Effects of eicosapentaenoic acid on biochemical failure after radical prostatectomy for prostate cancer.

AIM: To study the effects of eicosapentaenoic acid (EPA) on prostate-specific antigen (PSA) failure in prostate cancer patients who underwent prostatectomy. PATIENTS AND METHODS: Sixty-two prostate cancer patients whose PSA levels were less than 0.2 ng/ml 3 months after surgery were randomized to either an EPA group (n=32) or a control group (n=30). EPA (2.4 g/day) was administered in the EPA group for 2 years. PSA was measured every two months. RESULTS: The EPA concentration increased but the docosahexaenoic acid concentration decreased significantly (P<0.001) in erythrocytes. The PSA recurrence rates during a mean follow-up of 53.8 months were not different between the two groups (p=0.16). CONCLUSION: A longer and/or larger intervention or docosahexaenoic acid supplementation might be necessary to identify significant preventive effects of mega-3 polyunsaturated fatty acids on PSA recurrence.

Implications of insulin-like growth factor-I for prostate cancer therapies.

In the last decade, abundant evidence has suggested that the insulin-like growth factor (IGF) family comprises a multi-component network of molecules involved in the regulation of both physiological and pathological growth processes in the prostate. The IGF axis plays an important role in the tumorigenesis and neoplastic growth of prostate cancer. Epidemiological observations indicate that circulating IGF-I levels are positively associated with increased risk of prostate cancer. Activation of IGF-I receptor (IGF-IR) by IGF-I has mitogenic and anti-apoptotic effects on normal and malignant prostate cells. Therapeutic alternatives in men with progressive prostate cancer after androgen ablation are very limited and more effective therapies are needed for such patients. Inactivation of the IGF-I axis represents a potential target to treat androgen-independent prostate cancer. This review addresses epidemiological studies of IGF-I and therapeutic strategies including reduction of IGF-I levels, inhibition of IGF-IR and the signaling mechanisms involved.

[Two cases of spontaneous rupture of upper urinary tract caused by the primary ureteral or renal pelvic tumor: a case report].

We report two cases of spontaneous urinary rupture caused by primary ureteral or renal pelvic cancer. Case 1: A 76-year-old man presented with macrohematuria and left back pain. Magnetic resonance imaging showed left middle ureteral tumor and rupture of upper ureter. Left nephroureterectomy was performed. Histological findings revealed urothelial carcinoma, G2, pT1, lt-u0, ew0, ly0, v1. At five months postoperatively, he died of lymph node metastases after two courses of adjuvant chemotherapy. Case 2: A 59-year-old man presented with macrohematuria and left back pain. Computer tomography showed left renal pelvic tumor with extravasation of urine. Left nephroureterectomy was performed. Examination of surgical specimen revealed a renal pelvic tumor and rupture hole at the renal pelvis. Histological finding revealed urothelial carcinoma, G3, pT3, lt-u0, ly0, v1. One course of adjuvant chemotherapy was performed. At six months postoperatively, he was free from recurrence.

[Clinical study on operative treatment of acute scrotum].

Between July 1986 and March 2006, 102 patients underwent an operation for acute scrotum. Median age was 12.0 years old (range 0-51). Post-operative diagnosis revealed 50 cases (49%) of spermatic cord torsion, 29 cases (28%) of epididymal appendix torsion, and 13 cases (13%) of acute epididymitis. Spermatic cord torsion was most frequent in the age between 0 and 5, and 11 and 20, while epididymal appendix torsion was most frequent between 6 and 10. Moreover, acute epididymitis was most frequently seen in the age over 20. There were no apparent differences in the clinical symptoms such as scrotal pain, scrotal swelling, and abdominal pain. In the physical examinations, pyuria was the only finding to indicate acute epididymitis. In case of spermatic cord torsion, 'golden time' is defined as the time from onset to operation when testicular function can be expected for preservation. In this study golden time was defined as 8 hours because the testes was preserved in all 23 patients receiving the operation within 8 hours, but in only 10 (37%) out of 27 patients receiving the operation after 8 hours. Moreover, the operation within 24 hours saved the testes in approximately 90% of the patients. In patients with acute scrotum, emergency operation should be performed as speedily as possible for preservation of testicular function.

A case of venous air embolism during transurethral resection of the prostate.

Venous air embolism is a rare complication during transurethral resection of the prostate (TURP). We report a case of air embolism during TURP under general anesthesia in a 56-year-old man. Incorrect assembly of the resectoscope-drain aspiration system caused rapid entrainment of air into the vein of the prostate bed. Rapid recognition of the condition and prompt treatment are required.

Urachal signet ring cell carcinoma.

Urachal adenocarcinoma is a rare neoplasm associated with poor prognosis. We report a case of urachal signet ring cell carcinoma in a 65-year-old man. He was admitted with a chief complaint of microscopic hematuria. Cystoscopic examination and transurethral biopsy showed an urachal tumor. After undergoing radical cystectomy and intravenous chemotherapy, the patient developed bilateral hydronephroses as a result of bilateral ureteral metastases and bowel obstraction because of the Para-aortic lymphnode metastasis. He has been alive for 5 years after three courses of chemotherapy and a bypass operation.

A case of orbital metastasis from prostatic carcinoma as an initial symptom.

Orbital metastasis caused by prostate cancer is rare. We report a case of prostate cancer diagnosed from the initial ocular signs with complaints of decreased vision and exophthalmos. The orbital tumor was surgically removed and endocrine therapy was performed subsequently. Metastatic carcinoma of the prostate should be considered in the elderly male with exophthalmos.

Serum immunosuppressive acidic protein doubling time as a prognostic factor for recurrent renal cell carcinoma after nephrectomy.

OBJECTIVES: To identify the prognostic factors in patients with recurrent renal cell carcinoma after nephrectomy, various factors were assessed, with special attention to serum immunosuppressive acidic protein (IAP) and its doubling time. METHODS: Age, sex, stage, grade, histopathologic type, primary tumor size, site and number of metastatic organs, time to recurrence, IAP levels before nephrectomy and at the diagnosis of recurrence, and IAP doubling time just before recurrence were analyzed in 125 patients with recurrent renal cell carcinoma after nephrectomy. RESULTS: Univariate analysis identified stage, grade, histopathologic type, primary tumor size, time to recurrence, IAP level at the diagnosis of recurrence, and IAP doubling time as significant prognostic factors. After exclusion of confounding factors, multivariate analysis showed that IAP doubling time was the most potent independent prognostic factor. Patient survival rates dichotomized according to IAP doubling time were compared at 100-day intervals from 100 to 700 days and 1000 and 2000 days. The maximal difference in survival rate was found when the cutoff level in the IAP doubling time was set at 200 days. CONCLUSIONS: The results of our study have shown that the IAP doubling time is a potent prognostic factor in patients with recurrent renal cell carcinoma. Periodic checkups with serum IAP level monitoring are recommended to predict prognosis after recurrence.

Primary adenocarcinoma of the appendix invading the urinary bladder.

We report a case of adenocarcinoma of the appendix invading the urinary bladder in a 75-year-old man. Although cystoscopic examination and computed tomography suggested a primary or secondary bladder tumor, repeated transurethral bladder biopsy could not confirm the neoplasm. At operation a primary neoplasm of the appendix invading the bladder was discovered and en bloc resection of the urinary bladder with the adherent cecum followed by an ileocolonic anastomosis and ureterocutaneostomy was performed. The patient died of carcinoma 13 months later.

Clinical impact of tamsulosin on generic and symptom-specific quality of life for benign prostatic hyperplasia patients: using international prostate symptom score and Rand Medical Outcomes Study 36-item Health Survey.

AIM: To examine the efficiency of alpha1-blocker treatment on disease-specific and generic quality of life (QOL) in men with clinically diagnosed benign prostatic hyperplasia (BPH), the improvement of QOL scores with International prostate symptom score (I-PSS) and Rand Medical Outcomes Study 36-item Health Survey (SF-36) was prospectively analyzed. METHODS: A total of 68 newly diagnosed patients with symptomatic BPH that satisfied all inclusion and none of the exclusion criteria were prospectively recruited. All patients received 0.2 mg/day of tamsulosin for 12 weeks. All patients underwent pretreatment documentation of lower urinary tract symptoms (LUTS) and assessment of symptom-specific QOL. Symptoms and general health-related QOL (HRQOL) were assessed using the I-PSS and SF-36, respectively. Also, other objective variables, such as prostate volume, maximal urinary flow and postvoid residual urine volume, were evaluated. RESULTS: After 12 weeks, decrease in I-PSS was 27% compared with baseline (from 16.4 +/- 7.18 to 11.9 +/- 7.56). All questionnaires in the I-PSS showed improvement after tamsulosin treatment and the I-PSS QOL score was improved from 4.51 +/- 1.14 to 3.17 +/- 1.38 (P < 0.0001) at 12 weeks after tamsulosin administration. In intragroup comparisons of HRQOL scores with age-gender adjusted SF-36 Japanese national norms, three SF-36 subscales (bodily pain, BP; social function, SF; and mental health, MH) were worse in the BPH group aged over 70 years, while younger BPH groups aged <70 had better mean SF-36 physical function (PF) scores compared with age-gender adjusted Japanese national norms. In the BPH group with a prostatic volume > or =20 mL, three mean SF-36 scales (BP, SF and MH) were significantly improved after tamsulosin treatment. It is noteworthy that these SF-36 subscales were identical to those observed to worsen in the older BPH group compared to Japanese national norms. CONCLUSIONS: Treatment with tamsulosin for symptomatic BPH patients is associated with significant improvement in the generic HRQOL, in addition to disease-specific QOL and symptoms, at 3 months after drug administration. In particularly, for generic HRQOL with SF-36, tamsulosin treatment can efficiently improve three mean SF-36 subscales (BP, SF and MH) that are decreased in older BPH patients.

The effect of eicosapentaenoic acid on prostate-specific antigen.

The "Study of EPA Effects on Prostate Cancer" (SEEPC) Group has been conducting a clinical trial with patients who underwent radical prostatectomy. The main purpose of the SEEPC is to evaluate whether eicosapentaenoic acid (EPA) prevents prostate cancer (PC) recurrence. As the surrogate marker of recurrence, the prostate-specific antigen (PSA) level was measured. However, if EPA affects the PSA values independently of PC, PSA may not be a good marker of recurrence in the event of EPA treatment. Thus, in the present study, whether EPA affected the PSA values was investigated using non-PC volunteers. Twenty men, of at least 50 years of age, were recruited, mostly from hospital staff The volunteers were randomly allocated either to the EPA group or the control. The subjects in the EPA group were administered EPA-ethyl ester a dose of 2400 mg/day for 12 weeks, whereas the controls were administered none. Fasting blood samples were obtained before the start of EPA administration and 4 and 12 weeks later. The EPA concentrations in erythrocytes increased in all the subjects in the EPA group (174+/-96%) with no significant changes in the control group (8.5+/-14.0%). There were no significant differences between the two groups in the serum PSA levels, allowing the conclusion that the PSA is an appropriate surrogate marker of recurrence in prostate cancer.

Serum interleukin-11 in patients with benign prostatic hyperplasia and prostate cancer.

To clarify whether serum levels of interleukin-11 (IL-11) could be a useful marker in patients with prostate cancer, serum IL-11 was determined in 73 and 23 men with prostate cancer and benign prostate hyperplasia (BPH), respectively, before treatment. There were no statistical differences of IL-11 levels between patients with prostate cancer and BPH. Patients with hormone-resistant prostate cancer had a significantly higher level of IL-11 than those with untreated cancer. Serum IL-11 levels may be a potential tumor marker for prostate cancer progression.

[Treatment of traditional Chinese medicine for idiopathic male infertility].

Several Chinese herbal medicines have been used to treat patients with idiopathic male infertility and have been reported to improve semen quality. The clinical efficacy of these medicines was reviewed. The therapeutic effect of Hochu-ekki-to based on the pretreatment traditional diagnosis (Sho) was examined. Three months after the administration of Hochu-ekki-to, the semen count and motility significantly increased in comparison with pretreatment values. When the patients were classified into 3 categories based on "Sho", Hochu-ekki-to was effective in semen motility in patients with vacuity pattern (Kyo-Sho). Seminal plasma soluble Fas (sFas) levels before and three months after the administration of drug were analyzed. Seminal plasma sFas level elevated significantly after the administration of Hochu-ekki-to. After the administration of Hochu-ekki-to, seminal plasma sFas levels significantly correlated with sperm concentration. To make the best use of traditional medicine, it is important to give medication according to the traditional diagnosis (Sho).

Differential expression of integrin subunits in DU-145/AR prostate cancer cells.

We have established a clonal DU-145 prostate cancer cell line (DU-145/AR) stably transfected with androgen receptor cDNA. We investigated the expression of integrin subunits, adhesion to extracellular matrices, the invasion of DU-145/AR prostate cancer cells. The expression of various integrin subunits and adhesion to various extracellular matrices in DU-145, DU-145/Neo and DU-145/AR cells were examined. The haptoinvasion and the haptotactic migration of these cells were investigated using a Transwell cell culture chamber assay. DU-145/AR cells exhibited lower expression of alpha6 and beta4 integrin subunits and higher expression of alpha2 and alpha5 than DU-145 cells. DU-145/AR cells showed significantly lower adhesion to fibronectin, laminin-1 and laminin-5 than DU-145/ Neo cells, whereas DU-145/AR cells showed higher adhesion to type I and type IV collagen. Haptoinvasion of DU-145/AR cells into Matrigel/fibronectin-coated filter was significantly reduced as compared with DU-145/Neo or DU-145 cells, but there was no significant difference between DU-145/AR and control cells in the haptotactic migration to fibronectin. Dihydrotestosterone (DHT) inhibited the invasive ability of DU-145/AR cells. These results indicate that androgen receptor may play a role in the regulation of adhesion to the extracellular matrices and invasion of prostate cancer cells through influencing the expression of specific integrin subunits.

Tissue factor expression and prognosis in patients with metastatic prostate cancer.

OBJECTIVES: To assess immunohistochemically the pattern of tissue factor (TF) expression in patients with metastatic prostate cancer, because TF is aberrantly expressed in human cancer. TF is the primary initiator of the coagulation cascade. METHODS: Seventy-three patients with untreated metastatic prostate cancer who received hormonal therapy were included in the present study. Biopsy specimens were stained with anti-human TF antibody. We evaluated the histologic grade, extent of bony metastasis, clinical response to hormonal therapy, and patient prognosis. RESULTS: TF was detected in 75.3% of the tumors of the patients with metastatic prostate cancer. TF expression showed no association with histologic grade, extent of bony metastasis, or clinical response to hormonal therapy. Patients with TF-positive tumors had a poorer cause-specific survival than those with TF-negative tumors. Multivariate analysis showed that TF expression, clinical response to hormonal therapy, and extent of bony metastasis were significant prognostic factors. CONCLUSIONS: The TF content measured using immunohistochemical staining was a useful prognostic factor for patients with metastatic prostate cancer treated with androgen withdrawal therapy.

Prognostic significance of serum soluble Fas level and its change during regression and progression of advanced prostate cancer.

To evaluate the clinical usefulness of serum soluble Fas (sFas) and sFas ligand as a prognostic factor and for monitoring the regression and progression of metastatic prostate cancer treated with endocrine therapy, sFas and sFas ligand were measured in sera collected from 30 patients with untreated metastatic prostate cancer. sFas levels were measured sequentially in 16 patients who had progressed to a state of elevated prostate-specific antigen (PSA) and 5 patients who were in regression following endocrine therapy. Serum sFas levels in patients with metastatic prostate cancer were found to be significantly higher than that of control patients with benign prostate hyperplasia. Patients with low levels of serum sFas had a higher cause-specific survival rate and a higher PSA progression-free rate compared with patients with high levels of serum sFas. In patients who suffered PSA progression following endocrine therapy, serum sFas increased in parallel to the increase in PSA levels although the magnitude of change in sFas was very small. In patients whose tumor regressed following therapy, sFas levels did not change. sFas ligand levels were very low or below measurable levels in all specimens. sFas levels might be associated with poor prognosis in metastatic prostate cancer. Serum sFas ligand appears to have limited clinical relevance.

Clinical significance of expression of urokinase-type plasminogen activator in patients with prostate cancer.

BACKGROUND: Urokinase-type plasminogen activator (u-PA) has been reported to overexpress in several types of human cancers and correlate with cancer progression. The present study was performed to evaluate the significance of expression of u-PA on the progression of prostate cancer. MATERIALS AND METHODS: Expression of u-PA protein was investigated immunohistochemically on paraffin-embedded section from 61 patients with untreated prostate cancer. The correlation between the u-PA expression and clinical outcome was examined. RESULTS: u-PA was expressed in the cytoplasm of glandular cells of 56% patients. Higher expression of u-PA protein was positively correlated with bone metastasis (p = 0.011). The cause-specific survival rate was significantly lower in u-PA-positive patients than that in u-PA-negative patients (p = 0.0012). In those with bone metastasis, patients with u-PA expression had worse cause-specific survival than those without u-PA expression (p = 0.030). CONCLUSION: Increased expression of u-PA is a feature of bone metastasis in patients with prostate cancer. u-PA expression is a prognostic factor in patients with prostate cancer.

Cell proliferation, apoptosis and prognosis in patients with metastatic prostate cancer.

BACKGROUND: Since tumor growth is determined by an imbalance between cell growth and cell death, we assessed the incidence of cell proliferation and apoptosis in biopsy specimens from patients with metastatic prostate cancer treated with endocrine therapy. MATERIALS AND METHODS: In fifty-five patients with untreated metastatic prostate cancer, proliferation and apoptotic indices were determined by detection of Ki-67 immunostaining and the in situ end-labeling technique, respectively. The clinical parameters and prognosis of the patients were evaluated. RESULTS: The proliferation index in poorly-differentiated cancer was significantly higher than that in moderately-differentiated cancer. Good-responders to hormone therapy, as assessed by the decrease in prostate-specific antigen after the endocrine therapy, were likely to have a low proliferation index. The patients with a low proliferation index had better progression-free and cause-specific survival compared to those with a high proliferation index. Proliferation indices were significantly correlated with apoptotic indices. CONCLUSION: Metastatic prostate cancer shows an increase of malignant potential as assessed by the number of Ki-67-positive cells and proliferation in each tumor is correlated with apoptosis.

Prognostic significance of changes in short-term prostate volume and serum prostate-specific antigen after androgen withdrawal in men with metastatic prostate cancer.

OBJECTIVE: Endocrine therapy is the standard treatment for metastatic prostate cancer although progression to androgen independence is inevitable. To evaluate prognostic factors in metastatic prostate cancer, patients who had been treated with endocrine therapy were investigated especially for the change in prostate volume. METHODS: Fifty-nine patients with untreated metastatic prostate cancer who received endocrine therapy were included in the present study. Blood chemistry, histological grade, extent of bony metastasis, clinical response to hormone therapy including the short-term change in prostate volume and serum prostate-specific antigen (PSA), and prognosis of the patients were evaluated. RESULTS: With univariate analysis, hemoglobin concentration, serum alkaline phosphatase, lactate dehydrogenase (LDH), histological grade, extent of bony disease, the short-term change of prostate volume and response of PSA at 3 months were shown to be significant prognostic factors. Response of PSA, LDH and the change in prostate volume were significant for predicting prognosis with multivariate analyses. Five-year survival rate in patients whose prostate had regressed 20% or more at 1 month and whose PSA had been normalized at 3 months was 67%, whereas that in patients whose prostate had regressed less than 20% and whose PSA had not been normalized was 0%. CONCLUSIONS: The patients in whom PSA had not been normalized at 3 months and the prostate volume had regressed less than 20% at 1 month were in the high-risk group. New or more aggressive treatment should be considered.

Loss of heterozygosity at 7q31.1 and 12p13-12 in advanced prostate cancer.

BACKGROUND: Allelic losses on chromosome arms 2q, 3p, 5q, 6q, 7q, 8p, 9p, 10p, 10q, 11p, 11q, 12p, 13q, 16q, 17p, 17q, 18q, and 21q are reportedly associated with progression and/or initiation of prostate cancer. In the present study, we performed a polymerase chain reaction (PCR) analysis of polymorphic microsatellite loci on the human chromosomes 7 and 12p13-12 in prostate cancer tissue to investigate the extent of involvement of these regions, which may contain putative tumor suppressor genes. METHODS: Tissue samples were obtained at autopsy from 17 men who died of hormone-refractory prostate cancer at Chiba University, Japan, and affiliated hospitals between June of 1992 and June of 1995. DNA from normal tumor or metastatic tissue was used as the template for PCR amplification of a set of 16 polymorphic microsatellite loci on human chromosome 7 and 6 loci on the human chromosome region 12p13-12. RESULTS: The frequencies of cases with loss of heterozygosity (LOH) at 7q31.1 were 8% in primary tumor tissue and 11% in metastatic tissue. The frequencies of cases with LOH at 12p13-12 were 12% in primary tumor tissue and 25% in metastatic tumor tissue. CONCLUSIONS: In the present study, the frequencies of LOH at 7q31.1 were lower than in Western patients, suggesting that LOH in this region is not related to progression of prostate cancer in Japanese patients. The frequency of LOH at 12p13-12 was similar to that reported in Western countries, indicating that 12p13-12 may contain a tumor suppressor gene of prostate cancer.