Impact of adjuvant systemic chemotherapy on postoperative survival in patients with high-risk urothelial cancer

BACKGROUND: The objective of this study was to retrospectively investigate the effectiveness of adjuvant combination chemotherapy for locally advanced urothelial cancer. METHODS: Between 1987 and 1998, 56 patients with locally advanced bladder (n = 27) or upper urinary tract (n = 29) cancer (pathological stage T3, T4 or N1, N2 and M0) were treated by radical cystectomy or radical nephroureterectomy and regional lymphadenectomy. Thirty-one patients had lymph node-positive disease and 25 patients did not. Twenty patients underwent adjuvant chemotherapy and 36 patients were observed after surgery. Cox proportional hazards models were used to determine the impact of numerous clinicopathological findings on survival. A subgroup analysis of patients with lymph node-positive disease was conducted to evaluate disease-free survival and overall survival rates. RESULTS: In this series, the median follow-up period was 39 months (range, 4-163) after surgery. Disease-free and overall survival rates of all 56 patients were 45% and 58%, respectively, at 3 years. Only lymph node status was significantly associated with disease-free and overall survival in the multivariate analyses. In a subgroup analysis of patients with lymph node-positive disease, 16 patients who underwent adjuvant chemotherapy had superior disease-free survival compared to 15 patients with no adjuvant chemotherapy (P = 0.0376). CONCLUSION: These findings show that the prognosis of advanced urothelial cancer is significantly associated with nodal status. Furthermore, adjuvant combination chemotherapy has a positive impact on survival in patients with lymph node-positive disease.     

PROTO-ONCOGENE EXPRESSION IN HUMAN GLOMERULAR DISEASES

The expression of the protein products and mRNA of c- fos , c- myc , p53, and c- raf was examined in normal renal tissues and biopsy specimens from 73 patients with various glomerular diseases. Immunofluorescent staining showed that there were cell nuclei stained for c-Fos, c-Myc, and p53, and cytoplasm positive for c-Raf, in the glomeruli of patients with proliferative types of glomerulonephritis, including IgA nephritis and lupus nephritis, and in patients with focal glomerular sclerosis. Glomerular expression of c- fos and c- myc mRNA was detected by in situ hybridization. The number of proto-oncogene-positive glomerular cells was significantly higher in lupus nephritis, IgA nephritis, and focal segmental sclerosis, as compared with minimal change nephrotic syndrome and normal specimens. In IgA nephritis, the population of glomerular cells positive for c-Fos and c-Myc and the grade of c-Raf immunoreactivity were significantly correlated with the proportion of proliferating cell nuclear antigen (PCNA)-positive glomerular cells, with histological grading of mesangial hypercellularity and matrix increase, and with the magnitude of proteinuria. These data indicate that proto-oncogene expression is associated with mesangial proliferation and matrix expansion in proliferative types of glomerulonephritis and in focal glomerular sclerosis.     

The clinical values of squamous cell carcinoma antigen and carcinoembryonic antigen in patients with cervical cancer treated with concurrent chemoradiotherapy

The objective of this study was to determine the prognostic significance of the pre- and posttreatment serum levels of the squamous cell carcinoma antigen (SCC-Ag) and carcinoembryonic antigen (CEA). From 2001 to 2005, 211 patients were treated with concurrent chemoradiotherapy (CCRT). The SCC-Ag and CEA levels were measured before treatment, 1 month after treatment, and during the follow-up. The association between the pretreatment tumor marker levels and the clinical prognostic factors was evaluated. The frequency of complete remission (CR) and the normalization of the posttreatment tumor marker were also analyzed. The pretreatment serum levels of CEA and SCC-Ag were elevated in 68 (32.2%) and 148 (70.1%) patients, respectively. The number of patients with an elevated pretreatment SCC-Ag level was associated with the FIGO stage, tumor volume, and pelvic lymph node status. The pretreatment CEA was only significantly related to the tumor volume and pelvic lymph node involvement. One month after completing CCRT, the CEA and SCC-Ag levels were normalized in almost all patients with an incidence of 88.2% (60/68) and 93.2% (138/148), respectively. Among the patients who gained CR with a previously elevated pretreatment CEA and SCC-Ag, the values were normalized in 92.1% (58/63) and 96.4% (134/139) at 1 month, respectively. Combination assays of the pre- and posttreatment serum CEA and SCC-Ag levels appear to be useful for both predicting the prognosis and estimating the clinical response in cervical cancer. However, the routine combined measurement with SCC-Ag of CEA in all patients had limited additional effect in predicting the prognostic significance.     

Erythrocyte thiopurine methyltransferase activity in a Korean population

Thiopurine methyltransferase (TPMT) is the enzyme responsible for the S-methylation of thiopurine drugs. The enzyme, present in human red blood cells (RBC), is known to exhibit genetic polymorphism and interethnic differences in its activity have been demonstrated. We have studied the role of TPMT polymorphism in Koreans and compared enzyme activity between this and other ethnic groups. In a population of 360 unrelated healthy Korean subjects TPMT activity showed a large interindividual variation ranging from 3.2 to 22.9 nmol ml^-1 packed RBC h^-1 with a median value of 12.0 and mode of 11.0 nmol ml^-1 packed RBC h^-1. The enzyme activity was higher in male subjects than that in female (median values; 12.2 vs 11.2, 95% confidence interval of the difference; –2.1, 4.0 nmol ml^-1 packed RBC h^-1). All subjects had detectable TPMT activity, but contrary to previous reports in other ethnic groups, this was distributed unimodally. The median RBC TPMT activity was very similar to values found in Caucasian populations, higher than in Floridian blacks and lower than that of a Norwegian Saami population.     

Structure-antitumor and hemolytic activity relationships of synthetic peptides derived from cecropin A-magainin 2 and cecropin A-melittin hybrid peptides

The hybrid peptide (CA-ME) derived from cecropin A(1–8) and melittin(1–12) has potent antibacterial and antimalarial activities. Because the N-terminal sequence 1–12 of magainin 2 is similar to melittin(1–12), CA-MA with CA(1–8) and MA(1–12) and their analogues were designed and synthesized. Antitumor activities of these peptides were evaluated using three small cell lung cancer cell lines. Greater antitumor activity was observed when the residues 16, 18 and 19 of the peptide were hydrophobic (Leu or Val), basic (Lys) and basic (Lys), respectively. The IC₅₀ values of the peptides with the residues were 2 to 4 μm . Residue 12 was related to hemolytic activity rather than antitumor activity. Increase in amphipathicity of P4 enhanced hemolytic activity without significant change in antitumor activity. The α-helicity of the peptides in a 30 mm sodium dodecyl sulfate solution was more closely correlated to hemolytic activity than antitumor activity.     

Effect of Thioridazine or Chlorpromazine on Increased Hepatic NAD+ Level in Rats Fed Clofibrate,a Hypolipidaemic Drug

The effect of the phenothiazines, thioridazine and chlorpromazine, on the increased hepatic NAD+ level of rats fed clofibrate, a hypolipidaemic drug, has been investigated. Short-term (6 days) addition of phenothiazines to the diet negatively affected diet intake and body-weight gain, but increased liver weight and hepatic NAD+ levels, which was synergistic to clofibrate. The phenothiazines were shown to inhibit hepatic peroxisomal fatty acid oxidation in-vivo, as determined by the increased residual catalase activity. In hepatocytes prepared from clofibrate-fed rats, phenothiazines inhibited not only peroxisomal but also mitochondrial fatty acid oxidation to the same extent. In the hepatocytes, NAD+ was maintained at the high level until the phenothiazine concentration was increased to 0–2 mM. The result suggests that the increase of hepatic NAD+ in rats fed Clofibrate is not related to peroxisomal fatty acid oxidation.     

Significance of electrostimulation in detecting neurovascular bundle during radical prostatectomy

OBJECTIVE: The reported rate of erectile dysfunction after nerve-sparing prostatectomy varies according to physicians. Because exact preservation of the neurovascular bundle (NVB) solely depends on the judgment of the physician, he or she should try to correctly identify the NVB and also avoid neurophysiologic injury of the NVB during the procedure. The purpose of the present study is to assess the status of the NVB preservation by physician's judgment at the operation, the changes in intracavernous pressure related to intraoperative electrical stimulation and postoperative histopathological examination. PATIENTS AND METHODS: Thirty-eight patients who underwent nerve-sparing radical prostatectomy judged by intraoperative electrical stimulation of the NVB were included in this study. Bilateral, unilateral and non-nerve-sparing procedures were performed in 18, 17, and 3 cases, respectively. The NVB preservation evaluated by intraoperative physician's judgment was compared to that evaluated by postoperative histopathological examination. Furthermore, the NVB preservation evaluated by intraoperative electrical stimulation was compared to that by physician's judgment and postoperative histopathological examination. RESULTS: For 68 of 76 NVB (89.5%), intraoperative subjective judgment and histopathological assessment were identical. For 66 of 76 NVB (86.8%), electrical stimulation findings and the physician's judgments were identical, and for 70 of 76 NVB (92.1%), electrical stimulation findings and histopathological findings were identical. CONCLUSION: Even if physicians are convinced of a successful nerve-sparing procedure, there are some cases in which the NVB is not preserved accurately or neurophysiological damage is suffered. Therefore, intraoperative electrical stimulation of the NVB as well as the cavernosal nerve is very useful in evaluation of NVB preservation.     

正常人体呼吸频率调节下血压即时变异与心率变异关系的研究

目的探讨人体呼吸频率调节下血压即时变异(blood pressure instant variability,BPIV)与心率变异(HRV)的关系。方法将52名健康受试者随机分为两组,分别在改变呼吸频率5-10-15次/min(A组,n=25)和8-12-16次/min(B组,n=27)的条件下,同步记录心电,血压和呼吸,并进行分析。结果在10-15次/min和8-12-16次/min不同频率的呼吸调节下,R-R变化趋势、血压-血压变化趋势和呼吸波变化趋势完全同步。呼吸频率/心搏频率与呼吸峰中心频率(RSP)、BPIV、HRV的中心频率的相关系数分别为0.924、0.902、0.913。在5次/min频率的呼吸调节下,R-R变化趋势、血压-血压变化趋势和呼吸波变化趋势出现了不同步现象。结论在一定呼吸频率调节下,BPIV符合呼吸性窦性心律不齐的生理机制,也符合呼吸性窦性心律不齐形成的心率变异机制,是RR间期变化的二次效应。但当呼吸频率过低的情况下,BPIV不符合呼吸性窦性心律不齐形成的心率变异机制。