INTRODUCTION — Periampullary tumors are neoplasms that arise in the vicinity of the ampulla of Vater. They can originate from the pancreas, duodenum, distal common bile duct (CBD), or the structures of the ampullary (ampulla of Vater) 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 bifurcation of the distal CBD and the pancreatic duct (figure 2).
The papilla is a nipple-like structure on the medial aspect of the second portion of the duodenum best visualized with a side-viewing endoscope. The distal bile and ventral pancreatic ducts traverse the duodenal wall in this location and open into the duodenal lumen through the small mucosal elevation of the papilla of Vater.
The epidemiology, clinical features, diagnosis, and staging of ampullary carcinoma will be reviewed here. Treatment of ampullary cancers and the approach to the patient with ampullary adenoma are presented separately. (See "Ampullary carcinoma: Treatment and prognosis" and "Ampullary adenomas: Clinical manifestations and diagnosis" and "Ampullary adenomas: Management".)
EPIDEMIOLOGY AND BIOLOGIC BEHAVIOR — Neoplastic transformation of the intestinal mucosa occurs more commonly near the ampulla than at any other site in the small intestine. Despite this, primary ampullary tumors are rare, with an incidence of approximately 4 to 10 cases per million population [1-4]. They account for only 6 percent of lesions that arise in the periampullary region [5] but are responsible for 20 percent of all tumor-related obstructions of the common bile duct [6]. There is some evidence that the incidence has increased over the last 30 years [2], although this has not been seen in all studies [4].
Both benign and malignant ampullary tumors can occur sporadically or in the setting of a genetic syndrome. The incidence of ampullary tumors is increased 200- to 300-fold among patients with hereditary polyposis syndromes, such as familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome), compared with the general population [7-9]. Surveillance endoscopy is particularly important to detect early ampullary lesions in patients with FAP given the high incidence of coexisting premalignant duodenal adenomatous polyps. Up to 90 percent of patients with FAP develop adenomas in the upper gastrointestinal tract [10]. (See "Familial adenomatous polyposis: Screening and management of patients and families".)
Mismatch repair deficiency occurs in up to 18 percent of ampullary cancers, and often has a histopathologic profile that is suggestive of Lynch syndrome, which is caused by germline mutations in one or more DNA mismatch repair genes [11]; routine testing for Lynch syndrome is indicated in such cases. (See "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'Identification of individuals at risk for Lynch syndrome' and "Lynch syndrome (hereditary nonpolyposis colorectal cancer): Clinical manifestations and diagnosis", section on 'When to suspect Lynch syndrome'.)
The average age at diagnosis of sporadic ampullary carcinomas is 60 to 70 years old [8,12-14]. By contrast, patients whose ampullary carcinomas arise in the setting of an inherited polyposis syndrome usually present at an earlier age, due in part to endoscopic screening and surveillance programs.
Histology and biologic behavior — Several lines of evidence suggest that the biology of primary ampullary adenomas and carcinomas is more analogous to intestinal rather than pancreaticobiliary neoplasms:
●True ampullary cancers have a better prognosis than periampullary malignancies of pancreatic [15-17] or extrahepatic biliary [18] origin. Resectability rates are higher (over 90 percent in some contemporary series), and five-year survival rates are approximately 30 to 50 percent, even in patients with lymph node involvement. By contrast, fewer than 10 percent of patients with completely resected, node-positive pancreatic cancer are alive at two years. (See "Overview of surgery in the treatment of exocrine pancreatic cancer and prognosis" and "Ampullary carcinoma: Treatment and prognosis".)
●The histology of primary ampullary neoplasms more often resembles that of adenomas and adenocarcinomas of intestinal origin rather than pancreaticobiliary origin. In one study of 170 ampullary carcinomas, the most common histologic subtype was intestinal (47 percent), followed by pancreatobiliary (24 percent), poorly differentiated adenocarcinomas (13 percent), intestinal-mucinous (8 percent), and invasive papillary (5 percent) [19].
●Ampullary carcinomas are thought to arise from ampullary adenomas, a premalignant precursor lesion displaying the adenoma-carcinoma sequence observed in colorectal neoplasia. Moreover, patients with FAP have a significantly increased incidence of both ampullary and colorectal cancers relative to the general population, suggesting that the mechanisms of ampullary and colorectal carcinogenesis may be similar [20].
●K-ras mutations are an early event in ampullary carcinogenesis, with an incidence (37 percent) that is similar to that in colon cancer (up to 50 percent) [21]. (See "Molecular genetics of colorectal cancer", section on 'Oncogenes'.)
●Immunohistochemistry may aid in classification [22,23]. Expression profiling of cyclooxygenase-2 (COX-2) by ampullary carcinomas is more consistent with a neoplasm of intestinal origin than with one of pancreaticobiliary origin. In one series, high COX-2 expression was detected in 78 percent of ampullary carcinomas [22]. Of the ampullary carcinomas classified as having an intestinal origin, 95 percent had high COX-2 expression, whereas only 50 percent of lesions with a pancreaticobiliary origin demonstrated high COX-2 expression.
Implications for prognosis and treatment — Subdividing adenocarcinomas of the ampulla of Vater according to histologic subtype and immunohistochemical staining pattern into distinct subsets with differing biologic behavior has prognostic importance [24-27]. In a retrospective study of 208 patients treated for ampullary adenocarcinoma in Sydney, Australia, those with a histomolecular pancreaticobiliary phenotype (CDX negative, MUC1 positive) had a significantly worse outcome than did those with an intestinal phenotype (CDX positive, MUC1 negative), with median survival of 16 versus 116 months [24]. When histomolecular phenotype was combined with lymph node status, three subsets of ampullary adenocarcinomas emerged, with significantly different survival outcomes:
●Patients with a node-negative non-pancreaticobiliary histomolecular phenotype had an excellent prognosis (five-year survival 88 percent).
●Patients with a node-positive pancreaticobiliary phenotype had a poor prognosis (five-year survival 20 percent).
●The remaining patients (node-positive non-pancreaticobiliary phenotype, node-negative pancreaticobiliary phenotype) had an intermediate prognosis (five-year survival 47 percent).
The results were comparable in two additional independent cohorts of 90 patients from Glasgow, Scotland, and 46 from Verona, Italy. However, others have failed to find a significant overall survival difference between the intestinal and pancreaticobiliary subtypes of ampullary cancer [28]. Given the conflicting data, the most recent 2017 Tumor, Node, Metastasis (TNM) staging classification of the American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) did not include histomolecular phenotype as a component of its prognostic stage groups (table 1) [29].
Identification of prognostically relevant subgroups has also been achieved using gene expression profiling in conjunction with immunohistochemical staining for cytokeratins 7 and 20 [30]. However, molecular techniques such as these are not yet ready for clinical application.
Whether and how this information could be used to individualize treatment decisions, particularly about adjuvant therapy, are unclear. The impact of adjuvant therapy on outcomes according to histomolecular phenotype could not be addressed in the study described above, since only a minority of patients (64 of 208) in all three cohorts received adjuvant chemotherapy, and it was not randomly assigned [24]. A retrospective analysis of a prospective, randomized, cooperative group study exploring the role of adjuvant therapy in periampullary cancers found no significant improvement in the pancreaticobiliary type compared with the intestinal type of ampullary cancers when adjuvant therapy was compared with no adjuvant therapy [31]. However, prospective study of treatment selection based on histomolecular phenotype is needed before conclusions can be drawn as to the clinical significance of histomolecular phenotype. At present, adjuvant therapy recommendations for patients with ampullary cancer follow guidelines established for pancreatic cancer rather than intestinal cancer. (See "Ampullary carcinoma: Treatment and prognosis", section on 'Adjuvant therapy'.)
CLINICAL MANIFESTATIONS — As with ampullary adenomas, the most common presenting symptom of ampullary carcinoma is obstructive jaundice (80 percent) caused by compression of the distal bile duct by the tumor [12,32]. (See "Ampullary adenomas: Clinical manifestations and diagnosis".)
Ampullary cancers are not usually suspected as a cause of obstructive jaundice because of their lower incidence relative to other periampullary malignancies. Additional symptoms may include diarrhea due to fat malabsorption (steatorrhea), mild weight loss, and fatigue.
Up to one-third of patients have chronic, frequently occult gastrointestinal blood loss with an associated microcytic anemia or heme-positive stools. Patients occasionally present with frank bleeding due to sloughing of the tumor, a condition exacerbated by the use of antiplatelet agents such as aspirin and clopidogrel. In one report, nonspecific symptoms included abdominal pain (45 percent), fever (45 percent), mild nausea, and dyspepsia [33]. Large lesions may produce gastric outlet obstruction associated with severe nausea and vomiting.
DIAGNOSIS AND STAGING — The diagnosis of an ampullary carcinoma is established by a combination of endoscopic, radiologic, and histologic features. Accurate staging is essential for planning surgical treatment.
TNM staging system — The most commonly used staging system is the Tumor, Node, Metastasis (TNM) system of the combined American Joint Committee on Cancer (AJCC)/Union for International Cancer Control (UICC) (table 1) [34]. The current (eighth edition, 2017) version contains a number of significant changes compared with the seventh (2010) edition, including modified definitions of T1, T2, T3, and T4 disease, the redefining of N1 disease as one to three positive regional nodes, and the defining of a new category, N2, as four or more positive regional nodes. The prognostic relevance of the new T and N stage definitions and stage groupings is depicted in the figure (figure 3) [35].
In the absence of metastases, the prognosis of an ampullary carcinoma depends primarily on two factors: the degree of local tumor invasion, as reflected by the T stage, and the presence of lymphatic spread, as reflected by the N stage.
Diagnostic evaluation — The diagnostic evaluation of a jaundiced patient with a suspected malignant bile duct obstruction is designed to eliminate benign tumors or gallstones from the differential and to establish the extent of tumor invasion and spread. Although advanced endoscopic techniques can help to differentiate ampullary adenomas from carcinomas, it may be difficult to completely exclude a carcinoma without complete resection of the lesion. Ampullary adenomas have the potential to undergo malignant transformation, and an occult focus of carcinoma may be present within a predominantly benign adenoma. (See "Ampullary adenomas: Clinical manifestations and diagnosis".)
A transabdominal ultrasound is a reasonable first test in patients presenting with obstructive jaundice, but it will generally not show the tumor. Helical computed tomography (CT) scanning should be obtained to visualize the pancreas and surrounding structures. Although its spatial resolution is inadequate to determine the degree of local tumor invasion, it is the most useful test to exclude the presence of distant metastases. (See 'Transabdominal ultrasonography' below and 'Abdominal computed tomography' below.)
Endoscopic retrograde cholangiopancreatography (ERCP) is the single most useful endoscopic study for diagnosing ampullary carcinoma because it permits identification of the tumor, biopsy, and biliary decompression, if needed. While endoscopic ultrasound (EUS) is as sensitive as ERCP and superior to CT and transabdominal ultrasound for detecting small ampullary tumors, it is typically not required for diagnosis. It may have a role in preoperative staging but may result in overstaging. As a result, we do not routinely employ EUS for the diagnosis and staging of ampullary carcinoma. (See 'Endoscopic retrograde cholangiopancreatography' below and 'Endoscopic ultrasonography' below.)
Differentiating a primary ampullary carcinoma from other more common periampullary malignancies (arising in the pancreas, duodenum, or bile duct) is challenging. Although the distinction may be evident after radiographic and endoscopic evaluation, it may not be possible to determine the tissue origin of a malignant periampullary neoplasm until resection and a histopathologic evaluation of the entire surgical specimen are completed [36]. This is particularly true if the lesion is large and obstructs the duodenal lumen. From a surgical standpoint, the distinction between ampullary and periampullary cancers is not essential preoperatively since the treatment is the same for both lesions. However, the oncologic implications for adjuvant therapy and prognosis of ampullary and periampullary tumors are substantially different. (See "Ampullary carcinoma: Treatment and prognosis", section on 'Adjuvant therapy' and "Overview of surgery in the treatment of exocrine pancreatic cancer and prognosis" and "Adjuvant and neoadjuvant therapy for localized cholangiocarcinoma", section on 'Distal cholangiocarcinoma'.)
Transabdominal ultrasonography — Transabdominal ultrasound should be the first imaging study ordered for patients with jaundice, since ultrasound can identify intrahepatic and extrahepatic bile duct dilatation and gallstones. However, overlying bowel gas frequently obscures the distal bile duct, ampulla, and pancreas. In one study, only 10 of 127 ampullary masses were detected by ultrasound [37]. The overall accuracy was 15 percent according to one study [38]. As a result, abdominal CT should be ordered as the next diagnostic procedure if ultrasound does not demonstrate gallstones or an obvious pancreatic head mass in a jaundiced patient.
Abdominal computed tomography — CT is more sensitive than ultrasound for evaluating the periampullary region (image 1). A "pancreatic mass protocol" CT should be ordered. Specifically, patients should receive water as the oral "contrast agent" (to distend the duodenum and improve visualization of the duodenal lumen and adjacent pancreas), and intravenous contrast is injected as a bolus to permit both arterial- and venous-phase imaging. Images are reconstructed at 1 to 2.5 mm intervals to improve the sensitivity of pancreatic imaging. (See "Clinical manifestations, diagnosis, and staging of exocrine pancreatic cancer", section on 'Imaging studies'.)
Although helical CT can detect masses obstructing the distal common bile duct (CBD), its sensitivity usually does not permit the visualization of small ampullary neoplasms within the duodenal lumen [39]. In one report, the overall accuracy was only 20 percent [38].However, a small retrospective study demonstrated multidetector CT to be 67 percent sensitive in detection of ampullary adenoma if adequate duodenal distention was achieved [40]. Furthermore, CT by itself is inadequate for staging ampullary cancers because it lacks the spatial resolution to determine the degree of local tumor invasion into the duodenal wall or adjacent pancreas, or the presence of major vascular involvement [41]. On the other hand, CT is generally the most useful study to evaluate for the presence of distant metastatic disease, which most frequently involves the regional lymph nodes, liver, peritoneum, lungs, and bone.
Endoscopic retrograde cholangiopancreatography — In a jaundiced patient with suspected malignant bile duct obstruction, ERCP is the preferred initial endoscopic study since it permits simultaneous endoscopic visualization of the ampulla, contrast-enhanced radiographic imaging of the pancreatic and bile ducts, biopsy from the papilla and ampullary segment of the CBD or pancreatic duct, and placement of a stent for biliary decompression, if necessary and technically feasible. However, ERCP cannot determine the extent of local tumor invasion of an ampullary carcinoma into the adjacent duodenum or pancreatic parenchyma, information that is essential for preoperative staging and surgical planning.
Most ampullary cancers are obvious endoscopically (image 2). If an exophytic ampullary tumor is identified that has the appearance of an adenoma, malignancy should be strongly suspected if the mass is ulcerated or over 3 cm in size. However, because the false negative rate of endoscopic biopsy is as high as 50 percent, a negative result is insufficient to exclude the presence of malignancy in an ampullary lesion [42-47]. The overall accuracy of diagnosis with ERCP in one report was 88 percent (p >0.05) [48].
Attempts to enhance the accuracy of endoscopic biopsy include the acquisition of tissue at least 48 hours following sphincterotomy [49,50], the performance of multiple biopsies [51], and the use of polymerase chain reaction (PCR) or immunohistochemical staining to detect p53 (a tumor suppressor gene that is frequently lost in periampullary neoplasms) or K-ras gene mutations [21,52-56]. Neither PCR nor immunohistochemical staining for p53 or K-ras gene mutations is used routinely in current clinical practice.
Magnetic resonance cholangiopancreatography and percutaneous transhepatic cholangiography — Ampullary obstruction can also be evaluated by magnetic resonance imaging with cholangiopancreatography (MRI-MRCP) or percutaneous transhepatic cholangiography (PTC) in patients with contraindications to ERCP or in whom ERCP can be technically limited (eg, those who have undergone gastric surgery, such as a Roux-en-Y gastrojejunostomy, with resultant anatomy that may make endoscopic access of the duodenum technically challenging or impossible, even with deep enteroscopy techniques). However, neither of these imaging modalities permits direct luminal visualization of the papillary aspect of the ampulla, nor do they provide access for tissue acquisition via direct forceps biopsy.
MRCP is a noninvasive method of imaging the pancreaticobiliary tree via MRI. MRCP is done in conjunction with an MRI of the abdomen with contrast (gadolinium). Some authors recommend this approach in place of ERCP in patients who will not tolerate invasive procedures or in whom a large tumor occludes the orifice of the pancreaticobiliary ducts, thus preventing cannulation and duct opacification at the time of ERCP. Ampullary carcinomas may appear as masses (filling defects) protruding into the duodenal lumen, with characteristic delayed enhancement and hyperintensity on diffusion-weighted imaging [57,58]. In one report, the overall accuracy of diagnosis with MRCP was 76 percent [48].
By contrast, PTC is an invasive procedure during which the biliary tree is accessed percutaneously using a needle inserted through the parenchyma of the liver into an intrahepatic bile duct, then contrast opacified under fluoroscopy. PTC is most commonly performed when the biliary tree is dilated and ERCP has failed to cannulate or adequately demonstrate the biliary anatomy. PTC provides not only cholangiography but also the opportunity for brush cytology (although not forceps biopsy for histology) of radiographic strictures, although ampullary lesions that do not extend into the distal CBD may not be amenable to tissue acquisition via this route. Another limitation of PTC is that it cannot directly visualize ampullary lesions, duodenal tumor ingrowth, or involvement of the pancreatic duct. (See "Percutaneous transhepatic cholangiography in adults".)
Endoscopic ultrasonography — EUS is as sensitive as ERCP and superior to CT and transabdominal ultrasound for detecting small ampullary tumors, although it is typically not required for diagnosis [38,57,59-67]. It may have a role in preoperative staging to look for tumor extension and to determine the depth of tumor invasion, but it may result in overstaging. As a result, we do not routinely employ EUS for the diagnosis and staging of ampullary carcinoma.
Because biliary and pancreatic sphincterotomy and stent placement cannot be performed using EUS equipment, patients who require therapeutic intervention must also undergo an ERCP, which can often be performed concomitantly. However, when a large ampullary neoplasm or duodenal obstruction preclude direct biliary drainage via ERCP, therapeutic EUS techniques offer an endoscopic alternative to percutaneous drainage. (See "Therapeutic endoscopic ultrasound", section on 'EUS-guided cholangiopancreatography'.)
Role in diagnosis — Most cancers are clearly seen endoscopically, and ampullectomy will provide tissue for histologic diagnosis, so EUS is generally not required for diagnosis. In addition, EUS will not be helpful for identifying foci of carcinoma within otherwise benign lesions. EUS may be indicated for the occasional biopsy-negative ampullary lesion that has equivocal endoscopic features of malignancy. (See "Ampullary adenomas: Management", section on 'Endoscopic papillectomy'.)
If malignancy is suspected in a patient undergoing EUS, fine-needle aspiration (FNA) of the ampulla, papilla, and surrounding deeper structures, including the local lymph nodes, can be obtained during the procedure. However, a negative result does not exclude the presence of a malignant focus within an adenoma. (See "Endoscopic ultrasound-guided fine needle aspiration in the gastrointestinal tract".)
In one report, the overall accuracy of EUS-guided FNA biopsy for primary masses of the ampullary region was 89 percent, with a sensitivity of 82 percent and a specificity of 100 percent [68].
Role in staging — EUS is the most accurate modality available to assess the T stage of ampullary tumors, which is critical for planning surgical intervention. Multiple series consistently document primary T staging accuracies of 70 to 90 percent [7,59,61,64,69-75]. Accuracy may be decreased in the presence of an endobiliary stent [63]. EUS is less helpful for N staging.
EUS is capable of obtaining images of the distal biliary and pancreatic ducts, permitting assessment of local intraductal tumor extension. EUS also accurately demonstrates tumor penetration into the duodenum by demonstrating obliteration of the interface between the tumor and the muscularis propria of the duodenum (a feature that upstages the tumor to T2). Tumor extension into the pancreas constitutes T3 disease, while invasion beyond the pancreas signifies T4 disease (image 3).
EUS is less accurate for N staging than it is for T staging. Ampullary cancers drain into two peripancreatic lymph node basins: the retroduodenopancreatic chain and the superior mesenteric chain. Regional lymph nodes also include the lymph nodes along the hepatic artery and portal vein [29]. One study reported sensitivity and specificity rates of 67 and 96 percent, respectively, for EUS detection of nodal metastases when abnormal nodes were seen (defined as those over 1 cm in diameter and located in the above two positions) [75]. Another series found sensitivity and specificity rates of 69 and 38 percent, respectively, when all visualized lymph nodes present around the duodenopancreatic block were presumed to be metastatic, regardless of size or position [74]. However, others have reported sensitivity rates as low as 21 percent for detection of nodal metastases by EUS [76].
EUS-guided FNA of suspicious lymph nodes may further increase the accuracy of nodal staging. This topic is discussed in detail separately. (See "Endoscopic ultrasound-guided fine needle aspiration in the gastrointestinal tract", section on 'Pancreatic lesions'.)
Intraductal ultrasonography — The technical evolution of EUS has led to the development of small-caliber intraductal ultrasound (IDUS) miniprobes (approximately 2 mm), which can be passed through standard endoscopes directly into the bile or pancreatic duct. The small caliber, flexibility, and excellent image quality produced by these catheters make them useful for evaluating a variety of biliary and pancreatic disorders. IDUS accurately visualizes the anatomy of the papilla and is the only procedure that reliably differentiates the sphincter of Oddi muscle from the remainder of the papilla. As a result, IDUS can be useful for diagnosing and assessing the size and extent of papillary tumors. In a study of 40 patients with ampullary neoplasms, 33 of whom had ampullary carcinoma, IDUS was more accurate than EUS for T staging and evaluating ductal invasion, making it useful in selecting cases that might be considered for endoscopic excision [77]. (See "Intraductal ultrasound for evaluating the pancreaticobiliary ductal system".)
Magnification endoscopy with narrow-band imaging — Narrow-band imaging uses optical filters to enhance visualization of microvessels and mucosal surface architecture in gastrointestinal diseases. The technique demonstrates abnormal vessels associated with high-grade dysplasia on the surface of high-grade adenomas and adenocarcinomas. Abnormal vessels have not been identified on the surface of benign ampullary adenomas with hyperplastic or inflammatory histology. Preliminary studies have suggested a potential role for the evaluation of ampullary lesions [78].
Liver biochemical tests — Blood chemistries cannot establish the diagnosis of ampullary carcinoma but may reflect the presence of cholestasis when an ampullary neoplasm results in partial or complete biliary obstruction. Patients generally have a cholestatic pattern of liver biochemical test abnormalities, although aminotransferases may also be elevated [33]. The prothrombin time may be elevated due to impaired absorption of fat-soluble vitamins, including vitamin K [79].
Serum tumor markers — Serum tumor markers are not specific for ampullary carcinomas and have limited diagnostic application. Nevertheless, some ampullary cancers are associated with increased serum levels of carbohydrate antigen 19-9 (CA 19-9) and/or carcinoembryonic antigen (CEA) [16,80], and serial assay of these tumor markers may be useful for post-treatment follow-up. (See "Ampullary carcinoma: Treatment and prognosis", section on 'Post-treatment surveillance'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ampullary neoplasms".)
SUMMARY AND RECOMMENDATIONS
●Clinical manifestations – Patients with ampullary cancer most commonly present with jaundice caused by obstruction of the distal bile duct by tumor. (See 'Clinical manifestations' above.)
●Diagnosis and staging – Diagnosis and staging are achieved by a combination of endoscopic, radiologic, and histologic features. There are two major considerations: identification of the tumor and distinction from an ampullary adenoma or tumor arising from outside of the ampulla (mainly pancreatic carcinoma or distal cholangiocarcinoma). (See 'Diagnosis and staging' above.)
●Imaging studies
•Transabdominal ultrasound – A transabdominal ultrasound is a reasonable first test in patients presenting with obstructive jaundice, but it will generally not show the tumor. (See 'Transabdominal ultrasonography' above.)
•Abdominal computed tomography – Multiphase helical abdominal computed tomography (CT) should be obtained to visualize the pancreas and surrounding structures. Although its spatial resolution is inadequate to determine the degree of local tumor invasion, it is the most useful test to exclude the presence of distant metastases. (See 'Abdominal computed tomography' above.)
●ERCP – Endoscopic retrograde cholangiopancreatography (ERCP) is the single most useful endoscopic study since it permits identification of the tumor, biopsy, and decompression, if needed. (See 'Endoscopic retrograde cholangiopancreatography' above.)
We do not routinely employ endoscopic ultrasound (EUS) for the diagnosis and staging of ampullary carcinoma. While EUS is as sensitive as ERCP and superior to CT and transabdominal ultrasound for detecting small ampullary tumors, it is typically not required for diagnosis. It may have a role in preoperative staging but may result in overstaging. (See 'Endoscopic ultrasonography' above.)
ACKNOWLEDGMENT — The editorial staff at UpToDate acknowledge A James Moser, MD, who contributed to an earlier version of this topic review.
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