Ampullary Carcinoma
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Ampullary carcinoma is a rare malignant tumor originating at the ampulla of Vater, in the last centimeter of the common bile duct, where it passes through the wall of the duodenum and ampullary papilla. Patients typically present with symptoms related to biliary obstruction. A high index of suspicion is paramount so that the appropriate laboratory and imaging studies may be obtained to facilitate early diagnosis.
Over the last decade, advances in technology have allowed improvements in the diagnosis and staging of this disease. Current imaging techniques enable more accurate staging of these tumors and permit preoperative determination of which tumors are surgically resectable.
Surgical resection with pancreaticoduodenectomy remains the gold standard for treatment, although local excision is an option for patients who may be unable to tolerate this. Several palliative options exist for patients with unresectable or metastatic disease. While certain features (eg, positive resection margins and lymph node positivity) portend poorer prognosis, patients with ampullary cancer generally have better overall survival than patients with pancreatic cancer.
The signs and symptoms of ampullary carcinoma are largely related to obstruction of the bile duct or pancreatic duct. They include the following [1] :
Jaundice secondary to biliary obstruction—most common clinical presentation
Abdominal pain
Dyspepsia
Malaise
Fever/chills
Anorexia
Pancreatitis—May be the first clinical manifestation, due to obstruction of the pancreatic duct
Pruritus—Secondary to biliary obstruction
Nausea
Vomiting
Weight loss
Diarrhea
Courvoisier gallbladder (ie, a distended, palpable gallbladder in a patient with jaundice)
See Presentation for more detail.
Laboratory studies
Routine laboratory studies include the following:
Complete blood count
Electrolyte panel
Liver function studies: Prothrombin time, bilirubin (direct and indirect), transaminases, and alkaline phosphatase
CA 19-9: Serum tumor marker that is often elevated in pancreatic malignancies and may have a role in assessing response to therapy and/or predicting tumor recurrence
Carcinoembryonic antigen (CEA): A nonspecific tumor marker that is sometimes elevated in pancreatic malignancies; it may have a role in assessing response to treatment or predicting tumor recurrence
Ultrasonography of the abdomen
Abdominal ultrasonography is the initial study to evaluate the common bile duct or pancreatic ducts
Dilatation of these ducts is essentially diagnostic for extrahepatic obstruction
Biliary or pancreatic ductal dilatation can explain abdominal pain, even in patients with localized and noninvasive disease
10-15% of patients with normal common bile duct findings on ultrasonography demonstrate extrahepatic biliary obstruction on a computed tomography (CT) scan
Ultrasonography and CT scanning can help reveal metastatic disease in the liver or regional lymph nodes
CT scanning of the abdomen and/or pelvis
Obtain a CT scan to evaluate the local region of interest and evaluate for possible metastases
CT scanning 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 may be the only abnormalities noted on the CT scan
Such findings are highly suggestive of pancreatic malignancy and require further evaluation, usually with endoscopic retrograde cholangiopancreatography (ERCP)
Dynamic CT scanning (ie, high-speed scans obtained during rapid intravenous administration of iodinated contrast material) can reveal tumor involvement of the vasculature
Other imaging studies
ERCP: Obtain ERCP to evaluate the ductal architecture further
Chest radiography: Obtain a chest radiograph to complete the workup (ie, for staging purposes)
Positron emission tomography (PET) or PET-CT scanning: PET or PET-CT scans can detect metastases that are too small to be reliably detected on a CT scan
See Workup for more detail.
The standard surgical approach to the treatment of ampullary carcinoma 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.
The operative mortality rate for pancreaticoduodenectomy was at one time reported to be approximately 20%, but several hospital centers have since reported large series with operative mortality rates in the range of 5%.
See Treatment for more detail.
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.
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). [2] 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. [3]
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%). [4] 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.
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. [5]
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 review of the last 130 pancreaticoduodenectomies performed at Stanford University Medical Center over the previous 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.
Because carcinoma of the ampulla of Vater is relatively uncommon, studies of the patterns of occurrence among different ethnic groups have not been conducted.
Ampullary cancer is more common in men, according to the National Cancer Institute’s SEER Program. [5]
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Stage
T
N
M
Stage 0
Tis
N0
M0
Stage IA
T1
N0
M0
Stage IB
T2
N0
M0
Stage IIA
T3
N0
M0
Stage IIB
T1-T3
N1
M0
Stage III
T4
Any N
M0
Stage IV
Any T
Any N
M1
Institution
Year
Patients, #
Resected, #
Mortality Rate, %
5-Year Survival Rate, %
Cleveland Clinic [11]
1950-1984
59
59
8
37
Leicester Royal Infirmary, United Kingdom [12]
1972-1984
52
24
13
56
University of Alabama [13]
1953-1988
24
24
13
61
Mayo Clinic [14]
1965-1989
104
104
5.7
34
Montebelluna Hospital, Italy [15]
1971-1990
36
31
3
56
Veterans Affairs hospitals [16]
1971-1993
123
64
14
20
Academic Medical Center, Amsterdam [17]
1984-1992
67
62
6
50
Hanover Hospital, Germany [18]
1971-1993
87
85
9
38
Johns Hopkins [19]
1969-1996
120
106
4
38
Memorial Sloan-Kettering [20]
1983-1995
123
101
5
44
Catholic University, Italy [21]
1981-2002
94
64
9
64
Institution
Node-Negative, % (#)
Node-Positive, % (#)
P Value
University of Alabama at Birmingham [13]
78 (19)
50 (5)
Not significant
Mayo Clinic, Minnesota [14]
43 (53)
16 (50)
.001
Montebelluna Hospital, Italy [15]
64 (22)
0 (9)
.36
Academic Medical Center, Amsterdam [17]
59 (32)
41 (35)
.05
Niigata University, Japan [22]
81 (17)
41 (18)
< .01
Johns Hopkins, Baltimore [19]
43 (53)
31 (50)
.05
Kanazawa University Hospital, Japan [23]
74 (21)
31 (15)
< .05
Memorial Sloan- Kettering, New York [20]
55 (55)
30 (46)
.04
Loyola University, Chicago [40]
78 (27)
25 (24)
< 0.05
Ayana Allard-Picou, MD Fellow in Surgical Oncology, Department of Surgery, Roger Williams Medical Center
Ayana Allard-Picou, MD is a member of the following medical societies: American College of Surgeons, American Medical Student Association/Foundation, Christian Medical and Dental Associations, Golden Key International Honour Society, Pennsylvania Medical Society, Sentinel Lymph Node Working Group, Society of Surgical Oncology
Disclosure: Nothing to disclose.
Abdul Saied Calvino, MD Assistant Professor of Surgery, Boston University School of Medicine; Associate Program Director, Complex Surgical Oncology Fellowship, Coordinator of General Surgery Residents, Surgical Oncology Attending, Department of Surgery, Roger Williams Medical Center
Abdul Saied Calvino, MD is a member of the following medical societies: American College of Surgeons, Americas Hepato-Pancreato-Biliary Association, Association for Academic Surgery, Society of Surgical Oncology
Disclosure: Nothing to disclose.
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Received salary from Medscape for employment. for: Medscape.
Benjamin Movsas, MD
Benjamin Movsas, MD is a member of the following medical societies: American College of Radiology, American Radium Society, American Society for Radiation Oncology
Disclosure: Nothing to disclose.
N Joseph Espat, MD, MS, FACS Harold J Wanebo Professor of Surgery, Assistant Dean of Clinical Affairs, Boston University School of Medicine; Chairman, Department of Surgery, Director, Adele R Decof Cancer Center, Roger Williams Medical Center
N Joseph Espat, MD, MS, FACS is a member of the following medical societies: Alpha Omega Alpha, American Association for Cancer Research, American College of Surgeons, American Medical Association, American Society for Parenteral and Enteral Nutrition, American Society of Clinical Oncology, Americas Hepato-Pancreato-Biliary Association, Association for Academic Surgery, Central Surgical Association, Chicago Medical Society, International Hepato-Pancreato-Biliary Association, Pancreas Club, Sigma Xi, Society for Leukocyte Biology, Society for Surgery of the Alimentary Tract, Society of American Gastrointestinal and Endoscopic Surgeons, Society of Surgical Oncology, Society of University Surgeons, Southeastern Surgical Congress, Southern Medical Association, Surgical Infection Society
Disclosure: Nothing to disclose.
Clarence Sarkodee Adoo, MD, FACP Consulting Staff, Department of Bone Marrow Transplantation, City of Hope Samaritan BMT Program
Clarence Sarkodee Adoo, MD, FACP is a member of the following medical societies: American College of Physicians-American Society of Internal Medicine, American Society of Hematology, American Society of Clinical Oncology
Disclosure: Nothing to disclose.
Vivek K Mehta, MD Radiation Oncologist, Director, Center for Advanced Targeted Radiotherapies, Department of Radiation Oncology, Swedish Cancer Institute
Vivek K Mehta, MD is a member of the following medical societies: American Society for Radiation Oncology, Phi Beta Kappa, Sigma Xi
Disclosure: Nothing to disclose.
Coauthor(s): George Fisher, MD, PhD, Associate Professor, Department of Internal Medicine, Division of Medical Oncology, Stanford University School of Medicine
Ampullary Carcinoma
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