Showing papers on "Urinary bladder published in 2019"

Urologic surgical pathology

Abstract: 1. Non-neoplastic Disease of the Kidney 2. Neoplasms of the Kidney, 3. Renal Pelvis and Ureter, 4. Fine needle aspiration of the kidney 5. Non-neoplastic Disorders of the Urinary Bladder, 6. Neoplasms of the Urinary Bladder, 7 Urine cytology 8. Non-neoplastic Diseases of the Prostate 9. Neoplasms of the Prostate, 10. Seminal Vesicles, 11. Urethra, 12. Non-neoplastic Diseases of the Testis, 13. Neoplasms of the Testis 14. Spermatic Cord and Testicular Adnexa 15. Penis and Scrotum 16. Adrenal Glands

Pathophysiology of interstitial cystitis.

Abstract: Interstitial cystitis/bladder pain syndrome is a chronic pain syndrome whose causes remains elusive with no generally accepted treatment. A hallmark of functional pain syndromes such as interstitial cystitis/bladder pain syndrome is pain in the absence of demonstrable pathology of the viscera or associated nerves. Patients with chronic pain experience a greater impairment in quality of life than healthy controls. In addition, interstitial cystitis/bladder pain syndrome symptoms can frequently overlap with other conditions including irritable bowel syndrome, fibromyalgia, chronic fatigue syndrome, anxiety disorders, and a number of other syndromes not directly related to the urinary bladder. Because of the complex pathophysiology, a number of animal models have been studied over the years to better understand mechanisms underlying patient symptoms. These models can include: bladder centric, complex mechanisms and psychological and physical stress models. Such animal models can aid in the investigation of aspects of interstitial cystitis/bladder pain syndrome that cannot be pursued in humans as well as to develop and test potential therapies. In addition, the search for urinary factors that may be a cause of interstitial cystitis/bladder pain syndrome has resulted in the discovery of a number of potential targets that could serve as predictive biomarkers which can aid in early diagnosis and treatment of this chronic disorder.

The Current Evidence on the Association Between the Urinary Microbiome and Urinary Incontinence in Women.

Abstract: Urinary incontinence (UI) is a burdensome condition with high prevalence in middle-aged to older women and an unclear etiology. Advances in our understanding of host-microbe interactions in the urogenital tract have stimulated interest in the urinary microbiome. DNA sequencing and enhanced urine culture suggest that similarly to other mucosal sites, the urinary bladder of healthy individuals harbors resident microbial communities that may play distinct roles in bladder function. This review focused on the urobiome (expanded quantitative urine culture-based or genomic sequencing-based urinary microbiome) associated with different subtypes of UI, including stress, urgency and mixed urinary incontinence, and related syndromes, such as interstitial cystitis and overactive bladder in women, contrasted to urinary tract infections. Furthermore, we examined clinical evidence for the association of the urinary microbiome with responses to pharmacotherapy for amelioration of UI symptoms. Although published studies are still relatively limited in number, study design and sample size, cumulative evidence suggests that certain Lactobacillus species may play a role in maintaining a healthy bladder milieu. Higher bacterial diversity in the absence of Lactobacillus dominance was associated with urgency UI and resistance to anticholinergic treatment for this condition. UI may also facilitate the persistence of uropathogens following antibiotic treatment, which in turn can alter the commensal/potentially beneficial microbial communities. Risk factors of UI, including age, menopausal status, sex steroid hormones, and body mass index may also impact the urinary microbiome. However, it is yet unclear whether the effects of these risks factors on UI are mediated by urinary host-microbe interactions and a mechanistic link with the female urogenital microbiome is still to be established. Strategies for future research are suggested.

Update of the International Consultation on Urological Diseases on bladder cancer 2018: non-urothelial cancers of the urinary bladder.

Abstract: To provide a comprehensive update of the joint consultation of the International Consultation on Urological Diseases (ICUD) for the diagnosis and management of non-urothelial cancer of the urinary bladder. A detailed analysis of the literature was conducted reporting on the epidemiology, etiology, diagnosis, treatment and outcomes of non-urothelial cancer of the urinary bladder. An international, multidisciplinary expert committee evaluated and graded the evidence according to the Oxford System of Evidence-based Medicine modified by the ICUD. The major non-urothelial cancers of the urinary bladder are squamous cell carcinoma, adenocarcinoma, and neuroendocrine tumors. Several other non-urothelial tumors are rare but important to identify because of their aggressive behavior when compared to urothelial bladder tumors. Radical cystectomy and urinary diversion, preceded by neoadjuvant radiation or chemotherapy in some of these tumors, is the main method or treatment for resectable disease. Adjuvant therapy is not usually successful and no novel targeted or immunotherapeutic agents have been identified to provide benefit. Patients with small cell neuroendocrine tumors of the bladder should be offered chemotherapy before surgery. Because non-urothelial cancers are usually locally advanced and/or metastatic at the time of diagnosis, 5-year survival is generally poor. Non-urothelial cancers of the urinary bladder are rare and mostly lack established protocols for treatment. The prognosis of most of these tumors is poor because they are usually advanced at the time of diagnosis. A multimodal treatment approach should be considered to improve outcomes.

β3 -Adrenoceptors in the normal and diseased urinary bladder-What are the open questions?

Abstract: β3 -Adrenoceptor agonists are used in the treatment of overactive bladder syndrome. Although the relaxant response to adrenergic stimulation in human detrusor smooth muscle cells is mediated mainly via β3 -adrenoceptors, the plasma concentrations of the therapeutic dose of mirabegron, the only clinically approved β3 -adrenoceptor agonist, are considerably lower than the EC50 for causing direct relaxation of human detrusor, suggesting a mechanism of action other than direct relaxation of detrusor smooth muscle. However, the site and mechanism of action of β3 -adrenoceptor agonists in the bladder have not been firmly established. Postulated mechanisms include prejunctional suppression of ACh release from the parasympathetic nerves during the storage phase and inhibition of micro-contractions through β3 -adrenoceptors on detrusor smooth muscle cells or suburothelial interstitial cells. Implications of possible desensitization of β3 -adrenoceptors in the bladder upon prolonged agonist exposure and possible causes of rarely observed cardiovascular effects of mirabegron are also discussed. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.

Inhibition of stearoyl CoA desaturase-1 activity suppresses tumour progression and improves prognosis in human bladder cancer

Abstract: Urinary bladder neoplasm is one of the most common cancers worldwide. Cancer stem cells (CSCs) have been proven to be an important cause of cancer progression and poor prognosis. In the present study, we established bladder CSCs and identified the crucial differentially expressed genes (DEGs) between these cells and parental bladder cancer cells. Analyses of bioinformatics data and clinical samples from local hospitals showed that stearoyl CoA desaturase-1 (SCD) was the key factor among the DEGs. A significant correlation between SCD gene expression and poor prognosis among patients with bladder cancer was observed in our data. Loss-of-function experiments further revealed that the SCD inhibitor A939572 and SCD gene interference reduced cell proliferation and invasion. The above data suggest that SCD may serve as a novel marker for the prediction of tumour progression and poor prognosis in patients with bladder cancer.

Congenital Disorders of the Human Urinary Tract: Recent Insights From Genetic and Molecular Studies

Abstract: The urinary tract comprises the renal pelvis, the ureter, the urinary bladder, and the urethra. The tract acts as a functional unit, first propelling urine from the kidney to the bladder, then storing it at low pressure inside the bladder which intermittently and completely voids urine through the urethra. Congenital diseases of these structures can lead to a range of diseases sometimes associated with fetal losses or kidney failure in childhood and later in life. In some of these disorders, parts of the urinary tract are severely malformed. In other cases, the organs appear grossly intact yet they have functional deficits that compromise health. Human studies are beginning to indicate monogenic causes for some of these diseases. Here, the implicated genes can encode smooth muscle, neural or urothelial molecules, or transcription factors that regulate their expression. Furthermore, certain animal models are informative about how such molecules control the development and functional differentiation of the urinary tract. In future, novel therapies, including those based on gene transfer and stem cell technologies, may be used to treat these diseases to complement conventional pharmacological and surgical clinical therapies.

Non‐urothelial carcinomas of the bladder

Abstract: Non-urothelial carcinomas involving the bladder are uncommon and often diagnostically challenging. These carcinomas may show squamous, adenocarcinomatous or neuroendocrine features, with immunohistochemical stains aiding the diagnosis in only a subset of cases. The clinical history in non-urothelial bladder carcinomas is important, given that the differential diagnosis often includes secondary involvement of the bladder by direct extension or metastasis from carcinomas at other sites. This paper will review non-urothelial carcinomas in each of these three morphological categories, emphasising recent changes in diagnostic grouping and challenges in the histopathological diagnosis. Review of bladder cancers with squamous morphology will include discussion of conventional squamous cell carcinoma and verrucous carcinoma and their distinction from urothelial carcinoma with extensive squamous differentiation. Bladder carcinomas with adenocarcinomatous change will include primary bladder adenocarcinoma, urachal adenocarcinoma and tumours of Mullerian type. Finally, neuroendocrine neoplasms of the bladder, including well-differentiated neuroendocrine tumour and neuroendocrine carcinomas, will be discussed. Associated surface findings, risk factors and prognostic features will be described.

Real-Time Bladder Pressure Estimation for Closed-Loop Control in a Detrusor Overactivity Model

Abstract: Overactive bladder (OAB) patients suffer from a frequent urge to urinate, which can lead to a poor quality of life. Current neurostimulation therapy uses open-loop electrical stimulation to alleviate symptoms. Continuous stimulation facilitates habituation of neural pathways and consumes battery power. Sensory feedback-based closed-loop stimulation may offer greater clinical benefit by driving bladder relaxation only when bladder contractions are detected, leading to increased bladder capacity. Effective delivery of such sensory feedback, particularly in real-time, is necessary to accomplish this goal. We implemented a Kalman filter-based model to estimate bladder pressure in real-time using unsorted neural recordings from sacral-level dorsal root ganglia, achieving a 0.88 ± 0.16 correlation coefficient fit across 35 normal and simulated OAB bladder fills in five experiments. We also demonstrated closed-loop neuromodulation using the estimated pressure to trigger pudendal nerve stimulation, which increased bladder capacity by 40% in two trials. An offline analysis indicated that unsorted neural signals had a similar stability over time as compared to sorted single units, which would require a higher computational load. We believe this paper demonstrates the utility of decoding bladder pressure from neural activity for closed-loop control; however, real-time validation during behavioral studies is necessary prior to clinical translation.

Directed differentiation of human induced pluripotent stem cells into mature stratified bladder urothelium.

Abstract: For augmentation or reconstruction of urinary bladder after cystectomy, bladder urothelium derived from human induced pluripotent stem cells (hiPSCs) has recently received focus. However, previous studies have only shown the emergence of cells expressing some urothelial markers among derivatives of hiPSCs, and no report has demonstrated the stratified structure, which is a particularly important attribute of the barrier function of mature bladder urothelium. In present study, we developed a method for the directed differentiation of hiPSCs into mature stratified bladder urothelium. The caudal hindgut, from which the bladder urothelium develops, was predominantly induced via the high-dose administration of CHIR99021 during definitive endoderm induction, and this treatment subsequently increased the expressions of uroplakins. Terminal differentiation, characterized by the increased expression of uroplakins, CK13, and CK20, was induced with the combination of Troglitazone + PD153035. FGF10 enhanced the expression of uroplakins and the stratification of the epithelium, and the transwell culture system further enhanced such stratification. Furthermore, the barrier function of our urothelium was demonstrated by a permeability assay using FITC-dextran. According to an immunohistological analysis, the stratified uroplakin II-positive epithelium was observed in the transwells. This method might be useful in the field of regenerative medicine of the bladder.

Assessment of HER2 Expression in Canine Urothelial Carcinoma of the Urinary Bladder

Abstract: Canine urothelial carcinoma (UC) has a poor prognosis and high metastatic rate. Human epidermal growth factor receptor 2 (HER2), a receptor tyrosine kinase involved in cell proliferation and differentiation regulation, has been attracting interest as a therapeutic target molecule for human breast cancer. This study investigated expression of the canine homolog of HER2 (ERBB2) in canine UC, and its association with clinical factors. Since it has been controversial whether commercial anti-human HER2 antibody (Dako A0485) correctly recognizes the canine homolog of HER2, an application of the antibody using a canine UC cell line was validated first. By Western blot, a single band at the appropriate size for canine HER2 (185 kDa) was recognized. Immunohistochemistry for HER2 was performed on 23 samples of UC, 8 samples of polypoid cystitis, and 8 samples of normal urinary bladder, and the results were scored as either 0, 1+, 2+, or 3+ with reference to the evaluation method for human UC. Intense membranous HER2 immunoreactivity was frequently observed in neoplastic cells, especially in grade 2 UC. Minor HER2 expression was found in the epithelial cells of polypoid cystitis and normal bladder. The incidence of HER2 positivity (scores of 2+ or 3+) was 14 of 23 (60.9%) in UC, 3 of 8 (37.5%) in polypoid cystitis, and 0 of 8 (0%) in normal bladder. There was no significant correlation between HER2 positivity and clinical factors. While increased HER2 expression was observed in a subset of urothelial carcinomas, further mechanistic studies are needed to determine its role in the pathogenesis and targeted therapy of this cancer.

Effects of varying degrees of partial bladder outlet obstruction on urinary bladder function of rats: A novel link to inflammation, oxidative stress and hypoxia.

Abstract: OBJECTIVES The aim of the present study was to investigate the effects of different degrees of obstruction, and the roles of inflammation, oxidative stress, and hypoxia parameters on bladder function. METHODS Thirty male Sprague-Dawley rats were divided into 3 groups (n = 10 in each group): (i) sham-operated control; (ii) severe partial bladder outlet obstruction (PBOO); and (iii) moderate PBOO. Severe and moderate PBOO were induced by urethral ligation using 3-Fr and 4-Fr catheters, respectively, for 6 weeks. After 6 weeks, the in vitro contractile responses to carbachol, electrical field stimulation, ATP and KCl were measured in bladder strips. In addition, mRNA and protein expression of nuclear factor kappa B (NF-κB) hypoxia-inducible factor (HIF) and nuclear factor, erythroid 2-like 2 (Nrf2) in bladder were determined by real-time polymerase chain reaction and western blotting. Malondialdehyde (MDA) levels in bladder tissues were also determined. RESULTS Rats in the severe PBOO group had the highest bladder weight. Detrusor strips from rats in the severe PBOO group exhibited 61%-82% smaller contractile responses to all four stimuli than those from the sham-operated group. Activity of NF-κB as an inflammatory marker was increased in the severe PBOO group, whereas HIF-1α and HIF-2β protein levels were increased significantly in the moderate PBOO group. A master regulator of oxidative stress, Nrf2 expression was increased in all obstructed rats. MDA levels were higher in the severe PBOO group than in sham-operated group. CONCLUSION The results of the present study reveal the importance of oxidative stress-induced NF-κB signaling in bladder dysfunction with severe obstruction. Altered HIF signaling may contribute to the functional impairment after PBOO. Novel and evolving therapies targeting oxidative and/or inflammatory pathways may be a reasonable strategy for the management of lower urinary tract symptoms or benign prostatic hyperplasia.

Mesh erosion into urinary bladder, rare condition but important to know.

Abstract: Although rare, mesh migration or erosion into viscera has been reported as case report, and most of the cases involved with the urinary bladder. With the increasing use of prosthetic mesh in hernia repair, this severe complication would increase in the future; thus, we feel that it is necessary to analyze the clinical patterns of mesh erosion into the urinary bladder, and to discuss the prevention and treatment of this severe complication. In the present study, we made a thorough identification of all published reports on mesh migration or erosion into the urinary bladder, and the data were summarized, analysed, and discussed. A total of 23 cases of mesh erosion into urinary bladder were reported since 1994. Among them, two cases were from incisional hernia repairs, and 21 cases were following inguinal hernia repairs. The most frequently reported procedures were TAPP, followed by TEP. The duration from initial hernia repair to the onset of mesh erosion into bladder varied greatly (3 months–20 years), and most of cases occurred in 1–5 years after the initial hernia repair (10/23, 43.5%), while a certain number of cases occurred 10 years after hernia repair (6/23, 26.1%). Most of these cases were treated with mesh removal via a open procedure (12/22, 54.5%), and in 7 cases (7/22, 31.8%), the partial cystectomy was performed as well as mesh removal. Laparoscopic or robotic treatment procedures were performed in three cases. Mesh erosion into the urinary bladder can occur after both open and laparoscopic inguinal hernia repairs in a wide range of duration. This complication most frequently happened following laparoscopic inguinal hernia repair. It was usually treated with partial or complete mesh removal, with or without partial cystectomy. A registry system is necessary for monitoring this complication.

Biodistribution and post-therapy dosimetric analysis of [177Lu]Lu-DOTAZOL in patients with osteoblastic metastases: first results.

Abstract: Preclinical biodistribution and dosimetric analysis of [177Lu]Lu-DOTAZOL suggest the bisphosphonate zoledronate as a promising new radiopharmaceutical for therapy of bone metastases. We evaluated biodistribution and normal organ absorbed doses resulting from therapeutic doses of [177Lu]Lu-DOTAZOL in patients with metastatic skeletal disease. Four patients with metastatic skeletal disease (age range, 64–83 years) secondary to metastatic castration-resistant prostate carcinoma or bronchial carcinoma were treated with a mean dose of 5968 ± 64 MBq (161.3 mCi) of [177Lu]Lu-DOTAZOL. Biodistribution was assessed with serial planar whole body scintigraphy at 20 min and 3, 24, and 167 h post injection (p.i.) and blood samples at 20 min and 3, 8, 24, and 167 h p.i. Percent of injected activity in the blood, kidneys, urinary bladder, skeleton, and whole body was determined. Bone marrow self-dose was determined by an indirect blood-based method. Urinary bladder wall residence time was calculated using Cloutier’s dynamic urinary bladder model with a 4-h voiding interval. OLINDA/EXM version 2.0 (Hermes Medical Solutions, Stockholm, Sweden) software was used to determine residence times in source organs by applying biexponential curve fitting and to calculate organ absorbed dose. Qualitative biodistribution analysis revealed early and high uptake of [177Lu]Lu-DOTAZOL in the kidneys with fast clearance showing minimal activity by 24 h p.i. Activity in the skeleton increased gradually over time. Mean residence times were found to be highest in the skeleton followed by the kidneys. Highest mean organ absorbed dose was 3.33 mSv/MBq for osteogenic cells followed by kidneys (0.490 mSv/MBq), red marrow (0.461 mSv/MBq), and urinary bladder wall (0.322 mSv/MBq). The biodistribution and normal organ absorbed doses of [177Lu]Lu-DOTAZOL are consistent with preclinical data. [177Lu]Lu-DOTAZOL shows maximum absorbed doses in bone and low kidney doses, making it a promising agent for radionuclide therapy of bone metastasis. Further studies are warranted to evaluate the efficacy and safety of radionuclide therapy with [177Lu]Lu-DOTAZOL in the clinical setting.

Dual benefit of supplementary oral 5‐aminolevulinic acid to pelvic radiotherapy in a syngenic prostate cancer model

Abstract: Background Normal tissue damage caused by radiotherapy remains the largest dose-limiting factor in radiotherapy for cancer. Therefore, the aim of this study was to investigate the supplementary oral 5-aminolevulinic acid (ALA) to standard radiation therapy as a novel radioprotective approach that would not compromise the antitumor effect of radiation in normal rectal and bladder mucosa in a syngenic prostate cancer (PCa) model. Methods To evaluate the radiosensitizing effect of ALA in vitro, clonogenic survival assays were performed in DU145, PC3, and MyC-CaP cell lines. To evaluate the effect of ALA in vivo a single dose (25 Gy) of radiation with or without ALA was given to healthy mice. Next, a syngenic PCa model of MyC-CaP cells in FVB mice was created, and multiple doses (12 Gy total) of radiation were administered to the mouse pelvic area with or without ALA administration. Resected tumors, recta, and urinary bladders were immunostained with antibodies against Ki-67, γ-H2AX, CD204, and uroplakin-III. Total RNA levels in recta and urinary bladders were analyzed via RT2 Profiler polymerase chain reaction (PCR) arrays related to "Stress & Toxicity PathwayFinder," "Mitochondria," and "Inflammasomes." Results The addition of in vitro single or in vivo repeated administration of exogenous ALA acted as a radiosensitizer for PCa cells. Rectal toxicity was characterized by histological changes including loss of surface epithelium, fibrosis, severe DNA damage, and the aggregation of M2 macrophages. Urinary bladder toxicity was characterized by bladder wall thickening and urothelium denuding. The higher dose (300 mg/kg/day) of ALA exerted a better radioprotective profile than the lower dose (30 mg/kg/day) in normal recta and urinary bladders. Out of the 252 genes tested, 35 (13.4%) were detected as relevant genes which may be involved in the radioprotective role of ALA administration. These included interleukin-1a (IL-1a), IL-1b, IL-12, chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL3, and NLRP3. Conclusions Our study provides novel and comprehensive insights into the dual benefits including radiosensitizing PCa tumor tissues and radioprotection of normal pelvic organs from radiation therapy. Knowledge of the underlying mechanism will facilitate the search for optimal treatment parameters for supplemental oral ALA during radiotherapy for PCa.

Bladder Augmentation (Enterocystoplasty): the Current State of a Historic Operation.

Abstract: The goal of this paper was to evaluate the current use of enterocystoplasty, a historical operation for bladder dysfunction but with continued and increasing modern relevance. Since the advent of third line neuromodulation techniques for neurogenic and idiopathic overactive bladder (OAB), the usage of enterocystoplasty has decreased. However, this procedure continues to be utilized in pediatric urology patients and the most refractory OAB patients. Adult urologist should be familiar with this operative technique in an effort to manage pediatric patients transitioning to adulthood. Minimally invasive techniques for this surgical procedure have been described with very limited outcome data. It is important for all urologists to be familiar with enterocystoplasty, both technically and with the unique needs of these patients postoperatively. Further studies evaluating the outcomes of this procedure in idiopathic overactive bladder patients and efforts to standardize recommendations for neurogenic bladder patients will help guide care in the future.