Kiichiro Kodaira

The Predictive Value of C-reactive Protein for Prognosis in Patients with Upper Tract Urothelial Carcinoma Treated with Radical Nephroureterectomy: A Multi-institutional Study

BACKGROUND Few studies have discussed the prognostic impact of serum C-reactive protein (CRP) level in upper tract urothelial carcinoma (UTUC). OBJECTIVE To investigate whether the perioperative level of CRP provides additional prognostic information following radical nephroureterectomy (RNU). DESIGN, SETTING, AND PARTICIPANTS A total of 564 patients with UTUC from a retrospective multi-institutional cohort were included. The median follow-up was 32 mo. INTERVENTION All patients underwent RNU without neoadjuvant chemotherapy, while 106 patients (18.8%) received adjuvant chemotherapy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Associations between perioperative CRP level and outcome were assessed using multivariate analysis. A serum CRP level >0.50mg/dl was defined as elevated. RESULTS AND LIMITATIONS Preoperative CRP (pre-CRP) level was elevated in 136 patients (24.1%). Multivariate analysis showed that pre-CRP elevation was an independent predictor of subsequent disease recurrence (hazard ratio [HR]: 1.47 for CRP 0.51-2.00; HR: 1.89 for CRP >2.00). Five-year recurrence-free survival rates were 69.2% in patients with pre-CRP levels ≤ 0.50 mg/dl, 54.3% in patients with pre-CRP levels between 0.51 and 2.00 mg/dl, and 35.4% in patients with pre-CRP levels >2.00 mg/dl (p<0.001). Similar results were found in cancer-specific mortality, showing that pre-CRP elevation was an independent predictor of worse outcome (HR: 1.74 for CRP 0.51-2.00; HR: 2.31 for CRP >2.00). In a subgroup analysis of the elevated pre-CRP group, postoperative normalisation of CRP level was an independent predictor of better outcome. This study is limited by its retrospective nature as well as its heterogeneous group of patients and variable follow-up protocols resulting from the multi-institution design. CONCLUSIONS Serum CRP may become a possible biomarker in UTUC, suggesting that patients with an elevated pre-CRP level could be predicted to have subsequent disease recurrence and cancer-specific mortality, while postoperative normalisation of CRP level was an independent predictor for prognosis.

Vitamin E succinate induced apoptosis and enhanced chemosensitivity to paclitaxel in human bladder cancer cells in vitro and in vivo

There have been several studies on the antitumor activities of vitamin E succinate (α‐TOS) as complementary and alternative medicine. In the present study, we investigated the cytotoxic effect of α‐TOS and the enhancement of chemosensitivity to paclitaxel by α‐TOS in bladder cancer. KU‐19‐19 and 5637 bladder cancer cell lines were cultured in α‐TOS and/or paclitaxel in vitro. Cell viability, flow cytometric analysis, and nuclear factor‐kappa B (NF‐κB) activity were analyzed. For in vivo therapeutic experiments, pre‐established KU‐19‐19 tumors were treated with α‐TOS and/or paclitaxel. In KU‐19‐19 and 5637 cells, the combination treatment resulted in a significantly higher level of growth inhibition, and apoptosis was significantly induced by the combination treatment. NF‐κB was activated by paclitaxel; however, the activation of NF‐κB was inhibited by α‐TOS. Also, the combination treatment significantly inhibited tumor growth in mice. In the immunostaining of the tumors, apoptosis was induced and proliferation was inhibited by the combination treatment. Combination treatment of α‐TOS and paclitaxel showed promising anticancer effects in terms of inhibiting bladder cancer cell growth and viability in vitro and in vivo. One of the potential mechanisms by which the combination therapy has synergistic cytotoxic effects against bladder cancer may be that α‐TOS inhibits NF‐κB induced by chemotherapeutic agents. (Cancer Sci 2009;)

Impact of an Adjuvant Chemotherapeutic Regimen on the Clinical Outcome in High Risk Patients with Upper Tract Urothelial Carcinoma: A Japanese Multi-Institution Experience

PURPOSE Current guidelines do not yet provide any recommendations for adjuvant chemotherapy in patients with upper tract urothelial carcinoma managed with radical nephroureterectomy. We evaluated whether an adjuvant chemotherapeutic regimen would affect the clinical outcome in patients with high risk upper tract urothelial carcinoma. MATERIALS AND METHODS We identified 873 patients who had undergone radical nephrouretectomy for localized upper tract urothelial carcinoma at 14 Japanese institutions between 1993 and 2011. We assessed whether the type of regimen, such as methotrexate, vinblastine, doxorubicin and cisplatin, and gemcitabine and cisplatin, in an adjuvant setting, could affect the subsequent clinical outcome of patients with upper tract urothelial carcinoma. RESULTS On multivariate analysis pathological T stage, tumor grade, lymphovascular invasion and lymph node involvement were prognostic factors for recurrence-free survival and cancer specific survival. We defined 229 patients with 3 or more of these factors as the high risk group. In an analysis according to adjuvant regimen, Kaplan-Meier curves showed that the 1 and 2-year recurrence-free survival rates in the methotrexate, vinblastine, doxorubicin and cisplatin treated group were 71.4% and 47.9%, which were significantly higher than in the gemcitabine and cisplatin treated group (48.2% and not reached, p=0.022) or those not treated with adjuvant chemotherapy (53.4% and 39.6%, p=0.039). Similar results were observed in terms of cancer specific survival. CONCLUSIONS Our study showed that pT3-4, tumor grade 3, positive lymphovascular invasion and lymph node involvement were independent risk factors for disease mortality in patients with upper tract urothelial carcinoma treated with radical nephroureterectomy. In the high risk group methotrexate, vinblastine, doxorubicin and cisplatin adjuvant chemotherapy contributed to improve subsequent mortality compared to gemcitabine and cisplatin or no adjuvant chemotherapy.

The Impact of HIF1α on the Per2 Circadian Rhythm in Renal Cancer Cell Lines

In mammals, the circadian rhythm central generator consists of interactions among clock genes, including Per1/2/3, Cry1/2, Bmal1, and Clock. Circadian rhythm disruption may lead to increased risk of cancer in humans, and deregulation of clock genes has been implicated in many types of cancers. Among these genes, Per2 is reported to have tumor suppressor properties, but little is known about the correlation between Per2 and HIF, which is the main target of renal cell carcinoma (RCC) therapy. In this study, the rhythmic expression of the Per2 gene was not detectable in renal cancer cell lines, with the exception of Caki-2 cells. In Caki-2 cells, HIF1α increased the amplitude of Per2 oscillation by directly binding to the HIF-binding site located on the Per2 promoter. These results indicate that HIF1α may enhance the amplitude of the Per2 circadian rhythm.

Efficacy of tension-free vaginal tape compared with transobturator tape in the treatment of stress urinary incontinence in women: analysis of learning curve, perioperative changes of voiding function

BackgroundIn this study, by comparing TVT surgery and TOT surgery for stress urinary incontinence in women, the characteristics and learning curves of both operative methods were studied.MethodsA total of 83 women with stress urinary incontinence treated with tension-free vaginal tape (TVT) (n = 38) or transobturator tape (TOT) (n = 45) at Saiseikai Central Hospital between April 2004 and September 2009 were included. We compare the outcomes and learning curves between TVT surgery and TOT surgery. In statistical analysis, Students t test, Fishers exact test, and Mann-Whitneys U test were used.ResultsThe surgical durations were 37.4 ± 15.7 minutes with TVT surgery and 31.0 ± 8.3 minutes with TOT surgery. A longer period of time was required for TVT surgery (p = 0.025). The residual urine at post-operative day 1 was higher in TVT surgery (25.9 ± 44.2 ml) than in TOT surgery (10.6 ± 19.2 ml) (p = 0.0452). The surgical duration of TVT surgery was shortened after the operator had performed 15 operations (p = 0.019).ConclusionsIn comparison of TVT surgery and TOT surgery, the surgical duration of TVT surgery was longer and the residual urine of TVT surgery was higher at post-operative day 1. Surgical experience could shorten the duration of TVT surgery.

Determining the optimum way to maintain quality of life for very elderly patients with advanced bladder cancer and poor performance status: A case report

Locally advanced bladder cancer causes unpleasant symptoms such as irritative voiding symptoms, lower abdominal pain, gross hematuria and urinary retention, and lowers the quality of life. Treatment decisions in elderly patients may be difficult, as elderly patients are physically and psychologically different from younger patients. An 89-year-old male was referred to hospital for the treatment of an invasive bladder tumor with right hydronephrosis from tumor obstruction. The patient was elderly and did not have a good performance status; therefore curative radical cystectomy or chemotherapy was not indicated. Left retroperitoneoscopic ureterocutaneostomy was performed to alleviate gross hematuria and voiding difficulty. Intensity-modulated radiotherapy was administered 9 days after the surgery to control bleeding in the bladder tumor. After completing 8 days of radiotherapy, the patient was discharged from hospital. The patient exhibited no signs of either postrenal failure or gross hematuria for 7 months prior to mortality. Retroperitoneoscopic ureterocutaneostomy for very elderly patients with advanced bladder cancer with a poor performance status may be an important procedure for alleviating symptoms and improving quality of life.