The GP Score, a Simplified Formula (Bioptic Gleason Score Times Prostate Specific Antigen) as a Predictor for Biochemical Failure after Prostatectomy in Prostate Cancer.

OBJECTIVES: We used a new GP score (Gleason score multiplied by prostate-specific antigen) without the T stage as a predictive value for biochemical failure (BCF) after prostatectomy. MATERIALS AND METHODS: We assessed 459 prostate cancer patients who underwent prostatectomies at our institution. Three sub-groups were defined in terms of D'Amico classification risk (low, intermediate, and high) and Gleason score (low, < 50; intermediate, 50-100; and high GP score, > 100). Risk factors for BCF were evaluated by multivariate analysis with a Cox hazard model. A log-rank test was used to compare the BCF rate in the 2 groups. RESULTS: There was nosignificant difference in the non-BCF rate between the lowrisk and low GP score subgroups or the intermediate risk andintermediate GP score subgroups. In contrast, the non-BCFrate of the high GP score subgroup (42.1%) was significantlylower than that of the high-risk subgroup (66.1%, log-rankp = 0.008). Based on multivariate analysis, a high GP score(p = 0.001; HR 3.78; 95%CI 1.95-7.35) was a significant independent risk factor for BCF after prostatectomy. CONCLUSION: The GP score, consisting of two absolute numbers, may be a valuable predictive factor for BCF after prostatectomy, especially in the high-risk failure group.

[Granulocyte-colony stimulating factor-producing urothelial carcinoma of right renal pelvis : a case report].

A 78-year-old female patient with fever and general malaise was referred to our hospital. Laboratory examination showed the marked elevation of leukocyte and serum granulocyte-colony stimulating factor (GCSF) concentration without any infectious sign. A computed tomography scan demonstrated irregular enhanced mass of the right kidney with liver metastasis. The pathological findings of the needle biopsy was high-grade urothelial cancer with positive staining for G-CSF antibody. Systemic chemotherapy with gemcitabine and cisplatin was administered. The patient showed a partial response and the serum G-CSF level was normalized after 1 course of chemotherapy. After four courses of chemotherapy, the extent of liver metastasis increased and the G-CSF concentration became elevated. Although combined chemotherapy with paclitaxel and gemcitabine was administered, the patient died 7 months after her first visit.

Histone H1 expression in human prostate cancer tissues and cell lines.

Histone H1, one of the histone superfamilies, is known to determine chromatin structure and alter gene expression. It also contributes to regulation of cell proliferation in breast cancer. We hypothesized a similar association in prostate cancer, and therefore examined relationships between histone H1 expression and Gleason pattern, Ki-67 and androgen receptor levels in a series of prostate cancer tissues and cell lines. Histone H1 positive cancer cells increased with the Gleason pattern. Gleason pattern 3 tumors were divided into two groups, one with high histone H1 positivity (H1-high cases, 60-100% positivity) and the other with low histone H1 positivity (H1-low cases, 0-20% positivity). Ki-67 or androgen receptor positivity in H1-high cases was significantly higher than in H1-low cases. PC3 cells demonstrated more frequent histone H1 and Ki-67 positivity as compared to LNCaP cells. Silencing of histone H1 by siRNA transfection significantly reduced cell proliferation in LNCaP and PC3. These findings suggest that histone H1 expression is associated with the Gleason pattern, cell proliferation and androgen receptor expression in prostate cancers.

[Clinical analysis of 278 radical prostatectomies].

A retrospective analysis was done on the outcomes of 278 patients who underwent radical prostatectomies at our institutions from November, 1994 to April, 2006. The treatment outcomes measured were disease-specific survival and prostate specific antigen (PSA) biochemical failure-free survival rates. Univariate and multivariate analyses were performed on patient age, clinical T-stage, Gleason sum at the time of prostate biopsy, PSA value before treatment, and any patient history of neoadjuvant hormone therapy. For all patients, the overall survival and the disease-specific survival rates at 10 years were 96.3 and 99.3%, respectively, with PSA biochemical failure-free survival rates at 5 and 10 years of 67.9 and 55.1%, respectively. On multivariate analysis, both the PSA values (> 20 ng/ml) and Gleason sums (> or = 7) were statistically significant independent risk factors for PSA biochemical failure after radical prostatectomy. Neoadjuvant hormone therapy was found to have no effect on PSA biochemical failure.

[Solitary fibrous tumor of a kidney: a case report].

The patient was a 44-year-old woman who had undergone a medical examination because of a left kidney mass. A radical nephrectomy was performed under diagnosis of renal cell carcinoma. Microscopically tumor consisted of spindle-shaped cells accompanied by fibrous connective tissue. Immunohistochemically the tumor cells were diffusely positive for CD34, negative for HMB45 antigen and tyrosinase. The final diagnosis was solitary fibrous tumor.

[Transanal repair of rectourethral fistula after radical retropubic prostatectomy: a case report].

A 65-year-old man underwent a radical retropubic prostatectomy for prostate cancer, and 5 days later fecaluria and serous diarrhea appeared suddenly. Cystourethrography domonstrated the flow of contrast material into the rectum through the fistula, so we diagnosed a rectourethral fistula. We first attempted conservative management, but the fistula did not close spontaneously. So we performed the transanal repair of rectourethral fistula about 2 months after surgery. This repair was effective, and the patient was alive without fistula recurrence at about 2 years after the repair surgery. This approach is simple and does not require a new incision, but it is only useful for low rectourethral

Expression of prothymosin alpha is correlated with development and progression in human prostate cancers.

BACKGROUND: Our previous study clearly demonstrated that decreased expression of prothymosin alpha (PTMA) was associated with inhibition of rat prostate carcinogenesis by isoflavones. The purpose of the present investigation was to provide a better understanding of the role of PTMA in human prostate cancers. METHODS AND RESULTS: PTMA expression in 68 prostate cancer cases and in prostate cancer cell lines was examined by immunohistochemistry and immunoblotting, and its levels were increased with progression from normal epithelium, through prostatic intraepithelial neoplasia (PIN) to carcinomas, correlating with the Gleason's pattern. All cell lines studied (LNCaP, 22Rv1, DU145, and PC3) showed high PTMA expression compared with prostate epithelial cells (PrEC). Knockdown of PTMA expression in PC3 cells by RNAi resulted in the inhibition of both cell growth and invasion in vitro. CONCLUSIONS: The present study clearly demonstrated that PTMA expression is intimately involved in the differentiation and progression of human prostate cancers, and could be a target for therapy and diagnostic purposes.

[Clinical analysis of bladder cancer patients undergoing radical cystectomy].

A retrospective clinicopathological study was performed on 96 bladder cancer patients who underwent radical cystectomy and pelvic lymphadenectomy at Aichi Cancer Center between April 1994 and July 2004. The follow-up period ranged from 4 to 109 months, with a mean of 39.1 months. The overall cancer-specific survival rates at 3, 5 and 7 years were 81.7%, 71.2% and 71.2%, respectively. The 5-year survival rate according to pathological stage was 97.3% for pT1 or lower, 66.4% for pT2, 47.6% for pT3, and 25.4% for pT4. Univariate analysis demonstrated the prognostic significance of pathological stage (p < 0.001), lymph node metastasis (p = 0.001), venous invasion (p < 0.001), lymphatic invasion (p = 0.010), preoperative creatinine clearance (p = 0.001) and preoperative hydronephrosis (p < 0.001). Multivariate analysis revealed strong independent correlations of venous invasion (p = 0.040) and preoperative hydronephrosis (p = 0.016) with prognosis.

[Treatment option for pT3 patient after radical prostatectomy].

With the spread of prostate specific antigen (PSA) examination, radical cure treatment by radical prostatectomy has increased rapidly and the survival rate is high. However, about 26-68% of disease of clinical stage cT1-2 are diagnosed as pT3 in postoperative pathology. Although the 5-year PSA nonrecurrence rate is 91-97% for pT1-2, that for pT3 aN0 and pT3 bN0 is 76% and 37-40%, respectively. Appropriate adjuvant or salvage therapy for pT3 patient is necessary. However, at present the standard treatment method has not yet been established. In this report, radiation and hormone therapy are evaluated as postoperative supporting treatments for pT3 and the appropriate treatment to be taken for pT3 is summarized.

[Salvage radiotherapy for pT3 prostate cancer with PSA failure after radical prostatectomy].

We assessed the effectiveness of salvage radiotherapy in 13 patients at pathologic stage T3 (pT3) with prostate specific antigen (PSA) failure after radical prostatectomy: 9 patients at pT3a and 4 patients at pT3b. Three-dimensional dynamic conformal radiotherapy was used for all patients in this study, and the median radiation dose was 57.7 Gy (range, 44-70 Gy) in daily amounts of 2 Gy. The median follow-up after salvage radiotherapy was 643 days (range, 193-1562 days). In 12 of the 13 patients, PSA levels decreased after salvage radiotherapy, but in 1 patient, the PSA level increased and hence the treatment was discontinued at 44 Gy. However, 10 patients exhibited a lasting PSA response. The 3-year biochemical progression-free rate was 74%, and no serious acute or late toxicity was observed during the follow-up. Salvage radiotherapy is likely to become one of the effective treatments for the patients at pT3 with PSA failure following radical prostatectomy.

[A young patient with invasive small cell carcinoma of the urinary bladder: a case report].

A 29-year-old woman with gross hematuria was referred to our hospital. Cystoscopy revealed a nonpapillary broad-based tumor on the right lateral wall of the urinary bladder, which a transurethral biopsy identified as transitional cell carcinoma (G2). CT and MRI suggested that the carcinoma invaded beyond the bladder wall. We performed a radical cystectomy with hysterectomy and the construction of an ileal neobladder. Pathological examination of the specimen indicated that it was small-cell undifferentiated carcinoma at the stage of pT2bpN0. For adjuvant chemotherapy, four cycles of CPT-11 and CDDP chemotherapy were performed, which is currently the usual chemotherapy for small-cell lung carcinoma in Japan. The patient is alive without any evidence of tumor recurrence at 12 months after surgery.

[Carcinoma of the urachus: a case report].

A 34-year-old married woman complaining of macrohematuria was admitted to our institute. Cystoscopy revealed a broad-stalk, nonpapillary tumor at the urinary bladder dome, and cold-punch biopsy proved it to be a mucus-producing adenocarcinoma. Abdominal managnetic resonance imaging demonstrated a tumor extending from the umbilicus to the bladder dome, and chest computed tomography (CT) demonstrated a small lung tumor with calcification. Examination of the upper gostroinstestinal tract, barium enema, and colon fiberscopy did not reveal abnormalities. We therefore diagnosed an urachal carcinoma with lung metastases. Total cystectomy, umbilical-urachal resection, hysterectomy, ileal neobladder, and partial resection of lung were performed, followed by partial resection of the left lung using thoracoscopy. About 6 months later, chest CT demonstrated multiple metastases in the right lung. After treatment with three courses of chemotherapy (paclitaxel and carboplatin), the right lung was partially resected. Serum CEA and CA19-9 levels were used to follow her disease, since both were elevated before the surgery and at the recurrence. Both indicators returned to their normal ranges after treatment. Such cases require careful observation using imaging modalities and tumor markers.

[The effect of radiotherapy on patients with prostate specific antigen failure after radical prostatectomy].

We studied the effect of radiotherapy on patients with re-elevation of prostate specific antigen (PSA) after radical prostatectomy. Radiotherapy was performed on 8 patients with re-elevated PSA after radical prostatectomy without any previous treatment. Pathological stages were B in 2 patients, and C in 6 patients. Patients received three-dimensional dynamic conformal radiotherapy, and irradiation doses ranged from 44 to 70 Gy (median 60). The target area of irradiation included prostatic bed and seminal vesicles. PSA levels before radiotherapy were 0.31-1.9 ng/ml (median 0.40). In 7 patients, PSA levels decreased and no increase has been observed thereafter. In one patient, PSA level increased during radiotherapy; therefore, the treatment was discontinued at 44 Gy. Two patients suffered grade 1 to 2 acute toxicities, and no late toxicity has been observed so far. Radiotherapy is considered one of the effective treatments for re-elevation of PSA after radical prostatectomy.

Regulation of carcinoma cell invasion by protein C inhibitor whose expression is decreased in renal cell carcinoma.

Protein C inhibitor (PCI), a member of the serine protease inhibitor family, is produced in various human tissues, including the liver, kidney and testis. In addition to inhibiting the anticoagulant protein C pathway, PCI also inhibits urinary plasminogen activator (uPA), which is a well-known mediator of tumor cell invasion. In the present study, to clarify the biologic significance of PCI in the kidney, we compared the expression of PCI between human renal cell carcinoma (RCC) tissue and nontumor kidney tissue. The PCI antigen level in RCC tissue was found to be significantly lower than in nontumor kidney tissue, and expression of PCI mRNA was detected in normal renal proximal tubular epithelial cells (RPTEC), but not in RCC or in an RCC cell line (Caki-1 cells). No differences were detected between the nucleotide sequence of the major cis-elements in the promoter region of the PCI gene from nontumor kidney and RCC tissues, RPTEC and Caki-1 cells, an RPTEC-derived RCC cell line. The in vitro invasiveness of Caki-1 cells transfected with a PCI expression vector was significantly decreased compared to mock-transfected Caki-1 cells, and it was blocked in the presence of anti-PCI antibody. Since PCI itself did not affect the proliferation rate of Caki-1 cells or cell expression of uPA in vitro, the effect of uPA, PCI, heat-inactivated PCI and plasminogen activator inhibitor (PAI)-1 on the invasive potential of cultured RCC cells was evaluated. The in vitro invasiveness of Caki-1 cells, which express uPA, was significantly enhanced by the addition of uPA, and it was inhibited by anti-uPA antibody, PCI and PAI-1, but not by heat-inactivated PCI. In addition, uPA activity was significantly decreased and uPA-PCI complex level was significantly increased in the culture medium of PCI expression vector-transfected Caki-1 cells as compared to mock-transfected Caki-1 cells. These findings strongly suggest that PCI regulates the invasive potential of RCC cells by inhibiting uPA secreted by these cells. The results of our study suggest that PCI might be a potential therapeutic agent for inhibiting renal tumor invasion.

[Treatment results of radical prostatectomy in clinical stage B and C prostate cancer: comparison of the neoadjuvant therapy group versus the surgery group; retrospective analysis of 80 cases].

Between 1994 and 2001, 80 patients underwent radical prostatectomy without adjuvant therapy for clinical stage B and C prostate cancer. The patients were not treated with adjuvant therapy before biochemical prostate specific antigen (PSA) failure. Of all 80 patients, 35 patients (43.8%) received neoadjuvant hormonal therapy prior to radical prostatectomy (the neoadjuvant therapy group), 45 patients (56.2%) underwent prostatectomy alone (the surgery alone group). Retrospective analysis to evaluate the effects of neoadjuvant therapy was performed from clinicopathological findings and the biochemical PSA failure-free rate. Of all patients, 58 (72.5%) were in clinical stage B and 22 (27.5%) were in clinical stage C. Of 58 patients in clinical stage B, 19 (32.8%) underwent prostatectomy combined with neoadjuvant therapy. Of the 22 patients in clinical stage C, 17 (77.3%) underwent prostatectomy combined with neoadjuvant therapy. Pathologically, 37 (46.3%) were in stage B, 38 (47.5%) in stage C and 2 (2.5%) in stage D1. Three patients in the neoadjuvant therapy group had no malignant findings in specimens of prostatectomy. In comparison with the clinical stage, pathologically 8 (22.9%) showed overstaging, 4 (5.0%) understaging and 23 (28.8%) accurate staging in the neoadjuvant therapy group, respectively, 0 (0.0%), 20 (44.4%), and 25 (55.6%) in the surgery alone group. In clinical stage B and C, there was no significant difference in the biochemical PSA failure-free rate between the neoadjuvant therapy group and the surgery alone group. On the other hand, in pathological stages B, the 5-year PSA failure-free rate was 63.2% in the neoadjuvant therapy group, but 100% in the surgery alone group. Although neoadjuvant therapy may have some effect on downstaging, our retrospective analysis suggests that it has no significant effect on PSA failure-free rate.

[Successful treatment for renal cell carcinoma with lung metastases by interleukin-2 and interferon-alfa: a case report].

We report a case in which a regimen of interleukin-2 (IL-2) and interferon alfa (IFN-alpha) was effective against renal cell carcinoma with lung metastases. A 69-year-old man diagnosed with right renal tumor had not received treatment for 28 months. He was admitted to our hospital for treatment. Computed tomographic (CT) findings showed a right renal tumor 11.5 cm in diameter and multiple lung metastases. Right nephrectomy was performed, and pathological examination was renal cell carcinoma (clear cell carcinoma, G2, pT3a). A regimen of IL-2 and IFN-alpha was selected as an adjuvant therapy. He received 70 x 10(4) JRU/day of IL-2 (div) 5 times a week, and 600 x 10(4) IU/day of IFN-alpha intramuscularly 3 times a week for 8 weeks. Thereafter, both treatments were continued 3 times a week. CT scan showed a complete response on lung metastases 12 months and no recurrence has been observed on CT scan for 16 months after operation.

Phenylacetate inhibits growth and modulates cell cycle gene expression in renal cancer cell lines.

BACKGROUND: Phenylacetate (PA), an aromatic fatty acid, is now undergoing evaluation as a potential anticancer reagent. Our previous study showed that PA induces cell growth inhibition in prostate cancer cells. Here, we investigated whether PA is effective against three renal cancer cell lines in vitro. MATERIALS AND METHODS: The cell viability of PA-treated renal carcinoma cell lines (Caki-1, Os-RC-2 and RCC10) was assessed by trypan-blue exclusion and cell cycle distribution by flow cytometry. The cell cycle-regulatory protein expression was evaluated by Western blot, immunoprecipitation and kinase assay. RESULTS: Growth inhibition occurred with PA treatment at a dose of 2-5 mM and an increased percentage of cells in G1 after 24 hours of exposure. Reduced phosphorylation of the retinoblastoma protein (Rb) and CDK2 activity, increased expression of p21Cip1 and enhanced binding of p21Cip1 to CDK2 were observed following treatment with PA. CONCLUSION: Overall, these results suggest that p21Cip1 is a critical target in PA-mediated cell growth inhibition in RCC cells playing a key role in CDK2 inactivation, hypophosphorylation of pRb and subsequent G1 cell cycle arrest.

[Renal oncocytoma with synchronous contralateral renal cell carcinoma].

A 60-year-old male was admitted with bilateral renal masses with a diameter of 50 mm (right kidney), and 15 mm (left kidney) found incidentally by computed tomography. Renal angiography demonstrated neovascularization in the lower pole of the right kidney, but no remarkable findings in the left kidney. We could not deny the possibility of bilateral renal cell carcinoma. Right radical nephrectomy and left partial nephrectomy were performed. The histopathological finding revealed diagnosis of right papillary renal cell carcinoma and left oncocytoma. To our knowledge, this is the third case of renal oncocytoma with synchronous contralateral renal cell carcinoma reported in Japan.