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© 2019 Wiley Periodicals, Inc. Background: To test the effect of radical cystectomy (RC) with chemotherapy vs only chemotherapy on overall mortality (OM) in metastatic urothelial carcinoma of the urinary bladder (mUCUB). Methods: Within the Surveillance, Epidemiology, and End Results registry (2004–2016), we identified patients with mUCUB. Stratification was made according to treatment: RC with chemotherapy vs only chemotherapy. Kaplan-Meier plots and multivariable Cox regression models were used before and after 1:1 propensity score (PS) matching and inverse probability of treatment weighting (IPTW). Results: Of 2414 patients with mUCUB, 500 (21.0%) vs 1914 (79.0%) were treated with RC with chemotherapy vs only chemotherapy, respectively. In multivariable Cox regression models, RC with chemotherapy was associated with lower OM in the overall cohort (hazard ratio [HR], 0.5; P <.001), after 1:1 PS matching (HR, 0.5; P <.001), after IPTW (HR, 0.5; P <.001) and after accounting for number and location of metastases (HR, 0.5; P <.001). However, higher overall survival after RC with chemotherapy was only observed in patients with one metastatic site (21 vs 16 months; P =.001). Conclusion: In contemporary patients with mUCUB, RC with chemotherapy is associated with lower OM rates, relative to chemotherapy alone, but only in patients with a single metastatic site. These individuals accounted for the vast majority of patients in whom an RC was performed, despite the presence of metastatic disease.

© 2019, Springer-Verlag GmbH Germany, part of Springer Nature. Background: Epidemiologic studies that investigated alcohol consumption in relation to the risk of bladder cancer (BCa) have demonstrated inconsistent results. We conducted a systematic review and meta-analysis of the literature to investigate the association of alcohol including different types of alcoholic beverages consumption with the risk of BCa. Materials and methods: A systematic search of Web of Science, Medline/PubMed and Cochrane library was performed in May 2018. Studies were considered eligible if they assessed the risk of BCa due to alcohol consumption (moderate or heavy dose) and different types of alcoholic beverages (moderate or heavy dose) in multivariable analysis in the general population (all genders, males or females) or compared with a control group of individuals without BCa. Study design: observational cohorts or case–control. Results: Sixteen studies were included in this meta-analysis. Moderate and heavy alcohol consumption did not increase the risk of BCa in the entire population. Sub-group and sensitivity analyses revealed that heavy alcohol consumption increased significantly the risk of BCa in the Japanese population, RR 1.31 (95% CI 1.08–1.58, P < 0.01) in the multivariable analysis, and in males RR of 1.50 (95% CI 1.18–1.92, P < 0.01), with no significant statistical heterogeneity. Moreover, heavy consumption of spirits drinks increased the risk of BCa in males, RR 1.42 (95% CI 1.15–1.75, P < 0.01). Conclusion: In this meta-analysis, moderate and heavy alcohol consumption did not increase the risk of bladder cancer significantly. However, heavy consumption of alcohol might increase the risk of BCa in males and in some specific populations.

© 2019 Context: This overview presents the updated European Association of Urology (EAU) guidelines for non–muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ (CIS). Objective: To provide practical recommendations on the clinical management of NMIBC with a focus on clinical presentation and recommendations. Evidence acquisition: A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines has been performed annually since the last published version in 2017. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Evidence synthesis: Tumours staged as Ta, T1, and/or CIS are grouped under the heading of NMIBC. Diagnosis depends on cystoscopy and histological evaluation of the tissue obtained by transurethral resection (TURB) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TURB is essential for the patient's prognosis and correct diagnosis. Where the initial resection is incomplete, where there is no muscle in the specimen, or where a T1 tumour is detected, a second TURB should be performed within 2–6 wk. The risks of both recurrence and progression may be estimated for individual patients using the European Organisation for Research and Treatment of Cancer (EORTC) scoring system. Stratification of patients into low-, intermediate-, and high-risk groups is pivotal to the recommendation of adjuvant treatment. In patients with tumours presumed to be at a low risk and in those presumed to be at an intermediate risk with a low previous recurrence rate and an expected EORTC recurrence score of <5, one immediate chemotherapy instillation is recommended. Patients with intermediate-risk tumours should receive 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1–3 yr is indicated. In patients at the highest risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is recommended in BCG-unresponsive tumours. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/. Conclusions: These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. Patient summary: The European Association of Urology Non–muscle-invasive Bladder Cancer (NMIBC) Panel has released an updated version of their guidelines, which contains information on classification, risk factors, diagnosis, prognostic factors, and treatment of NMIBC. The recommendations are based on the current literature (until the end of 2018), with emphasis on high-level data from randomised clinical trials and meta-analyses. Stratification of patients into low-, intermediate-, and high-risk groups is essential for deciding appropriate use of adjuvant intravesical chemotherapy or bacillus Calmette-Guérin (BCG) instillations. Surgical removal of the bladder should be considered in case of BCG-unresponsive tumours or in NMIBCs with the highest risk of progression.

© 2019 Elsevier Inc. Objectives: The role of adjuvant radiotherapy (ART) in patients with bladder cancer (BCa) and upper tract urothelial carcinoma (UTUC) is controversial. We systematically evaluated the oncologic efficacy of ART and its associated toxicity in patients treated with surgery and ART for BCa and UTUC. Materials and method: We performed a literature search on December 2018 using MEDLINE, Web of Science, Cochrane databases and Scopus according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Fourteen BCa studies and 14 UTUC studies were included in this systematic review. The data were too scarce and heterogeneous for meta-analytical analysis. Results: The quality and quantity of the data on ART in BCa and UTUC patients are limited. The combination of ART and chemotherapy appears to be beneficial in patients with locally advanced BCa or UTUC. The early and late adverse effects of ART are decreasing reflecting the progress in radiation technology. Conclusions: According to the currently available literature, there is no clear benefit of ART after radical surgery in BCa and UTUC. Future efforts should focus on evaluating multimodal approach using ART with chemotherapy. Until that time comes, ART should be used carefully in patients with BCa and UTUC on a case-by-case basis.

© 2019 Elsevier Inc. Objectives: To assess the role of the urokinase plasminogen activator (uPA) system as a prognostic biomarker in patients with nonmuscle invasive bladder cancer (NMIBC) treated with transurethral resection of the bladder (TURB) with or without adjuvant intravesical therapy. Material and methods: We stained TURB tissue from 827 NMIBC patients with uPA, its receptor (uPAR) and its inhibitor (PAI-1). The status of these markers was categorized as normal vs. overexpressed using the cutoffs of 30% for uPA, 50% for uPAR, and 30% for PAI-1. Multivariable Cox regression analyses were performed to evaluate the prognostic value of these markers. Results: uPA was overexpressed in 37.7% of patients, uPAR in 44.7% and PAI-1 in 44.6%. Overexpression of these markers was associated with high tumor grade. Within a median follow-up was 60 months (interquartile range: 22–109), uPA (hazard ratio [HR]: 1.40; P = 0.006), uPAR (HR: 1.70; P < 0.001), PAI-1 (HR: 1.35; P = 0.014), and the combination of all 3 markers (HR: 3.38; P < 0.001) were associated with recurrence-free survival (RFS); uPA (HR: 1.68; P = 0.035) and the combination of all 3 markers (HR: 8.79; P = 0.005) were associated with progression-free survival (PFS). The addition of the uPA system to a base model improved the discrimination by 1.3% for RFS and 2.1% for PFS. In subgroup analyses, uPA (HR: 2.19; P = 0.018) was associated with PFS in T1G3 patients and its addition to a base model improved the discrimination by 2.5%. uPA (HR: 1.44; P = 0.019), uPAR (HR: 1.54; P = 0.006), PAI-1 (HR: 1.46; P = 0.013) and the combination of all 3 markers (HR: 3.48; P < 0.001) were associated with RFS in TaG1-2 patients and their addition to a base model improved the discrimination by 2.1%. Conclusion: uPA, uPAR, and PAI-1 are overexpressed in one-third to half of patients with NMIBC. Their overexpression is an independent prognosticator of RFS and PFS which improved the predictive accuracy of current clinicopathological characteristics. Biomarkers that capture the biological and clinical behavior of individual tumors may help personalize clinical decision-making in patients with NMIBC.

© 2019, Pediatria Ltd. All rights reserved. Pyelonephritis treatment in children with neurogenic bladder (NB) has a number of peculiarities, which include incomplete bladder emptying after self-urination and causing difficulties in determining treatment tactics for primary care pediatricians. Residual urine is a risk factor for development and relapse of chronic pyelonephritis, and urinary incontinence is also a medical and social problem. The article presents an example of observing an 8-year-old girl after 2 years of ineffective treatment for chronic pyelonephritis with mistakes in primary diagnosis. It provides the analysis of 3 months treatment and examination of the child with NB, including monitoring of urination functional productivity. The scheme of combined correction of inflammatory process and urinary tract dysfunction is presented. A systematic step-by-step approach to diagnosis and treatment of recurrent pyelonephritis in children with NB allows to increase therapy efficacy and improve patient's quality of life. The presented clinical case differs because bladder dysfunction manifested itself at the age of 8 years with an increase of bladder residual volume. Peculiarity of pathogenetic mechanisms of this pathology development in the described observation is a combination of delayed mature urination formation and manifestation of acute pyelonephritis, which required a non-standard approach to diagnosis and treatment.

© Yu.I. OSMANOV1, Zh.A. GAIBOV, E.A. KOGAN, S.G. RADENSKA-LOPOVOK, Kh.Z. TURSUNOV. The molecular subtypes of urothelial carcinoma in each classification scheme have characteristic immunohistochemical features. At the same time, the results of conducted studies often demonstrate a discrepancy between the genomic profile of urothelial carcinoma and its immunophenotype, which complicates the immunohistochemical verification of the molecular subtypes of these tumors. Objective - to compare the morphological and immunophenotypic characteristics of the molecular subtypes of urothelial carcinoma. Material and methods. Surgical specimens from 196 patients diagnosed with urothelial carcinoma of the renal pelvis and bladder were investigated. Paraffin-embedded sections were immunohistochemically examined using the standard protocol. Antibodies against CK5/6, CK17, Rb1 (Dako), CK14, CK18, CK20, Cyclin D1, Cyclin E1, Cyclin A, Cyclin B, Chromogranin, E-Cadherin, P-Cadherin, p16, Uroplakin II, TUBB2B, Vimentin, ZEB-2 («Novocastra»), CD44, GATA-3, and Uroplakin III («Cell Marque») were used. Results. Out of 68 (35%) superficial papillary urothelial carcinomas, 24 (12%) tumors constituted Molecular Class I and 12 (6%) and 32 (16%) ones did Molecular Classes II and III, respectively. Of the 128 (65%) muscle-invasive urothelial carcinomas, 57 (29%) tumors were referred to as the luminal-papillary molecular subtype, and 24 (12%) and 14 (7%) were as the luminal-infiltrated and luminal molecular subtypes, respectively. The basal squamous molecular subtype was verified in 31 (16%) neoplasms and the neuronal phenotype was detected in 2 (1%) cases. Conclusion. Most pT1 tissues correspond to Molecular Class II. In the muscle-invasive urothelial carcinoma group, the neoplasms with a luminal phenotype predominate over the tumors with basal and neuronal phenotypes.

© 2019 Journal of Pediatric Urology Company Introduction: Urinary incontinence is one of the most commonly treated disorders in children at school age. Recently, a new, wearable bladder sensor became available, the SENS-U Bladder Sensor. The SENS-U is a small, wireless ultrasonic sensor, which continuously monitors the bladder filling and provides a personalized notification when it is time to go to the toilet. In this study, the aim was to examine the performance of the SENS-U as a full-bladder–based notification system in children during daily life activities. Patients and methods: In this pilot study, children (6–16 years) who were admitted for an inpatient bladder training were included. Parallel to one training day, the child would wear the SENS-U to estimate the bladder filling and it informed the child when the bladder was almost full. When the child received a full-bladder notification, the child was taught to inform the urotherapist/researcher, in order to determine the level of response. Results: Fifteen patients (boys/girls: 7/8; mean age: 11.5 ± 1.7 years) were included. Based on a personalized volume-based threshold, the SENS-U notified these children of a full bladder with a median notification rate of 92.9%. In the remaining cases, children voided before the threshold was reached (e.g. defecation). Children responded positively to the notification of the SENS-U, resulting in a median level of response equal to 100%. Conclusion: The SENS-U was able to monitor the natural bladder filling accurately during activities of daily living and provided a personalized notification to the children when it was almost time to go to the toilet. Future research will focus on investigating the efficacy of the SENS-U compared to daily clinical practices.[Figure presented]

© 2018 IEEE. Authors describe new effect of laser radiation in endoscopic urological surgery (BPH enucleation, en-bloc removal of bladder cancer, stricture endotomy): two-phase jet - a result of superintensive boiling in the area of laser radiation absorption and consisting of steam-gas microbubbles and hot water. In this case, the area of thermal influence appears significantly more, than thickness of a layer in which laser radiation is absorbed. Cutting soft tissue, the jet coagulates section walls due to heat generated at steam condensation. The same jet is formed behind the macrobubble, which is formed in liquid (Moses effect), because of boiling.

© Microscopy Society of America 2018. Radiation therapy, widely used in the treatment of a variety of malignancies in the pelvic area, is associated with inevitable damage to the surrounding healthy tissues. We have applied atomic force microscopy (AFM) to track the early damaging effects of ionizing radiation on the collagen structures in the experimental animals' bladder and rectum. The first signs of the low-dose radiation (2 Gy) effect were detected by AFM as early as 1 week postirradiation. The observed changes were consistent with initial radiation destruction of the protein matrix. The alterations in the collagen fibers' packing 1 month postirradiation were indicative of the onset of fibrotic processes. The destructive effect of higher radiation doses was probed 1 day posttreatment. The severity of the radiation damage was proportional to the dose, from relatively minor changes in the collagen packing at 8 Gy to the growing collagen matrix destruction at higher doses and complete three-dimensional collagen network restructuring towards fibrotic-type architecture at the dose of 22 Gy. The AFM study appeared superior to the optical microscopy-based studies in its sensitivity to early radiation damage of tissues, providing valuable additional information on the onset and development of the collagen matrix destruction and remodeling.

© ABC-press Publishing House. All rights reserved. Objectives to enhance the morphological diagnostic complex in order to predict postoperative outcomes in a more accurate way and to optimize patients with non-muscular invasive bladder cancer treatment. Materials and methods. The study included 34 patients from 25 to 71 years old underwent laser en-block resection, the most of them were males - 28. In 9 cases multiple carcinomas (2 or more) were found. Huge tumors (2 cm or more in one dimension) were resected in 6 patients. Results. The major part of tumors removed (n = 22) histologically appeared to be papillary urothelial carcinomas with low grade of malignancy and PUNLMP; in 6 cases G2 was verified, one tumor with high malignancy potention - G3. In 3 patients intramuscular invasion was found (invasive carcinoma T2) excluding them from the study. Discussion. Laser en-block resection of non-muscle-invasive bladder cancer appears to be the most optimal approach in operative treatment that provides representative histological material. For correct morphological estimate we recommend either to expand the resection zone to 1 cm which allows to remove circular resection margin or to take extra pinch biopsy from tumor crater (vertical margin). In 3 patients from our study positive circular margin was revealed histologically whereas foci of perineural and perivascular invasion were found in one case. A new subgrading of stage T1 depending on intramuscular invasion depth was suggested whereas the main criteria is the muscularis mucosae involvement. Conclusion. Morphological estimate of circular resection margin provides an ability to predict postoperative outcomes and correct the treatment in one or another way. Subgrading for T1-stage tumors is recommended for following correct postoperative prognosis and possibility of tumor recurrence.

© 2018 Stolichnaya Izdatelskaya Kompaniya. Hypertensive heart disease with biventricular cardiac failure is not common in clinical practice. This diagnosis requires an extensive diagnostic search. We present the clinical case of the male patient of 38 aged. He was admitted to the clinic with heart failure 3-4 NYHA class. EchoCG revealed symmetric hypertrophy of the left ventricle up to 18 mm without its dilatation, a decrease in ejection fraction up to 42%, restrictive hemodynamics, overload of the right chambers, severe pulmonary hypertension (60 mm Hg). The clinical status included persistent arterial hypertension (180-220 and 120-150 mm Hg), effusion in both pleural cavities and pericardium, ascites, renal failure. During examination (multispiral computed tomography, magnetic resonance imaging, scintigraphy with 131I-MIBG), bladder paraganglioma was diagnosed (normatenafrin 1468 μg/day). The resection of the tumor was performed, according to immunohistochemical research - neuroendocrine carcinoma, G1. After 3 months a partial regression of hypertension and cardiac failure was observed with the preservation of a high level of creatinine. The criteria and differential diagnosis of the hypertensive heart disease and the syndrome of primary myocardial hypertrophy, diagnostics of the urinary bladder paraganglioma, complex mechanisms of myocardial damage within the pheochromocytoma and its prognosis are discussed..

© 2018 ABC-press Publishing House. All rights reserved. Background. The high recurrence rate after conventional transurethral resection (cTUR) for bladder cancer (BC) requires search for more effective methods of surgical treatment. Objective: to evaluate the feasibility, safety, and efficacy of cTUR versus thulium laser en bloc resection of bladder tumors using new fiber laser "Urolaz". Materials and methods. 129 patients, who underwent surgical treatment for BC between 2015-2017 in urological department of I.M. Sechenov First Moscow State Medical University were included in the study. The cTUR were performed for 58 patients, 71 patients underwent thulium laser en bloc resection of bladder tumors. Results. The presence of detrusor muscle in specimen was 58.62 % in cTUR group and 91.55 % in thulium laser en bloc resection group respectively. Obturator nerve reflex, bladder perforation, and bleeding in thulium laser en bloc resection group were absent, therefore immediate instillation of chemotherapy was made in all these cases. Recurrence rate after 12 and 18 months after surgery in the group of en bloc resection was statistically lower compared to the cTUR group. Conclusion. The results, obtained in our study shows that thulium en bloc resection using thulium fiber laser "Urolaz" is feasible, effective and safe procedure for patients with BC. Thulium en bloc resection has a number of advantages over the cTUR: Absence of obturator nerve reflex, high quality of specimen for pathological examination (presence of detrusor muscle in specimen was 91.55 %) and low recurrence rate.

© 2018, Media Sphera Publishing Group. All rights reserved. Urothelial carcinoma is one of the most frequently diagnosed malignant tumors of the bladder and upper urinary tract, which ranks seventh in the pattern of cancer. Urothelial carcinoma of the renal pelvis is less common; but has a more aggressive clinical course and a worse prognosis than that of the bladder. This is due to the clinical and morphological features of this form of cancer, which, unlike bladder cancer, have not been studied enough. Objective — to comparatively analyze the morphological and immunophenotypic parameters of urothelial carcinomas of the renal pelvis and bladder. Subject and methods. Surgical specimens from 196 patients diagnosed with urothelial carcinoma of the renal pelvis and bladder were investigated. Paraffin sections were immunohistochemically examined using the standard protocol. Antibodies against CK5/6, CD138, CDX2 (≪Dako≫), CK7, CK14, CK20, CEA, CD10, CD117, EMA, E-Cadherin, HMWCK, p63, Uroplakin III, Vimentin (≪Novocastra≫), CD44, GATA-3, MUC1, MUC2, and MUC-5AC (≪Cell Marque≫) were used. Results. Most tumors (n=147 (75%)) were invasive. Of them, 65 (33%) cases had a histological structure of conventional urothelial cancer; and 3 (1.5%) had paradoxical differentiation. Divergent tumor zones were verified in 66 (34%) neoplasms; 4 (2%) cases showed an inverted growth pattern. Pseudosarcomatous stroma reaction in the invasion zones was verified in 9 (5%) cases. The tumor stage corresponded to pT2—pT4 in 128 (65%) tumors. Conclusion. Urothelial carcinomas of the renal pelvis and bladder show a broad spectrum of histological variants. The findings support that, unlike urothelial carcinomas of the bladder, the majority of primary urothelial carcinomas of the renal pelvis are high-grade and highly invasive.

© 2018 ABC-press Publishing House. All rights reserved. Bladder cancer (BC) is represented by non-muscle-invasive forms at the stage Ta, T1, CIS (NMBC) in 75 % of cases. The gold standard of treatment of NMBC patients is transurethral resection, but its implementation does not always allow the patient to be relieved of the recurrence of the disease. In this regard, patients with a low risk of progression after transurethral resection are administered by intravesical chemotherapy, with high risk (T1G2/3) – using instillation with BCG (Bacillus Calmette–Guerin) vaccine. Searching of NMBC markers for laboratory diagnostics, which would help to determine sensitivity or resistance to the planned type of adjuvant therapy remains an actual problem. The data published mainly in the last 5–7 years about genetic predictors of the response to adjuvant chemotherapy and, to a greater extent, immunotherapy with BCG vaccine, are reviewed in this work. Allele combinations in the genes involved in immune response, xenobiotic biotransformation and other loci that are associated with the response to the adjuvant NMBC therapy in meta-analyzes are systematized. Also, expression profiles of mRNA, microRNA and proteins, as well as panels of methylated loci associated with the effectiveness of chemotherapy and immunotherapy of NMBC are considered. It was demonstrated that the somatic mutations sequencing in the primary tumor and the total mutational load using high-throughput sequencing technologies (NGS) identified a number of potential prognostic markers. Perhaps, the mutational load will be more widely used as a highly informative predictor of immunotherapeutic effect in BC: BCG therapy of NMBC and BC targeted therapy using the inhibitors of immune control points, after the standardization of the analysis. This review is intended to oncologists, geneticists, molecular biologists, urologists, pathologists and other specialists working in the field of molecular genetics in oncological urology.

© 2018 Russian Photodynamic Association. All rights reserved. A comparative experimental study of the specific activity of drugs based on 5-aminolevulinic acid (5-ALA) and its hexyl ester (5-ALA HE) was carried out. Their ability to induce the synthesis of photoactive protoporphyrin IX in the healthy tissues of the rabbit bladder when instilling the drug solutions at various concentrations has been estimated. It was shown that 5-ALA HE results in the induction and accumulation of PPIX in the rabbit bladder epithelium at much lower concentrations than 5-ALA. Thus, a significant increase in the fluorescence intensity in comparison with the control was achieved by instillation of 5-ALA HE solution in the rabbit' bladder at a concentration of only 0.0001% (fluorescence intensity 2.20±0.60 a.u.), and for 5-ALA - only when using a solution at a concentration of 0.3% (fluorescence intensity 2.60±1.02 a.u.).

© 2018 Elsevier Inc. Objectives One of the most reliable methods for diagnosing bladder cancer is cystoscopy. Depending on the findings, this may be followed by a referral to a more experienced urologist or a biopsy and histological analysis of suspicious lesion. In this work, we explore whether computer-assisted triage of cystoscopy findings can identify low-risk lesions and reduce the number of referrals or biopsies, associated complications, and costs, although reducing subjectivity of the procedure and indicating when the risk of a lesion being malignant is minimal. Materials and methods Cystoscopy images taken during routine clinical patient evaluation and supported by biopsy were interpreted by an expert clinician. They were further subjected to an automated image analysis developed to best capture cancer characteristics. The images were transformed and divided into segments, using a specialised color segmentation system. After the selection of a set of highly informative features, the segments were separated into 4 classes: healthy, veins, inflammation, and cancerous. The images were then classified as healthy and diseased, using a linear discriminant, the naïve Bayes, and the quadratic linear classifiers. Performance of the classifiers was measured by using receiver operation characteristic curves. Results The classification system developed here, with the quadratic classifier, yielded 50% false-positive rate and zero false-negative rate, which means, that no malignant lesions would be missed by this classifier. Conclusions Based on criteria used for assessment of cystoscopy images by medical specialists and features that human visual system is less sensitive to, we developed a computer program that carries out automated analysis of cystoscopy images. Our program could be used as a triage to identify patients who do not require referral or further testing.