Search

Nonalcoholic steatohepatitis (NASH) can lead to cirrhosis and hepatocellular carcinoma in their advanced stages; however, there are currently no approved therapies. Here, we show that microRNA (miR)-33b in hepatocytes is critical for the development of NASH. miR-33b is located in the intron of sterol regulatory element-binding transcription factor 1 and is abundantly expressed in humans, but absent in rodents. miR-33b knock-in (KI) mice, which have a miR-33b sequence in the same intron of sterol regulatory element-binding transcription factor 1 as humans and express miR-33b similar to humans, exhibit NASH under high-fat diet feeding. This condition is ameliorated by hepatocyte-specific miR-33b deficiency but unaffected by macrophage-specific miR-33b deficiency. Anti-miR-33b oligonucleotide improves the phenotype of NASH in miR-33b KI mice fed a Gubra Amylin NASH diet, which induces miR-33b and worsens NASH more than a high-fat diet. Anti-miR-33b treatment reduces hepatic free cholesterol and triglyceride accumulation through up-regulation of the lipid metabolism-related target genes. Furthermore, it decreases the expression of fibrosis marker genes in cultured hepatic stellate cells. Thus, inhibition of miR-33b using nucleic acid medicine is a promising treatment for NASH., (© 2023 Miyagawa et al.)

Background: Although liver resection is the only potentially curative treatment for colorectal liver metastases, recurrence is frequent. We previously published the early results of a randomized controlled phase 3 trial showing that adjuvant therapy with uracil-tegafur and leucovorin significantly prolongs recurrence-free survival. This study sought to elucidate the impact of adjuvant chemotherapy on patient survival after an additional follow-up period, building upon the results of our previous study., Methods: After resection for colorectal liver metastases, patients were randomly assigned in a 1:1 ratio to receive adjuvant uracil-tegafur and leucovorin or surgery alone. Patients assigned to the uracil-tegafur and leucovorin group received 5 cycles of uracil-tegafur and leucovorin within 8 weeks after surgery., Results: Patients were assigned to an adjuvant uracil-tegafur and leucovorin (n = 90) or a surgery alone (n = 90) group; 3 patients were excluded because of protocol violations. After a median follow-up period of 7.36 years (95% confidence interval, 6.93-7.87), 60 (68.2%) patients in the uracil-tegafur and leucovorin group and 61 (68.5%) patients in the surgery alone group developed recurrences. The median recurrence-free survival was 1.45 years (95% confidence interval, 0.96-2.16) in the uracil-tegafur and leucovorin group and 0.70 years (95% confidence interval, 0.44-1.07) in the surgery alone group. The locations and treatments of the first recurrences did not differ between the groups, nor did the overall survival (hazard ratio, 0.86; 95% confidence interval, 0.54-1.38; P = .54). The overall survival was significantly longer in patients who underwent curative repeated resection than in patients who received non-surgical treatment (hazard ratio, 0.25; 95% confidence interval, 0.15-0.40; P < .0001)., Conclusion: Adjuvant uracil-tegafur and leucovorin significantly prolonged the recurrence-free survival but not the overall survival. The repeated resection was the most important factor influencing overall survival., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The effect of cetuximab plus mFOLFOX on downsizing of the tumors for curative resection has yet to be assessed for patients with advanced colorectal liver metastases (CRLMs). This study aimed to assess the oncologic benefit of cetuximab plus mFOLFOX for wild-type KRAS patients with advanced CRLMs., Methods: In this multicenter phase 2 trial, patients with technically unresectable tumor and/or five or more CRLMs harboring wild-type KRAS were treated with mFOLFOX plus cetuximab. The patients were assessed for resectability after 4 treatments, and then every 2 months up to 12 treatments. Patients with resectable disease were offered surgery after a waiting period of 1 month. The primary end point of the study was the R0 resection rate. The secondary end points were safety, progression-free survival (PFS), and overall survival (OS). The study is registered with the University Hospital Medical Information Network-Clinical Trials Registry Clinical Trials Registry (no. C000007923)., Results: Between 2012 and 2015, 50 patients from 13 centers were enrolled in this trial. Two patients were excluded because they had not received induction therapy. The 48 patients had a complete response rate of 0% and a partial response rate of 64.6%. For 26 R0 resections (54.2%) and 5 R1 resections (10.4%), no mortality occurred. During a median follow-up period of 31 months, the median OS for all the patients was calculated to be 41 months (95% confidence interval, 28-not reached). The 3-year OS rate was 59%., Conclusion: For patients with advanced CRLMs harboring wild-type KRAS, cetuximab administered in combination with mFOLFOX yields high response rates, leading to significantly high R0 resection rates and favorable prognoses.

Background: The high recurrence rate after surgery for colorectal cancer liver metastasis (CLM) remains a crucial problem. The aim of this trial was to evaluate the efficacy of adjuvant therapy with uracil-tegafur and leucovorin (UFT/LV)., Methods: In the multicenter, open-label, phase III trial, patients undergoing curative resection of CLM were randomly assigned in a 1:1 ratio to either the UFT/LV group or surgery alone group. The UFT/LV group orally received 5 cycles of adjuvant UFT/LV (UFT 300mg/m2 and LV 75mg/day for 28 days followed by a 7-day rest per cycle). The primary endpoint was recurrence-free survival (RFS). Secondary endpoints included overall survival (OS)., Results: Between February 2004 and December 2010, 180 patients (90 in each group) were enrolled into the study. Of these, 3 patients (2 in the UFT/LV group and 1 in the surgery alone group) were excluded from the efficacy analysis. Median follow-up was 4.76 (range, 0.15-9.84) years. The RFS rate at 3 years was higher in the UFT/LV group (38.6%, n = 88) than in the surgery alone group (32.3%, n = 89). The median RFS in the UFT/LV and surgery alone groups were 1.45 years and 0.70 years, respectively. UFT/LV significantly prolonged the RFS compared with surgery alone with the hazard ratio of 0.56 (95% confidence interval, 0.38-0.83; P = 0.003). The hazard ratio for death of the UFT/LV group against the surgery alone group was not significant (0.80; 95% confidence interval, 0.48-1.35; P = 0.409)., Conclusion: Adjuvant therapy with UFT/LV effectively prolongs RFS after hepatic resection for CLM and can be recommended as an alternative choice., Trial Registration: UMIN Clinical Trials Registry C000000013., Competing Interests: NK reports personal fees for seminar presentations from Merck Serono, Chugai Pharma, and Taiho Pharmaceutical during the conduct of the study. All other authors declare no competing interests. We now confirm that this does not alter our adherence to PLOS ONE policies on sharing data and materials.

We report the case of a 58-year-old man referred to our hospital for liver tumor treatment. The patient had a history of neurosurgery for a meningeal hemangiopericytoma 16 years previously. Pre-operative imaging revealed a hypervascular tumor extending from Couinaud segment 4 to segment 8 of the liver, measuring 95 mm in diameter, indicating an atypical hepatocellular carcinoma. Because right trisectionectomy of the liver was considered to be high risk, living-donor liver transplantation (LDLT) was indicated. After transcatheter arterial embolization, LDLT was performed with the use of a left-lobe liver graft from the patient's son. Post-operative histological findings of the liver tumor were identical to those for meningeal hemangiopericytoma, therefore the patient was diagnosed with meningeal hemangiopericytoma that had metastasized to the liver. After LDLT, the patient had a healthy, active life for 2 years; then, a subcutaneous relapse was discovered in the left chest. The patient did not undergo any systemic chemotherapy in response to the relapse. After thoracic and orthopedic surgeries and radiotherapy for multiple metastases, the patient died 5 years and 5 months after LDLT. LDLT could be an effective treatment for localized metastatic hemangiopericytoma in the liver, but it should be indicated only for carefully selected patients., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to analyze the influence of age on both the risk of hepatectomy and the prognosis in patients with hepatocellular carcinoma (HCC)., Methods: Patients undergoing an initial hepatectomy for HCC were classified into 2 age groups: 75 years or over (n = 113) and less than 75 years (n = 499)., Results: A zero 90-day mortality was achieved in the elderly. Although the recurrence rate and recurrence sites were almost similar between the 2 groups, the 5-year survival rate in the elderly patients was significantly lower than that in the younger patients (46.0% vs 57.6%; P = .018), possibly because of the higher incidence of deaths from other causes (26.8% vs 10.4%; P = .011) in the elderly., Conclusion: Selected elderly HCC patients can undergo a hepatectomy safely and can benefit from long-term HCC control comparable with that of their younger counterparts., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Purpose: The aim of this study was to construct a prediction model for posthepatectomy liver failure (PHLF), as defined by the International Study Group of Liver Surgery, and evaluate its accuracy in hepatocellular carcinoma (HCC) patients with cirrhosis or chronic hepatitis., Methods: A total of 277 consecutive hepatectomies for HCC between 2005 and 2013 were analyzed retrospectively. Multivariate logistic regression analysis was used to develop a predictive model for PHLF. The sensitivity, specificity, and area under the receiver operating characteristic (AUROC) curve were evaluated. The Hosmer-Lemeshow goodness-of-fit test was used to assess the model calibration. The constructed model was internally validated by k-fold cross-validation (k=5)., Results: PHLF developed in 12.6% of hepatectomies. Multivariate analysis identified the following variables as predictors of PHLF: elevated preoperative serum bilirubin level, elevated preoperative international normalized ratio, and intraoperative packed red blood cell transfusion. The predictive model allowed discrimination between patients who developed PHLF and those who did not, with a sensitivity of 82.9%, specificity of 72.3%, and AUROC curve of 0.81 (95% CI, 0.74 to 0.89). The Hosmer-Lemeshow test indicated a good fit (P=0.545). The AUROC curve of the developed model was significantly greater than that of the model for end-stage liver disease (MELD) score (P=0.014), suggesting that the former model is better at predicting the PHLF than the latter one., Conclusions: The developed model could be useful for predicting the occurrence of PHLF in HCC patients with underlying liver disease.

Purpose: The aim of the present study was to evaluate whether serum alpha-fetoprotein (AFP) and des-gamma-carboxy prothrombin (DCP) trends might be correlated with overall survival rates in patients with recurrent hepatocellular carcinoma (HCC) undergoing trans-catheter arterial chemo-embolization (TACE)., Methods: We performed a retrospective cohort study of 142 patients with recurrent HCC who were treated by TACE at our hospital from April 1990 to December 2011. Patients were divided into three groups, as follows, according to the trends of the two tumor markers AFP and DCP: the low group, comprising patients with tumor marker levels below the cutoff values (AFP 100 ng/mL and DCP 100 mAU/mL) both pre- and post-TACE; the decreased group, comprising patients with elevated tumor marker levels pre-TACE in whom the levels decreased post-TACE; and the elevated group, comprising patients with elevated tumor marker levels post-TACE., Result: Analysis using a Cox proportional hazards model identified the DCP trend (elevated group vs. low group, hazard ratio 8.47, 95 % confidence interval 4.53-15.84, p < 0.0001), but not the AFP trend, as an independent prognostic factor for survival. While the AFP trend was correlated only with the overall response rate assessed using the modified Response Evaluation Criteria in Solid Tumors (mRECIST; p = 0.041), the DCP trend was strongly associated with both the overall response rate (p = 0.009) and the disease control rate (p = 0.004)., Conclusion: The DCP trend might be useful for assessing treatment outcomes after TACE in patients with recurrent HCC.

The use of adjuvant systemic chemotherapy for resectable liver metastases from colorectal cancer (CRC) is controversial because no trial demonstrated its benefit. We conducted the phase III trial to evaluate UFT/leucovorin (LV) for colorectal liver metastases (CRLM). The primary endpoint has not been available until 2014, we first report the feasibility and safety data of UFT/LV arm. In this multicenter trial, patients who underwent curative resection of liver metastases from colorectal cancer were randomly assigned to receive surgery alone or surgery followed by adjuvant chemotherapy with UFT/LV. The primary endpoint was relapse-free survival. Secondary endpoints included overall survival and safety. A total of 180 patients were enrolled, 90 were randomly assigned to receive UFT/LV therapy. Eighty two of whom were included in safety analyses. In the UFT/LV group, the completion rate of UFT/LV was 54.9%, the relative dose intensity was 70.8% and grade 3 or higher adverse events occurred in 12.2% of the patients. Elevated bilirubin levels, decreased hemoglobin levels, elevated alanine aminotransferase levels, diarrhea, anorexia were common. Most other adverse events were grade 2 or lower and tolerable. In conclusions, UFT/LV is a safe regimen for postoperative adjuvant chemotherapy in patients who have undergone resection of liver metastases from colorectal cancer. Further studies are warranted to improve completion rate, but UFT/LV is found to be a promising treatment in this setting.

Genetic alterations and deregulation of the miRNA biogenesis pathway components have been reported in human tumors. Tissue-specific deletion of the Dicer gene, which encodes an essential miRNA processing enzyme, promotes carcinogenesis in animal models. These features indicate that aberrant miRNA biogenesis components are directly associated with cancer. For the present study, we conducted quantitative RT-PCR of 14 genes that are related to the miRNA biogenesis pathway in 47 paired samples of primary hepatocellular carcinoma (HCC) and matched non-cancerous liver. Expression of seven genes (Dgcr8, p68, p72, Dicer, Ago3, Ago4 and Piwil4) was significantly decreased in primary HCC, especially in non-viral HCC subtypes, compared to the non-cancerous liver. Combinations of decreased expression of the miRNA biogenesis components in non-cancerous liver were related to cigarette smoking, alcohol intake and diabetes, which are known to be risk factors for HCC, and were also associated with the occurrence of multicentric tumors. Reduction of two of these genes (Dicer and p68) in HCC was associated with poor prognosis. Trimethylation of histone H3 lysine 27 in the promoters is implicated in the deregulation of these miRNA-biogenesis-related genes in non-HBV genome integrated HCC cell lines. In conclusion, deregulation of the miRNA biogenesis pathway components is frequently observed in non-viral-associated HCC and is linked to etiological risk factors and poor prognosis. Our study further showed that epigenetic regulation could be implicated in the deregulation of these genes during hepatocarcinogenesis., (© 2013 Japanese Cancer Association.)

Background: Although a right hepatectomy (RH) traditionally has been performed for liver tumors infiltrating the main trunk of the right hepatic vein (RHV), the presence of drainage veins of the posterior section (DVPS) beside the RHV provides a chance to preserve their draining area even if the main trunk of the RHV is removed., Methods: Since 2005, we systematically have performed DVPS-preserving hepatectomies whenever possible. In the present study, we describe our experience treating 12 consecutive patients who underwent this procedure., Results: We performed the following types of liver resections concomitant with the main trunk of the RHV without packed red cell transfusion, liver failure, or 90-day mortality: extended right anterior sectionectomy in 2 patients, extended segmentectomy 7 in 3, extended segmentectomy 8 in 2, and partial resection of segment 7 in 2 and segment 8 in 3. Postoperative morbidity was observed in 4 (33%) cases, all of which had pleural effusion requiring a tap. A free resection margin was obtained in all patients., Conclusions: This procedure could be a useful alternative to RH, providing a chance for radical liver resection with minimal parenchymal sacrifice in selected patients with DVPS., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Purpose: We report two cases in which portal blood flow via the peribiliary vascular plexus (PBP) was clearly demonstrated using contrast-enhanced intra-operative ultrasonography (CE-IOUS)., Methods: Two patients who underwent hemihepatectomies were investigated using CE-IOUS. Before injection of the contrast medium, both the hepatic arterial and portal venous flows of the hemiliver to be resected were interrupted by ligating those corresponding vessels at the hepatic hilum. Subsequently, the perfluorobutane microbubbles were injected intravenously., Results: In the early vascular phase, a remarkable intermittent flow was visualized in the lumen of the portal branches whose inflows were interrupted. The flow of the portal vein then disappeared as a result of ligating the hepatic duct concomitantly with the surrounding connective tissue. We considered that the portal venous flow appearing under the condition of total disruption of original inflow was supplied from the hepatic artery through the PBP., Conclusions: This is the first report of blood flow via the PBP in human liver visualized by dynamic image study.

Cholangiocarcinoma (CCA) is a common carcinoma of the liver, and the majority of patients with CCA have a poor prognosis due to the lack of effective nonsurgical therapies in addition to its rapid progression and inoperability at the time of diagnosis. The development of novel nonsurgical therapeutics that efficiently target CCA could significantly improve the prognosis for patients presenting with CCA. Here, we describe the iterative production and characterization of a novel peptide, designated COP35 (CCA-binding oligopeptide 35), which binds selectively to human CCA, identified by bacteriophage biopanning using the intrahepatic CCA cell line RBE and the normal cholangiocyte cell line MMNK-1. COP35 was found to augment the growth inhibitory effects of 5-fluorouracil (5-FU) against RBE cells. Utilizing pull-down assay and liquid chromatography, we identify the clathrin heavy chain accompanied by GRP78/BiP as a COP35-binding partner. In summary, we identify COP35 as a possible candidate for peptide-targeted therapies for CCA.

We report a 50-year-old male patient with primary liver carcinoma exhibiting dual hepatocellular and biliary epithelial differentiations associated with citrin deficiency (asymptomatic adult-onset type II citrullinemia, CTLN2). Although so far 14 CTLN2 patients with hepatocellular carcinoma have been reported, this report describes a unique case of liver carcinoma showing the features of both hepatocellular and cholangiocellular carcinoma. In addition to the clinical data of the 14 patients reported previously, the findings in our patient suggest that the citrin deficiency might be one of the key disorders causing hepatocellular carcinoma especially at younger ages and can also play an important role in hepatocarcinogenesis of the hepatic progenitor cells, which have the bipotential to differentiate into both hepatocytes and cholangiocytes.

Background/aims: The prognosis of hepatocellular carcinoma (HCC) is poor because of frequent intrahepatic metastasis (IM) or multicentric carcinogenesis (MC). This study compared the effectiveness of microarray analysis in the diagnosis of these 2 forms with that of conventional histopathological diagnosis. The aim was to identify IM- or MC-associated genes through delineation of the clonality of multinodular liver cancer., Methodology: The clonal relationship of 23 tumor foci obtained from 11 surgically resected liver specimens was investigated by genome-wide expression profiling via an in-house cDNA microarray consisting of 4,608 genes., Results: The gene expression signature of primary HCCs with IM was very similar to that of their corresponding IMs, implying that genes favoring progression of metastasis were initiated in the primary tumors. In comparison, different gene expression was observed in multicentric HCCs. The gene for adrenomedullin, which has been identified as a lead gene in the gene expression signature, was overexpressed in HCCs with IM, as confirmed by real time-PCR and immunohistochemistry., Conclusions: Analysis of expression profiles by microarray could provide a reliable method of delineating the clonal relationship of multiple nodules of liver cancer and identifying metastasis-associated genes. Adrenomedullin is a factor associated with progression of IM in human HCC.

We examined whether the expression of thioredoxin-1 (Trx-1) was associated with patient prognosis after liver resection for metastatic colorectal cancer. Eighty-four patients underwent resection of liver metastases from colorectal cancer, leaving no macroscopic evidence of residual tumor. Immunohistochemical study was performed to evaluate the relation among Trx-1, vascular endothelial growth factor (VEGF), and redox factor-1 (Ref-1) expression and the clinicopathologic characteristics and patient survival. Thirty-seven patients (44.0%) with Trx-1-positive metastases had shorter survival after primary liver resection (P = .0003) than the 47 patients (56.0%) with Trx-1-negative metastases. The percentage VEGF-positive and Ref-1-positive metastases was significantly higher in patients with Trx-1 expression (P = .0009 and .0002, respectively). Multivariate analysis revealed that Trx-1 expression was an independent prognostic factor. Expression of VEGF and Ref-1 is associated with Trx-1 overexpression, which is related to a poor prognosis in patients with liver metastases from colorectal cancer.

Bone marrow cells (BMCs) have been reported to behave as tissue-specific stem cells in some organs and to participate in tumorigenesis. However, the roles of BMCs in hepatic regeneration and carcinogenesis are still unknown. A choline-deficient, ethionine-supplemented (CDE) diet leads to the appearance of oval cells, a type of hepatic progenitor cell, and activates their replication. Furthermore, this type of diet induces preneoplastic nodules and hepatocellular carcinomas (HCCs) derived from oval cell progenitors. The aims of this study were to determine whether oval cells are derived from BMCs and whether preneoplastic nodules or HCCs originate from BMCs in the CDE diet rat model. To clarify the origin of constituent cells in the liver, we transplanted BMCs from green fluorescent protein (GFP) transgenic female rats into male Lewis rats, which were then exposed to a CDE diet to induce hepatocarcinogenesis. Some oval cells showed both donor-derived GFP expression and the recipient-specific Y chromosome, indicating that donor BMCs fused with recipient oval cells. Several preneoplastic nodules (precancerous lesions) identified by their glutathione S-transferase placental (GSTp) positivity were induced by CDE treatment. However, these preneoplastic GSTp-positive nodules were not GFP positive. In conclusion, this study has produced two major findings. First, BMCs fuse with some oval cells. Second, BMC-fused oval cells and BMCs might not have malignant potential in the CDE-treated rat model.

Background/purpose: Little has been addressed regarding the impact of the type of resection, which can be anatomical or nonanatomical, for patients with hepatocellular carcinoma (HCC), from the viewpoint of early (< or =2-year) and late (>2-year) intrahepatic recurrence. The aim of the present study was to investigate this issue., Methods: Between 1990 and 2004, we performed 365 potentially curative liver resections. Among these, 233 patients with a solitary tumor were the subjects of this study. They were classified into two groups: anatomical resection (n = 106) and nonanatomical resection (n = 127). We evaluated the following outcomes: (1) early and late recurrence rates; (2) topography of the recurrent tumors; and (3) risk factors for early recurrence., Results: The early recurrence rate after anatomical resection was significantly lower than that after nonanatomical resection: recurrence rates at 1 and 2 years were 13.8% and 29.8%, respectively, in the former group; while they were 22.6% and 46.3%, respectively, in the latter group (P = 0.01; log-rank test). However, late recurrence rates were similar in the two groups (P = 0.36). Local recurrence was observed in 25 of the 89 patients with intrahepatic recurrence after nonanatomical resection (28%), whereas it was observed in 3 of the 64 patients with intrahepatic recurrence after anatomical resection (5%), showing a significantly lower local recurrence rate in the anatomical resection group (P = 0.0002). Cox multivariate analysis identified the type of resection employed as one of the variables contributing to early HCC recurrence (nonanatomical resection: hazard ratio, 1.84; 95% confidence interval [CI], 1.01-3.37)., Conclusions: Anatomical resection would be a more appropriate strategy than nonanatomical resection for preventing early intrahepatic recurrence in patients with solitary HCC. However, the type of resection has no significant influence on late recurrence.

Goals: The specificity and sensitivity of intravenous-enhanced multidetector row computed tomography (MDCT), superparamagnetic iron oxide-enhanced magnetic resonance imaging (SPIO-MRI), multidetector row computed tomography with arterioportography combined with multidetector row computed tomography with hepatic arteriography (CTAP/CTHA), and intraoperative ultrasonography (IOUS) for detecting hepatic metastases from colorectal carcinoma were evaluated based on histopathologic examination of resected livers., Study: MDCT, SPIO-MRI, CTAP/CTHA, and IOUS were performed routinely to determine surgical indications and methods in patients with hepatic metastases from colorectal carcinoma. The resected liver specimens were then cut serially into sections 3 to 5 mm thick for routine histologic examination., Results: Fifty metastatic lesions were detected by histopathologic study of a large amount of anatomically resected liver from 8 patients with colorectal liver metastasis. The tumors ranged in size from 3 to 53 mm (mean 13.8 mm) and 26 lesions (52%) were less than 10 mm in diameter. Histopathologic examination of the resected liver specimens showed that CTAP/CTHA was the most sensitive imaging modality, followed in order by IOUS, SPIO-MRI, and MDCT. Among all the tumors detected by CTAP/CTHA, SPIO-MRI overlooked 5, but all of the tumors detected by SPIO-MRI were also detected by CTAP/CTHA. The number of metastatic liver tumors detected differed significantly among MDCT, SPIO-MRI, and histopathologic examination. One false-positive lesion was detected by IOUS., Conclusions: CTAP/CTHA is a useful preoperative imaging modality for detecting small hepatic metastases from colorectal carcinoma.

Hypothesis: Although several staging systems for colorectal liver metastasis have been proposed, simple and generally accepted staging systems are not available for this disease. We hypothesized that more detailed analysis of primary colorectal cancer may make it possible to develop a simple staging system and that its stratification ability may be demonstrated by validation against data from unrelated patients., Design: Retrospective analysis of prospectively documented data, development of a stage, and validation against an unrelated cohort., Setting: Four tertiary referral centers., Patients: Twenty-two clinicopathologic factors were examined in 369 consecutive patients who underwent curative resection for liver metastasis from colorectal cancer (original cohort). Using the independent prognostic factors, a simplified staging system was developed and was validated by data from 229 unrelated patients (validation cohort)., Main Outcome Measures: Kaplan-Meier survival curve analyses between different prognostic groups in the cohorts., Results: Multivariate analysis revealed several independent prognostic variables, including hepatic lymph node metastasis (relative risk 4.39), 4 or more colorectal lymph node metastases (RR 1.50), carcinoembryonic antigen level of 50 ng/mL or higher (RR 1.29), and multiple hepatic metastases (RR 1.27). Patients with hepatic lymph node metastasis were assigned to stage 4, and the remaining patients were divided according to number of factors: none, stage 1; 1, stage 2; 2 or 3, stage 3. In the original cohort, median survival in stages 1, 2, 3, and 4 was 7.2, 3.5, 2.0, and 1.3 years, respectively. In the validation cohort, these values were 9.6, 4.1, 2.8, and 1.6 years, respectively., Conclusions: The proposed simplified staging system was easy to use, was highly predictive of patient outcome, and permitted categorization of patients into treatment groups. Although we validated this staging system, further validation and improvements are needed.

Hypothesis: While simultaneous resection has been shown to be safe and effective in patients with synchronous metastasis, neoadjuvant chemotherapy followed by hepatectomy has gradually gained acceptance for both initially nonresectable metastasis and resectable metastasis. The boundary between these treatments is becoming unclear. We hypothesized that factors associated with colorectal cancer may play an important role in the prognosis of patients with synchronous metastasis and may be useful for identifying patients who can be expected to have adequate results following simultaneous resection., Design: Outcome study., Setting: Tertiary referral center., Patients: From January 1980 to December 2002, 187 patients underwent curative resection for synchronous liver metastasis from colorectal cancer. One hundred forty-two patients received simultaneous resection, 18 underwent staged resection, and 27 underwent delayed hepatic resection. Twenty-one clinicopathological factors were analyzed, and long-term prognosis was assessed., Main Outcome Measures: Prognostic factors and patient survival., Results: There was no in-hospital death. In a multivariate analysis, the factors that significantly affected the prognosis of synchronous metastasis were 4 or more lymph node metastases around the primary cancer (P<.001) and multiple liver metastases (P = .003). In patients with 3 or fewer lymph node metastases around the primary cancer, the 5-year survival rates of those with 1, 2 to 3, and 4 or more liver metastases were 63%, 33%, and 40%, respectively, but these rates were 15%, 22%, and 0%, respectively, in patients with 4 or more lymph node metastases around the primary cancer., Conclusions: The results support the application of simultaneous resection in patients with 0 to 3 colorectal lymph node metastases. However, in patients with 4 or more colorectal lymph node metastases, biological selection by neoadjuvant chemotherapy may be more suitable.

Background/aims: To evaluate our treatment protocol applied to patients with hepatocellular carcinoma. The protocol consists of the selection criteria for hepatectomy, the use of techniques that minimize intraoperative blood loss, strict follow-up after surgery, and an aggressive surgical approach for intrahepatic recurrence., Methodology: We conducted a retrospective cohort study that included 337 patients with hepatocellular carcinoma treated between 1990 and 2001. The type of resection was selected according to the serum bilirubin value and the indocyanine green retention rate at 15 minutes. Perioperative data and long-term outcome were examined., Results: We performed 324 initial hepatectomies with an in-hospital mortality rate close to zero. There was one operative death and one hospital death (0.3% each), and the 5-year survival rate for all patients was 53.2%. Eighty repeat liver resections, including 18 third and two fourth, were performed with no mortality, and the 5-year survival rate was 52.9% after the second hepatic resection. The resectability rate for second and third hepatectomies reached 29% and 33% of all patients with isolated liver recurrence, respectively., Conclusions: Liver resection is a safe and effective treatment modality for hepatocellular carcinoma. Our results are likely attributable to the routine application of our treatment protocol.

Objectives: We carried out identification of a small peptide binding to human hepatocellular carcinoma (HCC) cells with the aim of applying the peptide for future HCC-targeted therapy or imaging., Methods: The biopanning technique using phage peptide display libraries was performed on HCC cells in vitro, and a phage clone expressing the HCC-binding peptide motif was selected. The binding activity of the selected phage was evaluated by plaque infection assay and immunofluorescence on cell lines. In addition, the binding activity of the peptide-expressing phage was investigated using HCC specimens derived from patients who had undergone hepatectomy for HCC., Results: A heptapetide, Thr-Thr-Pro-Arg-Asp-Ala-Tyr (TTPRDAY), was identified as a motif binding to HCC. TTPRDAY bound specifically to HCC cells in comparison with other cancer cells, and the binding to HCC cells was also confirmed by immunofluorescence. In addition, the synthesized TTPRDAY peptide showed binding activity and a non-mitogenic effect on HCC cells in vitro. TTPRDAY-presenting phage showed more significant binding to HCC cells derived from specimens obtained from actual patients than to non-cancerous liver tissue., Conclusion: The motif TTPRDAY, identified by the biopanning technique, shows significant binding to HCC cells.

Although dendritic cells (DCs) play an important role in tumor immunity, their prognostic significance and factors related to mature DCs have not been addressed in metastatic liver tumors. In surgically resected, paraffin-embedded tissue sections from 70 patients with colorectal liver metastasis, CD83 (a marker of mature DCs) positive cells and cancer cells positive for the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling assay were counted. Expression of gp96, which is considered to participate in the maturation of DCs, was also evaluated. CD83-positive cells were observed predominantly in the cancer invasive margin. Patients with CD83-positive cell counts of <2 per field had a significantly poorer prognosis (5-year survival rate 47.5% vs 23.1%; P=0.0184). Patients with >0.83% apoptotic cancer cells had significantly higher numbers of CD83-positive cells (7.3 +/- 7.3 vs 4.0 +/- 5.1; P=0.039). Patients with immunohistochemically positive gp96 expression in tumors had significantly higher numbers of CD83-positive cells than those with negative gp96 expression (6.0 +/- 6.5 vs 1.4 +/- 2.3; P=0.0108). Patients with metachronous occurrence of liver metastasis had significantly higher numbers of CD83 positive cells than those with synchronous detection (6.3 +/- 6.5 vs 3.9 +/- 5.9; P=0.0313). Although the number of apoptotic cancer cells, degree of tumor gp96 expression, and synchronous or metachronous occurrence of liver metastasis did not directly influence patient outcome, they did influence the number of CD83-positive cells in the cancer invasive margin, which was a significant prognostic factor in patients with colorectal liver metastasis.

UFT is an anti-cancer drug which combines uracil with tegafur at a mole rate of 1:4, and shows a high anti-tumor effect by raising the 5-FU level in a tumor. A 55-year-old man with hypochondriac pain was admitted to Shinshu University Hospital. The preoperative diagnosis was giant hepatocellular carcinoma (HCC) of the right hepatic anterior region, and extended anterior segmentectomy of the liver was performed. Three months later, serum alpha-fetoprotein (AFP) and PIVKA-II were elevated markedly, and computed tomography (CT) and magnetic resonance imaging (MRI) revealed a recurrence in the remnant liver and multiple lung metastasis. Chemotherapy with oral UFT (300 mg/day) administration alone was started for the unresectable HCC. Three months later, CT and MRI showed complete disappearance of the recurrent HCC and multiple lung metastasis. Also, the titers of AFP and PIVKA-II were reduced to normal levels. This case suggests that oral UFT administration is a safe and effective therapy for postoperative HCC, even with lung metastasis.

Background/aims: We conducted a retrospective cohort study to investigate factors to early and late phase recurrence of hepatocellular carcinoma (HCC)., Methods: The study population consisted of 249 patients including 157 with cirrhosis who underwent hepatectomy for HCC. The endpoint was time-to-recurrence. Using a Cox regression model, factors to early and late phase recurrences were investigated censoring recurrence-free patients at the 2-year time point and in patients without recurrence at 2 years., Results: Actuarial probability of overall recurrence at 1, 3, and 5 years were 0.301, 0.623, and 0.790, respectively, with a median follow-up of 624 days. Early recurrence was observed in 123 out of 249 patients; while late recurrence was found in 61 out of 113 patients. Factors to early recurrence were as follows: non-anatomical resection, presence of microscopic vascular invasion, and serum alpha-fetoprotein level >or=32 ng/ml. Those contributing to late phase recurrence were higher grade of hepatitis activity, multiple tumors, and gross tumor classification., Conclusions: Variables associated with metastatic recurrence were factors to early phase recurrence; whereas those related with elevated carcinogenesis contributed to late phase recurrence, thus providing an epidemiological evidence that different mechanisms, i.e. metastasis and de novo, are involved in intrahepatic recurrence after hepatectomy for HCC.

Kupffer cells, residential liver macrophages, have binding sites for carcinoembryonic antigen (CEA), but their role in metastatic liver tumor progression has not been well addressed clinically. Liver macrophages were analyzed morphometrically and their relationship with CEA and tumor microvessel density (MVD) was examined in 71 patients who underwent macroscopic curative hepatectomy for metastatic liver tumors from colorectal cancer. In paraffin-embedded sections, MVD was evaluated by CD34-positive cell counts, liver macrophages visualized using anti PG-M1 (CD68) antibody were analyzed, and membrane-bound CEA was assessed by immunoreactivity of tumor cells for CEA. The area of liver macrophages in peritumoral regions (43.0 +/- 11.6 microm2) was significantly larger than that in non-tumor regions (25.2 +/- 24.2 microm2) (P < 0.0001). The liver macrophage density in peritumoral regions was 154 +/- 49 per field, and was significantly higher than in non-tumor regions (74 +/- 24 per field) (P < 0.001). The density and the area of liver macrophages had no correlation with serum CEA levels and the degree of tumor CEA expression. A weak positive correlation was observed between MVD and liver macrophage density (P = 0.0104, Spearman rank correlation coefficient = 0.31). Cox multivariate regression analysis showed that MVD greater than 50 (P = 0.0233, hazard ratio = 2.463), and the area of liver macrophages larger than 40.9 microm2 (P = 0.0485, hazard ratio = 2.127), were significant independent prognostic factors. The present morphometric analysis suggests that the liver macrophages are accumulated and activated in peritumoral regions in patients with colorectal liver metastasis and this accumulation and activation of liver macrophages, with which soluble or membrane-bound CEA might not be associated, are related with patients' poor prognosis.

Objective: The aim of this study is to determine the absolute contraindication for hepatic resection for colorectal metastases and investigate the value of hepatectomy for gastric metastases by comparing it with the results of colorectal metastases performed with the same criteria., Methods: A retrospective cohort study was conducted in patients undergoing hepatic resection for metastatic colorectal (n = 64) and gastric (n = 17) carcinomas. Common predictive factors for both metastases were analyzed by the stratified Cox proportional hazard model. In this model, the different baseline hazard was set for each disease, whereas the risk of each covariate was assumed to be equal in both gastric and colorectal metastases., Results: Overall 1-, 2-, and 5-yr survival rates after hepatectomy for colorectal and gastric metastases were 90%, 73%, 42%, and 47%, 22%, 0%, respectively. Factors controlling prognosis were as follows: age > or = 60, extrahepatic metastases, serosal invasion, grade of lymph node metastases, tumor cell differentiation of the primary lesion(s), carcinoembryonic antigen level, tumor-exposed surgical margin, and blood transfusion. In particular, presence of extrahepatic metastases showed the markedly high-risk ratio among these eight variables., Conclusions: Hepatectomy, if possible, is indicated in patients with hepatic metastases from colorectal carcinoma if there are no extrahepatic metastases and if the primary disease is controlled. It is indicated only in carefully selected patients with metastases from gastric carcinoma.

Objective: To compare the diagnostic accuracies of Lipiodol computed tomography (CT) and helical biphasic CT as preoperative imaging modalities for hepatocellular carcinoma (HCC)., Summary Background Data: Lipiodol CT after digital subtraction angiography has long been used as a highly sensitive imaging modality for HCC. The recent advent of helical CT has allowed scanning the entire liver during both the arterial and portal venous phase of contrast enhancement., Methods: The authors analyzed data from 164 patients who underwent hepatic resection for HCC to calculate the sensitivity and specificity of these modalities. Findings of intraoperative ultrasonography followed by histologic confirmation were set as the gold standard., Results: Although sensitivity decreased with both modalities as tumors became small and well differentiated, helical CT showed a higher sensitivity than Lipiodol CT in detecting well-differentiated HCC nodules smaller than 2 cm. In contrast, Lipiodol CT was superior to helical CT for the detection of small but moderately to poorly differentiated nodules. The overall sensitivity of helical CT was higher than that of Lipiodol CT. These findings suggest that helical CT is superior in delineating early HCC, whereas Lipiodol CT is specific to the detection of intrahepatic metastases. In terms of specificity, helical CT was superior to Lipiodol CT., Conclusions: Helical CT and Lipiodol CT are complementary modalities. At present, helical biphasic CT does not obviate the need for invasive techniques such as angiography and Lipiodol CT as preoperative examinations for HCC.

Preoperative portal embolization (PVE) is now widely used to induce hypertrophy of the anticipated liver remnant. Here, pathophysiology, indications, technical procedures, and problems of PVE are reviewed and our experience of 105 PVEs is presented. The reported complication rate after PVE is low (0-10%) and the increment of the future remnant liver volume is 12% of total liver volume (range: 7-27%). The resection rate after PVE ranged from 58% to 100%. In our series of 105 PVEs, the morbidity rate was 3.8%, the future remnant liver increased by about 10% of total liver volume, and 34 patients (32.4%) did not undergo planned extended hepatectomy. After hepatectomy, hepatic failure occurred in one patient (< 1%). In conclusion, although PVE is a safe procedure for enlarging the future remnant liver, more appropriate indication criteria should be established.

Objective: Resection of the hepatic vein because of the proximity of tumors may result in increased congestion in the noncancerous parenchyma, which in turn may lead to functional hepatic volume loss and postoperative hepatic failure, especially in a case of low hepatic reserve. However, to our knowledge, no technique for estimating the extent of dependent hepatic venous territories before hepatic resection has been established. We examined the possibility of using color Doppler ultrasonography for this purpose., Methods: A color Doppler system and a linear array transducer equipped with multiple Doppler frequencies ranging from 7 to 13 MHz were used intraoperatively. Two patients with hepatocellular carcinomas were examined. By tracking entire branches of the targeted vessel, from the trunk to the terminal branches extending to the liver surface, it was possible for the boundaries of the dependent areas to be projected and marked on the liver surface with either ink or electrocautery., Results: In both cases, this method was effective for either minimizing the congestive area or preserving the hepatic mass that was being drained via aberrant routes., Conclusions: Identification of hepatic venous territories by means of color Doppler ultrasonography may provide new information about intrahepatic blood circulation and may increase the safety and curability of hepatic resection.

Background: Liver resection is currently accepted as the only potential cure for patients with metastases of colorectal tumors in the liver. However, cancer will recur in more than 70% of patients., Methods: In the 7 years to December 1997, 60 patients underwent liver resections for colorectal metastases at our institute. Of these, 20 patients had repeated surgical resections for recurrent disease of the liver and other organs. Another 2 patients had undergone previous hepatectomy elsewhere. The clinical data for these patients were reviewed., Results: The median interval between the 2 resections was 16 months. Eighteen hepatectomies, 6 lung resections, and 1 pancreatoduodenectomy were performed in 22 patients. Operative mortality and complication rates were 0% and 18%, respectively. At a median follow-up of 25 months after repeated resection, the survival rate in these patients was 73% at 2 years (12 of 16 evaluable patients are surviving) and 22% at 5 years (2 of 10 evaluable patients are surviving); the median survival time was 44 months., Conclusions: Repeated resections for recurrent colorectal metastases yield comparable results to first liver resections in operative mortality and morbidity rates, survival time, and pattern of recurrence. Although the number of patients surviving more than 5 years is still limited, the absence of other proven treatments supports the concept of an aggressive resectional approach for these patients.

Background: Portal venous tumour extension and intrahepatic metastasis result in a poor prognosis following hepatectomy for hepatocellular carcinoma (HCC). Anatomical resection is, in theory, preferable for eradicating these types of invasion. Des-gamma-carboxy prothrombin (DCP) has been reported to be associated with adverse pathological variables. This study investigated the significance of anatomical resection and DCP as predictive factors for postoperative recurrence of HCC., Methods: A retrospective cohort study was carried out in 138 consecutive patients who underwent hepatectomy for HCC smaller than 5 cm using the Cox proportional hazards model., Results: Eight factors were univariately related to poor prognosis (in decreasing order of hazard ratio): intrahepatic metastasis, multiple tumours, alpha-fetoprotein 32 ng/ml or more; DCP greater than 0.1 arbitrary units (AU), tumour-exposed surgical margin, vascular invasion, non-anatomical resection and tumour 2.5 cm or more. Three variables (DCP, vascular invasion and tumour-exposed surgical margin) were excluded by a stepwise procedure in multivariate analysis. Although DCP was not an independent prognostic factor, a model replacing intrahepatic metastasis with DCP showed similar predictive accuracy in a receiver-operating characteristic curve., Conclusion: Anatomical resection appeared to have a beneficial effect on recurrence-free survival after hepatectomy for HCC. DCP measurement was effective in predicting HCC recurrence and had the advantage that it can be assessed before operation.

Background: Staged hepatectomy after emergency transcatheter arterial embolization (TAE) has been advocated in ruptured hepatocellular carcinoma (HCC). However, there have been no reports of clinical series of this strategy. The purpose of this study was to evaluate the protocol of this therapeutic strategy., Methods: Sixteen patients with suspected rupture of HCC were included in the study. After emergency TAE, tumor resectability was assessed, followed by staged hepatectomy or repeated TAE. The patients were reevaluated with regard to rupture of HCCs., Results: Primary hemostasis was achieved successfully in all patients. Eleven patients were finally judged to have experienced HCC rupture. Seven of them underwent staged hepatectomy; the other four underwent repeated TAE because their tumors were considered unresectable. Survival time tended to be longer, but not to a significant extent, in patients who underwent hepatectomy (range, 139 to 1527 days; median, 375 days) than in those treated by TAE alone (range, 43 to 1317 days; median, 158 days)., Conclusions: Staged hepatectomy after TAE is a rational treatment for patients with ruptured HCC. Although TAE is highly effective for initial hemostasis, hepatectomy appears to provide better long-term survival.

In the past 20 years, thanks to the early detection of hepatocellular carcinomas (HCCs), good perioperative care, the evaluation of functional liver reserve, preoperative portal embolization and the improvement in surgical techniques such as intraoperative ultrasonography, the surgical resection of HCC has become very safe. We have performed 367 hepatectomies on 352 patients since 1990 with a surgical mortality, hospital mortality, blood transfusion rate and 5-year survival rate of 0.27, 0.82, and less than 10 and 47.4%, respectively. Our standard method for selecting surgical procedures and perioperative care resulting in low blood transfusion rates and almost no mortality are described. Since 1990, ethanol injection for HCC ablation has been extensively used in Europe and Japan, but results are poorer than with surgical intervention. Therefore, in patients with small HCCs and good liver function, the first choice treatment should not be ethanol injection, but surgical resection.

Background: The doubling times of liver metastases were calculated in order to clarify their usefulness in predicting the presence of residual cancer in the abdominal cavity in patients who had undergone curative resection of primary colorectal cancer., Patients and Methods: Tumor doubling times were calculated retrospectively in 22 patients by serial measurement of the size of their liver metastases., Results: Patients with a tumor doubling time of less than 92.4 days had a significantly poorer prognosis than those with a doubling time more than or equal to 92.4 days (p < 0.05). Local recurrence or peritoneal dissemination was significantly more likely to occur when the tumor doubling time was less than 92.4 days than when it was more than or equal to 92.4 days (p < 0.01)., Conclusion: The doubling time of hepatic metastases in patients with colorectal carcinoma may be a useful prognostic indicator, with patients who have a shorter tumor doubling time carrying a greater risk of residual primary cancer in the abdominal cavity.

Background/aims: We determined the optimal therapeutic strategy for improving survival in patients with hepatocellular carcinoma (HCC), based on an analysis of our surgical results., Methodology: Between January 1990 and December 1996, 205 patients underwent initial curative hepatectomy. The liver volume to be resected was decided according to the plasma retention of indocyanine green 15 minutes after injection. The appropriate subsegmental and segmental areas were disclosed by staining under ultrasonographic guidance. Limited resection or tumor enucleation was performed in 119 patients, subsegmentectomy or segmentectomy in 71, and lobectomy or extended lobectomy in 15., Results: Intrahepatic recurrence was documented in 115 patients, 46 of whom died from cancer recurrence. Disease free survival was 65% after 1 year, 35.1% after 3 years and 25.3% after 5 years. The type of hepatectomy (limited vs. subsegmental or segmental resection) significantly affected the cumulative survival (p = 0.047) and disease free survival rates (p < 0.01). Among the 115 patients with recurrence, 22 patients underwent repeated hepatectomy combined with TAE (transcatheter arterial embolization) and the remainder underwent TAE alone. Patients who underwent repeated hepatectomy combined with TAE survived significantly longer after recurrence than those who underwent TAE alone (p = 0.0197)., Conclusion: Initial subsegmentectomy or segmentectomy prolongs disease free survival, and patients eligible for repeated hepatectomy combined with TAE after recurrence have a good chance of long-term survival. Subsegementectomy or segmentectomy should be performed in a lot more HCC patients in order to improve survival.

Heterogeneity of DNA content in multiple hepatocellular carcinomas (HCCs) was investigated by flow cytometry in 62 tumours from 26 patients who had undergone surgical treatment for multiple synchronous HCCs. Heterogeneity of DNA content was defined (a) when tumours had a different DNA ploidy pattern or (b) when the difference in the DNA index of the aneuploid clone was more than 0.1. A tumour with DNA aneuploidy was observed in 17 (66%) of the 26 patients. Heterogeneity of the DNA content was demonstrated in 12 (46%) out of 26 patients: in ten cases by definition (a) and in two cases by definition (b). Histological examination revealed that, of the 12 patients with a heterogeneous tumour DNA content, seven (58%) had a heterogeneous and the remaining five (42%) had a homogeneous type and grade of differentiation among the tumours, showing the absence of a relationship between histological heterogeneity and DNA content. The present results suggest the clinical relevance of DNA content analysis for identifying the clonal origin of multiple HCCs.

Clinicopathological and prognostic features in patients who had undergone hepatectomy for hepatocellular carcinoma (HCC) were examined in relation to viral infection. Among 175 patients, cirrhosis was diagnosed histologically in 134, while 41 had noncirrhotic livers. One hundred twenty-four patients were positive for antibody to hepatitis C virus (anti-HCV) (HC group), 32 for hepatitis B virus surface antigen (HBsAg) (HB group), and 19 negative for both anti-HCV and HBsAg (non-B, non-C group). In the HB group, the mean patient age was significantly younger, and liver function in terms of the plasma retention rate of indocyanine green at 15 minutes and the serum total bilirubin level was significantly better than in either the HC or the non-B, non-C group. Seventeen patients had synchronous multicentric HCCs: the HC group showing a significantly higher incidence than the HB group (P < .05). In the HC group, the proportion of cirrhotic liver in patients with multicentric HCCs was significantly larger than in patients with unicentric HCC (P < .05). No significant differences in disease-free survival rate after hepatectomy were observed between the three groups. The present retrospective study of surgically treated patients showed that anti-HCV-positive HCCs tended to occur in older individuals who showed worse liver function and a higher incidence of cancer multicentricity compared with HBsAg-positive HCCs. The prognosis of anti-HCV-positive HCCs, which had the disadvantageous characteristic of multicentricity, did not differ from that of HBsAg-positive HCCs.

The results of 122 hepatic resections in 112 patients with hepatocellular carcinoma are described. The type of liver resection performed was selected according to the patient's liver function. Forty-nine patients underwent anatomic resections, including 1 trisegmentectomy, 5 lobectomies, 11 segmentectomies, and 32 subsegmentectomies; the remaining 63 patients had nonanatomic resections. The 1-, 2-, and 3-year survivals after liver resection for all patients, taking into account one operative and one hospital death (0.9% each), were 92.4%, 85.0%, and 78.9%, and disease-free survivals at 1, 2, and 3 years were 68.6%, 46.2%, and 32.6%, respectively. Twenty-one repeat hepatic resections (17.2% of the total of 122 resections) were performed with no hospital mortality. Cumulative survival from the time of repeat hepatectomy in these 21 patients was 84.2% and 56.3% at 1 and 2 years, respectively. Among the factors that may affect survival or disease-free survival, the absence of vascular invasion (p < 0.05) and intrahepatic metastases (p < 0.01) were significantly related to the disease-free survival time. A good outcome was obtained after liver resection in 112 patients with hepatocellular carcinoma through appropriate choice of the type of resection, careful follow-up, and a vigorous surgical approach for recurrence.

Objective: Factors that were likely to cause hyperamylasemia following hepatic resection were studied., Design: Case-comparison study., Setting: Institutional practice., Patients: Seventy-one patients who underwent hepatic resection because of primary or secondary liver tumors and other benign disease, and who had no history of pancreatitis, were divided into four groups. Patients were divided into groups according to the presence or absence of underlying liver disease and the vascular occlusion methods used during hepatic resection (Pringle maneuver or the hemihepatic vascular occlusion technique). The Pringle maneuver was chosen for patients in whom the duration of liver parenchymal transection was expected to be short and/or the hepatic hilum had severe adhesion precluding the safe dissection of the hepatic artery and portal vein., Main Outcome Measures: Serum amylase levels were measured on the preoperative day and on postoperative days 1, 2, 4, 6, 7, 10, and 14. Preoperative liver function, operative blood loss, operative time, and vascular occlusion time were examined., Results: Patients with chronic liver disease (CLD group) had high serum amylase levels during the preoperative and postoperative periods. Patients in the CLD group who underwent the Pringle maneuver (Pringle-L group) had significantly elevated postoperative serum amylase levels in comparison with their preoperative serum amylase levels. Pancreatitis developed in two patients in the Pringle-L group--one of them died., Conclusion: These results strongly suggest that prolonged complete occlusion of the portal vein for hepatectomy in patients with chronic liver disease has a serious influence on postoperative serum amylase levels.

Background: Five patients with bilateral multiple liver metastases (3 to 12 lesions) from colorectal cancer who underwent extensive liver resection after portal embolization are described., Methods: Portal embolization of the right portal branch was performed 9 days to 8 months before hepatic resection. The location and number of metastases were determined by intraoperative ultrasonography at the time of liver resection to accomplish complete resection of the tumors. Extended right lobectomy was carried out in four patients, two of whom underwent additional wedge resection of nodules located in the left lateral segment. The other patient underwent right lobectomy associated with local resection of the tumor in the left lobe., Results: The postoperative course in the five patients was uneventful, with no serious complication or liver dysfunction. Although one patient died of recurrence 28 months after liver resection, the remaining four patients were alive and free of cancer between 36 and 74 months after hepatectomy., Conclusions: The presence of bilateral multiple (four or more) metastatic liver lesions from colorectal cancer is not considered a contraindication for hepatic resection if thorough examination of the liver is performed with intraoperative ultrasonography and the surgical risk is minimal. Portal embolization appears effective for increasing the safety of hepatectomy for patients with small metastases who require major right-sided resection combined with wedge resection of the left lobe.

During the last 12 years, hepatic resection was carried out on 268 patients with a diagnosis of hepatocellular carcinoma. Of these, 78% developed tumor recurrence in the remaining liver within 5 years. The indications for repeat hepatectomy were evaluated in the same way as for the first operation. Eighteen second hepatic resections and six third hepatic resections were performed 4 to 63 months after the first hepatectomy, with no operative deaths. The cumulative survival rate of these 24 patients was 87.1% at 3 years, 87.1% at 5 years and 72.6% at 7 years after the first hepatic resection, respectively. The present results show that repeat hepatectomy can be safely indicated for recurrent tumors in patients whose liver functional status has been relatively stable since the first hepatic resection.

During the last 16 years, we have resected small hepatocellular carcinomas (HCCs) measuring 5 cm or less from 362 patients, 266 of whom also had liver cirrhosis. The operative and hospital mortality rate were 1.7% and 1.9%, respectively. These showed a gradual decrease year by year in parallel with reduction of intraoperative blood loss achieved by the selective vascular occlusion technique and Pringle method. In 1989, 87% of hepatectomy patients were discharged without the need for whole blood transfusion, and 5-year survival was 43.7%. Tumor size, number of tumors, intrahepatic metastasis, vascular invasion, and capsular invasion were significant prognostic factors. Edmondson grade and the operative procedure employed were significantly related to outcome. Our standard policy for selection of operative procedures and perioperative care is described, and the selection of treatment modalities is discussed.

A rare case is reported of a large liver cell adenoma originating in the caudate lobe of the liver in a 38-year-old women with no history of liver cirrhosis or use of oral contraceptives: Caudate lobectomy of the liver is described. Passing tapes around the inferior vena cava was useful for controlling the bleeding from a torn short hepatic vein. This resection of a large hepatocellular adenoma originating in the caudate lobe is to our knowledge only the second case to be reported in the English literature.