Most (>95%) ampullary lesions are adenomas or adenocarcinomas. Side viewing endoscopy, endoscopic ultrasound, and endoscopic retrograde cholangiopancreatography are complementary procedures that have an important role in the diagnosis, staging, and treatment of ampullary lesions. Here the authors review their epidemiology and discuss the evidence for endoscopic modalities, with an emphasis on techniques for endoscopic resection. Although endoscopic papillectomy represents one of the highest-risk endoscopic interventions, it has largely replaced surgical modalities for the treatment of adenomatous lesions. Appropriate patient selection and use of preventive maneuvers will minimize the likelihood of persistent or recurrent lesions and postprocedure complications.
Key Points
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Most (>95%) ampullary lesions are adenomas or adenocarcinomas.
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Ampullary adenomas may arise sporadically or in the setting of a polyposis syndrome (eg, familial adenomatous polyposis).
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Cross-sectional imaging (eg, computed tomography) has poor sensitivity for diagnosing ampullary lesions but is superior to endoscopic modalities for the evaluation of distant metastases in the setting of confirmed malignancy.
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Endoscopic inspection using a side-viewing endoscope with directed biopsies is the most accurate diagnostic test. However, submucosal lesions and early adenocarcinoma (within an adenoma) may be missed.
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Endoscopic ultrasound and endoscopic retrograde cholangiopancreatography are important tools for characterizing submucosal lesions, T staging, and assessment of intraductal (biliary, pancreatic, or both) involvement.
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Ampullary adenomas without intraductal extension or extensive duodenal involvement can be excised via endoscopic papillectomy, which has a more favorable risk profile than surgical approaches.
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Limited data support particular techniques for endoscopic resection of adenomas (eg, electrocautery settings, type of snare, use of pancreatobiliary sphincterotomy).
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The clinician should be familiar with the indications, advantages, and limitations of endoscopic papillectomy in the management of these lesions.
Introduction
Lesions of the ampulla of Vater represent an uncommon group of gastrointestinal malignancies. However, their prognosis can be devastating, so early detection is paramount. Advances in endoscopy, particularly endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS), have significantly impacted the clinical approach to patients with suspected premalignant or malignant lesions of this region. Here, the authors discuss the epidemiology of ampullary adenomas; the role of endoscopy, EUS, and ERCP for the diagnosis and local staging of these lesions; and the current evidence evaluating the diagnostic and therapeutic role of endoscopy in their management.
Introduction
Lesions of the ampulla of Vater represent an uncommon group of gastrointestinal malignancies. However, their prognosis can be devastating, so early detection is paramount. Advances in endoscopy, particularly endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS), have significantly impacted the clinical approach to patients with suspected premalignant or malignant lesions of this region. Here, the authors discuss the epidemiology of ampullary adenomas; the role of endoscopy, EUS, and ERCP for the diagnosis and local staging of these lesions; and the current evidence evaluating the diagnostic and therapeutic role of endoscopy in their management.
Epidemiology
Lesions of the ampulla of Vater may be classified as benign, premalignant, and malignant ( Table 1 ). Because the overwhelming majority (>95%) are either adenomas or adenocarcinomas, this article is primarily devoted to the workup and endoscopic treatment of this subtype. The annual incidence of ampullary lesions in the United States is 3,000, with reported prevalence rates of 0.04%–0.12% in autopsy series. Ampullary adenomas may occur sporadically or in the setting of hereditary polyposis syndromes, including familial adenomatous polyposis (FAP) with adenomatous polyposis coli gene mutations. In patients with FAP, ampullary adenomas occur in up to 80% of individuals during their lifetime and progress to malignancy in 4%.
| Benign | Premalignant | Malignant |
|---|---|---|
| Impacted gallstone |
| Adenocarcinoma |
| Papillitis | Choledochocele (type III choledochal cyst) |
|
| Hamartoma | Intra-ampullary papillary tubular neoplasm |
|
| Heterotopic gastric mucosa | ||
| Lipoma |
Ampullary adenomas are likely to follow an adenoma-to-carcinoma sequence similar to colorectal adenocarcinoma. Heidecke and colleagues emphasized the correlation between the preoperative dysplasia grade and the malignant transformation rate during follow-up. Therefore, these lesions are considered premalignant, with an incidence of transformation to carcinoma ranging from 25%–85% for sporadic adenomas. As with all neoplasms, tumor stage dictates the appropriate therapy. Several classification systems have been proposed ( Table 2 ).
| Classification System | Description |
|---|---|
| TNM |
|
| Vienna |
|
| Spigelman , a | Based on scoring and staging system, specifically in FAP patients
|
a Spigelman classification pertains to duodenal pathology (in addition to the ampulla) in patients with FAP.
Clinical presentation and approach to the patient
Patients with ampullary lesions may present with biliary colic, obstructive jaundice, or nonspecific upper abdominal pain with or without fluctuating liver function tests, malaise, and anorexia. However, ampullary lesions often are found incidentally on cross-sectional imaging or during upper endoscopy performed for a different indication. For ampullary adenomas, options include observation with surveillance biopsies or attempts to completely resect the lesion via endoscopy or surgery. Surveillance of an ampullary adenoma in the setting of FAP is reasonable if the lesion is small (<1 cm) and asymptomatic. In patients with ampullary adenocarcinoma, palliative stenting can be performed in individuals who have a short life expectancy.
Historically, surgical resection has been the standard for ampullary resection. Treatment modalities include pancreatoduodenectomy (traditional or pylorus preserving) and transduodenal excision. Pancreatoduodenectomy is associated with higher morbidity (50%–60%) and mortality (0%–9%) compared with transduodenal excision (morbidity, 14%–27%; mortality 0%–4%). However, the largest series of surgical excision of ampullary adenomas and adenocarcinomas reported high recurrence rates (30%) with transduodenal excision, obligating close endoscopic surveillance after surgery.
In patients with ampullary adenomas, endoscopic resection represents an alternative to surgical therapy in appropriately selected patients. Endoscopic papillectomy was first described in 1983 by Suzuki and colleagues and the first large case series described in 1993 by Binmoeller and colleagues. Since, many other series have reported low morbidity and mortality with endoscopic therapy.
Diagnosis and local staging
Cross-sectional imaging, including multidetector computed tomography (MDCT), magnetic resonance imaging, and positron emission tomography (PET), have a low sensitivity for the primary diagnosis of ampullary lesions. Their utility is typically limited to staging of known ampullary cancers. Therefore, endoscopy and endoscopic ultrasound represent the principal modalities for diagnosis.
Endoscopy
Endoscopic inspection with a forward-viewing endoscope is inadequate for distinguishing a prominent but otherwise normal ampulla from alternate etiologies; thus, inspection with a side-viewing endoscope is essential. Endoscopic features of noncancerous lesions include the presence of a regular margin, absence of ulceration or spontaneous bleeding, and having a soft consistency. A principal advantage of side-viewing endoscopy is its ability to easily obtain tissue biopsies at the time of the procedure. Forceps biopsies have high sensitivity (>90%) for confirming the presence of adenoma but lower sensitivity for confirming adenocarcinoma, missing the diagnosis in up to 30% of cases. The frequency of malignant foci in ampullary adenomas is reported in the literature at 26%–30%. Therefore, a negative biopsy result does not exclude the presence of cancer, and a minimum of 6 forceps biopsies has been recommended. For this reason, surveillance of sporadic (ie, non-FAP-associated) ampullary adenomas generally is not recommended.
Endoscopic Ultrasound
EUS is consistently more accurate than MDCT, transabdominal ultrasound scan, magnetic resonance imaging, and angiography for T staging of ampullary cancers. EUS is a useful adjunct to side-viewing endoscopy to assess for infiltration of the periampullary wall layers, the common bile duct, or ventral pancreatic duct ( Fig. 1 ). Specifically, the accuracy of EUS for classifying a cancer as at least a T1 tumor (and thus excluding endoscopic or limited surgical resection) is approximately 90%. Most reported discrepancies result from the understaging of T3 and overstaging of T2 lesions, which is unlikely to impact the decision for surgical resection. However, EUS is less accurate than MDCT in the nodal staging of ampullary carcinomas, with estimates of 53%–87%. EUS is also useful for diagnosing nonadenomatous lesions, such as carcinoid tumors of the ampulla. This is germane when forceps biopsies of a prominent ampulla return normal-appearing mucosa.
Several trials have compared standard EUS using radial or linear array echoendoscopes with intraductal ultrasound (IDUS) ( Table 3 ). In 2 studies, IDUS was superior to EUS in terms of tumor visualization and T staging. However, because of its more cumbersome application and increased risk compared with standard EUS, the clinical utility of IDUS remains unclear. Although EUS may obviate the need for ERCP to evaluate for intraductal extension in some cases, it does not have to be universally incorporated into the diagnostic evaluation of an ampullary adenoma. If the clinical suspicion for invasive carcinoma is low (eg, absence of jaundice and endoscopic features described above), and the lesion appears amenable to endoscopic resection, then EUS may not impact the endoscopist’s decision to stage the lesion via papillectomy.
| Overall Accuracy | ||
|---|---|---|
| Study | EUS | IDUS |
| Itoh et al, 1997 | 90% (29/32) | 88% (28/32) |
| Menzel et al, 1999 | 62% (5/8) | 93% (14/15) |
| Ito et al, 2007 | 63% (25/40) | 78% (31/40) |
Endoscopic Retrograde Cholangiopancreatography
Tumor involvement of the bile or pancreatic duct significantly reduces the likelihood of complete resection via endoscopic papillectomy. Therefore, ERCP is an important part of the pretreatment staging of ampullary adenomas and for the palliation of obstructive jaundice in the setting of ampullary adenocarcinoma. In the absence of confirmed malignancy, ERCP typically is performed at the time of endoscopic papillectomy to (1) evaluate for intraductal extension and (2) deploy a prophylactic pancreatic duct stent to minimize the risk of post-ERCP pancreatitis after ampullectomy. The accuracy of ERCP compared with EUS for delineating ductal extension of tumor requires further study. Therefore, most endoscopists will perform a cholangiopancreatogram at the time of resection unless EUS had previously confirmed ductal involvement. In that case, endoscopic resection is usually not attempted. The authors’ practice typically follows a diagnostic and treatment algorithm based on the presence of adenoma and polyposis syndrome ( Fig. 2 ).
