Reliable Visualization of the Treatment Effect of Transperineal Focal Laser Ablation in Prostate Cancer Patients by Magnetic Resonance Imaging and Contrast-enhanced Ultrasound Imaging.

Background: Transperineal focal laser ablation (TPLA) treatment for prostate cancer (PCa) is an experimental focal ablative therapy modality with low morbidity. However, a dosimetry model for TPLA is lacking. Objective: To determine (1) the three-dimensional (3D) histologically defined ablation zone of single- and multifiber TPLA treatment for PCa correlated with magnetic resonance imaging (MRI) and contrast-enhanced ultrasound (CEUS) and (2) a reliable imaging modality of ablation zone volumetry. Design setting and participants: This was a prospective, multicenter, and interventional phase I/II pilot study with an ablate-and-resect design. TPLA was performed in 12 patients with localized prostate cancer divided over four treatment regimens to evaluate potential variation in outcomes. Intervention: TPLA was performed approximately 4 wk prior to robot-assisted radical prostatectomy (RARP) in a daycare setting using local anesthesia. Outcome measurements and statistical analysis: Four weeks after TPLA, ablation zone volumetry was determined on prostate MRI and CEUS by delineation and segmentation into 3D models and correlated with whole-mount RARP histology using the Pearson correlation index. Results and limitations: Twelve office-based TPLA procedures were performed successfully under continuous transrectal ultrasound guidance using local perineal anesthesia. No serious adverse events occurred. A qualitative analysis showed a clear demarcation of the ablation zone on T2-weighted MRI, dynamic contrast-enhanced MRI, and CEUS. On pathological evaluation, no remnant cancer was observed within the ablation zone. Ablation zone volumetry on CEUS and T2-weighted MRI compared with histology had a Pearson correlation index of r = 0.94 (95% confidence interval [CI] 0.74-0.99, p < 0.001) and r = 0.93 (95% CI 0.73-0.98, p < 0.001), respectively. Conclusions: CEUS and prostate MRI could reliably visualize TPLA ablative effects after minimally invasive PCa treatment with a high concordance with histopathological findings and showed no remnant cancer. Patient summary: The treatment effects of a novel minimally invasive ablation therapy device can reliably be visualized with radiological examinations. These results will improve planning and performance of future procedures.

Image-guided in-Vivo Needle-Based Confocal Laser Endomicroscopy in the Prostate: Safety and Feasibility Study in 2 Patients.

Purpose: To assess the safety and technical feasibility of in-vivo needle-based forward-looking confocal laser endomicroscopy in prostate tissue. Methods: For this feasibility study, 2 patients with a suspicion of prostate cancer underwent transperineal needle-based confocal laser endomicroscopy during ultrasound-guided transperineal template mapping biopsies. After intravenous administration of fluorescein, needle-based confocal laser endomicroscopy imaging was performed with a forward-looking probe (outer diameter 0.9 mm) in 2 trajectories during a manual push-forward and pullback motion. A biopsy was taken in a coregistered parallel adjacent trajectory to the confocal laser endomicroscopy trajectory for histopathologic comparison. Peri- and postprocedural adverse events, confocal laser endomicroscopy device malfunction and procedural failures were recorded. Needle-based confocal laser endomicroscopy image quality assessment, image interpretation, and histology were performed by an experienced confocal laser endomicroscopy rater and uro-pathologist, blinded to any additional information. Results: In both patients, no peri- and post-procedural adverse events were reported following needle-based confocal laser endomicroscopy. No confocal laser endomicroscopy device malfunction nor procedural failures were reported. Within 1.5 min after intravenous administration of fluorescein, needle-based confocal laser endomicroscopy image quality was sufficient for interpretation for at least 14 min, yielding more than 5000 confocal laser endomicroscopy frames per patient. The pullback confocal laser endomicroscopy recordings and most of the push-forward recordings almost only visualized erythrocytes, being classified as non-representative. During the push-forward recordings, prostate tissue was occasionally visualized in single frames, insufficient for histopathologic comparison. Prostate carcinoma was identified by biopsy in one patient (Gleason score 4 + 3 = 7, >50%), while the biopsy from the other patient showed no malignancy. Conclusion: Needle-based confocal laser endomicroscopy imaging of in-vivo prostate tissue with a forward-looking confocal laser endomicroscopy probe is safe without device malfunctions or procedural failures. Needle-based confocal laser endomicroscopy is technically feasible, but the acquired confocal laser endomicroscopy datasets are non-representative. The confocal laser endomicroscopy images' non-representative nature is possibly caused by bleeding artifacts, movement artifacts and a lack of contact time with the tissue of interest. A different confocal laser endomicroscopy probe or procedure might yield representative images of prostatic tissue.

How Reliable Is Endoscopic Stone Recognition? A Comparison Between Visual Stone Identification and Formal Stone Analysis.

Objective: To assess the diagnostic accuracy and intra-observer agreement of endoscopic stone recognition (ESR) compared with formal stone analysis. Introduction: Stone analysis is a corner stone in the prevention of stone recurrence. Although X-ray diffraction (XRD) and infrared spectroscopy are the recommended techniques for reliable formal stone analysis, this is not always possible, and the process takes time and is costly. ESR could be an alternative, as it would give immediate information on stone composition. Materials and Methods: Fifteen endourologists predicted stone composition based on 100 videos from ureterorenoscopy. Diagnostic accuracy was evaluated by comparing the prediction from visual assessment with stone analysis by XRD. After 30 days, the videos were reviewed again in a random order to assess intra-observer agreement. Results: The median diagnostic accuracy for calcium oxalate monohydrate was 54% in questionnaire 1 (Q1) and 59% in questionnaire 2 (Q2), whereas calcium oxalate dihydrate had a median diagnostic accuracy of 75% in Q1 and 50% in Q2. The diagnostic accuracy for calcium hydroxyphosphate was 10% in Q1 and 13% in Q2. The median diagnostic accuracy for calcium hydrogen phosphate dihydrate and calcium magnesium phosphate was 0% in both questionnaires. The median diagnostic accuracy for magnesium ammonium phosphate was 20% in Q1 and 40% in Q2. The median diagnostic accuracy for uric acid was 22% in both questionnaires. Finally, there was a diagnostic accuracy of 60% in Q1 and 80% in Q2 for cystine. The intra-observer agreement ranged between 45% and 72%. Conclusion: Diagnostic accuracy of ESR is limited and intra-observer agreement is below the threshold of acceptable agreement.

B/A Measurement of Clear Cell Renal Cell Carcinoma versus Healthy Kidney Tissue.

The acoustic parameter of non-linearity B/A has been found capable of discriminating some types of pathological tissue from healthy tissue. The literature on the utility of B/A for cancer diagnostics is very limited, with measurements on the human breast and liver. This work expands the current research on cancer diagnostics by B/A assessment of eight slices of human clear cell renal cell carcinoma (ccRCC) from two patients and four slices of healthy kidney tissue from two healthy kidney samples. The Wilcoxon test identified the B/A distribution of malignant tissue as not significantly different from that of healthy tissue. An alternative way of defining outliers resulted in median B/A values of 8.1 for ccRCC and 6.8 for healthy tissue (p < 0.05). Acoustic attenuation at 2.1 MHz was significantly greater (p < 0.05) for ccRCC (1.7 dB/cm) than for healthy tissue (1.0 dB/cm). The observed differences in the measured values suggest that B/A and acoustic attenuation may represent potential diagnostic markers of ccRCC. More data and an improved experimental design are required to provide a definitive conclusion on the utility of B/A for cancer diagnostics.

Pulmonary embolism at autopsy in cancer patients.

BACKGROUND: Pulmonary embolism (PE) is a potentially fatal disease, but data on the incidence of fatal PE in cancer patients are scant. OBJECTIVE: We sought to estimate the proportion of cancer patients with PE at autopsy. METHODS: For this retrospective cohort study, all autopsy reports of cancer patients were retrieved from PALGA: Dutch Pathology Registry and used for data extraction. The primary outcome was PE at time of autopsy, defined as any clot obstructing a pulmonary artery. The secondary outcome was venous thromboembolism, defined as the composite of thrombotic PE, deep vein thrombosis, splanchnic vein thrombosis, or internal jugular vein thrombosis. RESULTS: A total of 9571 cancer patients were included. In 1191 (12.4%; 95% confidence interval [CI], 11.8-13.1) patients, one or more PE events were observed at autopsy, of whom 1074 (90.2%) had a thrombotic embolism, 168 (14.1%) a tumor embolism, 9 (0.8%) a septic embolism, 7 (0.6%) a fat tissue embolism, and 3 (0.3%) a bone marrow embolism. Among patients with PE for whom the cause of death was specified in the autopsy report, death was considered PE-related in 642 patients (66.7%), which was 6.7% of the total study population. Venous thromboembolism was observed in 1223 (12.8%; 95% CI, 12.1-13.5) patients. CONCLUSION: The proportion of PE in cancer patients at autopsy is substantial. Although the study population is not representative for the total cancer population, it suggests that PE is an important disease complication in cancer patients.

The Diagnostic Yield and Concordance of Ureterorenoscopic Biopsies for Grading of Upper Tract Urothelial Carcinoma: A Dutch Nationwide Analysis.

Objectives: To evaluate the diagnostic yield and concordance of upper tract urothelial carcinoma (UTUC) grading between ureterorenoscopic biopsies and surgical resections. Materials and Methods: The nationwide Dutch Pathology Registry (nationwide network and registry of histo- and cytopathology in the Netherlands [PALGA]) was searched for UTUC-positive renal units (RUs) with histopathology excerpts from ureterorenoscopic biopsies and surgical resections, matched for laterality and localization of the tumor, from 2011 until 2018. The positive predictive value (concordance) of the biopsy grade with regard to the final grade according to the World Health Organization (WHO) 2004 classification was calculated. Results: A total of 1002 UTUC-positive rental units were included, of which 776 UTUC-positive RUs were graded according to the WHO 2004 classification in the ureterorenoscopic biopsy, the localization-matched surgical resection, or in both. The diagnostic yield of biopsies for a classifying diagnosis was 89% with a sensitivity for UTUC of 84%. In case of UTUC, the diagnostic yield for biopsy-based grading and staging was 97% and 72%, respectively. The concordance of high-grade biopsies with regard to the final histopathology was 97% and 62% for low-grade biopsies. Upgrading to final high grade occurred in 33% of the low-grade biopsies. Downgrading to final low grade occurred in 2% of high-grade biopsies. Conclusions: This is the first study to portray the limitations of ureterorenoscopic biopsies for UTUC in a nationwide cohort. The diagnostic yield of ureterorenoscopic biopsies for a classifying diagnosis is suboptimal, but the diagnostic yield for grading according to the WHO 2004 classification is high. Yet, a worrisome amount of ureterorenoscopic biopsies are upgraded with regard to the surgical resection. Consequently, one-third of patients, who qualify for kidney-sparing treatment according to one of the criteria recommended for risk stratification, might be stratified incorrectly. These findings stress the importance of a timely and stringent ureterorenoscopic follow-up after kidney-sparing surgery and highlight the need for improvements in the diagnostic approach to optimize the risk stratification.

Validation of Confocal Laser Endomicroscopy Features of Bladder Cancer: The Next Step Towards Real-time Histologic Grading.

BACKGROUND: Cystoscopy enables the visualisation of suspicious bladder lesions but lacks the ability to provide real-time histopathologic information. Confocal laser endomicroscopy (CLE) is a probe-based optical technique that can provide real-time microscopic images. This high-resolution optical imaging technique may enable real-time tumour grading during cystoscopy. OBJECTIVE: To validate and adapt CLE criteria for bladder cancer diagnosis and grading. DESIGN, SETTING, AND PARTICIPANTS: Prospectively, 73 patients scheduled for transurethral resection of bladder tumour(s) were included. CLE imaging was performed intraoperatively prior to en bloc resection. Histopathology was the reference standard for comparison. INTERVENTION: Cystoscopic CLE imaging. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Three independent observers evaluated the CLE images to classify tumours as low- or high-grade urothelial carcinoma (UC), or benign lesions. Interobserver agreement was calculated with Fleiss kappa analysis and diagnostic accuracy with 2×2 tables. RESULTS AND LIMITATIONS: Histopathology of 66 lesions (53 patients) revealed 25 low-grade UCs, 27 high-grade UCs, and 14 benign lesions. For low-grade UC, most common features were papillary configuration (100%), distinct cell borders (81%), presence of fibrovascular stalks (79%), cohesiveness of cells (77%), organised cell pattern (76%), and monomorphic cells (67%). A concordance between CLE-based classification and histopathology was found in 19 cases (76%). For high-grade UC, pleomorphic cells (77%), indistinct cell borders (77%), papillary configuration (67%), and disorganised cell pattern (60%) were the most common features. A concordance with histopathology was found in 19 cases (70%). In benign lesions, the most prevalent features were disorganised cell pattern (57%) and pleomorphic cells (52%), and a concordance with histopathology was found in four cases (29%). CONCLUSIONS: The CLE criteria enable identification of UC. CLE features correlate to histopathologic features that may enable real-time tumour grading. However, flat lesions remain difficult to classify. PATIENT SUMMARY: Confocal laser endomicroscopy may enable real-time cancer differentiation during cystoscopy, which is important for prognosis and disease management.

Toward Automated In Vivo Bladder Tumor Stratification Using Confocal Laser Endomicroscopy.

Purpose: Urothelial carcinoma of the bladder (UCB) is the most common urinary cancer. White-light cystoscopy (WLC) forms the corner stone for the diagnosis of UCB. However, histopathological assessment is required for adjuvant treatment selection. Probe-based confocal laser endomicroscopy (pCLE) enables visualization of the microarchitecture of bladder lesions during WLC, which allows for real-time tissue differentiation and grading of UCB. To improve the diagnostic process of UCB, computer-aided classification of pCLE videos of in vivo bladder lesions were evaluated in this study. Materials and Methods: We implemented preprocessing methods to optimize contrast and to reduce striping artifacts in each individual pCLE frame. Subsequently, a semiautomatic frame selection was performed. The selected frames were used to train a feature extractor based on pretrained ImageNet networks. A recurrent neural network, in specific long short-term memory (LSTM), was used to predict the grade of bladder lesions. Differentiation of lesions was performed at two levels, namely (i) healthy and benign vs malignant tissue and (ii) low-grade vs high-grade papillary UCB. A total of 53 patients with 72 lesions were included in this study, resulting in ∼140,000 pCLE frames. Results: The semiautomated frame selection reduced the number of frames to ∼66,500 informative frames. The accuracy for differentiation of (i) healthy and benign vs malignant urothelium was 79% and (ii) high-grade and low-grade papillary UCB was 82%. Conclusions: A feature extractor in combination with LSTM results in proper stratification of pCLE videos of in vivo bladder lesions.

Upper Tract Urothelial Carcinoma Grade Prediction Based on the Ureteroscopic Appearance: Caution Should be Taken.

OBJECTIVES: To investigate the diagnostic accuracy, inter-rater and intrarater agreement of grade predictions based on the visual appearance of papillary upper tract urothelial carcinoma (UTUC) during digital ureteroscopy. METHODS: Nine urologists predicted the histopathologic grade of 64 papillary UTUC (low-grade vs high-grade) by assessing the visual appearance of the tumors in videos from digital ureteroscopy. The diagnostic accuracy was estimated by comparing the grade predictions with the histopathology from colocalized biopsies. Inter-rater agreement was assessed by pairwise inter-rater percentage agreement and Fleiss Kappa analysis. The videos were rated in a random order again 30 days after the first assessment to evaluate the intrarater percentage agreement. RESULTS: Low-grade tumors were predicted correctly in 37%-85% of the cases with a median concordance of 59% for questionnaire 1 and 66% for questionnaire 2. High-grade tumors were predicted correctly in 26%-91% of the cases with a median concordance of 52% and 61% for each questionnaire. The median pairwise inter-rater percentage agreement was 66% for both questionnaires with a Fleiss Kappa of 0.29 and 0.38, respectively. The median intrarater percentage agreement was 81%. CONCLUSION: The histopathologic grade of UTUC is essential to the risk-stratification for treatment selection. Predictions of the histopathologic grade based on the visual appearance of papillary UTUC with digital ureteroscopy are often incorrect in comparison with biopsy results and yield low inter-rater agreement. Urologists must be aware of these limitations in the assessment of the tumor grade during digital ureteroscopy to warrant good clinical practice.

Grading upper tract urothelial carcinoma with the attenuation coefficient of in-vivo optical coherence tomography.

INTRODUCTION: With catheter based optical coherence tomography (OCT), high resolution images of the upper urinary tract can be obtained, thereby facilitating the detection of upper tract urothelial carcinomas (UTUC). We hypothesized that the attenuation coefficient of the OCT signal (µOCT ) is related to the histopathologic grade of the tumor. OBJECTIVES: In this study, we aimed to define the µOCT cut-off for discriminating high grade and low grade papillary UTUC. METHODS: For this post-hoc analysis, data from OCT imaging of papillary UTUC was obtained from patients during ureterorenoscopy. OCT images and raw data were simultaneously analyzed with in-house developed software. The µOCT determined in papillary UTUCs and corresponding histopathologic grading from either biopsies or radical resection specimens were compared. RESULTS: Thirty-five papillary UTUC from 35 patients were included. µOCT analysis was feasible in all cases. The median µOCT was 3.3 mm-1 (IQR 2.7-3.7 mm-1 ) for low-grade UTUC and 4.9 mm-1 (IQR 4.3-6.1 mm-1 ) for high-grade UTUC (P = 0.004). ROC analysis yielded a µOCT cut-off value of >4.0 mm-1 (AUC = 0.85, P < 0.001) with a sensitivity of 83% and a specificity of 94% for high-grade papillary UTUC. CONCLUSIONS: This study proposes a µOCT cut-off of 4.0 mm-1 for quantitative grading of UTUC with ureterorenoscopic OCT imaging. The promising diagnostic accuracy calculations justify further studies to validate the proposed cut-off value. Implementation of the software for the µOCT analysis in OCT systems may allow for µOCT assessment at real time during ureterorenoscopy. Lasers Surg. Med. 51:399-406, 2019. © 2019 Wiley Periodicals, Inc.

Pre-Use Ureteroscope Contamination after High Level Disinfection: Reprocessing Effectiveness and the Relation with Cumulative Ureteroscope Use.

PURPOSE: We assessed the frequency of preoperative and persistent microbial contamination of flexible ureteroscopes after reprocessing and the relation of contamination to cumulative ureteroscope use. MATERIALS AND METHODS: We evaluated the effectiveness of high level disinfection with peracetic acid as well as data on ureteroscope use for 20 new flexible ureteroscopes from December 2015 to December 2017 at a single center. In the operating room pre-use and postuse microbial samples of the ureteroscope shaft and working channel were collected to evaluate microbial contamination after reprocessing. Positive cultures were defined as 30 cfu/ml or greater of skin flora, or 10 cfu/ml or greater of uropathogenic microorganisms. A generalized estimating equation model was used to analyze whether cumulative ureteroscope use was associated with positive pre-use cultures. RESULTS: Microbial samples were collected during 389 procedures. Pre-use ureteroscope cultures were positive in 47 of 389 procedures (12.1%), of which uropathogens were found in 9 of 389 (2.3%) and skin flora in 38 of 389 (9.8%). Urinary tract infection symptoms did not develop in any of the patients who underwent surgery with a uropathogen contaminated ureteroscope. In 1 case the pre-use culture contained the same bacteria type as the prior postuse culture. Cumulative ureteroscope use was not associated with a higher probability of positive cultures. CONCLUSIONS: Microbial contamination of reprocessed ureteroscopes was found in an eighth of all procedures. Notably uropathogenic microorganisms were discovered in a small proportion of all procedures. Persistent ureteroscope contamination with uropathogens was only rarely encountered. Cumulative ureteroscope use was not associated with a higher probability of microbial contamination.

Durability of Flexible Ureteroscopes: A Prospective Evaluation of Longevity, the Factors that Affect it, and Damage Mechanisms.

BACKGROUND: Flexible ureteroscopy is an established treatment modality for evaluating and treating abnormalities in the upper urinary tract. Reusable ureteroscope (USC) durability is a significant concern. OBJECTIVE: To evaluate the durability of the latest generation of digital and fiber optic reusable flexible USCs and the factors affecting it. DESIGN, SETTING, PARTICIPANTS: Six new flexible USCs from Olympus and Karl Storz were included. The primary endpoint for each USC was its first repair. Data on patient and treatment characteristics, accessory device use, ureteroscopy time, image quality, USC handling, disinfection cycles, type of damage, and deflection loss were collected prospectively. INTERVENTION: Ureteroscopy. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: USC durability was measured as the total number of uses and ureteroscopy time before repair. USC handling and image quality were scored. After every procedure, maximal ventral and dorsal USC deflection were documented on digital images. RESULTS AND LIMITATIONS: A total of 198 procedures were performed. The median number of procedures was 27 (IQR 16-48; 14h) for the six USCs overall, 27 (IQR 20-56; 14h) for the digital USCs, and 24 (range 10-37; 14h) for the fiber optic USCs. Image quality remained high throughout the study for all six USCs. USC handling and the range of deflection remained good under incremental use. Damage to the distal part of the shaft and shaft coating was the most frequent reason for repair, and was related to intraoperative manual forcing. A limitation of this study is its single-center design. CONCLUSIONS: The durability of the latest reusable flexible USCs in the current study was limited to 27 uses (14h). Damage to the flexible shaft was the most important limitation to the durability of the USCs evaluated. Prevention of intraoperative manual forcing of flexible USCs maximizes their overall durability. PATIENT SUMMARY: Current flexible ureteroscopes proved to be durable. Shaft vulnerability was the most important limiting factor affecting durability.

Surgical teaching in urology: patient safety and educational value of 'LIVE' and 'SEMI-LIVE' surgical demonstrations.

PURPOSE: To evaluate the opinion of urologists and their audience regarding patient safety and educational value of live surgical demonstrations (LSD) and semi-live surgical demonstrations (semi-LSD). METHODS: Following the '2017 Challenges in Endourology' meeting, a survey addressing patient safety and the educational value of LSD and semi-LSD was disseminated online to all participants. Survey outcomes of LSD and semi-LSD were compared. RESULTS: All 279 respondents attended both LSD and semi-LSD. Overall, 53% of said respondents stated that patient safety was always the highest priority for LSD, while 74% noted the same for semi-LSD. The complication risk in LSD was perceived equal by 57% of the respondents when compared to cases of similar difficulty in routine practice, while 38% perceived it as a greater risk. For semi-LSD, the complication risk was perceived equal by 84%, while 5% perceived it to be a greater risk in comparison to general practice. On a scale from 0 (no value) to 10 (highly valuable), the average educational value of LSD and semi-LSD was rated 8.4 and 8.3, respectively. A substantial percentage of the surgeons who perform LSD express concerns that live surgery is not the optimal setting to ensure patient safety. CONCLUSIONS: LSD remains a popular tool for surgical education among urologists and their audience. However, patient safety remains a concern and is perceived less of a concern for semi-LSD. The educational value of LSD and semi-LSD was scored equally high. Therefore, we should consider to advocate the use of semi-LSD more often.

Confocal Laser Endomicroscopy for the Diagnosis of Urothelial Carcinoma in the Bladder and the Upper Urinary Tract: Protocols for Two Prospective Explorative Studies.

BACKGROUND: Visual confirmation of a suspicious lesion in the urinary tract is a major corner stone in diagnosing urothelial carcinoma. However, during cystoscopy (for bladder tumors) and ureterorenoscopy (for tumors of the upper urinary tract) no real-time histopathologic information can be obtained. Confocal laser endomicroscopy (CLE) is an optical imaging technique that allows for in vivo high-resolution imaging and may allow real-time tumor grading of urothelial lesions. OBJECTIVE: The primary objective of both studies is to develop descriptive criteria for in vivo CLE images of urothelial carcinoma (low-grade, high-grade, carcinoma in situ) and normal urothelium by comparing CLE images with corresponding histopathology. METHODS: In these two prospective clinical trials, CLE imaging will be performed of suspicious lesions and normal tissue in the urinary tract during surgery, prior to resection or biopsy. In the bladder study, CLE will be performed in 60 patients using the Cystoflex UHD-R probe. In the upper urinary tract study, CLE will be performed in 25 patients during ureterorenoscopy, who will undergo radical treatment (nephroureterectomy or segmental ureter resection) thereafter. All CLE images will be analyzed frame by frame by three independent, blinded observers. Histopathology and CLE-based diagnosis of the lesions will be evaluated. Both studies comply with the IDEAL stage 2b recommendations. RESULTS: Presently, recruitment of patients is ongoing in both studies. Results and outcomes are expected in 2018. CONCLUSIONS: For development of CLE-based diagnosis of urothelial carcinoma in the bladder and the upper urinary tract, a structured conduct of research is required. This study will provide more insight in tissue-specific CLE criteria for real-time tumor grading of urothelial carcinoma. TRIAL REGISTRATION: Confocal Laser Endomicroscopy: ClinicalTrials.gov NCT03013894; https://clinicaltrials.gov /ct2/show/NCT03013894?term=NCT03013894&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPZ378I); and Dutch Central Committee on Research Involving Human Subjects NL55537.018.15; https://www.toetsingonline.nl /to/ccmo_search.nsf/fABRpop?readform&unids=6B72AE6EB0FC3C2FC125821F001B45C6 (Archived by WebCite at http://www.webcitation.org/6wwJQvqWh). Confocal Laser Endomicroscopy in the upper urinary tract: ClinicalTrials.gov NCT03013920; https://clinicaltrials.gov/ct2/show/NCT03013920? term=NCT03013920&rank=1 (Archived by WebCite at http://www.webcitation.org/6wiPkjyt0); and Dutch Central Committee on Research Involving Human Subjects NL52989.018.16; https://www.toetsingonline.nl/to/ccmo_search.nsf/fABRpop?readform&unids=D27C9C3E5755CFECC12581690016779F (Archived by WebCite at http://www.webcitation.org/6wvy8R44C).

New technologies for upper tract urothelial carcinoma management.

PURPOSE OF REVIEW: Image enhancement techniques and optical diagnostic tools have emerged in the quest to improve diagnostics and treatment in patients with upper urinary tract carcinoma (UTUC). The aim of the present report is to describe their mechanisms of action and to assess the current evidence on applicability and utility in UTUC. RECENT FINDINGS: Image enhancement techniques including narrow band imaging, Image1 S, and photodynamic diagnosis aim at better visualization of malignant urothelium and especially flat tumours or carcinoma in situ which are often difficult to see with white light endoscopy. Conducted studies in the upper tract are scarce but first results show that tumour detection seems to be better for narrow band imaging and photodynamic diagnosis-guided inspection.Optical diagnostic tools as confocal laser endomicroscopy and optical coherence tomography aim at providing real time optical biopsies giving pathologic information. A pilot study of optical coherence tomography proved its feasibility to visualize, grade and stage low and high-grade UTUC. SUMMARY: Better visualization of suspect lesions and optical diagnostic techniques providing real time optical biopsies aim to facilitate in higher diagnostic precision and optimal individualized treatment of our patients with UTUC. As the disease is rare, studies are scarce but indispensable for future implication of these techniques.

Midterm Follow-Up After Biventricular Repair of the Hypoplastic Left Heart Complex.

BACKGROUND: In neonates with hypoplastic left heart complex (HLHC), biventricular repair is considered superior to univentricular repair. The Z-scores of the mitral and the aortic valve annulus are primary factors for the choice of repair. Predictive cutoff values for the feasibility and optimal outcome of biventricular repair are unknown. This study assesses the growth of left side heart structures and the midterm outcome after biventricular repair with an interatrial fenestration in our HLHC population. METHODS: Retrospective study of 19 HLHC patients who underwent biventricular repair in a single tertiary referral center between 2004 and 2013. The cardiac dimensions (mitral and aortic valve annulus, left ventricle inlet length, left ventricular internal diastolic dimension) were measured before and at 6, 12, 24, and 48 months after biventricular repair. RESULTS: The follow-up ranged from 2 to 98 months. There was no early mortality, and the midterm survival rate was 95%. One patient died of a noncardiac- and nonintervention-related cause. Seven patients (37%) required a total of 8 reinterventions because of recurring or residual obstructive lesions. After biventricular repair, the left cardiac structures grew significantly. CONCLUSIONS: Neonatal biventricular repair is successful and safe in HLHC patients, even with preoperative mitral and aortic valve annulus Z-scores of -4.5 and -5.5, respectively. Residual or restenosis required reintervention in 37% of our HLHC population, but was not significantly correlated with the magnitude of the preoperative Z-scores. Within the first 6 months of follow-up, the Z-scores almost normalized.