Malignant Neoplasms of the Small Intestine 

  • Author: N Joseph Espat, MD, MS, FACS; Chief Editor: Jules E Harris, MD   more...
 
Updated: Dec 2, 2011
 

Background

Malignant neoplasms of the small bowel are among the rarest types of cancer, accounting for only 2% of all GI cancers. Research into the natural history and prognosis of patients with small-bowel cancer has been limited by the small number of cases and the heterogeneity of tumor types, including adenocarcinomas, carcinoids, sarcomas, and lymphomas. Each of these tumor subtypes has its own distinct clinical behavior and, therefore, dictates a different treatment approach. Unfortunately, malignant lesions are often discovered when they have metastasized to distant sites or at surgery when indicated for other diagnosis or intestinal obstruction.

This review focuses on adenocarcinoma, as it is the most common histologic type of small-bowel malignancy in the United States. Sarcomas are also briefly discussed. Carcinoid tumors and lymphomas are described in other articles of this journal (eg, Carcinoid Tumor, Intestinal). Around 98% of small bowel tumors are made up of adenocarcinomas, carcinoid tumors, lymphomas or sarcoma /gastrointestinal stromal tumors (GISTs).

Next

Pathophysiology

Approximately 64% of all small-bowel tumors are malignant, and approximately 40% of these tumors are adenocarcinomas. Epidemiologically, small-bowel adenocarcinomas have a striking resemblance to large-bowel adenocarcinomas. For example, although small-bowel adenocarcinomas are only one fiftieth as common as large-bowel adenocarcinomas, they share a similar geographic distribution, with predominance in Western countries. In addition, they tend to co-occur in the same individuals, with an increased risk of small-bowel adenocarcinoma in survivors of colorectal cancer and vice versa.

Furthermore, similar to adenocarcinomas in the colon, those in the small bowel arise from premalignant adenomas. This occurs both sporadically and in the context of familial adenomatous polyposis. Through a stepwise accumulation of genetic mutations, these adenomas become dysplastic and progress to carcinomas in situ and then to invasive adenocarcinomas. They then metastasize via the lymphatics or portal circulation to the liver, lung, bone, brain, and other distant sites.

Despite these similarities with colon cancer, small-bowel adenocarcinomas tend to cluster away from the colon, toward the gastric end of the small intestine. Approximately 50% arise in the duodenum, 30% in the jejunum, and 20% in the ileum. The duodenum is the first portion of the small bowel to be exposed to ingested chemicals and pancreaticobiliary secretions. This fact, combined with the higher prevalence of cancer in the duodenum, may indicate that the substances (ie, ingested chemicals, pancreaticobiliary secretions) may have carcinogenic properties. Animal studies have demonstrated that diverting bile decreases the prevalence of experimentally induced small-bowel cancers, which suggests that bile may be carcinogenic.

In addition, genetic analyses of sporadic small-bowel adenocarcinomas suggest similarities and differences from the pathogenesis from colorectal carcinomas. Although K-ras mutation and p53 overexpression appear to be as common in small-bowel adenocarcinoma as in colorectal carcinoma, mutation of the APC tumor suppressor gene, which is characteristic of colorectal carcinoma, does not commonly occur in small-bowel adenocarcinoma.[1, 2] The SMAD4/DPC4 gene, which is often mutated in pancreatic and colorectal carcinomas, also appears to be inactivated in small-bowel adenocarcinomas.[3, 4]

Sarcomas account for approximately 15% of small-bowel malignancies in the United States. While some may exhibit clear histologic features of smooth muscle origin, many tumors display only partial differentiation with incomplete expression of muscle-associated antigens. Because they are mesenchymal neoplasms believed to be derived from the interstitial cells of Cajal in the GI tract, they have recently been named with the more general term GI stromal tumors (GISTs). Recent studies have demonstrated that nearly all GISTs, unlike true sarcomas, express a growth-factor receptor with tyrosine kinase activity encoded by the proto-oncogene c-kit. As reported by Miettinen et al in 1999, mutations in c-kit that cause constitutive tyrosine kinase activity and result in uncontrolled cell proliferation have been detected in approximately 60% of GISTs and appear to play a central role in tumorigenesis.[5]

While most GISTs are located in the stomach, 30% of GISTs are found in the small bowel. These tumors are distributed more evenly throughout the small bowel compared with adenocarcinomas, and they tend to grow extraluminally. Because they are highly vascular lesions that commonly ulcerate, intestinal bleeding is a frequent symptom. Compared with gastric GISTs, small-bowel GISTs tend to be more aggressive and have a worse prognosis. Metastases develop primarily via the hematogenous route, commonly involving the liver and lungs. GISTs also may invade adjacent organs directly or spread via peritoneal seeding. Lymphatic metastases are rare but are believed to be a marker for more widespread metastatic disease.

Previous
Next

Epidemiology

Frequency

United States

The incidence of small-bowel cancers in the United States in 2007 was projected to be 5640 cases, of which 2940 cases were projected to be in males and 2700 were projected to be in females. An estimated 1090 persons (males 570; females 520) were projected to die of the disease in 2007.[6]

International

In general, small-bowel cancer prevalence is lower in Asia and in less industrialized countries than in Western countries. In addition, several hospital-based series indicate a predominance of lymphomas in less developed countries.

Mortality/Morbidity

The 5-year overall survival rate for patients with adenocarcinoma has been estimated to be 30-35%. The 5-year survival rate for patients with small-bowel sarcomas is approximately 25%.[7]

Race

Population-based studies in the United States have suggested somewhat higher prevalence rates of small-bowel cancer for blacks than for whites. According to one study, blacks have almost twice the incidence of carcinomas than whites do (10.6 versus 5.6 per million population).[8]

Sex

Men have higher rates of all types of small bowel cancer than women do, with a male-to-female ratio of 1.4:1.[8]

Age

The prevalence of small-bowel cancer tends to increase with age, with a mean age at diagnosis of approximately 60 years. Adenocarcinomas, more than the other histologic subtypes, tend to be diagnosed in somewhat older patients.

Previous
Proceed to Clinical Presentation
 
 
Contributor Information and Disclosures
Author

N Joseph Espat, MD, MS, FACS  Harold J Wanebo Professor and Chief of Surgical Oncology, Director, Adele R Decof Cancer Center, Vice-Chair of Department of Surgery, Roger Williams Medical Center, Boston University School of Medicine

N Joseph Espat, MD, MS, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Surgeons, American Hepato-Pancreato-Biliary Association, American Medical Association, American Society for Parenteral and Enteral Nutrition, American Society of Clinical Oncology, Association for Academic Surgery, Central Surgical Association, Chicago Medical Society, International Hepato-Pancreato-Biliary Association, Pancreas Club, Sigma Xi, Society for Leukocyte Biology, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Surgical Oncology, Society of University Surgeons, Southeastern Surgical Congress, Southern Medical Association, and Surgical Infection Society

Disclosure: Nothing to disclose.

Coauthor(s)

Ponnandai S Somasundar, MD, FACS  Assistant Chief of Surgical Oncology, Assistant Professor of Surgery, Boston University; Hepatopancreatobiliary/Surgical Oncologist, Roger Williams Medical Center

Ponnandai S Somasundar, MD, FACS is a member of the following medical societies: American College of Surgeons, American Hepato-Pancreato-Biliary Association, Association for Academic Surgery, Association of Surgeons of India, and Society of Surgical Oncology

Disclosure: Nothing to disclose.

Piero Marco Fisichella, MD  Assistant Professor of Surgery, Stritch School of Medicine, Loyola University; Director, Esophageal Motility Center, Loyola University Medical Center

Piero Marco Fisichella, MD is a member of the following medical societies: American College of Surgeons, American Medical Association, Association for Academic Surgery, Society for Surgery of the Alimentary Tract, and Society of American Gastrointestinal and Endoscopic Surgeons

Disclosure: Nothing to disclose.

Specialty Editor Board

Lodovico Balducci, MD  Professor of Oncology and Medicine, University of South Florida College of Medicine; Division Chief, Senior Adult Oncology Program, H Lee Moffitt Cancer Center and Research Institute

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD  Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

Benjamin Movsas, MD  Vice-Chairman, Department of Radiation Oncology, Fox Chase Cancer Center

Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, and American Society for Therapeutic Radiology and Oncology

Disclosure: Nothing to disclose.

Rajalaxmi McKenna, MD, FACP  Southwest Medical Consultants, SC, Department of Medicine, Good Samaritan Hospital, Advocate Health Systems

Rajalaxmi McKenna, MD, FACP is a member of the following medical societies: American Society of Clinical Oncology, American Society of Hematology, and International Society on Thrombosis and Haemostasis

Disclosure: Nothing to disclose.

Chief Editor

Jules E Harris, MD  Clinical Professor of Medicine, Division of Hematology/Medical Oncology, Department of Internal Medicine, University of Arizona College of Medicine; Consulting Staff, Arizona Cancer Center

Jules E Harris, MD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Association of Immunologists, American Society of Hematology, and Central Society for Clinical Research

Disclosure: GlobeImmune Salary Consulting

Additional Contributors

eMedicine extends its thanks to Alfred I Neugut, MD, PhD , Head, Cancer Prevention and Control, Herbert Irving Comprehensive Cancer Center; Professor, Department of Medicine and Public Health, Columbia University College of Physicians and Surgeons and Allen C Chen, MD, MS, Assistant Professor, Department of Medicine, Division of Medical Oncology, New York University School of Medicine for previous versions of this article.

References

  1. Arai M, Shimizu S, Imai Y, et al. Mutations of the Ki-ras, p53 and APC genes in adenocarcinomas of the human small intestine. Int J Cancer. Feb 7 1997;70(4):390-5. [Medline].

  2. Wheeler JM, Warren BF, Mortensen NJ, et al. An insight into the genetic pathway of adenocarcinoma of the small intestine. Gut. Feb 2002;50(2):218-23. [Medline].

  3. Svrcek M, Jourdan F, Sebbagh N, et al. Immunohistochemical analysis of adenocarcinoma of the small intestine: a tissue microarray study. J Clin Pathol. Dec 2003;56(12):898-903. [Medline].

  4. Blaker 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. Jan 3 2002;21(1):158-64. [Medline].

  5. Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol. Oct 1999;30(10):1213-20. [Medline].

  6. American Cancer Society. Statistics for 2007. Available at http://www.cancer.org/docroot/stt/stt_0_2007.asp?sitearea=STT&level=1.

  7. DeMatteo RP, Lewis JJ, Leung D, Mudan SS, Woodruff JM, Brennan MF. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg. Jan 2000;231(1):51-8. [Medline].

  8. Haselkorn T, Whittemore AS, Lilienfeld DE. Incidence of small bowel cancer in the United States and worldwide: geographic, temporal, and racial differences. Cancer Causes Control. Sep 2005;16(7):781-7. [Medline].

  9. Offerhaus GJ, Giardiello FM, Krush AJ, et al. The risk of upper gastrointestinal cancer in familial adenomatous polyposis. Gastroenterology. Jun 1992;102(6):1980-2. [Medline].

  10. Kashiwagi H, Spigelman AD, Talbot IC, et al. p53 and K-ras status in duodenal adenomas in familial adenomatous polyposis. Br J Surg. Jun 1997;84(6):826-9. [Medline].

  11. Lowenfels AB, Sonni A. Distribution of small bowel tumors. Cancer Lett. Jul 1977;3(1-2):83-6. [Medline].

  12. Chow WH, Linet MS, McLaughlin JK, et al. Risk factors for small intestine cancer. Cancer Causes Control. Mar 1993;4(2):163-9. [Medline].

  13. Chen CC, Neugut AI, Rotterdam H. Risk factors for adenocarcinomas and malignant carcinoids of the small intestine: preliminary findings. Cancer Epidemiol Biomarkers Prev. Apr-May 1994;3(3):205-7. [Medline].

  14. Potter DD, Murray JA, Donohue JH, et al. The role of defective mismatch repair in small bowel adenocarcinoma in celiac disease. Cancer Res. Oct 1 2004;64(19):7073-7. [Medline].

  15. Hemminki A. Inherited predisposition to gastrointestinal cancer: The molecular backgrounds of Peutz-Jeghers syndrome and hereditary nonpolyposis colorectal cancer [dissertation/master's thesis]. University of Helsinki; 1998.

  16. Filiz G, Yerci O, Adim SB, Gurel S, Dolar E, Memik F. Periampullary carcinomas. Hepatogastroenterology. Jun 2007;54(76):1247-9. [Medline].

  17. Fernandes DD, Galwa RP, Fasih N, Fraser-Hill M. Cross-sectional Imaging of Small Bowel Malignancies. Can Assoc Radiol J. Aug 26 2011;[Medline].

  18. Sieg A. Capsule endoscopy compared with conventional colonoscopy for detection of colorectal neoplasms. World J Gastrointest Endosc. May 16 2011;3(5):81-5. [Medline]. [Full Text].

  19. Cobrin GM, Pittman RH, Lewis BS. Increased diagnostic yield of small bowel tumors with capsule endoscopy. Cancer. Jul 1 2006;107(1):22-7. [Medline].

  20. Zeh H III. Cancer of the small intestine. In: DeVita VT Jr, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2005:1035-48.

  21. Jigyasu D, Bedikian AY, Stroehlein JR. Chemotherapy for primary adenocarcinoma of the small bowel. Cancer. Jan 1 1984;53(1):23-5. [Medline].

  22. Ouriel K, Adams JT. Adenocarcinoma of the small intestine. Am J Surg. Jan 1984;147(1):66-71. [Medline].

  23. Crawley C, Ross P, Norman A, et al. The Royal Marsden experience of a small bowel adenocarcinoma treated with protracted venous infusion 5-fluorouracil. Br J Cancer. Aug 1998;78(4):508-10. [Medline].

  24. Polyzos A, Kouraklis G, Giannopoulos A, et al. Irinotecan as salvage chemotherapy for advanced small bowel adenocarcinoma: a series of three patients. J Chemother. Oct 2003;15(5):503-6. [Medline].

  25. Bettini AC, Beretta GD, Sironi P, et al. Chemotherapy in small bowel adenocarcinoma associated with celiac disease: a report of three cases. Tumori. Mar-Apr 2003;89(2):193-5. [Medline].

  26. Koo DH, Yun SC, Hong YS, Ryu MH, Lee JL, Chang HM, et al. Adjuvant chemotherapy for small bowel adenocarcinoma after curative surgery. Oncology. 2011;80(3-4):208-13. [Medline].

  27. Fernandez-Trigo V, Sugarbaker PH. Sarcomas involving the abdominal and pelvic cavity. Tumori. Apr 30 1993;79(2):77-91. [Medline].

  28. Zalupski M, Metch B, Balcerzak S, et al. Phase III comparison of doxorubicin and dacarbazine given by bolus versus infusion in patients with soft-tissue sarcomas: a Southwest Oncology Group study. J Natl Cancer Inst. Jul 3 1991;83(13):926-32. [Medline].

  29. Blair SC, Zalupski MM, Baker LH. Ifosfamide and etoposide in the treatment of advanced soft tissue sarcomas. Am J Clin Oncol. Dec 1994;17(6):480-4. [Medline].

  30. Plaat BE, Hollema H, Molenaar WM, et al. Soft tissue leiomyosarcomas and malignant gastrointestinal stromal tumors: differences in clinical outcome and expression of multidrug resistance proteins. J Clin Oncol. Sep 15 2000;18(18):3211-20. [Medline].

  31. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. Aug 15 2002;347(7):472-80. [Medline].

  32. van Oosterom AT, Judson IR, Verweij J, et al. Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer. Sep 2002;38 Suppl 5:S83-7. [Medline].

  33. Bakaeen FG, Murr MM, Sarr MG, et al. What prognostic factors are important in duodenal adenocarcinoma?. Arch Surg. Jun 2000;135(6):635-41; discussion 641-2. [Medline].

  34. Ryder NM, Ko CY, Hines OJ, et al. Primary duodenal adenocarcinoma: a 40-year experience. Arch Surg. Sep 2000;135(9):1070-4; discussion 1074-5. [Medline].

  35. Emory TS, Sobin LH, Lukes L, Lee DH, O'Leary TJ. Prognosis of gastrointestinal smooth-muscle (stromal) tumors: dependence on anatomic site. Am J Surg Pathol. Jan 1999;23(1):82-7. [Medline].

  36. Bauer RL, Palmer ML, Bauer AM, et al. Adenocarcinoma of the small intestine: 21-year review of diagnosis, treatment, and prognosis. Ann Surg Oncol. May 1994;1(3):183-8. [Medline].

  37. Beebe-Dimmer JL, Schottenfeld D. Cancers of the small intestine. In: Schottenfeld D, Fraumeni J, eds. Cancer. Epidemiology and Prevention. 3rd ed. Oxford University Press; 2006:801-8.

  38. Blanchard DK, Budde JM, Hatch GF 3rd, et al. Tumors of the small intestine. World J Surg. Apr 2000;24(4):421-9. [Medline].

  39. Cobrin GM, Pittman RH, Lewis BS. Increased diagnostic yield of small bowel tumors with capsule endoscopy. Cancer. Jul 1 2006;107(1):22-7. [Medline].

  40. Cunningham JD, Aleali R, Aleali M, et al. Malignant small bowel neoplasms: histopathologic determinants of recurrence and survival. Ann Surg. Mar 1997;225(3):300-6. [Medline].

  41. Dabaja BS, Suki D, Pro B, Bonnen M, Ajani J. Adenocarcinoma of the small bowel: presentation, prognostic factors, and outcome of 217 patients. Cancer. Aug 1 2004;101(3):518-26. [Medline].

  42. Goldblum JR, Appelman HD. Stromal tumors of the duodenum. A histologic and immunohistochemical study of 20 cases. Am J Surg Pathol. Jan 1995;19(1):71-80. [Medline].

  43. Green PHR SN, Stavropoulos SG, Panagi SL, et al. Characteristics of adult celiac disease in the USA: results of a national survey. Am J Gastroenterol. Jan 2001;96(1):126-31. [Medline].

  44. Hemminki A. The molecular basis and clinical aspects of Peutz-Jeghers syndrome. Cell Mol Life Sci. May 1999;55(5):735-50. [Medline].

  45. Howe JR, Karnell LH, Menck HR, Scott-Conner C. The American College of Surgeons Commission on Cancer and the American Cancer Society. Adenocarcinoma of the small bowel: review of the National Cancer Data Base, 1985-1995. Cancer. Dec 15 1999;86(12):2693-706. [Medline].

  46. Jemal A, Murray T, Ward E, et al. Cancer statistics, 2005. CA Cancer J Clin. Jan-Feb 2005;55(1):10-30. [Medline].

  47. Miettinen M, Lasota J. Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. Jan 2001;438(1):1-12. [Medline].

  48. Miettinen M, Sobin LH, Sarlomo-Rikala M. Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT). Mod Pathol. Oct 2000;13(10):1134-42. [Medline].

  49. National Comprehensive Cancer Network. Clinical Practice Guidelines in Oncology. Available at http://www.nccn.org/professionals/physician_gls/default.asp.

  50. Neugut AI, Arber N. Epidemiology, molecular epidemiology, and molecular biology of small bowel and appendiceal adenocarcinomas. In: Abbruzzese J, ed. Principles and Practice of Gastrointestinal Oncology. Baltimore, Md: Lippincott Williams & Wilkins; 2001.

  51. Neugut AI, Marvin MR, Rella VA, Chabot JA. An overview of adenocarcinoma of the small intestine. Oncology (Huntingt). Apr 1997;11(4):529-36; discussion 545, 549-50. [Medline].

  52. Rodriguez-Bigas MA, Vasen HF, Lynch HT, et al. Characteristics of small bowel carcinoma in hereditary nonpolyposis colorectal carcinoma. International Collaborative Group on HNPCC. Cancer. Jul 15 1998;83(2):240-4. [Medline].

  53. Sturgeon C, Chejfec G, Espat NJ. Gastrointestinal stromal tumors: a spectrum of disease. Surg Oncol. Jul 2003;12(1):21-6. [Medline].

  54. Suster S. Gastrointestinal stromal tumors. Semin Diagn Pathol. Nov 1996;13(4):297-313. [Medline].

  55. Talamonti MS, Goetz LH, Rao S, Joehl RJ. Primary cancers of the small bowel: analysis of prognostic factors and results of surgical management. Arch Surg. May 2002;137(5):564-70; discussion 570-1. [Medline].

  56. Tworek JA, Appelman HD, Singleton TP, Greenson JK. Stromal tumors of the jejunum and ileum. Mod Pathol. Mar 1997;10(3):200-9. [Medline].

 
Previous
Next
 
 
 
 
All material on this website is protected by copyright, Copyright © 1994-2012 by WebMD LLC.
This website also contains material copyrighted by 3rd parties.

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.