Effect of Submucosal Formalin Injection on Bladder Wall in Rats

백서에서 Formalin의 방광점막하주사가 방광벽에 미치는 영향

The effect of intravesical formalin instillation as a therapeutic modality for intractable bladder hemorrhage is well known. And despite clear evidence of therapeutic efficacy of intravesical cytotoxic drugs and/or BCG immunotherapy, there have been substantial recurrences during followup after transurethral resection for superficial bladder tumor. If formalin injected at the bed of superficial bladder tumor is able to coagulate and necrotize the tumor, it will be greatly helpful to the patients With recurrent bladder tumor developed during followup. Since this technique is applicable on outpatient basis, an economical as well as a psychological burden of the patients can be reduced considerably. The purpose of this study is to evaluate the effect of submucosal formalin injection on rat bladder wall, 36 healthy adult male Sprague-Dawley rats (weighing 350gm in average) were divided into 3 groups: In Group I (control group), 0.01ml of normal saline was injected submucosally at the left posterolateral wall of the bladder opened under intraperitoneal Nembutal anesthesia ; In Group II and III, 0.01 ml of 10% and 4% formalin, respectively, were administered at the same site as in the Group I, two rats in each group were sacrificed at day 1, 2, and 3, and week 1, 2 and 4 after injection, respectively. Gross and microscopic examination of the cystectomized specimen were done in each group. In the Group II, bladder stones were formed at week I, and in both the Group I and III, stones were seen at week 2 post injection. There was no significant difference III histologic findings of the bladder between the group II and III. Mucosal ulcer and/or prominent mucosal disruption was observed at 24 hours after injection in both Group II and III. Epithelial regeneration began at day 2, and was marked at day 3, and epithelial lining was almost normalized one week after injection. Subepithelial edema, telangiectasia and inflammatory reaction were prominent at 24 hours post formalin injection. Subepithelial edema persisted in moderate degree for 1 week. Telangiectasia and inflammatory reaction were noted for 4 weeks. Mild degree of these findings also appeared In the control group. Fibroblastic proliferation appeared at day 2 and persisted in moderate degree for 4 weeks. There has been no mortality or bladder perforation. These results suggest that clinical application of this technique is feasible for the selected cases of recurrent, solitary superficial bladder tumor. However, optimal dosage of formalin in relation to the size of the lesion remains to be investigated.

백서에서 formalin의 방광점막하주사가 상피의 탈락을 일으키는지의 여부와 기타 방광벽에 나타나는 변화를 알아보기 위하여 건강한 Sprague-Dawley 수컷 흰쥐(체중 350gm 내외) 36마리를 3군으로 나누어 Nembutal 복강내 마취하에 방광을 노출한 다음 생리적 식염수, 10% formalin과 4% formalin을 각각 0.01ml씩 각군 동물의 방광점막하에 주사한 후 1일, 2일, 3일, 1주, 2주 그리고 4주째에 방광을 적출하여 방광벽에 나타나는 육안적, 병리조직학적 소견을 관찰하여 다음과 같은 결과를 얻었다. 1. 10% formalin 주사군에서는 제 1주부터 4% formalin 주사군과 생리적 식염수 주사군에서는 제 2주부터 방광결석 형성을 볼 수 있었다. 2. 10% formalin 주사군과 4% formalin 주사군에 있어서 조직학적 소견의 차이는 없었다. 3. Formalin 주사군에서는 점막궤양 또는 현저한 정막붕괴가 24시간째에 나타나고 점막재생은 제 2일부터 시작하여 제 3일에 현저하였고 제 1주에는 거의 정상적인 상피화를 보였다. 4. 상피하 부종, 혈판확장 및 염증반응은 24시간 째에 현저하였고, 상피하 부종은 제 1주까지, 혈판확장과 염증반응은 제4주까지 중등도로 지속되었다. 섬유아세포증식은 제2일부터 나타나 제4주까지 중등도로 지속되었다. 5. 본 실험중 동물이 죽거나 방광천공을 일으킨 예는 없었다. 이상의 결과로 미루어보아 formalin의 방광점막하 주사는 이로 인해 파괴되는 조직의 범위와 그 재생과의 관계가 보다 명백히 규명되면 재발성 표재성 방광암 환자의 선별적인 예의 치료에 응용해, 볼 가치가 있을 것으로 생각된다.