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  • Review Article
  • Published:

Small bowel adenocarcinomas—existing evidence and evolving paradigms

Nature Reviews Clinical Oncology volume 10, pages 534–544 (2013)Cite this article

Subjects

Key Points

  • Small bowel tumours are rare cancers and their incidence worldwide is increasing

  • Clinical presentation is nonspecific and specialized diagnostic modalities, such as enteroclysis, enterography, enteroscopy and video-capsule endoscopy are needed for early diagnosis

  • Surgery is the mainstay treatment for locoregional disease and the benefit from adjuvant chemotherapy is unclear

  • Systemic fluoropyrimidine and oxaliplatin-based chemotherapy has shown clinical benefit in metastatic disease

  • Recent molecular characterization efforts have revealed distinct molecular biology and pathogenesis compared to colorectal cancers

  • Large-scale collaborative research efforts are necessary to improving our knowledge regarding the management of these uncommon tumours

Abstract

Small bowel cancers account for 3% of all gastrointestinal malignancies and small bowel adenocarcinomas represent a third of all small bowel cancers. Rarity of small bowel adenocarcinomas restricts molecular understanding and presents unique diagnostic and therapeutic challenges. Better cross-sectional imaging techniques and development of enteroscopy and capsule endoscopy have facilitated earlier and more-accurate diagnosis. Surgical resection remains the mainstay of therapy for locoregional disease. In the metastatic setting, fluoropyrimidine and oxaliplatin-based chemotherapy has shown clinical benefit in prospective non-randomized trials. Although frequently grouped under the same therapeutic umbrella as large bowel adenocarcinomas, small bowel adenocarcinomas are distinct clinical and molecular entities. Recent progress in molecular characterization has aided our understanding of the pathogenesis of these tumours and holds potential for prospective development of novel targeted therapies. Multi-institutional collaborative efforts directed towards cogent understanding of tumour biology and designing sensible clinical trials are essential for developing improved therapeutic strategies. In this Review, we endeavour to outline an evidence-based approach to present-day management of small bowel adenocarcinoma, describe contemporary challenges and uncover evolving paradigms in the management of these rare 'orphan' neoplasias.

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Figure 1: Epidemiology of small bowel tumours from the NCDB (1985–2005) and US SEER (1973–2005) cohorts and Connecticut Tumour Registry 1980–2000.2,3,6
Figure 2: The adenoma–carcinoma sequence in small bowel adenocarcinomas.
Figure 3: Algorithm showing the management of patients with small bowel adenocarcinomas.
Figure 4: Role of chemotherapy in metastatic small bowel adenocarcinoma.

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References

  1. Hatzaras, I. et al. Small-bowel tumours: epidemiologic and clinical characteristics of 1260 cases from the connecticut tumour registry. Arch. Surg. 142, 229–235 (2007).

    Article  PubMed  Google Scholar 

  2. Schottenfeld, D., Beebe-Dimmer, J. L. & Vigneau, F. D. The epidemiology and pathogenesis of neoplasia in the small intestine. Ann. Epidemiol. 19, 58–69 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Chow, J. S., Chen, C. C., Ahsan, H. & Neugut, A. I. A population-based study of the incidence of malignant small bowel tumours: SEER, 1973–1990. Int. J. Epidemiol. 25, 722–728 (1996).

    Article  CAS  PubMed  Google Scholar 

  4. Siegel, R., Naishadham, D. & Jemal, A. Cancer statistics, 2013. CA Cancer J. Clin. 63, 11–30 (2013).

    Article  PubMed  Google Scholar 

  5. Bilimoria, K. Y. et al. Small bowel cancer in the United States: changes in epidemiology, treatment, and survival over the last 20 years. Ann. Surg. 249, 63–71 (2009).

    Article  PubMed  Google Scholar 

  6. Lu, Y., Frobom, R. & Lagergren, J. Incidence patterns of small bowel cancer in a population-based study in Sweden: increase in duodenal adenocarcinoma. Cancer Epidemiol. 36, e158–e163 (2012).

    Article  PubMed  Google Scholar 

  7. Haselkorn, T., Whittemore, A. S. & Lilienfeld, D. E. Incidence of small bowel cancer in the United States and worldwide: geographic, temporal, and racial differences. Cancer Causes Control 16, 781–787 (2005).

    Article  PubMed  Google Scholar 

  8. Howe, J. R., Karnell, L. H., Menck, H. R. & 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 86, 2693–2706 (1999).

    Article  CAS  PubMed  Google Scholar 

  9. Halfdanarson, T. R., McWilliams, R. R., Donohue, J. H. & Quevedo, J. F. A single-institution experience with 491 cases of small bowel adenocarcinoma. Am. J. Surg. 199, 797–803 (2010).

    Article  PubMed  Google Scholar 

  10. Chang, H. K. et al. Adenocarcinoma of the small intestine: a multi-institutional study of 197 surgically resected cases. Hum. Pathol. 41, 1087–1096 (2010).

    Article  PubMed  Google Scholar 

  11. Goodman, M. T., Matsuno, R. K. & Shvetsov, Y. B. Racial and ethnic variation in the incidence of small-bowel cancer subtypes in the United States, 1995–2008. Dis. Colon Rectum 56, 441–448 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  12. Overman, M. J. et al. A population-based comparison of adenocarcinoma of the large and small intestine: insights into a rare disease. Ann. Surg. Oncol. 19, 1439–1445 (2012).

    Article  PubMed  Google Scholar 

  13. Rodriguez-Bigas, M. A. et al. Characteristics of small bowel carcinoma in hereditary nonpolyposis colorectal carcinoma. International Collaborative Group on HNPCC. Cancer 83, 240–244 (1998).

    Article  CAS  PubMed  Google Scholar 

  14. Giardiello, F. M. et al. Very high risk of cancer in familial Peutz-Jeghers syndrome. Gastroenterology 119, 1447–1453 (2000).

    Article  CAS  PubMed  Google Scholar 

  15. Koornstra, J. J. et al. Management of extracolonic tumours in patients with Lynch syndrome. Lancet Oncol. 10, 400–408 (2009).

    Article  CAS  PubMed  Google Scholar 

  16. ten Kate, G. L. et al. Is surveillance of the small bowel indicated for Lynch syndrome families? Gut 56, 1198–1201 (2007).

    Article  CAS  PubMed  Google Scholar 

  17. Galiatsatos, P. & Foulkes, W. D. Familial adenomatous polyposis. Am. J. Gastroenterol. 101, 385–398 (2006).

    Article  PubMed  Google Scholar 

  18. Centre, M. M., Jemal, A. & Ward, E. International trends in colorectal cancer incidence rates. Cancer Epidemiol. Biomarkers Prev. 18, 1688–1694 (2009).

    Article  Google Scholar 

  19. Dabaja, B. S., Suki, D., Pro, B., Bonnen, M. & Ajani, J. Adenocarcinoma of the small bowel: presentation, prognostic factors, and outcome of 217 patients. Cancer 101, 518–526 (2004).

    Article  PubMed  Google Scholar 

  20. Sellner, F. Investigations on the significance of the adenoma-carcinoma sequence in the small bowel. Cancer 66, 702–715 (1990).

    Article  CAS  PubMed  Google Scholar 

  21. Perzin, K. H. & Bridge, M. F. Adenomas of the small intestine: a clinicopathologic review of 51 cases and a study of their relationship to carcinoma. Cancer 48, 799–819 (1981).

    Article  CAS  PubMed  Google Scholar 

  22. Vogelstein, B. et al. Genetic alterations during colorectal-tumour development. N. Engl. J. Med. 319, 525–532 (1988).

    Article  CAS  PubMed  Google Scholar 

  23. Haan, J. C. et al. Small bowel adenocarcinoma copy number profiles are more closely related to colorectal than to gastric cancers. Ann. Oncol. 23, 367–374 (2012).

    Article  CAS  PubMed  Google Scholar 

  24. Chan, O. T. et al. Lack of HER2 overexpression and amplification in small intestinal adenocarcinoma. Am. J. Clin. Pathol. 134, 880–885 (2010).

    Article  CAS  PubMed  Google Scholar 

  25. Kountourakis, P. et al. Clinicopathologic significance of EGFR and Her-2/neu in colorectal adenocarcinomas. Cancer J. 12, 229–236 (2006).

    Article  CAS  PubMed  Google Scholar 

  26. Shitara, K. et al. Prognosis of patients with advanced gastric cancer by HER2 status and trastuzumab treatment. Gastric Cancer 16, 261–267 (2012).

    Article  CAS  PubMed  Google Scholar 

  27. DeSesso, J. M. & Jacobson, C. F. Anatomical and physiological parameters affecting gastrointestinal absorption in humans and rats. Food Chem. Toxicol. 39, 209–228 (2001).

    Article  CAS  PubMed  Google Scholar 

  28. Lowenfels, A. B. Why are small-bowel tumours so rare? Lancet 1, 24–26 (1973).

    Article  CAS  PubMed  Google Scholar 

  29. Calman, K. C. Why are small bowel tumours rare? An experimental model. Gut 15, 552–554 (1974).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Blaker, H. et al. Mutational activation of the RAS-RAF-MAPK and the Wnt pathway in small intestinal adenocarcinomas. Scand. J. Gastroenterol. 39, 748–753 (2004).

    Article  CAS  PubMed  Google Scholar 

  31. Miyaki, M. et al. Characteristics of somatic mutation of the adenomatous polyposis coli gene in colorectal tumours. Cancer Res. 54, 3011–3020 (1994).

    CAS  PubMed  Google Scholar 

  32. Pan, S. Y. & Morrison, H. Epidemiology of cancer of the small intestine. World J. Gastrointest. Oncol. 3, 33–42 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  33. Green, P. H. & Cellier, C. Celiac disease. N. Engl. J. Med. 357, 1731–1743 (2007).

    Article  CAS  PubMed  Google Scholar 

  34. Jess, T., Winther, K. V., Munkholm, P., Langholz, E. & Binder, V. Intestinal and extra-intestinal cancer in Crohn's disease: follow-up of a population-based cohort in Copenhagen County, Denmark. Aliment. Pharmacol. Ther. 19, 287–293 (2004).

    Article  CAS  PubMed  Google Scholar 

  35. Jess, T., Gamborg, M., Matzen, P., Munkholm, P. & Sorensen, T. I. Increased risk of intestinal cancer in Crohn's disease: a meta-analysis of population-based cohort studies. Am. J. Gastroenterol. 100, 2724–2729 (2005).

    Article  PubMed  Google Scholar 

  36. Green, P. H. et al. Risk of malignancy in patients with celiac disease. Am. J. Med. 115, 191–195 (2003).

    Article  PubMed  Google Scholar 

  37. Wu, A. H., Yu, M. C. & Mack, T. M. Smoking, alcohol use, dietary factors and risk of small intestinal adenocarcinoma. Int. J. Cancer 70, 512–517 (1997).

    Article  CAS  PubMed  Google Scholar 

  38. Negri, E. et al. Risk factors for adenocarcinoma of the small intestine. Int. J. Cancer 82, 171–174 (1999).

    Article  CAS  PubMed  Google Scholar 

  39. Kaerlev, L. et al. Is there an association between alcohol intake or smoking and small bowel adenocarcinoma? Results from a European multi-centre case-control study. Cancer Causes Control 11, 791–797 (2000).

    Article  CAS  PubMed  Google Scholar 

  40. Boffetta, P. et al. Body mass, tobacco smoking, alcohol drinking and risk of cancer of the small intestine--a pooled analysis of over 500,000 subjects in the Asia Cohort Consortium. Ann. Oncol. 23, 1894–1898 (2012).

    Article  CAS  PubMed  Google Scholar 

  41. Chen, C. C., Neugut, A. I. & Rotterdam, H. Risk factors for adenocarcinomas and malignant carcinoids of the small intestine: preliminary findings. Cancer Epidemiol. Biomarkers Prev. 3, 205–207 (1994).

    CAS  PubMed  Google Scholar 

  42. Chow, W. H. et al. Risk factors for small intestine cancer. Cancer Causes Control 4, 163–169 (1993).

    Article  CAS  PubMed  Google Scholar 

  43. Cross, A. J. et al. A prospective study of meat and fat intake in relation to small intestinal cancer. Cancer Res. 68, 9274–9279 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Schatzkin, A., Park, Y., Leitzmann, M. F., Hollenbeck, A. R. & Cross, A. J. Prospective study of dietary fibre, whole grain foods, and small intestinal cancer. Gastroenterology 135, 1163–1167 (2008).

    Article  CAS  PubMed  Google Scholar 

  45. Wolk, A. et al. A prospective study of obesity and cancer risk (Sweden). Cancer Causes Control 12, 13–21 (2001).

    Article  CAS  PubMed  Google Scholar 

  46. Samanic, C. et al. Obesity and cancer risk among white and black United States veterans. Cancer Causes Control 15, 35–43 (2004).

    Article  PubMed  Google Scholar 

  47. Bjørge, T., Tretli, S. & Engeland, A. Height and body mass index in relation to cancer of the small intestine in two million Norwegian men and women. Br. J. Cancer 93, 807–810 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  48. Jagelman, D. G., DeCosse, J. J. & Bussey, H. J. Upper gastrointestinal cancer in familial adenomatous polyposis. Lancet 1, 1149–1151 (1988).

    Article  CAS  PubMed  Google Scholar 

  49. Saurin, J. C. et al. Surveillance of duodenal adenomas in familial adenomatous polyposis reveals high cumulative risk of advanced disease. J. Clin. Oncol. 22, 493–498 (2004).

    Article  PubMed  Google Scholar 

  50. Fu, T. et al. CpG island methylator phenotype-positive tumours in the absence of MLH1 methylation constitute a distinct subset of duodenal adenocarcinomas and are associated with poor prognosis. Clin. Cancer Res. 18, 4743–4752 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Rashid, A. & Hamilton, S. R. Genetic alterations in sporadic and Crohn's-associated adenocarcinomas of the small intestine. Gastroenterology 113, 127–135 (1997).

    Article  CAS  PubMed  Google Scholar 

  52. Wheeler, J. M. et al. An insight into the genetic pathway of adenocarcinoma of the small intestine. Gut 50, 218–223 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Miyoshi, Y. et al. Somatic mutations of the APC gene in colorectal tumours: mutation cluster region in the APC gene. Hum. Mol. Genet. 1, 229–233 (1992).

    Article  CAS  PubMed  Google Scholar 

  54. Diosdado, B. et al. High-resolution array comparative genomic hybridization in sporadic and celiac disease-related small bowel adenocarcinomas. Clin. Cancer Res. 16, 1391–1401 (2010).

    Article  CAS  PubMed  Google Scholar 

  55. Lee, H. J. et al. Combined loss of E-cadherin and aberrant beta-catenin protein expression correlates with a poor prognosis for small intestinal adenocarcinomas. Am. J. Clin. Pathol. 139, 167–176 (2013).

    Article  PubMed  Google Scholar 

  56. Murata, M. et al. Molecular and biological analysis of carcinoma of the small intestine: beta-catenin gene mutation by interstitial deletion involving exon 3 and replication error phenotype. Am. J. Gastroenterol. 95, 1576–1580 (2000).

    CAS  PubMed  Google Scholar 

  57. Bläker, H., von Herbay, A., Penzel, R., Gross, S. & Otto, H. F. Genetics of adenocarcinomas of the small intestine: frequent deletions at chromosome 18q and mutations of the SMAD4 gene. Oncogene 21, 158–164 (2002).

    Article  PubMed  Google Scholar 

  58. Breuhahn, K., Singh, S., Schirmacher, P. & Blaker, H. Large-scale N-terminal deletions but not point mutations stabilize beta-catenin in small bowel carcinomas, suggesting divergent molecular pathways of small and large intestinal carcinogenesis. J. Pathol. 215, 300–307 (2008).

    Article  CAS  PubMed  Google Scholar 

  59. Ilyas, M., Tomlinson, I. P., Rowan, A., Pignatelli, M. & Bodmer, W. F. Beta-catenin mutations in cell lines established from human colorectal cancers. Proc. Natl Acad. Sci. USA 94, 10330–10334 (1997).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Cho, K. R. et al. The DCC gene: structural analysis and mutations in colorectal carcinomas. Genomics 19, 525–531 (1994).

    Article  CAS  PubMed  Google Scholar 

  61. Reiss, M., Santoro, V., de Jonge, R. R. & Vellucci, V. F. Transfer of chromosome 18 into human head and neck squamous carcinoma cells: evidence for tumour suppression by Smad4/DPC4. Cell Growth Differ. 8, 407–415 (1997).

    CAS  PubMed  Google Scholar 

  62. Thiagalingam, S. et al. Evaluation of candidate tumour suppressor genes on chromosome 18 in colorectal cancers. Nat. Genet. 13, 343–346 (1996).

    Article  CAS  PubMed  Google Scholar 

  63. Svrcek, M. et al. Immunohistochemical analysis of adenocarcinoma of the small intestine: a tissue microarray study. J. Clin. Pathol. 56, 898–903 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Blaker, H. et al. Loss of SMAD4 function in small intestinal adenocarcinomas: comparison of genetic and immunohistochemical findings. Pathol. Res. Pract. 200, 1–7 (2004).

    Article  CAS  PubMed  Google Scholar 

  65. Nishiyama, K. et al. Overexpression of p53 protein and point mutation of K-ras genes in primary carcinoma of the small intestine. Oncol. Rep. 9, 293–300 (2002).

    PubMed  Google Scholar 

  66. Boland, C. R. et al. A National Cancer Institute Workshop on Microsatellite Instability for cancer detection and familial predisposition: development of international criteria for the determination of microsatellite instability in colorectal cancer. Cancer Res. 58, 5248–5257 (1998).

    CAS  PubMed  Google Scholar 

  67. Overman, M. J. et al. Immunophenotype and molecular characterisation of adenocarcinoma of the small intestine. Br. J. Cancer 102, 144–150 (2010).

    Article  CAS  PubMed  Google Scholar 

  68. Planck, M. et al. Microsatellite instability and expression of MLH1 and MSH2 in carcinomas of the small intestine. Cancer 97, 1551–1557 (2003).

    Article  CAS  PubMed  Google Scholar 

  69. Potter, D. D. et al. The role of defective mismatch repair in small bowel adenocarcinoma in celiac disease. Cancer Res. 64, 7073–7077 (2004).

    Article  CAS  PubMed  Google Scholar 

  70. Minardi, A. J. Jr, Zibari, G. B., Aultman, D. F., McMillan, R. W. & McDonald, J. C. Small-bowel tumours. J. Am. Coll. Surg. 186, 664–668 (1998).

    Article  PubMed  Google Scholar 

  71. Talamonti, M. S., Goetz, L. H., Rao, S. & Joehl, R. J. Primary cancers of the small bowel: analysis of prognostic factors and results of surgical management. Arch. Surg. 137, 564–570 (2002).

    Article  PubMed  Google Scholar 

  72. Zaanan, A. et al. Chemotherapy of advanced small-bowel adenocarcinoma: a multicenter AGEO study. Ann. Oncol. 21, 1786–1793 (2010).

    Article  CAS  PubMed  Google Scholar 

  73. Maglinte, D. D., O'Connor, K., Bessette, J., Chernish, S. M. & Kelvin, F. M. The role of the physician in the late diagnosis of primary malignant tumours of the small intestine. Am. J. Gastroenterol. 86, 304–308 (1991).

    CAS  PubMed  Google Scholar 

  74. Bessette, J. R., Maglinte, D. D., Kelvin, F. M. & Chernish, S. M. Primary malignant tumors in the small bowel: a comparison of the small-bowel enema and conventional follow-through examination. AJR Am. J. Roentgenol. 153, 741–744 (1989).

    Article  CAS  PubMed  Google Scholar 

  75. Dudiak, K. M., Johnson, C. D. & Stephens, D. H. Primary tumors of the small intestine: CT evaluation. AJR Am. J. Roentgenol. 152, 995–998 (1989).

    Article  CAS  PubMed  Google Scholar 

  76. Pilleul, F. et al. Possible small-bowel neoplasms: contrast-enhanced and water-enhanced multidetector CT enteroclysis. Radiology 241, 796–801 (2006).

    Article  PubMed  Google Scholar 

  77. Van Weyenberg, S. J. et al. MR enteroclysis in the diagnosis of small-bowel neoplasms. Radiology 254, 765–773 (2010).

    Article  PubMed  Google Scholar 

  78. Minordi, L. M., Vecchioli, A., Mirk, P. & Bonomo, L. CT enterography with polyethylene glycol solution vs CT enteroclysis in small bowel disease. Br. J. Radiol. 84, 112–119 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Laurent, F. et al. Diagnosis and categorization of small bowel neoplasms: role of computed tomography. Gastrointest. Radiol. 16, 115–119 (1991).

    Article  CAS  PubMed  Google Scholar 

  80. Cronin, C. G. et al. Utility of positron emission tomography/CT in the evaluation of small bowel pathology. Br. J. Radiol. 85, 1211–1221 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Fry, L. C., Bellutti, M., Neumann, H., Malfertheiner, P. & Monkemuller, K. Incidence of bleeding lesions within reach of conventional upper and lower endoscopes in patients undergoing double-balloon enteroscopy for obscure gastrointestinal bleeding. Aliment. Pharmacol. Ther. 29, 342–349 (2009).

    Article  CAS  PubMed  Google Scholar 

  82. Lewis, B. S., Eisen, G. M. & Friedman, S. A pooled analysis to evaluate results of capsule endoscopy trials. Endoscopy 37, 960–965 (2005).

    Article  CAS  PubMed  Google Scholar 

  83. Cobrin, G. M., Pittman, R. H. & Lewis, B. S. Increased diagnostic yield of small bowel tumors with capsule endoscopy. Cancer 107, 22–27 (2006).

    Article  PubMed  Google Scholar 

  84. Wiarda, B. M. et al. Small bowel Crohn's disease: MR enteroclysis and capsule endoscopy compared to balloon-assisted enteroscopy. Abdom. Imaging 37, 397–403 (2012).

    Article  PubMed  Google Scholar 

  85. Huprich, J. E. et al. Prospective blinded comparison of wireless capsule endoscopy and multiphase CT enterography in obscure gastrointestinal bleeding. Radiology 260, 744–751 (2011).

    Article  PubMed  Google Scholar 

  86. Ross, A. et al. Double balloon enteroscopy detects small bowel mass lesions missed by capsule endoscopy. Dig. Dis. Sci. 53, 2140–2143 (2008).

    Article  PubMed  Google Scholar 

  87. Bakaeen, F. G. et al. What prognostic factors are important in duodenal adenocarcinoma? Arch. Surg. 135, 635–641 (2000).

    Article  CAS  PubMed  Google Scholar 

  88. Abrahams, N. A., Halverson, A., Fazio, V. W., Rybicki, L. A. & Goldblum, J. R. Adenocarcinoma of the small bowel: a study of 37 cases with emphasis on histologic prognostic factors. Dis. Colon Rectum 45, 1496–1502 (2002).

    Article  PubMed  Google Scholar 

  89. Sohn, T. A. et al. Adenocarcinoma of the duodenum: factors influencing long-term survival. J. Gastrointest. Surg. 2, 79–87 (1998).

    Article  CAS  PubMed  Google Scholar 

  90. Overman, M. J., Hu, C. Y., Wolff, R. A. & Chang, G. J. Prognostic value of lymph node evaluation in small bowel adenocarcinoma: analysis of the surveillance, epidemiology, and end results database. Cancer 116, 5374–5382 (2010).

    Article  PubMed  Google Scholar 

  91. Nicholl, M. B. et al. Small bowel adenocarcinoma: understaged and undertreated? Ann. Surg. Oncol. 17, 2728–2732 (2010).

    Article  PubMed  Google Scholar 

  92. Edge, S., Byrd, D. R. & Compton, C. C. in AJCC Cancer Staging Manual, 7th edn Ch. 17 (eds Edge, S. B. et al.) 181–190 (Springer, New York, 2010).

    Google Scholar 

  93. Barnes, G. Jr, Romero, L., Hess, K. R. & Curley, S. A. Primary adenocarcinoma of the duodenum: management and survival in 67 patients. Ann. Surg. Oncol. 1, 73–78 (1994).

    Article  PubMed  Google Scholar 

  94. Kaklamanos, I. G. et al. Extent of resection in the management of duodenal adenocarcinoma. Am. J. Surg. 179, 37–41 (2000).

    Article  CAS  PubMed  Google Scholar 

  95. Joesting, D. R., Beart, R. W. Jr, van Heerden, J. A. & Weiland, L. H. Improving survival in adenocarcinoma of the duodenum. Am. J. Surg. 141, 228–231 (1981).

    Article  CAS  PubMed  Google Scholar 

  96. Poultsides, G. A. et al. Duodenal adenocarcinoma: clinicopathologic analysis and implications for treatment. Ann. Surg. Oncol. 19, 1928–1935 (2012).

    Article  PubMed  Google Scholar 

  97. Lepage, C., Bouvier, A. M., Manfredi, S., Dancourt, V. & Faivre, J. Incidence and management of primary malignant small bowel cancers: a well-defined French population study. Am. J. Gastroenterol. 101, 2826–2832 (2006).

    Article  PubMed  Google Scholar 

  98. Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Lancet 345, 939–944 (1995).

  99. Overman, M. J., Kopetz, S., Lin, E., Abbruzzese, J. L. & Wolff, R. A. Is there a role for adjuvant therapy in resected adenocarcinoma of the small intestine. Acta Oncol. 49, 474–479 (2010).

    Article  PubMed  Google Scholar 

  100. Singhal, N. & Singhal, D. Adjuvant chemotherapy for small intestine adenocarcinoma. Cochrane Database Systematic Reviews, Art. No.: CD005202, http://dx.doi.org/10.1002/14651858.CD005202.pub2.

  101. Keat, N. et al. International rare cancers initiative. Lancet Oncol. 14, 109–110 (2013).

    Article  PubMed  Google Scholar 

  102. Swartz, M. J. et al. Adjuvant concurrent chemoradiation for node-positive adenocarcinoma of the duodenum. Arch. Surg. 142, 285–288 (2007).

    Article  PubMed  Google Scholar 

  103. Kelsey, C. R. et al. Duodenal adenocarcinoma: patterns of failure after resection and the role of chemoradiotherapy. Int. J. Radiat. Oncol. Biol. Phys. 69, 1436–1441 (2007).

    Article  PubMed  Google Scholar 

  104. Onkendi, E. O. et al. Neoadjuvant treatment of duodenal adenocarcinoma: a rescue strategy. J. Gastrointest. Surg. 16, 320–324 (2012).

    Article  PubMed  Google Scholar 

  105. Fishman, P. N. et al. Natural history and chemotherapy effectiveness for advanced adenocarcinoma of the small bowel: a retrospective review of 113 cases. Am. J. Clin. Oncol. 29, 225–231 (2006).

    Article  CAS  PubMed  Google Scholar 

  106. Koo, D. H. et al. Systemic chemotherapy for treatment of advanced small bowel adenocarcinoma with prognostic factor analysis: retrospective study. BMC Cancer 11, 205 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  107. Czaykowski, P. & Hui, D. Chemotherapy in small bowel adenocarcinoma: 10-year experience of the British Columbia Cancer Agency. Clin. Oncol. (R. Coll. Radiol.) 19, 143–149 (2007).

    Article  CAS  Google Scholar 

  108. Ouriel, K. & Adams, J. T. Adenocarcinoma of the small intestine. Am. J. Surg. 147, 66–71 (1984).

    Article  CAS  PubMed  Google Scholar 

  109. Gibson, M. K., Holcroft, C. A., Kvols, L. K. & Haller, D. Phase II study of 5-fluorouracil, doxorubicin, and mitomycin C for metastatic small bowel adenocarcinoma. Oncologist 10, 132–137 (2005).

    Article  CAS  PubMed  Google Scholar 

  110. Overman, M. J. et al. Phase II study of capecitabine and oxaliplatin for advanced adenocarcinoma of the small bowel and ampulla of Vater. J. Clin. Oncol. 27, 2598–2603 (2009).

    Article  CAS  PubMed  Google Scholar 

  111. McWilliams, R. R. et al. Pharmacogenetic dosing by UGT1A1 genotype as first-line therapy for advanced small-bowel adenocarcinoma: A North Central Cancer Treatment Group (NCCTG) trial [abstract]. J. Clin. Oncol. 30 (Suppl. 4), a314 (2012).

    Article  Google Scholar 

  112. Xiang, X. J. et al. A phase II study of modified FOLFOX as first-line chemotherapy in advanced small bowel adenocarcinoma. Anticancer Drugs 23, 561–566 (2012).

    Article  CAS  PubMed  Google Scholar 

  113. Locher, C. et al. Combination chemotherapy in advanced small bowel adenocarcinoma. Oncology 69, 290–294 (2005).

    Article  CAS  PubMed  Google Scholar 

  114. Zaanan, A. et al. Second-line chemotherapy with fluorouracil, leucovorin, and irinotecan (FOLFIRI regimen) in patients with advanced small bowel adenocarcinoma after failure of first-line platinum-based chemotherapy: a multicentre AGEO study. Cancer 117, 1422–1428 (2011).

    Article  CAS  PubMed  Google Scholar 

  115. Zhang, L. et al. Efficacy of the FOLFOX/CAPOX regimen for advanced small bowel adenocarcinoma: a three-centre study from China. J. BUON 16, 689–696 (2011).

    PubMed  Google Scholar 

  116. Jigyasu, D., Bedikian, A. Y. & Stroehlein, J. R. Chemotherapy for primary adenocarcinoma of the small bowel. Cancer 53, 23–25 (1984).

    Article  CAS  PubMed  Google Scholar 

  117. Crawley, C., Ross, P., Norman, A., Hill, A. & Cunningham, D. The Royal Marsden experience of a small bowel adenocarcinoma treated with protracted venous infusion 5-fluorouracil. Br. J. Cancer 78, 508–510 (1998).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Tsushima, T. et al. Multicenter retrospective study of 132 patients with unresectable small bowel adenocarcinoma treated with chemotherapy. Oncologist 17, 1163–1170 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  119. Overman, M. J. et al. Chemotherapy with 5-fluorouracil and a platinum compound improves outcomes in metastatic small bowel adenocarcinoma. Cancer 113, 2038–2045 (2008).

    Article  CAS  PubMed  Google Scholar 

  120. Santini, D. et al. Cetuximab in small bowel adenocarcinoma: a new friend? Br. J. Cancer 103, 1305 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. De Dosso, S., Molinari, F., Martin, V., Frattini, M. & Saletti, P. Molecular characterisation and cetuximab-based treatment in a patient with refractory small bowel adenocarcinoma. Gut 59, 1587–1588 (2010).

    Article  PubMed  Google Scholar 

  122. Jeurnink, S. M., van Eijck, C. H., Steyerberg, E. W., Kuipers, E. J. & Siersema, P. D. Stent versus gastrojejunostomy for the palliation of gastric outlet obstruction: a systematic review. BMC Gastroenterol. 7, 18 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  123. Ercolani, G. et al. The role of liver resections for noncolorectal, nonneuroendocrine metastases: experience with 142 observed cases. Ann. Surg. Oncol. 12, 459–466 (2005).

    Article  PubMed  Google Scholar 

  124. Adam, R. et al. Hepatic resection for noncolorectal nonendocrine liver metastases: analysis of 1,452 patients and development of a prognostic model. Ann. Surg. 244, 524–535 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

M. Overman is supported in part by the Kavanagh Family Foundation.

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  1. Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Centre, Unit #426, 1515 Holcombe Boulevard, Houston, 77030, TX, USA

    Kanwal Raghav & Michael J. Overman

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  1. Kanwal Raghav
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  2. Michael J. Overman
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Both authors researched data for the article, made substantial contributions to discussion of content, and wrote, reviewed and edited the manuscript before submission.

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Correspondence to Michael J. Overman.

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Raghav, K., Overman, M. Small bowel adenocarcinomas—existing evidence and evolving paradigms. Nat Rev Clin Oncol 10, 534–544 (2013). https://doi.org/10.1038/nrclinonc.2013.132

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