Chao-Yuan Huang

Changing trends of prostate cancer in Asia

Although Asian people have the lowest incidence and mortality rates of prostate cancer in the world, these rates have risen rapidly in the past two decades in most Asian countries. Prostate cancer has become one of the leading male cancers in some Asian countries. In 2000, the age-adjusted incidence was over 10 per 100 000 men in Japan, Taiwan, Singapore, Malaysia, the Philippines and Israel. Although some of the increases may result from enhanced detection, much of the increased incidence may be associated with westernization of the lifestyle, with increasing obesity and increased consumption of fat. The differences in incidences between native Americans and Asian immigrants are getting smaller, reflecting a possible improvement of diagnostic efforts and changes of environmental risk factors in Asian immigrants. Nevertheless, the huge variations in incidences among ethnic groups imply that there are important genetic risk factors. The stage distributions of prostate cancer in Asian populations are still unfavorable compared to those of Western developed countries. However, a trend towards diagnosing cancer with more favorable prognosis is seen in most Asian countries. Both genetic and environmental risk factors responsible for elevated risks in Asian people are being identified, which may help to reduce prostate cancer incidence in a chemopreventive setting.

Stopping smoking might reduce tumour recurrence in nonmuscle-invasive bladder cancer

To evaluate effects of stopping smoking on the outcome of nonmuscle‐invasive bladder cancer, as cigarette smoking is a risk factor for bladder cancer and little is known about whether stopping smoking reduces the risk of recurrence or progression.

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.

Micro-Raman for diamond film stress analysis

Abstract The residual stress in microwave plasma-enhanced CVD diamond film was analyzed using a Raman spectrometer with micrometer spatial resolution. This enables effective study of isolated crystals grown in the same deposition run. A variation of the Raman line shape near 1332 cm −1 was observed from different crystals in the same sample. A phenomenological model was used to describe the shift and splitting of the diamond Raman line, from which the type and the magnitude of the stress in PECVD grown diamond can be assessed. The interrelationship and the origin of the stress in the film is discussed.

Aristolochic acid-induced upper tract urothelial carcinoma in Taiwan: clinical characteristics and outcomes.

Aristolochic acid (AA), a component of all Aristolochia‐based herbal medicines, is a potent nephrotoxin and human carcinogen associated with upper urinary tract urothelial carcinoma (UUC). To investigate the clinical and pathological characteristics of AA‐induced UUC, this study included 152 UUC patients, 93 of whom had been exposed to AA based on the presence of aristolactam‐DNA adducts in the renal cortex. Gene sequencing was used to identify tumors with A:T‐to‐T:A transversions in TP53, a mutational signature associated with AA. Cases with both aristolactam‐DNA adducts and A:T‐to‐T:A transversions in TP53 were defined as AA‐UUC, whereas patients lacking both of these biomarkers were classified as non‐AA‐UUC. Cases with either biomarker were classified as possible‐AA‐UUC. Forty (26%), 60 (40%), and 52 (34%) patients were classified as AA‐UUC, possible‐AA‐UUC and non‐AA‐UUC, respectively. AA‐UUC patients were younger (median ages: 64, 68, 68 years, respectively; p=0.189), predominately female (65%, 42%, 35%, respectively; p=0.011), had more end‐stage renal disease (28%, 10%, 12%, respectively; p=0.055), and were infrequent smokers (5%, 22%, 33%, respectively; p=0.07) compared to possible‐AA‐UUC and non‐AA‐UUC patients. All 14 patients who developed contralateral UUC had aristolactam‐DNA adducts; ten of these also had signature mutations. The contralateral UUC‐free survival period was shorter in AA‐UUC compared to possible‐ or non‐AA‐UUC (p=0.019 and 0.002, respectively), whereas no differences among groups were observed for bladder cancer recurrence. In conclusion, AA‐UUC patients tend to be younger and female, and have more advanced renal disease. Notably, AA exposure was associated with an increased risk for developing synchronous bilateral and metachronous contralateral UUC.

Cell Therapy for Salivary Gland Regeneration

There are still no effective therapies for hyposalivation caused by irradiation. In our previous study, bone marrow stem cells can be transdifferentiated into acinar-like cells in vitro. Therefore, we hypothesized that transplantation with bone marrow stem cells or acinar-like cells may help functional regeneration of salivary glands. Bone marrow stem cells were labeled with nanoparticles and directly co-cultured with acinar cells to obtain labeled acinar-like cells. In total, 140 severely combined immune-deficiency mice were divided into 4 groups for cell therapy experiments: (1) normal mice, (2) mice receiving irradiation around their head-and-neck areas; (3) mice receiving irradiation and intra-gland transplantation with labeled stem cells; and (4) mice receiving irradiation and intra-gland transplantation with labeled acinar-like cells. Our results showed that salivary glands damaged due to irradiation can be rescued by cell therapy with either bone marrow stem cells or acinar-like cells for recovery of saliva production, body weight, and gland weight. Transdifferentiation of bone marrow stem cells into acinar-like cells in vivo was also noted. This study demonstrated that cell therapy with bone marrow stem cells or acinar-like cells can help functional regeneration of salivary glands, and that acinar-like cells showed better therapeutic potentials than those of bone marrow stem cells.

Association of vitamin D receptor FokI polymorphism with prostate cancer risk, clinicopathological features and recurrence of prostate specific antigen after radical prostatectomy

To investigate the effect of vitamin D receptor (VDR) FokI polymorphism on susceptibility to prostate cancer and the outcome of the disease in a Taiwanese population, we genotyped a total of 416 prostate cancer patients, 502 age‐matched male controls and 189 non age‐matched symptomatic benign prostatic hyperplasia. Although we did not find a significant association between VDR FokI genotypes and overall prostate cancer risk, we found that in men aged less than or equal to the median age of 73 years with VDR FokI F allele specifically had an increased risk of prostate cancer with a marginal significant trend (OR, 2.08; 95% CI, 1.00–4.34, p for trend = 0.056). The FF genotype was also highly associated with more aggressive prostate cancer (Gleason score 8–10) (OR, 2.47; 95% CI, 1.20–5.08) than did the Ff and ff genotypes. After adjusting other covariates, we found that in patients who had localized prostate cancer for which a radical prostatectomy was performed (n = 131), the VDR FokI FF genotype was associated with worse prostate‐specific antigen (PSA) recurrence‐free survival (hazard ratio = 3.25, 95% CI = 1.32–8.00, p = 0.010). Our findings suggest that the VDR FF genotype may increase the risk of early‐onset prostate cancer and is associated with more aggressive disease. Furthermore, the VDR polymorphism could be used as a prognostic marker for localized prostate cancer after radical prostatectomy.

Arsenic trioxide as a novel anticancer agent against human transitional carcinoma--characterizing its apoptotic pathway.

Arsenic trioxide (As2O3) has been shown to be an active agent against acute promyelocytic leukemia. Little is known about its therapeutic efficacy in human transitional carcinomas. In this study, the arsenic-mediated apoptotic pathway in transitional carcinoma cells was investigated. Three bladder transitional carcinoma cell lines were used, including a parental sensitive line and two resistant daughter lines (cisplatin and As2O3 resistant). The As2O3-mediated cytotoxicity to the three cell lines was studied in vitro in the presence or absence of buthionine sulfoximine (BSO), a chemotherapy modulator. In results, although a lesser extent of apoptosis was seen in cells treated with As2O3 alone, more significant apoptotic events were observed in the combined treatment of As2O3 and non-toxic concentrations of BSO (up to 10 μ M). These included the accumulation of sub-G1 fractions and internucleosomal DNA breakdown, which were preceded by production of reactive oxygen species, loss of mitochondrial membrane potential and activation of caspase-3. In conclusion, As2O3 in the presence of BSO may be an active agent against both chemonaive and cisplatin-resistant transitional carcinomas. The As2O3-mediated cytotoxicity appeared to go through the conventional apoptotic pathway. Our results have clinical implications and warrant further investigation.

Impact of prostate-specific antigen (PSA) nadir and time to PSA nadir on disease progression in prostate cancer treated with androgen-deprivation therapy

The influence of PSA kinetics on the outcome of metastatic prostate cancer after androgen deprivation therapy (ADT) is not well understood. We evaluated the prognostic significance of PSA nadir and time to PSA nadir as well as their potential interactive effect on the progression of disease after ADT.

Genetic polymorphisms in oestrogen receptor-binding sites affect clinical outcomes in patients with prostate cancer receiving androgen-deprivation therapy

Abstract.  Huang C‐N, Huang S‐P, Pao J‐B, Hour T‐C, Chang T‐Y, Lan Y‐H, Lu T‐L, Lee H‐Z, Juang S‐H, Wu P‐P, Huang C‐Y, Hsieh C‐J, Bao B‐Y (Kaohsiung Medical University Hospital, Kaohsiung; Kaohsiung Medical University, Kaohsiung; Taipei City Hospital, Taipei; Kaohsiung Medical University, Kaohsiung; China Medical University, Taichung; National Taiwan University Hospital; Oriental Institute of Technology; National Taiwan University, Taipei; China Medical University Hospital, Taichung, Taiwan). Genetic polymorphisms in oestrogen receptor‐binding sites affect clinical outcomes in patients with prostate cancer receiving androgen‐deprivation therapy. J Intern Med 2012; 271: 499–509.