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1.
Heliyon ; 10(8): e29198, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38644863

RESUMO

Objectives: To describe a bladder cuff excision method modified with ureteral catheterization to better visualize the ureteral orifice during robot-assisted nephroureterectomy (RANU). Methods: We retrospectively analyzed 66 patients with upper urinary tract urothelial carcinoma of the renal pelvis and/or upper-mid ureter treated between January 2020 and January 2023. Among them, 32 patients (group A) underwent RANU supported by ureteral catheterization, and the remaining patients (group B) received routine transperitoneal RANU. Postoperative cystoscopy was performed routinely to compare the rates of residual ureteral orifice between the two groups. Results: Surgeries were completed uneventfully in all 66 patients, without blood transfusion or conversion to open procedures. The operative time, estimated blood loss, and postoperative length of hospital stay were similar between both groups. However, the mean time required for BCE in group A was shorter than that in group B (9.5 min vs. 16.0 min, p = 0.006). Cystoscopy at postoperative three months showed no ipsilateral ureteral orifice in group A, but residual ureteral orifice was found in 23.5% of patients in group B. During a short follow-up period of 16 months, no patients in group A experienced bladder tumor recurrence. However, two patients (5.9%) in group B developed bladder tumor recurrence, with one experiencing local tumor recurrence at the level of the ureteral stump. Conclusions: Our novel technique enables complete ureteral retrieval, accurate and rapid bladder cuff excision, which makes the procedure less invasive and safely reproducible during robot-assisted nephroureterectomy.

2.
Mol Pharm ; 21(4): 1705-1718, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38466144

RESUMO

Photodynamic therapy (PDT) is often applied in a clinical setting to treat bladder cancer. However, current photosensitizers report drawbacks such as low efficacy, low selectivity, and numerous side effects, which have limited the clinical values of PDT for bladder cancer. Previously, we developed the first bladder cancer-specific aptamer that can selectively bind to and be internalized by bladder tumor cells versus normal uroepithelium cells. Here, we use an aptamer-based drug delivery system to deliver photosensitizer chlorine e6 (Ce6) into bladder tumor cells. In addition to Ce6, we also incorporate catalase into the drug complex to increase local oxygen levels in the tumor tissue. Compared with free Ce6, an aptamer-guided DNA nanotrain (NT) loaded with Ce6 and catalase (NT-Catalase-Ce6) can specifically recognize bladder cancer cells, produce oxygen locally, induce ROS in tumor cells, and cause mitochondrial apoptosis. In an orthotopic mouse model of bladder cancer, the intravesical instillation of NT-Catalase-Ce6 exhibits faster drug internalization and a longer drug retention time in tumor tissue compared with that in normal urothelium. Moreover, our modified PDT significantly inhibits tumor growth with fewer side effects such as cystitis than free Ce6. This aptamer-based photosensitizer delivery system can therefore improve the selectivity and efficacy and reduce the side effects of PDT treatment in mouse models of bladder cancer, bearing a great translational value for bladder cancer intravesical therapy.


Assuntos
Clorofilídeos , Fotoquimioterapia , Porfirinas , Neoplasias da Bexiga Urinária , Animais , Camundongos , Catalase/uso terapêutico , Linhagem Celular Tumoral , Oxigênio , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Neoplasias da Bexiga Urinária/tratamento farmacológico , Humanos
3.
J Magn Reson Imaging ; 59(4): 1179-1190, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37602726

RESUMO

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) is widely used to assess the muscle-invasive status of bladder cancer. However, the current classification efficacy of VI-RASD 2 tumors of stalk is unsatisfactory. PURPOSE: To develop a nomogram to assess muscle-invasive bladder cancer (MIBC) in VI-RADS 2 tumors with stalk. STUDY TYPE: Retrospective. POPULATION: A total of 186 patients (age: 67.8 ± 12.7 years) with 15.1% females, divided randomly into a training cohort (N = 130) and validation cohort (N = 56). FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin-echo), and dynamic contrast-enhanced imaging (gradient-echo). ASSESSMENT: Twenty-one MRI features of tumors and stalks were developed from training cohort. The mean apparent diffusion coefficient (ADC) values of the tumor, stalk, and psoas muscles were calculated from the three circular regions of interest. The normalized T value = mean ADC tumor mean ADC muscle . The normalized ST value = mean ADC stalk mean ADC tumor . Three readers assessed the morphology of tumors and stalks. STATISTICAL TESTS: The final features of nomogram were selected by univariable logistic and the least absolute shrinkage and selection operator (LASSO) regression. The performance of the nomogram was assessed by the receiver operating characteristic (ROC) curve, calibration, and decision curve analysis. RESULTS: In VI-RADS 2 tumors with stalk, tumor size over 3 cm, increased stalk width, stalk morphology, decreased normalized T value, and increased normalized ST value were selected as the risk factors for MIBC. The AUC, accuracy, sensitivity, and specificity of the nomogram to assess MIBC were 0.969 (95% CI: 0.941-0.997), 92.3%, 94.1%, and 92.0% in training cohort and 0.940 (95% CI: 0.859-1.000), 89.3%, 75.0%, and 91.7% in validation cohort. DATA CONCLUSION: This study constructed a nomogram for preoperative assessment of MIBC and modifying the current VI-RADS. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.


Assuntos
Nomogramas , Neoplasias da Bexiga Urinária , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Estudos Retrospectivos , Imageamento por Ressonância Magnética/métodos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia , Músculos/patologia
4.
Materials (Basel) ; 16(23)2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38068206

RESUMO

Carbon segregation is the major and classical internal defect in the continuous casting process of carbon steel. Based on the combined electromagnetic stirring equipment for new billet in a steel plant, China, the influence of combined electromagnetic stirring (M-EMS + F-EMS) on the carbon segregation of 300 mm × 340 mm special-shaped billet was studied via numerical simulation and on-site industrialization tests. The Lorentz force and carbon solute distribution were simulated under different EMS parameters. The formation mechanism of the carbon segregation of medium carbon steel with different combined electromagnetic stirring processes was analyzed. The results show that: (1) with the combined action of "solute flushing" effect and gravity, the carbon concentration in the loose side of the medium carbon steel casting billet is gradually lower than the fixed side, while the carbon concentration on the fixed side gradually accumulates more; and (2) under the action of combined electromagnetic stirring, the segregation index of casting billet could be controlled to remain between 0.96-1.05 and shows an increasing change in solidification from the skin to the center. When the current and frequency of M-EMS are 250 A and 2.0 Hz and the F-EMS are 180 A and 8.0 Hz, the carbon segregation defects in the special-shaped (300 mm × 340 mm) casting billet can be significantly improved.

5.
Sci Rep ; 13(1): 21502, 2023 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-38057353

RESUMO

Vesical Imaging Reporting and Data System (VI-RADS) shows good potential in determining muscle-invasive bladder cancer (MIBC) patients. However, whether VI-RADS could predict the prognosis of radical cystectomy (RC) patients has not been reported. Our purpose is to determine whether VI-RADS contributed to predict oncologic outcomes. In this retrospective study, we analysed the information of bladder cancer patients who admitted to our centre from June 2012 to June 2022. All patients who underwent multiparametric magnetic resonance imaging (mpMRI) and underwent RC were included. VI-RADS scoring was performed by two radiologists blinded to the clinical data. Patients' clinical features, pathology data, and imaging information were recorded. Kaplan-Meier method was used to estimate patients' overall survival (OS) and progression-free survival (PFS). Log-rank test was used to assess statistical differences. COX regression analysis was used to estimate risk factors. Ultimately, we included 219 patients, with 188 males and 31 females. The median age was 66 (IQR = 61-74.5) years. The VI-RADS scores were as follows: VI-RADS 1, 4 (1.8%); VI-RADS 2, 68 (31.1%); VI-RADS 3, 40 (18.3%); VI-RADS 4, 69 (31.5%); and VI-RADS 5, 38 (17.4%). Patients with VI-RADS ≥ 3 had poorer OS and PFS than those with VI-RADS < 3. The AUC of VI-RADS predicting 3-year OS was 0.804, with sensitivity of 0.824 and negative predictive value of 0.942. Multivariate COX analysis showed that VI-RADS ≥ 3 was risk factors for OS (HR = 3.517, P = 0.003) and PFS (HR = 4.175, P < 0.001). In the MIBC subgroup, patients with VI-RADS ≥ 4 had poorer OS and PFS. In the non-muscle invasive bladder cancer (NMIBC) subgroup, the prognosis of patients with VI-RADS ≥ 3 remained poorer. VI-RADS scores could effectively predict the survival of patients after RC.


Assuntos
Neoplasias da Bexiga Urinária , Bexiga Urinária , Masculino , Feminino , Humanos , Idoso , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/cirurgia , Bexiga Urinária/patologia , Cistectomia , Estudos Retrospectivos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Prognóstico , Imageamento por Ressonância Magnética/métodos
6.
J Magn Reson Imaging ; 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38153874

RESUMO

BACKGROUND: Vesical Imaging-Reporting and Data System (VI-RADS) has been developed for assessing bladder cancer from multiparametric (mp) MRI but its performance in diagnosing muscle-invasive bladder cancer (MIBC) is suboptimal. PURPOSE: To investigate associations between normalized apparent diffusion coefficient (NADC) and clinicopathological characteristics and to determine whether the inclusion of NADC can improve the performance of VI-RADS in diagnosing MIBC. STUDY TYPE: Retrospective. POPULATION: Two hundred seventy-five patients with pathologically confirmed bladder cancer (101 MIBC and 174 non-MIBC [NMIBC]) underwent preoperative mpMRI (233 male, 42 female). FIELD STRENGTH/SEQUENCE: 3-T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (free-breathing spin-echo), and dynamic contrast-enhanced imaging (gradient-echo). ASSESSMENT: NADC was the mean ADC of tumor divided by that of the iliopsoas muscles in trans caput femoris plane. Associations between NADC and clinicopathological characteristics were evaluated. Models were established for differentiating MIBC and NMIBC: VI-RADS model; VN model (VI-RADS and NADC), Images model (significant variables from imaging associated with MIBC), LN model (Images model without NADC), and Full model (all significant variables associated with MIBC). STATISTICAL TESTS: Variables for model development were based on logistic regression. Models were evaluated by receiver operating characteristic (ROC) curve. Comparison of the area under the curves (AUCs) for the models used DeLong's test. A P value <0.05 was considered statistically significant. RESULTS: NADC was significantly lower in lesions with diameter ≥ 3 cm, MIBC, histological high grade, lymph node metastasis, and lymphovascular invasion. Compared with VI-RADS model, the AUCs for VN model (VI-RADS score and NADC), Images model (VI-RADS score, NADC and tumor size) and Full model (VI-RADS score, NADC, tumor size and histological grade) were significantly higher. No significant differences were observed between the AUCs for VN model and Images model (P = 0.051). DATA CONCLUSION: NADC reflects information about the aggressiveness of bladder cancer. Combining VI-RADS with NADC can improve performance in diagnosing MIBC. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

7.
J Magn Reson Imaging ; 2023 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-37902432

RESUMO

BACKGROUND: The relationship between tumor and muscle layer in the vesical imaging-reporting and data system (VI-RADS) 3 is ambiguous, and there is a lack of preoperative and non-invasive procedures to detect muscle invasion in VI-RADS 3. PURPOSE: To develop a nomogram based on MRI features for detecting muscle invasion in VI-RADS 3. STUDY TYPE: Retrospective. POPULATION: 235 cases (Age: 67.5 ± 11.5 years) with 11.9% females were randomly divided into a training cohort (n = 164) and a validation cohort (n = 71). FIELD STRENGTH/SEQUENCE: 3T, T2-weighted imaging (turbo spin-echo), diffusion-weighted imaging (breathing-free spin echo), and dynamic contrast-enhanced imaging (gradient echo). ASSESSMENT: 3 features were selected from the training cohort, including tumor contact length greater than maximum tumor diameter (TCL > Dmax), flat tumor morphology, and lower standard deviation of apparent diffusion coefficient (ADCSD ). Three readers assessed VI-RADS scores and the tumor morphology. STATISTICAL TESTS: Interobserver agreement was assessed by Kappa analysis. Features for final analysis were selected by logistic regression. The performance of the nomogram was evaluated by the receiver operating characteristic curve, decision curve analysis, and calibration curve. RESULTS: TCL > Dmax, flat morphology, and lower ADCSD were the independent risk factors for muscle invasive in VI-RADS 3. The AUCs, accuracy, sensitivity, and specificity of the nomogram 1 composed of three features for detecting muscle invasion were 0.852 (95% CI: 0.793-0.912), 0.756, 0.917, and 0.663 in the training cohort, and 0.885 (95% CI: 0.801-0.969), 0.817, 0.900, and 0.784 in the validation cohort. The nomogram 2 without ADCSD has nearly the same performance as the nomogram 1. DATA CONCLUSION: Nomogram can be an efficient tool for preoperative detection of muscle invasion in VI-RADS 3. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

8.
Urol Int ; 107(7): 742-746, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36889288

RESUMO

Angiomyolipoma (AML) complicated with tumour thrombus extending to the confluence of inferior vena cava (IVC) with right atrium is rarely observed. We report a female AML patient admitted to our centre on January 21, 2020, with complication of tumour thrombus extending to the confluence of IVC with right atrium and had no sign of difficult breathing. She underwent whole-abdominal enhanced CT for abdominal pain and was diagnosed with a possible renal AML with tumour thrombus. Open radical nephrectomy and thrombectomy of vena cava were performed. Intraoperative transoesophageal echocardiography indicated that the tumour thrombus has reached the confluence of IVC with right atrium. The operation took 255 min with an intraoperative haemorrhage of 800mL. The patient was discharged 7 days after surgery. Pathology revealed lipoma-like AML. Immunohistochemistry showed vimentin (+), EMA (-), HMB45 (+), S-100 (-), SMA (+), TFE-3 (-), melan A (+). After 2 years of follow-up, we found that the patient showed full recovery and had no recurrence. Therefore, lipoma-like AML should also be followed closely for recurrence and metastasis. When AML involves IVC tumour thrombus, open thrombectomy and radical nephrectomy are safe and effective methods.


Assuntos
Angiomiolipoma , Carcinoma de Células Renais , Neoplasias Renais , Leucemia Mieloide Aguda , Lipoma , Trombose , Trombose Venosa , Humanos , Feminino , Veia Cava Inferior/diagnóstico por imagem , Veia Cava Inferior/cirurgia , Veia Cava Inferior/patologia , Carcinoma de Células Renais/cirurgia , Angiomiolipoma/complicações , Angiomiolipoma/diagnóstico por imagem , Angiomiolipoma/cirurgia , Neoplasias Renais/complicações , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/cirurgia , Trombose/diagnóstico por imagem , Trombose/cirurgia , Trombose/complicações , Trombose Venosa/diagnóstico por imagem , Trombose Venosa/etiologia , Trombose Venosa/cirurgia , Trombectomia/efeitos adversos , Nefrectomia/métodos , Lipoma/complicações , Lipoma/diagnóstico por imagem , Lipoma/cirurgia , Átrios do Coração , Leucemia Mieloide Aguda/complicações , Leucemia Mieloide Aguda/patologia , Leucemia Mieloide Aguda/cirurgia
9.
Zhonghua Nan Ke Xue ; 29(10): 894-898, 2023 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-38639658

RESUMO

OBJECTIVE: To explore the safety, feasibility, and technical points of the improved circumcision procedure assisted by a precise marking method circumcision device. METHOD: A retrospective analysis was conducted on 41 cases of modified foreskin circumcision using precise marking method in the urology department of our hospital from February 2021 to January 2023 as the observation group, and 60 cases of traditional foreskin circumcision assisted by traditional foreskin circumcision during the same period as the control group. Compare and analyze indicators such as the distance from the anastomotic margin to the coronal sulcus, postoperative erectile tension, edema, hematoma, postoperative infection, and the presence of sexual intercourse pain between two groups of patients. The number of patients in the observation group who experienced erectile tension at 3 months after surgery was lower than that in the control group (P<0.05), and the number of patients with sexual pain was lower than that in the control group (P<0.05). The distance from the incision edge to the coronal sulcus was closer to 0.5 cm in the observation group (P<0.05). CONCLUSION: Compared with traditional circumcision, the precise marking method assisted by a modified circumcision device can more accurately control the position of the cutting edge, reduce the incidence of postoperative erectile tension and sexual pain, and is a feasible and safe surgical method.


Assuntos
Circuncisão Masculina , Fimose , Masculino , Humanos , Prepúcio do Pênis/cirurgia , Estudos Retrospectivos , Fimose/cirurgia , Dor
10.
Eur J Radiol ; 157: 110587, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36345088

RESUMO

PURPOSE: Magnetic resonance imaging (MRI) has been applied to predict the neoadjuvant chemotherapy (NAC) response of bladder cancer at an early stage, but the performance remains poor. A tool for the selection of patients with muscle-invasive bladder cancer (MIBC) with high probability of benefitting from NAC is not yet available. We designed a prospective study to assess a quantitative MRI for predicting the early response of MIBC to NAC. METHODS: All individuals underwent a time-course MRI at pre-NAC, 24 h after initial cisplatin medication (24 h-NAC) and post-NAC.Chemosensitivity was evaluated according to pathological response.The transfer constant (Ktrans), plasma volume (Vp), extravascular extracellular space (Ve), and apparent diffusion coefficient (ADC) were quantitated based on dynamic contrast-enhanced and diffusion-weighted imaging.Quantitative RECIST criteria were constructed by modelling pre-NAC and 24 h-NAC MRI measures, and then compared with conventional RECIST by using pre- and post-NAC MRI measures. RESULTS: In this pilot study, a total of 24 patients were enrolled into the study. Eight patients were pathologically confirmed to be NAC-responders. After a thorough evaluation of these parameters, different parameters showed good discrimination at different point in time. ROC curves showed quantitative MRI can predict the response to NAC, especially ADC_M (AUC = 0.859, P = 0.005) and ADC index (AUC = 0.844, P = 0.007) at pre-NAC timing and ADC_M (AUC = 0.816, P = 0.013) at 24 h-NAC timing. Then, a qRECIST model was established for predicting NAC sensitivity, with AUC of 0.91, TP rate of 0.8, and accuracy of 0.75. CONCLUSION: The diagnostic performance of mpMRI parameters for NAC response is excellent. The qRECIST derived between pre- and 24 h NAC MRI could predict the early response of MIBC to NAC and help for candidate selection.


Assuntos
Imageamento por Ressonância Magnética Multiparamétrica , Neoplasias da Bexiga Urinária , Humanos , Terapia Neoadjuvante/métodos , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/tratamento farmacológico , Estudos Prospectivos , Projetos Piloto , Resultado do Tratamento , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodos
11.
Oncol Rep ; 48(5)2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36129145

RESUMO

Following the publication of the above article, an interested reader drew to the authors' attention that the cell and invasion migration assay data featured in Figs. 2C and 5D contained two pairs of overlapping panels, such that the data appeared to have been derived from the same original sources, even though the data panels were intending to show the results from differently performed experiments. Moreover, there was also an instance of duplicated data panels comparing between the si­NC/cell invasion and si­NC/cell migration assay panels in Fig. 4C. After having examined their original data, the authors have realized that inadvertent errors were made during the process of compiling these figures. Corrected versions of Figs. 2, 4 and 5, incorporating all the data from one of the repeated experiments, are shown opposite and on the next page. The authors all agree to the publication of this corrigendum, and are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this. They also regret any inconvenience caused to the readership of the Journal. [Oncology Reports 57: 3502­3508, 2017; DOI: 10.3892/or.2017.5607].

12.
BMC Urol ; 22(1): 111, 2022 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-35850869

RESUMO

PURPOSE: To develop and validate a preoperative cystoscopic-based predictive model for predicting postoperative high-grade bladder cancer (BCa), which could be used to guide the surgical selection and postoperative treatment strategies. MATERIALS AND METHODS: We retrospectively recruited 366 patients with cystoscopy biopsy for pathology and morphology evaluation between October 2010 and January 2021. A binary logistic regression model was used to assess the risk factors for postoperative high-grade BCa. Diagnostic performance was analyzed by plotting receiver operating characteristic curve and calculating area under the curve (AUC), sensitivity, specificity. From January 2021 to July 2021, we collected 105 BCa prospectively to validate the model's accuracy. RESULTS: A total of 366 individuals who underwent transurethral resection of bladder tumor (TURBT) or radical cystectomy following cystoscopy biopsy were included for analysis. 261 (71.3%) had a biopsy pathology grade that was consistent with postoperative pathology grade. We discovered five cystoscopic parameters, including tumor diameter, site, non-pedicled, high-grade biopsy pathology, morphology, were associated with high-grade BCa. The established multi-parameter logistic regression model ("JSPH" model) revealed AUC was 0.917 (P < 0.001). Sensitivity and specificity were 86.2% and 84.0%, respectively. And the consistency of pre- and post-operative high-grade pathology was improved from biopsy-based 70.5% to JSPH model-based 85.2%. In a 105-patients prospective validation cohort, the consistency of pre- and post-operative high-grade pathology was increased from 63.1 to 84.2% after incorporation into JSPH model for prediction. CONCLUSION: The cystoscopic parameters based "JSPH model" is accurate at predicting postoperative pathological high-grade tumors prior to operations.


Assuntos
Neoplasias da Bexiga Urinária , Cistectomia , Cistoscópios , Humanos , Estudos Retrospectivos , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia
13.
Metabolites ; 12(6)2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35736490

RESUMO

Numerous patients with muscle-invasive bladder cancer develop low responsiveness to cisplatin. Our purpose was to explore differential metabolites derived from serum in bladder cancer patients treated with neoadjuvant chemotherapy (NAC). Data of patients diagnosed with cT2-4aNxM0 was collected. Blood samples were retained prospectively before the first chemotherapy for untargeted metabolomics by 1H-NMR and UPLC-MS. To identify characterized metabolites, multivariate statistical analyses were applied, and the intersection of the differential metabolites discovered by the two approaches was used to identify viable biomarkers. A total of 18 patients (6 NAC-sensitive patients and 12 NAC-resistant patients) were enrolled. There were 29 metabolites detected by 1H-NMR and 147 metabolites identified by UPLC-MS. Multivariate statistics demonstrated that in the sensitive group, glutamine and taurine were considerably increased compared to their levels in the resistant group, while glutamate and hypoxanthine were remarkably decreased. Pathway analysis and enrichment analysis showed significant alterations in amino acid pathways, suggesting that response to chemotherapy may be related to amino acid metabolism. In addition, hallmark analysis showed that DNA repair played a regulatory role. Overall, serum metabolic profiles of NAC sensitivity are significantly different in bladder cancer patients. Glycine, hypoxanthine, taurine and glutamine may be the potential biomarkers for clinical treatment. Amino acid metabolism has potential value in enhancing drug efficacy.

14.
Chem Asian J ; 17(16): e202200342, 2022 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-35713953

RESUMO

Intravesical instillation of chemotherapeutic drugs such as epirubicin (EPI) is routinely used to prevent tumor recurrence and progression after transurethral resection of bladder tumor. However, the lack of tumor selectivity often causes severe damage to normal bladder urothelium leading to intolerable side effects. Here, we analyzed abnormal changes in glycosylation in bladder cancer and identified mannose as the most aberrantly expressed glycan on the surface of bladder cancer cell lines and human bladder tumor tissues. We then constructed a lectin-drug conjugate by linking concanavalin A (ConA) - a lectin that specifically binds to mannose, with EPI through a pH-sensitive linker. This ConA-EPI conjugate conferred EPI with mannose-targeting ability and selectively internalized cancer cells in vitro. This conjugate showed selective cytotoxicity to cancer cells in vitro and better antitumor activity in an orthotopic mouse model of bladder cancer. Our lectin-drug conjugation strategy makes targeted intravesical chemotherapy of bladder cancer possible.


Assuntos
Neoplasias da Bexiga Urinária , Administração Intravesical , Animais , Antibióticos Antineoplásicos , Concanavalina A/farmacologia , Epirubicina/efeitos adversos , Humanos , Manose , Camundongos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia
15.
J Immunother Cancer ; 10(3)2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35361729

RESUMO

BACKGROUND: Bladder cancer is a common disease worldwide with most patients presenting with the non-muscle-invasive form (NMIBC) at initial diagnosis. Postoperational intravesical instillation of BCG is carried out for patients with high-risk disease to reduce tumor recurrence and progression to muscle invasive disease. However, BCG can also have side effects or be ineffective in some patients because it cannot enter the cancer cells. Thus, to improve the efficacy of BCG immunotherapy is the long-term pursuit of the bladder cancer field. METHODS: To increase the adhesion of BCG to the urothelium we overexpressed FimH, a mannose binding protein naturally used by uropathogenic Escherichia coli to adhere to human urothelium, onto the surface of BCG. The adhesion/internalization ability of rBCG-S.FimH was examined in mouse bladder by fluorescence microscopy. Preclinical evaluation of antitumor efficacy was carried out in orthotopic mouse models of bladder cancer and in human peripheral blood mononuclear cells. Mechanistic studies were carried out using toll-like receptor 4 (TLR4) knockout mice. Immune cells and cytokines in the serum, tumor and lymph nodes were analyzed by flow cytometry, PCR, ELISA and ELISPOT. RESULTS: rBCG-S.FimH exhibited markedly improved adhesion and more rapid internalization into urothelial cells than wild-type BCG, resulting in more potent antitumor activity in orthotopic murine models of bladder cancer. To our surprise, rBCG-S.FimH elicited a much more prominent Th1-biased immune response known to be positively correlated with BCG efficacy. Mechanistic studies using TLR4 knockout mouse showed that rBCG-S.FimH could induce enhanced dendritic cell activation and tumor antigen-specific immune response in a TLR4-dependent manner. Furthermore, human peripheral blood mononuclear cells stimulated by rBCG-S.FimH also showed better tumoricidal effects than those using wild-type BCG. CONCLUSION: rBCG-S.FimH is a novel BCG strain with significantly improved efficacy against bladder cancer. Since intravesical BCG immunotherapy is the first-line treatment for NMIBC, which accounts for more than 70% of all bladder cancer cases, our results provide a compelling rationale for clinical development.


Assuntos
Vacina BCG , Neoplasias da Bexiga Urinária , Animais , Humanos , Imunoterapia/métodos , Leucócitos Mononucleares , Manose , Camundongos , Recidiva Local de Neoplasia , Neoplasias da Bexiga Urinária/tratamento farmacológico
16.
BMC Urol ; 22(1): 41, 2022 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-35313884

RESUMO

BACKGROUND: To investigate whether Pentafecta is suitable for bladder cancer patients receiving laparoscopic radical cystectomy (LRC). METHODS: From November 2013 to December 2020, muscle invasive Bladder Cancer (MIBC) and non-muscle invasive Bladder Cancer (NMIBC) patients who received LRC and urinary diversion were retrospectively analyzed. Pentafecta was defined as meeting five criteria: negative soft margin, ≥ 16 lymph nodes (LNs) removed, major complications free, urinary diversion related sequelae free and clinical recurrence free within 1 year. Analyze the achievement of five criteria and compare the overall survival (OS) of Pentafecta group with non-attainment group. Multivariable Cox's regression was performed to evaluate the impact of Pentafecta on OS. Multivariable logistic regression was performed to explore the effect of surgical experience on Pentafecta attainment. RESULTS: A total of 340 patients were included, negative soft margin, ≥ 16 lymph nodes (LNs) removed, major complications free, urinary diversion related sequelae free and clinical recurrence free within 1 year were observed in 95.3%, 30.3%, 83.8%, 75.0% and 85.6% of patients, respectively. Pentafecta group had a significantly longer OS than the non-attainment group (P = 0.027). The group with 10-15 LNs removed and meeting the other four criteria had a similar OS to group with ≥ 16 LNs removed (Pentafecta group) (5-year OS: 67.3% vs 72.7%, P = 0.861). Pentafecta (HR = 0.33, P = 0.011), positive lymph nodes (HR = 2.08, P = 0.028) and MIBC (HR = 3.70, P < 0.001) were all significant predictors of OS in multivariable Cox's regression. Surgical experience (OR = 1.05, P < 0.001), conduit (OR = 2.09, P = 0.047) and neobladder (OR = 2.47, P = 0.048) were all independent predictors of Pentafecta attainment in multivariable logistic regression. CONCLUSIONS: Pentafecta is suitable for bladder cancer patients receiving LRC and has the potential to be a valuable tool for evaluating the quality of LRC. Based on Pentafecta analysis, removing 10 LNs instead of 16 LNs as the one of the five criteria may be more appropriate for bladder cancer patients.


Assuntos
Cistectomia/métodos , Laparoscopia , Excisão de Linfonodo , Avaliação de Resultados em Cuidados de Saúde/métodos , Neoplasias da Bexiga Urinária/cirurgia , Bexiga Urinária/cirurgia , Idoso , Feminino , Humanos , Modelos Logísticos , Masculino , Margens de Excisão , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/normas , Estudos Retrospectivos , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/mortalidade
17.
Front Oncol ; 12: 803221, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35223481

RESUMO

BACKGROUND: Radical cystectomy (RC) is the standard treatment for muscular invasive bladder cancer (MIBC) and some high-risk non-muscular invasive bladder cancer (NMIBC). Cutaneous ureterostomy is a common form of urinary diversion. However, after radical cystectomy, recurrence of upper urinary tract malignancies is possible. There is no relevant report on how to improve this situation's management. CASE PRESENTATION: This case is a 56-year-old male patient hospitalized due to the development of a new tumor in the ureteral cutaneous stoma following radical cystectomy for more than five years. A biopsy of the tumor revealed high-grade urothelial carcinoma. Computed tomography (CT) revealed that the local soft tissue around the cutaneous stoma was thickened, but no other lesions were visible. After evaluating the case, we chose robot-assisted completely intracorporeal resection of cutaneous ureterostomy tumor and ileal conduit surgery. The total time for the operation and the blood loss were 400 minutes and 150 ml, respectively. Following surgery, the patient got standard chemotherapy in combination with immunotherapy. Additionally, ten months following the surgery, the patient did not experience disease progression or complications. CONCLUSION: The robot-assisted operation is safe and feasible for upper urinary tract tumor recurrence following radical cystectomy with cutaneous ureterostomy.

18.
Cancer Res ; 82(6): 1128-1139, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35064018

RESUMO

Bladder cancer is common worldwide, with most patients presenting with nonmuscle invasive disease. Multiple intravesical recurrences lead to reduced quality of life and high costs for patients with this form of bladder cancer. Intravesical chemotherapy aimed at reducing recurrence is the standard-of-care but has significant side effects from nonspecific cytotoxicity to normal urothelium. Importantly, toxicity limits doses that can be administered. Thus, tumor-specific drug targeting could reduce toxicity and enhance effectiveness by allowing higher doses. Here, using cell internalization systematic evolution of ligands by exponential enrichment (SELEX), we identify a novel bladder cancer-specific, chemically modified nucleic acid aptamer that can be preferentially internalized into tumor cells but not normal urothelial cells. The 35-nucleotide B1 aptamer is internalized into bladder cancer cells through clathrin-mediated endocytosis and macropinocytosis. As proof of principle, a B1-guided DNA nanotrain delivery vehicle for epirubicin was constructed as a targeted intravesical chemotherapy. The B1-nanotrain-epirubicin construct exhibited selective cytotoxicity towards bladder cancer cells and outperformed epirubicin in murine orthotopic xenograft models of human bladder cancer. This aptamer-based delivery system makes targeted chemotherapy possible for bladder cancer, providing a compelling rationale for clinical development. SIGNIFICANCE: These findings identify a bladder cancer-specific aptamer that can be used for targeted delivery of chemotherapy, potentially reducing toxicity and enhancing therapeutic efficacy.


Assuntos
Neoplasias da Bexiga Urinária , Administração Intravesical , Animais , Epirubicina/uso terapêutico , Humanos , Camundongos , Qualidade de Vida , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia
19.
Int J Urol ; 29(3): 186-195, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34923686

RESUMO

The objective of this study is to systematically evaluate the diagnostic performance of the Vesical Imaging-Reporting and Data System for predicting muscle-invasive bladder cancer. Embase, PubMed and Web of Science were systematically searched from 1 September 2018 to 30 July 2021 to include proper studies. We included studies that included data on Vesical Imaging-Reporting and Data System and their associated pathological findings, and we assessed their quality using the Quality Assessment of Diagnostic Accuracy Studies-2 tool. The pooled sensitivity and specificity were calculated and plotted using hierarchical summary receiver operating characterisijutic modeling. Meta-regression analysis was carried out to detect heterogeneity. A total of 20 studies with 2725 patients were included. When the cut-off point was 3, the pooled sensitivity and specificity were 0.92 (0.89-0.94) and 0.85 (0.78-0.90), respectively, and 0.82 (0.75-0.88) and 0.95 (0.91-0.97), respectively, when the cut-off point was 4. The area under the curve was 0.95 and 0.95, respectively. Heterogeneity was substantially considerable in sensitivity and specificity. All subgroup variables, including patient number, study design, magnetic resonance imaging field strength, number of radiologists, surgery pattern, diffusion-weighted imaging, and dynamic contrast-enhanced magnetic resonance imaging, contributed to sensitivity heterogeneity when the cut-off point was 3 and specificity heterogeneity when the cut-off point was 4. Multiple image acquisition plane of diffusion-weighted imaging achieved a higher sensitivity than single image acquisition plane of diffusion-weighted imaging in both the Vesical Imaging-Reporting and Data System 3 and 4 groups, and higher specificity in the Vesical Imaging-Reporting and Data System 4 group. Another significant source of heterogeneity was the cut-off point. The diagnostic performance of the Vesical Imaging-Reporting and Data System for predicting muscle-invasive bladder cancer was excellent in both cut-off points of the Vesical Imaging-Reporting and Data System 3 and 4. Multiple image acquisition planes of diffusion-weighted imaging should be given more attention in the Vesical Imaging-Reporting and Data System.


Assuntos
Neoplasias da Bexiga Urinária , Imagem de Difusão por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética/métodos , Músculos , Sensibilidade e Especificidade , Bexiga Urinária/diagnóstico por imagem , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia
20.
J Laparoendosc Adv Surg Tech A ; 32(5): 545-549, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-34534001

RESUMO

Background: Retroperitoneal approach and segmental renal artery clamping in partial nephrectomy are techniques that facilitate postoperative recovery and renal function preservation. This study aimed to compare the renal function preservation and perioperative outcomes of robot-assisted partial nephrectomy (RAPN) and laparoscopic partial nephrectomy (LPN) with these techniques. Materials and Methods: Clinical parameters of 43 patients who had undergone retroperitoneal RAPN from March 2017 to December 2019 were retrospectively collected and compared with those of 52 patients who had undergone retroperitoneal LPN at the same period in our institution. Differences in operating time, warm ischemia time, estimated blood loss, complications, postoperative hospital stay, as well as renal function loss were compared between the two groups. Results: Background characteristics between RAPN and LPN groups such as age, gender, BMI, and tumor characteristics were comparable. All RAPNs and LPNs were successfully completed without conversion to open surgery or nephrectomy. No significant difference in operating time, estimated blood loss, complications, and postoperative hospital stay was observed between RAPN and LPN groups. The warm ischemia time in RAPN group was slightly shorter than that of LPN groups (P = .054). Compared with the LPN group, the RAPN group was significantly associated with less glomerular filtration rate reduction and renal volume loss rate (P = .042 and P = .013, respectively). Conclusions: The perioperative outcomes were comparable between the two groups. However, compared with LPN, RAPN had superiority in preserving renal function in our series.


Assuntos
Neoplasias Renais , Laparoscopia , Procedimentos Cirúrgicos Robóticos , Robótica , Constrição , Feminino , Humanos , Rim/patologia , Rim/fisiologia , Rim/cirurgia , Neoplasias Renais/patologia , Neoplasias Renais/cirurgia , Laparoscopia/métodos , Masculino , Nefrectomia/métodos , Artéria Renal/patologia , Artéria Renal/cirurgia , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/métodos , Resultado do Tratamento
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