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Biomedical subjects

W Y Chang

Publications and source records attributed to W Y Chang.

At least 19 recordsLinked to original sources

Distinct regions of allelic loss on chromosome 4 in human primary bladder carcinoma.

Accumulating evidence implicates the presence of putative tumor suppressor genes on human chromosome 4 that are potentially inactivated in the genesis of several different neoplasms. To accurately determine the frequency of allelic loss on both arms of human chromosome 4, we screened 282 fresh-frozen human bladder carcinomas for allelic loss. Loss of heterozygosity of at least one marker for chromosome 4 was identified in 129 tumors (45.7%). Fine mapping was accomplished using up to 15 polymorphic markers on the p arm and 19 markers on the q arm. We identified a 3-cM minimal area of loss on the p arm between microsatellite markers D4S1608 and D4S404 deleted in 82 tumors (29%). A total of 68 tumors (24%) targeted a 14-cM critical region identified on the distal q arm between markers D4S426 and D4S408. Loss of these two regions correlated with advanced stage and grade of the lesions. These data identify distinct regions of loss on chromosome 4 potentially involved in the late progression of bladder carcinoma.

Chromosome Deletion

Novel suppressor loci on chromosome 14q in primary bladder cancer.

Two hundred eighty-five primary human carcinomas of the urinary bladder were examined for allelic loss on chromosome 14q. Seventeen highly polymorphic dinucleotide markers spanning the long arm of this acrocentric chromosome were selected for fine PCR-based mapping. Loss of heterozygosity for at least one marker was observed in 72 (25.3%) tumors. Thirty-four of these 72 tumors (47.2%) lost the entire long arm (monosomy), as suggested by loss of heterozygosity at all informative sites. Allelic loss on 14q occurred in all grades and stages of bladder cancer but was more commonly associated with muscle-invasive tumors (Ta, 9.4%; T1, 24.1%; and > or = T2, 41%). A deletion map of 16 primary tumors with partial losses delineated two minimal regions of loss. One region (approximately 2 cM) was bounded by markers D14S75 and D14S288 and the other (approximately 3 cM) by D14S51 and D14S267. Our results demonstrate that 14q loss is common in invasive bladder cancer and suggest that two potential suppressor loci at 14q12 and 14q32.1-32.2 may contribute to the genetic progression of this common cancer.

Chromosome Mapping

Circulating immune complexes in chronic hepatitis C.

For assessing the role of circulating immune complexes (CIC) in chronic hepatitis C, the relative frequency of CIC was determined in 54 patients with chronic hepatitis C, 15 asymptomatic hepatitis C virus (HCV) carriers, and 54 healthy controls. IgM and IgG containing CIC were studied using both C1q and conglutinin (K) in an immunoglobulin-specific solid-phase enzyme immunoassay. CIC were a common feature of chronic hepatitis C with 96.3% of patients with at least one abnormal test result. The prevalence of elevated IgG-K, IgM-K, IgG-C1q, and IgM-C1q CIC was 70.3%, 50.0%, 64.8%, and 35.1%, respectively. The prevalence of IgG class CIC was higher than IgM class CIC (P = 0.038 for K-CIC and P = 0.01 for C1q-CIC, respectively). There is correlation between IgG-K CIC and IgG-C1q CIC (r = 0.445, P = 0.002), IgG-K CIC and IgM-C1q CIC (r = 0.348, P = 0.020), IgM-K CIC and aspartic aminotransferase (r = 0.321, P = 0.015), IgM-K CIC and alanine aminotransferase (r = 0.301, P = 0.027). Compared to patients with chronic persistent hepatitis and chronic lobular hepatitis, patients with chronic active hepatitis have a higher prevalence of elevated IgG-K CIC (77.2% vs. 40.0%, P = 0.029) and IgM-K CIC (56.8% vs. 20.0%, P = 0.038). The concentration of IgG-K, IgM-K, and IgM-C1q CIC in the former was significantly higher than that in the latter, respectively. In conclusion, IgG class CIC is the major type of CIC in chronic hepatitis C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Circulating immune complexes in chronic hepatitis related to hepatitis C and B viruses infection.

Circulating immune complexes (CIC) may be involved in tissue damage and/or viral clearance in viral hepatitis. To assess the frequency of raised CIC in chronic hepatitis related to hepatitis B and C, IgM, IgG, and hepatitis B surface antigen (HBsAg) containing CIC were determined, by conglutinin (K) and C1q assays, in 101 patients with chronic hepatitis B alone, 24 patients with chronic hepatitis B and C, 48 patients with chronic hepatitis C alone, and 54 healthy controls. Compared to patients with hepatitis B alone, patients with dual infection had higher frequency of raised IgM-C1q CIC (P < 0.001) and IgM-K CIC (P < 0.01). There is no difference in the prevalence of HBsAg-CIC between patients with hepatitis B alone and those with dual infection. Among patients with chronic hepatitis C alone, conglutinin-binding CIC is the predominant type of raised CIC and correlated with more severe liver damage. In conclusion, CIC may play a role in the pathogenesis of chronic hepatitis C virus infection.

Adult

Clinical evaluation of serum alpha-fetoprotein and circulating immune complexes as tumour markers of hepatocellular carcinoma.

To evaluate the diagnostic application of serum alpha-fetoprotein (AFP) and circulating immune complexes (CICs), AFP, 3% polyethylene glycol (PEG)-CICs, 4% PEG-CICs, and C1q-CICs were determined in 101 patients with cirrhosis alone, 101 sex-matched and age-matched cirrhotic patients with hepatocellular carcinoma (HCC) and 54 healthy controls. Multivariate analysis indicated that AFP (odds ratio 1.014; 95% confidence interval 1.004-1.024) and 3% PEG-CICs (odds ratio 1.011; 95% confidence interval 1.005-1.017) are associated, in a dose-related fashion, with an increased risk for HCC. A receiver operative characteristic (ROC) curve was used to determine the optimal cut-off values of AFP (120 ng ml-1) and 3% PEG-CICs (310 micrograms aggregated IgG equivalent ml-1). The area under ROC curve was 0.875 for AFP and 0.812 for 3% PEG-CIC. Both AFP and 3% PEG-CICs show a high specificity (100%) and positive likelihood ratio. The sensitivity was 65.3% for 3% PEG-CICs and 67.3% for AFP. Determination of both markers in parallel significantly increase the diagnostic accuracy (92.1%) and sensitivity (84%), with a high specificity (100%) and positive likelihood ratio (> 84). In conclusion, both 3% PEG-CICs and AFP are independent risk factors of HCC, and may be used as complementary tumour markers to discriminate HCC from cirrhosis. Determination of 3% PEG-CICs should be performed in cirrhotics negative for AFP to improve detection of HCC.

Adult

Prevalence and size of simple hepatic cysts in Taiwan: community- and hospital-based sonographic surveys.

Simple hepatic cysts are now being diagnosed more frequently with the widespread availability of sonographic imaging. Among the general population, the prevalence was reported to be between 0.1 and 2.5%, more so in women, and more often in the right lobe. We conducted this large scale community-based sonographic screening on simple hepatic cysts to explore the age- and sex-specific prevalence in Taiwan. We also conducted another hospital-based study to record the size of simple hepatic cysts. A total of 3,600 subjects in 8 communities were recruited and 156 simple hepatic cysts in 132 study subjects were detected. The overall prevalence is 3.60%. An increasing prevalence with age is demonstrated, ranging from 0.83% from below the age of 40 up to 7.81% of patients over 60 years old. The sizes of 219 simple hepatic cysts of 167 patients out of the hospital-based 5,893 patients were recorded in detail; 53% of cysts were of a diameter of between 1 and 3 cm, and only 7% were larger than 5 cm.

Adult

Antibodies to hepatitis E virus among Chinese patients with acute hepatitis in Taiwan.

The prevalence of antibodies to hepatitis E virus (anti-HEV) was investigated in patients with acute hepatitis, and correlated with the clinical features. Sera from 110 patients with acute hepatitis and 60 healthy controls were tested for anti-HEV, antibody to hepatitis C virus (anti-HCV), and hepatitis B surface antigen (HBsAg). There were significant differences in the prevalence of anti-HEV, anti-HCV, and HBsAg between patients and controls (21.8% vs. 0%, 16.3% vs. 1.6% and 58.1% vs. 18.0%, respectively). Anti-HEV was detected in 6 (25.0%) of 24 patients with anti-HCV, 6 (9.3%) of 64 patients with HBsAg, and another 6 (22.2%) of 27 patients with acute hepatitis non-A, non-B, non-C. Anti-HEV was found in 15 men and three women, whose ages ranged from 34 to 75 (median, 57) years old. The median age of patients with anti-HEV was older than that in patients without this antibody (57 vs. 38 years; P = 0.001). The prevalence of anti-HEV in patients with anti-HCV alone (35.2%) was higher than that (11.1%) in patients with HBsAg alone (P = 0.03). Compared to patients without anti-HEV, HEV-infected patients had a higher frequency of travel to a foreign country (P = 0.0001), had a lower HBsAg rate (P = 0.019), and had higher serum alkaline phosphatase levels (P = 0.04) and gamma-glutamyl transpeptidase levels (P = 0.01). In conclusion, HEV infection occurs in 22.2% of patients with acute hepatitis non-A, non-B, non-C. HEV superinfection may occur in patients with chronic hepatitis B or C virus infection.

Acute Disease

Effects of hepatitis C and B viruses infection on the development of hepatocellular carcinoma.

A case control study consisting of 102 patients with HCC, 102 sex-matched and age-matched patients with nonhepatic disease, and 204 matched healthy controls was carried out to investigate the effect of hepatitis B virus (HBV) and hepatitis C virus (HCV) infection on the development of hepatocellular carcinoma (HCC). The prevalence of antibody to HCV (anti-HCV) in HCC (34.3%) was higher than in nonhepatic disease (10.7%, P < 0.001) or in healthy controls (2.4%, P < 0.001). The prevalence of hepatitis B surface antigen (HBsAg) in HCC (77.4%) was higher than in nonhepatic disease (16.6%, P < 0.001) or in healthy controls (19.6%, P < 0.001). Anti-HCV positivity in nonhepatic disease was higher than in healthy controls (P < 0.01). Using patients with nonhepatic disease as controls, stepwise logistic regression analysis indicated that both anti-HCV (odds ratio, 3.4; 95% confidence interval, 2.1-5.6) and HBsAg (odds ratio, 5.6; 95% confidence interval, 3.6-8.5) are independent risk factors for HCC. Using healthy controls, the development of HCC was also strongly associated with anti-HCV (odds ratio, 8.0; 95% confidence interval, 4.3-14.6) and HBsAg (odds ratio, 5.5; 95% confidence interval, 3.7-8.2). Calculation of incremental odds ratio indicated that there is no interaction between HBV and HCV. In conclusion, HBV and HCV are risk factors of HCC. They act independently and without interaction.

Adult

Hepatitis B and C virus infection as risk factors for liver cirrhosis and cirrhotic hepatocellular carcinoma: a case-control study.

To investigate whether hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are risk factors for liver cirrhosis and hepatocellular carcinoma (HCC), a case-control study of 102 cirrhotic HCC patients, 102 sex-matched and age-matched patients with liver cirrhosis, and 102 matched patients with non-hepatic disease controls was performed. The prevalences of hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) in HCC (70.5%, 39.2%) and liver cirrhosis (74.5%, 27.4%) were higher than controls (16.6%, 10.5%) (P = 0.0001). In HBsAg-negative patients, the prevalence of anti-HCV in cirrhotic HCC (66.6%) and liver cirrhosis (46.1%) was higher than in controls (10.5%; P = 0.0001). There was no such difference in HBsAg-positive patients. Multivariate analysis revealed that both HBsAg and anti-HCV were important risk factors for HCC (odds ratio, 6.52 and 4.59, respectively) and liver cirrhosis (odds ratio, 4.22 and 2.29, respectively). There was no difference in odds ratio when HCC and liver cirrhosis were compared. Our result implies that both HBV and HCV are independent risk factors for cirrhotic HCC and liver cirrhosis in Taiwan.

Carcinoma, Hepatocellular

Hepatitis C virus infection as a risk factor for non-alcoholic liver cirrhosis in Taiwan.

To assess whether hepatitis C virus infection was a risk factor for the development of non-alcoholic liver cirrhosis, antibody to hepatitis C virus (anti-HCV; detected by a second generation HCV enzyme immunoassay), hepatitis B surface antigen (HBsAg; detected by radioimmunoassay) were tested in 150 cirrhotics and 150 sex-matched and age-matched healthy controls. The prevalence of anti-HCV and HBsAg in cirrhotics was higher than in controls (22.0%, 73.3% vs. 2%, 18.7%; P = 0.001). The prevalence of anti-HCV in HBsAg-negative cirrhotics (45.0%) was higher than that in HBsAg-positive patients (13.6%; P = 0.001). Both the anti-HCV and carriage of HBsAg were associated significantly with liver cirrhosis, showing odds ratio of 12.0 for HBsAg carriers and 13.8 for patients with anti-HCV. Compared with those without HBsAg and anti-HCV, there was a significantly positive linear trend for developing cirrhosis with the presence of HBsAg alone (odds ratio = 19.9), anti-HCV alone (odds ratio = 49.0), and those positive for HBsAg and anti-HCV (odds ratio = 81.8) (P = 0.00001). The population-attributable risk for developing liver cirrhosis was estimated as 10.8% for anti-HCV alone, 55.2% for HBsAg alone, and 9.4% for both anti-HCV and HBsAg in southern Taiwan. In conclusion, this study shows that hepatitis B and C virus infection act independently and synergistically in the development of non-alcoholic liver cirrhosis among Chinese in Taiwan.

Age Factors

The role of hepatitis C virus in chronic hepatitis B virus infection.

To investigate the influence of hepatitis C virus (HCV) infection on patients with chronic hepatitis B virus (HBV), the presence of antibody against C100-3 antigen of HCV (anti-HCV) was examined in 420 patients with chronic HBV infection and 275 healthy subjects. It was found that the prevalence of HCV infection increased in parallel with the severity of liver damage. The positive rates of anti-HCV were as follows: healthy subjects, 2.9% (8/275); asymptomatic carriers, 2.6% (5/193); chronic hepatitis, 5.2% (3/58); liver cirrhosis, 11.4% (8/70); hepatocellular carcinoma (HCC), 12.1% (12/99). To elucidate the interaction of these two viruses in hepatocellular carcinoma, 128 HCC patients and 384 age-matched and sex-matched subjects were further analyzed. Eighty-seven of 128 HCC patients (68.0%) were only positive for HBsAg, 13 patients (10.1%) were only anti-HCV positive, and 12 (9.4%) were positive for both markers. The presence of HBsAg and anti-HCV was associated strongly with HCC. Moreover, the risk of HCC was significantly higher when both HBsAg and anti-HCV were present simultaneously. These results suggested that concurrent HCV infection might accelerate the progression of chronic HBV infection and may contribute to the pathogenesis of HCC in patients with chronic HBV infection.

Carcinoma, Hepatocellular

The role of hepatitis B and C viruses in hepatocellular carcinoma in a hepatitis B endemic area. A case-control study.

To investigate the role of hepatitis B (HBV) and C viruses (HCV) in hepatocellular carcinoma (HCC) in an HBV endemic area and elucidate the interaction of these two viruses, a case-control study of 128 patients with HCC and 384 age-matched and sex-matched control subjects was done. The positive rates of hepatitis B surface antigen (HBsAg, 77.3%, 99 of 128) and anti-HCV (19.5%, 25 of 128) in patients with HCC were significantly higher than in control subjects (P less than 0.001). Both HBsAg and anti-HCV were important risk factors for HCC (relative risks, 13.96 and 27.12, respectively), and the risk for HCC was elevated significantly to 40.05 (95% confidence interval, 12.57 to 127.6) when HBsAg and anti-HCV were considered simultaneously. These results suggested that HBV and HCV were associated highly with HCC in an HBV endemic area and that these two viruses might contribute independent but synergistic effects to the pathogenesis of HCC.

Adult

Treatment of hepatocellular carcinoma by transcatheter arterial chemoembolization and analysis of prognostic factors.

A total of 100 patients with histologically proven hepatocellular carcinoma (HCC) underwent transcatheter arterial chemoembolization (TACE) and were followed for more than 1 year and 10 months. Portal vein branch thrombosis was diagnosed in 14 patients, and extrahepatic metastasis was noted in 11 subjects. The embolization material used was iodized oil (0.1-0.2 ml/cm tumor area at its maximal diameter), which was prepared by pumping with contrast agent and then mixed with anticancer drugs; Gelfoam particles measuring 1-2 mm in size were subsequently injected. The overall cumulative 0.5- 1-, 2-, and 3-year survival rates were 81%, 57%, 31%, and 21%, respectively. Patients with an intact capsule and those with solitary lesions, especially when the tumor diameter was < 5 cm, achieved a higher survival rate. In contrast, incomplete TACE, extrahepatic metastasis, and portal vein thrombosis were associated with the worst outcome. Patients with positive HBsAG and diffuse or multiple tumors also showed a poor outcome. Early diagnosis and early treatment of HCC are the keys for the achievement of better clinical results.

Adult

Radiotherapy in the treatment of hepatocellular carcinoma and its metastases.

A study was conducted to evaluate the effect of external radiation therapy on hepatocellular carcinoma (HCC) and its metastatic lesions. A total of 33 patients with cytopathologically proven HCC were subjected to radiation therapy over a 4-year period, and treatment was discontinued in 8 cases due to jaundice, severe discomfort, or early mortality. Thus, 25 patients with 28 lesions underwent irradiation with a total dose ranging between 3000 and 5600. Of these, seven were irradiated for liver tumors, and the results showed that two lesions decreased in size, the symptoms improved in 1 case, and another patient maintained stable disease for 4 months. Among the 21 metastatic lesions treated, only 2 patients failed respond to the treatment. Nine subjects were irradiated for bone metastases, and the bone pain subsided in all but one case. The survival for bone metastasis was as long as 23 months when the primary tumor was treated effectively. Three of the four cases of irradiated skin nodules disappeared and had not recurred after 5 months, 1 year, and 4 years, respectively. Tumor shrinkage or symptoms of relief were noted for three abdominal lymph nodes, one neck lymph node, one pleural tumor, and one lung tumor. Clinical improvement associated with a stable lesion was observed in two patients with brain metastasis. Follow-up revealed regrowth of the tumor or recurrence of symptoms in most of the patients. However, none of the patients died as a direct result of a metastatic lesion. Although external radiation therapy is palliative in intent, it appears to be useful in the treatment of HCC and its metastatic lesions.

Adult

Duplex pulsed Doppler sonography in the differential diagnosis of hepatocellular carcinoma and other common hepatic tumours.

180 previously untreated consecutive patients with liver tumours (308 lesions), including 104 hepatocellular carcinomas (148 lesions), 43 metastases (116 lesions) and 33 haemangiomas (44 lesions), were studied to determine the value of duplex sonography in the differentiation of hepatocellular carcinoma from other tumours. For lesions measuring less than or equal to 5 cm in diameter, hepatocellular carcinoma demonstrated the highest rate and haemangioma demonstrated the lowest rate of Doppler signals from within the lesions. To differentiate malignancy from haemangioma, the presence or absence of Doppler signals from these lesions were used as criteria. The specificity and positive predictive value were very high (100%, 100%), but the sensitivity, negative predictive value and accuracy were low (61.5%, 48.3%, 71.7%, respectively). With one exception, all lesions measuring less than 3 cm in diameter with detectable Doppler signals were hepatocellular carcinoma. Using these results it is possible to differentiate hepatocellular carcinoma from metastases and haemangioma with high sensitivity, specificity, positive and negative predictive value, and accuracy (80.8%, 96.4%, 95.5%, 84.4%, 88.9%, respectively, for metastases; 80.8%, 100%. 100%, 81.5%, 89.6%, respectively, for haemangioma). We conclude that Doppler signals from within a lesion in combination with its size can aid differentiation of hepatocellular carcinoma from two other kinds of common hepatic tumour.

Adult