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 evaluate the clinical value of inflammation-related markers in predicting the prognosis of patients with ureteral urothelial carcinoma. METHODS: 200 patients with ureteral urothelial carcinoma were randomly divided into two groups by split sample validation: modeling group and validation group. Paraffin embedded pathological specimens of the patients were reviewed. Immunohistochemical method was used to detect tumor-infiltrating neutrophil (TIN) (CD66b⁺), tumor-associated macrophage (TAM) (CD163⁺), lymphocyte (CD⁺, CD4⁺, CD8⁺) counts, peripheral blood neutrophil / lymphocyte ratio (NLR) and tumor tissue neutrophil/monocyte ratio (NMR). According to the results of pathological staging, the patients were divided into non-muscle-invasive and muscle-invasive ureteral urothelial carcinoma group. The resolution of the models was evaluated, and the prognostic nomogram models including only peripheral blood parameters and all parameters were established to compare the accuracy of the two models in predicting the prognosis of patients with urothelial carcinoma of the ureter. RESULTS: The median follow-up time was 36 months, the progression-free survival was 40 months, and 42 cases (21.0%) showed tumor progression within 3 years. Tumor size, pathological stage and pathological grade were all single-factor variables predicting the first recurrence of ureteral urothelial carcinoma three years after operation. Tumor size, pathological stage, pathological grade, TIN, TAM, NLR and NMR were multi-factor variables predicting the first recurrence three years after operation. Among 104 cases of non-muscle-invasive ureteral urothelial carcinoma, 10 cases (9.6%) recurred for the first time 3 years after operation, 96 cases (33.3%) of muscle invasive ureteral urothelial carcinoma, and the diffe-rence between the two groups was statistically significant (χ²=15.53, P < 0.05). The predictive nomogram model of progression free survival was established. The concordance index of progression free survi-val was 0.722 (95%CI: 0.70-0.78) in non-muscle-invasion group, and 0.725 (95%CI: 0.71-0.79) in muscle-invasion group, which was in good agreement with the observed 3-year survival rate. The results of discrimination test showed that the concordance index of the whole parameter prediction model of ureteral urothelial carcinoma was 0.726, which was higher than that of peripheral blood parameters (consistency index 0.672). The immune microenvironment of ureteral urothelial carcinoma improved the prediction accuracy of the model. CONCLUSION The prognosis prediction model based on immune inflammation-related markers was established as a perfection and supplement for the existing pathological grading and staging system, providing a basis for accurate individualized treatment of patients with urete-ral urothelial carcinoma. The prognosis prediction model based on the relevant indicators of peripheral blood samples is established, which is easy to obtain specimens, and the detection method is simple and economical, which is more conducive to clinical application.
Biomarkers ; Carcinoma, Transitional Cell/diagnosis* ; Humans ; Neoplasm Recurrence, Local ; Prognosis ; Retrospective Studies ; Tumor Microenvironment ; Ureteral Neoplasms/diagnosis*

Post-therapeutic whole body scan (RxWBS) after radioactive iodine (RAI) remnant ablation (RRA) is useful for detect recurrent or metastatic foci of differentiated thyroid carcinoma (DTC) after total thyroidectomy. However, there is rare possibility of false positive iodine uptake in WBS. Here, we report a case of a 72-year-old woman, who underwent RRA after total thyroidectomy due to follicular variant papillary thyroid carcinoma. There is an abnormal iodine uptake in RxWBS in pelvic cavity. Additional single photon emission computed tomography (SPECT)-computed tomography (CT) imaging showed an intensive I-131 avid mass in left ovary. There was a multiple calcified mass in left ovary and enhancing wall thickening in left ureter with hydronephrosis in contrast enhanced CT. She underwent hysterectomy, oophorectomy, left ureterectomy and nephrectomy and diagnosed as mature cystic teratoma with thyroid tissues and ureter cancer. Struma ovarii should be considered if there was abnormal RAI uptake in pelvic cavity. I-131 SPECT-CT is useful for differential diagnosis of abnormal iodine uptakes in WBS.
Aged ; Diagnosis, Differential ; Female ; Humans ; Hydronephrosis ; Hysterectomy ; Iodine ; Nephrectomy ; Ovariectomy ; Ovary ; Struma Ovarii* ; Teratoma ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Tomography, Emission-Computed, Single-Photon ; Ureter ; Ureteral Neoplasms ; Whole Body Imaging*

Post-therapeutic whole body scan (RxWBS) after radioactive iodine (RAI) remnant ablation (RRA) is useful for detect recurrent or metastatic foci of differentiated thyroid carcinoma (DTC) after total thyroidectomy. However, there is rare possibility of false positive iodine uptake in WBS. Here, we report a case of a 72-year-old woman, who underwent RRA after total thyroidectomy due to follicular variant papillary thyroid carcinoma. There is an abnormal iodine uptake in RxWBS in pelvic cavity. Additional single photon emission computed tomography (SPECT)-computed tomography (CT) imaging showed an intensive I-131 avid mass in left ovary. There was a multiple calcified mass in left ovary and enhancing wall thickening in left ureter with hydronephrosis in contrast enhanced CT. She underwent hysterectomy, oophorectomy, left ureterectomy and nephrectomy and diagnosed as mature cystic teratoma with thyroid tissues and ureter cancer. Struma ovarii should be considered if there was abnormal RAI uptake in pelvic cavity. I-131 SPECT-CT is useful for differential diagnosis of abnormal iodine uptakes in WBS.
Aged ; Diagnosis, Differential ; Female ; Humans ; Hydronephrosis ; Hysterectomy ; Iodine ; Nephrectomy ; Ovariectomy ; Ovary ; Struma Ovarii* ; Teratoma ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Tomography, Emission-Computed, Single-Photon ; Ureter ; Ureteral Neoplasms ; Whole Body Imaging*

12E7 Antigen ; Aged ; Antigens, CD ; metabolism ; Carcinoma, Transitional Cell ; pathology ; Carcinosarcoma ; pathology ; Cell Adhesion Molecules ; metabolism ; Cystectomy ; methods ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Male ; Nephrectomy ; Osteosarcoma ; metabolism ; pathology ; surgery ; Ureter ; surgery ; Ureteral Neoplasms ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

A 70-yr-old man presented with painless gross hematuria. He underwent right nephrectomy for benign disease 9 yr ago. Computed tomography and cystoscopy showed a mass in the distal region of the right ureteral stump. He underwent right ureterectomy and bladder cuff resection. Pathological examination showed T1 and WHO grade 2 transitional cell carcinoma. At 6 months postoperatively, the patient is alive without any evidence of recurrence.
Aged ; Carcinoma, Transitional Cell/*diagnosis/pathology/surgery ; Cystoscopy ; Hematuria/urine ; Humans ; Kidney Diseases/*surgery ; Male ; Nephrectomy ; Tomography, X-Ray Computed ; Ureteral Neoplasms/*diagnosis/pathology/surgery

Adenocarcinoma ; diagnosis ; secondary ; surgery ; Aged ; Biopsy ; Cystoscopy ; Diagnosis, Differential ; Follow-Up Studies ; Humans ; Laparoscopy ; Male ; Prostatic Neoplasms ; diagnostic imaging ; pathology ; surgery ; Radiography ; Transurethral Resection of Prostate ; methods ; Ureteral Neoplasms ; diagnosis ; secondary ; surgery ; Ureteroscopy ; Urethral Neoplasms ; diagnosis ; secondary ; surgery ; Urothelium ; pathology

Adenoma, Villous ; metabolism ; pathology ; surgery ; Diagnosis, Differential ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Lymphoma ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Myosins ; metabolism ; Neoplasms, Multiple Primary ; metabolism ; pathology ; surgery ; Rhabdomyosarcoma, Alveolar ; metabolism ; pathology ; surgery ; Ureteral Neoplasms ; metabolism ; pathology ; surgery ; Vimentin ; metabolism

Adenocarcinoma ; diagnosis ; surgery ; Aged ; Humans ; Male ; Treatment Outcome ; Ureteral Neoplasms ; diagnosis ; surgery

OBJECTIVETo analyse the clinicopathological features and discuss the diagnosis, therapy and prognosis of primary ureteral carcinoma.

METHODSOne hundred and seventy four cases of primary ureteral carcinoma diagnosed pathologically between January 1971 and July 2002 in our institution were followed up and retrospectively studied.

RESULTSThe incidence of primary ureteral carcinoma was increasing during the last 30 years. The mean age of occurrence was 63.7 years. The most useful methods of detecting tumors preoperatively were retrograde urogram, CT, magnetic resonance urography and ureteroscopy, with positive percentage of 87.8% (86/98), 96.0% (48/50), 95.8% (23/24), 87.0% (20/23) respectively. 131 (75.3%) cases underwent nephroureterectomy with a cuff of bladder. 171 (98.3%) cases were transitional cell carcinoma. T(a-2) and G(1, 2) tumors account for 70% of all respectively. The 5 year and 10 year survival rates were 53.1% (52/98) and 30.5% (18/59) respectively. The subsequent bladder cancer occurred in 38 cases (23.8%), and the subsequent contralateral ureteral carcinoma occurred in 6 cases (3.8%).

CONCLUSIONSThe prognosis of primary ureteral carcinoma is poor. Tumor stage and grade are both the prognostic factors. Precise preoperative diagnosis and more effective adjuvant therapy may improve the prognosis.

Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Ureteral Neoplasms ; diagnosis ; epidemiology ; pathology ; surgery