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PubMed2005

Therapeutic effect of Fe2O3 nanoparticles combined with magnetic fluid hyperthermia on cultured liver cancer cells and xenograft liver cancers.

The therapeutic effect of Fe2O3 nanoparticles combined with magnetic fluid hyperthermia (MFH) on human hepatocarcinoma SMMC-7721 cells in vitro and xenograft liver cancer in nude mice is studied. We examined growth and apoptosis of SMMC-7721 cells treated with MFH containing Fe2O3 nanoparticles at various concentrations (2, 4, 6, and 8 g/liter) for 30-60 min by using MTT, flow cytometry (FCM), and transmission electron microscopy (TEM). We also observed weight and volume inhibitory rates of the tumors of SMMC-7721-bearing nude mice by using animal experiments. The results showed that Fe2O3 nanoparticles combined with MFH could significantly inhibit the proliferation and increase the ratio of apoptosis of SMMC-7721 cells, and the effect was dose-dependent. The inhibitory rate was 26.5%, 33.53%, 54.4%, and 81.2%, respectively, and the apoptosis rate was 30.26%, 38.65%, 50.28%, and 69.33%, respectively. Animal experiments showed that tumors became small. The weight inhibitory ratio was 42.10%, 66.34%, 78.5%, and 91.46%, and the volume inhibitory ratio was 58.77%, 80.44%, 93.40%, and 98.30%, respectively. Compared with the control and experimental groups, each group had statistically significant difference (p < 0.05). So, Fe2O3 nanoparticles combined with MFH could inhibit the proliferation and induce apoptosis of SMMC-7721 cells and also has a significant inhibitory effect on the weight and volume of xenograft liver cancer. However, the mechanism remains to be further investigated.

Animals↗
PubMed1979

Radiocolloid imaging in primary liver cancer and amoebic liver abscess. Accuracy of differential diagnosis and extent of inter-observer variability.

Radiocolloid liver scans from 58 patients with primary liver cancer and 56 patients with amoebic liver abscess were examined 'blind' and independently by three nuclear physicians and one registrar in training in order to evaluate the accuracy of the differential diagnosis between the two conditions and to assess the extent of inter-observer variability in the interpretation of these scans. Each of the observers incorrectly interpreted about 12% of scintiphotographs and at least one observer was wrong in 25% of the scans. The difference in diagnostic accuracy between individual observers was not statistically significant. Observers disagreed in 21,6% of the scans. The main reasons for misdiagnosis were failure to realize that excessive extrahepatic uptake of radiocolloid can occur with liver abscesses, and the indistinguishable appearance of the defect or defects in some cases of primary liver cancer and amoebic liver abscess. This margin of error and of inter-observer variability must be borne in mind when interpreting liver scans of patients thought to have either primary liver cancer of amoebic liver abscess.

Colloids↗
PubMed2006

Outcome of 1000 liver cancer patients evaluated at the UPMC Liver Cancer Center.

We evaluated 1000 consecutive patients with liver tumors at the University of Pittsburgh Medical Center (UPMC) Liver Cancer Center over the 4-year period from August 2000 to August 2004. Of the 1000 patients seen, 573 had primary liver cancer and 427 had metastatic cancer to the liver. The mean age of the patients evaluated was 62.2 years, and 61% were male. Treatment consisted of a liver surgical procedure (resection or radiofrequency ablation) in 369 cases (36.9%), hepatic intra-arterial regional therapy (transarterial chemoembolization or (90)yttrium microspheres) in 524 cases (52.4%), systemic chemotherapy in 35 cases (3.5%), and palliative care in 72 patients (7.2%). For treated patients, median survival was 884 days for those undergoing resection/radiofrequency ablation, compared to 295 days with regional therapy. These data indicate that over 90% of patients with liver cancer evaluated at a tertiary referral center can be offered some form of therapy. Survival rates are superior with a liver resection or ablation procedure, which is likely consistent with selection bias. Hepatocellular carcinoma was the most common tumor seen due to referral pattern and screening of hepatitis patients at a major liver transplant center. The most common reason for offering palliative care was hepatic insufficiency usually associated with cirrhosis.

Age Factors↗
PubMed2005

Usefulness of granular BCAA after hepatectomy for liver cancer complicated with liver cirrhosis.

OBJECTIVE: Nutritional disturbances such as ascites and hypoalbuminemia frequently arise after hepatectomy for liver cancer with liver cirrhosis. We examined the possibility of maintaining a favorable state of nutrition by outpatient administration of branched-chain amino acid (BCAA) granules. METHODS: Forty-three patients who had gross liver cirrhosis complicated by liver cancer and underwent surgery up to May 2002 were given BCAA granules (n = 21, BCAA group) or no granules (n = 22, control group). RESULTS: 1) Background details such as age, sex, surgical technique, blood loss, and duration of surgery showed no significant differences. 2) Among objective findings, improvement of ascites and edema tended to occur sooner in the BCAA group, but without a significant difference. 3) Although serum albumin recovered its preoperative value 9 mo after surgery in the control group, only 6 mo was required for recovery in the BCAA group. Total protein showed similar changes, but neither group showed any difference in changes of aspartate aminotransferase, alanine transferase, or platelets. 4) One year postoperatively, the change from the preoperative indocyanine green retention rate at 15 min after intravenous administration tended to be worse in the control group, but not significantly so. 5) In the BCAA group, hyaluronic acid and type IV collagen 7S improved significantly sooner than in the control group. CONCLUSIONS: BCAA supplementation after hepatectomy promotes rapid improvement in protein metabolism and inhibits progression to liver cirrhosis. Administration of BCAA after hepatectomy is considered beneficial to a patient's nutritional state.

Aged↗
PubMed1990

The association of selected cancers with service in the US military in Vietnam. III. Hodgkin's disease, nasal cancer, nasopharyngeal cancer, and primary liver cancer. The Selected Cancers Cooperative Study Group.

As part of a series of investigations into the health of Vietnam veterans, we conducted case-control studies involving 310 men with Hodgkin's disease, 48 with nasal carcinoma, 80 with nasopharyngeal carcinoma, 130 with primary liver cancer, and 1776 controls between 1984 and 1988. All men born between 1929 and 1953 and diagnosed in an area covered by eight cancer registries were considered eligible as cases; controls were recruited by random-digit dialing. Whereas the study had excellent power (96%) to detect a twofold increase in risk for Hodgkin's disease among Vietnam veterans, its ability to detect a similarly elevated risk in the other cancers was limited, ranging from 38% (nasal carcinoma) to 75% (primary liver cancer). Analyses showed that risks among Vietnam veterans relative to other men were 1.1 (Hodgkin's disease), 0.7 (nasal carcinoma), 0.5 (nasopharyngeal carcinoma), and 1.2 (primary liver cancer). None of these relative risks was significantly different from 1.0. Similar results were obtained if Vietnam veterans were compared with (1) other veterans or (2) men who never served in the military. An examination of several attributes of military service in Vietnam (eg, branch, duration of service, and other characteristics that may have been associated with the use of Agent Orange) failed to identify any groups of veterans who were at increased risk for Hodgkin's disease. Small numbers limited further analyses of nasal, nasopharyngeal, and liver cancer. These results provide no evidence that, 15 to 25 years following service in Vietnam, the risk of these malignant neoplasms is higher among veterans.

Adult↗
PubMed2003

Smoking and liver cancer in China: case-control comparison of 36,000 liver cancer deaths vs. 17,000 cirrhosis deaths.

Liver cancer and liver cirrhosis are common causes of death in China, where chronic lifelong hepatitis B infection is a major cause of both diseases. To help determine whether smoking is a cofactor for the development of liver cancer, we ascertained retrospectively the smoking habits of 36,000 adults who had died from liver cancer (cases) and 17,000 who had died from cirrhosis (controls) in 24 Chinese cities and 74 rural counties. Calculations of the smoker vs. nonsmoker risk ratios (RR) for liver cancer mortality were standardised for age and locality. Among adult men (aged 35+) there was a 36% excess risk of death from liver cancer among smokers (smoker vs. nonsmoker standardised risk ratio [RR] =1.36, with 95% confidence interval [CI] 1.29-1.43, 2p<0.00001; attributable fraction 18%). In the general male population this indicates absolute risks of death from liver cancer before age 70 of about 4% in smokers and 3% in nonsmokers (in the absence of other causes). Most liver cancer, however, occurs among the 10-12% of men with haematological evidence of chronic hepatitis B infection, so among them the corresponding risks would be about 33% in smokers and 25% in nonsmokers. The RR was approximately independent of age, was similar in urban and rural areas, was not significantly related to the age when smoking started but was significantly (p<0.001) greater for cigarette smokers than for smokers of other forms of tobacco. Among men who smoked only cigarettes, the RR was significantly (p<0.001 for trend) related to daily consumption, with a greater hazard among those who smoked 20/day (RR 1.50, 95% CI 1.39-1.62) than among those who smoked fewer (mean 10/day: RR=1.32, 95% CI 1.23-1.41). Smoking was also associated with a significant excess of liver cancer death in women (RR 1.17, 95% CI 1.06-1.29, 2p=0.003; attributable fraction 3%), but fewer women (17%) than men (62%) were smokers, and their cigarette consumption per smoker was lower. Among women who smoked only cigarettes, there was a significantly greater hazard among those who smoked at least 20/day (mean 22/day: RR=1.45, 95% CI 1.18-1.79) than among those who smoked fewer (mean 8/day: RR=1.09, 95% CI 0.94-1.25). These associations indicate that tobacco is currently responsible for about 50,000 liver cancer deaths each year in China, chiefly among men with chronic HBV infection.

Adult↗
PubMed2001

Aberrant expression of fetal RNA-binding protein p62 in liver cancer and liver cirrhosis.

p62 is a RNA-binding protein that was isolated by immunoscreening a cDNA expression library with autoantibodies from patients with hepatocellular carcinoma (HCC). This autoantigen binds to mRNA encoding insulin-like growth factor II, which has been found to be overexpressed in HCC and is tumorigenic in transgenic animals. Immunohistochemical analysis of HCC liver showed that 33% (9 of 27) exhibited readily detectable staining of p62 protein in the cytoplasm of all malignant cells in cancer nodules, whereas it was undetectable in adjacent nonmalignant liver cells. In addition one of two patients with cholangiocarcinoma expressed p62 in malignant bile duct epithelial cells. p62 expression was also detected in scattered cells in cirrhotic nodules in contrast to uniform expression in all cells in HCC nodules. In HCC nodules, p62 mRNA was also detected by reverse transcriptase-polymerase chain reaction analysis. Nine normal adult livers did not contain detectable p62 mRNA or p62 protein whereas five fetal livers were all positive for mRNA and protein. The observations show that p62 is developmentally regulated, expressed in fetal, but not in adult liver, and aberrantly expressed in HCC and could be playing a role in abnormal cell proliferation in HCC and cirrhosis by modulating expression of growth factors such as insulin-like growth factor II.

Adult↗
PubMed1987

Primary liver cancer in Japan. Sixth report. The Liver Cancer Study Group of Japan.

The Liver Cancer Study Group of Japan statistically analyzed 4658 cases of primary liver cancer diagnosed from January 1, 1980 to December 31, 1981 in over 400 hospitals throughout the country. The study group comprised 2038 cases of hepatocellular carcinoma, 146 of cholangiocarcinoma, 33 of mixed carcinoma, 30 of hepatoblastoma, six of sarcoma, and 33 others. In 2286 cases (49.1%) a histologic diagnosis was available. The survey, based mostly on the histologically proven cases, describes histologic features of the tumors, grade of anaplasia and growth patterns of the tumor cells, pathology in noncancerous portions of the liver, distant metastases, medical history, frequency of hepatitis in the history, frequency of positive HBsAg and anti-HBs, age distribution, subjective symptoms, radiographic features (angiogram, scintiscan, computed tomography), ultrasonography, surgical procedures, extent of hepatic resection, and survival.

Adenoma, Bile Duct↗
PubMed2003

Lipiodol solution of 188Re-HDD as a new therapeutic agent for transhepatic arterial embolization in liver cancer: preclinical study in a rabbit liver cancer model.

UNLABELLED: It has been reported that lipiodol solution of (188)Re-labeled 2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol (TDD), an N(2)S(2) derivative, shows excellent targeting of liver cancer after transhepatic arterial embolization (TAE). However, its tumor retention is not high enough to treat liver cancer. Therefore, a new form of TDD, 4-hexadecyl-TDD (HDD), was developed to improve tumor retention by introducing a long alkyl chain. In this study, we compared the tumor retention properties of (188)Re-HDD/lipiodol and (188)Re-TDD/lipiodol, using a rabbit liver cancer model, and performed dosimetry using the results. METHODS: The VX2 cancer cell line was implanted into the livers of 7 rabbits. TAE was performed on 3 rabbits with (188)Re-TDD/lipiodol and on 4 rabbits with (188)Re-HDD/lipiodol, and conjugated anterior and posterior planar scans were obtained at 1, 2, 6, 24, and 48 h after TAE. From these images, tumor retention was calculated and compared between (188)Re-TDD and (188)Re-HDD. Afterward, the required dose of radioactivity and the radiation dosimetry for exposure of major organs were calculated using MIRDOSE3.1 software. RESULTS: The residence times of radioactivity in the liver were 10.2 +/- 1.0 h in the (188)Re-TDD group and 17.6 +/- 0.8 h in the (188)Re-HDD group (P = 0.034). The required radioactivity for 100 Gy of irradiation to 2.64- to 5.27-cm tumors was 142-1,070 MBq of (188)Re-HDD in the rabbit model. The radiation exposures for the major organs were within the tolerable range, and the S-value for the whole body (effective dose equivalent) was calculated to be 0.209 mSv/MBq. CONCLUSION: Introduction of a long alkyl chain significantly improved the tumor retention of (188)Re-HDD/lipiodol, compared with that of (188)Re-TDD/lipiodol. Moreover, the required radioactivity for humans and the radiation exposure were within the feasible range for clinical application.

Animals↗
PubMed2003

Expressions of Lewis antigens in human non-small cell pulmonary cancer and primary liver cancer with different pathological conditions.

The expressions of three X series Lewis antigens, including Lewis X (Le(x)), sialyl Lewis X (SLe(x)) and sialyl dimeric Lewis X (SDLe(x)) were studied with immuno-histochemical methods in human non-small cell pulmonary cancer (NSCPC) and primary liver cancer (PLC) with different pathological conditions. The Lewis antigens are mainly expressed on the cell surfaces, medially or slightly in the cytoplasm, but not in the cell nuclei of the cancer tissues. The regions adjacent to the cancer tissues do not express any Lewis antigens. The positive rates of these antigens in NSCPC were within the range of 75% to approximately 86%. There was no apparent difference in positive rates between the cases with different differentiation and the presence or absence of metastasis in peripheral lymph nodes, nor among the three antigens, except that the positive rate of SDLe(x) was lower (about 56%) in the cases with well/medium differentiation and without metastasis. However, the expression-intensities (SI indexes) of all three antigens were significantly higher in the samples of poor differentiation and with metastasis as compared to those with well/medium differentiation and without metastasis. The two sialyl Lewis antigens increased more significantly than non-sialylated Le(x). The expressions of these antigens were also observed in the peripheral lymph nodes with metastasis, but not in those without metastasis. The positive rates of Le(x), SLe(x) and SDLe(x) in human primary liver cancer were 83.3%, 88.9% and 77.8%, respectively. In the cases with cancer cell thrombosis (CCT) in portal vein (an index of metastasis), the expressions of all these three antigens were stronger than those in the cases without CCT. SLe(x) was the most abundant and most highly increased Lewis antigen on the surface of NSCPC and PLC, especially in the cases with poor differentiation and metastasis. In the study of the enzymatic basis of the increased Lewis antigens in PLC by using Northern blot, it was found that the level of alpha1,3 FucT-III/VI mRNA in PLC tissues was much higher than that in the adjacent regions, and more significantly higher in the cancer tissues from patients with CCT in portal vein. In contrast, the expression of alpha1,3 FucT-VII was rather low in cancer tissues and not different from the adjacent regions in spite of the presence or absence of CCT. These results reveal that the SLe(x) in PLC is mainly synthesized by alpha1,3 FucT-III/VI (especially VI) and is the most important Lewis antigen involved in the metastasis of PLC.

Carcinoma, Non-Small-Cell Lung↗