BACKGROUND Current noninvasive assays for urothelial carcinoma (UC) lack clinical sensitivity and specificity. Given the utility of plasma cell-free DNA (cfDNA) biomarkers, the development of urinary cfDNA biomarkers may improve the diagnostic sensitivity. METHODS 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. RESULTS 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. CONCLUSIONS Our findings underscore the potential utility of urinary cfDNA CNA profiles as a basis for noninvasive UC detection and surveillance.
BackgroundIleal ureter replacement is an alternative treatment for various length ureter defects. We present our experience and outcome of ileal ureter replacement in China.MethodsWe 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.ResultsThere 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.ConclusionsIleal ureter replacement is an efficacious and safe procedure for the therapy of long ureteral defects. With appropriate technical considerations, the complication rate may decrease.Electronic supplementary materialThe online version of this article (10.1186/s12893-019-0472-1) contains supplementary material, which is available to authorized users.
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.
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