Hilar CC has an extremely poor prognosis, with an average five-year survival rate of 5%-10%. Surgery provides the only possibility for a cure, but due to its anatomical location and natural history, the disease is locally advanced in most patients at the time of diagnosis. Therefore, effective palliation to alleviate symptoms associated with jaundice and the prevention of biliary sepsis are the fundamental goals for most patients with hilar CC[5
]. Although relief of biliary obstruction by endoscopic placement of metal stents is regarded as an optimal palliative measure in hilar CC, the clinical course after even successful stent insertion is one of disease progression and death from liver failure or cholangitis within 4-9 mo[10
]. This clinical course[1
] is related to the ability to decompress affected proximal segments[2
] and recurrent stent occlusion, because these stents are unable to remodel malignant tissues[11
PDT is an evolving therapy for treatment of cancers that are resistant to standard oncologic treatment. PDT involves the injection of an intravenous photosensitizing drug followed by endoscopic application of light to the tumor bed. The interaction between light and the photoagent causes death of cancer cells and tumor thrombosis by generating oxygen free radicals. PDT is currently being used for cases of hilar cholangiocarcinoma[12,13
]. Even in patients with advanced hilar CC, PDT has been shown to improve survival, quality of life, and to have a performance superior to that of biliary stenting in uncontrolled and randomized controlled trials[6,14-16
]. In our study, Kaplan-Meier analysis demonstrated improved survival in the PDT group compared with the stent-only group (356 d vs
230 d, P
= 0.006), in accordance with previous reports[11,14,17
Effective palliation is essential, because biliary drainage and prevention of cholestasis are crucial for prevention of pruritus, cholangitis, and death in patients with hilar CC. The approach to palliative decompression has evolved from surgery and percutaneous to endoscopic management in order to prevent cholestasis and improve mortality. Endoscopy of hilar CCs is generally challenging and complex due to the involvement of multiple bile ducts requiring two or more stents; indeed, patency rates of endobiliary stents are lower than those of distal tumors[16,18,19
]. Moreover, the efficacy of endoscopic stenting in a hilar CC is often limited by stent patency, which is related to proximal tumor obstruction, because the stent does not affect tissue remodeling, unlike benign conditions[11,20,21
]. To address this issue, multiple studies have investigated the positive effects of the combination of bile duct stenting with PDT on patient survival[6,14,15
]. However, a paucity of information exists regarding the effect of PDT on stent patency.
In our study, metal stent patency was longer in the PDT group than in the stent-only group. The median stent patency was 244 d in the PDT group and 177 d in the control group (P
= 0.002). The main causes of obstruction of metal stents in bile ducts is tumor ingrowth or overgrowth[22
]. PDT offers the possibility of tumor “remodeling”, which can enhance or prolong the decompression effect[23
]. Accepting this hypothesis, the ability of PDT to destroy cancer cells and lessen cholestasis may prolong stent patency. In this context, this study is meaningful because the longer stent patency that is achieved by PDT may diminish the need for further procedures, such as stent revision or percutaneous biliary drainage, improving the quality of life of hilar CC patients whose prognosis is poor.
This study was limited because of its retrospective nature and small sample size. Thus it may be not possible to reach statistical significance in terms of differences in overall survival between the groups. Because hilar CC is a rare malignancy and PDT is offered at few tertiary centers in South Korea, inclusion of sufficient patients to complete a well-designed palliative study is problematic. However, the study population was derived from a larger cohort of patients with CC, who were followed until death. Median survival of this cohort was comparable to that of other cohorts reported in the literature, which may decrease the possibility of significant selection bias.
In summary, metal stenting after one session of PDT may be safe with acceptable complication rates. The PDT group was associated with a significantly longer stent patency period and patient survival compared with the control group in patients with unresectable hilar CC. A prospective randomized multicenter study is required to confirm these data.