Bladder Pathology Research Articles

Histopathological Changes in the Gall Bladder Mucosa Associated with Helicobacter Pylori Gastritis

Objective: To identify Helicobacter Pylori (HP) gastritis-associated histopathological changes in Gall Bladder (GB) mucosa in patients undergoing cholecystectomy. Methodology This prospective comparative cross-sectional study was conducted in the Gastroenterology department of Liaquat National Hospital, Karachi, Pakistan, from December 2021 to December 2022. The study included all patients admitted with a diagnosis of any Gall Bladder pathology and those who were electively scheduled for cholecystectomy. Participants were categorized into two groups based on the presence of HP: group A (HP positive) and group B (HP negative) in gastric mucosa before cholecystectomy. HP detection was performed using various methods, including HP stool antigen (HPSA), Urea breath test (UBT), HP antibodies, and biopsy confirmation through gastroscopy. Results: The mean age of patients in group A was 42.88 ± 8.28 years, and in group B, it was 43.35 ± 8.74 years (p=0.458). According to the GB histological findings, Chronic cholecystitis with focal Cholesterolosis was significantly more common in group A (75.4%), while Chronic cholecystitis alone was significantly higher in group B (66.2%) (p=0.001). Dysplasia was observed more frequently in group B compared to group A. Erosion was more prevalent in group A, patients than in group B (p=0.001). Although symptom improvement in the HP positive group with persistent symptoms post-eradication was not statistically significant, it did show some improvement (p=0.527). Conclusion: The histological findings of chronic cholecystitis with focal Cholesterolosis were significantly higher in the HP positive group compared to the HP negative group, while chronic cholecystitis alone was significantly more common in the HP gastritis negative group. Some HP gastritis group patients experienced symptom improvement after HP eradication.

Role of MRCP in Patients with Jaundice When Biliary Tree Is Normal on Previous Imaging

Background Obstructive jaundice is one of the most frequent and grave form of hepatobiliary disease. It is important for treatment planning to detect level and cause of obstruction. Aim of the Work To assess the role of MRCP in patients presented with jaundice, right hypochondrial pain with the absence of dilated biliary system by ultrasound. Patients and Methods This was cross sectional study that included 38 patients who presented with obstructive jaundice or right hypochondrial pain with normal biliary system by ultrasound referred to the Radio diagnosis Department for MRCP. Results MRCP has high sensitivity reaching 100% and high specificity reaching 93.33% in gall bladder pathology and high specificity 100% in biliary and pancreatic pathology in comparison to ultrasound. Conclusion if there is high clinical suspicion of ductal pathology when patient presented by jaundice or right hypochondrial pain with abnormal liver function tests despite normal biliary tree by ultrasound, an MRCP examination should be strongly considered as next imaging modality of choice

Infection with swim bladder nematode Anguillicola crassus in relation to European eel growth, age, and habitat along the German Baltic coast.

One possible reason for the European eel (Anguilla anguilla) population decline is the neozoan eel swim bladder nematode Anguillicola crassus. To investigate whether the prevalence of A. crassus and the associated swim bladder pathology is related to eel habitat, growth rate, and age, 728 yellow eels from 6 habitats differing in salinity and located along the German Baltic coast were examined between 2005 and 2009. The prevalence of A. crassus varied between habitats, ranging from 9 to 57%. Infection prevalence and the percentage of eels with a damaged swim bladder were significantly higher in inner coastal waters compared to more saline open coastal water. In infected eels, 1 to 32 adult and preadult individuals of A. crassus were observed. The mean infection intensity varied between habitats from 2 to 7 nematodes per eel but did not significantly differ between inner and open coastal waters. Infection prevalence and intensity decreased significantly with age when all open coastal waters and all habitats were combined. Both the lower prevalence of A. crassus and the swim bladder damage of older eels and of eels originating from open coastal water habitats suggest that these eels have a higher fitness for spawning migrations than eels from inner coastal waters. The present study underlines the importance of eel screening on a sufficiently small geographical scale for the accurate estimation of eel recruitment and the identification of priority areas that are likely to produce healthy silver eels.

A grading system for evaluation of bladder trabeculation.

To establish a parameter-based grading system for evaluating bladder trabeculation (BT). A retrospective analysis was conducted on children diagnosed with posterior urethral valve (PUV) or neurogenic bladder (NB) who underwent voiding cystourethrogram (VCUG), urodynamic testing, and urological ultrasonography between January 2016 and October 2022. Cases involving urologic surgery, secondary bladder pathology, and an interval of more than 12months between examinations were excluded. A parameter named Bladder Dispersion (BD) was calculated through fluoroscopic images, and the grading system was developed as follows: BD < 40 (Grade 0), 40 ≤ BD < 60 (Grade 1), 60 ≤ BD < 90 (Grade 2), BD ≥ 90 (Grade 3). Grades 0-1 were classified as low-risk group, while grades 2-3 were classified as high-risk group. Analysis of variance, Kruskal-Wallis test, and Chi-square test were performed to compare urodynamic results and complications across different grades and groups. A total of 74 patients were eligible to participate, which included 46 boys (62.2%) and 28 girls (37.8%), the mean age was 75.18 ± 48.39months. Among them, 11 (14.9%) were PUV, 50 (67.6%) were NB, and 13 (17.5%) were PUV and NB. Significant differences were observed in maximum detrusor pressure, post-void residual urine ratio, and compliance among grades 0-3. Severe hydronephrosis and histories of urinary tract infection were more prevalent in the high-risk group. A reliable grading system with objective standards was proposed which could aid in the assessment of BT severity.

Voiding efficiency in children is significantly impaired by the presence of the urethral catheter during pressure-flow studies

Little is known about the effect of catheterization during pressure-flow studies (PFS) on voiding efficiency in children. Our objective was to determine the effect of urethral catheterization on Qmax and flow index (FI) during PFS compared to the free flow of uroflowmetry (UF). We retrospectively reviewed 63 consecutive children who underwent UF and PFS at our center on the same day (2019-2022). Voiding data was available for 46 patients. Patients first underwent a UF with full bladder, then PFS after urethral catheter insertion. Patients with urethral pathologies (n=6), on clean intermittent catheterization (CIC) (n=2) and with major comorbidities (n=2) were excluded. Indications for UF/PFS were LUTS, recurrent UTIs, incontinence or neurosurgical pre-operative evaluation. Data was collected from the UF and the PFS and compared using paired t-test. The idealized Qmax and flow index (FI) were calculated for UF and PFS using the formulas described by Franco etal.: Male Qmax=11.26+0.0701(TBC [total bladder capacity])-0.0000513(TBC); Female Qmax=10.723+0.073(TBC)-0.0000423(TBC), FI=Actual Qmax/Expected Qmax (Franco and etal., 2016; Franco etal., 2018; Franco and etal., 2016). Median age was 7 years old (IQR 5-11). Twenty-one (40%) patients were male and 32 (60%) patients were female. Of the 53 patients, 3 boys and 4 girls (n=7; 13%) were unable to void with the catheter in place during PFS but able to void after its removal. Of the remaining 46 cases, the Qmax during PFS was 5mL/s slower than the Qmax recorded on the UF without catheter, representing a decrease of 29% (12.3 vs 17.3mL/s; p<0.0001). The impact of urethral catheter during PFS was more important in males vs females (Qmax decreased by 7.7 vs 3.3mL/s, or 45 vs 19%). The mean FI during PFS was 44%, which was a 30% reduction compared to the 74% FI obtained with UF (p<0.00001). In males, the FI decreased by 37% on PFS, whereas it decreased 26% in females, similar to the Qmax decrease. Voiding efficiency, as assessed by Qmax and FI, is decreased during PFS compared to uroflow studies. Our data documents for the first time the impact of urethral catheterization on pediatric voiding efficiency. Abnormal flow rates and elevated PVRs should be used to guide patient management only if obtained by uroflow. Prospective validation comparing free flow with PFS studies will help characterize the impact of urethral catheter relative to bladder pathology, age, gender and catheter size used.

Open versus robotic-assisted radical cystectomies: A risk analysis.

4593 Background: Radical cystectomy (RC) is standard of care for muscle-invasive bladder cancer, but it comes with significant perioperative risk with half of patients experiencing major postoperative complications. Robot-assisted radical cystectomies (RARC) have aimed to decrease patient morbidity and have become increasingly adopted in North America. Currently, both open radical cystectomies (ORC) and RARC are frequently performed. To contribute to the existing literature using newly available data from the American College of Surgeons National Surgical Quality Improvement Project (NSQIP), representing one of the most recent, largest multi-institutional studies, while uniquely accounting for a variety of factors including type of urinary diversion, cancer staging, and neoadjuvant chemotherapy. Methods: RC procedures performed between 2019-2020 were identified in NSQIP and the corresponding Cystectomy Targeted database. Cases in the ORC group were planned open procedures, and cases in the RARC group were robotic with intra- or extracorporeal diversions, including unplanned conversion to open cases for intention-to-treat. Chi-square and t-tests were performed to compare baseline demographics and operative parameters. Multivariate analysis was performed for outcomes including major complications, minor complications, and 30-day mortality, while adjusting for operative approach, medical comorbidities, functional status, age, race, sex, BMI, ASA-classification, preoperative labs, type of urinary diversion, pathological staging, prior pelvic surgery or radiation, need for preoperative transfusion, preoperative sepsis, emergent or elective surgery, and recent chemotherapy. Results: 4,022 RC cases were identified. Of these, 3,146 (78.2%) received planned ORC while 876 (21.8%) received RARC. Baseline demographics of the patients who received ORC versus RARC were largely similar, with no significant difference in age or medical comorbidities. RARC was associated with longer operative times and shorter hospital length of stay compared to ORC. On multivariate analysis, ORC was associated with a higher rate of 30-day mortality [OR 3.1; 95% CI 1.3-7.2; p=0.009], reintubation, cardiac arrest, superficial wound infection, bleeding requiring transfusion [OR 4.7; 95%CI 3.6 - 6.1; p&lt;0.001], prolonged postoperative nasogastric tube use, rectal injury, and ureteral fistula or urine leak compared to RARC. Conclusions: In the NSQIP database, ORC is associated with higher rates of 30- day mortality and operative complications, most notably bleeding, compared to RARC. This study is unique in the size of the cohorts compared, the timeliness of the data (2019-2020), and the ability to control for factors, such as type of urinary diversion, pathological bladder cancer staging, and use of neoadjuvant chemotherapy.

Demographic, Clinical and Radiological Findings among Patients with CTU Detected Urolithiasis in a Tertiary Hospital

Background: Computed tomography urography (CTU) is the current radiological imaging modality for the evaluation of the kidneys, ureters and urinary bladder pathologies. CTU has largely replaced intravenous urography in centers that has computed tomogram machines.&#x0D; Objectives: The aim of this study is to identify the common location of urolithiasis in the urinary tract and correlate it with age, sex, stone size and Hounsfield unit (HU) using CT scan in the Radiology department of Rivers State University Teaching Hospital.&#x0D; Methods: A retrospective study with descriptive study design was employed. A total of 140 patient’s data were used. A P-value below 0.05 was considered statistically significant.&#x0D; Results: One-hundred and forty patients were studied over a 24 months period. The median age was 43.50 years. The prevalence of stones (n=47, 33.6%) and age range with the highest prevalence is 41-50 years. The male: female was 1.8:1. Renal stones are commonly found in the inferior pole. Vesicoureteric junction stones were more prevalent in females. There was significant association between age and sex. (P=0.005).&#x0D; Conclusion: Urolithiasis is commonly seen in males. The location of calculi in the urinary tract is in the kidney, pelviureteric junction (PUJ), vesicoureteric junction (VUJ), ureters and the urinary bladder in a downhill order correspondingly. The inferior pole is the most prevalent site for renal stones and VUJ stones are more frequent in females while other locations are seen more in males. Interestingly, age and sex showed significant association.

Urinary microbiota and metabolic signatures associated with inorganic arsenic-induced early bladder lesions

Inorganic arsenic (iAs) contamination in drinking water is a global public health problem, and exposure to iAs is a known risk factor for bladder cancer. Perturbation of urinary microbiome and metabolome induced by iAs exposure may have a more direct effect on the development of bladder cancer. The aim of this study was to determine the impact of iAs exposure on urinary microbiome and metabolome, and to identify microbiota and metabolic signatures that are associated with iAs-induced bladder lesions. We evaluated and quantified the pathological changes of bladder, and performed 16S rDNA sequencing and mass spectrometry-based metabolomics profiling on urine samples from rats exposed to low (30 mg/L NaAsO2) or high (100 mg/L NaAsO2) iAs from early life (in utero and childhood) to puberty. Our results showed that iAs induced pathological bladder lesions, and more severe effects were noticed in the high-iAs group and male rats. Furthermore, six and seven featured urinary bacteria genera were identified in female and male offspring rats, respectively. Several characteristic urinary metabolites, including Menadione, Pilocarpine, N-Acetylornithine, Prostaglandin B1, Deoxyinosine, Biopterin, and 1-Methyluric acid, were identified significantly higher in the high-iAs groups. In addition, the correlation analysis demonstrated that the differential bacteria genera were highly correlated with the featured urinary metabolites. Collectively, these results suggest that exposure to iAs in early life not only causes bladder lesions, but also perturbs urinary microbiome composition and associated metabolic profiles, which shows a strong correlation. Those differential urinary genera and metabolites may contribute to bladder lesions, suggesting a potential for development of urinary biomarkers for iAs-induced bladder cancer.

Management of male stress urinary incontinence in high-risk patients: a narrative review.

The artificial urinary sphincter (AUS) remains the gold standard for treatment of stress urinary incontinence (SUI). However, highly complex patients such as those with bulbar urethral compromise, bladder pathology, and lower urinary complications pose a particular challenge for the surgeon. In this article, we will address critical risk factors and synthesize existent data across relevant disease states to support surgeons in successful management of SUI in high-risk patients. A comprehensive review of current literature was performed utilizing the search term "artificial urinary sphincter" in conjunction with any of the following additional terms: "radiation", "urethral stricture", "posterior urethral stenosis", "vesicourethral anastomotic stenosis", "bladder neck contracture", "pelvic fracture urethral injury", "penile revascularization", "inflatable penile prosthesis", and "erosion". Guidance is provided based upon expert opinion where existing literature was sparse or nonexistent. Several known patient risk factors are associated with AUS failure and can ultimately lead to device explantation. Each risk factor requires careful consideration and investigation, or intervention as appropriate, prior to device placement. Optimization of urethral health, confirmation of anatomic and functional stability of the lower urinary tract, and thorough patient counseling are a necessity for these high-risk patients. Several surgical strategies to decrease device complications can be considered: optimization of testosterone, avoidance of 3.5 cm AUS cuff, transcorporal AUS cuff placement, relocation of AUS cuff site, use of lower pressure-regulating balloon, penile revascularization, and intermittent nocturnal deactivation. A number of patient risk factors are associated with AUS failure and can ultimately lead to device explantation. We present an algorithm for management of high-risk patients. Optimization of urethral health, confirmation of anatomic and functional stability of the lower urinary tract, and thorough patient counseling are a necessity for these high-risk patients.

Abstract 17: Sex disparities in a murine model of BBN-induced bladder cancer

Abstract Bladder cancer is one of the most common cancers in the US, with an estimated incidence of 83,730 cases in 2021. Males are four times more likely to develop bladder cancer than females. Ninety percent of cases are diagnosed as urothelial carcinomas, and most cases are not muscle-invasive at the time of diagnosis. Even with treatment, there is a 50-80% chance of bladder cancer recurrence within five years of diagnosis. While non-invasive disease has a five-year survival rate of 77%, if recurrence leads to metastatic disease, the five-year survival rate is only 6%. Therefore, there is a need to predict which patients will recur and progress to metastatic disease. N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) is a cigarette smoke-mimicking carcinogen that can be used in mice to induce urothelial cell proliferation and progression to invasive bladder cancer. This study used a BBN-induced bladder cancer model to evaluate sex differences in urothelial proliferation and bladder pathologies in male and female mice treated with BBN (0.05%) in their drinking water for up to 12 weeks. Mice were then given a 2–20-week period of no treatment following BBN exposure. Bladder specimens were stained with Ki-67 to analyze urothelial proliferation and characterized based on pathology. Male bladder samples characterized as having reactive atypia showed greater proliferation rates than male bladder samples with urothelial dysplasia. Overall, compared to female bladder samples, male bladders showed greater urothelial proliferation in both reactive atypia and dysplasia categories. Additionally, male mice had more tumor initiation and aggressive disease at all examination timepoints, with the most pronounced difference seen at 10-weeks post-BBN exposure. The development of carcinoma in situ (CIS) and invasive disease was seen in 100% of males at 12 weeks post-BBN, while only 40% of female mice had CIS or invasive disease at the same timepoint. Overall, these findings indicate that mouse sex plays a role in bladder tumor progression, with females having delayed tumor initiation and less aggressive disease. This may be due, in part, to varied immune cell profiles in males versus females. A short 2-week exposure to BBN caused a similarly profound neutrophil and macrophage infiltrate in the bladder of both sexes but no changes in immunosuppressive populations such as regulatory T cells (Tregs). In stark contrast, a 12-week exposure to BBN with a 2-week rest period resulted in significantly more macrophages and immunosuppressive PD-L1+ neutrophils and Tregs in the bladders of male mice when compared with females. Chronic exposure to BBN leads to an increase in immunosuppressive immune infiltrates in male bladders and may contribute to sex disparities observed in bladder cancer. Citation Format: Gabrielle E. Kennelley, Jordan J. McDonald, Norbert Sule, Barbara A. Foster, Craig M. Brackett, Wendy J. Huss. Sex disparities in a murine model of BBN-induced bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 17.

Long-term prevention of bladder cancer progression by alpha1-oleate alone or in combination with chemotherapy.

Bladder cancer is common and one of the most costly cancer forms, due to a lack of curative therapies. Recently, clinical safety and efficacy of the alpha1-oleate complex was demonstrated in a placebo-controlled study of nonmuscle invasive bladder cancer. Our study investigated if long-term therapeutic efficacy is improved by repeated treatment cycles and by combining alpha1-oleate with low-dose chemotherapy. Rapidly growing bladder tumors were treated by intravesical instillation of alpha1-oleate, Epirubicin or Mitomycin C alone or in combination. One treatment cycle arrested tumor growth, with a protective effect lasting at least 4 weeks in mice receiving 8.5 mM of alpha1-oleate alone or 1.7 mM of alpha-oleate combined with Epirubicin or Mitomycin C. Repeated treatment cycles extended protection, defined by a lack of bladder pathology and a virtual absence of bladder cancer-specific gene expression. Synergy with Epirubicin was detected at the lower alpha1-oleate concentration and in vitro, alpha1-oleate was shown to enhance the uptake and nuclear translocation of Epirubicin, by tumor cells. Effects at the chromatin level affecting cell proliferation were further suggested by reduced BrdU incorporation. In addition, alpha1-oleate triggered DNA fragmentation, defined by the TUNEL assay. The results suggest that bladder cancer development may be prevented long-term in the murine model, by alpha1-oleate alone or in combination with low-dose Epirubicin. In addition, the combination of alpha1-oleate and Epirubicin reduced the size of established tumors. Exploring these potent preventive and therapeutic effects will be of immediate interest in patients with bladder cancer.

Overactive Bladder Patients With and Without Urgency Incontinence: A Spectrum of One Condition or Different Phenotypes?

ABSTRACT The International Continence Society classifies overactive bladder (OAB) as a storage symptom syndrome characterized by “urgency, with or without urgency urinary incontinence, usually with increased daytime frequency and nocturia.” Although heterogenous in nature, some OAB patients exhibit only frequency and urgency (“OAB-dry”), whereas others exhibit frequency and urgency with urgency incontinence (“OAB-wet”). This study aimed to further explore the unique features of each of these diagnoses via comparison of data for women seeking lower urinary tract symptom (LUTS) care, including data such as physical examination findings, self-reported symptoms, and demographic data. Better understanding of OAB-wet and OAB-dry definitive features may lead to more effective treatment. Through the LURN (Lower Urinary Tract Dysfunction Research Network)—sponsored via the research network NIDDK (National Institute of Diabetes and Digestive and Kidney Diseases)—physical examination, demographic data, and questionnaire data were obtained for women seeking LUTS-based care at 6 centers in the United States. Enrollment entailed categorization of patients into urinary incontinence subtypes, as determined by LURN clinical staff from patient LUTS Tool responses. Subgroups included both OAB-dry and OAB-wet categories, as well as a control LUTS group lacking symptoms. The multicenter data set found 545 LUTS-presenting women, with 84 patients being defined as OAB-wet, 56 patients defined as OAB-dry, and 67 patients defined as the control population. The study population was predominantly White (83%), with mean age of the cohort as 58.8 ± 14.1 years. Demographics did not vary between the categories. The groups experienced very similar symptoms, except OAB-wet patients had urgency incontinence, and OAB-dry reported significantly more bladder pain, incomplete emptying, and straining to urinate. Both OAB groups exhibited identical levels of frequency, nocturnal, urgency, and level of bother. Both OAB groups experienced more bother than controls. However, bother for OAB-wet was directly related to severity of incontinence, and bother for OAB-dry was directly related to pelvic floor tenderness on examination. These results may indicate that the individual conditions hail from divergent etiologies, which contradicts traditional disease concepts. Since OAB-dry patients commonly report sensations of incomplete emptying, bladder pain, and straining to urinate, the authors hypothesized that these symptoms may represent a pelvic floor muscle dysfunction rather than a true bladder pathology. This hypothesis is based on the significant overlap between bladder symptoms of OAB-dry and bladder symptoms in high-tone pelvic floor dysfunction (HTPFD) patients (or those with myofascial pelvic pain). Possible causes were this to be the case might be changes in muscle function leading to alterations in the resting angle of the urethrovesical junction and irritation of the bladder neck or urethra. In addition, neuromuscular dysfunction may lead to symptoms of HTPFD and OAB. Strengths of this study include its large study parameters involving multiple centers across the nation, including all patients seeking care for LUTS. Because most women in the study were White, generalizability of the study to a more diverse patient population is limited. In addition, patient self-reporting of incontinence type lacked simultaneous objective testing. Moreover, significant pelvic pain excluded patients from this cohort, which may have excluded patients with more severe forms of OAB-dry from the study population. Although traditionally grouped and treated together under a larger OAB diagnosis, OAB-wet and OAB-dry have unique symptomatic features, suggesting divergent etiologies. Unique symptoms such as pain, a feeling of incomplete emptying, and straining with urination all suggest pelvic floor myofascial dysfunction for OAB-dry patients. Further examination of a distinct pathophysiology for these 2 groups is warranted.

MP56-06 PATHOLOGIC DOWNSTAGING RATE AND PREDICTIVE BIOMARKER EXPLORATION IN PATIENTS WITH BIOPSY-PROVEN CLINICALLY NODE POSITIVE BLADDER CANCER UNDERGOING CHEMOTHERAPY FOLLOWED BY RADICAL CYSTECTOMY

You have accessJournal of UrologyCME1 Apr 2023MP56-06 PATHOLOGIC DOWNSTAGING RATE AND PREDICTIVE BIOMARKER EXPLORATION IN PATIENTS WITH BIOPSY-PROVEN CLINICALLY NODE POSITIVE BLADDER CANCER UNDERGOING CHEMOTHERAPY FOLLOWED BY RADICAL CYSTECTOMY Amy Lim, Akshay Sood, Vikram Narayan, Mohammed Seif, Justin Matulay, Kelly Bree, Matt Campbell, Ashish Kamat, Colin Dinney, and Neema Navai Amy LimAmy Lim More articles by this author , Akshay SoodAkshay Sood More articles by this author , Vikram NarayanVikram Narayan More articles by this author , Mohammed SeifMohammed Seif More articles by this author , Justin MatulayJustin Matulay More articles by this author , Kelly BreeKelly Bree More articles by this author , Matt CampbellMatt Campbell More articles by this author , Ashish KamatAshish Kamat More articles by this author , Colin DinneyColin Dinney More articles by this author , and Neema NavaiNeema Navai More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003309.06AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Studies assessing the efficacy of preoperative chemotherapy in bladder cancer rarely include clinically node positive (cN+) patients. Further, the cN+ patients that are included are frequently categorized as cN+ based on imaging only. Therefore, true nodal response rates and oncological outcomes in this select patient group are generally unknown. Additionally, studies examining responder characteristics are lacking. METHODS: Data were collected retrospectively on patients with cTanyN1-3M0 bladder cancer who underwent radical cystectomy at the University of Texas MD Anderson Cancer Center (2006-2017). Complete nodal response (pN0) and bladder tumor response (pT0), recurrence free survival (RFS) and overall survival (OS) for patients with a positive lymph-node (LN) biopsy were recorded. Tissue mRNA microarray expression profiling was performed on LN and primary tumor tissue (pre-therapy) and compared among responders (pN0) and non-responders. RESULTS: Among the 120 patients identified with cTanyN1-3M0 disease, 26 (21.7%) patients had a positive LN biopsy. Induction chemotherapy was administered in all patients. Nine (34.6%) were pN0 and 9 (34.6%) were pT0 after primary chemotherapy. Seven were pT0N0. Lower stage disease on final pathology was associated with improved RFS and OS (p<0.001). Fourteen differentially expressed genes in the LNs and 68 differentially expressed genes in the bladder were predictive of pN0 response to primary chemotherapy in the LNs (FDR<0.1; Figure). CONCLUSIONS: Among cN+ patients, the true response rate to primary chemotherapy appears to be∼35%. Pathologic bladder response correlates well with nodal response. Finally, our study suggests that a panel of genes may be useful in distinguishing cN+ chemo-responders vs not, and thus could help reduce over- and undertreatment. These exploratory findings need prospective validation. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e775 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Amy Lim More articles by this author Akshay Sood More articles by this author Vikram Narayan More articles by this author Mohammed Seif More articles by this author Justin Matulay More articles by this author Kelly Bree More articles by this author Matt Campbell More articles by this author Ashish Kamat More articles by this author Colin Dinney More articles by this author Neema Navai More articles by this author Expand All Advertisement PDF downloadLoading ...

Recent Advances in the Classification of Bladder Cancer - Updates from the 5th Edition of the World Health Organization Classification of the Urinary and Male Genital Tumors.

The World Health Organization Classification (WHO) of Urinary and Male Genital Tumors has recently been updated to its 5th edition. The new edition presents a comprehensive approach to the classification of urinary and male genital tumors with an incorporation of morphologic, clinical, and genomic data. This review aims to update the new classification of bladder cancer in the 5th edition and to highlight important changes in nomenclatures, diagnostic criteria, and molecular characterization, as compared to the 4th edition. The pathologic classification of bladder cancer in the 5th edition of WHO Classification of Urinary and Male Genital Tumours was compared to that in the 4th edition. PubMed was searched using key words, including bladder cancer, WHO 1973, WHO 1998, WHO 2004, WHO 2016, histology, pathology, genomics, and molecular classification in the time frame from 1973 to August of 2022. Other relevant papers were also consulted, resulting in the selection of 81 papers as references. The binary grading of papillary urothelial carcinoma (UC) is practical, but it may be oversimplified and contribute to "grade migration" in recent years. An arbitrary cutoff (5%) has been proposed for bladder cancers with mixed grades. The diagnosis of papillary urothelial neoplasm with low malignant potential has been dramatically reduced in recent years because of overlapping morphology and treatment with low-grade papillary UC. An inverted growth pattern should be distinguished from true (or destructive) stromal invasion in papillary UC. Several methods have been proposed for pT1 tumor substaging, but it is often challenging to substage pT1 tumors in small biopsy specimens. Bladder UC shows a high tendency for divergent differentiation, leading to several distinct histologic subtypes associated with an aggressive clinical behavior. Molecular classification based on the genomic analysis may be a useful tool in the stratification of patients for optimal treatment. The 5th edition of WHO Classification of Urinary and Male Genital Tumours has made several significant changes in the classification of bladder cancer. It is important to be aware of these changes and to incorporate them into routine clinical practice.

Urinary Oxidative Stress Biomarker Levels Might Be Useful in Identifying Functional Bladder Disorders in Women with Frequency and Urgency Syndrome.

lower urinary tract dysfunctions (LUTDs) are difficult to diagnose based on symptoms. This study used a cluster of urinary biomarkers, including inflammatory cytokines, neurogenic proteins, and oxidative stress biomarkers, to identify LUTDs in women with frequency and urgency symptoms. in total, 253 women with video urodynamics (VUDS)- and cystoscopy-confirmed detrusor overactivity (DO), interstitial cystitis/bladder pain syndrome (IC/BPS), dysfunctional voiding (DV), and hypersensitive bladder (HSB), and normal controls were included. Before diagnosis and treatment, urine samples were collected for analysis of biomarkers. The urine levels of biomarkers were compared between groups with bladder dysfunctions and controls and were combined to test the sensitivity in identifying total pathological bladder diseases and specific bladder diseases. After video urodynamic study, VUDS, and urological examinations, bladder dysfunctions were classified into DO (n = 31), IC/BPS (n = 114), DV (n = 45), HSB (n = 29), and control (n = 34) groups. By using a cystomeric bladder capacity of ≤350 mL, 186/219 (84.9%) of the patients with DO, IC/BPS, DV, and HSB can be discriminated from the controls. Among these urine biomarkers, oxidative stress biomarkers 8-isoprostane, 8-hydroxydeoxyguanosine (8-OHdG), or total antioxidant capacity (TAC) are useful for identifying pathological bladder dysfunction (DO, IC/BPS, and DV) and HSB. With elevated IL-1β and lower IL-2, and elevated TNF-α levels, most patients with DV can be identified. Between DO and IC/BPS, a higher NGF level can identify 58.3% of IC/BPS cases, whereas a lower NGF level can identify 75.0% of DO cases. by using a cluster of urine biomarkers, DO, IC/BPS, and DV cases can be identified based on elevated levels of urine oxidative stress biomarkers 8-isoprostane, TAC, or 8-OHdG, and HSB cases with a low TAC. These urine biomarkers are useful for identifying specific LUTDs in women with frequency and urgency symptoms.

Scope of Laparoscopic Cholecystectomy in Patients with Previous Upper Abdominal Surgery

Background: Laparoscopic cholecystectomy has become the treatment of choice for symptomatic gallstones. Previous upper abdominal surgery has been reported as a relative contraindication to laparoscopic cholecystectomy.This study specifically examined the effect of previous upper abdominal surgery on the feasibility and safety of laparoscopic cholecystectomy.&#x0D; Methods: A number of 50 patients of adult age group (25 to 60 years) who were admitted suffering from gall bladder pathology and having history of previous upper abdominal surgery in the surgery units of a tertiary level hospitalwithin the time period of September, 2013 to August, 2014 were included in this prospective observational study. With the consent of the patients, laparoscopic cholecystectomy was chosen as the surgical procedure. All these data were analyzed to find out the feasibility and safety of laparoscopic cholecystectomy in the patients with previous upper abdominal surgery.&#x0D; Results: The patients were classified into 3 groups: group 1, patients with no adhesions, group 2, patients with minimum adhesions and group 3, patients with moderate dense adhesions. The 3 groups were similar with respect to age and sex (P&gt;0.05). Conversion to laparotomy was required in 5 (10%) patients (1 in group 1, 2 in group 2, and 3 in group 3). No statically significant difference was noted among groups with respect to the conversion rate (P&gt;0.05). No per-operative complications occurred in any of the groups. The post-operative complication rates among groups were not statistically different (P&gt;0.05).&#x0D; Conclusion: Previous upper abdominal surgery is not a contraindication to safe laparoscopic cholecystectomy. However, previous upper abdominal surgery is associated with an increased need for adhesiolysis, a chance for open conversion and a prolonged operation time.&#x0D; AKMMC J 2021; 12(1) : 11-15

POST-PROSTATEKTOMİ İNKONTİNANSTA İNTRİNSİK SFİNKTER DİSFONKSİYONU DIŞINDAKİ NEDENLER DE AKILDA BULUNDURULMALIDIR

Objective: This study aims to determine the causes of urinary incontinence and accompanying bladder pathologies in patients with persistent incontinence 12 months after radical prostatectomy.&#x0D; Methods: Thirty-four patients who underwent open radical retropubic prostatectomy (RRP) due to localized prostate cancer and incontinent after surgery between January 2015 and December 2020 and underwent urodynamic study (UDS) were retrospectively reviewed. All UDSs were performed according to the ICS protocol of good urodynamic practice and assessed by the same doctor. Patients were assessed by demographic and clinical parameters including age, body mass index (BMI), comorbidity, preoperative PSA level, prostate volume (PV), transrectal prostate biopsy Gleason score, clinical stage, pathological ISUP grade, pathological stage, lymph node positivity, international consultation on incontinence questionnaire-short form and subjective questionnaire for daily pad use.&#x0D; Results: Urodynamic studies showed that 29 patients (85.2%) had intrinsic sphincter deficiency (ISD). Nine (26.4%) of 29 patients with ISD had a secondary diagnosis of overactive bladder (OAB), impaired detrusor contractility (IDC) and OAB+IDC 9 (11.6%), 4 (11.6%), 1 (2.9%), respectively. Nineteen patients (55.8%) had a sole diagnosis of ISD, whereas 15 patients (44.1%) had another primary diagnosis or a secondary diagnosis other than ISD. &#x0D; Conclusion: Although ISD is the most common cause of persistent urinary incontinence in patients after radical prostatectomy, it should be taken into account that overactive bladder and impaired detrusor contractility are also accompanied by a significant proportion of patients.

Insights into the Safety and Versatility of 4D Printed Intravesical Drug Delivery Systems.

This paper focuses on recent advancements in the development of 4D printed drug delivery systems (DDSs) for the intravesical administration of drugs. By coupling the effectiveness of local treatments with major compliance and long-lasting performance, they would represent a promising innovation for the current treatment of bladder pathologies. Being based on a shape-memory pharmaceutical-grade polyvinyl alcohol (PVA), these DDSs are manufactured in a bulky shape, can be programmed to take on a collapsed one suitable for insertion into a catheter and re-expand inside the target organ, following exposure to biological fluids at body temperature, while releasing their content. The biocompatibility of prototypes made of PVAs of different molecular weight, either uncoated or coated with Eudragit®-based formulations, was assessed by excluding relevant in vitro toxicity and inflammatory response using bladder cancer and human monocytic cell lines. Moreover, the feasibility of a novel configuration was preliminarily investigated, targeting the development of prototypes provided with inner reservoirs to be filled with different drug-containing formulations. Samples entailing two cavities, filled during the printing process, were successfully fabricated and showed, in simulated urine at body temperature, potential for controlled release, while maintaining the ability to recover about 70% of their original shape within 3 min.

Risk analysis of open vs. robotic assisted radical cystectomy.

576 Background: Radical cystectomy (RC) is standard of care for muscle-invasive bladder cancer, but it comes with significant perioperative risk with half of patients experiencing major postoperative complications. Robot-assisted radical cystectomies (RARC) have aimed to decrease patient morbidity and have become increasingly adopted in North America. Currently, both open radical cystectomies (ORC) and RARC are frequently performed. To contribute to the existing literature using newly available data from the American College of Surgeons National Surgical Quality Improvement Project (NSQIP), representing one of the most recent, largest multi-institutional studies, while uniquely accounting for a variety of factors including type of urinary diversion, cancer staging, and neoadjuvant chemotherapy. Methods: RC procedures performed between 2019-2020 were identified in NSQIP and the corresponding Cystectomy Targeted database. Cases in the ORC group were planned open procedures, and cases in the RARC group were robotic with intra- or extracorporeal diversions, including unplanned conversion to open cases for intention-to-treat. Chi-square and t-tests were performed to compare baseline demographics and operative parameters. Multivariate analysis was performed for outcomes including major complications, minor complications, and 30-day mortality, while adjusting for operative approach, medical comorbidities, functional status, age, race, sex, BMI, ASA-classification, preoperative labs, type of urinary diversion, pathological staging, prior pelvic surgery or radiation, need for preoperative transfusion, preoperative sepsis, emergent or elective surgery, and recent chemotherapy. Results: 4,022 RC cases were identified. Of these, 3,146 (78.2%) received planned ORC while 876 (21.8%) received RARC. Baseline demographics of the patients who received ORC versus RARC were largely similar, with no significant difference in age or medical comorbidities. RARC was associated with longer operative times and shorter hospital length of stay compared to ORC. On multivariate analysis, ORC was associated with a higher rate of 30-day mortality [OR 3.1; 95% CI 1.3-7.2; p=0.009], reintubation, cardiac arrest, superficial wound infection, bleeding requiring transfusion [OR 4.7; 95%CI 3.6 - 6.1; p&lt;0.001], prolonged postoperative nasogastric tube use, rectal injury, and ureteral fistula or urine leak compared to RARC. Conclusions: In the NSQIP database, ORC is associated with higher rates of 30-day mortality and operative complications, most notably bleeding, compared to RARC. This study is unique in the size of the cohorts compared, the timeliness of the data (2019-2020), and the ability to control for factors, such as type of urinary diversion, pathological bladder cancer staging, and use of neoadjuvant chemotherapy.

Compound 48/80 increases murine bladder wall compliance independent of mast cells

A balance between stiffness and compliance is essential to normal bladder function, and changes in the mechanical properties of the bladder wall occur in many bladder pathologies. These changes are often associated with the release of basic secretagogues that in turn drive the release of inflammatory mediators from mast cells. Mast cell degranulation by basic secretagogues is thought to occur by activating an orphan receptor, Mas-related G protein-coupled receptor B2 (Mrgprb2). We explored the effects of the putative mast cell degranulator and Mrgprb2 agonist Compound 48/80 on urinary bladder wall mechanical compliance, smooth muscle contractility, and urodynamics, and if these effects were mast cell dependent. In wild-type mice, Mrgprb2 receptor mRNA was expressed in both the urothelium and smooth muscle layers. Intravesical instillation of Compound 48/80 decreased intermicturition interval and void volume, indicative of bladder overactivity. Compound 48/80 also increased bladder compliance while simultaneously increasing the amplitude and leading slope of transient pressure events during ex vivo filling and these effects were inhibited by the Mrgprb2 antagonist QWF. Surprisingly, all effects of Compound 48/80 persisted in mast cell-deficient mice, suggesting these effects were independent of mast cells. These findings suggest that Compound 48/80 degrades extracellular matrix and increases urinary bladder smooth muscle excitability through activation of Mrgprb2 receptors located outside of mast cells. Thus, the pharmacology and physiology of Mrgprb2 in the urinary bladder is of potential interest and importance in terms of treating lower urinary tract dysfunction.