Raman Spectroscopy for Instant Bladder Tumor Diagnosis: System Development and In Vivo Proof-Of-Principle Study in Accordance with the European Medical Device Regulation (MDR2017/745).

This work reports on an in vivo Raman-based endoscopy system, invaScope, enabling Raman measurements of healthy and tumor bladder tissue during an endoscopic procedure in the operating theatre. The presented study outlines the progression from the initial concept (validated through previously performed ex vivo studies) to the approval and implementation of a clinical investigational device according to the requirement within the framework of the European Medical Device Regulation (MDR2017/745). The study's primary objective was to employ the invaScope Raman system within the bladder, capturing in vivo spectroscopic Raman data followed by standard histo- and cytopathological examinations of urological tissue (considered the gold standard).

Outpatient Photodynamic Diagnosis-guided Laser Destruction of Bladder Tumors Is as Good as Conventional Inpatient Photodynamic Diagnosis-guided Transurethral Tumor Resection in Patients with Recurrent Intermediate-risk Low-grade Ta Bladder Tumors. A Prospective Randomized Noninferiority Clinical Trial.

Background: Transurethral resection of recurrent low-grade intermediate-risk Ta bladder tumor (BT) in general anesthesia (GA) is burdensome to patients and health care system. Laser technologies enable treatment in office-based settings, reducing morbidity and costs.

Objective: To compare 4-mo recurrence-free survival after outpatient department (OPD) diode laser coagulation of BT in local anesthesia and gold standard transurethral resection of BT (TUR-BT) in GA in intermediate-risk Ta low-grade BT, and to evaluate treatment-related morbidity.

External Validation of the 2003 Leibovich Prognostic Score in Patients Randomly Assigned to SORCE, an International Phase III Trial of Adjuvant Sorafenib in Renal Cell Cancer.

Purpose: The 2003 Leibovich score guides prognostication and selection to adjuvant clinical trials for patients with locally advanced renal cell carcinoma (RCC) after nephrectomy. We provide a robust external validation of the 2003 Leibovich score using contemporary data from SORCE, an international, randomized trial of sorafenib after excision of primary RCC.

Methods: Data used to derive the 2003 Leibovich score were compared with contemporary data from SORCE.

Morpho-molecular signal correlation between optical coherence tomography and Raman spectroscopy for superior image interpretation and clinical diagnosis.

The combination of manifold optical imaging modalities resulting in multimodal optical systems allows to discover a larger number of biomarkers than using a single modality. The goal of multimodal imaging systems is to increase the diagnostic performance through the combination of complementary modalities, e.g.

An integrated multi-omics analysis identifies prognostic molecular subtypes of non-muscle-invasive bladder cancer.

The molecular landscape in non-muscle-invasive bladder cancer (NMIBC) is characterized by large biological heterogeneity with variable clinical outcomes. Here, we perform an integrative multi-omics analysis of patients diagnosed with NMIBC (n = 834). Transcriptomic analysis identifies four classes (1, 2a, 2b and 3) reflecting tumor biology and disease aggressiveness.

Adjuvant Sorafenib for Renal Cell Carcinoma at Intermediate or High Risk of Relapse: Results From the SORCE Randomized Phase III Intergroup Trial.

Purpose: SORCE is an international, randomized, double-blind, three-arm trial of sorafenib after surgical excision of primary renal cell carcinoma (RCC) found to be at intermediate or high risk of recurrence.

Patients And Methods: We randomly assigned participants (2:3:3) to 3 years of placebo (arm A), 1 year of sorafenib followed by 2 years of placebo (arm B), or 3 years of sorafenib (arm C). The initial sorafenib dose was 400 mg twice per day orally, amended to 400 mg daily.

Do repeated transurethral procedures under general anesthesia influence mortality in patients with non-invasive urothelial bladder cancer? A Danish national cohort study.

To investigate the effect of repeated transurethral procedures under general anesthesia on overall mortality in patients with non-invasive bladder cancer. All Danish residents with non-invasive papillary urothelial carcinoma or primary urothelial carcinoma diagnosed between 1 January 2000 and 1 January 2011 were included and followed until death or 31 March 2017. All transurethral procedures under general anesthesia, intravesical instillation therapy, recurrences and progression to invasive disease or cystectomy were recorded during follow-up.

Morpho-molecular ex vivo detection and grading of non-muscle-invasive bladder cancer using forward imaging probe based multimodal optical coherence tomography and Raman spectroscopy.

Non-muscle-invasive bladder cancer affects millions of people worldwide, resulting in significant discomfort to the patient and potential death. Today, cystoscopy is the gold standard for bladder cancer assessment, using white light endoscopy to detect tumor suspected lesion areas, followed by resection of these areas and subsequent histopathological evaluation. Not only does the pathological examination take days, but due to the invasive nature, the performed biopsy can result in significant harm to the patient.

Bladder tissue characterization using probe-based Raman spectroscopy: Evaluation of tissue heterogeneity and influence on the model prediction.

Existing approaches for early-stage bladder tumor diagnosis largely depend on invasive and time-consuming procedures, resulting in hospitalization, bleeding, bladder perforation, infection and other health risks for the patient. The reduction of current risk factors, while maintaining or even improving the diagnostic precision, is an underlying factor in clinical instrumentation research. For example, for clinic surveillance of patients with a history of noninvasive bladder tumors real-time tumor diagnosis can enable immediate laser-based removal of tumors using flexible cystoscopes in the outpatient clinic.

National incidence and survival of patients with non-invasive papillary urothelial carcinoma: a Danish population study.

Objective: To estimate national relative survival of low and high grade non-invasive papillary urothelial carcinoma (Ta LG and Ta HG) and urothelial carcinoma in situ (CIS).

Materials And Methods: All Danish citizens (17,941 patients) with a primary urothelial bladder tumour diagnosis in the period 2000- 2010 were followed until 1 January 2016 and recorded in the Danish Bladder Cancer Cohort database. Survival was compared to the background population matched on age and gender and adjusted by civil status, income, education, and comorbidity.

Can routine outpatient follow-up of patients with bladder cancer be improved? A multicenter prospective observational assessment of blue light flexible cystoscopy and fulguration.

Background: The aim of this prospective cohort study was to determine the feasibility of incorporating blue light flexible cystoscopy (BLFC) and biopsy/fulguration into routine outpatient follow-up of non-muscle invasive bladder cancer patients.

Methods: The study included patients with non-muscle-invasive bladder cancer (NMIBC) who were scheduled for routine follow-up. Hexaminolevulinate was instilled in the outpatient department, and the bladder was examined under white light and then with BLFC.

Outpatient diode laser treatment of intermediate-risk non-invasive bladder tumors without sedation: efficacy, safety and economic analysis.

Objective: This study aimed to validate a new method for outpatient diode laser ablation of bladder tumors without sedation or pain control.

Methods: Twenty-one patients with stage Ta low-grade intermediate-risk bladder tumors underwent photodynamic-guided laser ablation of their bladder tumors and 1 month later follow-up cystoscopy with photodynamic and IMAGE1 S™-guided biopsies. Pain was measured using a visual analog scale (range 0-10).

Molecular Markers Increase Precision of the European Association of Urology Non-Muscle-Invasive Bladder Cancer Progression Risk Groups.

The European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC) recommend risk stratification based on clinicopathologic parameters. Our aim was to investigate the added value of biomarkers to improve risk stratification of NMIBC. We prospectively included 1,239 patients in follow-up for NMIBC in six European countries.

Outpatient photodynamic-guided diagnosis of carcinoma in situ with flexible cystoscopy: an alternative to conventional inpatient photodynamic-guided bladder biopsies in the operating theatre?

Objective: The aim of this prospective open comparative study was to establish whether conventional photodynamic-guided bladder biopsies using general anaesthesia and rigid resectoscopes (inpatient) can be replaced with less traumatic flexible cystoscopy in non-sedated patients (outpatient), without compromising the diagnosis of carcinoma in situ (CIS).

Materials And Methods: Thirty-one patients were included. After BCG instillation for CIS, bladder biopsies were obtained using photodynamic-guided flexible cystoscopy.

Prognostic Impact of a 12-gene Progression Score in Non-muscle-invasive Bladder Cancer: A Prospective Multicentre Validation Study.

Background: Progression of non-muscle-invasive bladder cancer (NMIBC) to muscle-invasive bladder cancer (MIBC) is life-threatening and cannot be accurately predicted using clinical and pathological risk factors. Biomarkers for stratifying patients to treatment and surveillance are greatly needed.

Objective: To validate a previously developed 12-gene progression score to predict progression to MIBC in a large, multicentre, prospective study.

Non-muscle-invasive bladder cancer: a vision for the future.

The management of non-muscle-invasive bladder cancer (NMIBC) has evolved from the first reports on bladder endoscopy and transurethral resection to the introduction of adjuvant intravesical treatment. However, disease recurrence and progression remain an ongoing risk, placing a heavy burden on healthcare resources and on patients' quality of life. Deeper understanding of the molecular basis of the disease and developments in optics, lasers and computer science are already offering opportunities to revolutionize care and improve long-term prognosis.

An optical method for reducing green fluorescence from urine during fluorescence-guided cystoscopy.

Photodynamic diagnosis (PDD) of bladder tumour tissue significantly improves endoscopic diagnosis and treatment of bladder cancer in rigid cystoscopes in the operating theatre and thus reduces tumour recurrence. PDD comprises the use of blue light, which unfortunately excites green fluorescence from urine. As this green fluorescence confounds the desired red fluorescence of the PDD, methods for avoiding this situation particularly in cystoscopy using flexible cystoscopes are desirable.

Investigation of the mechanisms of action behind Electromotive Drug Administration (EMDA).

Objective: Bladder cancer is a cause of considerable morbidity worldwide. Electromotive Drug Administration is a method that combines intravesical chemotherapy with local electric field application. Electroporation has been suggested among other mechanisms as having a possible role in the therapy, so the goal of the present study was to investigate the electric fields present in the bladder wall during the treatment to determine which mechanisms might be involved.

Comprehensive Transcriptional Analysis of Early-Stage Urothelial Carcinoma.

Non-muscle-invasive bladder cancer (NMIBC) is a heterogeneous disease with widely different outcomes. We performed a comprehensive transcriptional analysis of 460 early-stage urothelial carcinomas and showed that NMIBC can be subgrouped into three major classes with basal- and luminal-like characteristics and different clinical outcomes. Large differences in biological processes such as the cell cycle, epithelial-mesenchymal transition, and differentiation were observed.

Hospitalization for transurethral bladder resection reduces quality of life in Danish patients with non-muscle-invasive bladder tumour.

Objective The aim of the study was to evaluate the impact of transurethral resection of bladder tumour (TURBT) on patients' quality of life (QoL) and to validate a tool to quantify problems associated with TURBT in a Danish population. Materials and methods A prospective study was carried out using a combination of questionnaires and interviews. The study included 165 consecutive patients undergoing a TURBT owing to non-muscle-invasive bladder cancer (NMIBC) from 1 May 2011 to 30 April 2012.

A five-factor biomarker profile obtained week 4-12 of treatment for improved prognostication in metastatic renal cell carcinoma: Results from DARENCA study 2.

Background: Several biomarkers of treatment efficacy have been associated with a better prognosis in patients with metastatic renal cell carcinoma (mRCC). The prognostic significance of biomarkers in the early treatment phase is unclear.

Material And Methods: In a complete national cohort of mRCC patients receiving first-line tyrosine kinase inhibitors (TKI) or interleukin-2 based immunotherapy (IT) from 2006 to 2010, overall survival (OS) was analysed for baseline International mRCC Database Consortium (IMDC) classification factors and on-treatment time-dependent biomarkers obtained day 1 each cycle week 4-12 after treatment initiation with multivariate analysis and bootstrap validation.

Office-based transurethral devascularisation of low grade non-invasive urothelial cancer using diode laser. A feasibility study.

Background And Objective: Frequent recurrence of non-muscle invasive bladder tumours (NMIBC) requiring transurethral resection of bladder tumour (TUR-BT) and lifelong monitoring makes the lifetime cost per patient the highest of all cancers. A new method is proposed for the removal of low grade NMIBCs in an office-based setting, without the need for sedation and pain control and where the patient can leave immediately after treatment.

Study Design/patients And Methods: An in vitro model was developed to examine the dose/response relationship between laser power, treatment time, and distance between laser fibre and target, using a 980 nm diode laser and chicken meat.

A clinical and molecular review of inverted papilloma of the urinary tract: how to handle?

Inverted papilloma (IP) of the urinary tract is classified by the World Health Organisation as a non-invasive urothelial tumour with normal to minimal cytological atypia of the neoplastic cells. During the 1980s, it came under suspicion of having a premalignant or malignant potential and of being concurrent with urothelial cell carcinoma (UCC). This quandary has been proven difficult to solve, due to the fact that IP is very rare and literature mostly consists of case reports with varying levels of information, making strong meta-analyses problematic.

Budget impact of incorporating one instillation of hexaminolevulinate hydrochloride blue-light cytoscopy in transurethral bladder tumour resection for patients with non-muscle-invasive bladder cancer in Sweden.

Objectives: To explore the cost impact on Swedish healthcare of incorporating one instillation of hexaminolevulinate hydrochloride (HAL) blue-light cystoscopy into transurethral resection of bladder tumour (TURBT) in patients with suspected new or recurrent non-muscle-invasive bladder cancer (NMIBC).

Materials And Methods: A decision tree model was built based on European Association of Urology guidelines for the treatment and management of NMIBC. Input data were compiled from two recent studies comparing recurrence rates of bladder cancer in patients undergoing TURBT with either the current standard of care (SOC) of white-light cystoscopy, or with the SOC and HAL blue-light cystoscopy.