Sporadic adenomas are most frequently discovered in patients over the age of 40, and most commonly in the seventh decade of life, during evaluation for signs or symptoms of biliary obstruction. Painless jaundice is by far the most common presenting symptom found in 50–75 % of these patients [22, 23]. Other symptoms include biliary colic, weight loss, and vague abdominal pain with reports of acute pancreatitis. In general, unlike FAP-associated adenomas , sporadic adenomas of the ampulla require resection especially when symptoms are present or histology is consistent with high-grade dysplasia.

Endoscopy provides useful information from both endoscopic visualization of the ampullary lesion and histology from forceps biopsy. It is important to recognize foci of cancer may still exist within an otherwise benign-appearing adenoma, and furthermore, false-negative biopsy results may occur in 17–40 % [24–28]. Accuracy of forceps biopsy of ampullary lesions may improve by performing biopsies after sphincterotomy . An old study reported that the false-negative rate dropped to 0 % by waiting to take biopsies at least 10 days after sphincterotomy [29] while another report confirmed improved accuracy when biopsies were taken immediately after sphincterotomy [30]. However, a prospective study of ampullary biopsy before and after sphincterotomy found sensitivity of forceps biopsy for malignancy improved insignificantly from 21 % to only 37 % following sphincterotomy [31]. In addition, this practice is likely not feasible unless the patient has had prior sphincterotomy or is having an ERCP for other indications necessitating a sphincterotomy at the time an ampullary lesion is discovered. Care should be taken to avoid the pancreatic orifice during biopsy as pancreatitis has been reported following ampullary biopsies [32].

Despite the problem of biopsy sampling error, recently confirmed by a large series where 53 % of invasive cancers were missed by biopsy, only 5 % of these invasive cancers were deemed endoscopically resectable. The following endoscopic findings are believed to indicate potential malignancy and therefore unsuitable for endoscopic ampullectomy : friability, ulceration, more than 50 % lateral extension, obvious duodenal infiltration with induration and firmness, and intraductal extension more than 1 cm from the papilla [10, 33]. There are growing reports of adjunctive endoscopic technologies in the evaluation of ampullary lesions including narrow band imaging and magnification endoscopy [34]. Given the inaccuracy of endoscopic biopsy for diagnosing invasive malignancy in ampullary adenomas , further evaluation may be needed. This could ultimately entail endoscopic resection of the ampulla to obtain a definitive diagnosis in addition to providing potentially curative therapy.

Transabdominal ultrasound is commonly used as a first-line examination in patients with jaundice and may demonstrate ductal dilatation proximal to the ampullary adenoma. Pancreatic protocol multidetector row CT of the abdomen with contrast is often used to rule out a pancreatic mass and metastatic disease in patients with painless jaundice and should be performed for this indication prior to ERCP and ampullectomy. Spiral CT is likely the best modality for the evaluation of vascular invasion though its role in evaluating the presence of carcinoma in ampullary lesions is limited [35]. Magnetic resonance cholangiopancreatography (MRCP) provides non-invasive imaging of pancreatic and biliary ductal anatomy, which may not be necessary in all patients, but is useful in high-risk populations. Finally, percutaneous transhepatic cholangiography (PTC) may be used to evaluate the biliary tree in the case of a failed or difficult ERCP although this is rarely necessary.

EUS offers several advantages in the workup of ampullary adenomas to evaluate for the presence of invasive cancer. Ultrasonographic architecture and three-dimensional reconstruction of the lesion may be used to detect invasive carcinoma which is not evident on forceps biopsy or other imaging techniques [36, 37]. Ampullary carcinomas are staged using the TNM staging similar to other cancers (Table 18.3). As with other cancers, M staging is best performed with radiologic imaging, typically CT or MRI. EUS and IDUS are the modalities of choice for local T staging of ampullary carcinoma (Table 18.4). Overall accuracy of EUS T staging is estimated at 78–84 % with greatest accuracy for T2 and T3 stages (T1 60 %, T2 92 %, T3 92 %, T4 50 %) [35]. Overstaging can occur from peritumoral inflammation or concomitant pancreatitis [38]. EUS accuracy for N staging ranges from 50 to 100 %. Intraductal ultrasound has the highest accuracy (70–100 %) of all modalities for T staging [39]. A recent study comparing IDUS and EUS for T staging demonstrated similar overall accuracy (78 versus 63 %, p = 0.1) although there was a trend toward increased accuracy with IDUS for T1 and T2 (T1: 86 versus 62 %, T2: 64 versus 45 %, T3-4: 75 versus 88 %) [40]. While EUS is performed before ERCP and ampullectomy , IDUS is more invasive and occurs only during ERCP after achieving bile duct cannulation by passing a 20- to 30-MHz probe over a guidewire into the bile duct and slowly withdrawing through the ampulla. A recent retrospective study reported that EUS and ERCP had comparable accuracy (91% and 84%) for determining intraductal extension of ampullary lesions. In addition, there was no difference in accuracy between radial and linear echoendoscopes [41]. Most experts agree that EUS is indicated for lesions > 3 cm, displaying potentially malignant endoscopic features, or demonstrating high-grade dysplasia or carcinoma in situ on histology [42]. Others also advocate EUS for lesions > 2 cm in size [35, 43]. Small benign-appearing lesions, especially those less than 1 cm, are unlikely to harbor malignancy, and EUS evaluation is generally unnecessary prior to proceeding to endoscopic snare resection [43].

The technique of EUS imaging of the ampulla uses water or saline to fill the duodenum. Once in the second portion of the duodenum, the echoendoscope is rotated counterclockwise maintaining apposition to the duodenal wall until the ampulla is visualized by EUS. Alternatively, the ampulla can be located endoscopically followed by EUS imaging of this region. It is important to assess the lesion for tissue invasion, ductal infiltration, and evidence of local lymphadenopathy . The choice of a radial or linear echoendoscope is personal preference although the ability to perform fine-needle aspiration (FNA) favors the linear scope. EUS-FNA should be performed on lymph nodes as well as ampullary masses using a 22- or 25-gauge needle as 19-gauge needles are typically difficult to use in the duodenum.

Two procedures, pancreaticoduodenectomy and transduodenal resection, may be considered. For benign adenomas, transduodenal resection is preferred given the reduced morbidity and mortality associated with the procedure although it comes with a higher recurrence rate. Using a midline or subcostal laparotomy, the mass is identified and lateral duodenectomy is performed. Circumferential ampullary resection is undertaken using needle-tip electrocautery. Morbidity and potential mortality associated with surgery may be undesirable or unacceptable for some patients with comorbid conditions.

Endoscopic ampullectomy (EA) may be considered in patients meeting the previously described indications for endoscopic resection and for non-surgical candidates. The technique varies greatly across centers. Regardless, the procedure requires proficiency with a side-viewing therapeutic duodenoscope, which is used to visualize the lesion and allows use of thermal ablation probes. Many institutions perform the procedure under conscious sedation , though general anesthesia may also be employed.

After inspection, a double-lumen sphincterotome and hydrophilic guidewire are used for biliary and pancreatic duct cannulation (Fig. 18.1 and Video 18.1). Contrast should be injected into both ducts to assess for intraductal extension of the ampullary adenoma . Generally, biductal sphincterotomy is performed to allow for decompression and stenting post-ampullectomy although there is a concern for potential increased risk of complications of bleeding and perforation and interference with pathologic evaluation of the resected specimen from cautery [49, 50]. Furthermore, with larger lesions it may be difficult to identify appropriate landmarks to perform sphincterotomy safely. Post-resection sphincterotomies may be done as well. Some centers place wires into the ducts and proceed with ampullectomy with wires in place. Next, submucosal injection of epinephrine diluted in saline 1:20,000 may be used to facilitate lifting the tumor from the muscularis propria. This also may provide evidence of unidentified carcinomatous invasion if lift is not accomplished (absence of the “positive lift sign”) [51]. The risk of bleeding and deeper penetration of tissue burning is also mitigated by the submucosal lift technique [52]. Nevertheless, this step may make snare placement and resection more challenging and distort the ampullary anatomy, and the author usually avoids submucosal injection.

Ampullectomy is then performed, preferably en bloc, using a monopolar polypectomy snare (as in colon mucosal polypectomy) with electrocautery at 40–60 W using blended current, though currently there are neither guidelines regarding power output nor mode of current. The snare may be groomed prior to insertion to generate a slight curve at the tip of the snare to aid in en bloc resection. Typically the tip of the snare is anchored immediately above the lesion and opened to unfold around the lesion in a cephalad to caudal direction. Lesions greater than 2 cm may require piecemeal resection.