Circulating proteomic signature for detection of biomarkers in bladder cancer patients.

The identification of clinically-relevant early diagnostic and prognostic protein biomarkers is essential to maximize therapeutic efficacy and prevent cancer progression. The aim of the current study is to determine whether aberrant plasma protein profile can be applied as a surrogate tool for early diagnosis of bladder carcinoma. Plasma samples from patients with low grade non-muscle invasive bladder cancer and healthy controls were analyzed using combined 2D-DIGE and mass-spectrometry to identify differentially expressed proteins. Validation was performed using western blotting analysis in an independent cohort of cancer patients and controls. Fifteen differentially-expressed proteins were identified of which 12 were significantly up-regulated and three were significantly down-regulated in tumors compared to controls. The Ingenuity Pathways Analysis revealed functional connection between the differentially-expressed proteins and immunological disease, inflammatory disease and cancer mediated through chemokine and cytokine signaling pathway and NF-kB transcription factor. Among the three validated proteins, haptoglobin was able to distinguish between patients with low grade bladder cancer and the controls with high sensitivity and specificity (AUC > 0.87). In conclusion, several biomarker proteins were identified in bladder cancer. Haptoglobin is a potential candidate that merit further investigation to validate its usefulness and functional significance as potential biomarkers for early detection of bladder cancer.

Sonic Hedgehog Expression is Associated with Lymph Node Invasion in Urothelial Bladder Cancer.

Bladder cancer (BC) is a deadly disease characterized by high recurrence rates and frequent progression to an aggressive phenotype. Dysregulation of various signaling pathways have been implicated in BC tumorigenesis, however, the clinical relevance of sonic hedgehog pathway (Shh) remains under investigated. The aim of the current study was to analyze the prognostic value of Shh expression in patients with bladder carcinoma. Immunohistochemical expression of Shh was performed using tissue microarray with 128 specimens from bladder cancer patients. Kaplan-meier survival was analysed and correlation between Shh protein expression and patients' clinicopathological parameters wasexamined using Fisher's exact test. The immuno-staining results revealed that Shh protein exhibits cytoplasmic localization and is expressed in 49% of the analyzed bladder cancer cohort. Our data indicated that high Shh expression significantly correlated with increased lymph node metastasis (p = 0.02), however no association was reported between Shh expression and other clinicopatholigical parameters. High expression of sonic hedgehog was associated with lymph node invasion which may indicate that Shh might play an important role in progression and metastasis of bladder cancer.

Prognostic value of HER2 status in bladder transitional cell carcinoma revealed by both IHC and BDISH techniques.

BACKGROUND: Her2/neu is an oncogene that plays an important role in the pathogenesis of many cancer types. In bladder carcinoma (BC), the clinical significance of Her2/neu status remains under-investigated and poorly linked to the patients' clinic-pathological features and survival status. Thus, the current study was conducted to assess Her2/neu status in a cohort of patients' in Saudi Arabia, and to explore its prognostic value in BC. METHODS: A total of 160 consent patients of transitional cell carcinoma (TCC) of bladder were arranged on a tissue microarray (TMA) and stained by immunohistochemistry (IHC) and bright-field dual in situ hybridization (BDISH) methods. The intensity of Her2/neu protein receptor immunostaining was evaluated, correlated to Her2/neu gene amplification status in TCC and assessed for potential clinical value by correlation measures. RESULTS: IHC data demonstrated that Her2/neu protein is expressed in 60 % (2+ and 3+) of our TCC patient's cohort from Saudi Arabia. Her2/neu gene amplification is detected in 25 % by BDISH. There was a strong association between Her2/neu protein levels and lymph node invasion (p = 0.04), tumor stage (p = 0.002), vascular invasion and borderline significance with distant metastasis (p = 0.07). Amplification of Her2/neu gene was associated with tumor grade (p = 0.03) and poor disease-specific survival (p = 0.02), in that, patients with non-amplified Her2/neu gene live longer. Interestingly, there was a reasonable concordance rate (71 %) between IHC and BDISH data in the analyzed cohort. CONCLUSION: The study showed that 25 % of our patients' cohort has Her2/neu over-expression. This Her2/neu (over-expression/amplification) status was concordant using either IHC or BDISH and significantly associated with disease aggressiveness and poor outcome. These findings suggested a potential impact of anti-Her2 targeted therapy in the treatment of bladder cancer with amplified/overexpressed HER2 that needs further investigation.

Randomized controlled trial of virtual reality and hybrid simulation for robotic surgical training.

OBJECTIVE: To evaluate if two commonly used laparoscopic simulators could be adapted and used successfully for the robotics platform in a laparoscopic and robotic naïve medical student population. MATERIALS AND METHODS: We identified two widely validated laparoscopic simulation programs, LapSim(®) (Surgical Science Sweden AB), and ProMIS(®) (Haptica, Ireland)for inclusion in the study. The McGill Inanimate System for Training and Evaluation of Laparoscopic Skills(®) task set was used for ProMIS, and adapted for the DaVinci(®) console (Intuitive Surgical, Inc., Sunnyvale, CA, USA) robotic platform. We then randomized 20 naïve medical students to receive training on either LapSim or ProMIS, both or neither, and evaluated them before and after training. RESULTS: When the groups were compared at baseline, there were no statistical differences in mean scores amongst the groups in univariate analysis (α= 0.05). When comparing mean scores within groups before and after training sessions, statistically significant performance enhancement in all four robotic tasks were identified in the groups receiving dual training. CONCLUSION: We have shown that the use of ProMIS hybrid and LapSim virtual reality (VR) simulators in conjunction with each other can considerable improve robotic console performance in novice medical students compared with hybrid and VR simulation alone.

Results of prostate biopsies in a teaching hospital in Western Saudi Arabia.

OBJECTIVE: To evaluate the prostate cancer detection rate in 45 patients who underwent transrectal ultrasound scan (TRUS) guided biopsies at King Abdul-Aziz University Hospital (KAUH), Jeddah, Kingdom of Saudi Arabia (KSA) and compare it with the previously reported national and international rates. METHODS: Forty-five charts reviewed for patients underwent TRUS guided biopsies in the period between July 1997 through to November 2002 at KAUH. Patients were entered in the study either as of high serum prostatic specific antigen (PSA) or abnormal digital rectal examination (DRE), or both. Cases with large prostate size or suspected elevation of PSA due to causes other than prostatic cancer was excluded from the study. RESULTS: Out of the 45 patients who underwent TRUS guided biopsy; cancer of the prostate was detected in 13 (28.8%). The cancer detection rate in patients presented with abnormal DRE alone was 7.6%, and was 15.3% in the group with elevated PSA but normal DRE (stage T1c). When PSA was elevated to 4-10 ng/ml TRUS guided biopsy detected cancer in 21.4%, elevation of PSA to10-20 ng/ml lead to cancer detection in 40% of the patients, and when PSA was above 20 ng/ml all cases were positive for cancer. CONCLUSION: Cancer prostate is common in Western countries; national studies reported a low incidence of prostate cancer in KSA. Yet in our local patients using this precise method of investigation, our study confirms that the detection rate of prostate cancer through TRUS guided biopsies match the results of previously reported national studies and still lower than the international rates. Although the number of cases are small to draw solid and final conclusions; this study should stimulate further research and more reports on this important subject.