Clinical implications and perspectives of portal venous circulating tumor cells in pancreatic cancer

Table 1 Comparison of the circulating tumor cell detection rate and number between peripheral and portal venous blood in patients with pancreatic cancer

Ref.	Patients, N	Cancer stage	Blood source	PoV sample	CTC isolation method	Detection rate, % (n/N)	Number of CTCs (mean ± SD)	Main findings
Catenacci et al[22], 2015	18	All	PoV, PV	EUS-guided	CellSearch	PoV: 100 (18/18), PV: 22.2 (4/18)	PoV: 118.4 ± 36.8/7.5 mL, PV: 0.8 ± 0.4/7.5 mL	Both the detection rate and number of CTCs were higher in the PoV than in the PV
Tien et al[29], 2016	41	Resectable	PoV, PV	Intraoperative	CMx platform	PoV: 58.5 (24/41), PV: 39.0 (16/41)	PoV: 313.4/3 mL, PV: 92.9/3 mL	Both the detection rate and number of CTCs were higher in the PoV than in the PV
Liu et al[23], 2018	29	Locally advanced, metastatic	PoV, PV	Transabdominal US-guided	ClearCell FX system	PoV: 100 (29/29), PV: 54 (8/14)	PoV: 282.0/7.5 mL, PV: 21.0/7.5 mL	Both the detection rate and number of CTCs were higher in the PoV than in the PV
Chapman et al[30], 2020	171	All	PoV, PV	EUS-guided	CellSearch	PoV: 100 (17/17), PV: 23.5 (4/17)	PoV: 118.4 (1-516)/7.5 mL2, PV: 0.67 (0-7)/7.5 mL2	Both the detection rate and number of CTCs were higher in the PoV than in the PV
Song et al[37], 2020	32	Resectable	PoV, PV	Intraoperative	Microfabricated Filter	PoV: 62.5 (20/32), PV: 68.8 (22/32)	Not shown	No differences in detection rate and number of CTCs between the PoV and PV
Padillo-Ruiz et al[38], 2021	35	Resectable	PoV, CV	Intraoperative	IsoFluxTM	PoV: 100 (35/35), CV: 100 (35/35)	PoV: 310 (132.1-446.0)/mL3, CV: 405.7 (130.7-533.8)/mL3	No differences in detection rate and number of CTCs between the PoV and CV
White et al[40], 2021	34	Resectable	PoV, PV	Intraoperative	CellSearch	PoV: 71 (22/31), PV: 50 (11/22)	Not shown	No differences in detection rate and number of CTCs between the PoV and PV
Zhang et al[31], 2021	31	All	PoV, PV	EUS-guided	Cyttel detection kit	PoV: 97 (31/30), PV: 87 (27/31)	PoV: 10/5 mL4, PV: 6/5 mL4	Number of CTCs was higher in the PoV than in the PV
Choi et al[32], 2022	33	All	PoV, PV	Intraoperative	SMART BIOPSYTM	PoV: 75.8 (25/33), PB: 92.1 (23/28)	PoV: 2.5/7.5 mL4, PV: 1/7.5 mL4	Number of CTCs was higher in the PoV than in the PV

¹Included two patients with cholangiocarcinoma and one with ampullary cancer.

²Expressed as mean (range).

³Expressed as median (range).

⁴Expressed as median.

PoV: Portal vein; PV: Peripheral vein; PB: Peripheral blood; CV: Central vein; CTCs: Circulating tumor cells; EUS: Endoscopic ultrasound; US: Ultrasound.

Table 2 Clinical impact of portal venous circulating tumor cells on prognosis in patients with pancreatic cancer

Ref.	Patients, N	Cancer stage	Blood source	PoV sample	CTC isolation method	OS, median (95%CI)	PFS, median (95%CI)	Main findings
Bissolati et al[36], 2015	20	Resectable	PoV, PV	Intraoperative	CellSearch	CTCs (-): 23.1 (15.1-31.1) mo, CTCs (+): 26.2 (18.7-33.8) mo	CTCs (-): 19.4 (10.9-27.8) mo, CTCs (+): 18.9 (10.4-27.3) mo	PoV CTC-positive patients had a higher rate of liver metastases than CTC-negative patients.
Tien et al[29], 2016	41	Resectable	PoV, PV	Intraoperative	CMx platform	Not shown	Not shown	Number of CTCs in the PoV was the only significant risk factor of liver metastases within 6 mo after surgery.
Liu et al[23], 2018	29	Locally advanced, metastatic	PoV, PV	Transabdominal US-guided	ClearCell FX system	CTCs < 150/7.5 mL: 19.8 (16.8-25.4) wk, CTCs ≥ 150/7.5 mL: 9.2 (7.8-11.8) wk	Not shown	Higher CTC count in the PoV was associated with liver metastases and shorter OS.
Chapman et al[30], 2020	14	All	PoV, PV	EUS-guided	CellSearch	CTCs < 185/7.5 mL: 40.0 wk, CTCs ≥ 185/7.5 mL: 12.8 wk	CTCs < 185/7.5 mL: 75.4 wk, CTCs ≥ 185/7.5 mL: 29.5 wk	Every 10 CTC increase in the PoV was associated with a 5% and 4% increase in the likelihood of progression and death, respectively.
Padillo-Ruiz et al[38], 2021	35	Resectable	PoV, CV	Intraoperative	IsoFluxTM	CTCs < 185/mL: 24.5 (19.6-29.4) mo, CTCs ≥ 185/mL: 10.0 (7.4-12.5) mo	Not shown	Higher number of CTCs in the PoV was associated with poorly differentiated cancer and shorter OS.
Pan et al[48], 2021	32	Resectable	PoV, PV	Intraoperative	CanPatrolTM	Not shown	Not shown	Mesenchymal CTCs in the PoV ≥ 1/5 mL was a significant risk factor for metastasis, PFS, and OS.
White et al[40], 2021	34	Resectable	PoV, PV	Intraoperative	CellSearch	Not shown	Not shown	Patients with undetectable PoV CTCs showed a higher 18-mo survival rate (100%).
Zhang et al[31], 2021	31	All	PoV, PV	EUS-guided	Cyttel detection kit	Not shown	Not shown	The number of PoV CTCs, especially mesenchymal CTCs, was positively correlated with the advanced stage.
Choi et al[32], 2022	33	All	PoV, PV	Intraoperative	SMART BIOPSYTM	CTCs < 3/7.5 mL: NA, CTCs ≥ 3/7.5 mL: 16.5 mo	CTCs < 3/7.5 mL: 13.4 mo, CTCs ≥ 3/7.5 mL: 7.5 mo	Higher number of PoV CTCs was associated with higher stage, lymph node metastasis, and poorer PFS and OS.
Song et al[37], 2020	32	Resectable	PoV, PV	Intraoperative	Microfabricated Filter	CTCs < 1/10 mL: 40.0 mo, CTCs ≥ 1/10 mL: 17.6 mo	Not shown	CTC count in the PoV was not significantly associated with OS.

CTCs: Circulating tumor cells; PoV: Portal vein; PV: Peripheral vein; OS: Overall survival; PFS: Progression free survival; US: Ultrasound; EUS: Endoscopic ultrasound; NA: Not achieved.