Abstract
BACKGROUND: Surgical resection is the only curative treatment for perihilar cholangiocarcinoma (pCCA); however, the majority of patients experience postoperative recurrence. While recurrence typically occurs within five years after surgery, recurrence after prolonged relapse-free survival has been occasionally observed. This study aimed to investigate the clinicopathological factors associated with late recurrence of pCCA. METHODS: Among the 258 consecutive patients who underwent radical hepatectomy with extrahepatic bile duct resection for pCCA at our institution between 1996 and 2019, 9 patients (3.4%) had postoperative recurrence more than five years after surgery. For this study, late recurrence was defined as recurrence occurring more than five years after surgery. Clinicopathological characteristics of late recurrence (beyond five years) were analyzed and compared with those of the patients who remained recurrence-free for over 12 years (no recurrence group, n=14). RESULTS: Among the nine cases of late recurrence, local recurrence was the most common, followed by liver metastasis. Chemotherapy was the primary treatment after recurrence, while surgical resection was performed in two cases. A comparison between the late recurrence and no recurrence group revealed similar demographics; however, the late recurrence group exhibited significantly higher cases with pathological perineural invasion (p=0.016), hepatopancreatoduodenectomy (HPD) (p=0.034) and neoadjuvant chemotherapy (NAC) (p=0.034) were performed significantly more frequently in the no recurrence group. Notably, all late recurrence cases demonstrated positive perineural invasion. CONCLUSIONS: The presence of pathological perineural invasion is significantly associated with late recurrence of pCCA. This finding provides significant insights for the long-term follow-up and managemant of pCCA patients.