Significant Influence of Accompanying Chronic Hepatitis Status on Recurrence of Hepatocellular Carcinoma after Hepatectomy

Ko, Saiho; Nakajima, Yoshiyuki; Kanehiro, Hiromichi; Hisanaga, Michiyoshi; Aomatsu, Yukio; Kin, Tastuya; Yagura, Kazuaki; Ohyama, Takao; Nishio, Kazushi; Ohashi, Kazuhiko; Sho, Masayuki; Yamada, Takatsugu; Nakano, Hirofumi

doi:10.1097/00000658-199611000-00001

Cited by 137 publications

(100 citation statements)

References 20 publications

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“…It also must be noted that the histologic status of the noncancerous regions of the liver influence tumor recurrence, especially secondary growths of HCC. 30,[33][34][35] Interestingly, 2 recent articles dealing with the prognosis of patients with HCC have been correlated with physical parameters such as performance status and the presence or absence of symptoms. 36,37 However, we did not compare those classifications in this study, because the physical parameters would have been difficult to determine and organize retrospectively.…”

Section: Discussionmentioning

confidence: 99%

Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients

2001

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To reliably estimate the prognoses of patients with hepatocellular carcinoma (HCC), both liver function and tumorrelated factors should be accounted for. However, there are few worldwide staging systems that assess prognostic value in the context of selecting individual patients for randomized stratification in therapeutic and clinical trials. We investigated the value of known prognostic systems and verified the usefulness of the new scoring system proposed by the Cancer of the Liver Italian Program (CLIP), as determined from 662 Japanese patients. A retrospective analysis of the HCC diagnoses at 4 Japanese institutions from 1990 and 1998 was performed. Overall survival was the only end point used in the analysis. Discriminatory ability and predictive power of the CLIP score were compared with those of Okuda stage and AJCC TNM stage. Compared with the Okuda and AJCC staging systems, the CLIP score's enhanced discriminatory capacity, which was tested by the linear trend test and Harrels' c-index, revealed a class of patients with an impressively more favorable prognosis and another class with a relatively shorter life expectancy. Moreover, the likelihood ratio test showed that the CLIP score had additional homogeneity of survival within each score above that of the Okuda stage or the AJCC stage. This was true for 3 subgroups of patients who received surgery, transcatheter arterial chemoembolizations, and percutaneous ethanol injections. Collectively, these findings indicate that the CLIP score has the highest stratification ability with regard to prognosis in patients with HCC. The CLIP score could be used internationally to stratify randomization groups in therapeutic and clinical trials. (HEPATOLOGY 2001; 34:529-534.) Hepatocellular carcinoma (HCC) is a relatively common malignant tumor worldwide, accounting for almost one million deaths annually. In the past 2 decades, some newly developed therapeutic options have been applied with varying degrees of success (i.e., liver resection and transplantation, transcatheter arterial chemoembolization [TACE], and percutaneous ethanol injection [PEI]). To reliably estimate the prognoses of patients with HCC, both liver function and tumor-related factors should be accounted for 1-3 ; however, there are few data collection systems that include both. 4 In fact, the well-known UICC and AJCC staging (TNM) criteria do not define the relative prognostic weight of variables, in terms of residual liver function. 5 Although several studies have examined predictive factors for prognosis in relation to treatment, 1,6-16 most of these have been performed in Asian institutions. Accordingly, these facilities and patient populations possess early detection plans, risk factors for primary liver cancer, a high proportion of expanding tumors, and differing rates of resectability, respectively, with regard to those in Western countries. 2,9,12

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Section: Discussionmentioning

confidence: 99%

Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients

2001

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“…These patients would receive an unnecessary graft in primary OLT. Although such a low recurrence rate is difficult to obtain in the general population of HCC patients submitted to resection, it can be achieved in selected groups, such as patients with low inflammatory activity 38 and low transaminase values 39 or with the advent of medications that lower the recurrence rate, as shown in a pilot study using retinoids. 40 Cost analysis in our model showed that the cost per additional year offered by the strategy of primary transplantation varied between $25,530 and $92,422 according to the different scenarios.…”

Section: Discussionmentioning

confidence: 99%

Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: An outcome-oriented decision analysis

et al. 2000

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Two treatments are accepted for patients with solitary hepatocellular carcinoma Յ5 cm in size and with preserved hepatic function: (1) liver resection, which can be performed without delay but has a high recurrence rate, and (2) liver transplantation, which has a better long-term survival, but is not easily available because grafts are scarce. A third possibility is to offer liver resection first and liver transplantation for tumor recurrence or deteriorating liver function (''salvage'' transplantation). We investigated the implications of such a strategy with a Markov-based decision analytic model. Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide, and its incidence is increasing in the western world because of the epidemics of the hepatitis C virus. 1 In patients aged less than 65 years, 2 therapies are currently accepted for early HCC (Յ5 cm): partial hepatectomy (PH) and orthotopic liver transplantation (OLT). 2,3 Although studies comparing the 2 treatments are retrospective and concern patients with disparate tumor characteristics and liver function, 4-6 it is agreed that OLT is preferable to partial hepatectomy in patients with hepatic insufficiency and in patients with more than 1 tumor, in whom the results of liver resection are poor.Patients with single tumors and preserved liver function present a therapeutic dilemma. Partial hepatectomy can cure the tumor immediately, with low mortality. The underlying cirrhosis, however, is responsible for a high recurrence rate, and the patient is exposed to the long-term complications of portal hypertension and hepatocellular failure. 7 OLT, by treating both the tumor and the cirrhosis, offers a better long-term survival. The tumor, however, can outgrow the criteria accepted for transplantation while waiting for donor organs, affecting the ultimate outcome as shown in a previous analysis. 2 For patients with a single resectable HCC, an alternative strategy to either partial hepatectomy or OLT would be to offer resection first and transplantation if the tumor recurs or if the liver function deteriorates (salvage OLT). Before such a strategy can be tested in a prospective controlled trial, the present study examines its implications in terms of patient outcome, graft use, and costs, using a decisional analysis model based on the data available in the literature. PATIENTS AND METHODS Decision Analytic ModelWe investigated the impact of 2 options: (1) primary liver transplantation and (2) partial hepatectomy followed by salvage liver transplantation (Fig. 1A) in patients with compensated cirrhosis and solitary HCC Յ5 cm in diameter, with a Markov simulation (Decision Maker 7

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“…Pathological and genetic analyses have indicated two features in HCC recurrence: multicentric occurrence of new tumours (MO) and intrahepatic metastasis of the original tumour (im) (Tsuda et al, 1992;Matsumoto et al, 2001). It has been reported that MO is significantly influenced by the underlying liver status, such as the presence of active hepatitis (Belghiti et al, 1991;Ko et al, 1996). On the other hand, im is thought to be more closely associated with tumour factors, especially portal vein invasion (vp) (Vauthey et al, 1995;Shimada et al, 1999).…”

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confidence: 99%

Snail accelerates cancer invasion by upregulating MMP expression and is associated with poor prognosis of hepatocellular carcinoma

et al. 2005

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We have previously demonstrated in an in vitro study that Snail increased the invasion activity of hepatoma cells by upregulating matrix metalloproteinase (MMP) gene expression. In the present study, we examined whether Snail gene expression correlates with cancer invasion and prognosis of patients with hepatocellular carcinoma (HCC). Quantitative reverse transcription -polymerase chain reaction (RT -PCR) was performed to evaluate Snail, E-cadherin, and MMP mRNA expressions in eight nodule-in-nodule tumours and 47 ordinary HCC tissues. In the nodule-in-nodule tumours, Snail expression significantly increased with tumour dedifferentiation (P ¼ 0.047). In the ordinary HCC tissues, Snail expression was significantly correlated with portal vein invasion (P ¼ 0.035) and intrahepatic metastasis (P ¼ 0.050); it also showed a significant correlation with MT1-MMP expression (r ¼ 0.572, Po0.001). In recurrence-free survival, the group with high Snail expression showed significantly poorer prognosis (P ¼ 0.035). Moreover, high Snail expression was an independent risk factor for early recurrence after curative resection. During the progression of HCC, Snail expression may be induced and accelerate invasion activity by upregulating MMP expression, resulting in portal invasion, intrahepatic metastasis, and poor prognosis. British Journal of Cancer (2005) Hepatocellular carcinoma (HCC) is one of the most prevalent malignancies in the world and a frequent cause of cancer fatalities in Japan. Improvements in early diagnosis, surgical techniques, and perioperative management have contributed to decreases in mortality and morbidity among patients with HCC (Okuda et al, 1985;Fran et al, 1999). However, the long-term prognosis of patients with HCC after hepatectomy has been still poor because of a high incidence of recurrence after initial treatment (Fong et al, 1999;Poon et al, 2000b). Several centres have reported a cumulative 5-year recurrence rate ranging from 75 to 100% (Chen et al, 1994;Fong et al, 1999;Poon et al, 2000b). Pathological and genetic analyses have indicated two features in HCC recurrence: multicentric occurrence of new tumours (MO) and intrahepatic metastasis of the original tumour (im) (Tsuda et al, 1992;Matsumoto et al, 2001). It has been reported that MO is significantly influenced by the underlying liver status, such as the presence of active hepatitis (Belghiti et al, 1991;Ko et al, 1996). On the other hand, im is thought to be more closely associated with tumour factors, especially portal vein invasion (vp) (Vauthey et al, 1995;Shimada et al, 1999). Several published studies have demonstrated that vp plays an important role in the im process and influences the survival rate of patients with HCC (Fuster et al, 1996;Mitsunobu et al, 1996; The Liver Cancer Study Group of Japan, 1994). Therefore, it is important to elucidate the molecular mechanisms of vp and im; the subsequent establishment of markers for predicting vp and im may contribute to improvement in the prognosis of patients with HCC.Recently, the z...

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Significant Influence of Accompanying Chronic Hepatitis Status on Recurrence of Hepatocellular Carcinoma after Hepatectomy

Abstract: The results of this study indicated the significant influence of histologic activity of hepatitis on recurrence of HCC. This might support the concept of significant contribution of multicentric hepatocarcinogenesis to recurrence of HCC after hepatectomy.

Cited by 137 publications

References 20 publications

Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients

Discrimination value of the new western prognostic system (CLIP score) for hepatocellular carcinoma in 662 Japanese patients

Primary liver resection and salvage transplantation or primary liver transplantation in patients with single, small hepatocellular carcinoma and preserved liver function: An outcome-oriented decision analysis

Snail accelerates cancer invasion by upregulating MMP expression and is associated with poor prognosis of hepatocellular carcinoma

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