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In our previous study, monoclonal antibody RM2, established toward the glycosyl epitope, reflected grade of malignancy of prostate cancer cells whereas RM2 reactivity to benign glands was negative or weak. RM2 reactivity was also detected in stroma, suggesting the glycoprotein RM2 recognizes could be released into the bloodstream. Then, we explored RM2 reactivity to sera of early prostate cancer. We compared RM2 reactivity to sera between 62 patients with early prostate cancer and 43 subjects with benign prostatic disease, and examined RM2 reactivity before and after radical prostatectomy in 15 patients by Western blotting. We also examined RM2 reactivity to sera of the other urogenital cancers. RM2 reactivity was significantly enhanced on a serum glycoprotein with molecular mass approximately 40 kDa, hereby termed GPX, in the patients with early prostate cancer when compared with those with benign prostatic disease (p < 0.0001). Setting an appropriate cutoff level, RM2 reactivity to GPX for detection of prostate cancer had sensitivity of 87% and specificity of 84%, respectively. Furthermore, the level of RM2 reactivity significantly decreased after radical prostatectomy (p = 0.006). However, increased RM2 reactivity to GPX was also observed in the other urogenital cancers. The proteomics approach identified GPX as haptoglobin-beta chain and RM2 showed preferential reactivity toward haptoglobin-beta chain derived from prostate cancer when compared with polyclonal anti-haptoglobin antibody. Haptoglobin-beta chain defined by RM2 is a novel serum marker that may be useful for detection of early prostate cancer when coupled with prostate-specific antigen because it is not specific to prostate cancer.

Objectives: To report our therapeutic results in prostate cancer using double-mutated adenovirus AxdAdB-3, which has a mutation of E1A and deletion of E1B 55KD. Advanced prostate cancer can harbor multiple genetic alterations, including p53 and Rb/E2F/p16, and is often refractory to hormonal ablation. Virotherapy has been used to target these genetic abnormalities using mutant oncolytic adenovirus for the management of other cancers., Methods: The cytopathic effects of AxdAdB-3 were examined in human prostate carcinoma cell lines (DU145, PC3, and LNCaP) and human normal prostate-derived cell lines (PrEC and PrSC) with AxE1AdB and dl922-947 by crystal violet staining and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The therapeutic efficacy of AxdAdB-3 for the treatment of prostate cancer was investigated in an orthotopic prostate cancer model established with DU145 in severe combined immunodeficiency (SCID) mice., Results: AxdAdB-3 induced potent cytopathic effects in the prostate cancer cell lines tested. AxdAdB-3 showed no cytotoxicity in the normal prostate-derived cell lines PrEC and PrSC. In vivo, AxdAdB-3 showed apparent antitumor effect in the orthotopic prostate cancer model and significantly improved survival., Conclusions: These results suggest that AxdAdB-3 could be a promising tool for virotherapy against prostate cancer in patients with disease resistant to hormonal therapy.

Aim: We examined whether postoperative urinary function after radical prostatectomy is associated with immediate incontinence just after catheter removal., Patients and Methods: The current study included 80 patients with clinically localized prostate cancer, who underwent radical retropubic prostatectomy between January 2002 and May 2004. The amount of immediate incontinence was measured with a 24-h pad test just after catheter removal. The patients were categorized into the three groups based on the stratified grade of immediate urinary incontinence: groups I (0 g; 47 patients), II (1-99 g; 23 patients) and III (100 g and above; 10 patients), respectively. Urinary function and bother were assessed by a self-administered questionnaire using the University of California Los Angeles, Prostate Cancer Index at baseline, and at 3, 6 and 12 months postoperatively. The differences in scores of urinary function, bother and clinicopathological parameters were assessed in the three groups with one-way analysis of variance., Results: No significant difference was observed in the clinicopathological parameters in the three groups. Preoperatively significant difference of urinary function scores was not evident and that of urinary bother scores was not observed in the three groups. Postoperatively urinary function scores were significantly different throughout the postoperative periods investigated, whereas difference in urinary bother scores observed at 3 months tended to disappear with time., Conclusion: Postcatheter removal incontinence might be related to postoperative urinary function after radical prostatectomy, although further investigation is necessary regarding the criteria for categorization because of a small number of the patients.

Objectives: To report results from a 2-year longitudinal survey of lower urinary tract function and quality of life (QOL) in men after radical retropubic prostatectomy (RP) for localized prostate cancer., Methods: Between November 2001 and September 2003, self-report assessments were provided to 225 patients who underwent RP alone. The University of California Los Angeles Prostate Cancer Index (UCLA PCI), the International Prostate Symptom Score (IPSS), and the IPSS QOL score were administered before and 3, 6, 12, 18, and 24 months after RP., Results: The overall mean total IPSS and IPSS QOL score progressively improved with time. The mean scores of several components improved significantly postoperatively. No significant difference was observed in nocturia between the baseline assessment and any of the postoperative follow-up assessments. The IPSS of the younger patients continued to recover significantly more rapidly than that of the older patients after RP. According to the UCLA PCI scores, urinary function substantially declined just after RP and continued to recover but scored lower than the baseline. The mean total IPSS and IPSS QOL scores observed in men with a UCLA PCI urinary function score of 80 or more were significantly better than in men with scores less than 80 at 24 months postoperatively., Conclusions: Radical retropubic prostatectomy has a significant beneficial effect on lower urinary tract symptoms. The rate of improvement was lowest for nocturia among the seven symptoms of IPSS. Urinary continence after RP and age can affect the recovery of voiding function.

Objective: No previous studies have reported the longitudinal health-related quality of life (HRQOL) for intensity modulated radiation therapy (IMRT). We compared HRQOL after IMRT with that after conventional and after conformal radiation therapy (XRT)., Methods: A total of 110 patients underwent XRT (34 patients underwent conventional radiation therapy and 76 underwent conformal radiation therapy) and 30 underwent IMRT for clinically localized prostate cancer between 2000 and 2002. We measured the general and disease-specific HRQOL using the Medical Outcomes Study 36-Item Health Survey and University of California, Los Angeles, Prostate Cancer Index, respectively., Results: There were no significant differences in the preoperative characteristics and HRQOL scores of the two groups. Repeated measure analyses of variance revealed significantly different patterns of alteration in several general HRQOL domains between XRT and the IMRT groups. In the urinary domain, there was no difference in the alteration patterns between the two groups. The XRT group suffered worse bowel function at 3 and 6 months than the IMRT group (P < 0.05). In the XRT group, sexual function decreased at 3 months and remained substantially lower than the baseline level. However, the IMRT group showed no significant difference from the baseline level at any of the observation periods. At 18 months the XRT group showed worse sexual function than the IMRT group., Conclusion: The two approaches showed different longitudinal profiles regarding general and disease-specific HRQOL during the first 2 years after treatment. The IMRT approach produced little impairment in bowel and sexual function.

Objective: We investigated the longitudinal recovery of urinary and sexual function after radical retropubic prostatectomy (RP) using an intraoperative electrophysiological test to confirm the functional preservation of the neurovascular bundle (NVB)., Methods: A total of 70 patients who underwent RP for localized prostate cancer were prospectively enrolled in our survey. During RP, electrophysiological testing was performed to confirm the NVB preservation. The NVB was electrostimulated and the responses were observed by monitoring the intracavernous or intraurethral pressure changes. All patients were classified into three groups according to the degree of nerve-sparing [a bilateral nerve-sparing group (BNS), a unilateral nerve-sparing group (UNS) and a non-nerve-sparing group (NNS)] based on the macroanatomical as well as the electrophysiological assessment. Both urinary and sexual function were measured before and 3, 6, 12 and 24 months after RP by a self-administered questionnaire., Results: The concordance rate of nerve-sparing or non-nerve-sparing between the electrophysiological and macroanatomical assessment was 80%. According to the electrophysiological data, the BNS maintained significantly better urinary function at 3 months after RP than the NNS and UNS. After 6 months, each group had almost recovered continence. When considering sexual function, the BNS showed better sexual function scores than the NNS throughout the post-operative periods and the UNS at 2 years. According to the macroanatomical assessment, however, these differences were significant., Conclusions: Nerve-sparing RP as confirmed by intraoperative electrophysiological test may contribute significantly to the early recovery of continence and greater rate of sexual function after RP.

Objective: We performed a 2 year longitudinal survey of health-related quality of life (HRQOL) after radical retropubic prostatectomy (RP) in Japanese men with localized prostate cancer., Patients and Methods: We measured 112 patients who underwent RP with SF-36 and University of California, Los Angeles Prostate Cancer Index before and 3, 6, 12, 18 and 24 months after surgery., Results: Patients who underwent RP showed problems in some domains of general HRQOL, but these problems diminished over time. Mental health significantly improved throughout the follow-up period. The urinary function substantially declined at 3 months and continued to recover gradually but never returned to the baseline. Urinary bother at 3 months showed a significant decrease, but at 6 months it returned to baseline. The data of sexual function and bother showed a substantially lower score after RP. Patients lost their sexual desire significantly throughout the post-operative period. After 12 months, the nerve sparing group had significantly better improvement in sexual function than the non-nerve sparing group and this improvement continued up to 2 years after operation., Conclusion: Despite reports of problems with sexuality and urinary continence, general HRQOL was mostly unaffected by RP after 6 months. RP had a favorable impact on mental health. Although urinary function did not completely return to the baseline level even at 2 years after RP, recovery from urinary bother was rapid. RP had serious consequences on libido, erectile function and sexual activity. In the second year, the sexual function of those who underwent RP with bilateral nerve sparing procedure continued to improve.

Although prostate-specific antigen (PSA) has been widely used for early detection of prostate cancer, PSA has problems with specificity and prediction of pathological stage. Therefore, a new marker for prostate cancer is urgently required. We examined expression of a novel carbohydrate antigen, beta1,4-GalNAc-disialyl-Lc(4), defined by the monoclonal antibody RM2, in prostate cancer using 75 cases of radical prostatectomy specimens. RM2 immunoreactivity was negative to weak in all benign glands, and weak to moderate in high-grade prostatic intraepithelial neoplasia. In prostatic adenocarcinoma, RM2 immunoreactivity was negative to weak (lower expression) in 20 cases, and moderate to strong (higher expression) in 55 cases. A clear difference of RM2 expression level was observed between Gleason patterns 3 and >/=4. Higher expression of RM2 antigen was significantly associated with primary Gleason pattern >/=4, high Gleason score (>/=8), larger tumor volume and advanced tumor stage. Furthermore, 5-year PSA failure-free survival was significantly lower in the higher expression group. However, no significant relationship was observed between RM2 expression level and preoperative serum PSA. Western blot analysis in prostate cancer cell lines PC3 and LNCap revealed that major 49-kDa and minor 39-kDa glycoproteins were common to both cells, but there was an increase of 59- and 125-kDa glycoproteins unique to LNCap and an increase of 88- and 98-kDa glycoproteins unique to PC3. RM2 antigen is a new histological marker for prostate cancer that may reflect the Gleason grading system. Identification of the glycoproteins carrying the RM2 antigen will provide new insights into the properties of prostate cancer., ((c) 2005 Wiley-Liss, Inc.)

With widespread use of PSA screening, radical prostatectomy has gained popularity among Japanese urologists over the last decade. Recent understanding of pelvic anatomy and improvement in surgical technique have substantially reduced its morbidity. Early recovery of urinary continence is possible and improvement of sexual function after surgery may be enhanced by use of sildenafil and nerve reconstructive surgery. As prostate cancer is increasingly diagnosed at early stages and therefore with more favorable survival outcomes, the basis on which patients select primary therapy has shifted toward considerations of health-related quality of life. Accordingly, QOL assessment has become an important form of outcomes based research that may weigh heavily on the treatment selection by patients.

Background: We performed a longitudinal survey of health related quality of life (HRQOL) after radical retropubic prostatectomy (RP) in Japanese men with localized prostate cancer., Methods: The present study started with self-reported HRQOL assessments provided by 72 patients who received only RP. The RAND 36-Item Health Survey and the University of California, Los Angeles Prostate Cancer Index were administered before and 3, 6 and 12 months after RP., Results: Patients who underwent RP showed problems in some domains of general HRQOL, but these problems diminished over time. Urinary function declined substantially at 3 months and continued to recover at 6 and 12 months, but scored lower than the baseline. Urinary bother at 3 months had a significant decrease, but at six months it turned out to be the same as the baseline. The data of sexual function and bother showed a substantially lower score after RP. The sexual bother score of the younger men was significantly worse than that of the older men. Those who underwent nerve sparing procedures experienced significantly better recovery of urinary and sexual functions than the non-nerve sparing group., Conclusion: Despite reports of problems with sexuality and urinary continence, general HRQOL was mostly unaffected by RP after 6 months. Although there was a substantial decrease in urinary function, recovery from urinary bother was rapid. Deterioration of the sexual domain was remarkable throughout the postoperative period. Therefore, careful attention should be given to preoperative counseling, especially for younger patients.

Background: We performed a retrospective survey of general and disease specific health-related quality of life (HRQOL) after radical prostatectomy (RP) and external beam radiotherapy (XRT) in Japanese men., Methods: A total of 186 patients underwent RP and 78 underwent XRT for clinically localized prostate cancer between 2000 and 2002. We measured the general and disease specific HRQOL with the MOS 36-Item Health Survey and the University of California, Los Angeles Prostate Cancer Index, respectively. Each treatment group was further divided into four subgroups according to the time scale., Results: Patients from the RP group were significantly younger than those from the XRT group. The tumor characteristics differed significantly in their distributions among the treatment groups. Patients undergoing XRT had low scores in most of the general measures of HRQOL just after treatment, but after 6 months there were no differences between the treatment groups, except for the physical domains. The RP group was associated with worse urinary function, whereas the XRT group had worse bowel function and bother during the first 6 months after treatment. Thereafter, however, urinary and bowel domain did not differ between the groups. Both groups reported poor sexual function, although the RP group scored lower sexual bother., Conclusion: The patients who underwent RP had significantly worse urinary and better bowel function than those treated with XRT. Both treatment groups had decrements in sexual function throughout the post-treatment period; careful attention should be paid to this side-effect in preoperative counselling, especially in younger patients, regardless of the primary treatments.

We assessed the 1-year charges in the group of patients undergoing radical prostatectomy and the changes in hospital costs and resource use following implementation of a clinical care path. A total of 69 consecutive men treated with radical prostatectomy for clinically localized prostate cancer were enrolled in the study. Hospital and outpatient records were analyzed for each patient in regard to preoperative, operative and postoperative charges of a 12-month period. Parameters included number of encounters, diagnostic and therapeutic interventions, hospitalization and operative charges, and follow-up visits, diagnostic tests and interventions for 1 year. The mean first-year cost of treatment with radical prostatectomy for localized prostate cancer was 144 x 10(4) yen. The increases in the first-year cost with higher prostate specific antigen (PSA) level for the diagnosis level appeared to primarily be associated with increased inpatient resource use and greater use of hormonal therapy. Length of the stay in a hospital significantly influenced the first-year cost. After implementation of the radical prostatectomy care path hospital costs decreased by 30% (66 x 10(4) yen vs 46 x 10(4) yen), total costs decreased 40% (190 x 10(4) yen vs 113 x 10(4) yen) and length of hospital stay decreased by 56% (37.0 vs 16.6). The first-year costs with radical prostatectomy are influenced greatly by the hormonal therapy and the number of hospital days. By standardizing preoperative and postoperative management for patients undergoing radical prostatectomy, significant savings can be achieved toward shorter hospital stays and lower hospital costs.

Elevated expression of sialyl Lewis X has been postulated to be a prognostic indicator of prostate cancer. However, direct evidence for the relationship between increased expression of sialyl Lewis X and malignancy of prostate cancer is still lacking. To determine whether increased levels of sialyl Lewis X leads to malignancy in prostate tumor, we transfected the human prostate cancer cell line PC-3 with alpha1,3-fucosyltransferase III (FTIII) to obtain stable transfectants, PC-3-FTIII lines, that highly express sialyl Lewis X. When inoculated in the prostate of nude mice, PC-3-FTIII cells produced large prostate tumors, while mock-transfected PC-3 cells, which are negative for sialyl Lewis X antigen, produced small prostate tumors. The aggressive tumor formation by PC-3-FTIII cells was inhibited by preincubation of the tumor cells with anti-sialyl Lewis X antibody, by the presence of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide but not by control peptide. PC-3-FTIII cells and mock-transfected PC-3 cells exhibited no significant difference in cell numbers when cultured in vitro. Remarkably, PC-3-FTIII adhered to prostatic stromal cells in vitro with higher affinity than mock-transfected PC-3. Such adhesion was inhibited by preincubation of PC-3-FTIII cells with antisialyl Lewis X antibody, by the addition of sialyl Lewis X oligosaccharide or by selectin ligand mimic peptide. However, anti-E-selectin, anti-P-selectin or anti-L-selectin antibodies did not inhibit the adhesion of PC-3-FTIII cells to the stromal cells. These results suggest that prostate cancer cells gain aggressiveness through adhesive interaction with prostatic stromal cells by a novel mechanism involving sialyl Lewis X., (Copyright 2003 Wiley-Liss, Inc.)

Purpose: We evaluated retrospectively health-related quality of life (HRQOL) after radical prostatectomy (RP) in Japanese men with localized prostate cancer., Methods: The study was based on self-reported HRQOL of 280 patients. Patients were divided into seven groups: time 0 (T0), baseline before operation; T1, 1-3 months after RP; T2, 4-6 months after RP; T3, 7-12 months after RP; T4, 13-24 months after RP; T5, 25-36 months after RP; and T6, more than 36 months after RP. We measured the general and disease-specific HRQOL using the RAND 36-item Health Survey 1.0 (SF-36) and the University of California, Los Angeles Prostate Cancer Index (UCLA PCI)., Results: The general HRQOL of the postoperative groups was assessed by SF-36. The postoperative groups showed almost the same or higher scores than those of the baseline group. Urinary function scores decreased substantially after surgery. In contrast, there was no difference in urinary bother between the baseline and postoperative groups. Sexual function deteriorated substantially in all postoperative groups. Similarly, the sexual bother score significantly deteriorated after RP. The sexual bother score of men aged 65-years or younger was significantly worse than that of their counterparts in the T1-2 groups., Conclusion: Despite reports of problems with sexual activity and urinary continence, general HRQOL was mostly unaffected by RP. Although there was a substantial decrease in urinary function, recovery from urinary bother was rapid. Since the deterioration of sexual function was marked through the postoperative period, careful attention should be paid to this issue during preoperative counseling, especially for younger patients.

Many types of chemotherapy are now being attempted all over the world for hormone-refractory prostate cancer (HRPC) patients, and prostate-specific antigen (PSA) reduction in almost half of the treated patients has been reported. However, only a few studies have reported the response of bone metastasis. The authors report a patient with HRPC who obtained complete regression of bone metastases on super bone scan by biochemical modulation (BM), dexamethasone, and endocrine therapy.

Objectives: Biochemical modulation (BM) was initially used to enhance the effect of 5-fluorouracil (5-FU) by modulating its pharmacological action with the addition of other drugs. BM with low-dose cisplatin and 5-FU or UFT has been examined in cases of advanced gastric or pancreas cancer and 30 to 40% response rates have been reported. In the present study, the effect of BM on hormone refractory prostate cancer (HRPC) patients was examined., Methods: BM consisting of 5 mg/body of cisplatin 3 times per week and 300-450 mg of UFT/day was given to 30 HRPC patients (median and range of age: 66 and 52-72, respectively). The ECOG performance status was 0 to 1. Gleason score was 7 in 8 patients, 8 in 10 patients and 9 in 12 patients, respectively. The metastatic site was bone in 29 patients (extent of disease on bone scan [EOD] grade 1: 10, 2: 10, 3: 8, 4: 1), lymph node in 8 and liver in 1., Results: Among the 29 patients assessable for bone metastasis, 5 (17%) obtained marked improvement on bone scan. One was EOD grade 4 (super bone scan) and 4 were EOD grade 1-3. Eight (28%) were stable and 16 (55%) progressed on bone scan. Among 8 patients with lymph node metastasis, 4 (50%) showed partial response and 4 (50%) progression. One patient with liver metastasis showed complete response. Fourteen (47%) out of 30 patients showed a PSA decline of 50% or greater. Their median response duration was 8 months (range; 2 to 44 months). Among the 25 patients assessable for bone pain, 7 (28%) improved, 12 (48%) remained stable and 6 (24%) progressed. A side effect of Grade II anemia was seen in one patient., Conclusion: BM is effective in almost half of hormone refractory prostate cancer patients.