Case report/series

975

Outcomes of endoscopic papillectomy in elderly patients with ampullary adenoma or early carcinoma

Authors Institution

N. Nguyen, J. N. Shah, K. F. Binmoeller Interventional Endoscopy Services, California Pacific Medical Center, San Francisco, USA

submitted 18 May 2010 accepted after revision 5 August 2010 Bibliography DOI http://dx.doi.org/ 10.1055/s-0030-1255875 Endoscopy 2010; 42: 975977 Georg Thieme Verlag KG Stuttgart New York ISSN 0013-726X Corresponding author K. F. Binmoeller, MD Interventional Endoscopy Services California Pacific Medical Center San Francisco, California, USA Fax: +1-415-600-1416 BinmoeK@sutterhealth.org

Outcomes for 14 elderly (age 70 years) patients (79.4 1.0 years) who underwent endoscopic papillectomy for ampullary tumors were compared with those of 22 younger (age < 70 years) patients (52.5 1.9 years). There were no differences in procedural success (100 %), bleeding (5/14 vs. 6/ 22), adenoma recurrence (0/14 vs. 2/22) and median survival (24.0 vs. 25.5 months) between the elderly and younger patients. In younger patients, although adenoma recurrences (n = 2) were managed endoscopically, invasive adenocarcinomas (n = 3) were treated by pancreatoduodenectomy.

All elderly patients with invasive (T2) tumors (n = 5) were not surgically fit and underwent successful palliation with further endoscopic resection and stenting. Whilst all younger patients survived, five elderly patients died but three of these deaths were not cancer-related. Advanced age, therefore, did not adversely influence the outcomes of endoscopic papillectomy, suggesting it may be a treatment of choice for elderly patients with ampullary tumors or early cancer who are deemed unfit for surgery.

Introduction
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Case series
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Although pancreatoduodenectomy is considered a more definitive treatment of ampullary tumors [1, 2], it is associated with higher mortality (up to 10 %) and morbidity (80 %) [1, 2] than local surgical or endoscopic resection; the latter may be more appropriate for patients with early-stage ampullary tumors and who are surgically unfit. Apart from lower morbidity and mortality [3 5], endoscopic papillectomy is also associated with a much shorter recovery time [6]. Local resection, however, has a high rate of recurrence (5 % to 30 %) and requires ongoing postoperative endoscopic surveillance [3 5, 7, 8]. Concerns that are specific to endoscopic papillectomy as a curative treatment include the technical difficulties, the risk of procedure-related complications, and the fear of incomplete removal, especially in the presence of intraductal growth or high grade dysplasia or carcinoma. Although the median age of presentation for ampullary tumors is 68 to 70 years [7, 9], data regarding the outcomes of endoscopic papillectomy in elderly patients are lacking. This case series reports the clinical outcomes of endoscopic papillectomy for benign ampullary adenoma or localized ampullary carcinoma in patients who were 70 years and deemed unfit for surgery.

Methods
Over three years, outcome data for 14 elderly (age 70 years) patients (7 women, 7 men; 79.4 1.0 years) who underwent endoscopic papillectomy for ampullary adenomas or early carcinoma were compared with those from 22 younger (age < 70 years) patients (10 women, 12 men; 52.5 1.9 years). Data were retrieved and collected from case notes and electronic medical records from the hospital. The cause of death was checked with death registries of the local hospitals and from the Social Security Death Index Interactive Search website (http://ssdi.rootsweb.ancestry. com/cgi-bin/ssdi.cgi), and was characterized as cancer related and non-cancer related. All analyses were performed using GraphPad Prism 4 statistical software (v.4.02, San Diego, California, USA). P values of < 0.05 were considered significant. The study was approved by the Human Research Ethics Committee of the hospital. Prior to endoscopic papillectomy, all patients had: (i) a computer tomography (CT) scan of the abdomen, that showed no local spread or distant metastasis; and (ii) endoscopic ultrasound (EUS) staging with either the electronic Olympus radial or linear electronic echo endoscope using the wa-

Nguyen N et al. Endoscopic papillectomy in elderly patients with ampullary adenoma or early carcinoma Endoscopy 2010; 42: 975 977

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Case report/series

ter-filled balloon technique. All pre-existing biliary stents were removed prior to the examination. The T and N staging was performed in accordance with the methods of the American Joint Committee on Cancer Staging (6th edition, [10]).

Table 1 Demographic data and clinicopathological details of two groups of patients, based on an age cutoff of 70 years, who underwent endoscopic papillectomy for ampullary tumors. Patients Patients < 70 years n = 22
52.5 1.9* 12 : 10 9 3 1 2 5 2 23.1 2.0 7.3 0.5 2.6 0.2

Ampullectomy technique
Endoscopic papillectomy was performed by a single experienced endoscopist (K.F.B.), using a 20-mm oval rigid polypectomy snare (SnareMaster; Olympus America Inc., Melville, New York, USA) with a standard duodenoscope (TJF-140; Olympus America). The snare was positioned over the tumor, aiming for a uniform en bloc resection to the level of the muscularis propria. Blended cut (Erbe Vio 200D; ERBE USA, Marietta, Georgia, USA) was used to decrease the risks of bleeding. Piecemeal excision was carried out for complete removal of large tumors. All resected specimens were immediately retrieved. Any bleeding related to the resection was controlled immediately with hot-biopsy forceps (Coagrasper; Olympus) and/or hemoclips (Olympus). Biliary sphincterotomies were done in all patients to ensure adequate biliary drainage. Although a pancreatic stent (5-Fr) was inserted in all patients to prevent pancreatitis, a biliary stent was only inserted if there was evidence of biliary obstruction. In four patients, argon plasma coagulation was used as small islands of visible adenomatous tissue were observed after snare excision. Surveillance duodenoscopy with random periampullary biopsy was performed at 6-month intervals for the first year in all patients. Except for patients with familial adenomatous polyposis, surveillance was ceased after two negative endoscopic and histological examinations for patients with sporadic ampullary tumors.
Age, years Gender (male : female), n Presentations, n Abnormal LFTs Pancreatitis Abdominal pain Jaundice Incidental on screening Dilated duct on CT scan Tumor size, mm Duct diameter, mm Bile duct Pancreatic duct Histology, forceps: resected specimens, n Adenoma Carcinoma Staging, T1 : T2, n Prepapillectomy EUS Histological Pancreatoduodenectomy, n Media Length of follow-up, months

70 years n = 14
79.4 1.0* 7:7 9 2 1 2 0 0 25.2 1.9 7.1 0.7 3.5 0.4

10 : 9 4:5 13 : 1 10 : 4 0 56.0 (44.5 74.5)

22 : 19 0:3 21 : 1 20 : 2 3 52.5 (46 72.5)

Results
Prior to endoscopic papillectomy, forceps biopsies from the tumors indicated that 32 were adenomas and 4 were carcinomas. EUS staging suggested that 30 adenomas and 4 carcinomas were limited to the mucosal and submucosal layers (i. e., that there were 34 T1-stage tumors). In two of the patients with adenomas, EUS suggested the presence of tumor in the distal portion of bile duct in one patient, and extending into the muscularis propria in the other patient (i. e., two T2-stage tumors). There were no differences in gender, clinical presentations, size of tumor, prepapillectomy stage of tumor, and length of follow-up between pa" tients who were 70 years and < 70 years ( Table 1). Endoscopic papillectomy was performed successfully in all patients. Bleeding complication occurred during the procedure in 11/36 (30 %) patients, and the rate was similar between the groups (5/14 vs. 6/22, P = 0.71). Hemostasis was achieved in all. There was no clinically relevant post-resection pancreatitis or bleeding that required re-admission. There was no procedurerelated death. Among the 30 patients with a preresection diagnosis of T1 adenoma, curative resection was achieved in 93 % (28/30). The remaining two adenomas that had been sonographically staged as T1 adenomas, and were found in younger patients, showed invasive adenocarcinoma and high grade dysplasia extending into the muscularis propria; the two patients subsequently underwent Whipple resections. All the adenocarcinomas that had been sonographically staged as T1, in four elderly patients were found to be T2 on histology, and were managed endoscopically as the patients were unfit for surgery. Both of the tumors staged sonographically as T2 were confirmed on histology, and management was guided by age: the younger patient with the T2 adenocarcinoma underwent pancreatoduodenectomy, whereas the elderly patient with

LFT, Liver function test; CT, computed tomography; EUS, endoscopic ultrasound * P < 0.05 Data expressed as mean SEM, unless otherwise stated.

a common bile duct (CBD) invasive villous adenoma had the ductal component resected endoscopically, due to the high risk of surgery. Overall, endoscopic papillectomy was characterized as curative in 26/36 patients (72 %), diagnostic for histologic staging in 3/ 36 patients (8 %), and palliative in 5/36 patients (14 %). After a median follow up period of 54 months (interquartile range [IQR] 45 73), the overall survival rate was 86 % (31/36). Compared with the 100 % survival rate in younger patients, five of 14 elderly patients (35 %) died during follow-up. Among those who died, two were cancer-related deaths (invasive carcinomas), and three were not cancer-related (cardiac causes). The median survival after endoscopic papillectomy in the elderly patients was similar to that of younger patients (48.0 months [34.0 59.0] vs. 52.5 months [46.0 72.5]; P = 0.35). Recurrence of adenoma at the resection site occurred after 1 year in two of the patients younger than 70 years, but there was none in the elderly patients. Both were successfully treated with further endoscopic snare resection and argon plasma coagulation. There was no further evidence of recurrence in these two patients after re-treatment. Amongst the elderly patients, the median survival was not statistically different between those with and without invasive adenocarcinoma (38.5 months [21.8 70.3] vs. 52.0 months [34.0 63.8]; P = 0.52).

Nguyen N et al. Endoscopic papillectomy in elderly patients with ampullary adenoma or early carcinoma Endoscopy 2010; 42: 975 977

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Discussion
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The therapeutic role, either curative or palliative, of endoscopic papillectomy in elderly patients deserves special attention because: (i) the median age of patients who present with ampullary tumors is in the seventh decade [7, 9, 11]; (ii) a significant proportion of these patients have co-morbidities that render them surgically unfit [12]; and (iii) these patients tend to have a higher rate of morbidity and mortality from radical pancreatoduodenectomy [13]. Unlike the situation with surgery, age has not been shown to be a discriminating factor for outcomes of therapeutic upper gastrointestinal endoscopy [14]. This is the first report that has specifically examined the outcomes of endoscopic papillectomy in elderly patients. Apart from confirming that endoscopic papillectomy is a safe and effective therapeutic modality for ampullary tumors, our findings showed that endoscopic papillectomy resulted in curative resection in all elderly patients with ampullary adenomas. Even in patients with locally invasive ampullary carcinoma (n = 5), endoscopic papillectomy provided an effective mode of palliation that resulted in median survival duration of 26 months. Deaths directly related to invasive carcinoma were uncommon (7 %), with most deaths due to coexisting illnesses, especially cardiac disease. Thus, endoscopic papillectomy appears to be the treatment of choice in elderly patients, particularly those who are unfit for surgical resection. Another potential benefit of endoscopic papillectomy is its ability to provide specimen(s) for accurate histological staging and diagnosis. Given the small rate of false negatives from forceps biopsy and EUS staging [15], the risk of preoperative understaging can occur up to 10 % 15 % [16]. Endoscopic papillectomy is only considered to be curative if the histological examination of the resected specimen confirms the neoplasm to be intramucosal. As illustrated in this study and others [4, 5, 7 9], incomplete resection or the presence of invasive carcinoma can be further managed by radical pancreatoduodenectomy if the patient is surgically fit. Current data suggest no adverse effects of performing endoscopic papillectomy on the outcomes of subsequent pancreatoduodenectomy [4, 5, 7 9]. As previously found [4, 5, 7 9], endoscopic papillectomy was safe and complications were uncommon when performed by an experienced endoscopist at a major referral centre. Although intraprocedural bleeding occurred in 30 % of patients, it was adequately controlled by endoscopic modalities. The absence of clinically significant pancreatitis in the current study may be related to the routine placement of pancreatic stents after endoscopic papillectomy, which has been shown to minimize the development of post-resection pancreatitis [17]. Overall, the excellent outcomes in this series are probably related to the considerable skill and experience of the endoscopist.

In conclusion, endoscopic papillectomy was safe and considered curative in over 90 % of patients with ampullary adenoma, and advanced age did not adversely influence either the short- or longterm outcomes of the procedure. Even in elderly patients with locally invasive ampullary carcinoma, papillectomy provided an effective mode of palliation with reasonable median survival. Competing interests: None

References
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