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Background/Aim: The aim of this study was to elucidate the relationship between the progression of bladder cancer (BCa) and TLR4 expression. Materials and Methods: The relationship between TLR4 expression and prognosis of BCa patients was analyzed using a publicly available database and immunohistochemical staining of clinical samples. The effect of TLR4 knockdown was also examined on the invasive capabilities of BCa cells. Finally, to investigate the biological function of TLR4, the gene expression profile of TLR4-depleted BCa cells was analyzed by microarray analysis. Results: Expression of TLR4 was inversely associated with prognosis of patients with invasive BCa, and depletion of TLR4 significantly enhanced the invasive capability of BCa cells. Gene expression profiling revealed that depletion of TLR4 led to high expression of epithelial differentiation genes. Furthermore, expression of TLR4 was found to be extremely low in areas of squamous differentiation. Conclusion: Low TLR4 expression was correlated with tumor progression.

A case of intra-abdominal testis with loop-like epididymis and intra-canalicular vas and vessels is presented. A 3-year-old male with left impalpable testis since birth was admitted to our department. Physical examination and ultrasonography were inconclusive. Laparoscopy revealed a small left abdominal testis with surrounding adhesions close to the left-obliterated umbilical artery. The vas deferens and spermatic vessels were entering into the internal inguinal ring. The processus vaginalis was patent. At inguinal exploration the testis was atrophic and the epididymis was loop-like, joining the vas deferens in the inguinal canal. The spermatic vessels continued to the atrophic testis in a looplike manner. The testis, epididymis and the vas deferens were removed. Histopathological examination of the testis revealed Sertoli cells only. If inguinal exploration had been performed without laparoscopy, the presence of the vas deferens and spermatic vessels in the inguinal canal with the absence of the testis could have been misdiagnosed as vanishing testis. Abdominal testis would thus have been missed, with increased risk of complications, particularly malignancy.

Adenocarcinomas of the bladder and urachus represent a rare subtype of urinary tract cancer and account for 2% of all tumors originating from the bladder. Localized disease can be managed with surgical extirpation alone; however, less than 40% of patients with advanced disease will achieve an objective response with platinum-based chemotherapy. We hypothesized that bladder and urachal adenocarcinomas harbor a distinct mutational profile that may make them susceptible to targeted agents.METHODS: After Institutional Review Board approval, 16 patients with primary bladder adenocarcinoma (PBA) and 10 patients with urachal adenocarcinoma (UA) were identified. Histopathologic review was performed, and tumor DNA isolated from representative paraffinembedded sections as well as matched normal DNA were subjected to Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) sequencing, an exon-capture assay that interrogates the mutation and copy number status of 379 oncogenes and tumor suppressor genes known to be commonly altered in cancer. Somatic alterations including point mutations, insertions/deletions, truncations, and copy number changes were detected.RESULTS: The study population consisted of 17 (65%) males and 9 (35%) females with local or locally advanced PBA or UA. 17 (65%) were ever smokers and 9 (35%) were never smokers. 4 (15%) patients received neoadjuvant chemotherapy, 14 (54%) underwent partial cystectomy, and 12 (46%) underwent radical cystectomy. Median overall survival was 41.2 months (95% CI: 12-129) in patients with PBA and 80.5 months (95% CI: 11-263) in patients with UA. Mutational analysis revealed that mutations resulting in upregulation of the mitogen-activated protein kinase (MAPK) pathway are common in PBA and UA (Table 1).CONCLUSIONS: The mutational landscape of PBA and UA is more similar to that of colorectal adenocarcinoma than urothelial carcinoma of the bladder. Alterations predicted to upregulate the MAPK pathway such as activating KRAS and GNAS mutations are common in PBA and UA, and agents targeting this pathway may provide a novel therapeutic avenue for the treatment of PBA and UA.

cancer cells. Also our findings suggest that through the inhibition of HSP90 activity, antitumor effect of PI3K/mTOR inhibitor and platinum combination therapy can be synergistically potentiated.