Stenting and interventional radiology for obstructive jaundice in patients with unresectable biliary tract carcinomas

Together with biliary drainage, which is an appropriate procedure for unresectable biliary cancer, biliary stent placement is used to improve symptoms associated with jaundice. Owing to investigations comparing percutaneous transhepatic biliary drainage (PTBD), surgical drainage, and endoscopic drainage, many types of stents are now available that can be placed endoscopically. The stents used are classifi ed roughly as plastic stents and metal stents. Compared with plastic stents, metal stents are of large diameter, and have long-term patency (although they are expensive). For this reason, the use of metal stents is preferred for patients who are expected to survive for more than 6 months, whereas for patients who are likely to survive for less than 6 months, the use of plastic stents is not considered to be improper. Obstruction in a metal stent is caused by a tumor that grows within the stent through the mesh interstices. To overcome such problems, a covered metal stent was developed, and these stents are now used in patients with malignant distal biliary obstruction. However, this type of stent has been reported to have several shortcomings, such as being associated with the development of acute cholecystitis and stent migration. In spite of these shortcomings, evidence is expected to demonstrate its superiority over other types of stent.

# Introduction
More than 20 years have passed since stents began to be used for treating unresectable bile duct stricture in patients with obstructive jaundice. Previously, percutaneous transhepatic cholangial drainage (PTCD); also known as percutaneous transhepatic biliary drainage (PTBD) was employed for patients with this disease, and the patients were often forced to stay in hospital for a long period of time with an external biliary fi stula. The creation of an internal fi stula is now widely used because it is as useful as surgical bypass in improving not only quality of life (QOL) but also survival rates. Today, noninvasive endoscopic stent placement is being used for most patients with this disease as an alternative procedure to the percutaneous approach. Plastic stents (PS), which have been used until now, are economical, but their shortcoming is that they give rise to obstruction at an earlier stage, so several improvements have been made. On the other hand, metal stents (MS), in which the insertion of the stents is enabled with a slender delivery system and the stents expand to a large diameter by themselves, have conferred noticeably extended patency compared with PS. However, their shortcomings are that they are more expensive than PS and replacing them is diffi cult once they have been placed.
Here we pose clinical questions (CQs) regarding stenting for obstructive jaundice in patients with unresectable biliary carcinoma, with responses in the form of recommendations (grades of the recommendations are defi ned in [fig_ref] Table 1: Strength of recommendations 1 A, Strongly recommend performing the clinical action B,... [/fig_ref]. Also, levels of evidence are given (in parentheses) for fi ndings in reference citations (see defi nitions of levels in [fig_ref] Table 1: Strength of recommendations 1 A, Strongly recommend performing the clinical action B,... [/fig_ref].

## Biliary drainage should be performed (recommendation b).
There are many studies reporting the approach route of drainage for unresectable malignant distal biliary obstruction, methods of stenting, and the quality of stent materials. In view of this situation, it is thought that the relief of jaundice should be conducted as a matter of CQ 1 Is biliary drainage recommended for patients with unresectable disease? course. Also, the creation of an internal fi stula, where possible, is recommended. For the drainage route, there are reports of randomized controlled trials (RCTs) 2,3 (level II) comparing endoscopic drainage, PTBD, and surgical drainage. The success rate for the creation of an internal fi stula is reported to be 95%-100% 4,5 (levels II, IV). According to these reports, endoscopic drainage is preferable to the other two methods. A metaanalysis showed that endoscopic drainage was associated with a lower risk of complications, but a higher risk of recurrent biliary obstruction than surgical drainage 4 (level II). The percutaneous procedure is performed in patients in whom the endoscopic procedure has been unsuccessful.
Concerning the types of stent available, there are several RCTs suggesting the superiority of metal stents over plastic stents with respect to stent patency 4-12 (level II).
For hepatic hilar bile duct stricture, placement of multiple stents has been reported to confer better drainage effects than those brought about by single-stent placement 13 (level IV), although there are also prospective trials demonstrating that single stents are as effective as including hospitalization expenses, is thought to be lower compared with that of plastic stents because of the reduced frequency of re-intervention. [bib_ref] Randomized trial of self-expandanding metal stents versus polyethylene stents for distal malignant..., Davids [/bib_ref] [bib_ref] A prospective randomized, controlled trial of metal stents for malignant obstruction of..., Knyrim [/bib_ref] According to recent reports, the cost of plastic stents is low for the reasons that, in patients for whom prognosis is poor, long-term survival is not expected (patients with liver metastasis) and re-intervention is also unnecessary. [bib_ref] A randomized trial of endoscopic drainage methods for inoperable malignant strictures of..., Prat [/bib_ref] [bib_ref] Plastic or metal stents for malignant stricture of the common bile duct?..., Kaassis [/bib_ref] [bib_ref] Tannenbaum and metal stents in the palliative treatment of malignant distal bile..., Katsinelos [/bib_ref] In patients for whom long-term survival exceeding 6 months is expected, metal stents may be used from the initial intervention, while in patients for whom survival exceeding 6 months is not expected, similar results are achieved by using plastic stents (level IV). In metal stents, which are made of mesh materials, obstruction due to the ingrowth of tumors has often occurred. To cope with this problem, polyurethanecovered metal stents have become available in clinical settings [fig_ref] Figure 2: Covered metal stent [/fig_ref] [bib_ref] Treatment of malignant biliary obstruction with polyurethane-covered Wallstents, Hausegger [/bib_ref] (level IV), and their superior patency has been demonstrated by an RCT 22 (level II). Recent case series studies, however, reported that no signifi cant difference in patency rate was found between covered and uncovered metal stents, because covered metal stents have several drawbacks, such as stent-migration and the occurrence of acute cholecystitis [bib_ref] Covered versus uncovered Wallstent for malignant extrahepatic biliary obstruction: a cohort comparative..., Park [/bib_ref] [bib_ref] A comparison of covered and uncovered Wallstents for the management of distal..., Yoon [/bib_ref] [bib_ref] Similar performance but higher cholecystitis rate with covered biliary stents: results from..., Fumex [/bib_ref]. Furthermore patients with pancreatic cancer have been included in the results of studies of stent treatment for malignant distal biliary stricture. Accumulation of evidence is awaited.
There is much controversy as to the importance of establishing drainage of both liver lobes in malignant hilar biliary obstruction. Drainage with a unilateral uncovered metal stent is reported to be effective for hilar biliary obstruction [bib_ref] Unilateral placement of metallic stents for malignant hilar obstruction: a prospective study, Palma [/bib_ref] [bib_ref] Endoscopic palliation of patients with biliary obstruction caused by nonresectable hilar cholangiocarcinoma:..., Cheng [/bib_ref] [bib_ref] Selective MRCP and CT-targeted drainage of malignant hilar biliary obstruction with self-expanding..., Freeman [/bib_ref] (level III, IV); however, there are no RCTs regarding unilateral or bilateral metal stent drainage. Concerning plastic stents, an RCT failed to fi nd any difference in drainage effects between single stents and multiple stents 15 (level II). Although an RCT 12 (level II) regarding plastic stents and metal stents showed that both success and patency rates were better for metal stents than for plastic stents, the RCT

## Cq 2 which type of biliary stent is appropriate for unresectable cases?

## A metal stent is preferable in view of stent patency (recommendation c1).
Plastic stents with an outer diameter of 8-10 Fr are now in use [fig_ref] Figure 1: Plastic stents [/fig_ref]. These are easily clogged, so stents with a larger diameter have occasionally been employed in the past. However, due to the pain and technical diffi culties accompanying the insertion of these stents, they have fallen into disuse. Improvements have been made in the quality of materials and the shape of stents, but no difference in patency rates has been observed [bib_ref] Prospective randomized single-center trial comparing three different 10-F plastic stents in malignant..., Schilling [/bib_ref] [bib_ref] Prospective randomized trial comparing Tannenbaum Tefl on and standard polyethylene stents in..., Terruzzi [/bib_ref] [bib_ref] A prospective randomised multicentre trial comparing 10F Tefl on Tannenbaum stents with..., Barkun [/bib_ref] [bib_ref] A prospective randomized trial of Tannenbaum-type Tefl on-coated stents versus polyethylene stents..., Van Berkel [/bib_ref].
There are RCTs comparing plastic stents with metal stents in the palliative treatment of distal malignant biliary obstruction 4-11 (level II). As for the median patency of stents, metal stents (3.6-9.1 months) are signifi cantly superior to plastic stents (1.8-5.5 months), but no difference was found in median survival [fig_ref] Table 3: Prospective and randomized controlled trials for plastic versus metal stents in the... [/fig_ref]. [bib_ref] Palliation of malignant extrahepatic biliary obstruction with plastic versus expandable metal stents:..., Levy [/bib_ref] Although metal stents are expensive, their overall cost, multiple stents [bib_ref] Unilateral versus bilateral endoscopic hepatic duct drainage in patients with malignant hilar..., Palma [/bib_ref] [bib_ref] Unilateral placement of metallic stents for malignant hilar obstruction: a prospective study, Palma [/bib_ref] (levels II, III). However, there are several questions as to hepatic hilar bile duct stricture, such as the presence of segments for which drainage is unable to be achieved and the clogging of stents, so stent placement in these patients is still controversial.
included only 20 patients with hilar biliary obstruction. Hence, it is still controversial which type of stents should be used in patients with hilar biliary obstruction.
[fig] Figure 1: Plastic stents. From left, plastic stents with outer diameters of 10, 8.5, and 7 Fr, are shown [/fig]
[fig] Figure 2: Covered metal stent (Wallstent; Boston Scientifi c, Natick, MA, USA). This metal stent is partially covered [/fig]
[table] Table 3: Prospective and randomized controlled trials for plastic versus metal stents in the palliative treatment of distal malignant biliary obstruction[6][7][8][9][10][11]20 [/table]
[table] Table 1: Strength of recommendations 1 A, Strongly recommend performing the clinical action B, Recommend performing the clinical action C1, The clinical action may be considered although there is a lack of high-level scientifi c evidence for its use. May be useful C2, Clinical action not defi nitively recommended because of insuffi cient scientifi c evidence. Evidence insuffi cient to support or deny usefulness D, Recommend not performing the clinical action Table 2. Levels of evidence 1 [/table]