Third metal stent for revision of malignant hilar biliary strictures

• Introduction
• Methods
• The endoscopic technique
• Results
• Discussion
• References

Background and study aim: Endoscopic stent-in-stent (SIS) placement of multiple metal stents is technically demanding. In the present study, we explored the technical feasibility and efficacy of endoscopic deployment of a third metal stent to create a triple SIS placement in patients with a bilateral SIS configuration for inoperable high grade malignant hilar biliary stricture (HBS) that had failed clinically.

Methods: Eighteen patients with histologically proven inoperable HBS underwent deployment of an additional third metal stent as a revisionary method after early clinical failure following technically successful bilateral SIS placement using cross-wired metal stents. The main outcome measures were the technical and clinical success rates, and adverse events.

Results: The overall technical and clinical success rates were 88.9 % (16/18) and 87.5 % (14/16), respectively. The early and late complications were cholangitis (n = 2) and cholecystitis (n = 1). Stent occlusion developed in 35.7 % (5/14) of patients in whom a third metal stent for revision of a bilateral SIS configuration was clinically successful. The median (range) times for stent patency and patient survival were 176 days (49 – 372) and 216 days (52 – 384), respectively.

Conclusions: Endoscopic deployment of an additional third metal stent into a bilateral SIS configuration was technically feasible and effective in patients with inoperable high grade malignant HBS in whom bilateral SIS placement had failed clinically.

Introduction

Although endoscopic palliation may be the preferred treatment of choice for malignant hilar biliary strictures (HBSs), palliation of advanced HBSs remains technically challenging. The insertion of multiple biliary drains is recommended if a single stent cannot drain more than 50 % of the liver volume. Indeed, adequate drainage, especially of advanced HBSs, may require multi-sectoral drainage of the bile duct as the risk of cholangitis increases if only one side is drained [1]. In terms of technical methods, percutaneous transhepatic biliary drainage (PTBD) remains the classical biliary palliative method. A percutaneous approach is preferable to endoscopic drainage in patients with Bismuth type III or IV strictures [2].

However, recent studies have shown that endoscopic deployment of bilateral metal stents to treat malignant HBSs is associated with good technical and clinical success rates [3] [4] [5] [6] [7] [8] [9]. Accordingly, triple stent-in-stent (SIS) deployment using a self-expandable metal stent (SEMS) may represent a valuable primary endoscopic approach or revisionary method when bilateral SIS deployment has been clinically unsuccessful.

This trial assessed the clinical outcomes of deployment of an additional third metal stent into a bilateral SIS configuration with cross-wired metal stents as a revisionary method in patients with inoperable high grade malignant HBS in whom technically successful primary bilateral SIS placement had failed clinically.

Methods

Patients were enrolled from January 2011 to December 2014 and were followed up until July 2015. Patients who underwent technically successful bilateral SIS placement using cross-wired metal stents for histologically proven inoperable malignant HBSs (Bismuth class III or IV) were initially enrolled. Among these patients, those who underwent deployment of a third metal stent as a revisionary method having experienced early clinical failure (failure to achieve a > 50 % reduction in the bilirubin level during the first week, without cholangitis) or medically uncontrolled cholangitis during the first week were selected.

Inoperability was decided on the basis of data from computed tomography (CT), magnetic resonance imaging (MRI) or magnetic resonance cholangiopancreatography (MRCP), cholangiography, and/or positron emission tomography, as well as taking account of the views of surgeons. MRI or MRCP was routinely performed prior to endoscopic procedures. Patients with a malignant HBS caused by a metastatic lesion were excluded because of their inherently poor survival rates. Other exclusion criteria were: an atrophic lobe, uncontrolled coagulopathy, uncontrolled medical illness, and patient refusal.

Two tertiary academic centers participated in the study, and the institutional review board of each center approved the work. Written informed consent was obtained from all enrolled patients.

The endoscopic technique

All patients underwent endoscopic retrograde cholangiopancreatography (ERCP) in the prone position using a standard duodenoscope (TJF 260 or 240; Olympus Optical Co. Ltd., Tokyo, Japan) following an overnight fast. Prophylactic antibiotics and analgesics were permitted.

Cross-wired metal stents (Bonastent M-Hilar; Standard Sci Tech Inc., Seoul, South Korea) that were specially designed to treat malignant HBSs were inserted as the first, second, and third stents, as described in our previous reports [3] [10]. The cross-wired metal stents are made of nitinol wire, with a high degree of flexibility and elasticity, and a narrow stent mesh (cavity size 2 × 2 mm), have a thin delivery shaft (7 Fr) and good pushability. The first stent had two spiral radiopaque markings (X mark) on the central portion and four spot markings on each end. This stent had a conventional hook and cross-wired structure at the proximal and distal portions. However, on the central portion, which was 30 mm in length, the stent had only a cross-wired structure to facilitate crosswise placement of the contralateral stent. The second stent was of the same design, except that it had four radiopaque spot markings on each end of the central portion to differentiate it from the first stent.

All endoscopic procedures were performed by endoscopists experienced in endoscopic stenting for malignant HBSs. A third metal stent for endoscopic revision was inserted using the same SIS deployment technique as previously described [3], thereby yielding a triple-branched configuration.

For selective cannulation into an undrained right anterior or posterior side intrahepatic duct (IHD) during SIS deployment of the third stent, a 0.025-inch guidewire (VisiGlide 1 or 2; Olympus) with a triple lumen sphincterotome (Tri-tome PC; Cook Medical, Winston-Salem, North Carolina, USA) or Autotome (Boston Scientific, Natick, Massachusetts, USA) was inserted through the central mesh, with its cross-wired structure, of the previously inserted metal stents. At this time, we injected contrast material into the peripheral ducts, using the smallest possible volume to avoid iatrogenic cholangitis. The third cross-wired stent was then introduced over a guidewire through the central mesh of the metal stents as per the SIS method, resulting in a triple-branched configuration of the hilar portion ([Fig. 1]; [Video 1]). The distal ends of all the metal stents in the single stent lumen were located above the level of the papilla.

If passage of the delivery catheter for the metal stent through the stricture or central portion of the metal stent was unsuccessful because the stricture was tight, a balloon dilation catheter with a 4-mm diameter (Hurricane RX; Boston-Scientific) was used to dilate the stricture. In patients who were unsuitable for endoscopy owing to a septic condition, primary PTBD followed by ERCP with insertion of the third metal stent into the bilateral SIS configuration was attempted 2 – 5 days later.

Results

A total of 156 patients underwent bilateral SIS placement during the study period, and this was technically successful in 146 patients (93.6 %). Among these patients, 21 (14.4 %) who developed early clinical failure (n = 16) or who newly developed severe cholangitis (n = 5) were enrolled, but three were then excluded ([Fig. 2]). A total of 18 patients were therefore analyzed, their final histopathological diagnoses being cholangiocarcinoma (n = 15) and gallbladder cancer (n = 3). The Bismuth classifications were as follows: IIIA (n = 7), IIIB (n = 1), and IV (n = 10) ([Table 1]).

The overall technical success rate of deployment of an additional third metal stent into the bilateral SIS configuration was 88.9 % (16/18). The clinical success rate was 87.5 % (14/16). The technical success rate for insertion of an additional third metal stent into a bilateral SIS configuration in a single session was 100 % (16 /16) per protocol and 66.7 % (12/18) as intention to treat. Four patients underwent PTBD to treat severe cholangitis before they underwent endoscopic placement of a third metal stent. Two patients in whom placement of the third metal stent was unsuccessful subsequently underwent PTBD.

There were no significant endoscopic procedure-related adverse events and no deaths. An early complication developing within 4 weeks after triple-stenting was cholangitis (n = 2), which was managed conservatively, including the use of antibiotics. Cholecystitis developed as a late complication in one patient, who was managed by endoscopic ultrasound (EUS)-guided gallbladder drainage. Stent occlusion during follow-up developed in 35.7 % (5/14) of patients in whom the insertion of the third metal stent into the bilateral SIS configuration had been clinically successful. Three of these patients required endoscopic revision and the remaining two underwent PTBD because they were unable to undergo endoscopy.

The median (range) times for stent patency and patient survival were 176 days (49 – 372) and 216 days (52 – 384), respectively ([Table 2]).

Discussion

We have shown that deployment of an additional third metal stent into a bilateral SIS configuration as a revisionary method is technically feasible and efficacious when the bilateral metal SIS configuration has failed clinically. The extent of stent patency and the frequency of adverse events were comparable to those associated with the use of bilateral metal stents to treat patients with advanced HBSs [3] [6] [7] [8] [9] [10] [11].

Bilateral drainage of advanced HBSs using SEMSs remains controversial because of the technical challenges this poses, the risk of adverse events, and the difficulty with revision. A recent meta-analysis suggested that bilateral stenting should be avoided because it afforded no greater benefit than that imparted by unilateral stenting in terms of either occlusion rate or therapeutic failure [12]. The risk of adverse events (such as cholangitis or an abscess) may increase when several unsuccessful attempts are made to selectively cannulate the IHD, to inject contrast material in the absence of adequate drainage, or when technical failure occurs. However, recent reports on bilateral drainage employing SEMSs specially designed for use in patients with malignant HBSs showed that the procedure was technically feasible and clinically successful, even following revision when a stent became occluded [3] [6] [9] [10]. The overall technical success rate of bilateral SEMS deployment ranged from 73.3 % to 100 % [3] [4] [6] [13] [14] [15]. As metal stents improve, and as multiple drainage techniques (SIS placement or side-by-side [SBS] deployment) are refined, the technical and clinical success rates have been increasing, without any rise in complications rates, to levels greater than those associated with unilateral drainage [3] [4] [5] [6] [9].

Multi-sectoral drainage may be a reasonable option when it is sought for maximal preservation of the functional liver volume. The advantages of SIS include placement of multiple metal stents of a single caliber at the common bile duct (CBD), which may be considered to be physiologically ideal. Conversely, the SBS technique, if placed across the papilla, is technically simple both at the time of initial placement and during re-intervention where stent occlusion has occurred [16]. In such circumstances, triple SIS or SBS deployment is also technically possible; however, triple-SBS deployment may distend the CBD excessively, with adverse results such as portal vein thrombosis, especially when the CBD is normal. In addition, if clinical failure develops after bilateral SBS deployment, additional stenting of the undrained branch is technically difficult. In contrast, SIS placement does not overextend the bile duct, and additional metal stenting of an undrained bile duct is technically feasible as the new stent can be inserted through the cross-wired mesh. Therefore, deployment of a third metal stent using the SIS method may be a valuable alternative physiological option when bilateral SEMSs exhibit clinical failure.

Previously, we evaluated the efficacy of (primary and revision) bilateral endoscopic placement of cross-wired metal stents using SIS placement in patients with malignant HBSs [3]. The cross-wired nature of the central region (25 mm in length) of the metal stent facilitates cross-placement of the contralateral metal stent, even on revision endoscopy. Therefore, triple SIS placement through deployment of an additional stent uses the same technique as primary or revisionary stenting when clinical failure or occlusion has developed.

Theoretically, triple drainage of the right anterior, right posterior, and left-sided bile ducts is ideal when treating high grade malignant HBSs. The pioneering study of Kawamoto et al. [8] showed that placement of triple-branched metal stents (Jostent SelfX stents; Abbott Vascular Devices, Redwood City, California, USA) was technically feasible and efficacious in nine patients. We also found that deployment of a third metal stent into a bilateral SIS configuration was associated with a high level of technical success when clinical failure developed after successful bilateral SIS deployment.

In terms of technical difficulty, triple stenting may indeed be problematic if the wire mesh exhibits strong resistance or if a severe stricture is present in the hilar portion of the duct. Kawamoto et al. [8] used a Soehendra stent retriever as a drill to break through the stent mesh and the stricture. We used dilation with a pneumatic balloon (4 mm in diameter) to facilitate the placement of the third metal stent in three patients. Guidewire insertion did not require any additional devices; the wire structure allowed insertion. However, placement of the third metal stent failed in two patients because of difficulty with passage of the balloon catheter and/or the delivery system. The previously inserted wire mesh and a severe stricture may resist device passage in such cases.

In terms of adverse events, we recorded no serious procedure-related adverse events or mortality. Stent dysfunction during follow-up developed in 35.7 % of patients (5/14) who underwent functionally successful placement of a third metal stent. Endoscopic revision was possible in three patients, even after triple SIS placement. In these three patients, endoscopic revision was successfully performed bilaterally using 7-Fr plastic stents.

Our case study has a few limitations. The number of enrolled patients was small, and there was no randomization. Second, early clinical failure was defined in our study as a reduction in the bilirubin level within 1 week. A < 75 % reduction in the bilirubin level within the first month could also be used to define clinical failure. Third, all endoscopic procedures were performed at two tertiary referral centers by three endoscopists who were highly experienced in bilateral metal stenting. Therefore our findings may not be generalizable to other endoscopists, and successful deployment of multiple metal stents requires experience. Larger studies involving endoscopists with various levels of experience and evaluating the primary efficacy or comparative results of triple stenting are required.

In conclusion, as a revisionary method, deployment of an additional third metal stent into a bilateral SIS configuration with cross-wired metal stents is technically feasible and is effective when clinical failure develops after technically successful primary bilateral SIS placement. In patients with an inoperable advanced HBS, multi-sectoral drainage via metal stents may be theoretically ideal; however, larger studies are required to confirm our results.

Competing interests: None.

Acknowledgment

We thank Mr. Sang Koo Jeon and Standard Sci-Tech for their dedication during the development of the Bonastent M-Hilar. Professor Jong Ho Moon is the inventor of the Bonastent M-Hilar. We thank the nursing staff for assistance with the procedures. This study was supported in part by the SoonChunHyang University Research Fund.

• References

• 1 Chang WH, Kortan P, Haber GB. Outcome in patients with bifurcation tumors who undergo unilateral versus bilateral hepatic duct drainage. Gastrointest Endosc 1998; 47: 354-362
  CrossrefPubMedSearch in Google Scholar
• 2 Rerknimitr R, Angsuwatcharakon P, Ratanachu-ek T et al. Asia-Pacific consensus recommendations for endoscopic and interventional management of hilar cholangiocarcinoma. J Gastroenterol Hepatol 2013; 28: 593-607
  CrossrefPubMedSearch in Google Scholar
• 3 Lee TH, Moon JH, Kim JH et al. Primary and revision efficacy of cross-wired metallic stents for endoscopic bilateral stent-in-stent placement in malignant hilar biliary strictures. Endoscopy 2013; 45: 106-113
  Thieme ConnectPubMedSearch in Google Scholar
• 4 Lee TH, Park do H, Lee SS et al. Technical feasibility and revision efficacy of the sequential deployment of endoscopic bilateral side-by-side metal stents for malignant hilar biliary strictures: a multicenter prospective study. Dig Dis Sci 2013; 58: 547-555
  CrossrefPubMedSearch in Google Scholar
• 5 Chennat J, Waxman I. Initial performance profile of a new 6F self-expanding metal stent for palliation of malignant hilar biliary obstruction. Gastrointest Endosc 2010; 72: 632-636
  CrossrefPubMedSearch in Google Scholar
• 6 Hwang JC, Kim JH, Lim SG et al. Y-shaped endoscopic bilateral metal stent placement for malignant hilar biliary obstruction: prospective long-term study. Scand J Gastroenterol 2011; 46: 326-332
  CrossrefPubMedSearch in Google Scholar
• 7 Kato H, Tsutsumi K, Harada R et al. Endoscopic bilateral deployment of multiple metallic stents for malignant hilar biliary strictures. Dig Endosc 2013; 25: 75-80
  CrossrefPubMedSearch in Google Scholar
• 8 Kawamoto H, Tsutsumi K, Fujii M et al. Endoscopic 3-branched partial stent-in-stent deployment of metallic stents in high-grade malignant hilar biliary stricture (with videos). Gastrointest Endosc 2007; 66: 1030-1037
  CrossrefPubMedSearch in Google Scholar
• 9 Kogure H, Isayama H, Nakai Y et al. Newly designed large cell Niti-S stent for malignant hilar biliary obstruction: a pilot study. Surg Endosc 2011; 25: 463-467
  CrossrefPubMedSearch in Google Scholar
• 10 Park do H, Lee SS, Moon JH et al. Newly designed stent for endoscopic bilateral stent-in-stent placement of metallic stents in patients with malignant hilar biliary strictures: multicenter prospective feasibility study (with videos). Gastrointest Endosc 2009; 69: 1357-1360
  CrossrefPubMedSearch in Google Scholar
• 11 Kawamoto H, Tsutsumi K, Harada R et al. Endoscopic deployment of multiple JOSTENT SelfX is effective and safe in treatment of malignant hilar biliary strictures. Clin Gastroenterol Hepatol 2008; 6: 401-408
  CrossrefPubMedSearch in Google Scholar
• 12 Sawas T, Al Halabi S, Parsi MA et al. Self-expandable metal stents versus plastic stents for malignant biliary obstruction: a meta-analysis. Gastrointest Endosc 2015; 82: 256-267
  CrossrefPubMedSearch in Google Scholar
• 13 Naitoh I, Hayashi K, Nakazawa T et al. Side-by-side versus stent-in-stent deployment in bilateral endoscopic metal stenting for malignant hilar biliary obstruction. Dig Dis Sci 2012; 57: 3279-3285
  CrossrefPubMedSearch in Google Scholar
• 14 Chahal P, Baron TH. Expandable metal stents for endoscopic bilateral stent-within-stent placement for malignant hilar biliary obstruction. Gastrointest Endosc 2010; 71: 195-199
  CrossrefPubMedSearch in Google Scholar
• 15 Cheng JL, Bruno MJ, Bergman JJ et al. Endoscopic palliation of patients with biliary obstruction caused by nonresectable hilar cholangiocarcinoma: efficacy of self-expandable metallic Wallstents. Gastrointest Endosc 2002; 56: 33-39
  CrossrefPubMedSearch in Google Scholar
• 16 Moon JH, Rerknimitr R, Kogure H et al. Topic controversies in the endoscopic management of malignant hilar strictures using metal stent: side-by-side versus stent-in-stent techniques. J Hepatobiliary Pancreat Sci 2015; 22: 650-656
  CrossrefPubMedSearch in Google Scholar

Corresponding author

• References

• 1 Chang WH, Kortan P, Haber GB. Outcome in patients with bifurcation tumors who undergo unilateral versus bilateral hepatic duct drainage. Gastrointest Endosc 1998; 47: 354-362
  CrossrefPubMedSearch in Google Scholar
• 2 Rerknimitr R, Angsuwatcharakon P, Ratanachu-ek T et al. Asia-Pacific consensus recommendations for endoscopic and interventional management of hilar cholangiocarcinoma. J Gastroenterol Hepatol 2013; 28: 593-607
  CrossrefPubMedSearch in Google Scholar
• 3 Lee TH, Moon JH, Kim JH et al. Primary and revision efficacy of cross-wired metallic stents for endoscopic bilateral stent-in-stent placement in malignant hilar biliary strictures. Endoscopy 2013; 45: 106-113
  Thieme ConnectPubMedSearch in Google Scholar
• 4 Lee TH, Park do H, Lee SS et al. Technical feasibility and revision efficacy of the sequential deployment of endoscopic bilateral side-by-side metal stents for malignant hilar biliary strictures: a multicenter prospective study. Dig Dis Sci 2013; 58: 547-555
  CrossrefPubMedSearch in Google Scholar
• 5 Chennat J, Waxman I. Initial performance profile of a new 6F self-expanding metal stent for palliation of malignant hilar biliary obstruction. Gastrointest Endosc 2010; 72: 632-636
  CrossrefPubMedSearch in Google Scholar
• 6 Hwang JC, Kim JH, Lim SG et al. Y-shaped endoscopic bilateral metal stent placement for malignant hilar biliary obstruction: prospective long-term study. Scand J Gastroenterol 2011; 46: 326-332
  CrossrefPubMedSearch in Google Scholar
• 7 Kato H, Tsutsumi K, Harada R et al. Endoscopic bilateral deployment of multiple metallic stents for malignant hilar biliary strictures. Dig Endosc 2013; 25: 75-80
  CrossrefPubMedSearch in Google Scholar
• 8 Kawamoto H, Tsutsumi K, Fujii M et al. Endoscopic 3-branched partial stent-in-stent deployment of metallic stents in high-grade malignant hilar biliary stricture (with videos). Gastrointest Endosc 2007; 66: 1030-1037
  CrossrefPubMedSearch in Google Scholar
• 9 Kogure H, Isayama H, Nakai Y et al. Newly designed large cell Niti-S stent for malignant hilar biliary obstruction: a pilot study. Surg Endosc 2011; 25: 463-467
  CrossrefPubMedSearch in Google Scholar
• 10 Park do H, Lee SS, Moon JH et al. Newly designed stent for endoscopic bilateral stent-in-stent placement of metallic stents in patients with malignant hilar biliary strictures: multicenter prospective feasibility study (with videos). Gastrointest Endosc 2009; 69: 1357-1360
  CrossrefPubMedSearch in Google Scholar
• 11 Kawamoto H, Tsutsumi K, Harada R et al. Endoscopic deployment of multiple JOSTENT SelfX is effective and safe in treatment of malignant hilar biliary strictures. Clin Gastroenterol Hepatol 2008; 6: 401-408
  CrossrefPubMedSearch in Google Scholar
• 12 Sawas T, Al Halabi S, Parsi MA et al. Self-expandable metal stents versus plastic stents for malignant biliary obstruction: a meta-analysis. Gastrointest Endosc 2015; 82: 256-267
  CrossrefPubMedSearch in Google Scholar
• 13 Naitoh I, Hayashi K, Nakazawa T et al. Side-by-side versus stent-in-stent deployment in bilateral endoscopic metal stenting for malignant hilar biliary obstruction. Dig Dis Sci 2012; 57: 3279-3285
  CrossrefPubMedSearch in Google Scholar
• 14 Chahal P, Baron TH. Expandable metal stents for endoscopic bilateral stent-within-stent placement for malignant hilar biliary obstruction. Gastrointest Endosc 2010; 71: 195-199
  CrossrefPubMedSearch in Google Scholar
• 15 Cheng JL, Bruno MJ, Bergman JJ et al. Endoscopic palliation of patients with biliary obstruction caused by nonresectable hilar cholangiocarcinoma: efficacy of self-expandable metallic Wallstents. Gastrointest Endosc 2002; 56: 33-39
  CrossrefPubMedSearch in Google Scholar
• 16 Moon JH, Rerknimitr R, Kogure H et al. Topic controversies in the endoscopic management of malignant hilar strictures using metal stent: side-by-side versus stent-in-stent techniques. J Hepatobiliary Pancreat Sci 2015; 22: 650-656
  CrossrefPubMedSearch in Google Scholar