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Background and Aims: This study aimed to determine the safety and efficacy of atezolizumab + bevacizumab therapy in hepatocellular carcinoma patients receiving anti-platelet agents or anticoagulants., Methods: Patients were divided into those using (IM out) and those not using (IM in) anti-platelet agents or anticoagulants, who violated the exclusion criteria of the IMbrave150 trial, and were retrospectively examined., Results: The study included 185 patients (IM in: 157; IM out: 28). For first-line treatment, progression-free survival was 184 days for IM in and 266 days for IM out (p = .136). Overall survival was 603 days for IM in and not reached for IM out (p = .265), with no significant between-group difference. Similarly, there were no significant between-group differences in progression-free survival or overall survival for later-line treatment. Haemorrhagic adverse events of ≥grade 3 were observed in 11 IM in patients and 3 IM out patients. No significant factors associated with haemorrhagic adverse events of ≥grade 3 were identified in the multivariate analysis including IM out classification, whose p value was .547. Regarding thrombotic/embolic adverse events in the IM out group, one case of exacerbation of portal vein thrombosis was observed. No deaths were directly attributable to bleeding events or exacerbations of thrombosis., Conclusion: Atezolizumab + bevacizumab therapy shows similar safety and efficacy in patients receiving and those not receiving anti-platelet agents or anticoagulants; therefore, it can be considered for patients with hepatocellular carcinoma receiving anti-platelet agents or anticoagulants., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: The Japan criteria (Milan criteria + 5-5-500 rule) was established recently to select cirrhotic patients with hepatocellular carcinoma for liver transplantation. We evaluated factors associated with poor prognosis after liver transplantation and investigated whether a further extension of the criteria would be worthwhile., Methods: We retrospectively analyzed 86 patients who underwent liver transplantation for hepatocellular carcinoma at Kumamoto University Hospital since 2004; 69 patients (80.2%) met the Japan criteria (the JC IN group), and 17 patients (19.8%) did not (the JC OUT group)., Results: The 5-year cancer-specific survival rates of the JC IN group (92.2%) were significantly better than that of the JC OUT group (39.2%; P < .001). In univariable analysis, alfa-fetoprotein and des-gamma-carboxy prothrombin were significant independent factors associated with cancer-specific survival rates. According to the receiver operating characteristic curves, the cutoff values of alfa-fetoprotein and des-gamma-carboxy prothrombin that predicted hepatocellular carcinoma recurrence after liver transplantation were 756 ng/mL and 1976 mAU/mL, respectively. The JC OUT group was divided into 2 subgroups according to alfa-fetoprotein and des-gamma-carboxy prothrombin: low risk (alfa-fetoprotein level <756 ng/mL and des-gamma-carboxy prothrombin level <1976 mAU/mL) and high risk (alfa-fetoprotein level ≥756 ng/mL and/or des-gamma-carboxy prothrombin level ≥1976 mAU/mL). The 5-year cancer-specific survival rate in the low-risk group (67.5%) was significantly better than that in the high-risk group (0%; P < .001)., Conclusions: Alfa-fetoprotein levels of <756 ng/mL and des-gamma-carboxy prothrombin levels of <1976 mAU/mL may help identify cirrhotic patients with hepatocellular carcinoma who do not meet the Japan criteria but still benefit from liver transplantation., Competing Interests: DISCLOSURES The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Although R0 resection for colorectal cancer liver metastasis (CRLM) is a promising treatment with improved prognosis, the recurrence rate is still high. No prognostic markers have been reported after resection of CRLM. In this study, we investigated the association between inflammation-based score and prognosis after R0 resection in patients with CRLM., Methods: We retrospectively investigated 90 patients who underwent R0 resection for CRLM between 2008 and 2018. We calculated colon inflammatory index (CII) (CII0, low risk; CII1, intermediate risk; and CII2, high risk), modified Glasgow prognostic score, prognostic nutritional index, and CRP-to-albumin ratio; and retrospectively assessed the relationship between these scores, the clinicopathological features, and prognosis., Results: The median follow-up period was 44 months (range, 2-101 months). Five-year relapse-free survival (RFS) (CII2; 12.5%, CII1; 14.5%, CII0; 42.9%) and 5-year overall survival (OS) (CII2; 32.4%, CII1; 25.4%, CII0; 57.7%) were significantly lower in the high CII groups (CII1-2) compared with the low CII group (CII0) (p = 0.021 and p = 0.006, respectively). CEA level was significantly higher in the high CII group than the low CII group (12.4 vs 7.3, p = 0.004). Multivariate analysis showed CII score as an independent predictor of RFS (hazard ratio 2.128, 95%CI 1.147-3.430, p = 0.015) and OS (hazard ratio 2.639, 95%CI 1.331-5.323, p = 0.005)., Conclusion: CII shows promise as a prognostic marker after R0 liver resection in patients with CRLM., Competing Interests: The authors have declared that no competing interests exist.

Background: The recurrence rate after hepatectomy for colorectal cancer liver metastasis (CRLM) is high, and there is no consensus regarding the effect of adjuvant chemotherapy (AC) using oxaliplatin (doublet AC) in these patients., Methods: The present study included 91 patients who underwent hepatectomy for complete resection at our hospitals between 2008 and 2018. Based on whether or not they had undergone doublet AC, patients were divided into AC (n = 35) and non-AC (n = 56) groups. The recurrent risk was evaluated by the Memorial Sloan Kettering Cancer Center clinical risk score (MSKCC-CRS)., Results: The number of females and median age were higher in the AC group (51.4% vs 25.0%, p = 0.010 and 67 vs 61 years, p = 0.012, respectively). The median follow-up period was 45 months (range, 6-101 months). Doublet AC was an independent prognostic factor for 5-year relapse-free survival (hazard ratio, 0.225; 95%CI, 0.097-0.522; p < 0.001) and for 5-year overall survival (hazard ratio, 0.165; 95%CI, 0.057-0.476; p < 0.001) in multivariate analysis. In patients with a high risk of recurrence (MSKCC-CRS 3-5), 5-year relapse-free survival and 5-year overall survival was higher in the doublet AC group than in the non-AC group (p < 0.01). In low-risk patients (MSKCC-CRS 0-2), 5-year relapse-free survival and 5-year overall survival were similar between the groups., Conclusions: Doublet AC could have a positive effect on prognosis after curative resection of CRLM, especially in high-risk patients. The selection of patients and AC regimen should take into consideration the risk of recurrence., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Intrahepatic cholangiocarcinoma (ICC) has a poor prognosis, as the resectability rate is low due to its diagnosis at a late/advanced stage. Moreover, most patients with resected ICC eventually relapse. Hepatic arterial infusion chemotherapy (HAIC) has been indicated only by a few reports to be effective in patients with advanced ICC; thus, its efficacy for these patients remains unclear. This study aimed to evaluate the efficacy of HAIC using gemcitabine, cisplatin, and 5-fluorouracil in patients with advanced ICC. A total of 18 patients who underwent HAIC were retrospectively investigated. The patients received gemcitabine, cisplatin, and 5-fluorouracil through one artery. In patients who received gemcitabine plus cisplatin (n = 10), the response and disease control rates were 0% and 80.0%, respectively; the median overall survival (OS) and progression-free survival (PFS) after treatment initiation were 6.3 and 3.7 months, respectively. In patients who never received chemotherapy (n = 8), the response and disease control rates were 37.5% and 75%, respectively; the median OS and PFS were 20.6 and 8.1 months, respectively. Moreover, we compared the patients who received HAIC using gemcitabine, cisplatin, and 5-fluorouracil to patients whose tumors were refractory to systemic gemcitabine and cisplatin therapy. The OS of the patients who received HAIC was better than that of the patients who received standard chemotherapy cohort since the gemcitabine plus cisplatin combination therapy-refractory response and disease onset (P = 0.045, 0.006). HAIC using gemcitabine, cisplatin, and 5-fluorouracil may be effective as a therapeutic option for patients with advanced ICC., Competing Interests: The authors have declared that no competing interests exist.

Purpose: An indwelling arterial access system via the brachial artery, System-i, has been previously reported. We have modified the technique for the femoral artery approach. This study aimed to evaluate the feasibility and safety of the modified System-i for patients with malignant liver tumors., Materials and Methods: The modified System-i is an indwelling catheter that provides vascular access for inserting a microcatheter without repeated punctures to the femoral artery. Between 2018 and 2020, the system was implanted for 50 patients with malignant liver tumors. We used the system for patients with difficulty in inserting the conventional indwelling catheter system. To place the system, a side-holed catheter was implanted in the femoral artery, and the tip of the catheter was placed in the superficial femoral artery through the contralateral iliac artery. Using this system, transcatheter arterial chemoembolization or hepatic arterial infusion chemotherapy was performed. A shaped high-flow microcatheter and a non-tapered microcatheter were used with the system. The technical aspects and outcomes of the system were also assessed., Results: Implantation of the system was successful in all patients. The median implantation time was 40 min. The main reason for implantation was obstruction or stenosis of the hepatic artery. Among the 50 patients, 11 (22%) showed complications, of which four had major complications/class C based on the SIR criteria., Conclusion: The modified System-i is a safe system that can be a feasible repeated interventional radiological treatment via the femoral approach. We need to evaluate the efficacy of this system in the treatment of advanced cancers in the future. The modified System-i is a novel indwelling catheter system that allows vascular access to perform intermittent transarterial therapy, such as transcatheter arterial chemoembolization and hepatic arterial infusion chemotherapy via the femoral approach. In this study, we report the technical details and safety of the system., (© 2021. Japan Radiological Society.)

Introduction: Although many treatment options are available for patients with advanced hepatocellular carcinoma (HCC) and Child-Pugh (CP) class A, those for patients with CP class B remain limited. We aimed to assess the safety and efficacy of hepatic arterial infusion chemotherapy (HAIC) using 5-fluorouracil and cisplatin in patients with advanced HCC and CP class B., Methods: Sixty patients who received HAIC with 5-fluorouracil and cisplatin at Kurume Chuo Hospital between April 2012 and March 2021 were recruited. Cisplatin (30 mg administered over 2 h) and 5-fluorouracil (1,250 mg, 72-h constant infusion) were administered to the tumor-feeding artery every 2 weeks. The primary endpoint was overall survival (OS), while the secondary endpoints were progression-free survival and adverse effects., Results: Among the 60 patients, CP class A and class B were noted in 30 patients each. OS did not significantly differ between the two classes. After 4 weeks of HAIC with 5-fluorouracil and cisplatin, 12 patients in the class B group exhibited improved CP scores (CPSs) relative to those at the start of treatment. There was a significant difference in OS between patients whose CPSs had improved and those whose scores remained unchanged or had worsened., Conclusions: HAIC using 5-fluorouracil and cisplatin is effective and safe for patients with CP class B, and improvements in CPSs after 4 weeks of this therapy may represent a predictive marker of treatment efficacy regardless of pretreatment CPS in patients with CP class B., (© 2022 S. Karger AG, Basel.)

Purpose: Predicting increased blood loss based on anatomical intervascular relationships is essential in major hepatectomy., Methods: We assessed 63 consecutive patients undergoing anatomical hepatectomy exposing the hepatic vein (HV) trunk at two institutes. Correlations between anatomical alterations of the hepatic inferior vena cava (IVC), HV, hepatic IVC, or right atrium (RA) and the blood loss per standard weight (BLSW) or blood transfusion (n = 18) were analyzed. The results of IVC partial clamping (PC) were additionally examined., Results: The BLSW in type V-up anatomical morphology was significantly higher than that in straight type (p < 0.05). The parameters associated with an increased BLSW (> 13.5 mL/kg) were tumor size (> 4 cm), prothrombin activity (< 87%), CVP (> 7 mmHg), area of suprahepatic IVC (< 360 mm 2 ), IVC-RA gap (> 28 mm), longitudinal angle of IVC (< 160°), and axial angle of the MHV (< 55°). A multivariate analysis revealed that a high IVC-RA gap was a significant independent risk factor (odds ratio; 4.32, p < 0.05). Among 25 patients undergoing IVC-PC, only three showed a remarkable decrease in hepatic venous bleeding. No other statistically significant differences in the surgical records were observed in most cases., Conclusion: The IVC-RA gap might be a promising novel predictive parameter reflecting increased blood loss leading to blood transfusion in anatomical hepatectomy., (© 2021. Springer Nature Singapore Pte Ltd.)

Introduction: Laparoscopic liver resection (LLR) in obese patients has been reported to be particularly challenging owing to technical difficulties and various comorbidities., Methods: The safety and efficacy outcomes in 314 patients who underwent laparoscopic or open nonanatomical liver resection for colorectal liver metastases (CRLM) were analyzed retrospectively with respect to the patients' body mass index (BMI) and visceral fat area (VFA)., Results: Two hundred and four patients underwent LLR, and 110 patients underwent open liver resection (OLR). The rate of conversion from LLR to OLR was 4.4%, with no significant difference between the BMI and VFA groups ( P = .647 and .136, respectively). In addition, there were no significant differences in terms of operative time and estimated blood loss in LLR ( P = .226 and .368; .772 and .489, respectively). The incidence of Clavien-Dindo grade IIIa or higher complications was not significantly different between the BMI and VFA groups of LLR ( P = .877 and .726, respectively). In obese patients, the operative time and estimated blood loss were significantly shorter and lower, respectively, in LLR than in OLR ( P = .003 and < .001; < .001 and < .001, respectively). There was a significant difference in the incidence of postoperative complications, organ/space surgical site infections, and postoperative bile leakage between the LLR and OLR groups ( P = .017, < .001, and < .001, respectively)., Conclusion: LLR for obese patients with CRLM can be performed safely using various surgical devices with no major difference in outcomes compared to those in nonobese patients. Moreover, LLR has better safety outcomes than OLR in obese patients.

Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related mortality in Japan. Prognosis is poor, and until recently sorafenib was the only treatment option available for patients with unresectable disease. Lenvatinib is the first therapy to demonstrate noninferiority to sorafenib. An analysis was conducted using clinical data from Japanese patients in the phase III REFLECT trial to assess the cost-effectiveness of lenvatinib versus sorafenib for first-line treatment of unresectable HCC in Japan., Methods: A partitioned survival model was implemented adopting the perspective of the Japanese healthcare system, with costs and outcomes modeled over a lifetime horizon and using a discount rate of 2%, as per Japanese guidelines. Population data from the Japanese subpopulation of REFLECT were used to extrapolate outcomes, and costs and resource use were based on Japanese sources. The Japanese tariff was applied to EQ-5D data collected during the REFLECT clinical trial to obtain utility values reflecting the preferences of the Japanese population., Results: Compared with sorafenib, lenvatinib is dominant because it is associated with a reduction in incremental costs of ¥156 799 and incremental quality-adjusted life-years of 0.31. These results were robust to changes in key assumptions, and probabilistic outcomes aligned with deterministic outcomes., Conclusion: Given the use of Japan-specific data in the cost-effectiveness model, it is expected that the use of lenvatinib as a first-line treatment in Japan will be associated with cost savings and improved clinical outcomes versus sorafenib for patients with unresectable HCC., (Copyright © 2020. Published by Elsevier Inc.)

Background: Liver resection is an effective treatment for benign and malignant liver tumors. However, a method for preoperative evaluation of hepatic reserve has not yet been established. Previously reported assessments of preoperative hepatic reserve focused only on liver failure in the early postoperative period and did not consider the long-term recovery of hepatic reserve. When determining eligibility for hepatectomy, the underlying pathophysiology needs to be considered to determine if the functional hepatic reserve can withstand both surgery and any postoperative therapy., Aim: To identify pre-hepatectomy factors associated with both early postoperative liver failure and long-term postoperative liver function recovery., Methods: This study was a retrospective cohort study. We retrospectively investigated 215 patients who underwent hepatectomy at our hospital between May 2013 and December 2016. Early post-hepatectomy liver failure (PHLF) was defined using the International Study Group of Liver Surgery's definition of PHLF. Long-term postoperative recovery of liver function was defined as the time taken for serum total bilirubin and albumin levels to return to levels of < 2 mg/dL and > 2.8 g/dL, respectively, and the time taken for Child-Pugh score to return to Child-Pugh class A., Results: Preoperative type IV collagen 7S was identified as a significant independent factor associated with both PHLF and postoperative long-term recovery of liver function. Further analysis revealed that the time taken for the recovery of Child-Pugh scores and serum total bilirubin and albumin levels was significantly shorter in patients with type IV collagen 7S ≤ 6 ng/mL than in those with type IV collagen 7S > 6 ng/mL. In additional analyses, similar results were observed in patients without chronic viral hepatitis associated with fibrosis., Conclusion: Preoperative type IV collagen 7S is a preoperative predictor of PHLF and long-term postoperative liver function recovery. It can also be used in patients without chronic hepatitis virus., Competing Interests: Conflict-of-interest statement: All other authors have nothing to disclose., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: Reduced port surgery (RPS) has been garnering interest as a novel minimally invasive surgery lately., Aim: The authors examined the relationship between the number of ports and surgical outcomes after laparoscopic hepatectomy (LH)., Materials and Methods: Between January 2012 and April 2019, 209 patients who underwent laparoscopic partial resection and lateral sectionectomy were retrospectively analyzed with respect to operative variables and surgical outcomes. Patients were divided into 5 groups by the number of ports used. Student's t test, the χ test, the likelihood-ratio test, Fisher exact test, or Mann-Whitney U test were used to analyze the data., Results: Operative duration was significantly longer in patients with a larger number of ports than in those with a smaller number of ports. Chronological pain scores according to the visual analog scale (VAS) on postoperative days 1, 2, 4, and 7 were not associated with the number of ports and wound length in the umbilical region. The frequency of using additional analgesic agents was not significantly different between the groups. VAS scores and the number of additional analgesic agents used were smaller in patients in whom non-steroidal anti-inflammatory drugs were regularly administered postoperatively than in those in whom the drug was not regularly administered postoperatively. LH had a 3.4% complication rate (Clavien-Dindo classification >IIIA); however, this was not significantly different between the groups., Conclusions: No significant difference in postoperative pain was observed between RPS and conventional methods, although operative durations were shorter with RPS. However, RPS for LH may be associated with excellent cosmetic results compared with conventional methods.

Background: Hepatectomy is currently recommended as the most reliable treatment for colorectal liver metastases. However, the association between the choice of treatment for recurrence and the timing of recurrence remains controversial., Methods: Two-hundred ninety-five patients who underwent hepatectomy were retrospectively analyzed for the risk factors and the outcomes for early recurrence within 6 months. The remnant liver volumes (RLVs) and laboratory data were measured postoperatively using multidetector computed tomography on days 7 and months 1, 2, and 5 after the operation., Results: Early recurrence developed in 88/295 patients (29.8%). Colorectal cancer lymph node metastasis, synchronous liver metastasis, and multiple liver metastases were independent risk factors for the occurrence of early recurrence (p < 0.001, 0.032, and 0.019, respectively). Patients with early recurrence had a poorer prognosis than did patients who developed later recurrence (p < 0.001). Patients who underwent surgery or other local treatment had better outcomes. The changes in RLV and laboratory data after postoperative month 2 were not significantly different between the 2 groups., Conclusion: Patients with early recurrence within 6 months had a poorer prognosis than did patients who developed later recurrence. However, patients who underwent repeat hepatectomy for recurrence had a better prognosis than did those who underwent other treatments, with good prospects for long-term survival., (© 2019 S. Karger AG, Basel.)

Background: Laparoscopic hepatic resection has been developed as a minimally invasive surgery; however, laparoscopic repeat minor hepatic resection (LRH) carries a higher risk of damage to other organs because of postoperative changes to and losses of anatomical landmarks. The current standard approach at many facilities has been to perform open repeat minor hepatic resection (ORH). This paper describes the surgical outcomes, procedure safety, and utility of ORH versus LRH, as well as the laparoscopic techniques used in LRH., Methods: Between February 2010 and May 2018, the data of 142 patients who underwent LRH or ORH at a single institution were retrospectively reviewed. Surgical outcomes, procedure safety, and procedure utility data were analyzed., Results: Forty-five patients underwent LHR and 97 patients underwent ORH. The conversion rate from LHR to OHR was 13.3%. After propensity score matching (PSM), the estimated blood loss was significantly lower in the LRH group than in the ORH group (50 mL vs. 350 mL; P < 0.001). The LRH group had an 8.1% complication rate, while the ORH group had a complication rate of 24.3% (P = 0.044). The postoperative length of stay was significantly shorter in the LHR group than in the OHR group (9 days vs. 11 days) (P = 0.024)., Conclusion: LRH can be performed safely using various surgical devices. More favorable results are achieved with LRH than with ORH in terms of surgical outcomes including intraoperative bleeding, postoperative complications, and postoperative lengths of stay.

Background: Postoperative chemotherapy for treating colorectal liver metastasis (CLM) has been introduced with the aim of improving therapeutic outcomes. However, there is no consensus on the utility of multidisciplinary treatments with postoperative chemotherapy. Therefore, we evaluated surgical outcomes in patients with CLMs who underwent hepatectomy, while focusing on the effects of post-hepatectomy chemotherapy on remnant liver regeneration., Methods: Two hundred ninety patients who underwent hepatectomy were retrospectively analyzed using propensity score matching. Postoperative outcomes were evaluated with a focus on the effects of post-hepatectomy chemotherapy on regeneration of the remnant liver in patients with CLM. The remnant liver volumes (RLVs) were measured postoperatively using multi-detector computed tomography on day 7 and months 1, 2, 5, and 12 after the operation., Results: RLV regeneration and postoperative blood laboratory data did not differ significantly between patients who received postoperative chemotherapy and those who did not receive postoperative chemotherapy immediately after surgery or at any time point from postoperative day 7 to postoperative month 12. The recurrence rates, including same and other segmental intrahepatic recurrences, as well as the resection frequency of the remnant liver were not significantly different between the two groups., Conclusion: Postoperative chemotherapy may be of small significance for patients with CLM in terms of the remnant liver volume regeneration and functional recovery.

Background: Lenvatinib demonstrated a treatment effect on overall survival by the statistical confirmation of non-inferiority to sorafenib for the first-line treatment of uHCC. The objective of this study was to evaluate the cost-effectiveness of lenvatinib compared with sorafenib for patients with uHCC in Japan., Methods: A partitioned-survival model was developed to estimate the cost-effectiveness of lenvatinib versus sorafenib when treating uHCC patients over a lifetime horizon and considering total public healthcare expenditure. Efficacy and safety data were extracted from the REFLECT trial. Utility values were derived from the European Quality-of-Life 5-Dimension Questionnaire, conducted with patients enrolled in the REFLECT trial. Direct medical costs, such as primary drug therapy, outpatient visits, diagnostic tests, hospitalization, post-progression therapy, and adverse-event treatments, were included. Cost parameters unavailable in the clinical trial or publications were obtained based on the consolidated clinical standards from a Delphi panel of four Japanese medical experts., Results: For lenvatinib versus sorafenib, the incremental cost was - 406,307 Japanese Yen (JPY), and the incremental life years and quality-adjusted life years (QALYs) were 0.27 and 0.23, respectively. Thus, lenvatinib dominated sorafenib, due to the mean incremental cost-effectiveness ratio falling in the fourth quadrant, conferring more benefit at lower costs compared with sorafenib. The probabilistic sensitivity analysis showed that 81.3% of the simulations were favorable to lenvatinib compared with sorafenib, with a payer's willingness-to-pay-per-QALY of 5 million JPY., Conclusions: Lenvatinib was cost-effective compared with sorafenib for the first-line treatment of uHCC in Japan.

Background: Post-hepatectomy liver regeneration is of great interest to liver surgeons, and understanding the process of regeneration could contribute to increasing the safety of hepatectomies and improving prognoses., Methods: Five hundred thirty-eight patients who underwent hepatectomy were retrospectively analyzed. Postoperative outcomes were evaluated, with a focus on the effects of portal vein resection and resected liver volume on remnant liver regeneration in patients with liver tumors. Remnant liver volumes (RLVs) and laboratory data were measured postoperatively using multidetector computed tomography on day 7 and months 1, 2, 5, 12, and 24 after the operation., Results: Liver regeneration speed peaked at 1 week postoperatively and gradually decreased. Regeneration with large resections was longer than that with small resections, with the remnant liver regeneration rate being significantly lower in the former at all time points. Remnant liver regeneration plateaued around 5 months postoperatively, when regeneration is almost complete. Up to 1 month postoperatively, laboratory data were significantly worse when more portal veins was resected. After 2 months postoperatively, these data recovered to near normal levels., Conclusion: The speed and rate of remnant liver regeneration primarily showed a strong correlation with the number of resected portal veins and the amount of removed liver parenchyma. The larger the resection ratio, the longer it took the liver to regenerate. We confirmed that recovery of the liver's functional aspects accompanies recovery of the RLV.

Introduction: The rising proportion of elderly patients (aged 80 yearsor above) in our population means that more elderly patients are undergoing hepatectomy., Methods: Five-hundred and thirty patients who underwent hepatectomy for hepatocellular carcinoma (HCC) were retrospectively analyzed with respect to their preoperative status and perioperative results, including remnant liver regeneration. The remnant liver volume was postoperatively measured with multidetector CT on postoperative day 7 and 1, 2, 5, and 12 months after surgery. An elderly group (aged 80 or older) was compared with a non-elderly group (aged less than 80 years)., Results: Underlying diseases of the cardiovascular system were significantly more common in the elderly group (57.8%, p = 0.0008). The postoperative incidence of Clavien-Dindo Grade IIIa or higher complications was 20.0% in the elderly group and 24.3% in the non-elderly group, and this difference was not significant. As for regeneration of the remnant liver after resection, this was not morphologically delayed compared to the non-elderly group., Conclusions: In this study, we have demonstrated that safe, radical hepatectomy, similar to procedures performed on non-elderly patients, can be performed on patients with HCC aged 80 and older with sufficient perioperative care., (© 2018 S. Karger AG, Basel.)

Background: Various chemotherapy regimens have been shown to improve outcomes when administered before tumor excision surgery. However, there is no consensus on the utility of multidisciplinary treatment with preoperative chemotherapy for treating colorectal liver metastasis (CLM)., Materials and Methods: Two hundred-fifty patients who underwent hepatectomy were retrospectively analyzed using propensity score matching. Postoperative outcomes were evaluated with a focus on the effect of pre-hepatectomy chemotherapy on regeneration of the remnant liver in patients with CLM. The remnant liver volumes (RLVs) were postoperatively measured with multidetector computed tomography on days 7 and months 1, 2, 5, and 12 after the operation., Results: RLV regeneration and blood test results did not significantly differ between patients who underwent preoperative chemotherapy versus those who did not immediately after surgery or at any time point from postoperative day 7 to postoperative month 12. The 1-, 2-, and 3-year overall survival (OS) rates for all patients were 94.6, 86.2, and 79.9%, respectively; the corresponding disease-free survival (RFS) rates were 49.3, 38.6, and 33.7%, respectively. There were no significant differences in OS and RFS between the two groups after hepatic resection. The recurrence rates, including marginal and intrahepatic recurrences, as well as resection frequency of the remnant liver were not significantly different between the two groups., Conclusion: Preoperative chemotherapy may have no appreciable benefit for patients with CLM in terms of perioperative and long-term outcomes.

Background: Laparoscopic hepatic resection (LHR) has been developed as a novel minimally invasive surgery. However, despite improvements in equipment and procedures, intraoperative hemorrhage remains an issue that requires great precaution. To reduce the amount of intraoperative blood loss, we perform the Pringle maneuver, aimed at occluding the inflow of blood into the liver during LHR. This article describes our experience performing LHR using the Pringle maneuver, including postoperative results, and discusses the safety and effectiveness of the Pringle maneuver., Methods: Data from 83 patients who underwent laparoscopic partial right hepatic resection with or without the Pringle maneuver were retrospectively analyzed with respect to surgical outcomes, safety, and utility., Results: In LHR, the amount of bleeding was significantly lower in cases that included the Pringle maneuver (P = .0314). However, there were no differences in the duration of surgery, surgical margin, rate of curative resections, and incidence of postoperative complications. Laboratory data collected after surgery showed no significant difference between the two groups regardless of whether blood flow was occluded or not., Conclusions: The Pringle maneuver may be effective in reducing the amount of intraoperative blood loss during laparoscopic partial right hepatic resection, although the difference is not clinically significant. Rather, the reduction in bleeding can reduce the stress experienced by the operator while keeping the transection stump of the liver dry. Particularly, the extracorporeal Pringle maneuver using cotton tape is simple and convenient and can be carried out within a short amount of time.

Background: Laparoscopic liver resection (LLR) has been developed as a minimally invasive surgery. However, challenges such as difficulty securing visibility and limited control of forceps make it difficult to complete LLR in hepatic segments VI, VII, and VIII. To overcome these challenges, we devised a surgical technique using intercostal ports. We termed this approach the lateral approach. This work describes our experience performing LLR using this approach and discusses the safety and effectiveness of this approach., Methods: Between April 2011 and December 2016, data from 91 patients who underwent LLR with or without the intercostal port at a single institution were retrospectively analyzed regarding surgical outcomes, safety, and utility., Results: LLR was performed for 32 patients with the intercostal port and for 59 patients without the intercostal port. The conversion rates to open surgery with and without intercostal ports were 3.1 and 25.4% (P = 0.008). In hepatic segments VII and VIII, the rates of conversion to open surgery were significantly lower for cases involving intercostal ports (6.7 vs. 42.9 and 0 vs. 38.9%; P = 0.035 and 0026, respectively); however, there were no differences in hepatic segment VI (0 vs. 7.4%; P = 0.563). There were no differences in operative time, blood loss volume, surgical margin, curative resection rate, or postoperative complication rate for LLR in all segments (VI, VII, and VIII). No adverse events due to placement of the intercostal port were observed in this set of patients., Conclusion: LLR using the lateral approach and intercostal ports for hepatic segments VII and VIII resulted in a significant decrease in conversion rates to open surgery.

Background: This study aimed to compare the radicality for and clinical advantages of laparoscopic liver resection, which is increasingly used, and the corresponding open procedure by propensity score matching analysis., Methods: We analyzed 260 hepatocellular carcinoma patients who underwent initial liver resection at our department between January 2003 and June 2011, including 60 laparoscopic (the Lap group) and 200 open cases (the Open group). Propensity scores were calculated for each patient via the use of various clinicopathologic features as covariates, and patients' survival was compared., Results: The Lap group had more women and patients of advanced age (n = 60) than the Open group (n = 200). Tumor size (2.3 cm vs 3.5 cm median), multiple tumors (18.3% vs 41.0%), vascular invasion (15.0% vs 36.5%), poor differentiation status (11.2% vs 24.5%), intraoperative bleeding (110 mL vs 420 mL; median), and operative time (277 minutes vs 312 minutes; median) were significantly more favorable in the Lap group than in the Open group because of a selection bias of the patients (Lap vs Open). The postoperative recurrence-free and overall survival rates were greater in the Lap group than in the Open group; however, when 35 patients from each group were analyzed after propensity score matching of clinicopathologic characteristics of the patients, intraoperative bleeding was lesser in the Lap group. The recurrence-free survival rates at 1, 3, and 5 years were 75.0%, 43.8%, and 43.8%, respectively, in the Lap group and 73.6%, 49.3%, and 37.2%, respectively, in the Open group, which indicated no significant differences (P = .954). Similarly, the overall survival rates at 1, 3, and 5 years were 93.9%, 82.1%, and 82.1%, respectively, in the Lap group and 94.3%, 85.2%, and 61.8%, respectively, in the Open group, indicating no significant differences between the 2 groups (P = .672)., Conclusion: Our results indicate that laparoscopic liver resection is comparable with the corresponding open procedure in clinical safety and prognostic efficacy., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Hepatocellular adenoma (HCA) is a rare primary benign tumor of the liver, which occurs predominantly in young and middle-aged women. Recently, the subclassification of HCA was proposed by the Bordeaux group. Subsequently, characteristic radiological and clinical features have been revealed in each HCA subtype. According to the previous literature, diffuse intratumoral fat deposition is a very common finding in hepatocyte nuclear factor 1α-negative HCA, but this finding has been reported in β-catenin-positive HCA in the literature for only one case. In this case report, we report the second case of β-catenin-positive HCA with MR imaging sign of diffuse intratumoral fat deposition, confirmed immunohistologically on the basis of a surgical specimen. In addition, our case showed hypovascularity and isointensity on the hepatobiliary phase which have been reported as characteristic findings in β-catenin-positive HCA. Diffuse intratumoral fat deposition can be observed in β-catenin-positive HCA, which has a greater probability of malignant transformation than other types of HCA.

Aim: To clarify the utility of using des-γ-carboxy prothrombin (DCP) and α-fetoprotein (AFP) levels to predict the prognosis of hepatocellular carcinoma (HCC) in patients with hepatitis B virus (HBV) and the hepatitis C virus (HCV) infections., Methods: A total of 205 patients with HCC (105 patients with HBV infection 100 patients with HCV infection) who underwent primary hepatectomy between January 2004 and May 2012 were enrolled retrospectively. Preoperative AFP and DCP levels were used to create interactive dot diagrams to predict recurrence within 2 years after hepatectomy, and cutoff levels were calculated. Patients in the HBV and HCV groups were classified into three groups: a group with low AFP and DCP levels (LL group), a group in which one of the two parameters was high and the other was low (HL group), and a group with high AFP and DCP levels (HH group). Liver function parameters, the postoperative recurrence-free survival rate, and postoperative overall survival were compared between groups. The survival curves were compared by log-rank test using the Kaplan-Meier method. Multivariate analysis using a Cox forward stepwise logistic regression model was conducted for a prognosis., Results: The preoperative AFP cutoff levels for recurrence within 2 years after hepatectomy in the HBV and HCV groups were 529.8 ng/mL and 60 mAU/mL, respectively; for preoperative DCP levels, the cutoff levels were 21.0 ng/mL in the HBV group and 67 mAU/mL in the HCV group. The HBV group was significantly different from the other groups in terms of vascular invasion, major hepatectomy, volume of intraoperative blood loss, and surgical duration. Significant differences were found between the LL group, the HL group, and the HH group in terms of both mean disease-free survival time (MDFST) and mean overall survival time (MOST): 64.81 ± 7.47 vs 36.63 ± 7.62 vs 18.98 ± 6.17 mo (P = 0.001) and 85.30 ± 6.55 vs 59.44 ± 7.87 vs 46.57 ± 11.20 mo (P = 0.018). In contrast, the HCV group exhibited a significant difference in tumor size, vascular invasion, volume of intraoperative blood loss, and surgical duration; however, no significant difference was observed between the three groups in liver function parameters except for albumin levels. In the LL group, the HL group, and the HH group, the MDFST was 50.09 ± 5.90, 31.01 ± 7.21, and 14.81 ± 3.08 mo (log-rank test, P < 0.001), respectively, and the MOST was 79.45 ± 8.30, 58.82 ± 7.56, and 32.87 ± 6.31 mo (log-rank test, P < 0.001), respectively., Conclusion: In the HBV group, the prognosis was poor when either AFP or DCP levels were high. In the HCV group, the prognosis was good when either or both levels were low; however, the prognosis was poor when both levels were high. High levels of both AFP and DCP were an independent risk factor associated with tumor recurrence in the HBV and HCV groups. The relationship between tumor marker levels and prognosis was characteristic to the type of viral hepatitis.

Surgery involving elderly patients is becoming increasingly common due to the rapid aging of societies all over the world. The objective of this study was to elucidate the prognostic differences between elderly and young patients who undergo liver resection. A systematic review based on the PRISMA flow diagram was conducted. Ovid Medline and PubMed were used to search for relevant literature published between January 2000 and March 2013, and the modified MINORS score was used to assess the methodological quality. In cases of hepatocellular carcinoma and miscellaneous liver tumors, the morbidity and mortality rate did not differ significantly between the elderly and young patients. For patients with colorectal metastatic liver cancer, the mortality of the young patients was 2.7 times lower than that of elderly patients. Our review of high-quality retrospective studies was able to elucidate the clinical risks of age on the outcomes after liver surgery in specific patient populations.

Aim: The present study was designed to define the clinicopathological characteristics of multiple cancers (MC) in 597 patients with hepatobiliary and pancreas (HBP) malignancies who underwent curative resection, in order to clarify risk factors and prognostic significance., Patients and Methods: Patients' demographics, clinicopathological parameters and survival rates were compared between solitary (SC) and MC HBP malignancies for 267 patients with hepatocellular carcinoma (HCC), 77 with intrahepatic cholangiocarcinoma (ICC), 84 with extrahepatic bile duct carcinoma (BDC), 72 with gallbladder carcinoma (GBC) and 97 with pancreatic cancer (PC)., Results: MC was observed in 66 patients (11%) and more than three cancers were observed in 13 (2.2%). The mean age of patients of the MC group was significantly higher than that of the SC group. The proportion of Nagasaki atomic bomb survivors among the MC group was significantly higher than among the SC group. These findings were significant in HCC and ICC. The histopathological aggressiveness of malignancies was lower with HCC, BDC and PC. In HCC, the disease-free survival of MC patients with more than three tumors was significantly lower than those with SC and double cancers. In GBC, the overall survival of the MC group was significantly better than the SC group. In PC, the disease-free and overall survival were significantly better in MC than SC., Conclusion: Careful follow-up for second or third occurrence of primary malignancies after primary curative treatment for HBP malignancy is necessary., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Interferon-α (IFN-α) is used clinically to treat hepatocellular carcinoma (HCC), although the detailed therapeutic mechanisms remain elusive. In particular, IFN-α has long been implicated in control of the cell cycle, but its actual point of action has not been clarified. Here, using time lapse imaging analyses of the human HCC cell line HuH7 carrying a fluorescence ubiquitination-based cell cycle indicator (Fucci), we found that IFN-α induced cell cycle arrest in the G0/G1 phases, leading to apoptosis through an IFN-α type-2 receptor (IFNAR2)-dependent signaling pathway. Detailed analyses by time lapse imaging and biochemical assays demonstrated that the IFN-α/IFNAR2 axis sensitizes cells to apoptosis in the S/G2/M phases in preparation for cell death in the G0/G1 phases. In summary, this study is the first to demonstrate the detailed mechanism of IFN-α as an anticancer drug, using Fucci-based time lapse imaging, which will be informative for treating HCC with IFN-α in clinical practice., (© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.)

Aim: To compare the prognoses of hepatocellular carcinoma (HCC) patients that underwent anatomic liver resection (AR) or non-anatomic liver resection (NAR) using propensity score-matched populations., Methods: Between January 2002 and December 2010, 268 consecutive HCC patients, including 110 and 158 patients that underwent AR and NAR, respectively, were retrospectively enrolled in this study. Forty-four patients from each group were selected and matched using logistic multivariate analysis followed by propensity score analysis., Results: In the whole analysis set, the histological background of the liver, liver function, and tumor marker levels differed significantly among the groups. Although the overall survival (OS) and recurrence-free survival rates of the two groups did not differ significantly in the whole analysis set, the OS of the AR group was significantly longer than that of the NAR group after propensity matching (76.2 ± 6.3 mo vs 58.9 ± 6.3 mo; P = 0.0039). Although AR (HR = 0.456, P = 0.039) was found to be a prognostic factor in the univariate analysis, only vascular invasion (HR = 0.228, P = 0.002) and the hepatocyte growth factor level (HR = 52.366, P = 0.035) were subsequently found to be independent prognostic factors., Conclusion: AR conveys a survival advantage over NAR in specific subpopulations of HCC patients with tumors of less than 5 cm in diameter, single tumor, and good liver function.

This retrospective study was performed to examine the outcomes of patients with liver metastasis of colorectal cancer, who received mFOLFOX6 regimen prior to hepatic metastatectomy. The reasons for introducing mFOLFOX6 prior to hepatectomy were unresectable hepatic lesions in two patients, presence or suspicion of extrahepatic lesions in four patients, and patient's refusal for hepatectomy in one patient. The mean number of cycles of administering mFOLFOX6 was 12.7 (range 10-18), two patients received additional FOLFIRI regimen after mFOLFOX6 treatment. The therapeutic efficacy revealed complete response in two, partial response in two, and stable disease in two by RECIST criteria. Histological examination revealed that six from 15 resected nodules were classified into grade 3. Histological examination of the non-cancerous liver tissue revealed stage I sinusoidal dilation (Rubbia-Brandt's classification) in five and grade 1 steatohepatitis (Brunt's classification) in two who received additional FOLFIRI regimen. Blood loss and duration of surgery of the subjects were identical to those (n=17) who underwent hepatic metastatectomy without preoperative chemotherapy during the same study period. It does not seem easy to determine the optimal timing of hepatic metastatectomy after FOLFOX treatment in clinical practice. However, our results suggest that preoperative FOLFOX treatment may have little adverse impact on the safety of hepatic metastatectomy.

Metastatic liver tumors are highly malignant and refractory to conventional therapies. TRAIL-resistant CT-26 cells underwent apoptosis in vitro in the presence of both recombinant TRAIL (rTRAIL) and a suboptimal dose of actinomycin D (ACD). Co-administration of soluble TRAIL (sTRAIL) gene and ACD suppressed the metastatic liver tumors of CT-26, significantly inducing apoptosis in the tumors, while such effects were not demonstrated in mice that received either the sTRAIL gene or ACD alone. The gene therapy of sTRAIL with a suboptimal dose of an anticancer drug is a new strategy for treatment of multiple liver metastasis.

Background/aims: A major polyphenol of green tea, epigallocatechin-3-gallate (EGCG), has previously been shown to induce cell-cycle arrest and apoptosis in various cancers. However, little is known about its effects on hepatocellular carcinomas (HCCs)., Methods: Four HCC cell lines, HLE, HepG2, HuH-7 and PLC/PRF/5, were treated with EGCG or vehicle. Cell viability was assessed by trypan blue staining and WST-8 assay. Cell-cycle, apoptosis and apoptosis-related proteins in HLE cells were evaluated by flow cytometry and Western blotting. The effect of EGCG was also studied in vivo using a xenograft model. The effect of co-treatment with EGCG and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was also assessed., Results: EGCG inhibited the growth of all HCC cell lines at concentrations of 50-100 microg/ml. In HLE cells, EGCG induced apoptosis but not cell-cycle arrest and appears to have down-regulated Bcl-2alpha and Bcl-xl by inactivation of NF-kappaB. Oral administration of EGCG showed similar effects in HLE xenograft tumors. Co-treatment with EGCG and TRAIL synergistically induced apoptosis in HLE cells., Conclusions: EGCG induced apoptosis in HLE cells, both in vitro and in vivo. Moreover, it enhanced TRAIL-induced apoptosis. Therefore, EGCG treatment may be useful for improving the prognosis of HCCs.

To identify the genes associated with dedifferentiation of hepatocellular carcinoma (HCC), gene expression profiles of HCCs of well-and moderately differentiated grades were compared by means of oligonucleotide arrays. One tumor showed a nodule-in-nodule appearance (NIN), which is occasionally observed in the course of progression of HCC from well to less differentiated grade, when an inner, moderately differentiated tumor (MD) develops sequentially from the outer, well-differentiated tumor (WD). Seventy-six genes were identified to be up-regulated more than 3-fold and 33 genes were down-regulated in the inner nodule in NIN. By statistical analysis of the profiles from 10 individual additional liver tumors, 5 WDs and 5 MDs, we were able to identify 12 genes, LAMA3, PPIB, ADAR, PSMD4, NDUFS8, D9SVA, CCT3, GBAP, ARD1, RDBP, CSRP2, and TLE1, with significantly elevated expression, and 4 genes, CP, IL7R, CD48, and PLGL, with decreased expression in MD. These selected genes were further validated using another 12 tumors, 5 WDs and 7 MDs, with semi-quantitative RT-PCR. We also applied neighborhood analysis to list the genes with high predictability values as most closely correlated with WD-MD distinction. Seven genes, ADAR, PSMD4, D9SVA, CCT3, GBAP, RDBP, and CSRP2, whose expression was elevated and one gene, IL7R, whose expression was decreased, were included among the top 50 predictor genes. These genes are likely to be associated with dedifferentiation of HCC and their identification may help to elucidate the mechanism of liver cancer progression.

Immunosuppression and transplantation have been reported to induce porokeratosis (PK), especially its variant, disseminated superficial PK (DSP). On the other hand, there is ample evidence of a relationship between hepatitis C virus (HCV) infection, liver cirrhosis (LC), and hepatocellular carcinoma (HCC). We report 3 cases of DSP in which the outbreak of DSP was suspected to have occurred during the development of HCC in patients with HCV-positive LC. The patients had undergone ultrasonographic study regularly, and no signs of malignancy had been found before the development of DSP. Their outbreaks of DSP were very acute, and the period between the development of DSP and diagnosis of HCC ranged from 2 to 6 months. The association of HCV-related HCC and DSP has never been previously reported. HCV-induced immunomodulation or its effect on the p53 system may be the basis for this type of association. It is necessary to consider development of HCC whenever DSP is found in HCV-positive patients. DSP may be a new paraneoplastic dermadrome.

Objective: We evaluated the measurements of serum alpha-fetoprotein (AFP) and the protein induced by vitamin K absence (PIVKA-II) in 734 patients with chronic hepatitis (CH) and liver cirrhosis (LC) who had been followed-up for the development of hepatocellular carcinoma (HCC)., Methods: Serum AFP and PIVKA-II were measured every month and abdominal ultrasonography was performed every 3 months. Youden's index (sensitivity + specificity -1) was calculated., Results: On an average follow-up period of 374.5 days, HCC was detected in three HBsAg-positive LC patients (10.0%/yr), four anti-HCV-positive CH patients (1.35%/yr), 21 anti-HCV-positive LC patients (7.8%/yr), and one patient with both HBsAg- and anti-HCV-positive LC (22.7%/yr). At the time of HCC detection, the size of HCC was 4.7+/-0.6 (mean +/- SD) cm in HBsAg-positive patients and 2.4+/-1.3 cm in anti-HCV-positive patents. Cut-off values of 20 ng/ml for AFP (Youden's index = 0.422) and 60 mAU/ml for PIVKA-II (Youden's index = 0.316) gave the highest index for each marker. When these two markers were combined, cut-off values of 40 ng/ml for AFP and 80 mAU/ml for PIVKA-II gave the highest index (Youden's index = 0.500, sensitivity = 65.5%, specificity = 85.5%, positive predictable value = 14.8%, negative predictable value = 98.3%). The levels of AFP or PIVKA-II increased within three months before the detection of HCC., Conclusions: Simultaneous measurements of serum AFP and PIVKA-II levels that are performed every 3 months are useful for detecting a developing HCC. The optimal cut-off values for AFP and PIVKA-II may be 40 ng/ml and 80 mAU/ml, respectively.

Aims/background: Transcatheter arterial chemoembolization (TAE) of hepatocellular carcinoma (HCC) causes anoxia. Escape of cancer cells from anoxic injury may be enhanced by induction of proteins which provide resistance to apoptosis., Methods: We examined HCCs immunohistochemically for Bcl-2, vascular endothelial growth factor (VEGF), p53, and Ki67. The staining intensity for VEGF, a protein induced by anoxia, was assessed morphometrically with a computer-assisted image-analyzer., Results: The frequency of Bcl-2 positive cells was higher in HCCs that had undergone TAE (TAE HCC) than that in HCCs that had not undergone TAE (41.75+/-15.06 vs. 1.01+/-0.79 cells/1000 cells, p = 0.0173). The frequency of p53- or Ki67-positive cells was not increased after TAE. Of 12 TAE HCCs, 7 had Bcl-2 positive HCC cells and 6 had clusters of Bcl-2 positive cells. In contrast, 2 of 11 HCCs that had not undergone TAE had only a few, sporadically distributed, Bcl-2-positive cells. The staining intensity for VEGF was higher in Bcl-2 positive than in Bcl-2 negative areas (1.208+/-0.091 vs. 1.071+/-0.017, p = 0.0222). Furthermore, the VEGF staining intensity in Bcl-2 positive areas of TAE HCCs was higher than in Bcl-2 negative areas (1.296+/-0.126 vs. 1.066+/-0.024, p = 0.0186), while in HCCs that had not undergone TAE the staining intensity was similar., Conclusions: TAE of HCC can induce Bcl-2 expression, possibly through anoxic stress.

Aims/background: Expression of urokinase-type plasminogen activator receptor (uPAR) was studied in 25 hepatocellular carcinomas (HCCs) and seven cholangiocellular carcinomas (CCCs) by immunohistochemistry., Methods and Results: uPAR was expressed mostly by host cells distributed along the tumour-host interface in all cases of HCC and CCC, and its expression was higher in CCC. These uPAR-positive cells were identified as macrophages by observation of serial sections stained for CD68, a marker for macrophages. Cancer cells were positive for uPAR in only one case of poorly differentiated HCC with sarcomatous changes and in three cases of CCC. Hepatocellular carcinomas were classified into two types: those with a fibrous capsule (expansive type) and those without a fibrous capsule (invasive type). Invasive-type HCCs showed more prominent expression of uPAR by macrophages than expansive HCCs (p<0.001), to approximately the same degree as that of CCC. Extrahepatic metastasis was observed in two of 16 expansive HCCs, five of nine invasive HCCs and six of seven CCCs., Conclusions: Our findings suggest that uPAR expression mainly by macrophages is associated with invasive growth of cancer cells into the surrounding tissue in primary carcinoma of the liver.

Purpose: To assess the arterial supply to hepatocellular carcinomas (HCCs) by inferior phrenic arteries (IPA)., Material and Methods: A total of 126 consecutive cases of HCC were studied by contract-enhanced CT and conventional arteriography. Blood supply from an IPA was suspected when the size of the HCC mass as seen on contrast-enhanced CT did not match the size of the tumor mass as seen on hepatic arteriography. Inferior phrenic arteriography was employed to confirm these findings. HCCs fed by the IPA were analyzed in terms of size, location, and history of prior treatment., Results: In 14 (11%) of the 126 cases, the tumor was found to have a blood supply from an IPA. Eleven of these tumors were located in segments 2 and 7. Three tumors, which had not been treated previously, had a blood supply from an IPA. Six tumors were almost exclusively fed by an IPA and were located in segments 1, 1, and 4., Conclusion: HCCs located in segments which form the bare area of the liver (S1, S2, S7) can be supplied by an IPA. This should be suspected when a lesion or part of a lesion is identified on contrast-enhanced CT but not on hepatic arteriography.

The purpose of this study is to evaluate hemodynamic characteristics of various hepatic tumors using color Doppler echography administered galactose-based intravenous contrast medium "SH/TA 508 (Levovist)". Subject were 9 cases of hepatocellular carcinomas, 5 cases of metastatic liver tumors and a case of hemangioma. We evaluated the characteristics of blood flows inside various hepatic tumors, and also evaluated the first pass through the hepatic tumors during administration of Levovist. The strongly pulsatile branched blood flows inside tumor and the slow-increased and plateau patterns were observed in the all cases of hepatocellular carcinomas, the weakly pulsatile blood flows surrounding tumor and the rapid-increased and slow-decreased patterns were observed in the cases of metastatic liver tumors, and the continuous blood streams in the margin of tumor and the slow-increased and slow-decreased pattern were observed in the case of hemangioma. These findings were characteristic in various hepatic tumors, and color Doppler echography enhanced by Levovist was very useful to distinguish hepatic tumors.

Surgically placed inflatable vascular occluders temporarily increased or restricted the target volume for intra-arterial therapy for tumors in the liver and pancreas. Proximal occlusion of the common hepatic artery directed retrograde flow from the cannulated gastroduodenal artery into a variant left hepatic artery in one patient with carcinoma of the liver. Occlusion of the distal splenic artery and common hepatic artery after distal gastrectomy with cannulation of the left gastric artery gave selective perfusion of the tumor-bearing pancreatic head in three patients. The occlusions had no untoward effects and the regional infusions seemed to retard local tumor growth.

Three hundred and sixty-eight case-control sets (male 287 pairs; female 81 sets) were collected for a hospital-based case-control study of primary hepatocellular carcinoma (HCC) conducted in Northern Kyushu, Japan. All incident cases of HCC were collected weekly from the inpatients (aged 40-69) of the Second Department of Internal Medicine, Kurume University Hospital between April, 1986 and May, 1992. One control for a male case and 4 controls for a female case were sampled, being matched to a case on age (same 5-year age class), sex, residence (prefecture) and time of hospitalization (within 2 months after a case interview) from the inpatients of two general hospitals in Kurume. Information was collected by interview in person by a well-trained interviewer and from a review of hospital records by the authors. Multivariate analyses based on a conditional logistic regression model without an interaction term revealed that hepatitis B surface antigen (HBsAg) positive status (odds ratio (OR) = 8.67; 95% confidence interval (95%CI) = 2.54-29.57), history of blood transfusion over 10 years previously (2.40; 1.26-4.56), parental history of hepatic diseases (2.31; 1.11-4.80) and heavy alcohol drinking (60 < or = drink-years) by age 40 (3.23; 1.61-6.51) were statistically significant risk factors of male HCC. Univariate analysis for females also showed an elevated OR of HBsAg (7.58; 1.96-29.35). Although the sample size was limited, univariate analysis indicated that anti-hepatitis C virus antibody by c100-3 antigen positive status had a statistically significant OR for HCC in both sexes.

Hepatocellular carcinomas measuring less than 5 cm in diameter became completely necrotic after arterial chemoembolization with Lipiodol, doxorubicin, and gelfoam more often than larger lesions. In 60 patients, we surgically debulked large unresectable tumors, with the aim of subsequently embolizing residual small tumors transarterially. Forty-seven patients were actually embolized. The rate of major non-fatal complications was similar to that seen after radical resections, but the hospital mortality rate was 30%, as compared with 4%. Stage I disease, including non-embolized patients and hospital mortality, had an estimated 5-year survival rate of 27%. This result approached that obtained after curative resections, and was better than that seen after embolization only. Stage II disease had no five-year survivors and its survival curve was intermediate, lying between those of curatively resected and embolization patients. No stage I patients with tumor growth in the portal trunk or lobar branches survived for 2 years. The results warrant further study of this treatment strategy.

Almost one tenth of more than 370 hepatectomies, mostly for tumors, involved resection of major parts of the caudate lobe, subsegment 1. Five of them were for tumors or hemangiomas here, compressing or invading the vena cava; two were for metastases of colorectal cancer located very close to the junctions of the right and middle hepatic veins with the vena cava. We would previously have deemed these tumors unresectable. In these patients the vein was banded above and below the liver, an internal shunt tube placed in preparation for shunting of blood, and the afferent liver blood flow controlled. Control of the vena cava by tightening of the bands was needed in two cases. Tumor-invaded parts of the vein wall were resected in two other cases, in whom the presence of the tube facilitated the resection but the bands did not have to be tightened. The procedure did not cause morbidity and we conclude that tumors close to the vena cava can often be resected without complex vascular exclusion techniques, even when they invade the vein.

An endoscope was equipped with a saline-filled latex rubber balloon at its tip to displace contaminating blood, bile, or gastric contents during operative portoscopy, biliary endoscopy, or upper gastrointestinal endoscopy. A fiber with its tip inside the balloon transmitted energy from an Nd:YAG laser for coagulation of tumors in one bile duct cancer, in six portal vein growths from primary liver cancers, and in a superficially growing stomach cancer. The balloon increased the precision of irradiation by making lesions easier to identify through displacement of bile or blood and by keeping the fiber tip at a fixed position relative to the lesion. The technique, basic experimental studies, and clinical experiences are reported.

The antitumoral effect of gamma-Interferon (Re-IFN-gamma, KW-2202) on nine patients with hepatocellular carcinoma (HCC) has been investigated. gamma-IFN was administered intravenously biweekly at a dose of 8-24 x 10(6) units/day for 5 consecutive days. As all patients had measurable disease determined by an abdominal CT, the antitumoral effect was evaluated by CT, according to the criteria of Koyama and Saito, During gamma-IFN therapy, one patient, who received a total of 4.4 x 10(8) units of gamma-IFN, achieved a partial response (PR) 133 days after onset of treatment. Another patient showed a minor response (MR) 43 days after start of therapy. The duration of the PR and MR were 7.8 weeks and 10.8 weeks, respectively. Two patients were assessed as having had no change (NC), and 5 patients as still manifesting a progressive disease (PD). Marked falls in serum alpha-fetoprotein levels during therapy were observed in 2 cases of which one was graded as having obtained a PR, and the other, a NC. The toxicities observed were fever, general malaise, headaches, and joint pains, which were slight and transient in most cases. In one case, however, a therapy was stopped because of a continuous and severe shoulder pain with no metastasis. Further studies on the use of IFN, possibly in combination with other chemotherapeutic agents, should be performed in patients with HCC.

The presence of specific gamma-glutamyl transpeptidase isoenzyme (gamma-GTPI) and variant alkaline phosphatase (VAALP) were concurrently determined, and levels of basic fetoprotein (BFP) and carcinoembryonic antigen (CEA) in addition to alpha-fetoprotein (AFP) were measured in 144 hepatocellular carcinoma (HCC) patients in order to evaluate the diagnostic value of these tumor markers with respect to AFP-low or -negative patients and the tumor stage. Serum AFP levels below 400 ng/ml, commonly seen in sera of hepatobiliary diseases other than HCC, were noted in 42% of the patients. The diagnostic usefulness was increased by combination assay of these markers except for CEA. A definitive diagnosis of HCC could be made in 78% of the patients by a combination of gamma-GTPI, VAALP and AFP. Moreover, a diagnosis of malignancy could be made in 87% of cases by the inclusion of BFP. The prevalence of BFP and CEA increased in proportion to the tumor stage, whereas that of AFP and gamma-GTPI were independent of stage and were high even in patients in comparatively early stages. Furthermore, secreting type markers such as AFP and gamma-GTPI were relatively useful for diagnosis of HCC when the lesions were still small.

The authors evaluated specific gamma-GTP isoenzyme (specific gamma-GTP) found in sera of patients with hepatocellular carcinoma (HCC). In addition to band II and II' which had been reported in our previous publication, band I' also had a high specificity for HCC. One or more of these bands were detectable in 109 (55%) of 200 patients with HCC, but only in seven (3%) of 279 patients with other hepatobiliary diseases. Specific gamma-GTP was found in 38% of HCC patients with alpha-fetoprotein (AFP) levels below 400 ng/ml. The incidence of this isoenzyme was independent of the clinical stage as classified by liver scanning. Even in Stage I, where filling defects were not seen, the incidence was 52%. We conclude that the specific gamma-GTP is useful in diagnosis of HCC patients with low levels of AFP or at a relatively early stage.

Transcatheter arterial embolization using lipiodol ultra-fluid (L-TAE) is frequently used for hepatocellular carcinoma (HCC). Its advantages are: (1) Excellent therapeutic and diagnostic ability in our pathological study of 153 resected tumors. (2) Preoperatively, we can localize HCC and prevent spreading of cancer cells by manipulation at hepatectomy. (3) Postoperatively, we can detect and treat recurrence early, and we hope to prevent recurrence by repeated L-TAE. (1) Liver infarction has occurred after L-TAE, because some lipiodol flows into the portal vein. Lipiodol remains long in the infarction area and interferes with the diagnosis of HCC. (2) Liver abscess has rarely occurred. (3) Repeated L-TAE does not impair the liver function much.