Notes: Abstract:  CD4+CD25+ T cells are an important population that plays a crucial role in the maintenance of peripheral self-tolerance. Recently, it was shown that the elimination of these cells by in vivo administration of anti-CD25 monoclonal antibody (mAb) caused the regression of highly immunogenic tumors in syngeneic mice. In this study, we examined whether B16F10 melanoma cells regressed with the elimination of CD25+ regulatory T cells. We found the melanoma cells were not affected at all by in vivo anti-CD25 mAb administration alone but tumor rejection resulted in all mice when the administration was combined with IL-12 gene transfer to tumor cells. In vivo, depletion of natural killer (NK) cells or CD8+ T cells cancelled the tumor rejection. NK-cell depletion allowed IL-12-transfected B16F10 melanoma (B16/IL-12) to grow from an early stage and resulted in a more rapid tumor growth of B16/IL-12 than that in mice without administration of anti-CD25 mAb. On the other hand, CD8+ T-cell depletion did not affect the tumor growth in the early phase but allowed B16/IL-12 to grow in rather a late phase and resulted in almost the same degree of tumor growth as in mice without administration of anti-CD25 mAb. In a previous study, we showed that the elimination of CD4+ T cells enhanced the antitumor effect of B16/IL-12 and induced vitiligo-like coat color alteration. Therefore, we also examined the frequency of the change to a vitiligo-like coat color in mice showing tumor rejection caused by CD25+ T-cell elimination to compare with the mechanism enhancing the antitumor effects by cell elimination. The elimination of CD25+ T cells did not induce vitiligo-like coat color changes, though that of CD4+ T cells induced the change in 60% of mice. Furthermore, we confirmed that elimination of CD25+ T cells did not affect the T-helper (Th) 1/Th2 cytokine profile, while that of CD4+T cells abrogated the Th2 cytokines (IL-4 and IL-10) and resulted in a Th1-dominant cytokine profile in the tumor-draining lymph nodes (TDLNs) of B16/IL-12-bearing mice. These results indicate that in vivo depletion of CD25+ regulatory T cells is a potent useful adjuvant in immunotherapy of B16F10 melanoma, when combined with IL-12 gene transfer and that the enhancement of the antitumor effect by CD25+ T-cell depletion is mediated through CD8+ T cells and may differ from the enhancing mechanism caused by CD4+ T-cell depletion.

Notes: Bacillus Calmette-Guerin (BCG) instillation therapy is now a standard therapy for high-risk superficial bladder cancer patients. Although the complete response rate is approximately 70%, extra-vesical progression is sometimes observed. In particular, those patients who present a positive urinary cytology even after complete response from bladder lesion should be thoroughly examined. We present two cases of stromal invasion of the prostate after complete remission by BCG therapy of carcinoma in situ of the ureter and bladder found by transrectal prostate biopsy.

Notes: Background:  The objective of this study was to determine whether renal function influences the acid–base metabolism in patients undergoing orthotopic bladder replacement using intestinal segment.Methods:  Acid–base balance, serum electrolytes and renal function were studied in 30 patients with colon neobladder and 18 patients with ileal neobladder. Mean follow up was 51 months. Effects of renal function on acid–base metabolism in both types of bladder replacement were compared. Therapeutic efficacy of the sodium bicarbonate administration was also evaluated in cases with hyperchloremic acidosis.Results:  No significant differences were observed in any of the variables examined between the colon and ileal neobladder groups, except for potassium concentration. Although metabolic acidosis was detected using the Siggard–Anderson acid–base nomogram in eight (26.7%) and seven (38.9%) patients in the colon and ileal neobladder groups, respectively, this difference was not significant. In both the colon and ileal neobladder groups, the serum creatinine concentrations in patients diagnosed with metabolic acidosis were significantly higher than in those diagnosed with a normal metabolic status. Furthermore, as a result of severe metabolic acidosis, three (10.0%) and three (16.7%) patients in the colon and ileal neobladder groups, respectively, were administered sodium bicarbonate and their metabolic status was fully normalized.Conclusions:  Despite there being no statistical difference, patients with ileal neobladder may more easily develop metabolic acidosis compared with those with colon neobladder. In addition, a close association between the serum creatinine level and the degree of metabolic acidosis was observed in both groups. However, even if severe metabolic acidosis occurs, it is relatively easy to correct using sodium bicarbonate. These findings suggest that it might be safe to use a colon segment for orthotopic bladder reconstruction in patients with higher serum creatinine levels, despite no significant difference in acid–base metabolism and detection rates of metabolic acidosis between the colon and ileal neobladder groups.

Notes: Abstract  We report the case of a female patient with bilateral metachronous adrenocortical cancer who survived long-term after adrenalectomy. In 1991, the patient underwent left adrenalectomy to remove a huge adrenal mass (10 × 9 cm) displaying no hormonal abnormality. Histological diagnosis was adrenocortical cancer. A right adrenal mass (7 × 6 cm) was found 4 years after left adrenalectomy. Right adrenalectomy was performed, and histological diagnosis was again adrenocortical cancer. The patient remains alive with no evidence of disease 8 years after last surgery.

Notes: Background: The objective of the present study was to globally characterize the changes in the gene expression profile in the ileum after long-term urine exposure in a rat ileal augmented bladder model using cDNA microarrays.Methods: Bladder augmentation using the ileum was performed in female 8-week-old rats. The ileal epithelia used for bladder augmentation were harvested 1 and 3 months postoperatively and changes in the gene expression in these tissues were compared with that of intact ileal epithelia from sham-operated rats using cDNA microarrays consisting of 1176 rat genes.Results: Marked changes in gene expression in the ileum used for bladder augmentation were observed for 30 genes (16 up-regulated and 14 down-regulated genes). The differentially expressed genes include those associated with signal transduction, cell adhesion and stress response. Subsequent evaluation of changes in two randomly selected genes from the 30 differentially expressed genes by semiquantitative reverse transcription-polymerase chain reaction demonstrated the reliability of the present cDNA microarray analyses.Conclusion: The present experiments identified an extensive list of genes differentially expressed in the ileum after bladder augmentation, providing valuable information for the pathophysiological assessment of patients who undergo urinary reconstruction and representing a source of novel targets for treating complications after urinary diversion.

Notes: Background: The objective of this study was to retrospectively investigate the effectiveness of transurethral resection of bladder tumor (TURBT) and intravesical instillation therapy for stage T1, grade 3 (T1G3) transitional cell carcinoma (TCC) of the urinary bladder.Methods: Between January 1995 and December 1997, 97 patients with T1G3 TCC of the urinary bladder were treated by TURBT and adjuvant intravesical instillation with bacillus Calmette-Guérin (BCG) or other anticancer agents. The recurrence-free survival rates were evaluated according to several clinicopathological factors. The cases that progressed to muscle invasive disease were also analysed.Results: In this series, the median follow-up period was 25 months (range, 5– 41) after the initial TURBT. Intravesical recurrence was noted in 44 patients (45%), and the 1, 2, and 3 year recurrence-free survival rates were 72%, 58%, and 42%, respectively. Multivariate analyses revealed that the risk of intravesical recurrence was significantly higher for patients who did not receive BCG therapy, irrespective of age, gender, tumor size, multiplicity, pathological stage, concomitant carcinoma in situ, and lymphovascular involvement. Moreover, after a median of 10 months, disease progression occurred in seven patients (7%), of which only one patient was treated by BCG therapy after initial TURBT.Conclusion: These findings suggest that intravesical instillation with BCG combined with TURBT is an effective conservative treatment for T1G3 TCC of the bladder. Patients with negative prognostic factors should be treated by BCG rather than other anticancer agents after TURBT.

Notes: Abstract  Background:  The objectives of the present study were to investigate whether buttressing sutures, which prevent the bladder neck from pulling open as the bladder fills, can promote earlier recovery from urinary incontinence after radical retropubic prostatectomy (RRP) and to identify possible risk factors associated with urinary incontinence after RRP.Methods:  The present study included 72 patients who underwent non-nerve-sparing RRP without neoadjuvant therapy between January and December 2003. Among these 72 patients, intussusception of the bladder neck was performed in 24 who consented to this procedure. In the present series, continence was defined as the absence of any need to use sanitary pads or diapers. Continence was evaluated by a patient interview 1, 3 and 6 months after RRP.Results:  There were no significant differences in clinicopathological characteristics between patients with and without intussusception of the bladder neck. The percentage of continent patients 1, 3 and 6 months after RRP was 34.7%, 63.9% and 95.8%, respectively, and there were no significant differences in continence between the two groups at any time point. Among several factors examined, only bladder neck preservation was an independent predictor of recovery from urinary incontinence 1 and 3 months after RRP.Conclusions:  These findings suggest that it would be important to preserve the bladder neck for early return to continence after non-nerve-sparing RRP; however, intussusception of the bladder neck may not offer significant improvement in earlier return of urinary control.

Notes: Aim: To evaluate the feasibility and usefulness of high dose chemotherapy including paclitaxel (T-ICE) combined with peripheral blood stem cell transplantation (PBSCT) for male germ cell tumor.Methods: Five male patients with advanced germ cell tumor underwent 1–6 courses of high dose chemotherapy including paclitaxel (T-ICE; 175 mg/m2 of paclitaxel, 1250 mg/m2 of carboplatin, 1500 mg/m2 of etoposide and 7.5 g/m2 of ifosfamide) with PBSCT after 2–3 courses of induction chemotherapy (PEB or VIP).Results: In all patients, serum marker levels decreased to within the normal range by T-ICE. Two patients underwent resection of residual tumor. In one patient, viable cancer cells were detected in resected lymph node tissue and adjuvant chemotherapy was then performed. Although the follow-up period was short (7–15.5 months), four of the five patients (80%) showed no evidence of recurrent disease. No significant differences in side-effects were noted between T-ICE and conventional high dose ICE, which was previously performed in 39 patients at the Division of Urology, Kobe University Graduate School of Medicine, Japan.Conclusions: High dose chemotherapy, including T-ICE, combined with PBSCT showed an almost identical degree of side-effects as seen in previous high dose chemotherapy without paclitaxel. Although 80% of the patients showed no evidence of disease so far, the efficacy of T-ICE should be evaluated with more patients and longer follow up.