Objective: To explore the diagnostic values of HK2 testing and single-cell sequencing in the urothelial carcinoma (UC). Methods: The qualified urine specimens of 265 suspected UC patients or postoperative patients from the Cancer Hospital of Chinese Academy of Medical Sciences, Beijing, China were collected. Both exfoliative cytology and HK2 testing were performed on clinically suspected UC or postoperative patients. The performance of diagnostic cytology and HK2, including consistency, sensitivity, specificity, positive predictive value and negative predictive value, was evaluated based on histopathological, clinical and imaging diagnosis. Isolated HK2 metabolically abnormal cells were subject to single-cell sequencing to verify the reliability of HK2 detection performance and to explore the molecular characteristics of UC. Results: The concordance rate of HK2 testing and cytology for detecting UC was 90.3% (102/113, Kappa=0.604). Compared with cytology, the sensitivity of HK2 was significantly higher (85.2% versus 75.6%, P=0.024). The detection sensitivity of combined HK2 testing and cytology was increased to 91.1%. HK2 testing was significantly more sensitive than cytology for diagnosing UC in the upper urinary tract (81.8% versus 65.5%, P=0.022). It was also more sensitive than cytology for diagnosing early-stage UC (82.6% versus 69.5%, P=0.375) and low-grade UC (69.6% versus 47.8%, P=0.125). Single-cell sequencing of the ten patients, whose samples were positive for HK2, demonstrated highly concordant copy number variations (CNVs) in tumor cells from the same UC patient, with heterogeneity in CNV profiles among different patients. Deletion of chromosome 8p was found in 3 of the 4 urine samples of renal pelvis UC. The 2 patients with benign lesions had no CNVs in all sequenced cells. Conclusions: The test for abnormal urinary glycolytic HK2 metabolism can assist urine cytology to improve the sensitivity of UC diagnosis, and it provides a novel and reliable approach for early detection of upper urinary tract UC and lower grade UC. Meanwhile, this study has preliminarily revealed the feasibility of single-cell sequencing in urinary samples, which is expected to improve the diagnostic specificity of HK2 testing.
Humans ; Urinary Bladder Neoplasms/diagnosis* ; Carcinoma, Transitional Cell/pathology* ; Reproducibility of Results ; DNA Copy Number Variations ; Kidney Neoplasms ; Ureteral Neoplasms ; Sensitivity and Specificity

Objective: To investigate the gene mutation of telomerase reverse transcriptase (TERT) promoter in inverted urothelial lesions of the bladder and its significance in differential diagnosis. Methods: From March 2016 to February 2022, a total of 32 patients with inverted urothelial lesions diagnosed in Department of Pathology at Qingdao Chengyang People's Hospital and 24 patients at the Affiliated Hospital of Qingdao University were collected, including 7 cases of florid glandular cystitis, 13 cases of inverted urothelial papilloma, 8 cases of inverted urothelial neoplasm with low malignant potential, 17 cases of low-grade non-invasive inverted urothelial carcinoma, 5 cases of high-grade non-invasive inverted urothelial carcinoma, and 6 cases of nested subtype of urothelial carcinoma were retrospectively analyzed for their clinical data and histopathological features. TERT promoter mutations were analyzed by Sanger sequencing in all the cases. Results: No mutations in the TERT promoter were found in the florid glandular cystitis and inverted urothelial papilloma. The mutation rates of the TERT promoter in inverted urothelial neoplasm with low malignant potential, low grade non-invasive inverter urothelial carcinoma, high grade non-invasive inverted urothelial carcinoma and nested subtype urothelial carcinoma were 1/8, 8/17, 2/5 and 6/6, respectively. There was no significant difference in the mutation rate of TERT promoter among inverted urothelial neoplasm with low malignant potential, low-grade non-invasive inverted urothelial carcinoma, and high-grade non-invasive inverted urothelial carcinoma (P>0.05). All 6 cases of nested subtype of urothelial carcinoma were found to harbor the mutation, which was significantly different from inverted urothelial neoplasm with low malignant potential and non-invasive inverted urothelial carcinoma (P<0.05). In terms of mutation pattern, 13/17 of TERT promoter mutations were C228T, 4/17 were C250T. Conclusions: The morphology combined with TERT promoter mutation detection is helpful for the differential diagnosis of bladder non-invasive inverted urothelial lesions.
Humans ; Urinary Bladder Neoplasms/genetics* ; Carcinoma, Transitional Cell/pathology* ; Urinary Bladder/pathology* ; Diagnosis, Differential ; Retrospective Studies ; Mutation ; Cystitis/genetics* ; Neoplasms, Glandular and Epithelial/diagnosis* ; Papilloma/diagnosis* ; Telomerase/genetics*

Artificial Intelligence ; Forecasting ; Humans ; Rare Diseases ; Urinary Bladder Neoplasms/diagnosis*

OBJECTIVE: To determine the optimal cystoscopic frequency for intermediate-risk non-muscle invasive bladder cancer. METHODS: Patients with intermediate-risk non-muscle invasive bladder cancer, who underwent transurethral resection of bladder tumor in Peking University People's Hospital from January 2001 to October 2019, were retrospectively analyzed. Their clinical, pathological and follow-up data were collected. In postoperative 2-year period, the patients were underwent cystoscopy every 3 to 6 months. Depending on recurrence and progression of the patients, we hypothesized three strategies of surveillance intensity in the first 2 years after surgery: model 1: 3-month intervals, model 2: 6-month intervals, and model 3: 12-month intervals. The differences in the numbers and time of delayed detection of recurrence and progression were compared among the three models. RESULTS: A total of 185 patients were enrolled, including 144 males (77.8%) and 41 females (22.2%). The median age was 68 (59-76) years. There were 118 cases (63.8%) with single tumor and 67 cases (36.2%) with multiple tumor. Of the patients 179 (96.8%) had stage Ta and 6 (3.2%) had stage T1. There were 108 cases (58.4%) with high-grade disease and 77 cases (41.6%) with low-grade disease. During the follow-up period of the first 2 years, 52 patients (28.1%) had recurrence, 133 cases (71.9%) had no recurrence, 11 cases (5.9%) had progression and 174 cases (94.1%) had no progression. Compared with model 1, 29 (55.8%) delayed detection of recurrence in model 2 vs. 41 (78.8%) delayed detection of recurrence in model 3, and the difference was statistically significant (P=0.012). The median delayed time of detecting recurrence was 1.00 months in model 1, 1.99 months in model 2 and 4.19 months in model 3, respectively. There were statistically significant differences between mode 1 and model 3 (P=0.001), and between model 2 and model 3 (P=0.013). Compared with model 1, 5 (45.4%) delayed detection of progression in model 2 vs. 8 (72.7%) delayed detection of progression in model 3, and the difference was not statistically significant. The median delayed time of detecting progression was 1.00 month in model 1, 2.00 months in model 2 and 3.00 months in model 3, respectively. There was no statistically significant difference among them. CONCLUSION Although providing slightly slower detection of tumor recurrence and progression, compared with 3-month intervals of cystoscopy, 6-month intervals do not result in serious adverse outcomes and reduce cost and pain of the patients, which is feasible in intermediate-risk non-muscle invasive bladder cancer.
Aged ; Cystoscopy ; Disease Progression ; Female ; Humans ; Male ; Neoplasm Recurrence, Local/diagnosis* ; Retrospective Studies ; Urinary Bladder Neoplasms/surgery*

Bladder cancer (BC) is the most common malignant tumor of the genitourinary system. The age of individuals diagnosed with BC tends to decrease in recent years. A variety of standard therapeutic options are available for the clinical management of BC, but limitations exist. It is difficult to surgically eliminate small lesions, while radiation and chemotherapy damage normal tissues, leading to severe side effects. Therefore, new approaches are required to improve the efficacy and specificity of BC treatment. Synthetic biology is a field emerging in the last decade that refers to biological elements, devices, and materials that are artificially synthesized according to users' needs. In this review, we discuss how to utilize genetic elements to regulate BC-related gene expression periodically and quantitatively to inhibit the initiation and progression of BC. In addition, the design and construction of gene circuits to distinguish cancer cells from normal cells to kill the former but spare the latter are elaborated. Then, we introduce the development of genetically modified T cells for targeted attacks on BC. Finally, synthetic nanomaterials specializing in detecting and killing BC cells are detailed. This review aims to describe the innovative details of the clinical diagnosis and treatment of BC from the perspective of synthetic biology.
Humans ; Synthetic Biology ; Urinary Bladder Neoplasms/diagnosis*

Bladder cancer has high morbidity and mortality rates worldwide. Its incidence is high in western countries and has shown an increasing trend in China. While radical cystectomy combined with pelvic lymph node dissection (PLND) is the standard treatment for bladder cancer,the optimal range of PLND remains controversial. In addition,the prognostic value of lymph node factors is also unclear. This article reviews research advances in PLND.
China ; Humans ; Lymph Node Excision ; Lymph Nodes ; Pelvis ; Urinary Bladder Neoplasms ; diagnosis

Consensus ; Humans ; Specimen Handling ; Urinary Bladder Neoplasms ; diagnosis

Objective To investigate the clinical value of preoperative lymphocyte-to-monocyte ratio(LMR)in evaluating the prognosis of patients with stage T1 non-muscle invasive bladder cancer(NMIBC).Methods A total of 215 patients with stage T1 NMIBC who underwent transurethral resection of bladder tumor were enrolled.Clinical data were collected.Patients were followed up and their disease-free survival(DFS)and overall survival(OS)were recorded.The receiver operating characteristic(ROC)curve of preoperative LMR in detecting patient prognosis was used to determine the optimal cut-off value for LMR.Patients were divided into low LMR group(LMR <3.86,=77)and high LMR group(LMR ≥ 3.86,=138).Kaplan-Meier survival curves were explored to compare cumulative DFS and OS rates in patients with different LMR levels,and COX proportional hazards regression model was used to analyze factors associated with DFS and OS.Results All these 215 patients with T1 stage NMIBC were followed up for 2-92 months,and the DFS rate was 59.07% and OS rate was 65.12%.Kaplan-Meier curves showed that the cumulative DFS rate(=4.784,=0.029)and cumulative OS rate(=7.146, =0.008)in the low LMR group were significantly lower than those in the high LMR group.Tumor size ≥ 3 cm(=1.398,95% :1.042-1.875,=0.025),pathological grade G3(=1.266,95% :1.026-1.563,=0.028),and LMR ≥ 3.86(=2.347,95% :1.080-5.101,=0.031)were independent factors associated with DFS in patients with stage T NMIBC.In addition,tumor size ≥ 3 cm(=1.228,95% :1.015-1.484,=0.034),pathological grade G3(=1.366,95% :1.017-1.834,=0.038),and LMR<3.86(=2.008,95% :1.052-3.832,=0.035)were independent factors associated with OS in patients with T1 stage NMIBC. Conclusion Preoperative LMR is an independent factor associated with patients' prognosis in T1 stage NIMBC.Patients with low LMR tend to have higher risk of NMIBC progression and death.
Disease-Free Survival ; Humans ; Lymphocytes ; cytology ; Monocytes ; cytology ; Prognosis ; Retrospective Studies ; Survival Rate ; Urinary Bladder Neoplasms ; diagnosis ; pathology

Bladder cancer is a urological malignant tumor with high morbidity and mortality. Masses protruding into the bladder cavity is an important feature for clinical diagnosis of bladder cancer. However,patients with encrusted bladder cancer(EBC)do not present with masses protruding into the bladder cavity and thus this malignancy is often misdiagnosed. Four patients were admitted in Peking University People's Hospital from July 2015 to February 2017. All of them were males aged 40 to 77 years(mean:58 years). Patients were mainly manifested as frequent urination,urgency,nocturia,and decreased bladder capacity,with or without difficulty of voiding.Although the bladder walls were markedly thickened,there was no obvious mass on imaging scans. Three patients received urodynamic test,which showed the maximum capacity of the bladder was 41 to 128 ml(mean:91 ml). One patient presented with gross hematuria,two patients presented with microscopic hematuria,and the remaining one patient had no hematuria. No mass was observed by cystoscopy. All of the patients were diagnosed with bladder cancer by repeated biopsy or intraoperative frozen section analysis.
Adult ; Aged ; Biopsy ; Cystoscopy ; Hematuria ; Humans ; Male ; Middle Aged ; Urinary Bladder Neoplasms ; diagnosis ; pathology

Diffuse large B-cell lymphoma associated with chronic inflammation (DLBCL-CI), specifically arising in ileal neobladder, is a rare neoplasm. We present an unusual case of Epstein–Barr virus (EBV)–positive DLBCL-CI arising within neobladder with detailed clinical, histological, and immunophenotypical features in an immunocompetent patient. An 88-year-old male was admitted for gross hematuria. He had undergone radical cystectomy and ileal neobladder 17 years ago for invasive bladder cancer. Computed tomography showed enhancing lesions on dome and posterior wall of neobladder with mucosal thickening and multiple enlarged retroperitoneal lymphadenopathies. Transurethralresection of neobladder lesion revealed the diffuse infiltration of large lymphoid cells which were positive for CD20, CD30, and multiple myeloma oncogen-1 with EBV-encoded small RNAs co-localizing, and diagnosis of EBV-positive DLBCL-CI was made. After multi-agent chemotherapy, the lesion disappeared. We suggest that clinicians should consider the possibility of DLBCL-CI in patients presented with hematuria during follow-up after bladder reconstruction.
Aged, 80 and over ; B-Lymphocytes ; Cystectomy ; Diagnosis ; Drug Therapy ; Follow-Up Studies ; Hematuria ; Humans ; Inflammation ; Lymphocytes ; Lymphoma, B-Cell ; Male ; Multiple Myeloma ; RNA ; Urinary Bladder ; Urinary Bladder Neoplasms