Can random bladder biopsies be eliminated after bacillus Calmette–Guérin therapy against carcinoma in situ?

Purpose

Intravesical bacillus Calmette–Guérin (BCG) is the standard of care for bladder carcinoma in situ (CIS). The response to BCG therapy against CIS is generally assessed by random bladder biopsy (RBB). In this study, we examined the necessity of routine RBB after BCG therapy.

Methods

We retrospectively identified 102 patients who were initially diagnosed with CIS with or without papillary tumor and received subsequent 6–8-week BCG therapy. Thereafter, all patients underwent voiding cytology analysis, cystoscopy, and RBB to evaluate the effects of BCG therapy. We evaluated the association between clinical parameters (voiding cytology and cystoscopy findings) and the final pathological results by RBB specimens.

Results

According to the pathological results of RBB, 30 (29%) patients had BCG-unresponsive disease (remaining urothelial carcinoma was confirmed pathologically) and 20 were diagnosed with CIS. Positive/suspicious voiding cytology and positive cystoscopy findings were well observed in patients who had BCG-unresponsive disease compared with their counterparts (p?=?0.116, and p?<?0.001, respectively). The sensitivity (Sen.), specificity (Spe.), positive predictive value (PPV), and negative predictive value (NPV) of voiding cytology were 50%, 68%, 39%, and 77%, respectively. The values for cystoscopy findings were as follows: Sen.: 87%, Spe.: 57%, PPV: 46%, and NPV: 91%. The values for their combination (having either of them) were as follows: Sen.: 100%, Spe.: 44%, PPV: 43%, and NPV: 100%.

Conclusion

RBB after BCG therapy for patients with negative voiding cytology and negative cystoscopy may be omitted because their risk of BCG-unresponsive disease is significantly low (NPV: 100%).

     

Hypothermia after cardiopulmonary bypass in man: effects of prostaglandin E1 and phentolamine

The "afterdrop" in body temperature (TEMP) following adequate rewarming from hypothermic cardiopulmonary bypass (CPB) is frequently observed. This temperature drop sometimes accompanied by shivering results in increased myocardial oxygen demand. We investigated the relations between the afterdrop and use of vasodilators after CPB. For vasodilator therapy, PGE1 at the rate of 0.025-0.088 microgram.kg-1.min-1 (Prostaglandin Low Doses, PLD; n = 8), 0.107-0.136 microgram.kg-1.min-1 (Prostaglandin High Doses, PHD; n = 7), or phentolamine at 4.1-5.9 micrograms.kg-1.min-1 (PHENT; n = 8) were intravenously infused in 23 adult patients after CPB. During three hour period after CPB, esophageal, rectal, and forehead TEMP are lower in PHENT than in PGE1 groups. There were significant differences between PHD and PHENT group. Finger tip TEMP was lower in PGE1 groups than in PHENT group. There were significant differences between PHD and PHENT group. There were no differences in systemic arterial pressure, cardiac index (CI) and systemic vascular resistance (SVR) at any point between PHD and PHENT groups. It is concluded that PHENT increases the peripheral skin blood flow and TEMP but decreases the visceral TEMP possibly due to vasodilatation of the skin vessels, while PGE1 decreases skin blood flow and TEMP but increases the visceral TEMP, although SVR clearly decreases at the same rate in the two groups.     

Nondomain biopolymers: Flexible molecular strategies to acquire biological functions

A long-standing assumption in molecular biology posits that the conservation of protein and nucleic acid sequences emphasizes the functional significance of biomolecules. These conserved sequences fold into distinct secondary and tertiary structures, enable highly specific molecular interactions, and regulate complex yet organized molecular processes within living cells. However, recent evidence suggests that biomolecules can also function through primary sequence regions that lack conservation across species or gene families. These regions typically do not form rigid structures, and their inherent flexibility is critical for their functional roles. This review examines the emerging roles and molecular mechanisms of “nondomain biomolecules,” whose functions are not easily predicted due to the absence of conserved functional domains. We propose the hypothesis that both domain- and nondomain-type molecules work together to enable flexible and efficient molecular processes within the highly crowded intracellular environment.     

p53 mutations of lung cancer are not significantly affected by CYP1A1 or GSTM1 polymorphisms

Cytochrome p4501A1 gene (CYP1A1) and glutathione S-transferase mu gene (GSTM1) are involved in the metabolic activation or detoxification of environmental carcinogens including benzo[a]pyrene in tobacco smoke. Individuals with both Val/Val and C type of CYP1A1 (CYP1A1; Val/Val and CYP1A1; C) or homozygous null (-/-) genotype of GSTM1 gene (GSTM1; -/-) show increased susceptibility to lung cancer. The incidence of p53 gene mutations are related to the smoking index of the lung cancer patients. Therefore we determined genotypes of these enzymes and screened p53 gene mutations in 123 non-small cell lung cancer (NSCLC) patients. p53 gene mutations were found in 35% (43/123) of the patients. The incidence of p53 gene mutation CYP1A1; Val/Val (60.0%), CYP1A1; C (50.0%) tended to be higher than those of CYPIAI; Ile/Ile and Ile/Val (40.4%) or CYP1A1; A and B (40.5%). We conclude that the incidence of the p53 mutations does not seem to be significantly affected by only CYP1A1 or GSTM1 polymorphisms in lung cancer patients.     

The anti-proliferative effect of proliferating cell nuclear antigen-specific antisense oligonucleotides on human gastric cancer cell lines

The proliferating cell nuclear antigen (PCNA) is a nuclear protein that leads DNA synthesis by the DNA polymerase delta. As the PCNA gene is strongly expressed in invasive gastric cancer cells with high proliferative activity, PCNA is suspected of playing an important role in the proliferation and advancement of gastric cancer. Thus, the effects of antisense oligonucleotides specific for PCNA mRNA were examined in seven gastric cancer cell lines. It was found that treatment with antisense oligonucleotides at concentrations of 10–40 M dose-dependently inhibited the growth of all cell lines; however, random sequence oligonucleotides did not modify the proliferation of any type of cells. These results indicate that PCNA is essential for cell proliferation in gastric cancer cells, and that the growth inhibitory effect results from the inhibition of PCNA gene expression. Therefore, PCNA-specific antisense oligonucleotides may be effective in the treatment of gastric cancer.     

Mesangial factor V expression colocalized with fibrin deposition in IgA nephropathy

BACKGROUND: Factor V in its active form (Va) plays a key role at the termination of the intrinsic coagulation pathway, serving as a membrane-bound cofactor for the conversion of prothrombin to thrombin by factor Xa. Cross-linked fibrin (XFb) is often observed in mesangial areas in active types of human glomerulonephritis. In this study, to clarify contribution of factor V in intramesangial coagulation, mesangial factor V expression and its relationship to mesangial proliferation and fibrin deposition in IgA nephropathy (IgAN) were investigated. METHODS: Twenty-two patients with IgAN were studied. XFb was detected in renal biopsy specimens using anti-d-dimer antibody combined with plasmin exposure, and factor V was detected with rabbit antibody against human factor V. Double-labeling immunohistochemistry was used to investigate the relationship of the glomerular distribution of factor V to XFb. The relationship of factor V staining to the activity index or XFb deposition was evaluated. The expression of factor V mRNA was assessed by in situ hybridization in relationship to the antigen staining of alpha-smooth muscle actin (alpha-SMA). The ultrastructural distribution of factor V in glomeruli was studied by immunoelectron microscopy. RESULTS: XFb and factor V were observed in the mesangium and along capillary loops in seven and nine specimens, respectively. Factor V had intense, frequent expression in the proliferating and necrotizing areas, showing a significant relationship to XFb (P < 0.05). Furthermore, XFb deposition and factor V expression were markedly correlated with disease activity (P = 0.005 and P = 0.008, respectively). By double-labeling experiments, XFb and factor V were often seen colocalized in mesangial areas of the glomeruli, which showed necrotizing lesions and/or intense cellular proliferation. By in situ hybridization, factor V mRNA was detected mainly in the mesangial cells, which were positive for alpha-SMA, and partly in the endothelial cells. By immunoelectron microscopy, factor V presence was confirmed in the mesangium and endothelium. CONCLUSION: The present findings suggest that factor V is strongly expressed in mesangial cells in active IgAN accompanied with mesangial proliferation and may exert procoagulant activity, leading to intramesangial coagulation.     

Fetal alcohol spectrum disorders (FASD) among Japanese children of alcoholic mothers]

OBJECTIVE: This study was carried out to examine fetal alcohol spectrum disorders (FASD) among Japanese children of alcoholic mothers. This is the first report concerning FASD in Japan. METHODS: The subjects were 30 alcoholic women who were inpatients in the Kurihama Alcoholism Center and had given birth to children. They were subjected to a semi-structured interview by the author. Sixty healthy women who had not drunk during pregnancy were used as a control group, and they also underwent semi-structured interviews. The alcoholic women were divided into two groups, 13 who drunk during pregnancies and 17 who did not drink. Twenty children experienced of prenatal alcohol exposure and 40 children did not. The three groups; i.e., 13 alcoholic mothers who had drunk during pregnancy and their 20 children (ALD group), 17 alcoholic mothers who had not drunk during pregnancy and their 40 children (ALND group) and 60 non-alcoholic control mothers and their 80 children (Control group), were compared concerning the mothers' drinking problems and abnormal deliveries, children's birth weights, congenital abnormalities, abnormalities of the central nervous system and psychological problems. RESULTS: The mean age of onset of problem drinking of the mothers in the ALD group was significantly lower than that in the mothers of the ALND group, and some of the mothers in the ALD group showed alcohol dependence before their pregnancies. The mean birth weights of the children of the ALD group, ALND group and Control group were 2816 g, 3128 g and 3142 g, respectively and the differences were significant. The children of the ALD group had significantly more abnormal birth episodes, developmental retardation and psychiatric symptoms than those in the other two groups. Among 20 children in the ALD group, FASD was suspected in 6 children (10% of the children of alcoholic mothers). Six children had low birth weights, abnormal birth episodes, mental retardation and psychiatric symptoms. CONCLUSION: One third of the Japanese children of alcoholic mothers had experiences of prenatal alcohol exposure and 10% of them had suspected FASD abnormalities.