Efficacy of Intravesical Instillation Therapy with Low-Dose Tokyo-172 Bacillus Calmette-Guérin to Prevent Recurrence of Non-Muscle-Invasive Bladder Cancer and Treat Carcinoma in situ: A Multi-Institutional Retrospective Study.

INTRODUCTION: There are various doses, durations, and strains of bacillus Calmette-Guérin (BCG) intravesical instillation therapy, but optimal treatment has not yet been established. We retrospectively investigated the efficacy and safety of low-dose BCG therapy for non-muscle-invasive bladder cancer (NMIBC) and carcinoma in situ (CIS) in a multicenter study. METHODS: From 1991 to 2019, 323 patients who received BCG therapy to prevent recurrence of NMIBC were analyzed as group A. Similarly, 147 patients who received BCG therapy for the treatment of CIS were analyzed as group B. Patients received low- or full-dose Tokyo-172 strain or full-dose Connaught strain, and the three strains were compared. Survival curves were estimated by the Kaplan-Meier method, and independent risk factors for intravesical recurrence were examined by multivariate logistic regression. RESULTS: Recurrence-free survival (RFS) in group A was significantly better for the Connaught strain than the low-dose Tokyo-172 strain (p = 0.026), but not between the low- and full-dose Tokyo-172 strains (p = 0.443). RFS of group B, cancer-specific survival, and progression-free survival in both groups did not show statistically significant differences. Logistic analysis of group A showed that for intravesical recurrence, only pT1 was a significant risk factor, and there were no differences between the BCG strain and dose and no significant factors in group B. There were also no differences in the completion rate in both groups, but adverse events such as urinary frequency and feeling of residual urine were significantly lower with the low-dose Tokyo-172 strain. CONCLUSION: There was no difference in efficacy between the low- and full-dose Tokyo-172 strains, but to minimize adverse events, the low-dose Tokyo-172 strain may be worth considering.

Patients with Non-Muscle-Invasive Bladder Cancer Previously Treated with Nephroureterectomy Have a High Risk of Recurrence after Bacillus Calmette-Guérin Intravesical Instillation Therapy.

BACKGROUND: There is a high incidence of intravesical recurrence after transurethral resection of bladder tumor for non-muscle-invasive bladder cancer (NMIBC). Intravesical instillation of bacillus Calmette-Guérin (BCG) is widely used to prevent recurrence and progression. There are two types of NMIBC: primary NMIBC and subsequent NMIBC after radical nephroureterectomy (RNU). We compared the clinical outcomes of BCG intravesical instillation therapy between the two types of NMIBC. PATIENTS AND METHODS: This study included a total of 357 patients, who received BCG intravesical instillation therapy to prevent recurrence of NMIBC (pTa/pT1) between 1991 and 2019. Among them, 34 patients had subsequent NMIBC after RNU, and the remaining 323 patients had primary NMIBC. This retrospective study analyzed 68 patients extracted by propensity score matching. Survival curves were estimated using the Kaplan-Meier method, and independent prognostic factors for survival were examined by the Cox proportional hazards model. RESULTS: The 3-year recurrence-free survival (RFS) rates in patients with primary NMIBC and subsequent NMIBC after RNU were 70.7% and 54.8%, respectively (p = 0.036). However, there were no significant differences between the two groups in progression-free survival and cancer-specific survival. Multivariate analysis of RFS showed that only a previous history of upper tract urothelial carcinoma was an independent prognostic and predictive factor. CONCLUSION: Patients with subsequent NMIBC after RNU treated with BCG intravesical instillation therapy have a higher risk of recurrence than those with primary NMIBC. Thus, stringent follow-up is necessary for patients with subsequent NMIBC after RNU.

New sandwich-type enzyme-linked immunosorbent assay for human MxA protein in a whole blood using monoclonal antibodies against GTP-binding domain for recognition of viral infection.

OBJECTIVES: To develop a clinically significant and practical enzyme-linked immunosorbent assay (ELISA) for the detection of MxA protein in human whole blood, a biological marker of viral infection. DESIGN AND METHODS: A sandwich ELISA suitable for the measurement of human MxA protein in whole blood was developed using mouse monoclonal antibodies (mAbs) raised against the GTP-binding domain of human MxA protein. Prior to the assay, the whole blood sample was treated with special buffer to extract the MxA protein, improve its stability, and avoid interference from hemoglobin. RESULTS: This ELISA meets all the requirements for use in routine clinical assays, especially in terms of sensitivity (detection limit: 1.3 ng/ml whole blood), accuracy (recovery: 93.0-100.0%), and rapidity (<1.5 h). The present ELISA had a sensitivity of 100% and a specificity of 100% for viral infection when compared to samples from healthy control and 87.1% and 90.9% when compared to samples from the bacterial infection group. CONCLUSION: We have developed a new ELISA for measuring MxA protein in human whole blood using mAbs specific for the GTP-binding domain of MxA. This ELISA has analytical performance enough for routine clinical assay and can be used in detecting the possibility of viral infection.

MxA-based recognition of viral illness in febrile children by a whole blood assay.

Febrile children are often given antibiotics empirically and unnecessarily. MxA is a protein induced in peripheral lymphoid cells by type 1 interferons during active viral infection. The ability of a whole blood ELISA assay for MxA to identify children with viral illness was studied in 122 children who presented with acute onset fever and 52 age-matched healthy controls. The febrile children were divided into three groups according to their final diagnoses: etiologically diagnosed viral infection, clinically diagnosed viral infection, and bacterial infection. MxA levels in the bacterial infection group and controls were similar and low (90.9 +/- 69.7 and 76.9 +/- 63.2 ng/mL, respectively). In contrast, mean MxA levels in the two viral infection groups were higher than in both the bacterial and control groups (719.2 +/- 386.4 and 827.0 +/- 651.1, respectively). A receiver operating characteristic analysis showed that the area under the curve of the MxA level was greater than under the curves of both the white blood cell count and the C-reactive protein concentration. Whole blood assay of MxA is a clinically useful tool for diagnosing viral illness in febrile children and should help reduce use of unnecessary antibiotics.