HOXA9, ISL1 and ALDH1A3 methylation patterns as prognostic markers for nonmuscle invasive bladder cancer: array-based DNA methylation and expression profiling.

DNA methylation patterns are associated with the development and prognosis of cancer. The aim of this study was to identify novel methylation markers for the prediction of patient outcomes using microarray analysis of DNA methylation and RNA expression patterns in samples from long-term follow-up patients with nonmuscle invasive bladder cancer (NMIBC). A total of 187 human bladder specimens were used for microarray array or pyrosequencing (PSQ) analyses: 6 normal controls (NC) and 181 NMIBC. Tumor-specific hypermethylated genes were selected from a data set comprising 24 matched microarray-based DNA methylation and gene expression profiles (6 controls and 18 NMIBC), and their clinical relevance was verified by quantitative PSQ analysis. The methylation status of Homeobox A9 (HOXA9), ISL LIM homeobox 1 (ISL1) and Aldehyde dehydrogenase 1 family, member A3 (ALDH1A3) was significantly associated with decreased gene expression levels and aggressive clinicopathological characteristics. Multivariate regression analyses showed that hypermethylation of these genes was an independent predictor of disease recurrence (HOXA9, ISL1 and ALDH1A3, either alone or in combination) and progression (ISL1 and ALDH1A3, either alone or in combination) (each p < 0.05). The results of this study suggest that these novel methylation markers are independent prognostic indicators in NMIBC patients, which may facilitate the assessment of disease recurrence and progression in NMIBC patients and inform clinical decision making regarding treatment.

Tubal Buccal Mucosa Graft without Anastomosis of the Proximal Urethra for Long Segment Posterior Urethral Defect Repair.

A 31-year-old man was referred for further management of a urethral stricture. He was a victim of a traffic accident and his urethral injury was associated with a pelvic bone fracture. He had previously undergone a suprapubic cystostomy only owing to his unstable general condition at another hospital. After 3 months of urethral injury, direct urethral anastomosis was attempted, but the surgery failed. An additional 4 failed internal urethrotomies were performed before the patient visited Chungbuk National University Hospital. Preoperative images revealed complete posterior urethral disruption, and the defect length was 4 cm. We performed a buccal mucosa tubal graft without anastomosis of the proximal urethra for a long segment posterior urethral defect. The Foley catheter was removed 3 weeks after the operation and the patient was able to void successfully. After 8 months, he had normal voiding function without urinary incontinence.

Elevated insulin and insulin resistance are associated with the advanced pathological stage of prostate cancer in Korean population.

The study was designed to investigate the effect of serum glucose, insulin and insulin resistance on the risk of prostate cancer (CaP) and on the clinicopathological characteristics in Korean men. Subjects were retrospectively recruited from 166 CaP patients underwent radical prostatectomy and 166 age-matched benign prostatic hyperplasia (BPH) patients. The serum was taken on the morning of the day of operation and insulin resistance was assessed by homeostasis model assessment insulin resistance index (HOMA-IR). Men in highest tertile of insulin was associated with 55% reduced odds of CaP than those with the lowest tertile (OR = 0.45, 95% CI = 0.23-0.89, P = 0.022). The patients in highest tertile of insulin had a more than 5.6 fold risk of locally advanced stage than those in the lowest tertile (OR = 5.62, 95% CI = 1.88-16.83, P = 0.002). Moreover, the patients in the highest tertile HOMA-IR group was associated with an increased risk of locally advanced stage than the lowest tertile group (OR = 3.10, 95% CI = 1.07-8.99, P = 0.037). These results suggest that elevated insulin and insulin resistance are associated with the advanced pathological stage of prostate cancer in Korean patients.

Docetaxel-induced fatal interstitial pneumonitis in a patient with castration-resistant prostate cancer.

A 69-year-old man with castration-resistant prostate cancer (CRPC) received docetaxel and a corticosteroid. After the third cycle of docetaxel administration, he presented with dyspnea, cough, sputum, and fever of 39.2℃. The chest X-ray and chest computed tomography (CT) revealed a diffuse reticulonodular shadow in both lungs, which suggested interstitial pneumonitis. Initially, we used empiric broad-spectrum antibiotics and high-dose corticosteroids. However, his condition progressively became worse and he was transferred to the intensive care unit, intubated, and placed on mechanical ventilation. He died 4 days after hospital admission. Here we report this case of fatal interstitial pneumonitis after treatment with docetaxel for CRPC. We briefly consider docetaxel-induced pneumonitis to make physicians aware of the possibility of pulmonary toxicity so that appropriate treatment can be begun as soon as possible.

Usefulness of a combined approach of t1-weighted, t2-weighted, dynamic contrast-enhanced, and diffusion-weighted imaging in prostate cancer.

PURPOSE: We evaluated the value of a combined approach of T1-weighted (T1W) imaging, T2-weighted (T2W) imaging, dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), and diffusion-weighted imaging (DWI) for the detection of prostate cancer and extracapsular extension (ECE) in patients with prostate cancer by using pathologic data after radical prostatectomy. MATERIALS AND METHODS: From April 2009 to December 2011, 126 patients who underwent radical prostatectomy and prostate MRI for prostate cancer were analyzed retrospectively. The MRI findings were compared with the pathologic findings of the radical prostatectomy specimens in each patient. The sensitivity, specificity, and accuracy of the detection of prostate cancer and extracapsular extension were analyzed. RESULTS: The prostate cancer detection rate by use of T1W and T2W imaging, DCE-MRI, and their combination was 65.1%, 69.0%, and 80.2%, respectively (p=0.023). The detection rate using T1W and T2W imaging, DCE-MRI, DWI, and their combination was 57.7%, 65.4%, 67.3%, and 80.8%, respectively (p=0.086). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of combination MRI (T1W, T2W, and DCE-MRI) for ECE were 46.4%, 91.4%, 83.9%, and 68.1%, respectively. The sensitivity of combination MRI (T1W, T2W, and DCE-MRI) for ECE tended to increase as the prostate-specific antigen level rose (p=0.010). The sensitivity, specificity, PPV, and NPV of combination MRI (T1W, T2W, DCE-MRI, and DWI) for ECE were 65.0%, 87.5%, 76.5%, and 80.0%, respectively. CONCLUSIONS: A combined approach of T1W, T2W, and DCE-MRI with DWI demonstrated an accurate detection rate of prostate cancer. Also, combination approaches showed a high specificity for predicting ECE, although sensitivity was relatively lower. Therefore, these methods are reliable for predicting prostate cancer. However, a new protocol is necessary to enhance the sensitivity for predicting ECE.

Alpha-methylacyl-coenzyme a racemase-expressing urachal adenocarcinoma of the abdominal wall.

Urachal adenocarcinomas are very rare and about one third of these neoplasms arise in urachal remnants. To demonstrate the origin of the urachal adenocarcinoma is not easy, but it is very important for managing patient care. We report on a 35-year-old man who complained of a palpable mass in the periumbilical area. The mass was incidentally identified 10 days earlier. Computed tomography revealed a well-defined enhancing mass with internal calcification and septation abutting on the dome of the urinary bladder. The clinical diagnosis was urachal cancer, which seemed to invade the urinary bladder. Thus, we performed mass excision and partial resection of the bladder. Histopathologically, the mass was diagnosed as mucinous cystadenocarcinoma originating from urachal remnants that showed an unusual expression of alpha-methylacyl-coenzyme A racemase (AMACR). To our knowledge, this report is the first case of AMACR-expressing urachal adenocarcinoma arising in the abdominal wall.