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

Bone Neoplasms ; pathology ; Carcinoma, Neuroendocrine ; pathology ; Humans ; Osteosarcoma ; pathology ; Ureter ; pathology ; Ureteral Neoplasms ; pathology

PURPOSE: To investigate oncological outcomes based on bladder cuff excision (BCE) during radical nephroureterectomy (RNU) for upper tract urothelial carcinoma (UTUC) and to provide clinical evidence of tumor recurrence in patients without BCE. MATERIALS AND METHODS: We retrospectively collected data of 372 consecutive patients who underwent RNU at our institution from May 1989 through October 2010. After excluding some data, we reviewed 336 patients for the analysis. RESULTS: Of the patients who underwent RNU with BCE (n=279, 83.0%) and without BCE (n=57, 17.0%), patients without BCE had poorer cancer-specific and overall survival rates. Among 57 patients without BCE, 35 (61.4%) experienced tumor recurrence. Recurrence at the remnant ureter resulted in poor oncological outcomes compared to those in patients with bladder recurrence, but better outcomes were observed compared to recurrence at other sites. No significant predictors for tumor recurrence at the remnant ureter were identified. In patients without BCE, pathological T stage [hazard ratio (HR), 5.73] and lymphovascular invasion (HR, 3.65) were independent predictors of cancer-specific survival, whereas age (HR, 1.04), pathological T stage (HR, 5.11), and positive tumor margin (HR, 6.50) were independent predictors of overall survival. CONCLUSION: Patients without BCE had poorer overall and cancer-specific survival after RNU than those with BCE. Most of these patients experienced tumor recurrence at the remnant ureter and other sites. Patients with non-organ confined UTUC after RNU without BCE may be considered for adjuvant chemotherapy with careful follow-up.
Adult ; Aged ; Carcinoma, Transitional Cell/*surgery ; Chemotherapy, Adjuvant ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local/*pathology ; Nephrectomy/*methods ; Retrospective Studies ; Survival Rate ; Treatment Outcome ; Ureter/*surgery ; Ureteral Neoplasms/*surgery ; Urinary Bladder/pathology ; Urinary Bladder Neoplasms/*pathology ; Urologic Neoplasms/pathology/*surgery ; *Urologic Surgical Procedures ; Urothelium/*pathology

PURPOSE: To evaluate the impact of adjuvant chemotherapy (AC) in patients with upper tract urothelial carcinoma and lymphovascular invasion (LVI) after radical nephroureterectomy (RNU). MATERIALS AND METHODS: We retrospectively analyzed the clinical records and clinicopatholgic outcomes of patients (n=552) treated with RNU between 1986 and 2013. Patients treated with neoadjuvant chemotherapy and those for whom LVI status was not recorded were excluded. Patients were divided into two groups according to LVI (n=86) or no LVI (n=256). RESULTS: The study included 344 patients (240 men and 104 women) with a median of 53.9 months of follow-up (range, 1-297 months) after RNU. Tumors were organ confined (T2/N0) in 211 (61.3%) and tumor grade high in 291 (84.6%). AC was administered in 64 patients (18.6%). A total of 280 patients (81.4%) were treated with surgery alone. Patients with LVI tended to be older (p=0.049), have a higher pT stage (pT3/T4, p<0.001), be pN+ (p<0.001), have a high tumor grade (p<0.001), and experience recurrence (p<0.001). In the multivariate analysis, LVI was an independent prognostic factor for cancer-specific survival and overall survival (p=0.002 and p<0.001, respectively). The multivariate analysis demonstrated that in the subgroup of patients with LVI, AC was a significant prognostic factor for cancer-specific survival and overall survival (hazard ratio, 0.51; p=0.027 and hazard ratio, 0.50; p=0.025, respectively). CONCLUSIONS: AC does not seem to reduce mortality in patients with advanced upper tract urothelial carcinoma after RNU. In the subgroup of patients with LVI, AC had a positive impact on cancer-specific survival and overall survival. LVI would be helpful for selecting patients who are appropriate for AC.
Aged ; Carcinoma, Transitional Cell/drug therapy/*mortality/surgery ; *Chemotherapy, Adjuvant ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms/drug therapy/*mortality/surgery ; Lymphatic Metastasis ; Male ; Middle Aged ; Multivariate Analysis ; Neoplasm Grading ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Nephrectomy ; Prognosis ; Retrospective Studies ; Survival Rate ; Ureter/pathology ; Ureteral Neoplasms/drug therapy/*mortality/surgery ; Urinary Tract/pathology

PURPOSE: The objective was to investigate the impact of statin use on prognosis after radical nephroureterectomy for upper urinary tract urothelial carcinoma (UTUC). MATERIALS AND METHODS: A retrospective review of medical records identified 277 patients who underwent radical nephroureterectomy for primary UTUC at Asan Medical Center between January 2006 and December 2011. Information on preoperative statin use was obtained from patient charts in an electronic database. We assessed the impact of statin use on recurrence-free survival (RFS), cancer-specific survival (CSS), and overall survival (OS). RESULTS: Of these 277 patients, 62 (22.4%) were taking statin medications. Compared to the statin nonusers, the statin users were older, had a higher body mass index, and had higher rates of cardiovascular disease and diabetes. The 5-year RFS rates of statin users and nonusers were 78.5% and 72.5%, respectively (p=0.528); the 5-year CSS rates were 85.6% and 77.7%, respectively (p=0.516); and the 5-year OS rates were 74.5% and 71.4%, respectively (p=0.945). In the multivariate analysis, statin use was not an independent prognostic factor for RFS (hazard ratio, 0.47; p=0.056), CSS (hazard ratio, 0.46; p=0.093), or OS (hazard ratio, 0.59; p=0.144) in patients who underwent radical nephroureterectomy for UTUC. CONCLUSIONS: Statin use was not associated with improved RFS, CSS, or OS in the sample population of patients with UTUC.
Aged ; Carcinoma, Transitional Cell/pathology/*surgery ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*therapeutic use ; Kidney Neoplasms/pathology/*surgery ; Male ; Middle Aged ; Neoplasm Grading ; Neoplasm Staging ; Nephrectomy/methods ; Preoperative Care/methods ; Prognosis ; Recurrence ; Retrospective Studies ; Survival Analysis ; Ureteral Neoplasms/pathology/*surgery

OBJECTIVE: To study the effect and outcome of Boari bladder flap plasty surgery for the treatment of kidney-sparing strategy for patients with middle and lower ureteral carcinoma. METHODS: Database at the department of urology in the Second Xiangya Hospital from 2002-2007 was screened and all cases of primary solitary lower ureteral carcinoma treated with Boari bladder flap plasty surgery or radical nephroureterectomy were collected. We performed a retrospective review of the clinical data including sex, age, smoking history, tumor site, size, stage, grade, bladder recurrence, renal function et al and evaluated survival rate. The Cox proportional hazards regression model was build to analyze the correlation between each variable and survival time. RESULTS: Thirty nine patients in total were enrolled, including 16 cases underwent Boari bladder flap plasty surgery and 23 cases underwent radical nephroureterectomy. The median follow-up time was 53 months (range 10-84 months). During the follow-up time, 18 patients died, including 6 patients treated with Boari bladder flap plasty surgery and 12 patients treated with radical nephroureterectomy. The estimated bladder recurrence-free survival rate and cancer-specific survival rate at 5 years were 63% vs 59% and 73.8% vs 73.5%, respectively (P>0.05). The survival rate at 5 years and the overall survival rate were 61% vs 57 % and 64.8% vs 58.1% respectively in the 2 groups (P>0.05). There was no significant difference in renal function before surgery between the two groups [creatinine clearance 57 (32-104 ) mL/ min vs 55 (30-102) mL/ min, P>0.05]. Patients underwent Boari bladder flap plasty showed better renal function than patients underwent radical nephroureterectomy [creatinine clearance 55 (35-102) mL/ min vs 43 (30-89) mL/min, P<0.05]. In multivariate Cox regression analysis, the tumor size, pT stage, tumor cell grade and the estimated glomerular filtration rate level were independent factors that affected the overall survival rate of the patients (P<0.05). The tumor size, pT stage and tumor cell grade were positively correlated to the survival time, and the estimated glomerular filtration rate was negatively correlated to the survival time. CONCLUSION Boari bladder flap plasty surgery could be used to treat lower ureteral carcinoma. Compared with radical nephroureterectomy, Boari bladder flap plasty surgery has equal survival rate and shows superior postoperative renal function.
Carcinoma ; surgery ; Humans ; Kidney ; Neoplasm Recurrence, Local ; Nephrectomy ; Postoperative Period ; Proportional Hazards Models ; Retrospective Studies ; Surgical Flaps ; Survival Rate ; Ureter ; pathology ; Ureteral Neoplasms ; surgery ; Urinary Bladder ; surgery ; Urologic Surgical Procedures ; methods

OBJECTIVETo explore the clinicopathological features, immunophenotype, differential diagnosis, pathogenesis and prognosis of villous adenoma with poorly differentiated adenocarcinoma of the urinary tract.

METHODSClinical and pathologic findings of 3 cases of villous adenoma with poorly differentiated adenocarcinoma of the urinary tract were analyzed by gross examination, microscopic investigation and immunohistochemical staining. The related literatures were reviewed.

RESULTSAll of the three cases were middle-aged or elderly patients. Three cases all presented with hematuria and mucusuria. Endoscopic examination identified that case 1 had a polyp with broad attachment in the dome of bladder, case 2 had a solid mass in the ureter, and case 3 had a exophytic fungating tumor in the renal pelvis. Microscopically, case 1 revealed a papillary lesion with finger-like processes lined by pseudostratified columnar epithelium with abundant goblet cells. The cells demonstrated moderate degree dysplasia. In case 2 and case 3, both villous adenomas and poorly differentiated adenocarcinoma were observed, the adenoma cells arranged in a cribriform pattern, and the tumor cells showed severe atypia, mitotic activity, and transition with invasive poorly differentiated adenocarcinoma. Immunohistochemically, the tumor cells in three cases were positive for CK20, CEA,EMA and MUC-1; none of them expressed cdx-2 and PSA; In case 2 and 3, the same immunophenotype of villous adenomas and their associated adenocarcinomas was observed, but the number of the positive cells of p53 and Ki-67 staining were significantly increased in the area of adenocarcinomas than in that of the villous adenomas.

CONCLUSIONSVillous adenoma of the urinary tract is rare. It can occur in the urinary bladder, urachus, renal pelvis, ureter and urethra. These lesions may have malignant potential and frequently coexist with other malignant tumors. So, villous adenoma of the urinary tract should be removed completely and sampled thoroughly to avoid missing a more aggressive component.

Adenocarcinoma ; metabolism ; pathology ; surgery ; Adenoma, Villous ; metabolism ; pathology ; secondary ; surgery ; Adult ; Aged ; Carcinoembryonic Antigen ; metabolism ; Follow-Up Studies ; Humans ; Keratin-20 ; metabolism ; Kidney Neoplasms ; metabolism ; pathology ; surgery ; Kidney Pelvis ; Lung Neoplasms ; secondary ; Male ; Mucin-1 ; metabolism ; Neoplasms, Multiple Primary ; metabolism ; pathology ; surgery ; Ureteral Neoplasms ; metabolism ; pathology ; surgery ; Urinary Bladder Neoplasms ; metabolism ; pathology ; surgery

OBJECTIVETo study the clinical and pathologic characteristics of small cell neuroendocrine carcinoma of urinary tract.

METHODSAll cases of urinary tract carcinoma encountered in the General Hospital of People Liberation Army during the period from 1999 to 2010 were retrospectively reviewed. The clinicopathologic data of small cell neuroendocrine carcinomas were further analyzed, with literature review.

RESULTSA total of 16 cases of small cell neuroendocrine carcinoma were identified, including 10 from urinary bladder, 2 from ureter, 3 from renal pelvis, and 1 multifocal tumor involving renal pelvis and ureter. There were altogether 8 males and 8 females. The median age of the patients was 63 years (range = 24 to 79 years). Gross hematuria (11 cases) represented the main presenting symptom. Four patients had flank pain and 4 had urinary irritation symptoms. Seven patients underwent radical cystectomy. Six other patients underwent radical nephroureterectomy, 1 partial cystectomy, 1 TURBT and the remaining case biopsy only. The size of the tumor ranged from 0.8 to 8.0 cm (median = 4.5 cm). Histologically, 15 cases represented mixed small cell neuroendocrine carcinoma (with 13 mixed with transitional cell carcinoma and 2 with adenocarcinoma). Immunohistochemical study showed positive staining for neuroendocrine markers. On presentation, 1 patient was in stage pT1, 7 in stage pT2, 6 in stage pT3, 2 in stage pT4. Six patients died of the disease after operation. The overall survival was 25 months and the 5-year survival rate was 32.4%.

CONCLUSIONSSmall cell neuroendocrine carcinoma of urinary bladder is a highly malignant disease and associated with poor prognosis. The diagnosis relies on detailed histologic examination. Early diagnosis, when coupled with cystectomy or nephroureterectomy and adjuvant chemotherapy, represents the mainstay of management.

Adult ; Aged ; CD56 Antigen ; metabolism ; Carcinoma, Neuroendocrine ; drug therapy ; metabolism ; pathology ; surgery ; Carcinoma, Small Cell ; drug therapy ; metabolism ; pathology ; surgery ; Chemotherapy, Adjuvant ; Cystectomy ; Female ; Follow-Up Studies ; Humans ; Keratins ; metabolism ; Kidney Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Male ; Middle Aged ; Neoplasm Staging ; Nephrectomy ; Phosphopyruvate Hydratase ; metabolism ; Retrospective Studies ; Survival Rate ; Synaptophysin ; metabolism ; Ureteral Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Urinary Bladder Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Urologic Neoplasms ; drug therapy ; metabolism ; pathology ; surgery ; Young Adult

OBJECTIVETo define the clinicopathological risk factors of intravesical recurrence of primary transitional cell carcinoma of the ureter after surgical intervention.

METHODSPatients with primary carcinoma of the ureter treated between January 2000 and December 2010 were retrospectively analyzed. The intravesical recurrence-free survival rate was calculated using Kaplan-Meier method. Multivariate analysis was conducted with Cox's regression.

RESULTSA total of 104 patients were enrolled, who were followed up for a median of 46 months (13-89 months). Thirty-nine of the patients showed postoperative intravesical recurrence. Urine exfoliative cytology (P=0.000), number of tumors (P=0.006), tumor grade (P=0.039) and co-existence of bladder tumor (P=0.014) were found to independently influence the postoperative intravesical recurrence. Patients with more risk factors had poorer intravesical recurrence-free survival.

CONCLUSIONUrine exfoliative cytology, number of tumors, tumor grade and co-existence of bladder tumor are independent risk factors for postoperative intravesical recurrence of primary transitional cell carcinoma of the ureter. Close follow-up and rigorous treatment are essential for patients with high risk factors.

Adult ; Aged ; Carcinoma, Transitional Cell ; pathology ; surgery ; Causality ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Regression Analysis ; Retrospective Studies ; Risk Factors ; Ureteral Neoplasms ; pathology ; surgery ; Urinary Bladder Neoplasms ; pathology

Carcinoma, Renal Cell ; metabolism ; pathology ; surgery ; Carcinoma, Transitional Cell ; metabolism ; pathology ; surgery ; Carcinosarcoma ; metabolism ; pathology ; surgery ; Female ; Follow-Up Studies ; Humans ; Keratins ; metabolism ; Kidney Neoplasms ; pathology ; surgery ; Lymphatic Metastasis ; Male ; Prostatic Neoplasms ; metabolism ; pathology ; surgery ; Retrospective Studies ; Survival Rate ; Ureteral Neoplasms ; metabolism ; pathology ; surgery ; Urinary Bladder Neoplasms ; metabolism ; pathology ; surgery ; Urologic Neoplasms ; metabolism ; pathology ; surgery ; Vimentin ; metabolism