SUMMARY:Epigenetic mechanisms including DNA methylation and histone deacetylation are thought to play important roles in gene transcriptional inactivation. Heterogenous expression of androgen receptor (AR), which appears to be related to variable responses to endocrine therapy in prostate cancer (PCa) may also be due to epigenetic factors. The methylation status of the 5Ј CpG island of the AR in 3 prostate cancer cell lines and 10 primary and 14 hormone-refractory PCa samples was determined using the bisulfite PCR methods. In DU145, CpG-rich regions of the AR were hypermethylated. By an immunohistochemical analysis, only one PCa sample had no AR expression, the others being heterogenous. Bisulfite sequencing and methylationspecific PCR analysis showed aberrant methylation of AR 5Ј-regulatory region in 20% of 10 primary and 28% of 14 hormone-refractory PCa samples. To clarify the effect of epigenetic regulation on AR expression, we treated three prostate cancer cell lines with a demethylating agent, 5-aza-2Ј-deoxycytidine (azaC), and a histone deacetylase inhibitor, Trichostatin A (TSA). In DU145, re-expression of AR mRNA was detected after treatment with azaC and/or TSA. Our results suggest that epigenetic regulations including CpG methylation and histone acetylation may play important roles in the regulation of the AR.

Abstract:Our objective was to determine the incidence of inguinal hernia (IH) after surgery for prostatic diseases. Medical records of 395 patients who underwent radical retropubic prostatectomy (RRP; n = 155), open simple prostatectomy (OP; n = 35), or transurethral resection of the prostate (TURP; n = 205) at the Chibaken Saiseikai Narashino Hospital from April 2000 to March 2007 were retrospectively evaluated. The incidence of IH was 23.9% in the RRP group, 18.9% in the OP group, and 2% in the TURP group. Overall, 91.9% in the RRP and 83.3% in the OP group developed an IH within 2 years postoperatively. The laterality of IH after open surgery was mainly on the right side. Subclinical IH were seen in 25% of RRP cases. The existence of subclinical IH was the only significant risk factor for postoperative IH in this analysis. Furthermore, OP and RRP procedures significantly increased the risk of postoperative IH compared with TURP. The hernia-free ratios were significantly lower after RRP and OP than after TURP (vs RRP: P < 0.001; vs OP: P < 0.001). Our findings confirm that a lower abdominal incision itself is associated with postoperative IH in patients undergoing prostate surgery. Attention must be paid to pre-existing subclinical IH through careful preoperative assessment. Patients should be followed for more than 2 years due to the high incidence of postoperative IH.

These results indicate an important role of CD44 methylation in the progression and metastasis of prostate cancer, although the amount of methylational heterogeneity is substantial among metastatic sites within the same patient.

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The Clinical Practice Guidelines for Bladder Cancer edited by the Japanese Urological Association were first published in 2009 and a revised edition was released in 2015. Four years has passed since the 2015 edition, and the clinical practice environment surrounding bladder cancer has drastically changed during that time. The main changes include: (i) insurance coverage of a new diagnostic method for nonmuscle-invasive bladder cancer; (ii) insurance coverage of an immune checkpoint inhibitor in advanced and metastatic bladder cancer; and (iii) advances in robot-assisted radical cystectomy as a minimally invasive treatment for muscle-invasive bladder cancer. A paradigm shift in bladder cancer diagnosis and treatment is occurring day by day. Therefore, in this 2019 edition, while dealing with the above changes, we carefully selected clinical questions with clear evidence and included other clinically important points in the general statement. We also added a new chapter on rare cancers of the urinary tract. As a new method for the evaluation of study evidence level, we introduce "The Grading of Recommendations Assessment, Development and Evaluation" system modified to Japanese by the Medical Information Network Distribution Service.

The objective of this study was to perform external validation of a previously developed prostate biopsy nomogram (the CHIBA nomogram) and to compare it with previously published nomograms developed in Japanese and overseas populations. Two different cohorts of patients were used: one from the Chiba Cancer Center (n = 392) in which transperineal 16-core biopsy was performed, and another from Chibaken Saiseikai Narashino Hospital (n = 269) in which transrectal 16-core biopsy was carried out. All patients were Japanese men with serum prostate-specific antigen levels less than 10 ng/mL. The predictive accuracy of our CHIBA nomogram and of four other published nomograms (Finne's sextant biopsy-based logistic regression model, Karakiewicz's sextant biopsy-based nomogram, Chun's 10-core biopsy-based nomogram and Kawakami's three-dimensional biopsy-based nomogram) was quantified based on area under the curve derived from receiver operating characteristic curves. Head-to-head comparison of area under the curve values demonstrated that our nomogram was significantly more accurate than all other models except Chun's (P = 0.012 vs Finne's, P = 0.000 vs Karakiewicz's, and P = 0.003 vs Kawakami's). Our nomogram appears to be more useful for the Japanese population than Western models. Moreover, external validation demonstrates that its predictive accuracy does not vary according to biopsy approach. This is the first report to demonstrate that the predictive accuracy of a nomogram is independent from the biopsy method.

Expression of the KAI1 gene, a metastasis-suppressor for prostate cancer, is reduced in all foci of prostatic metastasis. The altered regulatory mechanism is not strongly related to mutations or allelic losses of the KAI1 gene in prostate tumors. Since transcriptional silencing of genes has been found to be caused by epigenetic mechanisms, we have investigated the involvement of this epigenetic regulation of KAI1 expression in prostate cancers. The methylation status of the KAI1 promoter region was examined by restriction-enzyme digestion and sequencing, after amplifying a 331-bp fragment in the GC-rich promoter region from 4 human prostate cancer cell lines treated with bisulfite. The same 4 cell lines were also exposed to various concentrations of the demethylating agent, 5-aza-2′ ′ ′ ′-deoxycytidine