Introduction

Therapeutic options in the management of inoperable perihilar cholangiocarcinoma (pCCA) patients are very limited and include palliative chemotherapy and endoscopic drainage procedures. Recently, ERCP-guided intraductal radiofrequency ablation (RFA) has been proposed as a potential adjuvant therapy in these cases.

Aims & Methods

We aimed to evaluate the feasibility, clinical success rates and safety profile of an endoscopic treatment protocol including RFA and biliary stenting in inoperable pCCA patients.
We performed an interim analysis of a single center, randomized control trial of native papilla cases of pCCA patients with ECOG 0-2 performance status and localized disease who required endoscopic biliary drainage (NCT05563870). Patients in the control arm underwent palliative stenting with plastic stents while patients in the active arm received RFA ablation with the Habib probe and plastic stenting. Treatment in both arms was planned based on preprocedural CT and MRCP, with the aim of draining as much of the viable liver volume. All patients were referred for palliative chemotherapy according to the current standard of care. Technical and clinical success rates and procedure-related adverse event (AE) rates were evaluated prospectively at 30 days.

Results

We included 15 patients (6 in the RFA arm, 9 in the control arm) between April 2022-April 2023. Patients were predominantly female (9/15), mean age was 72 years and most cases were classified as Bismuth IV strictures (7/15). Median ECOG status was 1 (range 0-2) and mean bilirubin level prior to endoscopy was 15.9 mg/dL (range 1.8-36.8). Technical success was achieved in 14/15 patients and clinical success in 13/15 patients. Notably, there were 4 cases of cholangitis in the control arm compared to only 1 case in the active arm, 1 case of bleeding (control arm), 2 cases of cholecystitis (1 in each arm) and 1 perforation (active arm) and 1 case of severe pancreatitis requiring percutaneous drainage (control arm). There was no difference in the advent of moderate and severe AEs following the procedure (4 in the active arm vs. 7 in the control arm, p=0.64) and most cases were successfully managed by endoscopy, with only 1 case requiring surgery and 1 death recorded at 30 days after the procedure. 5 patients underwent systemic chemotherapy after endoscopic drainage.

Conclusion

Our preliminary data suggests that RFA followed by adequate biliary drainage is technically feasible even in difficult-to-treat cases such as high-grade hilar stricture, with no additional increase in complication rate in patients receiving ablation therapy.

Disclosure

No conflict of interest

Introduction

Intraductal radiofrequency ablation (RFA) has been proposed as an adjunctive therapeutic method for patients with inoperable perihilar
cholangiocarcinoma(pCCA). Because there is limited data regarding the benefits of RFA, we aimed to evaluate the feasibility, efficacy and safety of a RFA based endoscopic palliation protocol.

Aims & Methods

Consecutive inoperable patients presenting biliary obstruction secondary to pCCA were evaluated according to the ongoing, single center, randomized clinical trial(NCT05563870). Native-papilla patients were randomized 1:1 to biliary drainage of the viable liver territories with plastic stents (control) or drainage plus RFA of the entire length of the tumor (active arm). Following index procedure, patients were scheduled for stent exchange and additional RFA treatment (active arm only) at 8-10 weeks intervals. Primary outcome was clinical efficacy defined as bilirubin levels < 3mg/dL at 4 weeks after index ERCP; secondary outcomes included overall survival and safety outcomes.

Results

Heretofore we included 25 patients (13 active arm) undergoing 72 procedures (37 with RFA) for a median follow-up of 3 months (range 2-15). Most patients received either 2 (10/25) or 3 (3/25) plastic stents at index ERCP and 23/25 of the patients reached effective drainage at 4 weeks, only 7 patients receiving undelayed oncologic treatment. There were 11 deaths during follow-up - 6 unrelated to the cholangiocarcinoma, 3 from therapy-related complications and 2 from cancer progression. 20/25 patients experienced at least 1 adverse event - including 15 severe biliary events with no significant differences between the study groups.

Conclusion

Extensive liver drainage followed by iterative stent exchange with intraductal RFA applications seems feasible and effective in the
palliation of biliary obstruction in pCCA patients, with no additional risk related to RFA applications. However, adverse events related to biliary infection remain a frequent and life-threatening occurrence during follow-up in this patient population. Further data on the optimal timing and RFA application protocol is required.

Disclosure

No conflict of interest

Introduction

Endoluminal radiofrequency ablation (RFA) is a palliative treatment option for patients suffering from malignant biliary obstruction.

Aims & Methods

We aimed to conduct a meta-analysis to evaluate the impact of RFA on stent patency, patient survival, and adverse events. Major databases were searched from inception until November 2023 for patients who underwent stenting with or without RFA for extra-hepatic malignant biliary obstruction. A random effects model was employed for analysis and results conveyed using risk ratio (RR) and mean difference (MD) with 95% confidence interval (CI).

Results

Nine RCTs involving 750 subjects (n=374 RFA plus stent vs n=376 stent only) diagnosed with malignant biliary obstruction were included. Overall, there was no difference in stent patency between both groups (MD = 26 days [95% CI -2.63 – 54.85]; I²=53%, P=0.07), however, RFA showed improved overall survival (MD = 1.64 months [95% CI 0.21 – 3.07]; I²=100%, P=0.02). Subgroup analysis showed that patients with cholangiocarcinoma experienced an overall survival benefit with RFA (MD = 4.86 months [95% CI 4.61 – 5.07]; I²=0%, P<0.001), however, stent patency was unaffected (P=0.08). Subgroup analysis comparing plastic versus uncovered metal stents showed no difference in stent patency (P=0.63), however, plastic stents were associated with improved survival (MD = 2.05 months [95% CI 0.60 – 3.50]; I²=91%, P=0.002). An increased incidence of cholecystitis was noted with RFA versus stenting only (5% vs 0.2%, respectively).

Conclusion

Combining endoluminal RFA and stenting may improve overall survival in patients with malignant biliary obstruction. RFA did not impact stent patency significantly.

Introduction

The sensitivity and accuracy of diagnosis for extrahepatic cholangiocarcinoma (EHCC) can be greatly improved by Spyglass DS choledochoscope, which can realize direct observation and biopsy . Studies have shown that endoscopic radiofrequency ablation (RFA) could prolong stent patency and survival in patients with unresectable extrahepatic cholangiocarcinoma (EHCC) . However, there are few reports about Spyglass DS choledochoscopy and endoscopic RFA therapy in the same stage of diagnosis and treatmen for unresectable EHCC.

Aims & Methods

Aim: To investigate the feasibility and safety of Spyglass DS combined with endoscopic RFA)for unresectable EHCC on the same stage.
Methods A total of 90 patients with extrahepatic bile duct obstruction treated in Hangzhou First People's Hospital from January 2013 to January 2022 were divided into two groups according to the diagnosis and treatment process: conventional group: ERCP + cytobrush/ Spyglass DS cholangioscopy first, and ERCP + RFA again when the pathological results were positive; simultaneous group: ERCP was performed via Spyglass DS cholangioscopy to examine the bile duct and biopsy the lesion under direct vision, and RFA was performed on the same stage for patients identified as malignant tumor. The success rate of procedure, recovery of liver function, the number of ERCPs and the incidence of postoperative adverse events were compared between the two groups.

Results

The sensitivity of Spyglass DS choledochoscope biopsy for EHCC was 87.5% (35/40) significantly higher than that of the cell brush group (38.9% (14/36), and the difference was statistically significant (P<0.05); All patients in both groups successfully completed endoscopic RFA with a 100% of procedure success rate; there was no statistically significant difference in the improvement of bilirubin between the two groups (P>0.05); the mean number of ERCPs in simultaneous group was significantly less than that in conventional group (1.00 vs. 2.59, P<0.001), which was statistically different; the incidence of postoperative adverse events between the two groups was 14.7% (5/34) vs. 14.3% (5/35), with no statistical significance (P=0.889).

Conclusion

Spyglass direct vision diagnosis + biopsy combined with RFA for unresectable extrahepatic cholangiocarcinoma can significantly improve the diagnostic sensitivity, reduce the number of ERCPs, and not increase the incidence of postoperative adverse events, which is a safe and effective diagnosis and treatment method with a high cost-benefit ratio.

Disclosure

NO

Introduction

Endobiliary radiofrequency ablation (eRFA) is expected to prolong stent patency in malignant biliary obstruction. However, data on eRFA combined with uncovered self-expanding metal stents (uSEMS) in perihilar cholangiocarcinoma (pCCA) are scarce.(1,2)

Aims & Methods

Aim of this prospective single-centre pilot study was to evaluate whether eRFA prior to uSEMS placement is feasible in patients with inoperable pCCA. This study included 10 patients with inoperable pCCA undergoing eRFA prior to endoscopic placement of uSEMS. Endobiliary RFA was performed using a temperature controlled RFA electrode at 7 watt, 90 sec, 75°C. All patients were followed up until death or the end of the study (after at least 12 months follow up). Primary endpoints were technical success, clinical success and adverse events (AEs). Secondary endpoints were time to recurrent biliary obstruction, stent patency at 6 months, and overall survival.

Results

Baseline characteristics are presented in the table. All patients underwent previous successful drainage with plastic stents and/or percutaneous in-/external drainage catheters. In 7 patients the procedure was scheduled electively, where in 3 patients there was an increase in cholestasis and/or fever in the days before the intervention.
The procedure was technically and clinically successful in all patients. One patient was admitted due to self-limiting bleeding after the intervention preceded by sphincterotomy. No other procedure related serious AEs occurred <30 days. Seven patients experienced transient abdominal discomfort after the procedure, sufficiently treated with oral analgesics. The median score on a Numeric Rating Scale (NRS) was 2 (IQR 0.25-3.75) after 1 day and the median duration of pain was 1 day (IQR 0-2.5) after the procedure.
During follow-up 7 patients experienced recurrent biliary obstruction caused by tumor ingrowth (n=6) or sludge (n=1) after a median of 6 months (range 1-8). Of the 3 patients with a patent stent at end of follow-up, two patients deceased after 2 and 6 months follow-up, the other patient still had a patent stent at the end of follow-up. Stent patency rate at 6 months follow-up was 67% (6/9). Four patients died after a median of 16 months (range 4-24) since diagnosis, not related to stent dysfunction.

Table. Baseline characteristics of 10 patients with pCCA undergoing eRFA and uSEMS placement

Conclusion

This pilot study confirms the safety and feasibility of eRFA in patients with pCCA. Risk of adverse events seems low and abdominal pain after the procedure mild. Randomised controlled trials are warranted to assess the efficacy of eRFA for pCCA.

References

1. Sofi AA, Khan MA, Das A, Sachdev M, Khuder S, Nawras A, et al. Radiofrequency ablation combined with biliary stent placement versus stent placement alone for malignant biliary strictures: a systematic review and meta-analysis. Gastrointest Endosc. 2018;87(4):944-51.e1.
2. de Jong DM, Fritzsche JA, Audhoe AS, Yi SSL, Bruno MJ, Voermans RP, et al. Comparison of Intraductal RFA Plus Stent versus Stent-Only Treatment for Unresectable Perihilar Cholangiocarcinoma-A Systematic Review and Meta-Analysis. Cancers (Basel). 2022;14(9).

Disclosure

Jeska A. Fritzsche, Mattheus C.B. Wielenga, Otto M. van Delden and Joris I. Erdmann have no conflicts of interest or financial ties to disclose.
Heinz-Josef Klümpen performed in advisory board for Janssen, Astra-Zeneca, and IPSEN. Received Speaker’s fee from CCO and MedTalks. Roy L.J. van Wanrooij performed as a consultant for Boston Scientific. Paul Fockens performed as a consultant for Olympus and Cook Endoscopy.
Cyriel Y. Ponsioen reports research grants from Gilead and Perspectum, performed as a consultant for Pliant, Takeda and Shire, and received speaker’s fees from Tillotts.
Rogier P. Voermans reports research grants from Boston Scientific and Prion Medical, performed as a consultant for Boston Scientific, and received speaker’s fee from Mylan and Zambon.
All outside the submitted work.

Introduction

Patients with perihilar cholangiocarcinoma (PHC) often require lengthy preoperative management, resulting in a long time to surgery (TTS). However, the relationship between the TTS length and postoperative survival outcome remains unknown.

Aims & Methods

This retrospective single-center study included 224 patients with PHC (2011–2020). TTS was defined as the period from the date of the diagnosis by computed tomography to the date of surgery; the median TTS was 64 (range, 19–212) days. The patients were divided into 2 groups with a TTS cutoff value of 64 days. The surgical and oncological outcomes were then compared between the long- (n=116) and short-TTS (n=108) groups.

Results

Radical resection rate was 74% in long-TTS group and 84% in short-TTS group. The frequencies of preoperative biliary infection (52% vs. 33%, P=0.004) and portal vein embolization (84% vs. 49%, P<0.001) were significantly higher in the long-TTS group than in the short-TTS group. There was no marked difference in the postoperative mortality rate (2% vs. 3%, P=0.697) and histopathological findings, such as lymph node metastasis (41% vs. 43%, P=0.871) and R1 resection rate (15% vs. 9%, P=0.193), between the groups. The overall survival was comparable between the groups (median survival time, 47 vs. 43 months, P=0.627). In the multivariate analysis, only lymph node metastasis was an independent prognostic factor (hazard ratio, 1.494; P=0.044), although TTS was not associated with the survival.

Conclusion

TTS did not affect the survival outcomes of patients who underwent surgical resection for PHC. It is essential to achieve radical resection safely with appropriate preoperative management, regardless of the length of TTS.