) Rarity of severe bleeding and perforation in endoscopic ultrasound-guided fine needle aspiration for submucosal tumors. Dig Dis Sci 58:2634–2638PubMedCrossRefGoogle Scholar
  43. Hamed MO, Roberts KJ, Merchant W, Lodge JPA (2015) Contemporary management and classification of hepatic leiomyosarcoma. HPB 17:362–367PubMedCrossRefGoogle Scholar
  44. Hassan MM, Phan A, Li D, Dagohoy CG, Leary C, Yao JC (2008) Risk factors associated with neuroendocrine tumors: a U.S.-based case–control study. Int J Cancer 123(4):867–873PubMedCrossRefGoogle Scholar
  45. Hernando E, Charytonowicz E, Dudas ME, Menendez S, Matushansky I, Mills J, Socci ND, Behrendt N, Ma L, Maki RG, Pandolfi PP, Cordon-Cardo C (2007) The AKT-mTOR pathway plays a critical role in the development of leiomyosarcomas. Nat Med 13:748–753PubMedCrossRefGoogle Scholar
  46. Hilal L, Barada K, Mukherji D, Temraz S, Shamseddine A (2016) Gastrointestinal (GI) leiomyosarcoma (LMS) case series and review on diagnosis, management, and prognosis. Med Oncol Northwood Lond Engl 33:20CrossRefGoogle Scholar
  47. Hill MA, Gong C, Casey TJ, Menon AG, Mera R, Gillespie AT, Giardina JF, Levine EA, Hunt JD (1997) Detection of K-ras mutations in resected primary leiomyosarcoma. Cancer Epidemiol Biomark Prev Publ Am Assoc Cancer Res Cosponsored Am Soc Prev Oncol 6:1095–1100Google Scholar
  48. Hörsch D, Ezziddin S, Haug A, Gratz KF, Dunkelmann S, Miederer M, Schreckenberger M, Krause BJ, Bengel FM, Bartenstein P, Biersack H-J, Pöpperl G, Baum RP (2016) Effectiveness and side-effects of peptide receptor radionuclide therapy for neuroendocrine neoplasms in Germany: a multi-institutional registry study with prospective follow-up. Eur J Cancer Oxf Engl 1990(58):41–51CrossRefGoogle Scholar
  49. Huang L-Y (2014) Endoscopic full-thickness resection and laparoscopic surgery for treatment of gastric stromal tumors. World J Gastroenterol 20:8253PubMedPubMedCentralCrossRefGoogle Scholar
  50. Hwang JH, Saunders MD, Rulyak SJ, Shaw S, Nietsch H, Kimmey MB (2005) A prospective study comparing endoscopy and EUS in the evaluation of GI subepithelial masses. Gastrointest Endosc 62:202–208PubMedCrossRefGoogle Scholar
  51. Imhof A, Brunner P, Marincek N, Briel M, Schindler C, Rasch H, Mäcke HR, Rochlitz C, Müller-Brand J, Walter MA (2011) Response, survival, and long-term toxicity after therapy with the radiolabeled somatostatin analogue (90Y-DOTA)-TOC in metastasized neuroendocrine cancers. J Clin Oncol Off J Am Soc Clin Oncol 29:2416–2423CrossRefGoogle Scholar
  52. Italiano A, Saada E, Cioffi A, Poulette S, Bouchet S, Molimard M, Adenis A, Isambert N, Collard O, Le Cesne A, Maki RG, Bui B (2013) Treatment of advanced gastrointestinal stromal tumors in patients over 75 years old: clinical and pharmacological implications. Target Oncol 8(4):295–300PubMedCrossRefGoogle Scholar
  53. Joensuu H, Eriksson M, Sundby Hall K, Reichardt A, Hartmann JT, Pink D, Ramadori G, Hohenberger P, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Nilsson B, Sihto H, Bono P, Kallio R, Junnila J, Alvegård T, Reichardt P (2016) Adjuvant imatinib for high-risk GI stromal tumor: analysis of a randomized trial. J Clin Oncol 34(3):244–250PubMedCrossRefGoogle Scholar
  54. Karavasilis V, Seddon BM, Ashley S, Al-Muderis O, Fisher C, Judson I (2008) Significant clinical benefit of first-line palliative chemotherapy in advanced soft-tissue sarcoma: retrospective analysis and identification of prognostic factors in 488 patients. Cancer 112:1585–1591PubMedCrossRefGoogle Scholar
  55. Katai H, Sasako M, Sano T, Maruyama K (1998) Surgical treatment for gastric leiomyosarcoma. Ann Chir Gynaecol 87:293–296PubMedGoogle Scholar
  56. Kato T, Noda H, Abe I, Alonso S, Yokoyama N, Rikiyama T (2016) Curative resection for leiomyosarcoma of the descending mesocolon with metachronous liver metastasis: a case report and literature review. Mol Clin Oncol 5:53–56PubMedPubMedCentralCrossRefGoogle Scholar
  57. Kawanowa K, Sakuma Y, Sakurai S, Hishima T, Iwasaki Y, Saito K, Hosoya Y, Nakajima T, Funata N (2006) High incidence of microscopic gastrointestinal stromal tumors in the stomach. Hum Pathol 37:1527–1535PubMedCrossRefGoogle Scholar
  58. Kim GH, Park DY, Kim S, Kim DH, Kim DH, Choi CW, Heo J, Song GA (2009) Is it possible to differentiate gastric GISTs from gastric leiomyomas by EUS? World J. Gastroenterol 15:3376–3381Google Scholar
  59. Kim GH, Kim JI, Jeon SW, Moon JS, Chung IK, Jee SR, Kim HU, Seo GS, Baik GH, Lee YC, Korean College of Helicobacter and Upper Gastrointestinal Research (2014) Endoscopic resection for duodenal carcinoid tumors: a multicenter, retrospective study. J Gastroenterol Hepatol 29(2):318–324PubMedCrossRefGoogle Scholar
  60. King J, Quinn R, Glenn DM, Janssen J, Tong D, Liaw W, Morris DL (2008) Radioembolization with selective internal radiation microspheres for neuroendocrine liver metastases. Cancer 113:921–929PubMedCrossRefGoogle Scholar
  61. Kölby L, Persson G, Franzén S, Ahrén B (2003) Randomized clinical trial of the effect of interferon alpha on survival in patients with disseminated midgut carcinoid tumours. Br J Surg 90:687–693PubMedCrossRefGoogle Scholar
  62. Kouvaraki MA et al (2004) Fluorouracil, doxorubicin, and streptozocin in the treatment of patients with locally advanced and metastatic pancreatic endocrine carcinomas. J Clin Oncol 22(23):4762–4771PubMedCrossRefGoogle Scholar
  63. Kumar R, Sharma P, Singh H, Bal C (2014) PET/CT imaging of neuroendocrine tumors with 68 Gallium-labeled somatostatin analogues: an overview and single institutional experience from India. Indian J Nucl Med 29:2PubMedPubMedCentralCrossRefGoogle Scholar
  64. Kuo EJ, Salem RR (2013) Population-level analysis of pancreatic neuroendocrine tumors 2cmor less in size. Ann Surg Oncol 20(9):2815–2821PubMedCrossRefGoogle Scholar
  65. Kvols LK (1994) Metastatic carcinoid tumors and the malignant carcinoid syndrome. Ann N Y Acad Sci 733:464–470PubMedCrossRefGoogle Scholar
  66. Lamarca A, Barriuso J, McNamara MG, Hubner RA, Valle JW (2016) Telotristat ethyl: a new option for the management of carcinoid syndrome. Expert Opin Pharmacother 17:2487–2498PubMedCrossRefGoogle Scholar
  67. Landerholm K, Falkmer S, Järhult J (2010) Epidemiology of small bowel carcinoids in a defined population. World J Surg 34:1500–1505PubMedCrossRefGoogle Scholar
  68. Landerholm K, Zar N, Andersson RE, Falkmer SE, Järhult J (2011) Survival and prognostic factors in patients with small bowel carcinoid tumour. Br J Surg 98:1617–1624PubMedCrossRefGoogle Scholar
  69. Lee LC et al (2012) Small, nonfunctioning, asymptomatic pancreatic neuroendocrine tumors (PNETs): role for nonoperative management. Surgery 152(6):965–974PubMedCrossRefGoogle Scholar
  70. Lee M, Min B-H, Lee H, Ahn S, Lee JH, Rhee P-L, Kim JJ, Sohn TS, Kim S, Kim K-M (2015) Feasibility and diagnostic yield of endoscopic ultrasonography-guided fine needle biopsy with a new core biopsy needle device in patients with gastric subepithelial tumors. Medicine (Baltimore) 94, e1622CrossRefGoogle Scholar
  71. Lee SH, Ha HK, Byun JY, Kim AY, Cho KS, Lee YR, Park HW, Kim PN, Lee MG, Auh YH (2000) Radiological features of leiomyomatous tumors of the colon and rectum. J Comput Assist Tomogr 24:407–412PubMedCrossRefGoogle Scholar
  72. Levy MJ, Abu Dayyeh BK, Fujii LL, Boardman LA, Clain JE, Iyer PG, Rajan E, Topazian MD, Wang KK, Wiersema MJ, Gleeson FC (2014) Prospective evaluation of adverse events following lower gastrointestinal tract EUS FNA. Am J Gastroenterol 109:676–685PubMedCrossRefGoogle Scholar
  73. Luis J, Ejtehadi F, Howlett DC, Donnellan IM (2015) Leiomyosarcoma of the small bowel: report of a case and review of the literature. Int J Surg Case Rep 6C:51–54PubMedCrossRefGoogle Scholar
  74. Madura JA et al (1997) Nonfunctioning islet cell tumors of the pancreas: a difficult diagnosis but one worth the effort. Am Surg 63(7):573–577; discussion 577–578PubMedGoogle Scholar
  75. Mahmood ST, Agresta S, Vigil CE, Zhao X, Han G, D’Amato G, Calitri CE, Dean M, Garrett C, Schell MJ, Antonia S, Chiappori A (2011) Phase II study of sunitinib malate, a multitargeted tyrosine kinase inhibitor in patients with relapsed or refractory soft tissue sarcomas. Focus on three prevalent histologies: leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma. Int J Cancer 129:1963–1969PubMedPubMedCentralCrossRefGoogle Scholar
  76. Matthews BD et al (2000) Surgical experience with nonfunctioning neuroendocrine tumors of the pancreas. Am Surg 66(12):1116–1122; discussion 1122–1123PubMedGoogle Scholar
  77. Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J (2000) Gastrointestinal stromal tumors and leiomyosarcomas in the colon: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases. Am J Surg Pathol 24:1339–1352PubMedCrossRefGoogle Scholar
  78. Miller MD, Paradis CF, Houck PR, Mazumdar S, Stack JA, Rifai AH, Mulsant B, Reynolds CF (1992) Rating chronic medical illness burden in geropsychiatric practice and research: application of the Cumulative Illness Rating Scale. Psychiatry Res 41(3):237–248PubMedCrossRefGoogle Scholar
  79. Mir O, Brodowicz T, Italiano A, Wallet J, Blay J-Y, Bertucci F, Chevreau C, Piperno-Neumann S, Bompas E, Salas S, Perrin C, Delcambre C, Liegl-Atzwanger B, Toulmonde M, Dumont S, Ray-Coquard I, Clisant S, Taieb S, Guillemet C, Rios M, Collard O, Bozec L, Cupissol D, Saada-Bouzid E, Lemaignan C, Eisterer W, Isambert N, Chaigneau L, Cesne AL, Penel N (2016) Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Oncol.  https://doi.org/10.1016/S1470-2045(16)30507-1Google Scholar
  80. Mitry E, Walter T, Baudin E, Kurtz J-E, Ruszniewski P, Dominguez-Tinajero S, Bengrine-Lefevre L, Cadiot G, Dromain C, Farace F, Rougier P, Ducreux M (2014) Bevacizumab plus capecitabine in patients with progressive advanced well-differentiated neuroendocrine tumors of the gastro-intestinal (GI-NETs) tract (BETTER trial) – a phase II non-randomised trial. Eur J Cancer Oxf Engl 1990(50):3107–3115CrossRefGoogle Scholar
  81. Moertel CG et al (1992) Streptozocin-doxorubicin, streptozocin-fluorouracil or chlorozotocin in the treatment of advanced islet-cell carcinoma. N Engl J Med 326(8):519–523PubMedCrossRefGoogle Scholar
  82. Modlin IM et al (2010a) Review article: somatostatin analogues in the treatment of gastroenteropancreatic neuroendocrine (carcinoid) tumours. Aliment Pharmacol Ther 31(2):169–188PubMedGoogle Scholar
  83. Modlin IM, Gustafsson BI, Moss SF, Pavel M, Tsolakis AV, Kidd M (2010b) Chromogranin A – biological function and clinical utility in neuro endocrine tumor disease. Ann Surg Oncol 17:2427–2443PubMedCrossRefGoogle Scholar
  84. Molinas Mandel N, Selcukbiricik M, Kanitez M, Yalcin S, Tural D, Erdamar S, Dogusoy G, Demir G (2016) Clinical and pathological characteristics and their effect on survival in elderly patients with gastrointestinal stromal tumors. J BUON 21(2):360–365PubMedGoogle Scholar
  85. Mucciarini C, Rossi G, Bertolini F, Valli R, Cirilli C, Rashid I, Marcheselli L, Luppi G, Federico M (2007) Incidence and clinicopathologic features of gastrointestinal stromal tumors. A population-based study. BMC Cancer 7:230PubMedPubMedCentralCrossRefGoogle Scholar
  86. Nakamichi S, Nokihara H, Yamamoto N, Yamada Y, Honda K, Tamura Y, Wakui H, Sasaki T, Yusa W, Fujino K, Tamura T (2015) A phase 1 study of lenvatinib, multiple receptor tyrosine kinase inhibitor, in Japanese patients with advanced solid tumors. Cancer Chemother Pharmacol 76:1153–1161PubMedPubMedCentralCrossRefGoogle Scholar
  87. Nakano A, Akutsu Y, Shuto K, Uesato M, Kono T, Hoshino I, Akanuma N, Maruyama T, Isozaki Y, Matsubara H (2015) Giant esophageal gastrointestinal stromal tumor: report of a case. Surg Today 45:247–252PubMedCrossRefGoogle Scholar
  88. Nasta A, Nandy K, Bansod Y (2016) An unusual case of abdominal leiomyoma presenting as a free lying intraperitoneal mass in an elderly gentleman. Case Rep Surg 2016:1–3CrossRefGoogle Scholar
  89. Naswa N, Sharma P, Kumar A, Nazar AH, Kumar R, Chumber S, Bal C (2011) Gallium-68-DOTA-NOC PET/CT of patients with gastroenteropancreatic neuroendocrine tumors: a prospective single-center study. AJR Am J Roentgenol 197:1221–1228PubMedCrossRefGoogle Scholar
  90. Oberg K (2009) Genetics and molecular pathology of neuroendocrine gastrointestinal and pancreatic tumors (gastroenteropancreatic neuroendocrine tumors). Curr Opin Endocrinol Diabetes Obes 16(1):72–78PubMedCrossRefGoogle Scholar
  91. Pape UF et al (2008) Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors. Cancer 113(2):256–265PubMedCrossRefGoogle Scholar
  92. Partelli S et al (2017) Systematic review of active surveillance versus surgical management of asymptomatic small non-functioning pancreatic neuroendocrine neoplasms. Br J Surg 104(1):34–41PubMedCrossRefGoogle Scholar
  93. Pavel M et al (2016) Consensus guidelines update for the management of distant metastatic disease of intestinal, pancreatic, bronchial neuroendocrine neoplasms (NEN) and NEN of unknown primary site. Neuroendocrinology.  https://doi.org/10.1159/000443167Google Scholar
  94. Perini MV, Fink MA, Yeo DA, Carvalho CA, Morais CF, Jones RM, Christophi C (2013) Primary liver leiomyoma: a review of this unusual tumour: primary liver leiomyoma. ANZ J Surg 83:230–233PubMedCrossRefGoogle Scholar
  95. Raymond E et al (2011) Sunitinib malate for the treatment of pancreatic neuroendocrine tumors. N Engl J Med 364(6):501–513PubMedCrossRefGoogle Scholar
  96. Regenet N et al (2016) Is the 2-cm size cutoff relevant for small nonfunctioning pancreatic neuroendocrine tumors: a French multicenter study. Surgery 159(3):901–907PubMedCrossRefGoogle Scholar
  97. Reynolds I, Healy P, Mcnamara DA (2014) Malignant tumours of the small intestine. Surg J R Coll Surg Edinb Irel 12:263–270Google Scholar
  98. Rinke A et al (2009) Placebo-controlled, double-blind, prospective, randomized study on the effect of octreotide LAR in the control of tumor growth in patients with metastatic neuroendocrine midgut tumors: a report from the PROMID Study Group. J Clin Oncol 27(28):4656–4663PubMedCrossRefGoogle Scholar
  99. Rocco G, Trastek VF, Deschamps C, Allen MS, Miller DL, Pairolero PC (1998) Leiomyosarcoma of the esophagus: results of surgical treatment. Ann Thorac Surg 66:894–896PubMedCrossRefGoogle Scholar
  100. Russolillo N, Vigano’ L, Razzore P, Langella S, Motta M, Bertuzzo F, Papotti M, Ferrero A (2015) Survival prognostic factors of gastro-enteric-pancreatic neuroendocrine tumors after primary tumor resection in a single tertiary center: comparison of gastro-enteric and pancreatic locations. Eur J Surg Oncol J Eur Soc Surg Oncol Br Assoc Surg Oncol 41:751–757Google Scholar
  101. Ruszniewski P et al (2004) Rapid and sustained relief from the symptoms of carcinoid syndrome: results from an open 6-month study of the 28-day prolonged-release formulation of lanreotide. Neuroendocrinology 80(4):244–251PubMedCrossRefGoogle Scholar
  102. Ryan CW, Desai J (2013) The past, present, and future of cytotoxic chemotherapy and pathway-directed targeted agents for soft tissue sarcoma. Am Soc Clin Oncol Educ Book Am Soc Clin Oncol Meet.  https://doi.org/10.1200/EdBook_AM.2013.33.e386Google Scholar
  103. Sato I, Shimbo T, Kawasaki Y, Mizokami M, Masaki N (2015) Efficacy and safety of interferon treatment in elderly patients with chronic hepatitis C in Japan: a retrospective study using the Japanese Interferon Database. Hepatol Res Off J Jpn Soc Hepatol 45:829–886CrossRefGoogle Scholar
  104. Scherübl H et al (2013) Clinically detected gastroenteropancreatic neuroendocrine tumors are on the rise: epidemiological changes in Germany. World J Gastroenterol 19(47):9012–9019Google Scholar
  105. Schindl M, Kaserer K, Niederle B (2001) Treatment of gastric neuroendocrine tumors: the necessity of a type-adapted treatment. Arch Surg 136(1):49–54PubMedCrossRefGoogle Scholar
  106. Schönknecht C, Hadjamu M, Oechsner M, Andratschke N, Duma M-N (2015) Long-term survival in metastasized leiomyosarcoma: a case report and review of the literature. Tumori 101:e141–e144PubMedCrossRefGoogle Scholar
  107. Schuetze SM, Wathen JK, Lucas DR, Choy E, Samuels BL, Staddon AP, Ganjoo KN, von Mehren M, Chow WA, Loeb DM, Tawbi HA, Rushing DA, Patel SR, Thomas DG, Chugh R, Reinke DK, Baker LH (2016) SARC009: phase 2 study of dasatinib in patients with previously treated, high-grade, advanced sarcoma: dasatinib in patients with sarcoma. Cancer 122:868–874PubMedCrossRefGoogle Scholar
  108. Seidel C, Bartel F, Rastetter M, Bluemke K, Wurl P, Taubert H, Dammann R (2005) Alterations of cancer-related genes in soft tissue sarcomas: hypermethylation of RASSF1A is frequently detected in leiomyosarcoma and associated with poor prognosis in sarcoma. Int J Cancer 114:442–447PubMedCrossRefGoogle Scholar
  109. Sharma J, Duque M, Saif MW (2013) Emerging therapies and latest development in the treatment of unresectable pancreatic neuroendocrine tumors: an update for clinicians. Therap Adv Gastroenterol 6(6):474–490PubMedPubMedCentralCrossRefGoogle Scholar
  110. Shen C, Dasari A, Zhou S, Chu Y, Ying X, Shih Y-CT, Yao JC, Halperin DM (2016a) Functional status of neuroendocrine tumors among elderly patients: a large population-based study using SEER-Medicare data. J Clin Oncol 34(15 Suppl)Google Scholar
  111. Shen C, Shih Y-CT, Xu Y, Yao JC (2014) Octreotide long-acting repeatable use among elderly patients with carcinoid syndrome and survival outcomes: a population-based analysis. Cancer 120:2039–2049PubMedCrossRefGoogle Scholar
  112. Shen C, Xu Y, Dasari A, Shih Y-CT, Yao JC (2016b) Octreotide LAR dosage and survival among elderly patients with distant-stage neuroendocrine tumors. Oncologist 21:308–313PubMedPubMedCentralCrossRefGoogle Scholar
  113. Smith JD, Nandakumar G (2016) Hindgut neuroendocrine neoplasia. Indian J Surg Oncol 7:73–78PubMedCrossRefGoogle Scholar
  114. Sornmayura P, Howannapakorn J, Karnsombut P (2009) Revision of gastrointestinal mesenchymal tumors. J Med Assoc Thail Chotmaihet Thangphaet 92:87–95Google Scholar
  115. Strosberg JR, Choi J, Cantor AB, Kvols LK (2006) Selective hepatic artery embolization for treatment of patients with metastatic carcinoid and pancreatic endocrine tumors. Cancer Control J Moffitt Cancer Cent 13:72–78eCrossRefGoogle Scholar
  116. Strosberg J, Wolin EM, Chasen B, Kulke MH, Bushnell DL, Caplin ME, Baum RP, Hobday TJ, Hendifar AE, Oberg KE, Sierra ML, Kwekkeboom DJ, Ruszniewski P, Krenning E, Kunz PL (2016) NETTER-1 phase III: efficacy and safety results in patients with midgut neuroendocrine tumors treated with 177Lu-DOTATATE. J Clin Oncol 34(15 Suppl)Google Scholar
  117. Stuart K, Levy DE, Anderson T, Axiotis CA, Dutcher JP, Eisenberg A, Erban JK, Benson AB III, Eastern Cooperative Oncology Group (2004) Phase II study of interferon gamma in malignant carcinoid tumors (E9292): a trial of the Eastern Cooperative Oncology Group. Invest New Drugs 22:75–81PubMedCrossRefGoogle Scholar
  118. Taghavi S, Jayarajan SN, Powers BD, Davey A, Willis AI (2013) Examining rectal carcinoids in the era of screening colonoscopy: a surveillance, epidemiology, and end results analysis. Dis Colon Rectum 56:952–959PubMedCrossRefGoogle Scholar
  119. Tap WD, Jones RL, Van Tine BA, Chmielowski B, Elias AD, Adkins D, Agulnik M, Cooney MM, Livingston MB, Pennock G, Hameed MR, Shah GD, Qin A, Shahir A, Cronier DM, Ilaria R, Conti I, Cosaert J, Schwartz GK (2016) Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial. Lancet Lond Engl 388:488–497CrossRefGoogle Scholar
  120. Tham CK, Poon DY, Li HH, Tan MH, Choo SP, Foo KF (2009) Gastrointestinal stromal tumour in the elderly. Crit Rev Oncol Hematol 70(3):256–261PubMedCrossRefGoogle Scholar
  121. Tsai S-J (2015) Benign esophageal lesions: endoscopic and pathologic features. World J Gastroenterol 21:1091PubMedPubMedCentralCrossRefGoogle Scholar
  122. Van der Graaf WTA, Blay J-Y, Chawla SP, Kim D-W, Bui-Nguyen B, Casali PG, Schöffski P, Aglietta M, Staddon AP, Beppu Y, Le Cesne A, Gelderblom H, Judson IR, Araki N, Ouali M, Marreaud S, Hodge R, Dewji MR, Coens C, Demetri GD, Fletcher CD, Dei Tos AP, Hohenberger P, EORTC Soft Tissue and Bone Sarcoma Group, PALETTE Study Group (2012) Pazopanib for metastatic soft-tissue sarcoma (PALETTE): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Lond Engl 379:1879–1886CrossRefGoogle Scholar
  123. Verschraegen CF, Movva S, Ji Y, Schmit B, Quinn RH, Liem B, Bocklage T, Shaheen M (2013) A phase I study of the combination of temsirolimus with irinotecan for metastatic sarcoma. Cancers 5:418–429PubMedPubMedCentralCrossRefGoogle Scholar
  124. Verweij J, Baker LH (2010) Future treatment of soft tissue sarcomas will be driven by histological subtype and molecular aberrations. Eur J Cancer Oxf Engl 1990(46):863–868CrossRefGoogle Scholar
  125. Vinik A, Feliberti E, Perry RR (2000) Carcinoid Tumors. In: De Groot LJ, Chrousos G, Dungan K, Feingold KR, Grossman A, Hershman JM, Koch C, Korbonits M, McLachlan R, New M, Purnell J, Rebar R, Singer F, Vinik A (Hrsg) Endotext. MDText.com, Inc., South DartmouthGoogle Scholar
  126. Vinik AI, Wolin EM, Liyanage N, Gomez-Panzani E, Fisher GA, ELECT Study Group * (2016) Evaluation of lanreotide depot/autogel efficacy and safety as a carcinoid syndrome treatment (ELECT): a randomized, double-blind, placebo-controlled trial. Endocr Pract Off J Am Coll Endocrinol Am Assoc Clin Endocrinol 22:1068–1080Google Scholar
  127. Wang L, Fan C-Q, Ren W, Zhang X, Li Y-H, Zhao X-Y (2011) Endoscopic dissection of large endogenous myogenic tumors in the esophagus and stomach is safe and feasible: a report of 42 cases. Scand J Gastroenterol 46:627–633PubMedCrossRefGoogle Scholar
  128. White TJ et al (1994) Is there a prognostic difference between functional and nonfunctional islet cell tumors? Am J Surg 168(6):627–629; discussion 629–630PubMedCrossRefGoogle Scholar
  129. Wu GX, Ituarte PHG, Paz IB, Kim J, Raz DJ, Kim JY (2015) A population-based examination of the surgical outcomes for patients with esophageal sarcoma. Ann Surg Oncol 22(Suppl 3):S1310–S1317PubMedCrossRefGoogle Scholar
  130. Yang HK, Kim YH, Lee YJ, Park JH, Kim JY, Lee KH, Lee HS (2015) Leiomyomas in the gastric cardia: CT findings and differentiation from gastrointestinal stromal tumors. Eur J Radiol 84:1694–1700PubMedCrossRefGoogle Scholar
  131. Yao JC, Hassan M, Phan A, Dagohoy C, Leary C, Mares JE, Abdalla EK, Fleming JB, Vauthey J-N, Rashid A, Evans DB (2008) One hundred years after „carcinoid“: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol Off J Am Soc Clin Oncol 26:3063–3072CrossRefGoogle Scholar
  132. Yao JC et al (2011) Everolimus for advanced pancreatic neuroendocrine tumors. N Engl J Med 364(6):514–523PubMedPubMedCentralCrossRefGoogle Scholar
  133. Yao JC, Fazio N, Singh S, Buzzoni R, Carnaghi C, Wolin E, Tomasek J, Raderer M, Lahner H, Voi M, Pacaud LB, Rouyrre N, Sachs C, Valle JW, Delle Fave G, Van Cutsem E, Tesselaar M, Shimada Y, Oh D-Y, Strosberg J, Kulke MH, Pavel ME, RAD001 in Advanced Neuroendocrine Tumours, Fourth Trial (RADIANT-4) Study Group (2016) Everolimus for the treatment of advanced, non-functional neuroendocrine tumours of the lung or gastrointestinal tract (RADIANT-4): a randomised, placebo-controlled, phase 3 study. Lancet Lond Engl 387:968–977CrossRefGoogle Scholar
  134. Ye JX, Liu Y, Qin Y, Ma XL, Zhong HH, Zhang Y, Shi XY (2015) Mast cells or not? – CD117 positive cells in esophageal leiomyoma. Histol Histopathol 30:581–588PubMedGoogle Scholar
  135. Yu Q-X (2014) Clinical presentations of gastric small gastrointestinal stromal tumors mimics functional dyspepsia symptoms. World J Gastroenterol 20:11800PubMedPubMedCentralCrossRefGoogle Scholar
  136. Zhang J, Huang K, Ding S, Wang Y, Nai T, Huang Y, Zhou L (2016) Clinical applicability of various treatment approaches for upper gastrointestinal submucosal tumors. Gastroenterol Res Pract 2016:1–9Google Scholar
  137. Zurac S, Tudose I, Micu G, Bastian A, Gamada E, Stăniceanu F, Popp C, Simeanu D, Haidar A (2009) Rectal leiomyoma – report of two cases originating in muscularis mucosae. Romanian J Intern Med Rev Roum Med Interne 47:97–100Google Scholar

Copyright information

© Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature 2018

Authors and Affiliations

  • Michael Rassner
    • 1
  • Harald Lahner
    • 2
  • Nikolas von Bubnoff
    • 1
  • Frank Lammert
    • 3
  1. 1.Klinik für Innere Medizin IUniversitätsklinikum FreiburgFreiburgDeutschland
  2. 2.Klinik für Endokrinologie, Diabetologie und StoffwechselUniversitätsklinikum EssenEssenDeutschland
  3. 3.Klinik für Innere Medizin IIUniversitätsklinikum des SaarlandesHomburgDeutschland

Section editors and affiliations

  • Nicolai Härtel
    • 1
  1. 1.Interdisziplinäres TumorzentrumUniversitätsmedizin MannheimMannheimDeutschland

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