Multistep and multicentric development of hepatocellular carcinoma: histological analysis of 980 resected nodules

BACKGROUND/AIMS: Histological observations support the concept of multistep and multicentric development of hepatocellular carcinoma (HCC) in cases of chronic liver disease. However, the relationship between the incidence of such a modality of development of HCC and the type of background liver disease has not been fully investigated. METHODS: A total of 980 HCC nodules resected from 664 patients were analyzed. Multistep HCC was defined as well differentiated HCC containing the portal tracts (early HCC), or the presence of early HCC-like areas in the periphery of the nodule. In cases with multiple nodules, if the smaller nodule showed the features of multistep HCC, or if each nodule showed a distinct histology, the case was defined to have multicentric HCC. RESULTS: Of the 980 nodules, 369 (37.7%) met the criteria of multistep HCC. Of the 664 patients, 177 (26.7%) had multiple nodules that met the criteria of multicentric HCC. Both the incidences of multistep and multicentric HCC were significantly higher in HCV-Ab-positive cases than in HBs-Ag-positive cases (46.0 vs. 19.1%, P<0.001 and 34.1 vs. 16.5%, P=0.005, respectively). CONCLUSIONS: Multistep and multicentric HCC develops most frequently in patients with HCV infection.     

Clonality and clonal evolution of hepatocellular carcinoma with multiple nodules.

To determine the clonal evolution of hepatocellular carcinoma, the integrated hepatitis B virus DNA patterns of the main tumor, satellites and/or metastatic lesions were analyzed by Southern-blot hybridization in 28 hepatocellular carcinomas, including three HBsAg-seronegative cases. Unicentric or multicentric hepatocellular carcinoma was confirmed by histopathological criteria in 89% of the cases. Among 17 unicentric hepatocellular carcinomas, minor changes of the integration pattern--including partial loss or addition of the integration sites or both--were detected in the metastatic lesions in 29% of the cases. Furthermore, none of five cases with free-form hepatitis B virus DNA in the primary tumor had detectable free hepatitis B virus DNA in the metastatic lesions. These results suggest that the alteration of integrated hepatitis B virus DNA pattern during the course of tumor growth and metastasis may occur more often than previously perceived and that the switch-off of virus replication may be related to tumor metastatic potential. In eight cases with unilateral, multicentric hepatocellular carcinoma, two clones were detected in six cases, three were seen in another and four were seen in one. One case of note was a 9-yr-old boy with two histological types and two different integration patterns, one associated with vascular invasion and lung metastasis. Three patients with bilateral hepatocellular carcinoma were confirmed to have bicentric or tricentric hepatocellular carcinoma rather than intrahepatic dissemination and had survival rates similar to those in unicentric hepatocellular carcinoma. Three invasive HBsAg-seronegative hepatocellular carcinomas were found to have hepatitis B virus DNA integration and were of unicentric origin.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinicopathological risk factors linked to recurrence pattern after curative hepatic resection for hepatocellular carcinoma--results of 152 resected cases

BACKGROUND/AIMS: The recurrence rate after hepatectomy of hepatocellular carcinoma (HCC) remains high. Although the cause of recurrence seems to be the multicentric occurrence and metastasis of cancer cells in the patients after curative resection of HCC, the mechanism of HCC recurrence in each case is still uncertain. The recurrence pattern may illuminate these mechanisms. METHODOLOGY: A data analysis of 152 patients who underwent HCC resection, and had observed for more than 5 years was conducted. These patients were divided into three groups; group I (n=32), the patients without HCC recurrence, group II (n=86), the patients with fewer than four recurrent nodules of HCC, group III (n=34), the patients with four or more recurrent nodules of HCC. We compared the clinicopathological data of groups I and II, and of groups I and III. The linkage of risk factors linked to recurrence patterns was clarified. RESULTS: The risk factors linked to group II by comparison with group I were high serum levels of alanine aminotransferase, low serum levels of albumin, high values in the indocyanine green retention test at fifteen minutes, hepatitis C antibody positivity. low platelet counts, and high histological hepatitis activity. The risk factors linked to group III were large tumor size, histological presence of portal vein invasion by cancer cells, intrahepatic metastasis, and poor differentiation of cancer cells. CONCLUSIONS: The risk factors linked to recurrence with no more than three HCC nodules recurrence were related to host-related factors such as hepatic function, and hepatitis activity, but not tumor related. The risk factors linked to multiple recurrence were tumor related. The analysis of recurrence patterns revealed that completely different mechanisms exist in the patients with recurrence involving no more than four nodules, which may be related to multicentric occurrence, and patients with multiple recurrence, which may be related to the metastasis of cancer cells.     

Early Stage Hepatocellular Carcinoma Detected during Intraoperative Ultrasonography

Objectives: Recently, it has been recognized that there are increasing incidences of hepatocellular carcinoma (HCC) multicentricity. Thus, intraoperatively detected hepatic lesions that were once thought to be metastatic lesions now need to be carefully reexamined to determine whether they are true metastatic lesions or the multicentric development of HCC. Methods: We investigated the histological characteristics of small nodular lesions detected during intraoperative ultrasonography in 33 consecutive patients with small HCC wbo underwent laparotomy at our institution. Results: Fourteen nodular lesions were found incidentally in 10 of 33 patients (30.3%), and were classified into tbe following three groups: 11 nodules in nine patients (27.3%) were HCC, two nodules in two patients (6.1%) were hemangioma, and one nodule in one patient (3.0%) was a large regenerative nodule. HCC therefore comprised 78.6% of tbe intraoperatively detected nodular lesions. Of the 11 HCCs, six were hyperechoic, four were hypoechoic, and one was isoechoic. Five (83.3%) of six small hyperechoic HCCs and two (50.0%) of four hypoechoic HCCs were well differentiated and retained their preexisting liver structure. Tbese findings closely coincide with the characteristics of early stage HCC. Thus, early stage HCC comprised 63.6% of tbe intraoperatively detected HCC cases. Conclusions: A certain proportion of small satellite HCCs detected during intraoperative ultrasonography in patients with small HCC, which were previously thought to be metastatic lesions from tbe main HCC, may instead he early stage HCCs. Such findings would also support the concept of the multicentric development of HCC. Approximately 60% of all small HCC cases detected intraoperatively may be early stage HCC. As a result, it is predicted that the emergence of HCC is either multicentric or unicentric, with early intrabepatic spread, altbough the former seems to be more common.     

Recurrence of hepatocellular carcinoma: multicentric occurrence or intrahepatic metastasis? A viewpoint in terms of pathology

Recurrence after successful surgical or nonsurgical treatment of hepatocellular carcinoma (HCC) is caused either by intrahepatic metastasis or by metachronously multicentric occurrence. Intrahepatic metastasis is a major cause of recurrence of advanced HCCs with varying degrees of vascular invasion, and multicentric occurrence is a frequent cause of recurrence in small HCCs with no obvious vascular invasion. It is estimated that at least 20% of small HCCs have a high probability of recurrence due to multicentric occurrence, based on the finding that adenomatous hyperplasia (AH) and/or atypical adenomatous hyperplasia (AAH), which are considered premalignant lesions, are found in the vicinity of resected small HCCs with liver cirrhosis. However, because neither AH nor AAH occur in HCC cases without liver cirrhosis, most recurrence of HCC in noncirrhotic liver is considered to be due to intrahepatic metastasis or to de novo hepatocarcinogenesis. In a survey of autopsy cases of liver cirrhosis with small HCC, smaller HCC nodules were found in other liver slices in 50% of cases, and it is estimated that approximately 50% of HCC is already multicentric in the early stage.     

Classification tool for the systematic histological assessment of hepatocellular carcinoma, macroregenerative nodules, and dysplastic nodules in cirrhotic liver

AIM: To design a classification tool for the histological assessment of hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative nodules (MRN) in cirrhotic liver. METHODS: Two hundred and twelve hepatocellular nodules (106 HCC; 74 MRN; 32 DN) were assessed systematically, quantitatively, and semiquantitatively as appropriate for 10 histological features that have been described as helpful in distinguishing small HCC, DN, and MRN in cirrhotic livers. The data were analyzed by multiple correspondence analysis (MCA). RESULTS: MCA distributed HCC, DN, and MRN as defined by traditional histological evaluation as well as the individual histological variables, in a "malignancy scale". Based on the MCA data representation, we created a classification tool, which categorizes an individual nodular lesion as MRN, DN, or HCC based on the balance of all histological features (i.e., vascular invasion, capsular invasion, tumor necrosis, tumor heterogeneity, reticulin loss, capillarization of sinusoids, trabecular thickness, nuclear atypia, and mitotic activity). The classification tool classified most (83%) of a validation set of 47 nodules in the same way as the routine histological assessment. No discrepancies were present for DN and MRN between the routine histological assignment and the classification tod. Of 25 HCC assigned by routine assessment in the validation set, 8 were assigned to the DN category by the classification tool. CONCLUSION: We have designed a classification tool for the histological assessment of HCC and its putative precursors in cirrhotic liver. Application of this tool systematically records histological features of diagnostic importance in the evaluation of small HCC.     

Classification tool for the systematic histological assessment of hepatocellular carcinoma, macroregenerative nodules, and dysplastic nodules in cirrhotic liver

AIM: To design a classification tool for the histological assessment of hepatocellular carcinoma (HCC), dysplastic nodules (DN), and macroregenerative nodules (MRN) in cirrhotic liver.METHODS: Two hundred and twelve hepatocellular nodules (106 HCC;74 MRN;32 DN) were assessed systematically, quantitatively, and semiquantitatively as appropriate for 10 histological features that have been described as helpful in distinguishing small HCC, DN, and MRN in cirrhotic livers. The data were analyzed by multiple correspondence analysis (MCA).RESULTS: MCA distributed HCC, DN, and MRN as defined by traditional histological evaluation as well as the individual histological variables, in a "malignancy scale".Based on the MCA data representation, we created a classification tool, which categorizes an individual nodular lesion as MRN, DN, or HCC based on the balance of all histological features (i.e., vascular invasion, capsular invasion, tumor necrosis, tumor heterogeneity, reticulin loss,capillarization of sinusoids, trabecular thickness, nuclear atypia, and mitotic activity). The classification tool dassified most (83%) of a validation set of 47 nodules in the same way as the routine histological assessment. No discrepandes were present for DN and MRN between the routine histological assignment and the classification tool. Of 25 HCC assigned by routine assessment in the validation set, 8were assigned to the DN category by the classification tool.CONCLUSION: We have designed a classification tool for the histological assessment of HCC and its putative precursors in cirrhotic liver. Application of this tool systematically records histological features of diagnostic importance in the evaluation of small HCC.     

Clinical analysis of the risk factors for recurrence of HCC and its relationship with HBV

AIM: To comprehend the risk factors of recurrence of hepatocellular carcinoma (HCC) and its relationship with the infection patterns of hepatitis B virus (HBV).METHODS: All materials of 270 cases of postoperative HCC were statistically analyzed by SPSS software.Recurrence and metastasis were classified into early( ≤2 years) and late phase (&gt;2 years). Risk factors for recurrence and metastasis after surgery in each group were analyzed.RESULTS: Out of 270 cases of HCC, 162 cases were followed up in which recurrence and metastasis occurred in 136 cases. There were a lot of risk factors related to recurrence and metastasis of HCC; risk factors contributing to early phase recurrence were serum AFP level, vascular invasion, incisal margin and operative transfusion, gross tumor classification and number of intrahepatic node to late phase recurrence. The HBV infective rate of recurrent HCC was 94.1%, in which ““HBsAg, HBeAb, HBcAb““ positive pattern reached 45.6%. The proportion of HBV infection in solitary large hepatocellular carcinoma (SLHCC)evidently decreased compared to nodular hepatocellular carcinoma (NHCC) (P&lt;0.05).CONCLUSION: The early and late recurrence and metastasis after hepatectomy of HCC were associated with different risk factors. The early recurrence may be mediated by vascular invasion and remnant lesion, the late recurrence by tumor‘s clinical pathology propert, as multicentric carcinogenesis or intrahepatic carcinoma de novo. HBV replication takes a great role in this process.From this study, we found that SLHCC has more satisfactory neoplasm biological behavior than NHCC.     

Multicentric occurrence of hepatocellular carcinoma: In terms of pathology study

The remarkable advances in diagnostic techniques and in the pathomorphologic study of minute hepatocellular carcinomas (HCCs) in the early stage indicate that many HCCs are multicentric in origin. Morphologically, combinations of HCC nodules and other nodules, such as adenomatous hyperplasia containing cancerous foci, well-differentiated HCC, or well-differentiated HCC containing moderate or poorly differentiated cancerous tissue are considered to originate and proliferate in situ. These combinations are considered to be HCC of synchronous multicentric origin. We found that, in HCC associated with liver cirrhosis, 6 of 74 consecutively resected HCCs (8.3%) and 4 of 8 autopsy cases (50%) satisfied the above criteria for multicentric origin. This discrepancy between surgical and autopsy cases can be explained thus: In surgical cases, morphologic examination is limited to only the vicinity of the main tumor and patients with multiple minute tumors HCC tend not to be sent to the operation table. Thus, the frequency seen in autopsy cases may reflect the true figures for multicentric origin. In 94 HCCs associated with chronic hepatitis, we found none showing coexistence of the above nodules that are suggestive of synchronous multicentric origin.     

Comparison of liver resection for hepatocellular carcinoma in hepatitis B and hepatitis C-related cirrhotic patients.

BACKGROUND/AIMS: The differences of liver resection for hepatocellular carcinoma (HCC) between hepatitis B and C-related cirrhotic liver remain unknown. This study compares the surgical results of HCC in hepatitis B and hepatitis C-related cirrhotic patients in an area endemic of hepatitis B. METHODOLOGY: A retrospective comparison of the clinicopathological features and early and long-term results of 110 cirrhotic patients with seropositive hepatitis B surface antigen only (group B) and 55 patients with seropositive anti-hepatitis C antibody only (group C) was carried out. RESULTS: Group C patients were older, had a lower serum alpha-fetoprotein level, greater indocyanine retention rate, and higher incidence of multicentric tumors. Tumor size was larger and there was a higher incidence of combined satellite nodules in group B patients. There were no significant differences in operative morbidity and mortality between the two groups. Group B patients had a slightly shorter disease-free interval (p = 0.07) but a better actuarial survival rate (p = 0.05) than group C patients. CONCLUSIONS: The hepatitis status did not affect the operative risks in cirrhotic livers. However, after resection of HCC, poorer liver functional reserve in hepatitis C-related cirrhotic patients caused poorer actuarial survival rate when compared with hepatitis B-related cirrhotic patients.     

Analysis of the cellular origin of hepatocellular carcinoma by p53 genotype

The polymerase chain reaction andHaeIII enzymatic digestion were used to study the seventh exon of the p53 gene in 29 primary and recurrent hepatomas in paraffin-embedded samples from 11 patients. The mutation rate of the p53 gene and its geno-types in samples of primary and recurrent tumours and multiple nodules were investigated. The cellular origins of hepatocellular carcinoma were analysed by p53 genotype. p53 mutation rates were found to be 69.0% (20/29) in the primary and recurrent tumours, 58.8% (10/17) in tumours with a single nodule and 83.3% (10/12) in tumours with multiple nodules. The p53 genotypes were found to be different in 6 pairs of primary and recurrent tumours, and another 5 pairs had the same p53 genotypes. The samples with multiple nodules in the same patients had the same p53 geno-types. Seven recurrences were of multicentric origin and four were of unicentric origin. It is suggested that the recurrent lesions developed from both unicentric and multicentric origins.Abbreviations HCC hepatocellular carcinoma This work was supported partially by China Medical Board Grant 93-583     

A case of hepatocellular carcinoma consisting of two solitary poorly differentiated polyclonal intrahepatic tumor nodules

Two intrahepatic solitary tumors consisting of poorly differentiated hepatocellular carcinoma (HCC) were identified as polyclonal HCC nodules by analysis of the pattern of integration of hepatitis B viral DNA into nuclear DNA. After the removal of each nodule by partial liver resection, recurrent multiple tumors appeared within 10 months postoperatively. The findings in this case suggest that the effectiveness of reduction surgery for intrahepatic multiple tumors is limited in solitary multicentric HCC that consists of poorly differentiated HCC.     

Limitations of imaging diagnosis for small hepatocellular carcinoma: Comparison with histological findings

BACKGROUND AND AIMS: The purpose of this study was to clarify the value and limitation of imaging modalities for diagnosing small hepatocellular carcinoma (HCC). METHODS: Nodules (n = 207) with diameters of 20 mm or less detected by periodic ultrasonography and computed tomography in 139 patients with chronic liver disease were investigated with digital subtraction angiography (DSA) and magnetic resonance imaging (MRI). These findings were compared with histological findings. RESULTS: Histological diagnoses were adenomatous hyperplasia (AH, n = 27), well-differentiated HCC (n = 99), moderately differentiated HCC (n = 79) and poorly differentiated HCC (n = 2). We compared two groups: group A (n = 62), nodules of 10 mm diameters or less; and group B (n = 145), nodules 11-20 mm. Adenomatous hyperplasia accounted for approximately 30% of group A, but was difficult to diagnose with imaging modalities alone. We diagnosed those nodules showing hypervascular staining on DSA or hyperintensity on MRI T2-weighted images as HCC. Imaging alone was sufficient to diagnose HCC in 58% of the well-differentiated nodules and 87% of the moderately and poorly differentiated nodules (P < 0.01). It was possible to diagnose HCC by imaging alone in 60% of all nodules or 45% of group A and 68% of group B (A vs B, P < 0.005). CONCLUSIONS: With decreasing differentiation and increasing diameter of nodules, the use of imaging modalities to diagnose HCC improved. Tumour biopsy was required to diagnose 55% of the cases in group A and 32% of the cases in group B.     

Multicentric occurrence of hepatocellular carcinoma: diagnosis and clinical significance

To evaluate current knowledge on the multicentric occurrence (MO) of hepatocellular carcinoma (HCC) and its clinical significance was the purpose of this review. The criteria for MO of HCC are defined as follows: (1) the recurrent tumor consists of well differentiated HCC occurring in a different hepatic segment from moderately or poorly differentiated preexisting HCC, (2) both the primary and recurrent tumors are well differentiated HCC, (3) the recurrent tumors contain regions of dysplastic nodules in peripheral areas and, (4) multiple HCCs, indicating the “nodule‐in‐nodule” form, in which nodules consisting of moderately or poorly differentiated HCC cells are contained in a nodule of well differentiated HCC cells. However, these criteria assume rare or no metastasis of well differentiated HCC, and are also not applicable to cases in which some HCCs of multicentric origin are rapidly dedifferentiated, presenting morphologic features of moderately or poorly differentiated tumors. Diagnostic methods, besides histopathologic methods, for determining multicentric origin in multiple HCCs in the liver, or recurrent tumor(s) of HCC, include clonal analysis of the integration pattern of hepatitis B virus (HBV) DNA in HBV carrier patients, and analysis of thep53 mutation patterns or loss of heterozygosity of chromosomal DNA. The prognosis of patients with MO of HCC after curative resection is significantly better than that of patients with intrahepatic HCC metastasis. Moreover, the Liver Cancer Study Group of Japan has reported that patients with hepatic resection for small‐sized HCCs showed higher survival rates than a nonsurgical treatment group. Consequently, HCC with MO, whether this is synchronous or metachronous, should be surgically removed as the treatment of first choice.     

Univariate and multivariate analysis of prognostic factors in the surgical treatment of hepatocellular carcinoma in cirrhotic patients

BACKGROUND/AIMS: Evaluation of the short- and long-term outcome of liver resections for HCC in cirrhotic patients. METHODOLOGY: A retrospective analysis was performed on 106 consecutive cirrhotic patients with HCC resected between June 1974 and September 2002. Univariate and multivariate analyses were performed on several clinicopathological variables to analyze factors affecting the long-term outcome and intrahepatic recurrence. RESULTS: Overall mortality and morbidity were 10.7% and 26% respectively. These rates significantly decreased in the last years: from 1997 to 2002 no hospital mortality has been recorded. After a median follow-up of 19 months (interquartile range: 10-36), tumor recurrence appeared in 25 patients (23.5%). The 1-, 3-, and 5-year overall survival rates were 86.6%, 70.3%, and 60.6%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 86.3%, 58.1%, and 40.7%. Univariate analysis showed that viral etiology of cirrhosis (p=0.03), presence of multiple nodules (p=0.02) and vascular invasion (p=0.05) are related to a worse long-term survival. Multivariate analysis showed that only the viral etiology of cirrhosis and the presence of multiple nodules were significant independent prognostic factors. CONCLUSIONS: Results after hepatic resection for HCC in cirrhotic patients can be improved by using a limited surgical approach. The viral etiology of cirrhosis, the presence of multiple nodules and vascular invasion negatively affected recurrence rate and long-term survival.     

Prognosis of hepatocellular carcinoma accompanied by microscopic portal vein invasion

AIM： To investigate the prognostic factors in patients with hepatocellular carcinoma （HCC） accompanied by microscopic portal vein invasion （PVI）.
METHODS： Of the 267 patients with HCC undergoing hepatic resection at Aso Iizuka Hospital, 71 had PVI. After excluding 16 patients with HCC that invaded the main trunk and the first and second branches of the portal vein, 55 patients with microscopic PVI were enrolled.
RESULTS： The patients with HCC accompanied by microscopic invasion were divided into two groups： solitary PVI （PVI-S： n = 44）, and multiple PVIs （PVI-M： n = 11）. The number of portal vein branches invaded by tumor thrombi was 5.4 ± 3.8 （2-16） in patients with PVI-M. In cumulative survival, PVI-M was found to be a significantly poor prognostic factor （P = 0.0019）; while PVI-M and non-anatomical resection were significantly poor prognostic factors in disease-free survival （P = 0.0213, and 0.0115, respectively）. In patients with PVI-M, multiple intrahepatic recurrence was more common than in the patients with PVI-S （P = 0.0049）. In patients with PVI-S, non-anatomical resection was a significantly poor prognostic factor in disease-free survival （P = 0.0370）. Operative procedure was not a significant prognostic factor in patients with PVI-M.
CONCLUSION： The presence of PVI-M was a poor prognostic factor in patients with HCC, accompanied by microscopic PVI. Anatomical resection is recommended in these patients with HCC. Patients with HCC and PVI-M may also be good candidates for adjuvant chemotherapy.     

The influence of perioperative blood transfusion on intrahepatic recurrence after curative resection of hepatocellular carcinoma

OBJECTIVE: This study retrospectively evaluated the association between perioperative blood transfusion and intrahepatic recurrence in patients with hepatocellular carcinoma (HCC) who had undergone curative hepatic resections. METHODS: Hepatic resection was performed with curative intent in 195 patients with primary HCC between 1985 and 1996. Patients who had received perioperative blood transfusion (transfused group: n = 117) and those who had no perioperative blood transfusion (nontransfused group: n = 78) were compared in terms of conventional prognostic variables and cancer-free survival by the univariate and multivariate analyses. RESULTS: The 1-, 3-, and 5-yr cancer-free survival rates in the nontransfused and transfused groups were 83.4% and 67.9%, 43.0% and 36.7%, and 23.1% and 24.6%, respectively (p = 0.175). Multivariate analysis of prognostic factors in all patients revealed that vascular invasion, tumor size (> or =5 cm), and Child's class were independent factors for intrahepatic recurrence. Further analyses in various stratified groups showed that perioperative blood transfusion was an independent predictor of prognosis in HCC patients with portal vein invasion (RR: 2.8, p = 0.0038). The 1-, 3-, and 5-yr survival rates in the nontransfused and transfused groups with portal vein invasion were 71.9% and 41.6%, 54.5% and 10.9%, and 26% and 0%, respectively (p = 0.0003). CONCLUSIONS: We conclude that perioperative blood transfusions enhance the risk of intrahepatic recurrence of HCC in patients with portal vein invasion. As well, the more difficult surgery and the increased manipulation of the liver that occur in these cases create a greater possibility of tumor dissemination.     

Postoperative adjuvant arterial chemoembolization improves survival of hepatocellular carcinoma patients with risk factors for residual tumor:A retrospective control study

AIM:To evaluate the effect of postoperative adjuvanttranscatheter arterial chemoembolization(TACE)on theprognosis of hepatocellular carcinoma(HCC)patients withor without risk factors for the residual tumor.METHODS:From January 1995 to December 1998,549consecutive HCC patients undergoing surgical resectionwere included in this research.There were 185 patientswho underwent surgical resection with adjuvant TACE and364 patients who underwent surgical resection only.Tumorswith a diameter more than 5 cm,multiple nodules,andvascular invasion were defined as risk factors for residualtumor and used for patient stratification.Kaplan-Neiermethod was used to analyze survival curve and Coxproportional hazard model was used to evaluate theprognostic significance of adjuvant TACE.RESULTS:In the patients without any risk factors for theresidual tumor,the 1-,3-,5-year survival rates were 93.48%,75.85%,62.39% in the control group and 97.39%,70.37%,50.85% in the adjuvant TACE group,respectively.Therewas no significant difference in the survival between twogroups(P=0.3956).However,in the patients with riskfactors for residual tumor,postoperative adjuvant TACEsignificantly prolonged the patients' survival.There was astatistically significant difference in survival between twogroups(P=0.0216).The 1-,3-,5-year survival rates were69.95%,49.86%,37.40% in the control group and 89.67%,61.28%,44.36% in the adjuvant TACE group,respectively.Cox proportional hazard model showed that tumor diameterand cirrhosis,but not the adjuvant TACE,were the significantlyindependent prognostic factors in the patients without riskfactors for residual tumor.However,in the patients withrisk factors for residual tumor adjuvant TACE,and alsotumor diameter,AFP level,vascular invasion,were thesignificantly independent factors associated with thedecreasing risk for patients'death from HCC.CONCLUSION:Postoperative adjuvant TACE can prolongthe survival of patients with risk factors for residual tumor,but can not prolong the survival of patients without riskfactors for residual tumor.     

Use of transcatheter arterial infusion of anticancer agents with lipiodol to prevent recurrence of hepatocellular carcinoma after hepatic resection.

BACKGROUND/AIMS: Hepatectomy has been accepted as a reliable cure for primary hepatocellular carcinoma (HCC). However, the residual liver recurrence rate after hepatectomy remains high. To improve the prognosis after hepatectomy for HCC, repeated post-operative transcatheter arterial infusions of anticancer drugs and lipiodol (TAI) was given. This study evaluates the efficacy of this treatment for preventing residual liver recurrence after hepatectomy. METHODOLOGY: TAI after hepatectomy was performed in 24 (TAI group) of 65 cases showing tumor invasion such as infiltration to the capsule, intraportal spread, and intrahepatic metastasis. In TAI, a mixture of Mitomycin C (MMC) and Adriamycin (ADM) is administered with lipiodol via the hepatic artery. The recurrence and survival rates of the TAI (n = 24) and non-TAI (n = 41) groups were compared to evaluate the efficacy of TAI after hepatectomy. RESULTS: The TAI group had a lower cumulative residual liver recurrence rate than the non-TAI group (p < 0.01). Division of residual liver recurrence cases into two groups according to the duration of recurrence showed that the rate of recurrence within 1 year after hepatectomy was lower in the TAI group (10.0%) (1/10) than in the non-TAI group (48.4%) (15/31) (p = 0.07). Also, the cumulative survival rate in the TAI group was significantly higher (p < 0.05). The morbidity rate was 16.6%. Bilomas occurred without infection in 2 cases, and liver abscess in one. CONCLUSIONS: TAI may be an effective surgical adjuvant against residual liver recurrence, and we suggest that its effectiveness results from suppression of intrahepatic micrometastases rather than multicentric carcinogenesis.     

Postoperative adjuvant arterial chemoembolization improves survival of hepatocellular carcinoma patients with risk factors for residual tumor： A retrospective control study

AIM: To evaluate the effect of postoperative adjuvant transcatheter arterial chemoembolization (TACE) on the prognosis of hepatocellular carcinoma (HCC) patients with or without risk factors for the residual tumor. METHODS: From January 1995 to December 1998, 549 consecutive HCC patients undergoing surgical resection were included in this research. There were 185 patients who underwent surgical resection with adjuvant TACE and 364 patients who underwent surgical resection only. Tumors with a diameter more than 5 cm, multiple nodules, and vascular invasion were defined as risk factors for residual tumor and used for patient stratification. Kaplan-Meier method was used to analyze survival curve and Cox proportional hazard model was used to evaluate the prognostic significance of adjuvant TACE.RESULTS: In the patients without any risk factors for the residual tumor, the 1-, 3-, 5-year survival rates were 93.48%,75.85%, 62.39% in the control group and 97.39%, 70.37%,50.85% in the adjuvant TACE group, respectively. There was no significant difference in the survival between two groups (P = 0.3956). However, in the patients with risk factors for residual tumor, postoperative adjuvant TACE significantly prolonged the patients‘ survival. There was a statistically significant difference in survival between two groups (P= 0.0216). The 1-, 3-, 5-year survival rates were 69.95%, 49.86%, 37.40% in the control group and 89.67%,61.28%, 44.36% in the adjuvant TACE group, respectively. Cox proportional hazard model showed that tumor diameter and cirrhosis, but not the adjuvant TACE, were the significantly independent prognostic factors in the patients without risk factors for residual tumor. However, in the patients with risk factors for residual tumor adjuvant TACE, and also tumor diameter, AFP level, vascular invasion, were the significantly independent factors associated with the decreasing risk for patients‘ death from HCC. CONCLUSION: Postoperative adjuvant TACE can prolong the survival of patients with risk factors for residual tumor,but can not prolong the survival of patients without risk factors for residual tumor.