Hong-Jen Yu

Resistance to Paclitaxel Is Proportional to Cellular Total Antioxidant Capacity

Paclitaxel, one of the most commonly prescribed chemotherapeutic agents, is active against a wide spectrum of human cancer. The mechanism of its cytotoxicity, however, remains controversial. Our results indicate that paclitaxel treatment increases levels of superoxide, hydrogen peroxide, nitric oxide (NO), oxidative DNA adducts, G2-M arrest, and cells with fragmented nuclei. Antioxidants pyruvate and selenium, the NO synthase inhibitor N(omega)-nitro-L-arginine methyl ester, and the NO scavenger manganese (III) 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazoline-1-oxyl-3-oxide all decreased paclitaxel-mediated DNA damage and sub-G1 cells. In contrast, the glutamylcysteine synthase inhibitor buthionine sulfoximine (BSO) and the superoxide dismutase (SOD) inhibitor 2-methoxyestradiol (2-ME) increased the sub-G1 fraction in paclitaxel-treated cells. These results suggest that reactive oxygen and nitrogen species are involved in paclitaxel cytotoxicity. This notion is further supported with the observation that concentrations of paclitaxel required to inhibit cell growth by 50% correlate with total antioxidant capacity. Moreover, agents such as arsenic trioxide (As2O3), BSO, 2-ME, PD98059, U0126 [mitogen-activated protein/extracellular signal-regulated kinase inhibitors], and LY294002 (phosphatidylinositol 3-kinase/Akt inhibitor), all of which decrease clonogenic survival, also decrease the total antioxidant capacity of paclitaxel-treated cells, regardless whether they are paclitaxel sensitive or paclitaxel resistant. These results suggest that paclitaxel chemosensitivity may be predicted by taking total antioxidant capacity measurements from clinical tumor samples. This, in turn, may then improve treatment outcomes by selecting out potentially responsive patients.

Major Complications and Associated Risk Factors of Transrectal Ultrasound Guided Prostate Needle Biopsy: A Retrospective Study of 1875 Cases in Taiwan

BACKGROUND/PURPOSE Complications from transrectal ultrasound (TRUS) guided prostate needle biopsy are occasionally encountered in the daily practice of urologists. We tried to determine the associated risk factors of patients who suffered from major complications that required hospitalization after TRUS guided prostate needle biopsies. METHODS We did a retrospective review of 1875 TRUS guided prostate biopsies performed between January 2002 and December 2005. We defined major complications as patients with complications that needed hospitalization. We analyzed the association between biopsy complications and suspected factors, including age, prostate volume, patients underlying disease, selection of prophylactic antibiotics, biopsy core numbers (6, 12, and 15 cores), and antiplatelet/anticoagulant usage. RESULTS There were 124 patients (6.6%) with major complication. These major complications were categorized as acute prostatitis (3.8%), acute urinary retention (2.1%), hematuria (1.9%), rectal bleeding (0.2%), epididymitis (0.2%), sepsis (0.05%), and vasovagal syncope (0.05%). Patients with larger prostate size were noted to have higher risk of developing transient acute prostatitis and acute urinary retention after prostate biopsy. In contrast, age, prophylactic antibiotics (levofloxacin and pipemidic acid), underlying diseases (diabetic mellitus, hypertension, hyperlipidemia, cerebrovascular accident, coronary artery disease), increased biopsy core numbers, and antiplatelet/anticoagulant usage were not associated with major complications after prostate biopsy. CONCLUSION TRUS guided prostate needle biopsy is a safe diagnostic tool in most elderly males with or without systemic underlying disease.

Comparison of 6- and 12-Core Prostate Biopsy in Taiwanese Men: Impact of Total Prostate-Specific Antigen, Prostate-Specific Antigen Density and Prostate Volume on Prostate Cancer Detection

Introduction: We retrospectively compared 6- and 12-core prostate biopsies in Taiwanese men and evaluated the impact of prostate volume (PV), prostate-specific antigen (PSA), and PSA density (PSAD) on the prostate cancer detection rate (PCDR). Patients and Methods: 1,086 consecutive patients with a total PSA of 4.1–20.0 ng/ml and/or abnormal digital rectal examination undergoing first-time transrectal ultrasound-guided biopsy were included. Group I patients (n = 562) underwent sextant biopsy and group II patients (n = 524) underwent sextant biopsy with an extra three lateral cores on both sides. The patients were further stratified into subgroups according to PV (cut-off: 35 ml), PSA (cut-off: 10.0 ng/ml), and PSAD (cut-off: 0.2). Results: Prostate cancer was diagnosed in 228/1,086 (21.0%) patients. The PCDR was higher in group II (23.7%) than group I (18.5%). 12-Core biopsy yielded a significantly higher PCDR than 6-core biopsies in patients with PV >35 ml, PSA 4.1–10.0 ng/ml, PSAD ≤0.20, but not in patients with PV ≤35 ml, PSA 10.1–20.0 ng/ml, PSAD >0.20. Conclusions: 12-Core biopsy yielded a significantly higher PCDR in Taiwanese men with a total PSA of 4.1–20.0 ng/ml, especially in patients with PSA 4.1–10.0 ng/ml, PSAD ≤0.20, and PV >35 ml.

Tuberculous Epididymitis Presenting as Huge Scrotal Tumor

Genitourinary tract tuberculosis is a specific chronic granulomatous infection. However, epididymal tuberculosis presented as a huge scrotal mass is uncommon. We report one case of epididymal tuberculosis that was noted 5 months after the prostate biopsy and was managed with unilateral simple epidymo-orchiectomy. Antituberculous drugs have been given as the medical treatment of tuberculosis postoperatively. Urinalysis became normalized and the scrotal ultrasonography showed normal left epididymis and testicle at 6-month follow up.

Impact of androgen-deprivation therapy on the outcome of dose-escalation prostate cancer radiotherapy without elective pelvic irradiation.

The benefit of androgen-deprivation therapy (ADT) in combination with dose-escalated radiotherapy (DERT) for localized prostate cancer has not been determined in randomized studies. In this study, the benefit of ADT was assessed in patients uniformly treated with dose-escalated intensity-modulated radiation therapy (IMRT) to the prostate and seminal vesicles but not pelvis. In all, 419 patients with localized prostate adenocarcinoma underwent definitive IMRT (cumulative dose 78 Gy), with 32.6%, 33.1%, 32.1%, and 2.1% having T1 through T4 disease, respectively, and 51.2% having high-risk disease. ADT was given to 76.1% of patients. With a median follow-up of 60 months, 5-year biochemical failure-free, disease-free, and overall survival rates were 87%, 86%, and 87%, respectively. T stage was an independent predictor of all three rates. Five-year pelvic nodal recurrence rate was 2.9%. ADT improved biochemical failure-free and disease-free survival but not overall survival. ADT showed benefit in high-risk disease but not intermediate-risk disease. Late gastrointestinal and genitourinary toxicities ≥ grade 2 occurred in 11.0% and 6.7%, respectively. In conclusion, DERT with 78 Gy yields good disease control and low rate of pelvic nodal recurrence. ADT improves disease-free survival in patients with high-risk but not intermediate-risk disease.

Dual-timing PSA as a biomarker for patients with salvage intensity modulated radiation therapy for biochemical failure after radical prostatectomy

We investigated the outcomes and the associated clinical-pathological factors in patients with prostate cancer (PCa) undergoing salvage intensity modulated radiation therapy (IMRT) for post-radical-prostatectomy (RP) biochemical failure. We report clinical outcomes of post-RP salvage IMRT, and describe chronic toxicity in these patients. Fifty patients with PCa underwent post-RP salvage IMRT. The median dose of IMRT was 70 Gy to the prostatic and seminal vesicle bed. Clinical-pathological and toxicity information were collected. The prostate cancer-specific survival (PCSS), disease-free survival (DFS), and biochemical-failure-free survival (BFFS) were calculated. Prognostic factors were analyzed for their association with disease control. The median follow-up time was 74 months. The 5-year PCSS, DFS, and BFFS after salvage IMRT were 95%, 88%, and 60%, respectively. Two patients (4%) experienced late gastrointestinal toxicity ≥ grade 3, and 5 patients (10%) had late genitourinary toxicity ≥ grade 3. On multivariate analysis, post-RP prostate-specific antigen (PSA) nadir ≤0.1 ng/ml (P=0.018) and PSA ≤0.5 ng/ml at salvage IMRT (P=0.016) were independent factors predicting better BFFS. Patients with both post-RP PSA nadir ≤0.1 ng/ml and PSA ≤0.5 ng/ml at salvage IMRT had a 5-year BFFS of 83% as compared with 43% in other patients (P=0.001). In conclusion, with hormonal therapy in most PCa patients, the addition of salvage IMRT for post-RP biochemical failure can achieve a good outcome with low toxicity. Patients with a post-RP PSA nadir ≤0.1 ng/ml and PSA ≤0.5 ng/ml at salvage IMRT could benefit the most from salvage IMRT.