Predictive value of neutrophil-to-lymphocyte ratio in diagnosis of early prostate cancer among men who underwent robotic transperineal prostate biopsy.

ABSTRACT: To evaluate the predicted value of neutrophil-to-lymphocyte ratio (NLR) in the diagnosis of early prostate cancer by using standardized Full blood count (FBC) performed within 4 weeks before biopsy and histology results from transperineal prostate biopsy (RTPB).Patients who underwent RTPB under general anesthesia (GA), at Urology Department, Singapore General Hospital between September 2006 and Febuary 2016 were retrospectively reviewed.NLR was calculated using full blood count (FBC) that was done as a pre-admission test before GA within 4 weeks before the biopsy. Statistical analyses were done to establish the correlation of NLR and different clinical parameters such as biopsy histology, pre-biopsy PSA, and prostate volume.A total of 652 patients who underwent RTPB for diagnostic purposes with a valid PSA level were included in this study. There was total of 409 (62.7%) benign histology and 243 (37.3%) prostate cancer. There was no significant difference in median NLR between the benign and prostate cancer group (2.00 vs 1.99; P = .29).In the subgroups analysis, there was also no significant difference of median NLR value in clinical significant cancer (defined as Gleason 3 + 4 and above) and benign histology group (NLR 2.00 vs 2.01, P = .41), as well as prostate cancer and benign group according to different pre-biopsy PSA levels: PSA (ug/l) < 4, 4 to 10, 10 to 20, and >20, respectively. (Median NLR 1.34 vs 1.76; 1.97 vs 1.97; 1.97 vs 2.18; 2.18 vs 1.98, P > .05). NLR is neither associated with prostate cancer using logestic regression model nor a strong predictor of the Gleason grade group and D'Amico risk stratification group using ordinal regression model. (P > .05)There was no statistically significant difference of NLR between the benign and prostate cancer group as a whole or in the subgroup analyses for patients who underwent robotic transperineal prostate biopsy. NLR may have a limited role in predicting early-stage prostate cancer.

Defining prostate cancer size and treatment margin for focal therapy: does intralesional heterogeneity impact the performance of multiparametric MRI?

OBJECTIVES: To evaluate the impact of intralesional heterogeneity on the performance of multiparametric magnetic resonance imaging (mpMRI) in determining cancer extent and treatment margins for focal therapy (FT) of prostate cancer. PATIENTS AND METHODS: We identified men who underwent primary radical prostatectomy for organ- confined prostate cancer over a 3-year period. Cancer foci on whole-mount histology were marked out, coding low-grade (LG; Gleason 3) and high-grade (HG; Gleason 4-5) components separately. Measurements of entire tumours were grouped according to intralesional proportion of HG cancer: 0%, <50% and ≥50%; the readings were corrected for specimen shrinkage and correlated with matching lesions on mpMRI. Separate measurements were also taken of HG cancer components only, and correlated against entire lesions on mpMRI. Size discrepancies were used to derive the optimal tumour size and treatment margins for FT. RESULTS: There were 122 MRI-detected cancer lesions in 70 men. The mean linear specimen shrinkage was 8.4%. The overall correlation between histology and MRI dimensions was r = 0.79 (P < 0.001). Size correlation was superior for tumours with high burden (≥50%) compared to low burden (<50%) of HG cancer (r = 0.84 vs r = 0.63; P = 0.007). Size underestimation by mpMRI was more likely for larger tumours (51% for >12 mm vs 26% for ≤12 mm) and those containing HG cancer (44%, vs 20% for LG only). Size discrepancy analysis suggests an optimal tumour size of ≤12 mm and treatment margins of 5-6 mm for FT. For tumours ≤12 mm in diameter, applying 5- and 6-mm treatment margins would achieve 98.6% and 100% complete tumour ablation, respectively. For tumours of all sizes, using the same margins would ablate >95% of the HG cancer components. CONCLUSIONS: Multiparametric MRI performance in estimating prostate cancer size, and consequently the treatment margin for FT, is impacted by tumour size and the intralesional heterogeneity of cancer grades.

Survival outcomes of Asian younger men (< 55 years) undergoing radical prostatectomy: a review of prostate cancer database in a tertiary hospital in Singapore.

PURPOSE: Prostate cancer largely affects older men. This study aims to investigate prostate cancer in younger men (< 55 years) to shed light on the survival outcomes of this unique subset of patients in Asian context. METHODS: Data were obtained from the Singapore General Hospital Prostate Cancer Registry. Data on all men with clinically organ confined prostate cancer who underwent radical prostatectomy between 1998 and 2016 were obtained from the registry. Tumor characteristics, follow-up data, and cause of death were acquired. RESULTS: A total of 1120 men underwent radical prostatectomy between 1998 and 2016. Of these, 12 were aged ≤ 44 years, 106 were aged 45-54 years, 596 were aged 55-64, 397 were aged 65-74 and 9 were aged ≥ 75. There was no difference across age groups when comparing Gleason ≤ 7 vs Gleason ≥ 8 disease, T1/2 vs T3/4 disease and the median PSA values were similar. No difference was observed in overall survival or prostate cancer specific survival among 4 age groups (≤ 44, 45-54, 55-64, 65-74) (p = 0.156 and p = 0.227 respectively). Although there was a trend of increasing rate of biochemical recurrence for older patients, it's not statistically significant (p = 0.157). Time to biochemical recurrence was similar as well (p = 0.257). CONCLUSION: This large cohort of Asian patients who underwent radical prostatectomy did not show significant age-related differences in important parameters and outcomes.

Stereotactic robot-assisted transperineal prostate biopsy under local anaesthesia and sedation: moving robotic biopsy from operating theatre to clinic.

This IRB-approved prospective pilot study evaluates the safety and feasibility of performing stereotactic robot-assisted transperineal MRI-US fusion targeted prostate biopsy under local anaesthesia (LA) with sedation. 30 patients who underwent robotic transperineal prostate biopsy between September 2017 and June 2018 were recruited. All biopsies were performed with the iSR'obot Mona Lisa® and BK3000 ultrasound system. Intravenous paracetamol 1 g, with midazolam and fentanyl were given at positioning. After administration of 5 mL of 1%-lidocaine into the perineal skin 2 cm above and lateral to the anus, periapical prostatic block with 10 mL mixture of 1%-Lidocaine and 0.5%-Marcaine was given. The median age of patients was 66 years (range 53-80 years). Median PSA and mean prostate volume were 8.1 ng/ml (range 4.2-20.6 ng/ml) and 40.1 cc (range 18.6-70 cc). 24 (80.0%) patients had targeted prostate biopsy, with median number of targeted cores of 8 (range 5-16). All patients had saturation biopsy and median number of saturation cores was 21 (range 9-48). Mean dose of intravenous midazolam given was 1.5 mg (range 0-5 mg) and intravenous fentanyl was 75 mcg (10-150 mcg). No patient required conversion to GA. Two patients required motion compensation of 3 mm and 7.5 mm, respectively, due minor movement. Immediate post-operative pain score was 0 for all patients. 29 of 30 patients (96.7%) were discharged within 24 h of procedure. There were no immediate severe complications. Adenocarcinoma was detected in 19/30 (63.3%) cases. This pilot feasibility study showed that stereotactic robotic transperineal MRI-US fusion targeted prostate biopsy can be safely and accurately performed under LA with sedation.

Evaluation of neutrophil-to-lymphocyte ratio as a prognostic indicator in a Singapore cohort of patients with clinically localized prostate cancer treated with prostatectomy.

PURPOSE: Recent evidence suggests that the presence of a systemic inflammatory response plays an important role in the progression of several solid tumors. The neutrophil-to-lymphocyte ratio (NLR) has been proposed as easily assessable markers of systemic inflammation and has been shown to represent a prognostic marker in prostate cancer in previous studies. METHODS: Data from 668 patients with localized prostate cancer treated with prostatectomy (open and robot assisted) in Singapore General Hospital from 1998 to 2014 were analyzed. Correlation between NLR and histopathological status was analyzed. Association between NLR and distant metastases-free survival (MFS), cancer-specific survival (CSS), overall survival (OS), and biochemical disease-free survival (BDFS) was assessed. RESULTS: NLR was not significantly correlated with histopathological status, including Gleason score (≤ 6 versus 7 versus ≥ 8, p = 0.159), lymph node metastasis (negative versus positive, p = 0.159), or surgical margin status (negative versus positive, p = 0.494). NLR was categorized into two groups (< median and ≥ median, median = 2.09) and NLR ≥ 2.09 was not a prognostic factor for decreased MFS (p = 0.609), CSS (p = 0.302), OS (p = 0.722) and BDFS (p = 0.589). No difference was observed for NLR even in high-risk subgroup patients compared to the rest (p = 0.058). The area under the ROC curve (AUC) of NLR as a prognosticator for biochemical recurrence was only 0.53. CONCLUSION: Our findings indicate that pre-treatment NLR may not predict prognosis in patients with localized prostate cancer treated with prostatectomy in an Asian cohort.

Neutrophil-to-lymphocyte ratio independently predicts advanced pathological staging and poorer survival outcomes in testicular cancer.

Purpose: An elevated neutrophil-to-lymphocyte ratio (NLR) has been associated with adverse outcomes in various malignancies. However, its role in prognosticating testicular cancer (TC) has not been validated. We aim to study the relationship between NLR and TC. Materials and Methods: We retrospectively reviewed 160 patients with histological proven TC from January 2005 to June 2016. Youden's index was used to analyse NLR and a cut-off point of 3.0 was obtained, with statistical receiver operating characteristics of 0.755. Chi-square test, Kaplan-Meier (log rank test) and logistics regression models were used to predict NLR association with survival outcomes. Results: Median age was 34 years old (range, 17-68 years old). There were 102 pure seminomas and 58 non-seminomatous germ cell tumours. Median follow-up period was 8 years (range, 2.5-17 years). NLR ≥3.0 was independently associated with lymph node involvement (p=0.031; odds ratio [OR], 2.91; 95% confidence interval [CI], 1.67-5.83; p=0.038; OR, 4.12; 95% CI, 1.26-6.51) and metastatic disease (p=0.041; OR, 2.48; 95% CI, 1.22-3.98; p=0.043; OR, 2.21; 95% CI, 1.17-3.65) in both seminomatous and non-seminomatous germ cell tumours, translating to a more advanced disease. Moreover, NLR ≥3.0 also predicts poorer cancer specific survival in these patients. Conclusions: NLR can be an inexpensive haematological marker in predicting advanced TC staging and poorer survival outcome. NLR complements the traditional cancer staging by identifying a group of high risk patients who may benefit from multimodal treatment and closer surveillance to achieve long term survival.

External validation of the updated Leibovich prognostic models for clear cell and papillary renal cell carcinoma in an Asian population.

PURPOSE: The Leibovich model was updated to prognosticate oncological outcomes in postnephrectomy nonmetastatic renal cell carcinoma (RCC) for each major histological subtype including clear cell (ccRCC), papillary (papRCC), and chromophobe RCC. We evaluated its performance in an independent population of predominantly Asian patients from Singapore. MATERIALS AND METHODS: Nine hundred and forty two binephric patients with nonmetastatic unilateral RCC treated with radical/partial nephrectomy from 1990 to 2015 from Singapore were retrospectively reviewed. Based on the Leibovich model, ccRCC patients were scored from 0 to 25 and papRCC patients divided into 3 risk groups. Primary outcomes of progression-free survival (PFS) and cancer-specific survival (CSS) were assessed with the Kaplan-Meier method. Receiver operating characteristic curves and calibration plots were obtained to determine discrimination and calibration respectively. RESULTS: Eight hundred and twenty nine patients (88%) had ccRCC where 16.2% experienced disease progression while 11.9% died of RCC over a median follow-up of 76 (42-117) months. There was good discrimination (c-index 0.81 for PFS, 0.83 for CSS) and calibration (PFS calibration-in-the-large 0.002 and calibration slope 0.99, CSS calibration-in-the-large 0.005 and calibration slope 0.96). One hundred and thirteen patients (12%) had papRCC, where 18.6% progressed while 14.2% died from RCC over a median follow-up of 69.5 (36.0-112.0) months. Discrimination was slightly weaker (c-index 0.72 for PFS, 0.74 for CSS), and the model was only calibrated for CSS (calibration-in-the-large 0.002, calibration slope 0.98), not for PFS (calibration-in-the-large 0.09, calibration slope 1.93). CONCLUSIONS: The updated Leibovich score is applicable for prognostication of progression and death in both ccRCC and papRCC, even when applied to an independent population of Asian patients. Further validation is required to ensure accuracy in prognosticating PFS for papRCC.

Primary androgen deprivation therapy as monotherapy in unfavourable intermediate- and high-risk localised prostate cancer: a Singaporean single-centre perspective.

PURPOSE: Primary ADT (pADT) monotherapy is used significantly for patients with clinically localised disease in Asia and is acceptable even by guidelines, especially in intermediate- and high-risk disease. This occurs despite controversy in the West and data suggesting association with adverse effects, notably cardiovascular events. We therefore sought to assess the impact of pADT on all-cause mortality and prostate cancer-specific mortality (PCSM) in Asian men with high-risk and unfavourable intermediate-risk PCa. METHODS: With cancer registry data, men from a single centre in Singapore with clinically localised high-risk/unfavourable intermediate-risk PCa diagnosed between 2004 and 2014 and either treated conservatively with no therapy or started on pADT within 1 year of diagnosis were followed up through January 2017. Patients with non-localised PCa (clinical stage T4, regional/distant lymph node involvement, metastases), or receipt of local therapy (radical prostatectomy/radiotherapy) were excluded. The primary outcomes of all-cause mortality and PCSM were analysed with Cox proportional hazards regression models. RESULTS: Three hundred and forty Asian men were analysed, and 177 (52.1%) were started on pADT, with mean age of 77 (49-98) years. There were 119 deaths in the cohort, and 68 (38.4%) occurred in patients treated with pADT (median follow-up, 4.4 years). After adjusting for comorbidities and clinical characteristics, pADT did not provide benefit to all-cause mortality, PCSM or cardiovascular mortality. CONCLUSION: For clinically localised unfavourable intermediate-risk and high-risk PCa, starting pADT within 12 months of diagnosis is not associated with improved 5-year all-cause mortality or PCSM compared to patients treated conservatively with no therapy and should be discouraged due to lack of mortality benefit.

Automating the Renal Cell Carcinoma Registry in Singapore: A Case Study on the Integration of the Research Electronic Data Capture System with the Enterprise Data Warehouse.

The renal cell carcinoma registry (RCCR) at the Singapore General Hospital was established in the 1980s. In 2012, the registry transited to a partially automated system using Research Electronic Data Capture (REDCap) and Oracle Business Intelligence Enterprise Edition (OBIEE), which is a platform for retrieval of electronic data from the Electronic Health Intelligence System (eHIntS). A committee was formed of experts from the department of urology and the health services research center, as well as an information technology (IT) team to evaluate the efficacy of the partially automated system. In the 5 years after the new system was implemented, 1,751 cases were recorded in the RCCR. The casefinding completeness increased by 1.9%, the data accuracy rate was 97%, and the efficiency increased by 12%. Strengths of the new system after partial automation were: (1) secure access to the registry via the hospital Web, (2) direct access to REDCap via the electronic medical records system, (3) automated and timely data extraction, and (4) visual presentation of data. On the other hand, we also encountered several challenges in the process of automating the registry, including limited IT support, limited expertise in matching data variables from RCCR and eHIntS, and limited availability and accessibility of eHIntS information for import into REDCap. In summary, despite these challenges, partial automation was achieved with the REDCap/OBIEE system, enhancing efficiency, data security, and data quality.

High neutrophil-to-lymphocyte ratio predicts worse overall survival in patients with advanced/metastatic urothelial bladder cancer.

OBJECTIVES: To study the role of the neutrophil-to-lymphocyte ratio in predicting survival outcomes for patients with advanced bladder cancer. METHODS: We retrospectively reviewed 150 patients diagnosed with advanced or metastatic bladder cancer between January 2004 and June 2014. The neutrophil-to-lymphocyte ratio was computed on diagnosis and after the first cycle of chemotherapy. A neutrophil-to-lymphocyte ratio cut-off of 3.0 was determined, with a concordance index of 0.89. Kaplan-Meier curves, log-rank tests, Cox proportional hazards and logistic regression models were used to predict the association of the neutrophil-to-lymphocyte ratio with survival outcomes. RESULTS: Just five patients were alive at the end of the study; the rest died from metastatic bladder cancer. On multivariate analysis, higher Eastern Cooperative Oncology Group status, lymphadenopathy, visceral metastases and neutrophil-to-lymphocyte ratio ≥3.0 were associated with poorer overall survival (hazard ratio 1.67, P = 0.03; hazard ratio 1.97, P = <0.01; hazard ratio 2.02, P = <0.01; hazard ratio 5.06, P = <0.01), whereas chemotherapy conferred better overall survival (hazard ratio 0.546, P = 0.01). Furthermore, the role of chemotherapy prolonged survival longer in patients with a neutrophil-to-lymphocyte ratio <3.0 (median overall survival 13.0 vs 22.0 months, hazard ratio 0.273, P = 0.008) compared with a neutrophil-to-lymphocyte ratio ≥3.0 (median overall survival 4.0 vs 7.0 months, hazard ratio 0.452, P = 0.020). More importantly, when dichotomized to the four different pre- and post-chemotherapy groups, patients with a pre- and post-chemotherapy neutrophil-to-lymphocyte ratio <3.0 had the best additional median overall survival of 19.0 months compared with patients with a pre- and post-chemotherapy neutrophil-to-lymphocyte ratio ≥3.0 (3.0 months). CONCLUSIONS: Elevated neutrophil-to-lymphocyte ratio is independently associated with poorer chemotherapeutic response and overall survival in patients with advanced or metastatic bladder cancer. The neutrophil-to-lymphocyte ratio can be an inexpensive novel factor in prognosticating disease progression and providing better patient counseling.

A rapid and label-free SERS detection method for biomarkers in clinical biofluids.

A metal carbonyl-functionalized nanostructured substrate can be used in a rapid and simple assay for the detection of A1AT, a potential biomarker for bladder cancer, in clinical urine samples. The assay involves monitoring changes in the carbonyl stretching vibrations of the metal carbonyl via surface-enhanced Raman spectroscopy (SERS). These vibrations lie in the absorption spectral window of 1800-2200 cm(-1), which is free of any spectral interference from biomolecules.

Sensitive SERS glucose sensing in biological media using alkyne functionalized boronic acid on planar substrates.

In this work, we propose a novel glucose binding mechanism on a highly sensitive SERS substrate, in order to overcome challenges in specific glucose detection in bio-fluids. We make use of phenylboronic acid as a receptor for saccharide capture onto the substrate and the ability of the captured glucose molecule to undergo secondary binding with an alkyne-functionalized boronic acid to form a glucose-alkyne-boronic acid complex. The formation of this complex shows high selectivity for glucose, over other saccharides. In addition, the alkyne group of the alkyne-functionalized boronic acid exhibits a distinct Raman peak at 1996 cm(-1) in a biological silent region (1800-2800 cm(-1)) where most endogenous molecules, including glucose, show no Raman scattering, thus offering a high sensitivity over other SERS glucose sensing. The substrate offers long-term stability, as well as high SERS enhancement to the glucose-alkyne boronic acid complex on substrate. In addition, the reversibility of SERS signals at various incubation stages also shows reusability capabilities, whereas positive results in clinical urine samples demonstrate clinical feasibility. All these strongly suggest that this newly developed SERS-based assay offers great potential in glucose sensing.

Sensitive SERS-pH sensing in biological media using metal carbonyl functionalized planar substrates.

Conventional nanoparticle based Surface enhanced Raman scattering (SERS) technique for pH sensing often fails due to the aggregation of particles when detecting in acidic medium or biosamples having high ionic strength. Here, We develop SERS based pH sensing using a novel Raman reporter, arene chromium tricarbonyl linked aminothiophenol (Cr(CO)3-ATP), functionalized onto a nano-roughened planar substrates coated with gold. Unlike the SERS spectrum of the ATP molecule that dominates in the 400-1700 cm(-1) region, which is highly interfered by bio-molecules signals, metal carbonyl-ATP (Cr(CO)3)-ATP) offers the advantage of monitoring the pH dependent strong CO stretching vibrations in the mid-IR (1800-2200 cm(-1)) range. Raman signal of the CO stretching vibrations at ~1820 cm(-1) has strong dependency on the pH value of the environment, where its peak undergo noticeable shift as the pH of the medium is varied from 3.0 to 9.0. The sensor showed better sensitivity in the acidic range of the pH. We also demonstrate the pH sensing in a urine sample, which has high ionic strength and our data closely correlate to the value obtained from conventional sensor. In future, this study may lead to a sensitive chip based pH sensing platform in bio-fluids for the early diagnosis of diseases.

A transition metal carbonyl probe for use in a highly specific and sensitive SERS-based assay for glucose.

A triosmium carbonyl cluster-boronic acid conjugate is used as a secondary carbohydrate probe in a SERS-based assay. The assay does not require conjugation of the metal carbonyl probe to a SERS-active species, and it utilizes the CO stretching vibrations of the metal carbonyl, which lies in a silent region of the SERS spectrum (1800-2200 cm(-1)), for quantification. High selectivity for glucose over fructose and galactose is obtained, and a human urine sample doped with glucose is detected accurately.

Combination of the ERK inhibitor AZD6244 and low-dose sorafenib in a xenograft model of human renal cell carcinoma.

Sorafenib, a multikinase inhibitor, is currently used as monotherapy for advanced renal cell carcinoma (RCC). However, adverse effects associated with its use have been experienced by some patients. In this study, we examined the antitumor and antiangiogenic activities of low-dose sorafenib in combination with the MEK inhibitor AZD6244 (sorafenib/AZD6244) in a preclinical model of RCC. Primary RCC 08-0910 and RCC 786-0 cells as well as patient-derived RCC models were used to study the antitumor and antiangiogenic activities of sorafenib/AZD6244. Changes of biomarkers relevant to angiogenesis and cell cycle were determined by western immunoblotting. Microvessel density, apoptosis and cell proliferation were analyzed by immunohistochemistry. Treatment of RCC 786-0 cells with sorafenib/AZD6244 resulted in G1 cell cycle arrest and blockade of serum-induced cell migration. Sorafenib/AZD6244 induced apoptosis in primary RCC 08-0910 cells at low concentrations. In vivo addition of AZD6244 to sorafenib significantly augmented the antitumor activity of sorafenib and allowed dose reduction of sorafenib without compromising its antitumor activity. Sorafenib/AZD6244 potently inhibited angiogenesis and phosphorylation of VEGFR-2, PDGFR-ß and ERK, p90RSK, p70S6K, cdk-2 and retinoblastoma. Sorafenib/AZD6244 also caused upregulation of p27, Bad and Bim but downregulation of survivin and cyclin B1. These resulted in a reduction in cellular proliferation and the induction of tumor cell apoptosis. Our findings showed that AZD6244 and sorafenib complement each other to inhibit tumor growth. This study provides sound evidence for the clinical investigation of low-dose sorafenib in combination with AZD6244 in patients with advanced RCC.

Altered expression of cell adhesion molecules leads to differential uptake of hypericin in urothelial cancer.

OBJECTIVE: To elucidate the mechanism behind selective uptake of hypericin in bladder cancer after intravesical instillation for photodynamic diagnosis of urothelial cell carcinoma of bladder. PATIENTS AND METHODS: Clinical studies were done on a series of 60 bladder cancer biopsies obtained from 28 patients who received intravesical instillations with 8 µM hypericin. Serial 5 µm cryosections were cut from 43 biopsies, and expression of the E-cadherin and associated catenins were determined using immunohistochemical and immunofluorescence staining. Hypericin was assessed using fluorescence confocal laser scanning microscopy. In addition, mRNA expression of these cell-adhesion molecules was analyzed in 17 biopsies using reverse transcription-PCR. RESULTS: Increased variability in the expression of E-cadherin and associated molecules was found in high-grade, advanced stage bladder carcinoma. An inverse association was found between immunoreactivity for E-cadherin, ß- and γ-catenin, and both stage and grade of cancer (P < 0.05). A positive association was observed between the hypericin fluorescence and tumor grade. There was a significant down-regulation of E-cadherin and ß-catenin mRNA in grade 2 and 3 tumors. Although a small sample size was studied, it provided sufficient proof to support the hypothesis that altered expression of cell adhesion molecules would lead to preferential hypericin uptake in urothelial cell carcinoma. CONCLUSIONS: Our study has unraveled one of the many factors contributing to the selective uptake of hypericin in bladder cancer. We have thus identified the effects of alteration of E-cadherin-catenin complex and transformed intercellular junction in the modified paracellular uptake of hypericin that provides the rationale for using this photosensitizer in photodynamic diagnosis of bladder carcinoma.

New frontier in hypericin-mediated diagnosis of cancer with current optical technologies.

Photosensitizers (PSs) have shown great potentials as molecular contrast agents in photodynamic diagnosis (PDD) of cancer. While the diagnostic values of PSs have been proven previously, little efforts have been put into developing optical imaging and diagnostic algorithms. In this article, we review the recent development of optical probes that have been used in conjunction with a potent PS, hypericin (HY). Various fluorescence techniques such as laser confocal microscopy, fluorescence urine cytology, endoscopy and endomicroscopy are covered. We will also discuss about image processing and classification approaches employed for accurate PDD. We anticipate that continual efforts in these developments could lead to an objective PDD and complete surgical clearance of tumors. Recent advancements in nanotechnology have also opened new horizons for PSs. The use of biocompatible gold nanoparticles as carrier for enhanced targeted delivery of HY has been attained. In addition, plasmonic properties of nanoparticles were harnessed to induce localized hyperthermia and to manage the release of PS molecules, enabling a better therapeutic outcome of a combined photodynamic and photothermal therapy. Finally, we discuss how nanoparticles can be used as contrast agents for other optical techniques such as optical coherence tomography and surface-enhanced Raman scattering imaging.

The natural history of voiding function after robot-assisted laparoscopic radical prostatectomy.

OBJECTIVES: We report the natural history of voiding function in men with clinically localized prostate cancer after robot-assisted laparoscopic radical prostatectomy (RLRP), describing the trend of functional recovery, which is currently not well described using the robot-assisted laparoscopic approach. MATERIALS AND METHODS: We determined the impact on voiding function by prospectively evaluating 100 consecutive men who underwent RLRP between May 2005 and December 2006 and compared their reported International Prostate Symptom Score (IPSS) and Quality of Life (QOL) scores at 3, 6, and 12 months with preoperative scores after surgery. Patients with preoperative IPSS of 0-7 and 8-35 were defined as having mild lower urinary tract symptoms (LUTS) and moderate to severe LUTS, respectively. RESULTS: Continence was achieved in 82%, 87%, and 91% of men at 3, 6, and 12 months after RLRP, respectively. There were statistically and clinically significant improvements in both IPSS and QOL preoperative scores at all studied time points for patients with moderate to severe preexisting LUTS. The mean IPSS scores for these patients preoperatively and at 3, 6, and 12 months after surgery were 14.1, 5.2, 3.0, and 2.9, respectively and the corresponding mean QOL scores were 3.4, 2.1, 1.6, and 1.6, respectively. Patients with mild preexisting LUTS showed no statistically significant improvement in IPSS at 3 and 6 months after surgery but significant improvement was found at 1 year (P = 0.04). CONCLUSIONS: Good continence recovery is expected in most patients undergoing RLRP. Patients with moderate to severe preexisting LUTS can expect early and clinically significant symptom and QOL improvements after RLRP. Patients with mild preexisting LUTS show significant symptom improvement at 1 year.

Chlorin e6-polyvinylpyrrolidone mediated photodynamic therapy--A potential bladder sparing option for high risk non-muscle invasive bladder cancer.

BACKGROUND: Bladder sparing treatment options for high risk non-muscle invasive blader cancer (NMIBC) after intravesical Bacillus Calmette-Guerin (BCG) failure are limited. OBJECTIVE: To evaluate photodynamic therapy (PDT) using chlorin e6-polyvinylpyrrolidone (Ce6-PVP) as a bladder sparing therapy for NMIBC refractory to intravesical BCG therapy. MATERIALS AND METHODS: Between July 2004 and June 2009, patients with recurrent NMIBC after induction intravesical BCG therapy were treated with PDT performed with a 665nm laser and light dosimetry of 10-24J/cm(2). The patients underwent cystoscopic surveillance for tumour recurrence post PDT. Post treatment lower urinary tract symptoms and bladder capacity were also monitored. Serum and urine samples were collected for spectrometric quantification of photosensitizer levels. RESULTS: Five patients underwent PDT, with a total of seven treatments performed. One patient received intravenous Ce6-PVP, while the rest received intravesical Ce6-PVP.The median age was 80 years (mean 79 years, range 72-88 years). There were three patients with primary CIS of the bladder and two with T1 high grade TCC and CIS of the bladder. At a median follow-up of 29 months (mean 25 months, range 6-36 months), two patients were disease free, two patients developed recurrence and one patient progressed to muscle invasive disease. There were no immediate adverse effects. The patient receiving intravenous Ce6-PVP developed an enterovesical fistula 16 months post PDT. CONCLUSIONS: Despite being a small pilot study, intravesical Ce6-PVP mediated PDT is a feasible bladder sparing treatment option for recurrent high risk non-muscle invasive bladder carcinoma in selected individuals.