Metastatic Liver Cancer Patients Research Articles

Salvage Radiotherapy Improves Survival in Patients with Metastatic Liver Cancer after Immunotherapy Oligoprogression

Immune checkpoint inhibitors (ICIs) have ameliorated the survival outcome of liver cancer, a majority of patients receiving ICIs have eventually developed progression. Local therapy, especially radiotherapy (RT), is increasingly being considered in the setting of oligoprogression to delay the need to change systemic therapy. The aim of this study was to evaluate the efficacy and safety of RT as a salvage treatment in patients with oligoprogression after ICIs. This retrospective study was performed to evaluate the use of salvage radiotherapy in oligoprogressive metastatic liver cancer patients. Patients with metastatic liver cancer who had previous stability or response after ≥ 6 mo of ICIs were eligible if they developed progression of five of fewer metastases. Overall, 178 patients treated between August 2018 and March 2022 were included. The patients were followed for a median of 17.2 months. The overall response rate (ORR) and disease control rate (DCR) were 38.2% and 57.8%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 6.5 (95% CI:5.116-7.884) and 17.3 (95% CI:11.166-23.434) months. In multivariate analysis, factors associated with OS included tumor size, tumor number, and radiated tumor site (intrahepatic vs. extrahepatic). The most frequent AEs were fatigue, decreased appetite, rash, fever, and nausea. The above-mentioned AEs were reversible and manageable. Salvage radiotherapy has a potential activity and is tolerable for oligoprogression after ICIs with appropriate radiated tumor site and patient selection. A prospective randomized trial is ongoing to validate this finding (ChiCTR2200060664).

A comparative study of efficacy and safety of transarterial chemoembolization with CalliSpheres and conventional transarterial chemoembolization in treating unresectable intrahepatic cholangiocarcinoma patients.

Objective: Previous studies reported that drug-eluting beads transarterial chemoembolization (DEB-TACE) with CalliSpheres is effective and safe to treat hepatocellular carcinoma patients and metastatic liver cancer patients, however few studies reported its clinical application in intrahepatic cholangiocarcinoma (ICC) patients. Therefore, this study aimed to compare the efficacy between DEB-TACE versus conventional transarterial chemoembolization (cTACE) in unresectable ICC patients.Methods: Between January 2016 and June 2020, 89 patients with unresectable ICC were retrospectively analyzed, and enrolled into DEB-TACE group (N=40) and cTACE group (N=49) based on the transarterial treatment. Treatment response was assessed according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Time to progression (TTP) and overall survival (OS) were analyzed by using the Kaplan-Meier curve. Factors affecting OS and TTP were determined by Cox's proportional hazards regression model.Results: DEB-TACE group showed higher DCR (87.5% vs. 65.3%, P=0.011), while similar ORR (67.5% vs. 57.1%, P=0.317) compared to cTACE group. Furthermore, DEB-TACE group had longer OS (median 10 months vs 6 months, P=0.006), while similar TTP compared to cTACE group (median 4 months vs 2 months, P=0.098). After adjustment by multivariant Cox's regression, DEB-TACE (versus cTACE) independently correlated with longer OS (P=0.031). Further subgroup analyses displayed that OS was prolonged in DEB-TACE group compared to cTACE group in patients with multiple tumors (P=0.032) and patients with no lymph node metastasis (P=0.023). Apart from abdominal pain, no difference of adverse events between the two groups was observed. There was no difference in liver function (Bilirubin, Albumin, Prothrombin time) before and after treatment (4 weeks) in both groups.Conclusion: In patients with unresectable ICC, DEB-TACE significantly improved the OS when compared with cTACE and was well tolerated.

Frequency and Characteristics of Occult Hepatitis B Infection Among Hepatocellular Carcinoma Patients in Japan

Introduction and aim. Occult hepatitis B virus (HBV) infection (OBI) represents a state without detectable hepatitis B surface antigen, but positive for HBV DNA. The correlation between OBI and hepatocellular carcinoma (HCC) carcinogenesis is controversial. We studied the frequency and characteristics of OBI among HCC patients and metastatic liver cancer patients.Material and methods. DNA was obtained from tumor and non-tumor tissues from 75 HCC patients (15 chronic hepatitis B (CHB), 39 chronic hepatitis C (CHC), 21 cryptogenic) and 15 metastatic liver cancer patients who underwent liver resection. HBV DNA and covalently-closed circular (ccc) DNA were detected using real-time polymerase chain reaction (PCR), and four HBV DNA regions were detected by nested PCR. Clinicopathological factors were compared between patients with and without OBI.Results. HBV DNA was detected in 14 (93.3%) CHB, five (22.7%) cryptogenic and four (10.3%) CHC patients. cccDNA was detected in 12 (80.0%) CHB, three (14.3%) cryptogenic and two (5.1%) CHC patients. All CHB, eight (38.1%) cryptogenic and ten (25.6%) CHC patients tested positive with nested PCR. No metastatic liver cancer patients were positive for any HBV DNA regions. OBI patients had shorter prothrombin times (P = 0.0055), and lower inflammation activity score in non-tumor liver (P = 0.0274). There were no differences in anti-HBV antibodies.Conclusions. OBI was detected in 38% of cryptogenic and 25.6% of CHC patients. There was no correlation between OBI and anti-HBV antibodies, but fewer patients with OBI had high inflammatory activity, suggesting that factors other than inflammation may be involved in HCC carcinogenesis in patients with OBI.

Diagnostic value of contrast-enhanced ultrasound for the maximum diameter ≤2 cm metastatic liver cancer: compared with contrast-enhanced CT

Objective To compare the diagnostic performance of contrast-enhanced ultrasound (CEUS) with contrast-enhanced computed tomography (CECT) for the maximum diameter ≤2 cm metastatic liver cancer (MLC). Methods Sixty-nine pathologically diagnosed MLC patients (maximum diameter ≤2 cm) were retrospectively recruited. The lesion detection rate, diagnostic confidence and enhancement pattern of CEUS and CECT for MLC were analyzed. Diagnostic value of CEUS and CECT for MLC were evaluated and compared by using diagnostic test. Results The cases of 0, 1, 2, multiple lesions detected by CEUS and CECT in these 69 patients with ≤2 cm MLC were 0 case (0%), 41 cases(59.42%), 13 cases(18.84%), 15 cases(21.74%) and 9 cases(13.04%), 29 cases(42.03%), 13 cases(18.84%), 18 cases(26.09%), respectively. The positive cases detected by CEUS and CECT were 69 cases(100%) and 60 cases(86.96%) respectively, with a statistically significant difference between the two groups (P=0.006). However, for the detection rate of non-single-lesion cases, there was no statistical difference between CEUS and CECT (P=0.409). The cases showed typical manifestation in CEUS and CECT were 56 cases(81.16%)and 29 cases(42.03%)(P<0.001). The cases with diagnostic confidence level of 3, 4, 5 in CEUS were 3 cases(0.04%), 11 cases(15.94%), 55 cases(79.71%), and those of CECT were 19 cases(27.54%), 20 cases(28.99%), 20 cases(28.99%), respectively. The diagnostic sensitivity of CEUS and CECT for ≤2 cm MLC were 100% (69/69) and 85.51% (59/69), with statistically significant difference(P=0.001). Conclusions The lesion detection rate and diagnostic value of CEUS for the maximum diameter ≤2 cm MLC might be superior to that of CECT, but the detection rate shows no significant difference in the non-single-lesion cases. CEUS has important clinical value in the diagnosis of ≤2 cm MLC. Key words: Contrast-enhanced ultrasound; Metastatic liver cancer; Contrast-enhanced CT

The curcumin derivative WZ35 activates ROS-dependent JNK to suppress hepatocellular carcinoma metastasis.

Tumor metastasis is the leading cause of cancer death; due to the progress made in the elucidation of the mechanism of cancer cell metastasis, there is hope for patients with severe stages of cancer. Curcumin, as a novel anti-cancer drug, has been applied in cancer therapy; however, the toxicity of curcumin hinders its application. Herein, we constructed a novel derivative, WZ35, and evaluated its metastatic inhibition properties in vitro and in vivo. CCK-8 assay was performed to evaluate the tumor suppressive activity of WZ35. Cell apoptosis was detected by flow cytometry analysis. Transwell cell migration assay and RTCA were used to detect cell migration in mock and WZ35-treated cells. Western blotting was performed to analyze molecular alteration with different treatments. In this study, we found that curcumin and its derivative WZ35 could dramatically suppress proliferation, invasion, and migration of the hepatocellular HCCLM3, HepG2, and Huh7 cancer cells. Moreover, the cancer cell metastatic markers MMP-2, MMP-9, and N-cadherin were decreased, and E-cadherin was up-regulated. In addition, our data show that WZ35 promotes ROS-dependent JNK activation that is essential for WZ35-caused cell metastasis suppression. Moreover, the NAC and JNK inhibitor SP600125 could dramatically reverse WZ35-caused MMP-2, MMP-9, and N-cadherin reduction and E-cadherin up-regulation. We have also found that WZ35 exhibits powerful anti-metastasis activity of HCCLM3 in vivo. In conclusion, our data indicated that WZ35 could be a candidate for the treatment of metastatic liver cancer patients.

Biodegradable radiopaque water responsive shape memory polymer-hydrogel composite: a device for temporary embolization therapy for liver cancer

Event Abstract Back to Event Biodegradable radiopaque water responsive shape memory polymer-hydrogel composite: a device for temporary embolization therapy for liver cancer Abhijit V. Salvekar1, 2, 3, Yee Shan Wong3, Weimin Huang2, Kiang Hiong Tay4 and Subbu S. Venkatraman3 1 Nanyang Technological University, Nanyang Institute of Technology in Health and Medicine, Singapore 2 Nanyang Technological University, Mechanical & Aerospace Engineering, Singapore 3 Nanyang Technological University, Materials Science & Engineering, Singapore 4 Singapore General Hospital, Department of Diagnostic Radiology, Singapore Introduction: Liver cancer (Hepatocellular Carcinoma) is fifth-most common type of cancer and the second-most reason for cancer-related death worldwide and is highly prevalent in Asia [1]. Whilst the surgery is the only curative way, only 10% of primary and metastatic liver cancer patients are eligible for resection while the remaining patients can only opt for palliative treatments such as Transcatheter arterial chemoembolization (TACE) and Selective internal radiation therapy (SIRT) [2],[3]. Embolization is crucial step in the TACE or SIRT treatments for enhancing the efficacy of therapy while reducing systemic exposure. Repeat sessions at six- to twelve-weeks intervals of these treatments are recommended so the patency of the hepatic arteries needs to be restored before next treatment. With existing embolic devices the major problems are unpredictable occlusion level, uncontrollable target embolization and degradation rate. In this work we report on fully biodegradable radiopaque solid embolic plug, which can precisely occlude the blood vessel and degrade at a predictable rate. The plug can be delivered to the target site in a low profile temporary shape by catheterization. Upon contact with the body fluid at target location it will self-expand to the fully functional shape, giving perfect occlusion in less than two minutes. Materials and Methods: The embolic device consists of biodegradable Poly(DL-lactide-co-glycolide) (PLGA) filament coated with Poly(ethylene glycol) (PEG) hydrogel. The water induced buckling effect of the PEG hydrogel filament, synthesized using photo-crosslinking method and stretched to different deformation strains at above-melting transition temperature, was explored. Different PLGA compositions modified with the varying amount plasticizer and radiopaque fillers were extruded in filament form and were investigated in terms of their thermo-mechanical properties, degradation timeframe, the effect of programming conditions on the shape memory behaviour and the extent of radiopacity for imaging. The shape memory polymer-hydrogel composite was then fabricated using optimized formulation derived from the individual characterization results of the PLGA and PEG hydrogel. In-vitro performance of the device, in terms of occlusion rate using a custom-built peristaltic flow system and biocompatibility, was evaluated. Based on the material characterization results, the mechanism for water-responsive shape memory effect in such a polymer-hydrogel composite was elucidated. Results: 7.5% (w/v) PEG-diacrylate hydrogel photo-crosslinked using 2% (w/w) Irgacure-2959 initiator was found to be optimum. Pre-stretched hydrogel filaments displayed deformation strain dependent water induced buckling phenomena. PEG hydrogel stretched to 500-550% uniaxial strain at 70°C exhibited faster buckling without breaking of gel. From the radiopacity and thermo-mechanical testing it was found that the PLGA formulation with 2% plasticizer and 50% bismuth oxychloride exhibited best properties. The results demonstrated that the prototypes were visible under fluoroscopy and complete vascular occlusion occurred in less than 2 minutes in-vitro. Conclusion: In conclusion, the developed embolic plug possesses promising characteristics crucial to the temporary vascular embolization for liver cancer treatment. Figure1: In-vitro embolization by the developed embolic plug Figure2: Water-responsive shape memory mechanism of the PLGA-PEG composite system This project was supported by A*STAR Grant No. 132 148 0011 (Singapore).

SIMPLE is a good idea (and better with context learning).

Selective and iterative method for performance level estimation (SIMPLE) is a multi-atlas segmentation technique that integrates atlas selection and label fusion that has proven effective for radiotherapy planning. Herein, we revisit atlas selection and fusion techniques in the context of segmenting the spleen in metastatic liver cancer patients with possible splenomegaly using clinically acquired computed tomography (CT). We re-derive the SIMPLE algorithm in the context of the statistical literature, and show that the atlas selection criteria rest on newly presented principled likelihood models. We show that SIMPLE performance can be improved by accounting for exogenous information through Bayesian priors (so called context learning). These innovations are integrated with the joint label fusion approach to reduce the impact of correlated errors among selected atlases. In a study of 65 subjects, the spleen was segmented with median Dice similarity coefficient of 0.93 and a mean surface distance error of 2.2 mm.

Evaluation of Lipid Peroxidation and Some Antioxidant Activities in Patients with Primary and Metastatic Liver Cancer

HCC is the 6th most common cancer in the world. The main risk factors associated with HCC are hepatitis B (HBV) and hepatitis C viral infections and other factors that play a role in HCC development, include aflatoxin B1 (AFB1) cigarette smoking, and chronic inflammation. The aim of this study is to investigate lipid peroxidation and some antioxidant enzyme activities in patients with primary and metastatic liver cancer. For this purpose, 25 primary and metastatic liver cancer patients and 15 healthy controls were included in the study. In blood samples taken from the patient and control groups, the main product of lipid peroxidation MDA and SOD, GSH, GPx activity levels were examined. In result of study serum MDA level is higher and erythrocyte SOD, GSH, and GPx activities were found to be significantly lower in the patient group compared with the control group (p 0.05). As a result, liver cancer is associated with oxidative stress and antioxidant system weakens, which is an important indicator of oxidative stress, lipid peroxidation levels increased and promotes the tissue damage.

Long-term outcomes after hepatic resection combined with radiofrequency ablation for initially unresectable multiple and bilobar liver malignancies

BackgroundHepatic resection (HRE) combined with radiofrequency ablation (RFA) offers a surgical option to a group of patients with multiple and bilobar liver malignancies who are traditionally unresectable for inadequate functional hepatic reserve. The aims of the present study were to assess the perioperative outcomes, recurrence, and long-term survival rates for patients treated with HRE plus RFA in the management of primary hepatocellular carcinoma (HCC) and metastatic liver cancer (MLC). MethodsData from all consecutive patients with primary and secondary hepatic malignancies who were treated with HRE combined with RFA between 2007 and 2013 were prospectively collected and retrospectively reviewed. ResultsA total of 112 patients, with 368 hepatic tumors underwent HRE combined with ultrasound-guided RFA, were included in the present study. There were 40 cases of HCC with 117 tumors and 72 cases of MLC with 251 metastases. Most cases of liver metastases originated from the gastrointestinal tract (44, 61.1%). Other uncommon lesions included breast cancer (5, 6.9%), pancreatic cancer (3, 4.2%), lung cancer (4, 5.6%), cholangiocarcinoma (4, 5.6%), and so on. The ablation success rates were 93.3% for HCC and 96.7% for MLC. The 1-, 2-, 3-, 4-, and 5-y overall recurrence rates were 52.5%, 59.5%, 72.3%, 75%, and 80% for the HCC group and 44.4%, 52.7%, 56.1%, 69.4%, and 77.8% for the MLC group, respectively. The 1-, 2-, 3-, 4-, and 5-y overall survival rates for the HCC patients were 67.5%, 50%, 32.5%, 22.5%, and 12.5% and for the MLC patients were 66.5%, 55.5%, 50%, 30.5%, and 19.4%, respectively. The corresponding recurrence-free survival rates for the HCC patients were 52.5%, 35%, 22.5%, 15%, and 10% and for the MLC patients were 58.3%, 41.6%, 23.6%, 16.9%, and 12.5%, respectively. ConclusionsHRE combined with RFA provides an effective treatment approach for patients with primary and secondary liver malignancies who are initially unsuitable for radical resection, with high local tumor control rates and promising survival data.

Clinical Significance of Microvessel Count in Patients with Metastatic Liver Cancer Originating from Colorectal Carcinoma

Microvessel count (MVC) has been correlated with patient prognosis in hepatocellular carcinoma. We investigated whether MVC assessed by staining with CD34 antibody was associated with disease-free and overall survival in patients with metastatic liver cancer (MLC). We examined relationships between MVC and clinicopathologic factors or postoperative outcomes in 139 MLC patients who underwent hepatectomy between 1990 and 2006. CD34 expression was analyzed by the immunohistochemical method. MVC was associated with fibrous pseudocapsular formation on histological examination. By means of the modern Japanese classification of liver metastasis, poorer survival was associated with higher score, poorly differentiated adenocarcinoma, higher preoperative carcinoembryonic antigen (CEA) level, fibrous pseudocapsular formation, and smaller surgical margin. Shorter disease-free survival was associated with higher score when the Japanese classification of liver metastasis was used, multiple or bilobar tumor, regional lymph node metastasis in primary colon carcinoma, preoperative CEA level, fibrous pseudocapsular formation, and smaller surgical margin (<5 mm). Higher MVC (>or=406/mm(2)) was associated with decreased disease-free and overall survival by univariate analysis (P = .034 and P = .021, respectively), and higher MVC represented an independently poor prognostic factor in overall survival by Cox multivariate analysis (risk ratio, 2.71; P = .023) in addition to histological differentiation. Tumor MVC seems to be a useful prognostic marker of MLC patient survival.

Expression and significance of KL-6 mucin in the tissue and serum of hepatoma.

Objective To detect the expression of KL-6 mucin in the tissue and serum of hepatoma in different hepatoma patients,and to investigate the value of KL-6 mucin as a tumor marker in the diagnosis of hepatoma.Methods The expression of KL-6 mucin in the hepatoma tissues of 81 patients with hepatocellular carcinoma(HCC),21 patients with cholangiocarcinoma(CC),12 patients with combined hepatocellular and cholangiocarcinoma(HCC-CC)and 56 patients with metastatic liver cancer(MLC)was detected by immunohistochemical analysis.The expression of KL-6 mucin in the serums of 34 HCC patients,8 CC patients,30 MLC patients and 19 healthy individuals was detected by enzyme-linked immunosorbent assay,and all the data were analyzed by t test.Results Expression of KL-6 mucin was detected in the cholangiocarcinoma tissues in all CCand HCC-CC patients.In several hepatoma cells and partial hepatoma tissues of patients with MLC,the expression of KL-6 mucin was detected.No expression of KL-6 mucin was detected in the hepatocellular carcinoma tissuesand non-cancerous tissues of patients with HCC or HCC-CC.The serum levels of KL-6 mucin expression in CC patients were signifcantly higher than those in healthy individuals,HCC and MLC patients(t=5.58,5.34,4.00.P＜0.01).The difference of the serum levels of KL-6 mucin expression between MLC patients and healthy individuals had statistical significance(t=2.77,P＜0.01).However,no significant difference in serum levels of KL-6 mucin expression was found between HCC patients and healthy individuals and between HCC patients and MLC patients(t=2.03,1.89,P＞0.05).Conclusion The expression of KL-6 inucin in CC patients is significantly higher than in patients with other types of hepatoma in both tissue and serum levels.Thus,KL-6 may be a usetul new tmnor marker for distinguishing CC from other types of hepatoma. Key words: Carcinoma,hepatoeellular; KL-6 mucin; cholangiocarcinoma; Metastatic liver cancer

Expression of Aurora B and alternative variant forms in hepatocellular carcinoma and adjacent tissue

Surgical resection is the effective treatment modality for hepatocellular carcinoma (HCC); however, rapid recurrence of the tumors are frequently observed even after apparently curative resection. The recurrence and prognostic assessment of patients with HCC after resection is an important clinical issue. We recently reported that aberrant expression of Aurora B is observed in primary HCC, and that it can be a predictive factor for HCC recurrence exceeding Milan criteria after curative hepatectomy. In this study we investigated the expression of the newly observed Aurora B splicing variant forms in HCC, and their roles in hepatocarcinogenisis. The expression of Aurora B and splicing variant forms were screened in 125 HCC patients (94 chronic hepatitis with cirrhosis background liver specimens), 18 metastatic liver cancer patients and 16 normal liver specimens by cDNA microarray, reverse transcription -- polymerase chain reaction (RT-PCR) and Real time quantitative Reverse Transcription PCR (qRT-PCR). The results showed that expression of Aurora B splicing variant 2 (AURKB-Sv2) variant form was absent in normal liver and was higher in metastatic liver cancer than HCC. This aberrant expression was associated with the advanced stages of HCC (P < 0.01), correlated with a poor outcome (P = 0.008) and short disease-free period (P = 0.018). Furthermore, AURKB-Sv2 variant form is associated with a higher level of serum alpha-fetoprotein, protein induced by vitamin K absence or antagonist-II (PIVKAII), tumor capsular invasion, multiple tumor formation and at an age younger than those with other variant forms (P < 0.05). The results thus suggest that AURKB-Sv2 variant form is more significantly associated with the advanced stages of HCC than others and is a marker of poor prognosis. Founded in the tumor capsular invasion and multiple tumor regions, suggests that this might play a role in enhancing multiple malignant tumor formation and recurrence of HCC in hepatocarcinogenesis. This is the first study to report clinicopathological significance of aberrant expression of AURKB-Sv2 variant form in hepatocellular carcinoma.

A modified grading system for post‐hepatectomy metastatic liver cancer originating from colorectal carcinoma

There is no appropriate grading system for prediction of survival of patients with metastatic liver cancer (MLC) from colorectal carcinoma. We propose the modified grading system for MLC from the present Japanese system. We compared predictive accuracies of survival of 121 Japanese MLC patients of five systems, including clinical risk score (CRS) proposed by Memorial-Sloan-Kettering-Cancer-Center, original H-number (OHN) by Japanese Society for Cancer of the Colon and Rectum, revised H-number (RHN) and Grade by the same society (GJSCCR), and our modified Grade (MGJSCCR) based on OHN and presence of primary lymph node metastasis. Univariate analysis showed that discrimination of both disease-free and overall survival rates was significant for CRS, OHN and MGJSCCR (P < 0.05) but not for RHN and GJSCCR. Multivariate analysis showed CRS and MGJSCCR as the best systems for predicting disease-free and overall survival according to disease stage, for which Akaike information criteria (AIC) value was the lowest (423.7 and 313.9, hazard ratio 1.73 and 1.47, respectively for CRS, 423.9 and 313.5, hazard ratio 1.75 and 1.69, respectively for MGJSCCR; P < 0.05). The simpler system of MGJSCCR is a better predictive grading system of prognosis of MLC patients who had undergone hepatic resection.

Estrogens, Testosterone and Sex Hormone Binding Globulin in Relation to Liver Cancer in Men

Objective: Liver disease in men has been associated with an imbalance of serum estradiol and testosterone. We have evaluated whether serum estradiol and testosterone levels are altered in male liver cancer patients as a result of a specific effect of the disease or because of the associated liver damage. Methods: We have performed a hospital-based case-control study in Greece. The study subjects were all men; 73 patients with hepatocellular carcinoma (HCC), 25 with metastatic liver cancer (MLC) patients and 111 control subjects. Serum estradiol, testosterone and sex hormone binding globulin (SHBG) levels were measured for each subject. Data were analyzed by multiple linear regression. Results: Mean serum estradiol levels were significantly higher among HCC patients as well as among patients with MLC compared to controls. Mean serum testosterone levels were significantly lower among HCC patients as well as among patients with MLC compared to controls. The mean SHBG levels did not differ significantly between the groups. After controlling for the degree of liver damage, the elevated serum estradiol and reduced serum testosterone levels among HCC and MLC patients were no longer significant. Conclusions: Changes in sex steroid levels among patients with liver damage are due to the liver damage per se and not to specific disease processes.

Regulating factors of liver regeneration after hepatectomy

The factors regulating liver regeneration were studied by measuring changes in the liver volume and serum hepatocyte growth factor (HGF) levels after hepatectomy. Changes in the liver volumes were studied in 68 hepatectomized patients, including (A) hepatoma patients who had chronic hepatitis or liver cirrhosis (n = 44) and (B) metastatic liver cancer patients who had normal liver parenchyma (n = 24). The hepatic volume increased by 13.8% of the remnant hepatic volume in group A and by 49.1% in group B. The examined factors included the percentage of resected liver volume (%RLV) and the results of laboratory tests. Regression analysis showed that in group A, both %RLV (beta = 0.46) and the serum total bilirubin (T-Bil) level (beta = -0.33) correlated significantly with the extent of liver regeneration and that in group B, only %RLV (beta = 0.78) correlated significantly with the regeneration. Serum HGF levels after hepatectomy were studied in 21 hepatectomized patients, including 11 hepatoma patients and 10 patients with some types of metastatic liver cancer. Serum HGF levels increased significantly after surgery in all 21 patients. Regression analysis, however, showed that the change in HGF was related to liver cirrhosis (beta = 0.46) and to the maximal postoperative T-Bil level (beta = 0.51) but not to the extent of liver regeneration after hepatectomy. These results suggest that liver regeneration is regulated primarily by factors relating to the percentage of the resected liver parenchyma and that serum HGF levels do not directly relate to liver regeneration after surgery.

Combined effects of hepatic arterial embolization using degradable starch microspheres (DSM) in hyperthermia for liver cancer

Regional hyperthermia with a radiofrequency capacitive heating apparatus in combination with hepatic arterial embolization with degradable starch microspheres (DSM) was performed in 20 primary and six metastatic liver cancer patients. Efficacy was assessed primarily with regard to the improvement in heating efficiency. An angiocatheter was inserted into the hepatic artery in order to determine the DSM dosage adequate to arrest blood flow. The temperature rise in the tumours after heating alone and after heating combined with DSM embolization was compared. The maximum temperature and initial temperature rise within tumours were significantly improved by the combination therapy. Local tumour response could be evaluated in 10 primary and three metastatic liver cancer patients and tumour reduction over 50% was obtained in 40% and 33% respectively. Abdominal pain, nausea and vomiting, presumably due to reflux of the DSM, were experienced by several patients. In three patients heating could not be continued. However, all the symptoms were transient and responsive to symptomatic treatment, and no significant late complications were observed. Hepatic arterial embolization with DSM for liver tumours is considered effective and safe when combined with regional hyperthermia.

Effects of transcatheter arterial chemoembolization with oral chemotherapy on hepatic neoplasmas

An investigation was carried out into the effects of lipiodol-transcatheter arterial chemoembolization (L-TACE) therapy on hepatocellular carcinoma (HCC) and metastatic liver cancer, as well as the effects of oral 5-fluorouracil administration after L-TACE. For L-TACE, lipiodol mixed with adriamycin (doxorubicin) was injected through a catheter inserted into the tumor feeding artery and this was followed by embolization with a gelatin sponge. Twenty national hospitals throughout Japan participated in this multicenter co-operative open trial. A total of 102 patients became the subjects of study, including 75 HCC patients, 12 metastatic liver cancer patients treated with L-TACE, and 15 HCC patients who had hepatectomy after L-TACE. In 22% of the HCC patients and in 42% of the metastatic liver cancer patients, the tumor size was reduced by more than 50% after L-TACE. 73% of the 63 HCC patients showed a more than 50% reduction of the levels of serum alpha-fetoprotein. Although the survival rates of the HCC patients who had a hepatic resection were better than those who had not, there was no statistically significant difference between the survival rates of the HCC patients and those of the metastatic liver cancer patients treated with L-TACE. The survival rates of the HCC patients after L-TACE did not change as a result of oral 5-fluorouracil administration. It was therefore concluded that L-TACE is an effective way of treating both HCC patients and metastatic liver cancer patients, and that repeated L-TACE should be considered for some patients whose serum levels of alpha-fetoprotein rose again after L-TACE. Further follow-up studies will be needed to discover the effects of oral chemotherapy after L-TACE.

Intra-hepato-arterial infusions of cis-diamminedichloroplatinum (II) and 5-fluorouracil clinically effective for malignant liver tumors.

Four hepatocellular cancer patients and 11 metastatic liver cancer patients were treated with intra-hepato-arterial infusions of cis-diamminedichloroplatinum (II) plus 5-fluorouracil. Cis-diamminedichloroplatinum (II) (25-35 mg/m2) was given once a week, 5-fluorouracil (150-180 mg/m2) was infused daily. A partial response was obtained in 3 of 4 patients with primary cancer and in 5 of 9 evaluable metastatic cancer patients; the mean response durations were 27+ weeks in the former and 47+ weeks in the latter. However, severe bone marrow suppression occurred in 4 patients; 3 died of septicemia (2 cases) and massive intra-tracheal bleeding, respectively. This combined intra-hepato-arterial chemotherapy exerts a synergistic anticancer effect on malignant liver tumors, however, the related bone marrow suppression remains to be overcome.