Hepatocellular carcinoma with tumor thrombus in bile duct: A proposal of new classification according to resectability of primary lesion

Table 1 Basic clinical data of the patients of hepatocellular carcinoma with tumor thrombus in bile duct

No.	Sex	Age	Jaundice before treatment for BDTT		AFP, ng/mL	BDTT with first occurring/recurrent HCC or metastasis	BDTT with PVTT	History of hepatectomy before BDTT diagnosed	Time interval from hepatectomy to diagnosis of BDTT	Location of BDTT	Classification		Treatment for BDTT	Survival state during follow-up
			T-bil, μmol/L	D-bil, μmol/L							Satoh	Ours
1	M	58	16.0	0.0	9420.00	fo-HCC	Yes	/	/	IBD	N/A4	I	Resected with HCC	Dead
2	M	68	53.1	34.4	97.23	rHCC	No	Yes	6 yr	CBD	3	III	Extraction	Dead
3	M	70	16.7	6.2	737.00	rHCC/LgMT/ACMT	Yes	Yes	19 mo19 mo2	IBD	N/A5	IV	Lenvatinib+Sintilizumab	Alive with tumor
4	M	65	145.5	76.7	176.54	fo-HCC	No	/	/	LHD/RHD/CHD	2	IIa	Extrahepatic bile duct resection3	Dead
5	M	75	146.9	51.90	1.37	No	No	/	/	CBD	3	III	Extraction	Alive with tumor
6	M	68	224.1	183.8	1.84	rHCC/LNMT/ACMT	No	Yes	2 mo	CBD	3	III	Extraction	Dead
7	F	58	37.2	27.6	45.22	fo-HCC	No	/	/	CBD	3	IIb	Extraction	DFS

¹The patient received his first hepatectomy for HCC.

²The patient received his second operation for removal of the recurrent isolated HCC lesion in abdominal cavity.

³The patient received right hepatectomy accompanied with extrahepatic bile duct resection.

⁴BDTT diagnosed under microscope.

⁵BDTT located in the left intrahepatic bile ducts. ACMT: Abdominal cavity metastasis; AFP: Alpha-fetoprotein; BDTT: Bile duct tumor thrombi; CBD: Common bile duct; CHD: Common hepatic duct; D-bil: Direct bilirubin; DFS: Disease free survival; fo-HCC: First occurring hepatocellular carcinoma; IBD: Intrahepatic bile duct; LgMT: Lung metastasis; LHD: Left hepatic duct; LNMT: Lymph node metastasis; PVTT: Portal vein tumor thrombus; rHCC: Recurrent hepatocellular carcinoma; RHD: Right hepatic duct; T-bil: Total bilirubin.

Table 2 Results of antigens and antibodies tests of hepatitis B virus and hepatitis C virus

No.	HBsAg		HBsAb		HBeAg		HBeAb		HBcAb		HBcIgM		HCV-AB-IgG
	Qualitative	Value (IU/mL)	Qualitative	Value (mIU/mL)	Qualitative	Value (S/CO)	Qualitative	Value (S/CO)	Qualitative	Value (S/CO)	Qualitative	Value (S/CO)	Qualitative	Value (S/CO)
1	+	> 250	-	0.00	-	0.304	+	0.02	+	13.70	-	0.26	-	0.02
2	-	0	-	4.05	-	0.270	+	0.02	+	8.68	-	0.05	-	0.09
3	-	0.01	+	97.28	-	0.397	+	0.07	+	9.79	-	0.14	+	1.71
4	+	> 250	-	0.00	-	0.107	+	0.04	+	15.80	-	0.07	-	0.01
5	+	16.94	-	5.43	-	0.317	+	0.01	+	7.96	-	0.15	-	0.14
6	+	161.53	-	0.19	-	0.230	+	0.01	+	8.46	-	0.08	-	0.06
7	-	0.02	-	0.00	-	0.400	+	0.09	+	13.57	-	0.05	-	0.03

HBcAb: Hepatitis B core antibody; HBcIgM: IgM antibodies to hepatitis B core antigen; HBeAb: Hepatitis B e antibody; HBeAg: Hepatitis B e Antigen; HBsAb: Hepatitis B surface antibody; HBsAg: Hepatitis B surface antigen; HCV-AB-IgG: IgG antibodies to hepatitis C.

Table 3 Pathological characteristics of bile duct tumor thrombi and primary or recurrent hepatocellular carcinoma lesions when bile duct tumor thrombi was diagnosed

No.	Pathological characteristics of primary or recurrent HCC lesion when BDTT was diagnosed							Pathological characteristics of BDTT
	Location	Size in cm	Morphology of tumor		Differentiation	Necrosis	Extrahepatic infiltration	Location	Size incm	Infiltration outward bile duct	Differentiation
			Macroscopic	Microscopic
1	Left lobe	8 × 6 × 6	Fish-meat like	Platelet/nested/papillary	Poor	+	Full thickness of the stomach wall	LIBD	MicroscopicBDTT	No	Poor
2	Cannot be detected	/	/	/	/	/	/	CBD	5.5 × 4 × 2	No	Moderate
31	Cannot be detected	/	/	/	/	/	/	IBD	/	/	/
4	Right lobe	9 × 4 × 9	Fish-meat like	Nodular	Moderate	+	No	LHD/RHD/CHD	5 × 3 × 3	Yes	Moderate
52	Cannot be detected	/	/	/	/	/	/	CBD	6 × 2 × 2	No	Poor
62	Cannot be detected	/	/	/	/	/	/	CBD	3.5 × 3.5 × 2	No	Moderate
7	Right lobe	7 × 4 × 1	Fish-meat like	Large area of necrosis	Moderate	+	No	CBD	3 × 3 × 2	No	Moderate

¹The patient had metastatic hepatocellular carcinoma lesions in the liver, lymph nodes and abdominal cavity so that adjunctive therapy was adopted without surgery.

²No primary or recurrent hepatocellular carcinoma tumors could be detected so that only bile duct tumor thrombi was extracted. BDTT: Bile duct tumor thrombi; CBD: Common bile duct; CHD: Common hepatic duct; HCC: Hepatocellular carcinoma; IBD: Intrahepatic bile duct; LHD: Left hepatic duct; LIBD: Left intrahepatic bile duct; RHD: Right hepatic duct.

Table 4 Summary of studies focused on misdiagnosis of hepatocellular carcinoma with bile duct tumor thrombi

No.	Ref.	Time period	No. of included patients of HCC with BDTT	No. of misdiagnosed patients, %	Diagnostic method	Misdiagnosed as	Treatment	Prognosis
1	Zhou et al[12], 2020	2011/01-2018/08	58	32 (55.2)	CT	Hilar cholangiocarcinoma	Hepatectomy	DFS: 16.1 mo
							Hepatectomy with bile duct excision	DFS: 7.3 mo
2	Zheng et al[13], 2014	2007/01-2012/12	-	5 (-)	CT/MRI/ERCP	Choledocholithiasis and cholangitis	ENBD and choledochojejunostomy	POS: 6-22 mo1 alive4 dead
							thrombus extraction
							ENBD
3	Long et al[14], 2010	2000/01-2008/11	61	4 (66.7)1	US/CT/MRI/ERCP	Choledocholithiasis and cholangiocarcinoma	Hepatectomy	Not mentioned
							thrombus extraction
4	Peng et al[15], 2005	1984/07-2002/12	53	3 (5.7)	US/CT/MRI	Hilar cholangiocarcinoma	PTCD + biliary stent	Median survival of 2-17 mo
							Hepatectomy with thrombus extraction
							TACE
							thrombus extraction
							Hepatectomy
5	Qin et al[16], 2004	1987/06-2003/01	34	9 (26.5)	US/CT	Cholangiocarcinoma	liver resection and thrombus extraction	Survival ≤ 1 yr 10Survival > 1 yr 20Survival > 3 yr 3Survival > 15 yr 1
							thrombus extraction combined with TACE

¹All of the patients had bile duct tumor thrombi without obvious intrahepatic hepatocellular carcinoma mass. BDTT: Bile duct tumor thrombi; CT: Computed tomography; DFS: Disease free survival; ENBD: Endoscopic nasobiliary drainage; ERCP: Endoscopic retrograde cholangiopancreatography; HCC: Hepatocellular carcinoma; MRI: Magnetic resonance imaging; POS: Postoperative survival; PTCD: Percutaneous transhepatic cholangio drainage; TACE: Transhepatic arterial chemotherapy and embolization; US: Ultrasound.