Background
Carcinoma of the ampulla of Vater is 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 relatively uncommon, accounting 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. Grossly, carcinomas originating in the ampulla of Vater 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 and Connolly divided acid mucins into sulphomucins and sialomucins; in general, ampullary cancers produce sialomucins, whereas periampullary tumors secrete sulfated mucins. These researchers demonstrated that ampullary tumors secreting sialomucins had a better prognosis (100% vs 27% 5-y survival rate).[1] Other investigators have confirmed the prognostic power of the pattern of mucin secretion.
Carter et al suggest that, histologically, ampullary tumors can be classified as either pancreaticobiliary or intestinal, and that the clinical behavior of these tumors reflects this classification; the course of intestinal ampullary adenocarcinomas is similar to that of their duodenal counterparts, whereas pancreaticobiliary tumors follow a more aggressive course, similar to that of pancreatic adenocarcinomas.[2]
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%).[3] 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.
Epidemiology
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. A review of data from the National Cancer Institute’s Surveillance, Epidemiology and End Results (SEER) Program found 5,625 cases of ampullary cancer between 1973 and 2005; the frequency of the disease has been increasing since 1973.[4]
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 revealed 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 the ampulla of Vater is relatively uncommon, studies of the patterns of occurrence among different ethnic groups have not been conducted.
Sex
Ampullary cancer is more common in men, according to the National Cancer Institute’s SEER Program.[4]
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| 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 |
| Institution | Year | Patients, # | Resected, # | Mortality Rate, % | 5-Year Survival Rate, % |
| Cleveland Clinic[9] | 1950-1984 | 59 | 59 | 8 | 37 |
| Leicester Royal Infirmary, United Kingdom[10] | 1972-1984 | 52 | 24 | 13 | 56 |
| University of Alabama[11] | 1953-1988 | 24 | 24 | 13 | 61 |
| Mayo Clinic[12] | 1965-1989 | 104 | 104 | 5.7 | 34 |
| Montebelluna Hospital, Italy[13] | 1971-1990 | 36 | 31 | 3 | 56 |
| Veterans Affairs hospitals[14] | 1971-1993 | 123 | 64 | 14 | 20 |
| Academic Medical Center, Amsterdam[15] | 1984-1992 | 67 | 62 | 6 | 50 |
| Hanover Hospital, Germany[16] | 1971-1993 | 87 | 85 | 9 | 38 |
| Johns Hopkins[17] | 1969-1996 | 120 | 106 | 4 | 38 |
| Memorial Sloan-Kettering[18] | 1983-1995 | 123 | 101 | 5 | 44 |
| Catholic University, Italy[19] | 1981-2002 | 94 | 64 | 9 | 64 |
| Institution | Node-Negative, % (#) | Node-Positive, % (#) | P Value |
| University of Alabama at Birmingham[11] | 78 (19) | 50 (5) | Not significant |
| Mayo Clinic, Minnesota[12] | 43 (53) | 16 (50) | .001 |
| Montebelluna Hospital, Italy[13] | 64 (22) | 0 (9) | .36 |
| Academic Medical Center, Amsterdam[15] | 59 (32) | 41 (35) | .05 |
| Niigata University, Japan[20] | 81 (17) | 41 (18) | < .01 |
| Johns Hopkins, Baltimore[17] | 43 (53) | 31 (50) | .05 |
| Kanazawa University Hospital, Japan[21] | 74 (21) | 31 (15) | < .05 |
| Memorial Sloan- Kettering, New York[18] | 55 (55) | 30 (46) | .04 |
| Loyola University, Chicago[28] | 78 (27) | 25 (24) | < 0.05 |
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