UROLOGICAL SURVEY   ( Download pdf )

 

INVESTIGATIVE UROLOGY

Comprehensive evaluation of ureteral healing after electrosurgical endopyelotomy in a porcine model: original report and review of the literature
Andreoni CR, Lin HK, Olweny E, Landman J, Lee D, Bostwick D, Clayman RV
From the Division of Urology, Federal University (CRA), Sao Paulo, Brazil, Division of Urologic Surgery, Department of Surgery, Washington University School of Medicine (H-KL, EO, JL, DL), St. Louis, Missouri, Bostwick Laboratories (DB), Richmond, Virginia, and Department of Urology, University of California-Irvine (RVC), Irvine, California
J Urol. 2004; 171 (2 Pt 1): 859-69

  • Purpose: Endopyelotomy (EP) has yet to equal the success achieved with open dismembered pyeloplasty. To understand better the ureteral response to EP we performed a timed histopathological evaluation of the porcine ureter after Acucise (Applied Medical, Rancho Santa Margarita, California) EP.
  • Materials and Methods: In 28 domestic pigs bilateral Acucise EPs were performed and bilateral 7Fr stents were placed. The kidneys, ureters and bladder were harvested after EP at 0, 1, 2, 3, 6, 12 and 18 hours, 1, 3 and 5 days, and 1, 2, 4 and 8 weeks. The stents were removed after 4 weeks. The healing area of the ureter was sectioned. Half was fixed in formalin 10%, stained and evaluated by light microscopy. The other half was frozen and reverse transcriptase-polymerase chain reaction was performed to measure steady state levels of epidermal growth factor, transforming growth factor (TGF)-alpha, TGF-beta 1, TGF-beta 2, TGF-beta 3, keratinocyte growth factor, vascular endothelial growth factor, insulin-like growth factor, platelet derived growth factor, collagen type 1, integrin and fibronectin transcript expression. Immunohistochemistry for actin, desmin and myosin expression was completed. The same studies were applied to the mid portion of the unoperated ureter.
  • Results: Initial sealing of the ureterotomy defect was by blood clot and periureteral fat. Complete healing of the mucosa was observed at 2 weeks in animals without an associated urinoma. However, in no case did the muscle layer bridge the whole circumference of the ureter despite followup out to 8 weeks. In the operated ureter elevated expression of keratinocyte growth factor, vascular endothelial growth factor, TGF-alpha, TGF-beta 1, TGF-beta 3 and integrin was detected 2 hours after the operation and sustained for 7 to 14 days after the procedure. Immunohistochemistry revealed that most presumed myocytes seen in the defect were actually myofibroblasts. Persistent urinoma formation beyond the first few days appeared to slow the healing process.
  • Conclusions: Urothelium regenerated rapidly over an iatrogenic ureteral defect despite the absence of a lamina propria. Muscle cell coverage failed to occur completely at 8 weeks. In the initial 8 weeks of the healing process myofibroblasts appear to be prevalent. A persistent urinoma negatively impacts the healing process.

  • Editorial Comment
    This paper by Andreoni and colleagues is welcome, because it updates our knowledge on the natural response of the ureter to an endoureterotomy, since current understanding on this topic is based on papers from 1940’s (1). Using current methods in histopathology (eg cell specific stains) and immunohistochemistry (eg growth factors) the authors evaluated the acute and chronic impact on the ureter and renal pelvis of an Acucise catheter incision in the pig.
    The authors found that in the pig the urothelium rapidly regenerates and covers the incision site within a few weeks, and that an urinoma formation appears to slow the healing process.Functional smooth muscle cells or smooth muscles bundles failed to bridge the defect completely even 8 weeks after endopyelotomy. In addition, the authors suggest that growth factors, including TGF-â1, TGF-á and KGF, may have a role in promoting ureteral healing after endopyelotomy.
    The most distinguished finding of the present study was that the nonepithelial cells found in the endopyelotomy defect appeared to be myofibroblasts and not smooth muscles cells, which was possible to be identified by immunohistochemical techniques. It is likely that the classic studies of intubated ureterotomy erroneously concluded that there was true regeneration of the ureter. The authors suggest that it might have been myofibroblasts and not smooth muscle cells responsible for apparent closure of the ureterotomy defect. Future investigations using electron microscopy or biochemical techniques would better clarify this issue.

Reference
1. Davis, D. M.: Intubated ureterotomy: a new operation for ureteral and ureteropelvic stricture. Surg Gynec Obstet. 1943; 76: 513.

Dr. Francisco J.B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, Brazil