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Extracellular adenosine disrupted mitochondrial membrane potentials in HuH-7 cells, a Fas-deficient human hepatoma cell line, and the effect was inhibited by the adenosine transporter inhibitor dipyridamole or by overexpressing Bcl-X(L). Adenosine downregulated the expression of mRNAs and proteins for Bcl-X(L) and inhibitor of apoptosis protein 2 (IAP2) to directly inhibit caspase-3, -7, and -9, but it otherwise upregulated the expression of mRNA and protein for DIABLO, an inhibitor of IAPs. Those adenosine effects were attenuated by dipyridamole. Caspase-3 and -8 were implicated in adenosine-induced HuH-7 cell death, and adenosine actually activated caspase-3 without caspase-9 activation. The caspase-3 activation was inhibited by overexpressing Bcl-X(L) or IAP2. Taken together, the results of the present study indicate that intracellularly transported adenosine activates caspase-3 by neutralizing caspase-3 inhibition due to IAP as a result of decreased IAP2 expression and reduced IAP activity in response to increased DIABLO expression and perhaps DIABLO release from damaged mitochondria, in addition to caspase-8 activation. This represents further insight into adenosine-induced HuH-7 cell apoptotic pathway.

Extracellular adenosine-induced apoptosis of HepG2 cells, a human hepatoma cell line, in a concentration (0.1-20mM)- and treatment (24-72h)-dependent manner by activating caspase-3, -8, and -9. In the gene expression assay using a DNA microalley, adenosine upregulated mRNAs for tumor necrosis factor (TNF), TNF receptor 1-associated death domain protein (TRADD), TNF related apoptosis-inducing ligand receptor 2 (TRAIL-R2), TRADD/receptor-interacting protein kinase 1 (RIPK1), Fas-associated death domain protein (FADD), and caspase-9, involving activation of caspase-8 and -9 followed by the effector caspase-3. The results of the present study suggest that adenosine induces HepG2 cell apoptosis by activating those caspases as a result from tuning apoptosis-mediator gene transcription.

Background: Interferon (IFN) reduces the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). However, HCC develops in the some patients who have achieved a sustained virological response (SVR). The aim of this study was to clarify the features and prognosis of SVR patients who developed HCC., Materials and Methods: Twenty-six patients who underwent curative hepatectomy for initial HCC after IFN therapy were closely investigated. Twenty patients who were seropositive for HCV-RNA (non-SVR), and a further 6 patients who achieved SVRs (SVR) were included. We analyzed the clinicopathological features, immunological expression levels of p53 and whether HCV-RNA is present in the excised liver., Results: The liver functions of the SVR group were almost better than those of the non-SVR group. However, there was no significant difference in pathological features, surgical factors and prognosis between the groups. In one case with SVR out of eight specimens tested was HCV-RNA detected in the non-cancerous tissue. Immunohistochemistry revealed overexpression of p53 in eight HCCs (100%) from SVR patients., Conclusion: Recurrent HCC still developed after the curative hepatectomy, even if viral elimination had been successful. And molecular alterations in hepatocarcinogenesis of SVR patients might be different from those of CHC patients.

Extracellular adenosine induced apoptosis of HuH-7 cells, a Fas-deficient human hepatoma cell line. The adenosine action was inhibited by dipyridamole, an adenosine transporter inhibitor, or 5'-amino-5'-deoxyadenosine, an inhibitor of adenosine kinase to convert from adenosine to AMP, but it was not affected by inhibitors for adenosine A(1), A(2a), A(2b), and A(3) adenosine receptors. Adenosine activated caspase-3 and -8, but not caspase-9, in HuH-7 cells, and the activation was abolished by dipyridamole. In the real-time RT-PCR and Western blot analysis, extracellular adenosine downregulated mRNA and protein levels for c-FLIP, and the effect was suppressed by dipyridamole. Furthermore, overexpression of c-FLIP short in HuH-7 cells inhibited adenosine-induced caspase-8 activity. Taken together, these results suggest that intracellularly transported adenosine, perhaps converted AMP as the ensuing event, activates caspase-8 and the downstream effector caspase caspase-3 by neutralizing caspase-8 inhibition due to c-FLIP as a consequence of decreased c-FLIP expression, leading to apoptosis. This extends our understanding of adenosine-induced molecular apoptotic pathways.

Background/aims: Early detection and treatment of recurrent hepatocellular carcinoma (HCC) are keys to patient survival after hepatic resection. In attempts at early detection, we make use of the alpha-fetoprotein (AFP) test every month and abdominal ultrasound (US) and computed tomography (CT) are carried out every three months after hepatectomy. The objective of the present study was to evaluate the most appropriate interval for follow-up re-examinations after resection for HCC., Patients and Methods: Eighty-five patients with recurrent HCC were divided into two groups according to the state of the tumor when recurrence was detected: Group I (n = 70); tumor size < or = 2.0 cm, and group II (n = 15); tumor size > or = 2.1 cm. Clinicopathological comparisons were made between the two groups., Results: AFP positivity in group I was significantly lower than group II at the time of recurrence. Rates of extrahepatic intra-abdominal recurrences, i.e. recurrence at the surgical stump and in the abdominal cavity and lymph nodes around the liver, were more frequent in group II than in group I (47% vs 4%; p < 0.001). The average tumor size was larger in 10 patients with extrahepatic intra-abdominal recurrence than in 75 patients with intrahepatic recurrence (3.4 +/- 2.0 vs 1.6 +/- 0.6 cm; p < 0.0001). There was a statistically significant difference regarding the histological grade of initial HCC between the two patterns of recurrence., Conclusions: Measurements of AFP were seen to have limited value for detecting recurrence, at an early stage. Close postoperative follow-up, including bedside US in the outpatient clinic, should be carried out when the initial HCC is histologically less differentiated HCC.

Objectives: To clarify the indications for and the significance of palliative reduction surgery in the multidisciplinary treatment of advanced hepatocellular carcinoma (HCC) and to propose the use of a remnant tumor index (RTI) as a simplified criterion for palliative reduction surgery in cases of advanced HCC., Design: A comparison of survival based on the RTI., Setting: A large university hospital in Japan., Patients: Twenty-five patients with advanced HCC who underwent palliative reduction surgery were divided into 3 groups as follows: group 1 (n = 9), the remnant tumor after operation existed only in the liver and the RTI was less than 5.0; group 2 (n = 11), the remnant tumor after operation existed only in the liver and the RTI was greater than 5.0; and group 3 (n = 5), extrahepatic metastatic tumor existed after operation., Main Outcome Measures: Pathological findings and survival rate after surgery., Results: There was no significant difference in the degree of macroscopic intrahepatic metastases among the 3 groups; however, both the portal vein invasion and the histological grade tended to be more severe in groups 2 and 3. The respective 1-year and 3-year survival rates for group 1 were 67% and 33%, and those for group 2 were 21% and 0%. There were no survivors in group 3 at 1 year after surgery. Significant differences were found in the survival rates between groups 1 and 2 (P < .05), and between groups 1 and 3 (P < .05)., Conclusion: Palliative reduction surgery for advanced HCC is only considered effective for patients with both an RTI of less than 5.0 and no extrahepatic metastasis.

Background & Aims: Little has been addressed on the characteristics and prognostic factors of recurrent hepatocellular carcinoma after undergoing a hepatic resection for primary hepatocellular carcinoma. The aim of this study was to clarify the aforementioned matters of recurrent hepatocellular carcinoma., Methods: One hundred fifty-nine patients with recurrent hepatocellular carcinoma were studied retrospectively. Twenty-four clinicopathologic variables, including the period until recurrence (less than or more than 1 year), types of recurrence (intrahepatic nodular type, intrahepatic multiple type, and extrahepatic type), and types of treatment after recurrence (no treatment, lipiodolization, ethanol injection, or hepatectomy) were univariately and multivariately analyzed., Results: The following three variables were finally selected as independent and prognostic indicators after recurrence: (1) period until recurrence, (2) type of recurrence, and (3) types of treatment after recurrence., Conclusions: The prognostic factors in patients with recurrent hepatocellular carcinoma were as follows: (1) period until recurrence, (2) types of recurrence, and (3) types of treatments received after recurrence. The establishment of a follow-up system, including an examination for extrahepatic recurrence, and the development of an effective method of adjuvant chemotherapy are required to obtain better treatment results.

Background: This study was conducted to identify the prognostic indicators for patients with stage IV hepatocellular carcinoma (HCC), as well as to clarify the strategy of surgical treatment for those patients., Methods: Forty-six patients with stage IV HCC were included in this study. Prognostic factors were univariately and multivariately analyzed. Furthermore, the significance of intraoperative treatment for residual tumors was investigated in patients with an absolute noncurative operation., Results: The poor prognostic factors were as follows: host factors, Child's classification of B and C and immunosuppressive acidic protein level of greater than 400 micrograms/ml; tumor factors, tumor diameter of greater than 5 cm, poorly differentiated histologic features, positive portal vein invasion, and intrahepatic metastases involving more than three segments; others, an absolute noncurative operation and no preoperative treatment. Tumor diameter of more than 5 cm was then suggested to be an independent prognostic indicator. Survival of patients with stage IV-A HCC who underwent a curative operation was similar to that of those with stages III HCC: Furthermore, the survival of patients with Stage IV-A who had an absolute noncurative operation but underwent either intraoperative microwave coagulation or ethanol injection to the residual HCCs was not statistically different from that of those with a curative operation., Conclusions: Therefore for stage IV-A HCC surgical treatment is considered to be both useful and the first choice of treatment when all the tumors in the liver can be removed or when the residual tumors can be treated during operation by either microwave coagulation or ethanol injection as a result of an incomplete removal of the tumors.

Objectives: This study was conducted to clarify the characteristics of patients with extrahepatic primary cancers (EHPC) associated with hepatocellular carcinoma (HCC), as well as to investigate the influence of EHPC on both patient survival and disease-free survival after hepatic resection., Methods: Forty-one of 463 patients who underwent hepatic resection were included. The clinicopathological factors, including survival, were compared between patients with and without EHPC. We also compared the same factors among the prehepatectomy, synchronous, and posthepatectomy groups. Different types of extrahepatic cancers were also investigated in detail., Results: Gastric and colorectal cancers were the most common EHPC. No definite relationship was observed between HCC and other specific cancers such as B-cell lymphoproliferative disorders. There also were no differences in either the liver function tests, alpha-fetoprotein, or prognostic pathological indicators such as portal vein invasion and intrahepatic metastases. In addition, we found no difference in patient survival between the patients with and without EHPC. However, disease-free survival rates in patients with EHPC were significantly higher than in those without EHPC. Patients in the prehepatectomy group were older than those in the synchronous and posthepatectomy groups, and no positive hepatitis B surface antigen was found in the prehepatectomy group. Patient survival was significantly higher in the posthepatectomy group than in the prehepatectomy group; however, no significant difference in disease-free survival was found among the three groups. Only one patient died of EHPC., Conclusions: No specific clinicopathological factors were observed in patients with HCC associated with EHPC. Furthermore, EHPC had no adverse effect on either patient survival or disease-free survival after hepatic resection. The predominant cancer was gastric cancer, whereas the most frequent cause of death was HCC itself. Therefore, a strict follow-up of HCC--as well as screening for the most common cancers, such as gastric cancers in southern Japan--should be required for patients with HCC associated with EHPC.

Objective: To evaluate the recent results of liver resection in patients with hepatocellular carcinoma., Design: Retrospective study., Setting: A university hospital in Japan., Patients: Two hundred eighty patients who underwent liver resection with complete extirpation of hepatocellular carcinoma from 1985 to 1993., Main Outcome Measures: Morbidity and survival after operation and the pathologic features of hepatocellular carcinoma according to the TNM classification of the International Union Against Cancer., Results: More than 40% of the patients with stages I and II disease underwent a partial resection of the liver, whereas 50% of those with stages III and IVA were operated on with more than a bisegmentectomy. Fifty percent of all patients had no postoperative complications. The morbidities included intra-abdominal abscess (7%), bile leakage (5%), and hepatic failure (4%, of whom half died; mortality rate, 2%). Histopathologically, 32% of the stage I tumors were well differentiated (grade 1), while, in stage III, 56% had portal invasion and 61% had daughter lesions in the liver. The cumulative survival rates of patients with stages I, II, and III disease and all patients at 5 years were 69%, 52%, 32%, and 50%, respectively, while the disease-free survival rates at 5 years were 38%, 34%, 17%, and 29%, respectively., Conclusion: The recent results of liver resection for hepatocellular carcinoma are generally satisfactory; however, the recurrence rate is still high.

Despite recent progress in diagnostics for hepatocellular carcinoma, the rate of resectability remains low, mainly because of the advancement of the underlying liver disease. We report a case of a 54-year-old man with a hepatocellular carcinoma and poor liver function that was treated successfully with a laparoscopic hepatic resection. Laparoscopic hepatic resection is considered to be feasible with the aid of an ultrasonic dissector and a microwave coagulator; however, close attention should be paid to the development of air embolism and hepatic vein injury.

Seventeen patients with ruptured hepatocellular carcinoma (HCC) underwent a hepatic resection from 1985 to 1992 at either Kyushu University Hospital or Iizuka Hospital in Japan. They all underwent elective surgical procedures except for one patient who experienced a repeated rupture during hospitalization. A comparative study between the patients with ruptured HCC and non-ruptured large HCC measuring more than 6 cm in size (n = 29) revealed that the 3-year disease-free survival rate of the ruptured HCC group was 14.5% which was worse than that of the non-ruptured group at 39.9%. There was no difference in the rates of peritoneal dissemination, distant metastasis or intrahepatic recurrence between the two groups. Regarding the intrahepatic recurrence pattern, widespread multinodular recurrence frequently occured in the ruptured patients, which was thought to be caused by the high incidence of venous invasion in the primary tumor. The intratumor pressure of the ruptured HCC appeared to be elevated and is considered to be one of the main reasons for the high incidence of venous invasion.

A hepatectomy in cirrhotic patients with hepatocellular carcinoma, located in either the posterior or superior part of the right lobe, inevitably requires a forced mobilization of the right lobe. Such a forced procedure causes a decreased hepatic blood flow resulting in postoperative morbidity and mortality, as well as an increased risk of the intrahepatic dissemination of cancer cells during the operation. We have thus refined the method of trans-thoracoabdominal hepatectomy to minimize those demerits of conventional transabdominal hepatectomies. The main characteristics of our refinements are as follows; (1) an optimal incision for the best short-cut to the hepatocellular carcinoma is determined by a three-dimensional imaging of either helical computed tomography and/or magnetic resonance imaging before operation; (2) a complete view of the operative field is obtained by the pertinent use of rotating the operation table, on which the patient is placed in a left semi-lateral position; (3) this method is suitable for resecting a tumor located in the posterior segment such as a posterior segmentectomy. This refined method is considered to decrease the postoperative morbidity including post-operative hepatic dysfunction and is also useful for cirrhotic patients with hepatocellular carcinoma.

To assess the differences in the surgical results between patients with hepatitis B- and hepatitis C-related hepatocellular carcinoma (HCC), the operative outcomes of 30 patients with hepatitis B surface antigen (HBsAg)-positive (the B-HCC group) and 96 patients with hepatitis C antibody (HCVAb)-positive (the C-HCC group), who had undergone hepatic resection from 1989 to 1993, were compared. The mean age of the patients in the C-HCC group was higher than that in the B-HCC group (61.7 years vs. 57.0 years, P < .05). The C-HCC group demonstrated both a greater decrease in liver function and a larger enhancement of inflammatory changes in the liver under a pathological examination (the current rate of active hepatitis: 69% vs. 27%, P < .001). There was also a higher incidence of total postoperative complications in the C-HCC group (60% vs. 37%, P < .05); however, regarding each individual complication, the rate was similar between the two groups. Two of the six patients with postoperative hepatic failure in the C-HCC group died. The mortality rate in the C-HCC group was 2%, but no operative death was encountered in the B-HCC group. The crude survival and the disease-free survival rates at 5 years were similar, 61.8% and 46.2% in the B-HCC group and 52.8% and 23.2% in the C-HCC group, respectively. The patterns of recurrence were also similar in both groups. The pathological features of HCC were similar between the two groups. In conclusion, the surgical results between the two groups were almost identical.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipiodolization--selective regional cancer chemotherapy using Lipiodol plus an anticancer drug (LPD)--can prolong survival time of patients with an unresectable hepatocellular carcinoma (HCC). To enhance understanding of LPD's influence on the cirrhotic liver, we carried out related studies. Forty-three cirrhotic patients with HCC were treated with LPD (epirubicin in a dose of 15-40 mg/m2 and Lipiodol of 0.02-0.25 ml/kg). Seven cirrhotic patients with HCC were subjected to hepatic angiography alone, and these subjects selected randomly served as controls. Among the 43 treated with LPD, 23 belonged to Child's class A, 15 to class B, and 5 to class C. Blood samples were taken before angiography (pre) and at 24 hours after angiography (post) from each patient. Post/pre ratio of the following parameters were compared between patients of the two groups: sGOT, sGPT, and LDH as a marker for hepatocyte injury; t. bilirubin and hepaplastin test (HPT) as hepatocyte function; alkaline phosphatase and gamma-GTP to examine bile duct injury; and serum hyaluronic acid level to determine an endothelial cell functions. Post/pre ratio of serum GOT, GPT, LDH levels, and HPT in patients treated with vs. without LPD were 1.32 +/- 0.59 vs. 0.92 +/- 0.09 (P < 0.001), 1.18 +/- 0.43 vs. 0.88 +/- 0.09 (P < 0.001), 1.11 +/- 0.20 vs. 1.00 +/- 0.07 (P < 0.05), and 0.95 +/- 0.10 vs. 1.09 +/- 0.12 (P < 0.01), respectively. There were no significant differences in post/pre LPD ratio of other parameters, rates of complications, and hospital stay after LPD for patients with Child's class A, B, and C. Hepatocytes are apparently the primary site of injury in cases of LPD. LPDs, using epirubicin in a dose of 15-40 mg/m2 and Lipiodol in a dose of 0.02-0.25 ml/kg, proved to be safe for cirrhotic patients with HCC.

Background: To determine a feasible postoperative adjuvant chemotherapy for patients with hepatocellular carcinoma, orally-administered chemotherapy (OC) and prophylactic lipiodolization (selective regional cancer chemotherapy using lipid contrast medium plus an anticancer drug) (PL) were compared prospectively., Patients and Methods: Forty-eight patients who had undergone hepatic resection from 1989 to 1992 were divided into three groups: the control group (n = 19), given no chemotherapy; the OC group (n = 12), given 300 to 400 mg/d of 5-FU derivatives (either 1-hexylcarbamoyl-5-fluorouracil or uracil and tegafur, mean total dosage: 188 g, mean administrative duration: 18 months); and the PL group (n = 17), who underwent prophylactic lipiodolization 1.8 times on average using a 44-mg mean dose of epirubicin per treatment., Results: No statistical differences were found either in the 25 variables studied as a background analysis, or among the survival curves of the 3 groups. Recurrence was found in 23 remnant livers of the 48 patients. The 3-year, disease-free survival rate was 15%, 50%, and 86% in the control, OC, and PL groups, respectively. The disease-free survival curve of the PL group was significantly higher compared to either the control (P = 0.001) or the OC group (P = 0.025)., Conclusions: Prophylactic lipiodolization was found to be an effective treatment for patients with hepatocellular carcinoma for reducing intrahepatic recurrence after resection.

The functional reserve of the liver should be estimated prior to hepatectomy. While the experienced liver surgeon often relies on the findings of manual palpation intra-operatively, this approach remains a subjective one. In 22 of our patients scheduled for hepatectomy, we measured intra-operatively hepatic consistency as well as the parameters of liver function. Hepatic consistency is augmented during progression from non-fibrosis to cirrhosis. We found a statistically significant correlation between liver consistency and the indocyanine green retention rate at 15 minutes (r = 0.682; p = 0.0009) and portal vein pressure (r = 0.733; p = 0.0008). Prothrombin time, the hepaplastin test, total bilirubin and glutamic pyruvic transaminase showed no significant correlation with hepatic consistency. The safety limits of the hepatic blood circulation for the performance of hepatectomy can be estimated using parameters of consistency in this organ.

Total parenteral nutrition can be used to overcome amino acid imbalance in cancer patients. Because there is little documentation of treatment for amino acid imbalance in patients with hepatocellular carcinoma (HCC), we designed a study 1) to compare tissue levels of amino acids between HCC and the adjacent liver and 2) to determine which serum amino acids correlate to tumor volume. A significant elevation of methionine and a significant decrease of glycine and cystine were observed in HCC compared with adjacent liver tissue, and a significant correlation was found between tumor volume and serum methionine levels (r = -0.636, p < 0.01). Thus the tumor tissue competes successfully with host tissue for nitrogen substrates, particularly methionine, and an accelerated protein synthesis in HCC consumes large amounts of these amino acids. The possibility of methionine-depleted treatment could be considered for patients with HCC.

Objective: To estimate the effectiveness of hepatic resection on hepatocellular carcinoma (HCC) in the elderly., Design: Comparison with younger patients., Setting: A municipal hospital and a large university hospital in Japan., Patients: The study included 39 patients (age > or = 70 years [the elderly group]) and 229 patients (age < 70 years [the younger group]) who underwent hepatic resection from April 1985 to March 1993. The preoperative clinical features (Child's classification, association of cirrhosis and liver functions) were comparable between two groups. The positive rate for hepatitis C virus antibody was higher in the elderly group (88% vs 59%; P = .016)., Main Outcome Measures: Morbidity and survival following operation and the pathological features of HCC., Results: The incidence of postoperative hepatic failure was higher in the elderly group (10% vs 2%; P = .018). However, the incidence of operative death in the elderly group (5% vs 1%) as well as the incidence of other postoperative complications and rates of long-term survival (75.9% vs 51.6% at 5 years) and disease-free survival (30.4% vs 31.0% at 5 years) were similar to those in the younger group. The pathological features of HCC were identical between the two groups., Conclusion: The outcome of surgical treatment of HCC in the elderly group was satisfactory when compared with that in the younger group.

We experienced two patients with a prosthetic heart valve, who underwent hepatic resection for hepatoma while on anticoagulation therapy. Patients with a prosthetic heart valve have the following characteristics; an increased risk of thromboembolism due to diminished anticoagulation in the perioperative period, a greater risk of endocarditis due to the artificial material in the heart, and impaired cardiopulmonary function including possible arrhythmia and heart failure. Furthermore, when such patients also have liver cirrhosis with a hepatoma, there is an increased risk of perioperative bleeding while on anticoagulation due to coagulopathy and also a risk of infection due to decreased cellular immunity. Patients with a prosthetic heart valve therefore require special care and attention whenever they have to undergo hepatic resection. With respect to anticoagulation, a minimal level is required to prevent bleeding and thromboembolism. Warfarin being administered preoperatively may be switched to heparin while closely monitoring the activated clotting time (biomaterial valve: 130-150 sec, non-biomaterial valve: 150-180 sec); the heparin should then be changed back to warfarin immediately after starting oral intake following operation. For the prevention of infection, a broad spectrum antibiotic should be used prophylactically both intra-operatively and postoperatively. The cardiopulmonary function must also be carefully monitored. For the assessment of postoperative liver function, lecithin: cholesterol acyltransferase, serum bilirubin and albumin are useful because there is no relevance of coagulation parameters such as prothrombin time under anticoagulation.

To assess the features of multicentric occurrence in hepatocellular carcinoma, we analyzed 10 of 72 patients (14%) who had undergone hepatic resection for hepatocellular carcinoma from May 1989 to October 1992 both clinically and pathologically. The multicentric occurrence of hepatocellular carcinoma was defined among the simultaneously detected small tumors as (a) at least one tumor consisting of extremely well-differentiated (grade I) hepatocellular carcinoma growing in a replacing pattern or (b) one of a group of hepatocellular carcinomas growing in an area of adenomatous hyperplasia. Of the 10 patients, the tumors in 9 were diagnosed as synchronous multicentric hepatocellular carcinomas, whereas the tumor in 1 was considered metachronous. All patients had cirrhosis; one of them had hepatitis B virus infection and nine patients had HCV infection. The inflammatory findings in the parenchyma were determined on the basis of serum enzyme values (AST, 89 +/- 27 IU/L; ALT, 96 +/- 43 IU/L). One or two tumors in 9 of 10 patients had thin trabecular or trabecular patterns showing replacing growth. In addition, one of the two tumors in two of nine patients was observed growing in areas of adenomatous hyperplasia. Recurrences were found in 4 of 10 patients. The 3-yr disease-free survival rate was 23%. Multiple recurrences were recognized in the two patients, and in the patients who underwent repeat surgery, grade I tumors were also found. Even though these tumors were small and well-differentiated, the recurrence rate was high. Therefore to detect the recurrence of metachronous multicentric hepatocellular carcinoma at an earlier stage, careful follow-up after surgery should be carried out.

Background: The effects of preoperative transcatheter arterial chemoembolization (TAE) for hepatocellular carcinoma (HCC) remain a matter of controversy., Methods: Seventy-two patients with HCC were entered in the study; the patients did not have the risk factors for disease recurrence of tumor larger than 5 cm in diameter, the presence of venous invasion, or intrahepatic metastasis. Only patients with 3 years of follow-up after curative resection were selected. Forty-six underwent TAE (Group I) and 26 did not undergo TAE (Group II). Group I was divided into three subgroups according to the degree of tumor necrosis: IA, complete necrosis; IB, partial necrosis; and IC, no necrosis. Group II was divided into two subgroups: IIB, partial necrosis; and IIC, no necrosis., Results: Preoperative TAE did not improve the average disease-free survival rates of the group as a whole. For patients undergoing TAE, the survival rate of Group IB was significantly worse than that of Groups IA or IC. The survival rate of Group IB was worse than that of Group II, but the difference was not significant. In Group II, the survival of Group IIB was worse than that of Group IIC. Histologically, residual tumor cells lacking mutual contact were detected in some patients in Group IB., Conclusion: These results indicate that partial tumor necrosis caused by preoperative TAE or spontaneous tumor necrosis per se might facilitate postoperative disease recurrence. This may occur because in patients with partial necrosis, the remaining tumor cells are less firmly attached and more likely to be dislodged into the bloodstream during hepatic resection.

A review of seven hepatic resections in six patients undergoing maintenance hemodialysis is presented. These cases consisted of hepatocellular carcinoma in four, and cholangiocellular carcinoma, myelolipoma and focal nodular hyperplasia in one each. The last preoperative hemodialysis was undertaken within 24 h prior to the operation with heparin. Intraoperatively, infused solutions containing no potassium, along with strict attention to preventing overhydration, allowed us to manage the patients without hemodialysis on the day of the operation. No specific intra-operative complications related to hemodialysis were noted. Postoperative hemodialysis was performed on the first or second day after operation, using nafamstat mesilate, a synthetic protease-inhibiting agent. The morbidity rate in the hemodialyzed patients was 85.7% (6/7), which was significantly higher than that in the non-hemodialyzed patients who underwent hepatic resections in our hospital. Fluid collection in the pleural and/or peritoneal cavities was frequent and difficult to control, but transient. Our experience suggests that hepatic resection is an acceptable procedure for hemodialyzed patients, when used in conjunction with careful perioperative management.

To determine the optimal surgical therapy for patients with pedunculated hepatocellular carcinoma (HC), we evaluated findings in ten patients with pedunculated HC among 350 patients with HC who underwent hepatectomy from 1975 to 1991 at Kyushu University Hospital. These patients were classified into three groups: Group I (n = 4) Pedunculated HC with no intrahepatic HC, Group II (n = 2) Pedunculated HC with a single intrahepatic HC, and Group III (n = 4) Pedunculated HC with multiple intrahepatic HC. Patients in group I and II were treated by partial hepatic resections or subsegmentectomies. In two patients there was an intrahepatic recurrence in the same lobe, after radical resection. All patients in group III who underwent palliative resection died within 8 months after surgery. Retrospectively, we favour the view that patients in Groups I or II may have had a better prognosis if lobectomy rather than partial hepatectomies had been done.

Using selective angiograms of the liver, we analyzed the patterns of intrahepatic recurrence of hepatocellular carcinomas following curative surgery. In 33 patients with intrahepatic recurrences, seven patients (21%) had a recurrence near the resected hepatic stump. The remaining 26 had either a nodular recurrence in segments away from the resected margin or a widespread multinodular recurrence in the liver remnant. There was a recurrence within the first postoperative year in five of 16 patients with a nodular recurrence and in eight of 10 patients with a widespread multinodular recurrence. In these patients, particularly those with a widespread multinodular recurrence, tumor thrombi in the portal vein present before the operation and/or disseminated during operation from such an advanced main tumor seemed to be the most important and significant factor related to the early recurrence in the remnant liver. This evidence suggests that in cases of surgery for hepatocellular carcinoma it is important to establish a technique to prevent dissemination of cancer cells due to operative manipulation and also adequate adjuvant therapy rather than attempting to obtain an ample resection margin.

Between 1982 and 1987, selective regional cancer chemotherapy using Lipiodol plus an anticancer drug (lipiodolization) was prescribed for 200 patients with hepatocellular carcinoma. One hundred forty-nine patients were given lipiodolization alone, and the remaining 51 underwent hepatic resection following lipiodolization. The grades of deposits of the oily contrast medium in the neoplastic tissue seen on the plain X-ray correlated well with the antitumor effect. In the resected specimens of 17 patients treated with lipiodolization prior to surgery, concentrations of adriamycin in the malignant liver tissues were 13.2 +/- 18.2 micrograms per gm, whereas the adjacent liver parenchyma contained 1.4 +/- 2.0 micrograms per gm of adriamycin; the difference was statistically significant (p less than 0.05). In the 149 patients treated with lipiodolization, 1-, 2-, 3- and 4-year survival rates were 56.1, 28.9, 17.3 and 7.4%, respectively. Thus, lipiodolization was considerably more effective, compared to the results achieved by hepatic artery ligation and cannulation into the hepatic artery for patients in Stages I and II. In this sequential nonrandomized study, the survival rates for patients undergoing hepatic resection were superior to those for patients in Stage I and treated with lipiodolization. The significant difference appeared to depend on incomplete killing of tumor cells, which are most often present in the fibrous capsule, by lipiodolization. We conclude from these data that lipiodolization is an effective treatment for hepatocellular carcinoma when the tumor is not curatively resectable. When the clinical status is good, then surgery is warranted.