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Abstract

Background:

Malignant hilar biliary obstruction (MHBO) can be treated by stent deployment under endoscopic retrograde cholangiopancreatography. In case of unresectable MHBO, uncovered self-expandable metal stent (UCSEMS) deployment might be recommended. However, endoscopic revision is challenging. To overcome this issue, we previously described a novel revision technique called the “molting technique,” but its technical feasibility is still unclear.

Objective:

The present study aimed to evaluate the technical feasibility of the molting technique in a prospective setting.

Design:

A single-center prospective study.

Methods:

Results:

A total of 20 patients were prospectively enrolled in this study. The technical success rate was 90% (18/20). The mean procedure time was 20.6 ± 8.5 min, and clinical success was obtained in 94.4% of patients (17/18). The mean duration of stent patency after endoscopic revision was 118.2 days. Finally, adverse events were observed in three patients (pancreatitis, n = 2, cholangitis, n = 1), all of whom were successfully treated conservatively.

Conclusion:

In conclusion, the molting technique might be helpful as an option for endoscopic revision for multiple UCSEMS deployments for selected patients.

Trail registration:

University Hospital Medical Information Network 000044572.

Plain language summary

Novel technique to treat stent blocks

Why was the study done?

When cancer blocks the bile ducts near the liver (malignant hilar biliary obstruction), doctors often place a stent (a small tube) to keep the bile flowing. If surgery is not possible, uncovered metal stents (UCSEMS) are commonly used because they stay open longer than plastic ones. However, if the stent becomes blocked again, replacing or revising it with another endoscopic procedure can be difficult. We previously developed a new method called the “molting technique” to help with this, but we weren’t sure how well it would work. This study aimed to find out how safe and effective the molting technique is in real patients.

What did the researchers do?

We looked at whether the molting technique could successfully fix a blocked stent. If the technique failed on either side of the bile ducts in the liver, it was considered a failure. We also checked how well patients improved after the procedure and whether they had any complications.

What did the researchers find?

We included 20 patients who needed their stents fixed because cancer had grown into them. The molting technique was successful in 18 out of 20 patients (90%). On average, the procedure took about 21 minutes. Of the 18 successful cases, 17 patients (94.4%) showed clinical improvement. After the revision, the new stents remained open for an average of 118 days. Three patients had complications (2 had pancreatitis and 1 had cholangitis), but all recovered with medication.

What do the findings mean?

The molting technique may be a useful option for fixing blocked metal stents in the bile ducts. However, more research “especially larger, controlled studies” is needed to confirm these findings.

Keywords

dilation ERCP hilar biliary obstruction malignant biliary obstruction revision

Introduction

Malignant hilar biliary obstruction (MHBO) can be treated by stent deployment under endoscopic retrograde cholangiopancreatography (ERCP). In case of unresectable MHBO, uncovered self-expandable metal stent (UCSEMS) deployment might be recommended because of the longer stent patency compared with plastic stents.^1
–4 Although it is unclear whether unilateral or bilateral stenting is preferable, recent randomized controlled trials have shown favorable results, such as longer stent patency and prolonged overall survival, with bilateral UCSEMS deployment compared with unilateral UCSEMS.⁵ However, bilateral drainage might be preferred from the viewpoint of obtaining adequate drainage volume.^6,7 Side-by-side (SBS) or stent-in-stent (SIS) procedures are often selected for performing bilateral UCSEMS deployment. Although no clinical differences in technical and clinical success rates and survival rates have been identified between these two techniques, a recent randomized controlled trial found more favorable stent patency rates at 3 and 6 months with the SIS technique.⁸

Recently, the frequency of endoscopic revision after stent deployment has increased due to advances in systemic chemotherapy, such as the introduction of immune checkpoint inhibitors.^9,10 However, endoscopic revision is sometimes challenging in cases with multiple UCSEMS deployments using the SIS technique, because the stent delivery system needs to be inserted into the obstructed biliary tract through the mesh of the previously deployed UCSEMS. To overcome this issue, we previously described a novel revision technique called the “molting technique,”¹¹ although its technical feasibility is still unclear because of the retrospective nature of that study.

The present study aimed to evaluate the technical feasibility and safety of the molting technique in a prospective setting.

Patients and method

Consecutive patients with MHBO who required endoscopic revision because of dysfunction of a previously deployed UCSEMS at our hospital were eligible for enrollment in this study. The inclusion criteria were as follows: (1) age > 18 years, (2) number of previous UCSEMS deployed ⩾2, (3) UCSEMS deployment using the SIS technique, (4) stent dysfunction due to stent obstruction caused by tumor ingrowth, and (5) performance status 0–2. Exclusion criteria were as follows: (1) inaccessible papilla, such as with duodenal obstruction caused by a malignant tumor and (2) refusal to participate in this study. The present study was a single-center, prospective, single-arm trial. The study was conducted according to the tenets of the Declaration of Helsinki for biomedical research involving human subjects, and all patients provided written informed consent for study participation.

Technical tips for the molting technique and procedure protocol

Figure 1(a) shows the novel stent delivery system with dilation function (EndoSheather; Piolax Medical Devices, Kanagawa, Japan). The diameter of the outer sheath of this device is 7.2 Fr, and that of the inner sheath is 5.9 Fr. In addition, the tip of this device is extremely tapered (3.9 Fr), conforming to a 0.035-inch guidewire. These characteristics allow it to penetrate stricture sites and allow insertion of various devices less than 5.9 Fr in size after removal of the inner sheath. During the procedure, the inner sheath is first removed (Figure 1(b)), following which the proximal side of the outer sheath is cut to allow device insertion (Figure 1(c)). Next, the stent delivery system is inserted into the outer sheath (Figure 1(d) and (e) and deployed to the appropriate site (Figure 1(f)). Because the diameter of the stent delivery system that is less than 7.2 Fr can be inserted into the outer sheath, we used SEMS with a 7 Fr stent delivery system (BILERUSH selective; Piolax Medical Devices Inc., Kanagawa, Japan).

Figure 1.

Molting technique. The inner sheath is removed (a and b), following which the proximal side of the outer sheath is cut to allow device insertion (c). Next, the stent delivery system is inserted into the outer sheath (d and e) and deployed to the appropriate site (f).

Figure 2 shows endoscopic revision using the molting technique in patients with MHBO whose previously deployed UCSEMS is obstructed by tumor ingrowth. First, a duodenoscope (TJF 290V, Olympus Optical, Tokyo, Japan) is advanced into the ampulla of Vater. Biliary cannulation is then attempted using an ERCP catheter (MTW Endoskopie, Düsseldorf, Germany). A 0.025-inch guidewire (VisiGlide 2, Olympus; J-Wire, JMIT, Shiga, Japan) is inserted into the biliary tract, and contrast medium is injected to evaluate the obstruction site. Then, the guidewire is advanced through the previously deployed UCSEMS into the upstream biliary tract (Figure 2(a)). If guidewire insertion failed, guidewire insertion under cholangioscopic guidance or a controllable ERCP catheter was attempted. If these procedures failed, endoscopic ultrasound-guided biliary drainage (EUS-BD) was considered. Next, the novel stent delivery system is inserted over the guidewire. If this procedure is successful (Figure 2(b)), the inner sheath is removed, and the stent delivery system of the UCSEMS is inserted (Figure 2(c)). Subsequently, the outer sheath is removed (Figure 2(d)), keeping the stent delivery system within the biliary tract (Figure 2(e)). Finally, stent deployment was performed (Figure 2(f)) (Supplemental Video; https://d.kuku.lu/87mk2u2c8). After stent deployment, the ERCP catheter was inserted again, and aspirated bile juice and contrast medium to prevent infection. If EndoSheather insertion is unsuccessful, the mesh of the previous stent is dilated using a balloon catheter, and stent deployment through the mesh of the previous UCSEMS is subsequently attempted. If both procedures fail, percutaneous transhepatic or EUS-BD is considered a rescue technique (Supplemental Material).

Figure 2.

Endoscopic revision using the molting technique in patients with malignant biliary obstruction whose previously deployed UCSEMS. (a) The guidewire is advanced through the previously deployed UCSEMS into the upstream biliary tract. (b) The novel stent delivery system insertion is attempted over the guidewire (red arrow). (c) The stent delivery system of UCSEMS (yellow arrow) is inserted into the biliary tract within the novel stent delivery system (red arrow). (d) The outer sheath of the novel stent delivery system is removed (red arrow), keeping the stent delivery system of UCSEMS within the biliary tract (yellow arrow) (e). (f) Stent deployment is performed.

Definitions and statistical analysis

Technical success was defined as successful endoscopic revision using the molting technique. If endoscopic revision using the molting technique in the hepatic bile duct failed on either side, the technique was considered a technical failure. The secondary outcomes assessed were clinical success and adverse events. Clinical success was defined as a decrease in serum bilirubin levels to <50% of the pre-procedure level or to normal levels (<1.3 mg/dL) within 14 days. Adverse events were graded according to the severity grading system of the American Society for Gastrointestinal Endoscopy lexicon.¹²

The site of obstruction was classified according to the Bismuth-Corlette classification.¹³ Stent patency was measured from the day of stent revision to stent dysfunction or death of the patient. Procedure time was measured from scope insertion to removal.

Descriptive statistics are presented as the median (interquartile range), mean (±standard deviation), and frequency for continuous and categorical variables, respectively.

Results

From March 2022 to April 2024, stent dysfunction after UCSEMS deployment for MHBP was observed in 62 patients. Among them, patients with non-occluded stent dysfunction, such as reflux cholangitis (n = 19), single UCSMES deployment (n = 12), and inaccessible papilla due to tumor ingrowth (n = 10), and those who refused to participate in the present study (n = 1) were excluded. These patients underwent conservative treatment, EUS-guided biliary drainage, or endoscopic revision under ERCP guidance. Finally, in the present study, a total of 20 patients (mean age, 77.6 years; 14 men) requiring endoscopic revision for stent dysfunction due to tumor ingrowth were prospectively enrolled in this study (Table 1). The primary disease was hilar cholangiocarcinoma (n = 17) or gallbladder cancer (n = 3). The type of biliary duct obstruction before primary UCSEMS deployment according to the Bismuth-Corlette classification was mainly type II (n = 9) or type III (n = 8). In most cases (n = 15), two UCSEMS had been previously placed. As the kind of UCSEMS previously deployed, laser-cut and braded type UCSEMS were deployed in 10 patients each. The target drainage site was the left bile duct in four cases, the anterior bile duct in 10 cases, and the posterior bile duct in 4 cases.

Table 1.

Patients’ characteristics.

Total number of patients, n	20
Mean age, years (±SD)	76.6 ± 10.1
Male:female	14:6
Disease
Hilar cholangiocarcinoma	17
Gallbladder cancer	3
Performance status
0:1:2	14:1:5
ASA
1:2:3:4	13:5:2:0
Bile duct occlusion type according to Bismuth-Corlette classification
2:3a:3b:4	9:4:4:3
Mean serum bilirubin, mg/dL (±SD)	15.11 ± 5.77
Number of previously deployed metal stents, n (%)
2:3	15:3
Types of previously deployed metal stents, n (%)
Braded type	10
Laser-cut type	10
Target drainage site
Left hepatic bile duct	6
Anterior bile duct	10
Posterior bile duct	4

Table 2 shows the clinical outcomes of the study participants. The technical success rate was 90% (18/20). Technical failure was observed in two patients who underwent triple SEMS deployment previously. One patient underwent EUS-guided hepaticogastrostomy because the EndoSheather could not be inserted through the mesh. The second patient underwent successful biliary stenting for the obstruction site, although balloon dilation was needed for insertion of the EndoSheather through the mesh of the previously placed UCSEMS. The mean procedure time was 20.6 ± 8.5 min, and clinical success was obtained in 94.4% of patients (17/18). The mean duration of stent patency after endoscopic revision was 118.2 days. Finally, adverse events were observed in three patients (pancreatitis, n = 2, cholangitis, n = 1), all of whom were successfully treated conservatively.

Table 2.

Clinical outcomes.

Technical success rate, % (n)	90.0 (18/20)
Procedure time, min (mean ± SD)	20.6 ± 8.5
Clinical success, % (n)	94.4 (17/18)
Adverse event, n
Pancreatitis	2
Cholangitis	1
Mean stent patency, days (±SD)	118.2 ± 104.6
Median follow-up period, days (range)	198 (48–229)

Discussion

Due to recent developments in systemic chemotherapy, patients with cholangiocarcinoma currently have a better prognosis. Morimoto et al conducted a retrospective study to assess the optimal liver drainage rate that improves survival in patients with UMHBO receiving chemotherapy using a three-dimensional (3D) image volume analyzer.⁷ In their study, which included 90 patients with unresectable MHBO, overall survival time was 376 (95% CI, 271–450) days, and patients with >80% drainage (n = 67) had significantly longer survival times than those with <80% drainage (n = 23) (450 days vs 224 days, p = 0.0033). Multivariate Cox proportional hazards regression analysis revealed >80% liver drainage (HR 0.35, 95% CI, 0.20–0.62, p = 0.0003) and hilar cholangiocarcinoma (HR 0.30, 95% CI, 0.17–0.50, p < 0.0001) as significant positive prognostic factors related to survival. They concluded that in patients with unresectable MHBO scheduled for chemotherapy, >80% drainage is associated with improved survival. Therefore, to obtain this benefit and enough drainage, bilateral biliary drainage should be performed as far as possible in cases with unresectable MHBO. However, along with prolonged survival, we should consider facts such as increasing the frequency of endoscopic revision. Compared with UCSEMS, endoscopic revision might be easy after plastic stent insertion because plastic stents can be removed. In addition, to obtain longer stent patency, inside plastic stent deployment can be selected as an effective drainage technique. Kanno et al.¹⁴ conducted a multicenter randomized controlled study comparing an inside plastic stent and UCSEMS for MHBO. Among 87 patients, inside plastic stents were deployed in 38 patients, and UCSEMS were deployed in 46 patients. In their study, while technical success rates were 100% (38 of 38) and 96.6% (44 of 46), respectively, clinical success rates were not significantly different between inside plastic stents (90.0%, n = 35/39) and metal stents (88.9%, n = 40/45). In addition, the median times to recurrent biliary obstruction with the two types of stents were 250 (95% CI, 85–415) and 361 (95% CI, 107–615) days (p = 0.34), respectively. In addition, according to a recent meta-analysis of inside plastic stents versus UCSEMS for MHBO,¹⁵ the clinical success rate of inside plastic stent (99.3%) was not significantly different compared with UCSEMS (98.6%) (p = 0.32), and the adverse events were also not significantly different between inside plastic stent (10.7%) and UCSEMS (9%) (p = 0.32). The median duration of stent patency of the inside plastic stent was 172.5 days and of UCSEMS was 200.2 days, with no significant difference between them (p = 0.38). Therefore, recently, the inside plastic stent technique has been considered an option for treating MHBO, because it might be associated with comparable efficacy. On the other hand, UCSEMS deployment can also still be considered because several studies have shown favorable stent patency with UCSEMS. However, the technical success rate of endoscopic revision still needs to be improved because, in the case of bilateral UCSEMS deployment, endoscopic revision is sometimes challenging. Inoue et al conducted a multicenter retrospective study to examine the outcomes of endoscopic revision for occluded UCSEMS using the SBS technique.¹⁶ In their study of 67 patients, the technical success rate of endoscopic revision was 79.1% (53/67). In the 14 patients in whom the procedure was technically unsuccessful, the reasons for failure were inappropriate advancement of the guidewires into both stent lumens in seven, inability to advance the associated devices due to interference with the stent wires in four, and duodenal obstruction in three patients. According to multivariate analysis, common bile duct diameter (OR 2.62, 95% CI, 1.37–5.01; p = 0.003) and metastatic disease (OR 0.11, 95% CI, 0.02–0.64; p = 0.015) were identified as risk factors for failed endoscopic revision. If the proximal end of the stent is located across the papilla, selective guidewire insertion may be easy. However, pancreatitis should be carefully considered because double stents are deployed, which might cause pancreatic duct obstruction. Therefore, this technique might not be indicated for all patients. On the other hand, Son et al evaluated the efficacy of endoscopic revision after UCSEMS deployment using the SIS technique.¹⁷ In their study, including 38 patients, the technical success rate was 76.3% (29/38). The reasons for failure of endoscopic revision were tight biliary strictures (n = 6), duodenal obstruction (n = 2), and instability during ERCP (n = 1). Therefore, since technical failure of endoscopic revision for occluded UCSEMS occurs with both the SIS and SBS techniques, device insertion into the biliary tract through the stricture or the mesh of the previously deployed UCSEMS should be overcome to improve the benefits of bilateral UCSEMS deployment.

On the other hand, we consider that the molting technique has several advantages. First, because the EndoSheather has an ultra-tapered tip and strong push ability, its insertion through the stricture site is feasible. Second, after successful EndoSheather insertion into the biliary tract through the mesh of the UCSEMS, performance of additional UCSEMS deployment is certain. On the other hand, despite successful guidewire deployment or stricture dilation or the mesh of previous deployment UCSEMS, successful stent delivery system insertion cannot always be obtained because the insertion vector might be misaligned during device exchange. As a result, the stent delivery system might adhere to the mesh of the UCSEMS. In this situation, the mesh of previously deployed SEMS should be dilated using a balloon catheter. However, to insert a stent delivery system into the biliary tract through the mesh of previously deployed SEMS, the axis of pushing force is important. As the number of procedure steps such as dilation increasing, the axis can be misalignment. On the other hand, our technique can be only a single step. Therefore, the molting technique might be an option as an endoscopic revision technique. Indeed, our technical success rate of endoscopic revision using the molting technique was high, along with a short procedure time.

Our study has several limitations, including that it was a single-center, non-comparative study. Yet, we believe that our study might be a landmark study for further randomized controlled trials because it was a prospective feasibility study. However, technical failure was only observed in triple SEMS deployment cases; therefore, our technique might not be suitable for such cases.

In conclusion, the molting technique might be helpful as an option for endoscopic revision for multiple UCSEMS deployments using the SIS technique for selected patients, although further randomized controlled trials are needed to confirm our results.

Supplemental Material

sj-doc-1-tag-10.1177_17562848251359410 – Supplemental material for Prospective evaluation study of a novel endoscopic revision technique after metal stent deployment for hepatic hilar obstruction

Supplemental material, sj-doc-1-tag-10.1177_17562848251359410 for Prospective evaluation study of a novel endoscopic revision technique after metal stent deployment for hepatic hilar obstruction by Kouji Kamawaki, Takeshi Ogura, Saori Ueno, Atsushi Okuda, Nobu Nishioka, Jun Sakamoto, Nobuhiro Hattori, Junichi Nakamura, Kimi Bessho and Hiroki Nishikawa in Therapeutic Advances in Gastroenterology

Supplemental Material

sj-docx-2-tag-10.1177_17562848251359410 – Supplemental material for Prospective evaluation study of a novel endoscopic revision technique after metal stent deployment for hepatic hilar obstruction

Supplemental material, sj-docx-2-tag-10.1177_17562848251359410 for Prospective evaluation study of a novel endoscopic revision technique after metal stent deployment for hepatic hilar obstruction by Kouji Kamawaki, Takeshi Ogura, Saori Ueno, Atsushi Okuda, Nobu Nishioka, Jun Sakamoto, Nobuhiro Hattori, Junichi Nakamura, Kimi Bessho and Hiroki Nishikawa in Therapeutic Advances in Gastroenterology

Footnotes

Acknowledgements

None.

Declarations

ORCID iD

Takeshi Ogura

Supplemental material

Supplemental material for this article is available online.

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Supplementary Material

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