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Introduction
Benign tumors of the ampulla of Vater, or major duodenal papilla, can be treated with endoscopic resection termed papillectomy or ampullectomy with or without adjunctive ablative therapy. Ampullary adenomas occur in 0.04 to 0.12% of the general population and in 50% to 100% of persons with familial adenomatous polyposis (FAP)1. These lesions can progress through an adenoma-carcinoma sequence, as do colorectal adenomas2. Ampullary carcinomas are a frequent cause of death in persons with FAP3.
Pancreaticoduodenectomy or local surgical resection have been the traditional treatment. However, perioperative mortality occurs in 4% to 15% and morbidity in up to 50% following pancreaticoduodenectomy4-6. Local resection has a morbidity rate of 19% to 25% with recurrence in up to 32% at 5 years7.
Endoscopic therapy entails snare resection of ampullary adenomas with or without ablation with ionized argon coagulation, bipolar or heat probe, or Nd:YAG laser4,8-16. Photodynamic therapy has also been used.11 Frequently, a combination of mechanical and thermal therapy is necessary and there is no universally accepted technique.
Diagnosis
Ampullary tumors are usually diagnosed during endoscopic evaluation for symptoms or at routine surveillance of FAP patients. A side-viewing duodenoscope is optimal for assessing for ampullary lesions. Ampullary adenomas may be polypoid, fungating, ulcerated, or sessile goatee appearance particularly in FAP as shown in Figures 1a-d. Endoscopic biopsy may miss advanced dysplasia and carcinomas in about 30% of cases; even after sphincterotomy2,17. Endoscopic removal of the entire ampulla provides ample tissue for diagnosis and usually a resection margin to assess for complete resection.
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Figure 1a |
Figure 1b |
Figure 1c |
Figure 1d |
Multi-detector computed tomography (CT) with water for duodenal contrast should be performed as an initial diagnostic and staging test. Most authorities perform ERCP at the time of ampullectomy to determine if there is neoplastic involvement of the pancreatic and bile ducts14. The role of endoscopic ultrasound (EUS) is not well established but may add information regarding invasion and/or ductal involvement as shown in Figures 2a-b. The balloon on the EUS instrument may flatten the papilla and impair accurate diagnosis. For T stage, EUS accuracy is reported to be 78%, CT 24% and magnetic resonance imaging (MRI) 46%, but for N stage EUS is 68%, CT 59%, and MRI 77%18,19. Intraductal ultrasound probes appear to be superior to echoendoscopes and CT scans20. This author reserves EUS for large or otherwise suspicious appearing lesions.
Principles of Endoscopic Papillectomy
There is no standardized technique for papillectomy. This author uses a polypectomy snare through a duodenoscope with pure coagulation or pulsed cutting and coagulation current for en-bloc resection. Pancreatic and usually bile duct stents are then inserted In FAP patients, ionized argon coagulation is applied to the resection site, and around and between the stents. Figures 3a-e shows resection and ablation of an ampullary adenoma. (Video 1) Plastic stents do not melt because they do not transmit the monopolar energy generated by ionized argon coagulation. The thermal beam preferentially travels to the nearest site that transmits electricity and coagulates the tissue. Large lesions occasionally require piecemeal resection and adjuvant ionized argon coagulation. Superficial extension of adenomatous tissue into the pancreatic and/or bile ducts is treated with ionized argon or multipolar probe ablation before stenting. Others have used snare resection14. The resected specimen is retrieved with suction, or grasped with the resection snare or a netted snare. Snare resection usually removes tissue down to the level of the muscularis propria. Submucosal injection of saline and/or epinephrine is rarely necessary. However, flat lesions may be treated with sphincterotomy, injection, snare resection, stenting and ablation Figures 4a-e.
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Figure 3a |
Figure 3b |
Figure 3c |
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Figure 4a |
Figure 4b |
Figure 4c |
Perforations and other significant mucosal defects can be closed with clips as shown in Figure 5. (Video 2) Bleeding may be treated with epinephrine and saline injection followed by endoscopic clipping as shown in Figure 6. Occasionally, ionized argon energy is applied to the clips in order to coagulate the contiguous tissue.
The literature consists of mostly retrospective case series using variable techniques and inconsistent definitions of efficacy and complications. Recognizing these limitations, Table 1 shows that from a compilation of series involving 338 patients treated with an average of 1.1 to 2.7 procedures, initial ablation was achieved in 83% or more. Complications occurred in about 20% including bleeding, pancreatitis and perforation, which may be severe13-16. With an average of 13 to 37 months of follow up, adenomas recurred in 20%. Bohnacker and colleagues demonstrated that persons with lesions invading the bile duct or pancreatic duct had only a 46% eradication rate and required more endoscopic sessions. However, recurrence rates were similar for patients with or without ductal neoplasia14. Following Nd:YAG laser ablation as primary therapy, 66% of patients remained in remission with a mean follow up of 66 months and no patient developed periampullary cancer with an average of 81 months of follow up17. Late-occurring complications were uncommon but included ductal orifice stenosis.
This author performed ampullectomy as described above on 50 FAP patients and prospectively followed them for a mean of 8 months (range, 1 to 39 months) as part of a National Cancer Institute sponsored study. The mean ampullary diameter was 26 mm (range, 6 to 60 mm) and the pathology was tubular adenoma in 36, tubulovillous in 10, adenoma with high-grade dysplasia in 2, adenocarcinoma in 1 and inflammatory in 1. With a mean of 1.2 procedures per patient (range, 1 to 13 procedures), ablation was successful in 90% following the initial procedure and 100% after subsequent procedures, including the patient with carcinoma. Morbid events occurred following 20% of procedures and were severe in 4%. For individual patients, complications developed in 30% and were severe in 8%. There was one death due to cardiac arrhythmia during a surveillance endoscopy.
Prophylactic pancreatic duct stenting appears to decrease the risk of pancreatitis after high-risk ERCP. Most authorities advocate prophylactic stenting after papillectomy but supportive data are limited. Harewood and colleagues performed a randomized clinical trial involving 19 patients and pancreatitis developed in 33% of the unstented patients and none of the stented group (p = 0.002)15. Catalano and colleagues stented 88 of the 103 patients in their series and 15 patients were not stented because of technical difficulty, pancreas divisum or endoscopist preference. Pancreatitis developed in 3.3% of the stented group versus 17% of patients in whom they could not place a stent for technical reasons13. However, Bohnacker and colleagues found similar rates of pancreatitis in patients who had stents and those that did not14.
Post-ampullectomy Surveillance
There are few data on appropriate surveillance after papillectomy. In FAP patients, recurrent adenoma frequently develops and routine endoscopic surveillance should be done at intervals of months to years, depending upon the size and histology of the lesion. Once eradication is confirmed by routine biopsy of the papillae, suggested follow-up may be at intervals of months, and then annually4. Others recommend duodenoscopy at 6 month intervals for at least 2 years and then only when clinically indicated if 2 consecutive biopsies have no residual adenomatous tissue. FAP patients should then be surveilled at 1 to 3 year intervals13.
Endoscopic papillectomy is an important technique for expert endoscopists. It effectively removes the neoplastic tissue with acceptable recurrence and morbidity rates. Prophylactic pancreatic stent placement appears to minimize pancreatitis and should be done if technically possible. Post-papillectomy surveillance is indicated at intervals of months to years.
Zadorova8 |
16 |
≥ 12 |
≥ 1.4 |
16 (100) |
3 (19) |
4 (25) |
Desilets9 |
13 |
19 |
2.7 |
12 (92) |
0 |
1 (8) |
Norton10 |
26 |
13 |
1.1 |
26 (100) |
2/21 (10) |
9 (35) |
Catalano13 |
103 |
36 |
not given |
93 (90) |
10 (10) |
10 (10) |
Cheng11 |
55 |
30 |
1.4 |
42 (76) |
28 (51) |
10 (15) |
| Harewood15 |
19 |
NA |
1 |
not given |
NA |
3 (16) |
| Bohnacker14 |
106 |
43 |
1 |
76 (72)* |
15 (15) |
40 (38) |
Total |
338 |
13 - 37 |
1.1 - 2.7 |
265/319(83)* |
58/314(19) |
39 (20) |
*62/75 (83%) patients without intraductal neoplasia and 14/31 (46%) with intraductal neoplasia
References
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19. Chen CH, Tseng LJ, Yang CC, Yeh YH, Mo LR et al. The accuracy of endoscopic ultrasound, endoscopic retrograde cholangiopancreatography, computed tomography, and transabdominal ultrasound in the detection and staging of primary ampullary tumors. Hepatogastroenterology 2001; 48:1750-1753.
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