Prostatic Neoplasms: Kakehi Y

Ito K, Kakehi Y, Naito S, Okuyama A, Anonymous00017. · Department of Urology, Gunma University Graduate School of Medicine, Gunma, Japan. · Int J Urol. · Pubmed #18786203 No free full text.

Abstract: The exposure rate of screening for prostate cancer using prostate-specific antigen (PSA) in Japan is still very low compared with that in the USA or Western Europe. The mortality rate of prostate cancer will increase in the future and in 2020 it will be 2.8 times higher than in 2000. Therefore, there is an urgent need to determine the best available countermeasures to decrease the rate of prostate cancer death.

Kamidono S, Ohshima S, Hirao Y, Suzuki K, Arai Y, Fujimoto H, Egawa S, Akaza H, Hara I, Hinotsu S, Kakehi Y, Hasegawa T, Anonymous00384. · No affiliation provided · Int J Urol. · Pubmed #18184166 No free full text.

This publication has no abstract.

Kuwata Y, Kakehi Y. · Department of Urology, Faculty of Medicine, Kagawa University. · Nippon Rinsho. · Pubmed #15714985 No free full text.

Abstract: Prostate cancer is increasingly detected at early stages and patients can choose various forms of treatment which have favorable survival outcomes. Radical prostatectomy is a major procedure for treating early stage prostate cancer curatively. The instruments of measuring health related QOL (HRQOL) accurately for early prostate cancer treatment were developed. Some of the instruments were useful in Japan after translating into Japanese and pilot testing. Many authors have reported QOL data after radical prostatectomy. These data suggested that general and urinary domains of HRQOL recovered rapidly after radical prostatectomy, but recovery of sexual domains of HRQOL took longer. Recently several authors have reported that HRQOL were affected with ethnic and cultural differences. These results strongly suggested a need for longitudinal surveys in Japanese patients.

Kakehi Y. · Department of Urology, Faculty of Medicine, Kagawa Medical University, Kita-gun, Kagawa, Japan. · Jpn J Clin Oncol. · Pubmed #12604715 links to  free full text

Abstract: The incidence rate of early-stage prostate cancer has dramatically increased since the introduction of the widespread use of PSA testing in developed countries, including Japan. With the downward stage migration there has been much interest in the concept of watchful waiting not only for elderly patients with a life expectancy of less than 10 years but also in younger patients with good social and sexual activity. The results of a recent randomized comparison between radical prostatectomy and watchful waiting for localized disease indicated comparable overall survival but superiority of surgery in disease-specific survival. The predictive value of clinico-pathological parameters including biopsy features and serum PSA seems insufficient to predict tumor growth potential. Our ongoing prospective study is aimed at clarifying whether PSA doubling time assessment for 6 months in patients with favorable biopsy features can be a good indicator for further watchful waiting or immediate aggressive treatment without any survival disadvantage.

Kakehi Y. · Department of Urology, Kagawa Medical University. · Nippon Rinsho. · Pubmed #12599566 No free full text.

This publication has no abstract.

Kinoshita H, Kamoto T, Mitsumori M, Kiyokawa T, Habuchi T, Kakehi Y, Hiraoka M, Ogawa O. · Department of Urology, Kyoto University Graduate School of Medicine, 54 Shogoin-kawaramachi, Sakyo-ku, Kyoto 606-8507, Japan. · Gan To Kagaku Ryoho. · Pubmed #12557702 No free full text.

Abstract: Prostate specific antigen (PSA) failure occurs in 20% to 50% of patients who undergo radical prostatectomy. There is no consensus on how PSA failure should be managed. Recently, salvage radiotherapy is reported to be an effective treatment for PSA failure, and 20%-70% of cases are recurrence-free. The aim of salvage radiotherapy is a cure and this is quite different from other options, for example, endocrine therapy. Salvage radiotherapy is likely to become more important as a treatment for PSA failure after radical prostatectomy.

Kakehi Y. · Department of Urology, Kyoto University Graduate School of Medicine. · Nippon Rinsho. · Pubmed #11022764 No free full text.

This publication has no abstract.

Kuwata Y, Muneuchi G, Igawa HH, Tsukuda F, Inui M, Kakehi Y. · Department of Urology, Kagawa University, Faculty of Medicine, Kagawa, Japan. · Int J Urol. · Pubmed #17593095 No free full text.

Abstract: AIM: We prospectively investigated health-related quality of life (HR-QOL), including sexual function and sexual bother, in patients who underwent nerve grafting during a radical prostatectomy in comparison with those who underwent a non-nerve-sparing radical prostatectomy. METHODS: Between August 2001 and May 2004, radical prostatectomies were performed on 69 patients with clinical T1-T2N0/M0 prostate cancer. Of these, 66 patients (22: nerve-grafting patients, 44: non-nerve-sparing and non-nerve-grafting patients) were enroled into this study. The observation periods ranged from 12-46 months (median: 29 months). The general HR-QOL was measured with the SF-36 General Health Survey and disease-specific HR-QOL was measured with the University of California Los Angeles-Prostate Cancer Index. RESULTS: Penile tumescence was observed in 11 out of 15 (73.3%) prostate-specific antigen failure-free patients who underwent unilateral nerve grafting with contra-lateral nerve-sparing or bilateral nerve grafting. Vaginal penetration was observed in six out of 15 (40.0%) patients. The time for partial erection and for intercourse, respectively, ranged from 3-21 months (median = 6 months) and 6-36 months (median = 13.5 months). There were no significant differences in general HR-QOL changes over time between the nerve-grafting patients and the patients without any nerve-preserving procedures. The sexual function score was significantly better in the nerve-grafting (bilateral nerve graft or unilateral nerve graft with contra-lateral nerve-sparing) patients than in the non-nerve-sparing/non-nerve-grafting patients. The sexual bother score, however, was more serious for the patients who underwent nerve-grafting surgery than for the non-nerve-sparing/non-nerve-grafting patients. CONCLUSION: Sexual bother is serious for patients who attempt to maintain sexual function after special surgical procedures, such as nerve-grafting surgery. We should be aware that careful counseling is needed to avoid impatient and excessive hope for the recovery of sexual function.

Yokomizo A, Kawamoto H, Nihei K, Ishizuka N, Kakehi Y, Tobisu K, Naito S, Anonymous00028. · Department of Urology, Graduate School of Medical Science, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan. · Jpn J Clin Oncol. · Pubmed #15681602 links to  free full text

Abstract: A randomized controlled trial has started in Japan to evaluate radiotherapy and endocrine therapy for prostate-specific antigen (PSA) failure after radical prostatectomy. Patients who have PSA failure after radical prostatectomy for localized prostate cancer (T1-2N0M0) are randomized into treatment groups of either radiotherapy +/- endocrine therapy or endocrine therapy alone. The Urologic Oncology Study Group (UOSG) in the Japan Clinical Oncology Group (JCOG) composed of 36 specialized institutions will recruit 200 patients. The primary end-point is time to treatment failure (TTF) of bicalutamide, and secondary end-points are TTF of protocol treatment, progression-free survival, overall survival, adverse events and quality of life (QOL). The Clinical Trial Review Committee of the JCOG approved the protocol on April 13, 2004, and the study was activated on May 17, 2004.

Taoka R, Shimada O, Kitamura Y, Okazoe H, Taniguchi S, Tsunemori H, Wu X, Inui M, Sugimoto M, Kakehi Y. · The Department of Urology, Faculty of Medicine, Kagawa University. · Hinyokika Kiyo. · Pubmed #19068725 No free full text.

Abstract: The lower urinary tract anatomy in men after radical prostatectomy (RP) resembles that in women. Out of 112 male patients who had undergone RP for localized prostate cancer, 102 (91%) of them responded to a questionnaire survey. The mean age of the responders at the time of RP was 65.9 +/- 5.3 years. The time of response after RP ranged from 2 months to 6 years (median: 44 months). The instruments used for the assessment of urinary status were the International Prostate Symptom Score (IPSS) and QOL score, the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Overactive Bladder Symptom Score (OABSS). Urinary status of 40 elderly female patients aged 59.5 +/- 6.9 years who consulted our outpatient clinic due to conditions (microhematuria, simple renal cyst, etc.) unrelated to lower urinary tract disorders were assessed with the IPSS. In the male patients, total IPSS and QOL score showed significant improvement over time after RP (P = 0.0004, P = 0.0015, respectively). In particular, the voiding symptom score of IPSS showed significant improvement (P < 0.0001). The improvement of incontinence within 1 year after RP was confirmed with ICIQ-SF (p = 0.06). In contrast, the storage symptom score of IPSS after RP was not different with time after RP. Furthermore, the OABSS rose with time after RP (p = 0.08). On the other hand, in the elderly female controls, the storage symptom score of IPSS was significantly higher than voiding symptom score (P = 0.0019). Men who underwent RP showed significant improvement in their voiding symptoms and continence status, but the storage symptoms, progressively worsened following RP. Consequently, careful follow-up and appropriate medical intervention are needed in men after RP as in aging women.

Zeng Y, Kakehi Y, Nouh MA, Tsunemori H, Sugimoto M, Wu XX. · Department of Urology, Kagawa University Faculty of Medicine, Kita-gun, Kagawa, Japan. · Prostate. · Pubmed #19025891 No free full text.

Abstract: OBJECTIVE: To elucidate gene expression profiles of lysophosphatidic acid (LPA)-related molecules in cancer, pre-cancerous lesion, and benign hyperplasia of the prostate. MATERIALS AND METHODS: Prostate tissue samples were surgically obtained from 10 patients with localized prostate cancer and seven patients with invasive bladder cancer. Cancer cells and the corresponding stromal cells from normal prostate, high grade intraepithelial neoplasia (HGPIN), benign hyperplastic glands were isolated by laser capture microdissection. mRNA levels of three LPA receptors, LPA1, LPA2, LPA3, two LPA-synthesizing enzymes, autotaxin (ATX), acylglycerol kinase (AGK), and a LPA-degradation enzyme, prostatic acid phosphatase (PAP), were quantitatively assessed. The expression levels of the same genes were also determined in three human prostate cancer cell lines LNCaP, PC-3, and DU-145. RESULTS: LPA1 mRNA level was significantly decreased in HGPIN and cancer epithelia when compared to the benign glands. LPA3 mRNA level was elevated in cancer epithelia compared to benign glands. LPA3, AGK, and PAP were predominantly expressed in LNCaP cells while LPA1 and ATX gene expressions were found in PC-3 and Du-145 cells. In BPH, AGK was abundantly expressed in the stroma while PAP was predominant in epithelial cells. CONCLUSIONS: By acting via LPA3, LPA may play an important role in the development of prostate cancer. Switching of LPA receptor expression from LPA3 to LPA1, may be involved in prostate cancer progression and/or androgen independence. LPA may also play a key role in the development of benign prostatic hyperplasia.

Wang J, Zhao LY, Uyama T, Tsuboi K, Wu XX, Kakehi Y, Ueda N. · Department of Biochemistry, Kagawa University School of Medicine, Kagawa, Japan. · J Biochem. · Pubmed #18806270 No free full text.

Abstract: N-acylethanolamines (NAEs) are a class of bioactive lipid molecules in animal tissues, including the endocannabinoid anandamide and the anti-inflammatory substance N-palmitoylethanolamine. Enzymatic hydrolysis of NAEs is considered to be an important step to regulate their endogenous levels. Lysosomal NAE-hydrolysing acid amidase (NAAA) as well as fatty acid amide hydrolase (FAAH) is responsible for this reaction. Here, we report relatively high expression of NAAA in human prostate cancer cells (PC-3, DU-145 and LNCaP) and prostate epithelial cells (PrEC), with the highest mRNA level in LNCaP cells. FAAH and the NAE-forming enzyme N-acylphosphatidylethanolamine-hydrolysing phospholipase D (NAPE-PLD) were also detected in these cells. NAAA activity in LNCaP cells could be distinguished from coexisting FAAH activity, based on their different pH dependency profiles and specific inhibition of FAAH activity by URB597. These results showed that both the enzymes were functionally active. We also found that NAAA was partly secreted from LNCaP cells, which underlined possible usefulness of this enzyme as a biomarker of prostate cancer.

Sugimoto M, Takegami M, Suzukamo Y, Fukuhara S, Kakehi Y. · Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan. · Int J Urol. · Pubmed #18422571 No free full text.

Abstract: OBJECTIVES: To evaluate health related quality of life (HRQOL) using the Medical Outcomes Study 8-items Short Form Health Survey (SF-8) questionnaire in Japanese patients with early prostate cancer. METHODS: A cross-sectional analysis was done in 457 patients with prostate cancer treated with radical prostatectomy, external beam radiotherapy, brachytherapy, androgen deprivation therapy, and watchful waiting or a combination these therapies. General HRQOL was measured using the Japanese version of the SF-8 questionnaire and disease-specific HRQOL was assessed using the Japanese version of the Extended Prostate Cancer Index Composite. RESULTS: The external beam radiotherapy group reported significantly lower values for the physical health component summary score (PCS) in comparison to the radical prostatectomy and brachytherapy groups (P < 0.05). In the analysis of both the PCS and the mental health component summary score (MCS) over time after treatment, higher scores with time were found in the radical prostatectomy group. No significant change over time after androgen deprivation therapy in the PCS was found. In contrast, the MCS was found to deteriorate in the early period, showing a significant increase over time. CONCLUSIONS: SF-8 in combination with the Extended Prostate Cancer Index Composite has shown to be a helpful tool in the HRQOL assessment of Japanese patients treated for localized prostate cancer.

Kakehi Y, Kamoto T, Shiraishi T, Ogawa O, Suzukamo Y, Fukuhara S, Saito Y, Tobisu K, Kakizoe T, Shibata T, Fukuda H, Akakura K, Suzuki H, Shinohara N, Egawa S, Irie A, Sato T, Maeda O, Meguro N, Sumiyoshi Y, Suzuki T, Shimizu N, Arai Y, Terai A, Kato T, Habuchi T, Fujimoto H, Niwakawa M. · Department of Urology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. · Jpn J Clin Oncol. · Pubmed #18272471 links to  free full text

Abstract: OBJECTIVE: Selection criteria for active surveillance (AS) program of localized prostate cancer remain to be standardized. The purpose was to evaluate the validity of selection criteria and investigate the feasibility of this AS program. METHODS: Patients meeting the criteria (i) stage T1cN0M0, (ii) age 50-80, (iii) serum prostate-specific antigen (PSA) </=20 ng/ml, (iv) one or two positive cores per 6-12 systematic biopsy cores, (v) Gleason score </=6, and (vi) cancer involvement in positive core </=50% were enrolled and encouraged to start AS for at least 6 months during the period between January 2002 and December 2003. PSA was measured bimonthly for 6 months and every 3 months thereafter. Trigger of treatment recommendation was PSA-doubling time (PSADT) of </=2 years or pathological progression at re-biopsy. Primary endpoint was '%PSADT > 2y', which was defined as the proportion of patients who showed PSADT assessed at 6 months >2 years out of all the patients who chose AS. Point estimate of '%PSADT > 2y' was expected to be >80%. RESULTS: One hundred and eighteen patients opted for AS and 16 chose immediate treatment at enrollment. PSADT for the initial 6 months based on four measurements could be assessed in 106 patients. Intent-to-treat analysis of '%PSADT > 2y' was 71.2% (84/118, 95% CI: 62.1-79.2). Pathological progression rate at 1-year re-biopsy was 33%. Fifty-four (46%) patients remained on AS for maximal observation of 54 months. General health-related QOL in patients undergoing AS was not impaired. CONCLUSIONS: The primary endpoint, '%PSADT > 2y', did not meet the pre-specified decision criteria. Further prospective study with revised program and endpoint is needed.

Namiki S, Takegami M, Kakehi Y, Suzukamo Y, Fukuhara S, Arai Y. · Department of Urology, Tohoku University Graduate School of Medicine, Sendai, Japan. · J Urol. · Pubmed #17561164 No free full text.

Abstract: PURPOSE: We evaluated the correspondence between UCLA PCI and the Extended Prostate Cancer Index Composite for Japanese patients with localized prostate cancer. MATERIALS AND METHODS: A total of 385 patients treated with retropubic radical prostatectomy, external beam radiation, hormonal therapy or select watchful waiting from 2002 to 2006 were enrolled. For this study we used equipercentile linking, a technique that identifies scores on the 2 measures that have the same percentile rank. RESULTS: Urinary and sexual functions showed a strong correlation (r = 0.85 and 0.93, respectively, p <0.0001). In contrast, the correlation for bowel function was relatively weak (r = 0.47, p <0.0001). The correlations of each Extended Prostate Cancer Index Composite bother domain with UCLA PCI were 0.6 (p <0.0001). The linking between each scale of the Extended Prostate Cancer Index Composite and UCLA PCI domains showed that an Extended Prostate Cancer Index Composite urinary function score of 73 was equivalent to a UCLA PCI score of 60. With regard to urinary bother an Extended Prostate Cancer Index Composite score of 69 to 84 was equivalent to a UCLA PCI score of 75. A sexual function score of 18 on UCLA PCI corresponded to an Extended Prostate Cancer Index Composite score of 12 and a sexual bother score of 50 on UCLA PCI corresponded to an Extended Prostate Cancer Index Composite score of 56 to 88. CONCLUSIONS: The urinary and sexual domains of UCLA PCI and the Extended Prostate Cancer Index Composite showed strong correlations. In contrast, the correlation for the bowel domain was relatively weak. The results of the linking analysis between UCLA PCI and the Extended Prostate Cancer Index Composite may have implications useful for their interpretation.

Kakehi Y, Takegami M, Suzukamo Y, Namiki S, Arai Y, Kamoto T, Ogawa O, Fukuhara S. · Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan. · J Urol. · Pubmed #17437836 No free full text.

Abstract: PURPOSE: Health related quality of life in Japanese men with localized prostate cancer treated with current multidisciplinary treatment modalities was assessed using a newly developed Japanese version of the Extended Prostate Cancer Index Composite. We evaluated psychometric properties of the Japanese version of the Extended Prostate Cancer Index Composite. MATERIALS AND METHODS: A cross-sectional analysis of health related quality of life was done in 460 patients treated with radical prostatectomy, external beam radiation therapy, permanent (125)I seed implantation androgen deprivation therapy or watchful waiting. Patients were enrolled in January to July 2005. Serum testosterone was measured in all participants. RESULTS: Missing values ranged from 0.4% to 16.3% with 10% or greater observed for 15 of 50 items (30%). A missing value of 10% or greater correlated with higher age and lower educational background (p<0.05). Internal consistency reliability was 0.7 or higher for almost all subscales except the bowel function and hormonal function subscales. Test-retest reliability and factor validity were successfully verified. Known groups validity revealed significant improvement in urinary domain scores with time in patients treated with radical prostatectomy plus permanent (125)I seed implantation. Bowel domain scores were worse in patients treated with external beam radiation therapy compared to the other modalities. Decreased hormonal domain scores correlated with low serum testosterone (p<0.001). Salvage androgen deprivation therapy after radical prostatectomy negatively influenced sexual function but not sexual bother. CONCLUSIONS: Reliability and validity of the Japanese version of the Extended Prostate Cancer Index Composite were verified, although revision is needed for it to be more comprehensible for elderly patients and those with low education. It can be used for cross-cultural assessment of health related quality of life in patients with localized prostate cancer treated with current multidisciplinary treatment modalities.

Shimada O, Wu X, Jin X, Nouh MA, Fiscella M, Albert V, Matsuda T, Kakehi Y. · Department of Urology, Kagawa University Faculty of Medicine, Kagawa, Japan. · Urology. · Pubmed #17320696 No free full text.

Abstract: OBJECTIVES: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in a variety of tumor cells through two of its receptors: TRAIL-R1 and TRAIL-R2. In this study, we investigated the susceptibility of human prostate cancer and bladder cancer cells to HGS-ETR2, a human monoclonal agonistic antibody specific for TRAIL-R2. METHODS: The cell surface expression of TRAIL-R1 and TRAIL-R2 on prostate cancer and bladder cancer cells was determined using flow cytometry. Cytotoxicity was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and caspase activities were measured by a quantitative colorimetric assay. RESULTS: HGS-ETR2 effectively induced apoptotic cell death in DU145, PC3, and LNCaP human prostate cancer cells and J82 and T24 human bladder cancer cells. The increased effectiveness of HGS-ETR2 for inducing cell death might have been affected by differences in the cell surface expression of the two TRAIL receptors, in that TRAIL-R2, but not TRAIL-R1, was frequently expressed in the prostate cancer and bladder cancer cells. HGS-ETR2 significantly activated the caspase cascade, including caspase-3, -6, -8, and -9, which were the downstream molecules of the death receptors in prostate cancer cells. Caspase-3, -6, and -9 were also significantly activated with HGS-ETR2-induced apoptosis in the bladder cancer cells. CONCLUSIONS: These findings suggest the potential utility of TRAIL-R2 antibody as a novel therapeutic agent against prostate cancer and bladder cancer.

Sugimoto M, Kakehi Y. · Dept. of Urology, Kagawa University. · Gan To Kagaku Ryoho. · Pubmed #16912523 No free full text.

Abstract: The introduction of PSA screening has led to confirming a shift towards an earlier pathological stage in the diagnosis of prostate cancer. Consequently, the proportion of detecting early stage prostate cancer has clearly been increasing. On the other hand, progressive cancers in the form of distant metastases and locally advanced ones that have been confirmed at the initial diagnosis exhibit a constant rate. In addition, there have been a lot of cases where hormonal resistance was acquired during hormonal therapy which resulted in advanced metastases of the prostate. Prostate cancer has a tendency to be metastatic to bones. Combining the fact that the survival period of patients undergoing treatment is prolonged after metastases, the length of suffering caused by complications, such as ostealgia, pathological fracture and myelopathy, becomes an issue in which QOL and ADL of the patient are sacrificed for a long time. As for treatment of prostate cancer with metastases, a palliative treatment is common in the clinical scene. However, we can extend a life prognosis with use of radiotherapy and surgical treatment in addition to the palliative treatment at an appropriate time. It appears that a combination of new chemotherapy and hormonal therapy will be promising. In the future, we believe that the appearance of new anticancer drugs, endocrine therapies, bisphosphonates and strontium treatment could be used as a part of the treatment strategy for prostate cancer with bone metastases.

Takegami M, Suzukamo Y, Sanda MG, Kamoto T, Namiki S, Arai Y, Ogawa O, Fukuhara S, Kakehi Y. · Department of Outcome Research, Institute for Health Outcomes and Process Evaluation Research. · Nippon Hinyokika Gakkai Zasshi. · Pubmed #16363651 No free full text.

Abstract: PURPOSE: To develop a Japanese version of the Expanded Prostate Cancer Index Composite (EPIC): originally designed to measure the Quality of Life of localized prostate cancer patients, after careful assessments of cross-cultural equivalence, face validity and practically. METHODS: We translated the original version that consisted of 50 items into a preliminary Japanese version. This multi-stage procedure included a forward-translation, back-translation and discussion with the original developer. Additionally, we tested the preliminary Japanese version on 11 localized prostate cancer patients and identified problems with its cross-cultural equivalence, practicality. Based on the findings of this pretest, we revised the Japanese version. Consensus by discussion among all researchers was obtained through out this process. RESULTS: The original developer reviewed the back-translation of the preliminary Japanese version: some wording was revised. In the pretest, the average age of patients was 68.8 years old. Four of the sexual subscale showed over 10 percent missing data. In five items, all patients chose identical answers. We conducted an in-depth qualitative investigation of these items. The average response time was 11.7 minutes. We revised the Japanese to reflect patients' opinions as much as possible. Items which were showed problems in terms of cross-cultural adaptation included questions measuring 'bother' and two items of the sexual subscale. The wordings of these items were revised so that Japanese patients could easier understand them. We ensured that the original developer's intentions remained the same. The original developed approved all revisions. CONCLUSION: We translated and adapted the original EPIC to the Japanese culture. The Japanese version of EPIC was found to be functional in the pretest.

Muneuchi G, Kuwata Y, Taketa S, Inui M, Tsukuda F, Shimada O, Igawa HH, Kakehi Y. · Department of Plastic and Reconstructive Surgery, Kagawa University, Kagawa, Japan. · J Reconstr Microsurg. · Pubmed #16292727 No free full text.

Abstract: The authors performed cavernous nerve reconstruction by nerve grafting in 22 patients (unilateral-16, bilateral-6) between August 2001 and June 2004. Harvesting of the sural nerve was unexpectedly more difficult than nerve grafting in the extremities or the head and neck, because a knee and lumbar bending position was impossible due to the pelvic surgical field. Suture of the grafted nerve on the distal side required great effort, because there was only sufficient space for one hand at the maximum in a deep region of the pelvic cavity, and the nerve ends easily become invisible by inflow of even a small amount of urine or blood. The mean time of the nerve harvesting and grafting was 1 hr 50 min for unilateral grafting and 2 hr 40 min for bilateral grafting. Recovery of erectile function was observed in about half the patients who had undergone surgery nearly 1 year before. Since harvesting of the sural nerve and nerve grafting were more difficult than expected, modification and improvement of many surgical elements, such as improvement of surgical devices and application of endoscopic techniques, are necessary.

Akaza H, Tsuruo T, Saijo N, Sone S, Isonishi S, Ohashi Y, Noguchi S, Kurebayashi J, Kakehi Y, Ishikawa H, Blackledge G. · Dept. of Urology, Institute of Clinical Medicine, University of Tsukuba. · Gan To Kagaku Ryoho. · Pubmed #16227757 No free full text.

Abstract: The 12 th Oncology Forum discussed the progress and future strategy of cancer prevention in Japan. The National Cancer Center has established a research center for screening focusing on the most common six cancer, stomach, lung, liver, colon, breast and uterus cancer. The program so far had a cumulative detection rate of 3.3%, which is high,and may reflect the selection of subjects. Screening and chemoprevention is also being investigated in prostate cancer, but the issues centre on how to make this widely available. High risk subjects can also be identified for breast cancer. Obesity and family history are especially important. In colorectal cancer studies are evaluating different diets, but general application is not yet possible and the infrastructure to implement any general screening and prevention does not exist. Development of pharmaceutical treatments for prevention is difficult because of the need for very safe treatments, and also because of the length of time needed to carry out studies. Overall, cancer prevention is still in evolution. New approaches are needed, and new infrastructure will be needed at a government level to implement this.

Uetsuki H, Tsunemori H, Taoka R, Haba R, Ishikawa M, Kakehi Y. · Departments of Urology, Faculty of Medicine, Kagawa University, Kagawa, Japan. · J Urol. · Pubmed #16006883 No free full text.

Abstract: PURPOSE: EPCA, a nuclear matrix protein, has been identified as a novel prostate cancer marker through protein profiling analyses comparing prostate cancer and its normal counterpart. A recent study of prostate biopsy specimens revealed that EPCA stained positive in the cancer negative biopsy cores of individuals with cancer at later biopsy. We clarified the relationship between EPCA expression and clinicopathological parameters, including grade and stage. Morphological characteristics of EPCA positive cells in noncancerous tissues were also analyzed. MATERIALS AND METHODS: Prostate tissue specimens were obtained from 50 patients with localized prostate cancer and 10 with invasive bladder cancer. EPCA expression was analyzed with a polyclonal antibody. Anti-P504S/anti-p63/anti-34betaE12 monoclonal antibodies were used for adjunct diagnosis for prostatic intraepithelial neoplasia. A monoclonal antibody, CD45RO, was used to confirm inflammatory infiltrates surrounding focal atrophic glands. RESULTS: EPCA staining was positive in the prostate samples of 94% of patients with prostate cancer but it was completely negative in samples from patients with bladder cancer. There was no correlation of EPCA staining intensity with Gleason grade or pT stage. In noncancerous tissues adjacent to major cancer foci EPCA was positive in 86% of prostate cancers. Most EPCA positive glands adjacent to cancer consisted of prostatic intraepithelial neoplasia and proliferative inflammatory atrophy. CONCLUSIONS: EPCA seems to reflect nuclear matrix alterations that occur in the earlier stage of prostate carcinogenesis. Individuals in whom the prostate is influenced by this field effect may be detected with this new biomarker.

Kamoto T, Isogawa Y, Shimizu Y, Minamiguchi S, Kinoshita H, Kakehi Y, Mitsumori K, Yamamoto S, Habuchi T, Kato T, Ogawa O. · Department of Urology, Kyoto University Graduate School of Medicine, Shogoin Kawahara-cho 54, Sakyo-ku, Kyoto City, Kyoto 606-8507, Japan. · Jpn J Clin Oncol. · Pubmed #15741307 links to  free full text

Abstract: The E-cadherin gene has been identified as having a physiological role in cellular attachment, and is hypothesized to participate in carcinogenesis. A polymorphism (an A to C substitution) in the 5'-untranslated region has a direct effect on E-cadherin gene transcriptional regulation. We explored the association between E-cadherin gene polymorphism and the risk of prostate cancer in a Japanese population. The subjects consisted of 236 patients with prostate cancer, 209 benign prostatic hyperplasia (BPH) patients and 139 male controls. A marginally significant difference was found between prostate cancer patients and male controls (P = 0.053). No significant difference was observed between prostate cancer and BPH patients. When patients with prostate cancer were divided into two groups, stage A+B and stage C+D, a significant difference was observed between progressive cancer patients (stage C+D) and male controls (odds ratio = 1.93, P = 0.016). It is possible that the presence of one A allele resulted in an increased risk of cancer progression.

Zeng Y, Yokohira M, Saoo K, Takeuchi H, Chen Y, Yamakawa K, Matsuda Y, Kakehi Y, Imaida K. · Onco-Pathology, Department of Pathology and Host-Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan. · Carcinogenesis. · Pubmed #15731164 links to  free full text

Abstract: The chemopreventive efficacies of raloxifene and nimesulide, an anti-estrogen but with anti-androgen action and a cyclooxygenase-2 (COX-2) selective inhibitor, respectively, were evaluated in probasin/SV40 T antigen (Tag) transgenic (TG) rats. The treatment groups were placebo, nimesulide (400 p.p.m. in basal diet p.o.), raloxifene (slow-release pellets implanted s.c., 5 mg/kg/day), raloxifene (5 mg/kg/day) plus nimesulide (400 p.p.m.), and raloxifene (10 mg/kg/day) plus nimesulide (400 p.p.m.). Animals were killed at 17 weeks of age, and prostate tissues were harvested and weighed by lobes. Tissues were evaluated by histology, immunohistochemistry, and western blot analyses and blood was collected to measure the testosterone levels. All the animals in the placebo group had tumors in each lobe compared with only 43% each in the dorsolateral (DLP) and anterior prostate (AP) of the animals treated with raloxifene (10 mg/kg/day) plus nimesulide. The total prostate weights and adenocarcinoma portions were significantly reduced in the three raloxifene-treated groups, whereas atrophic glands were increased. There were no significant differences between the nimesulide alone and placebo groups or between the raloxifene (5 mg/kg/day) alone and raloxifene (5 mg/kg/day) plus nimesulide group, suggesting a lack of cancer preventive effects of the COX-2 inhibitor in this animal model. PCNA positive rates in ventral prostate (VP) and DLP, and androgen receptor (AR) levels in VP were significantly reduced in the three raloxifene-treated groups. Furthermore, circulating testosterone was decreased after raloxifene (10 mg/kg/day) plus nimesulide treatment. These results demonstrate that raloxifene, but not nimesulide, inhibits prostate carcinogenesis in SV40 Tag TG rats associated with a decline in circulating testosterone levels and a loss of AR expression, as well as an inhibition of cell proliferation.

Taketa S, Shimada O, Tsukuda F, Inui M, Kuwata Y, Kakehi Y, Mitani M, Takashima H. · Department of Urology, Faculty of Medicine, Kagawa University. · Hinyokika Kiyo. · Pubmed #15518125 No free full text.

Abstract: Three dimensional conformal radiotherapy (3D-CRT) for localized prostate cancer under field adjustment with gold marker implantation was performed according to the treatment strategy based on the clinical risk factors to the patients who chose external beam radiotherapy. The treatment strategy contains indications for laparoscopic staging lymphadenectomy and neoadjuvant combined androgen blockade (CAB). This protocol was applied to 19 patients at Kagawa University Hospital from July 2001 to December 2003. The patients were divided into high-risk group (n=14): T3-4N0M0 or PSA > or = 20 ng/ml or Gleason sum > or = 8 or suspicious node, and low-risk group (n=5): T1c-2bN0M0 and PSA < 20 ng/ml and Gleason sum < or = 7 and no suspicious nodes. Basically, high-risk patients underwent laparoscopic staging lymphadenectomy prior to radiotherapy. One of the 14 patients had a positive node and underwent endocrine therapy. The high-risk group received neoadjuvant CAB for 3 to 4 months, followed by gold marker implantation. One patient chose endocrine therapy at this point. Low-risk patients underwent marker implantation without endocrine therapy. Every patient successfully completed planned irradiation. The changes of prostate volume and serum PSA after neoadjuvant CAB were significant [28.7 ml to 15.7 ml (p=0.004) and 53.9 ng/ml to 1.4 ng/ml (p=0.023), respectively]. Only one patient in the high-risk group had biochemical failure. No grade 3 or 4 adverse events occurred in NCI-CTC grading. The analysis of gravity center migration of the implanted gold markers in the first 8 patients showed that the planned safety margin might not be wide enough to avoid neighboring organ irradiation. These results suggested that 3D-CRT under field adjustment with implanted gold markers contributes to both higher efficacy and lower morbidity.