Cheng-Chuan Su

Diagnostic value of Her-2/neu, Cyfra 21-1, and carcinoembryonic antigen levels in malignant pleural effusions of lung adenocarcinoma

Aims: Cytology fails to detect neoplastic cells in 40–50% of cases of malignant pleural effusion, a condition that frequently accompanies lung adenocarcinoma. Published reports of diagnostic sensitivity of various tumour markers are inconsistent, and optimal cut‐off points have not been determined. This study aimed to evaluate the ability of three markers to discriminate lung adenocarcinoma‐associated malignant pleural effusion (LAC‐MPE) from benign effusion. Methods: Pleural effusion samples were collected from 41 patients with LAC‐MPE, and from 93 with various benign conditions. The diagnostic sensitivity and specificity for Her‐2/neu, Cyfra 21‐1, and carcinoembryonic antigen (CEA) were evaluated. Cut‐off points for these markers are optimally set at 3.6 µg/L, 60 µg/L, and 6.0 µg/L, respectively. Results: Her‐2/neu, Cyfra 21‐1, and CEA vary in their diagnostic accuracy to differentiate LAC‐MPE from benign pleural effusion: 79.85%, 88.81%, and 94.03%, respectively. CEA combined with Cyfra 21‐1 increases diagnostic sensitivity to 97.6%, with a specificity of 91.4%. Conclusions: With appropriate cut‐off points, CEA currently provides the best diagnostic accuracy. Combining CEA with Cyfra 21‐1 increases diagnostic sensitivity to nearly 100%. The results of the present study may help clinicians decide whether to obtain a cytological/histological specimen by invasive means to investigate a possible diagnosis of malignancy.

Nicotinamide abrogates acute lung injury caused by ischaemia/reperfusion

Poly (ADP-ribose) synthase or polymerase (PARS and PARP, respectively) is a cytotoxic enzyme which causes cellular damage. Nicotinamide, a compound of vitamin B complex, has been reported to exert an inhibitory effect on PARS or PARP. The present study tests the effects of nicotinamide on acute lung injury and associated alterations following ischaemia/reperfusion (I/R) of the isolated perfused rats lung. I/R increased the lung weight (LW) to body weight ratio, LW gain, protein and dye tracer leakage, pulmonary arterial pressure and capillary permeability. The insult also increased nitrate/nitrite, methyl guanidine, tumour necrosis factor-α and interleukin-1β in lung perfusate, while it decreased adenosine triphosphate content with an increase in PARP activity in lung tissue. Most of the I/R-induced changes were abrogated by post-treatment (30 min after I/R) with nicotinamide (100 mg·kg−1 body weight). However, the increase in pulmonary arterial pressure was enhanced by nicotinamide post-treatment. Following I/R, the inducible nitric oxide synthase (iNOS) mRNA expression was enhanced. Nicotinamide reduced the iNOS expression. The results suggest that nicotinamide exerted a protective effect on the acute lung injury caused by ischaemia/reperfusion. The mechanisms may be mediated through the inhibition on the poly (adenosine diphosphate-ribose) polymerase activity, inducible nitric oxide synthase expression and the subsequent suppression of nitric oxide, free radicals and pro-inflammatory cytokines with restoration of adenosine triphosphate.

Diagnostic value of tumor markers in lung adenocarcinoma-associated cytologically negative pleural effusions.

Cytology fails to detect neoplastic cells in approximately 40% to 50% of malignant pleural effusions (PEs), which commonly accompany lung adenocarcinomas. The diagnostic accuracy of various tumor markers in lung adenocarcinoma‐associated cytologically negative pleural effusions (LAC‐CNPEs) has been poor. The current study attempted to maximize diagnostic efforts in distinguishing LAC‐CNPEs from benign PEs.

High seroprevalence of human herpesvirus type 8 in patients with end-stage renal disease in Taiwan

BACKGROUND Human herpesvirus type 8 (HHV-8) is the aetiologic agent of Kaposis sarcoma (KS). The incidence of KS in renal transplant patients is much higher than in healthy controls. The risk is even higher among recipients seropositive for HHV-8 before transplantation. Patients with end-stage renal disease (ESRD) are immunocompromised and are candidates for renal transplantation, but HHV-8 seroprevalence in ESRD patients has not been well documented. OBJECTIVES This study aimed to evaluate HHV-8 seroprevalence in ESRD patients in a cohort in Taiwan. STUDY DESIGN Blood samples collected from 149 ESRD patients and 149 age- and sex-matched healthy controls were analysed for HHV-8 antibody with immunofluorescence assay (IFA) and enzyme-linked immunosorbent assay (ELISA) and for HHV-8 DNA with polymerase chain reaction. RESULTS Seropositivity and titres for HHV-8 antibodies with IFA as well as seropositivity with ELISA were significantly greater in ESRD patients than in healthy controls (P=0.006, 0.001 and 0.003, respectively). Patients with a history of taking herbal medicine had significantly greater ELISA positivity than those without such a history (P=0.004). ELISA positives, particularly patients, had much higher IFA antibody titres than ELISA negatives (P<0.0001). Seropositivity in ESRD patients was not related to lymphopaenia, monocytosis, dialysis duration or a history of transfusion. Two diabetic ESRD patients were positive for HHV-8 DNA. CONCLUSIONS ESRD patients had significantly greater HHV-8 seropositivity than healthy controls in Taiwan. This association seems to be related to the geographic location of the cohort and invites further studies for the early association of HHV-8 infection in ESRD patients and risk for KS.

Human Herpesvirus Type 8 in Patients With Cirrhosis Correlation With Sex, Alcoholism, Hepatitis B Virus, Disease Severity, and Thrombocytopenia

Immunologic abnormalities in patients with cirrhosis strongly correlate with severity of liver cirrhosis. The association between cirrhosis and human herpesvirus type 8 (HHV-8) infection is unclear. Plasma samples were obtained from 74 healthy control subjects and 59 patients with cirrhosis. The seropositive rates for HHV-8 antibodies in patients with cirrhosis (25/59 [42%]) were significantly higher than that in healthy control subjects (18/74 [24%]; P = .027), particularly in men (P = .027), patients with alcohol-related cirrhosis (P = .032), and patients with thrombocytopenia (P = .019) or Child-Pugh class C cirrhosis (P = .018) or both (P = .015), or hepatitis B virus (HBV) infection (P = .003). Antibody titers in seropositive patients also significantly exceeded those in healthy control subjects (P = .008). All subjects were negative for anti-HIV. In Taiwan, cirrhosis is associated with HHV-8 infection, particularly in men, patients with Child-Pugh class C cirrhosis and/or thrombocytopenia, and patients with alcohol- or HBV-related cirrhosis.

Expression of Estrogen and Progesterone Receptor in Tumor Stroma Predicts Favorable Prognosis of Cervical Squamous Cell Carcinoma

Objectives The aim of this study was to investigate the expression of estrogen receptor &agr; (ER&agr;) and progesterone receptor B (PRB) in the stroma and carcinoma tissues of cervical cancer and their relationship to clinical characteristics and the status of human papillomavirus (HPV) infection. Methods Expressional levels of ER&agr; and PRB in tissue blocks of 95 cervical carcinomas were independently scored by 2 pathologists. Human papillomavirus DNA, viral load, and genotypes were determined by polymerase chain reaction. Clinical characteristics were reviewed from chart and cancer registry. Results Estrogen receptor &agr; and PRB were mainly expressed in the stroma but not in the carcinoma tissues of the cervical cancer, and their expressions were highly correlated. More stromal ER&agr;s were found in early-stage tumors than in advanced-stage tumors. Greater stromal expressions of ER&agr; and PRB were associated with a more favorable prognosis (P = 0.018 and P = 0.004, respectively). The expressions were not related to the differentiation of cancer, the status of HPV infection, the HPV load, or the genotype. In multivariate analysis, stromal ER&agr; and PRB expressions were independently associated with a lower risk of mortality. The adjusted hazard ratios of mortality for low and high expressions of ER&agr; were 0.19 (95% confidential interval [95% CI], 0.04–0.87) and 0.15 (95% CI, 0.03–0.81), respectively, whereas for low and high expressions of PRB hazard ratios were 0.46 (95% CI, 0.19–1.16) and 0.24 (95% CI, 0.06–0.96), respectively. Conclusions This study showed that stromal ER&agr; and PRB expressions are independent prognostic indicators of cervical squamous cell carcinoma.

Predictors of seropositivity for human herpesvirus type 8 in patients with mild cirrhosis

The high seroprevalence of human herpesvirus type 8 (HHV-8) in moderate or severe cirrhotics appears to be associated with male sex, hepatitis B virus (HBV) infection, alcoholism, and disease severity. The status of HHV-8 infection in mild cirrhotics remains unclear. Plasma samples collected from 93 mild cirrhotics and 93 age- and sex-matched healthy controls were analyzed for HHV-8 antibody and HHV-8 DNA. Mild cirrhotics had higher seropositivity for HHV-8 antibodies than healthy controls (P=0.0001). Univariate logistic regression analysis revealed that an age ≥55 years (odds ratio (OR) 2.88, P=0.02), hepatitis C virus (HCV) infection (OR 3.42, P=0.01), and hepatitis activity (OR 4.10, P=0.004) were associated with HHV-8 seropositivity in cirrhotics. Stepwise multivariate logistic regression analysis confirmed that age ≥55 years (adjusted OR (aOR) 1.92, P=0.04) and hepatitis activity (aOR 3.55, P=0.005) were independent factors. The rate of hepatitis activity was higher in HCV-infected than in HBV-infected patients (P<0.0001) and in women than in men (P=0.0001). Cirrhotics who were seropositive for HHV-8 or HCV or had hepatitis activity were significantly older (P=0.02, <0.0001 and <0.0001, respectively). Plasma samples from all participants were negative for HHV-8 DNA. HHV-8 antibody titers in mild cirrhotics also markedly exceeded those in controls (P<0.0001), as did those in patients ≥55 years old vs. younger patients (P=0.01), those in patients with vs. without HCV infection (P=0.0008), and those in patients with vs. without hepatitis activity (P=0.0005). Mild cirrhotics had high HHV-8 seroprevalence and HCV infection, and, in particular, old age and hepatitis activity were predictors.

Effect of uraemic status on immunofluorescence and enzyme-linked immunosorbent assays for detection of human herpesvirus type 8 antibodies

Summary Our previous study showed that human herpesvirus type 8 (HHV-8) seroprevalence was significantly higher in patients with end-stage renal disease (ESRD) immediately after haemodialysis than in healthy controls based on an immunofluorescence assay (IFA) and an enzyme-linked immunosorbent assay (ELISA). However, other studies indicated that ESRD patients and healthy controls had similar HHV-8 seroprevalence. This study aimed to investigate whether this discrepancy is due to the effect of uraemic status. Plasma samples from 162 ESRD patients, taken immediately before and after haemodialysis, and 162 age and sex matched healthy controls were analysed for HHV-8 antibodies using both IFA and ELISA. HHV-8 seropositivities based on IFA and ELISA, both before and after haemodialysis, were significantly greater in ESRD patients than in healthy controls (p < 0.008 for all comparisons). The seropositivities and antibody titres of ESRD patients obtained with IFA were similar before and after haemodialysis. Seropositivities based on ELISA were identical before and after haemodialysis. The seropositivities obtained with the IFA markedly exceeded those with ELISA in each group of subjects (p < 0.0001 for all comparisons). Uraemic status did not significantly affect the IFA or ELISA results for HHV-8 antibodies.