Prostate­specific antigen density and preoperative MRI findings as predictors of biochemical recurrence in high­risk and very high­risk prostate cancer.

Patients with high-risk prostate cancer after prostatectomy have a particularly high chance of being diagnosed with biochemical recurrence (BCR). Patients with BCR have a greater risk of disease progression and mortality. The present retrospective observational study aimed to clarify the risk factors for the BCR of prostate cancer after radical prostatectomy in patients with high-risk and very high-risk prostate cancer. Patients diagnosed with prostate cancer who received radical prostatectomy in a single center from January 2009 to June 2020 were included in the study. Data from medical records were reviewed and the patients were followed up for ≥6 years. The primary outcome was BCR within 1 year after surgery. A total of 307 patients were included, with 187 in the high-risk group and 120 in the very high-risk group as classified by the National Comprehensive Cancer Network (NCCN) guidelines. Patients in the very high-risk group had a lower BCR-free survival rate compared with those in the high-risk group, with a high risk of BCR even if their PSA levels were initially undetectable after prostatectomy, and a high risk of postoperatively detectable PSA. In patients with undetectable PSA after prostatectomy, BCR was associated with the initial PSA density, imaging stage (T3aN0M0 and T3bN0M0), and pathologic stage (any N1). Postoperatively detectable PSA was associated with pathologic stage (T3bN0M0 and any N1) In conclusion, preoperative MRI imaging stage and PSA density are predictors for short-term BCR after prostatectomy. NCCN-defined high-risk patients with a high initial PSA density, imaging stage (T3aN0M0 and T3bN0M0), and pathologic stage (any N1) had a higher risk of BCR when compared with other patients with undetectable PSA, while those with pathologic stage (T3bN0M0 or any N1) displayed a higher risk of postoperatively detectable PSA. These findings may help urologists to identify patients for whom active therapeutic protocols are necessary.

Efficacy of a protocol including heparin ointment for treatment of multikinase inhibitor-induced hand-foot skin reactions.

PURPOSE: The purpose of this study is to evaluate the efficacy of a protocol including topical heparin therapy for hand-foot skin reactions (HFSR) during multikinase (MKI) treatment. METHODS: We prospectively collected 26 patients who had HFSRs during treatment with the MKIs, sunitinib, sorafenib, or axitinib. The age distribution ranged from 46 to 87 years, with a mean of 66 years. The distribution of HFSR severity was 12 patients with grade 1, 12 with grade 2, and 2 with grade 3. A heparin-containing topical ointment treatment, combined with hand-foot shock absorbers and skin moisturizers, was used at the lesion sites. Changes in the grade of HFSR, MKI dosage, and interruptions of MKI therapy were recorded. RESULTS: The results showed that 66.7% of grade 1 patients were cured of disease, 83.3% of grade 2 patients had improved symptoms, and both grade 3 patients (100%) had improved symptoms and were downgraded to grade 2. Four (15.4%) patients required reduction of MKI dosage, but there were no treatment interruptions or dropouts. CONCLUSION: Our protocol is beneficial in promoting resolution of HFSRs induced by MKIs. Further validation in large control studies should be investigated.

Leaf Extracts of Calocedrus formosana (Florin) Induce G2/M Cell Cycle Arrest and Apoptosis in Human Bladder Cancer Cells.

Calocedrus formosana (Florin) bark acetone/ethylacetate extracts are known to exert an antitumor effect on some human cancer cell lines, but the mechanism is yet to be defined. The aim of this study was to determine the effects of Florin leaf methanol extracts on the growth and apoptosis of human bladder cancer cell lines. MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay showed that the growth of these bladder cancer cells was potently inhibited by the Florin leaf extracts. The cell cycle of these extract-treated cells (TCCSUP cells) was arrested at the G2/M phase as determined by flow cytometry. Western blot analysis revealed the increases of cyclin B1 and Cdc2 kinase levels, alone with the decrease of phosphorylated Cdc2 kinase, after treating these cells with the extracts. An immunofluorescence assessment of ß-tubulin showed decreased levels of polymerized tubulin in treated cells. However, the proteolytic cleavage of poly ADP-ribose polymerase and the activation of caspase-3/-8/-9 were all increased upon treatments of extracts. The concurrent increase of Bax and decrease of Bcl-2 levels indicated that the extracts could induce apoptosis in these treated cells. Taken together, these results suggest that the Florin leaf extracts may be an effective antibladder cancer agent.

Comparative nephrotoxicity of aristolochic acid and tetrandrine in vitro and in vivo.

Aristolochic acid (AA) and tetrandrine (TET) are the major bioactive components in Chinese herbs used for weight loss. The nephropathy caused by the 2 Chinese herbs has not been simultaneously investigated. The aim of this study was to examine the potential nephrotoxicity of AA and TET using Madin-Darby canine kidney (MDCK) cells and mice. The results showed that TET was more potent than AA in inhibiting MDCK cell growth via inducing apoptosis, as determined by annexin-V staining, 4', 6'-diamino-2-phenylindole (DAPI) staining, DNA fragmentation, and caspase 3 activity. Mice treated with AA (10 mg/kg) by intraperitoneal administration for 3 months showed nephrotoxicity, elevated blood urea nitrogen, and increased renal tubular injuries. In contrast, mice treated with 50 mg/kg of TET in the same time period had moderate hydropic degeneration of the distal tubules in the kidneys. These results suggest that TET is more cytotoxic than AA in MDCK cells but shows less nephrotoxic than AA in mice.

Surgical tip to prevent bladder perforation during transurethral resection of bladder tumors.

INTRODUCTION: Transurethral resection of bladder tumors is performed for the treatment of bladder cancer. We describe our surgical technique for transurethral resection of bladder tumors. It is easy to control the tissue depth of resection using the lateral resecting portion of the conventional right-angle loop electrode. TECHNICAL CONSIDERATIONS: Since April 2006, we have performed this technique on 57 consecutive lesions in 37 patients. The surgeon rotates the resectoscope and uses the lateral resecting portion of the right-angle loop electrode to control the tissue depth during transurethral resection. The tissue depth of resection can be precisely controlled by the surgeon using this technique. No bladder perforation or uncontrollable bleeding was observed. CONCLUSIONS: The described surgical tip is a safe technique to prevent bladder perforation during transurethral resection of bladder tumors.

The 5th Conference on Asian Trends in Prostate Cancer Hormone Therapy.

The Conference on Asian Trends in Prostate Cancer Hormone Therapy is an annual forum for Asian urologists now in its 5th year. The 2006 conference, held in Bali, Indonesia, was attended by 27 leading urologic oncologists from China, Indonesia, Japan, Korea, Singapore, and Taiwan and featured a packed program of presentations and discussions on a wide range of topics such as relationships among clinicians and the newly opened Asia Regional Office for Cancer Control of the International Union Against Cancer (UICC), detection rates of prostate cancer by biopsy in each of the 6 Asian countries, and favored treatment modalities for hormone-refractory prostate cancer (HRPC) in each country. The first session of the conference kicked off with a keynote lecture entitled "Activities of the UICC ARO". UICC's new office will be the nerve center for its activities in the Asia region. Along with the Asian Pacific Organization for Cancer Prevention (APOCP), UICC aims to shift the focus of attention to cancer control. As such APOCP's long-running publication the APJCP is to be re-launched as the Asian Pacific Journal of Cancer Control. Although UICC is primarily concerned with cancer, several risk factors for cancer are common also to other non-communicable diseases such as diabetes and heart disease, and an important strategy is to implement measures to control these various pathologic conditions as a whole. Apart from contributing to an Asian prostate cancer registry the UICC-ARO will provide training courses, working groups, and assistance in collecting and processing data. The keynote lecture was followed by a roundtable discussion on possible ways in which clinicians from each Asian country can work with UICC. A number of suggestions were put forth including better registration, epidemiology research, possible implementation of UICC prostate cancer guidelines, early detection and screening, and roles of diet and phytotherapy. The underlying reasons for the large but dwindling difference in incidence rates of prostate cancer in various regions of Asia should be studied while the opportunity lasts. Session 2 was devoted to 6 presentations on detection rates by biopsy in each country. Although biopsy is the gold standard for detecting prostate cancer in most areas, indications for conducting biopsy are different in each country. For example, in Indonesia doctors may use PSAD 0.15 as the cutoff level. TRUS-guided biopsy is most widely used in Asian countries. Traditional sextant biopsy is often performed, although multiple-core biopsy is commonly available and associated with better detection rates, especially in men with large prostate volume. Positive DRE, high PSA, and older age were identified as factors associated with high biopsy detection rate, although elevated PSA has limited specificity. First biopsy in men with elevated PSA had a positive detection rate of approximately 30% in all countries. Community-based screening in some countries has an overall detection rate of approximately 1%. The favorable treatment modality for HRPC was the subject of the final session. First priority for doctors in all 6 countries is to maintain serum testosterone at castration level. Many therapeutic options are available, from cytotoxic drugs to traditional herbal medicines Chemotherapeutic agents such as estramustine, docetaxel, cyclophosphamide, and mitoxantrone are often given to patients with HRPC although not all are available in every country. Prednisone and dexamethasone are used for secondary hormonal therapy. External beam radiotherapy, radioisotopic drugs such as strontium 89, and bisphosphonates are common choices to control bone pain.

Asian trends in prostate cancer hormone therapy.

The first Conference on Asian Trends in Prostate Cancer Hormone Therapy was held in September 2001 to serve as a forum for Asian urologists to compare data on prostate cancer and discuss issues regarding the use of hormone therapy. The conference revealed that due to various cultural and philosophical factors, differences exist in prostate cancer management among the Asian countries. In addition, a lack of databases on hormone therapy was exposed in some countries. It was noted that many decisions in the treatment of prostate cancer are influenced by the strategies adopted in Western countries, and that attempts to formulate uniform guidelines for the Asian region have hitherto been unsuccessful. The main findings of the conference are reported in this review.