Real-time in vivo periprostatic nerve tracking using multiphoton microscopy in a rat survival surgery model: a promising pre-clinical study for enhanced nerve-sparing surgery.

OBJECTIVES: To assess the ability of multiphoton microscopy (MPM) to visualise, differentiate and track periprostatic nerves in an in vivo rat model, mimicking real-time imaging in humans during RP and to investigate the tissue toxicity and reproducibility of in vivo MPM on prostatic glands in the rat after imaging and final histological correlation study. MATERIALS AND METHODS: In vivo prostatic rat imaging was carried out using a custom-built bench-top MPM system generating real-time three-dimensional histological images, after performing survival surgery consisting of mini-laparotomies under xylazine/ketamine anaesthesia exteriorising the right prostatic lobe. The acquisition time and the depth of anaesthesia were adjusted for collecting multiple images in order to track the periprostatic nerves in real-time. The rats were then monitored for 15 days before undergoing a new set of imaging under similar settings. After humanely killing the rats, their prostates were submitted for routine histology and correlation studies. RESULTS: In vivo MPM images distinguished periprostatic nerves within the capsule and the prostatic glands from fresh unprocessed prostatic tissue without the use of exogenous contrast agents or biopsy sample. Real-time nerve tracking outlining the prostate was feasible and acquisition was not disturbed by motion artefacts. No serious adverse event was reported during rat monitoring; no tissue damage due to laser was seen on the imaged lobe compared with the contralateral lobe (control) allowing comparison of their corresponding histology. CONCLUSIONS: For the first time, we have shown that in vivo tracking of periprostatic nerves using MPM is feasible in a rat model. Development of a multiphoton endoscope for intraoperative use in humans is currently in progress and must be assessed.

Calcium oxalate calculi-induced clusterin expression in kidney.

The aim of the study was to investigate clusterin expression in the kidney and evaluate the urine clusterin level in the kidney stone formers. (1) In vitro, we treated the Madin-Darby canine kidney (MDCK) cell line with different concentrations of calcium oxalate (CaOx), and then the clusterin protein expression in the cells was evaluated by Western blotting. (2) Kidney stone patients who received percutaneous nephrolithotomy were enrolled in our study. Urine samples were collected before surgery, the kidney punctured to obtain kidney tissue guided by ultrasound intraoperatively. Clusterin expression in the human kidney tissue was evaluated by immunochemistry. The urine clusterin level was determined by enzyme-linked immunosorbent assay. Non-kidney disease subjects were chosen as controls. In vitro, the clusterin expression was up-regulated in the MDCK cells induced by CaOx. The study included 49 patients and 41 non-kidney disease subjects. All calculi were composed of calcium oxalate monohydrate or calcium oxalate dihydrate and a few also contained protein or uric acid. Mean ± SD urine clusterin level was 17.47 ± 18.61 µg/ml in patients, and 3.31 ± 5.42 µg/ml in non-kidney disease subjects, respectively (p < 0.001). Immunohistochemistry revealed the clusterin was located in the cytoplasm of the renal distal and collecting tubular epithelial cells. Also the tissue clusterin expression increased significantly in the kidney stone formers compared to the control groups (p = 0.001). CaOx could induce clusterin expression in renal tubular cells, and increase clusterin levels in the kidney and urine from the kidney stone formers.

Cytoreductive prostatectomy: evidence in support of a new surgical paradigm (Review).

Prostate cancer (PCa) remains the second ranked cause of cancer deaths in the United States. The current standard of care for metastatic prostate cancer (mPCa) includes systemic therapies with no option for surgery. In contrast, in other malignancies such as breast and kidney cancer, cyto-reduction plays an integral role in the treatment of metastatic disease. In this framework, there are emerging data that suggest a potential oncologic benefit to cytoreduction in mPCa. The majority of the data are retrospective in nature suggesting that patients with mPCa who had prior radical prostatectomy (RP) had a better survival, as well as improved response to systemic therapy. Similarly, patients who presented with metastatic disease and received definitive local therapy (RP or radiation) had greater survival than patients who received no treatment. In order to confer maximum potential benefit, operating in the setting of mPCa must be technically feasible with acceptable morbidity. It has been demonstrated in many studies that operating on locally advanced disease (T3a/b) does have similar morbidity as lower stage cancer. This may be applicable in the metastatic setting, because although PCa may have metastasized, it may remain locally advanced. On the molecular level there are a number of explanations concerning the potential benefit of cytoreduction. However, these ideas remain speculative with no concrete evidence to date.

The role of prostatitis in prostate cancer: meta-analysis.

OBJECTIVE: Use systematic review methods to quantify the association between prostatitis and prostate cancer, under both fixed and random effects model. EVIDENCE ACQUISITION: Case control studies of prostate cancer with information on prostatitis history. All studies published between 1990-2012, were collected to calculate a pooled odds ratio. SELECTION CRITERIA: the selection criteria are as follows: human case control studies; published from May 1990 to July 2012; containing number of prostatitis, and prostate cancer cases. EVIDENCE SYNTHESIS: In total, 20 case control studies were included. A significant association between prostatitis and prostate cancer was found, under both fixed effect model (pooled OR=1.50, 95%CI: 1.39-1.62), and random effects model (OR=1.64, 95%CI: 1.36-1.98). Personal interview based case control studies showed a high level of association (fixed effect model: pooled OR=1.59, 95%CI: 1.47-1.73, random effects model: pooled OR= 1.87, 95%CI: 1.52-2.29), compared with clinical based studies (fixed effect model: pooled OR=1.05, 95%CI: 0.86-1.28, random effects model: pooled OR= 0.98, 95%CI: 0.67-1.45). Additionally, pooled ORs, were calculated for each decade. In a fixed effect model: 1990's: OR=1.58, 95% CI: 1.35-1.84; 2000's: OR=1.59, 95% CI: 1.40-1.79; 2010's: OR=1.37, 95% CI: 1.22-1.56. In a random effects model: 1990's: OR=1.98, 95% CI: 1.08-3.62; 2000's: OR=1.64, 95% CI: 1.23-2.19; 2010's: OR=1.34, 95% CI: 1.03-1.73. Finally a meta-analysis stratified by each country was conducted. In fixed effect models, U.S: pooled OR =1.45, 95%CI: 1.34-1.57; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90. In random effects model, U.S: pooled OR=1.50, 95%CI: 1.25-1.80; China: pooled OR =4.67, 95%CI: 3.08-7.07; Cuba: pooled OR =1.43, 95%CI: 1.00-2.04; Italy: pooled OR =0.61, 95%CI: 0.13-2.90. CONCLUSIONS: the present meta-analysis provides the statistical evidence that the association between prostatitis and prostate cancer is significant.