Ampullary adenomas: Management

INTRODUCTION — Adenomas are the most common benign lesions of the ampulla but have the potential to undergo malignant transformation to ampullary carcinomas [1-10]. Approximately 15 to 60 percent of ampullary adenomas harbor small foci of adenocarcinoma [7,11-15]. Ampullary adenomas can occur sporadically or in the setting of an adenomatous polyposis syndrome (eg, familial adenomatous polyposis and MUTYH-associated polyposis). This topic reviews the management of ampullary adenomas. The clinical manifestations and diagnosis of ampullary adenomas and the management of ampullary carcinoma are discussed separately. (See "Ampullary adenomas: Clinical manifestations and diagnosis" and "Ampullary carcinoma: Epidemiology, clinical manifestations, diagnosis and staging".)

MANAGEMENT

General approach — In the absence of randomized trials comparing different treatment strategies, recommendations for the management of ampullary adenomas are based on observational studies and clinical experience.

●Sporadic ampullary adenoma – We excise all sporadic ampullary adenomas. Excision is particularly important in patients with adenomas that are causing symptoms or that have foci of high-grade dysplasia. In patients who do not undergo excision, we perform surveillance duodenoscopy (upper endoscopy using a side-viewing endoscope) every 6 to 12 months, performing multiple cold-forceps biopsies of the papilla of Vater.

●Adenomatous polyposis syndrome – We also resect ampullary adenomas in patients with an adenomatous polyposis syndrome. The choice and timing of excision in patients with a familial polyposis syndrome should be individualized based on symptoms, histologic considerations, the patient's age and the number of concurrent duodenal adenomas, and is discussed in detail separately. (See "Familial adenomatous polyposis: Screening and management of patients and families", section on 'Duodenal polyps'.)

Selection of a treatment modality — The choice of treatment modality depends on the characteristics of the adenoma, the presence of concurrent duodenal polyposis, the presence of endoscopic expertise, and the willingness of the patient to undergo long-term endoscopic surveillance following endoscopic papillectomy or surgical ampullectomy [16]. The role of endoscopy in ampullary adenomas was reviewed in a guideline statement published by the American Society for Gastrointestinal Endoscopy in 2015 [16], and also in the guideline statement published by the European Society of Gastrointestinal Endoscopy in 2021 [17]. The following discussion is largely consistent with the guideline recommendations. (See 'Post-treatment follow-up' below.)

●We perform endoscopic ampullectomy in patients with ampullary adenomas with all of the following characteristics:

•Less than 2 to 3 cm in size – While there are no universally accepted criteria for the maximum size of adenoma amenable to endoscopic excision, we typically limit endoscopic snare papillectomy to lesions less than 2 to 3 cm in size. While some experts have suggested that endoscopic excision may be reasonable for sporadic adenomas less than 4 to 4.5 cm in largest dimension with no evidence of intraductal growth or malignancy, studies have demonstrated adenocarcinomas can be present within smaller polyps [11,18-21].

•Less than 2 cm ingrowth into the bile or pancreatic duct.

•Absence of advanced duodenal polyposis (Modified Spiegelman stage IV) (table 1).

●We suggest surgical management in patients with any one the following characteristics [17,22]:

•Adenoma too large to be excised endoscopically (>2 to 3 cm).

•Significant (≥2 cm) ingrowth of the adenoma into the bile or pancreatic duct.

•Advanced duodenal polyposis (Modified Spiegelman stage IV).

For patients undergoing surgical excision, we suggest pancreaticoduodenectomy rather than surgical ampullectomy. Surgical ampullectomy may have lower morbidity and perioperative mortality rates as compared with pancreaticoduodenectomy but requires endoscopic surveillance due to the risk of adenoma recurrence. (See 'Endoscopic surveillance' below.)

●We reserve endoscopic drainage for patients with symptomatic ampullary obstruction who are unable or unwilling to undergo endoscopic papillectomy or surgery. (See 'Endoscopic palliation' below.)

Endoscopic papillectomy — Endoscopic papillectomy involves resection of tissue from the papilla and requires expertise in interventional endoscopy [23-27].

Endoscopic resection technique — The goal of endoscopic excision is to achieve complete removal of the ampullary neoplasm [18,28,29]. En bloc excision is the preferred method since it increases the likelihood of complete removal, especially if the adenoma is abutting the biliary and pancreatic orifices. In addition, en bloc excision provides a pathologic specimen with margins that can be assessed in the event carcinoma is detected. En bloc excision using the standard snare technique may not be technically feasible in the presence of one or more of the following: large adenoma size, limited endoscopic accessibility, or sessile nature of the adenoma, including laterally-spreading extra-papillary extension. In these cases, piecemeal excision may be undertaken with adjuvant ablative therapy [30]. (See 'Adjunctive techniques' below.)

Endoscopic papillectomy is typically performed with the standard monopolar diathermic snare used in colonoscopic polypectomy. The snare should be relatively soft and flexible to allow manipulation across the elevator of a duodenoscope. We routinely groom the snare to create a gentle curve at the tip. This facilitates passage of the snare through the right-angle turn in the accessory channel of the duodenoscope and across the elevator. We use the larger channel therapeutic duodenoscope to allow easier passage of both the snare and thermal ablation probes. The larger channel also permits aspiration of insufflated air and argon gas when a snare or probe is present in the channel. In patients with an intraductally extending adenoma we use a balloon-tipped catheter to improve exposure and allow for more complete endoscopic excision [31].

The excised specimen can migrate distally in the duodenum and should be retrieved immediately after excision. The tissue should be retrieved with a snare or a retrieval net so that the margins can be clearly assessed. Aspiration through the accessory channel of the duodenoscope into a trap can fragment the specimen and should be avoided.

Adjunctive techniques — Adjunctive techniques have been used to increase the technical success and decrease the incidence of complications. (See 'Complications' below.)

●Sphincterotomy and stent placement – A biliary sphincterotomy can facilitate complete excision of the adenomatous tissue if it is situated partly in the biliary orifice. A pancreatic or biliary sphincterotomy can also facilitate placement of a stent. Prophylactic placement of a pancreatic duct stent decreases the risk of post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis following ampullectomy [18,19,32-37].

If the size or irregularity of the adenoma margins favors piecemeal removal, placement of a pancreatic stent prior to the excision may protect the orifice from thermal injury from the snare. However, with an en bloc excision, the stent cannot be placed beforehand, because the snare encircles the ampulla from which the stent would be protruding (such that, in order to remove the ampulla, the stent would have to be transected). However, stent placement following papillectomy can be technically challenging. Pre-resection stenting with an insulated pancreatic stent, with retrieval of the specimen via perpendicular needle-knife incision of the snared ampullary neoplasm has been described, but is not widely performed [38].

The pancreatic stent is generally removed two or three weeks later, at which time any suspicious-appearing residual polypoid tissue can be removed to ensure complete excision.

●Ablation of residual tissue – In patients with residual tissue around the biliary and pancreatic duct orifices, fulguration (thermal ablation) is necessary to decrease the risk of adenoma recurrence. We employ argon plasma coagulation (APC) to ablate residual tissue and typically use a 7 Fr probe at a setting of 50 to 60 watts, paying careful attention to avoid aggressive tissue destruction around the orifices [19,34]. We perform a biliary sphincterotomy prior to fulguration to lay open the lower end of the bile duct, and place a pancreatic stent before thermally coagulating around the pancreatic orifice. Fulguration of residual tissue can also be performed with monopolar coagulation, bipolar coagulation, Nd:YAG laser, or photodynamic therapy [22-25,34].

●Avoid submucosal saline injection – Submucosal injection of saline should not be performed prior to snare papillectomy [17]. While local saline injection prevents a deeper burn into the duodenal wall, it is associated with significant disadvantages that have limited its use [19,34]. As the center of the ampullary lesion is tethered down by the biliary and pancreatic ducts, it may not lift with saline injection. In addition, the surrounding normal mucosa, which does lift, may "mushroom" around the adenoma and partially bury its central aspect, preventing adequate snare placement and compromising complete excision. (See "Endoscopic removal of large colon polyps", section on 'Submucosal injection'.)

Prophylaxis for post-ERCP pancreatitis — Patients undergoing papillectomy are at increased risk for post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis. In addition to pancreatic stent placement, we administer rectal indomethacin immediately after endoscopic papillectomy to decrease the incidence of post-ERCP pancreatitis. (See 'Complications' below and "Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis".)

Complications — Approximately 15 percent of patients develop complications after endoscopic papillectomy [6,18-20,23,25,28,36,39-45]. Early complications include acute pancreatitis (8 to 15 percent), bleeding (2 to 13 percent), perforation (0 to 4 percent), and cholangitis (0 to 2 percent). Papillary stenosis is a late complication that has been reported in up to 8 percent of patients, and can develop within 7 days to 24 months after endoscopic papillectomy. While some observational studies have reported lower complication rates with endoscopic papillectomy as compared with pancreaticoduodenectomy, it is unclear if they are attributable to publication bias [46].

Surgery — Surgical options for resecting ampullary adenomas include pancreaticoduodenectomy and surgical ampullectomy.

Pancreaticoduodenectomy — Pancreaticoduodenectomy is the definitive approach for achieving curative excision of ampullary adenomas. A major advantage compared with less aggressive approaches is that it eliminates the risk of local recurrence in patients who do not have an adenomatous polyposis syndrome and do not harbor occult adenocarcinoma [47-49]. It also eliminates the need for surveillance endoscopy in patients with sporadic adenomas.

The major disadvantages of this approach are largely related to the high postoperative morbidity and mortality rates. Data from multiple series of pancreaticoduodenectomy performed for benign and malignant ampullary tumors demonstrated an operative mortality rate of 0 to 10 percent and operative morbidity of 25 to 65 percent [24,47-59]. Perioperative mortality rates are lowest (less than 4 percent) in centers with a high procedure volume. (See "Surgical resection of lesions of the head of the pancreas", section on 'Perioperative morbidity and mortality' and "Overview of surgery in the treatment of exocrine pancreatic cancer and prognosis", section on 'Pancreaticoduodenectomy'.)

Surgical ampullectomy — Ampullectomy involves removal of the entire ampulla of Vater. Surgical ampullectomy entails mobilization of the duodenum and longitudinal duodenotomy, followed either by simple excision of the ampullary neoplasm or an extended excision, involving the ampulla and adjacent duodenal and ductal tissue. The latter approach typically requires operative reconstruction of the biliary and pancreatic ducts using a sphincteroplasty technique [60-64]. Robotic transduodenal ampullectomy has been described in a small series with no recurrence in short-term follow up [65].

Complications of surgical ampullectomy include gastric outlet obstruction, pancreatitis, cholangitis, and common bile duct stricture formation [12]. Small observational studies suggest that surgical ampullectomy is associated with lower morbidity and perioperative mortality rates as compared with pancreaticoduodenectomy [12,47-49,53]. However, one review of 66 patients found higher morbidity but a higher rate of complete treatment and better long-term results with surgical ampullectomy [66]. All of these studies are at risk for selection bias because patients with smaller neoplasms may have been more likely to undergo local excision. However, the potentially lower morbidity and perioperative mortality with surgical ampullectomy must be balanced against a higher recurrence rate and the potential for inadequate excisional margins, which may be a particular problem if an occult carcinoma is found in the resected specimen. As with endoscopic papillectomy, surgical ampullectomy requires endoscopic surveillance.

Endoscopic palliation — Endoscopic drainage of ductal obstruction in ampullary tumors via papillotomy or transpapillary stent placement provides effective symptomatic relief in patients with obstruction of the biliary or pancreatic ducts [67-73]. Obstruction extending proximal to the papilla may require placement of a biliary or pancreatic stent, with or without concomitant sphincterotomy. Common bile duct stones, sometimes encountered in association with ampullary adenomas, can be removed with a Dormia basket or extraction balloon catheter following sphincterotomy.

Biliary radiofrequency catheter ablation during ERCP has been used for primary management of ampullary adenoma in patients who were not candidates for surgical or endoscopic excision [22,74-76]. (See "Endoscopic management of bile duct stones".)

POST-TREATMENT FOLLOW-UP

Incomplete resection and adenoma recurrence — Primary success rates for endoscopic papillectomy range from 46 to 92 percent, with recurrence rates of up to 33 percent [28,29]. The risk of adenoma recurrence is higher with increasing adenoma size, the presence of genetic predisposition to adenoma formation (eg, familial adenomatous polyposis, MUTYH-associated polyposis), and intraductal adenoma growth [34,77]. Pancreaticoduodenectomy eliminates the risk of adenoma recurrence in patients without an adenomatous polyposis syndrome. However, recurrence rates after surgical ampullectomy range from 5 to 50 percent [5,8,12,13,47,48,60,61,78]. In a 2016 meta-analysis of five retrospective studies that included 466 patients, surgical treatment of ampullary adenomas was associated with a higher primary success rate and lower recurrence rates as compared with endoscopic papillectomy [46]. However, the meta-analysis was limited by significant heterogeneity.

Adenoma recurrence can often be managed endoscopically. However, surgery may be needed in patients with large adenomas or advanced duodenal polyposis. (See 'Selection of a treatment modality' above.)

Endoscopic surveillance — The frequency of endoscopic surveillance depends on the presence of an adenomatous polyposis syndrome, the treatment modality, and the characteristics of the ampullary adenoma [16].

Sporadic adenoma — Patients with sporadic adenomas who have undergone endoscopic papillectomy or surgical ampullectomy require endoscopic surveillance for recurrence.

Initial surveillance — The frequency of endoscopic surveillance varies by adenoma size and the degree of dysplasia.

●In patients with a large polyp (≥2 cm) or high grade dysplasia, we perform a duodenoscopy in one to three months. In the absence of recurrence, we repeat examinations with a duodenoscope every six months for two years.

●In patients with ampullary adenomas (<2 cm) and no high-grade dysplasia, we perform a duodenoscopy six months following excision. In the absence of adenoma recurrence, we perform duodenoscopy every 12 months for two years.

Subsequent surveillance — In patients with sporadic adenomas, we continue to perform duodenoscopy every three years in patients with a large polyp (≥2 cm) or high-grade dysplasia and every five years in patients with smaller polyps without high-grade dysplasia.

Adenomatous polyposis syndrome — In patients with an adenomatous polyposis syndrome (eg, familial adenomatous polyposis and MUTYH-associated polyposis), surveillance is required both for recurrent adenoma and for concurrent duodenum adenomas. The frequency of surveillance must be individualized based on the characteristics of the ampullary adenoma and the Modified Spigelman stage of duodenal polyposis and is discussed in detail elsewhere. (See "Familial adenomatous polyposis: Screening and management of patients and families", section on 'Duodenal polyps'.)

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

●Adenomas are the most common benign lesions of the ampulla but have the potential to undergo malignant transformation to ampullary carcinomas. Approximately 15 to 60 percent of ampullary adenomas harbor small foci of adenocarcinoma. Ampullary adenomas can occur sporadically or in the setting of an adenomatous polyposis syndromes (eg, familial adenomatous polyposis and MUTYH-associated polyposis). (See 'Introduction' above.)

●In the absence of randomized trials comparing different treatment strategies, recommendations are based on observational studies and clinical experience. (See 'General approach' above.)

•We excise all sporadic ampullary adenomas. Excision is particularly important in patients with adenomas that are causing symptoms or that have foci of high-grade dysplasia. In patients who do not undergo excision, we perform surveillance duodenoscopy (upper endoscopy using a side-viewing endoscope) every 6 to 12 months, performing multiple cold-forceps biopsies of the papilla of Vater.

•We also resect ampullary adenomas in patients with an adenomatous polyposis syndrome (eg, familial adenomatous polyposis or MUTYH-associated polyposis). The choice and timing of excision in patients with an adenomatous polyposis syndrome should be individualized based on the patient's age and the number of concurrent duodenal adenomas.

●The choice of treatment modality depends on the characteristics of the adenoma, the presence of concurrent duodenal polyposis, presence of endoscopic expertise, and willingness of the patient to undergo long-term endoscopic surveillance following endoscopic papillectomy or surgical ampullectomy. (See 'Selection of a treatment modality' above.)

●Pancreaticoduodenectomy achieves curative excision of ampullary adenomas and eliminates the risk of local recurrence in patients who do not have an adenomatous polyposis syndrome and do not harbor occult adenocarcinoma. Surgical ampullectomy involves removal of the entire ampulla of Vater. Surgical ampullectomy has a potentially lower morbidity and perioperative mortality as compared with pancreaticoduodenectomy but may result in inadequate excisional margins and adenoma recurrence. (See 'Surgery' above.)

●Endoscopic papillectomy involves resection of tissue from the papilla and requires expertise in interventional endoscopy. Primary success rates for endoscopic papillectomy range from 46 to 92 percent, with recurrence rates of up to 33 percent. The risk of adenoma recurrence is higher with increasing adenoma size, the presence of genetic predisposition to adenoma formation, and intraductal adenoma growth. (See 'Endoscopic papillectomy' above.)

●For most patients without evidence of malignancy within the adenoma on imaging or endoscopy, we suggest endoscopic papillectomy for ampullary adenomas rather than surgical excision, provided the patient has access to an interventional endoscopist experienced in ampullectomy (Grade 2C). Exceptions are patients with evidence of significant (≥2 cm) intraductal tumor growth, patients with adenomas larger than 2 to 3 cm, or patients who prefer to undergo a definitive surgical procedure, in whom surgical excision is appropriate. We reserve endoscopic drainage for patients with symptomatic ampullary obstruction who are unable or unwilling to undergo endoscopic papillectomy or surgery. (See 'Selection of a treatment modality' above.)

●In patients undergoing endoscopic ampullectomy, we recommend prophylactic stenting of the pancreatic duct (Grade 1B). In addition, we administer rectal indomethacin immediately post-endoscopic retrograde cholangiopancreatography after endoscopic ampullectomy. (See 'Endoscopic papillectomy' above and 'Prophylaxis for post-ERCP pancreatitis' above.)

●Endoscopic surveillance is required following surgical ampullectomy or endoscopic ampullectomy due to the risk of adenoma recurrence with these procedures. The frequency of endoscopic surveillance depends on the presence of an adenomatous polyposis syndrome, the treatment modality, and the characteristics of the ampullary adenoma. (See 'Endoscopic surveillance' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Gregory B. Haber, MD, for his past contributions as an author to prior versions of this topic review.