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High tumor budding is a strong predictor of poor prognosis in the resected perihilar cholangiocarcinoma patients regardless of neoadjuvant therapy, showing survival similar to those without resection

  • Ito, Takahiro1
  • Kuriyama, Naohisa1
  • Kozuka, Yuji2
  • Komatsubara, Haruna2
  • Ichikawa, Ken1
  • Noguchi, Daisuke1
  • Hayasaki, Aoi1
  • Fujii, Tekehiro1
  • Iizawa, Yusuke1
  • Kato, Hiroyuki1
  • Tanemura, Akihiro1
  • Murata, Yasuhiro1
  • Kishiwada, Masashi1
  • Mizuno, Shugo1
  • Usui, Masanobu1
  • Sakurai, Hiroyuki1
  • Isaji, Shuji1
  • 1 Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan , Tsu (Japan)
  • 2 Mie University Hospital, 2-174 Edobashi, Tsu, Mie, 514-8507, Japan , Tsu (Japan)
Published Article
BMC Cancer
Springer (Biomed Central Ltd.)
Publication Date
Mar 12, 2020
DOI: 10.1186/s12885-020-6695-9
Springer Nature


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.

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