Biomedical subjects

J H Chiu

Publications and source records attributed to J H Chiu.

At least 37 records · Page 2Linked to original sources

PubMed1999

Prognosis of esophageal squamous cell carcinoma: analysis of clinicopathological and biological factors.

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is rather common among the Chinese, but the therapeutic outcome is dismal. Knowledge of the prognostic factors in cancerous patients may influence therapeutic strategy. However, systemic analyses of clinicopathological and biological factors for patients with ESCC are few, and the results are controversial. METHODS: Between 1985 and 1996, 117 patients undergoing en bloc esophagectomy and gastric substitution were enrolled. None had neoadjuvant treatment. Postoperative adjuvant therapy was provided for patients at and beyond stages IIa. Clinical responses were followed routinely. Flow cytometry was used to measure DNA ploidy and synthesis-phase fraction (SPF) of the resected esophageal tissues from all patients. Immunohistochemistry was also used to examine the expression of proliferating cell nuclear antigen (PCNA), epidermoid growth factor receptor (EGFR), HER-2/neu, and p53 in the pathological sections. Clinical correlation was evaluated by chi2 with Fisher's exact test, and survival by log-rank test. RESULTS: The overall survival rates were 74% for 1 yr, 48% for 3 yr, and 38% for 5 yr. TNM tumor staging, the number of diseased lymph nodes (N < or = 3 or N > 3), degree of cell differentiation, DNA ploidy, SPF, and lymphovascular invasion were more useful than biological markers, such as PCNA, EGFR, HER-2/neu, and p53, for the prognosis of ESCC. Multivariate analysis revealed significant correlation of tumor staging and number of diseased lymph nodes with patient survival after surgery. CONCLUSIONS: En bloc esophagectomy may provide a rather satisfactory survival rate for patients with early stage ESCC. However, for patients with distant lymph node metastasis and those with more than three lymph nodes involved, radical surgical resection, even combined with postoperative chemoradiotherapy, cannot improve survival. The prognostic value of biological markers, including PCNA, EGFR, HER-2/neu, and p53, however, is limited.

Adult↗

PubMed1999

Evaluation of a simplified staging system for prognosis of hepatocellular carcinoma.

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.

Carcinoma, Hepatocellular↗

PubMed1998

Parallel hybridization analysis of multiple protein kinase genes: identification of gene expression patterns characteristic of human hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is one of the major causes of human cancer deaths worldwide. To identify alterations of the genetic program associated with human HCC, we designed a new protocol based on the high-density replica method to analyze protein kinase gene expression in normal liver, HCC, and HCC-derived cell lines. RNA was prepared for reverse transcription and cDNA was used for PCR amplification of the conserved catalytic domain of protein kinase genes. Initially, from a pair of HCC and the adjacent noncancerous tissues, we sequenced 228 samples and identified 26 genes that represent different tyrosine kinase subfamilies. High-density grid filters were then prepared to assist the identification, by hybridization, of genes that are differentially expressed in normal vs HCC samples. Eleven tyrosine kinase genes were tested, and positive signals were reliably scored by doubly offset duplicates and by two independent gene-specific probes. Of the 11 genes tested, PDGF receptor-beta, MEKK-3, axl, and FGFR-4 are preferentially expressed in tumor samples. Additionally, we analyzed protein kinase gene expression in five HCC cell lines and identified distinct kinase gene expression patterns in different cell lines. Our results suggest that multiple kinases are activated in different tumors and confirm that there is molecular heterogeneity in the mechanisms sustaining autonomous cell growth in liver tumor formation.

Blotting, Northern↗

PubMed1998

Overexpression of cyclin A but not Skp 2 correlates with the tumor relapse of human hepatocellular carcinoma.

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.

Adult↗

PubMed1998

Local somatothermal stimulation inhibits the motility of sphincter of Oddi in cats, rabbits and humans through nitrergic neural release of nitric oxide.

To examine whether and how local somatothermal stimulation inhibits the function of the sphincter of Oddi (SO) in humans and in animals with different types of SO, we measured the activity of SO in anesthetized cats and rabbits by using continuously perfused open-tip manometric methods. Local somatothermal stimulation was achieved by applying an electroheating rod 0.5 cm away from the skin area near the right subcostal region. A heating pad was applied to the corresponding area in patients undergoing endoscopic retrograde cholangiopancreatography and biliary manometry. The motility of the biliary tract in cats, in terms of gall bladder pressure, tonic and phasic contraction pressure and frequency of SO before and during local heat were significantly different, respectively. The local heat-induced SO relaxation was not inhibited by pretreatment with atropine, propranolol, phentolamine or anti-cholecystokinin-octapeptide, but was almost completely blocked by infiltration of local anesthetics. Pretreatment with a nitric oxide synthesis inhibitor also blocked the relaxation, which was reversed by pretreatment with L-arginine, but not by D-arginine. The inhibition of SO motility by local heat in rabbits was also blocked by pretreatment with L-NAME, and this blockade was reversed by L-arginine. Application of local heat on patients demonstrated obvious inhibitory SO responses. We conclude that local somatothermal stimulation inhibits the SO motility in animals with different types of SO through the activation of heat-sensitive neural release of nitric oxide. This procedure may represent a simplified approach for the treatment of diseases with hypofunction of the L-arginine/NO pathway.

Animals↗

PubMed1998

Establishment and characterization of a strial marginal cell line maintaining vectorial electrolyte transport.

E6/E7 genes of human papilloma virus type 16 were used to immortalize a primary culture of marginal cells (MC) from gerbils. One of the cloned lines was selected which demonstrated preservation of the main characteristics of the MC, both morphologically and physiologically. Electron microscopic examination showed well-developed junctional complexes and apical microvilli which suggested its epithelial origin. Polymerase chain reaction (PCR) demonstrated the incorporation of E6/E7 genes with the genome. Reverse transcription PCR revealed the existence of mRNA of the IsK channel, a unique marker of MC among the inner ear cells, in this clone. Flow cytometric analysis of this cell line's DNA content was diploid. Numerous large domes formed after confluence of the cell monolayer. Electrophysiologic studies displayed evidence of apical K+ and Na+ channels which were blocked by Ba2+ (2 mM) and amiloride (10(-5) M), respectively. Existence of basolateral Na,K-ATPase and Na+/Cl-/K+ cotransporter was shown by blockage by ouabain (10(-3) M) and bumetanide (50 microM), individually. Injection of the cell line to nude mice failed to induce growth of tumors. This cell line was serum-, density- and anchorage-dependent when cultured in plastic dishes. In conclusion, this cell line shows characteristics of well-differentiated MC maintaining the major ionic transport processes, and provides us a good model to study the possible mechanisms and regulating factors of endolymph production.

Animals↗

PubMed1998

Flow-cytometric DNA content analysis of oesophageal carcinoma. Comparison between tumour and sequential non-tumour mucosae.

The DNA content in oesophageal carcinoma and in sequential non-tumour mucosa was evaluated in 35 patients with oesophageal carcinoma, to explore the hypotheses that DNA distribution pattern and S-phase fraction can reflect malignant potential and that DNA aneuploidy can provide an early-warning signal of developing cancer. DNA flow cytometry was performed on 129 specimens from the tumours and on 119 specimens from non-tumour mucosa. Control specimens from gastric fundus had normal diploid DNA content and low S-phase fraction. Aneuploidy was found in 94.3% of the carcinoma specimens and intratumoral heterogeneity in 54.3%. Of the non-tumour specimens, 43.7% showed aneuploidy and none multiple aneuploidy. Pattern III distribution was present in 8.6% of the tumour specimens but not in non-tumour mucosa, where the incidence of aneuploidy rose with closeness to the tumour (p < 0.001). S-phase fraction was smaller in non-tumour than in tumour specimens (p < 0.0001). The study indicated that histologically tumour-free oesophageal mucosa may have a high malignant potential in patients with oesophageal carcinoma. The relative instability of such mucosa, with aneuploid cells and low S-phase fraction, may facilitate transition to abnormally proliferating cells in response to environmental signals. Cigarette smoking and alcohol may increase the risk of multicentric cancer development.

Adult↗

PubMed1998

Cordyceps sinensis increases the expression of major histocompatibility complex class II antigens on human hepatoma cell line HA22T/VGH cells.

Previous studies suggest that down-regulation of the major histocompatibility complex (MHC) antigens on the cell surface of certain tumors results in an escape of immune surveillance. Cordyceps sinensis is well known for its modulatory effect on host immune system. To investigate the modulatory effect of Cordyceps sinensis on MHC class II antigen expression on hepatoma cells, immunostaining with monoclonal antibody (MAb) L243, against the HLA DR region of MHC class II antigens on human hepatoma cell line HA22T/VGH was analyzed by using flow cytofluorimetry. The degree of fluorescence intensity on L243(+) cells was expressed as relative mean fluorescence intensity (RMFI). The extract of Cordyceps sinensis (VGH-CS-ME-82, 40 micrograms/ml) was found to increase the MHC class II antigen expression on HA22T/VGH cells with the percentage of L243(+) cells 40.2 +/- 2.5 and RMFI 6.6 +/- 0.4; whereas cells without treatment disclosed the percentage of L243(+) cells 17.2 +/- 1.4 and RMFI 5.4 +/- 0.3, respectively (p < 0.05). There was a dose-related increase in the degree of fluorescence intensity in terms of RMFI on VGH-CS-ME-82 induced cells. The RMFI in cells treated with IFN-gamma 0, 0.2 and 5 ng/ml were 5.4 +/- 0.3, 8.2 +/- 0.4, and 24.9 +/- 1.5, respectively; whereas the RMFI in cells co-incubated with VGH-CS-ME-82 (40 micrograms/ml) and IFN-gamma 0, 0.2 ng/ml and 5 ng/ml were 6.7 +/- 0.2 (p < 0.05), 9.2 +/- 0.9 (p < 0.1) and 29.5 +/- 1.2 (p < 0.005), respectively. We conclude that VGH-CS-ME-82, either alone or with IFN-gamma induction, increases the MHC class II antigen expression on hepatoma cell line HA22T/VGH, which will shed light into the present immunotherapy, and make the host immune surveillance more effective against tumor cells with down-regulated MHC class II antigen expression.

Carcinoma, Hepatocellular↗

PubMed1998

p53 gene alternation in squamous cell carcinoma of the esophagus detected by PCR-cold SSCP analysis.

Mutations of the p53 tumor suppressor gene play an important role in the development of common human malignancies. Previous reports revealed that the frequencies of p53 alternations in esophageal carcinoma varied from 26% to 87%. The clinical significance of p53 alternations is still disputed. In the present study, we used polymerase chain reaction--"cold" single-strand conformation polymorphism (PCR-"cold" SSCP)--to investigate p53 genetic alternations in 63 surgical specimens of esophageal squamous cell carcinoma (ESC). Our experiments showed that the optimum buffer temperature for "cold" SSCP analysis was 14 degrees C while the PCR products were around 200-300 bp in size. Among 63 tumorous samples, p53 alternations was detected in 47 tumors, or an incidence rate of 74.6%. For nontumorous mucosal samples, the incidence of p53 alternations was 55.5% (35/63 samples). Additionally, p53 alternations occurred most frequently at exon 6 (50.8%), followed by exon 7 (33.3%), exon 8 (17.5%) and exon 5 (12.7%). Multiple genetic alternations (> or = 2 exons) between p53 exons 5-8 in the same examined samples were found in 21 (33.3%) of 63 tumors, and in 8 (12.7%) of 63 nontumorous mucosal specimens. Our results further showed that p53 alternations did not correlate with age, depth of tumor invasion, lymph node metastasis, tumor stage, cell differentiation or lymphovascular invasion in ESC (P > 0.05). Moreover, the survival rate in patients with p53 alternations was similar to that in patients without p53 alternations (P > 0.05). In conclusion, PCR-"cold" SSCP is a rapid and sensitive method for identifying p53 genetic alternations. p53 genetic alternations occur with a relatively high incidence for ESC, but p53 abnormality has no impact on prognosis.

Age Factors↗

PubMed1998

Effects of acute brainstem compression on auditory brainstem response in the guinea pig.

BACKGROUND: The purpose of this study was to establish the norm for parameters of auditory brainstem response (ABR) in the guinea pig and to investigate if acute brainstem compression results in significant changes to these parameters. METHODS: Thirty-six guinea pigs with positive Preyer's reflex were anesthetized. A craniectomy was performed to remove the right occipital bone and the dura mater was opened to expose the brain, cerebellum and cerebellopontine angle (CPA). A small inflatable balloon was placed into the CPA precisely and slowly. ABR was recorded before incision of the skin as a baseline value, after placement and after inflation of the balloon with water at 0.1-ml intervals. RESULTS: Five stable peaks were recorded in 27 experimental animals. When the balloon was inflated with 0.1 ml water, the absolute latency (AL) of peaks IV and V and the interpeak latency (IPL) of peaks III and IV, and IV and V were prolonged. The amplitude ratios (AR) of peaks II, III, IV and V to peak I decreased. Inflation of the balloon with 0.2 ml of water caused further elongation of ALs of peaks IV and V and decreases in each AR. When the balloon volume increased to 0.3 ml, peak V became unrecognizable and peaks III and IV showed significant elongation of AL; peaks I and II did not show significant change in ALs. Further increase of the balloon volume to 0.4 ml resulted in disappearance of peaks III, IV and V; AL of peak II was also elongated. However, the amplitude and AL of peak I remained unchanged. Similar changes were observed in IPLs. CONCLUSIONS: This study establishes the norm of parameters of ABR in guinea pigs and demonstrates that acute brainstem compression causes elongation of ALs and IPLs of peaks II, III, IV and V. This suggests that peaks II, III, IV and V come from the brainstem and that peak I is not generated from the brainstem in the guinea pig.

Animals↗

PubMed1997

Class I and class II major histocompatibility complex antigens expression on human hepatocytes and hepatoma cells: an approach with high sensitivity and specificity.

The expression of gene products of the major histocompatibility complex (MHC) on the cell surface is known to play an important role in immunological responses. While some studies have reported the presence of MHC antigens on hepatocytes, information about specific, sensitive hepatocyte MHC antigen expression in various liver diseases is minimal. To investigate the expression of class I and class II MHC antigens on hepatocellular carcinoma (HCC) specimens, two-color flow cytometry was used to demonstrate MHC antigen expression on non-malignant and malignant hepatocytes using the hepatocyte-specific monoclonal antibody (MAb) 9B2 for selective gating and either MHC-specific W6/32 (class I) or Q5/13 (class II) MAb for MHC antigen detection. Non-malignant liver tissues demonstrated variable MHC antigen expression. Malignant hepatocytes isolated from resected HCC specimens as well as non-tumorous hepatocytes from these HCC specimens also disclosed various degrees of MHC antigen expression. Although we were not able to demonstrate a clear correlation between clinical outcome and MHC antigen expression in HCC, we conclude that the expression of MHC antigens on human hepatocytes and hepatoma cells can be accurately detected by flow cytometry using hepatocyte-specific MAb for selective gating and MHC-specific MAbs. Of note, two cases of non-malignant fetal liver tissues indicated that >95% of fetal hepatocytes expressed class I MHC antigens and <25% of fetal hepatocytes expressed class II MHC antigens. These findings may lead to further investigations into the progression of HCC cells or into the possible mechanisms of the hepatocellular carcinogenesis.

Antibodies, Monoclonal↗

PubMed1997

Prognostic significance of surgical margin in hepatocellular carcinoma resection: an analysis of 165 Childs' A patients.

BACKGROUND AND OBJECTIVES: The clinical significance of the width of the surgical margin in the resection of hepatocellular carcinoma (HCC) has yet to be clarified. METHODS: Childs' A patients (165) who underwent resections of HCC were studied. Patients were divided into a wide margin group (1.0 cm or more, group W, n = 85), and a narrow margin group (< 1.0 cm, group N, n = 80). RESULTS: Multivariate analysis showed that preoperative alpha-fetoprotein level (P = 0.0202), venous invasion (P = 0.0226), surgical margin (P = 0.0012), and TNM stage (P = 0.0023) were significant predictors of disease-free survival. By the log-rank test, the disease-free survival rate of the group W patients was significantly higher than that of the group N patients (P = 0.0007). Group N had a higher percentage of patients undergoing minor resection (wedge resection or subsegmentectomy) (44% vs. 26%, P = 0.016) and had a higher percentage of patients with centrally located tumor (62% vs. 29%, P = 0.000) than group W. CONCLUSIONS: The results of this study indicated the significant influence of surgical margin on HCC recurrence after resection. Minor resection and centrally located tumor are factors related to a narrow surgical margin.

Adult↗

PubMed1997

In vitro and in vivo protective effect of honokiol on rat liver from peroxidative injury.

Honokiol, a compound extracted from the Chinese medicinal herb Magnolia officinalis, has a strong antioxidant effect on the inhibition of lipid peroxidation in rat heart mitochondria. To investigate the protective effect of honokiol on hepatocytes from peroxidative injury, oxygen consumption and malondialdehyde formation for in vitro iron-induced lipid peroxidation were assayed, and the mitochondrial respiratory function for in vivo ischemia-reperfusion injury were evaluated in rat liver, respectively. The inhibitory effect of honokiol on oxygen consumption and malondialdehyde formation during iron-induced lipid peroxidation in liver mitochondria showed obvious dose-dependent responses with a concentration of 50% inhibition being 2.3 x 10(-7) M and 4.96 x 10(-7) M, respectively, that is, 550 times and 680 times more potent than alpha-tocopherol, respectively. When rat livers were introduced with ischemia 60 min followed by reperfusion for 60 min, and then pretreated with honokiol (10 micrograms/kg BW), the mitochondrial respiratory control ratio (the quotient of the respiration rate of State 3 to that of State 4) and ADP/O ratio from the honokiol-treated livers were significantly higher than those of non-treated livers during reperfusion. The dose-dependent protective effect of honokiol on ischemia-reperfusion injury was 10 microgram-100 micrograms/Kg body weight. We conclude that honokiol is a strong antioxidant and shed insight into clinical implications for protection of hepatocytes from ischemia-reperfusion injury.

Animals↗

PubMed1997

Diagnostic laparoscopy: indication and benefit.

BACKGROUND: Patients with an obscure and unrelievable abdominal condition may be forced to receive open laparotomy for diagnosis. Diagnostic laparoscopy has been suggested as an alternative to diagnostic laparotomy in selected cases. The aim of this article is to evaluate the circumstances suitable for laparoscopic diagnosis of certain abdominal conditions and the possible advantages of that approach. METHODS: Among 256 patients undergoing elective laparoscopic operations using conventionally pneumoperitoneal techniques from January 1994 to June 1995, twenty patients received diagnostic laparoscopy. The correlation between preoperative diagnosis, laparoscopic diagnosis and pathologic diagnosis as well as the outcome of laparoscopic diagnosis and treatment have been assessed. RESULTS: Major indications for diagnostic laparoscopy included acute abdominal pain (n = 4), chronic abdominal pain (n = 6), differentiating intraabdominal tumor (n = 4), staging known malignancy (n = 3) and evaluating intraperitoneal implantation (n = 3). Two of the four patients with acute abdominal conditions, one of the six patients with chronic abdominal pain. Four of the seven patients with undifferentiated/unstaged abdominal tumors and all of the three patients with intraperitoneal-implanted drainage tubes had no reasons for a further exploratory procedure, thus preventing the morbidity or mortality which might occur after unnecessary laparotomy. The duration of operation and hospitalization was shorter than the group without laparotomy. CONCLUSIONS: Diagnostic laparoscopy benefits patients by avoiding unnecessary surgery, avoiding unnecessary delay in diagnosis and treatment and shortening the operative and hospitalized period. However, it provides only an alternative not a substitute for traditional diagnostic procedures and will never lessen the importance of conventional laparotomy.

Abdomen, Acute↗

PubMed1997

Prognostic factors affecting long-term survival after partial hepatectomy for human hepatocellular carcinoma.

BACKGROUND: Various prognostic factors have been studied during the past few years to predict early tumor recurrence and survival in patients undergoing hepatectomy for primary hepatocellular carcinoma. However, the relationship between these factors and long-term survival has not been clarified. The purpose of this study was to identify the factors linked to long-term prognosis in patients with resectable hepatocellular carcinoma after hepatectomy. METHODS: Records of 370 patients undergoing curative hepatectomy during a period from July 1981 to July 1994 were retrospectively reviewed. Only 110 patients with disease-free survival > or = 36 months were eligible for long-term survival analysis. Their further outcomes, including disease-free survival and overall survival, were analyzed in correlation with various prognostic factors by Kaplan-Meier's method, log rank test; and Cox's regression model. Analysis of prognostic factors linked to early tumor recurrence after curative hepatectomy was also performed in 324 patients who were followed up > or = 12 months. RESULTS: Tumor behaviors were found to be the principal prognostic factors determining the early tumor recurrence and patients' survival (p < 0.05). However, when long-term survival was analyzed, the pathological status of the liver remnant such as the presence or absence of hepatitis B virus infection, chronic active hepatitis, hepatocyte dysplasia and age (< or = 60 y/o vs. > 60 y/o), as well as preoperative liver function (total serum bilirubin < or = 1.5 mg/dl vs. > 1.5 mg/dl), were found to make significant disease-free survival differences (p < 0.05), whereas the factors linked to tumor behaviors and surgical factors showed no influence on long-term prognosis. CONCLUSIONS: Pathological status and host factors (age and liver function) have effect upon long-term prognosis after hepatic resection for hepatocellular carcinoma.

Adult↗

PubMed1997

Clinicopathological comparison of resectable hepatocellular carcinoma between the young and the elderly patients.

BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most common cancers in many parts of the world. In Taiwan it is the leading cause of death in male cancer patients. The peak age of onset of HCC varies according to geographic barriers, which indicates different hepatocarcinogenesis among different age groups. This study aims to evaluate whether there exists significantly different clinicopathological features between young and elderly HCC patients. METHODS: During a six-year period, a total of 248 patients with HCC underwent liver curative resection at Veterans General Hospital-Taipei, Taiwan. Among them, 22 patients were younger than 40 years of age, and 43 patients were older than 70 years of age. Important clinicopathological characteristics of the patients (including sex, family history of HCC, smoking habits and alcohol consumption patterns, hepatitis B or C infection, indocyanine-green retention rate at 15 minutes (ICGR-15), serum alpha-fetoprotein value, tumor size, tumor number, tumor venous invasion, capsular formation, tumor staging, cirrhosis, and tumor DNA ploidy) and postresectional prognosis were compared between young and elderly HCC patients. RESULTS: The frequency of presence of family history (22.7% versus 4.7%), hepatitis B surface antigen carrier rate (81.8% versus 48.8%), and patients with large-sized tumors (31.8% versus 7.0%) were significantly higher in young patients than in elderly patients. The male:female ratio (4.5:1 versus 42:1), degree of liver damage (reflected by the ICGR-15 value, 5.6 +/- 5.0% versus 13.1 +/- 8.8%) and the incidences of liver cirrhosis (18.2% versus 48.8%) were significantly lower in young patients than in elderly patients. However, there were no significant differences in postresectional survival rates between these two groups. CONCLUSIONS: There are age-related differences in clinicopathological characteristics of HCC patients. Accordingly, different mechanisms of hepatocarcinogenesis may exist between young and elderly HCC patients.

Adolescent↗

PubMed1996

Surgical resection of primary hepatocellular carcinoma extending to adjacent organ(s).

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.

Carcinoma, Hepatocellular↗

PubMed1996

Establishment and characterization of two cell lines derived from a single hepatocellular carcinoma containing multiploid DNA distribution.

Previous studies showed that patients with resectable multiploid hepatocellular carcinoma (HCC) had lower overall survival rate and higher recurrent rate than did those with diploid or single aneuploid tumors after hepatic resection. We describe in this study the establishment and characterization of cell lines derived from a single HCC nodule containing multiploid DNA distribution. Two human HCC cell lines, designated HAGS 2.1 and HAGS 2.2, were established by primary culture and single cell cloning methods from a patient with a multiploid HCC tumor. Both cell lines expressed bile canalicular domain-specific antigen of human hepatocyte. The HAGS 2.1 cells were spindle-shaped without prominent intracellular vesicles and had a doubling time of 38 h with DNA ploidy of 4.4 N; cells of HAGS 2.2 were polygonal with many intracellular vesicles and had a doubling time of around 42 h with DNA ploidy of 5.1 N. Hepatitis B surface antigen was detectable in HAGS 2.2 but negative in HAGS 2.1 cells. Both HAGS 2.1 and HAGS 2.2 expressed major histocompatibility complex (MHC) class I antigen, but the former expressed more MHC class II antigen than did the latter. Polymerase chain reaction and subsequent single strain conformation polymorphism analysis disclosed the presence of preS and S regions and the absence of C and X regions of HBV genome in cells of both HAGS 2.1 and HAGS 2.2. We conclude that the establishment of cell lines derived from a single HCC tumor containing multiploid DNA distribution might provide a good in vitro model to study the carcinogenesis and the recurrence mechanism of human hepatocellular carcinoma.

Antigens, Neoplasm↗