REPEATED PLASTIC STENT EXCHANGE IN UNRESECTABLE HILAR CHOLANGIOCARCINOMA: A SURVIVAL ANALYSIS

BACKGROUND AND AIMS
Ampullary neoplasia (AN) is a rare disease, but its incidence is increasing. In the last 20 years, endoscopic papillectomy (EP) has become the gold standard treatment for ampullary adenomas and early stage adenocarcinomas, thereby replacing surgical resection, which is burdened by higher rates of morbidity and mortality. However, the data supporting safety and efficacy of EP derive from multiple retrospective studies, that included procedures mostly performed before 2015, when first guidelines on endoscopic management of AN were available. This had an impact on large variability in patient selection criteria and endoscopic techniques, resulting in heterogenous outcomes. Therefore, the aim of our study is to provide data on the efficacy and safety of this technique, by including consecutive patients treated after the standardization of this technique.

METHODS
All patients who underwent EP at 19 Italian centers between January 2016 and December 2021 were included. Clinical success was defined by the complete endoscopic management of the neoplasm and any eventual recurrence found in the follow-up period. EP-related adverse events and recurrences were recorded.

RESULTS
A total of 225 patients were included. The mean lesion’s size was 20 mm (5–80 mm). En bloc resection was possible in 72.5% of cases, with an overall R0 resection rate of 50.7%. During a mean follow-up period of 23.2 months, recurrences were diagnosed in 17.2% of patients, 61,3% of which were successfully treated with an additional endoscopic treatment. Thus, clinical success was achieved in 76.7% of the cases. In multivariate analysis, R1 resection, lesion size and histological diagnosis were predictors for recurrence. Intra-procedural bleeding occurred during 12,4% of EP. Post-EP adverse events (AE) occurred in 39,5% of patients, including delayed bleeding (20,9%), pancreatitis (13.3%) and perforation (2.2%). Complications were mild or moderate in 88,9%, while the 11.1% were severe, according the ASGE Lexicon. No EP-related deaths were recorded.

CONCLUSIONS
The results of our study confirm the efficacy of endoscopic papillectomy in the treatment of ampulla of Vater neoplasms in the current clinical practice. Most of recurrences were successfully endoscopically managed. However, even if performed by expert endoscopists, EP is a procedure associated with not negligible risk of complications.

Aim:

Endoscopic papillectomy is the recommended treatment for adenoma, in situ carcinoma and intramucosal adenocarcinoma of the papilla but positive margin resection and recurrence are common and led to complementary surgery with significant mortality rate (3-10%).
Radiofrequency ablation (RFA) as complementary treatment of papillectomy margin seems to be efficient and feasible.

Methods:

This single-center retrospective study included all patients who had a first biliary RFA following papillectomy in our institution, indicated when pathological margins were positive or in case of relapse.
Primary aim was the clinical success defined by the absence of recurrence at papillectomy site macroscopically and/or histologically 12 months after the first or the second RFA session. The second aims were the number of sessions needed for clinical success, the early (<30 days) and late (> 30 days) complications. Eradication failure was defined when more than 2 sessions were realized.

Results:
Thirty-four patients were treated with RFA as complementary treatment after papillectomy, 25 of them (mean age 71 years) had more than 12 month follow-up and were included, median follow-up was 36 months (12-80).
RFA were performed in cases of positive resection margin n=20 (Low-grade dysplasia (LGD) n=10, high-grade dysplasia n=5, in situ carcinoma (CIS) n=3, adenocarcinoma pT1a R1 refusing surgery n=1, neuroendocrine tumor grade 2 n=1) or relapse n=5 (LGD n=5).

Clinical success was 88% (22/25) with median number of RFA session needed of 1.1 (1-2).
Two patients had eradication failure, one after 12 RFA session (unfit for surgery) and one had a Whipple surgery (progression of LGD into the common bile duct inaccessible with RFA).
One patient died from a severe acute pancreatitis after a second RFA session (pancreatitis prophylactic stent introduction fail).
Our patient with adenocarcinoma is free from disease after 44 month of follow-up.
One patient with CIS had a lymph node relapse at the 33^th month, still treated by chemotherapy at the 55^th month.

We reported 3 early complications (12%): two acute pancreatitis (mild and fatal) and one bleeding requiring a new endoscopy. Twelve late complications occurred (48%) of a stenosis type, successfully managed endoscopically with a median follow-up of 17.6 months (0-56). Eight of these stenosis occurred in patient who had 1 or 2 additional resections sessions after the initial papillectomy.

Conclusion:
Our study is one of the largest series reporting biliary RFA following endoscopic papillectomy. RFA is an effective treatment to eradicate residual ampullary or recurrent lesions with 88% of clinical success. Late stenosis is the principal complication (48%) favored by the association of an additional resections sessions however, they are managed effectively by endoscopy. RFA seems to be a safe alternative to surgery in well-selected cases.

Introduction:
The endoscopic management of unresectable hilar cholangiocarcinoma is centered on the maintenance of biliary patency. While self-expandable metal stents have been shown to have higher stent patency, selection bias in comparative data limits interpretation and difficulty with re-intervention on metal stents make plastic stents (PS) a viable option for many patients. We aimed to review our single-center experience with the routine exchange of bilateral plastic stents in patients with unresectable hilar cholangiocarcinoma to identify factors associated with recurrent biliary obstruction.

Methods
Patients with unresectable cholangiocarcinoma undergoing ERCP for undergoing unilateral or bilateral plastic stent placement were eligible for inclusion. Patients receiving metal stents or percutaneous placement of external drains were excluded. Recurrent biliary obstruction (RBO) was defined according to the 2014 Tokyo guidelines as signs/symptoms consistent with obstruction or migration. Kaplan-Meier curves were used to evaluate RBO-free survival during the follow-up period. Cox regression was used to identify factors associated with RBO after plastic stent exchange, using a shared frailty model for recurrent events.

Results:
Consecutive patients treated for unresectable hilar cholangiocarcinoma between January of 2015 and June of 2022 were considered for eligibility. 62 patients were included in the analysis, encompassing a total of 199 ERCP’s. The average age of patients at the time of ERCP was 63.9 years (SD 14.7). 45% of patients were female. Patients received an average of 3.2 ERCP’s (SD 3.4) over a mean follow-up period of 40.5 months (SD 97.1). 85 ERCP’s (42.7%) were performed prior to a scheduled procedure (due to RBO). 58/85 (68%) emergent ERCP’s were performed for cholangitis. The Kaplan-Meier curve for RBO-free survival is shown in Figure 1. The median RBO-free survival was 98 days. The 12-week cumulative probability of RBO was 59% (95% CI 50%-69%). Results of univariable and multivariable Cox-proportional hazards regression are reported in Table 1; procedures performed ‘emergently’ (prior to scheduled stent exchange) were associated with greater risk of recurrent biliary obstruction. There was non-significant association between higher total bilirubin (p=0.055) and AST (p=0.062) two weeks following biliary drainage and early RBO.

Discussion:
Plastic stents are generally exchanged at 12-week intervals, currently based largely on expert opinion. We demonstrated that at 12-weeks, nearly 60% of patients have developed signs or symptoms of recurrent obstruction, and in nearly 70% of these cases this manifested as cholangitis. A shorter interval to routine plastic stent exchange, particularly in patients that have previously required emergent endoscopy, may be warranted to minimize the risk of recurrent biliary obstruction and its complications.