AUTHOR AND EDITOR INFORMATION

Section 1 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

INTRODUCTION

Section 2 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Background

Carcinoma of the ampulla of Vater is defined as a malignant tumor arising in the last centimeter of the common bile duct where it passes through the wall of the duodenum and ampullary papilla. The pancreatic duct (of Wirsung) and common bile duct merge and exit by way of the ampulla into the duodenum. The ductal epithelium in these areas is columnar and resembles that of the lower common bile duct.

Adenocarcinoma of the ampulla of Vater is a relatively uncommon tumor that accounts for approximately 0.2% of gastrointestinal tract malignancies and approximately 7% of all periampullary carcinomas.

Pathophysiology

The periampullary region is anatomically complex, representing the junction of 3 different epithelia, pancreatic ducts, bile ducts, and duodenal mucosa. Carcinomas originating in the ampulla of Vater by gross inspection can arise from 1 of 4 epithelial types, (1) terminal common bile duct, (2) duodenal mucosa, (3) pancreatic duct, or (4) ampulla of Vater.

Distinguishing between true ampullary cancers and periampullary tumors is critical to understanding the biology of these lesions. Each type of mucosa produces a different pattern of mucus secretion. In a complete histochemical study, Dawson et al divided acid mucins into sulphomucins and sialomucins and demonstrated that ampullary tumors secreting sialomucins had a better prognosis (100% vs 27% 5-y survival rate). In general, ampullary cancers produce sialomucins, whereas periampullary tumors secrete sulfated mucins. Other investigators have confirmed the prognostic power of the pattern of mucin secretion.

Immunohistochemical stains for expressions of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9, Ki-67, and p53 have been studied for prognostic power. In a series of 45 patients, expression of CA 19-9 labeling intensity and apical localization both were statistically significant predictors of poor prognosis. The 5-year survival rates were markedly different between tumors that expressed CA 19-9 and those that did not (36% vs 100%). CEA expression also might be a marker for prognosis, but it is much weaker. Ki-67 and p53 were not demonstrated to have an effect on outcome. Research along these avenues ultimately might provide the rationale for discriminative administration of adjuvant therapy.

Frequency

United States

Adenocarcinoma of the ampulla of Vater is a relatively uncommon tumor that accounts for approximately 0.2% of gastrointestinal tract malignancies and approximately 7% of all periampullary carcinomas.

Mortality/Morbidity

Pancreaticoduodenectomy is a formidable operation, and the morbidity and mortality rates associated with this procedure historically have been high.

• Until recently, the operative mortality rate was reported to be approximately 20%. In the past few years, several centers have reported large series with an operative mortality rate in the range of 5%. A recent review of the last 130 pancreaticoduodenectomies performed at Stanford University Medical Center over the last 5 years reveals an operative mortality rate of 3%. This improvement can be attributed to increased surgical experience, improved patient selection, improved anesthesia, better preoperative imaging, and general improvement in the management of ill patients.
• The morbidity rate associated with the surgery is approximately 65%. In some series, 13% of patients required a repeat laparotomy for complications. Patients may experience fistula formation, delayed intestinal function, pneumonitis, intra-abdominal infection, abscess, or thrombophlebitis. Marginal ulceration, diabetes, pancreatic dysfunction (steatorrhea), and gastrointestinal motility disorder all can manifest as late complications of the surgery.

Race

Because carcinoma of ampulla of Vater is relatively uncommon, studies of the patterns of occurrence among different ethnic groups have not been conducted.

Sex

In most published series, the incidence of carcinoma of the ampulla of Vater is relatively equal between men and women. The rarity of this tumor precludes a careful and accurate estimate of the true incidence between the sexes.

CLINICAL

Section 3 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

History

• Patients with carcinoma of the ampulla of Vater often complain of anorexia, nausea, vomiting, jaundice, pruritus, or weight loss.
• Many patients complain of abdominal pain.
• Diarrhea, a common but not universal symptom, might be associated with an absence of lipase within the gut because of pancreatic duct obstruction.

Physical

• Upon physical examination, some patients might demonstrate a distended, palpable Courvoisier gallbladder (ie, palpable gall bladder in a patient with jaundice).
• Fever can be present, particularly when the biliary tract has been explored previously (eg, after common duct exploration for stones).
• A rising bilirubin level due to obstructive jaundice often is the sole presenting symptom.
• Ultrasound of the abdomen is the initial study to evaluate the common bile duct or pancreatic ducts (dilation of these ducts essentially is diagnostic for extrahepatic obstruction). However, 10-15% of patients with normal common bile duct findings after ultrasound still might have extrahepatic biliary obstruction on computed tomography (CT) scan findings. Biliary or pancreatic ductal dilation can explain abdominal pain, even with localized and noninvasive disease.
• CT scan often demonstrates a mass but is not helpful in differentiating ampullary carcinoma from tumors of the head of the pancreas or periampullary region. If the lesion is smaller than 2 cm, pancreatic or bile duct dilation might be the only abnormalities noted on CT scan findings.
• Such findings are highly suggestive of pancreatic malignancy and require further evaluation, usually with endoscopic retrograde cholangiopancreatography (ERCP). Findings on ERCP that suggest pancreatic cancer include irregular pancreatic duct narrowing, displacement of the main pancreatic duct, destruction or displacement of the side branches of the duct, and pooling of contrast material in necrotic areas of tumor. Both CT scan and ultrasound findings can help reveal metastatic disease in the liver or regional lymph nodes.
• Dynamic CT scanning, ie, high-speed scans obtained during rapid intravenous administration of iodinated contrast material, can reveal tumor involvement of the vasculature. Some centers still rely on angiography to help identify patients with potentially resectable disease.

DIFFERENTIALS

Section 4 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Other Problems to be Considered

Biliary cirrhosis

WORKUP

Section 5 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Lab Studies

• Routine laboratory studies include a complete blood cell count, electrolyte panel, liver function studies (prothrombin time, bilirubin [direct and indirect], transaminases, alkaline phosphatase), CEA, and CA 19-9.
• • CA 19-9 is a recently discovered tumor marker that is detectable in serum. It often is elevated in pancreatic malignancies and might have a role in assessing response to therapy, predicting tumor recurrence, or both.
  • CEA is another nonspecific tumor marker that sometimes is elevated in pancreatic malignancies. It might have a role in assessing response to treatment or predicting tumor recurrence. Because CEA also is elevated in patients with other gastrointestinal malignancies (eg, colon and rectal in particular), exclude the possibility of a second primary tumor in these patients.

Imaging Studies

• Ultrasound of the abdomen
• • Obtain an ultrasound image of the abdomen to evaluate the common bile duct and the pancreatic ducts.
  • Dilatation of these ducts essentially is diagnostic for extrahepatic obstruction.
• CT scan of the abdomen and/or pelvis: Obtain a CT scan image to evaluate the local region of interest and evaluate for possible metastases.
• Endoscopic retrograde cholangiopancreatography
• • Obtain ERCP findings to evaluate the ductal architecture further.
  • Narrowing or irregularities might suggest malignancy.
• Chest radiograph: Obtain a chest x-ray film to complete the workup (ie, for staging purposes).
• Positron emission tomography (PET) or PET-CT scans: These scans have been widely adopted in the author's clinic as a means of imaging the metabolic activity of a particular tumor. When metastases are smaller than they can be reliably detected on a CT scan, PET or PET-CT scans can detect them.

Staging

Over the years, multiple systems for staging this tumor have been proposed.

• Martin proposed a 4-stage system, as follows:
• • Stage I - Vegetating tumor limited to the epithelium with no involvement of the sphincter of Oddi
  • Stage II - Tumor localized in the duodenal submucosa without involvement of the duodenal muscularis propria but possible involvement of the sphincter of Oddi
  • Stage III - Tumor of the duodenal muscularis propria
  • Stage IV - Tumor of the periduodenal area or pancreas, with proximal or distal lymph node involvement
• The classification system of Yamaguchi and Enjoji is similar to the Martin classification.
• Talbot et al devised a system that scored tumors according to the degree of infiltration (from 1-4 according to increasing infiltration) and according to tumor differentiation (from 1-3 for well, moderately, and poorly differentiated tumors), the sum of which separated the patients into 2 groups (scores 2-4 and scores 5-7).
• The currently accepted American Joint Committee on Cancer staging system for ampullary carcinoma emphasizes the importance of pancreatic invasion and lymph node metastases (see below and see Table 1, below). Size has little impact on tumor stage. The definition of primary tumor (T), regional lymph node (N), and remote metastases (M) for classification and staging of thyroid node metastasis and staging for cancer of the ampulla of Vater is as follows:
• • Primary tumor
  • • TX – Primary tumor cannot be assessed
    • T0 – No evidence of primary tumor
    • Tis – Carcinoma in situ
    • T1 – Tumor limited to ampulla of Vater
    • T2 – Tumor invades duodenal wall
    • T3 – Tumor invades less than 2 cm into pancreas
    • T4 – Tumor invades more than 2 cm into pancreas or other organs
  • Regional lymph nodes
  • • NX – Regional lymph nodes cannot be assessed
    • N0 – No regional lymph node metastases
    • N1 – Lymph node metastases
  • Distant metastases
  • • MX – Presence of distant metastases cannot be assessed
    • M0 – No distant metastases
    • M1 – Distant metastases
• Table 1. Staging of Ampullary Cancers by the TNM System

  Stage	T	N	M
  Stage 0	Tis	N0	M0
  Stage I	T1	N0	M0
  Stage II	T2-3	N0	M0
  Stage III	T1-3	N1	M0
  Stage IV	T4	N0-1	M0
  …	T1-4	N0-1	M1

TREATMENT

Section 6 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Surgical Care

The standard surgical approach is pancreaticoduodenal resection (Whipple procedure). The procedure involves en bloc resection of the gastric antrum and duodenum; a segment of the first portion of the jejunum, gallbladder, and distal common bile duct; the head and often the neck of the pancreas; and adjacent regional lymph nodes.

Results after radical resection of ampullary of Vater carcinoma have been improving. During the past decade, 5-year survival rates have ranged from 20-61%, averaging higher than 35%. The reported mortality rates from this operation are decreasing. A summary follows in Table 2.

Table 2. Results of Pancreaticoduodenal Resection for Carcinoma of the Ampulla of Vater

Institution	Year	Patients, #	Resected, #	Mortality Rate, %	5-Year Survival Rate, %
Cleveland Clinica	1950-1984	59	59	8	37
Leicester Royal Infirmary, United Kingdomb	1972-1984	52	24	13	56
University of Alabamac	1953-1988	24	24	13	61
Mayo Clinicd	1965-1989	104	104	5.7	34
Montebelluna Hospital, Italye	1971-1990	36	31	3	56
US Veterans Hospitalf	1971-1993	123	64	14	20
Academic Medical Center, Amsterdamg	1984-1992	67	62	6	50
Hannover Hospital, Germanyh	1971-1993	87	85	9	38
Johns Hopkinsi	1969-1996	120	106	4	38
Memorial Sloan Ketteringj	1983-1995	123	101	5	44
Catholic University, Italyk	1981-2002	94	64	9	64

^a Tarazi, 1986

^b Neoptolemos, 1988

^c Shutze, 1990

^d Monson, 1991

^e Sperti, 1994

^f El-Ghazzawy, 1995

^g Allema, 1995

^h Klempnauer, 1995

ⁱ Talamini, 1997

^j Howe, 1998

^k Di Giorgio, 2005

• Resectability
• • In a review of more than 1100 patients published in a surgical series, Howe reported that the overall rate of resectability was 82%. This most likely overestimates the true resectability rate because many patients with radiographically unresectable disease often are not included in retrospective surgical series.
  • A review of veterans' hospitals across the United States by el-Ghazzawy revealed that only 63% of presenting patients undergo surgery for cure. At disease presentation, 30-50% have involved lymph nodes.
  • A few studies have been conducted on the pattern of lymphatic spread of ampullary cancer. These studies have been difficult to interpret because of the lack of standardized nomenclature for lymph node groups, variability in the degree of superior mesenteric lymph node dissection, and the small number of patients.
    • Shirai and colleagues meticulously reviewed 21 cases of ampullary cancer and documented the pattern of lymphatic spread. The site of greatest nodal involvement, the first echelon group, is the posterior pancreaticoduodenal nodal group. The nodal groups surrounding the inferior pancreaticoduodenal artery were the superior mesenteric lymph nodes involved most often. Finally, the paraaortic lymph node groups were involved in 3 patients with resectable disease.
    • Kayahara reported that the inferior pancreaticoduodenal nodes (13b) and the superior mesenteric nodes (14) were the groups most often involved with metastatic carcinoma.
• Local excision
• • Because of the mortality and morbidity associated with pancreaticoduodenectomy, physicians have been interested in performing local excisions of cancers of the ampulla of Vater to avoid a major resection.
  • Transduodenal excision of ampullary tumors has been proposed as an intermediate option between radical resection and palliative bypass for high-risk patients. Some have argued that this approach is simpler, better tolerated, and might provide a comparable cure rate (mortality rate 8-13%, 5-y survival rate of 0-43%). This approach generally has been reserved for poor operative candidates (eg, elderly patients, those with other comorbid conditions) with favorable tumors (generally <2 cm, polypoid). Unfortunately, this approach compromises local control. The local failure rate for the 18 cases collected from the contemporary literature was 50%. One patient required 3 repeat excisions for local recurrence.
• Prognostic factors
• • Recent reviews of single-institution surgical experiences of ampullary cancer have focused on the identification of histopathologic features associated with prognosis and survival. Retrospective review, small patient numbers, and long periods of enrollment limit what can be learned from these studies. However, common themes emerge from these published clinicopathologic analyses.
  • Survival after surgical resection is related to the extent of local invasion of the primary lesion, lymph node involvement, vascular invasion, perineural invasion, cellular differentiation, and uninvolved surgical margins. Even a single lymph node with evidence of metastatic carcinoma portends a poor outcome with surgery alone. Exactly which factors are truly independent remains controversial.
  • El Ghazzawy reviewed experiences in the US Department of Veterans Affairs hospitals from 1987-1991, during which time 123 patients were diagnosed with ampullary cancer. In the group that underwent surgical resection, perineural invasion, microlymphatic invasion, vascular invasion, or tumor differentiation did not independently influence survival when the tumors were controlled for stage.
  • When Yamaguchi compared 18 variables among 8 long-term survivors and 12 short-term survivors with ampullary cancer, only perineural invasion and histologic grade were significant parameters.
  • In the series from Johns Hopkins, operative blood transfusions conferred a poorer 5-year survival rate on univariate analysis but not on multivariate analysis.
  • Akwari noted that papillary histological features portended a more favorable prognosis, with a reported 40% survival rate at 5 years versus only 16% in those with invasive lesions. The Cleveland Clinic experience also confirmed the favorable nature of papillary histology. Table 3 summarizes the outcomes for patients with involved lymph nodes.

    Table 3. Summary of 5-Year Survival After Resection for Lymph Node Negative and Positive Carcinoma of the Ampulla of Vater

    Institution	Node-Negative, % (#)	Node-Positive, % (#)	P Value
    University of Alabama at Birmingham*	78 (19)	50 (5)	Not significant
    Mayo Clinic, Minnesota†	43 (53)	16 (50)	.001
    Montebelluna Hospital, Italy‡	64 (22)	0 (9)	.36
    Academic Medical Center, Amsterdam§	59 (32)	41 (35)	.05
    Niigata University, JapanII	81 (17)	41 (18)	<.01
    Johns Hopkins, Baltimore¶	43 (53)	31 (50)	.05
    Kanazawa University Hospital, Japan#	74 (21)	31 (15)	<.05
    Memorial Sloan Kettering, New York**	55 (55)	30 (46)	.04
    Loyola University, Chicago††	78 (27)	25 (24)	<0.05

    * Shutze, 1990
    ^† Monson, 1991
    ^‡ Sperti, 1994
    ^§ Allema, 1995
    ^II 1997
    ^¶ Talamini, 1997
    ^# Kayahara, 1997
    ** Howe, 1998
    ^†† Brown, 2006
• Patterns of failure
  • Unfortunately, most patients with carcinoma of the ampulla of Vater die from recurrent disease. Treatment fails in nearly 70% of patients with poor prognostic features, and these patients ultimately die of their disease.
  • Kopelson and associates described regional nodal recurrences in 3 of 12 patients with ampullary cancers following potentially curative resection. From pooled data on 80 patients with ampullary cancer, they found that 54% developed locoregional recurrence.
• Adjuvant therapy
• • Because local and systemic failures remain problematic, physicians continue to be interested in offering adjuvant therapy. The relative rarity of this disease limits research in this area.
  • Willett and colleagues summarized their experience with adjuvant radiotherapy for high-risk tumors of the ampulla of Vater (included invasion into the pancreas, poorly differentiated histology, involved lymph nodes, or positive resection margins). Twelve patients received adjuvant radiotherapy (40-50.4 Gy) to the tumor bed and some received concurrent 5-fluorouracil (5-FU) as a radiosensitizer. This group was compared to 17 patients who underwent surgical resection alone. When these 2 groups were compared, the trend was toward better locoregional control, but no advantage in survival was observed. Distant metastasis to liver, peritoneum, and pleura was the dominant failure pattern in this group of patients.
  • Barton and Copeland reported on the M.D. Anderson Cancer Center experience of using postoperative chemotherapy for carcinoma of the ampulla of Vater. Seventeen patients received a variety of chemotherapeutic regimens (5-FU was used in combination with doxorubicin, carmustine, vincristine, methyl-lomustine, or mitomycin-C). Although no analysis was presented, the authors concluded "no combination of drugs appeared to prolong life."
  • Sikora and colleagues presented their experience from a hospital in India in a recent retrospective review. Patients who underwent a pancreaticoduodenectomy with adjuvant chemotherapy and radiation did not do any better than the group treated with surgery alone.
  • In a retrospective review, Chan reported that 13 patients who received adjuvant chemotherapy (predominantly involving 5-FU, mitomycin-C, and doxorubicin) had a significantly better survival than 16 patients who underwent resection only.
  • Yeung and colleagues used neoadjuvant chemoradiotherapy for 20 patients with presumed carcinoma of the head of the pancreas, including 4 patients with duodenal/ampullary carcinomas. Interestingly, no residual tumor was found in pancreaticoduodenectomy specimens of the 4 patients thought to have had ampullary/duodenal carcinomas.
  • Adjuvant chemotherapy and radiation (chemoradiation) has resulted in modest gains in treatment of pancreatic cancer. The Gastrointestinal Tumor Study Group (GITSG) randomized patients following resection of pancreatic cancer with negative margins to adjuvant chemoradiation or observation. The chemoradiation arm improved the median survival (11-21 mo) and more than doubled the 2- and 5-year survival rates (18% vs 43% at 2 y and 8% vs 18% at 5 y). The GITSG also demonstrated that chemoradiation improved median and overall survival compared to radiation alone. In addition, higher-dose radiation (60 Gy) combined with 5-FU might result in improved survival over lower-dose chemoradiation (40 Gy + 5-FU). The GITSG further demonstrated the superiority of chemoradiation over chemotherapy alone for unresectable pancreatic cancer, with a more than 2-fold improvement in 1-year survival rates (19% vs 41%) for chemoradiation.
  • At Stanford University, physicians have adopted a similar treatment strategy for periampullary carcinomas. All patients with ampullary carcinoma are discussed and reviewed in detail by a multidisciplinary team including surgical oncologists, medical oncologists, radiation oncologists, a pathologist, a gastroenterologist, and a radiologist. All resected tumors are reviewed. Patients with tumors with poor prognostic features (eg, involved surgical margins, lymph nodes, invasion of the pancreas, perineural invasion, or poor histologic grade) are enrolled in a single-arm investigational protocol to receive adjuvant radiotherapy (45 Gy) and concurrent protracted venous infusion of 5-FU (225 mg/m²/d) during the entire treatment course.
  • Considerable recent advancements have been made in the treatment planning and delivery of adjuvant and definitive radiotherapy for patients with pancreatic cancer. Patients with carcinoma of the ampulla of Vater may also benefit from these techniques.
• Standard of care
  • Staging of ampullary cancer is critical to treatment. While ampullary polypectomy and ampullectomy have been performed successfully on some patients with ampullary cancer, reserve this treatment for patients whose overall performance status makes the risks associated with a formal pancreaticoduodenectomy excessive.
  • Recently, carcinoma in situ has been diagnosed with increasing frequency. It has been associated with polypoid growth and is treated with endoscopic polypectomy. In these circumstances, remove the entire polyp and carefully study the base of the polyp to ensure that no cancer is at the margin. In the case of an incomplete excision, a prompt pancreaticoduodenectomy is essential. Patients who undergo polypectomy only should be monitored endoscopically at yearly intervals to guard against recurrence.
  • Pancreaticoduodenectomy is the procedure of choice for patients with resectable disease, but local recurrence plagues all surgical series, particularly when the pancreas has been invaded or lymph node metastases are discovered. In fact, whether major resection impacts survival in the setting of disease spread to the lymph nodes remains unclear. Postoperative irradiation of at least 45 Gy with 5-FU as a radiosensitizer is a reasonable treatment and reduces local recurrence in pancreatic cancer.
  • For patients with unresectable disease, endoscopic stenting to achieve biliary decompression is an appropriate palliative procedure. No established answer exists to the question of further therapy. Very little has been published on adjuvant treatment for locally advanced and advanced ampullary carcinoma. Confining one's approach to relief of symptoms is reasonable.
  • Given the paucity of effective standard treatment options, encourage patients to enroll in clinical trials. Radiotherapy, chemotherapy, and chemoradiotherapy have been tried, but response rates probably are low, and an effect on survival is questionable.

FOLLOW-UP

Section 7 of 8  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

Further Outpatient Care

• Follow-up guidelines are not well established for this disease. If treatment ultimately fails, it often does so within 5 years.
• Unfortunately, good salvage therapies do not yet exist.
• Palliative chemotherapeutic agents and good medications for pain relief exist.
• Reasonable practice includes blood studies, chest radiograph, and CT scan of the abdomen and/or pelvis every 6 months.

REFERENCES

Section 8 of 8

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Follow-up
• References

• Akwari OE, van Heerden JA, Adson MA, Baggenstoss AH. Radical pancreatoduodenectomy for cancer of the papilla of Vater. Arch Surg. Apr 1977;112(4):451-6. [Medline].
• Allema JH, Reinders ME, van Gulik TM, et al. Results of pancreaticoduodenectomy for ampullary carcinoma and analysis of prognostic factors for survival. Surgery. Mar 1995;117(3):247-53. [Medline].
• Barton RM, Copeland EM 3d. Carcinoma of the ampulla of Vater. Surg Gynecol Obstet. Mar 1983;156(3):297-301. [Medline].
• Brown KM, Tompkins AJ, Yong S, et al. Pancreaticoduodenectomy is curative in the majority of patients with node-negative ampullary cancer. Arch Surg. Jun 2005;140(6):529-32; discussion 532-3.
• Chan C, Herrera MF, de la Garza L, et al. Clinical behavior and prognostic factors of periampullary adenocarcinoma. Ann Surg. Nov 1995;222(5):632-7. [Medline].
• Dawson PJ, Connolly MM. Influence of site of origin and mucin production on survival in ampullary carcinoma. Ann Surg. Aug 1989;210(2):173-9. [Medline].
• Di Giorgio A, Alfieri S, Rotondi F, et al. Pancreatoduodenectomy for tumors of Vater''s ampulla: report on 94 consecutive patients. World J Surg. Apr 2005;29(4):513-8.
• Dorandeu A, Raoul JL, Siriser F, et al. Carcinoma of the ampulla of Vater: prognostic factors after curative surgery: a series of 45 cases. Gut. Mar 1997;40(3):350-5. [Medline].
• Duffy JP, Hines OJ, Liu JH, et al. Improved survival for adenocarcinoma of the ampulla of Vater: fifty-five consecutive resections. Arch Surg. Sep 2003;138(9):941-8; discussion 948-50. [Medline].
• Gastrointestinal Tumor Study Group. A multi-institutional comparative trial of radiation therapy alone and in combination with 5-fluorouracil for locally unresectable pancreatic carcinoma. The Gastrointestinal Tumor Study Group. Ann Surg. Feb 1979;189(2):205-8. [Medline].
• Gastrointestinal Tumor Study Group. Treatment of locally unresectable carcinoma of the pancreas: comparison of combined-modality therapy (chemotherapy plus radiotherapy) to chemotherapy alone. Gastrointestinal Tumor Study Group. J Natl Cancer Inst. Jul 20 1988;80(10):751-5. [Medline].
• Howe JR, Klimstra DS, Moccia RD, et al. Factors predictive of survival in ampullary carcinoma. Ann Surg. Jul 1998;228(1):87-94. [Medline].
• Kamisawa T, Fukayama M, Koike M, et al. Carcinoma of the ampulla of Vater: expression of cancer-associated antigens inversely correlated with prognosis. Am J Gastroenterol. Oct 1988;83(10):1118-23. [Medline].
• Kayahara M, Nagakawa T, Ohta T, et al. Surgical strategy for carcinoma of the papilla of Vater on the basis of lymphatic spread and mode of recurrence. Surgery. Jun 1997;121(6):611-7. [Medline].
• Klempnauer J, Ridder GJ, Pichlmayr R. Prognostic factors after resection of ampullary carcinoma: multivariate survival analysis in comparison with ductal cancer of the pancreatic head. Br J Surg. Dec 1995;82(12):1686-91. [Medline].
• Kopelson G, Galdabini J, Warshaw AL, Gunderson LL. Patterns of failure after curative surgery for extra-hepatic biliary tract carcinoma: implications for adjuvant therapy. Int J Radiat Oncol Biol Phys. Mar 1981;7(3):413-7. [Medline].
• Moertel CG, Frytak S, Hahn RG, et al. Therapy of locally unresectable pancreatic carcinoma: a randomized comparison of high dose (6000 rads) radiation alone, moderate dose radiation (4000 rads + 5-fluorouracil), and high dose radiation + 5-fluorouracil: The Gastrointestinal Tumor Study Group. Cancer. Oct 15 1981;48(8):1705-10. [Medline].
• Neoptolemos JP, Talbot IC, Carr-Locke DL, et al. Treatment and outcome in 52 consecutive cases of ampullary carcinoma. Br J Surg. Oct 1987;74(10):957-61. [Medline].
• Padilla D, Cubo T, Pardo R, et al. Late development of cholangiocarcinoma after hepaticojejunostomy due to ampullary carcinoma. Gut. Mar 2004;53(3):472-3. [Medline].
• Saurin JC, Chavaillon A, Napoleon B, et al. Long-term follow-up of patients with endoscopic treatment of sporadic adenomas of the papilla of vater. Endoscopy. May 2003;35(5):402-6. [Medline].
• Shirai Y, Ohtani T, Tsukada K, Hatakeyama K. Patterns of lymphatic spread of carcinoma of the ampulla of Vater. Br J Surg. Jul 1997;84(7):1012-6. [Medline].
• Shutze WP, Sack J, Aldrete JS. Long-term follow-up of 24 patients undergoing radical resection for ampullary carcinoma, 1953 to 1988. Cancer. Oct 15 1990;66(8):1717-20. [Medline].
• Sikora SS, Balachandran P, Dimri K, et al. Adjuvant chemo-radiotherapy in ampullary cancers. Eur J Surg Oncol. Mar 2005;31(2):158-63.
• Sperti C, Pasquali C, Piccoli A, et al. Radical resection for ampullary carcinoma: long-term results. Br J Surg. May 1994;81(5):668-71. [Medline].
• Talamini MA, Moesinger RC, Pitt HA, et al. Adenocarcinoma of the ampulla of Vater. A 28-year experience. Ann Surg. May 1997;225(5):590-9; discussion 599-600. [Medline].
• Talbot IC, Neoptolemos JP, Shaw DE, Carr-Locke D. The histopathology and staging of carcinoma of the ampulla of Vater. Histopathology. Feb 1988;12(2):155-65. [Medline].
• Tarazi RY, Hermann RE, Vogt DP, et al. Results of surgical treatment of periampullary tumors: a thirty-five-year experience. Surgery. Oct 1986;100(4):716-23. [Medline].
• Willett CG, Warshaw AL, Convery K, et al. Patterns of failure after pancreaticoduodenectomy for ampullary carcinoma. Surg Gynecol Obstet. Jan 1993;176(1):33-8. [Medline].
• 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. Feb 1 1987;59(3):506-15. [Medline].
• Yamaguchi K, Nishihara K. Long- and short-term survivors after pancreatoduodenectomy for ampullary carcinoma. J Surg Oncol. Jul 1992;50(3):195-200. [Medline].
• Yeung RS, Weese JL, Hoffman JP. Neoadjuvant chemoradiation in pancreatic and duodenal carcinoma. A Phase II Study. Cancer. Oct 1 1993;72(7):2124-33. [Medline].
• el-Ghazzawy AG, Wade TP, Virgo KS, Johnson FE. Recent experience with cancer of the ampulla of Vater in a national hospital group. Am Surg. Jul 1995;61(7):607-11. [Medline].

Article Last Updated: Jul 18, 2006