Lasers in Medical Science

, Volume 34, Issue 6, pp 1217–1227 | Cite as

Observation and mechanism study of bladder wound healing after transurethral holmium laser resection of bladder tumor

  • Sha Han
  • Kai Dong
  • Mengjun Shen
  • Xingjie Wang
  • Wanzi Jiang
  • Wei ZhaoEmail author
  • Dongliang XuEmail author
Original Article


This research aims to observe and compare the wound healing process of urethral bladder after transurethral holmium laser resection of bladder tumor (HoLRBT) and transurethral resection of bladder tumor (TURBT) and explore the possible mechanism of wound healing and bladder re-epithelialization after HoLRBT. An animal model of canine achieving HoLRBT and TURBT was established. Cystoscopy was performed at different time points (3 days and 1, 2, 3, and 4 weeks) after operation to observe the wound healing and re-epithelialization of bladder epithelium. Bladder mucosa specimens were obtained and histopathological changes of the bladder epithelium were observed under light microscope after HE staining. Immunochemistry was used to determine the cell expression ofCK5, CK14, EGF, EGFR; microRNA expressions of CK5, CK14, EGF, and EGFR were measured by qRT-PCR. The changes of urinary EGF concentration were detected by ELISA. The bladder epithelial wound was repaired and re-epithelialized at 1 week after HoLRBT. At the 4th week, the bladder wound was basically completed and re-epithelialized; repair of bladder epithelial wounds recapitulates the wounds with the proliferation and migration of residual epithelial cells under the wound and the bladder epithelium that proliferates alongside the wound surface to complete re-epithelialization. The process begins at 1 week after surgery and basically completes at 4 weeks after surgery. CK5 and CK14 positive cells were detected in the basal cells of the bladder epithelium after HoLRBT, and the expression of CK5 and CK14 mRNA in the basal cells of the bladder epithelium under hyperplasia was significantly higher than that of the normal bladder epithelial basal cells. Bladder epithelial wound repair of TURBT group was performed by the proliferative differentiation of the peri-bladder epithelium adjacent to the wound edge and crawled to the wound surface to complete the re-epithelialization process. The wound repair and re-epithelialization were significantly slower than HoLRBT group. The CK5 and CK14 positive cells can also be detected in the basal cells of marginal hyperplasia of basal margin, and the expression of CK5 and CK14 mRNA in the basal cells of the peri-bladder hyperplasia is obviously higher than that of the normal bladder epithelial basal cells. The expression of EGF in bladder regenerating epithelium gradually increased with time after HoLRBT. Bladder basal cells and bladder regenerating epithelium express high levels of EGFR after HoLRBT. The concentration of EGF in urine after HoLRBT and TURBT increased significantly after surgery, and peaked at 3 days after operation. The urinary EGF concentration in HoLRBT group was higher than that in TURBT group at 3 and 4 weeks after operation. The re-epithelialization process can be seen 1 week after the cystectomy with holmium laser cystectomy, and the epithelialization rate is faster than the traditional transection surgery. This is because the residual bladder epithelial stem cells and wound marginal epithelial cells are involved in the process of wound repair and re-epithelialization following HoLRBT. But only the marginal epithelial tissue participates in the re-epithelialization process after TURBT, so the repair rate of TURBT is slower. The repair of bladder epithelium after HoLRBT is related to the stimulation of tissue factor EGF. The regenerated bladder epithelium also participates in the wound repair process by means of autocrine of EGF.


Bladderepithelial stem cells Wound repair HoLRBT 


Role of funding source

The present study was supported financially by grants from Shanghai Science and Technology Committee (13DZ1940602), Shanghai Hospital Development Center (SHDC12014215), and Foundation of Shanghai Municipal Commission of Health and Family Planning (20134423).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

Approval for the animal studies was obtained from the Medical Science Ethics Committee of Shanghai First People’s Hospital.


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Copyright information

© Springer-Verlag London Ltd., part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Andrology and UrologyChangzhou TCM HospitalChangzhouChina
  2. 2.Department of Urology, Shanghai General HospitalShanghai Jiao Tong University School of MedicineShanghaiChina
  3. 3.Nanjing Medical UniversityNanjingChina
  4. 4.Department of Urology, Shanghai General Hospital, School of MedicineShanghai Jiao Tong UniversityShanghaiChina
  5. 5.Department of Urology, Changzheng HospitalSecond Military Medical UniversityShanghaiChina

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