Abstract
BackgroundTumor budding (TB) is used as an indicator of poor prognosis in various cancers. However, studies on TB in perihilar cholangiocarcinoma are still limited. We examined the significance of TB in resected perihilar cholangiocarcinoma with or without neoadjuvant therapy.MethodsSeventy-eight patients who underwent surgical resection at our institution for perihilar cholangiocarcinoma from 2004 to 2017, (36 with neoadjuvant therapy), were enrolled in this study. TB was defined as an isolated cancer cell or clusters (< 5 cells) at the invasive front and the number of TB was counted using a 20 times objective lens. Patients were classified into two groups according to TB counts: low TB (TB < 5) and high TB (TB ≥5).ResultsIn this 78 patient cohort, high TB was significantly associated with advanced tumor status (pT4: 50.0% vs 22.2%, p = 0.007, pN1/2: 70.8% vs 39.6%, p = 0.011, M1: 20.8% vs 1.9%) and higher histological grade (G3: 25.0% vs 5.7%, p = 0.014). Disease specific survival (DSS) in high TB was significantly inferior compared to that in low TB group (3-y DSS 14.5% vs 67.7%, p < 0.001). Interestingly, DSS in high TB showed similar to survival in unresected patients. In addition, high TB was also associated with advanced tumor status and poor prognosis in patients with neoadjuvant therapy. Multivariate analysis identified high TB as an independent poor prognostic factors for DSS (HR: 5.206, p = 0.001).ConclusionThis study demonstrated that high TB was strongly associated with advanced tumor status and poor prognosis in resected perihilar cholangiocarcinoma patients. High TB can be a novel poor prognostic factor in resected perihilar cholangiocarcinoma regardless of neoadjuvant therapy.
Highlights
Tumor budding (TB) is used as an indicator of poor prognosis in various cancers
Ogino et al [11] demonstrated that high TB grade was an independent adverse prognostic factor in 195 perihilar cholangiocarcinoma patients by multivariate analysis
Tanaka et al [13] demonstrated that TB tumor budding was a significant prognostic factor in 107 cases of intrahepatic cholangiocarcinoma and 54 cases of perihilar cholangiocarcinoma
Summary
Tumor budding (TB) is used as an indicator of poor prognosis in various cancers. Surgical resection remains the only curative treatment for perihilar cholangiocarcinoma, resection is considered a significant challenge for surgeons, and the prognosis of nonresected patients is very poor [3]. TB is widely used in the field of colorectal carcinoma as a prognostic factor and a correlated factor with advanced stage [6]. Okubo et al [12] reported the prognostic significance of TB in resected 299 patients with biliary tree carcinoma (intrahepatic: n = 47 (16%), extrahepatic: n = 144 (48%), gallbladder: n = 50 (17%), ampulla: n = 58 (19%)). Tanaka et al [13] demonstrated that TB tumor budding was a significant prognostic factor in 107 cases of intrahepatic cholangiocarcinoma and 54 cases of perihilar cholangiocarcinoma
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