Abiraterone acetate withdrawal syndrome: Speculations on the underlying mechanisms.

A 72-year-old man initially presented with lumbar and right chest pain, but was later found out to also have an elevated prostate-specific antigen (PSA) level at 2,000.0 ng/ml. Further evaluation disclosed metastatic prostate cancer involving the bones and lymph nodes. The patient was initially treated with combined androgen blockade (CAB) with leuprolide acetate and bicalutamide. After 6 months of CAB, the patient's PSA level began to rise from the nadir (85.1 ng/ml) to 113.3 ng/ml. Bicalutamide was withdrawn in anticipation of anti-androgen withdrawal syndrome and the PSA level declined temporally. However, it increased up to 517.0 ng/ml thereafter. Consequently, a year after CAB, abiraterone acetate (AA) was initiated at a standard dose of 1,000 mg daily in combination with 10 mg of prednisolone. PSA rapidly decreased to the nadir of 20.1 ng/ml thereafter. The PSA level remained stable until 2 years after AA administration. However, he decided to reduce the dose of AA to half of the standard dose (500 mg daily). Contrary to our expectations, the serum PSA level promptly decreased to a nadir of 8.1 ng/ml. Thereafter, the PSA level remained stable until 3 years and 9 months after AA administration. Subsequently, the patient stopped taking AA and prednisolone. However, to our surprise, the patient's serum PSA level decreased further to <1.0 ng/ml after AA discontinuation. His PSA remained <1.0 ng/ml without clinical or radiological progression for 1 year after AA withdrawal. Recently, it was reported that cessation of AA is associated with AA withdrawal syndrome in metastatic castration-resistant prostate cancer, defined as a PSA decrease after AA discontinuation, mimicking anti-androgen withdrawal syndrome. In the present study, explanations of the mechanisms underlying this phenomenon were explored, including mutant AR activation by alternative ligands.

Use of cell-free circulating schistosome DNA in serum, urine, semen, and saliva to monitor a case of refractory imported schistosomiasis hematobia.

This case of imported refractory schistosomiasis has highlighted the usefulness of cell-free parasite DNA as a diagnostic marker to assess active schistosome infection. In contrast to the rapid disappearance of ova in urine, parasite DNA remained persistent in several other specimen types even after the fourth treatment with praziquantel. This result was consistent with the presence of morphologically intact ova in bladder biopsy samples and with the corresponding symptoms.

[Retardation of hemodialysis by recombinant human erythropoietin in patients with chronic kidney disease].

UNLABELLED: Renal anemia is a serious complication of chronic kidney disease (CKD) and accelerates its progress. Recombinant human erythropoietin (rHuEPO) therapy not only improves anemia but also has a renoprotective effect. This study aimed to determine whether treatment with rHuEPO can retard the initiation of hemodialysis (HD) in patients with CKD. METHODS: Clinical data of CKD patients who had already been treated with HD were analyzed retrospectively. Twenty-one patients who had received rHuEPO therapy constituted the treated group (EPO(+) group), and twenty-one other patients without rHuEPO constituted the non-treated group (EPO(-) group). The study start-point was the day of kidney function deterioration, judged as CKD stage 5. The end-point of the study was the initiation of HD. RESULTS: During the evaluation period, mean values of hemoglobin (Hb) in the EPO(+) group remained lower than those in the EPO(-) group. Survival analysis limited to the two-year period from the beginning of evaluation showed that the renal survival rate of the EPO(+) group was significantly better than that of the EPO(-) group [EPO(+): 42.1% vs. EPO(-): 12.5%, p<0.05]. Duration of renal survival was 29.8 +/- 4.07 months in the EPO(+) group and 19.1 +/- 3.27 months in the EPO(-) group (p<0.05). CONCLUSION: Although the mean values of Hb remained lower in the EPO(+) group than in the EPO(-) group during the observation period, the renal survival rate and duration of renal survival in the EPO(+) group were significantly superior than in the EPO(-) group. The study suggests that rHuEPO exerts a renoprotective effect via a mechanism other than the correction of anemia.

Sustained prophylactic effect of intravesical bacille Calmette-Guérin for superficial bladder cancer: a smoothed hazard analysis in a randomized prospective study.

OBJECTIVES: A previous meta-analysis had revealed that intravesical chemotherapy was effective in reducing the recurrence of superficial bladder cancer only in the early phase, the phase thought to be caused by tumor cell implantation and/or residual tumor cells. To ascertain the sustained prophylactic effect of intravesical bacille Calmette-Guérin (BCG) after transurethral resection of bladder tumor (TURBT), we compared the estimation of the duration of the effect with that of doxorubicin. METHODS: Eighty eligible patients with superficial bladder cancer (Stage Ta or T1, grade 1 or 2) were included. Patients were randomly allocated into two groups: the BCG group (six weekly instillations of 80 mg BCG [Tokyo 172 strain]) and the doxorubicin group (17 instillations of 20 mg doxorubicin). A comparison between the smoothed hazards of tumor recurrence was performed using a kernel function method. RESULTS: All 80 patients (40 each in the BCG and doxorubicin groups) were compared. The median follow-up period was 667 days (range 64 to 1607). The risk of recurrence was significantly lower in the BCG group than in the doxorubicin group (P = 0.017, log-rank test). A smoothed hazard curve depicting the reduced risk of recurrence in the BCG group suggested that BCG is not only efficacious in the early phase of recurrence (up to 500 days after TURBT), but also in the late phase, and the latter is thought to include second primary tumors (new tumors). CONCLUSIONS: BCG instillation may prevent tumor recurrence caused by both tumor cell implantation and second primary tumors.

Intermittent androgen suppression for locally advanced and metastatic prostate cancer: preliminary report of a prospective multicenter study.

OBJECTIVES: To clarify the effect of intermittent androgen suppression on the time to androgen-independent progression and changes in quality of life (QOL). METHODS: Patients with locally advanced or metastatic prostate cancer were treated with a combination of leuprolide acetate and flutamide for 36 weeks. When the serum prostate-specific antigen (PSA) levels at 24 and 32 weeks were less than 4.0 ng/mL, treatment was withheld until the PSA level reached 15 ng/mL or the pretreatment level. This cycle of on-treatment and off-treatment was repeated until PSA failure (three consecutive increases in PSA level greater than 4.0 ng/mL during the on-treatment period) or symptomatic progression was observed. Changes in QOL were assessed by a self-assessment questionnaire. RESULTS: Forty-nine patients (26 with T3N0M0, 8 with T2-T3N1M0, 2 with T4N0M0, and 13 with T2-T3N0M1) were enrolled. The mean follow-up period was 136.5 weeks. Thirty-one patients finished cycle 1, six finished cycle 2, and three finished cycle 3. The mean off-treatment duration in cycles 1, 2, and 3 was 46.1, 36.9, and 23.3 weeks, respectively. In the off-treatment period, statistically significant improvements in the QOL score were observed in the categories of potency (11.4 versus 2.4) and social/family well-being (20.3 versus 16.1) compared with those in the on-treatment period. PSA failure occurred in 6 patients (3 with T3N0M0 and 3 with T2-T3N1M0), and all patients were alive at last follow-up. CONCLUSIONS: Our interim analysis indicated that QOL is remarkably improved during the off-treatment period. Intermittent androgen suppression would be a viable option for treatment of advanced prostate cancer, although a randomized controlled study is required to determine whether intermittent androgen suppression prolongs the time to androgen-independent cancer. We will continue follow-up in this study to a minimum of 3 years.

Phase I/II clinical trials of carbon ion therapy for prostate cancer.

BACKGROUND: Heavy ion beams possess high linear energy transfer components and a prominent Bragg peak in the human body, resulting in higher relative biological effectiveness and improved dose distribution. To establish heavy ion therapy techniques for the treatment of prostate cancer, phase I/II clinical trials were initiated. METHODS: For 96 patients with T1b-T3 prostate cancer, three carbon ion beams were used to irradiate the prostate and seminal vesicles (20 times/5 weeks) with or without endocrine therapy. Radiation dose was expressed in GyE which was initially thought to be equivalent to photon dose. Total dose was gradually increased from 54 to 72 GyE. RESULTS: Carbon ion therapy was completed in 20 cases of T1b/T1c/T2aN0M0 as monotherapy, in 8 cases of T2b/T3pN0M0 with neoadjuvant endocrine therapy, and in 68 cases of T2b/T3N0/pN1M0 with neoadjuvant and adjuvant endocrine therapy. Median observation period was 47 months. Grade 3 late radiation morbidity of rectum and/or bladder/urethra developed in one and five cases who received 66 and 72 GyE of radiation, respectively. After these adverse effects were observed, total dose was decreased to 66 GyE and the radiation field was coned down during the treatment course. At 5 years, overall, cause-specific, clinical recurrence-free, and biochemical recurrence-free survival rates were 87.7, 94.9, 90.0, and 82.6%, respectively. Local control was achieved in all patients except one patient who received 54 GyE of radiation. CONCLUSIONS: The therapeutic techniques of carbon ion therapy have been established for patients with prostate cancer. Carbon ion therapy may exert excellent effect to the tissues of prostate cancer.

Expression of thymidine phosphorylase in primary human renal cell carcinoma by ELISA method.

Thymidine phosphorylase (TP) expression in 100 paired samples of renal cell carcinoma (RCC) and normal adjacent tissue was analyzed by an ELISA method. We also investigated whether TP expression correlates with clinicopathological findings and clinical outcomes of these patients. Median TP expression was 9-fold (range, 0.5-56) higher in primary tumor than in non-cancerous renal tissue (P < 0.0001). There was a significant difference with respect to tumor venous invasion. TP expression was significantly higher in patients with such venous invasion than in those without (P = 0.018). However, there was no correlation between TP level and other clinicopathological findings and the survival curves. These results suggest that ELISA is useful for evaluating TP expression of human RCC and may provide a novel approach to therapy for patients with RCC.

[Intravesical instillation of doxorubicin or epirubicin for chemoprophylaxis of superficial bladder cancer--the fifth study of the Japanese Urological Cancer Research Group for Adriamycin/Farumorubicin].

A total of 465 patients with primary and multiple or recurrent, stages Ta and T1 superficial bladder cancer were included in this randomized multicenter trial to compare the prophylactic effect by 17 times instillation of 40 mg doxorubicin or 40 mg epirubicin with no instillation after transurethral resection of tumor(s). The primary endpoint was first recurrence after transurethral resection. Endoscopic examination as well as urinary cytology was performed in each case every three months. It became evident that the recurrence rate in the doxorubicin or epirubicin instillation arm was lower that in the no instillation arm. Toxicity was mainly restricted to bladder irritation in about 10% of patients in each instillation arm.