Noninvasive Tests for Bladder Cancer Detection and Surveillance: A Systematic Review of Commercially Available Assays.

BACKGROUND: An important reason for the high health care costs associated with bladder cancer is the need for frequent cystoscopy for detection and surveillance of this disease. Cytologic analysis of voided urine specimens can assist, but is too inaccurate to replace cystoscopy. In an effort to create reliable, objective, noninvasive mechanisms for detecting bladder cancer, a number of urine-based molecular tests have been developed with the ultimate goal of reducing the frequency of cystoscopy. OBJECTIVE: To summarize the performance of urine-based biomarker tests, currently commercially available in the US, as part of the initial workup for hematuria and for bladder cancer surveillance. METHODS: In accordance with PRISMA guidelines we performed a systematic review of the literature on the performance of NMP22, BTA, UroVysion, ImmunoCyt/uCyt, CxBladder, and Bladder EpiCheck. Median sensitivity, specificity, negative (NPV) and positive predictive values (PPV) were calculated for each test based on the included studies. RESULTS: Twenty-eight studies met inclusion criteria for the performance of five urine-based biomarker tests in the setting hematuria workup. Median sensitivity ranged from 65.7% -100% and specificity ranged from 62.5% -93.8%. Median NPV ranged from 94.2% -98.3% and PPV ranged from 29% -58.7%. Fourteen studies met inclusion criteria for the performance of six tests in the setting of bladder cancer surveillance. Median sensitivity ranged from 22.6% -92.0% and specificity from 20.5% -97.9%. Median NPV ranged from 52.9% -96.5% and PPV ranged from 48.1% -75.7%. CONCLUSIONS: Our analysis finds that while these tests may provide some clinical utility, none of the assays have thus far demonstrated objective evidence to supplant the gold diagnostic standard.

Potential of an mRNA-Based Urine Assay (Xpert® Bladder Cancer Detection1) in Hematuria Patients - Results from a Cohort Study.

BACKGROUND AND OBJECTIVE: Assessment of patients with hematuria (aH) remains a challenge in urological practice, balancing the benefits of diagnosing a potentially underlying bladder cancer (UCa) against the risks of possibly unnecessary diagnostic interventions. This study analyzes the potential of an mRNA-based urine assay, the Xpert® Bladder Cancer Detection- CE-IVD (Xpert BC-D), in patients with hematuria. MATERIALS AND METHODS: Overall, 368 patients with newly observed painless hematuria and no history of UCa were included in this observational study. Patients received urological workup, including urethrocystoscopy (WLC), upper tract imaging, urine cytology and Xpert BC-D. Patients with positive WLC were recommended to undergo tumor resection (TUR-B). RESULTS: After excluding non-assessable cases, 324 patients were considered for analysis (188 males, 136 females; median age: 61 years). Eight of twenty-eight patients with a positive TUR-B had Ta low grade (LG) tumors; the others were diagnosed with high grade (HG) lesions (Ta: 4, CIS: 2, T1:11, > T1:3). The Xpert BC-D was more sensitive than urine cytology (96% vs. 61%) (p = 0.002). Increased risk ratios (RR) were observed for gross hematuria, gender, urine cytology, and positive Xpert BC-D (all p < 0.05). Age and positive Xpert BC-D remained independent predictors of UCa in multivariate analysis. Simulating a triage with WLC restricted to patients with positive Xpert BC-D could have saved 240 (74.1%) assessments at the cost of missing one pTa LG tumor. CONCLUSIONS: The results suggest a potential role for Xpert BC-D in preselecting patients with hematuria for either further invasive diagnosis or an alternate diagnostic procedure.

Arteriovenous malformation in the kidney allograft: A rare cause of hematuria in the post-transplant patient.

Gross hematuria is one of the most common complications in postrenal transplant patients, accounting for 12% of all renal recipients. The management plan in these cases varies depending on different entities, including infection, renal cell carcinoma, chronic graft rejection, kidney calculus, or recurrence of primary disease. On the other hand, vascular malformation like arteriovenous malformation was less likely to be mentioned due to a lack of consensus in the natural history, pathogenesis, and current management. In this article, we report a 62-year-old man presenting with spontaneous hematuria for a week and 2 days of anuria after 3 years of renal transplantation. Abdominal ultrasound and abdominopelvic computed tomography noted an obstruction of the renal pelvis due to blood clots without signs of vascular injuries. An emergency operation was performed to remove blood clots in the renal pelvis, but after that, hematuria was still recurrence. A digital renal graft subtraction angiography (DSA) revealed an arteriovenous malformation (AVM)in the kidney allograft. This lesion was then successfully selective embolized with glue. Given the high accuracy of DSA, our case highlights the potential role of this imaging modality in diagnosing and treating AVM after failure with other modalities.

Comparative efficacy of palliative radiotherapy dose schedules in advanced bladder cancer-associated gross hematuria.

Introduction: Gross hematuria (GH) in advanced/inoperable bladder cancer patients causes significant morbidity. Patients frequently need multiple transfusions. Hypofractionated radiotherapy (RT) has been shown to be effective in symptom palliation. In this study, we explore the efficacy of various fractionation regimens in these patients. Methods: This single institute retrospective analysis was conducted on 60 consecutive patients treated with palliative RT. Fractionation (single versus multiple) and biologically equivalent doses (BED; high ≥36 Gy versus low <36 Gy) were used to compare the efficacy of various fractionation regimens. The primary outcome was the difference in objective response rate (ORR) between various strata at 2, 4, 8 and 12 weeks. Major secondary outcomes were differences in ORR according to Eastern Cooperative Oncology Group (ECOG) performance status (PS) and tumour node metastases (TNM) stage, and the proportion of patients requiring re-transfusion(s) at 12 weeks. Data were analysed using SPSS 23. Results: Overall ORR at 2, 4, 8 and 12 weeks was 86%, 77%, 67% and 55%, respectively. There was no statistically significant difference in response rates between single or multi-fraction, or high versus low BED groups (All p = >0.05). Moreover, ECOG PS (p = 0.11) or TNM stage (p = 0.58) also had no impact on the response rate at 12 weeks. Nearly one-third (31%) of patients required further transfusions at 12 weeks. Conclusion: RT is an effective modality to control GH. No difference in ORR was found between single fractions versus multiple fractions, or high versus low BED regimens. Single fraction RT can be offered to these patients considering low cost, patient convenience and minimal side effects.

Delayed hematuria after prostatic photovaporization: risk factors to know.

OBJECTIVE: characterize delayed hematuria (DH) after photoselective vaporization of the prostate (PVP) and identify its associated risk factors. METHODS: 1014 patients who underwent PVP at an expert center, from September 2005 through December 2021, were prospectively enrolled in a database registry. Risk factors of DH included age, prostate volume, ASA score, history of BPH surgery, history of prostate cancer, use of anticoagulation or 5ARIs, concomitant procedure, operative factors, and the duration of follow-up. RESULTS: The median operating time was 60 ± 11 min. The median specific applied energy was 318,500 Joules ± 101,347. After PVP, the mean catheterization duration was 1.6 days with a postoperative hospitalization time of 1.8 days. The median follow-up was 52 months (range 2-95 months). Hematuria occurred in 206 patients (20.3%), with 10% requiring an ER visit and 8.3% requiring hospital admission, transfusion or endoscopic clot removal. Almost 80% of hematuria episodes occurred within the first 3 months. The overall retreatment rate for clot retention was 3.7% after a mean time of 50 months. Hematuria-free survival was 97.2% after 1 year, and 89.3% after 4 years. Delayed hematuria occurred in 32 patients (3.1%). In the multivariate analysis, age, preoperative prostate volume, anticoagulant use, total applied energy, lasing time and operative time were identified as risk factors for delayed hematuria after PVP. CONCLUSION: Larger prostate volume, longer operative time, longer lasing time, and use of oral anticoagulation increase the odds of delayed hematuria after PVP, while older age is protective.

Predicting the Lymphovascular Invasion in Carcinoma Bladder at Transurethral Resection.

INTRODUCTION: Bladder cancer is among the most common malignant neoplasms in the world. Transurethral resection of bladder tumor (TURBT) is considered the standard procedure for diagnosis, staging, and risk classification of bladder tumors. Lymphovascular invasion (LVI) is considered a poor prognostic factor. Its assessment of TURBT is very important for risk stratification and decision-making for further treatment. The purpose of our clinical study is to attempt to predict/assess the correlation between LVI and various preoperative (age, gender, history of smoking, hematuria, urine cytology, and hydronephrosis/hydroureteronephrosis), intraoperative (tumor number, size, and appearance - sessile/ pedunculated) and histopathological (tumor histology, grading, and muscle invasion) factors. METHODOLOGY: In this prospective study, 75 patients with bladder tumors underwent TURBT (standard monopolar TURBT with 1.5% glycine as irrigation solution) in the Department of Urology at Sri Venkateswara Institute of Medical Sciences (SVIMS), Tirupati between October 2021 and March 2023. Histopathological examination (HPE) reports were looked for the presence or absence of LVI. Accordingly, patients were divided into two groups, i.e., those with LVI and those without LVI. Various preoperative and intraoperative variables were analyzed for each subject in both groups. Statistically significant variables occurring in those patients with LVI compared to those without LVI were considered predictors of LVI in bladder tumors.  Results: Sixteen patients out of 75 (21.33%) had LVI on their histopathology examination. The mean age was 68.19 years in the group with LVI and 64.14 years in the group without LVI. A total of 60 men (80%) and 15 women (20%) were included in our study. Thirteen men (21.7%) and three women (20%) were found to have LVI. We observed a significant association between the appearance of the tumor and LVI. Fifty-four subjects in our study had sessile tumors. Fifteen out of them (27.8%) had LVI, while only one out of 21 patients (4.8%) with pedunculated tumors had LVI (p-value=0.028). 30% of subjects who had high-grade tumors on HPE also had LVI. On the contrary, only one of 25 patients (4%) with low-grade tumors had LVI (p-value=0.010). Our study also showed a significant association between muscle invasion and LVI. Thirty-four (45.3%) and 41 (54.7%) patients had muscle-invasive and non-muscle-invasive tumors, respectively. While 12 (35.3%) patients with muscle-invasive tumors had LVI, only four (9.8%) patients with non-muscle-invasive tumors showed LVI (p-value=0.007). CONCLUSION: We observed that LVI of bladder tumors at first TURBT is significantly associated with tumor grade, tumor appearance, and depth of invasion of the tumor. Though statistically not significant, we further observed that LVI was more commonly found in smokers, patients with hematuria, and larger tumor sizes. We conclude that these factors can be used as reliable predictors of LVI of bladder tumors at their first TURBT.

Alport Syndrome.

Alport syndrome (AS) is characterized by progressive kidney failure, hematuria, sensorineural hearing loss, and ocular abnormalities. Pathogenic variants in the COL4A3-5 genes result in a defective deposition of the collagen IV α3α4α5 protomers in the basement membranes of the glomerulus in the kidney, the cochlea in the ear and the cornea, lens capsule and retina in the eye. The presence of a large variety of COL4A3-5 gene(s) pathogenetic variants irrespective of the mode of inheritance (X-linked, autosomal recessive, autosomal dominant, or digenic) with and without syndromic features is better defined as the "Alport spectrum disorder", and represents the most common cause of genetic kidney disease and the second most common cause of genetic kidney failure. The clinical course and prognosis of individuals with AS is highly variable. It is influenced by gender, mode of inheritance, affected gene(s), type of genetic mutation, and genetic modifiers. This review article will discuss the epidemiology, classification, pathogenesis, diagnosis, clinical course with genotype-phenotype correlations, and current and upcoming treatment of patients with AS. It will also review current recommendations with respect to when to evaluate for hearing loss or ophthalmologic abnormalities.

Multisystem Involvement in a Pediatric Patient With Hypermobile Ehlers-Danlos Syndrome: A Case Report of the Diagnostic Complexity and Management Challenges.

Ehlers-Danlos syndrome (EDS) is a collection of genetic disorders caused by abnormalities in collagen and typified by hyperflexible joints, hyperextensible skin, and a tendency for easy bruising and tissue injuries. Hypermobile Ehlers-Danlos syndrome (hEDS), the most common subtype, presents a diagnostic challenge due to the lack of specific genetic markers. This case report describes a 13-year-old girl with hEDS, presenting with hypermobility, thoracolumbar scoliosis, constipation, glucosuria, microscopic hematuria, urticaria, and intermittent episodes of bilateral hand and feet swelling. Genetic testing revealed a variant of uncertain significance in the COL9A2 gene. An echocardiogram showed a mildly dilated aortic root. The complexity of her presentation underscores the challenges in diagnosing and managing hEDS with multisystem involvement.

Successful transvaginal repair of a vesicouterine fistula with delayed presentation.

A G4P4 woman in her 30s with a type II vesicouterine fistula, as defined by the Jozwik classification system, presented with symptoms of menouria, vaginal menses and urinary incontinence 8 years after caesarean delivery, the time of probable origination of the fistula tract. Transvaginal ultrasound identified a fistula tract communicating between the bladder and uterus, a rare finding that many years remote from caesarean delivery. Traditional surgical technique includes laparoscopic, abdominal and endoscopic methods of repair, sometimes using a transvesical approach. Transvesical repair can be associated with subsequent inpatient hospital stays and prolonged catheterisation. Our technique proposes a transvaginal surgical approach as an outpatient procedure with decreased operating time (40 min), postoperative pain and catheterisation requirement. It is the authors' belief that a transvaginal approach is less invasive and allows for better preservation of the uterus for future pregnancies and vaginal deliveries, as desired by the patient.

A Rare Presentation of Systemic Lupus Erythematosus (SLE) With Hemoptysis and Hematuria: A Case Report.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by type II and type III hypersensitivity reactions that affect multiple organs, including the joints, heart, lungs, brain, skin, and kidneys. Patients with SLE can experience a range of symptoms, ranging from fever and joint pain to a distinctive butterfly facial rash. Severe complications may encompass conditions such as diffuse alveolar hemorrhage (DAH), pulmonary hypertension, and lupus nephritis, among others. Among them, DAH, a critical pulmonary complication in SLE, involves bleeding from interstitial capillaries and alveoli due to immune complex damage. This case report describes a patient who was initially misdiagnosed but later confirmed to have SLE. The patient presented with persistent symptoms, including cough, dyspnea, and fever, over two weeks and subsequently developed hematuria and hemoptysis within the last two days. The progression of symptoms led to an acute exacerbation, resulting in her admission to the emergency department. Subsequent evaluations confirmed the diagnosis of lupus nephritis and DAH. This case highlights the importance of considering SLE in the differential diagnosis of unexplained systemic symptoms and underscores the urgent need for medical intervention in DAH to substantially reduce mortality.

Unusual presentation of metastatic melanoma.

Urinary bladder with concurrent colonic melanoma is an exceptionally uncommon occurrence, posing a diagnostic challenge for clinicians. While rare, it warrants consideration as a potential differential diagnosis, particularly in patients without a history of melanoma who present with persistent hematuria due to its aggressive nature. We present a case of a 55-year-old female with malignant melanoma involving the colon and urinary bladder presenting with hematuria. Given the scarcity of cases and variability in clinical management approaches, there is a pressing need for research efforts to establish standardized protocols and conduct trials to guide clinical practice in this rare entity.

National Trends of Inpatient Radiation Cystitis: 2016-2019.

INTRODUCTION: Radiation cystitis with hematuria (RCH) is a potentially devastating complication after pelvic radiation. The cumulative incidence of RCH is debated, and certain severe manifestations may require hospital admission. We aimed to evaluate demographics and outcomes of patients hospitalized for RCH. METHODS: We performed a retrospective review of hospitalized patients with a primary or secondary diagnosis of RCH from 2016 to 2019 using the National Inpatient Sample. Our unit of analysis was inpatient encounters. Our primary outcome was inpatient mortality. Secondary outcomes included need for inpatient procedures, transfusion, length of stay (LOS), and cost of admission. We then performed multivariate analysis using either a logistic or linear regression to identify predictors of mortality and LOS. Cost was analyzed using a generalized linear model controlling for LOS. RESULTS: We identified 21,320 weighted cases of hospitalized patients with RCH. The average patient age was 75.4 years, with 84.7% male and 69.3% White. The median LOS was 4 days, and the median cost was $8767. The inpatient mortality rate was 1.3%. The only significant predictor for mortality was older age. The only significant predictor of both higher cost and longer LOS was an Elixhauser Comorbidity Score ≥ 3. CONCLUSIONS: RCH represents a significant burden to patients and the health care system, and we observed an increasing number of hospitalized patients over time. Additional research is needed to identify underlying causes of RCH and effective treatments for this sometimes-severe complication of pelvic radiation.

Proteinuria and hematuria as early signs of renal involvement in juvenile idiopathic arthritis.

Objectives: To evaluate glomerular and tubular renal functions and analyze blood pressure in a cohort of pediatric patients with juvenile idiopathic arthritis (JIA). Methods: A total of 40 pediatric patients, 20 (50%) with JIA and 20 (50%) healthy control subjects, were studied, and performed the renal function on 24-h collection and the 24-h ambulatory blood pressure monitoring (ABPM). Moreover, we compared renal function and blood pressure trends between the groups of JIA patients with different disease activities. Results: No statistically significant differences were observed between patients with JIA and healthy children in terms of glomerular filtration rate (GFR), fractional excretion of sodium (FENa), tubular reabsorption of phosphate (TRP), and calcium-creatinine urine ratio (CaU/CrU). In contrast, we observed significantly higher values in JIA patients than in controls for the presence of hematuria (p < 0.0001) and proteinuria (p < 0.0001). Compared to the control group there were significantly higher values of hematuria and proteinuria/day in both groups of JIA patients with low disease activity (respectively, p = 0.0001 and p = 0.0002) and moderate disease activity (respectively p = 0.0001 and p = 0.0012). Systolic and diastolic dipping were significantly reduced in patients with JIA compared with healthy controls (p < 0.0001 and p < 0.0001, respectively). Conclusions: Our study showed that children with JIA, already in the early stages of the disease, have higher values of hematuria and proteinuria, which are early warning signs of nephropathy. Therefore, detailed screening of renal function and pressure monitoring in patients are necessary to monitor their evolution over time.

A Clinicopathologic Study of Urinary Bladder Lesions Amongst North Indian Population: An Experience From a Tertiary Care Centre.

BACKGROUND: Urinary bladder cancer (UBC) is amongst the most common urological malignancies. AIM: To study different types of urinary bladder lesions in the north Indian population and to correlate various clinical and pathological findings. MATERIALS AND METHODS: The present prospective study was conducted on 100 cases undergoing transurethral resection of bladder tumor (TURBT) and/or radical cystectomy over a period of 2.5 years followed by histopathological examination. Liquid-based cytology for malignant cells in urine was also performed. Immunohistochemistry was employed for tumor typing wherever needed. RESULTS: A total of 100 cases were studied. Male to female ratio was 15.7:1 and most of the patients were in the sixth decade (40%). Painless hematuria was the commonest clinical presentation (60%) and smoking was the commonest risk factor (80%). The most common lesion was infiltrating urothelial carcinoma seen in 72 cases followed by papillary urothelial neoplasm of low malignant potential (PUNLMP) seen in eight cases. Grade and depth of invasion were assessed and correlated. Several variants of infiltrating urothelial carcinoma such as squamous differentiation, glandular differentiation, microcystic, clear cell, nested, and micropapillary were also identified. Clinical, cystoscopic and histopathological findings were correlated in all the cases. CONCLUSION: Infiltrating urothelial carcinoma high grade was the most common bladder lesion identified and muscle invasion was more common with higher-grade lesions. A decade-younger age group was found to be more affected in the present series. Urine cytology for malignant cells is useful for early diagnosis of cancer. Immunohistochemistry is an important ancillary adjunct.

Complicated obstructive uropathy after kidney biopsy: A case report highlighting the risk of biopsy-related acute kidney injury in a patient with unilateral kidney hypoplasia.

Unilateral kidney hypoplasia is a congenital condition characterized by the underdevelopment of one kidney. Although often asymptomatic, it can cause severe renal complications in patients combined with contralateral renal injury, leading to acute renal failure. This case report describes a patient with unilateral kidney hypoplasia who underwent a kidney biopsy on the contralateral normal-sized kidney and subsequently developed oliguric acute kidney injury. This report discusses the challenges encountered while diagnosing and managing this rare case, highlighting the importance of awareness and recognition to perform timely intervention and optimize the patient's outcome.

Diagnostic Problem in a Child With an Isolated Renal Hydatid Cyst: A Case Report.

Cystic hydatid disease is a parasitic disease caused by the larvae of the small tapeworm Echinococcus granulosus. It is still a serious public health problem in endemic regions such as the Mediterranean basin, especially in the Balkans. Usually, the complaints caused by the cysts are non-specific and there are rarely abnormalities in routine laboratory tests. The most common is the involvement of the liver. The frequency of isolated kidney involvement, especially in a child, is uncommon. We describe a rare pediatric case of an isolated renal hydatid cyst presenting with a urinary tract infection-like clinical presentation, leading to misdiagnosis and delayed treatment.

Case Report: Intravesical and extravesical urachal cyst in children with lower abdominal pain and hematuria.

Bladder urachal cysts in children are a rare form of urachal abnormality. In this paper, we present a case of atypical imaging that presented with lower abdominal pain accompanied by hematuria, resulting in the formation of both internal and external urachal cysts in a child. A 6-year-old male child presented with repeated abdominal pain over a span of 4 days. Color ultrasound and pelvic CT scans revealed a soft tissue lesion on the right anterior wall of the bladder with an unclear boundary from the bladder wall. Voiding Cystourethrography (VCUG) showed no significant abnormalities in the bladder, while routine urine testing was positive for hematuria. A cystoscopy was simultaneously performed with a laparoscopic resection of the urachal cyst. Intraoperative cystoscopy identified the intravesical lesion, which was precisely removed using a cystoscope-assisted laparoscopy. Postoperative pathology confirmed that both extravesical and intravesical lesions were consistent with a urachal cyst. No complications were observed after the operation, and no recurrence was noted during a six-month follow-up. Therefore, for urachal cysts at the bladder's end, the possibility of intravesical urachal cysts should not be excluded, especially in patients with microscopic hematuria. We recommend performing cystoscopy simultaneously with laparoscopic urachal cyst removal to avoid missing intravesical lesions.

Methotrexate­associated B­cell lymphoproliferative disease that exhibits hematuria due to urinary bladder lesions: A case report.

Methotrexate (MTX)-related lymphoproliferative disease (LPD) is one of the most prominent late complications associated with MTX treatment. Although MTX-related LPD exhibits a relatively high incidence of extranodal disease, the incidence of disease in a urinary bladder is very low. The present study reports the case of a patient with MTX-related LPD involving a urinary bladder mass. A 75-year-old female patient, who had been receiving MTX for ~15 years, was referred to the hospital due to fever and hematuria. A computed tomography scan revealed the thickening of the urinary bladder wall, hydronephrosis and lymph node swelling. The histopathological findings of the urinary bladder mass resulted in a diagnosis of MTX-related LPD. Although MTX withdrawal did not have any effect, the subsequent chemotherapy resulted in complete remission. Although MTX-related LPD in the bladder is rare, it is pertinent to consider MTX-related LPD when hematuria is observed during MTX therapy.

Crohn's disease-associated IgA nephropathy may prone to better renal outcome.

BACKGROUND AND AIM: Renal involvement in Crohn's Disease (CD) was rare in the population. Little was known between IgA nephropathy and CD. This study aimed to investigate the differences in clinical and outcome features of CD-associated IgA nephropathy (CD-IgAN) and primary IgA nephropathy (PIgAN). METHODS: Clinical data of patients diagnosed with IgAN by kidney biopsy were collected in the Sixth Affiliated Hospital of Sun Yat-sen University from January 1st, 2016 to June 1st, 2023. 17 patients with CD-IgAN and 87 patients with PIgAN were enrolled in this retrospective study. RESULTS: Compared with PIgAN patients, CD-IgAN patients had lower levels of urinary protein excretion (1.57 g per 24 h vs. 0.33 g per 24 h, p < 0.01), but higher levels of estimated glomerular filtration rate (77.63 ± 40.11 ml per min per 1.73m2 vs. 104.53 ± 32.97 ml per min per 1.73m2, p = 0.008). From the point of renal pathology of PIgAN, patients with CD-IgAN had a less incidence of tubular atrophy or interstitial fibrosis (p = 0.001). CD-IgAN patients had a higher incidence of complete remission of proteinuria (45.8% vs. 81.8%, p = 0.031) or hematuria (10.4% vs. 45.4%, p = 0.019) than PIgAN patients after twelve-month treatments. CONCLUSIONS: CD-IgAN manifests a milder progression of renal function than those PIgAN. After the treatment, proteinuria or hematuria are more prone to remit in patients with CD-IgAN.