Predictive factors for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy

Arii, Shigeki; Tanaka, Junji; Yamazoe, Yoshihiro; Minematsu, Souhei; Morino, Takaharu; Fujita, Ken‐ichi; Maetani, Shunzo; Tobe, Takayoshi

doi:10.1002/1097-0142(19920215)69:4<913::aid-cncr2820690413>3.0.co;2-t

Cited by 190 publications

(111 citation statements)

References 15 publications

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“…These are the conventional factors used for predicting postoperative recurrence of HCC, but have been found to be unsatisfactory in clinical settings. Portal vein invasion has already been recognized as having strong prognostic value, however, a recurrence rate of over 50% within 5 years has been reported in cases without portal vein invasion (Arii et al, 1992). The HTRS and CNIC spots were signi®-cantly associated with recurrence even in the cases without portal vein invasion (Figure 5a,b).…”

Section: Discussionmentioning

confidence: 88%

“…Thus, it has been reported that factors such as tumor size, portal venous invasion, and intrahepatic metastasis are signi®cantly correlated with recurrence (Hsu et al, 1988;Arii et al, 1992;Sirabe et al, 1991). In addition, liver function data and severity of cirrhosis have also been utilized as prognostic markers for postoperative recurrence (Lise et al, 1998;Kubo et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences

Itano

Ueda

Kikuchi³

et al. 2002

Oncogene

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Restriction landmark genomic scanning (RLGS) was utilized to identify novel genomic alterations in hepatocellular carcinoma (HCC). Thirty-one HCC samples were examined by RLGS. Two high intensity spots were common to several RLGS pro®les of di erent HCCs. Nucleotide sequencing and homology search analysis showed that these spots represented repetitive sequences, Human tandem repeat sequence (Genbank, L09552) and centromeric NotI cluster (Genbank, Y10752). These intensi®ed signals were attributable to the occurrence of demethylated areas in the recognition sequence of the NotI site of the corresponding fragments. The intensity of these spots in the RLGS pro®le re¯ects their degree of demethylation, which was signi®cantly correlated with postoperative recurrence, even in patients regarded as belonging to the good prognosis group by conventional prognostic factors. Multivariate analysis showed that the intensities of the two spots retained independent prognostic value. This is a new type of predictive factor for HCC based on epigenetic changes in hepatocarcinogenesis, and in the future it is expected to be of great value in making preoperative diagnosis and selecting postoperative therapy.

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Section: Discussionmentioning

confidence: 88%

Section: Introductionmentioning

confidence: 99%

Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences

Itano

Ueda

Kikuchi³

et al. 2002

Oncogene

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“…According to the results of in our study, as well as in a nationwide study of Japan. 5,7,12 the animal experiments, the kan-1(BAT) ratio of each patient Next to portal involvement, the kan-1(BAT) ratio proved to was expected to be always õ1. However, in 13 of 37 patients be the next most significant prognostic indicator for recur-(35%), the kan-1(BAT) mRNA levels of the tumors were acturence-free survival.…”

Section: Discussionmentioning

confidence: 94%

Kan–1 (Bile Acid Coa:Amino Acid N –Acyltransferase) Messenger Rna As A Novel Predictive Indicator for Prognosis of Hepatocellular Carcinoma Patients After Partial Hepatectomy

et al. 1996

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Hepatocellular carcinoma (HCC) is one of the most commonWe identified kan-1 complementary DNA (cDNA), the cancers in the Orient and in South Africa. Over the past 10 sequence of which is identical to bile acid CoA:amino years, great progress has been made in the diagnosis and acid N-acyltransferase (BAT), a liver enzyme that catatreatment of HCC patients, and consequently, the number lyzes the conjugation of bile acids with glycine or tauof resectable cases has increased. 3,4 However, despite this rine. Kan-1(BAT) messenger RNA (mRNA) levels of the remarkable progress, the survival rate remains poor. One of resected specimens obtained from 37 hepatocellular carthe major barriers to the attainment of longer survival seems cinoma (HCC) patients were studied in an attempt to to be intrahepatic recurrence even after total removal of the evaluate prognostic significance in HCC patients after tumor macroscopically. 5,6 In this regard, great effort has been partial hepatectomy. Using Northern blot hybridization, given to determining the predictive factors affecting intrahekan-1(BAT) mRNA levels were quantified in tumorous patic recurrence and long-term survival. New molecular and nontumorous tissues, and the ratio of the former to markers that add predictive value to the conventional clinical the latter was defined as the kan-1(BAT) ratio. Twelve predictive factors, such as portal involvement, a-fetoprotein patients had a kan-1(BAT) ratio õ 0.5 (low kan-1[BAT](AFP) level, tumor size, number of tumors, are still deratio), and 25 patients had a ratio ú0.5 (high kan-1[BAT]sired. 4,5,[7][8][9] In this context, the present study was designed to ratio). The patients with a low kan-1(BAT) ratio demonevaluate the prognostic significance of the expression of the strated poorer survival than the patients with a high kan-1(BAT) gene in HCC patients after curative resection. kan-1(BAT) ratio (P Å .0013). The overall estimated haz-Evidence will be presented to demonstrate that kan-1(BAT) ard ratio for death in patients with a low kan-1(BAT) mRNA level is a novel molecular marker for estimating progratio was 68.05 according to a multivariate model (P Å nosis and for differentiating HCC from other liver tumors, .0005). Thus, the kan-1(BAT) ratio may serve as a new and the rationale for this conclusion will be discussed. molecular prognostic marker in HCC patients, following hepatic resection. (HEPATOLOGY 1996;24:1441-1445.) PATIENTS AND METHODSStudy Population. A total of 28 men and 9 women (age range, 39Recently, we identified a novel gene, kan-1, in the rat liver to 76 years; mean, 61.4 years), whose profiles are listed in Table 1, using an RNA-polymerase chain reaction cloning strategy. 1 were studied. All HCC patients underwent partial hepatic resection at the Kyoto University Hospital, and tumorous and contiguous nonKan-1 complementary DNA (cDNA) encodes a 46-kd protein, tumorous tissues were collected with the consent of the patients. the messenger RNA (mRNA) for which is expressed mainly Each patient underwent transarterial ch...

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“…No difference in the portal tract. [1][2][3] weight of the liver, serum albumin, alanine transamiSince 1988, we have performed continuous intrahenase, or TB was observed in any groups at 1, 2, or 4 patic administration of interleukin-2 (IL-2) combined days after hepatectomy. Neither IL-2 nor splenectomy with anticancer agents for the treatment of unresectinfluenced MI and BrdU LI at all three points.…”

Section: Japanese Reference Units [Jru]/d) or Saline Was Admin-mentioning

confidence: 99%

“…Recurrences of HCC in remnant liver after hepatecmagnification groups C and D) was recognized 1 day earlier than in tomy are seen with considerable frequency. [1][2][3] It has nonsplenectomized rats (groups A and B). A delay in gap junction been reported that peripheral lymphocytes from pa-reappearance in liver treated with IL-2 was also observed in the splenectomized group on day 4 but was not observed on day 6. tients with HCC show a reduced natural cytotoxicity.…”

Section: Group)mentioning

confidence: 99%

Influence of Continuous Interleukin–2 Administration Via the Portal Vein on Liver Regeneration Following Partial Hepatectomy in Rats

Wadamori¹,

Oka²,

Tokuda³

et al. 1996

Hepatology

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suppression may not be harmful for overall recovery of We have reported the efficacy of intraarterial-comthe resected liver. However, it seems that hepatic IL-2 bined immunochemotherapy including interleukin-2 administration can be performed without serious com-(IL-2) for unresectable hepatocellular carcinoma (HCC).plications after hepatectomy. (HEPATOLOGY 1996;23:1578-To further test this therapy for prevention of intrahe-1583.) patic recurrence after hepatectomy, the influence of IL-2 on liver regeneration was examined using mitotic index (MI) and the bromodeoxyuridine (BrdU) labeling index Although significant progress has been made in the (LI) in 70% hepatectomized Donryu rats. In addition, gap surgical treatment of human hepatocellular carcinoma junction appearance, which may change during liver re-(HCC), as well as in the detection of small HCC with generation, was analyzed using a monoclonal antibody diagnostic techniques such as ultrasonography and (HAM8). Serum albumin, alanine transaminase, and tocomputed tomography, cancer recurrence, including intal bilirubin (TB) levels were also evaluated. IL-2 (45,000 trahepatic recurrence, is observed in about 50% of pa- Japanese reference units [JRU]/d) or saline was admin-istered continuously via the portal vein immediately tients with HCC in the year following hepatic resecafter hepatectomy using an infusion pump. We also ex-tion. 1 Most of the recurrences involve the remnant amined the influence of IL-2 on liver regeneration after liver, with intrahepatic metastasis occurring via the hepatectomy with splenectomy. No difference in the portal tract. [1][2][3] weight of the liver, serum albumin, alanine transamiSince 1988, we have performed continuous intrahenase, or TB was observed in any groups at 1, 2, or 4 patic administration of interleukin-2 (IL-2) combined days after hepatectomy. Neither IL-2 nor splenectomy with anticancer agents for the treatment of unresectinfluenced MI and BrdU LI at all three points. Gap junc-able HCC with satisfactory response. The response rate tions began to disappear after hepatectomy and reached was 58.3%, including four cases of complete response. a minimum on day 2 in all groups. Four days after hepa-The overall 2-year survival rate was 52% and the 2-tectomy, the density of the reappearing gap junctions was markedly lower in groups treated with IL-2 than year survival rate of responders was 80%. 4 Before this in those receiving saline with or without splenectomy. therapy is introduced to prevent intrahepatic recurHowever, the density returned to close to preoperative rence, the influence of IL-2 on liver regeneration should levels 6 days after hepatectomy in all groups. Continu-be evaluated, although we experienced no severe side ous portal infusion of IL-2 transiently disturbed gap effects concerning hepatic function in our clinical protojunction reappearance during liver regeneration. How-col. A previous experimental study reported that ILever, no other parameters of liver regeneration or liver 2 exerts inhibitory influence ...

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Predictive factors for intrahepatic recurrence of hepatocellular carcinoma after partial hepatectomy

Cited by 190 publications

References 15 publications

Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences

Correlation of postoperative recurrence in hepatocellular carcinoma with demethylation of repetitive sequences

Kan–1 (Bile Acid Coa:Amino Acid N –Acyltransferase) Messenger Rna As A Novel Predictive Indicator for Prognosis of Hepatocellular Carcinoma Patients After Partial Hepatectomy

Influence of Continuous Interleukin–2 Administration Via the Portal Vein on Liver Regeneration Following Partial Hepatectomy in Rats

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