According to our findings, in a retrospective review of 480 patients, the palliation of hilar CCA with SEMS was associated with successful stent insertion and successful drainage in the ITT analysis as well as a lower complication rate and increased cumulative stent patency compared with PS placement for all Bismuth classifications. The outcome in terms of FS after PS insertion in patients with advanced disease (Group 3) was very poor. In a subset of patients with Bismuth type II hilar strictures, the cumulative stent patency of bilateral SEMS or PS placement was significantly higher than that of unilateral SEMS or PS stenting, with lower occlusion rates. In this group of patients, bilateral SEMS placement offered the best results in terms of cumulative stent patency and occlusion rates.
Our data results from a single academic tertiary center which is a referral center for ERCPs especially difficult cases and tumors. It is the largest center in the country receiving patients from 20–30 hospitals all over the southern part of the country. We perform an average of 850 ERCPs per year, thus having a huge inclusion potential as far as hilar CCAs are concerned. Furthermore our center is the main referral center for endoscopic palliation of malignancies, coming from oncology, gastroenterology and surgical centers.
There have been few comparative studies regarding PS and SEMS placement in hilar CCA, and because such data are scarce, no clear consensus has been reached regarding the optimal approach in these patients. A recent randomized trial randomly allocated 108 patients to SEMS or PS placement [13
]. The authors reported that endoscopic biliary drainage with SEMS was associated with significantly successful drainage rate and longer survival compared with PS placement. [Raju et al. 15
] recently presented a retrospective review of 100 patients who underwent PS and SEMS placement for inoperable hilar CCA. Patients were divided into 3 groups according to the Bismuth classification, similarly to our study. The SEMS group demonstrated a significantly higher patency (5.56 vs. 1.86
months) and required fewer re-interventions for stent obstruction. The authors concluded that the patency of metallic stents was superior to that of PS in all Bismuth classifications, although a clear comparison between the groups was not presented in the paper.
Our study suggests that patency of SEMS is significantly longer with lower occlusion rates when compared with PS. In our paper, the duration of patency in the plastic stent group was longer than previously reported [15
]. This finding may be due to the result of the high number of patients with Bismuth type I strictures enrolled in our study, as PS placed in patients with more advanced disease tend to have shorter patency times [15
]. The use of SEMS in hilar CCA has multiple theoretical advantages, including a small and flexible delivery system that allows for better technical success and flexibility and a mesh network that enables not only a more stable conformation with the tortuous hilar anatomy but also drainage of subsegmental ducts. In our study, we found better TS when using SEMS, which could be related to the inherent characteristics of the stents, as long and inflexible large-bore plastic stents are difficult to place in complex strictures. Overall, the TS was high in both groups (88.3% in the PS group and 98.8
% in the SEMS group), and these differences were significant. More complex strictures showed greater differences in TS when comparing PS with SEMS. Even in Group 1, there were significant differences between the two stent types (95.7% versus 100%), and this finding reflects our large sample size. As expected, the FS of PS placement in patients with more advanced disease (Group 3) was lowest, not only in the ITT analysis but also in the PP analysis. This finding could be the result of the lack of side holes in this type of stent, which can result in reduced drainage from secondary branch ducts. In our study, PS were not routinely changed, which was the main cause of the significantly higher rate of late complications associated with stent failure in patients treated with PS. Overall, our study suggests that PS stenting is associated with worse outcomes than SEMS placement; therefore, endoscopic palliation with PS should be reserved for pre-surgical biliary drainage when needed and for patients with a short expected survival time.
The optimal technique for endoscopic palliative metal placement and the benefits of bilateral versus unilateral stenting are still controversial and highly debated. [De Palma et al. 20
] reported the only prospective randomized controlled study comparing unilateral and bilateral drainage using plastic stents in 157 patients. In the ITT analysis, unilateral placement had a significantly higher rate of stent insertion (88.6% vs. 76.9%) and a lower rate of complications and early cholangitis than bilateral placement. The authors concluded that the routine insertion of more than one stent would not be justified and that single stent insertion avoids the risk of further procedure-related complications and mortality. However these results need to be interpreted with caution because of some study biases. Information about stent patency and occlusion rates in both groups was not available. Furthermore subgroup analysis of patients was not done and there was a high number of patients with Bismuth type I stricture included for which placement of one stent is sufficient; thus it is impossible to find out how results might have been affected by their inclusion. A recent retrospective review of 46 patients with hilar malignant obstruction compared unilateral with bilateral SEMS stenting [22
]. Cumulative stent patency was significantly increased with bilateral stenting (median patency of 488
days vs. 210
0.009), especially in cases of CCA.
Endoscopic bilateral metal drainage poses particular challenges for endoscopists and has been considered to be more technically challenging than unilateral stenting [5
]. Various techniques have been described for bilateral SEMS placement, and in the absence of a truly Y-shaped SEMS, the creation of a Y-shaped stent configuration across the hilar bifurcation requires the placement of straight SEMS in either a nested or parallel configuration. Most endoscopists use the stent-within-stent technique previously described [23
] in this paper. Theoretically, stent-within-stent deployment may prevent bile influx into the area of stent overlap, leading to sludge formation. Furthermore, tumor ingrowth can occur more easily through an expanded stent mesh in the area of overlap. In addition, a nested SEMS configuration can be difficult to revise when cancer ingrowth obstructs the stents. To facilitate nested Y-shaped SEMS placement across the biliary confluence, SEMS placement with an extra-large open mesh in the central portion of the stent has been described. [Kim et al. 25
] reported their experience in 34 patients, in which TS was achieved in 85.3% patients, and the FS in the PP analysis was noted to be 100%. Stent obstruction occurred in 31% of the patients, and the median duration of stent patency was 239
Endoscopic bilateral metal stenting can also be accomplished using a parallel arrangement known as side-by-side deployment [5
]. It has been reported that this technique occasionally causes portal vein occlusion and increases the rate of cholangitis because of the excessive expansion of the bile duct by parallel stents [22
]. In some cases, this technique is impossible once one SEMS has been deployed, even if a second guidewire is already in the contralateral duct, because the first stent may press into the bile-duct wall and prevent passage of the delivery system for the second SEMS. One solution for this problem [5
] is to place a temporary plastic stent in a sub-hilar position, with 2 guidewires placed in the right and left hepatic ducts, before deployment of the first SEMS. After the placement of the first SEMS beside the plastic stent, the delivery catheter for the second SEMS is advanced into the contralateral duct, with the plastic stent maintaining the passage. Following the deployment of the second SEMS, the plastic stent is removed. Another solution to side-by-side SEMS placement is to use the novel SEMS with a 6
F delivery system. Using this technique, [Chennat et al. 27
] reported a TS of 100% (10/10 patients) and a median stent patency of 130
days. The side-by-side approach may facilitate subsequent endoscopic access to both drained ductal segments. A recent study [32
] compared side-by-side versus stent-within-stent deployment in 52 consecutive patients with malignant hilar obstruction. The authors found no differences in TS and FS between groups. Side-by-side deployment was associated with a higher rate of complications and a significantly better stent patency in Kaplan-Meyer analysis but not on multivariate analysis. Overall is not clear that a technique is better than the other and further studies on this issue are needed.
In our study, bilateral stenting was only reported in patients with Bismuth type II strictures because in our retrospective review, patients with Bismuth type III and IV strictures who underwent bilateral stenting were short in numbers and had an incomplete follow-up with important data missing; therefore, they could not be included in the study. Furthermore we avoid attempting bilateral stenting in very advanced disease because in cases of complex hilar strictures bilateral stenting may not be sufficient for complete drainage. In these patients complete drainage is achieved by 3 or more metal stents and even successful bilateral stenting in advanced disease can leave some ducts filled with contrast undrained [33
]. Injection of contrast into intrahepatic ducts that cannot be adequately drained should be avoided, as this practice is associated with worse outcomes [19
]. A recent study by Costamagna group suggests that multiple SEMS can be placed in hilar malignant strictures with promising results and that SEMS malfunctions can be easily managed [34
]. In our study using metal stents, bilateral placement was successful in 42/45 (94.3%) patients, and these results are comparable to those of other reports that found a TS rate between 80-100% [17
]. The median stent patency time of our bilateral metal stenting was 29
weeks, which was similar to the 130 to 239
day range [17
] reported by other authors, except for [Naitoh et al. 21
], who reported a median stent patency of 488
days. We found a significantly lower occlusion rate with bilateral metal stenting (11.9% versus 31.4%) compared with unilateral SEMS placement. Our bilateral stent occlusion rate compares favorably to previously reported values of between 23 and 40% [22
], although a recent study reported an occlusion rate of 6% [26
We also found that bilateral PS stenting was significantly better than unilateral PS placement in terms of patency and occlusion rates. The differences in patency were small (median 17
weeks; mean 15
weeks for unilateral versus median 18
weeks; mean 18
weeks for bilateral) but statistically significant. In contrast to the present study, [De Palma et al. 20
] did not report stent patency and occlusion rates. Furthermore, in the study of De Palma et al., the poor results of bilateral stenting from the ITT analysis with high rates of cholangitis and lower TS suggest that the opacification of both lobes was performed even in patients with advanced disease. As mentioned earlier in this paper we did not attempt to place 2 PS stents in patients with advanced disease (Bismuth III and IV strictures) where bilateral stenting may not be sufficient for complete drainage, leaving ducts undrained with associated cholangitis. Taken together, these findings suggest that bilateral stenting is better than unilateral stenting, and the best results are produced with bilateral metal placement especially in patients with Bismuth type II strictures.
We did not find significant differences in survival, although some of the patients with bilateral metal stenting had improved survival time especially those free from re-intervention and occlusion with cholangitis. Although cholangitis has a negative impact on survival time, survival depends mainly on the disease stage and we had more patients (49 vs. 72) with advanced disease (Group 3) in the SEMS group, and we can speculate that was the main reason why, in this study, SEMS placement did not translate into a survival benefit. A recent randomized trial comparing PS with SEMS has shown a survival benefit for patients treated with SEMS [13
]. In our study patients treated with SEMS had a lower rate of re-interventions and complications and we can speculate that can be translated into a better quality of life. Furthermore, although a cost/benefit analysis was not done, the lower number of re-interventions, days at hospital and hospital re-admission found in patients submitted to SEMS placement suggests a clear benefit for SEMS and in future studies that type of analysis, along with quality of life improvement should be undertaken.
Several limitations of our study should be taken into account. This was a retrospective study from a single tertiary center. Bilateral stenting was only reported in patients with Bismuth type II hilar strictures. The study was performed over 15
years using different materials, guidewires, stents and techniques, and this variation could have affected the rates of TS and FS, especially considering the plastic stents used in the 1990s. We suggest that further studies with a prospective randomized controlled design are needed in which bilateral and multiple metal stenting (in complex hilar strictures and advanced disease) can be compared with unilateral placement of SEMS across all Bismuth classifications of hilar CCA in terms of TS, stent patency, need for re-intervention, complications and improvement of the quality of life. In these proposed studies, different techniques for bilateral metal stent placement should also be compared.
The strengths of our study are the large number of patients included, both overall and in the different Bismuth classifications, when comparing plastic with metal stents, as well as the examination of bilateral stenting using both plastic and metal stents in a large subset of patients, which allowed comparisons between the outcomes. To our knowledge, this is the largest series of endoscopic palliation of hilar CCA ever reported.