Endoscopic Ultrasonography and Intraductal Ultrasound

Endoscopic ultrasonography (EUS) and intraductal ultrasound (IDUS) have been shown to be useful in the accurate T staging of the ampullary lesions. EUS operating at 7.5 to 10 MHz provides useful information as to the depth of the invasion of the duodenal wall and/or pancreatobiliary ducts, size and echogenicity of the tumor, and status of regional lymph nodes. ² , ⁷ The reported accuracy of EUS in T staging varies between 56 and 91%, while N-stage accuracy varies between 50 and 81%. ² EUS has been shown to be more accurate than computed tomography (CT) and magnetic resonance imaging (MRI) for T staging.

In a study of two centers comprising 50 patients, the accuracy of EUS for assessment of the T stage of ampullary neoplasms was 78% compared to 24% for CT and 46% for MRI. T-staging accuracy of EUS is decreased in the presence of a transpapillary endobiliary stent (84–72%). However, in nodal staging all three modalities were of similar efficacy (EUS 68%, CT 59%, MRI 77%, p > 0.05). ² , ¹⁸

IDUS utilizes frequencies between 20 and 30 MHz and is performed by advancing the ultrasound probe into the common bile duct (CBD) over a guidewire. ¹⁹ In three studies evaluating the accuracy of IDUS in T staging of ampullary neoplasms, the overall accuracy ranged between 78 and 93%. ¹⁹ , ²⁰ , ²¹ , ²² In a prospective study of 27 patients, it was noted that IDUS was superior to EUS and CT in tumor visualization and staging (100 vs. 59.3 vs. 29.6%, respectively). ²² In another study by Ito et al, the overall accuracy of IDUS and EUS in tumor staging were similar (78 vs. 63%, respectively, p = 0.14). ²¹ Based on the limited evidence available IDUS has been shown to be slightly superior to EUS in T staging. However, IDUS is not widely utilized, is more invasive, and does not evaluate regional lymph node status. ²

Is EUS needed in staging all the ampullary lesions? The consensus is divided among experts. In a survey of 79 expert biliary endoscopists (58% response rate), EUS was always utilized prior to ampullectomy by 67% responders, but only selectively by 31% of responders. ²³ Some experts suggest foregoing EUS examination for lesions less than 1 cm in size and for those without obvious signs of malignancy as described earlier. ²¹ Suggested criteria for the performance of EUS/IDUS prior to therapy for ampullary lesions include size greater than 3 cm, malignant features observed on endoscopy, and biopsies showing high-grade dysplasia (HGD) or carcinoma in situ/T1 cancer. ²⁴

Computed Tomography, Magnetic Resonance Imaging

MRI with cholangiopancreatography provides noninvasive assessment of the distal CBD and pancreatic ducts. It provides information about intraductal extension, ductal dilation, and anatomical variants such as pancreatic divisum. ²⁵ CT is the most suitable for evaluation of vascular invasion and distant metastasis. ⁷

Indications

The 2015 American Society of Gastrointestinal Endoscopy (ASGE) guidelines on the role of endoscopy in the management of ampullary adenomas do not define precise indications for EA. ⁵ The general recommendations for endoscopic resection are benign histology, lack of malignant features at endoscopy, and absence of intraductal extension on EUS/IDUS. However, endoscopic techniques to manage intraductal extension have been described.

There is no consensus on the size of the ampullary adenoma that is amenable to endoscopic resection. Based on a retrospective review of 33 patients, Kim et al suggested that polyps greater than 1.5 cm or those with HGD may not be suitable for endoscopic resection due to coexistence of cancer and a high recurrence rate. In this study, polyps with low-grade dysplasia (LGD) were 1.27 +/– 0.089 cm in size, polyps with HGD were 1.81 +/– 0.99 cm in size and cancer group had a size of 1.98+/– 1.08 cm. There was a significant correlation between the size of the polyp and final pathology (p = 0.036). ³² In another retrospective study of 157 patients, benign ampullary lesions had a median size of 1.3 cm while adenocarcinomas had a size of 2 cm. ⁹ On the other hand some experts recommend that ampullary lesions up to 4 to 5 cm can be removed endoscopically as long as these are benign. ² , ²⁸ , ³¹ , ³³ , ³⁴ Although there is a correlation between size and the risk of malignancy, in the absence of evidence for invasive cancer, size alone is not a contraindication to endoscopic resection.

Another area of controversy in EA is the presence of intraductal extension. Some experts suggest that EA can be attempted when intraductal extension is limited to less than 10 mm. ² , ²⁸ , ³⁵ , ³⁶ In a study by Bohnacker et al, 31 patients had extension of adenomatous growth into the biliary or pancreatic ducts (two patients had extension into both the ducts) and 75 patients had no intraductal extension. The rate of curative successful endoscopic therapy in the group with intraductal extension was 43% whereas in the group without intraductal extension it was 83%. Surgery was more frequently needed in the group with intraductal extension either due to incomplete removal or recurrence (37% vs. 12%, p < 0.001). The authors concluded that in experienced endoscopist hands limited intraductal involvement is accessible to endoscopic removal and suitable for endoscopic therapy, because in about 50% surgery can be avoided. ³⁷

In summary, size alone is not a contraindication to endoscopic resection provided there is no optical or sonographic evidence for submucosal invasion, the endoscopic features of ulceration, woody hard tissue, or submucosal extension are worrisome features for invasion. Further evaluation by EUS should then be considered. As noted in the study by Kim et al, lesions with HGD may harbor foci of cancer and the pathology of the resected tumor will determine the need for subsequent surgery. ³²

EA Technique

EA is an advanced endoscopic procedure which needs considerable expertise and experience. ²⁵ The basic technique of EA is similar to the principle used for colonoscopic polypectomy. Complete en bloc resection is preferred because it allows more accurate histologic assessment and negligible recurrence. ²⁵ Complete en bloc resection also ensures complete removal of adenomatous tissue abutting the biliary and pancreatic orifices. For lesions with extrapapillary extension to adjacent duodenal mucosa, the papilla should be resected as a single piece and the remainder resected in as few pieces as possible (▶Fig. 32.2). ²⁵ Use of chromoendoscopy (using methylene blue or indigo carmine) and narrow-band imaging (NBI) has been described to define the lateral margins of the ampullary polyps. ³⁸ , ³⁹ , ⁴⁰ , ⁴¹ Itoi et al noted that NBI had a statistically significant advantage over chromoendoscopy with indigo carmine in defining the lateral margins (p < 0.05). ⁴¹

Equipment

There is no evidence to suggest that one type of snare is superior to others. The snare size is chosen according to the size of the adenoma to ensure en bloc resection. A comparison of “braided” polypectomy snares and fine wire snares has been reported. ⁵ Use of thin wire snares is advocated by some experts because they maximize current density for swift resection of the adenoma and limit dispersion of energy. ²⁵ We prefer soft wire oval or hexagonal snare, which facilitates positioning of the snare over the ampulla when advanced across the elevation of the duodenoscope. We also groom the snare by manually creating a gentle curve at the tip of the closed snare prior to insertion into the accessory channel to allow smooth passage of the snare across the right angle turn over the elevator of the duodenoscope.

There are no standardized electrocautery settings for EP. The goal of the thermal energy is to achieve cutting with enough coagulation to seal vessels, but avoiding thermal injury to the pancreas. We typically use an ERBE generator with a setting of Endocut Q, effect 3, duration 2, and interval 3 (ERBE USA Inc., Marietta, Georgia, United States; Olympus ESG-100, Tokyo, Japan). ²⁵

Technique

First step is to perform endoscopic retrograde cholangiopancreatography (ERCP) with deep cannulation and contrast injection to obtain a cholangiogram and a pancreatogram. This will identify strictures or intraductal extension of the tumor (▶Fig. 32.3; Video 32.1, Video 32.2). It also helps recannulation postresection as a roadmap of the ductal anatomy is shown. In some cases cannulation is not possible prior to resection due to distortion of the anatomy and friability and bleeding in more advanced lesions may be present. In such cases postresection cannulation is often easier once the tumor bulk has been removed. ²⁵ Some experts suggest injecting methylene blue along with contrast into the pancreatic duct to help identify the pancreatic duct orifice postpapillectomy as the flow of blue contrast marks the orifice. ⁴² Sphincterotomy should generally be performed postpapillectomy. Pre-EA sphincterotomy can hinder en bloc resection and complete histologic evaluation of the resected specimen due to thermal injury. It may increase the risk of bleeding, perforation, and tumor seeding. ⁸ Use of submucosal fluid injection prior to resection is controversial. Fluid injection may increase technical success and decrease complications. ³¹ , ⁴³ Epinephrine helps to decrease bleeding and methylene blue or indigo carmine enhances endoscopic visualization of the margins of the adenoma. However, submucosal injection may cause difficulty in the resection of small lesions. The center of the ampullary lesion is tethered down by the biliary and pancreatic ducts and may not lift. Fluid injection results in elevation of the mucosa at the margins of the papilla with a resultant “donut” effect in which the adenoma is partially buried by the elevated surrounding mucosa. This may prevent good snare entrapment and compromise complete excision. ⁴³

The snare is advanced through the accessory channel of the duodenoscope. The snare is opened in a line corresponding to the long axis of the mound. The snare tip is fixed above the top of the papilla and snare is carefully opened and drawn over the papilla with the heel of the snare laid down below the inferior margin of the lesion while maintaining the position of the tip of the snare. Then snare is closed slowly entrapping the papilla and resection completed using electrocautery. ²⁵ After the resection, the specimen should be retrieved as soon as possible before it migrates distally into the small bowel. Antiperistaltic agents such as hyoscine butylbromide 10 to 20 mg or glucagon 0.5 to 1 mg may be given intravenously prior to starting resection to decrease peristalsis. ²⁵ Expeditious retrieval of the specimen can be achieved simply using the same snare used for resection. The specimen can be pulled up to the stomach and if it is 2 cm or greater, it is easier to drop the specimen and retrap it with a retrieval net before pulling it up through the esophagus. Alternatively, the retrieval net may be used from the outset provided the specimen is not falling down the duodenal sweep. Aspiration of the specimen through the accessory channel should be avoided to prevent fragmentation of the lesion. ⁵

Pancreatic Stenting

The first priority after EP should be placement of a pancreatic duct stent. ²⁵ EP is associated with increased risk of post-procedural pancreatitis. ⁵ A meta-analysis of five studies (481 patients) showed that prophylactic pancreatic duct stenting prevents post-ERCP pancreatitis. Patients in no stent group had threefold higher odds of developing pancreatitis compared to the stent group (15.5 vs. 5.8%, OR = 3.2, 95% CI 1.6–6.4). ⁴⁴ In general, the PD stent is placed postampullectomy but the option of preampullectomy stent placement has been evaluated. Placing the pancreatic duct stent prior to EP might be technically easier as there is no edema or cautery-related changes. A preresection pancreatic stent may also protect the pancreatic orifice from thermal injury. ² The problem is that a preresection stent may interfere with en bloc resection. Recently Hwang et al described use of an insulated pancreatic stent in 11 patients. They placed a 5 F polytetrafluoroethylene-insulated pancreatic stent prior to EA. Then the stent and tumor were simultaneously grasped with snare. Tumor was resected with stent in place and then specimen retrieved by perpendicular needle knife incision of the snared ampullary tumor along the edge of the stent. There was no stent migration or stent-related complications. No episodes of acute pancreatitis or perforation occurred. There were four episodes of mild bleeding and one episode of late papillary stenosis. ⁴⁵ Although this approach is well crafted and a way to ensure a pancreatic stent is left in situ, it is unlikely that postampullectomy stent placement in the same patients would be a problem. The same patients in whom pancreatic stent placement is difficult postprocedure are the ones in whom preampullectomy stent placement would be difficult.

The size of the pancreatic stent is not standardized. In most reported case series 5-F stents have been used, followed by 3 F and 7 F. Placing a 5-F stent might be easier and faster. ² The principle for pancreatic stenting is to minimize damage to the duct while maintaining adequate drainage in the immediate postampullectomy period. The stent size which best approximates the duct diameter with no internal flange is most suitable. If there is tortuosity at the genu, a shorter stent which is limited to the duct in the head of the pancreas is preferable. Duration of the pancreatic stent varies widely from 24 hours to 3 months. ² Some experts recommend stent removal after 1 to 3 days to minimize stent-induced ductal changes, while others suggest leaving the stents for 1 to 2 months to prevent stenosis. ² As the majority of stents will migrate out spontaneously, especially postampullectomy in which the sphincter is often removed or reduced in function, we wait 2 weeks to assess migration and if the stent is still in place, it is removed endoscopically. At the same time we will inspect the resection site and remove any residual polyp tissue. ⁴³ In spite of the general recommendation for prophylactic pancreatic stents this is not mandatory. In patients in whom the pancreatic orifice is widely patulous postampullectomy, there is no utility in placing a pancreatic stent.