Cop+Ed+fisse 2006 Archivio Italiano di Urologia e Andrologia 2020; 92, 3200 CASE REPORT No conflict of interest declared. DOI: 10.4081/aiua.2020.3.200 Gelatin sponge (Spongostan®) and N-butyl-2-cyanoacrylate: Utility on percutaneous treatment of persistent urinary leakage after partial nephrectomy. Case report and review of the literature. Bernardino de Concilio 1, Francesca Vedovo 1, 2, Maria Carmen Mir 3, Tommaso Silvestri 1, 2, Andrea Casarin 4, Antonio Celia 1 1 Department of Urology, San Bassiano Hospital, Bassano del Grappa, Italy; 2 Department of Urology, Azienda Sanitaria Universitaria Integrata di Trieste, Trieste, Italy; 3 Fundación Instituto Valenciano Oncologia, Valencia, Spain; 4 Department of Radiology, San Bassiano Hospital, Bassano del Grappa, Italy. Introduction: Percutaneous treatment of persistent urinary fistula after partial nephrectomy using N-butyl-2-cyanoacrylate and gelatin sponge (Spongostan®) is an effective and relatively non-inva- sive procedure that should be considered when a conservative approach fails. Three successful cases of percutaneous embolization by using N-butyl-2-cyanoacrylate have been reported in the literature. To our knowledge, the use of Spongostan for the treatment of urinary fistula after partial nephrectomy has not been previously described. Case report: We present the case of an 82-year old man who underwent percutaneous closure of a urinary fistula following partial nephrectomy by using gelatin sponge (Spongostan®) and N-butyl-2-cyanoacrylate. Conclusions: We encourage the use of this technique in select- ed cases. Collaboration amongst urologists and skilled inter- ventional radiologist is strongly recommended. KEY WORDS: Cyanoacrylates; Fibrin foam; Gelatin sponge; Urinary fistula. Submitted 18 August 2020; Accepted 1 September 2020 Summary INTRODUCTION Partial nephrectomy (PN) is gold standard for treatment of small renal masses. PN is not exempt of complica- tions, urinary fistula (UF) is one of the most common. Its incidence rates between 2 and 10%, depending on the complexity of the surgery. The vast majority of fistu- las are self-limited within short-term. However, a small percent of urinary fistula may require active treatment, either by open repair or by percutaneous approach. In the current case, we report the use of N-butyl-2- cyanoacrylate and gelatin sponge (Spongostan®) in a per- sistent urinary fistula. CASE REPORT An 82-year-old man was assessed for an incidentally detected left renal mass at our institution. A CT scan confirmed the presence of a 46 mm round partially, pos- terior, upper pole mass. (Figure 1) Patient’s significant past medical history included hypertension, pace-maker implantation and left hip replacement. A robotic assist- ed laparoscopic partial nephrectomy was performed. The procedure required intraoperative conversion to open procedure due to sclerolipomatosis. Pathology report showed a pT1a Fuhrman 1-2 clear cell renal car- cinoma with negative surgical margins. Patient’s post- operative course showed prove of urinary leakage on post-operative day 1 (POD1). A double-J catheter was inserted to improve urinary drainage. At retrograde pyel- ography, a leakage on the central calix was observed. Patient was discharged on POD10 and readmitted one week after due to fevers and diarrhea. A CT scan revealed a left retroperitoneal urinoma 3 cm in diameter with actual drainage through the chest wall and skin (Figure 2). The double-J catheter was exchanged to a single-J 8 Ch for better drainage. Ten day after the exchange a CT scan showed persistent leakage. Fistula consisted in a large cavity opened to the perirenal tissue. A percutaneous approach was used to have a direct way to the fistula. There absorbable gelatin sponge (Spongostan®) was applied to the fistulous cavity to reduce the volume. Five strips of approximately 5 mm x 50 mm were pushed through the introducer to create a scaffold into the renal breach. Then 1 mL of N-butyl-2- cyanacrilate (Glubran 2®; GEM, Italy) was located over the leakage orifice above the gelatin sponge. The post- procedure retrograde pyelography showed a substantial reduction on the fistulous tract. A 6 Ch drainage pigtail tube outside the kidney in the urinoma as well as a sin- gle-J stent were placed at the end of the procedure. (Figure 3). Patient was discharged home the day after the procedure. Follow-up CT scan performed within 30 days of procedure showed a decreased debit and com- plete reduction in urinoma size. Both catheters were removed after the control CT scan, 1 month after the procedure and patient never develop any relapse. DISCUSSION AND LITERATURE REVIEW According to AUA and EAU Guidelines, PN is consid- ered the standard treatment for T1a tumors and it 09De Concilio_Stesura Seveso 24/09/20 14:20 Pagina 200 201Archivio Italiano di Urologia e Andrologia 2020; 92, 3 Gelatin sponge (Spongostan®) and N-butyl-2-cyanoacrylate should be favored over radical nephrectomy in patients with T1b, whenever feasible. Controversial data has been published regarding oncological outcomes of small renal masses in surgical terms. Retrospective data by Van Poppel et al. and EORTC group supports the use of PN, however, the only prospective randomized trial compar- ing both techniques did not show large advantage for PN (1). It is well known that PN is not exempt of complica- tions. Tumor size, blood loss, ischemia time and endo- phytic mass location are factors related to UF formation. Several authors have described conservative and non- conservative approaches for UF management. Kundu et al. reported a conservative approach perinephric drainage (2). Ureteric stent placement is a widely accept- ed strategy in case of persistent urinary leak and a mini- mum of 30-45 days might be required for resolution. Other authors have used endoscopic fulguration of the fistula for sealing. Hemostatic agents and tissue sealants are now being used commonly during laparoscopic and robotic (LPN or RPN). The use of fibrin glues may offer adequate hemostasis in patients undergoing LPN when the collecting system is not opened, but in case of enter- ing, a sutured bolster is recommended. Nevertheless, in 2007, Porpiglia and coworkers published results to the contrary (3). The use of surgical sealants and biologic agents like thrombin, fibrin and collagen glues can be considered when a persistent leakage is present after PN, and they have been successfully used for over one decade. Percutaneous embolization of UF is a relatively novel technique that has been used in the last decade (4). More recently the application of cyanoacrylate glues has been reported in different branches of surgery for endoscopic treatment of refractory bile leaks, gastroenteric fistulae, intracranial vascular malformations and also for the man- agement of urinary fistulas. To our knowledge few cases in literature described the endoscopic utilization of cyanoacrylate in repairing UF after urological maneuvers and until now there are only 4 single cases reports of percutaneous successful utiliza- tion of cyanoacrylate glue in repairing UF after PN have been reported till date (5, 6). In addition, two clinical case series: one of 13 cases in 9 years by Muto et al that reported the use of cyanoacrylate glue in repairing endo- scopic percutaneous and endovaginal urinary fistula of various etiologies with a high success rate and few com- plications (7). The second by Selli et al. described 5 patients presenting UF, but only 3 following PN treated with cyanoacrylate glue endoscopically (8). Our case describes the association and combination of Spongostan to the already approved N-butyl-2-cyanacrilate (Glubran 2®). N-butyl-2-cyanacrilate is composed of N-butyl-2- cyanoacrylate monomer and metacryloxysulpholane monomer. This compound presents favorable properties such as a good biocompatibility and progressive reab- sorption without causing foreign body granulomas. The property of nearly instantaneous bonding makes cyanoacrylates an effective haemostatic agent and tissue adhesive. Its polymerization time is rather fast in a wet environment, specifically with weak bases, such as water and blood. The gluing of the catheter tip is a potential complication of the technique especially in case of no dilution of the cyanoacrylate. Moreover, accidental glue injection directly into the collecting system may cause urinary obstruction. A skilled interventional radiologist is required for these procedures. Spongostan® is a dry artificial sterile sponge of fibrin prepared by clotting with thrombin a foam or solution of fibrinogen. It is used to provide effective local hemostasis in cases of venous ooz- ing where traditional hemostasis has failed. Moreover, Spongostan® serves as a scaffold for proteins or cells implanted into defects fulfilling its function as a cell scaf- fold (9). The combination of sealants in our case was critical to obtain a success of treatment with the purpose of decreasing the defects of parenchyma, filling in the cavity and avoiding a large contact with the urine that could compromise the polymerization of glue. Ishii K. et al. in a PN animal model study demonstrated that fibrin Figure 1. CT scan confirmed the presence of a 46 mm round partially, posterior, upper pole mass. Figure 2. CT scan revealed a left retroperitoneal urinoma 3 cm in diameter with actual drainage through the chest wall and skin. Figure 3. The post-procedure retrograde showed a substantial reduction on the fistulous tract. A 6 Ch nephrostomy tube as well as a single-J stent were placed at the end of the procedure. 09De Concilio_Stesura Seveso 24/09/20 14:20 Pagina 201 Archivio Italiano di Urologia e Andrologia 2020; 92, 3 B. de Concilio, F. Vedovo, M.C. Mir, T. Silvestri, A. Casarin, A. Celia 202 sealant plus the collagen or gelatin hemostat have a stronger hemostatic effect than fibrin sealant applied alone (10). The histological investigation showed that the fibrin sealant adhered well to kidney tissue when it was applied with the collagen or gelatin hemostat, show- ing the advantage of combining these two materials for achieving effective hemostasis and closure effect. In our case Spongostan sheets are not only important as a bol- ster at the site of glue application, but also because a new complex is formed at the fistula site when the two sub- stances are used in combination. Finally, one critical fac- tor for success in UF closure using cyanoacrylate is the ratio between the length and the diameter of the fistulous tract. Tissue losses greater than 1 cm are unlikely to be completely plugged, and urine may continue to flow around the cast. The fistula diameter to length ratio is the more relevant prognostic factor for success and the com- bination of two sealants in our cases was the key to obtain a complete resolution. CONCLUSIONS In conclusion, minimally invasive techniques to solve urinary refractory leakage after PN is a safe option. The application of gelatin sponge (Spongostan®) and N- butyl-2-cyanoacrylate improves the outcome resolution, particularly in difficult and high volume UF, without implying increased risk of urinary obstruction. We encourage the use of this technique in selected cases. Collaboration amongst urologists and skilled interven- tional radiologist is strongly recommended. Acknowledgments: the authors would like to thank Dr. Andrea Casarin whose expertise made this procedure possible. REFERENCES 1. Van Poppel H, Da Pozzo L, Albrecht W, et al. A prospective ran- domized EORTC intergroup phase 3 study comparing the complica- tions of elective nephron-sparing surgery and radical nephrectomy for low-stage renal cell carcinoma. Eur Urol 2007; 51:1606-15. 2. Kundu SD, Thompson RH, Kallingal GJ, et al. Urinary fistulae after partial nephrectomy. BJU Int. 2010; 106:1042-4. 3. Porpiglia F, Renard J, Billia M, et al. Biological glues and collagen fleece for hemostasis during laparoscopic partial nephrectomy: tech- nique and results of prospective study. J Endourol. 2007; 21:423-8. 4. Tekin MI, Peskircioglu L, Boyvat F, Özkardes H. Practical approach to terminate urinary extravasation: Percutaneous fistula tract embolization with N-butyl cyanoacrylate in a case with partial nephrectomy. Tech Urol. 2001; 7:67-9. 5. Aslan G, Men S, Gülcü A, et al. Percutaneous embolization of persistent urinary fistula after partial nephrectomy using N-butyl-2- cyanoacrylate. Int J Urol. 2005; 12:838-41. 6. Aning JJ, Stott MA, Watkinson AF. Glue ablation of a late-presen- tation urinary fistula after partial nephrectomy. Br J Radiol. 2009; 82:e246-8. 7. Muto G, D’Urso L, Castelli E, et al. Cyanoacrylic glue: A mini- mally invasive nonsurgical first line approach for the treatment of some urinary fistulas. J Urol. 2005; 174:2239-43. 8. Selli C, De Maria M, Manica M, et al. Minimally invasive treat- ment of urinary fistulas using N-butyl-2-cyanoacrylate: a valid first line option. BMC Urol. 2013; 13:55. 9. Singh I, Saran RN, Jain M. Does sealing of the tract with absorbable gelatin (Spongostan®) facilitate tubeless PCNL? A prospective study. J Endourol. 2008; 22:2485-93. 10. Ishii K, Kawashima H, Hayama T, et al. Combination of a liq- uid fibrin sealant with sheet-type hemostatic agents: experimental evaluation in partial nephrectomy animal model. Int J Urol. 2011; 18:478-82. Correspondence Bernardino de Concilio, MD Antonio Celia, MD Department of Urology, San Bassiano Hospital, Bassano del Grappa (Italy) Francesca Vedovo, MD (Corresponding Author) francesca.vedovo@gmail.com Tommaso Silvestri, MD Department of Urology, Azienda Sanitaria Universitaria Integrata di Trieste Strada di Fiume 447, 34149 Trieste (Italy) Department of Urology, San Bassiano Hospital, Bassano del Grappa (Italy) Maria Carmen Mir, MD Fundación Instituto Valenciano Oncologia, Valencia (Spain) Andrea Casarin, MD Department of Radiology, San Bassiano Hospital, Bassano del Grappa (Italy) 09De Concilio_Stesura Seveso 24/09/20 14:20 Pagina 202