市川 智彦

2004年に発足した泌尿器腹腔鏡技術認定制度も5年を超えた．今回，泌尿器腹腔鏡技術認定制度によって技術認定を受けた術者による泌尿器腹腔鏡手術の安全性，妥当性や質（integrity）を検証するために，初回の技術認定を受けた136名を対象としてアンケート調査を行った．結果として130名より2590件の泌尿器腹腔鏡手術の術中術後データが得られた．更新申請者130名の5年間の泌尿器腹腔鏡手術経験件数と合わせてこれらを解析した．130名の技術認定医が経験した泌尿器腹腔鏡件数は2004年から2009年まで年々増加し，2009年には4599件に及んだ．腹腔鏡下腎部分切除術や腹腔鏡下前立腺全摘除術の件数は年々増加していたが，これらの手術を5年間，経験していない認定医はそれぞれ19.2%，54.6%であった．2590例の調査の結果，開放手術の移行率は2.5%，同種血輸血率は1.6%，重大な術中合併症（Satava分類のⅡ以上）の頻度は1.2%，重大な術後合併症（修正版Clavien分類のⅢ以上）の頻度は0.9%，全ての合併症の頻度は3.7%であった．これらのadverse eventの頻度は欧米やアジアの泌尿器腹腔鏡の経験豊富な施設からの報告と遜色無いか低い数字であった．周術期の死亡例は無かった．技術認定医が手術に参加する場合に，術者か指導者かの役割の違いでこれらのadverse eventの発生頻度に有意な違いは無かったが，副腎摘除術，腎腫瘍に対する腎摘除術，前立腺全摘除術においては経験数が多い認定医は指導医的立場で参加する頻度が有意に高かった．認定医の5年間の経験件数とこれらのadverse eventとの関係を検討すると，全ての泌尿器腹腔手術の解析では開放手術の移行頻度は経験数が少ないと有意に高い結果であったが，その他の合併症や同種血輸血率などでは経験数との関係は明らかでなかった．しかしながら腎部分切除術における開放手術への移行率，前立腺全摘除術における同種血輸血率などでは経験数が少ないと有意に高かった．手術時間では腎尿管全摘除術，前立腺全摘除術，腎盂形成術などで経験数が豊富であると有意に短い結果であった．<br> 初回の泌尿器腹腔鏡技術認定医は認定後の5年間，術者，指導者としての経験数は術者間に大きな違いがあったが，おおむね経験数に関係なく，低い術中，術後合併症頻度で様々な泌尿器腹腔鏡手術を術者あるいは指導者として施行していることがうかがわれた．

UNLABELLED: Objective. The aim of the present study was to evaluate initial learning curves of laparoscopic radical prostatectomy (LRP) with regard to complications, urinary continence, and oncologic outcome. Materials and Methods. We retrospectively reviewed 100 consecutive patients with clinically localized prostate cancer. All 100 patients underwent LRP performed by the same urologist at one institution. RESULTS: Mean operating time (208.4 ± 48.6 min), estimated blood loss (495.8 ± 436.5 mL), allogeneic blood transfusion rate (0%), and intraoperative complications diminished with surgical experience. Positive margin rate varied greatly among pathological stage (positive margin rates: pT2 = 20.5%; pT3 = 63.0%). A trend towards reduction of positive surgical margins in pT2 cases was apparent with increasing experience. Intraoperative and early complications occurred in 2.0% of patients. In all patients, 85.9% used none or no more than one pad per 24 h at 6 months postoperatively. Prostate-specific antigen recurrence was seen in only 2 patients. Conclusions. In the present series of 100 patients, our retrospective evaluation confirms that LRP provides satisfactory results.

Objective. The aim of this study is to develop a prognostic model capable of predicting the probability of significant upgrading among Japanese patients. Methods. The study cohort comprised 508 men treated with RP, with available prostate-specific antigen levels, biopsy, and RP Gleason sum values. Clinical and pathological data from 258 patients were obtained from another Japanese institution for validation. Results. Significant Gleason sum upgrading was recorded in 92 patients (18.1%) at RP. The accuracy of the nomogram predicting the probability of significant Gleason sum upgrading between biopsy and RP specimens was 88.9%. Overall AUC was 0.872 when applied to the validation data set. Nomogram predictions of significant upgrading were within 7.5% of an ideal nomogram. Conclusions. Nearly one-fifth of Japanese patients with prostate cancer will be significantly upgraded. Our nomogram seems to provide considerably accurate predictions regardless of minor variations in pathological assessment when applied to Japanese patient populations.

Dendritic cells (DCs) play a crucial role in maintaining the immune system. Though DC-based cancer immunotherapy has been suggested as a potential treatment for various kinds of malignancies, its clinical efficacies are still insufficient in many human trials. Issues that limit the clinical efficacy of DC-based immunotherapy, as well as the difficulty of the industrial production of DCs, are largely due to the limited number of autologous DCs available from each patient. We here established a possible breakthrough, a simple cytokine-based culture method to expand the log-scale order of functional human DCs. Floating cultivation of cord-blood CD34(+) cells under an optimized cytokine cocktail led these progenitor cells to stable log-scale proliferation and to DC differentiation. The expanded DCs had typical features of conventional myeloid DCs in vitro. Therefore, the concept of DC expansion should contribute significantly to the progress of DC immunotherapy.

We recently demonstrated highly efficient antitumor immunity against dermal tumors of B16F10 murine melanoma with the use of dendritic cells (DCs) activated by replication-competent, as well as nontransmissible-type, recombinant Sendai viruses (rSeV), and proposed a new concept, "immunostimulatory virotherapy," for cancer immunotherapy. However, there has been little information on the efficacies of this method: 1) in more clinically relevant situations including metastatic diseases, 2) on other tumor types and other animal species, and 3) on the related molecular/cellular mechanisms. In this study, therefore, we investigated the efficacy of vaccinating DCs activated by fusion gene-deleted nontransmissible rSeV on a rat model of lung metastasis using a highly malignant subline of Dunning R-3327 prostate cancer, AT6.3. rSeV/dF-green fluorescent protein (GFP)-activated bone marrow-derived DCs (rSeV/dF-GFP-DC), consistent with results previously observed in murine DCs. Vaccination of rSeV/dF-GFP-DC was highly effective at preventing lung metastasis after intravenous loading of R-3327 tumor cells, compared with the effects observed with immature DCs or lipopolysaccharide-activated DCs. Interestingly, neither CTL activity nor DC trafficking showed any apparent difference among groups. Notably, rSeV/dF-DCs expressing a dominant-negative mutant of retinoic acid-inducible gene I (RIG-I) (rSeV/dF-RIGIC-DC), an RNA helicase that recognizes the rSeV genome for inducing type I interferons, largely lost the expression of proinflammatory cytokines without any impairment of antitumor activity. These results indicate the essential role of RIG-I-independent signaling on antimetastatic effect induced by rSeV-activated DCs and may provide important insights to DC-based immunotherapy for advanced malignancies.

The objective of the present study was to document the treatment efficacy and safety of sorafenib in Japanese patients with advanced renal cell carcinoma (RCC). A retrospective analysis of 50 consecutive patients with metastatic RCC between January 2005 and December 2009 was carried out. Patients received sorafenib after failed cytokine therapy or first-line sorafenib treatment. All received 400 mg of sorafenib orally twice daily. Five of 14 patients with bone metastases were also given bisphosphonates. Tumor response was evaluated every 1-2 months according to the Response Evaluation Criteria in Solid Tumors. Adverse events (AE) were evaluated at each visit during and after treatment, and were recorded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0. Dose modification of sorafenib was permitted if grade 3 or 4 AE occurred. Treatment continued until disease progression or treatment intolerance occurred. Partial response, and stable disease as best objective responses were observed in 11 (22%) and 23 (46%) patients, respectively. Median progression-free survival was 7.3 months and median overall survival was 11.9 months. All patients experienced AE and one or more grade 3/4 AE occurred in 43 of 50 (86%) patients. Although it requires close monitoring, sorafenib treatment seemed to be effective in the present study population.

OBJECTIVES: To explore the rate of upgrading in a contemporary cohort from 2 Japanese institutions, and evaluating the predictive accuracy of the nomogram when applied to patients, regardless of race. Previous reports have indicated that a maximum of 43% of men with prostate cancer will show an upgraded Gleason score from biopsy to radical prostatectomy (RP). A preparative nomogram was developed at the University of Hamburg to predict the probability of upgrading from biopsy to RP specimen. METHODS: Clinical and pathologic data of 503 patients from 2 Japanese institutions were supplied for validation. Nomogram-predicted probabilities of upgrading from biopsy to RP specimen were compared with actual rate of upgrading. The area under the receiver operating characteristic curve (AUC) was calculated for all patients. Calibration of the nomogram was achieved by comparing the predicted upgrading rate with that of an ideal nomogram. RESULTS: Gleason sum upgrading was recorded in 29.8% of patients at RP. Accuracy of the nomogram was 79.2% (confidence interval, 75.1%-83.2%). Overall AUC was 0.79 when applied to the validation dataset, with individual institutional AUCs ranging from 0.79-0.80. Nomogram predictions of upgrading were not within 10% of an ideal nomogram. CONCLUSIONS: Gleason sum upgrading between biopsy and final pathology represents an important consideration in treatment decision-making, and nearly one third of patients with prostate cancer will be upgraded. The Hamburg nomogram seems to provide reasonably accurate predictions regardless of minor variations in pathologic assessment, but is not necessarily so accurate when applied to Japanese patient population.

OBJECTIVES: To assess the diagnostic accuracy of serum bone turnover markers for detection of bone metastasis in patients with prostate cancer (PCa) and to assess the usefulness of these markers as predictors of mortality from PCa. METHODS: Serum total alkaline phosphatase, bone-specific alkaline phosphatase, carboxy-terminal pyridinoline cross-linked telopeptide parts of type-I collagen (1CTP), tartrate-resistant acid phosphatase type 5 b, and prostate-specific antigen (PSA) levels were measured in 222 patients (58 with bone metastasis, 57 with T2M0 PCa, 55 with T3M0 PCa, and 52 without PCa). Multivariate stepwise logistic regression analysis was used to identify independent predictors of bone metastasis. Correlation of serum marker levels with bone metastasis was assessed using receiver operating characteristics analysis. Multivariate Cox proportional hazards analysis was used to predict cause-specific survival in PCa patients with bone metastasis. RESULTS: Serum total alkaline phosphatase, bone-specific alkaline phosphatase, 1CTP, tartrate-resistant acid phosphatase type 5 b, and PSA levels were significantly elevated in patients with bone metastasis, and correlated significantly with the extent of disease on bone scintigraphy. Multivariate stepwise logistic regression analysis demonstrated that serum PSA and 1CTP were significant predictors of bone metastasis. Receiver operating characteristics analyses showed that serum 1CTP level was the most reliable predictor of bone metastasis (area under the curve = 0.85). Multivariate Cox proportional hazards analysis revealed that only serum 1CTP was an independent prognostic factor for PCa-related death. CONCLUSIONS: Serum 1CTP level was a more reliable marker than the others to detect bone metastatic spread and to predict survival probability in PCa patients with bone metastasis.

OBJECTIVES: To investigate the benefit of alpha1-adrenoceptor antagonist naftopidil on the quality of life (QOL) of patients with lower urinary tract symptoms suggestive of benign prostatic hyperplasia (BPH/LUTS). METHODS: A total of 99 men with BPH/LUTS were prospectively recruited. The Short Form-8 (SF-8) was used for generic QOL assessment and each parameter was compared with the norm in these patients. Longitudinal changes were evaluated using the SF-8 and the International Prostatic Symptoms Score (I-PSS) at baseline, 4 and 8 weeks after naftopidil administration. The relationship between SF-8 and I-PSS was analyzed. RESULTS: Five of eight components in the SF-8 were significantly lower than the Japanese national norm at baseline. SF-8 score was improved by naftopidil at 4 and 8 weeks in general health (GH) and physical component summary (PCS) in the patients in their 70s. Mental health (MH) and mental component summary (MCS) were improved at 8 weeks in patients in their 60s. When analyzing the whole cohort, SF-8 GH, role emotional (RE) and MH had improved at 8 weeks, which was similar to the norm, and bodily pain (BP) results were better. Compared with the baseline, total I-PSS, storage/voiding symptoms and QOL index scores improved significantly under naftopidil. Each component of I-PSS (except for hesitancy) correlated with SF-8 sub-scales (except for BP) to some extent. CONCLUSIONS: BPH/LUTS impairs generic QOL, which is improved by naftopidil treatment. SF-8 can be a useful instrument to assess the efficacy of BPH/LUTS treatment because its simplicity to complete and analyze, and its meaningful relationship to I-PSS.

Patients with locally advanced prostate cancer(PCa) are thought to be at a significant risk of death from PCa or development of distant metastases. To improve the prognosis of those patients, a variety of clinical trials with adjuvant and/or neoadjuvant therapies have been performed. In this review, we described a benefit of integrating local and systemic therapies in the management of locally advanced PCa.

OBJECTIVE: To determine the association between obesity and prostate cancer in Japanese recurrence after primary treatment with radical prostatectomy. METHODS: The subjects were 173 Japanese patients with prostate cancer who had been treated with radical prostatectomy at Chiba University Hospital between April 1997 and March 2007. Clinicopathological characteristics and biochemical recurrence outcomes after radical prostatectomy were compared between the three body mass index cohorts. RESULTS: Mean body mass index was 23.4 kg/m(2) with a standard deviation of 2.4, and mean follow-up period was 37.4 months. Operative time was longer and estimated blood loss was much more in obese patients. Patients with pT3>or= had significantly higher serum prostate-specific antigen, total cholesterol levels, Gleason's sum and positive of surgical margin than pT2 patients. Recurrence rate was significantly higher in the 26.5 kg/m(2) and hyperlipidemia groups in pT3>or= patients. CONCLUSIONS: Obesity is an independent predictor of disease recurrence in Japanese patients with pT3>or= prostate cancer who underwent radical prostatectomy. Obese patients who underwent radical prostatectomy require vigilant follow-up care.

OBJECTIVE: For novice surgeons, successful laparoscopic radical nephrectomy depends on the treatment of the renal vessels, and the use of computed tomography assists in navigation during the surgery. METHODS: To navigate during surgery, three-dimensional volume-rendered images of the renal vessels, kidneys, and surrounding organs were created intraoperatively by the surgeon using an image-processing application. A surgeon adjusted the angle of view and the size of the images according to surgical views during the operation, using a wireless mouse enclosed in a sterilized bag. These images were simultaneously fused onto live video using image-capture software. RESULTS: Novice surgeons easily constructed the augmented reality images intraoperatively and were able to successfully treat the renal vessels. CONCLUSION: The combination of three-dimensional computed tomography volume-rendered images with live video is a valuable navigation system for use intraoperatively.

Recently, prostate cancer is one of the common cancer in Japanese men, with a high incidence of bone metastasis. Bone metastasis is incurable and contributes significantly to disease-specific morbidity and mortality. And more, there are many opportunity to perform androgen deprivation therapy in prostate cancer patients, but worsen osteoporosis and raise a risk of bone fracture. Thus, the management of bone metabolism in patients is a clinically significant issue. The bisphosphonates are targeted to osteoclasts and are considered to be standard management in the care of bone metastasis patients in combination with chemotherapy and hormone therapy. In this review, we summarized the current understanding and therapy of bone metastasis in prostate cancer in mainly respect to Zoredronic acid use.

We retrospectively evaluated the outcome of oral low-dose dexamethasone (DXM) therapy for androgen-independent prostate cancer (AIPC). Between January 1999 and April 2006, 99 consecutive patients with AIPC were enrolled in this study. The median patient age was 70 years (range 46-86), and the median pretreatment prostate-specific antigen (PSA) level was 243 ng/ml (range 8.2-29600). Median follow-up was 41.9 months (range 11.4-170.4). Upon biochemical failure, patients were treated with oral low-dose DXM. A total of 40 of the 99 cases (40.4%) showed a ≥50% decrease in serum PSA levels (PSA responders). Twenty-five cases (25.2%) showed a <50% decrease in PSA, and the remaining 34 cases (34.3%) had increased PSA levels (PSA non-responders). The median PSA progression-free survival was 3.0 (range 0-27) and 8.0 months (range 2-27) for the entire cohort and PSA responders, respectively. The PSA responders had a significantly increased survival (median 30.1 months) compared to the non-responders (median 8.8 months, P<0.001). Of the 34 patients who were under pain control for bone metastases before the administration of DXM, 23 (67.6%) were able to discontinue the regular use of analgesics. The PSA responders also showed an increase in hemoglobin levels. The change in serum interleukin-6 levels was significantly associated with a response to DXM (P=0.0065). Severe adverse events of DXM were rare. Clinicopathological factors predicting the PSA response to DXM were age, time from initial androgen deprivation therapy to DXM and PSA velocity prior to DXM. In conclusion, oral low-dose DXM led to an acceptable PSA response in patients with AIPC. Thus, this therapy may be an effective and safe alternative for the treatment of AIPC, particularly for patients who are not favourable candidates for chemotherapy.

OBJECTIVE: At present, computed tomography (CT) is used in almost all patients with renal tumors. We aimed to investigate the relationship between visceral adipose tissue (VAT), as assessed by CT, and various other factors in patients with renal cell carcinoma (RCC). METHODS: We undertook an examination of VAT in 117 male patients undergoing nephrectomy or partial nephrectomy at Chiba University Hospital using software designed to detect VAT in the horizontal plane of the body cavity. Pathological stage, microvascular invasion, tumor grade, performance status, C-reactive protein, BMI, hypertension, hyperlipemia, hyperglycemia, history of smoking and cause-specific survival rate were examined in relation to VAT, and multivariate Cox regression analysis was used to determine significant predictors of cause-specific survival. RESULTS: VAT in patients with stage I disease was significantly greater than that in patients with more advanced disease (p = 0.0219). VAT in patients with microvascular invasion was significantly smaller than in those without microvascular invasion (p = 0.0260). Patients with high VAT had significantly higher cumulative cause-specific survival when compared to patients with low VAT (p = 0.0257). CONCLUSION: VAT was associated with better clinical features in patients with RCC. Further study is necessary in order to clarify the role of VAT in RCC.

To evaluate the effects of bromocriptine on bladder function in Parkinson's disease (PD) patients and compare these effects with those of (L-dopa). We recruited 8 patients with PD. Urodynamic study (UDS) was performed before and 1 hour after administering 100 mg L-dopa/decarboxylase inhibitor (DCI) and 2.5 hours after administering 7.5 mg bromocriptine. After the bromocriptine administration, urinary urgency aggravated. UDS revealed a decreased bladder volume at which detrusor overactivity (DO) was initiated, a decreased bladder volume at first sensation of bladder filling (FSV) (P < 0.05), an increased maximum Watts Factor value (WFmax) (detrusor contractility), a decreased Abrams-Griffiths (AG) number (urethral obstruction), and a decreased postvoid residual (PVR) (P < 0.01). Similarly, after the L-dopa administration, urinary urgency aggravated. UDS revealed an aggravated DO (P < 0.05), a decreased FSV and bladder capacity (P < 0.01, 0.05), an increased WFmax (P < 0.05), an increased AG number, and a decreased PVR (P < 0.01). A single dose of bromocriptine proved to exacerbate urinary urgency and DO in the storage phase, and improve bladder emptying through increased detrusor contractility and decreased bladder outlet obstruction, within hours. With the exception of bladder outlet obstruction, these effects of bromocriptine are similar to the effects of L-dopa, albeit slightly less pronounced.

OBJECTIVES: To examine the pre-emptive analgesic effect of the non-steroidal anti-inflammatory drug zaltoprofen against rigid cystoscopy-associated pain, and compare it with the effect of an anesthetic gel. METHODS: Forty men periodically undergoing follow-up office cystoscopy were enrolled in this prospective study. The effects of lidocaine gel alone or in combination with zaltoprofen, were examined. The following parameters were assessed using an 11-point numerical rating scale: pain during injection of gel into the urethra, insertion of rigid cystoscope, and the endoscopic examination of the urinary bladder, pain at the first urination after cystoscopy, and at the first urination in the following morning at home. RESULTS: Pain scores with pre-emptive zaltoprofen plus lidocaine gel were significantly lower than the ones with lidocaine gel alone at the time points of inserting rigid cystoscope into the urethra, viewing inside the urinary bladder and the first urination after cystoscopy. The efficacy of zaltoprofen was more significant in the patients with higher baseline pain score. There was no correlation between pain scores and bladder cancer grading, number of tumors, and time from surgery. CONCLUSIONS: Pre-emptive zaltoprofen is able to control cystoscopy-associated pain, which translates into better quality of life for patients. Thus, its use is recommended in the management of these patients.

A 68-year-old man was referred to our hospital with complaints of palpation, hematemesis and melena. Esophagogastroduodenoscopy revealed a huge ulcer in the stomach, and based on biopsy findings, he was pathologically diagnosed as having diffuse large B-cell type malignant lymphoma. A computed tomographic scan demonstrated prostatic enlargement and swelling of the left external iliac lymph nodes. Since his serum PSA level was 13.0 ng/ml, prostatic needle biopsy was performed. Histological findings revealed diffuse large B-cell type malignant lymphoma and moderately differentiated adenocarcinoma of the prostate. The patient achieved complete response after eight cycles of combination chemotherapy with rituximab cyclophosphamide, adriamycin, vincristine and predonisolone. At the same time of chemotherapy, androgen deprivation therapy was initiated. The current his PSA level is 0.2 ng/ml or less.

We recently demonstrated efficient antitumor immunity against murine tumors using dendritic cells (DCs) activated by recombinant Sendai viruses (rSeVs), and proposed a new concept, "immunostimulatory virotherapy," for cancer immunotherapy. However, there has been little information on the efficacy of this method in preventing metastatic diseases. In this study, we investigated the efficacy of vaccinating DCs activated by fusion gene-deleted nontransmissible rSeV (rSeV/dF) using a murine model of lung metastasis. Bolus and i.v. administration of DCs harboring rSeV/dF-expressing GFP without pulsation of tumor Ag (DC-rSeV/dF-GFP) 2 days before tumor inoculation showed efficient prevention against lung metastasis of c1300 neuroblastoma, but not of RM-9 prostatic cancer. We found that the timing of DC therapy was critical for the inhibition of pulmonary metastasis of RM-9, and that the optimal effect of DCs was seen 28 days before tumor inoculation. Interestingly, the antimetastatic effect was sustained for over 3 mo, even when administered DCs were already cleared from the lung and organs related to the immune system. Although NK cell activity had already declined to baseline at the time of tumor inoculation, Ab-mediated depletion studies revealed that CD4+ cells as well as the presence of, but not the activation of, NK cells were crucial to the prevention of lung metastasis. These results are the first demonstration of efficient inhibition of lung metastasis via bolus administration of virally activated DCs that was sustained and NK/CD4+ cell-dependent, and may suggest a potentially new mechanism of DC-based immunotherapy for advanced malignancies.