Efficacy of a novel self-expandable metal stent with dumbbell-shaped flare ends for distal biliary obstruction due to unresectable pancreatic cancer

In patients with malignant DBO, SEMSs are associated with a lower rate of RBO than plastic stents, such that the frequency of re-intervention will be reduced2. The 2019 Clinical Practice Guidelines for Pancreatic Cancer of the Japan Pancreas Society recommend SEMSs over plastic stents in patients with DBO in the treatment of UPC17. A longer TRBO and less frequent re-intervention are desirable because some intense chemotherapy regimens prolong patient survival.

Both covered and uncovered SEMSs are currently in use. Covered SEMSs were introduced to overcome tumor ingrowth, an disadvantage of uncovered SEMSs7,8,9. However, tumor ingrowth in covered SEMSs is unlikely, while stent migration is more frequently observed with these SEMSs. There is a controversy as to which of the covered and uncovered SEMSs is superior in terms of the resistance to RBO8,10,11. Since it is difficult to overcome the adverse consequences of tumor ingrowth in uncovered SEMSs, covered SEMSs resistant to migration are needed.

Various structural devices have been applied to covered SEMSs in order to reduce the risk of migration. Two mechanical properties of SEMS are deterministic factors that influence the risk of stent migration in DBO; the axial force (AF), defined as the force that restores the SEMS to its original straight shape after it has been bent during placement, and the radial force (RF), which is the expansion force against the stricture. SEMSs with a high AF and a low RF tend to cause stent migration frequently18. In recent years, several types of covered SEMSs with ideal mechanical characteristics such as a low AF and a high RF have been developed19,20. Furthermore, various anti-migration systems have been developed to overcome the slipperiness of covered SEMSs, including uncovered flared ends11, anchoring fins21, and raised bands on the stent body15. Partially covered SEMSs have uncovered ~5-mm sections on either end, which are expected to reduce the risk of stent migration. There are some reports comparing the WFS and the WPS. A retrospective study reported that the incidence of stent migration was significantly higher in the WFS group than that in the WPS group16. However, a prospective multicenter study comparing them reported no significant difference in the rate of stent migration between two groups in patients with malignant DBO22. It is unclear whether the fully or partially covered SEMS is suitable for the palliation of malignant DBO. Since it has been shown that tumor shrinkage caused by anti-cancer treatment is likely to cause stent migration18, a high RF and effective anti-migration system are especially important properties for patients with DBO due to UPC.

The HILZO™ fully covered stent (HFS) has an inner and outer PTFE coating and dumbbell-shaped flares. The body of the novel SEMS has a nitinol-based braided hook-cross wire structure with a compositional ratio of cross and hook portions of 4 to 1. Among braided SEMSs, those with only a cross wire structure have a high AF that can cause shortening, bile duct kinking, sludge accumulation, and stent migration9. However, SEMSs with only a hook wire structure have a low RF and are thus also vulnerable to migration18. Although details of the AF and RF of the HFS have not been released by the manufacturer, both likely fall between the values of the cross wire types and hook wire types, such that a low AF and moderate RF can be expected. Furthermore, the inside and outside parts of the metal mesh are coated with PTFE (TeflonTM), which has a low coefficient of friction. As a result, the inner coating of the HFS appears to more effectively prevent sludge accumulation and food impaction in the stent lumen than standard silicone-coated SEMSs like the WPS and the WFS. In addition, the outer coating has high biocompatibility with the bile duct wall and its impermeable surface strongly resists tumor ingrowth. Although PTFE-coated SEMSs have been used from before21,23, the inner and outer coating of the HFS is unique. Moreover, an 1-cm flare on both ends of the HFS, which accounts for its dumbbell shape, has a diameter 4 mm larger than that of the stent body, and their silicone coating counteracts the slipperiness of the PTFE-coated stent body. The larger caliber of the distal flared end also allows anchoring to the duodenal papilla and reduces sludge accumulation.

This is the first clinical study comparing the performance of the novel HFS with that of other types of covered SEMSs, namely the WPS and the WFS, in patients with DBO due to UPC. During the follow-up periods, in which there was no significant difference between the three SEMS groups, the cumulative incidence of RBO in the HFS group was significantly lower than that in the other two groups. Compared to the HFS group, TRBO was significantly shorter in the WFS group, and the non-RBO rate at 12 months was lower in the WPS group. In previous studies evaluating the performance of different types of fully covered SEMSs, the median TRBO was 153–373 days11,12,14,16,20,22. Although it may be inappropriate to unconditionally compare the median TRBO of the HFS with the results of past studies due to the difference in clinical backgrounds, it is considered that our result is not inferior to them. It is notable that despite variations in clinical parameters (e.g. ascites and sphincterotomy) between the three SEMS groups in this study, the only factor contributing to long TRBO in multivariable analysis was placement of the HFS.

There were some differences in the cause of RBO between the three SEMS groups. The rate of RBO-inducing stent migration tended to be slightly higher in the WFS group, while there was almost no stent migration in the WPS group, probably because of the uncovered section on either end of the SEMS. The frequency of stent migration was also relatively low in the HFS group, which may be the effect of a low AF and dumbbell-shaped flare ends. Sludge accumulation and tumor ingrowth /mucosal hyperplasia were main causes of RBO in the WPS group and likely to occur in the uncovered section on either end of the SEMS. The low incidence of sludge accumulation in the HFS group may have been caused by an inner coating with PTFE and a larger caliber of the distal flared end. Although our study couldn’t identify the decisive reason why the HFS group had a longer TRBO than the WFS group, the slightly lower incidence of stent migration and sludge accumulation seemed to lead to better results for the HFS group.

The incidence of SEMS-related complications other than RBO, such as pancreatitis and cholecystitis, may increase with the increased opportunity to use covered SEMSs, as these stents compress the orifice of the pancreatic duct and cystic duct, respectively. In UPC patients, dilation of the pancreatic duct is thought to reduce the risk of pancreatitis even if a fully covered SEMS was placed24. In our study, there was no difference in the incidence of pancreatitis between the three types of SEMS. However, compared to the HFS group, the WFS group tended to develop pancreatitis more often. It has been reported that SEMS with a high AF was associated with a high incidence of pancreatitis in patients with malignant DBO other than UPC25. Similar results were obtained in our study which enrolled UPC patients only, and it is considered that a high AF of the WFS, which is a braided SEMS consisting of only a cross wire structure, makes pancreatitis more likely to occur. None of patients in the WPS group developed pancreatitis, probably because the uncovered section on the end of the WPS did not occlude the orifice of the pancreatic duct. Although the incidence of cholecystitis was not significantly different between the three groups, no patient developed cholecystitis in the WPS group, probably because the uncovered section on proximal end of the SEMS did not compress too hard the orifice of the cystic duct. Previous studies have reported that gallbladder stones, the tumor involvement of the orifice of the cystic duct, and the use of covered SEMS with a high AF were risk factors for cholecystitis after SEMS placement13,26. Of the three patients who had cholecystitis in our study, gallbladder stones / sludge and tumor involvement to the orifice of cystic duct was observed in one case each in the WFS group. Although the HFS is expected to have a low AF, its dumbbell-shaped flares may increase the risk of cholecystitis due to pressure on the orifice of the cystic duct. We should be careful about the development of cholecystitis in patients who need placement of the HFS such that it reaches the confluence of the cystic duct and common hepatic duct.

The limitations of our study included its retrospective design and the recruitment of patients from a single institution. Although each SEMS group consisted of consecutive UPC patients who received a SEMS for the palliation of DBO, patients in the HFS group and the other two groups did not undergo SEMS placement within the same period, suggesting that there are biases that affect TRBO and complications, such as patients’ characteristics, endoscopic procedures including sphincterotomy and SEMS placement, and anti-cancer treatment after SEMS placement. Similarly, there may have been a selection bias between the WFS and WPS groups. It is desirable to enroll sufficient patients in a prospective study in order to eliminate bias as much as possible. Furthermore, multicenter randomized controlled trials comparing other types of covered SEMS are necessary to confirm the true efficacy and safety of the HFS.

In conclusion, the HFS demonstrated a low incidence of RBO with a low risk of SEMS-related complications. Therefore, the HFS can be recommended for the palliation of DBO due to UPC.

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