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Objectives: Consensus has been reached that diabetes is a risk factor for development of HCC, but the impact on postoperative recurrence is still controversial. To clarify this point, we analyzed the relationship of postoperative recurrence rate of HCC and coexistence of diabetes in the patients with viral hepatitis., Methods: A total of 90 patients who had undergone curative resection for HCC were analyzed. They were divided into two groups with and without diabetes, and the recurrence-free survival rates after surgical treatment and the factors contributing to recurrence were examined., Results: Kaplan-Meier survival analysis showed the recurrence-free survival rates in the diabetic group were significantly lower than those in the nondiabetic group (P= 0.005) and overall survival rates in the diabetic group were significantly lower than those in the nondiabetic group (P= 0.005). These results were emphasized in the analysis of patients infected with hepatitis C virus. Univariate and multivariate analyses showed diabetes was a significant factor contributing to HCC recurrence after treatment. Furthermore, multivariate analysis in HCC patients with diabetes showed Child-Pugh classification B (P= 0.001) and insulin therapy (P= 0.049) were significant factors contributing to HCC recurrence after treatment., Conclusions: The results of the present study suggest that diabetes is a risk factor for the recurrence of HCV-related HCC and decreases the overall survival rates after surgical treatment. HCV-related HCC patients with diabetes should be closely followed for postoperative recurrence.

Background/aims: It is reported that some patients with undetectable hepatitis B surface antigen (HBsAg) have serum hepatitis B virus (HBV) DNA in patients with chronic hepatitis C (HCV). The aim of this study was to elucidate the impact of occult HBV infection on the efficacy and prognosis of interferon-alpha (IFN) therapy in HCV patients., Methods: One hundred and forty HCV patients without HBsAg who received IFN therapy were studied. Serum HBV DNA was quantified by real-time detection polymerase chain reaction., Results: Of 140 patients, 11 (7.9%) were HBV DNA-positive before IFN therapy. The serum HBV DNA levels ranged from 106 to 884 copies/ml. Four of these 11 patients showed a sustained virologic response by IFN, compared with 39 of 129 without HBV DNA (P = NS). Interestingly, two of the 11 patients developed hepatocellular carcinoma (HCC) after therapy, compared with 16 of 129 without HBV DNA (P = NS). In the serial study, serum HBV DNA was transiently undetectable during and after IFN; however, most became positive during follow-up., Conclusions: Occult HBV infection may not have a significant impact on response to IFN therapy for chronic HCV and development of HCC after therapy. Occult HBV may be sensitive to IFN although HBV is not completely eradicated., (Copyright Blackwell Munksgaard 2005)

Unlike normal liver with the sinusoids, hepatocellular carcinomas (HCCs) possess capillaries. Whether these capillaries derive from the sinusoids remains unclear in human HCCs. This study aimed to examine sinusoidal capillarization in human HCCs and its relationship to the tumor size, arterialization and dedifferentiation. Thirty-eight HCCs with a diameter of 10 - 140 mm were pathologically and angiographically examined. By electron microscopy, the microvasculature of tumors was classified into sinusoidal, intermediate and capillary types, which were all negative, partially positive and all positive, respectively, for four parameters, i.e., endothelial defenestration, continuous basement membrane, lack of Kupffer cells, and lack of lipid-containing hepatic stellate cells. Well-, moderately and poorly differentiated HCCs displayed sinusoidal / intermediate / capillary types, intermediate / capillary types and only capillary type, respectively, suggesting the transition from the sinusoids to capillaries in well-differentiated (and probably moderately differentiated) HCCs. Furthermore, well-differentiated HCCs with a diameter of less than 30 mm often received preferential portal venous blood, while moderately and poorly differentiated ones were all supplied with arterial blood, indicating a relationship between dedifferentiation and arterialization. In contrast, the microvascular type displayed no significant relationship with tumor size or arterialization in well-differentiated HCCs. The present study has demonstrated that sinusoidal capillarization occurs in human well-differentiated HCCs and seems to be related to dedifferentiation of parenchymal tumor cells, but not to tumor size or arterialization.

We examined the expression of smooth muscle cytoskeleton in spindle-shaped cells in the capsule of hepatocellular carcinoma (HCC) and the septa of liver cirrhosis (LC). Serial sections of livers resected from 11 patients were stained with monoclonal antibodies against vimentin, desmin, smooth muscle actin (1A4, HHF35, CGA7) and smooth muscle myosin heavy chain isoforms (SM1, SM2). Capsular spindle-shaped cells exhibited a cytoskeletal feature indicative of intermediately differentiated smooth muscle cells. Computer-assisted morphometry revealed that the proportions of 1A4-, HHF35-, CGA7- and SM1- positive areas to vimentin-positive area were 88.0+/-11.0%, 50.8+/-17.4%, 25.3+/-16.4% and 19.4+/-12.4% (n=11) in main tumours and 86.6+/-9.4%, 50.9+/-18.7%, 21.1+/-12.3% and 17.6+/-9.7% (n=12) in daughter tumours, indicating that spindle-shaped cells are heterogeneous in cytoskeletal expression. Septal spindle-shaped cells in LC lacked the cytoskeletal proteins specific to differentiated smooth muscle cells (CGA7, SM1, SM2 and desmin). Electron microscopically, capsular spindle-shaped cells contained more microfilaments and less rough endoplasmic reticulum than do septal cells. Intermediately differentiated smooth muscle cells are induced in the capsule of HCC but not in the septa of LC, suggesting a role for stromal interaction by tumour cells in the induction of smooth muscle cells.

Telomerase is a specialized type of reverse transcriptase that catalyzes the synthesis and extension of telomeric DNA. High levels of telomerase activity have been detected in most hepatocellular carcinoma (HCC) tissues; very weak telomerase activity is, however, detected in approximately half of nontumorous chronic liver disease tissues. The purpose of this study was to investigate the possible source of this weak telomerase activity in these tissues using quantitative competitive reverse transcription (RT)-polymerase chain reaction (PCR) and in situ RT-PCR. Competitive RT-PCR indicated that the relative amount of human telomerase RNA (hTR) was significantly higher in chronic hepatitis or liver cirrhosis compared with the normal liver (p < 0.005), and in HCC compared with the normal liver (p < 0.001) and with chronic hepatitis or liver cirrhosis (p < 0.0001). In the normal liver tissue, hTR was detected by in situ RT-PCR in occasional sinusoidal cells and nuclei of occasional hepatocytes. In tumor-free liver or tumor-bearing liver, hTR was detected in sinusoidal cells, infiltrating lymphocytes, occasional proliferative bile ductal epithelial cells, and the nuclei of occasional hepatocytes. In HCC, hTR was detected in nuclei of all HCC cells as an intense signal and in sinusoidal cells. These results indicate that the amount of hTR increases in the nuclei of hepatocytes during hepatocarcinogenesis, and that the cells associated with the weak telomerase activity in approximately half of the nontumorous chronic liver lesions are mainly migrating lymphocytes and sinusoidal cells.

Hepatocellular carcinoma with chondrosarcomatous variation is very rare. We report a case with the results of pathology examination, and review the literature. The patient, a 72-year-old may had a very large tumor in the liver revealed during follow-up for diabetes mellitus. The liver mass, which was 14 cm in diameter, was diagnosed as hepatocellular carcinoma by abdominal ultrasonography. Anterior segmentectomy and partial liver resection were performed. Histopathology examination revealed that the tumor consisted of two different components: the major one was hepatocellular carcinoma (HCC), which occupied most of the tumor; and a sarcomatous component, which occupied a smaller area, and included spindle-shaped cells with chondroscarcomatous variation. Intrahepatic metastases and tumor thrombi of HCC were also found in portal and hepatic veins. Investigations of the immunohistochemical localization of keratin (KRT), vimentin (VMT), and S-100 protein (S 100) were performed by the avidin-biotin complex method. Some of the spindle cells were immunohistochemically positive for both KRT and VMT, and the chondrosarcomatous cells were positive for S 100. These results strongly suggested that the sarcomatous lesion resulted from a sarcomatous change of HCC.

The phase S ratio in cell cycles were analyzed in livers with hyperplastic foci (HPF) and in livers without HPF by nuclear DNA determinations using flow cytometry, and by staining with argyrophilic proteins of the nucleolar organizer region (AgNOR). Flow cytometric analysis was done on 50 fresh frozen specimens of livers resected from 50 patients with hepatocellular carcinoma (HCC). Paraffin sections from the same patients were analyzed using AgNOR staining. There were 25 cases each with and without HPF. We examined the stage of fibrosis and the grade of inflammatory activity according to the modified Scheuer and Desmet scale. The incidence of HCC recurrence among these patients was also studied. The average phase S ratio of the livers of the patients with HPF was 6.5 +/- 3.2%, and that of the livers of the patients without HPF was 4.0 +/- 2.5%. The ratio differed significantly between the two groups (P < 0.01). The average AgNOR score for HPF lesions of the HPF-positive cases was 1.60 +/- 0.34, that for non-HPF lesions in the HPF-positive cases was 1.29 +/- 0.12, and that for the HPF-negative cases was 1.19 +/- 0.14. Significant differences were found between the average AgNOR scores for HPF lesions of the HPF-positive cases and the non-HPF lesions of the HPF-positive cases (P < 0.01), as well as between the non-HPF lesions in the HPF-positive cases and the HPF-negative cases (P < 0.05). Severe fibrosis (stage 3) and cirrhosis (stage 4) were found in 76% of HPF-positive cases and 48% of HPF-negative cases. The livers of HPF-positive patients were significantly more cirrhotic than those of HPF-negative patients (P < 0.05). The association between HPF and the inflammatory grade was not significant (P > 0.05). The incidence of HCC recurrence among HPF-positive cases was significantly higher than that among the HPF-negative cases (P < 0.05). The average phase S ratio of the recurrent HPF-positive patients was 7.48 +/- 3.48%, significantly higher than that of HPF negative cases (5.57 +/- 3.06%, P < 0.05). Hyperplastic foci of the liver was shown to be a highly proliferative lesion. The proliferative activity of the non-HPF lesions in the HPF-positive patients was also higher than that of the HPF-negative patients. Hyperplastic foci tended to be present in cirrhotic livers, but it was not associated with the grade of inflammatory activity of the liver. Hyperplastic foci may represent an important predictor of recurrence after hepatic resection.

The pathological features of 11 nodules of early hepatocellular carcinoma (EHCC) were studied. Their macroscopic features resembled those of adenomatous hyperplasia and differed from those of advanced hepatocellular carcinomas (AHCC). The EHCC extended along the hepatic lobular structure and lacked expansive growth. The endothelial cells in the sinusoids of EHCC did not react to Ulex europaeus agglutinin 1 (UEA1) like adenomatous hyperplasia or other liver parenchyma, whereas the endothelial cells in the AHCC did react to UEA1. Immunohistochemically, CD68-positive Kupffer cells were noted in the sinusoids of EHCC, whereas in the AHCC Kupffer cells were not seen. Tumor emboli in the portal vein and intrahepatic metastases were not identified in EHCC, which seemed to be carcinoma-in-situ or a microinvasive stage of hepatocarcinogenesis.

Hepatocellular carcinoma (HCC) is supplied only with arterial blood and has capillaries instead of sinusoids, unlike the normal hepatic tissue. In order to reveal the sequential changes of sinusoidal structure and blood supply during hepatocarcinogenesis, we examined hyperplastic nodules (HPN), atypical hyperplastic nodules (AHPN) and HCC in F344 rats fed with 2-acetylaminofluorene for 25-35 weeks. The extent of arterial blood supply and the degree of sinusoidal capillarization were assessed by the staining of hepatic nodules with arterially infused ink and by immunohistochemical and ultrastructural analyses of the sinusoids, respectively. The proportion of arterialized nodules was 47% in HPN, 57% in AHPN and 85% in HCC, which indicates that arterialization begins at the stage of HPN and a few HCC still receive portal venous blood. The proportion of Factor-VIII-related antigen (F-VIII)-positive nodules was 25% in HPN, 40% in AHPN and 100% in HCC. Non-arterialized nodules did not express F-VIII, while some F-VIII-negative nodules were already arterialized. Electron microscopically, non-arterialized HPN exhibited normal features of sinusoids, while arterialized HPN showed disappearance of Kupffer cells and partial defenestration of sinusoidal endothelial cells. In non-arterialized and arterialized AHPN, basement membrane became continuous and lipid droplet-containing stellate cells were no longer seen. In HCC, endothelial fenestrae were diminished and basement membrane became thick. The present study has demonstrated that sinusoids are altered in the following order as hepatocarcinogenesis advances from HPN to HCC; onset of arterialization and decrease of endothelial fenestrae, expression of F-VIII by endothelial cells, disappearance of Kupffer cells, diminution of lipid droplets in stellate cells and thickening of basement membrane.

The sinusoidal structure and blood supply of 38 liver nodules less than 2 cm in diameter were investigated. There were 18 cases of adenomatous hyperplasia (AH) and 20 cases of hepatocellular carcinoma (HCC). Growth pattern, encapsulation and vascularity were examined, and immunohistochemistry performed for factor VIII related antigen (factor VIII), type IV collagen (collagen IV), laminin and CD68. There were significant differences between AH and small HCC, except for the expression of CD68. There were differences in tumor size, vascularity and the components of the basement membrane between AH and small, well differentiated HCC. The cases of AH were supplied by the portal system and maintained the sinusoidal structure, but small well-differentiated' HCC were supplied by a mixture of portal and arterial vessels. In spite of their small size, moderately and poorly differentiated HCC had capillary and were supplied by branches of the hepatic artery.

To characterize hepatocellular carcinoma (HCC) cells with mutant (m) p53 protein histologically, we examined 68 main nodules and 20 accessory lesions of 72 patients with HCC who underwent hepatic resection between October 1990 and September 1993. Some sections were fixed in periodate-lysine-paraformaldehyde, embedded in OCT compound, and stained with the mouse monoclonal antibody PAb1801 to m-p53 protein by the immunoperoxidase technique with avidin-biotin complexes. Other sections were fixed in 20% buffered formalin, embedded in paraffin, and stained with the mouse monoclonal antibody DO-1 to m-p53 protein in the same way. Lesions in which cells had nuclei stained for m-p53 protein were defined as being positive for the protein; 25 of the 68 main nodules and 14 of the 20 accessory lesions were positive. Large main nodules were more likely to be positive than small ones. Microscopic examination showed that a larger proportion of poorly differentiated main nodules than well differentiated nodules were positive. Larger proportions of main nodules with extracapsular invasion, septa, portal thrombi, or intrahepatic metastases were positive than main nodules without these features. Accessory lesions that seemed to be metastatic were almost all positive, but few accessory lesions that seemed to be of multicentric occurrence were positive. Our results suggest that lesions with m-p53 protein had a high grade of malignancy and metastasized readily.

Two patients with mixed hepatocellular and cholangiocellular carcinoma underwent partial hepatectomy after magnetic resonance (MR) imaging. Correlation is made with the histopathologic manifestations. In both cases the tumors showed relative low signal intensities on T1-weighted spin-echo (SE) images and high signal intensities on T2-weighted SE images. Dynamic MR imaging showed the enhancement from the periphery of the tumor to the inner area gradually and the enhancement continued into the delayed phase. With both cases fibrosis was marked in the inner area of the tumor compared to the peripheral area. The extent and degree of fibrotic tissue is considered to reflect the enhancement on dynamic MR imaging.

An 81-year-old woman in whom liver dysfunction had been pointed out 3 years previously was diagnosed as having liver cirrhosis due to lupoid hepatitis. Considering the poor prognosis of cirrhosis and her age, immunosuppressive therapy was not adopted. Nine months later, a small liver tumor was found by ultrasonography and was diagnosed as hepatocellular carcinoma (HCC). The tumor was treated with transcatheter arterial embolization, but grew continuously. She also developed gingival lymphoma that was successfully treated. Three years after initial diagnosis of lupoid hepatitis, she died of hepatic failure. An autopsy was performed and confirmed the clinical diagnosis, liver cirrhosis with HCC. HCC is regarded as a rare complication of lupoid hepatitis, but cases of HCC complicating lupoid hepatitis may increase with progress in treatment methods and elongation of survival. The present case suggests that any malignancy can be developed in long-term surviving patients with lupoid hepatitis.

The response of 50 patients who underwent hepatectomy for hepatocellular carcinoma measuring 3 cm or less (at the time of surgery) to transcatheter oily chemoembolization was evaluated. The response was assessed in 5 categories, A: complete necrosis (100%), B: necrosis of at least 95%, C: at least 80%, but less than 95%, D: at least 50% but less than 80%, and E: less than 50% of the tumor cells. Response A was observed in 19 patients (38%), B in 7 (14%), C in 9 (18%), D in 7 (14%), and E in 8 (16%). These results were classified with respect to the histological degree of tumor differentiation, the WHO histological classification, the microscopic patterns of tumor growth, and macroscopic classification. The response was evaluated in relation to the histological grade of tumor differentiation and the WHO histological classification in all categories of response except response A, and there was no significant difference between the categories. The response was obviously better with the expansive type than with the replacing type. Single nodular type lesions were more responsive than the single nodular type lesions with extranodular growth and the contiguous multinodular type. Pretreatment estimation of the microscopic patterns of tumor growth and macroscopic classification appears to be valuable in predicting prognosis.

The relationship between pathologic prognostic factors and abnormal levels of des-gamma-carboxy prothrombin and alpha-fetoprotein was investigated in 42 patients with resectable hepatocellular carcinoma. The frequencies of macroscopic massive type, intrahepatic metastasis, and portal vein tumor thrombus were significantly higher in patients with positive des-gamma-carboxy prothrombin (p less than 0.05) but not with alpha-fetoprotein. Other histologic factors in tumorous and nontumorous tissues were not significantly different irrespective of the positivity of these markers. In patients with tumors not more than 6 cm in diameter, the frequency of intrahepatic metastasis was positively correlated with the positivity of des-gamma-carboxy prothrombin (p less than 0.05) and inversely with that of alpha-fetoprotein (p less than 0.05). Furthermore, intrahepatic metastasis was most frequently observed in patients with positive des-gamma-carboxy prothrombin and negative alpha-fetoprotein (eight of nine) and least frequently in cases with negative des-gamma-carboxy prothrombin and positive alpha-fetoprotein (one of eight). These findings indicated that both des-gamma-carboxy prothrombin and alpha-fetoprotein might be useful markers for the prediction of intrahepatic spread of hepatocellular carcinoma.

In the present study, we compared the survival of patients with multi tumor hepatocellular carcinoma (HCC) following their treatment with liver resection versus TAE. A total of 336 HCC patients were treated at Osaka University Hospital between 1980 and 1989. Of these, 140 patients underwent liver resection in the presence or absence of TAE and 173 subjects were treated with TAE alone. Our TAE protocol consisted of 50 mg Adriamycin, 3-5 ml lipiodol, and Gelfoam. The 1-, 3-, and 5-year survival values found for the liver resection group were 87.4%, 66.0%, and 47.4%, respectively, whereas the values calculated for the TAE group were 64.6%, 29.9%, and 15.8%, respectively. The survival of patients in the resection group was clearly better than that of subjects in the TAE group. Of the 140 patients who underwent resection, 36 cases were proven to have multiple lesions by histopathological examination. The 1- and 3-year survival values determined for this special group were 67.9% and 33.3%, respectively. Of the TAE cases, 113 were diagnosed as having multiple lesions by imaging examination, and their 1- and 3-year survival values were 59.7% and 24.9%, respectively. No significant differences in survival was found between these two different treatment modalities for these multiple-lesion cases. The results of this study indicate that it is unlikely that surgical resection is superior to TAE alone for the treatment of HCC patients with multiple lesions.

The radiologic and histologic findings are presented of the resection of 14 small hepatocellular carcinomas (HCC), less than 2 cm in maximum diameter, after transcatheter arterial chemoembolization (TCE) using iodized oil. The effect of TCE on small HCC depended on the morphologic type of the tumors. When no extracapsular invasion of tumor cells occurred, TCE was extremely effective against encapsulated tumors. However, in nine of the 14 resected specimens, viable tumor cells remained in or around the tumor. The authors suggest that small HCC are not always curable with TCE alone and that a multi-disciplinary approach is necessary for patients with small HCC.

Daughter nodules and intrahepatic metastases are resistant to conventional transcatheter arterial embolization therapy. To clarify the mechanism of this resistance, the boundaries of hepatocellular carcinomas and their relationship to the blood supply were studied. The boundaries of the hepatocellular carcinomas studied were classified as one of five types: encapsulated, granulation, stromal, replacing, or sinusoidal. The granulation and stromal types had a capsule-like structure, but lacked the hyalinization which is the hallmark of a true tumor capsule. The granulation and stromal types could also be differentiated from the encapsulated type because of their different blood supplies and the differing effects of transcatheter arterial embolization. When barium sulfate was infused into the portal vein, it did not enter into encapsulated tumors, but it entered granulation and stromal type tumors. Small nodules such as daughter nodules and intrahepatic metastases do not have capsules, and so have a blood supply that makes them resistant to conventional transcatheter arterial embolization therapy.

Blood from 394 unselected autopsy cases was examined for HB Ag, HB Ab and AFP. Liver morphology of 71 cases of cirrhosis with hepatoma and 32 cases of cirrhosis without hepatoma was studied in detail and correlated to HB Ag, HB Ab, and AFP. Significantly lowered humoral immunity to HB Ag exposure was established for the cirrhosis with hepatoma cases. The exposure rate for both cirrhosis cases with hepatoma and cirrhosis cases without hepatoma was the same (48%), but about 80% of each exposed group were either HB Ag or HB Ab positive. The cirrhosis with hepatoma group tended to be HB Ag positive and the cirrhosis without hepatoma group tended to be HB Ab positive. The lowered immune response seems to be specific to the hepatoma association, because the group with neoplasms other than the hepatoma reacted exactly the same as the group of the cirrhosis without hepatoma. Twenty-five per cent of the cirrhosis with hepatoma were associated with inactive cirrhosis and 75% were associated with active cirrhosis. Seventy-two per cent of the inactive cirrhosis cases with hepatoma were exposed to HB Ag, but only 42% of the active cirrhosis cases with hepatoma were exposed to HB Ag. On the morphological basis, the inactive cirrhosis was interpreted as an impaired cellular immunity and the active cirrhosis as a delayed hypersensitivity reaction. The possibility was discussed that both are important factors in the development of hepatoma preceded by cirrhosis. AFP tends to be positive in the inactive cirrhosis with hepatoma as well as HB Ag, but the relationship between AFP and HB Ag for hepatocarcinogenesis needs further investigation.

In 8 cases of hepatocellular carcinoma, hepatectomy was performed after hepatic artery embolization with Gelfoam. Complete necrosis of the tumor was found in 4 of these cases. Compared with the tumors that showed incomplete necrosis, the tumor in the complete necrosis group were small, thickly encapsulated, and located at sites remote from collateral circulation. Angiography and computed tomography after embolization accurately demonstrated tumor necrosis or continued viability, as confirmed by examination of resected specimens.

We studied the pathological findings in 28 small hepatocellular carcinomas (less than 5 cm in diameter), especially the mode of invasion. Seventeen of the 28 lesions were encapsulated. Capsular invasion was present in 14 of the 17 encapsulated tumours. Vascular invasion was found in 12 of the 28 tumours. The small hepatocellular carcinoma, even when encapsulated, frequently invaded blood vessels and adjacent liver tissue, in spite of frequent vascular invasion, distant metastasis was seen in only 1 of the 28 tumours.

In order to improve the survival rate after liver resection for hepatocellular carcinoma (HCC), 71 HCC patients were treated with transcatheter chemoembolization (TCE). In the present study, we analyzed the effects of TCE on the patients' survival rates, as well as on the liver specimens resected in a histopathological study, comparing those not treated with TCE (n = 21). The overall survival rates, including hospital mortality, for 1 year, 3 years and 5 years were 81%, 72% and 54% respectively. However, no differences were observed in the survival rates between the TCE and the non-TCE groups. A histopathological study demonstrated that TCE was quite effective on the main tumor but not on intrahepatic metastasis or on tumor thrombus in the portal vein. However, we found that most of the intrahepatic metastatic lesions were necrotized in 8 of the 30 cases with these lesions. The histopathological study proved that these particular cases had some abnormalities in the portal blood supply. All but one of them are currently alive 3-48 months after resection, although the prognosis of the patients who had intrahepatic metastasis or a tumor thrombus in the portal vein was extremely poor. Preoperative TCE may, therefore, be thought of as a useful modality when it is effective in killing intrahepatic metastases. To control the lesions, portal vein embolization may be a promising technique in the future.

A 57-year-old man with hepatocellular carcinoma and liver cirrhosis combined with Dubin-Johnson syndrome was successfully treated by extensive right hepatic lobectomy. While the preoperative serum bilirubin level is one of the criteria in determining the indication for radical hepatic resection, it does not play a decisive role in the case of combined Dubin-Johnson syndrome.

A histopathologic study was done on livers from 14 patients who underwent surgery for hepatocellular carcinoma and who had been pretreated by a combination of intra-arterial embolization of Gelfoam (Upjohn) plus intra-arterial chemotherapy. This technique was effective as the excess vascularity of the tumor and the tumor bulk were reduced and resection was readily facilitated. For solitary tumors of less than 4 cm in diameter, this approach was particularly effective. As this combined treatment almost invariably leads to liquefaction and necrosis of the tumor, the likelihood of metastases is diminished.

The authors report a case of needle tract implantation of hepatocellular carcinoma following percutaneous biopsy of the liver. The patient, a 62-year-old Japanese male, was found to have a small hepatocellular carcinoma diagnosed by needle biopsy; this was followed by transcatheter chemoembolization, a combination of transcatheter arterial infusion of adriamycin and transcatheter arterial embolization of Gelfoam, and right lobectomy. Eight months after the biopsy and the lobectomy, a nodule of hepatocellular carcinoma, measuring 3.5 cm in diameter, was found at the site of the previous biopsy and excised. The patient is doing well without further recurrence of tumor 23 months after the lobectomy and 15 months after the excision of the implanted tumor in the subcutis.

Transcatheter arterial chemo-embolization (chemo-embolization) for treatment of unresectable liver cell cancer has now been widely used. Histological appraisal of chemo-embolization had been reported by us and many of cancers thus treated fell into complete necrosis. The present report deals with histological examination on 14 resected specimen of hepatocellular cancer in order to clarify the prevention from intrahepatic spread and therefore to elucidate the justification of preoperative chemo-embolization. One year actuarial survival rate of chemo-embolization followed by hepatic resection was 83%, while that of hepatic resection was 46% and that of chemo-embolization was 59%. Capsular invasion was observed in 83% of cases, but complete necrosis of the capsular invasion was seen in 60% of cases. Eighty-three percent of small cancer, less than 5 cm in diameter, showed completed necrosis of the capsular invasion. This necrotizing effect is beneficial for prevention from the recurrence of the resected stump when local excision is underwent in high risk patients. But once the bulky tumor emboli embedded and grew extensively in the portal vein, they could not be erased .

Histopathology of cirrhosis was compared to the hepatic functional reserve and to the prognosis. One hundred and thirteen patients including 51 surgically treated for hepatocellular carcinoma (HCC) and 62 subjected to wedge biopsy of the liver during surgery for esophageal varices were studied. The type of cirrhosis associated with hepatocellular carcinoma was classified into 4 groups according to the degree of inflammation and the piecemeal necrosis. Of the 16 without cirrhosis, 13 (81 per cent) are living. Nine had an inactive cirrhosis and 5 (56 per cent) are living. Ten had a slightly active cirrhosis and 4 (40 per cent) are living. Sixteen had a fairly active cirrhosis and 7 (44 per cent) are alive. Immediate postoperative death due to acute hepatic failure occurred in 6, 4 of whom had a fairly active cirrhosis. In patients with active alcoholic hepatitis with numerous Mallory bodies and ballooning degeneration of liver cells, the prognosis was the poorest, if the liver was resected, even though the functional reserve seemed to be adequate. To prevent acute hepatic failure, liver histology during the surgery is predictive and wedge biopsy of the liver is recommended.

Transcatheter chemo-embolization is a technique for achieving a marked antitumor effect by embolizing the hepatic artery with a gelatin sponge immediately after infusion of adriamycin 60 mg into the same artery. Chemo-embolization was performed in 212 cases of hepatocellular carcinoma and 23 cases of metastatic liver cancer, a total of 235 patients. Of this population, 19 patients with hepatocellular carcinoma underwent hepatectomy, and in 7 of them, complete necrosis of tumors having thick capsules and less than 4 cm in diameter was confirmed. The cumulative survival rate of patients with unresected hepatocellular carcinoma was 75.6% at 6 months, 52.6% at 1 year, and 20.3% at 2 years. The longest survival time was 3 years and a half, and this patient is now living. As regards metastatic liver cancer, complete necrosis could be achieved in 1 of 2 patients undergoing resection, whereas the cumulative survival rate of unresected cases was 55% at 6 months and 44% at 1 year: only two patients survived for more than 1 year. Technically, the use of a balloon catheter (7F) resulted in the virtual elimination of unsuccessful cases and the prevention of adverse effects due to migration of the gelatin sponge.

Liver tissues of 180 autopsy cases of cirrhosis and hepatoma and 285 consecutive autopsy cases of other diseases were studied for liver cell dysplasia correlated with hepatitis B surface and core antigens (HBsAg and HBcAg) in liver cells and sera, and antibody to HBsAg (anti-HBs) in sera. Liver cell dysplasia was characteristic in cirrhotic livers, particularly with hepatoma. No significant difference was found in age and sex between cirrhotic cases with and without dysplasia. Rate of positive HBsAg in liver cells and sera was significantly high in cirrhotic cases with dysplasia with or without hepatoma. Massive pattern distribution of orcein-positive liver cells was statistically significant in cirrhotic livers with or without hepatoma, but morphological characteristics of orcein-positive liver cells could not be correlated in significance with dysplasia and hepatoma. HBcAg showed neither correlation with liver cell dysplasia nor hepatoma. It appears to correlate with active cirrhosis, marked liver cell degeneration and necrosis, and membranous diffuse type HBsAg in liver cells.

An autopsy case of hepatocellular carcinoma combined with hepatic sarcoma was presented. There were three main tumor nodes in the liver. They showed necrosis due to therapeutic embolization of the hepatic artery. Histologically, one of the three was a hepatocellular carcinoma, and the other two were of spindle cell sarcomas. Extrahepatic metastases all showed characteristics of sarcoma. In the present case report, some problems concerning hepatic sarcoma and sarcomatous representation of hepatocellular carcinoma were proposed in reviewing the literatures.

Factors determining the prognosis of patients with hepatocellular carcinoma (HCC) were analyzed. Small HCC was compared to large HCC. Small HCC is less encapsulated, but has less frequent vascular invasion with favorable prognosis if resectable. Liver transplantation would be indicated in small HCC, unresectable because of far-advanced liver cirrhosis.

A hepatocellular carcinoma (HCC) measuring 0.2 cm in diameter was found in the center of an adenomatous hyperplasia (AH) measuring 1.7 cm in diameter in a cirrhotic liver. The liver cells of the AH showed a marked fatty change and contained many Mallory bodies. The AH and HCC were studied in relation to liver cell dysplasia in 108 surgically resected livers. The AH was mainly associated with fully developed cirrhosis in 5 (71%) of the 7 cases. The liver cell dysplasia, however was accompanied largely by fibrosis and early-stage incomplete septal cirrhosis in 10 (67%) of the 15 cases. As far as the active inflammatory change was concerned, a fairly active inflammation was found in only 3 (20%) of the 15 livers with liver cell dysplasia, but in 4 (57%) of the 7 livers with AH.

We describe a case of hepatocellular carcinoma in which a tumor embolus in the portal vein and 3 of 4 intrahepatic metastases were necrosed completely by Lipiodol transcatheter chemo-embolization (Lipiodol-TCE). Tumor emboli in the portal vein and intrahepatic metastases usually cannot be necrosed by conventional transcatheter chemo-embolization alone, because small nodules such as intrahepatic metastases and tumor emboli in the portal vein are supplied blood from the portal vein. However, in this case, Lipiodol-TCE was effective against tumor emboli in the portal vein and intrahepatic metastases.

A multidisciplinary treatment for hepatocellular carcinoma including preoperative chemo-embolization with resection treatment was introduced. Recent attempts at combining lipiodol with chemo-embolization have been quite promising. An ideal multidisciplinary treatment should include an effective device using the transportal approach.

An autopsy case of a 65-year-old male who died of hepatocellular carcinoma superimposed on liver cirrhosis complicated with systemic sarcoidosis is presented. No organ metastasis of hepatocellular carcinoma was found except for a minute tumor embolus in the left upper lobe of the lung. Involved organs by sarcoidosis were the lymph nodes, lungs, heart, liver and spleen, but its presence was not noticed before death. Its cardiac involvement coincide with his clinical symptom of exertional dyspnea and the ECG finding of A-V block.