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1.
Eur Urol Open Sci ; 68: 18-24, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39257619

ABSTRACT

Background and objective: Few studies on endoscopic management of primary obstructive megaureter (POM) in adult patients have been reported. Our objective was to describe our technique and long-term outcomes for endoscopic management of adult POM. Methods: We included 76 adult POM patients undergoing endoscopic management between September 2015 and January 2024. Under endoscopic control, the stricture was dilated to 24-30 Fr while maintaining a balloon pressure of 25-35 atm for 3 min. An additional incision of the stenotic ring using either an electrode or holmium laser was performed in 39 patients. Data for patient characteristics, intraoperative variables, surgical complications, and follow-up results were analyzed. A descriptive statistical analysis was performed. Surgical success was defined as no tubes or stents in the body, stable or improved symptoms and renal function, and the absence of reflux or obstruction during the follow-up period. Key findings and limitations: All procedures were completed without conversion to open or laparoscopic surgery. The median operative time was 45 min (range 16-165) with median estimated blood loss of 2 ml (range 0-150). The median postoperative hospital stay was 3 d (range 1-15). No intraoperative complication occurred. At median postoperative follow-up of 42 mo (range 3-100) the overall success rate was 92.1%. Restenosis of the vesicoureteral junction (Clavien-Dindo grade III) occurred in five patients (6.6%), and high-grade vesicoureteral reflux occurred in one patient (1.3%), all of whom required secondary reconstruction surgery. Conclusions and clinical implications: The results indicate that our endoscopic management for adult POM is safe and effective, with favorable long-term outcomes. This approach could potentially serve as a first-line treatment option for adult POM. Patient summary: Primary obstructive megaureter (POM) occurs when the flow of urine is blocked because of a narrow segment in the tube between the kidney and bladder (ureter), which causes widening of the ureter further up. For our minimally invasive technique, a telescope is inserted through the urethra and bladder to reach the ureter for surgical treatment. Our results show that this is a safe procedure for POM in adults.

2.
Clin Genitourin Cancer ; : 102192, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39261258

ABSTRACT

OBJECTIVE: To provide a comprehensive understanding of the clinical features of patients with synchronous and metachronous upper tract urothelial carcinoma (UTUC) and bladder urothelial carcinoma (BUC) and inform surgical and postoperative adjuvant treatment planning. PATIENTS AND METHOD: A total of 292 consecutive patients with synchronous and metachronous UTUC-BUC were retrospectively enrolled and were categorized into three groups: (1) UTUC metachronous BUC (N = 185, UTUC-mBUC), (2) BUC-metachronous UTUC (N = 43, BUC-mUTUC), (3) synchronous UTUC-BUC (N = 64, sUTUC-BUC). We compared pathological characteristics and survival data among groups with Wilcoxon's rank sum tests, Pearson's chi-squared, and the Kaplan-Meier method. RESULTS: In the sUTUC-BUC group, a higher proportion of patients exhibited UTUC tumors with grade G3 (56%, P = .001) and stage T4 (6%, P < .001) than group UTUC-mBUC (G3 = 16%, T4 = 0%). The proportion of patients with variant histology subtype in group sUTUC-BUC was higher than that of metachronous UTUC-BUC, involving squamous (P = .003), adenoid (P = .012), and sarcomatoid (P < .001) differentiation. It was also observed that the maximum diameter of the UTUC tumor of group sUTUC-BUC (median = 3.5) was significantly larger than group UTUC-mBUC (median = 2.5, P = .002) and group BUC-mUTUC (median = 2.2, P < .001). Notably, sUTUC-BUC has an increased risk of cancer-specific death compared with UTUC-mBUC (P < .001) and BUC-mUTUC (P < .001). On multivariable Cox regression, synchronous UTUC-BUC was an independent predictor of both RFS (P < .001; vs. UTUC-mBUC: HR 0.555, P = .004; vs. BUC-mUTUC: HR 0.279, P < .001) and CSS (P < .001, HR 29.737). Moreover, sUTUC-BUC showed a better response to intravesical therapy and chemotherapy with higher cancer-specific survival (P < .001) and recurrence-free survival (P = .034). CONCLUSIONS: The prognosis and pathological characteristics among different metachronous and synchronous UTUC and BUC were diverse. The synchronous UTUC-BUC group showed variant histology subtype, high-grade tumors, advanced tumors, multifocal UTUC, worse cancer-specific survival, but better response to intravesical therapy and chemotherapy.

3.
Int Braz J Urol ; 50(6): 781-782, 2024.
Article in English | MEDLINE | ID: mdl-39226447

ABSTRACT

PURPOSE: Ureteroplasty using buccal or lingual mucosa graft Is feasible for complex proximal ureteral stricture (1, 2). Ileal ureter replacement is considered as the last resort for ureteral reconstruction. Totally intracorporeal robot-assisted ileal ureter replacement can be performed safely and effectively (3). In China, the KangDuo Surgical Robot 2000 Plus (KD-SR-2000 Plus) has been developed featuring two surgeon consoles and five robotic arms. This study aims to share our experience with totally intracorporeal robot-assisted bilateral ileal ureter replacement using KD-SR-2000 Plus. MATERIALS AND METHODS: A 59-year-old female patient underwent a complete intracorporeal robot-assisted bilateral ileal ureter replacement for the treatment of ureteral strictures using KD-SR-2000 Plus. The surgical procedure involved dissecting the proximal ends of the bilateral ureteral strictures, harvesting the ileal ureter, restoring intestinal continuity, and performing an anastomosis between the ileum and the ureteral end as well as the bladder. The data were prospectively collected and analyzed. RESULTS: The surgery was successfully completed with single docking without open conversion. The length of the harvested ileal ureter was 25 cm. The docking time, operation time and console time were 3.4 min., 271 min and 231 min respectively. The estimated blood loss was 50 mL. The postoperative hospitalization was 6 days. No perioperative complications occurred. CONCLUSIONS: It is technically feasible to perform totally intracorporeal robot-assisted bilateral ileal ureter replacement for the treatment of ureteral strictures using KD-SR-2000 Plus. A longer follow-up and a larger sample size are required to evaluate its safety and effectiveness.


Subject(s)
Ileum , Robotic Surgical Procedures , Ureter , Ureteral Obstruction , Humans , Female , Middle Aged , Robotic Surgical Procedures/methods , Ureter/surgery , Ileum/surgery , Treatment Outcome , Ureteral Obstruction/surgery , Constriction, Pathologic/surgery , Operative Time , Anastomosis, Surgical/methods , Urologic Surgical Procedures/methods
5.
Nature ; 2024 Sep 25.
Article in English | MEDLINE | ID: mdl-39322664

ABSTRACT

Despite a high response rate in chimeric antigen receptor (CAR) T cell therapy for acute lymphocytic leukaemia (ALL)1-3, approximately 50% of patients relapse within the first year4-6, representing an urgent question to address in the next stage of cellular immunotherapy. Here, to investigate the molecular determinants of ultralong CAR T cell persistence, we obtained a single-cell multi-omics atlas from 695,819 pre-infusion CAR T cells at the basal level or after CAR-specific stimulation from 82 paediatric patients with ALL enrolled in the first two CAR T ALL clinical trials and 6 healthy donors. We identified that elevated type 2 functionality in CAR T infusion products is significantly associated with patients maintaining a median B cell aplasia duration of 8.4 years. Analysis of ligand-receptor interactions revealed that type 2 cells regulate a dysfunctional subset to maintain whole-population homeostasis, and the addition of IL-4 during antigen-specific activation alleviates CAR T cell dysfunction while enhancing fitness at both transcriptomic and epigenomic levels. Serial proteomic profiling of sera after treatment revealed a higher level of circulating type 2 cytokines in 5-year or 8-year relapse-free responders. In a leukaemic mouse model, type 2high CAR T cell products demonstrated superior expansion and antitumour activity, particularly after leukaemia rechallenge. Restoring antitumour efficacy in type 2low CAR T cells was attainable by enhancing their type 2 functionality, either through incorporating IL-4 into the manufacturing process or by priming manufactured CAR T products with IL-4 before infusion. Our findings provide insights into the mediators of durable CAR T therapy response and suggest potential therapeutic strategies to sustain long-term remission by boosting type 2 functionality in CAR T cells.

6.
Cell Mol Immunol ; 21(10): 1089-1108, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39134804

ABSTRACT

In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies in both pediatric and adult patients. CAR-natural killer (CAR-NK) cell complements CAR-T cell therapy by offering several distinct advantages. CAR-NK cells do not require HLA compatibility and exhibit low safety concerns. Moreover, CAR-NK cells are conducive to "off-the-shelf" therapeutics, providing significant logistic advantages over CAR-T cells. Both CAR-T and CAR-NK cells have shown consistent and promising results in hematological malignancies. However, their efficacy against solid tumors remains limited due to various obstacles including limited tumor trafficking and infiltration, as well as an immuno-suppressive tumor microenvironment. In this review, we discuss the recent advances and current challenges of CAR-T and CAR-NK cell immunotherapies, with a specific focus on the obstacles to their application in solid tumors. We also analyze in depth the advantages and drawbacks of CAR-NK cells compared to CAR-T cells and highlight CAR-NK CAR optimization. Finally, we explore future perspectives of these adoptive immunotherapies, highlighting the increasing contribution of cutting-edge biotechnological tools in shaping the next generation of cellular immunotherapy.


Subject(s)
Immunotherapy, Adoptive , Killer Cells, Natural , Neoplasms , Receptors, Chimeric Antigen , Humans , Neoplasms/therapy , Neoplasms/immunology , Immunotherapy, Adoptive/methods , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/genetics , Killer Cells, Natural/immunology , Killer Cells, Natural/transplantation , Animals , Tumor Microenvironment/immunology , T-Lymphocytes/immunology , T-Lymphocytes/transplantation , Immunotherapy/methods
8.
Beijing Da Xue Xue Bao Yi Xue Ban ; 56(4): 640-645, 2024 Dec 18.
Article in Chinese | MEDLINE | ID: mdl-39041559

ABSTRACT

OBJECTIVE: To investigate the feasibility, safety and effectiveness of robot-assisted laparoscopic buccal mucosa graft ureteroplasty in the treatment of complex long proximal ureteral stricture. METHODS: The clinical data of 20 patients with proximal ureteral stricture undergoing robot-assisted laparoscopic buccal mucosa graft ureteroplasty admitted to the Department of Urology, Peking University First Hospital and Beijing Jiangong Hospital from July 2022 to January 2023 were prospectively collected and analyzed. Intraoperative conditions, postoperative complications and follow-up data were also recorded and analyzed. RESULTS: The operations under robot-assisted laparoscopy were performed successfully in all the 20 patients without conversion to traditional laparoscopic surgery or open surgery. The study included 14 males and 6 females with a mean age of (41±11) years (range: 19 to 60 years) and a mean body mass index of (24.3±3.6) kg/m2 (range: 18.2 to 31.8 kg/m2). There were 9 cases on the left side and 11 cases on the right side. The strictures of all the patients were located in the proximal segment of the ureter (including the ureteropelvic junction). The mean preoperative serum creatinine was (92.2±23.3) µmol/L (range: 49.2 to 138.9 µmol/L), and the mean length of ureteral stricture was (2.8±0.9) cm (range: 1.0 to 4.0 cm). Ten patients had previously undergone unsuccessful reconstructive surgery. During the operation, 12 patients received posteriorly augmented anastomosis with ventral onlay. The mean length of the buccal mucosa graft harvested during the operation was (3.1±0.6) cm (range: 2.0 to 4.3 cm), and the median width was 1.5 cm (range: 1.0 to 2.0 cm). The omentum flap was used to wrap the reconstructed ureteral segment in all the 20 cases. The median operative time was 154 min (range: 113 to 300 min), and the median estimated blood loss was 45 mL (range: 0 to 100 mL). The median postoperative hospital stay was 4 d (range: 4 to 14 d). The mean postoperative follow-up time was (15.0±1.7) months (range: 12.5 to 17.9 months), and the surgical success rate was 100.0% in this study. After surgery, 11 patients reported mild discomfort at the oral donor site, 2 patients deve-loped urinary tract infection, and no postoperative complications were reported in the other 7 patients. The mean serum creatinine was (90.9±23.9) µmol/L (range: 60.0 to 153.0 µmol/L) six months after surgery. CONCLUSION: Robot-assisted laparoscopic buccal mucosa graft ureteroplasty for the treatment of complex long proximal ureteral stricture has satisfactory efficacy without severe complications, which has shown good feasibility, safety and effectiveness. However, large sample studies and long-term follow-up are still needed to evaluate its long-term efficacy.


Subject(s)
Laparoscopy , Mouth Mucosa , Robotic Surgical Procedures , Ureter , Ureteral Obstruction , Humans , Male , Female , Adult , Mouth Mucosa/transplantation , Middle Aged , Laparoscopy/methods , Robotic Surgical Procedures/methods , Ureteral Obstruction/surgery , Ureter/surgery , Young Adult , Constriction, Pathologic , Urologic Surgical Procedures/methods , Operative Time , Postoperative Complications/etiology , Plastic Surgery Procedures/methods
9.
Transl Androl Urol ; 13(6): 940-948, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-38983470

ABSTRACT

Background: Ureteral strictures (US) could lead to impaired kidney function, which was alleviated by ureteral reconstruction surgery. However, solitary kidney (SK) patients with US were more complicated to treat. This study aimed to evaluate the impact of reconstruction surgery on renal function based on estimated glomerular filtration rate (eGFR) in patients with SK. Methods: We retrospectively enrolled patients who underwent reconstruction surgery between April 2014 to March 2022. eGFR was measured pre- and postoperatively. The 'static renal function' was defined as a change in eGFR of 20% or less at the last follow-up, and the 'worsening renal function group' was defined as a decrease of greater than 20%. Results: A total of 61 SK patients were involved. The success rate of ureteral reconstruction surgery was 90.16% (55/61). The median follow-up time was 20.8 months (range, 3.7-109.2 months). The median eGFR was 65.5 (range, 15.1-99.9) and 65.3 (range, 3.8-123.4) mL/min/1.73 m2 at the baseline and the last follow-up. No statistically significant difference in eGFR was observed between the preoperative baseline and last follow-up visits (P=0.58). However, in patients with baseline renal dysfunction [chronic kidney disease (CKD) stage 3-5], the eGFR significantly improved at the last follow-up compared to the baseline (P=0.02). Three patients developed a 'worsening renal function' (4.92%). Besides, the systolic blood pressures (SBP) at follow-up significantly reduced compared to the preoperative baseline (P=0.002). Conclusions: Ureteral reconstruction surgery is an effective treatment to preserve renal function, which also achieves a high success rate and is associated with the reduction of SBP for SK patients with US.

10.
Sci Rep ; 14(1): 16753, 2024 07 20.
Article in English | MEDLINE | ID: mdl-39033240

ABSTRACT

Data on prevalence of programmed death ligand-1 (PD-L1) expression and its correlation with tumor biomarkers in Chinese patients with muscle-invasive urothelial bladder cancer (MIUBC) are scarce. We investigated the prevalence of PD-L1 expression, PD-L1 expression in tumor cells (TC) and immune cells (IC), and its correlation with tumor biomarkers (CD8+ T cells and tumor mutation burden [TMB]) in Chinese patients with newly diagnosed MIUBC (NCT03433924). Of 248 patients enrolled, 229 with PD-L1 data available were analysed. High PD-L1 expression (≥ 25% of TC or IC with PD-L1 expression) was observed in 120 (52.4%) patients. 59 cases showed positive staining in ≥ 25% of TC, and 82 cases had positive staining in ≥ 25% of IC. High expression of CD8+ T cell and TMB (> 10 mutations/megabase) was observed in 44.5% and 54.1% patients, respectively. A positive correlation was observed between percentage of TC with membrane PD-L1 positivity and CD8+ T cells (0.34; P < 0.001) and between IC with membrane PD-L1 positivity and CD8+ T cells (0.44; P < 0.001). There is high prevalence of PD-L1 expression in Chinese patients with MIUBC, suggesting that a sizable subset of patients could benefit from immunotherapy. The correlation of PD-L1 expression with tumor biomarkers provide clues for mechanisms underlying the effects of biomarkers for predicting efficacy.


Subject(s)
B7-H1 Antigen , Biomarkers, Tumor , CD8-Positive T-Lymphocytes , Urinary Bladder Neoplasms , Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , B7-H1 Antigen/metabolism , B7-H1 Antigen/genetics , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , CD8-Positive T-Lymphocytes/metabolism , CD8-Positive T-Lymphocytes/immunology , China/epidemiology , East Asian People/genetics , Mutation , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/metabolism , Urinary Bladder Neoplasms/pathology
12.
Eur Urol Focus ; 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38862329

ABSTRACT

BACKGROUND: The KangDuo Surgical Robot (KD-SR) is a newly developed surgical robot. OBJECTIVE: To compare the safety and efficacy of robot-assisted radical prostatectomy (RARP) using the KD-SR with those of the da Vinci Si Surgical System (DV-SS-Si). DESIGN, SETTING, AND PARTICIPANTS: A prospective double-center noninferiority randomized controlled trial was conducted among 18-75-yr-old patients with suspected T1-2N0M0 prostate cancer (PCa) scheduled for RARP. INTERVENTION: RARP with the KD-SR (KD-RARP) versus RARP with the DV-SS-Si (DV-RARP). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was surgical success, defined as follows: surgery can be performed according to the established protocol, without switching to other surgical modalities, and without secondary surgery due to surgical complications after surgery. The secondary outcome was short-term functional and oncological outcomes. The noninferiority threshold was set at 10%. RESULTS AND LIMITATIONS: Eighty patients were enrolled, while the full analysis set finally included 79 patients (40 with KD-RARP and 39 with DV-RARP). The success rate was 100% in both groups. We could not find differences in urinary continence rate at 1, 2, 3, and 4 wk after catheter removal between the groups (p > 0.05). The rate of Clavien-Dindo grade II adverse events was 20% in the KD-RARP group and 17.9% in the DV-RARP group (p = 0.82), and no grade ≥III adverse events occurred. The median operation time was significantly longer in the KD-RARP group than in the DV-RARP group (177.5 vs 145 min, p = 0.012). The main limitations were the short follow-up period and that survival was not considered as the primary outcome. CONCLUSIONS: The KD-SR is a viable option for RARP, with acceptable short-term outcomes compared with the DV-SS-Si for T1-2 PCa. PATIENT SUMMARY: This is the first prospective randomized controlled trial to compare the KangDuo Surgical Robot (KD-SR) versus the da Vinci Si Surgical System (DV-SS-Si) for robot-assisted radical prostatectomy, which determines that the KD-SR is noninferior to the DV-SS-Si regarding safety and efficacy for T1-T2 prostate cancer.

13.
Minerva Urol Nephrol ; 76(2): 241-246, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38742557

ABSTRACT

BACKGROUND: To evaluate the feasibility and safety of dual-console telesurgery with the new KangDuo system in an animal experiment and clinical study. METHODS: Six canine models were performed radical prostatectomy with dual-console KanDuo surgical robot-1500 (KD-SR-1500-RARP). The perioperative outcomes, physical and mental workload of the surgeon were collected. Physical workload was evaluated with surface electromyography. Mental workload was evaluated with NASA-TLX. After conducting animal experiments to verify safety of dual-console KD-SR-1500-RARP, we conducted the clinical trial using 5G and wired networks. RESULTS: In the animal experiment, all surgeries were performed successfully. The operative time was 80.2±32.1 min. The docking time was 2.4±0.5 min. The console time was 49.7±25.3 min. There were no perioperative complications or equipment related adverse events. All dogs can micturate after catheter removal at one week postoperatively. The mental workload was at a low level (a scale ranging from 0 to 60), which scored 15.7±6.9. Among the eight recorded muscles, the fatigue degree of the right radial flexor and left biceps was the highest two (iEMG, resection, 299.8±344 uV, 109.9±16.9 uV; suture, 849.4±1252.5 uV, 423.1±621.3 uV, respectively). In the clinical study, the console time was 136 min. The mean latency time was ≤200 ms. The data pocket loss was <1%. The operation was successfully completed without malfunctions occurring throughout the entire process. CONCLUSIONS: Dual-console telesurgery with the KD-SR-1500 system was shown to be feasible and safe in radical prostatectomy using 5G and wired networks.


Subject(s)
Feasibility Studies , Prostatectomy , Robotic Surgical Procedures , Animals , Dogs , Robotic Surgical Procedures/methods , Robotic Surgical Procedures/adverse effects , Male , Prostatectomy/methods , Prostatectomy/adverse effects , Humans , Middle Aged , Equipment Design , Operative Time , Aged , Electromyography , Telemedicine/methods
14.
J Endourol ; 38(7): 661-667, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38623792

ABSTRACT

Purpose: To investigate the feasibility, safety, and efficacy of the KangDuo-Surgical Robot-01 (KD-SR-01) system for robot-assisted radical nephroureterectomy (RARNU). Materials and Methods: This prospective, single-center, single-arm clinical study of patients with upper tract urothelial carcinoma (UTUC) was conducted from August 2022 to July 2023 using the KD-SR-01 system. The perioperative and follow-up data were prospectively recorded. The National Aeronautics and Space Administration task load index was calculated to present ergonomics. The technique was described in detail. Results: A total of 13 patients underwent RARNU. None of the cases conversed to laparoscopic procedure or open procedure. The median docking time and console time were 524 seconds (range 139-963 seconds) and 102.2 minutes (range 55.3-249.3 minutes), respectively. The median estimated blood loss was 40 mL (range 10-100 mL). None of the patients required intraoperative blood transfusion. The median postoperative hospital stay was 4 days (range 2-7 days). Intraoperative or postoperative complications (Clavien-Dindo grade I) occurred in nine patients. The surgeon task load index global score achieved 1.05 ± 1.86. Three patients received the single-docking technique, demonstrating similar perioperative results compared with patients with redocking. The study is registered at www.chictr.org.cn (ChiCTR2200056672). Conclusions: The KD-SR-01 system was feasible, safe, and effective for RARNU.


Subject(s)
Nephroureterectomy , Robotic Surgical Procedures , Aged , Female , Humans , Male , Middle Aged , Feasibility Studies , Nephroureterectomy/methods , Operative Time , Postoperative Complications/etiology , Prospective Studies , Robotic Surgical Procedures/methods , Treatment Outcome
16.
EBioMedicine ; 103: 105070, 2024 May.
Article in English | MEDLINE | ID: mdl-38564827

ABSTRACT

BACKGROUND: Cholesteryl ester (CE) accumulation in intracellular lipid droplets (LDs) is an essential signature of clear cell renal cell carcinoma (ccRCC), but its molecular mechanism and pathological significance remain elusive. METHODS: Enabled by the label-free Raman spectromicroscopy, which integrated stimulated Raman scattering microscopy with confocal Raman spectroscopy on the same platform, we quantitatively analyzed LD distribution and composition at the single cell level in intact ccRCC cell and tissue specimens in situ without any processing or exogenous labeling. Since we found that commonly used ccRCC cell lines actually did not show the CE-rich signature, primary cancer cells were isolated from human tissues to retain the lipid signature of ccRCC with CE level as high as the original tissue, which offers a preferable cell model for the study of cholesterol metabolism in ccRCC. Moreover, we established a patient-derived xenograft (PDX) mouse model that retained the CE-rich phenotype of human ccRCC. FINDINGS: Surprisingly, our results revealed that CE accumulation was induced by tumor suppressor VHL mutation, the most common mutation of ccRCC. Moreover, VHL mutation was found to promote CE accumulation by upregulating HIFα and subsequent PI3K/AKT/mTOR/SREBPs pathway. Inspiringly, inhibition of cholesterol esterification remarkably suppressed ccRCC aggressiveness in vitro and in vivo with negligible toxicity, through the reduced membrane cholesterol-mediated downregulations of integrin and MAPK signaling pathways. INTERPRETATION: Collectively, our study improves current understanding of the role of CE accumulation in ccRCC and opens up new opportunities for treatment. FUNDING: This work was supported by National Natural Science Foundation of China (No. U23B2046 and No. 62027824), National Key R&D Program of China (No. 2023YFC2415500), Fundamental Research Funds for the Central Universities (No. YWF-22-L-547), PKU-Baidu Fund (No. 2020BD033), Peking University First Hospital Scientific and Technological Achievement Transformation Incubation Guidance Fund (No. 2022CX02), and Beijing Municipal Health Commission (No. 2020-2Z-40713).


Subject(s)
Carcinoma, Renal Cell , Cholesterol Esters , Kidney Neoplasms , Mutation , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Signal Transduction , Von Hippel-Lindau Tumor Suppressor Protein , Animals , Humans , Mice , Carcinoma, Renal Cell/genetics , Carcinoma, Renal Cell/metabolism , Carcinoma, Renal Cell/pathology , Cell Line, Tumor , Cholesterol Esters/metabolism , Disease Models, Animal , Disease Progression , Kidney Neoplasms/metabolism , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Von Hippel-Lindau Tumor Suppressor Protein/genetics , Von Hippel-Lindau Tumor Suppressor Protein/metabolism
17.
Urol Int ; 108(4): 314-321, 2024.
Article in English | MEDLINE | ID: mdl-38513631

ABSTRACT

INTRODUCTION: The aim of this study was to present the surgical technique and clinical outcomes of modified ileal conduit for pelvic lipomatosis (PL). METHODS: From 2020 to 2022, we prospectively enrolled 9 patients with PL undergoing modified ileal conduit. The patient characteristics, perioperative variables, and follow-up outcomes as well as the description of surgical technique were reported. RESULTS: All 9 patients successfully completed the operation. Two patients had perioperative complications of Clavien-Dindo grade I. The mean operation time and bleeding volumes were 253 ± 51.4 min and 238.9 ± 196.9 mL, with a mean postoperative follow-up time of 13.0 ± 5.6 months. The postoperative 3-month and 1-year creatinine values were significantly decreased versus the preoperative (p = 0.006 and p = 0.024). The postoperative 3-month and 1-year estimated glomerular filtration rate values were significantly increased compared with those before operation (p = 0.0002 and p = 0.018). The separation value of left renal pelvis collection system after operation was significantly reduced compared with preoperative evaluation (p = 0.023 at 3 months and p = 0.042 at 1 year) and so was the right side (p = 0.019 and p = 0.023). CONCLUSION: Modified ileal conduit is safe and feasible for PL. A large sample cohort with long-term follow-up is needed to evaluate the clinical outcomes of PL.


Subject(s)
Lipomatosis , Urinary Diversion , Humans , Male , Middle Aged , Female , Treatment Outcome , Prospective Studies , Urinary Diversion/methods , Lipomatosis/surgery , Adult , Aged , Urinary Bladder Diseases
19.
Otolaryngol Head Neck Surg ; 170(5): 1380-1390, 2024 May.
Article in English | MEDLINE | ID: mdl-38385787

ABSTRACT

OBJECTIVE: To probe the microbiota composition progressing from healthy individuals to those with laryngopharyngeal reflux disease (LPRD) and subsequently undergoing potassium-competitive acid inhibitor (P-CAB) therapy. STUDY DESIGN: Prospective case-control study. SETTING: Academic Medical Center. METHODS: Forty patients with LPRD and 51 patients without LPRD were recruited. An 8-week P-CAB therapy was initiated (post-T-LPRD), and 39 had return visits. In total, 130 laryngopharyngeal saliva samples were collected and sequenced by targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene using an Illumina MiSeq. Amplicon sequence variants (ASVs) and clinical indices were analyzed. RESULTS: Alpha and beta diversities were compared among the non-LPRD, LPRD, and post-T-LPRD groups, and the Observed_ASVs were not significantly different. At the same time, the Shannon and Simpson indices, unweighted Unifrac, weighted Unifrac, and binary Jaccard distance were significantly different between non-LPRD and LPRD groups. In addition, significant differences were found in the abundance of Streptococcus, Prevotella, and Prevotellaceae in the LPRD versus non-LPRD groups, and Neisseria, Leptotrichia, and Allprevotella in the LPRD versus post-T-LPRD groups. The genera model was used to distinguish patients with LPRD from those without, and a better receiver operating characteristic curve was formed after combining the clinical indices of reflux symptom index, reflux finding score, and pepsin, with an area under the curve of 0.960. CONCLUSION: Laryngopharyngeal microbial communities changed after laryngopharyngeal reflux and were modified further after P-CAB treatment, which provides a potential diagnostic value for LPRD, especially when combined with clinical indices.


Subject(s)
Laryngopharyngeal Reflux , Humans , Laryngopharyngeal Reflux/drug therapy , Laryngopharyngeal Reflux/microbiology , Laryngopharyngeal Reflux/diagnosis , Male , Female , Prospective Studies , Case-Control Studies , Middle Aged , Proton Pump Inhibitors/therapeutic use , Adult , Pharynx/microbiology , Microbiota , Saliva/microbiology , Aged
20.
Sci Rep ; 14(1): 4542, 2024 02 24.
Article in English | MEDLINE | ID: mdl-38402357

ABSTRACT

Laryngopharyngeal reflux disease (LPRD) is a condition characterized by the regurgitation of stomach and duodenal contents into the laryngopharynx, with variable and non-specific symptoms. Therefore, developing an accurate symptom scale for different regions is essential. Notably, the symptoms of "dryness and burning sensation in the laryngopharynx or mouth" are prevalent among the Chinese population but are often omitted from conventional symptom assessment scales, such as the Reflux Symptom Index (RSI) and Reflux Symptom Score-12 (RSS-12) scales. To address this gap, our study incorporated the symptoms into the RSI and RSS-12 scales, developing the RSI-10/RSS-13 scales. Afterward, we assessed the role of the new scale's reliability (Cronbach's α and test-retest reliability), construct validity (confirmatory factor analysis and confirmatory factor analysis), and diagnostic efficiency. Our study encompassed 479 participants (average = 39.5 ± 13.4 years, 242 female) and 91 (average = 34.01 ± 13.50 years, 44 female) completed 24 h MII-pH monitoring. The Cronbach's α values of 0.80 and 0.82 for the RSI-10 and RSS-13 scales, respectively. RSI-10 and RSS-13 exhibited strong test-retest reliability (ICCs = 0.82-0.96) and diagnostic efficacy (AUC = 0.84-0.85). Furthermore, the factor analysis identified the RSS-13 and its three sub-scales (ear-nose-throat, digestive tract, respiratory tract) exhibited good to excellent structural validity (χ2/df = 1.95, P < 0.01; CFI = 0.95, RMSEA = 0.06, SRMR = 0.05). The AUC optimal thresholds for the RSI-10 and RSS-13 in the Chinese population were 13 and 36, respectively. Besides, the inclusion of the new item significantly improved the diagnostic efficiency of the RSI scale (P = 0.04), suggesting that RSI-10 holds promise as a more effective screening tool for LPRD, and global validation is needed to demonstrate the impact of this new symptom on the diagnosis of LPRD.


Subject(s)
Laryngopharyngeal Reflux , Humans , Female , Laryngopharyngeal Reflux/diagnosis , Reproducibility of Results , Hypopharynx , Sensation
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