Multiparametric MRI Combined with Apparent Diffusion Coefficient Histogram Analysis for Assessing Variant Histology in Urothelial Carcinoma / 中山大学学报(医学科学版)

ObjectiveTo investigate the feasibility of multiparametric MRI （mpMRI） combined with histogram analysis of apparent diffusion coefficient （ADC） in the assessment of patients with variant histology （VH） of urothelial carcinoma （UC）. MethodWe retrospectively analyzed the data of patients pathologically diagnosed with UC who underwent mpMRI in the First Affiliated Hospital of Sun Yat-sen University between March 2015 and March 2023. The patients were divided into VH group （urothelial carcinoma mixed with other histologies） and non-VH group （pure urothelial carcinoma） according to pathological results. We performed propensity score 1：1 nearest-neighbor matching on the two groups based on age and gender and 49 patients were included in each group. The regions of interest （ROIs） of the whole tumor were delineated manually by using ITK-SNAP software and Pyradiomics was applied to extract ADC histogram parameters. We compared the clinicopathological data， MRI morphological features and ADC histogram parameters between the groups. Multivariate logistic regression was used to identify independent risk factors and construct the prediction model. Receiver operating characteristic （ROC） curve analyses were performed to evaluate the diagnostic performance of these parameters for determining VH of UC. ResultsMRI morphological features including the lesion shape， vesical imaging-reporting and data system （Ⅵ-RADS）score， enhancement pattern and suspicious lymph node metastasis were markedly different between the two groups （all P < 0.05）. ADC mean， ADC median， ADC25th， ADC75th， ADC10th and ADC90th were significantly lower in patients with VH than those in non-VH group （all P<0.05）. Multivariate logistic regression analysis showed enhancement pattern， ADC25th， ADC75th and ADC mean were independent predictors （P < 0.05）. The combined model yielded the best predictive performance， with an area under the ROC curve （AUC） of 0.91 （95% CI： 0.83-0.96）. ConclusionsMpMRI combined with whole-tumor histogram analysis of ADC can serve as a reliable method for evaluating the presence of VH in UC， further to assist the clinical decision making.

Tabaquismo y tumores mayores de 2 centímetros son predictores de mortalidad en pacientes sometidos a nefro-ureterectomías por carcinoma de urotelio alto / Prognostic factors in patients with upper urinary tract urothelial carcinoma undergoing nephro-ureterectomy

BACKGROUND: Upper urinary tract urothelial carcinoma (UTUC) represents 5-10% of urothelial carcinomas. It is managed with nephroureterectomy (NUR); however, kidney-sparing techniques are growingly used. AIM: To report the results of a 20-year series of NUR conducted in an academic center. Patients and Methods: Review of clinical and pathological characteristics of patients undergoing NUR between 1999 and 2020. Patients were followed for 63 months. Global survival curves (OS) and mortality predictors were established through Cox regression. RESULTS: We included 90 patients with a median age of 68 years undergoing NUR, of whom 68 (75%) had a pelvic tumor and 22 (25%) had a proximal ureteral tumor. A laparoscopic NUR was performed in 60 patients (66%). Thirty-three patients (37%) had tumors confined to the urothelium (pTa), penetrating the lamina propria (pT1) or carcinoma in situ (CIS), 10 patients (11%) had a tumor spreading to the muscle layer (pT2) and 47 (52%) had a tumor spreading to nearby organs (pT3 / T4). Average tumor size was 3.69 cm, nodal disease (pN) was present 12 patients (13%). Twelve patients (13%) received adjuvant chemotherapy. A higher mortality was observed among smokers (Hazard ratio (HR) 8.79, 95% confidence intervals (CI) 1.5-49.0, p = 0.01), patients with tumors classfied as pT≥ 2 (HR 1.09, 95% CI 0.01-1.0, p = 0.04) and those with tumors larger than 2 cm (HR 14.79, CI 95% 1.5-272, p = 0.01). CONCLUSIONS: Smoking patients, those with invasive tumors (T2-T4) and greater than 2 cm have higher mortality. Therefore, they should not be candidates for conservative management.

Ample dietary fat reduced the risk of primary vesical calculi by inducing macrophages to engulf budding crystals in mice

Although primary vesical calculi is an ancient disease, the mechanism of calculi formation remains unclear. In this study, we established a novel primary vesical calculi model with d,l-choline tartrate in mice. Compared with commonly used melamine and ethylene glycol models, our model was the only approach that induced vesical calculi without causing kidney injury. Previous studies suggest that proteins in the daily diet are the main contributors to the prevention of vesical calculi, yet the effect of fat is overlooked. To assay the relationship of dietary fat with the formation of primary vesical calculi, d,l-choline tartrate-treated mice were fed a high-fat, low-fat, or normal-fat diet. Genetic changes in the mouse bladder were detected with transcriptome analysis. A high-fat diet remarkably reduced the morbidity of primary vesical calculi. Higher fatty acid levels in serum and urine were observed in the high-fat diet group, and more intact epithelia in bladder were observed in the same group compared with the normal- and low-fat diet groups, suggesting the protective effect of fatty acids on bladder epithelia to maintain its normal histological structure. Transcriptome analysis revealed that the macrophage differentiation-related gene C-X-C motif chemokine ligand 14 (Cxcl14) was upregulated in the bladders of high-fat diet-fed mice compared with those of normal- or low-fat diet-fed mice, which was consistent with histological observations. The expression of CXCL14 significantly increased in the bladder in the high-fat diet group. CXCL14 enhanced the recruitment of macrophages to the crystal nucleus and induced the transformation of M2 macrophages, which led to phagocytosis of budding crystals and prevented accumulation of calculi. In human bladder epithelia (HCV-29) cells, high fatty acid supplementation significantly increased the expression of CXCL14. Dietary fat is essential for the maintenance of physiological functions of the bladder and for the prevention of primary vesical calculi, which provides new ideas for the reduction of morbidity of primary vesical calculi.

Carcinoma urotelial: presentación de un caso / Urothelial carcinoma: a case report

RESUMEN Fundamento: los tumores del urotelio se originan a partir del epitelio de revestimiento mucoso de tipo transicional y constituyen la casi totalidad de los tumores de las vías excretoras, altos. El adenocarcinoma primario de las vías urinarias, son extremadamente infrecuentes y suelen tener un comportamiento agresivo, con un pronóstico sombrío. Objetivo: exponer la forma de presentación de un paciente con carcinoma urotelial mostrando algunas características de los mismos. Presentación de caso: paciente masculino de 70 años de edad, jubilado, fumador inveterado y con antecedentes de ingerir café en grandes cantidades, acudió a consulta por hematuria macroscópica, dolor lumbar, a veces fijo, otras veces en forma de cólicos ureterales y fiebre de 39 grados. El estudio analítico solo mostró velocidad de deshidrogenasa láctica alterada. El estudio imagenológico con ecografía mostró hidronefrosis e ilio derecho agrandado con imagen heterogénea de 2 cm en el riñón, a nivel de la unión uretero pélvica, lo cual fue corroborado por la tomografía axial computarizada. El resto de los exámenes como endoscopia, colonoscopía, cistoscopia y de diferentes regiones fueron todos negativos. Se practicó nefroureterectomía derecha, encontrándose el paciente asintomático. Conclusiones: los tumores del urotelio superior son neoplasias infrecuentes, en las vías urinarias se debe descartar un origen extraurológicos. El diagnóstico diferencial debe de realizarse con el tumor de células renales o el de vejiga.

ABSTRACT Background: the urothelial carcinomas originate from the epithelium of mucous revetment of transitional type and constitute almost totality of the tumors of the excretory, high routes. The primary adenocarcinoma of the urinary tract, are extremely infrequent and they usually have an aggressive behavior, with a shaded prognosis. Objective: to express the way of presenting a patient with urothelial carcinoma showing some aspects from the sicknesses. Case report: a 70-years-old male patient, retired, inveterate smoker and with a history of ingesting coffee in large quantities, attended consultation for gross hematuria, lumbar pain, sometimes fixed, other times in the form of ureteral colic and fever of 39 degrees. The analytical study only showed altered lactic dehydrogenase rate. The imaging study with ultrasound showed hydronephrosis and enlarged right ilium with heterogeneous image of 2 cm in the kidney, at the level of the pelvic ureter junction, which was corroborated by computerized axial tomography. The rest of the examinations such as endoscopy, colonoscopy, and cystoscopy of different regions were all negative. Right nephroureterectomy was performed, and the patient is still asymptomatic. Conclusions: the tumors of the upper urothelium are infrequent neoplasias, in the urinary tract an extraurological origin must be ruled out. The differential diagnosis must be made with the renal cell tumor or the bladder tumor.

Urine-derived stem cells differentiate into urothelial cells and smooth muscle cells in vitro / 中国组织工程研究

BACKGROUND: Adult stem cells are pluripotent stem cells that exist in differentiated tissues. Urine-derived stem cells are newly discovered adult stem cells. They have attracted increasing attentions in the tissue engineering, due to its advantages of convenient sampling, highly proliferative ability and multidirectional differentiation potential. OBJECTIVE: To investigate the separation and extraction method of urine-derived stem cells and to investigate the feasibility of differentiation into urothelial cells and smooth muscle cells in vitro. METHODS: Urine specimens were collected from healthy adults, and urine-derived stem cells were obtained by isolation and culture in vitro. Cell counting kit-8 assay was used to detect cell proliferation and plot cell growth curve. Cell phenotype was detected by flow cytometry. The differentiation into urothelial and smooth muscle cells was induced by special medium respectively in vitro. The cell differentiation was detected by quantitative PCR, immunohistochemical staining, immunofluorescence cell staining and western blot assay. RESULTS AND CONCLUSION: Urine-derived stem cells were successfully isolated from the urine specimens of healthy adults. Urine-derived stem cells possessed high proliferation rate and the cell growth curve exhibited an S-shape. Urine-derived stem cells exhibited high expression of CD29 (98.11%) and CD90 (95.74%), both of which are mesenchymal stem cell surface markers. After 14 days of induction in vitro, urine-derived stem cells were able to express urothelial cell specific genes Cytokeratin 7, Cytokeratin 20, Uroplakin II and smooth muscle cell specific genes α-SMA and SM22. These results suggest that urine-derived stem cells can differentiate into urothelial cells and smooth muscle cells after induction in vitro and can be used as ideal seed cells for urinary tract tissue engineering.

Feline Interstitial Cystitis Enhances Mucosa-Dependent Contractile Responses to Serotonin / 대한배뇨장애요실금학회지

PURPOSE: To determine whether responses to serotonin are altered in bladder strips from cats diagnosed with a naturally occurring form of bladder pain syndrome/interstitial cystitis termed feline interstitial cystitis (FIC). METHODS: Full thickness bladder strips were isolated from aged matched healthy control cats and cats with clinically verified FIC. Bladder strips were mounted in an organ bath and connected to a tension transducer to record contractile activity. A serotonin dose response (0.01–10μM) was determined for each strip with the mucosa intact or denuded. RESULTS: Bladder strips from control and FIC cats contracted in response to serotonin in a dose-dependent manner. The normalized force of serotonin-evoked contractions was significantly greater in bladder strips from cats with FIC (n=7) than from control cats (n=4). Removal of the mucosa significantly decreased serotonin-mediated responses in both control and FIC bladder preparations. Furthermore, the contractions in response to serotonin were abolished by 1μM atropine in both control and FIC bladder strips. CONCLUSIONS: The effect of serotonin on contractile force, but not sensitivity, was potentiated in bladder strips from cats with FIC, and was dependent upon the presence of the mucosa in control and FIC groups. As atropine inhibited these effects of serotonin, we hypothesize that, serotonin enhances acetylcholine release from the mucosa of FIC cat bladder strips, which could account for the increased force generated. In summary, FIC augments the responsiveness of bladder to serotonin, which may contribute to the symptoms associated with this chronic condition.

On the Site and Mechanism of Action of β₃-Adrenoceptor Agonists in the Bladder / 대한배뇨장애요실금학회지

The clinical success of mirabegron as the first β₃-adrenoceptor (AR) agonist for treatment of the overactive bladder (OAB) syndrome, has resulted in substantial interest in its site and mechanism of action. Even if the adrenergic innervation of the bladder and urethra has been well studied, the location(s) of β₃-ARs in different structures within the bladder wall and urethra, and the mode(s) of action of β₃-AR stimulation have still not been established. The recent demonstration of β₃-ARs on cholinergic nerve terminals with no immunoreactivity in urothelium or detrusor smooth muscle, is not in agreement with previous morphological studies, and functional data strongly suggest that β₃-ARs can be found these structures. However, recent studies suggest that the β₃-ARs on detrusor smooth muscle may not be the functionally most relevant. The assumption that β₃-AR activation during bladder filling inhibits acetylcholine release from parasympathetic neurons by a prejunctional mechanism and that this decreases bladder micromotions that generate afferent activity, is an attractive hypothesis. It does not exclude that other mechanisms may be contributing, and supports combined approaches to reduce afferent activity for treatment of the OAB syndrome.

Abnormal Sensory Protein Expression and Urothelial Dysfunction in Ketamine-Related Cystitis in Humans / 대한배뇨장애요실금학회지

PURPOSE: The aim of this study was to analyze patterns of sensory protein expression and urothelial dysfunction in ketamine-related cystitis (KC) in humans. METHODS: Biopsies of bladder mucosa were performed in 29 KC patients during cystoscopy. Then specimens were analyzed for tryptase, zonula occludens-1 (ZO-1), E-cadherin, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) with immunofluorescence staining and quantification. In addition, 10 healthy control bladder specimens were analyzed and compared with the KC specimens. Another 16 whole bladder specimens obtained from partial cystectomy were also analyzed for the muscarinic receptors M2 and M3, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), β-3 adrenergic receptors (β3-ARs), and the P2X₃ receptor by western blotting. In addition, 3 normal control bladder specimens were analyzed and compared with the KC specimens. RESULTS: The KC bladder mucosa revealed significantly less expression of ZO-1 and E-cadherin, and greater expression of TUNEL and tryptase activity than the control samples. The expression of M3 and β3-AR in the KC specimens was significantly greater than in the controls. The expression of iNOS, eNOS, M2, and P2X3 was not significantly different between the KC and control specimens. CONCLUSIONS: The bladder tissue of KC patients revealed significant urothelial dysfunction, which was associated with mast-cell mediated inflammation, increased urothelial cell apoptosis, and increased expression of the M3 and β3-AR.

Impaired Na+/K+-ATPase Function in Patients with Interstitial Cystitis/Painful Bladder Syndrome

Na+/K+-ATPase (NKA) is abundantly expressed in the basolateral membrane of epithelial cells, which is necessary for tight junction formation. The tight junction is an urothelial barrier between urine and the underlying bladder. Impairment of tight junctions allows migration of urinary solutes in patients with interstitial cystitis/painful bladder syndrome (IC/PBS). We evaluated NKA expression and activity in bladder samples from patients with IC/PBS. The study group consisted of 85 patients with IC/PBS, and the control group consisted of 20 volunteers. Bladder biopsies were taken from both groups. We determined the expression and distribution of NKA using NKA activity assays, immunoblotting, immunohistochemical staining, and immunofluorescent staining. The protein levels and activity of NKA in the study group were significantly lower than the control group (1.08 ± 0.06 vs. 2.39 ± 0.29 and 0.60 ± 0.04 vs. 1.81 ± 0.18 micromol ADP/mg protein/hour, respectively; P < 0.05). Additionally, immunofluorescent staining for detection of CK7, a marker of the bladder urothelium, predominantly colocalized with NKA in patients in the study group. Our results demonstrated the expression and activity of NKA were decreased in bladder biopsies of patients with IC/PBS. These findings suggest that NKA function is impaired in the bladders from patients with IC/PBS.

Clinicopathologic features of nephreogenic metaplasia in urologic tract: a report of 6 cases / 临床与实验病理学杂志

Purpose To investigate the clinicopathologic and immunohistochemical features,and differential diagnosis of nephrogenic metaplasia (NM).Methods The clinical data,histological and immunohistochemical characteristics of 6 cases of NM were analyzed,with review of the literature.Results There were 1 case of female,5 cases of male,aged from 31 to 81 years,with average of 58.1 years.The history revealed lithiasis of urologic tact in 2 cases,previous transurethral resection for benign prostatic hyperplasia or cystitis glandularis in 3 cases,and concurrent urothelial carcinoma in 1 case.The lesion involved in the ureter in 3 cases,prostatic urethra in 2 cases,and bladder trigone in 1 case.Cystoscopic examination demonstrated mucosal rough or low villous protrude.Microscopically,the lesion was consisted of tubules,cysts,small nests and papillary structures with basement membrane-like eosinophilic sheath,and lined by cuboidal,or low column epithelial cells with cytological atypia in some area,and shown inflammation in stroma.Immunohistochemically,there was positive staining for PAX2,PAX8,CK7 and P504S,negative for p63,CD10,and PSA.Conclusion NM is a rare tumor-like lesion often with injure of urologic tract,and should be differential with urothelial carcinoma,prostatic carcinoma,clear cell adenocarcinoma and endometriosis.It's important to know the clinicopathological and immunohistochemical features of NM for the correct interpretation.

Sphingosine Kinase 1 urothelial expression is increased in patients with neurogenic detrusor overactivity

Objectives: To evaluate the expression of sphingosine kinase 1 (SPK1) in the bladder wall in patients with neurogenic lower urinary tract dysfunction and its association with clinical, urodynamic and pathological features. Materials and Methods: The expression of SPK1 was studied in bladder wall specimens obtained from cystectomy using immunohistochemistry in ten patients with spinal cord injury (n=8) or multiple sclerosis (n=2) with urodynamically proven neuropathic bladder dysfunction, and in controls (n=5). Inflammation and fibrosis were analysed with histological criteria and SPK1 expression was determined by individual immunohistochemical staining. Results: Significant increased SPK1 urothelial immunoreactivity was shown in patients compared to control group (p=0.03). By contrast, SPK1 immunoreactivity in patients was significantly decreased in the sub-urothelium, muscles and nerves, p=0.02; 0.01 and 0.003, respectively. Patients with neurogenic detrusor overactivity (NDO) had higher SPK1 urothelium expression than those without any DO (p=0.04). Conclusions: SPK1 is expressed in the human bladder wall, specifically the urothelium, in bladder specimens from patients with NDO. The role of SPK1 in the pathophysiology of NDO needs further elucidation.

Clinical and pathological analysis of urothelial carcinoma with clear cell variant / 中华泌尿外科杂志

Objective To investigate the clinical and pathological features of urothelial carcinoma with clear cell variant.Methods The pathological and clinical data of 7 cases pathological diagnosed urothelial carcinoma with clear cell variant between March 2005 and May 2014 were retrospectively reviewed.There were 6 males and 1 female,aged 46-75 years (mean,61 years).Clinical manifestations included gross hematuria in 5 cases,hematuria and backache in another 2 cases.The mean tumor size was 3.5 cm (ranged 2.0-6.0 cm).One case was multiple tumor and 6 cases were single tumor.Five cases were positive in urine cytology.All the 7 cases accepted surgical treatment,including radical nephroureterectomy in 2 cases,transurethral resection of bladder tumor plus pharmorubicin regular intravesicalinstillationin 1 case,and radical cystectomy in 4 patients.Results Pathological findings revealed that all the tumors were high-grade urothelial carcinoma with clear cell variant in different proportion.Among them,clear cell tumor was predominant in 1 case and focal in other 6 cases.Meanwhile,tumorsaccompanied by glandular differentiation were found in 2 cases,squamous differentiation was found in 1 case,and micropapillary variant was found in 1 case.Vascular tumor embolus was found in 4 cases.Pathological stage was pT2a (n =1),pT2b (n =3),and pT3a (n =3).Immunohistochemicalstaining revealed cytokeratin 7 (+),cytokeratin 20 (+),epithelial membrane antigen (+)and prostate specific antigen (-).Six cases were followed up.The bladder preservation case was followed up for 8 months without recurrence.In 3 radical cystectomy cases,1 died of cancer 25 months after surgery and another 2 case were followed up for 10 and 12 months after surgery without recurrence and metastasis.In 2 nephroureterectomy cases,1 died of tumor metastasis 18 months after surgery and the other case was followed up for 6 months without recurrence or metastasis.Conclusions Urothelialcarcinoma with clear cell variant is a malignancy often with advanced stage and poor prognosis.Radical surgery is recommended for the treatment.

The curative effect comparison between retroperitoneoscopy combined with inguen small incision surgery and open surgery in treatment of urothelium carcinoma / 中国医师进修杂志

Objective To analyze the clinical curative effect of retroperitoneoscopy combined with inguen small incision surgery in treatment of urothelium carcinoma.Methods Ninety-eight urothelium carcinoma patients were divided into observation group (56 cases) and control group (42 cases) according to the surgery method.The patients in observation group were treated with retroperitoneoscopy combined with inguen small incision surgery,and the patients in control group were treated with open surgery.The operation time,intraoperative bleeding volume,postoperative drainage volume,postoperative gastrointestinal function recovery time,postoperative ambulation time,drainage tube removal time,hospitalization time,incision fat liquefaction,incision hernia,incision prolapse,incision pain and discomfort,postoperative analgesia,postoperative 3 months incision satisfaction and postoperative 36 months tumor recurrence were observed.Results The operation time,intraoperative bleeding volume,postoperative gastrointestinal function recovery time,postoperative ambulation time and hospitalization time in observation group were significantly lower than those in control group:(135.23 ±32.18) min vs.(177.58 ±57.29) min,(119.33 ±35.02) ml vs.(161.29 ± 72.06) ml,(2.03 ± 0.73) d vs.(2.79 ± 0.79) d,(20.68 ± 9.75) h vs.(32.41 ± 11.12) h,(8.51 ± 0.93) d vs.(9.81 ± 2.21) d,and there were statistical differences (P ＜ 0.05 or ＜ 0.01).There were no statistical differences in postoperative drainage volume and drainage tube removal time between 2 groups (P ＞ 0.05).The rates of incision fat liquefaction,incision hernia,incision prolapse,incision pain and discomfort and postoperative analgesia in observation group were significantly lower than those in control group:1.79％ (1/56) vs.26.19％ (11/42),0 vs.11.90％ (5/42),0 vs.7.14％ (3/42),1.79％ (1/56) vs.11.90％ (5/42),1.79％ (1/56)vs.11.90％ (5/42),the rate of postoperative 3 months incision satisfaction in observation group (92.86％,52/56) was significantly higher than that in control group (78.57％,33/42),and there were statistical differences (P ＜ 0.01 or ＜ 0.05).The rate of tumor recurrence in observation group (14.29％,8/56) was significantly lower than that in control group (47.62％,20/42),and there was statistical difference (P ＜ 0.01).Conclusions Retroperitoneoscopy combined with inguen small incision surgery in treatment of urothelium carcinoma can significantly reduce the patients' treatment and recovery time,improve the beauty of incision and patients' satisfaction degree,and reduce the postoperative tumor recurrence rate.

Qualitative analysis of the deposit of collagen in bladder suture of rats treated with tacrolimus combined with mycophenolate-mofetil

PurposeTo evaluate the synthesis of type I (mature) and type III (immature) collagen in bladder suture of rats treated with a combination of tacrolimus and mycophenolate mofetil for 15 days.Materials and MethodsThirty rats were divided into 3 groups: the sham, control and experimental groups. All the animals underwent laparotomy, cystotomy and bladder suture in two planes with surgical PDS 5-0 thread. The sham group did not receive treatment. The control group received saline solution, and the experimental group received 0.1mg/kg/day of tacrolimus with 20mg/kg/day of mycophenolate mofetil, for 15 days. From then on, the tacrolimus was dosed. The surgical specimens of the bladder suture area were processed so that the total type I and type III collagen could be measured by the picrosirius red technique.ResultsThere was a predominance of type I collagen production in the sham and control groups compared to the experimental group, in which type III collagen was predominant. The production of total collagen did not change.ConclusionThe association of tacrolimus and mycophenolate mofetil in animals qualitatively changes the production of collagen after 15 days with a predominance of type III collagen.

Distributional Difference of CD3+T Lymphocyte in Tissue of Bladder Cancer and Epithelium of Paracancer Area / 昆明医科大学学报

Objective The purpose of this study was to observe the distribution of CD3+T lymphocyte in the tissue of bladder cancer and epithelium of paracancer area, and analyze the significance. Methods Biopsy was performed in 28 patients with bladder cancer, and the distribution and number of CD3+T lymphocyte in tissue of bladder cancer and epithelium of paracancer area were observed and compared using immunohistochemistry. Results Many of CD3+T lymphocytes could be observed in the epithelium of paracancer tissues, but CD3+T lymphocytes in cancer nests was few. The average number of CD3+T lymphocytes in every 5 typical microscope visual fields of paracancer tissues and cancer nests was 15 ±4.5 and 4 ±2.2, respectively, and the difference was significant ( <0.05) . Conclusion Distribution of CD3+T lymphocytes in bladder cancer nests and paracancer tissues was different, which may be related to the immune escape and prognosis of bladder cancer. It is worthy of further research.

Cytotoxicity evaluation of nano-Ag-SiO2urethral catheter for external urethral mucosa cells / 中国组织工程研究

BACKGROUND:Nano-Ag is increasingly used as antibacterial materials in medical products due to its excelent antibacterial activity. Antibacterial activated nano-Ag-SiO2 OBJECTIVE: To evaluate the biosecurity of nano-Ag-SiO urethral catheter can reduce the incidence of catheter-associated urinarytract infections obviously. As more and more nano-Ag medical products have been developed, their biological security is becoming a focused issue. 2 urethral catheter through comparing the active influence of nano-Ag-SiO2 METHODS: Mechanical separation and enzymatic digestion were used to isolate and culture urothelial mucosa of benign prostatic hyperplasia patients to make cellsuspension after proliferationin vitro. The medium was replaced by nano-Ag-SiO urethral catheter and ordinary urethral catheter extracts onin vitro cels of human prostatic urethra epithelial cels in different periods. 2 and general catheter tube extracts, respectively. MTT assay was performed to quantify thein vitro cytotoxicity of two extracts on human urethra epithelial cels which were cultured for 2, 5 and 7 days. Absorbance values of nano-Ag-SiO2 RESULTS AND CONCLUSION:The cytotoxicity of extract of nano-Ag-SiO and general urinary catheter groups were measured by enzyme-linked immunosorbent assay to calculate the relative growth rate, and toxicity evaluation was compared and evaluated. Under an inverted microscope, cellmorphology, growth and proliferation were observed. 2 catheter was 1 grade, and that of general medical catheter extract was 0 to 1 grade. There was no statistical difference in group effect of relative proliferation rate (F=0.544,P=0.475); there was statistical difference in time effect of relative proliferation rate (F=3.031,P=0.086); no statistical difference was found in the interaction between group and time (F=0.130, P=0.879). These findings indicate that nano-Ag-SiO2 catheter has no or low cytotoxicity effect on cellgrowth and proliferation, which is consistent with the biological evaluation standards of medical devices.

Alterações fisiopatológicas em bexiga urinária de camundongos obesos resistentes à insulina / Physiopathological alterations in urinary bladder from insulin resistant obese mice

Obesidade/síndrome metabólica são fatores de risco para o desenvolvimento dos sintomas do trato urinário inferior (LUTS), incluindo hiperatividade de bexiga. Em nosso estudo visamos investigar a relação entre resistência à insulina e hiperatividade de bexiga em modelo de obesidade induzida por dieta hiperlipídica (10 semanas) em camundongos C57BL6/J. Curvas concentração-resposta a diferentes agentes contráteis e à insulina foram realizadas em bexigas isoladas de camundongos e humanos. Estudo cistométrico foi conduzido em camundongos anestesiados. Expressão protéica de PKC, canais de Ca2+ do tipo L, eNOS (Ser1177) e AKT (Ser473) fosforiladas, bem como de marcadores da resposta a proteínas mal dobradas (UPR), TRIB3, CHOP e ATF4, foi determinada por western blot. Camundongos obesos exibiram aumento do peso corpóreo, gordura epididimal, glicemia de jejum e resistência à insulina. As respostas contráteis aos diferentes agentes foram maiores nos animais obesos, o que foi normalizado pela pré-incubação com o bloqueador dos canais de Ca2+ do tipo L, amlodipino. Animais do grupo obeso apresentaram hiperatividade de bexiga, como demonstrado por estudo cistométrico. As curvas concentração-resposta ao agonista muscarínico, carbacol, foram dependentes da ativação da PKC. A resposta contrátil ao ativador da PKC, PDBu, foi abolida pela incubação com amlodipino. O tratamento com metformina melhorou a sensibilidade à insulina assim como normalizou a hipercontratilidade in vitro, a hiperatividade de bexiga e os níveis de PKC e pAKT em camundongos obesos. A insulina (1-100 nM) produziu relaxamento concentração-dependente em bexigas de camundongos e humanos, o que foi reduzido pela remoção da camada urotelial ou inibição da via de sinalização da PI3K/AKT/eNOS. Em condições fisiológicas, o estímulo com insulina resultou em um aumento de aproximadamente 3 vezes nos níveis de GMPc; porém, o relaxamento e os níveis de GMPc foram menores em bexigas de animais obesos...

Obesity/metabolic syndrome are common risk factors for lower urinary tract symptoms, including overactive bladder. This study aimed to investigate whether insulin resistance affects bladder function in a model of obesity induced by high-fat diet (10 weeks) in C57BL6/J mice. Concentration-response curves to contractile agents and insulin were performed in human and mouse bladders. Cystometric study was performed in terminally anaesthetized mice. Western blot was performed in bladders to detect PKC, Cav1.2, phosphorylated eNOS (Ser1177) and AKT (Ser473), as well as the unfolded protein response (UPR) markers TRIB3, CHOP and ATF4. Obese mice exhibited higher body weight, epididymal fat mass, fasting glucose and insulin resistance. All the contractile agents produced greater bladder contractions in obese mice, which were fully reversed by the Cav1.2 blocker amlodipine. Cystometry evidenced overactive bladder in obese group that were also prevented by amlodipine. Carbachol induced contractions was dependent on the PKC activation, and PKC expression was increased in obese mice. Metformin treatment improved the insulin sensitivity, normalized the in vitro bladder hypercontractility, cystometric dysfunction and restored PKC and pAKT expression in the obese bladders. Insulin (1-100 nM) produced concentration-dependent mouse and human bladder relaxations that were markedly reduced by mucosal removal or inhibition of the PI3K/AKT/eNOS pathway. In mouse bladders, insulin produced a 3.0-fold increase in cGMP levels (P<0.05), that was prevented by PI3K/AKT/eNOS pathway inhibition. PI3K inhibition abolished insulin-induced phosphorylation of AKT and eNOS in bladder mucosa. Obese mice showed greater voiding frequency and non-voiding contractions, indicating overactive bladder...

Late-Onset Distant Metastatic Upper Urinary Tract Urothelial Carcinoma Mimicking Lung Adenocarcinoma / 결핵및호흡기질환

Urothelial carcinomas (UCs) can occur in the upper urinary tract or lower urinary tract. Upper urinary tract urothelial carcinoma (UUT-UC) is relatively a rare disease and accounts for only about 5% of UC cases. Sporadic cases of late-onset metastasis, associated with UC of the bladder, have occasionally been reported. In contrast, no late-onset distant metastatic UUT-UC without local recurrence has, to the best of our knowledge, been reported in the English literature. We report an extremely rare case of distant metastatic UC, mimicking lung adenocarcinoma that originated from UUT-UC 12 years previously.

Detrusor overactivity in diabetic and non-diabetic patients: is there a difference?

PURPOSE: To compare urodynamic characteristics in patients with idiopathic detrusor overactivity (IDO) with those of an age matched cohort with diabetes mellitus (DM) and detrusor overactivity (DO). Secondly, to determine whether urodynamic features could help distinguish these two groups of patients. MATERIALS AND METHODS: Urodynamic data was collected on 58 female patients; 29 with IDO and 29 with DM and detrusor overactivity. Eight urodynamic parameters were selected for analysis: amplitude of the first overactive contraction (AOFC), the volume at the first contraction, cystometric capacity, maximal detrusor pressure, maximal flow rate, voiding pressure at maximal flow, voided volume and postvoid residual (PVR) urine volume. Finally, sensitivity analysis for distinguishing urodynamic parameters between studied groups was performed. RESULTS: AOFC, volume at AOFC and maximal detrusor pressure were statistically greater in diabetic patients, compared with the non-diabetic group of women (16.00 cm H2O versus 9.00 cm H2O, 309.00 mL versus 167.00 mL and 76.48 cm H2O versus 55.41 cm H2O respectively). A specificity of 72.41% and positive predictive value of 71.43% were achieved for AOFC with cutoff value of 12 cm H2O. These parameters were further improved with cutoff value of 258 mL for volume at AOFC and were 75.86% and 73.08% respectively. CONCLUSIONS: Certain urodynamic parameters in diabetic female patients with DO are shown to be significantly different than those in women with IDO. Further prospective study should provide additional information about the pathogenesis and progression of DO in diabetic patients as well as the validity of diabetic screening in patients with IDO.

Uroplakins in the Lower Urinary Tract / 대한배뇨장애요실금학회지

The apical surface of mammalian urinary epithelium is covered by numerous scallop-shaped membrane plaques. This plaque consists of four different uroplakins (UPs) and integral membrane proteins. UPs, which are a member of the tetraspanin superfamily, are assembled into plaques that act as an exceptional barrier to water and toxic materials in urine. Within the plaques, the four UPs are organized into two heterodimers consisting of UP Ia/UP II and UP Ib/UP III in the endoplasmic reticulum. The two heterodimers bind to a heterotetramer, and then assemble into 16-nm particles in the Golgi apparatus. The aggregated UP complex ultimately covers almost all the mature fusiform vesicles in cytoplasm. These organelles migrate towards the apical urothelial cells, where they can fuse with the apical plasma membrane. As a result, the UPs are synthesized in large quantities only by terminally differentiated urothelial cells. For this reason, the UPs can be regarded as a major urothelial differentiation marker. In UP knockout (KO) mice, the incorporation of fully assembled UP plaques in cytoplasm into the apical surface is not functional. The mice with UP III-deficient urothelium show a significantly reduced number of UPs, whereas those with UP II-deficient urothelium have nearly undetectable levels of UPs. This finding strongly suggests that UP II ablation completely abolishes plaque formation. In addition, UP II KO mice contain abnormal epithelial polyps or complete epithelial occlusion in their ureters. UP IIIa KO mice are also associated with impairment of the urothelial permeability barrier and development of vesicoureteral reflux as well as a decrease in urothelial plaque size. In this review, I summarize recently published studies about UPs and attempt to explain the clinical significance of our laboratory results.