Current noninvasive assays for urothelial carcinoma (UC) lack clinical sensitivity and specificity. Given the utility of plasma cell-free DNA (cfDNA) bio-markers, the development of urinary cfDNA ...biomarkers may improve the diagnostic sensitivity.
We assessed copy number alterations (CNAs) by shallow genome-wide sequencing of urinary cfDNA in 95 cancer-free individuals and 65 patients with UC, 58 with kidney cancer, and 45 with prostate cancer. We used a support vector machine to develop a diagnostic classifier based on CNA profiles to detect UC (UCdetector). The model was further validated in an independent cohort (52 patients). Genome sequencing data of tumor specimens from 90 upper tract urothelial cancers (UTUCs) and CNA data for 410 urothelial carcinomas of bladder (UCBs) from The Cancer Genome Atlas were used to validate the classifier. Genome sequencing data for urine sediment from 32 patients with UC were compared with cfDNA. To monitor the treatment efficacy, we collected cfDNA from 7 posttreatment patients.
Urinary cfDNA was a more sensitive alternative to urinary sediment. The UCdetector could detect UC at a median clinical sensitivity of 86.5% and specificity of 94.7%. UCdetector performed well in an independent validation data set. Notably, the CNA features selected by UCdetector were specific markers for both UTUC and UCB. Moreover, CNA changes in cfDNA were consistent with the treatment effects. Meanwhile, the same strategy could localize genitourinary cancers to tissue of origin in 70.1% of patients.
Our findings underscore the potential utility of urinary cfDNA CNA profiles as a basis for non-invasive UC detection and surveillance.
Ureteroplasty using onlay grafts or flaps emerged as an innovative procedure for the management of proximal and midureteral strictures. Autologous grafts or flaps used commonly in ureteroplasty ...include the oral mucosae, bladder mucosae, ileal mucosae, and appendiceal mucosae. Oral mucosa grafts, especially buccal mucosa grafts (BMGs), have gained wide acceptance as a graft choice for ureteroplasty. The reported length of BMG ureteroplasty ranged from 1.5 to 11 cm with success rates of 71.4%-100%. However, several studies have demonstrated that ureteroplasty using lingual mucosa grafts yields better recipient site outcomes and fewer donor site complications than that using BMGs. In addition, there is no essential difference in the efficacy and complication rates of BMG ureteroplasty using an anterior approach or a posterior approach. Intestinal graft or flap ureteroplasty was also reported. And the reported length of ileal or appendiceal flap ureteroplasty ranged from 1 to 8 cm with success rates of 75%-100%. Moreover, the bladder mucosa, renal pelvis wall, and penile/preputial skin have also been reported to be used for ureteroplasty and have achieved satisfactory outcomes, but each graft or flap has unique advantages and potential problems. Tissue engineering-based ureteroplasty through the implantation of patched scaffolds, such as the small intestine submucosa, with or without cell seeding, has induced successful ureteral regeneration structurally close to that of the native ureter and has resulted in good functional outcomes in animal models.
Long-term prognosis and risk factors of de novo upper tract urothelial carcinoma after renal transplantation were rarely studied. Thus, the aim of this study was to investigate the clinical features, ...risk factors, and long-term prognosis of de novo upper tract urothelial carcinoma after renal transplantation, especially the impact of aristolochic acid on tumor, using a large sample.
106 patients were enrolled in retrospective study. The endpoints included overall survival, cancer-specific survival, bladder or contralateral upper tract recurrence-free survival. Patients were grouped according to aristolochic acid exposure. Survival analysis was performed using Kaplan-Meier curve. Log-rank test was used to compare the difference. Multivariable cox regression was conducted to evaluate the prognostic significance.
Median time from transplantation to development of upper tract urothelial carcinoma was 91.5 months. Cancer-specific survival rate at 1, 5, 10 years was 89.2%, 73.2%, 61.6%. Tumor staging (≥ T2), lymph node status (N +) were independent risk factors for cancer-specific death. Contralateral upper tract recurrence-free survival rate at 1, 3, 5 years was 80.4%, 68.5%, 50.9%. Aristolochic acid exposure was independent risk factor for contralateral upper tract recurrence. The patients exposed to aristolochic acid had more multifocal tumors and higher incidence of contralateral upper tract recurrence.
Both higher tumor staging and positive lymph node status were associated with a worse cancer-specific survival in patients with post-transplant de novo upper tract urothelial carcinoma, which highlighted the importance of early diagnosis. Aristolochic acid was associated with multifocality of tumors and higher incidence of contralateral upper tract recurrence. Thus, prophylactic contralateral resection was suggested for post-transplant upper tract urothelial carcinoma, especially for patients with aristolochic acid exposure.
Ileal ureter replacement is an alternative treatment for various length ureter defects. We present our experience and outcome of ileal ureter replacement in China.
We retrospectively collected data ...of patients who underwent ileal ureter replacement between January 2010 and January 2015. We reviewed the medical history, indications for surgery, operative data, perioperative data, and outcomes. Besides, follow-up data included symptom, urine routine test, serum creatinine, serum electrolyte status, and radiographic test.
There were 23 patients who underwent ileal ureter replacement by the same surgeon. Twenty patients were performed unilateral ileal ureter replacement, two patients underwent a combination of ileal ureter replacement and Boari flap-psoas hitch, and one received bilateral ileal ureter replacement. Among these patients, the main cause leading to surgical treatment was iatrogenic injuries (n = 15), especially urinary surgery procedure (n = 11). The median follow-up time was 45 months. There were 6 early complications and 6 late complications after operation. Only one patient suffered from small bowel-related complication and was cured by conservative treatment. Only the patient who underwent bilateral ileal ureter replacement had metabolic acidosis. And 22 patients (95.7%) had a good renal function.
Ileal ureter replacement is an efficacious and safe procedure for the therapy of long ureteral defects. With appropriate technical considerations, the complication rate may decrease.
The application of pelvic organ preserving-radical cystectomy (POPRC) in female patients with bladder cancer has attracted more and more attention in recent years. In current study, we aim to compare ...the long-term oncological outcomes of pelvic organ preserving-radical cystectomy (POPRC) versus standard radical cystectomy (SRC) in a large multicenter retrospective cohort.
Data on female patients with bladder cancer who underwent POPRC or SRC in January 2006 and April 2018 were included from three Chinese urological centers. The primary outcome was overall survival (OS). Secondary outcomes were cancer-specific survival (CSS) and recurrence-free survival (RFS). To decrease the effect of unmeasured confounders associated with treatment selection, 1:1 propensity score matching (PSM) was performed.
Among 273 enrolled patients, 158 underwent POPRC (57.9%), and 115 underwent SRC (42.1%). The median follow-up time was 38.6 (15.9-62.5) months. After PSM, each cohort included 99 matched patients. The OS (P=0.940), CSS (P=0.957), and RFS (P=0.476) did not differ significantly from the two matched cohorts. Subgroup analysis confirmed that the OS was similar between the patients treated with POPRC and SRC across all subgroups examined (all P > 0.05). In multivariable analysis, the surgical method (SRC vs. POPRC) was not an independent risk factor for OS (HR 0.874, 95% CI 0.592-1.290; P=0.498).
The results showed that no significant difference in long-term survival was determined between female patients undergoing SRC and those undergoing POPRC.
To summarize our experience with the Boari flap-psoas hitch and compare the indications, perioperative data and outcomes between open and laparoscopic procedures.
This study retrospectively reviewed ...35 patients with complex distal ureteral stricture between January 2015 and April 2019. All patients were treated with Boari flap-psoas hitch by either an open or a laparoscopic procedure. Selection criteria were based on the etiology, comorbidities, medical history, and patient preference.
All surgeries were performed successfully. The median operation time was 201 min (range, 120 to 300 min), and the median estimated blood loss was 50 mL (range, 20 to 400 mL). The median postoperative hospitalization was 9 days (range, 3 to 46 days). Nineteen patients were treated by the open procedure, and 16 were treated by the transperitoneal laparoscopic procedure. The surgical indication of open surgery was broader than that for laparoscopic surgery. For patients experiencing iatrogenic injury and ureterovesical reimplantation failure, no significant differences in sex, laterality, operative time, ASA score or postoperative hospitalization stay were observed between the two groups. The median estimated blood loss was lower in the laparoscopic group than in the open group (P=0.047). Patients in the open group had more surgical complications than patients in the laparoscopic group (P=0.049). The postoperative follow-up showed the radiological resolution of hydronephrosis in 33 patients.
With the appropriate surgical considerations, Boari flap-psoas hitch is a valid method to bridge distal ureteral defects. For select patients, laparoscopic surgery had advantages being a minimal invasive surgery with less estimated blood loss and fewer surgical complications.