8/13/2019 0702061

1/6

February 2010 COMMUNITY ONCOLOGY 61Volume 7/Number 2

Review

Commun Oncol 2010;7:6166 2010 Elsevier Inc. All rights reserved.

Ampullary cancer: review andclinical updateMelissa Chan, MD, and Douglas G. Adler, MD, FACG, FASGE

University of Utah School of Medicine, Huntsman Cancer Center, Department of Internal Medicine,Division of Gastroenterology and Hepatology, Salt Lake City, UT

Ampullary carcinoma is a malignant tumor arising from the ampulla of Vater, a complex structure connecting thedistal common bile duct and the pancreatic duct with the small intestine at the medial wall of the second part of theduodenum. Ampullary carcinoma is a relatively uncommon GI malignancy, representing about 2% of GI cancers.The triad of fluctuating painless jaundice, anemia, and a palpable gallbladder is relatively specific for ampullarycarcinoma, but most patients present with obstructive jaundice before a palpable gallbladder may be appreciated.Proper staging of these tumors via noninvasive imaging, endoscopy, and biopsy is critical to treatment planning.Patients with resectable lesions should undergo primary surgery when possible. Those with unresectable disease may

benefit from palliative procedures such as endoscopic stenting and may be considered for adjuvant therapy.

Manuscript received July 1, 2009; accepted January 15, 2010.

Correspondence to: Douglas G. Adler, MD, FACG, FASGE,Associate Professor of Medicine, Director of Therapeutic En-doscopy, Division of Gastroenterology and Hepatology, Hunts-man Cancer Center, University of Utah, Salt Lake City, UT84132; telephone: 801-581-5036; fax: 801-581-8007; e-mail:douglas.adler@hsc.utah.edu.

A61-year-old woman presents with 2months of vague, nonradiating. right-upper-quadrant abdominal fullnessand jaundice. Her past medical his-tory includes hyperlipidemia, hyper-

tension, and gout. She reports an unintentional 20-lbweight loss over the past 2 months with early satietyand fullness. She has a 40-pack-year tobacco history,is currently smoking one pack of cigarettes per day,

and denies any alcohol use.On exam, the patient is afebrile with stable vi-tal signs. She appears thin and is jaundiced withscleral icterus. She has right-upper-quadrant painwith palpation, although her abdomen is soft andnondistended without rebound tenderness orguarding. No organomegaly is appreciated. Rel-evant laboratory findings include total bilirubin,11.6 mg/dL (normal, 0.21.3 mg/dL); direct bili-rubin, 9.6 mg/dL (normal, 00.4 mg/dL); aspar-tate transaminase (AST), 110 U/L (normal, 1450U/L); alanine transaminase (ALT), 129 U/L (nor-mal, 952 U/L); alkaline phosphatase, 450 U/L

(normal, 38126 U/L); hematocrit, 32.7% (nor-mal, 34.3%46.6%); and hemoglobin, 10.9 g/dL(normal, 12.115.9 g/dL).

A right-upper-quadrant ultrasound shows a dis-tended gallbladder, but no evidence of cholecystitis.The common bile duct is dilated with a diameterof 22 mm, along with intrahepatic ductal dilation.Overlying bowel gas precludes imaging of the pan-creas. An upper endoscopy reveals a prominent am-pulla (Figure 1).

Answers

The ampulla is quite large, bulging, and dis-torted, and the patient has painless jaundice with

weight loss. The lesion is most consistent with anampullary carcinoma (answer B). An impacted

What is the most likely diagnosis?

A. Impacted stone

B. Ampullary carcinoma

C. Ampullary lipoma

D. Pancreatic cancer

E. Intraductal papillary mucinous neoplasm (IPMN)

What is the next step in the patients

management?

A. Endoscopic retrogradecholangiopancreatography (ERCP)

B. Magnetic resonance cholangiopancreatography

(MRCP)

C. Surgical consultation

D. Computed tomography (CT) scan of the

abdomen

E. Observation

8/13/2019 0702061

2/6

62 COMMUNITY ONCOLOGY February 2010 www.CommunityOncology.net

REVIEW Chan/Adler

stone could have a similar appear-ance, but would much more likelybe associated with pain, cholangitis,and/or pancreatitis, and would nothave a protracted clinical course of2 months duration. Ampullary li-pomas are extremely rare and wouldbe unlikely to cause obstruction. Pa-tients with pancreatic cancer oftenhave a normal-appearing ampulla.Patients with IPMN often have a

classic-appearing major papilla, de-scribed as a gaping fish mouth ori-fice, along with copious mucous ex-trusion into the duodenum, whichthis patient does not have.

An ERCP is the next best step(answer A). An ERCP would allowboth diagnostic tissue acquisitionfrom the ampullary mass and thera-peutic biliary decompression via the

placement of a stent. Although anMRCP or a CT scan will be requiredfor cancer staging, these tests facili-tate neither confirmatory histologicsampling nor the treatment of symp-tomatic biliary obstruction. Surgicalconsultation is appropriate once thediagnosis has been confirmed patho-logically and imaging studies have ex-cluded unresectable disease (eg, lackof metastases, inoperable vascular in-

volvement). Given the patients jaun-dice and weight loss, observation isinadequate at this time.

Outcome of case

An ERCP was performed. Thecommon bile duct was 22 mm widewith diffusely dilated intrahepaticducts bilaterally, concordant with theultrasound. Biliary sphincterotomywas performed exposing tissue with-in the ampullary mass that appearedhighly suspicious for malignancy

(Figure 2). Multiple biopsies were ob-tained, and a stent was placed in thebile duct. Biopsies revealed adenocar-cinoma (Figure 3). The patients jaun-dice resolved following stent place-ment. CT scan revealed no distantmetastases. A surgical consultationwas obtained, and the patient under-went a pylorus-preserving pancreati-coduodenectomy (Whipple proce-

dure). She did not have any malignantlymph nodes at the time of surgery.She is currently undergoing surveil-lance and is doing well clinically.

Discussion

The ampulla of Vater is a complexstructure connecting the distal com-mon bile duct and the pancreatic ductwith the small intestine at the medialwall of the second part of the duode-num. The ampulla of Vater regulatespancreatic and biliary flow via con-traction and relaxation of the sphinc-

ter of Oddi. Endoscopically, the am-pulla of Vater appears as a small areaof raised mucosa, known as the papil-la, upon which the ampullary orificecan be identified.

Ampullary carcinoma is a malig-nant tumor arising from the ampul-la of Vater. It may originate from theepithelium of the distal bile duct, orthe distal pancreatic duct, or the duo-denal mucosa overlying or within thedeeper tissues of the papilla.1Regard-less of the epithelium of origin, carci-

nomas involving the major papilla ap-pear as an enlarged or redundant massencroaching upon the duodenal lu-men.2Ampullary carcinoma accountsfor 20% of all tumor-related obstruc-tions of the common bile duct, repre-senting 2% of all gastrointestinal (GI)malignancies and 20% of all tumorsof the extrahepatic biliary tree.3

Published data demonstrate an

a

b

FIGURE 1 Large, bulging ampulla of Vater(major papilla) seen endoscopically (a).Representative normal ampulla of Vater (ma-jor papilla) for comparative purposes (b).

FIGURE 2 Same ampulla as seen in Figure1a following endoscopic biliary sphincter-otomy. Note underlying bulging, friable tis-sue. This appearance is highly suspiciousfor malignancy.

FIGURE 3 Histologic image of biopsyspecimen obtained in the patient showingampullary adenocarcinoma with disor-ganized, malignant-appearing glandularstructures (hematoxylin and eosin stain;magnification, 40).

8/13/2019 0702061

3/6

February 2010 COMMUNITY ONCOLOGY 63Volume 7/Number 2

Ampullary cancer REVIEW

overall incidence of 6 cases per 1 mil-lion individuals.4 The average age attime of diagnosis of ampullary carci-noma is 6070 years. Earlier presenta-tion may occur with inherited colorec-

tal cancer syndromes such as familialadenomatous polyposis (FAP).5,6 Pa-tients with FAP must undergo endo-scopic surveillance of their small bowelto assess for the development of am-pullary and duodenal adenomas.7

Clinical presentationObstructive jaundice, with an ele-

vated total and direct bilirubin, is themost common symptom, occurring in70%80% of patients with ampullarycarcinoma.8,9Ampullary cancer tendsto protrude both into the duodenallumen and into the common bile ductand/or the pancreatic duct.2Elevatedserum alkaline phosphatase levels andincreases in serum aminotransami-nase levels are also commonly seen asa consequence of biliary obstruction.

The triad of fluctuating painlessjaundice, anemia (with or withoutsymptoms of overt GI bleeding), anda palpable gallbladder is consideredto be relatively specific for ampullary

carcinoma. This triad, however, is sel-dom observed in patients with ampul-lary cancer because the developmentof obstructive jaundice causes patientsto present early before a palpable gall-bladder may be appreciated.10,11Tumorextension into the duodenum mayrarely cause intestinal obstruction.12,13

There are no specific tumor mark-ers for ampullary carcinoma. Carbo-hydrate antigen 19-9 (CA 19-9) is atumor marker that is often elevatedin pancreaticobiliary malignancies (as

well as some benign conditions) andshould be checked in patients withknown or suspected ampullary cancer.If elevated, it can be used to moni-tor for recurrence in patients who ul-timately undergo surgery.14

Carcinoembryonic antigen (CEA)is a less specific tumor marker for am-pullary carcinoma because it is elevatedin other GI malignancies, specifically

colon and rectal neoplasms, and thus isnot routinely checked in patients withampullary carcinoma.15 The clinicalpresentation of ampullary carcinomamay closely mimic or be identical to

that of pancreatic adenocarcinoma.

Noninvasive imaging

Transabdominal ultrasound is of-ten the first modality used to evalu-ate patients with obstructive jaundice,since gallstones are the most commoncause of biliary obstruction. Althoughsuch imaging may detect a dilatedcommon bile duct, it cannot identifythe ampulla itself.16

Helical contrast-enhanced CTscans may assess for the presence ofbiliary ductal dilation, examine theperiampullary region, differentiatebetween causes of distal biliary ob-struction, assess for the presence ofmalignant-appearing lymph nodes,evaluate for metastases, and estab-lish the relationship of the tumorto nearby abdominal vascular struc-tures. Although CT cannot routinelydetect small ampullary lesions, indi-rect signs of ampullary carcinoma,such as common bile duct and main

pancreatic duct dilation, distant me-tastases, or malignant lymph nodes,are often visualized.

MRI with magnetic resonancecholangiopancreatography can visual-ize the biliary tract and pancreatic ductsin great detail as well as identify pan-creatic, biliary, or ampullary pathol-ogy.17 Ampullary carcinomas appearas masses with periductal thickening.The tumor itself often appears as a fill-ing defect protruding into the duode-nal lumen, with a characteristic delayed

enhancement.18,19 MRI with magneticresonance cholangiopancreatographyhas a sensitivity of 94%, specificity of82%, positive predictive value of 89%,and negative predictive value of 90%for the detection of malignant causes ofobstruction. The overall diagnostic ac-curacy for detection of level of obstruc-tion and cause of obstruction is 96.3%and 89.65%, respectively.2,2022

Endoscopy

Esophagogastroduodenoscopy(EGD) is an endoscopic procedurethat allows direct visualization of the

upper-GI tract and may be used toidentify ampullary masses. Specificendoscopes for evaluating the majorpapilla (duodenoscopes) are recom-mended if there is a preexisting con-cern about ampullary pathology.23

Endoscopic retrograde cholangio-pancreatography (ERCP) is an en-doscopic procedure that uses a com-bination of video endoscopy andfluoroscopy to examine the ampulla aswell as the pancreaticobiliary tree. It isthe preferred initial endoscopic studyin patients with known or suspectedampullary masses, since it allows di-agnostic maneuvers such as direct vi-sualization of the ampulla and tis-sue acquisition via biopsy, along withtherapeutic interventions such as pan-creatic, biliary sphincterotomy and/orbiliary stenting to treat jaundice.24

Endoscopic biopsies have an es-timated accuracy of approximately86%. Associated inflammation or ul-ceration can contribute to nondiag-

nostic sampling. Thus, it is importantto recognize that a negative histolog-ic result does not absolutely excludethe presence of malignancy within anampullary mass, since biopsy resultscan be falsely negative, especially ifthere is inflammation or ulceration ofthe ampullary lesion.2532

Cholangiopancreatography viaERCP can provide valuable data re-garding the presence or absence of in-traductal tumor extension, which mayhelp guide surgical planning. During

an ERCP, if an ampullary mass is ul-cerated or large in size, malignancyis more likely. Unfortunately, ERCPonly provides endoscopic informa-tion about the superficial aspects ofthe major papilla along with fluoro-scopic information about the biliaryand pancreatic ducts. It fails to pro-vide critical information regardingthe depth of tumor invasion into the

8/13/2019 0702061

4/6

8/13/2019 0702061

5/6

February 2010 COMMUNITY ONCOLOGY 65Volume 7/Number 2

dergone Roux-en-Y gastric bypass).Patients with unresectable tumors

typically undergo placement of a per-manent (metal) biliary stent to pre-vent the recurrence of jaundice. Data

on the value of chemotherapy and ra-diation therapy in this subset of pa-tients are limited.

Adjuvant therapy

The role of adjuvant therapy forampullary carcinoma is controversial.Some studies have reported improvedoverall survival with the addition ofradiotherapy and/or chemotherapyin patients with lymph node involve-ment.6264More recent data on the useof adjuvant chemo-radiation therapyin patients with ampullary cancerhave also been encouraging.

One study from M.D. Ander-son Cancer Center published in 2008evaluated 54 patients who underwentpotentially curative pancreaticoduo-denectomy followed by chemotherapywith either fluorouracil or capecitabi-ne (Xeloda) and radiotherapy. In thisstudy, there was a trend toward in-creased overall survival that just failedto reach statistical significance, al-

though the authors noted that overallsurvival in these patients was far betterthan that seen in patients with prima-ry pancreatic adenocarcinoma.65Otherstudies that evaluated adjuvant thera-py in patients with ampullary cancershow no survival benefit, so this ques-tion remains unsettled.66,67

In patients with advanced diseasebut good overall performance status,the regimen of capecitabine and oxali-platin (Eloxatin) (CAPOX) has beenshown to have an overall response

rate of 50% (although this study in-cluded patients with small bowel ad-enocarcinoma in addition to patientswith ampullary cancer).68 Definitiveconsensus guidelines for the use ofadjuvant or neoadjuvant chemother-apy and radiation therapy in ampul-lary cancer are lacking, and, in gener-al, treatment is individualized and/orbased on institutional protocols.

Conclusion

Ampullary cancer remains a rela-tively uncommon GI malignancy.Proper staging of these tumors via

imaging, endoscopy, and biopsy iscritical to treatment planning. Pa-tients with resectable lesions shouldundergo primary surgical therapywhen possible. Patients with unre-sectable disease may benefit from pal-liative procedures such as endoscopicstenting and may be considered forchemotherapy and/or radiotherapy.

Acknowledgments: The authors wish tothank Jeffrey Tokar, MD, and Fred Clayton,MD, for their assistance with this manuscript.

References

1. Fischer HP, Zhou H. Pathogenesis ofcarcinoma of the papilla of Vater. J Hepatobili-ary Pancreat Surg 2004;11:301309.

2. Kim JH, Kim M-J, Chung J-J, et al. Dif-ferential diagnosis of periampullary carcinomasat MR imaging. Radiographics 2002;22:13351352.

3. Palazzo L. Staging of ampullary carcino-ma by endoscopic ultrasonography. Endoscopy1998;30(suppl 1):A128.

4. Neoptolemos JP, Talbot IC, Carr-LockeDL, et al. Treatment and outcome in 52 con-secutive cases of ampullary carcinoma. Br JSurg 1987;74:957961.

5. Talamini MA, Moesinger, RC, Pitt,

HA, et al. Adenocarcinoma of the ampulla ofVater. A 28-year experience. Ann Surg 1997;225:590599.

6. Spiegelman AD, Williams CB, TalbotIC, et al. Upper gastrointestinal cancer in pa-tients with familial adenomatous polyposis.Lancet 1989;2:783785.

7. Nugent KP, Spigelman AD, Phillips RK:Life expectancy after colectomy and ileorectalanastomosis for familial adenomatous polypo-sis. Dis Colon Rectum 1993;36:10591062.

8. Church J, Simmang C. Practice param-eters for the treatment of patients with dom-inantly inherited colorectal cancer (familialadenomatous polyposis and hereditary non-polyposis colorectal cancer). Dis Colon Rec-

tum 2003;46:10011012.9. Todoroki T, Koike N, Morishita Y, et alPatterns and predictors of failure after curativeresections of carcinoma of the ampulla of Vater.Ann Surg Oncol 2003;10:11761183.

10. Monson JR, Donohue JH, McEnteeGP, et al. Radical resection for carcinoma ofthe ampulla of Vater. Arch Surg 1991;126:353.

11. Smith RC. Surgical treatment forampullary carcinoma. Aust N Z J Surg1999;69:170171.

12. Beall MS, Dyer GA, Stephenson HE.Disappointments in the management of pa-

tients with malignancy of pancreas, duo-denum and common bile duct. Arch Surg1970;101:461465.

13. Yamaguchi K, Enjoji M. Carcinomaof the ampulla of Vater: a clinicopathologi-cal study and pathologic staging of 109 casesof carcinoma and 5 cases of adenoma. Cancer1987;205:572577.

14. Sherlock SH, Dooley J: Disease of theampulla of Vater and pancreas, in: SherlockSH, Dooley J, eds. Diseases of the Liver andBiliary System. 9th ed. London: Blackwell Sci-entific Publications; 1993, pp 599605.

15. Ashkar K, Deeb LS, Bikhazi K, ArnaoutMS. Unusual manifestation of an ampullarytumor presenting with severe upper gastroin-testinal bleeding. Digestion 1999;60:583586.

16. Woo SM, Ryu JK, Lee SH, et al. Re-currence and prognostic factors of ampullarycarcinoma after radical resection: comparisonwith distal extrahepatic cholangiocarcinoma.Ann Surg Oncol 2007;14:31953201.

17. Yamaguchi K, Nagai E, Ueki T, et al.Carcinoma of the ampulla of Vater. ANZ JSurg 1993;63:256262.

18. Songr Y, Temuin G, Sahin B. Endo-scopic ultrasonography in the evaluation of di-lated common bile duct. J Clin Gastroenterol2001;33:302305.

19. Tsukada K, Takada T, Miyazaki M,et al. Diagnosis of biliary tract and ampulla-ry carcinomas. J Hepatobiliary Pancreat Surg2008;15:3140.

20. Irie H, Honda H, Shinozaki K, et al.MR imaging of ampullary carcinomas. J Com-put Assist Tomogr 2002;26:711717.

21. Vaishali MD, Agarwal AK, UpadhyayaDN, et al. Magnetic resonance cholangiopan-

creatography in obstructive jaundice. J ClinGastroenterol 2004;38:887890.22. Fulcher AS, Turner MA, Capps GW, et

al. Half-Fourier RARE MR cholangiopancre-atography: experience in 300 subjects. Radiolo-gy 1998;207:2132.

23. Cohen J, Safdi MA, Deal SE, et al.Quality indicators for esophagogastroduode-noscopy. Gastrointest Endosc 2006;63(suppl4):S10S15.

24. NIH state-of-the-science statement onendoscopic retrograde cholangiopancreatogra-phy (ERCP) for diagnosis and therapy. NIHConsens State Sci Statements 2002 Jan 1416;19(1):123.

25. Roggin KK, Yeh JJ, Ferrone CR, et al.

Limitations of ampullectomy in the treatmentof nonfamilial ampullary neoplasms. Ann SurgOncol 2005;12:971980.

26. Ryan DP, Schapiro RH, Warshaw AL.Villous tumors of the duodenum. Ann Surg1986;203:301306.

27. Posner S, Colletti L, Knol J, et al. Safetyand long-term efficacy of transduodenal exci-sion for tumors of the ampulla of Vater. Sur-gery 2000;128:694701.

28. Clary BM, Tyler DS, Dematos P, etal. Local ampullary resection with careful in-traoperative frozen section evaluation for pre-

Ampullary cancer REVIEW

8/13/2019 0702061

6/6

66 COMMUNITY ONCOLOGY February 2010 www.CommunityOncology.net

sumed benign ampullary neoplasms. Surgery2000;127:628633.

29. Beger HG, Treitschke F, Gansauge F,et al. Tumor of the ampulla of Vater: experi-ence with local or radical resection in 171consecutively treated patients. Arch Surg1999;134:526532.

30. Yamaguchi K, Enjoji M, Kitamura K.Endoscopic biopsy has limited accuracy in di-agnosis of ampullary tumors. Gastrointest En-dosc 1990;36:588592.

31. Sauvanet A, Chapuis O, Hammel P, etal. Are endoscopic procedures able to predictthe benignity of ampullary tumors? Am J Surg1997;174:355358.

32. Klempnauer J, Ridder GJ, Maschek H,Pichlmayr R. Carcinoma of the ampulla ofVater: determinants of long-term survival in 94resected patients. HPB Surg 1998;11(1):111.

33. Cannon ME, Carpenter SL, Elta GH,et al. EUS compared with CT, magnetic res-onance imaging, and angiography and the in-fluence of biliary stenting on staging accuracyof ampullary neoplasms. Gastrointest Endosc1999;50:2733.

34. Mukai H, Nakajima M, Yasuda K, et al.Evaluation of endoscopic ultrasonography inthe pre-operative staging of carcinoma of theampulla of Vater and common bile duct. Ga-strointest Endosc 1992;38:676683.

35. Rosch T, Braig C, Cain T, et al. Stag-ing of pancreatic and ampullary carcinomaby endoscopic ultrasonography: comparisonwith conventional sonography, computed to-mography, and angiography. Gastroenterology1992;102:188199.

36. Tio TL, Mulder CJ, Eggink WF. En-dosonography in staging early carcinoma

of the ampulla of Vater. Gastroenterology1992;102:13921395.37. Chen CH, Tseng LJ, Yang CC, et al.

The accuracy of endoscopic ultrasound, endo-scopic retrograde cholangiopancreatography,computed tomography, and transabdominal ul-trasound in the detection and staging of prima-ry ampullary tumors. Hepatogastroenterology2001;48:17501753.

38. Midwinter MJ, Beveridge CJ, WilsdonJB, et al. Correlation between spiral computedtomography, endoscopic ultrasonography andfindings at operation in pancreatic and ampul-lary tumours. Br J Surg 1999;86:189193.

39. Muller MF, Meyenberger C, Bertschin-ger P, et al. Pancreatic tumors: evaluation with

endoscopic US, CT, and MR imaging. Radiol-ogy 1994;190:745751.40. Howard TJ, Chin AC, Streib EW, et al.

Value of helical computed tomography, angiog-raphy, and endoscopic ultrasound in determin-ing resectability of periampullary carcinoma.Am J Surg 1997;174:237241.

41. Snady H, Cooperman A, Siegel J. En-doscopic ultrasonography compared with com-puted tomography with ERCP in patients withobstructive jaundice or small peri-pancreaticmass. Gastrointest Endosc 1992;38:2734.

42. Bottgert TC, Boddin J, Heintz A, Jung-

inger T. Institution c linicopathologic study forthe assessment of resection for ampullary carci-noma. World J Surg 1997;21:379383.

43. Kubo H, Chijiiwa Y, Akahoshi K,et al. Preoperative staging of ampullary tu-mours by endoscopic ultrasound. Br J Radiol1999;72:443447.

44. Buscail L, Pages P, Berthelemy P, et al.Role of EUS in the management of pancreaticand ampullary carcinoma: a prospective studyassessing resectability and prognosis. Gastroin-test Endosc 1999;50:3440.

45. Tio TL, Sie LH, Kallimanis G, et al.Staging of ampullary and pancreatic carcino-ma: comparison between endosonography andsurgery. Gastrointest Endosc 1996;44:706713.

46. Yasuda K, Mukai H, Cho E, et al. Theuse of endoscopic ultrasonography in the diag-nosis and staging of carcinoma of the papilla ofVater. Endoscopy 1988;20:218222.

47. Quirk DM, Rattner DW, Fernandez-del Castillo C, et al. The use of endoscopicultrasonography to reduce the cost of treat-ing ampullary tumors. Gastrointest Endosc1997;46:334347.

48. Bhutani MS. Probing the endoscopicultrasound (EUS) catheter probe: a small stepfor EUS or a giant leap? Gastrointest Endosc1998;48:542545.

49. Ito K, Fujita N, Noda Y, et al. Preop-erative evaluation of ampullary neoplasm withEUS and transpapillary intraductal US: a pro-spective and histopathologically controlledstudy. Gastrointest Endosc 2007;66:740747.

50. Menzel J, Hoepffner N, Sulkowski U,et al. Polypoid tumors of the major duodenalpapilla: preoperative staging with intraductal

US, EUS, and CT. A prospective, histopatho-logically controlled study. Gastrointest Endosc1999;49:349357.

51. Greene FL, Page DL, Fleming ID, etal. AJCC Cancer Staging Manual, 6th edition,Springer, New York: Springer, 2002.

52. Greene FL. TNM staging for malig-nancies of the digestive tract: 2003 changes andbeyond. Semin Surg Oncol 2003;21:2329.

53. Qiao QL, Zhao YG, Ye ML, et al. Car-cinoma of the ampulla of Vater: factors influ-encing long-term survival of 127 patients withresection. World J Surg 2007;31:137143; dis-cussion 144146.

54. Sakata J, Shirai Y, Wakai T, et al. Num-ber of positive lymph nodes independently af-

fects long-term survival after resection in pa-tients with ampullary carcinoma. Eur J SurgOncol 2007;33:346351.

55. Sakata E, Shirai Y, Yokoyama N, et al.Clinical significance of lymph node microme-tastasis in ampullary carcinoma. World J Surg2006;30:985991.

56. Seiler CA, Wagner M, Bachmann T, etal. Randomized clinical trial of pylorus-pre-serving duodenopancreatectomy versus classi-cal Whipple resection: long term results. Br JSurg 2005;92:547556.

57. Srinarmwong C, Luechakiettisak P,

Prasitvilai W. Standard Whipples operationversus pylorus preserving pancreaticoduode-nectomy: a randomized controlled trial study. JMed Assoc Thai 2008;91:693698.

58. Memon MA, Shiwani MH, Anwer S.Carcinoma of the ampulla of Vater: results ofsurgical treatment of a single center. Hepato-gastroenterology 2004;51:12751277.

59. Duffy JP, Hines OJ, Liu JH, et al. Im-proved survival for adenocarcinoma of the am-pulla of Vater: fifty-five consecutive resections.Arch Surg 2003;138:941948; discussion 948950.

60. Lygidakis NJ, Jain S, Sacchi M, Vrach-nos P. Reappraisal of a method of reconstruc-tion after pancreatoduodenectomy. Hepatogas-troenterology 2005;52:10771082.

61. Gitrn A, Macas M, Abalid R, etal. The endoscopic treatment of carcinomaof Vaters ampulla. Rev Gastroenterol Mex1995;60:7883.

62. Bhatia S, Miller RC, Haddock MG, etal. Adjuvant therapy for ampullary carcinomas:the Mayo Clinic experience. Int J Radiat OncolBiol Phys 2006;66:514519.

63. Moertel CG, Childs DS, Reitemeier RJ,et al. Combined 5-fluorouracil and super volt-age radiation therapy of locally unresectablegastrointestinal cancer. Lancet 1969;2:865867.

64. Bakkevold KE, Arnesjo B, Dahl O, et al.Adjuvant combination chemotherapy (AMF)following radical resection of carcinoma of thepancreas and papilla of Vaterresults of a con-trolled, prospective, randomized multicentrestudy. Eur J Cancer 1993;5:698703.

65. Krishnan S, Rana V, Evans DB, et al.Role of adjuvant chemoradiation therapy in

adenocarcinomas of the ampulla of Vater. Int JRadiat Oncol Biol Phys 2008;70:735743.66. Willett CG, Warshaw AL, Convery K,

Compton CC. Patterns of failure after pancre-aticoduodenectomy for ampullary carcinoma.Surg Gynecol Obstet 1993;176:3338.

67. Lee JH, Whittington R, Williams NN,et al. Outcome of pancreaticoduodenectomyand impact of adjuvant therapy for ampulla-ry carcinomas. Int J Radiat Oncol Biol Phys2000;47:945953.

68. Overman MJ, Varadhachary GR, Ko-petz S, et al. Phase II study of capecitabine andoxaliplatin for advanced adenocarcinoma of thesmall bowel and ampulla of Vater. J Clin Oncol2009;27:25982603.

REVIEW Chan/Adler

ABOUT THE AUTHORS

Affiliations:Dr. Chan is a family practice resi-dent and Dr. Adler is Associate Professor ofMedicine, Department of Medicine, Division ofGastroenterology, and Director of TherapeuticEndoscopy, Gastroenterology and Hepatology,University of Utah School of Medicine, Hunts-man Cancer Center, Salt Lake City, UT.

Conflicts of interest: None to disclose.