Risk group stratification to predict recurrence after transurethral resection in Japanese patients with stage Ta and T1 bladder tumours: validation study on the European Association of Urology guidelines

Study Type – Therapy (case series)
Level of Evidence 4 What’s known on the subject? and What does the study add? EAU guidelines on non‐muscle‐invasive bladder tumours have been widely used for the prediction of recurrence after TUR. However, there are substantial differences in bladder cancer incidence and mortality rates between European countries and Japan. This study provides useful factors for predicting recurrence and validation of EAU guidelines on the risk group stratification to predict recurrence in Japanese patients with stage Ta and T1 bladder tumours.

OBJECTIVE

• ? To validate the European Association of Urology (EAU) guidelines on risk group stratification to predict recurrence in Japanese patients with stage Ta and T1 bladder tumours.

PATIENTS AND METHODS

• ? A cohort of 592 Japanese patients who were treated with transurethral resection (TUR) and histopathologically diagnosed with Ta and T1 urothelial carcinoma of the bladder were enrolled in this retrospective study.
• ? The primary endpoint of the present study was recurrence‐free survival, and the median follow‐up duration was 37 months in recurrence‐free survivors.

RESULTS

• ? Multivariate Cox proportional hazards regression analysis showed that the Eastern Cooperative Oncology Group performance status (ECOG PS), prior recurrence rate, number of tumours and T category were independent predictors of time to recurrence (P < 0.05). According to the EAU guidelines for predicting recurrence, the vast majority of Japanese patients were classified into intermediate risk.
• ? The intermediate‐risk patients were further divided into intermediate‐low‐risk and intermediate‐high‐risk subgroups based on the European Organization for Research and Treatment of Cancer risk table, and a significant difference in the recurrence‐free survival rates was found between these subgroups (P < 0.001).
• ? It was also found that patients with high risk combined with intermediate‐high risk had significantly poorer recurrence‐free survival rates than those with low risk combined with intermediate‐low risk (P < 0.001).

CONCLUSIONS

• ? This is the first report on the ECOG PS as a potentially useful predictor for bladder tumour recurrence.
• ? The risk group stratification of the EAU guidelines for recurrence might not be applicable to Japanese patients with Ta and T1 bladder tumours, but the subgroup classification of intermediate risk could be appropriate.

     

Efficacy of calcium channel blocker in the secondary prevention of myocardial infarction--retrospective analysis of the 10-year prognosis or coronary thrombolysis-treated patients.

BACKGROUND: Calcium channel blockers (CCBs) may have a positive influence on the long-term prognosis of Japanese patients with ischemic heart disease. METHODS AND RESULTS: The effect of nifedipine-retard (NR) (n=202) compared with that of non-CCB treatment (n=92) on the secondary prevention of myocardial infarction (MI) was retrospectively investigated in patients who had survived acute MI between 1987 and 1996. The primary endpoint was the occurrence of cardiac death or non-fatal MI. The median follow-up was 6.3+/-2.4 years. The incidence of cardiac events was 8.9% in the NR group and 14.1% in the non-CCBs group (p=0.14, odds ratio (OR): 0.584, 95% confidence interval (CI): 0.286-1,193). However, subanalysis revealed that NR significantly reduced the incidence of cardiac events in patients aged less than 55 years (4.2 vs 18.2%, p=0.016, OR: 0.180, 95%CI: 0.045-0.721) and those who did not smoke (8.6 vs 16.4%, p=0.048, OR: 0.462, 95%CI: 0.203-0.999). CONCLUSION: Although this was a retrospective analysis, it showed that NR did not cause an increase in the incidence of cardiac events in post-MI patients; it even prevented cardiac events, especially in those who were less than 55 years of age and in non-smokers, suggesting the potential usefulness of CCBs in the secondary prevention of MI in Japan.     

Long-term renoprotective effect of combination therapy with prostaglandin E1 and angiotensin-converting enzyme inhibitor in patients with chronic renal failure.

Angiotensin-converting enzyme inhibitors (ACE-I) have a renoprotective effect in patients with chronic renal failure. Prostaglandins (PGs) have also been shown to ameliorate renal impairment. Although these two have different mechanisms-ACE-I reduces intraglomerular pressure by dilating the efferent arterioles, while it is thought that PGs may increase intraglomerular pressure--coadministration of these drugs may have an additive effect. Administration of a PG with an ACE-I might have an additive effect on chronic renal failure. However, there have been no studies on the efficacy of such a combination therapy. This study was conducted to determine whether combination therapy with PGE1 and an ACE-I might have a long-term benefit on chronic renal failure. Sixty patients with chronic renal disease receiving an ACE-I in advance were assigned to receive an ACE-I alone or an ACE-I plus PGE1. Blood pressure, blood chemistry, urinary protein excretion, and the changes in the reciprocal of serum creatinine (delta1/Cr) were monitored once monthly for an average of 36.5 months. In patients treated only with an ACE-I, the progression of renal failure did not change with time. In contrast, the decline of renal function was significantly reduced with the combination therapy. The renoprotective effect of the combination therapy was not exerted by reduced proteinuria or by decreased blood pressure. PGE1 may reinforce the renoprotective effects of ACE-I to prevent the progression of chronic renal failure.     

Important role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice

We have recently demonstrated that endogenous erythropoietin (Epo)/Epo receptor (EpoR) system plays an important protective role in hypoxia-induced pulmonary hypertension. However, it remains to be examined whether vascular EpoR system contributes to angiogenesis in response to ischemia. We examined angiogenesis in EpoR(-/-)-rescued mice that lack EpoR in most organs including cardiovascular system except erythroid-lineage cells. Two weeks after femoral artery ligation, blood flow recovery, activation of VEGF/VEGF receptor system, and mobilization of endothelial progenitor cells were all impaired in EpoR(-/-)-rescued mice as compared with wild-type (WT) mice. Bone marrow (BM) transplantation with WT-BM cells in EpoR(-/-)-rescued mice partially but significantly improved blood flow recovery after hindlimb ischemia. The extent of VEGF upregulation and the number of BM-derived cells in ischemic tissue were significantly less in EpoR(-/-)-rescued mice compared with WT mice even after BM reconstitution with WT-BM cells. Similarly, the recovery of blood flow was significantly impaired in recipient EpoR(-/-)-rescued mice that had been transplanted with WT-BM or EpoR(-/-)-rescued-BM as compared with recipient WT mice. Furthermore, the Matrigel implantation assay and aortic ring assay showed that microvessel growth in vitro was significantly reduced in EpoR(-/-)-rescued mice as compared with WT mice. These results indicate that vascular EpoR system also plays an important role in angiogenesis in response to hindlimb ischemia through upregulation of VEGF/VEGF receptor system, both directly by enhancing neovascularization and indirectly by recruiting endothelial progenitor cells and BM-derived proangiogenic cells.     

Acute regulation of the epithelial sodium channel gene by vasopressin and hyperosmolality.

The amiloride-sensitive epithelial sodium channel (ENaC) plays a key role in sodium reabsorption in the collecting ducts. We examined ENaC mRNA distribution along the nephron and acute effects of vasopressin and hyperosmolality on ENaC mRNA expression. ENaCalpha, beta, and gamma mRNA expressions were observed in cortical, outer medullary and initial inner medullary collecting ducts (CCD, OMCD and ilMCD, respectively). ENaCalpha mRNA expression was also observed in medullary and cortical thick ascending limbs (MAL and CAL, respectively), while ENaCbeta and gamma mRNA expressions were not observed. Furthermore, ENaCalpha mRNA expression in MAL but not in collecting ducts was stimulated by acute exposure to arginine vasopressin (AVP), 8-(4-chlorophenylthio) (CPT)-cAMP and hyperosmolality. However, the physiological significance of these effects is not known, since ENaC protein is reported to be absent in MAL. These data suggest that ENaCalpha mRNA expression in MAL but not in collecting ducts is acutely regulated by AVP and hyperosmolality. The absence of stimulation of ENaCalpha mRNA expression in collecting ducts suggests the physiological significance of ENaCbeta and gamma mRNA for acute regulation by vasopressin. Determining the physiological significance of the acute effect of vasopressin in MAL will require further investigations.     

Detection of CMV in plasma and aqueous humor specimens from AIDS patients with CMV retinitis using the amplicor CMV test

A DNA hybridization test (the Amplicor CMV test) for CMV DNA was used to detect CMV DNA in paired plasma and aqueous humor specimens from 37 AIDS patients with ophthalmoscopically diagnosed CMV retinitis. CMV was detected in 25/37 (67.6%) plasma specimens and in 32/37 (86.5%) aqueous humor specimens. Thus, the Amplicor CMV test using aqueous humor specimens seems to be a useful diagnostic test for CMV retinitis and one that is more sensitive than determination of CMV DNA in plasma specimens.     

Space-time database for standardization of adult magnetocardiogram-making standard MCG parameters

Background: The magnetocardiogram (MCG) is a promising medical tool for detecting and visualizing abnormal cardiac electrical activation in heart-disease patients. However, there is no large-scale MCG database of healthy subjects, and there is little knowledge of gender- and age-related influences on MCG data.
Methods and Results: We obtained MCG data from 869 subjects (554 men, 315 women) using a conventional 64-channel MCG system, which covers the whole heart. Electrocardiogram (ECG) data were also obtained; 464 people (268 men, 196 women) were identified as a normal group using ECG data. Time intervals (PQ, QRS, QT, and QTc), current distributions (maximum current vector (MCV), and the total current vector (TCV)) of MCG data of the 464 normal subjects were analyzed to obtain basic MCG parameters.
Although mean values of PQ and QRS intervals of the male subjects were slightly longer than those of the female subjects, no intervals were correlated with gender or age. The correlation between PQ intervals of ECG and those of MCG was better than the correlation between QRS and QT intervals of ECG and those of MCG. Both MCV and TCV angles were much smaller than the electrical-axis angle in ECG. Although TCVs of the QRS and T waves were stable, the women's mean T-wave-TCV angles significantly increased with age. The maximum amplitude of the P wave was about 1.7 pT, and the value of the QRS complex was about 20–25 pT. Moreover, the T-wave amplitude decreases with age.
Conclusion: The MCG standard space-time parameters determined here provide a normal range for MCG parameters.