Clinical Significance of Hepatic Resection in Hepatocellular Carcinoma

Sakon, Masato; Umeshita, Koji; Nagano, Hiroaki; Eguchi, Hidetoshi; Kishimoto, S; Miyamoto, Atsushi; Ohshima, Satoshi; Dono, Keizo; Nakamori, S; Gotoh, Mitsukazu; Monden, Morito

doi:10.1001/archsurg.135.12.1456

Cited by 129 publications

(97 citation statements)

References 32 publications

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“…[13][14][15][16][17] In this study, 64 of 157 HCCs demonstrated expression of biliary-specific CK (CK7 and/or CK19). Some investigators have postulated that biliary-specific CK-positive HCC might be generated through carcinogenesis of biliary marker-positive hepatic progenitor cells, 16,17,[23][24][25] which are capable of differentiating into both hepatocytes and biliary epithelial cells. [26][27][28] However, the histogenesis of such biliary marker-positive HCC has not been established.…”

Section: Discussionmentioning

confidence: 99%

“…[23][24][25][26][27] Some authors have postulated that early recurrence arises mainly from intrahepatic metastases, whereas late recurrence is more likely to be multicentric in origin. [24][25][26][27] It has been reported that postoperative multicentric hepatocarcinogenesis proceeds steadily in the non-cancerous liver portion, at a rate of 3.4% per year, even in the late follow-up period. On the other hand, residual intrahepatic metastasis is an early postoperative event, and the annual incidence of intrahepatic metastasis was 19.7% within 2 years after surgery.…”

Section: Discussionmentioning

confidence: 99%

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Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence

et al. 2003

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. Semiquantitative analysis of expression levels demonstrated a significant correlation between CK7 and CK19 expression. Of various clinicopathologic parameters, tumor differentiation exhibited a significant correlation with CK7 and CK19 expression. All 15 patients with CK19-positive HCC also had anti-HBc. Log-rank test revealed that CK7 expression, CK19 expression, high aspartate aminotransferase (AST) activity, low albumin concentration, portal invasion, intrahepatic metastasis, and severe fibrosis (cirrhosis) reduced the tumor-free survival rate. Multivariate analysis demonstrated that CK19 expression, intrahepatic metastasis, and severe fibrosis were independent predictors of postoperative recurrence, while CK7 expression was not. Twelve of 15 patients with CK19-positive HCC had tumor recurrence within 2 years after surgery, a significantly higher incidence of early recurrence than for CK19-negative HCC. The incidence of extrahepatic disease, especially lymph node metastasis, was significantly higher for patients with CK19-positive HCC. These findings indicate that CK19 expression is a predictor of early postoperative recurrence due to increased invasiveness. atients with intrahepatic cholangiocarcinoma (ICC), including combined hepatocellular and cholangiocarcinoma (cHCC-CC), exhibit poorer postoperative prognosis than those with hepatocellular carcinoma (HCC) due to more aggressive invasion and higher frequency of extrahepatic metastasis. [1][2][3][4][5][6] Thus, it is important for surgeons to take into account the presence of CC components within hepatic tumors in selecting a surgical strategy. 6) Cytokeratins (CK) are cytoskeletal intermediate filaments present in both normal and malignant epithelial cells.7) Characteristic combinations of CK polypeptides are expressed in different epithelia depending on the organ and/or type of differentiation. 7,8) In normal human liver, hepatocytes express CK8 and CK18, while bile duct cells also contain CK7 and CK19. [8][9][10][11] Since this CK pattern has been believed to be preserved during neoplastic transformation, HCC would be expected to express CK8 and CK18, but not CK7 or CK19. [8][9][10][11] Thus, expression of biliary-specific CK (CK7 and CK19) is widely used to distinguish ICC from HCC. 6,[8][9][10][11][12] Maeda et al. 6) recommended that HCC with "suggestive" CC components (incomplete gland formation without mucin production) should be categorized as cHCC-CC when "suggestive" CC components are positive for biliary markers. However, some HCCs have been reported to express biliary markers even with typical HCC growth pattern and morphologic appearance, [13][14][15][16][17] although the histogenesis of such biliary marker-positive HCC is not wellunderstood. A previous report indicated that without treatment, the prognosis is poorer for patients with biliary differentiation marker [AE1-AE3, cytokeratin (CK) 19]-positive HCC than for those without it.16) There have, however, been no studies on the clinical usefulness of biliary marker expression by HC...

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence

et al. 2003

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“…Recurrence is particularly frequent with HCV-related HCC, and a substantial proportion of recurrence, especially in late phase, is thought to represent de novo, or multicentric, hepatocarcinogenesis [396][397][398]. Therefore, it could be reasonably assumed that antiviral therapy would reduce the overall incidence of recurrence by preventing de novo carcinogenesis.…”

Section: Tertiary Prevention Of Hcv-related Hccmentioning

confidence: 99%

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

et al. 2010

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Introduction The Asian Pacific Association for the Study of the Liver (APASL) convened an international working party on the management of hepatocellular carcinoma (HCC) in December 2008 to develop consensus recommendations. Methods The working party consisted of expert hepatologist, hepatobiliary surgeon, radiologist, and oncologist from Asian-Pacific region, who were requested to make drafts prior to the consensus meeting held at Bali, Indonesia on 4 December 2008. The quality of existing evidence and strength of recommendations were ranked from 1 (highest) to 5 (lowest) and from A (strongest) to D (weakest), respectively, according to the Oxford system of evidence-based approach for developing the consensus statements. 123Hepatol Int (2010) 4: 439-474 DOI 10.1007/s12072-010-9165-7 Results Participants of the consensus meeting assessed the quality of cited studies and assigned grades to the recommendation statements. Finalized recommendations were presented at the fourth APASL single topic conference on viral-related HCC at Bali, Indonesia and approved by the participants of the conference.

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“…Conversely, disease recurrence due to multicentric liver carcinogenesis occurs throughout the observation period at a constant rate that varies with the severity of liver disease and the type of hepatitis virus infection. 3 Recent studies also have shown that early disease recurrence is associated with a worse prognosis compared with late disease recurrence. 4 -8 A considerable number of patients develop early postoperative massive intrahepatic disease recurrence with poor prognosis, even after curative resection of relatively small HCC tumors.…”

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Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma

Nakanishi¹,

Sakamoto

Yamasaki

et al. 2005

Cancer

213

173

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BACKGROUND Patients with hepatocellular carcinoma (HCC) who showed early massive disease recurrence due to hematogenous intrahepatic metastasis after curative resection had a poor prognosis. The authors previously reported that Akt phosphorylation was correlated with hematogenous intrahepatic metastasis, using HCC cell lines. METHODS The authors analyzed clinicopathologic features and the status of selected biologic markers, including phosphorylated Akt, to identify risk factors for early disease recurrence and poor prognosis in HCC. In the current series, 49 postoperative patients developed intrahepatic disease recurrence within 6 months (Group 1) and 86 patients remained disease recurrence free > 3 years after resection (Group 2). Group 1 was further divided into 2 subgroups: 19 patients who died of disease recurrence within a year after resection (Group 1A) and 27 patients who survived > 1 year (Group 1B). RESULTS Using univariate analysis, the risk factors for early disease recurrence were tumor size, macroscopic classification, tumor differentiation, microscopic capsule infiltration, microscopic portal vein (MPV) invasion, microscopic intrahepatic metastasis (MIM), and positive immunostaining for phosphorylated Akt, Ki‐67, and p53 (P < 0.05). The risk factors for poor prognosis were the number of intrahepatic metastases, tumor differentiation, and positive immunostaining for phosphorylated Akt and Ki‐67 (P < 0.05). Multivariate analysis revealed that the risk factors for early disease recurrence were MPV invasion, MIM, and positive immunostaining for phosphorylated Akt, and that the risk factors for poor prognosis were positive immunostaining for phosphorylated Akt and Ki‐67 (P < 0.05). CONCLUSIONS The current clinical study showed the critical involvement of Akt phosphorylation in the aggressiveness of HCC. The potential benefits of surgery should be assessed carefully in patients with any of these risk factors. Cancer 2005. © 2004 American Cancer Society.

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Clinical Significance of Hepatic Resection in Hepatocellular Carcinoma

Cited by 129 publications

References 32 publications

Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence

Cytokeratin 19 expression in hepatocellular carcinoma predicts early postoperative recurrence

Asian Pacific Association for the Study of the Liver consensus recommendations on hepatocellular carcinoma

Akt phosphorylation is a risk factor for early disease recurrence and poor prognosis in hepatocellular carcinoma

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