Shiro Hinotsu

Combined Androgen Blockade With Bicalutamide for Advanced Prostate Cancer: Long-Term Follow-Up of a Phase 3, Double-Blind, Randomized Study for Survival

A previously reported, double‐blind, randomized, multicenter phase 3 trial in 205 patients with stage C/D prostate cancer compared combined androgen blockade (CAB) with luteinizing hormone‐releasing hormone agonist (LHRH‐A) plus bicalutamide 80 mg versus LHRH‐A plus bicalutamide‐matching placebo (LHRH‐A monotherapy). The analysis at a median follow‐up of 2.4 years indicated that CAB significantly (P < .001) prolonged the time to progression and the time to treatment failure. In the current report, survival data from a long‐term follow‐up (median, 5.2 years) were analyzed.

Bacillus calmette—Guérin treatment of existing papillary bladder cancer and carcinoma in situ of the bladder. Four-year results

Background. Intravesical instillation therapy of Bacillus Calmette‐Guérin (BCG) has become a standard treatment for carcinoma in situ (CIS) of the urinary bladder. However, there have been few reports concerning the direct effect of BCG on existing tumors classified as Ta or T1. In the first stage of this clinical study, 157 patients were treated with BCG intravesical instillation (Tokyo 172 strain [BCG Co. Ltd., Tokyo, Japan]; 80 mg weekly for eight times) by our Study Group. The efficacy on existing tumors was a complete response (CR) rate of 84.4% and 66.4% and a partial response (PR) of 6.3% and 20.8% for 32 cases of CIS and 125 cases of Ta or T1 tumors, respectively.

Tissue elasticity imaging for diagnosis of prostate cancer: A preliminary report

Background: Elastography is a diagnostic imaging technique that evaluates the hardness of a lesion. It is expected to become a new diagnostic modality for prostate cancer. The aim of this study was to examine the usefulness of elastography in the diagnosis of prostate cancer.

Risk assessment among prostate cancer patients receiving primary androgen deprivation therapy.

PURPOSE Prostate cancer epidemiology has been marked overall by a downward risk migration over time. However, in some populations, both in the United States and abroad, many men are still diagnosed with high-risk and/or advanced disease. Primary androgen deprivation therapy (PADT) is frequently offered to these patients, and disease risk prediction is not well-established in this context. We compared risk features between large disease registries from the United States and Japan, and aimed to build and validate a risk prediction model applicable to PADT patients. METHODS Data were analyzed from 13,740 men in the United States community-based Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry and 19,265 men in the Japan Study Group of Prostate Cancer (J-CaP) database, a national Japanese registry of men receiving androgen deprivation therapy. Risk distribution was compared between the two datasets using three well-described multivariable instruments. A novel instrument (Japan Cancer of the Prostate Risk Assessment [J-CAPRA]) was designed and validated to be specifically applicable to PADT patients, and more relevant to high-risk patients than existing instruments. RESULTS J-CaP patients are more likely than CaPSURE patients to be diagnosed with high-risk features; 43% of J-CaP versus 5% of CaPSURE patients had locally advanced or metastatic disease that could not be stratified with the standard risk assessment tools. J-CAPRA--scored 0 to 12 based on Gleason score, prostate-specific antigen level, and clinical stage--predicts progression-free survival among PADT patients in J-CaP with a c-index of 0.71, and cancer-specific survival among PADT patients in CaPSURE with a c-index of 0.84. CONCLUSION The novel J-CAPRA is the first risk instrument developed and validated for patients undergoing PADT. It is applicable to those with both localized and advanced disease, and performs well in diverse populations.

Lumbar Intervertebral Disk Degeneration in Athletes

Background Several studies have reported that physical loading related to competitive sports activities is associated with lumbar intervertebral disk degeneration. However, the association between types of sports activities and disk degeneration has not been clarified. Hypothesis The frequencies of disk degeneration may vary with the competitive sport because of the different postures and actions specific to each sport. Study Design Cross-sectional study (prevalence); Level of evidence, 3. Methods Study participants were 308 well-trained university athletes (baseball players, basketball players, kendo competitors, runners, soccer players, swimmers) and 71 nonathlete university students (reference group). Disk degeneration was evaluated using T2-weighted magnetic resonance imaging. A self-reported questionnaire concerning low back pain was also conducted. Results The proportions of the participants who had disk degeneration among the baseball players (odds ratio, 3.23) and the swimmers (odds ratio, 2.95) were significantly higher than among the nonathletes using logistic regression analysis. When all patients were grouped together, the association between lifetime experience of low back pain and participants with disk degeneration was significant, and a linear association between the degree of severest low back pain experienced and participants with disk degeneration, analyzed by a Cochran-Mantel-Haenszel test, was also significant. Conclusion Continuous competitive baseball and swimming activities during youth may be associated with disk degeneration. Furthermore, the study indicates that the experience of severe low back pain might be a predictor of disk degeneration in youth. The authors hope that preventive measures and management to protect against disk degeneration and low back pain in athletes will be established by further studies based on these results.

Transarterial chemotherapy alone versus transarterial chemoembolization for hepatocellular carcinoma: A randomized phase III trial

BACKGROUND/AIMS Transcatheter arterial chemoembolization (TACE) is a combination of transarterial infusion chemotherapy (TAI) and embolization, and has been widely used to treat patients with hepatocellular carcinoma (HCC). However, since the impact of adding embolization on the survival of patients treated with TAI had never been evaluated in a phase III study, we conducted a multi-center, open-label trial comparing TACE and TAI to assess the effect of adding embolization on survival. METHODS Patients with newly diagnosed unresectable HCC were randomly assigned to either a TACE group or a TAI group. Zinostatin stimalamer was injected into the hepatic artery, together with gelatin sponge in the TACE group and without gelatin sponge in the TAI group. Treatment was repeated when follow-up computed tomography showed the appearance of new lesions in the liver or re-growth of previously treated tumors. RESULTS Seventy-nine patients were assigned to the TACE group, and 82 were assigned to the TAI group. The two groups were comparable with respect to their baseline characteristics. At the time of the analysis, 51 patients in the TACE group and 58 in the TAI group had died. The median overall survival time was 646 days in the TACE group and 679days in the TAI group (p=0.383). CONCLUSIONS The results of this study suggest that treatment intensification by adding embolization did not increase survival over TAI with zinostatin stimalamer alone in patients with HCC.

Maintenance therapy with bacillus Calmette-Guérin Connaught strain clearly prolongs recurrence-free survival following transurethral resection of bladder tumour for non-muscle-invasive bladder cancer.

Study Type – Therapy (RCT)

Decreased expression of CXXC4 promotes a malignant phenotype in renal cell carcinoma by activating Wnt signaling

The Wnt signaling pathway is involved in normal embryonic development and controls the homeostatic self-renewal of stem cells in adult tissues. Constitutive activation of Wnt signaling contributes to cancer development and progression. We identified a CXXC4 homozygous deletion at 4q24 in an aggressive renal cell carcinoma (RCC) using single-nucleotide polymorphism (SNP) arrays. CXXC4 encodes Idax, which negatively regulates Wnt signaling by binding to the PDZ domain of Dishevelled. CXXC4 mRNA levels in tumor samples were significantly lower in patients with metastases compared with those without (P=0.0016). Patients whose tumors had lower CXXC4 expression than normal kidney showed a poorer cause-specific survival outcome than those with higher expression (P=0.0095). Decreased expression of CXXC4 also correlated with cytoplasmic staining of β-catenin. Knockdown of CXXC4 induced the nuclear translocation of β-catenin and altered expression of a set of genes involved in cell proliferation, invasion and survival. Furthermore, reduced expression of CXXC4 by small interfering RNAs promoted cell proliferation and inhibited apoptosis after 5-FU and doxorubicin treatment in RCC cells. These data suggest that CXXC4 plays a critical role in tumor progression of RCC through Wnt signaling. Wnt signaling could thus be a potential molecular target in RCC indicating decreased CXXC4 expression.

Relationship Between Low Back Pain and Competitive Sports Activities During Youth

Background Low back pain is a significant problem not only for the adult, but also during youth. However, the relationship between low back pain during youth and the duration or types of competitive sports has not been clarified. Hypothesis Low back pain during youth is associated with the duration and types of competitive sports. Study Design Cross-sectional study; Level of evidence, 4. Methods Study participants were 4667 new university students who, from 2004 to 2006, answered a questionnaire concerning low back pain and their participation in competitive sports. The participants were divided into a “no” group (NO), a middle group (MID), and a high group (HI) based on the duration of participation in competitive sports. The answers to the questionnaire were analyzed using the Cochran-Mantel-Haenszel test. Furthermore, we selected students who had participated in the same sport for 5 or more years and categorized the students according to the type of sport. Differences in low back pain among the groups were analyzed using logistic regression with the NO group as the reference group. Results There were statistically significant linear associations in the NO, MID, and HI groups, with 50.0%, 61.8%, and 71.7%, respectively, of the students experiencing low back pain. Among the NO, MID, and HI groups, 4.4%, 5.7%, 9.6%, respectively, had experienced school absence due to low back pain; and 4.0%, 8.5%, and 14.6%, respectively had low back pain with associated lower extremity pain and numbness. All 8 sports groups that were analyzed had experienced low back pain significantly higher than the NO group, and the odds ratios differed by sport with the highest (3.8) for the volleyball group. Conclusion Excessive exposure to competitive sports activities during youth was associated with low back pain and symptoms in the lower extremities, with the severity varying with the sport. To reduce low back pain in youth, factors that may be causing low back pain, such as sport-specific postures and motions, need to be investigated.

Prostate Cancer Working Group report.

The incidence of prostate cancer, while still lower than in Western nations, is increasing rapidly in Asian countries due to a more westernized lifestyle. Prostate cancer mortality is declining in the USA, where most prostate cancers are diagnosed in the early stage. In contrast, the mortality rates of prostate cancer in Asian countries are expected to continue to increase, because the percentage of advanced-stage prostate cancers remains high. Therefore, early detection by prostate-specific antigen screening and a comprehensive strategy for cancer prevention are essential for Asian people. The exposure rate of prostate-specific antigen screening is very low in Asian countries. Increased prostate-specific antigen screening may reduce the mortality rate. The stances regarding population screening differ among countries. Urological associations should promote population screening. Reliable data from Asian countries are needed. The prostate cancer incidence is low in Asian countries, perhaps due to high soy consumption. Isoflavones may prevent prostate cancer in Asian countries, but that is not yet clear. A large, multinational study in Asia is needed to clarify whether or not isoflavone consumption shows efficacy in preventing prostate cancer. Clinical data suggest that hormonal therapy is more effective in Asians than in Westerners. Clinical guidelines should consider including hormonal therapy as one of the options for the treatment of localized prostate cancer. At the same time, effort should be made to decrease the adverse effects of each treatment. Collaborative studies on the treatment of prostate cancer should be carried out among Asian countries.