Top

Journal of Gastrointestinal Cancer

Published in:

01-12-2014 | Review Article

Primary Small-Bowel Malignancy: Update in Tumor Biology, Markers, and Management Strategies

Author: Santosh Shenoy

Published in: Journal of Gastrointestinal Cancer | Issue 4/2014

Abstract

Purpose

Primary small-bowel malignancies (SBM) are rare tumors but their incidence is rising. An estimated 9160 new cases and 1210 deaths due to SBM may occur in the USA in 2014. We review advances made in tumor biology, immunohistochemistry, and discuss treatment strategies for these malignancies.

Methods

Relevant articles from PubMed/Medline and Embase searches were collected using the phrases “small-bowel adenocarcinoma, gastrointestinal carcinoids, gastrointestinal stromal tumors, small-bowel leiomyosarcoma, and small-bowel lymphoma”.

Results

Advances in imaging techniques such as wireless capsule endoscopy, CT and MRI enterography, and endoscopy (balloon enteroscopy) along with discovery of molecular markers such as c-kit and PDGFRA for GIST tumors have improved our ability to diagnose, localize, and treat these patients. Early detection and surgical resection offers the best chance for long-term survival in all tumors except bowel lymphoma where chemotherapy plays the main role. Adjuvant therapy with imatinib has improved overall survival for GIST tumors, somatostatin analogs have improved symptoms and also inhibited tumor growth and stabilized metastatic disease in carcinoid disease, but chemotherapy has not improved survival for adenocarcinoma.

Conclusions

Recent advances in molecular characterization holds promise in novel targeted therapies. Currently ongoing trials are exploring efficacy of targeted therapies and role of adjuvant therapy for adenocarcinoma and results are awaited. Early detection and aggressive surgical therapy for all localized tumors and lymph node sampling particularly for adenocarcinoma remains the main treatment modality.

Gill SS, Heuman DM, Mihas AA. Small intestinal neoplasms. J Clin Gastroenterol. 2001;33:267–82.PubMedCrossRef

Surveillance, Epidemiology, and End Results (SEER) Program. Available at www.seer.cancer.gov. SEER*Stat Database: Statistics at a glance: small intestine cancer.

Bilimoria KY, Bentrem DJ, Wayne JD, et al. Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years. Ann Surg. 2009;249:63–71.PubMedCrossRef

Talamonti MS, Goetz LH, Rao S, et al. Primary cancers of the small bowel: analysis of prognostic factors and results of surgical management. Arch Surg. 2002;137:564–70.PubMedCrossRef

Raghav K, Overman MJ. Small bowel adenocarcinomas–existing evidence and evolving paradigms. Nat Rev Clin Oncol. 2013;10:534–44.PubMedCrossRef

Goodman MT, Matsuno RK, Shvetsov YB. Racial and ethnic variation in the incidence of small-bowel cancer subtypes in the United States, 1995–2008. Dis Colon Rectum. 2013;56:441–8.PubMedCrossRef

Surveillance, Epidemiology, and End Results (SEER) Program. Available at www.seer.cancer.gov. SEER*Stat Database: trends in rates 1975–2006: small intestine cancer.

Jess T, Gamborg M, Matzen P, et al. Increased risk of intestinal cancer in Crohn’s disease: a meta-analysis of population-based cohort studies. Am J Gastroenterol. 2005;100:2724–9.PubMedCrossRef

Green PH, Fleischauer AT, Bhagat G, et al. Risk of malignancy in patients with celiac disease. Am J Med. 2003;115:191–5.PubMedCrossRef

10.

Rashid A, Hamilton SR. Genetic alterations in sporadic and Crohn’s-associated adenocarcinomas of the small intestine. Gastroenterology. 1997;113:127–35.PubMedCrossRef

11.

Bläker H, Helmchen B, Bönisch A, et al. Mutational activation of the RAS-RAF-MAPK and the Wnt pathway in small intestinal adenocarcinomas. Scand J Gastroenterol. 2004;39:748–53.PubMedCrossRef

12.

Schottenfeld D, Beebe-Dimmer JL, Vigneau FD. The epidemiology and pathogenesis of neoplasia in the small intestine. Ann Epidemiol. 2009;19:58–69.PubMedCentralPubMedCrossRef

13.

Overman MJ, Hu CY, Kopetz S, et al. A population-based comparison of adenocarcinoma of the large and small intestine: insights into a rare disease. Ann Surg Oncol. 2012;19:1439–45.PubMedCentralPubMedCrossRef

14.

Haan JC, Buffart TE, Eijk PP, et al. Small bowel adenocarcinoma copy number profiles are more closely related to colorectal than to gastric cancers. Ann Oncol. 2012;23:367–74.PubMedCrossRef

15.

Chan OT, Chen ZM, Chung F, et al. Lack of HER2 overexpression and amplification in small intestinal adenocarcinoma. Am J Clin Pathol. 2010;134:880–5.PubMedCrossRef

16.

Wheeler JM, Warren BF, Mortensen NJ, et al. An insight into the genetic pathway of adenocarcinoma of the small intestine. Gut. 2002;50:218–23.PubMedCentralPubMedCrossRef

17.

Lee HJ, Lee OJ, Jang KT, et al. Combined loss of E-cadherin and aberrant β-catenin protein expression correlates with a poor prognosis for small intestinal adenocarcinomas. Am J Clin Pathol. 2013;139:167–76.PubMedCrossRef

18.

Bläker H, von Herbay A, Penzel R, et al. Genetics of adenocarcinomas of the small intestine: frequent deletions at chromosome 18q and mutations of the SMAD4 gene. Oncogene. 2002;21:158–64.PubMedCrossRef

19.

Nishiyama K, Yao T, Yonemasu H, et al. Overexpression of p53 protein and point mutation of K-ras genes in primary carcinoma of the small intestine. Oncol Rep. 2002;9:293–300.PubMed

20.

Overman MJ, Pozadzides J, Kopetz S, et al. Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine. Br J Cancer. 2010;102:144–50.PubMedCentralPubMedCrossRef

21.

Planck M, Ericson K, Piotrowska Z, et al. Microsatellite instability and expression of MLH1 and MSH2 in carcinomas of the small intestine. Cancer. 2003;97:1551–7.PubMedCrossRef

22.

Diosdado B, Buffart TE, Watkins R, et al. High-resolution array comparative genomic hybridization in sporadic and celiac disease-related small bowel adenocarcinomas. Clin Cancer Res. 2010;16:1391–401.PubMedCrossRef

23.

Pilleul F, Penigaud M, Milot L, et al. Possible small-bowel neoplasms: contrast-enhanced and water-enhanced multidetector CT enteroclysis. Radiology. 2006;241:796–801.PubMedCrossRef

24.

Cronin CG, Scott J, Kambadakone A, et al. Utility of positron emission tomography/CT in the evaluation of small bowel pathology. Br J Radiol. 2012;85:1211–21.PubMedCentralPubMedCrossRef

25.

Ross A, Mehdizadeh S, Tokar J, et al. Double balloon enteroscopy detects small bowel mass lesions missed by capsule endoscopy. Dig Dis Sci. 2008;53:2140–3.PubMedCrossRef

26.

Adler SN, Bjarnason I. What we have learned and what to expect from capsule endoscopy. World J Gastrointest Endosc. 2012;4:448–52.PubMedCentralPubMedCrossRef

27.

Edge SB, Byrd DR, Compton CC et al. (2010) Small Intestine. AJCC Cancer Staging Manual. 7th ed. New York, NY: Springer pp 127–32.

28.

Abrahams NA, Halverson A, Fazio VW, et al. Adenocarcinoma of the small bowel: a study of 37 cases with emphasis on histologic prognostic factors. Dis Colon Rectum. 2002;45:1496–502.PubMedCrossRef

29.

Overman MJ, Hu CY, Wolff RA, et al. Prognostic value of lymph node evaluation in small bowel adenocarcinoma: analysis of the surveillance, epidemiology, and end results database. Cancer. 2010;116:5374–82.PubMedCrossRef

30.

Dabaja BS, Suki D, Pro B, et al. Adenocarcinoma of the small bowel: presentation, prognostic factors, and outcome of 217 patients. Cancer. 2004;101:518–26.PubMedCrossRef

31.

Kaklamanos IG, Bathe OF, Franceschi D, et al. Extent of resection in the management of duodenal adenocarcinoma. Am J Surg. 2000;179:37–41.PubMedCrossRef

32.

Agrawal S, McCarron EC, Gibbs JF, et al. Surgical management and outcome in primary adenocarcinoma of the small bowel. Ann Surg Oncol. 2007;14:2263–9.PubMedCrossRef

33.

Onkendi EO, Boostrom SY, Sarr MG, et al. Neoadjuvant treatment of duodenal adenocarcinoma: a rescue strategy. J Gastrointest Surg. 2012;16:320–4.PubMedCrossRef

34.

Fishman PN, Pond GR, Moore MJ, et al. Natural history and chemotherapy effectiveness for advanced adenocarcinoma of the small bowel: a retrospective review of 113 cases. Am J Clin Oncol. 2006;29:225–31.PubMedCrossRef

35.

Koo DH, Yun SC, Hong YS, et al. Systemic chemotherapy for treatment of advanced small bowel adenocarcinoma with prognostic factor analysis: retrospective study. BMC Cancer. 2011;11:205.PubMedCentralPubMedCrossRef

36.

Czaykowski P, Hui D. Chemotherapy in small bowel adenocarcinoma: 10-year experience of the British Columbia Cancer Agency. Clin Oncol (R Coll Radiol). 2007;19:143–9.CrossRef

37.

Overman MJ. Recent advances in the management of adenocarcinoma of the small intestine. Gastrointest Cancer Res. 2009;3:90–6.PubMedCentralPubMed

38.

Santini D, Fratto ME, Spoto C, et al. Cetuximab in small bowel adenocarcinoma: a new friend? Br J Cancer. 2010;103:1305.PubMedCentralPubMedCrossRef

39.

Jeurnink SM, Steyerberg EW, van Hooft JE, et al. Surgical gastrojejunostomy or endoscopic stent placement for the palliation of malignant gastric outlet obstruction (SUSTENT study): a multicenter randomized trial. Gastrointest Endosc. 2010;71:490–9.PubMedCrossRef

40.

Rosato Jr FE, Rosato EL. Current surgical management of intestinal metastases. Semin Oncol. 2008;35:177–82.PubMedCrossRef

41.

Jacks SP, Hundley JC, Shen P, et al. Cytoreductive surgery and intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis from small bowel adenocarcinoma. J Surg Oncol. 2005;91:112–7.PubMedCrossRef

42.

Adam R, Chiche L, Aloia T, et al. Hepatic resection for noncolorectal nonendocrine liver metastases: analysis of 1,452 patients and development of a prognostic model. Ann Surg. 2006;244:524–35.PubMedCentralPubMedCrossRef

43.

Cheung DY, Choi MG. Current advance in small bowel tumors. Clin Endosc. 2011;44:13–21.PubMedCentralPubMedCrossRef

44.

Strosberg J. Neuroendocrine tumours of the small intestine. Best Pract Res Clin Gastroenterol. 2012;26:755–73.PubMedCrossRef

45.

Yao JC, Hassan M, Phan A, et al. One hundred years after “carcinoid”: epidemiology of and prognostic factors for neuroendocrine tumors in 35,825 cases in the United States. J Clin Oncol. 2008;26:3063–72.PubMedCrossRef

46.

Bartlett EK, Roses RE, Gupta M, et al. Surgery for metastatic neuroendocrine tumors with occult primaries. J Surg Res. 2013;184:221–7.PubMedCrossRef

47.

Tichansky DS, Cagir B, Borrazzo E, et al. Risk of second cancers in patients with colorectal carcinoids. Dis Colon Rectum. 2002;45:91–7.PubMedCrossRef

48.

Dromain C, de Baere T, Lumbroso J, et al. Detection of liver metastases from endocrine tumors: a prospective comparison of somatostatin receptor scintigraphy, computed tomography, and magnetic resonance imaging. J Clin Oncol. 2005;23:70–8.PubMedCrossRef

49.

Kos-Kudła B, Blicharz-Dorniak J, Handkiewicz-Junak D, et al. Diagnostic and therapeutic guidelines for gastro-entero-pancreatic neuroendocrine neoplasms (recommended by the Polish Network of Neuroendocrine Tumours). Endokrynol Pol. 2013;64:418–43.PubMedCrossRef

50.

Shenoy S. Gastrointestinal carcinoids and colorectal cancers: is it a paracrine effect? Tumori. 2013;99:e141–3.PubMed

51.

Rorstad O. Prognostic indicators for carcinoid neuroendocrine tumors of the gastrointestinal tract. J Surg Oncol. 2005;89:151–60.PubMedCrossRef

52.

Rinke A, Müller HH, Schade-Brittinger C, et al. 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. 2009;27:4656–63.PubMedCrossRef

53.

Arnold R, Rinke A, Klose KJ, et al. Octreotide versus octreotide plus interferon-alpha in endocrine gastroenteropancreatic tumors: a randomized trial. Clin Gastroenterol Hepatol. 2005;3:761–71.PubMedCrossRef

54.

Pavel ME, Hainsworth JD, Baudin E, et al. Everolimus plus octreotide long-acting repeatable for the treatment of advanced neuroendocrine tumours associated with carcinoid syndrome (RADIANT-2): a randomised, placebo-controlled, phase 3 study. Lancet. 2011;378:2005–12.PubMedCrossRef

55.

Yao JC, Phan A, Hoff PM, et al. Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b. J Clin Oncol. 2008;26:1316–23.PubMedCrossRef

56.

Kalinowski M, Dressler M, König A, et al. Selective internal radiotherapy with Yttrium-90 microspheres for hepatic metastatic neuroendocrine tumors: a prospective single center study. Digestion. 2009;79(3):137–42.PubMedCrossRef

57.

Nakamura S, Matsumoto T. Gastrointestinal lymphoma: recent advances in diagnosis and treatment. Digestion. 2013;87:182–8.PubMedCrossRef

58.

Bautista-Quach MA, Ake CD, Chen M, et al. Gastrointestinal lymphomas: morphology, immunophenotype and molecular features. J Gastrointest Oncol. 2012;3:209–25.PubMedCentralPubMed

59.

Ghimire P, Wu GY, Zhu L. Primary gastrointestinal lymphoma. World J Gastroenterol. 2011;17:697–707.PubMedCentralPubMedCrossRef

60.

Nakamura S, Matsumoto T, Iida M, et al. Primary gastrointestinal lymphoma in Japan: a clinicopathologic analysis of 455 patients with special reference to its time trends. Cancer. 2003;97:2462–73.PubMedCrossRef

61.

Rohatiner A, d’Amore F, Coiffier B, et al. Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Ann Oncol. 1994;5:397–400.PubMedCrossRef

62.

Han SL, Cheng J, Zhou HZ, et al. Surgically treated primary malignant tumor of small bowel: a clinical analysis. World J Gastroenterol. 2010;16:1527–32.PubMedCentralPubMedCrossRef

63.

Bishton MJ, Haynes AP. Combination chemotherapy followed by autologous stem cell transplant for enteropathy-associated T cell lymphoma. Br J Haematol. 2007;136:111–3.PubMedCrossRef

64.

Qubaiah O, Devesa SS, Platz CE, et al. Small intestinal cancer: a population-based study of incidence and survival patterns in the United States, 1992 to 2006. Cancer Epidemiol Biomarkers Prev. 2010;19:1908–18.PubMedCentralPubMedCrossRef

65.

Chaudhry UI, DeMatteo RP. Advances in the surgical management of gastrointestinal stromal tumor. Adv Surg. 2011;45:197–209.PubMedCentralPubMedCrossRef

66.

Joensuu H, Hohenberger P, Corless CL. Gastrointestinal stromal tumor. Lancet. 2013;382:973–83.PubMedCrossRef

67.

Miettinen M. Smooth muscle tumors of soft tissue and non-uterine ;viscera: biology and prognosis. Mod Pathol. 2014;27 Suppl 1:S17–29.PubMedCrossRef

68.

Katz SC, DeMatteo RP. Gastrointestinal stromal tumors and leiomyosarcomas. J Surg Oncol. 2008;97:350–9.PubMedCrossRef

69.

Hirota S, Isozaki K, Moriyama Y, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science. 1998;279:577–80.PubMedCrossRef

70.

Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 2001;344:1052–6.PubMedCrossRef

71.

Miettinen M, Wang ZF, Lasota J. DOG1 antibody in the differential diagnosis of gastrointestinal stromal tumors. Am J Surg Pathol. 2009;33:1401–8.PubMedCrossRef

72.

Serrano C, George S. Leiomyosarcoma. Hematol Oncol Clin N Am. 2013;27:957–74.CrossRef

73.

Yamamoto H, Handa M, Tobo T, Setsu N, et al. Clinicopathological features of primary leiomyosarcoma of the gastrointestinal tract following recognition of gastrointestinal stromal tumors. Histopathology. 2013;63:194–207.PubMedCrossRef

74.

Demetri GD, Antonia S, Benjamin RS, et al. Soft tissue sarcoma. J Natl Compr Canc Netw. 2010;8:630–74.PubMed

Title: Primary Small-Bowel Malignancy: Update in Tumor Biology, Markers, and Management Strategies
Author: Santosh Shenoy
Publication date: 01-12-2014
Publisher: Springer US
Published in: Journal of Gastrointestinal Cancer / Issue 4/2014
Print ISSN: 1941-6628
Electronic ISSN: 1941-6636
DOI: https://doi.org/10.1007/s12029-014-9658-z

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2014

Evolving Role of Gene Expression Signatures as Biomarkers in Early-Stage Colon Cancer

HES1 as an Independent Prognostic Marker in Esophageal Squamous Cell Carcinoma

Primary Gastrointestinal Mantle Cell Lymphoma: A Retrospective Study

Overrepresentation of HLA-DQ2 in Small Intestinal Neuroendocrine Tumor Patients

TGFBR1*6A Polymorphism in Sporadic and Familial Colorectal Carcinoma: a Case-control Study and Systematic Literature Review

Post Hepatectomy Liver Failure: Concept of Management

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials