Evaluation of surgical procedures of mouse urethra by visualization and the formation of fistula

Taiju Hyuga,Daisuke Matsumaru,Shinichi Asamura,Kei-Ichi Katayama,Shinji Kumegawa,Hideo Nakai,Kentaro Suzuki,Daiki Hashimoto,Shigeru Nakamura,Gen Yamada

doi:10.1038/s41598-020-75184-5

Taiju Hyuga, Daisuke Matsumaru + Show 8 more

Open Access

https://doi.org/10.1038/s41598-020-75184-5

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Abstract

Visualization of the surgically operated tissues is vital to improve surgical model animals including mouse. Urological surgeries for urethra include series of fine manipulations to treat the increasing number of birth defects such as hypospadias. Hence visualization of the urethral status is vital. Inappropriate urethral surgical procedure often leads to the incomplete wound healing and subsequent formation of urethro-cutaneous fistula or urethral stricture. Application of indocyanine green mediated visualization of the urethra was first performed in the current study. Indocyanine green revealed the bladder but not the urethral status in mouse. Antegrade injection of contrast agent into the bladder enabled to detect the urethral status in vivo. The visualization of the leakage of contrast agent from the operated region was shown as the state of urethral fistula in the current hypospadias mouse model and urethral stricture was also revealed. A second trial for contrast agent was performed after the initial operation and a tendency of accelerated urethral stricture was observed. Thus, assessment of post-surgical conditions of urogenital tissues can be improved by the current analyses on the urethral status.

Highlights

Visualization of the surgically operated tissues is vital to improve surgical model animals including mouse
Application of indocyanine green (ICG)-mediated visualization of the urethra was first performed in the current study (Fig. 1A)
Faint signals were detected around the penis region containing urethra, but ICG signal was not detected in the posterior urethra (Fig. 2B,C)

Summary

Results

ICG‐mediated visualization of mouse bladder and urethra. Injection of ICG has been utilized to visualize the status of tubular structure such as the status of lymphatic vessels after their surgeries[13,14,15]. Surgical models for hypospadias‐like incision to the mouse urethra. The ventral urethra was incised with full-thickness (approximately 10 mm in length) from the meatus up to the base of penis vertically (Fig. 4A). The urethroplasty was performed for tubularization by three interrupted one-layer suture (7–0 PDS) at approximately 1.5 mm interval (Fig. 4D,E; white arrowhead). The elapsed region was shown as the state of urethral fistula (Fig. 5A,B; black arrowhead in B). Surgical models of the mouse urethral stricture demonstrate the morphology of anterior and posterior urethra by CA‐mediated visualization. (B,C) Post-operative surgical sites (3 interrupted sutures; white arrowheads) are shown (D,E). The anterior urethra, which shows the urethral stricture as post-hypospadias complication, was selected as the surgical site. Two urethral regions without CA signals are shown (Fig. 7A,B; white arrowheads). Enlarged urethral caliber was noted (black arrowhead) adjacent to the stricture (white arrowhead)

Discussion

Conclusions

Methods