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Ampullary carcinoma: Treatment and prognosis

David P Ryan, MD
Harvey Mamon, MD, PhD
Carlos Fernandez-del Castillo, MD
Section Editor
Kenneth K Tanabe, MD
Deputy Editor
Diane MF Savarese, MD


Periampullary tumors are neoplasms that arise in the vicinity of the ampulla of Vater. Neoplasms that arise in this site can originate from the pancreas, duodenum, distal common bile duct (CBD), or the structures of the ampullary complex.

The ampulla of Vater is formed by the duodenal aspect of the sphincter of Oddi muscle, which surrounds the confluence of the distal CBD and main pancreatic duct as well as the papilla of Vater, a mucosal papillary mound at the distal insertion of these ducts on the medial wall of the duodenum (figure 1). Ampullary carcinomas are defined as those that arise within the ampullary complex, distal to the confluence of the distal common bile duct and the pancreatic duct (figure 2).

This topic review will cover the treatment and prognosis of ampullary carcinomas. The epidemiology, biologic behavior, clinical manifestations, and diagnosis and staging are covered separately. (See "Ampullary carcinoma: Epidemiology, clinical manifestations, diagnosis and staging".)


The only potentially curative treatment for ampullary carcinoma is surgical resection. Complete tumor resection with negative margins (R0 resection) is a prerequisite for cure.

It can be difficult to distinguish a primary ampullary carcinoma from other periampullary tumors preoperatively. However, true ampullary cancers have a better prognosis than periampullary malignancies of pancreatic or bile duct origin. Resectability rates are higher, and five-year survival rates are approximately 30 to 50 percent in patients with limited lymph node involvement. In contrast, less than 10 percent of patients with completely resected node-positive pancreatic cancer are alive at two years. Thus, an aggressive approach to diagnosis and treatment of periampullary tumors is needed to ensure that patients with these comparatively favorable cancers are treated optimally.

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Literature review current through: Dec 2017. | This topic last updated: Jun 13, 2017.
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  1. Cloyd JM, Wang H, Overman M, et al. Influence of Preoperative Therapy on Short- and Long-Term Outcomes of Patients with Adenocarcinoma of the Ampulla of Vater. Ann Surg Oncol 2017; 24:2031.
  2. Diener MK, Knaebel HP, Heukaufer C, et al. A systematic review and meta-analysis of pylorus-preserving versus classical pancreaticoduodenectomy for surgical treatment of periampullary and pancreatic carcinoma. Ann Surg 2007; 245:187.
  3. Allema JH, Reinders ME, van Gulik TM, et al. Results of pancreaticoduodenectomy for ampullary carcinoma and analysis of prognostic factors for survival. Surgery 1995; 117:247.
  4. Bettschart V, Rahman MQ, Engelken FJ, et al. Presentation, treatment and outcome in patients with ampullary tumours. Br J Surg 2004; 91:1600.
  5. Yeo CJ, Sohn TA, Cameron JL, et al. Periampullary adenocarcinoma: analysis of 5-year survivors. Ann Surg 1998; 227:821.
  6. Roberts RH, Krige JE, Bornman PC, Terblanche J. Pancreaticoduodenectomy of ampullary carcinoma. Am Surg 1999; 65:1043.
  7. Sommerville CA, Limongelli P, Pai M, et al. Survival analysis after pancreatic resection for ampullary and pancreatic head carcinoma: an analysis of clinicopathological factors. J Surg Oncol 2009; 100:651.
  8. Herman JM, Pawlik TM, Merchant NB, et al.. Ampulla of Vater. In: AJCC Cancer Staging Manual, 8th, Amin MB (Ed), AJCC, Chicago 2017. p.327.
  9. Duffy JP, Hines OJ, Liu JH, et al. Improved survival for adenocarcinoma of the ampulla of Vater: fifty-five consecutive resections. Arch Surg 2003; 138:941.
  10. Brown KM, Tompkins AJ, Yong S, et al. Pancreaticoduodenectomy is curative in the majority of patients with node-negative ampullary cancer. Arch Surg 2005; 140:529.
  11. Howe JR, Klimstra DS, Moccia RD, et al. Factors predictive of survival in ampullary carcinoma. Ann Surg 1998; 228:87.
  12. Hsu HP, Yang TM, Hsieh YH, et al. Predictors for patterns of failure after pancreaticoduodenectomy in ampullary cancer. Ann Surg Oncol 2007; 14:50.
  13. Beger HG, Treitschke F, Gansauge F, et al. Tumor of the ampulla of Vater: experience with local or radical resection in 171 consecutively treated patients. Arch Surg 1999; 134:526.
  14. Yeo CJ. Pylorus-preserving pancreaticoduodenectomy. Surg Oncol Clin N Am 1998; 7:143.
  15. Matory YL, Gaynor J, Brennan M. Carcinoma of the ampulla of Vater. Surg Gynecol Obstet 1993; 177:366.
  16. Birkmeyer JD, Siewers AE, Finlayson EV, et al. Hospital volume and surgical mortality in the United States. N Engl J Med 2002; 346:1128.
  17. Birkmeyer JD, Warshaw AL, Finlayson SR, et al. Relationship between hospital volume and late survival after pancreaticoduodenectomy. Surgery 1999; 126:178.
  18. Birkmeyer JD, Stukel TA, Siewers AE, et al. Surgeon volume and operative mortality in the United States. N Engl J Med 2003; 349:2117.
  19. Abdullah SA, Gupta T, Jaafar KA, et al. Ampullary carcinoma: effect of preoperative biliary drainage on surgical outcome. World J Gastroenterol 2009; 15:2908.
  20. Monson JR, Donohue JH, McEntee GP, et al. Radical resection for carcinoma of the ampulla of Vater. Arch Surg 1991; 126:353.
  21. Chappuis CW, Divincenti FC, Cohn I Jr. Villous tumors of the duodenum. Ann Surg 1989; 209:593.
  22. Rattner DW, Fernandez-del Castillo C, Brugge WR, Warshaw AL. Defining the criteria for local resection of ampullary neoplasms. Arch Surg 1996; 131:366.
  23. Branum GD, Pappas TN, Meyers WC. The management of tumors of the ampulla of Vater by local resection. Ann Surg 1996; 224:621.
  24. Isaksson G, Ihse I, Andrén-Sandberg A, et al. Local excision for ampullary carcinoma. An alternative treatment for patients unfit for pancreatectomy. Acta Chir Scand 1982; 148:163.
  25. Schlippert W, Lucke D, Anuras S, Christensen J. Carcinoma of the papilla of Vater. A review of fifty-seven cases. Am J Surg 1978; 135:763.
  26. Gray G, Browder W. Villous tumors of the ampulla of Vater: local resection versus pancreatoduodenectomy. South Med J 1989; 82:917.
  27. Sharp KW, Brandes JL. Local resection of tumors of the ampulla of Vater. Am Surg 1990; 56:214.
  28. Newman RJ, Pittam MR. Local excision in the treatment of carcinoma of the ampulla of Vater. J R Coll Surg Edinb 1982; 27:154.
  29. Kahn MB, Rush BF Jr. The overlooked technique of ampullary excision. Surg Gynecol Obstet 1989; 169:253.
  30. Asbun HJ, Rossi RL, Munson JL. Local resection for ampullary tumors. Is there a place for it? Arch Surg 1993; 128:515.
  31. Chareton B, Coiffic J, Landen S, et al. Diagnosis and therapy for ampullary tumors: 63 cases. World J Surg 1996; 20:707.
  32. Tarazi RY, Hermann RE, Vogt DP, et al. Results of surgical treatment of periampullary tumors: a thirty-five-year experience. Surgery 1986; 100:716.
  33. Roggin KK, Yeh JJ, Ferrone CR, et al. Limitations of ampullectomy in the treatment of nonfamilial ampullary neoplasms. Ann Surg Oncol 2005; 12:971.
  34. Lindell G, Borch K, Tingstedt B, et al. Management of cancer of the ampulla of Vater: does local resection play a role? Dig Surg 2003; 20:511.
  35. Grobmyer SR, Stasik CN, Draganov P, et al. Contemporary results with ampullectomy for 29 "benign" neoplasms of the ampulla. J Am Coll Surg 2008; 206:466.
  36. Böttger TC, Boddin J, Heintz A, Junginger T. Clinicopathologic study for the assessment of resection for ampullary carcinoma. World J Surg 1997; 21:379.
  37. Woo SM, Ryu JK, Lee SH, et al. Feasibility of endoscopic papillectomy in early stage ampulla of Vater cancer. J Gastroenterol Hepatol 2009; 24:120.
  38. Yamaguchi K, Enjoji M. Carcinoma of the ampulla of vater. A clinicopathologic study and pathologic staging of 109 cases of carcinoma and 5 cases of adenoma. Cancer 1987; 59:506.
  39. Clary BM, Tyler DS, Dematos P, et al. Local ampullary resection with careful intraoperative frozen section evaluation for presumed benign ampullary neoplasms. Surgery 2000; 127:628.
  40. Hornick JR, Johnston FM, Simon PO, et al. A single-institution review of 157 patients presenting with benign and malignant tumors of the ampulla of Vater: management and outcomes. Surgery 2011; 150:169.
  41. National Comprehensive Cancer Network (NCCN). NCCN Clinical practice guidelines in oncology. http://www.nccn.org/professionals/physician_gls/f_guidelines.asp (Accessed on February 27, 2016).
  42. Eckel F, Jelic S. Biliary cancer: ESMO clinical recommendation for diagnosis, treatment and follow-up. Ann Oncol 2009; 20(4 suppl):iv46.
  43. Kozarek RA. Endoscopic resection of ampullary neoplasms. J Gastrointest Surg 2004; 8:932.
  44. Boix J, Lorenzo-Zúñiga V, Moreno de Vega V, et al. Endoscopic resection of ampullary tumors: 12-year review of 21 cases. Surg Endosc 2009; 23:45.
  45. Menzel J, Poremba C, Dietl KH, et al. Tumors of the papilla of Vater--inadequate diagnostic impact of endoscopic forceps biopsies taken prior to and following sphincterotomy. Ann Oncol 1999; 10:1227.
  46. Yamaguchi K, Enjoji M, Kitamura K. Endoscopic biopsy has limited accuracy in diagnosis of ampullary tumors. Gastrointest Endosc 1990; 36:588.
  47. Fowler AL, Barham CP, Britton BJ, Barr H. Laser ablation of ampullary carcinoma. Endoscopy 1999; 31:745.
  48. Sibata CH, Colussi VC, Oleinick NL, Kinsella TJ. Photodynamic therapy in oncology. Expert Opin Pharmacother 2001; 2:917.
  49. Abulafi AM, Allardice JT, Williams NS, et al. Photodynamic therapy for malignant tumours of the ampulla of Vater. Gut 1995; 36:853.
  50. Benhamiche AM, Jouve JL, Manfredi S, et al. Cancer of the ampulla of Vater: results of a 20-year population-based study. Eur J Gastroenterol Hepatol 2000; 12:75.
  51. Sellner FJ, Riegler FM, Machacek E. Implications of histological grade of tumour for the prognosis of radically resected periampullary adenocarcinoma. Eur J Surg 1999; 165:865.
  52. O'Connell JB, Maggard MA, Manunga J Jr, et al. Survival after resection of ampullary carcinoma: a national population-based study. Ann Surg Oncol 2008; 15:1820.
  53. Neoptolemos JP, Talbot IC, Shaw DC, Carr-Locke DL. Long-term survival after resection of ampullary carcinoma is associated independently with tumor grade and a new staging classification that assesses local invasiveness. Cancer 1988; 61:1403.
  54. Todoroki T, Koike N, Morishita Y, et al. Patterns and predictors of failure after curative resections of carcinoma of the ampulla of Vater. Ann Surg Oncol 2003; 10:1176.
  55. Willett CG, Warshaw AL, Convery K, Compton CC. Patterns of failure after pancreaticoduodenectomy for ampullary carcinoma. Surg Gynecol Obstet 1993; 176:33.
  56. Talamini MA, Moesinger RC, Pitt HA, et al. Adenocarcinoma of the ampulla of Vater. A 28-year experience. Ann Surg 1997; 225:590.
  57. Delcore R Jr, Connor CS, Thomas JH, et al. Significance of tumor spread in adenocarcinoma of the ampulla of Vater. Am J Surg 1989; 158:593.
  58. Shutze WP, Sack J, Aldrete JS. Long-term follow-up of 24 patients undergoing radical resection for ampullary carcinoma, 1953 to 1988. Cancer 1990; 66:1717.
  59. Yamaguchi K, Enjoji M, Tsuneyoshi M. Pancreatoduodenal carcinoma: a clinicopathologic study of 304 patients and immunohistochemical observation for CEA and CA19-9. J Surg Oncol 1991; 47:148.
  60. Lee JH, Whittington R, Williams NN, et al. Outcome of pancreaticoduodenectomy and impact of adjuvant therapy for ampullary carcinomas. Int J Radiat Oncol Biol Phys 2000; 47:945.
  61. Albores-Saavedra J, Schwartz AM, Batich K, Henson DE. Cancers of the ampulla of vater: demographics, morphology, and survival based on 5,625 cases from the SEER program. J Surg Oncol 2009; 100:598.
  62. Roder JD, Schneider PM, Stein HJ, Siewert JR. Number of lymph node metastases is significantly associated with survival in patients with radically resected carcinoma of the ampulla of Vater. Br J Surg 1995; 82:1693.
  63. Mori K, Ikei S, Yamane T, et al. Pathological factors influencing survival of carcinoma of the ampulla of Vater. Eur J Surg Oncol 1990; 16:183.
  64. Park JS, Yoon DS, Kim KS, et al. Factors influencing recurrence after curative resection for ampulla of Vater carcinoma. J Surg Oncol 2007; 95:286.
  65. Kim RD, Kundhal PS, McGilvray ID, et al. Predictors of failure after pancreaticoduodenectomy for ampullary carcinoma. J Am Coll Surg 2006; 202:112.
  66. Qiao QL, Zhao YG, Ye ML, et al. Carcinoma of the ampulla of Vater: factors influencing long-term survival of 127 patients with resection. World J Surg 2007; 31:137.
  67. Doepker MP, Thompson ZJ, Centeno BA, et al. Clinicopathologic and survival analysis of resected ampullary adenocarcinoma. J Surg Oncol 2016; 114:170.
  68. Robert PE, Leux C, Ouaissi M, et al. Predictors of long-term survival following resection for ampullary carcinoma: a large retrospective French multicentric study. Pancreas 2014; 43:692.
  69. Zhou H, Schaefer N, Wolff M, Fischer HP. Carcinoma of the ampulla of Vater: comparative histologic/immunohistochemical classification and follow-up. Am J Surg Pathol 2004; 28:875.
  70. Kim WS, Choi DW, Choi SH, et al. Clinical significance of pathologic subtype in curatively resected ampulla of vater cancer. J Surg Oncol 2012; 105:266.
  71. Chang DK, Jamieson NB, Johns AL, et al. Histomolecular phenotypes and outcome in adenocarcinoma of the ampulla of vater. J Clin Oncol 2013; 31:1348.
  72. Valsangkar NP, Ingkakul T, Correa-Gallego C, et al. Survival in ampullary cancer: potential role of different KRAS mutations. Surgery 2015; 157:260.
  73. Shaib WL, Sharma R, Brutcher E, et al. Treatment utilization and surgical outcome of ampullary and duodenal adenocarcinoma. J Surg Oncol 2014; 109:556.
  74. Neoptolemos JP, Moore MJ, Cox TF, et al. Effect of adjuvant chemotherapy with fluorouracil plus folinic acid or gemcitabine vs observation on survival in patients with resected periampullary adenocarcinoma: the ESPAC-3 periampullary cancer randomized trial. JAMA 2012; 308:147.
  75. Arroyo GF. Histomolecular phenotypes of adenocarcinoma of the ampulla of vater: more evidence is required. J Clin Oncol 2013; 31:3842.
  76. Falconi M, Crippa S, Domínguez I, et al. Prognostic relevance of lymph node ratio and number of resected nodes after curative resection of ampulla of Vater carcinoma. Ann Surg Oncol 2008; 15:3178.
  77. Sierzega M, Nowak K, Kulig J, et al. Lymph node involvement in ampullary cancer: the importance of the number, ratio, and location of metastatic nodes. J Surg Oncol 2009; 100:19.
  78. Sakata J, Shirai Y, Wakai T, et al. Number of positive lymph nodes independently affects long-term survival after resection in patients with ampullary carcinoma. Eur J Surg Oncol 2007; 33:346.
  79. Balci S, Basturk O, Saka B, et al. Substaging Nodal Status in Ampullary Carcinomas has Significant Prognostic Value: Proposed Revised Staging Based on an Analysis of 313 Well-Characterized Cases. Ann Surg Oncol 2015; 22:4392.
  80. Yeo CJ, Cameron JL, Lillemoe KD, et al. Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg 2002; 236:355.
  81. Kamisawa T, Tu Y, Egawa N, et al. Clinicopathologic features of ampullary carcinoma without jaundice. J Clin Gastroenterol 2006; 40:162.
  82. Yao HS, Wang Q, Wang WJ, Hu ZQ. Intraoperative allogeneic red blood cell transfusion in ampullary cancer outcome after curative pancreatoduodenectomy: a clinical study and meta-analysis. World J Surg 2008; 32:2038.
  83. Smith RA, Ghaneh P, Sutton R, et al. Prognosis of resected ampullary adenocarcinoma by preoperative serum CA19-9 levels and platelet-lymphocyte ratio. J Gastrointest Surg 2008; 12:1422.
  84. Balachandran P, Sikora SS, Kapoor S, et al. Long-term survival and recurrence patterns in ampullary cancer. Pancreas 2006; 32:390.
  85. Nathan H, Pawlik TM, Wolfgang CL, et al. Trends in survival after surgery for cholangiocarcinoma: a 30-year population-based SEER database analysis. J Gastrointest Surg 2007; 11:1488.
  86. Neoptolemos JP, Stocken DD, Friess H, et al. A randomized trial of chemoradiotherapy and chemotherapy after resection of pancreatic cancer. N Engl J Med 2004; 350:1200.
  87. Oettle H, Post S, Neuhaus P, et al. Adjuvant chemotherapy with gemcitabine vs observation in patients undergoing curative-intent resection of pancreatic cancer: a randomized controlled trial. JAMA 2007; 297:267.
  88. Bhatia S, Miller RC, Haddock MG, et al. Adjuvant therapy for ampullary carcinomas: the Mayo Clinic experience. Int J Radiat Oncol Biol Phys 2006; 66:514.
  89. Mehta VK, Fisher GA, Ford JM, et al. Adjuvant chemoradiotherapy for "unfavorable" carcinoma of the ampulla of Vater: preliminary report. Arch Surg 2001; 136:65.
  90. Chakravarthy A, Abrams RA, Yeo CJ, et al. Intensified adjuvant combined modality therapy for resected periampullary adenocarcinoma: acceptable toxicity and suggestion of improved 1-year disease-free survival. Int J Radiat Oncol Biol Phys 2000; 48:1089.
  91. Krishnan S, Rana V, Evans DB, et al. Role of adjuvant chemoradiation therapy in adenocarcinomas of the ampulla of vater. Int J Radiat Oncol Biol Phys 2008; 70:735.
  92. Kim K, Chie EK, Jang JY, et al. Role of adjuvant chemoradiotherapy for ampulla of Vater cancer. Int J Radiat Oncol Biol Phys 2009; 75:436.
  93. Palta M, Patel P, Broadwater G, et al. Carcinoma of the ampulla of Vater: patterns of failure following resection and benefit of chemoradiotherapy. Ann Surg Oncol 2012; 19:1535.
  94. Narang AK, Miller RC, Hsu CC, et al. Evaluation of adjuvant chemoradiation therapy for ampullary adenocarcinoma: the Johns Hopkins Hospital-Mayo Clinic collaborative study. Radiat Oncol 2011; 6:126.
  95. Sikora SS, Balachandran P, Dimri K, et al. Adjuvant chemo-radiotherapy in ampullary cancers. Eur J Surg Oncol 2005; 31:158.
  96. Zhou J, Hsu CC, Winter JM, et al. Adjuvant chemoradiation versus surgery alone for adenocarcinoma of the ampulla of Vater. Radiother Oncol 2009; 92:244.
  97. Klinkenbijl JH, Jeekel J, Sahmoud T, et al. Adjuvant radiotherapy and 5-fluorouracil after curative resection of cancer of the pancreas and periampullary region: phase III trial of the EORTC gastrointestinal tract cancer cooperative group. Ann Surg 1999; 230:776.
  98. Kwon J, Kim BH, Kim K, et al. Survival Benefit of Adjuvant Chemoradiotherapy in Patients With Ampulla of Vater Cancer: A Systematic Review and Meta-analysis. Ann Surg 2015; 262:47.
  99. Acharya A, Markar SR, Sodergren MH, et al. Meta-analysis of adjuvant therapy following curative surgery for periampullary adenocarcinoma. Br J Surg 2017; 104:814.
  100. Takada T, Amano H, Yasuda H, et al. Is postoperative adjuvant chemotherapy useful for gallbladder carcinoma? A phase III multicenter prospective randomized controlled trial in patients with resected pancreaticobiliary carcinoma. Cancer 2002; 95:1685.
  101. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med 2010; 362:1273.
  102. Jiang ZQ, Varadhachary G, Wang X, et al. A retrospective study of ampullary adenocarcinomas: overall survival and responsiveness to fluoropyrimidine-based chemotherapy. Ann Oncol 2013; 24:2349.