REGENERATIVE OF THE BLADDER WALL FOR THE TREATMENT OF A BIOABSORBABLE POLYMER SHEET

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1 REGENERATIVE OF THE BLADDER WALL FOR THE TREATMENT OF A BIOABSORBABLE POLYMER SHEET Katsuya Okada M.D., Mitsuo Miyazawa M.D.,Ph.D., Masayasu Aikawa M.D.,Ph.D., Isamu Koyama M.D.,Ph.D. Department of Surgery, Saitama Medical School International Medical Center, Saitama, Japan

2 Background(1) When the segmental resection of the bladder wall where the rectal cancer invased is required, the direct sutures of the bladder wall is mainly used because the extension, and expansion capability of the bladder wall are high. But when the bladder capacity is less than cc, it might cause micturition and long-term urethra catheter custody might be needed. Those would lead the decrease of QOL. If the surgery to extend of the bladder with intestinal canal of caulescent (augmentation) would be needed, it may be stressful for the patients. (augmentation)

3 Background(2) To solve this problem, it is ideal to reinforce the defect of bladder wall by patch! If the implantation was performed with non-absorption material such as polypropylene at the bladder defective site, or non-absorption thread is used for the sutures at the bladder wall, bladder calculus would be formed. (Bioabsorbable material has been already tried as the artificial bladder wall: those materials are as following) acellular dermal biomatrix porcine small intestinal submucosa latex biomembrane However, there is no reinforcing materials which can substitute to the defective site of the bladder wall. Our group succeeded the renovation of various organs using the bio absorbable polymer sheet. Bile duct Gastric wall IVC Abdominal wall

4 Background(3) 2012: The 112 th Annual Congress of Japan Surgical Society. The initial report 5 X 4 cm portion of the bladder wall was excised. Bioabsorbable polymer patch 5 4cm 3M (The site of the polymer implantation site after 3 monthes) no transformation in the appearance The same macroscopic view as a nontransplanting part With no vestigial remnant of polymer The bladder wall is repaired as native site histologically. The problems of the past results The bladder capacity does not decrease remarkably with direct sutures at the small defects. However if renovation is sucessed even at a small defect, using a patch transplant as a reinforcing material is deficient in the clinical significance of. We wonder if the same material is transplanted at the lager defects of the bladder wall!?

5 Aim In this study, we investigated the renovation of the bladder wall using bioabsorbable polymer sheet (;BAPS) at the larger defective site.

6 Method BAPS Hybrid pig(20~30kg) About 1/2 of bladder walls of the Mongrel(hybrid)pigs were excised, larger than a former experiment. 5 4cm 9 7cm 9 X 7 cm BAPS which was almost equivalent to the excised size was implanted with absorption thread with sutures all around. On the others, the excision part was sutured directly. 4 weeks later, We perform an operation again and resect a bladder. transplant. BAPS n=3 direct suture n=2 Evaluation Naked eye evidence (bladder capacity) Histologic evidence

7 Bioabsorbable Polymer Sheets(BAPS) Electron microscope image This is reinforced with fiber of PGA( ) Ingredient:PLA/PCL 50:50 with PGA Catabolic rate ;8 weeks air porosity > 95% This material has very small pore, and hydrophobicity which cause not to let the floating water on the surface pass easily. Seeding of the cell is not carrying out to this material.

8 The surgery findings resect ion half of the bladder direct suture transplant. BAPS The surgery findings of the patch transplant to the bladder wall, and direct suture by using BAPS

9 Excised specimen lumen side The BAPS graft site was distension and the palpation was firmly. The graft site formed a substantial ulcer at the lumen side, and significant shrinkage was recognized at 30%. 5000µm 100µm There was no recognition of the bladder wallregeneration in the macrophage including polymorphonuclear and the lump of inflammatory cells such as fibroblast at the BAPS transplant area histologically.

10 Bladder capacity A tube was inserted from the urethra of the extracted bladder and the ligation fixed with thread was performed. Measure the quantity to the infusion limit after water infusion into the bladder. Direct suture(n=2) mean 290ml We wonder why the BAPS graft site shrank remarkably and why it di not increase in sufficient capacity of the urinary bladder? The reason might come from the folding shape of BAPS at the end time of suture. transplant. BAPS(n=3)mean 378ml Even though there were not many cases, a significant difference was not observed in capacity of the urinary bladder statistically. In the further study, the maintenance of the BAPS shape at the graft site should be studied!

11 Support and reinforce the lumen for the maintenance of a bladder form 1 2 Create the plastic net to the rugby ball-like shape for protecting the bottle of glass. After excising a bladder wall 1/2, this plastic material is inserted. 3 4 A suture transplant at the excision site of the bladder wall using BAPS which may be covered the plastic material. BAPS maintained the constant shape because the bladder was maintained by the plastic material.

12 Excised specimen At the time of bladder extraction, the adhesion around the transplant part was obvious. There was no recognition with the adhesion of an organization, although a part of BAPS had adhered to the plastic material of lumen. 2.5cm no-reinforcemen 8cm Bladder Capacity;492ml There was only slight shrinkage of the BAPS graft site which was maintained the shape, compared with no-reinforcement group (Figure). Also, it had most capacity of the urinary bladder until now. (The white arrow shows the adhesion part of the nonabsorbing thread attached to both ends at the time of a transplant as a mark of BAPS contraction)

13 Histological findings(he,evg,sma) no-reinforcemen EVG HE SMA 5mm At 4 weeks after implantaion, only a lump of the inflammatory cells was recognizedn in the group with noreinforcement. On the other hand, the bladder wall repair was seen in all layers, including transitional epithelium and the muscle layer, and invasion of the inflammatory cell was not found in the group with reinforcement which maintain the shape.

14 Comparison with native Native HE EVG 5mm BAPS( with reinforcement ) There were slight differences between the areas with the BAPS transplant (with reinforcement) grafts and the native areas at the point of increasing of the hyperplastic shifting from transitional epithelium (Similar results are seen in a recovering process of peptic ulcer), and at the point of the thickness of the muscle layer, slightly thicker than the native. However, the renovation was succeed because the graft site had similar appearance to those of the native.

15 Native S100 protein BAPS( with reinforcement ) x40 500µm x40 500µm S100 x µm Although the relevance with a bladder function was unknown, the renovation of the nerve fiber was also observed for scattered, resembled native. x µm

16 Results When a bladder wall was excised more widely (about 1/2) and BAPS was transplanted, disrupted was not recognized in the graft site at 4 weeks. However, remarkable shrinkage and a lump of the inflammation cell invasion were observed histologically. There was no significant increase of the bladder capacity in the BAPS transplant group compared with the direct sutures group after 4 weeks implantation. When the graft site might be fixed for the maintaining the shape at the BAPS transplant, the bladder wall repair was observed at the transplant area, similar to the native tissue macroscopic and histologically after 4 weeks. Also, the securing of constant capacity was provided.

17 Conclusion When an artificial bladder wall made by bioabsorbable polymer was implanted at larger defects, there was a problem for the remarkable shrinkage at the implantation area. However we placed a stent to maintain the shape of the graft site, this method was successfully to renovation the bladder. It is suggested that this model using a substitute material for the defective tissue of bladder wall should approach the goal of clinical surgical use in future.

18 Financial Disclosure UEG Week Berlin 2013 Top auther ; Katsya Okada The authors have no financial conflicts of interest to disclose concerning the presentation.

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