Ampullary Neoplasia

Endoscopy

For complete endoscopic assessment of the ampulla, the examination must be done with a duodenoscope. Examination with an end-viewing endoscope will cause a significant proportion of abnormalities to be missed. Two recent studies have demonstrated that duodenoscopy with a forward-viewing endoscope missed 50% of gross lesions visible with the side-viewing endoscope. Endoscopy usually allows diagnosis of ampullary tumors and provides information regarding degree of lateral spread. A wide variation exists in the appearance of the ampulla, which often appears quite villiform. Endoscopy permits biopsy of the ampulla, although in one study endoscopic biopsy failed to diagnose deeper malignancy in 7 of 23 cases. Furthermore, care should be taken to avoid direct biopsy of the papillary orifice, as even cold biopsy has been associated with acute necrotizing pancreatitis. Biopsies from the interior of a biliary sphincterotomy may diagnose ampullary pathology more accurately.

Macroscopically, ampullary masses conform to one of four well-recognized variations ( Figs. 38.2 and 38.3 ):

• Macroscopically normal papilla: Suspicion of an ampullary lesion is usually attributable to pancreatic and biliary ductal dilation down to the level of the duodenal wall on cross-sectional imaging. Completely intraampullary neoplasms may become apparent only when a sphincterotomy is performed but may also be well visualized with endoscopic ultrasonography (EUS). In a series of 52 cases of adenomas or carcinomas, Ponchon and co-workers noted an ampulla appearing endoscopically normal in 37%. In these cases an underlying tumor became evident only after biliary sphincterotomy.

• Intramural protrusion: A bulge underneath a normal-appearing papilla (“prominent infundibulum”). The differential diagnosis of this appearance also includes type III choledochal cyst and impacted biliary or pancreatic duct stones.

• Exposed protrusion: Neoplastic-appearing tissue extending out from the papilla.

• Ulcerating tumor: This situation is suspicious for malignancy ( Fig. 38.4, A ). Another feature suggestive of malignancy is failure of the lesion to lift when a submucosal injection is performed (sometimes included in the technique of endoscopic ampullectomy; see Chapter 25 ). Other features suggesting malignancy include friability and induration. A recent study suggested that narrow band imaging (NBI) may be useful in differentiation of inflammatory lesions from neoplastic ampullary lesions.

  

Sporadic lesions are solitary, whereas those associated with FAP syndrome are usually accompanied by other duodenal polyps. These may have a varied appearance, ranging from discrete villous lesions to thickened plaques of tissue to myriad tiny dots scattered over the mucosa (“miliary” appearance).

Endoscopic Retrograde Cholangiopancreatography

The introduction of magnetic resonance cholangiopancreatography (MRCP) and EUS has lessened the diagnostic role for endoscopic retrograde cholangiopancreatography (ERCP). Nonetheless, ERCP continues to play an important therapeutic role in establishing biliary drainage, often accompanied by diagnostic biopsy. Biliary sphincterotomy permits deeper tissue sampling and targeted biopsies, avoiding the pancreatic orifice. Sphincterotomy is also used as part of the ampullectomy technique, either to inferiorly displace a small lesion away from the ductal orifice before snare removal or to prevent subsequent papillectomy stenosis. Cholangiography remains an important tool to assess intraductal extension of a tumor ( Fig. 38.5 ).

Forceps Biopsy

Endoscopic forceps biopsy, taken from the surface of an ampullary lesion, is the usual mode of diagnosis. However, these biopsies can have a significant false-negative rate for malignancy. To reduce sampling error, it is recommended that multiple biopsies should be obtained, taking care to avoid the pancreatic orifice. Malignant change within an ampullary adenoma may be seen in up to 30% (up to 50% in older series). Despite these limitations, recent series of endoscopic management of ampullary adenomas have quoted a malignancy rate of only 6% to 8% of ampullectomy specimens presumed to have benign disease. This change is probably related to improved staging before endoscopic papillectomy and surgical ampullectomy. As mentioned previously, biopsies obtained from within a sphincterotomy may have a higher yield for malignancy. The best yield of biopsy is seen when the sample is obtained more than 10 days after sphincterotomy when diathermy artifact has cleared. EUS-guided fine-needle aspiration may be useful in the assessment of ampullary masses, with reported sensitivity and specificity of 82% and 100%, respectively, though further data on the role of EUS tissue sampling are required.

Transabdominal Ultrasonography, Computed Tomography, and Magnetic Resonance Imaging

Obstructive jaundice is often initially investigated with transabdominal ultrasonography (US) because of its accessibility, cost, and safety. In the case of obstruction caused by an ampullary lesion, the common finding is dilation of the entire biliary tree down to the duodenal wall. The tumor itself is not usually visualized. Similarly, the overall sensitivity for computed tomography (CT) is relatively low at 20% to 30% but is higher in the presence of larger tumors. If a mass is not seen, EUS may be considered, with or without ERCP, depending on whether there is a need to relieve biliary obstruction. CT is a useful staging tool both for local staging (e.g., vascular involvement) and for distant metastases. Magnetic resonance imaging (MRI) and MRCP have not been extensively investigated for ampullary lesions but appear to be promising alternatives to EUS. CT cholangiography has recently been shown to be equivalent to MRCP in the evaluation of periampullary masses.

Endoscopic Ultrasonography

EUS may be used for different purposes in the setting of ampullary neoplasia:

• 1.

  Diagnosis. EUS has a role in diagnosing patients with obstructive jaundice without a visible mass by transabdominal US or CT. For the detection of ampullary lesions, EUS (95%) has been shown to be superior to US (15%) and CT (20% to 30%). However, the normal ampulla is usually hypoechoic and small lesions (<10 mm) may be missed with EUS. EUS can be used in the investigation of an abnormal-appearing ampulla seen at endoscopy. The limited literature on this subject suggests that the specificity of EUS in this setting is about 75%. False positives arise from an inflamed and swollen ampulla, possibly because of the recent passage of a calculus (see Fig. 38.4 ). In summary, EUS should be considered an important tool for clarifying the presence of an abnormal-appearing ampulla, but the diagnosis rests on tissue confirmation.

• 2.

  Staging advanced ampullary cancer. EUS is helpful in staging ampullary malignancy according to the TNM staging system ( Box 38.1 ). Compared with CT and MRI, EUS is the most accurate tool for preoperative T-staging. In a series of 50 patients, EUS was found to be more accurate (87%) than CT (24%) and MRI (46%) based on surgical and pathologic T-staging. The main limitation of EUS is in differentiating T2 and T3 lesions. Peritumoral pancreatitis may lead to overstaging a T2 lesion. Similarly, the presence of a biliary stent may lead to inflammatory changes that make T-staging more difficult. From a clinical perspective this is not a critical issue, because the surgical management of T2 and T3 lesions is identical (pancreaticoduodenectomy). N-stage accuracy has not been reported to be different between EUS, CT, and MRI. Metastatic regional nodes are detected by EUS with an accuracy of about 65% ( Fig. 38.6 ). Locoregional lymph node involvement usually does not influence surgical management. Surgical resectability depends mainly on vascular involvement and the presence of distant metastases. Because of the early presentation of ampullary tumors and relative distance from the mesenteric vessels, vascular involvement is uncommon. EUS is an accurate means of assessing vascular involvement and can allow imaging of the portal venous system from the proximal duodenum and of the celiac vessels from the gastric fundus.

  Box 38.1

  TNM Staging System for Ampullary Carcinomas

  From Sobin LH, Wittekind CH, eds. International union against cancer (UICC): the TNM classification of malignant tumors. 6th ed. New York: Wiley; 2002.

  T1	Tumor limited to the ampulla of Vater *
  T2	Tumor invades duodenal wall (muscularis propria)
  T3	Tumor invasion into the pancreas <2 cm
  T4	Tumor invasion into the pancreas >2 cm or into adjacent organs or vessels
  N0	No regional lymph node metastasis
  N1	Regional lymph node metastasis
  M0	No distant metastasis
  M1	Distant metastasis

  * Some divide T1 tumors into d0 (limited to Oddi's sphincter) and d1 (tumor invading the duodenal submucosa).

  

• 3.

  Staging early ampullary lesions. When local endoscopic or surgical intervention is being considered, accurate T-staging is of vital importance. Endoscopic resection is generally limited to premalignant lesions because early cancers have a 10% to 45% risk of lymph node metastasis and should be managed with radical resection (Whipple procedure) in operable patients. EUS relies on infiltration and destruction of normal tissue planes to differentiate benign from malignant disease. In the case of benign biopsies, the role of EUS is to exclude an infiltrative lesion deep to the endoscopically visible part of the lesion. The accuracy of EUS to distinguish lesions >T1 stage is high, between 87% and 95%. T1 tumors have further been subclassified into T1d0 (limited to the sphincter of Oddi) and T1d1 (invasion of the duodenal mucosa). Local resection is appropriate if the lesion is T1d0 and there is no evidence of malignancy. For the d0/d1 subgrouping, intraductal ultrasonography (IDUS) appears to have the best accuracy (see the following section) but is not readily available.

• 4.

  Extension of tissue into the distal bile duct or pancreatic duct is a relative contraindication for endoscopic resection. This may be assessed by carefully performed ERCP or EUS (see Fig. 38.5 ).