RESUMO
The murine kidney and ureter develop in a regionalized fashion from the ureteric bud and its surrounding mesenchyme. Whereas the factors that establish the metanephric cell lineages have been well characterized, much less is known about the molecular cues that specify the ureter. Here, we have identified a crucial patterning function in this process for Tbx18, a T-box transcription factor gene specifically expressed in the mesenchymal primordium of the ureter. Using misexpression and loss-of-function mice combined with molecular profiling approaches, we show that Tbx18 is required and sufficient to repress metanephric mesenchymal gene programs. We identify Wt1 as a functional target of TBX18. Our work suggests that TBX18 acts as a permissive factor in ureter specification by generating a mesenchymal domain around the distal ureteric bud where SHH and BMP4 signaling can occur.
Assuntos
Ureter , Camundongos , Animais , Ureter/metabolismo , Rim/metabolismo , Transdução de Sinais/genética , Linhagem da Célula/genética , Expressão Gênica , Mesoderma/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismoRESUMO
Isthmin-1 (Ism1) was first described to be syn-expressed with Fgf8 in Xenopus. However, its biological role has not been elucidated until recent years. Despite of accumulated evidence that Ism1 participates in angiogenesis, tumor invasion, macrophage apoptosis, and glucose metabolism, the cognate receptors for Ism1 remain largely unknown. Ism1 deficiency in mice results in renal agenesis (RA) with a transient loss of Gdnf transcription and impaired mesenchyme condensation at E11.5. Ism1 binds to and activates Integrin α8ß1 to positively regulate Gdnf/Ret signaling, thus promoting mesenchyme condensation and ureteric epithelium branching morphogenesis. Here, we propose the hypothesis underlying the mechanism by which Ism1 regulates branching morphogenesis during early kidney development.
Assuntos
Estruturas Embrionárias , Fator Neurotrófico Derivado de Linhagem de Célula Glial , Néfrons/embriologia , Ureter , Camundongos , Animais , Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Rim/anormalidades , Rim/metabolismo , Rim/patologia , Ureter/metabolismo , MorfogêneseRESUMO
Smooth muscle cells (SMCs) are a crucial component of the mesenchymal wall of the ureter, as they account for the efficient removal of the urine from the renal pelvis to the bladder by means of their contractile activity. Here, we show that the zinc-finger transcription factor gene Gata6 is expressed in mesenchymal precursors of ureteric SMCs under the control of BMP4 signaling. Mice with a conditional loss of Gata6 in these precursors exhibit a delayed onset and reduced level of SMC differentiation and peristaltic activity, as well as dilatation of the ureter and renal pelvis (hydroureternephrosis) at birth and at postnatal stages. Molecular profiling revealed a delayed and reduced expression of the myogenic driver gene Myocd, but the activation of signaling pathways and transcription factors previously implicated in activation of the visceral SMC program in the ureter was unchanged. Additional gain-of-function experiments suggest that GATA6 cooperates with FOXF1 in Myocd activation and SMC differentiation, possibly as pioneer and lineage-determining factors, respectively.
Assuntos
Ureter , Animais , Diferenciação Celular/genética , Camundongos , Desenvolvimento Muscular , Músculo Liso , Miócitos de Músculo Liso/fisiologia , Ureter/metabolismoRESUMO
The patterned array of basal, intermediate and superficial cells in the urothelium of the mature ureter arises from uncommitted epithelial progenitors of the distal ureteric bud. Urothelial development requires signaling input from surrounding mesenchymal cells, which, in turn, depend on cues from the epithelial primordium to form a layered fibro-muscular wall. Here, we have identified FGFR2 as a crucial component in this reciprocal signaling crosstalk in the murine ureter. Loss of Fgfr2 in the ureteric epithelium led to reduced proliferation, stratification, intermediate and basal cell differentiation in this tissue, and affected cell survival and smooth muscle cell differentiation in the surrounding mesenchyme. Loss of Fgfr2 impacted negatively on epithelial expression of Shh and its mesenchymal effector gene Bmp4. Activation of SHH or BMP4 signaling largely rescued the cellular defects of mutant ureters in explant cultures. Conversely, inhibition of SHH or BMP signaling in wild-type ureters recapitulated the mutant phenotype in a dose-dependent manner. Our study suggests that FGF signals from the mesenchyme enhance, via epithelial FGFR2, the SHH-BMP4 signaling axis to drive urothelial and mesenchymal development in the early ureter.
Assuntos
Proteína Morfogenética Óssea 4/metabolismo , Proteínas Hedgehog/metabolismo , Organogênese , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Transdução de Sinais , Ureter/metabolismo , Animais , Mesoderma/citologia , Mesoderma/metabolismo , Camundongos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Ureter/embriologia , Urotélio/citologia , Urotélio/metabolismoRESUMO
The coordinated development of the mesenchymal and epithelial progenitors of the murine ureter depends on a complex interplay of diverse signaling activities. We have recently shown that epithelial FGFR2 signaling regulates stratification and differentiation of the epithelial compartment by enhancing epithelial Shh expression, and mesenchymal SHH and BMP4 activity. Here, we show that FGFR1 and FGFR2 expression in the mesenchymal primordium impinges on the SHH/BMP4 signaling axis to regulate mesenchymal patterning and differentiation. Mouse embryos with conditional loss of Fgfr1 and Fgfr2 in the ureteric mesenchyme exhibited reduced mesenchymal proliferation and prematurely activated lamina propria formation at the expense of the smooth muscle cell program. They also manifested hydroureter at birth. Molecular profiling detected increased SHH, WNT and retinoic acid signaling, whereas BMP4 signaling in the mesenchyme was reduced. Pharmacological activation of SHH signaling in combination with inhibition of BMP4 signaling recapitulated the cellular changes in explant cultures of wild-type ureters. Additional experiments suggest that mesenchymal FGFR1 and FGFR2 act as a sink for FGF ligands to dampen activation of Shh and BMP receptor gene expression by epithelial FGFR2 signaling.
Assuntos
Ureter , Animais , Proteína Morfogenética Óssea 4/metabolismo , Diferenciação Celular , Proteínas Hedgehog/metabolismo , Mesoderma/metabolismo , Camundongos , Miócitos de Músculo Liso/metabolismo , Transdução de Sinais/genética , Ureter/metabolismoRESUMO
The contractile phenotype of smooth muscle cells (SMCs) is transcriptionally controlled by a complex of the DNA-binding protein SRF and the transcriptional co-activator MYOCD. The pathways that activate expression of Myocd and of SMC structural genes in mesenchymal progenitors are diverse, reflecting different intrinsic and extrinsic signaling inputs. Taking the ureter as a model, we analyzed whether Notch signaling, a pathway previously implicated in vascular SMC development, also affects visceral SMC differentiation. We show that mice with a conditional deletion of the unique Notch mediator RBPJ in the undifferentiated ureteric mesenchyme exhibit altered ureter peristalsis with a delayed onset, and decreased contraction frequency and intensity at fetal stages. They also develop hydroureter 2 weeks after birth. Notch signaling is required for precise temporal activation of Myocd expression and, independently, for expression of a group of late SMC structural genes. Based on additional expression analyses, we suggest that a mesenchymal JAG1-NOTCH2/NOTCH3 module regulates visceral SMC differentiation in the ureter in a biphasic and bimodal manner, and that its molecular function differs from that in the vascular system.
Assuntos
Diferenciação Celular , Miócitos de Músculo Liso/metabolismo , Transdução de Sinais , Ureter/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Diferenciação Celular/efeitos dos fármacos , Diaminas/farmacologia , Feminino , Regulação da Expressão Gênica no Desenvolvimento , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/deficiência , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/genética , Proteína de Ligação a Sequências Sinal de Recombinação J de Imunoglobina/metabolismo , Proteína Jagged-1/genética , Proteína Jagged-1/metabolismo , Masculino , Camundongos , Camundongos Knockout , Miócitos de Músculo Liso/citologia , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais/efeitos dos fármacos , Tiazóis/farmacologia , Transativadores/genética , Transativadores/metabolismo , Ureter/citologia , Ureter/crescimento & desenvolvimento , Vísceras/citologia , Vísceras/metabolismoRESUMO
Collagen 17A1 (COL17A1), an epidermal hemidesmosome component, is ectopically induced in the urothelium of mouse and human renal pelvis (RP) in parallel with urinary tract-associated lymphoid structure development. Here, COL17A1 was induced in obstructive uropathy-prone ureter of humans and cats. To ascertain its function, murine urinary organs with unilateral ureteral obstruction (UUO) were analyzed during 1 week after surgery. One day after UUO, COL17A1 expression increased in urothelial cells of RP and ureter, and was positively correlated with renal tubulointerstitial lesions. A portion of RP where the smooth muscle layer from the ureter was interrupted was sensitive to urothelium deciduation and COL17A1 induction, showing urine leaked from the RP lumen into the parenchyma. After urine stimulation, cultured immune cells expressed Cxcl2, also up-regulated in CD11b+ cells following COL17A1 stimulation. One day after UUO, CXCL2+ CD11b+ cells infiltrated the urothelium-disrupted area. However, these numbers were significantly lower in Col17a1-deficient mice. COL17A1+ urothelial cells partially co-expressed cytokeratin-14, a progenitor cell marker for urothelium, whereas Col17a1-deficient mice had lower numbers of cytokeratin-14+ cells. Gene Ontology analysis revealed that expression of epithelial- and immune-associated genes was up-regulated and down-regulated, respectively, in the ureter of Col17a1-deficient mice 4 days after UUO. Thus, COL17A1 maintains urothelium integrity by regulating urothelial cell adhesion, proliferation, and differentiation, and activates local immune responses during obstructive uropathy in mammals.
Assuntos
Células Epiteliais , Obstrução Ureteral , Urotélio , Animais , Urotélio/metabolismo , Urotélio/patologia , Urotélio/imunologia , Obstrução Ureteral/patologia , Obstrução Ureteral/metabolismo , Camundongos , Humanos , Células Epiteliais/metabolismo , Células Epiteliais/imunologia , Gatos , Masculino , Camundongos Endogâmicos C57BL , Ureter/patologia , Ureter/metabolismo , Ureter/imunologia , Pelve Renal/patologia , Pelve Renal/metabolismo , FemininoRESUMO
Renal tract defects and autism spectrum disorder (ASD) deficits represent the phenotypic core of the 19q12 deletion syndrome caused by the loss of one copy of the TSHZ3 gene. Although a proportion of Tshz3 heterozygous (Tshz3+/lacZ) mice display ureteral defects, no kidney defects have been reported in these mice. The purpose of this study was to characterize the expression of Tshz3 in adult kidney as well as the renal consequences of embryonic haploinsufficiency of Tshz3 by analyzing the morphology and function of Tshz3 heterozygous adult kidney. Here, we described Tshz3 expression in the smooth muscle and stromal cells lining the renal pelvis, the papilla and glomerular endothelial cells (GEnCs) of the adult kidney as well as in the proximal nephron tubules in neonatal mice. Histological analysis showed that Tshz3+/lacZ adult kidney had an average of 29% fewer glomeruli than wild-type kidney. Transmission electron microscopy of Tshz3+/lacZ glomeruli revealed a reduced thickness of the glomerular basement membrane and a larger foot process width. Compared to wild type, Tshz3+/lacZ mice showed lower blood urea, phosphates, magnesium and potassium at 2 months of age. At the molecular level, transcriptome analysis identified differentially expressed genes related to inflammatory processes in Tshz3+/lacZ compare to wild-type (control) adult kidneys. Lastly, analysis of the urinary peptidome revealed 33 peptides associated with Tshz3+/lacZ adult mice. These results provide the first evidence that in the mouse Tshz3 haploinsufficiency leads to cellular, molecular and functional abnormalities in the adult mouse kidney.
Assuntos
Nefropatias , Fatores de Transcrição/metabolismo , Ureter , Animais , Transtorno do Espectro Autista/genética , Células Endoteliais/patologia , Haploinsuficiência/genética , Rim/metabolismo , Nefropatias/metabolismo , Camundongos , Fatores de Transcrição/genéticaRESUMO
Ret signaling promotes branching morphogenesis during kidney development, but the underlying cellular mechanisms remain unclear. While Ret-expressing progenitor cells proliferate at the ureteric bud tips, some of these cells exit the tips to generate the elongating collecting ducts, and in the process turn off Ret. Genetic ablation of Ret in tip cells promotes their exit, suggesting that Ret is required for cell rearrangements that maintain the tip compartments. Here, we examine the behaviors of ureteric bud cells that are genetically forced to maintain Ret expression. These cells move to the nascent tips, and remain there during many cycles of branching; this tip-seeking behavior may require positional signals from the mesenchyme, as it occurs in whole kidneys but not in epithelial ureteric bud organoids. In organoids, cells forced to express Ret display a striking self-organizing behavior, attracting each other to form dense clusters within the epithelium, which then evaginate to form new buds. The ability of forced Ret expression to promote these events suggests that similar Ret-dependent cell behaviors play an important role in normal branching morphogenesis.
Assuntos
Movimento Celular , Células Epiteliais/metabolismo , Transdução de Sinais , Ureter/metabolismo , Animais , Análise por Conglomerados , Epitélio/metabolismo , Feminino , Rim/crescimento & desenvolvimento , Rim/metabolismo , Masculino , Mesoderma/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Morfogênese , Organoides , Proteínas Tirosina Quinases/metabolismo , Células-Tronco/metabolismoRESUMO
PURPOSE: We describe long-term outcomes, including UTIs and need for reimplantation, after ureterovesicostomy (UV) as a lasting surgical procedure for children with primary obstructive megaureter (POM). MATERIALS AND METHODS: Children referred to our institution between 2016 and 2023 who underwent refluxing UV were analyzed. POM was defined as hydroureteronephrosis with distal ureteral dilatation > 7 mm and a negative workup for other etiologies of hydronephrosis. We assessed for surgical outcomes, complications, rate of UTI, and improvement in upper tract dilatation. Statistical analyses assessed for change in hydronephrosis metrics over follow-up. RESULTS: Among 183 patients diagnosed with POM, 47 (24%) underwent UV. Median age of presentation, surgery, and follow-up was 2, 9, and 43 months, respectively. A total of 7 patients developed 30-day complications: Clavien-Dindo grade 1 in 2 (transient urinary retention) and grade 2 in 5 (UTIs). During monitoring 14 (30%) developed UTIs and 7 (15%) required ureteral reimplant or UV takedown. After surgery there was a significant decrease in the proportion of patients with high-grade hydronephrosis, anteroposterior renal pelvis diameter, and maximum ureteral dilatation. CONCLUSIONS: Refluxing UV is a safe alternative to cutaneous diversion in POM. Most patients had improvement in upper tract dilatation with an acceptable short-term complication rate and need for reoperation (in comparison to routine later reimplantation). Our experience suggests that monitoring alone after UV is feasible, and that selective subsequent reconstruction is a reasonable strategy.
Assuntos
Ureter , Obstrução Ureteral , Humanos , Masculino , Feminino , Obstrução Ureteral/cirurgia , Obstrução Ureteral/etiologia , Pré-Escolar , Lactente , Seguimentos , Estudos Retrospectivos , Ureter/cirurgia , Ureter/anormalidades , Ureter/diagnóstico por imagem , Resultado do Tratamento , Derivação Urinária/métodos , Derivação Urinária/efeitos adversos , Refluxo Vesicoureteral/cirurgia , Refluxo Vesicoureteral/etiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/epidemiologia , Hidronefrose/etiologia , Hidronefrose/cirurgia , Reimplante/métodos , Reimplante/efeitos adversos , Cistostomia/métodosRESUMO
This study aimed to investigate the regeneration of epithelial cells in the long-term observation of ureter reconstruction by excising the demucosalized ileum. First, 8 Beagle dogs were anesthetized and the abdominal cavity was inspected for abnormalities via an abdominal incision. The right kidney and ureter were subsequently separated, and the ureter was severed from its connection to the renal pelvis and bladder and ligated distally. The 10-15 cm of ileum was used to reconstruct the ureter. The biopsies of the proximal, middle, and distal reconstructed ureter (neo-ureter) were collected at the first, third, fifth, and sixth month postoperatively. The regeneration of ileal mucosa at the first, third, fifth, and sixth month was observed by hematoxylin-eosin (HE) staining and immunofluorescence staining cytokeratin 18 (CK18). HE staining results showed irregular cytoarchitecture, severe nuclear consolidation, and inflammatory infiltration in the proximal, middle, and distal neo-ureters of dogs at the first month after ureteral reconstruction. With longer follow-up, the injuries of the proximal, middle, and distal neo-ureters were alleviated at the third, fifth, and sixth month after surgery. The expression of CK18 was higher in the middle neo-ureters than that in the proximal and distal neo-ureters at different time points after ureteral reconstruction and decreased with time. In summary, the present study demonstrated that demucosalized ileum was feasible for ureteral reconstructive surgery with satisfying prognostic effects.
Assuntos
Cirurgia Plástica , Ureter , Animais , Cães , Ureter/cirurgia , Ureter/lesões , Ureter/patologia , Estudos de Viabilidade , Íleo/cirurgia , Células EpiteliaisRESUMO
Upper urinary tract urothelial carcinoma (UTUC) is an uncommon malignancy involving the renal pelvis and ureter. Careful pathologic analysis plays a critical role in the diagnosis and clinical management of UTUC. In combination with clinical and radiologic evaluation, pathologic features can be used to stratify patients into low-risk and high-risk groups. This risk stratification can help clinicians select the optimal treatment for patients with UTUC, such as kidney-sparing (conservative) treatment, radical nephroureterectomy or ureterectomy, and perioperative systemic therapy. However, due to the technical difficulty of obtaining sufficient tissue from the upper urinary tract, it is often challenging for pathologists to accurately grade the tumor and assess tumor invasion in small biopsy specimens. Although the majority of UTUCs are pure urothelial carcinoma, a considerable subset of UTUCs show histologic subtypes or divergent differentiation. Recent studies have identified genetically distinct molecular subtypes of UTUC by examining DNA, RNA, and protein expression profiles. The prognosis of pT3 UTUC, particularly renal pelvic UC, remains controversial, and several studies have proposed subclassification of pT3 UTUC. Lynch syndrome is a significant risk factor for UTUC, and screening tests may be considered in young patients and those with familial histories of the disease. Despite significant progress in recent years, several issues remain to be addressed in the pathologic diagnosis, molecular classification, and treatment of UTUC.
Assuntos
Carcinoma de Células de Transição , Neoplasias Renais , Ureter , Neoplasias da Bexiga Urinária , Sistema Urinário , Humanos , Carcinoma de Células de Transição/diagnóstico , Sistema Urinário/patologia , Ureter/patologia , Ureter/cirurgia , Neoplasias Renais/patologiaRESUMO
BACKGROUND: The prorenin receptor (PRR) plays a critical role in ureteric bud (UB) branching morphogenesis. DOT1 Like (DOT1L), a histone methyltransferase specific for Histone 3 lysine 79 (H3K79), is important for differentiation of the UB-derived renal collecting duct cells. In this study, we tested whether DOT1L/H3 dimethyl K79 (H3m2K79) are regulated by PRR deletion in the UB and UB-derived collecting ducts in the embryonic mouse kidneys. METHODS: Mutant Hoxb7Cre+/PRRflox/flox (PRRUB-/-) and control PRRUB+/+, mice were studied on embryonic (E) day E17.5. DOT1L mRNA and protein expression in the kidney was examined by real-time qRT-PCR and immunohistochemistry, respectively. H3m2K79 protein expression was determined by immunohistochemistry and Western blot analysis. RESULTS: DOT1L mRNA levels were decreased in mutant compared to control mice (0.68 ± 0.06 vs. 1.0 ± 0.01, p < 0.01). DOT1L and H3m2K79 immunostaining was reduced in the mutant vs. control kidneys (Dot1: 0.62 ± 0.03 vs. 1.0 ± 0.01, p < 0.05; H3m2K79: 0.64 ± 0.04 vs.1.1 ± 0.01. p < 0.05.). Western blot analysis revealed decreased H3m2K79 protein levels in mutant compared to control kidneys (1.0 ± 0.06 vs. 1.5 ± 0.02, p < 0.05). CONCLUSION: Targeted deletion of the PRR in the UB and UB-derived collecting ducts results in reduced DOT1L gene/protein and H3m2K79 protein expression in the embryonic mouse metanephroi in vivo. IMPACT: The role of histone methylation in mediating the effect of the prorenin receptor on the ureteric bud branching (UB) morphogenesis and urine acidification during kidney development is unknown. We demonstrate that histone H3 lysine (K) 79 dimethylation by methyltransferase Dot1 is reduced in the embryonic kidney of mice that lack the prorenin receptor in the UB lineage.
Assuntos
Histona-Lisina N-Metiltransferase , Histonas , Receptor de Pró-Renina , Receptores de Superfície Celular , Ureter , Animais , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Camundongos , Histonas/metabolismo , Receptores de Superfície Celular/metabolismo , Receptores de Superfície Celular/genética , Ureter/embriologia , Ureter/metabolismo , Transdução de Sinais , Camundongos Knockout , Deleção de Genes , Metilação , Rim/metabolismo , Rim/embriologia , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Regulação da Expressão Gênica no Desenvolvimento , Túbulos Renais Coletores/metabolismo , Túbulos Renais Coletores/embriologia , Proteínas de Homeodomínio/metabolismo , Proteínas de Homeodomínio/genética , Estruturas EmbrionáriasRESUMO
OBJECTIVES: To investigate the ability of propolis-coated ureteric stents to solve complications, especially urinary tract infections (UTIs) and crusting, in patients with long-term indwelling ureteric stents through antimicrobial and anti-calculus activities. MATERIALS AND METHODS: Polyurethane (PU) ureteric stents were immersed in the ethanol extract of propolis (EEP), a well-known antimicrobial honeybee product, and subjected to chemical, hydrophilic, and seismic tests. The antimicrobial activity of the EEP coating was then examined by in vitro investigation. Proteus mirabilis infection was induced in rats within uncoated and EEP-coated groups, and the infection, stone formation, and inflammation were monitored at various time points. RESULTS: The characterisation results showed that the hydrophilicity and stability of the EEP surface improved. In vitro tests revealed that the EEP coating was biocompatible, could eliminate >90% of bacteria biofilms attached to the stent and could maintain bacteriostatic properties for up to 3 months. The in vivo experiment revealed that the EEP-coating significantly reduced the amount of bacteria, stones, and salt deposits on the surface of the ureteric stents and decreased inflammation in the host tissue. CONCLUSIONS: Compared with clinically used PU stents, EEP-coated ureteric stents could better mitigate infections and prevent encrustation. Thus, this study demonstrated that propolis is a promising natural dressing material for ureteric stents.
Assuntos
Antibacterianos , Materiais Revestidos Biocompatíveis , Própole , Stents , Ureter , Animais , Ratos , Própole/farmacologia , Antibacterianos/farmacologia , Materiais Revestidos Biocompatíveis/farmacologia , Proteus mirabilis/efeitos dos fármacos , Masculino , Infecções Urinárias/prevenção & controle , Ratos Sprague-Dawley , Biofilmes/efeitos dos fármacos , Infecções por Proteus/prevenção & controle , PoliuretanosRESUMO
PURPOSE: To define a peak force of insertion (PFOI) threshold for ureteral damage during ureteral access sheath (UAS) placement on an experimental ureteral orifice model. METHODS: A specially designed water tank using 2 laparoscopic 5 mm ports and 2 different size (10 Fr and 8 Fr) sealing cap adaptors (SCA) as ureteral orifices was used to perform the test. A 10-12 Fr UAS was fixed to a load cell and the force of insertion (FOI) was continuously recorded with a digital force gauge.13 experts in the field of endourology who participated performed 3 UAS insertions. The FOI was recorded initially with 10 Fr followed by 8 Fr SCA. On the final insertion, the orifice was obstructed, leaving a 5 cm length to insert the UAS. The experts were asked to "Stop at the point they anticipate ureteral damage, and they would not proceed in real life". RESULTS: Using 10 Fr SCA the PFOI was 2.12 ± 0.58 Newton (N) (range:1.48-3.48) while 8 Fr SCA showed a PFOI 5.76 ± 0.96 N (range:4.05-7.35). Six of the experts, said they would stop proceeding when they reached above 5.1 N. Three experts had PFOI < 5.1 N and the other 4 stated they would go with PFOIs of 5.88, 6.16, 6.69 and 7.35 N when using SCA of 8 Fr.The highest load they would stop proceeding had a PFOI of 6.09 ± 1.87 N (range: 2.53-10.74). CONCLUSION: The PFOI threshold for ureteral damage inserting UAS of the experts is variable. Although FOI is a subjective perception, experience suggests that ureteral injury may occur at an average of 6.05 N perceived by surgeons' tactile feedback. In-vivo measurement of UAS PFOI may confirm a threshold.
Assuntos
Ureter , Ureter/lesões , Humanos , Procedimentos Cirúrgicos Urológicos/métodos , CirurgiõesRESUMO
PURPOSE: Commercial double J stents (DJS) have a uniform shape regardless of the specific nature of various ureteral diseases. We tested renovated DJS and compared them with conventional DJS using ureter models. METHODS: One straight ureter model included stenosis at the distal ureter near the ureterovesical junction and the other did not. We used conventional DJS and renovated 5- and 6-Fr soft DJS for ureter stones and 6-, 7-, and 8.5-Fr hard DJS for tumors. The DJS comprised holes in the upper, middle, or lower one-third of the shaft (length, 24 cm; 2-cm-diameter coils at both ends). More holes were created along the shaft based on the ureteral disease location. Conventional DJS had holes spaced 1 cm apart along the shaft. Renovated DJS had holes spaced 1 cm apart along the shaft with 0.5-cm intervals on the upper, middle, or lower one-third of the shaft. Urine flow was evaluated. RESULTS: As the DJS diameter increased, the flow rate decreased. The flow rates of DJS with holes in the lower shaft were relatively lower than those of conventional DJS and DJS with holes in the upper and middle shafts. In the ureter model without stenosis, 6-, 7-, and 8.5-Fr renovated stents exhibited significantly higher flow rates than conventional stents. In the ureter model with stenosis, 5-, 6-, 7-, and 8.5-Fr renovated stents did not exhibit significantly higher flow rates than conventional stents. CONCLUSION: Renovated stents and conventional stents did not exhibit significant differences in urine flow with stenosis.
Assuntos
Ureter , Ureterolitíase , Humanos , Ureter/cirurgia , Constrição Patológica , StentsRESUMO
PURPOSE: To evaluate the impact of ureteroscope position within renal cavities as well as different locations of the tip of the ureteral access sheath (UAS) on fluid dynamics during retrograde intrarenal surgery (RIRS). MATERIALS AND METHODS: A prospective observational clinical study was performed. Measurements with a flexible ureteroscope placed in the upper, middle and lower calyces were obtained with the tip of the UAS placed either 2 cm below the pyelo-ureteric junction (PUJ), or at the level of the iliac crest. RESULTS: 74 patients were included. The outflow rates from the middle and upper calyxes were statistically significantly higher compared to the lower calyx, both with the UAS close to the pyelo-ureteric junction and at the iliac crest. When the UAS was withdrawn and positioned at the level of the iliac crest, a significant decrease in outflow rates from the upper (40.1 ± 4.3 ml/min vs 35.8 ± 4.1 ml/min) and middle calyces (40.6 ± 4.0 ml/min vs 36.8 ± 4.6 ml/min) and an increase in the outflow from the lower calyx (28.5 ± 3.3 ml/min vs 33.7 ± 5.7 ml/min) were noted. CONCLUSIONS: Our study showed that higher fluid outflow rates are observed from upper and middle calyces compared to lower calyx. This was true when the UAS was positioned 2 cm below the PUJ and at the iliac crest. Significant worsening of fluid dynamics from upper and middle calyces was observed when the UAS was placed distally at the level of the iliac crest. While the difference was statistically significant, the absolute change was not significant. In contrast, for lower calyces, a statistically significant improvement was documented.
Assuntos
Ureter , Ureteroscópios , Humanos , Hidrodinâmica , Rim , Endoscopia , Ureter/cirurgiaRESUMO
PURPOSE: To experimentally measure renal pelvis pressure (PRP) in an ureteroscopic model when applying a simple hydrodynamic principle, the siphoning effect. METHODS: A 9.5Fr disposable ureteroscope was inserted into a silicone kidney-ureter model with its tip positioned at the renal pelvis. Irrigation was delivered through the ureteroscope at 100 cm above the renal pelvis. A Y-shaped adapter was fitted onto the model's renal pelvis port, accommodating a pressure sensor and a 4 Fr ureteral access catheter (UAC) through each limb. The drainage flowrate through the UAC tip was measured for 60 s each run. The distal tip of the UAC was placed at various heights below or above the center of the renal pelvis to create a siphoning effect. All trials were performed in triplicate for two lengths of 4Fr UACs: 100 cm and 70 cm (modified from 100 cm). RESULTS: PRP was linearly dependent on the height difference from the center of the renal pelvis to the UAC tip for both tested UAC lengths. In our experimental setting, PRP can be reduced by 10 cmH20 simply by lowering the distal tip of a 4 Fr 70 cm UAC positioned alongside the ureteroscope by 19.7 cm. When using a 4 Fr 100 cm UAC, PRP can drop 10 cmH20 by lowering the distal tip of the UAC 23.3 cm below the level of the renal pelvis. CONCLUSION: Implementing the siphoning effect for managing PRP during ureteroscopy could potentially enhance safety and effectiveness.
Assuntos
Pelve Renal , Pressão , Ureter , Ureteroscopia , Ureteroscopia/métodos , Ureter/fisiologia , Humanos , Modelos Anatômicos , Ureteroscópios , Técnicas In VitroRESUMO
INTRODUCTION: Stents with anti-reflux properties have been previously described in various studies but not widely adopted. We designed, constructed and tested a novel umbrella-looking anti-reflux skirt on a double J stent at the level of the ureteral orifice in a previous ex-vivo study. This study serves as a proof of concept of testing this prototype in a porcine model. METHODS: 3 Yorkshire-Landrace pigs were put under general anaesthesia. Conventional bilateral retrograde stenting with white-colored double-J stents were performed. Deployment of anti-reflux skirt was performed unilaterally. Capsaicin mixed with methylene blue and saline were instilled in the bladder. Both stents were removed and methylene blue stain were inspected to assess the level of reflux. Bilateral stenting was performed again and stents/skirt prototype were left in-situ for 1 week. The procedure was repeated on Day 7 to re-test the anti-reflux property of the prototype after ureteral dilatation. RESULTS: Intraluminal reflux was evident, with methylene blue stain seen on the inner surface of the stents. Extraluminal reflux was proved with blue stain seen on the outer surface of the stents, both in undilated and dilated ureters. Study also proved the anti-reflux property of the skirt as the blue stain didn't go beyond the skirt, whereas the contralateral stent was stained up to proximal ureter. CONCLUSION: In this porcine in-vivo study, we elucidated that reflux occurred were both intraluminal and extraluminally. As a proof of concept, it also showed the anti-reflux property of a novel ureteral skirt.
Assuntos
Estudo de Prova de Conceito , Desenho de Prótese , Stents , Ureter , Refluxo Vesicoureteral , Animais , Suínos , Ureter/cirurgia , Modelos Animais de Doenças , Sus scrofaRESUMO
OBJECTIVES: To compare the efficiency and safety of a novel flexible ureteral access sheath (f-UAS) and traditional ureteral access sheath (UAS) during retrograde intrarenal surgery (RIRS). PATIENTS AND METHODS: Between January 2022 and September 2022, a total of 152 consecutive cases with renal stones underwent RIRS with the f-UAS. Their outcomes were compared with those of another 152 consecutive cases undergoing RIRS with traditional UAS using a 1:1 scenario matched-pair analysis, with matching parameters including age and stone size. The f-UAS is a novel UAS with a 10-cm-long tube at the tip that can follow the bends of flexible ureteroscope (f-URS). RESULTS: Baseline characteristics were found to be similar between the two groups. The f-UAS group demonstrated significantly higher SFR (76.3% vs. 7.2%; P < 0.001) at 1 day postoperatively and a higher clearance rate of stone volume (98.11% vs. 91.78%; P < 0.001). The f-UAS group also had lower total complications rate (9.9% vs. 22.4%; P = 0.003), lower incidence of fever (5.9% vs 11.9%; P = 0.001), shorter operative times (56.5 min vs. 59.9 min; P = 0.047), and lower usage rate of baskets (17.1% vs. 100%; P < 0.001). There was no significant difference in SFR at 1 month postoperatively (P = 0.627) and in the length of postoperative hospital stay between the two groups (P = 0.225). CONCLUSION: Compared to the traditional UAS during RIRS, the f-UAS showed several advantages, including higher SFR at 1 day postoperatively, shorter operative times, lower incidence of complications, and less use of basket.