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

Takahiro Ito; Naohisa Kuriyama; Yuji Kozuka; Haruna Komatsubara; Ken Ichikawa; Daisuke Noguchi; Aoi Hayasaki; Tekehiro Fujii; Yusuke Iizawa; Hiroyuki Kato; Akihiro Tanemura; Yasuhiro Murata; Masashi Kishiwada; Shugo Mizuno; Masanobu Usui; Hiroyuki Sakurai; Shuji Isaji

doi:10.1186/s12885-020-6695-9

Table 3 Characteristics in the patients with or without neoadjuvant therapy

From: 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

	Patients with neoadjuvant therapy (n = 36)			Patients without neoadjuvant therapy (n = 42)
Factors	Low TB (n = 25)	High TB (n = 11)	p value	Low TB (n = 29)	High TB (n = 13)	p value
Age (y.o.)	70 (49–84)	69 (39–77)	0.520	67 (40–87)	69 (44–78)	> 0.999
Gender (Male / Female)	13 / 12	9 / 2	0.091	18 / 11	7 / 6	0.616
Type of Neoadjuvant therapy
Chemotherapy	17 (68.0%)	8 (72.7%)	0.777	–	–	–
Chemoradiotherapy	8 (32.0%)	3 (27.3%)
PTPE	4 (16.0%)	2 (18.2%)	0.871	8 (27.6%)	4 (30.8%)	0.833
Initial tumor marker
CEA (ng/mL)	3.7 (1.3–14.6)	3.9 (0.9–16.3)	0.685	2.9 (0.6–38.4)	2.6 (0.7–28.0)	0.936
CA19–9 (U/mL)	61.5 (1.0–7898)	140.3 (1.0–1325)	0.435	87.5 (7.0–1115.7)	65.1 (1.0–9278)	0.872
Preoperative tumor marker
CEA (ng/mL)	2.6 (0.9–9.6)	3.6 (1.1–24.4)	0.151	3.0 (0.7–32.2)	2.6 (0.5–32.3)	0.788
CA19–9 (U/mL)	33.2 (1.0–11,659)	151.3 (1.0–1158)	0.086	67.3 (13.7–977.2)	65.1 (1.0–9278)	0.936
Type of liver resection^a						0.114
No liver resection	0	0		5 (17.2%)	0
S1,5,6,7,8	9 (36.0%)	3 (27.3%)		10 (34.5%)	5 (38.5%)
S1,4,5,6,7,8	1 (4.0%)	1 (9.1%)		2 (6.9%)	3 (23.1%)
S1,2,3,4	9 (36.0%)	6 (54.5%)		7 (24.1%)	4 (30.8%)
S1,2,3,4,5,8	3 (12.0%)	1 (9.1%)		0	1 (7.7%)
Others	3 (12.0%)	0		5 (17.2%)	0
HPD	0	1 (9.1%)	0.126	3 (10.3%)	0	0.229
Combined HA and/or PV resection	12 (48.0%)	10 (90.9%)	0.015	11 (37.9%)	6 (46.2%)	0.616
Operation time (min)	625 (383–965)	672 (422–972)	0.261	597 (403–1030)	610 (435–746)	0.914
Blood loss (ml)	2212 (505–6916)	2170 (1459–6012)	0.612	1964 (166–9907)	1830 (587–3870)	0.727
Histological type
G1, 2 / G3	25 / 0 (0%)	6 / 5 (45.5%)	< 0.001	26 / 3 (10.3%)	12 / 1 (7.7%)	0.787
UICC 8th
pT: T0–3 / T4	19 / 6 (24.0%)	4 / 7 (63.6%)	0.023	23 / 6 (20.7%)	8 / 5 (38.5%)	0.226
pN: N0 / N1–2	17 / 8 (32.0%)	3 / 8 (72.7%)	0.023	16 /13 (44.8%)	4 / 9 (69.2%)	0.143
M: M0 / M1^a	25 / 0 (0%)	8 / 3 (27.3%)	0.006	28 / 1 (3.4%)	11 / 2 (15.4%)	0.165
Residual tumor status
R0 / R1 / R2 (M1 / margin positive)	17 / 6 / 2 (0 / 2)	6 / 1 / 4 (3 / 1)	0.092	21 / 5 / 3 (1 / 2)	9 / 2 / 2 (2 / 0)	0.895
Postoperative hospital stay (days)	45 (13–161)	37 (17–136)	0.308	49 (25–117)	56 (18–325)	0.374
Postoperative complication ≥ grade III^b	13 (52.0%)	6 (54.5%)	0.888	9 (31.0%)	4 (30.8%)	0.986
Postoperative chemotherapy	19 (76.0%)	9 (81.8%)	0.699	18 (62.1%)	10 (76.9%)	0.345

Patients in high TB groups had a significantly higher rate of combined vascular resection in patients received neoadjuvant therapy. In patients without preoperative therapy, there were no significant differences in preoperative and operative factors. Among 36 patients with neoadjuvant therapy, the rates of G3, T4, N1–2, and M1 in high TB group were significantly higher than those in low TB. As for postoperative factors, there were no differences between two groups in both patients with and without neoadjuvant therapy
^aM1 include 3 patients with intrahepatic metastasis. ^b Clavien-Dindo classification

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