RESUMEN
BACKGROUND: Benign uretero-ileal anastomotic stricture (UIAS) is a potentially serious complication that can arise after radical cystectomy (RC) and subsequent urinary diversion. To preserve residual renal function and improve prognosis, it is crucial to derive insights from experience and tailor individualized treatment strategies for different patients. PATIENTS AND METHODS: From October 2014 to June 2021, a total of 47 patients with benign UIAS underwent endoscopic management (n = 19) or reimplantation surgery (n = 28). The basic data, perioperative conditions, and postoperative outcomes of the two groups were compared and analyzed to evaluate efficacy. RESULTS: Comparing preoperative and postoperative clinical efficacy within the same group, the endoscopic group showed no significant differences in creatinine and blood urea nitrogen (BUN) levels before surgery or after extubation (p > 0.05). However, significant differences were observed in glomerular filtration rate (GFR) levels on the affected side before surgery and after extubation (p < 0.05). In contrast, the laparoscopic reimplantation group did not exhibit significant differences in creatinine, BUN, or GFR levels of affected side before surgery and after extubation (p > 0.05). Postoperative clinical efficacy showed no significant difference in creatinine and BUN levels between the two groups (p > 0.05). However, GFR values of affected side in the endoscopic treatment group decreased more than those in the laparoscopic reimplantation group (p < 0.05). Additionally, the laparoscopic reimplantation group was able to remove the single-J tube earlier than the endoscopic treatment group (p < 0.05), had a lower recurrence rate of hydronephrosis after extubation (p < 0.05), and experienced a later onset of hydronephrosis compared to the endoscopic treatment group (p < 0.05). CONCLUSIONS: Based on our experience in treating UIAS following RC combined with urinary diversion, laparoscopic reimplantation effectively addresses the issue of UIAS, allowing for the removal of the ureteral stent relatively soon after surgery. This approach maintains long-term ureteral patency, preserves residual renal function, reduces the risk of ureteral restenosis and hydronephrosis, and has demonstrated superior therapeutic outcomes in this study.
Asunto(s)
Anastomosis Quirúrgica , Cistectomía , Complicaciones Posoperatorias , Uréter , Derivación Urinaria , Humanos , Derivación Urinaria/efectos adversos , Derivación Urinaria/métodos , Cistectomía/efectos adversos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Constricción Patológica/etiología , Constricción Patológica/cirugía , Anastomosis Quirúrgica/efectos adversos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Uréter/cirugía , Tasa de Filtración Glomerular , Íleon/cirugía , Estudios Retrospectivos , Neoplasias de la Vejiga Urinaria/cirugía , Resultado del Tratamiento , Creatinina/sangre , Laparoscopía/efectos adversos , Obstrucción Ureteral/cirugía , Obstrucción Ureteral/etiologíaRESUMEN
Intravesical therapy (IT) is widely used to tackle various urological diseases. However, its clinical efficacy is decreased by the impermeability of various barriers presented on the bladder luminal surface, including the urinary mucus layer and the densely packed tissue barrier. In this study, we report a mucoadhesive-to-penetrating nanomotors-in-hydrogel system for urothelium-oriented intravesical drug delivery. Upon intravesical instillation, its poloxamer 407 (PLX) hydrogel gelated and adhered to the urothelium to prolong its intravesical retention. The urea afterwards diffused into the hydrogel, thus generating a concentration gradient. Urease-powered membrane nanomotors (UMN) without asymmetric surface engineering could catalyze the urea and migrate down this concentration gradient to deeply and unidirectionally penetrate the urothelial barrier. Moreover, the intravesical hybrid system-delivered gemcitabine could effectively inhibit the bladder tumor growth without inducing any side effect. Therefore, our mucoadhesive-to-penetrating nanomotors-in-hydrogel system could serve as an alternative to IT to meet the clinical need for more efficacious therapeutics for urological diseases.
Asunto(s)
Sistemas de Liberación de Medicamentos , Hidrogeles , Poloxámero , Neoplasias de la Vejiga Urinaria , Urotelio , Urotelio/metabolismo , Animales , Hidrogeles/química , Sistemas de Liberación de Medicamentos/métodos , Administración Intravesical , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/metabolismo , Ratones , Poloxámero/química , Desoxicitidina/análogos & derivados , Desoxicitidina/química , Desoxicitidina/administración & dosificación , Gemcitabina , Vejiga Urinaria/metabolismo , Humanos , Femenino , Línea Celular Tumoral , AdhesividadRESUMEN
A selective tumor-penetrating strategy generally exploits tumor-targeted ligands to modify drugs so that the conjugate preferentially enters tumors and subsequently undergoes transcellular transport to penetrate tumors. However, this process shields ligands from their corresponding targets on the cell surface, possibly inducing an off-target effect during drug penetration at the tumor-normal interface. Herein, we first describe a selective tumor-penetrating drug (R11-phalloidin conjugates) for intravesical therapy of bladder cancer. The intravesical conjugates rapidly translocated across the mucus layer, specifically bound to tumors, and infiltrated throughout the tumor via direct intercellular transfer. Notably, direct transfer from normal cells to tumor cells was unidirectional because the pathways required for direct transfer, termed F-actin-rich tunneling nanotubes, were more unidirectionally extended from normal cells to tumor cells. Moreover, the intravesical conjugates displayed strong anticancer activity and well-tolerated biosafety in murine orthotopic bladder tumor models. Our study demonstrated the potential of a selective tumor-penetrating conjugate for effective intravesical anticancer therapy.
Asunto(s)
Neoplasias de la Vejiga Urinaria , Ratones , Animales , Administración Intravesical , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
BACKGROUND: Bladder cancer (BCa) is a highly malignant tumor, and if left untreated, it can develop severe hematuria and tumor metastasis, thereby endangering the patient's life. The purpose of this paper was to detect the expression of ATAD3A in BCa and research the relationship between ATAD3A and pathological features of bladder cancer and the prognosis of patients. METHODS: First, the expression of ATAD3A in BCa and normal bladder tissues was analyzed based on the UALCAN and Oncomine public databases. Second, 491 cases of surgically resected bladder cancer specimens and 110 cases of normal adjacent tissues were immunohistochemically stained. The expression of ATAD3A was quantified, and the value and prognosis of ATAD3A as a biomarker of BCa were evaluated. RESULTS: The expression of ATAD3A in bladder cancer tissues was higher than that in normal bladder mucosa. High expression of ATAD3A was correlated with patient age, tumor size, number of tumors, distant metastasis, lymph node metastasis, lymphovascular invasion, and TNM stage (p < 0.05). Overexpression of ATAD3A is closely related to cancer patient survival. The mean survival time of bladder cancer patients with high ATAD3A expression was shorter than those with low ATAD3A levels. According to the relative comparing result, the high ATAD3A expression herald reduced overall survival in BCa patients. CONCLUSIONS: The abnormal overexpression of ATAD3A may be related to the initiation and progress of bladder cancer. The upregulation of ATAD3A can be used as an effective indicator to diagnose bladder cancer and predict tumor progression. Furthermore, the combination of information from public databases and the results of clinical sample analysis can help us better understand the mechanism of action of molecular oncogenes in bladder cancer.
Asunto(s)
Neoplasias de la Vejiga Urinaria , Humanos , Pronóstico , Neoplasias de la Vejiga Urinaria/metabolismo , Biomarcadores , Vejiga Urinaria/patología , Metástasis Linfática , ATPasas Asociadas con Actividades Celulares Diversas , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales/metabolismoRESUMEN
Objective: To assess the feasibility and safety of zero ischaemia robotic-assisted laparoscopic partial nephrectomy (RALPN) after preoperative superselective transarterial embolization (STE) of T1 renal cancer. Methods: We retrospectively analyzed the data of 32 patients who underwent zero ischaemia RALPN after STE and 140 patients who received standard robot-assisted laparoscopic partial nephrectomy (S-RALPN). In addition, we selected 35 patients treated with off-clamp RALPN (O-RALPN) from September 2017 to March 2022 for comparison. STE was performed by the same interventional practitioner, and zero ischaemia laparoscopic partial nephrectomy (LPN) was carried out by experienced surgeon 1-12 hours after STE. The intraoperative data and postoperative complications were recorded. The postoperative renal function, routine urine test, urinary Computed Tomography (CT), and preoperative and postoperative glomerular filtration rate (GFR) data were analyzed. Results: All operations were completed successfully. There were no cases of conversion to opening and no deaths. The renal arterial trunk was not blocked. No blood transfusions were needed. The mean operation time was 91.5 ± 34.28 minutes. The mean blood loss was 58.59 ± 54.11 ml. No recurrence or metastasis occurred. Conclusion: For patients with renal tumors, STE of renal tumors in zero ischaemia RALPN can preserve more renal function, and it provides a safe and feasible surgical method.
RESUMEN
Objective: To investigate the outcome of patients underwent anatomic periurethral reconstruction during robotic assisted laparoscopic radical prostatectomy (RARP). Materials and methods: During August 2016 to May 2018, periurethral structure anatomic reconstruction was performed during RARP in 58 consecutive patients. The control group consists of another 50 patients had no reconstruction procedure during RARP. Perioperative data of these patients were collected retrospectively, including operation time, anastomosis time, intraoperative blood loss, duration of indwelling catheter, length of hospital stay, complications, postoperative pathology, and continence outcome at 1,3,6 and 12 months. Results: All cases were successfully performed without conversion to open or laparoscopic surgery. There were no major intraoperative or postoperative complications.The percentage of patients maintain continence in the reconstruction group versus non-reconstruction group: At 1 month 84.5% (49/58)versus 70.0% (35/50), at 3 months 89.7% (52/58)versus 78.0% (39/50), at 6 months 91.3% (53/58)versus 86.0% (43/50) and 1 year after surgery 100.0% (58/58)versus 96.0% (48/50). Reconstruction group showed better continence outcome in 1 and 3 months (P<0.05). There is no statistical differences in 6 month and 1 year. Conclusion: Anatomic reconstruction of periurethral structure during RARP is safe and feasible with reduced duration of indwelling catheter and better continence outcome.
RESUMEN
The blood-prostate barrier (BPB), a non-static physical barrier, stands as an obstacle between the prostate stroma and the lumen of the prostate gland tube. The barrier has the ability to dynamically regulate and strictly control the mass exchange between the blood and the prostate, thereby limiting drug penetration into the prostate. The basement membrane, fibrous stromal layer, capillary endothelial cell, prostatic ductal epithelial cell, lipid layer, etc., have been confirmed to be involved in the composition of the barrier structure and altered membrane permeability mainly by regulating the size of paracellular ion pores. Various studies have been conducted to improve the efficiency of drug therapy for prostate diseases by changing the administration approaches, improving barrier permeability and increasing drug penetration. To gain a full understanding of BPB, the composition of BPB, the methodology for evaluating the permeability of BPB and alterations in barrier function under pathological conditions are summarized in this review. To find a shortcut for drug delivery across BPB, the biodistribution of drugs in the prostate and different methods of improving drug penetration across BPB are outlined. This review offers an applied perspective on recent advances in drug delivery across BPB.
RESUMEN
Background: Benign uretero-ileal anastomotic stricture (UIAS) is a major complication following radical cystectomy (RC) and ileal orthotopic bladder substitution, and it can occur in combination with other complications. But risk factors for patients with UIAS have not been well described. Material and methods: We retrospectively reviewed 198 patients treated with RC for bladder cancer from 2014 to 2019 at the Zhejiang Provincial People's Hospital. Patient demographic and clinical variables were examined to determine the risk factors associated with UIAS by univariate and multivariate logistic regression analysis. Results: A total of 180 patients into the group standards and in all 360 uretero-ileal anastomoses. Among the above cases, 22 patients developed UIAS, including 10 cases of left UIAS, nine cases of right UIAS, and three cases of bilateral UIAS. There was no difference in demographic, operative, or perioperative variables between patients with and without UIAS. In a multivariate analysis, after adjusting for gender, age, surgical methods, and underlying diseases, intraoperative or postoperative blood transfusion (HR = 0.144, P <0.01), postoperative urinary tract infection (HR = 3.624, P <0.01), and extracorporeal bladder anastomosis (HR = 3.395, P = 0.02) significantly increased the risk of UIAS. Conclusions: In our experience, intraoperative or postoperative blood transfusion, postoperative urinary tract infection, and extracorporeal neobladder anastomoses increased the risk of UIAS after radical cystectomy and ileal orthotopic bladder substitution surgery. Further studies with larger samples are necessary to validate this result.
RESUMEN
Cancer has long been a hot research topic, and recent years have witnessed the incidence of cancer trending toward younger individuals with great socioeconomic burden. Even with surgery, therapeutic agents serve as the mainstay to combat cancer in the clinic. Intensive research on nanomaterials can overcome the shortcomings of conventional drug delivery approaches, such as the lack of selectivity for targeted regions, poor stability against degradation, and uncontrolled drug release behavior. Over the years, different types of drug carriers have been developed for cancer therapy. One of these is liposome-in-gel (LP-Gel), which has combined the merits of both liposomes and hydrogels, and has emerged as a versatile carrier for cancer therapy. LP-Gel hybrids have addressed the lack of stability of conventional liposomes against pH and ionic strength while displaying higher efficiency of delivery hydrophilic drugs as compared to conventional gels. They can be classified into three types according to their assembled structure, are characterized by their nontoxicity, biodegradability, and flexibility for clinical use, and can be mainly categorized based on their controlled release, transmucosal delivery, and transdermal delivery properties for anticancer therapy. This review covers the recent progress on the applications of LP-Gel hybrids for anticancer therapy.
Asunto(s)
Liposomas , Neoplasias , Humanos , Liposomas/química , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/química , Hidrogeles/química , Neoplasias/tratamiento farmacológicoRESUMEN
Our previous study showed that growth arrest- and DNA damage-inducible gene 153 (GAD153/CHOP) plays an important role in intermittent hypoxia- (IH-) induced apoptosis and impaired synaptic plasticity. This study is aimed at determining which signaling pathway is activated to induce CHOP and the role of this protein in mitochondria-dependent apoptosis induced by IH. In the in vivo study, mice were placed in IH chambers for 8 h daily over a period of 2 weeks; the IH chambers had oxygen (O2) concentrations that oscillated between 10% and 21%, cycling every 90 s. In the in vitro study, PC12 cells were exposed to 21% O2 (normoxia) or 8 IH cycles (25 min at 21% O2 and 35 min at 0.1% O2 for each cycle). After 2 weeks of IH treatment, we observed that the expression levels of phosphorylated protein kinase-like endoplasmic reticulum kinase (p-PERK), activating transcription factor 4 (ATF-4) and phosphorylated eukaryotic initiation factor 2 alpha (p-elf2α), were increased, but the levels of activating transcription factor 6 (ATF-6) and inositol-requiring enzyme 1 (IRE-1) were not increased. GSK2606414, a specific chemical inhibitor of the PERK pathway, reduced the expression of p-PERK, ATF-4, p-elf2α, and CHOP and rescued ER structure. In addition, Bax and Bak accumulated in the mitochondria after IH treatment, which induced cytochrome c release and initiated apoptosis. These effects were prevented by GSK2606414 and CHOP shRNA. Finally, the impaired long-term potentiation and long-term spatial memory in the IH group were rescued by GSK2606414. Together, the data from the in vitro and in vivo experiments indicate that IH-induced apoptosis and impaired synaptic plasticity were mediated by the PERK-ATF-4-CHOP pathway. Suppressing PERK-ATF-4-CHOP signaling pathway attenuated mitochondria-dependent apoptosis by reducing the expression of Bax and Bak in mitochondria, which may serve as novel adjunct therapeutic strategy for ameliorating obstructive sleep apnea- (OSA-) induced neurocognitive impairment.
Asunto(s)
Disfunción Cognitiva/metabolismo , Hipoxia/metabolismo , Neuronas/metabolismo , Factor de Transcripción CHOP/biosíntesis , Proteína Destructora del Antagonista Homólogo bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Adenina/análogos & derivados , Adenina/farmacología , Adenina/uso terapéutico , Animales , Apoptosis/efectos de los fármacos , Apoptosis/fisiología , Disfunción Cognitiva/tratamiento farmacológico , Hipoxia/tratamiento farmacológico , Indoles/farmacología , Indoles/uso terapéutico , Masculino , Ratones , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Células PC12 , Ratas , Factor de Transcripción CHOP/antagonistas & inhibidoresAsunto(s)
Cuerpos Extraños/complicaciones , Cuerpos Extraños/cirugía , Granuloma de Células Plasmáticas/etiología , Granuloma de Células Plasmáticas/cirugía , Hepatopatías/etiología , Hepatopatías/cirugía , Hígado/cirugía , Cuerpos Extraños/diagnóstico por imagen , Cuerpos Extraños/patología , Granuloma de Células Plasmáticas/diagnóstico por imagen , Granuloma de Células Plasmáticas/patología , Hepatectomía/métodos , Humanos , Hígado/patología , Hepatopatías/patología , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
An effective and biodegradable Ficus tikoua leaves extract was studied as a corrosion inhibitor for carbon steel in hydrochloric acid. Systematic electrochemical experiments and morphological characterization were carried out to investigate the properties of the corrosion inhibitor. Meanwhile, quantum chemical calculations were performed to aid further understanding of the electrochemical mechanism. The electrochemical results reveal that the extract inhibitors act as a mixed-type with an inhibition efficiency up to 95.8% at 298â¯K. Moreover, this extract shows good inhibory activity at a wide range of temperatures and the corresponding results were further confirmed by morphological analysis. The chemical formulae of these major components are fully optimized in the DFT with B3LYP in the gas phase and the base set is 6-311++G (d, p).