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PubMed2005

Registry-based case-control studies of liver cancer and cancers of the biliary tract nested in a cohort of autoworkers exposed to metalworking fluids.

OBJECTIVE: Results are presented for a registry-based study of hepatobiliary cancer (liver and biliary tract) nested in a cohort of workers from three automobile manufacturing plants with potential exposure to metalworking fluids. METHODS: Altogether 63 cases of hepatobiliary cancer were identified from the cohort by the Michigan cancer registries. Each case was matched to 10 controls. Odds ratios (OR) were estimated in conditional logistic regression models for lifetime exposure to straight, soluble, and synthetic metalworking fluid and fluid components. RESULTS: Overall, hepatobiliary cancer was not associated with exposure to metalworking fluids. However, when the cases were stratified into liver cancer (N = 39) and biliary tract cancer (N = 24) the risk was nonhomogeneous across the two categories. While liver cancer was not associated with exposure to metalworking fluids, the results suggested a possible excess risk of biliary tract cancer with more than 1.0 mg/m3-years of exposure to straight metalworking fluids [OR 2.7, 95% confidence interval (95% CI) 0.9-7.6], as well as any exposure to chlorinated paraffins (OR 3.9, 95% CI 0.9-17). When exposures to straight metalworking fluids were separated into 10-year exposure periods, the odds ratio increased to 6.24 (95% CI 1.62-24.16) for exposures occurring > 20 years prior to the risk date. CONCLUSIONS: There is limited evidence that exposure to straight metalworking fluids is associated with biliary tract cancer. The small numbers of cases of these rare cancers were reflected in the wide confidence intervals, and these findings need to be examined further in other exposed populations.

Adult↗
PubMed1988

[Results of intra-arterial infusion chemotherapy in colorectal cancer patients with metastatic liver cancer].

Thirty-eight colorectal cancer patients (pts) with metastatic liver cancer who underwent intra-arterial infusion chemotherapy (IAIC) at the National Cancer Center Hospital from May 1986 to April 1988 were reviewed. Excisions of metastatic liver cancer were performed in 23 pts and 15 pts had nonresectable metastatic liver cancer. Catheter troubles including infections and obstructions occurred in 7 pts, and 4 pts (10.5%) were unable to receive IAIC. Fifteen resectable cases and 12 nonresectable cases were discussed. 5-Fluorouracil (5-FU) (700 mg/m2) and mitomycin C (MMC) (7 mg/m2) were infused through implantable pumps every week. Total infused doses of 5-FU and MMC were 0.5-12.2 g (mean, 5.3 +/- 3.8 g) and 4-144 mg (mean, 51.1 +/- 41.9 mg) in pts with 15 resectable cases, whereas 1.5-20.7 g (mean, 7.8 +/- 3.8 g) and 18-128 mg (mean, 49.7 +/- 29.2 mg) in 12 nonresectable cases. Four of 34 pts (11.8%) with IAIC had major complications; 2 obstructive jaundice, 1 gastric perforation, 1 toxic dermatitis. Four pts (26.7%) had recurrent liver cancer during 6-20 months follow-up after hepatic resection. Three of 12 nonresectable pts were responders (25.0%). Two completely and another partially responded. Another study is needed to clarify the effect of IAIC in survival. IAIC should be done not only for the treatment of nonresectable metastatic liver cancer, but also for resectable metastatic liver cancer in pts with colorectal advanced cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Occupational risk factors and liver cancer. A retrospective case-control study of primary liver cancer in New Jersey.

A retrospective case-control study was conducted to identify occupational risk factors associated with primary liver cancer in New Jersey, with particular focus on agricultural occupations and pesticide exposures. Hospital record room, tumor registry, and death certificate searches for the diagnosis of primary liver cancer resulted in identification of 959 cases of which 335 were subsequently confirmed. Interviews were completed for 265 persons with liver cancer diagnosed between January 1, 1975 and March 1, 1980 and for 530 matched controls; 96% of all interviews were conducted with family members of deceased or incompetent study subjects. Analyses of employment in agricultural occupations identified male farm laborers as having an odds ratio of 1.89 (95% confidence interval (CI) 1.19-3.00). An estimated relative risk of 3.20 (CI 1.11-9.21) was found for males engaged in winemaking. Among nonagricultural occupations, elevated risks were found for males working as bartenders and those employed in eating and drinking places, laundries and dry cleaning services, and gasoline service stations. An elevated risk of liver cancer was also associated with females employed as cleaning service workers. Hepatitis and cirrhosis could not be evaluated as risk factors in this study. Dose-response trends by level of alcohol consumption were found for both males and females.

Adult↗
PubMedDate not supplied

Kidney cancer, leukemia, and liver cancer. Part 3.

This is the third of a six-part series on metastatic spread and natural history of 18 common tumors. Part one summarized symptom/problem anticipation, cancer metastasis, and the 18 tumors that each cause more than 6,000 deaths per year in the United States. Bladder and brain cancers were discussed, with information given on tumor types, metastatic spread and invasion, and common symptoms. Part two charted the natural histories, problems, and assessment parameters of advanced breast, colon and rectum (colorectal), and esophageal cancers. Part three presents the natural histories, problems, and assessment parameters of advanced kidney cancer, leukemia, and liver cancer. Each of these cancers is presented separately, with information given on mortality rates, the most common tumor types, sites of metastases, common problems, and common oncologic emergencies. Sites of spread, resulting problems (including site-specific symptoms), and assessment parameters are presented as tables. Material is presented so that clinicians will be able to anticipate the spread of these cancers and can thus identify problems early in their development so that that they are more easily managed.

Humans↗
PubMed2003

Effect of spleen on immune function of rats with liver cancer complicated by liver cirrhosis.

OBJECTIVE: To establish a rat model of liver cancer complicated by liver cirrhosis and explore the effects of the spleen on immune function in this model. METHODS: Liver cirrhosis was inflicted in rats by percutaneous injection of 40% CCl4 on the back. Walker-256 tumor cells were inoculated in the cirrhotic liver and splenectomy was performed. Two weeks later, the growth and metastasis of tumor were observed and the amount of ascites and the activity of NK cells and CD25 cells were investigated. RESULTS: The amount of ascites and tumor volume were significantly higher in splenectomy group than in controls (P<0.01). Two weeks after inoculation, the activity of NK cells in both groups was decreased as compared with that before the inoculation (P<0.01). There was no significant difference between the two groups before and after the inoculation (P>0.05). The number of CD25 in both groups was higher than that before the inoculation (P<0.01). However, there was no significant difference between the two groups before and after the inoculation (P>0.05). CONCLUSIONS: Splenectomy in early stage of tumor inoculation can stimulate the tumor growth and metastasis. The activity of NK cells and the number of CD25 are inhibited by tumor itself, not by splenectomy.

Animals↗
PubMedDate not supplied

Elevation of serum type IV collagen in liver cancer as well as liver cirrhosis.

Studies on the level of serum type IV collagen (IV C) have usually been focused on the disease with diffuse hepatic fibrosis. To investigate whether serum level of IV C was predictive for the development of liver cancer as well as liver cirrhosis, serum IV C level was measured by a one-step sandwich enzyme immunoassay. The mean level of serum IV C was 73.3 +/- 31.3 ng/ml in 48 controls. The levels (ng/ml) of IV C were 396.4 +/- 254.9, 429.6 +/- 320.7, 420.6 +/- 322.8, and 362.9 +/- 247.4 respectively in 11 patients with chronic hepatitis, 11 with liver cirrhosis, 16 with hepatocellular carcinoma (HCC) with cirrhosis, 10 with HCC without cirrhosis, and 10 with metasatic liver cancer, which were significantly higher than that in controls (p < 0.05). Serum IV C levels were also evaluated using a cut-off value which was determined as the mean plus two standard deviations in the controls, 136 ng/ml. The elevations above the cut-off value were observed in 91, 100, 80, and 90% respectively of 11 patients with cirrhosis, 16 with HCC with cirrhosis, 10 with HCC without cirrhosis, and 10 with metastatic liver cancer, while only one (9%) of 11 chronic hepatitis patients and none (0%) of 48 controls had elevated levels. The levels of serum IV C were analysed with regard to age, sex, serum levels of albumin, globulin, transaminases, alpha-fetoprotein, and diameter of liver mass, a significant difference being observed only between the diameter of HCC and serum level of IV C (p < 0.01). These results indicate that the measurement of serum IV C is a useful for the determination of primary and metastatic liver cancer as well as liver cirrhosis.

Adult↗
PubMed1996

An immunohistochemical study of tumour vessels in metastatic liver cancers and the surrounding liver tissue.

To elucidate the phenotype of the blood vessels and the expression of the growth factors involved in angiogenesis in metastatic liver cancers, we carried out an immunohistochemical study of 57 surgically resected livers with metastatic cancer. Blood vessels in the metastatic liver cancers frequently expressed von Willebrand factor (vWF), Ulex europaeus agglutinin I (UEA I)-binding sites, alpha-smooth muscle actin (alpha-SMA), type IV collagen and laminin. Sinusoidal endothelial cells around the metastatic liver cancers were positive for vWF in 33.3% of the specimens examined and for UEA I in 28.1%. alpha-SMA-positive perisinusoidal cells accumulated in the vicinity of the metastatic liver cancers in 68.4% of the specimens. Type IV collagen was detected in the perisinusoidal space close to the metastatic cancers as well as distant from them (91.2%). Laminin was detected in the perisinusoidal space in only one specimen (1.8%). Tumour cells of the metastatic liver cancers were positive for vascular endothelial growth factor, basic fibroblast growth factor (bFGF), and acidic fibroblast growth factor (aFGF) in 78.9%, 38.4% and 7.0% of the specimens, respectively. Hepatocytes close to the metastatic liver cancers expressed bFGF more strongly than those distant from the metastatic liver cancers, and their expression of bFGF was more intense than that in the tumour cells. These results suggest that: (1) tumour vessels in metastatic liver cancers consist of endothelium, basement membrane and pericytes, (2) the sinusoids adjacent to tumours undergo capillarization, and (3) vascular endothelial growth factor may contribute to angiogenesis in metastatic liver cancer. Basic fibroblast growth factor may be responsible for the sinusoidal capillarization and the peritumoral fibrosis.

Fibroblast Growth Factors↗
PubMed1984

Age and cohort effects in primary liver cancer.

Primary liver cancer incidence data from 30 populations reported in Cancer Incidence in Five Continents were analyzed. After adjustment for time trends, log incidence increases linearly with log age. Liver cancer risk increases more rapidly with age than that of colon cancer, stomach cancer, or lung cancer in non-smokers; it increases less rapidly than that of prostatic cancer or of lung cancer in smokers. Over the past 20 years, most populations have been found to have increasing age-adjusted liver cancer incidence. There is no correlation between change in rates and magnitude of rates. Male rates are higher than female rates and the ratio of the two tends to be higher in high-risk areas.

Adenoma, Bile Duct↗
PubMed1989

[Results of intra-arterial infusion chemotherapy of colorectal cancer in patients with metastatic liver cancer].

Fifty-nine colorectal cancer patients with metastatic liver cancer who underwent intra-arterial infusion chemotherapy (IAIC) at the National Cancer Center Hospital from May 1986 to February 1989 were reviewed. Excisions of metastatic liver cancer were performed in 36 patients and 23 had nonresectable metastatic liver cancer. Catheter troubles, including severe infection (8), extravasations (3), obstruction (1) and other problems (1) occurred in 13 (22.0%) patients, and 6 patients (10.2%) were unable to receive IAIC. Three patients did not undergo IAIC because of hepatitis or other reasons. Serious complications following IAIC, including sclerosing cholangitis (6), extravasations (6) and obstructions (3) were observed in 15 patients (30.0%). Results of IAIC were discussed in 21 patients undergoing hepatic resection and 17 patients with nonresectable metastatic liver cancer. 5-Fluorouracil (5-FU) (700 mg/m2) and mitomycin C (MMC) (7 mg/m2) were infused through implantable pumps every week or every two weeks. Total infused doses of 5-FU ranged from 500 to 15,000 mg (mean: 8,300 +/- 3,400 mg) and those of MMC were from 26 to 144 mg (mean: 58.8 +/- 32.7 mg) in 21 patients undergoing hepatic resections, whereas 1,500-26,250 mg (mean: 11,000 +/- 7,800 mg) of 5-FU and 0-130 mg of MMC (mean: 57.3 +/- 33.3) were infused in 17 patients with nonresectable liver cancer. Seven patients (33.3%) had recurrent liver cancer during 7-31 months (mean: 16.2 +/- 6.0 m) follow-up after hepatic resections, whilst only 3 of 13 patients (23.1%) with solitary liver metastasis had recurrent liver cancer. Three of these recurrent liver cancer patients (37.5%) underwent hepatic re-excision. Seven of 17 nonresectable patients (41.2%) were responders. Three patients completely responded (CR) and 4 responded partially (PR). Another study is needed to clarify the effect of IAIC in survival. IAIC should be undertaken as a treatment not only for patients with nonresectable metastatic liver cancer, but also for those with resectable metastatic liver cancer in order to prevent hepatic recurrence.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Overweight and obesity increase the risk for liver cancer in patients with liver cirrhosis and long-term oral supplementation with branched-chain amino acid granules inhibits liver carcinogenesis in heavier patients with liver cirrhosis.

We conducted a multicenter, randomized, controlled trial to investigate the effect of long-term oral supplementation with branched-chain amino acids (BCAA) on the event-free survival in 622 patients with decompensated cirrhosis. In the present study, the development of liver cancer was analyzed as an endpoint in particular. Subjects received either treatment with BCAA at 12g/day or dietary therapy containing the matched daily energy and protein intake. A Cox regression analysis was carried out to estimate the hazard ratios for different background factors stratified by treatment group. Liver cancer was noted in 89 patients. The risk for liver cancer was significantly higher for males, patients with concurrent diabetes mellitus, patients with an alpha-fetoprotein (AFP) level of 20ng/mL or higher, patients with higher body mass index (BMI), and patients with lower serum albumin levels. When the BCAA group and the diet group were compared for factors that interacted with the treatment arms, the risk for liver cancer was significantly reduced in the BCAA group with a BMI of 25 or higher and with an AFP level of 20ng/mL or higher. Oral supplemental treatment with BCAA may reduce the risk of liver cancer in cirrhotic patients with these specific factors.

Journal Article↗
PubMed1989

[A high risk group of hepatocellular carcinoma in man, with special reference to its clinical significance for the screening of early liver cancer. Gifu Study Group for Early Liver Cancer].

A high risk group of hepatocellular carcinoma (HCC) was statistically established using multiple regression analysis of 331 cases with liver cirrhosis (LC), in which 78 cases later developed HCC. Highly contributing factors to hepatocarcinogenesis were found to be positive HBsAg, age, drinking history, sex (male), history of blood transfusion, history of acute hepatitis (or jaundice) and elevated plasma levels of alpha-fetoprotein. A prospective study was initiated in April, 1985 employing another 122 LC patients to clinically evaluate the significance of the high risk group of HCC. 28 cases with small HCC (less than 3 cm in diameter) were newly found: 4 with chronic hepatitis and 24 with LC, among whom 22 developed from the high risk group (sensitivity 92%, specificity 44%). Three year survival rate of 28 cases thus found was 56%, and causes of death of 9 fatal patients were 4 cancer death, 4 hepatic failure and 1 gastrointestinal bleeding. In conclusion, the high risk group is valuable for the screening of early liver cancers, and treatments of hepatic failure as well as of HCC itself are important to improve the prognosis of HCC patients thus diagnosed.

Carcinoma, Hepatocellular↗
PubMed2006

New intra-arterial drug delivery system for the treatment of liver cancer: preclinical assessment in a rabbit model of liver cancer.

BACKGROUND: In the fight against cancer, new drug delivery systems are attractive to improve drug targeting of tumors, maximize drug potency, and minimize systemic toxicity. We studied a new drug delivery system comprising microspheres, with unique properties allowing delivery of large amounts of drugs to tumors for a prolonged time, thereby decreasing plasma levels. Liver tumors, unlike nontumorous liver, draw most of their blood supply from the hepatic artery. Exploiting this property, we delivered drug-eluting microspheres/beads (DEB) loaded with doxorubicin, intra-arterially, in an animal model of liver cancer (Vx-2). PURPOSE: The purpose of our study was to determine the pharmacokinetics and tumor-killing efficacy of DEB. RESULTS: Our results show that plasma concentration of doxorubicin was minimal in the animals treated with DEB at all time points (0.009-0.05 micromol/L), suggesting high tumor retention of doxorubicin. This was significantly lower (70-85% decrease in plasma concentration) than control animals treated with doxorubicin intra-arterially. Within the tumor, doxorubicin concentration peaked at 3 days (413.5 nmol/g), remaining high to 7 days (116.7 nmol/g) before declining at 14 days (41.76 nmol/g), indicating continuous doxorubicin elution from beads. In control animals, peak tumor concentration of doxorubicin was 0.09 nmol/g. Tumor necrosis (approaching 100%) was greatest at 7 days, with minimal adverse local side effects reflected in liver function tests results. The plasma concentration of doxorubicinol (doxorubicin main metabolite) was minimal. CONCLUSIONS: Our results support the concept of DEBs as an effective way to deliver drugs to tumor. This new technology may prove to be a useful weapon against liver cancer.

Animals↗
PubMed1983

[Alteration of blood coagulation and fibrinolysis after intra-arterial one-shot chemotherapy in liver cancer].

Twenty liver cancer patients, including 9 hepatocellular carcinoma and 11 with metastatic liver cancer, were treated by intra-arteral one-shot chemotherapy. Alterations in blood coagulation and fibrinolysis were observed serially after one-shot chemotherapy by testing the levels of PT, APTT, FDP, fibrinogen, AT III, alpha 2-macroglobulin, and plasminogen. APTT was prolonged, FDP increased, Fbg increased after a transicent decrease, and AT III, alpha 2-M, and plasminogen decreased. The peaks of these alterations occurred within 7 days after the one-shot treatment; recovery was observed after about weeks. The more advanced the cancer, the greater were the alterations.

Antineoplastic Agents↗
PubMed1977

Mechanism of feminization in primary liver cancer.

Primary liver cancer occasionally presents with feminization. The mechanism is unknown. We studied a young man with primary liver cancer associated with feminization that disappeared after removal of the tumor. Before operation, the serum estrone level was markedly (1113 pg per milliliter) and estradiol and estriol levels were slightly elevated. Human placental lactogen was also increased (0.52 microng per milliliter). Luteinizing hormone, follicle-stimulating hormone and prolactin levels were normal, and testosterone reduced. Beta subunits of human chorionic gonadotropin were not detected in the serum. In vitro assay of tumor tissue showed estrogenic activity and high levels of these subunits. With a reversed isotope dilution technic with crystallization to constant specific activity, we showed the tumor tissue to convert dehydroepiandrosterone sulfate and dehydroepiandrosterone to estrone and estradiol. Production of beta subunits of chorionic gonadotropin and raised serum levels of placental lactogen provided further evidence that the tumor was functioning as trophoblastic tissue.

Adult↗
PubMed2002

Synergistic role of Ku80 and poly(ADP-ribose) polymerase in suppressing chromosomal aberrations and liver cancer formation.

Liver cancer is one of the major human tumors in the world. Basic and epidemiological studies have proposed that the major risk factors for liver cancer include alcohol and diet as well as infection with hepatitis B and C viruses. However, the mechanistic clues for the development of this type of cancer is largely unknown. Poly(ADP-ribose) polymerase (PARP-1) and a component of nonhomologous end-joining (NHEJ) machinery, Ku80, are two major DNA end-binding molecules that play a multifunctional role in DNA damage signaling and repair, recombination as well as the maintenance of genomic stability. Here we show that the interaction of PARP-1 and Ku80 is essential for development because PARP-1/Ku80 double null mice died at embryonic day (E) 9.5. Interestingly, haplo-insufficiency of Ku80 in PARP-1-/- mice promotes the development of hepatocellular adenoma and hepatocellular carcinoma (HCC). These tumors exhibited a multistage tumor progression associated with the loss of E-cadherin expression and the mutation of beta-catenin. Cytogenetic analysis revealed that Ku80 heterozygosity elevated chromosomal instability in PARP-1-/- cells and that these liver tumors harbored a high degree of chromosomal aberrations including fragmentations, end-to-end fusions, and recurrent nonreciprocal translocations (NRT). These features are reminiscent of human HCC. Taken together, these data implicate a synergistic function of Ku80 and PARP-1 in minimized chromosome aberrations and cancer development and suggest that defects in DNA end-processing molecules may be etiological factors in human HCC formation.

Animals↗