Cone Beam Computed Tomography-Assisted Percutaneous Nephrolithotomy in a Hybrid Operating Room: Optimization of Patient Selection.

Background: Cone beam computed tomography (CBCT) enables intraoperative cross-sectional and three-dimensional imaging of the urinary tract. CBCT in a hybrid operating room can be used for intraoperative detection of residual stones and potential additional stone extraction at the end of percutaneous nephrolithotomy (PCNL). This study describes our initial experience with intraoperative CBCT during PCNL and analyzes its role in potentially improving its outcomes. Methods: We conducted a single-center retrospective cohort study at a tertiary referral hospital between 2018 and 2021. The study aimed to evaluate the outcome of patients who underwent intraoperative noncontrast CBCT scan during PCNL. The CBCT scan was performed when the urologist determined the kidney to be endoscopically stone-free. In case any residual fragments were imaged, an additional effort was made to extract them. Patients were divided into three groups based on treatment outcome: stone-free upon CBCT, not stone-free with additional stone extraction after CBCT, and not stone-free without additional stone extraction. Procedure and patient characteristics were recorded to identify factors associated with additional stone extraction during CBCT-assisted PCNL. Results: A total of 102 procedures were included in this study. Intraoperative CBCT scans showed residual calcifications in 58 (57%) cases. In 39 cases, which is 38% of the total population and 61% of the cases with residual calcifications, one or more residual fragments imaged on the intraoperative CBCT-scan were extracted additionally within the same procedure. A higher Guy's Stone Score was associated with a higher likelihood of additionally extracting stones as a result of the CBCT. Conclusions: CBCT-assisted PCNL in a hybrid operating room can lead to additional stone extraction in the same procedure in 37% of all cases and in over 60% of the cases in which residual fragments are imaged. The value of CBCT-assisted PCNL appears to increase in the case of more complex stone surgery cases.

The significance of clinically insignificant residual fragments after percutaneous nephrolithotomy: an analysis into the relevance of complete stone clearance.

PURPOSE: After treatment for kidney stones, residual fragments with a diameter of ≤ 4 mm are traditionally referred to as 'clinically insignificant residual fragments'. We hypothesize that patients with these fragments are at an increased risk for stone-related morbidity, such as complaints, hydronephrosis, and stone regrowth, when compared to stone-free patients. This study aimed to investigate the relevance of complete stone clearance in surgical treatment of urolithiasis. METHODS: We conducted a single-center retrospective cohort study. Patients who underwent percutaneous nephrolithotomy between 2015 and 2020 were included if a CT-scan was available within 6 months after the procedure, and the follow-up duration was at least 1 year. The stone-free status at the end of the first stone episode during the study period was categorized as fully stone-free, not stone-free with small residual fragments (≤ 4 mm) and not stone-free with large residual fragments (> 4 mm). Follow-up data were collected, including stone-related events and re-intervention rates. RESULTS: A total of 103 subjects were included with a median follow-up of 21.4 months. Stone-related events occurred in 10 (29.4%) of the fully stone-free subjects, 20 (58.8%) of the subjects with small residual fragments and 25 (71.4%) of the subjects with large residual fragments. The stone-related event-free survival per subgroup resulted in a significantly different survival distribution in a log rank test (p = 0.008). CONCLUSION: A complete stone-free status seems to be of fundamental importance for decreasing stone-related morbidity. Further developments and research should focus on optimizing the full clearance of stone material during PCNL.

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.

Ex-vivo study in nephroureterectomy specimens defining the role of 3-D upper urinary tract visualization using optical coherence tomography and endoluminal ultrasound.

Minimal invasive endoscopic treatment for upper urinary tract urothelial carcinoma (UUT-UC) is advocated in patients with low-risk disease and limited tumor volume. Diagnostic ureterorenoscopy combined with biopsy is the diagnostic standard. This study aims to evaluate two alternative diagnostic techniques for UUT-UC: optical coherence tomography (OCT) and endoluminal ultrasound (ELUS). Following nephroureterectomy, OCT, ELUS, and computed tomography (CT) were performed of the complete nephroureterectomy specimen. Visualization software (AMIRA®) was used for reconstruction and coregistration of CT, OCT, and ELUS. Finally, CT was used to obtain exact probe localization. Coregistered OCT and ELUS datasets were compared with histology. Coregistration with three-dimensional CT makes exact data matching possible in this ex-vivo setting to compare histology with OCT and ELUS. In OCT images of normal-appearing renal pelvis and ureter, urothelium, lamina propria, and muscularis were visible. With ELUS, all anatomical layers of the ureter could be distinguished, besides the urothelial layer. ELUS identified suspect lesions, although exact staging and differentiation between noninvasive and invasive lesions were not possible. OCT provides high-resolution imaging of normal ureter and ureter lesions. ELUS, however, is of limited value as it cannot differentiate between noninvasive and invasive tumors.

Fluorescence in situ hybridization as prognostic predictor of tumor recurrence during treatment with Bacillus Calmette-Guérin therapy for intermediate- and high-risk non-muscle-invasive bladder cancer.

A significant number of patients with intermediate- or high-risk bladder cancer treated with intravesical Bacillus Calmette-Guérin (BCG) immunotherapy are non-responders to this treatment. Since we cannot predict in which patients BCG therapy will fail, markers for responders are needed. UroVysion® is a multitarget fluorescence in situ hybridization (FISH) test for bladder cancer detection. The aim of this study was to evaluate whether FISH can be used to early identify recurrence during treatment with BCG. In a multicenter, prospective study, three bladder washouts at different time points during treatment (t 0 = week 0, pre-BCG, t 1 = 6 weeks following TURB, t 2 = 3 months following TURB) were collected for FISH from patients with bladder cancer treated with BCG between 2008 and 2013. Data on bladder cancer recurrence and duration of BCG maintenance therapy were recorded. Thirty-six (31.6%) out of 114 patients developed a recurrence after a median of 6 months (range 2-32). No significant association was found between a positive FISH test at t 0 or t 1 and risk of recurrence (p = 0.79 and p = 0.29). A positive t 2 FISH test was associated with a higher risk of recurrence (p = 0.001). Patients with a positive FISH test 3 months following TURB had a 4.0-4.6 times greater risk of developing a recurrence compared to patients with a negative FISH. Patients with a positive FISH test 3 months following TURB and induction BCG therapy have a higher risk of developing tumor recurrence. FISH can therefore be a useful additional tool for physicians when determining a treatment strategy.

Current position of diagnostics and surgical treatment for upper tract urothelial carcinoma.

BACKGROUND: The applicability of urinary biomarkers and optical diagnostics in upper urinary tract carcinoma (UUT-UC) are increasingly debated. To receive insight in the opinion of the urological community involved in this field, a survey was sent out to identify the most promising techniques and understand the need for new diagnostics. Primary objective of this study was to provide an overview of current diagnostics in upper urinary tract urothelial carcinoma. Secondary objectives of this study was to assess the need for additional diagnostic techniques in the current diagnostic work-up for UUT-UC and to assess knowledge of novel techniques. METHODS: An electronic survey was distributed to all participants of the upper urinary tract tumor registration study by the Clinical Research Office of the Endourological Society. Additionally, based on publications, experts in the field were contacted. Analysis was performed on the results overviewed by the survey monkey website. RESULTS: In total 81 of the 112 invited individuals responded resulting in a response rate of 72.3%. Most urologists involved in the treatment of upper urinary tract tumors follow the guidelines in their diagnostic work-up of patients suspected for UUT-UC. 61.4% of all responders consider current available diagnostic methods insufficient to select patient candidates for conservative renal sparing surgery. According to the responders, digital endoscopes for retrograde intrarenal surgery (RIRS) including narrow-band imaging (NBI) are best known and most likely to be beneficial compared to all evaluated diagnostic tools currently available. CONCLUSIONS: Urologists consider current diagnostic techniques for upper urinary tract tumors insufficient for optimal patient selection for conservative renal sparing surgery. Among the new techniques, NBI and digital RIRS are best known and considered to be beneficial in the diagnostic work-up.

Prostate cancer diagnosis: the feasibility of needle-based optical coherence tomography.

The objective of this study is to demonstrate the feasibility of needle-based optical coherence tomography (OCT) and functional analysis of OCT data along the full pullback trajectory of the OCT measurement in the prostate, correlated with pathology. OCT images were recorded using a commercially available C7-XR™ OCT Intravascular Imaging System interfaced to a C7 Dragonfly™ intravascular 0.9-mm-diameter imaging probe. A computer program was constructed for automated image attenuation analysis. First, calibration of the OCT system for both the point spread function and the system roll-off was achieved by measurement of the OCT signal attenuation from an extremely weakly scattering medium (Intralipid® 0.0005 volume%). Second, the data were arranged in 31 radial wedges (pie slices) per circular segments consisting of 16 A-scans per wedge and 5 axial B-scans, resulting in an average A-scan per wedge. Third, the decay of the OCT signal is analyzed over 50 pixels ([Formula: see text]) in depth, starting from the first found maximum data point. Fourth, for visualization, the data were grouped with a corresponding color representing a specific [Formula: see text] range according to their attenuation coefficient. Finally, the analyses were compared to histopathology. To ensure that each single use sterile imaging probe is comparable to the measurements of the other imaging probes, the probe-to-probe variations were analyzed by measuring attenuation coefficients of 0.03, 6.5, 11.4, 17, and 22.7 volume% Intralipid®. Experiments were repeated five times per probe for four probes. Inter- and intraprobe variation in the measured attenuation of Intralipid samples with scattering properties similar to that of the prostate was [Formula: see text] of the mean values. Mean attenuation coefficients in the prostate were [Formula: see text] for parts of the tissue that were classified as benign (SD: [Formula: see text], minimum: [Formula: see text], maximum: [Formula: see text]) and [Formula: see text] for parts of tissue that were classified as malignant (SD: [Formula: see text], minimum: [Formula: see text], maximum: [Formula: see text]). In benign areas, the tissue looked homogeneous, whereas in malignant areas, small glandular structures were seen. However, not all areas in which a high attenuation coefficient became apparent corresponded to areas of prostate cancer. This paper describes the first in-tissue needle-based OCT imaging and three-dimensional optical attenuation analysis of prostate tissue that indicates a correlation with pathology. Fully automated attenuation coefficient analysis was performed at 1300 nm over the full pullback. Correlation with pathology was achieved by coregistration of three-dimensional (3-D) OCT attenuation maps with 3-D pathology of the prostate. This may contribute to the current challenge of prostate imaging and the rising interest in focal therapy for reduction of side effects occurring with current therapies.

Optical diagnostics for upper urinary tract urothelial cancer: technology, thresholds, and clinical applications.

PURPOSE: Developments in optical diagnostics have potential for less invasive diagnosis of upper urinary tract urothelial carcinoma (UUT-UC). This systematic review provides an overview of technology, applications, and limitations of recently developed optical diagnostics in the upper urinary tract and outlines their potential for future clinical applications. In addition, current evidence was evaluated. LITERATURE SEARCH: A PubMed literature search was performed and articles on narrow band imaging (NBI), photodynamic diagnosis (PDD), Storz professional imaging enhancement system (SPIES), optical coherence tomography (OCT), and confocal laser endomicroscopy (CLE) regarding UUT-UC were reviewed for data extraction. Study quality was reviewed according to Quality Assessment of Diagnostic Accuracy Studies and Innovation, Development, Exploration, Assessment, and Long-term follow-up (IDEAL) standards. RESULTS: Four articles available for quality assessment, demonstrated high level of evidence, but low level of IDEAL stage. NBI and SPIES enhance contrast of mucosal surface and vascular structures, improving tumor detection rate. A first in vivo study showed promising results. PDD uses fluorescence to improve tumor detection rate. However, due to the acute angle of the ureterorenoscopes there is an increased risk of false positives. OCT produces cross-sectional high-resolution images, providing information on tumor grade and stage. A pilot study showed promising diagnostic accuracy. CLE allows ultrahigh-resolution microscopy of tissue resulting in images of the cellular structure. CLE cannot be applied in vivo in the upper urinary tract yet, due to technical limitations. CONCLUSIONS: NBI, SPIES, and PDD aim at improving visualization of UUT-UC through contrast enhancement. OCT and CLE aim at providing real-time predictions of histopathological diagnosis. For all techniques, more research has to be conducted before these techniques can be implemented in the routine management of UUT-UC. All techniques might be of value in specific clinical scenarios and allow for integration, for example, OCT with NBI, and could therefore improve tumor detection and staging and help in selecting the optimal treatment for the individual patient.

[Urothelial carcinoma in the upper urinary tract: developments in diagnostics, treatment and follow-up]. / Urotheelcelcarcinoom in de hoge urinewegen: ontwikkelingen in de diagnostiek, behandeling en follow-up.

Ninety-five percent of all urothelial carcinomas are located in the bladder and 5% in the upper urinary tract. Therefore, upper urinary tract urothelial carcinoma is relatively rare, with an incidence of 2.1-2.4 per 100,000 persons per year. Diagnosis is based on imaging, endoscopy, urine cytology and histology. Histopathological diagnosis of upper urinary tract tumours is essential for choice of therapy and follow-up, as both tumour grade and stage are important prognostic factors. Radical nephroureterectomy is the standard treatment, but has a direct effect on kidney function. For this reason, an increasing number of patients with low-risk tumours undergo kidney-sparing surgery to maintain kidney function. After kidney-sparing surgery intensive follow-up of the ipsilateral upper urinary tract is mandatory because of a five-year recurrence-free survival rate of 17-63%, depending on tumour grade. Current diagnostics all have their limitations. Nowadays, research focuses on improving diagnosis in order to be able to offer better individual treatment.

Volumetric in vivo visualization of upper urinary tract tumors using optical coherence tomography: a pilot study.

PURPOSE: Knowledge of tumor stage and grade is paramount for treatment decision making in cases of upper urinary tract urothelial carcinoma but this condition cannot be accurately assessed by current techniques. Optical coherence tomography can hypothetically provide the urologist with real-time intraoperative information on tumor grade and stage. In this pilot study we report what are to our knowledge the first results of optical coherence tomography for grading and staging upper urinary tract urothelial carcinoma. MATERIALS AND METHODS: Eight consecutive patients underwent ureterorenoscopy for suspicion or followup of upper urinary tract urothelial carcinoma. Optical coherence tomography data sets were intraoperatively obtained from the ureter and renal pelvis. All patients eventually underwent nephroureterectomy. Optical coherence tomography staging was done by visual inspection of lesions found on optical coherence tomography images. Optical coherence tomography grading was done by quantifying optical coherence tomography signal attenuation in mm(-1) on lesions and comparing results with the histopathological diagnosis. The Wilcoxon rank sum test was used for statistical analysis. RESULTS: For 7 in vivo optical coherence tomography diagnoses staging was in accordance with histology. In patient 8 tumor thickness transcended optical coherence tomography imaging depth range and, therefore, invasiveness findings were inconclusive. For grading the median attenuation coefficient for grade 2 and 3 lesions was 1.97 (IQR 1.57-2.30) and 3.53 mm(-1) (IQR 2.74-3.94), respectively (p<0.001). Healthy urothelium was too thin to reliably determine the attenuation coefficient. CONCLUSIONS: Optical coherence tomography is a promising, minimally invasive tool for real-time intraoperative optical diagnosis of tumors in the upper urinary tract. Our results warrant future research in a larger sample size to determine the accuracy of grading and staging by optical coherence tomography, and its possible implementation in the diagnostic algorithm for upper urinary tract urothelial carcinoma.

Is photodynamic diagnosis ready for introduction in urological clinical practice?

The aim of this review is to provide an up-to-date review of the available literature on photodynamic diagnosis (PDD) for nonmuscle-invasive bladder cancer, to present the technique in a comprehensive approach and, finally, to discuss the relevance of PDD in clinical practice in terms of indications, outcomes and its development trend. A literature search was conducted up to July 2012, using MEDLINE and EMBASE via Ovid databases to identify published studies on PDD for nonmuscle-invasive bladder cancer. Only English-language and human-based full manuscripts that reported on case series and studies with >40 participants, concerning clinical evidence of the technique, its efficacy and safety data were included. Evidence showed that PDD significantly improves detection of bladder cancer compared with standard white-light cystoscopy, having proven to be more effective for the diagnosis of carcinoma in situ. This condition seems to facilitate more complete resections, resulting in a lower residual tumor rate, which, in turn consecutively leads to higher recurrence-free survival rates. The literature search demonstrated that for mid- and long-term follow-up, PDD showed acceptable outcomes in terms of tumor detection, as well as lower residual tumor and lower recurrence rates compared with white-light cystoscopy. It has proven to be safe and well tolerated; the major limitations of PDD are its low specificity and elevated costs.

Urothelial carcinoma in both adnexa following perforation during transurethral resection of a non-muscle-invasive bladder tumor: a case report and literature review.

In this article case report of urothelial carcinoma implantation in both adnexa is reported, following a perforation of the bladder wall during a transurethral resection of a bladder tumor. The 81-year-old female patient had an extensive history of multiple recurrent non-muscle-invasive urothelial carcinoma of the bladder. Intraperitoneal perforation was detected and managed conservatively. Fifteen months after the procedure, the patient presented at the gynecology department with a mass in the left adnex, which was suspicious for malignancy, for which she subsequently underwent hysterectomy in combination with bilateral resection of the adnexa. Pathology showed papillary urothelial carcinoma in both ovaries. A literature search was performed to present an up-to-date review of the available data on bladder perforations during transurethral resection of the bladder and tumor implantation, its management and oncological outcomes.

Cardiac autonomic neuropathy in patients with diabetes and no symptoms of coronary artery disease: comparison of 123I-metaiodobenzylguanidine myocardial scintigraphy and heart rate variability.

PURPOSE: The purpose of this study was to evaluate the prevalence of cardiac autonomic neuropathy (CAN) in a cohort of patients with type 2 diabetes, truly asymptomatic for coronary artery disease (CAD), using heart rate variability (HRV) and (123)I-metaiodobenzylguanidine ((123)I-mIBG) myocardial scintigraphy. METHODS: The study group comprised 88 patients with type 2 diabetes prospectively recruited from an outpatient diabetes clinic. In all patients myocardial perfusion scintigraphy, CAN by HRV and (123)I-mIBG myocardial scintigraphy were performed. Two or more abnormal tests were defined as CAN-positive (ECG-based CAN) and one or fewer as CAN-negative. CAN assessed by (123)I-mIBG scintigraphy was defined as abnormal if the heart-to-mediastinum ratio was <1.8, the washout rate was >25%, or the total defect score was >13. RESULTS: The prevalence of CAN in patients asymptomatic for CAD with type 2 diabetes and normal myocardial perfusion assessed by HRV and (123)I-mIBG scintigraphy was respectively, 27% and 58%. Furthermore, in almost half of patients with normal HRV, (123)I-mIBG scintigraphy showed CAN. CONCLUSION: The current study revealed a high prevalence of CAN in patients with type 2 diabetes. Secondly, disagreement between HRV and (123)I-mIBG scintigraphy for the assessment of CAN was observed.