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2.
Oncogene ; 25(14): 1991-2003, 2006 Mar 30.
Article in English | MEDLINE | ID: mdl-16301996

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide and is highly correlated with hepatitis virus infection. Our previous report shows that a DEAD box RNA helicase, DDX3, is targeted and regulated by hepatitis C virus (HCV) core protein, which implicates the involvement of DDX3 in HCV-related HCC development. In this study, the potential role of DDX3 in hepatocarcinogenesis is investigated by examining its expression in surgically excised human HCC specimens. Here we report the differential deregulation of DDX3 expression in hepatitis virus-associated HCC. A significant downregulation of DDX3 expression is found in HCCs from hepatitis B virus (HBV)-positive patients, but not from HCV-positive ones, compared to the corresponding nontumor tissues. The expression of DDX3 is differentially regulated by the gender and, moreover, there is a tendency that the downregulation of DDX3 expression in HCCs is more frequent in males than in females. Genetic knockdown of DDX3 with small interfering RNAs (siRNA) in a nontransformed mouse fibroblast cell line, NIH-3T3, results in a premature entry to S phase and an enhancement of cell growth. This enhanced cell cycle progression is linked to the upregulation of cyclin D1 and the downregulation of p21(WAF1) in the DDX3 knockdown cells. In addition, constitutive reduction of DDX3 expression increases the resistance of NIH-3T3 cells to serum depletion-induced apoptosis and enhances the ras-induced anchorage-independent growth, indicating the involvement of DDX3 in cell growth control. These findings together with the previous study suggest that the deregulation of DDX3, a DEAD box RNA helicase with cell growth-regulatory functions, is involved in HBV- and HCV-associated pathogenesis.


Subject(s)
Carcinoma, Hepatocellular/genetics , Cell Division/physiology , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Hepacivirus/pathogenicity , Liver Neoplasms/genetics , RNA Helicases/genetics , Animals , Base Sequence , Blotting, Western , Carcinoma, Hepatocellular/enzymology , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/virology , DEAD-box RNA Helicases , Humans , Liver Neoplasms/enzymology , Liver Neoplasms/pathology , Liver Neoplasms/virology , Mice , Molecular Sequence Data , NIH 3T3 Cells , RNA Helicases/physiology , RNA, Small Interfering/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Sequence Homology, Nucleic Acid
3.
Cancer Res ; 58(5): 985-90, 1998 Mar 01.
Article in English | MEDLINE | ID: mdl-9500460

ABSTRACT

Cyclin A is an S- and G2-M-phase regulatory protein, and its abnormal expression has been implicated in cellular transformation. This work was undertaken to investigate the frequency of cyclin A overexpression and the correlated clinical outcome in human hepatocellular carcinoma (HCC). Herein, 12 of 31 (39%) patients exhibited cyclin A overexpression in their tumorous tissues, resulting from gene amplification in 6 of 12 patients, (post)transcription in 4 of 12 patients, and (post)translation in 2 of 12 patients. Patients who overexpressed cyclin A had significantly more tumor cells in the S and G2-M phases compared with those expressing a normal cyclin A level (P = 0.007 and 0.039, respectively). Increased levels of Skp 2, a cyclin A-interacting protein, were also found in 17 of 31 (55%) of HCC patients who showed a trend to have more S-phase tumor cells (P = 0.07). By an unpaired Student's t test and a Fisher's exact or chi2 analysis, overexpression of cyclin A had a strong correlation with elevated Skp 2 expression and increased alpha-fetoprotein levels (P = 0.001 and 0.009, respectively), but it was not associated with patients' age, tumor size, cirrhosis, or the positive detection of hepatitis B virus surface antigen. In the disease-free survival analysis, patients whose tumors overexpressed cyclin A had a median disease-free survival of 6 months, whereas patients who lacked cyclin A overexpression exhibited a longer median period of 29 months (P = 0.046). The overall survival analysis revealed the same trend, i.e., cyclin A-overexpressing patients had shorter overall survival periods (median, 12 versus 50 months; P = 0.09). By multivariate analysis, the correlation of cyclin A overexpression with shorter disease-free periods remained significant after adjustment for Skp 2 overexpression and alpha-fetoprotein induction (P = 0.019). These data suggest that overexpression of cyclin A can be an independent prognostic factor for the tumor relapse of human HCC.


Subject(s)
Carcinoma, Hepatocellular/metabolism , Cell Cycle Proteins/biosynthesis , Cyclin A/biosynthesis , Liver Neoplasms/metabolism , Adult , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Cell Cycle/genetics , Cell Cycle Proteins/genetics , Cyclin A/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Middle Aged , Recurrence , S-Phase Kinase-Associated Proteins
4.
Cancer Gene Ther ; 8(1): 17-22, 2001 Jan.
Article in English | MEDLINE | ID: mdl-11219489

ABSTRACT

Interleukin-12 (IL-12) mediates significant antitumor effects in animal models but associated with dose-dependent toxicity in human. To achieve local expression of IL-12 at the tumor site without systemic toxicity, we performed intra-arterial administration of fibroblasts genetically engineered to produce IL-12 protein with or without retrovirus (CRIP- IL-12 or 3T3-IL-12) in liver metastasis model. Rat breast cancer cells ( MADB - 106) were injected into the portal vein of syngeneic Fisher rats on day 0, and fibroblasts were injected into the hepatic artery on day 7. On day 21, liver weight and number of liver tumors were examined. As controls, CRIP cells expressing retrovirus carrying lacZ marker gene (CRIP-lacZ) or saline (Hanks balanced salt solution, HBSS) were injected. Administration of CRIP-IL-12 significantly reduced tumor metastasis in liver measured by number of foci (CRIP- IL-12: 45.2 +/- 36.7, CRIP-lacZ: >250, HBSS: >250, P<.05) and by liver weight (CRIP-IL-12: 13.0+/-2.5 g, CRIP-lacZ: 30.4+/-8.5 g, HBSS: 26.0+/-7.6 g, P<.05). 3T3-IL-12, which produced only IL-12 protein but not IL-12 retrovirus, also had significant antitumor effects equivalent to CRIP-IL-12. Intra-arterial injection of IL-12--producing fibroblasts into the liver may be an effective therapy for liver tumors reducing systemic toxicity, and could be developed for clinical application.


Subject(s)
Fibroblasts/metabolism , Interleukin-12/metabolism , Liver Neoplasms/therapy , Liver/pathology , 3T3 Cells , Animals , Base Sequence , Cell Division/immunology , Cell Line , Female , Green Fluorescent Proteins , Immunotherapy , Injections, Intra-Arterial , Interleukin-12/genetics , Lac Operon/physiology , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Luminescent Proteins/metabolism , Mice , Molecular Sequence Data , Neoplasm Metastasis , Neoplasm Transplantation , Polymerase Chain Reaction , RNA, Messenger/metabolism , Rats , Rats, Inbred F344 , Retroviridae/genetics
5.
Surgery ; 127(6): 603-8, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10840353

ABSTRACT

BACKGROUND: Tumor venous invasion in patients with resectable hepatocellular carcinoma (HCC) is frequent and can be macroscopic and microscopic or microscopic alone. Although macroscopic invasion is a well-established prognostic indicator, the clinical significance of microscopic invasion remains unclear. METHODS: There were 322 patients enrolled who had undergone curative resection for HCC. The clinicopathologic factors and prognostic significance associated with macroscopic and microscopic venous invasion were analyzed. RESULTS: Macroscopic invasion was observed in 50 patients (15.5%) and microscopic invasion in 190 (59.0%). The larger the tumor, the more the incidence of venous invasion. There were 140 patients with microscopic invasion only (Group 1). Patients with macroscopic invasion (Group 2, n = 50) also had microscopic invasion. Compared with patients without venous invasion (Group 3, n = 132), Group 1 had a higher alpha-fetoprotein level, a larger tumor size, and more tumors without encapsulation. For group 1, the 1-, 3-, and 5-year disease-free survival rates were 65.6%, 41.6%, and 30.8%, respectively. The 1-, 3-, and 5-year overall survival rates were 87. 8%, 60.0%, and 52.7%, respectively. The survival rates of group 1 were lower than those of group 3 and higher than those of group 2 (P <.05). Multivariate analysis indicated that microscopic and macroscopic venous invasion, surgical margin, indocyanine-green retention, and tumor size and number were significant predictors of postresectional survival. CONCLUSIONS: In HCC patients, microscopic venous invasion is frequent and related independently to postresectional outcome.


Subject(s)
Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/secondary , Liver Neoplasms/pathology , Aged , Female , Hepatic Veins/pathology , Humans , Male , Middle Aged , Neoplasm Invasiveness , Portal Vein/pathology
6.
Arch Surg ; 131(4): 407-11, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8615727

ABSTRACT

OBJECTIVE: To evaluate the safety and feasibility of laparoscopic choledocholithotomy via choledochotomy for the treatment of choledocholithiasis. DESIGN: A prospective series of 1332 consecutive patients who underwent laparoscopic cholecystectomies, with a mean follow-up of 21.2 months. SETTING: University-affiliated referral center. PATIENTS: Forty-three patients (3%) with documented common bile duct stones from January 1991 to February 1995. INTERVENTIONS: Laparoscopic choledocholithotomy with choledochotomy and T tube drainage were performed in 40 patients. Postoperative endoscopic sphincterotomy after laparoscopic cholecystectomy was performed in three patients. MAIN OUTCOME MEASURES: Documented removal of common bile duct stones and procedure-related complications. RESULTS: Laparoscopic choledocholithotomy via choledochotomy was successful in 35 (88%) of 40 patients in whom this procedure was attempted. The mean (+/- SD) operation time was 191.3 +/- 75.4 minutes, and the mean (+/- SD) length of postoperative stay was 10.4 +/- 2.7 days. Seven complications (18%) were recorded, including three major complications (8%) and two retained stones (5%). CONCLUSIONS: Laparoscopic choledocholithotomy via choledochotomy can be performed safely, without increasing the morbidity rate as compared with that of open choledocholithotomy. Thus, some of the advantages of minimally invasive surgery are preserved.


Subject(s)
Common Bile Duct/surgery , Gallstones/surgery , Laparoscopy/methods , Aged , Female , Follow-Up Studies , Humans , Laparoscopy/adverse effects , Length of Stay , Male , Middle Aged , Postoperative Complications , Time Factors
7.
Arch Surg ; 130(10): 1090-7, 1995 Oct.
Article in English | MEDLINE | ID: mdl-7575122

ABSTRACT

OBJECTIVES: To evaluate the feasibility and results of segmentectomy for curative resection of hepatocellular carcinoma and to compare the clinicopathological findings of the patients according to the tumor location in the liver. DESIGN: Case series. SETTING: A tertiary care center. PATIENTS: Seventy-five patients with Child's grade A or B liver function who had hepatocellular carcinoma that was confined to one segment and who underwent segmentectomy for curative resection of the tumor. The patients were divided into four groups: group P (posterior segmentectomy, n = 23); group A (anterior segmentectomy, n = 10); group M (medial segmentectomy, n = 16); and group L (lateral segmentectomy, n = 26). MAIN OUTCOME MEASURE: Disease-free survival rate. RESULTS: Seventy-three percent of the patients had cirrhosis of the liver. The surgical mortality and morbidity rates were 5.3% and 36.0%, respectively. The 1-, 3-, and 5-year disease-free survival rates were 61.9%, 39.1%, and 26.3%, respectively, and were not significantly different among the four groups (P = .86). Group L had the least operative blood loss and shortest operative time when compared with the other three groups (P < .05). The postoperative liver function changes were mild and transient in the four groups of patients. With regard to pathological factors, only tumor size differed among the groups (tumors in group L were significantly larger than those in the other three groups, P < .05). Forty-three percent of the recurrent tumors were solitary in the early stage, with 81% involving the segment(s) adjacent to the resected one and 57% being confined solely to the segment adjacent to the resected segment. Patients having recurrent hepatocellular carcinomas had significantly larger tumors at the time of resection than did those without recurrence (P = .03). CONCLUSIONS: Hepatic segmentectomy is an effective therapeutic approach for small hepatocellular carcinomas and can be done safely even in patients with chronic liver disease and impaired liver function.


Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/physiopathology , Chi-Square Distribution , DNA, Neoplasm/analysis , Disease-Free Survival , Female , Follow-Up Studies , Hepatectomy , Humans , Liver Function Tests , Liver Neoplasms/mortality , Liver Neoplasms/physiopathology , Male , Middle Aged , Neoplasm Recurrence, Local/mortality , Ploidies , Reoperation
8.
J Am Coll Surg ; 190(5): 574-9, 2000 May.
Article in English | MEDLINE | ID: mdl-10801024

ABSTRACT

BACKGROUND: The benefits of liver resection for hepatocellular carcinoma (HCC) patients with concomitant impaired liver function were often considered questionable because of poor postoperative prognosis. This study will clarify whether an acceptable operative risk exists and whether limited resection will compromise the outcomes of these patients. STUDY DESIGN: Between July 1991 and December 1996, a total of 168 patients with HCC who underwent hepatectomies were enrolled and divided into normal (group A) and impaired (group B) liver function groups according to the value of indocyanine green retention rate at 15 minutes. Clinical features, surgical related features, pathologic features, and disease-free and overall survivals were compared between the groups. RESULTS: Operative morbidity and mortality in group A were 27.3% and 1.6%, and in group B were 40.0% and 2.5%, respectively (p = 0.129 and 0.506). Disease-free survival and overall survival at 5 years in group A were 43.2% and 59.6%, respectively, and in group B they were 30.6% and 56.8%, respectively (p = 0.607 and 0.378). CONCLUSIONS: Limited liver resection is safe and provides favorable prognosis in HCC patients with concomitant impaired liver function.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Neoplasms/surgery , Liver/physiopathology , Safety , Adult , Aged , Carcinoma, Hepatocellular/diagnosis , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/physiopathology , Disease-Free Survival , Female , Hepatectomy/statistics & numerical data , Humans , Intraoperative Care , Liver Neoplasms/diagnosis , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Liver Neoplasms/physiopathology , Male , Middle Aged , Neoplasm Staging , Postoperative Complications/epidemiology , Prognosis , Treatment Outcome
9.
J Gastroenterol ; 33(4): 512-6, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9719234

ABSTRACT

The association of viremia, elevated serum alanine aminotransferase (ALT) levels, and hepatocyte inflammatory activity in hepatocellular carcinoma (HCC) patients was studied. Serum samples from 114 HCC patients undergoing surgery were assayed for hepatitis B, C, and D viral nucleic acids by polymerase chain reaction (PCR) prior to surgery. Of these patients, 65 had HBV infection alone, 15 had HCV infection alone, 4 had HDV infection, 20 had HBV and HCV superinfection, 1 had triple viral infection, and 9 were negative for HBV and HCV infections. The prevalence of active viral replication was significantly higher in HCV than in HBV (92% versus 70%; P = 0.006) patients, and significantly higher mean serum ALT levels were also noted in the HCV group than in the HBV group (P = 0.02). The incidence of marked ALT elevation (>200 U/l) was highest in the HCV (27%) and the HDV (25%) groups. Patients in the HCV group were 10 years older than those in the HBV group. Viral superinfection did not accelerate the development of HCC. Viral replication persisted in a significant portion of HCC patients and a higher prevalence of hepatic inflammation was noted in patients with HCV- and, possibly, HDV-related HCC.


Subject(s)
Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/virology , DNA, Viral/blood , Hepatitis Viruses/isolation & purification , Liver Neoplasms/virology , RNA, Viral/blood , Adult , Aged , Aged, 80 and over , Female , Hepacivirus/isolation & purification , Hepatitis B virus/isolation & purification , Hepatitis Delta Virus/isolation & purification , Hepatitis Viruses/genetics , Humans , Liver Neoplasms/blood , Male , Middle Aged , Polymerase Chain Reaction/methods , Prevalence , Taiwan , Transcription, Genetic
10.
Eur J Surg Oncol ; 30(4): 414-20, 2004 May.
Article in English | MEDLINE | ID: mdl-15063895

ABSTRACT

AIM: The prognosis of patients with recurrent hepatocellular carcinoma (HCC) after hepatic resection varies widely. This study analyzed long-term survival and prognostic factors of patients with recurrent HCC after hepatectomy. METHODS: From July 1991 to December 2000, 623 patients underwent hepatic resection for HCC. Of those, 347 (56.5%) patients had tumour recurrence, and 286 patients with follow-up time more than 24 months after recurrence were enrolled. Twenty-seven clinicopathologic factors underwent both univariate and multivariate analysis. RESULTS: Of these 286 patients, survival times after tumour recurrence were mean 672+/-619 days; median 468 days; and, range 10-3753 days. The overall 1-, 3-, 5-, and 10-year post-recurrence survival rates were 61.5, 33.4, 18.2, and 9.0%, respectively. Seventy (24.5%) patients were alive at the time of study, and 10 of the 34 patients who underwent re-resection were disease-free. By Cox regression analysis, multiple initial tumours (relative risk (RR) 1.428), recurrent multiple (RR 1.372), extrahepatic recurrence (RR 2.434), recurrent tumour size >2 cm (RR 1.926), post-hepatectomy period until recurrence <1 year (RR 1.769), and non-resectional treatment of recurrent tumours (RR 3.527) were independent prognostic factors for post-recurrent survival rates. CONCLUSIONS: In patients with recurrent HCC after hepatectomy, both initial and recurrent tumour factors influenced their prognosis. Early detection of recurrent tumours is important. Re-resection correlated with better post-recurrent survival rates.


Subject(s)
Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Neoplasm Recurrence, Local/mortality , Aged , Aneuploidy , Carcinoma, Hepatocellular/mortality , Disease-Free Survival , Follow-Up Studies , Hepatectomy , Humans , Liver Neoplasms/mortality , Middle Aged , Prognosis , Survival Analysis , Treatment Outcome
11.
Eur J Surg Oncol ; 22(5): 516-20, 1996 Oct.
Article in English | MEDLINE | ID: mdl-8903496

ABSTRACT

Primary hepatocellular carcinoma (HCC) extending to the adjacent organ(s) is sometimes encountered in patients with large, peripherally located tumours. Over a 4-year period, a total of 151 patients received curative resection of HCC at the Surgical Department of Veterans General Hospital-Taipei, Taiwan. Of these patients, 21 underwent hepatic resection combined with en-bloc resection of the adjacent organ(s) because tumour extension was found during operation. Subsequent histological examination of the resected specimens found evidence of HCC invasion into the resected adjacent organ(s) in only nine patients (group I), and the remaining 12 patients showed no evidence of extrahepatic HCC invasion (group II). Twenty-seven HCC patients with clinico-pathologically matched tumours but without extrahepatic extension were selected as controls (group III). One patient in group I died of hepatic failure after the operation. The morbidity rate was 48% in group I and group II patients, and 30% in group III patients. The difference was not statistically significant. On evaluating the clinico-pathological factors, including DNA ploidy status of the tumours, there were no significant differences between tumours with and without extrahepatic invasion. Patients with locally invasive HCC (group I) had disease-free and overall survival rates comparable with those of the patients without local tumour invasion (group II and III). We conclude that HCC with invasion to the adjacent organ(s) does not seem to be directly related to the 'aggressiveness' of the tumour, and extrahepatic infiltration of the tumour does not preclude a chance of cure. Our results underscore the need for en-bloc resection as treatment of choice for these patients.


Subject(s)
Carcinoma, Hepatocellular/secondary , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/pathology , Disease-Free Survival , Feasibility Studies , Female , Humans , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Invasiveness , Ploidies
12.
Int J Mol Med ; 5(5): 521-4, 2000 May.
Article in English | MEDLINE | ID: mdl-10762656

ABSTRACT

The role of somatic deletions in chromosome 9 and chromosome 22 loci in hepatocellular carcinomas (HCC) was studied. Twenty-one paired HCC and adjacent tumor-free liver tissue samples were examined for loss of heterozygosity at six chromosome 9 and ten chromosome 22 loci. Among informative cases, the highest LOH rates were observed at 9p21 (40% or 4/10 at IFNA) and 9q23 (23% or 3/13 at D9S318). Our observed LOH rate at 9p21 was significantly higher than the background level previously reported for the same tumor type. Clinical data indicate that chromosome 9p21 deletions occurred preferentially in larger tumors (>5 cm diameter). However, a sequence analysis of the MTS1 gene coding region in cases of 9p21 LOH did not reveal any change, suggesting another tumor suppressor gene as the LOH target.


Subject(s)
Carcinoma, Hepatocellular/genetics , Chromosome Deletion , Chromosomes, Human, Pair 9 , Liver Neoplasms/genetics , Aged , Carcinoma, Hepatocellular/pathology , Chromosomes, Human, Pair 22 , Female , Humans , Liver Neoplasms/pathology , Loss of Heterozygosity , Male , Microsatellite Repeats , Middle Aged
13.
Eur J Gastroenterol Hepatol ; 11(3): 315-21, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10333206

ABSTRACT

OBJECTIVE AND DESIGN: Both surgical resection and transcatheter arterial chemoembolization (TACE) are effective treatments for hepatocellular carcinoma (HCC). Few reports have compared the different treatment modalities for resectable HCC based on clinically matched groups. The aim of this study was to compare the survival rate after surgery, TACE or supportive treatment in resectable HCC patients, and also in elderly patients (> or = 70 y/o). METHODS: From 1984 to 1993, 419 consecutive patients with resectable HCC were included in this study. Of these, 311 (74%) underwent resection of tumours and 46 (11%) refused operation, opting instead for TACE. The remaining 62 (15%) who refused both methods of treatment were given supportive care. Univariate and multivariate analyses for prognostic factors and the 5-year survival rate among the groups were studied. RESULTS: Both surgical resection and TACE groups had a better 5-year survival rate than the supportive treatment group (43% and 34% vs. 7%). There was no difference in survival between the surgery and TACE groups. However, the 5-year survival rate was 11% in TACE and 41% in the surgical group when the patients were > or = 70. In multivariate analysis, female sex (P = 0.0466), tumour size < or = 3 cm (P = 0.0001), alpha-fetoprotein (AFP) < 400 U/l (P = 0.0036), single tumour (P = 0.0474), serum creatinine < or = 1.5 mg/dl (P = 0.0006) and alkaline phosphatase (AP) < or = 100 U/l (P = 0.0007) are associated with good prognosis for resectable HCC. CONCLUSION: TACE is an alternative for resectable HCC. Tumour size, tumour number, AFP level, renal function, AP level and female sex are prognostic factors. In elderly people, TACE must be used prudently and has a worse prognosis.


Subject(s)
Carcinoma, Hepatocellular/surgery , Chemoembolization, Therapeutic/methods , Liver Neoplasms/surgery , Age Factors , Aged , Alkaline Phosphatase/blood , Analysis of Variance , Carcinoma, Hepatocellular/blood , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/therapy , Case-Control Studies , Catheterization, Peripheral , Creatinine/blood , Female , Humans , Liver Neoplasms/blood , Liver Neoplasms/pathology , Liver Neoplasms/therapy , Male , Middle Aged , Multivariate Analysis , Prognosis , Sex Factors , Survival Analysis , Survival Rate , Treatment Outcome , Treatment Refusal , alpha-Fetoproteins/analysis
14.
Med Hypotheses ; 55(4): 348-50, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11000065

ABSTRACT

Hepatocellular carcinoma is one of the most common cancers in the world. The male to female ratio is 3-6 to 1 in patients with hepatocellular carcinoma. Although steroid hormones and receptors have been examined extensively for their role in the growth regulation of hepatocellular carcinoma, the direct stimulation of hepatocellular carcinoma by steroid hormones still awaits elucidation. On the other hand, clinical trials using antagonists for steroid hormones to treat hepatocellular carcinoma were found to be mostly ineffective. Recently it has been found that 2-methoxyestradiol - an estrogen metabolite - is effective in growth inhibition of various tumor cells as well as in angiogenesis inhibition. Since estrogen is metabolized in the liver, it is conceivable that females with menstruation cycles have more estrogen metabolized in their liver, consequently more 2-methoxyestradiol produced which could inhibit tumor growth in situ. We propose that the low incidence and mortality of hepatocellular carcinoma found in females may have resulted from the high levels of 2-methoxyestradiol produced in the liver during their reproductive years. Consequently, the growth of hepatocellular carcinoma in females is delayed significantly as compared to males. The potential of using 2-methoxyestradiol for treatment of patients with hepatocellular carcinoma after resection of tumor should be explored.


Subject(s)
Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/therapy , Liver Neoplasms/etiology , Liver Neoplasms/therapy , 2-Methoxyestradiol , Androgens/metabolism , Carcinoma, Hepatocellular/epidemiology , Combined Modality Therapy , Estradiol/analogs & derivatives , Estradiol/metabolism , Estradiol/therapeutic use , Female , Humans , Liver/metabolism , Liver Neoplasms/epidemiology , Male , Models, Biological , Sex Factors
15.
Hepatogastroenterology ; 46(26): 640-5, 1999.
Article in English | MEDLINE | ID: mdl-10370589

ABSTRACT

BACKGROUND/AIMS: Both cirrhosis and old age have been reported to be risk factors for hepatic resection. This study evaluated the clinical results of hepatic resection in elderly hepatocellular carcinoma (HCC) patients with cirrhosis. METHODOLOGY: During a 5-year period, 248 patients with HCC underwent curative hepatic resection. Among them, 24 elderly patients (age: > or = 70 years) with cirrhosis (Group I), 24 patients (age: > or = 70 years) without cirrhosis (Group II), and 98 patients (age: < 70 years) with cirrhosis (Group III) were selected for the study. The clinical and pathologic parameters, including pre-operative demographic features, surgical factors, pathological factors, DNA flow-cytometric analysis of the resected specimen, and post-resection prognosis were compared among the three groups. RESULTS: Group I patients had a significantly higher incidence of small-size tumors, hepatitis C infection, concomitant esophageal varices, and minor resection with a shorter surgical margin in the resected specimen. The surgical morbidity and mortality of Group I was similar to that of Group II and III patients. However, the disease-free survival rate was significantly lower in the Group I patients than in Group II (p = 0.02) and Group III patients (p = 0.04). CONCLUSIONS: Our findings indicate that although hepatic resection can be done safely in elderly cirrhotic HCC patients, the prognosis for these patients was less favorable even when curative resection was performed.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Neoplasms/surgery , Adult , Aged , Aged, 80 and over , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Contraindications , Disease-Free Survival , Female , Follow-Up Studies , Hepatitis C, Chronic/mortality , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/surgery , Humans , Liver/pathology , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Prognosis , Risk
16.
Hepatogastroenterology ; 47(32): 446-9, 2000.
Article in English | MEDLINE | ID: mdl-10791210

ABSTRACT

BACKGROUND/AIMS: Hepatocellular carcinoma is notably more prevalent in male. The purpose of this study was to assess the surgical results in male and female cirrhotic patients. METHODOLOGY: The surgical outcomes of 129 hepatocellular carcinoma patients with cirrhosis, including 109 males and 20 females, who had undergone hepatic resection were studied. The clinical, histologic features, DNA ploidy and proliferative phase fraction of tumor and cirrhotic liver were compared between male and female patients. RESULTS: Female patients had significantly lower incidences of history of smoking (5.6% vs. 52.9%, P < 0.001), alcohol intake (5.6% vs. 42.3%, P = 0.003) and hepatitis B surface antigen positivity (47.1% vs. 73.5%, P = 0.028) than male. Cell-cycle analysis of tumor part revealed female had a significant lower G2M phase fraction (3.4%) than male (5.7%) (P = 0.027). The 1-, 3-, and 5-year disease-free survival rates in male and female patients were 65.5% and 88.2%, 36% and 64.4%, and 29.7% and 64.4%, respectively. Female patients had a significantly better disease-free survival than male (P = 0.034, log-rank test). CONCLUSIONS: Female hepatocellular carcinoma with cirrhosis had lower incidences of hepatitis B surface antigenemia, alcohol abuse and lower DNA postsynthetic phase fraction in tumor tissue than male. Consequently, female hepatocellular carcinoma with cirrhosis had better survival than male.


Subject(s)
Carcinoma, Hepatocellular/surgery , Hepatectomy , Liver Neoplasms/surgery , Postoperative Complications/mortality , Aged , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/mortality , Female , Humans , Liver Neoplasms/etiology , Liver Neoplasms/mortality , Male , Middle Aged , Risk Factors , Sex Factors , Survival Rate
17.
Adv Ther ; 15(5): 271-6, 1998.
Article in English | MEDLINE | ID: mdl-10345148

ABSTRACT

In geriatric patients with exudative ascites, malignant ascites is a common etiology. Tuberculous peritonitis is rarely seen and usually overlooked. We describe a 67-year-old man who suffered from exudative ascites for 1 month before admission. None of the noninvasive diagnostic methods utilized enabled us to make a correct diagnosis. Peritoneoscopic examination demonstrated multiple whitish miliary nodules and some larger nodules in the parietal and visceral peritoneum. Excisional biopsy confirmed the diagnosis of tuberculous peritonitis. This case reminds us that although malignant ascites is more prevalent in geriatric patients with exudative ascites, peritoneoscopy is indicated when noninvasive diagnostic methods allow no definite diagnosis.


Subject(s)
Ascites/diagnosis , Laparoscopy , Peritonitis, Tuberculous/diagnosis , Aged , Ascites/etiology , Biopsy , Diagnosis, Differential , Humans , Male , Mycobacterium tuberculosis/isolation & purification , Peritoneum/microbiology , Peritoneum/pathology , Peritonitis, Tuberculous/complications , Peritonitis, Tuberculous/drug therapy
18.
J Formos Med Assoc ; 100(7): 443-8, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11579608

ABSTRACT

BACKGROUND AND PURPOSE: Hepatitis B and C viral infections are important factors in the development of hepatocellular carcinoma (HCC). This study examined the clinicopathologic and prognostic differences in patients with hepatitis B- and C-related resectable HCC. METHODS: A total of 270 HCC patients who underwent hepatic resection were enrolled. Among these patients, 211 were positive for hepatitis B surface antigen (HBsAg) and 59 were positive for anti-hepatitis C virus antibody (anti-HCV). The clinical manifestations, pathologic features, and treatment outcomes were compared between the HBsAg-positive and anti-HCV-positive groups. RESULTS: Compared to anti-HCV-positive patients, HBsAg-positive patients were significantly younger, had a higher familial incidence of HCC, larger tumor size, and a higher incidence of multiple tumors. HCC patients who were anti-HCV positive had worse liver function and a higher incidence of history of blood transfusion. DNA flow cytometric analysis revealed significantly more proliferative activity in the non-tumor part of the liver in HBsAg-positive HCC patients. The 1-, 3-, and 5-year overall survival rates of HBsAg-positive patients were 79%, 57%, and 48%, respectively, and for anti-HCV-positive patients were 91%, 75%, and 62%, respectively. HBsAg-positive patients had a significantly lower overall survival rate than anti-HCV-positive patients (p = 0.018). CONCLUSIONS: HBsAg-positive patients with resectable HCC had a less favorable survival rate after tumor resection than anti-HCV-positive HCC patients. This survival difference might have been related to the relatively advanced stage of disease and the higher proliferative activity of the non-tumor part of the liver in HBsAg-positive HCC patients.


Subject(s)
Carcinoma, Hepatocellular/virology , Hepatitis B Surface Antigens/blood , Hepatitis C Antibodies/blood , Liver Neoplasms/virology , Adult , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Female , Hepatectomy , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Prognosis , Survival Rate
19.
J Formos Med Assoc ; 98(4): 248-53, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10389368

ABSTRACT

The current TNM (tumor, nodes, metastases) staging system for human hepatocellular carcinoma (HCC) has been challenged since a new T staging system was proposed to correlate the staging group with patient outcome after curative liver resection. The new T staging system proposed T1 as no vascular invasion, small size (< or = 5 cm), and solitary tumor. T2 was defined as the presence of one of the following factors: size greater than 5 cm, vascular invasion, or multiple tumors; T3 as the presence of two of the above three factors; and T4, the presence of all three factors. A total of 323 patients undergoing curative partial hepatectomy for HCC were studied. Kaplan-Meier survival analysis was used to evaluate the postoperative outcome. The new T staging showed good correlation between the staging group and patient outcome. The 1-year disease-free survival (DFS) rate and overall survival (OS) rate were 80.0% and 87.8% for stage 1 (n = 115), 67.6% and 81.6% for stage 2 (n = 136), 40.0% and 58.0% for stage 3 (n = 58), and 21.4% and 42.8% for stage 4 (n = 14), respectively. The 3-year DFS rate and OS rate were 61.0% and 64.5% for stage 1, 37.8% and 50.7% for stage 2, 21.4% and 29.8% for stage 3, and 21.4% and 34.3% for stage 4, respectively. When analyzed using the current International Union Against Cancer (UICC) pathologic (p) TNM staging system, the 1-year and 3-year DFS rates were 86.2% and 64.0% for stage 1 (n = 30), 73.9% and 50.0% for stage 2 (n = 182), and 46.8% and 22.3% for stage 3 (n = 111), respectively. Our results showed that, while both staging systems allow clear stratification of patients into prognostic groups, the modified TNM system is not superior to the UICCpTNM system in predicting survival of HCC patients after curative partial hepatectomy. A larger scale, multicenter study may be needed to test the revised TNM system.


Subject(s)
Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Neoplasm Staging/methods , Carcinoma, Hepatocellular/mortality , Evaluation Studies as Topic , Humans , Liver Neoplasms/mortality , Prognosis , Survival Rate
20.
Int Surg ; 78(3): 243-6, 1993.
Article in English | MEDLINE | ID: mdl-8161371

ABSTRACT

Retroperitoneal lymphangioma is an unusual disease, more customarily reported in infants, only occasionally in adults. This paper reports four cases of histologically-confirmed retroperitoneal cystic lymphangiomas detected in adulthood. All four patients presented with palpable abdominal mass. The diagnostic imaging methods used included abdominal ultrasonogram and CT scan. Correct preoperative diagnosis was made in only one case, but four tumors were totally excised. Biochemical analysis of the lymphangioma content from three of the patients proved protein and fat rich. The CT attenuation numbers of both serous and chylous lymphangioma were similar and near that of water and so were not helpful in differential diagnosis with other cystic lesions with watery density content.


Subject(s)
Lymphangioma, Cystic/diagnosis , Retroperitoneal Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Diagnosis, Differential , Female , Follow-Up Studies , Humans , Lymphangioma, Cystic/surgery , Male , Postoperative Care , Preoperative Care , Retroperitoneal Neoplasms/surgery , Tomography, X-Ray Computed
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