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PubMedDate not supplied

New trends in the surgical treatment of colorectal cancer liver metastases.

Colorectal cancer is one of the most common solid tumors affecting people around the world. A significant proportion of patients with colorectal cancer will develop or will present with liver metastases. In some of these patients, the liver is the only site of metastatic disease. Thus, surgical treatment approaches are an appropriate and important treatment option in patients with liver-only colorectal cancer metastases. Resection of colorectal cancer liver metastases can produce long-term survival in selected patients, but the efficacy of liver resection as a solitary treatment is limited by two factors. First, a minority of patients with liver metastases have resectable disease. Second, the majority of patients who undergo successful liver resection for colorectal cancer metastases develop recurrent disease in the liver, extrahepatic sites, or both. In this paper, in addition to the results of liver resection for colorectal cancer metastases, we will review the results of cryoablation, heat ablation, and hepatic arterial chemotherapy using a surgically implanted pump. Each of these surgical treatment modalities can produce long-term survival in a subset of patients with liver-only colorectal cancer metastases, whereas systemic chemotherapy used alone rarely results in long-term survival in these patients. While surgical treatments provide the best chance for long-term survival or, in some cases, the best palliation in patients with colorectal cancer liver metastases, it is clear that further improvements in patient outcome will require multimodality therapy regimens.

Antineoplastic Agents↗

PubMed1992

[Continuous intra-arterial infusion chemotherapy in colorectal cancer patients with nonresectable metastatic liver cancer].

Five colorectal cancer patients with nonresectable metastatic liver cancer underwent continuous intraarterial chemotherapy in our institute from January to December 1991. Patients included four rectal cancers and one colonic cancer. 5-fluorouracil (5-FU) was infused continuously through an Infuse-A-Port; 360 mg/m2/day for one week after operation, and 180 mg/m2/day for the following three weeks. Since the fifth week after operation, two weeks without infusion and two weeks of infusion (180 mg/m2/day) were alternated as long as possible. Total periods of 5-FU infusion therapy were from one to 11 months and total doses of 5-FU ranged from 8,750 mg to 25,650 mg. Three patients showed partial response (PR) and two patients progressive disease (PD) (response rate; 60%). In three cases of PR, lengths of infusion therapy and total doses of 5-FU before PR was first observed was 8 weeks, 10,750 mg, 6 weeks, 9,250 mg, and 4 weeks, 8,750 mg, respectively. Four patients presented nausea, appetite loss or abdominal pain, which were considered to be side effects of 5-FU. In one of these four patients, infusion could not be continued because symptoms were so severe. However, catheter troubles were not noticed among all cases.

Colonic Neoplasms↗

PubMed1992

The risk and predictive factors for developing liver cancer among patients with decompensated liver cirrhosis.

Patients with decompensated liver cirrhosis (n 1441) and those with post-transfusion hepatitis (n 343), whose medical expenses were subsidized by the Aichi Prefectural Government, were followed up for three years by record linkage with the Aichi Cancer Registry. During the follow-up period, 122 incident cases of liver cancer were identified. Compared with the general population, patients with decompensated liver cirrhosis were at a 64.9 times greater risk (50.5 times in males and 100.4 times in females) and those with post-transfusion hepatitis were at a 9.4 times greater risk (8.9 times in males and 13.7 times in females) of developing liver cancer. Information on prognostic factors for 1,068 patients with decompensated liver cirrhosis was also collected in a questionnaire survey by the physicians in charge. Patients positive to hepatitis B surface antigen (HBs Ag) and those positive to HBe Ag had a significantly increased risk of subsequent liver cancer. The risk of developing liver cancer was positively associated with base-line levels of GPT and AFP and age and, inversely associated with total alcohol intake and female sex. In multivariate analyses, the associations with HBe Ag, AFP, sex and age remained statistically significant, whereas the associations with GPT, total alcohol intake and HBs Ag were of borderline significance.

Age Factors↗

PubMed1996

[Early liver cancer].

There is no definition for early liver cancers. However, solitary liver cancers smaller than 2 cm in diameter are defined as small liver cancers and this term is often used as the meaning of early cancers. Small liver cancers are diagnosed by US, US-guided biopsies, computed tomography (CT), magnetic resonance imaging (MRI), and angiography. They are successfully treated by percutaneous ethanol injection (PEI), subsegmental transcatheter arterial embolization (TAE), operations and percutaneous microwave coagulation therapy (PMCT), 3-years survival rates being more than 70%. The choice of treatments depends on the techniques available in each institute and liver function, since most cases are complicated with liver cirrhosis.

Electrocoagulation↗

PubMed2000

Liver cancers in Mayak workers.

Liver cancer mortality risks were evaluated in 11,000 workers who started working at the "Mayak" Production Association in 1948-1958 and who were exposed to both internally deposited plutonium and external gamma radiation. Comparisons with Russian liver cancer incidence rates indicate excess risk, especially among those with detectable plutonium body burdens and among female workers in the plutonium plant. Comparisons within the Mayak worker cohort which evaluate the role of plutonium body burden with adjustment for cumulative external dose indicate excess risk among workers with burdens estimated to exceed 7.4 kBq (relative risk = 17; 95% CI = 8. 0-36) and among workers in the plutonium plant who did not have routine plutonium monitoring data based on urine measurements (relative risk = 2.8; 95% CI = 1.3-6.2). In addition, analyses treating the estimated plutonium body burden as a continuous variable indicate increasing risk with increasing burden (P < 0.001). Relative risks tended to be higher for females than for males, probably because of the lower baseline risk and the higher levels of plutonium measured in females. Because of limitations in current plutonium dosimetry, no attempt was made to quantify liver cancer risks from plutonium in terms of organ dose, and risk from external dose could not be reliably evaluated.

Body Burden↗

PubMed1994

Liver cancer.

The trends in liver cancer incidence and mortality were investigated by gender in Japan, Norway, Singapore, Spain, Sweden, the UK and the USA. Cancer Incidence in Five Continents, Vols I-VI, were the principal source of the analysis of age specific incidence rates by sex; additional incidence information was obtained from the published data of the Connecticut Tumor Registry and the Surveillance, Epidemiology and End Results Program in the USA. Mortality rates were calculated using the World Health Organization database. The trends observed were generally weak. Increasing occurrence of primary liver cancer was noted in Japan and the Nordic countries, although the rates seemed to be stabilizing or even decreasing in the most recent data from Sweden. By contrast, decreasing trends were apparent in Spain and Singapore. Changes in the rates appeared to be more evident or somewhat stronger for males than for females. Some biological explanations were offered to account for these trends. However, the dominant determinants of the apparent changes in the incidence and mortality of primary liver cancer were felt to be related to classification and coding revisions as well as to variations over time in diagnostic and certification practices.

Age Factors↗

PubMed2000

Liver resection for colorectal cancer: liver metastases in the aged.

The purpose of this study was to determine the morbidity and mortality in elderly patients undergoing liver resections for metastatic colon cancer and compare them with those of a control group of younger patients. The charts of all patients undergoing liver resection for colon cancer were retrospectively reviewed. Patients less than 70 years of age (Group A) were compared with patients 70 years of age or older (Group B). Between 1971 and 1995, 167 liver resections were performed for metastatic colorectal cancer. Of these, 41 patients were in Group A and 126 patients were in Group B. The mean age of Group A was 74.5 years, and that of Group B was 57 years. American Society of Anesthesiologists (ASA) classification was similar for both groups (Groups A and B were 75.6% and 81.1% ASA class II, respectively). Anatomic resections were performed in 49 per cent and wedge resections in 51 per cent of patients in Group A, and 68 and 32 per cent in Group B, respectively. Estimated blood loss was slightly less for Group A (1575 vs 1973 cm3), as was operative time (4.0 vs 4.7 hours). In-hospital mortality rate was 7.3 per cent for Group A and 2.4 per cent for Group B. The major morbidity rates were 29 and 17.5 per cent, respectively. Intensive care unit care was necessary in 73 per cent (mean length of stay 3.9 days) for Group A and 62.6 per cent (mean length of stay 2.0 days) for Group B. The average length of hospitalization was 13.1 days for Group A and 16.6 days for Group B. The recurrence rates were similar for the two groups [56% (Group A) vs 66% (Group B)], but mean survival was longer for younger patients (22.9 vs 33.5 months). We conclude that liver resection for colorectal cancer liver metastases in properly selected patients older than 70 years of age can be performed with acceptable morbidity and mortality rates. The long-term survival for older patients is less than that for younger patients, but is still a significant length of time. Therefore, we conclude that age alone is not a contraindication to liver resection for colorectal cancer metastases in patients older than 70.

Age Factors↗

PubMed2002

Influence of hepatic arterial blockage on blood perfusion and VEGF, MMP-1 expression of implanted liver cancer in rats.

AIM: To investigate the influence of hepatic arterial blockage on blood perfusion of transplanted cancer in rat liver and the expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase-1 (MMP-1), and to explore the mechanisms involved in transarterial embolization (TAE)-induced metastasis of liver cancer preliminarily. METHODS: Walker 256 carcinosarcoma was transplanted into rat liver to establish the liver cancer model. Hepatic arterial ligation (HAL) was used to block the hepatic arterial blood supply and simulate TAE. Blood perfusion of tumor in control, laparotomy control, and HAL group was analyzed by Hoechst 33342 labeling assay, the serum VEGF level was assayed by ELISA, the expression of VEGF and MMP-1 mRNA was detected by in situ hybridization. RESULTS: Two days after HAL, the number of Hoechst 33342 labeled cells which represent the blood perfusion of tumor directly and hypoxia of tumor indirectly in HAL group decreased significantly compared with that in control group (329+/-29 vs 384+/-19, P<0.01). The serum VEGF level in the HAL group increased significantly as against that of the control group (93 ng.L(-1)+/-44 ng.L(-1) vs 55 ng.L(-1)+/-19 ng.L(-1), P<0.05). The expression of VEGF and MMP-1 mRNA in the tumor tissue of the HAL group increased significantly compared with that of the control and the laparotomy control groups (P<0.05). The blood perfusion data of the tumor, represented by the number of Hoechst 33342 labeled cells, showed a good linear inverse correlation with the serum VEGF level (r=-0.606, P<0.05) and the expression of VEGF mRNA in the tumor tissue ( r =-0.338, P<0.01). CONCLUSION: Blockage of hepatic arterial blood supply results in decreased blood perfusion and increased expression of metastasis-associated genes VEGF and MMP-1 of transplanted liver cancer in rats. Decreased blood perfusion and hypoxia may be the major cause of up-regulated expression of VEGF.

Animals↗

PubMed1987

[Localization of oncoprotein P21ras in the human liver cancer].

Using the human liver cancer DNA transfected NIH/3T3 cell line, the human N-ras oncogene and the over expression of the oncoprotein P21ras was demonstrated, BALB/C mice were immunized. The spleen cells from the immunized mice were fused with SP2/0 myeloma cells. After the HAT medium selection and screening, two hybridoma cell lines, SCI-Oncogema 1 and 2, were established. In the immunoprecipitation test, the molecular weight of the protein reacting to Oncogema 1 was 21,000. This M.W 21,000 protein possessed the capability to bind with GTP, i.e. the character of P21ras. These data indicate that the Oncogema 1 is the monoclonal antibody against P21ras. Using Oncogema 1, specimens from 6 liver cancer patients were studied by immunopathology. With ABC stain, it was observed that the malignant cells in all the samples showed dark staining; the P21ras revealed over expression. Although the staining was heterogeneous, it implied that the ras oncogene was involved in the carcinogenesis of these six samples. No over expression was seen in the normal liver cells even in those around the cancerous lesion. However, dysplastic cells were moderately stained which means that the ras oncogene was activated and P21ras over expressed in these cells. The results suggest that the ras oncogene and P21ras play an important role in the early stage of liver cancer carcinogenesis.

Animals↗

PubMed2002

Sonographic differentiation of diffuse liver cancer from portal cirrhosis.

OBJECTIVE: To differentiate diffuse liver cancer from portal cirrhosis by using ultrasonography. METHODS: We analyzed the sonographic images of 15 patients with diffuse liver cancer and 30 patients with portal cirrhosis. RESULTS: The patients with diffuse liver cancer showed enlarged liver and obvious echo of nodules. The rate of portal embolism and swelling of lymph nodes around the porta hepatis was high. The patients with portal cirrhosis showed diminished liver and the obvious echo of fiber proliferation. The rates of spleen enlargement and ascites as well as gallbladder edema were high. CONCLUSIONS: To identify sonographic characteristics inside and outside of the liver. It is helpful in differentiating diffuse liver cancer from portal cirrhosis. The sonographic characteristics inside the liver include surface and size, node echo, echo of fibrous tissue hyperplasia. They are difficult to identify when diffuse liver cancer merges with considerable cirrhosis. The acoustic image characteristics of the two diseases overlap. Hence attention should be paid to the size of the liver, proliferation of cells of diffuse liver carcinoma. In sonographic characteristics outside the liver, embolism of the portal vein and swelling of lymph nodes in the porta hepatis are particularly useful to identify diffuse liver cancer or diffuse liver cancer combined with liver cirrhosis in particular.

Diagnosis, Differential↗

PubMed2006

Impact of age on screening and surveillance for primary liver cancer.

OBJECTIVES: Although screening and surveillance for liver cancers have become established practices, the impact of age on these practices is unknown. The age at which these could be stopped, if any, is unclear. Our aims were to assess the impact of age on developing or dying from liver cancer, and to define the relative impact of prematurely stopping screening. METHODS: Actuarial life-table analyses were performed using age-stratified mortality rates for primary liver cancers, and for all other causes combined, obtained from population-based databases from the United States. The impact of prematurely stopping screening at a given age was expressed as days of life lost compared to the maximal benefit expected from lifelong screening. RESULTS: Mortality from primary liver cancers increases with age and peaks at 37 per 100,000 persons at ages 85-90 yr. However, mortality from other causes increases even more with age. Consequently, the relative proportion of deaths from primary liver cancer is maximal at 1.34% of all deaths at age 50 yr, and gradually decreases thereafter. Eighty percent of the maximal potential benefit of lifetime screening from age 45 yr is achieved by age 77 yr, and 90% by age 82 yr. CONCLUSIONS: The relative benefits from screening for primary liver cancer are reduced in the elderly due to competing risks for death despite an increasing incidence of primary liver cancer with age. The majority of societal benefit is gained from screening at younger ages, when the relative proportions of death attributable to liver cancer are the greatest.

Age Factors↗

PubMed2005

[Pathological studies of tissue damage in experimental rabbit liver cancer induced by energy controllable steep pulses].

OBJECTIVE: To evaluate the efficacy of energy controllable steep pulses (ECSP) in the treatment of rabbit VX2 cancer implanted in livers. METHODS: A tumor model was successfully established using 30 rabbits. ECSP were applied to liver cancer in half of these rabbits and the rest were used as controls. After exposure to ECSP, tissues were obtained and subjected by routine HE and transmission electron microscopic (TEM) observation. The survival time of the animals and the statuses of each group were recorded. RESULTS: From pathological observations, ECSP showed effectively destructive action compared with that of the unexposed group. A clear borderline can be seen between necrotic cancer and its surrounding normal tissue. Irreversible cell changes were present under TEM. The survival periods of the experimental and control group were 83.1 days and 39.0 days respectively, and there was a significant difference between the two groups (Z = -2.943, P < 0.01). CONCLUSION: ECSP can effectively treat rabbit VX2 cancer implanted in the liver; also it is safe for its surrounding normal tissues. ECSP can be a useful method for local treatment of liver cancer.

Animals↗

PubMed1997

[TNM classification of liver cancer].

The current TNM classification of the liver was published in 1987 by UICC, which is the same as the staging system in the general Rules for the Clinical and Pathological Study of Primary Liver Cancer by the Liver Cancer Study Group of Japan (3rd Ed.) and was proposed by the Japanese TNM Committee. This was established based upon the data obtained before 1985. Thus, the current TNM classification does not always meet the latest knowledge of advanced hepatic oncology. The disease in which lesions are present both in the left and the right hepatic lobe is defined as Stage 4. Multiple liver cancers of multicentric carcinogenesis which are present in the two hepatic lobe and which are often detected recently, are stage 4 by the current TNM classification. But the postoperative prognosis of this kind of multiple liver cancer is found to be better than that of stage 4 of the advanced type, and equal to stage 3. Some proposals of reversed TNM classification of the liver, made with a small number of experienced cases have been published. However, not all of them would be convincing even with testing of a large number of cases.

Carcinoma, Hepatocellular↗

PubMed1987

[Evaluation of immunochemotherapy in patients with primary liver cancer. Osaka Research Society for Liver, Gallbladder and Pancreas].

The effectiveness of BRM (biological response modifier) for primary liver cancer was investigated in a prospective randomized and well controlled study. The protocol consisted of 3 groups: 1) Tegafur oral administration only, 2) OK-432 i.v. plus Tegafur, and 3) PSK oral application plus Tegafur. One hundred seventy-two Japanese patients were entered. The results revealed that BRM addition was more effective than Tegafur therapy alone with regard to tumor regression and the results of clinical examinations, but that there was no difference in subjective symptoms between the use of BRM and the other regimes. As to prognosis, patients given PSK survived longer than those given Tegafur alone, but OK-432 group had the same survival rate as the other two groups as a whole. The relationship among the three groups with regard to survival time, was similar to that of their respective total efficacies. Between the three groups, there was a significant difference in the incidence of adverse effects. The difference was sustained with the occurrence of fever symptoms as a result of OK-432 stimulation, with and BRM therapy decreased the gastro-intestinal side effects in comparison with the control group.

Adult↗

PubMedDate not supplied

Etiology of human liver cancer: controlled prospective study in liver cirrhosis.

The incidence of primary liver cell carcinoma was investigated in a prospective study over 6 yr and 5 mo in 403 clinically unselected patients derived from a homogeneous population by means of serial determination of alpha 1-fetoprotein (AFP) by radioimmunoassay. The diagnosis of liver cirrhosis was proved in 90% by laparoscopy and/or histology and/or autopsy. The incidence of primary liver cell carcinoma in liver cirrhosis in the clinically studied patients was 4.47%, significantly lower than in the autopsy material (11.03%; p less than or equal to 0.025). In the follow-up study, all patients with increasing AFP concentrations exhibited a primary liver cell carcinoma. A transitory rise of AFP (higher than 50 ng/ml) was observed in 15.1% of patients with liver cirrhosis without primary liver cell cancer. In contrast to the results of animal experiments, this transitory rise of AFP was not followed by malignant transformation of the cirrhotic tissue. Posthepatitic liver cirrhosis was observed in 21.57%, postalcoholic liver cirrhosis in 42.93%, and cryptogenic liver cirrhosis in 27.30%. Liver cirrhosis of other etiology occurred in 8.19%. The incidences of primary liver cell cancer in these 4 groups were 4.94, 4.62, 5.45, and 0%, respectively. These differences are not statistically significant, although in absolute figures postalcoholic liver cirrhosis is the main cause of primary liver cell carcinoma in this sample from West Germany. HBs antigen-positive liver cirrhosis was more often associated with primary liver cell cancer than HBs antigen-negative liver cirrhosis (6.58 versus 3.96%); this difference also is not statistically significant. Observations of larger groups of patients may show a higher risk of developing primary liver cell carcinoma in those with a combination of alcohol abuse and HBs antigenemia and/or acute hepatitis in the history. Patients without these 2 risk factors had an incidence of primary liver cell carcinoma of 2.61%; those with 1 risk factor, 5.77%; and those with both risk factors, 10.71%.

Carcinoma, Hepatocellular↗

PubMed2001

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.

Adult↗

PubMed1999

Alcohol consumption as a major risk factor for the rise in liver cancer mortality rates in Japanese men.

BACKGROUND: Age-adjusted liver cancer mortality rates have been increasing for both men and women in Japan since 1970; however, increases in mortality rates in men are much greater than those in women. Hepatitis C virus infections and heavy alcohol consumption are considered to be the major risk factors of liver cancer deaths in Japanese. The purpose of this study is (1) to examine the pattern of liver cancer mortality by gender and birth year to compare those with the pattern of other alcohol-related mortality and (2) to estimate the attributable risk per cent of heavy alcohol consumption for liver cancer deaths in Japanese men. METHODS: Age-specific liver cancer mortality rates by gender were compared with those of cirrhosis mortality rates. Then male-to-female mortality rate ratios were calculated by birth cohort and compared with cirrhosis mortality rate ratios and oesophageal cancer mortality rate ratios. The attributable risk per cent of alcohol consumption for liver cancer death was calculated, using female liver cancer mortality rates as standard rates. RESULTS: Examination of both gender and birth cohort mortality rates revealed that male-to-female liver cancer mortality rate ratios by birth cohort correspond well with those rate ratios for liver cirrhosis and oesophageal cancer mortality. The attributable risk per cent of alcohol consumption for liver cancer deaths in Japanese men was 70%. CONCLUSION: Alcohol consumption is more important than hepatitis C virus infections as a major cause of liver cancer deaths in Japanese men.

Adult↗

PubMed1988

[Immunohistochemical study on HBsAg, HBcAg and AFP in 104 patients with small liver cancer].

HBsAg, HBcAg and AFP in small liver cancer (less than or equal to 5 cm) and adjacent non-neoplastic liver tissue were assayed by peroxidase-antiperoxidase (PAP) method. The positive rates of HBsAg, HBcAg and AFP in liver cancer tissue were 13.8% (9/65), 9.2% (6/65) and 75.0% (42/56), while those in the uninvolved liver tissue were 93.3% (97/104), 46.2% (48/104), 66.1% (37/56), respectively. 3.6% (2/56) of cancer tissue and 33.9% (19/56) of unaffected liver tissue were found to have these three markers simultaneously. Pathologically all showed chronic hepatitis changes, and 66.3% (69/104) of them had cirrhosis. The development of liver cancer may be associated with HBV/DNA integration, but it does not rule out the possibility of HBV replication in the canceration. The phenotype patterns of HBAg possess variable clinical significance and HBV replication affects the long time survival of the patients with liver cancer. The results show that both cancer foci and their surrounding tissue could secrete AFP, and the AFP positive rate in liver cancer with negative sero-AFP is 30% (3/10). The sensitivity of assaying HBsAg in PAP method was 1.4 times as high as that of R-PHA or orcein stain. Small liver cancer is a valuable material to the study of human liver cancer.

Adolescent↗