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1.
Int J Urol ; 31(8): 846-851, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38700051

RESUMO

To preserve the bladder without compromising survival, further treatments need to be optimized to prevent the recurrence and progression of non-muscle invasive bladder cancer. In clinical practice, transurethral resection of bladder tumors is essential for bladder cancer management. The primary goal of surgery is to achieve accurate pathological evaluation and complete resection of bladder cancer; high resection quality is required for the procedure. A representative surrogate indicator of the resection quality is the presence of the detrusor muscle in the resection specimen. Therefore, complete visual resection of bladder cancer with a muscle layer is crucial for decreasing the recurrence and progression rates of non-muscle-invasive bladder cancer. However, this procedure is complex and requires sufficient experience and knowledge to be performed thoroughly, safely, and efficiently. Surgical checklists represent an approach to filling the knowledge and experience gaps and improving the quality and safety of surgery. By checking items during transurethral resection, it is expected that the recording of risk factors related to recurrence and progression will improve, the rate of visually complete resection with muscles will increase, and the rate of intravesical recurrence will decrease. The simplicity of checklists is an additional benefit. In recent years, surgical checklists have received increasing attention in order to achieve high-quality resections and reduce disparities between surgeons and institutions. This literature review outlines the evolving treatment strategies for patients with non-muscle-invasive bladder cancer, focusing on surgical checklists for the transurethral resection of bladder tumors.


Assuntos
Lista de Checagem , Cistectomia , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Humanos , Cistectomia/métodos , Cistectomia/normas , Recidiva Local de Neoplasia/prevenção & controle , Recidiva Local de Neoplasia/epidemiologia , Bexiga Urinária/cirurgia , Bexiga Urinária/patologia , Resultado do Tratamento , Progressão da Doença
2.
Neurourol Urodyn ; 42(2): 445-452, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36519669

RESUMO

INTRODUCTION: Bladder outlet obstruction alters detrusor contractility, reducing the bladder's ability to respond to large filling with a risk of urinary retention. The objective was to assess the effect of bladder filling volume on detrusor contractility in men with bladder outlet obstruction. METHODS: A prospective multicenter study in two pelviperineology departments. Male patients eligible for urodynamics (IPSS score > 7) were included from January to July 2022. In case of absence of bladder outlet obstruction on pressure-flow studies, they were secondarily excluded. The primary endpoint was the maximum isometric detrusor pressure during a stop-test, corresponding to detrusor contractility, measured at 3 filling volumes (50%, 75%, and 100% of cystometric capacity). RESULTS: Fifty-two patients performed urodynamics, of whom 12 were excluded because of lack of obstruction or inability to perform the stop-test. Detrusor contractility was significantly higher for a 75% bladder filling than 50% and for a 75% filling than 100%, with a mean difference of 19.5; confidence interval (CI) 95% [14.3; 24.8] and 12.2; CI 95% [6.9; 17.5] cmH2 O respectively (p < 0,01). CONCLUSION: In case of bladder outlet obstruction in men, detrusor contractility depends on bladder filling volume, with reduced contractility when the bladder was underfilled or overfilled. This phenomenon could help to explain the mechanisms of urinary retention in men with bladder outlet obstruction.


Assuntos
Obstrução do Colo da Bexiga Urinária , Retenção Urinária , Humanos , Masculino , Obstrução do Colo da Bexiga Urinária/etiologia , Bexiga Urinária , Retenção Urinária/complicações , Estudos Prospectivos , Procedimentos Cirúrgicos Urológicos/efeitos adversos , Urodinâmica
3.
Saudi Pharm J ; 30(3): 306-316, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35498220

RESUMO

Heavy metals have a deleterious effect on lower urinary tract functions. Scant data has been reported about metals' effect on altering detrusor muscle contractility. Rats were given lead acetate (3, 30 mg/kg), cadmium sulfate (0.1, 1 mg/kg) or ferrous sulfate-iron overload-(3, 30 mg/kg), in a subacute toxicity study (21 days, ip). In-vitro tension experiments were conducted using isolated rat detrusor muscle. Measurement of heavy metal concentrations in blood and tissue homogenates was performed, as well as histopathological examinations. Subacute toxicity induced by treatment with lead and cadmium was manifested as a decrease in EFS, ACh, and ATP-mediated contraction of isolated detrusor muscle. Iron overload only decreased EMAX of EFS and ACh-mediated contraction. Lead (30 mg/kg) caused an upward shift in the dose response curve of isoprenaline-induced relaxation, with a significant decrease in EMAX. Lead (30 mg/kg) or cadmium (1 mg/kg) inhibited adenosine (10-5 M)-induced relaxation. Comparisons to control tissues showed a selective accumulation of metals in the detrusor muscle. Histopathological examinations revealed edema and inflammation in the urinary bladder. Directly added lead (10 mM) inhibited detrusor muscle contraction in-vitro, and its effect was decreased in presence of atropine, and potentiated in presence of TEA, L-NAME, or MB. Cadmium's (0.1 mM) inhibitory effect was reduced in presence of nifedipine or trifluoperazine. In conclusion, lead, cadmium, or iron induce detrusor hypoactivity: The inhibitory effect of lead may be mediated by modulating muscarinic receptors but not the K+/NO/cGMP pathway, whereas cadmium inhibitory effect may be mediated by inhibiting the Ca2+/calmodulin pathway.

4.
Am J Physiol Renal Physiol ; 320(4): F537-F547, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33491563

RESUMO

Local or systemic inflammation can severely impair urinary bladder functions and contribute to the development of voiding disorders in millions of people worldwide. Isoprostanes are inflammatory lipid mediators that are upregulated in the blood and urine by oxidative stress and may potentially induce detrusor overactivity. The aim of the present study was to investigate the effects and signal transduction of isoprostanes in human and murine urinary bladders in order to provide potential pharmacological targets in detrusor overactivity. Contraction force was measured with a myograph in murine and human urinary bladder smooth muscle (UBSM) ex vivo. Isoprostane 8-iso-PGE2 and 8-iso-PGF2α evoked dose-dependent contraction in the murine UBSM, which was abolished in mice deficient in the thromboxane prostanoid (TP) receptor. The responses remained unaltered after removal of the mucosa or incubation with tetrodotoxin. Smooth muscle-specific deletion of Gα12/13 protein or inhibition of Rho kinase by Y-27632 decreased the contractions. In Gαq/11-knockout mice, responses were reduced and in the presence of Y-27632 abolished completely. In human UBSM, the TP agonist U-46619 evoked dose-dependent contractions. Neither atropine nor the purinergic receptor antagonist pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid decreased the effect, indicating that TP receptors directly mediate detrusor muscle contraction. 8-iso-PGE2 and 8-iso-PGF2α evoked dose-dependent contraction in the human UBSM, and these responses were abolished by the TP antagonist SQ-29548 and were decreased by Y-27632. Our results indicate that isoprostanes evoke contraction in murine and human urinary bladders, an effect mediated by the TP receptor. The G12/13-Rho-Rho kinase pathway plays a significant role in mediating the contraction and therefore may be a potential therapeutic target in detrusor overactivity.NEW & NOTEWORTHY Voiding disorders affect millions of people worldwide. Inflammation can impair urinary bladder functions and contribute to the development of detrusor overactivity. The effects and signal transduction of inflammatory lipid mediator isoprostanes were studied in human and murine urinary bladders ex vivo. We found that isoprostanes evoke contraction, an effect mediated by thromboxane prostanoid receptors. The G12/13-Rho-Rho kinase signaling pathway plays a significant role in mediating the contraction and therefore may be a potential therapeutic target.


Assuntos
Isoprostanos/farmacologia , Músculo Liso Vascular/efeitos dos fármacos , Antagonistas de Prostaglandina/farmacologia , Receptores de Prostaglandina/efeitos dos fármacos , Receptores de Tromboxanos/efeitos dos fármacos , Animais , Humanos , Prostaglandinas/farmacologia , Receptores de Tromboxanos/fisiologia
5.
Am J Physiol Regul Integr Comp Physiol ; 320(6): R897-R915, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33759573

RESUMO

We determined the effect of pelvic organ decentralization and reinnervation 1 yr later on urinary bladder histology and function. Nineteen canines underwent decentralization by bilateral transection of all coccygeal and sacral (S) spinal roots, dorsal roots of lumbar (L)7, and hypogastric nerves. After exclusions, eight were reinnervated 12 mo postdecentralization with obturator-to-pelvic and sciatic-to-pudendal nerve transfers, then euthanized 8-12 mo later. Four served as long-term decentralized only animals. Before euthanasia, pelvic or transferred nerves and L1-S3 spinal roots were stimulated and maximum detrusor pressure (MDP) recorded. Bladder specimens were collected for histological and ex vivo smooth muscle contractility studies. Both reinnervated and decentralized animals showed less or denuded urothelium, fewer intramural ganglia, and more inflammation and collagen, than controls, although percent muscle was maintained. In reinnervated animals, pgp9.5+ axon density was higher compared with decentralized animals. Ex vivo smooth muscle contractions in response to KCl correlated positively with submucosal inflammation, detrusor muscle thickness, and pgp9.5+ axon density. In vivo, reinnervated animals showed higher MDP after stimulation of L1-L6 roots compared with their transected L7-S3 roots, and reinnervated and decentralized animals showed lower MDP than controls after stimulation of nerves (due likely to fibrotic nerve encapsulation). MDP correlated negatively with detrusor collagen and inflammation, and positively with pgp9.5+ axon density and intramural ganglia numbers. These results demonstrate that bladder function can be improved by transfer of obturator nerves to pelvic nerves at 1 yr after decentralization, although the fibrosis and inflammation that developed were associated with decreased contractile function.


Assuntos
Músculo Liso/fisiopatologia , Transferência de Nervo , Traumatismos da Medula Espinal/fisiopatologia , Nervos Espinhais/fisiopatologia , Bexiga Urinária/inervação , Animais , Cães , Estimulação Elétrica/métodos , Contração Muscular/fisiologia , Regeneração Nervosa/fisiologia , Transferência de Nervo/métodos , Raízes Nervosas Espinhais/fisiopatologia , Bexiga Urinária/fisiopatologia
6.
Sensors (Basel) ; 20(15)2020 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-32727146

RESUMO

Ultrasound measurements of detrusor muscle thickness have been proposed as a diagnostic biomarker in patients with bladder overactivity and voiding dysfunction. In this study, we present an approach based on deep learning (DL) and dynamic programming (DP) to segment the bladder sac and measure the detrusor muscle thickness from transabdominal 2D B-mode ultrasound images. To assess the performance of our method, we compared the results of automated methods to the manually obtained reference bladder segmentations and wall thickness measurements of 80 images obtained from 11 volunteers. It takes less than a second to segment the bladder from a 2D B-mode image for the DL method. The average Dice index for the bladder segmentation is 0.93 ± 0.04 mm, and the average root-mean-square-error and standard deviation for wall thickness measurement are 0.7 ± 0.2 mm, which is comparable to the manual ground truth. The proposed fully automated and fast method could be a useful tool for segmentation and wall thickness measurement of the bladder from transabdominal B-mode images. The computation speed and accuracy of the proposed method will enable adaptive adjustment of the ultrasound focus point, and continuous assessment of the bladder wall during the filling and voiding process of the bladder.


Assuntos
Manejo de Espécimes , Bexiga Urinária , Automação , Humanos , Ultrassonografia , Bexiga Urinária/diagnóstico por imagem
7.
Am J Physiol Regul Integr Comp Physiol ; 314(3): R334-R341, 2018 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-29092859

RESUMO

The renal outer medullary potassium channel (ROMK; Kir1.1) plays an important role in Na+ and K+ homeostasis. ROMK knockout (KO) mice show a similar phenotype to Bartter's syndrome of salt wasting and dehydration due to reduced Na-2Cl-K-cotransporter activity but not in ROMK1 KO mice. ROMK KO mice also show hydronephrosis; however, the mechanism of this phenotype has not been understood. We have previously demonstrated a gender-sex difference in hydronephrosis and PGE2 production in ROMK KO mice. In this study we compared the gender-sex difference in bladder hypertrophy and hydronephrosis in ROMK KO mice. The bladder weight, bladder capacity, and the thickness of urothelium in male ROMK KO showed average increased two to approximately fourfold greater than wild-type (WT) mice, but there was no difference in either female or ROMK1 KO mice. The thickness of the urothelium was 648.8 ± 33.2 µm vs. 302.7 ± 16.5 µm ( P < 0.001) and the detrusor muscle 1,940.7 ± 98.9 µm vs. 1,308.2 ± 102.1 µm ( P = 0.013), respectively, in 12-mo male ROMK KO mice compared with the same age WT mice. Western blotting detected ROMK expression at 45~48 kDa, and both ROMK1 and ROMK2 mRNA were detected by quantitative PCR in the bladder. Immunofluorescence staining showed ROMK stained in the bladder, ureter, and urethra in WT but not in KO. In addition, there was a correlation between the severity of hydronephrosis and the bladder weight in male but not in female ROMK KO mice. In conclusion, ROMK expressed in the urinary tract at both protein and mRNA levels; significant enlargement and hypertrophy of the bladder may contribute to hydronephrosis in male ROMK KO mice.


Assuntos
Síndrome de Bartter/metabolismo , Hidronefrose/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Bexiga Urinária/metabolismo , Animais , Síndrome de Bartter/genética , Síndrome de Bartter/patologia , Modelos Animais de Doenças , Feminino , Predisposição Genética para Doença , Hidronefrose/genética , Hidronefrose/patologia , Hipertrofia , Masculino , Camundongos Knockout , Músculo Liso/metabolismo , Músculo Liso/patologia , Tamanho do Órgão , Fenótipo , Canais de Potássio Corretores do Fluxo de Internalização/deficiência , Canais de Potássio Corretores do Fluxo de Internalização/genética , Fatores Sexuais , Ureter/metabolismo , Ureter/patologia , Uretra/metabolismo , Uretra/patologia , Bexiga Urinária/patologia , Urotélio/metabolismo , Urotélio/patologia
8.
Pol J Pathol ; 69(3): 234-242, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30509050

RESUMO

Androgen receptor (AR) activation plays an important role in the promotion and progression of urothelial tumorigenesis. Also, dysregulation of the Wnt/ß-catenin signaling pathway has also been linked to bladder cancer growth. However, cross talk between the two pathways in remains unclear in bladder cancer. This study investigated the prognostic significance of AR and ß-catenin expression and their relationship to different clinic-pathological parameters, recurrence free and progression free survival. 106 urothelial carcinoma cases were used to study the immunohistochemical expression of AR and ß-catenin. Log-Rank test to compare survival between groups. Androgen receptor positivity was in 37 (34.9%) cases. Both aberrant ß-catenin and AR positivity were associated with higher tumor grade (p = 0.033 and p = 0.037 respectively) and muscle invasion (p = 0.007 and p = 0.039 respectively). Aberrant ß-catenin only showed statistically significant association with tumor diameter (p = 0.036), tumor stage (p = 0.038), LN metastasis (p = 0.001), tumor recurrence (p = 0.026) and tumor progression (p = 0.01). Cases with aberrant ß-catenin showed higher AR positivity (p = 0.018). Our study highlighted important information about the link between Wnt/ß-catenin and AR pathway during the progression of transitional urothelial carcinoma with aberrant ß-catenin could be used as a prognostic marker.


Assuntos
Carcinoma de Células de Transição/genética , Receptores Androgênicos/genética , Neoplasias da Bexiga Urinária/genética , beta Catenina/genética , Egito , Humanos , Imuno-Histoquímica , Músculos/patologia , Prognóstico
9.
Actas Urol Esp (Engl Ed) ; 48(6): 448-453, 2024.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-38160792

RESUMO

INTRODUCTION AND OBJECTIVES: Transurethral resection of bladder tumor (TURBT) is crucial in the treatment of bladder tumors and when incorrectly performed can cause staging mistakes. To avoid these errors, a second resection is recommended in selected cases. The aim of this study is to evaluate the surgeon's ability to predict histologically complete primary resection of newly diagnosed bladder tumors avoiding the need for a second TURBT. METHODS: This is a prospective, observational study involving 47 consecutive patients with newly diagnosed bladder tumors who had previously undergone primary TURBT, and met EAU criteria for second-look TURBT. Second-look TURBT specimens were analyzed for routine histological assessment and compared with the surgeon's impression of the tumor at initial resection. RESULTS: Of 91 patients submitted to primary TURBT, 47 met the criteria for second-look TURBT. Second-look specimens revealed residual disease in 20.9% of patients and 3 (6.4%) of patients showed upstaging disease. The sensitivity of a senior to detect disease on second-look TURBT in relation to muscle invasion was 75%, and the specificity was 85%. CONCLUSIONS: Second-look TURBT is crucial in the treatment of bladder cancer and cannot be replaced by a surgeon's opinion, so international recommendations should be followed. Supervision of less experienced surgeons is a cornerstone.


Assuntos
Cistectomia , Cirurgia de Second-Look , Neoplasias da Bexiga Urinária , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Humanos , Estudos Prospectivos , Masculino , Feminino , Idoso , Cistectomia/métodos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Competência Clínica , Uretra/cirurgia , Ressecção Transuretral de Bexiga
10.
Cureus ; 16(8): e68143, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39347322

RESUMO

OBJECTIVE: This study aimed to assess the quality of primary transurethral resection of bladder tumor (TURBT) procedures performed at Aga Khan University Hospital (AKUH) over nine years, focusing on proper documentation, completeness of tumor resection, quality of histopathology reports, complication rates, and adherence to European Association of Urology (EAU) guidelines. MATERIALS AND METHODS: A retrospective analysis of patients aged 25-75 who underwent primary TURBT at AKUH between 2010 and 2019 was done. Patients with incomplete records, concomitant procedures, or those who underwent emergency TURBT were excluded. Data was collected on patient demographics, clinical presentation, intraoperative details, and histopathology reports. Statistical analysis was performed using SPSS Version 27.0. RESULTS: 300 patients were initially identified, with 265 meeting the inclusion criteria. The mean age was 61.5 years, with 83% being male. Complete tumor resection was achieved in 35% (n=92) of cases, while deep biopsy was taken in 85% (n=226). Detrusor muscle (DM), a marker of resection quality, was noted in 75% (n=200) of histopathology reports. However, documentation quality varied, with 54% (n=143) of cases lacking clear information on resection completeness. The administration of a single instillation of a chemotherapeutic agent (SICA) was recorded in 79% (n=210) of patients, and the 30-day postoperative complication rate was monitored. CONCLUSION: The study highlights areas for improvement in the quality of TURBT procedures at AKUH, particularly in the documentation of resection completeness and adherence to established guidelines. Ensuring thorough resection and proper documentation is critical to optimizing patient outcomes and future management plans.

11.
J Neurosurg Spine ; 38(2): 258-264, 2023 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-36208430

RESUMO

OBJECTIVE: Bladder dysfunction after nerve injury has a variable presentation, and extent of injury determines whether the bladder is spastic or atonic. The authors have proposed a series of 3 nerve transfers for functional innervation of the detrusor muscle and external urethral sphincter, along with sensory innervation to the genital dermatome. These transfers are applicable to only cases with low spinal segment injuries (sacral nerve root function is lost) and largely preserved lumbar function. Transfer of the posterior branch of the obturator nerve to the vesical branch of the pelvic nerve provides a feasible mechanism for patients to initiate detrusor contraction by thigh adduction. External urethra innervation (motor and sensory) may be accomplished by transfer of the vastus medialis nerve to the pudendal nerve. The sensory component of the pudendal nerve to the genitalia may be further enhanced by transfer of the saphenous nerve (sensory) to the pudendal nerve. The main limitations of coapting the nerve donors to their intrapelvic targets are the bifurcation or arborization points of the parent nerve. To ensure that the donor nerves had sufficient length and diameter, the authors sought to measure these parameters. METHODS: Twenty-six pelvic and anterior thigh regions were dissected in 13 female cadavers. After the graft and donor sites were clearly exposed and the branches identified, the donor nerves were cut at suitable distal sites and then moved into the pelvis for tensionless anastomosis. Diameters were measured with calipers. RESULTS: The obturator nerve was bifurcated a mean ± SD (range) of 5.5 ± 1.7 (2.0-9.0) cm proximal to the entrance of the obturator foramen. In every cadaver, the authors were able to bring the posterior division of the obturator nerve to the vesical branch of the pelvic nerve (located internal to the ischial spine) in a tensionless manner with an excess obturator nerve length of 2.0 ± 1.2 (0.0-5.0) cm. The distance between the femoral nerve arborization and the anterior superior iliac spine was 9.3 ± 1.8 (6.5-15.0) cm, and the distance from the femoral arborization to the ischial spine was 12.9 ± 1.4 (10.0-16.0) cm. Diameters were similar between donor and recipient nerves. CONCLUSIONS: The chosen donor nerves were long enough and of sufficient caliber for the proposed nerve transfers and tensionless anastomosis.


Assuntos
Transferência de Nervo , Humanos , Feminino , Bexiga Urinária/cirurgia , Bexiga Urinária/inervação , Estudos de Viabilidade , Nervos Espinhais , Cadáver
12.
Eur J Pharmacol ; 952: 175807, 2023 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-37236435

RESUMO

Recent studies suggested smooth muscle contraction may involve mechanisms besides the myosin regulatory light chain (MLC) phosphorylation-induced actomyosin crossbridge cycling. This study aims to determine if focal adhesion kinase (FAK) activation is involved in mouse detrusor muscle contraction. The mouse detrusor muscle strips were preincubated with PF-573228 (2 µM), latrunculin B (1 µM), or the same volume of vehicle (DMSO) for 30 min. The contractile responses to KCl (90 mM), electrical field stimulation (EFS, 2-32 Hz), or carbachol (CCh, 10-7.5-10-4.5 M) were measured. In a separate experiment, the phosphorylated FAK (p-FAK) and MLC (p-MLC) levels were measured in the detrusor strips stimulated with CCh (10 µM) after incubation with PF-573228 or vehicle (DMSO) compared to those with vehicle incubation but without CCh stimulation. KCl-induced contractile responses decreased significantly after incubation with PF-573228 or latrunculin B compared to the corresponding vehicle-treated strips (p < 0.0001). The contractile responses induced by EFS were markedly inhibited by preincubation with PF-573228 at 8, 16, and 32 Hz (p < 0.05) or latrunculin B at 16 and 32 Hz (p < 0.01). Following the application of PF-573228 or Latrunculin B, CCh-induced dose-response contractions were lower than the corresponding vehicle group (p = 0.0021 and 0.0003, respectively). Western blot examination showed that CCh stimulation enhanced the expression of p-FAK and p-MLC, while preincubation with PF-573228 prevented the increase of p-FAK but not p-MLC. In conclusion, FAK activation involves tension development induced by contractile stimulation in the mouse detrusor muscle. This effect is likely caused by promoting actin polymerization rather than elevating MLC phosphorylation.


Assuntos
Dimetil Sulfóxido , Contração Muscular , Camundongos , Animais , Proteína-Tirosina Quinases de Adesão Focal , Dimetil Sulfóxido/farmacologia , Carbacol/farmacologia
13.
Biomed Pharmacother ; 158: 114155, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36916397

RESUMO

BACKGROUND: Solute carrier family nine isoform 3 (SLC9A3) is an Na+/H+ exchanger that regulates Ca2+ homeostasis. SLC9A3 is largely involved in the transepithelial absorption of Na+/H+ and frequently functions in pair with a Cl-/HCO3- exchanger. OBJECTIVE: To investigate the impact and pathophysiological mechanisms of long-term SLC9A3 deficiency on lower urinary tract symptoms (LUTS) in a mouse model MATERIALS AND METHODS: Slc9a3 knockout and wild-type mice (average >6 months) were used. The effects of SLC9A3 depletion on bladder and urethral functions and effectiveness of voiding were assessed using a cystometrogram (CMG). Histology, blood electrolytes, and gene expression were also analyzed. RESULTS: The SLC9A3-deficient mice had smaller gross bladders than the wild-type mice. The CMG analysis revealed normal peak micturition pressure, higher threshold pressure, short intercontraction interval, less voided volume, and poor compliance in the SLC9A3-deficient mice, similar to clinical LUTS. Histological analysis revealed loose detrusor muscle and loss of transformability of the urothelium in the SLC9A3-deficient mice. Masson's trichrome analysis revealed severe collagen deposition in the detrusor muscle. Immunofluorescence staining also demonstrated a significant decrease in cytokeratins 5 and 20. Gene and protein expression analyses confirmed that SLC9A3 does not act directly on bladder tissue. Homeostasis was correlated with bladder dysfunction in the SLC9A3-deficient mice. DISCUSSION: Fibrosis and collagen deposition in the bladder of the SLC9A3-deficient mice is due to bladder inflammation because of decreased blood flow and deregulated systemic homeostasis. Long-term SLC9A3 depletion causes progressive bladder dysfunction, similar to human LUTS. CONCLUSION: Electrolyte imbalance causes SLC9A3 deficiency-mediated progressive micturition dysfunction.


Assuntos
Bexiga Urinária , Micção , Animais , Humanos , Camundongos , Eletrólitos , Trocadores de Sódio-Hidrogênio , Bexiga Urinária/patologia
14.
Urologia ; 90(2): 266-271, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36756892

RESUMO

OBJECTIVES: To analyse the safety and efficacy of Thulium laser en bloc enucleation of bladder tumour (ThuLEBT) in comparison to transurethral resection of bladder tumour (TURBT) for treatment of non-muscle invasive bladder cancer (NMIBC). METHODS: Prospective observational study involving 30 patients in each group of ThuLEBT and TURBT admitted in tertiary care centre from 1st January 2021 to December 2021. RESULTS: Significant difference was found in terms of less operative time (p-0.01468), less intraoperative blood loss, a lower incidence of obturator nerve reflex (p-0.00006), bladder perforation (p-0.0455) and bladder irrigation (p-0.0027), better acquisition of detrusor muscle (p-0.0466), less recurrence rate (p-0.0455) in favour of ThuLEBT over TURBT group. The analysis also demonstrated faster postoperative recovery in terms of the duration of catheterisation, bladder irrigation and hospitalisation time in ThuLEBT group. CONCLUSIONS: ThuLEBT is an efficient and safe treatment for non-muscle invasive bladder cancer and it can be a better alternative choice in place of TURBT.


Assuntos
Carcinoma , Neoplasias da Bexiga Urinária , Humanos , Bexiga Urinária/patologia , Túlio , Neoplasias da Bexiga Urinária/cirurgia , Lasers
15.
Abdom Radiol (NY) ; 48(10): 3174-3182, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37328615

RESUMO

PURPOSE: To assess the diagnostic performance of biparametric magnetic resonance imaging (bp-MRI) in predicting detrusor muscle invasion for bladder cancer (BC) located at the ureteral orifice by comparing it with the Vesical Imaging Reporting and Data System (VI-RADS) system based on multiparametric MRI (mp-MRI). METHODS: Patients with histopathologically proven BC located at the ureteral orifice from December 2019 to November 2022 were analyzed retrospectively. Two sets, bp-MRI (set 1) and mp-MRI (set 2), were formed from the images. Both sets were evaluated independent of histopathology by three radiologists with different levels of experience in abdominal radiology. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic performance of VI-RADS in the prediction of muscle invasion. The intraclass correlation coefficient (ICC) was used to evaluate inter-reader agreement. RESULTS: Of 68 patients with BCs located at the ureteral orifice, 50 (48 males, median age: 72 years) met the study criteria. Out of the 50 patients, 36 had non-muscle invasive BC (pTa-T1) and 14 had muscle invasive BC (MIBC) (pT2-T4). In the comparison of VI-RADS categories with histopathologic data for MIBC detection, the area under the curve of the ROC analysis for the bp- and mp-MRI protocol was 1.000-0.986 for reader 1, 0.893-0.901 for reader 2, and 0.808-0.865 for reader 3. There was no statistically significant difference in predicting detrusor muscle invasion with the bp- and mp-MRI-based on VI-RADS categories for all readers (p = 0.126, 0.203, and 0.322, respectively). The ICCs between all the readers showed excellent agreement and were similar for both protocols. CONCLUSION: The bp-MRI consisting of DWI and T2-WI can be used as an alternative to the mp-MRI in predicting detrusor muscle invasion for BCs located at the ureteral orifice; however, less experienced readers should exercise caution.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Bexiga Urinária , Masculino , Humanos , Idoso , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/patologia , Bexiga Urinária/patologia , Imageamento por Ressonância Magnética/métodos
16.
Urol Oncol ; 41(12): 484.e7-484.e15, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37714725

RESUMO

PURPOSE: Detrusor muscle (DM) in the resected specimen of patients with pT1 bladder cancer (BCa) is a quality-of-care criteria. We aimed to assess whether obtaining adequate DM is dependent on surgeon's experience, whether is a surrogate for resection quality, and whether the degree of DM thickness is related to postoperative outcomes in en bloc resection for bladder tumors (ERBT). MATERIALS AND METHODS: We retrospectively analyzed the records of 106 pT1 high-grade BCa patients who underwent ERBT at several institutions. All specimens were reviewed by a single pathologist who assessed the presence or absence of DM and its thickness measured by a micrometer, when present. Early recurrence, defined as pathologically confirmed BCa on repeat resection or tumor recurrence at the first follow-up cystoscopy (within 3 months), was the endpoint reflective of the resection quality. RESULTS: Of 106 patients, DM was detected in 99 (93%), and the median DM thickness was 1.8 mm. Large tumor size (>30 mm) was associated with adequate DM sampling (>1.8mm) (odds ratio [OR]: 6.10, 95% confidence intervals [CIs]: 2.08-17.9, P = 0.001), while surgeon's experience was not. DM presence and DM thickness were both not associated with early recurrence, while positive surgical margin was an independent prognosticator for early recurrence (OR: 3.38, 95% CI: 1.12-10.2, P = 0.031). Excessive DM sampling (>2.1 mm) was associated with prolonged urethral catheterization (OR: 28.8, 95% CI: 3.36-248, P = 0.002). CONCLUSIONS: In ERBT, surgeon's experience seems irrelevant to obtain DM. Resection quality relies on surgical margin status, not the degree of DM. Obtaining excessive DM incurs adverse events/unnecessary medical care.


Assuntos
Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Cistectomia , Músculos/patologia
17.
Front Oncol ; 13: 1160463, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37333813

RESUMO

Introduction: Conventionally, we rely on transurethral resection of bladder tumour (TURBT) for local staging of muscle-invasive bladder cancer (MIBC). However, the procedure is limited by its staging inaccuracy which may delay the definitive treatment of MIBC. Methods: We conducted a proof-of concept study on endoscopic ultrasound (EUS)-guided biopsy of detrusor muscle in porcine bladders. Five porcine bladders were used in this experiment. Upon EUS, four layers of tissue including the mucosa (hypoechoic), submucosa (hyperechoic), detrusor muscle (hypoechoic) and serosa (hyperechoic) could be identified. Results: A total of 37 EUS-guided biopsies were taken from 15 sites (three sites per bladder), and the mean number of biopsies taken from each site was 2.47±0.64. Among the 37 biopsies, 30 of them (81.1%) obtained detrusor muscle in the biopsy specimen. For the per biopsy site analysis, detrusor muscle was obtained in 73.3% if only one biopsy was taken, and 100% if two or more biopsies were taken from the same biopsy site. Overall, detrusor muscle was successfully obtained from all 15 biopsy sites (100%). No bladder perforation was observed throughout all biopsy processes. Conclusion: EUS-guided biopsy of the detrusor muscle could be performed during the initial cystoscopy session, thus expediting the histological diagnosis and subsequent treatment of MIBC.

18.
Cancers (Basel) ; 15(7)2023 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-37046715

RESUMO

Current treatment for non-muscle invasive bladder cancer (NMIBC) is the conventional transurethral resection of bladder tumor (CTURBT), but the en bloc transurethral resection of bladder tumor (ERBT) has been gaining more attraction in recent years considering better specimen integrity. Thus, we conducted this meta-analysis to compare the safety and efficacy of ERBT versus CTURBT. Trials were collected from an online database. The primary outcomes included identification of detrusor muscle in specimen, residual tumor, 3, 12, and 24-month recurrence rates and same-site recurrence rate. A total of 31 trials were included. The ERBT group had a higher rate of identification of detrusor muscle in specimens (p = 0.003) and lower residual tumor (p < 0.001). Other than that, lower rates of 3-month (p = 0.005) and 24-month recurrence rate (p < 0.001), same-site recurrence rate (p < 0.001) and complications were also observed. For perioperative outcomes, shorter hospitalization time (HT) (p < 0.001), and catheterization time (CT) (p < 0.001) were also revealed in the ERBT group. No significant difference was found in operative time (OT) (p = 0.93). The use of ERBT showed better pathological outcomes and fewer complications, so it could be considered a more effective treatment option for NMIBC.

19.
Scand J Urol ; 56(5-6): 391-396, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36065477

RESUMO

OBJECTIVES: To assess the resection quality of transurethral bladder tumour resection (TURBT) and the association to surgeon experience depending on the presence of detrusor muscle. METHODS: A retrospective study on 640 TURBT procedures performed at Zealand University Hospital, Denmark, from 1 January 2015 - 31 December 2016. Data included patient characteristics, procedure type, surgeon category, supervisor presence, surgical report data, pathological data, complications data and recurrence data. Analysis was performed using simple and multiple logistic regression on the association between surgeon experience and the presence of detrusor muscle in resected tissue from TURBT. RESULTS: Supervised junior residents had significant lower detrusor muscle presence (73%) compared with consultants (83%) (OR = 0.4, 95% CI = 0.21-0.83). Limitations were the retrospective design and the diversity of included TURBT. CONCLUSIONS: It was found that surgical experience predicts detrusor muscle presence and supervised junior residents performing TURBT on patients resulted in less detrusor muscle than consultants.


Assuntos
Cirurgiões , Neoplasias da Bexiga Urinária , Humanos , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Cistectomia/métodos , Músculos/patologia
20.
Life Sci ; 289: 120237, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34922942

RESUMO

Tadalafil, a phosphodiesterase-5 (PDE5) inhibitor, shown to exert a protection to heart failure (HF) associated damage or lower urinary tract symptoms (LUTS). Thus, we investigated the contribution of tadalafil chronic treatment in the alterations of LUTS in HF rats. Male rats were subjected to aortocaval fistula model for HF induction. Echocardiography, cystometric, renal function and redox cell balance, as well as concentration-response curves to carbachol, KCl, ATP and frequency-response curves to electrical field stimulation (EFS) were evaluated in Sham, HF, Tadalafil and HF-Tadalafil (12 weeks endpoint) groups. HF group to present increased in left-ventricle (LV) mass and in LV end-diastolic- and LV end-systolic volume, with a decreased ejection fraction. Tadalafil treatment was able to decrease in hypertrophy and improve the LV function restoring cardiac function. For micturition function (in vivo), HF animals shown an increase in basal pressure, threshold pressure, no-voiding contractions and decreased bladder capacity, being that the tadalafil treatment restored the cystometric parameters. Contractile mechanism response (in vitro) to carbachol, KCl, ATP and EFS in the detrusor muscles (DM) were increased in the HF group, when compared to Sham group. However, tadalafil treatment restored the DM hypercontractility in the HF animals. Moreover, renal function as well as the oxidative mechanism was impaired in the HF animals, and the tadalafil treatment improved all renal and oxidative parameters in HF group. Our data shown that tadalafil has potential as multi-therapeutic drug and may be used as a pharmacological strategy for the treatment of cardiovascular, renal and urinary dysfunctions associated with HF.


Assuntos
Insuficiência Cardíaca , Rim , Sintomas do Trato Urinário Inferior , Tadalafila/farmacologia , Bexiga Urinária , Animais , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Rim/metabolismo , Rim/fisiopatologia , Sintomas do Trato Urinário Inferior/tratamento farmacológico , Sintomas do Trato Urinário Inferior/metabolismo , Sintomas do Trato Urinário Inferior/fisiopatologia , Masculino , Oxirredução/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Bexiga Urinária/metabolismo , Bexiga Urinária/fisiopatologia
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