Computer-assisted three-dimensional analysis of multifocal/multicentric prostate cancer.

In order to study multiple contiguous prostate cancer lesions, we constructed computer-assisted, three-dimensional models of multifocal prostate cancer specimens obtained by radical prostatectomy. We then examined the genetic heterogeneity among the specimens by DNA microarray analysis. Cancer foci with high Gleason patterns were found to occur de novo, whereas those with low Gleason patterns occurred contiguously with cancers of low Gleason patterns. Three-dimensional analysis showed that distinct, noncontiguous cancerous foci were genetically independent and multicentric. In contrast some contiguous multifocal lesions had the same genetic origin.

Immunohistochemical analysis of inflammatory cells in benign and precancerous lesions and carcinoma of the prostate.

OBJECTIVE: Inflammation is an important cause of tumorigenesis in various types of malignancy. Mediators derived from inflammatory cells are associated with cancer proliferation, angiogenesis, and DNA damage. In the present study, we immunohistochemically examined the infiltration patterns of inflammatory cells in benign glands including glandular hyperplasia, and in prostatic intraepithelial neoplasia and adenocarcinoma. METHODS: Formalin-fixed, paraffin-embedded tissues were obtained from 100 patients with prostate cancer. All patients underwent radical prostatectomy. We assessed the number of infiltrating T cells (CD3(+)), B cells (CD20(+), CD79alpha(+)), and macrophages (CD68(+), CD204(+)) in benign and malignant prostate tumors. RESULTS: CD68(+) macrophages infiltrated benign glands to a higher extent than those of adenocarcinoma. In contrast, the number of CD204(+) cells was higher in malignant glands than in benign glands. There was no significant difference in the number of infiltrating T cells between benign and malignant tumors; however, the number of infiltrating B cells was significantly reduced in malignant glands. CONCLUSIONS: Inflammation of the prostate may act on prostate carcinomas; particularly that involving M2 macrophage infiltration may play a significant role in prostate carcinogenesis.

Clinical significance of subepithelial growth patterns in non-muscle invasive bladder cancer.

BACKGROUND: We evaluated the clinical significance and prognostic value of histopathological features of bladder cancer, such as subepithelial growth patterns and tumor growth pattern at the invasion front. METHODS: In total, 130 patients newly diagnosed with non-muscle invasive bladder cancer and underwent transurethral resection between 1998 and 2009 were enrolled. Subepithelial growth patterns consisting of endophytic growth pattern (EGP) and von Brunn's nest involvement (VBNI) were investigated using hematoxylin and eosin-stained slides, and their frequency of occurrence, prognostic value, and correlation with other clinicopathological features was evaluated. RESULTS: EGP and VBNI were found in 40 (30.8%) and 5 (3.9%) of the 130 cases, respectively. Of the 26 pT1 tumors, the growth pattern at the invasion front was trabecular in 17 (65.4%) and infiltrative in 9 (34.6%). Although 8 (47.1%) of 17 trabecular tumors coexisted with EGP, no cases with infiltrative tumors had EGP (p = 0.023). VBNI correlated with high tumor grades (p = 0.006) and lymphovascular involvement (p = 0.026). The multivariate Cox proportional hazards analysis revealed that tumor diameter less than 3 cm (p = 0.04) and intravesical bacillus Calmette-Guérin therapy (p = 0.004) were independent favorable prognostic factors for recurrence-free survival, whereas tumor stage was an independent poor prognostic factor for disease progression (p = 0.006). CONCLUSIONS: Subepithelial growth patterns were not a significant prognostic factor in this study. Additionally, no tumors with an infiltrative growth pattern coexisted with EGP, suggesting that determining the presence of EGP might be helpful for managing non-muscle invasive bladder cancers.

Role of syndecan-1 (CD138) in cell survival of human urothelial carcinoma.

Heparan sulfate proteoglycan syndecan-1, CD138, is well known to be associated with cell proliferation, adhesion, and migration in various types of malignancies. In the present study, we focused on the role of syndecan-1 in human urothelial carcinoma of the urinary bladder. Silencing of syndecan-1 by siRNA transfection down-regulated transcriptional factor junB and the long isoform of FLICE-inhibitory protein (FLIP long), resulting in the induction of apoptosis in the urothelial carcinoma cell lines UMUC2 and UMUC3. Knockdown of junB and FLIP long as well as syndecan-1 silencing mediated apoptosis that was inhibited by pan-caspase inhibitors. Transurethral injection of syndecan-1 siRNA into the urinary bladder significantly reduced syndecan-1 gene expression and growth of red fluorescent-labeled KU-7/RFP bladder cancer cells in the mouse orthotopic bladder cancer model. Immunohistochemical examination showed high syndecan-1 protein expression in high-grade, superficial, and deep invasive carcinomas (pT1 and >or=pT2) as well as carcinoma in situ, but not in low-grade and noninvasive phenotypes (pTa). In addition, the percentage of cancer cells positive for syndecan-1 at initial diagnosis was statistically associated with the frequency of bladder cancer recurrence after transurethral resection. In conclusion, syndecan-1 might contribute to urothelial carcinoma cell survival and progression; therefore, this molecule could be a new therapeutic target in human urinary bladder cancer.

HRK inactivation associated with promoter methylation and LOH in prostate cancer.

OBJECTIVES: Recent studies in selected human tumors have demonstrated reduced expression of HRK with hypermethylation. Because no similar study has been performed specifically in prostatic lesions, we examined whether the methylation status of HRK is altered in prostate cancers. METHODS: We chose to analyze the hypermethylation status of HRK, the expression of HRK protein and mRNA with 12q13.1 loss of heterozygosity (LOH) and with p53 mutation, and lesion apoptotic indices as determined by transferase-mediated digoxigenin-tagged 16-desoxy-uridine-triphosphate nick end-labeling (TUNEL) assays in 53 prostate cancers. RESULTS: Twenty of the 53 prostate cancers (38%) demonstrated hypermethylation in either the promoter or in exon 1 and, more significantly, the loss of HRK expression observed in 14 cancers by immunohistochemistry (IHC) was associated with promoter methylation. In addition, high apoptotic indices in tumors were related to positive HRK expression. Prostate cancers demonstrating HRK methylation also showed methylation of multiple other genes, such as p14(ARF), p16(INK4a), O(6)-MGMT, and GTS-P, but, with the exception of one case, p53 mutations were not detected. When compared to tumors having a Gleason score (GS) of 5-6, a significant difference in the apoptotic indices was found among prostate cancers of GS 7 (P < 0.001) or GS 8-9 (P = 0.007). We also detected a close correlation between the loss of HRK expression and decreased apoptosis in GS 5-6 and GS 7 tumors (P = 0.008, P < 0.001, respectively). CONCLUSIONS: HRK appears to be inactivated principally by promoter hypermethylation in prostate cancers. We further suggest that the decreased expression of HRK may play an important role in tumor progression by modulating apoptotic cell death.

[Paravesical suture abscess diagnosed 4 years after transvaginal uterectomy].

A 47-year-old woman with previous history of transvaginal uterectomy 4 years before, presented to another hospital complaining of pollakisuria and pain during micturition. She was treated with antibiotics, but symptoms failed to resolve. So she referred to our department for investigations and treatments. On cystoscopy, there was a large mass with edematous mucosa in the anterior wall of bladder. Magnetic resonance image demonstrated an 8 cm irregularly-formed cystic mass which occupied dome of bladder. Resection of the mass including partial cystectomy was performed. This cystic mass contained retained 3 silk sutures surrounded by green color pus. Microscopic examination revealed inflammatory granulations without any malignancy. Because of the previous history, she was diagnosed as paravesical suture abscess due to infected silk materials at transvaginal uterectomy. Paravesical suture abscess is very rare complication of inguinal herniorrhaphy and mimics bladder or urachal neoplasm. In review of previously reported cases, the symotoms were predominantly urological. For avoiding unnecessary examinations and treatments, it is important to consider paravesical suture abscess in cases with histories of inguinal herniorrhaphy or other intra-pelvic operations. To our knowledge, there is no case report of paravesical abscess formation associated with transvaginal uterectomy and the present case is the first one for report.

[Analysis of sports hematuria after running in summer].

BACKGROUND: The recent sport promotion and healthy boom brought increasing the sport population. Running especially is the most popular activity. Various urinary abnormalities are induced by strenunous exercise. Hematuria has been found after various sports activities and noted as sports hematuria by some studies. We evaluated relation between hematuria and running as the most popular sport in summer. MATERIAL AND METHODS: Urine samples were obtained from 109 healthy volunteers participated in 5 km run, at rest before and immediately after running. We could evaluate 90 of all and investigate counts and morphpology of urinary red cells by microscopic finding of urine sediments and analysis of flowcytometry for urinary cells. RESULTS: Eighty-three subjects had increased counts of urinary red cells after running. Of these, 32 had counts above the normal range, microscopic hematuria (RBC above 3/hpf). In analysis of these 32 had dysmorphic pattern mostly. CONCLUSION: This study confirms that exercise induces hematuria easily and sports hematuria has a glomerular source chiefly.