Gelatin Matrix Hemostatic Sealant Research Articles

Intravesical Hemostatic Gelatin Matrix Instillation in the Management of Intractable Hematuria

The objective of the present study was to evaluate the safety and feasibility of a novel and minimally invasive approach, namely, intravesical instillation of a gelatin matrix hemostatic sealant (GMHS) in the management of intractable hematuria. Six consecutive patients with intractable hematuria not responding to standard treatment underwent intravesical instillation of a hemostatic bovine-derived gelatin matrix mixed with a human-derived thrombin component. The technical aspects of this approach are described in detail. The mean age of the patients was 70 ± 4 years (median 71, range 50-79). All patients had pelvic malignancy: 5 had prostate cancer, and 1, cervical cancer. Mean duration of hematuria before intervention was 6 ± 1 days (median 6, range 2-9). Mean preoperative hemoglobin level was 9.2 ± 0.5 g/dL (median 9.0, range 8.0-10.2). Complete control of bleeding was achieved in 5 patients (83%) and all 6 patients (100%) on day 1 and 7, respectively. At a mean follow-up of 10 ± 6 months (median 13, range 1-15), permanent control of bleeding was achieved in 5 of 6 patients (83%). A second GMHS instillation was performed in 1 patient (17%) and it was successful. During the follow-up, there were no complications related to GMHS instillation. Two patients died because of their underlying malignant disease. Intravesical GMHS instillation appears to be a safe and feasible option in the management of intractable hematuria in the short-term.

Hemostatic Sandwich to Control Percutaneous Nephrolithotomy Tract Bleeding

Significant bleeding necessitating use of a tamponade balloon, embolization, or renal exploration is a rare but catastrophic complication after percutaneous nephrolithotomy (PCNL). The purpose of this study is to review the success of a novel, minimally invasive technique for controlling percutaneous tract bleeding that is refractory to conventional measures. A retrospective review was performed on four patients with refractory tract hemorrhage that was managed with a novel gelatin matrix hemostatic sandwich technique. In this technique, a 5F angiographic reentry catheter was placed through the kidney into the bladder and a 22F Councill-tip catheter balloon was passed over this catheter and positioned so that the inflated balloon would occlude the inner surface of the nephrostomy tract. Next, a 16F Councill-tip catheter was placed over a second wire so that the uninflated balloon was just underneath the skin surface. Gelatin matrix hemostatic sealant was then injected to fill the tract. Inflation of the outer balloon completely sealed the tract, completing the hemostatic sandwich. This technique was successfully applied to four patients with tract bleeding that would not stop with pressure or a conventional nephrostomy tube alone. The average estimated blood loss was 562 mL, and three of four patients avoided transfusion. All postoperative hemoglobin values stabilized within 2 days of surgery. There were no major or minor complications after use of this technique. No patients needed angioembolization or renal exploration. This novel hemostatic sandwich technique should be considered as an option for the control of refractory tract hemorrhage after PCNL.

Therapeutic effects of gelatin matrix-embedded IL-12 gene-modified macrophages in a mouse model of residual prostate cancer

We evaluated the potential use of intraoperative gelatin matrix hemostatic sealant (GMHS; FloSeal; Baxter Healthcare) embedded with macrophages (Mphi) transduced with murine interleukin (IL)-12 recombinant adenoviral vector (G/Mphi/AdmIL-12) for prevention of recurrence of prostate cancer following radical prostatectomy. Application of G/Mphi/AdmIL-12 resulted in significant suppression of tumor growth and spontaneous lung metastases, a statistically significant survival advantage of the G/Mphi/AdmIL-12-treated animals, more efficient trafficking of Mphi to lymph nodes draining from the prostate and generation of systemic natural killer cell activity and tumor-specific cytolytic T lymphocyte responses compared to the controls in a preclinical mouse model of residual prostate cancer. Our data recommend this treatment as a novel adjuvant for prevention of local recurrence of prostate cancer following radical prostatectomy.

Effects of Commonly Used Hemostatic Agents on the Porcine Collecting System

Topical hemostatic agents have been particularly useful for preventing bleeding in tubeless percutaneous nephrolithotomy. In the present study, we investigated the effect of gelatin matrix hemostatic sealant (FloSeal), fibrin glue (Tisseel,), polyethylene glycol polymers (CoSeal), and bovine serum albumin/ glutaraldehyde (BioGlue) in the pig urinary collecting system after injection through a percutaneous nephrostomy (PCN) tract. Percutaneous nephrostomy was performed in 40 kidneys in 24 domestic pigs. Animals were divided into four groups of six each: (1) FloSeal; (2) Tisseel; (3) CoSeal; and (4) BioGlue. In 16 animals that tolerated the procedure, the contralateral kidney was used as a control for PCN only. All tracts were dilated to 30F with the Amplatz dilator, and 2 mL of the hemostatic agent was injected into the collecting system before pulling back to seal the puncture. Among the control PCN kidneys, no obstruction was detected at the end of a 5-day period. However, three of six kidneys injected with FloSeal, Tisseel, or CoSeal and four of six kidneys injected with BioGlue were obstructed. In each of these cases, there was an associated retroperitoneal urinoma. FloSeal, Tisseel, CoSeal, and BioGlue, if injected directly into the porcine collecting system, can result in significant obstruction that does not resolve over a 5-day period. Until there are clinical data to the contrary, we believe that when using one of these hemostatic agents in association with a tubeless percutaneous procedure, a retrograde occlusion balloon catheter should be considered to prevent inadvertent injection of these materials into the collecting system.

Introducing a New Sealant Applicator for Easy, Safe, and Quick Closure of a Mini-Percutaneous Nephrolitholapaxy Access Tract

To achieve better hemostasis after mini-percutaneous nephrolitholapaxy (mini-PCNL), we developed a new application device that can be used to close the renal-access tract with gelatin matrix hemostatic sealant (GMHS). After mini-PCNL was performed on 11 patients, a Double-J ureteral stent was placed antegrade. After retraction of the 18F Amplatz sheath out of the collecting system under vision without irrigation, the urothelium collapsed. The 15F metal applicator with a 10F working channel was then inserted and GMHS injected during further retraction of both the device and the Amplatz sheath. The skin was closed with Steri-strips. The renal parenchymal tract of the mini-PCNL can be sealed in 15 to 50 seconds. Postoperatively, no urinoma was observed. All patients had an uneventful follow-up. Closing the track of the mini-PCNL with the new application device and GMHS is a safe, easy, and quick alternative to the common nephrostomy tube.

Damage Control Management of Experimental Grade 5 Renal Injuries: Further Evaluation of FloSeal Gelatin Matrix

We developed a porcine grade 5 renal laceration damage control model to evaluate the hemostatic efficacy of FloSeal gelatin matrix (Baxter Healthcare, Corp., Deerfield, Ill). Ten commercial swine underwent celiotomy, contralateral nephrectomy, and cooling to 32 degrees C after a well-established hypothermia protocol to simulate a damage control scenario. Following prospective randomization, a complex grade 5 renal injury was uniformly produced on the remaining kidney. Control animals (group 1, n = 5) were treated with direct manual compression with a gelatin sponge. Experimental animals (group 2, n = 5) were treated by application of FloSeal gelatin matrix followed by direct compression with a gelatin sponge. Operative blood loss and efficacy of hemostasis were compared. Creatinine levels were obtained daily until postoperative day 7. Abdominal computed tomography was performed at 10 days. Use of FloSeal gelatin matrix hemostatic sealant resulted in significantly less mean blood loss than gelatin sponge bolster compression alone (202.4 mL vs. 540.4 mL, respectively, p = 0.016). Hemostasis was complete in 60% (three out of five) of experimental animals after 2 minutes, but was incomplete in all control animals. After an initial increase, serum creatinine approached baseline by postoperative day 7 in all animals. Axial imaging 10 days postoperatively revealed no evidence of significant delayed perirenal hemorrhage. FloSeal gelatin matrix performed well as a rapidly deployable, effective hemostatic agent in a hypothermic grade 5 renal injury damage control model. The absence of delayed bleeding and nephrotoxicity suggests a possible increased role for FloSeal in the treatment of devastating renal injuries in damage control surgery.

278. Therapeutic Activities of IL-12 Gene- Modified Macrophages Embedded in Gelatin Matrix Hemostatic Sealant (FloSeal®) in a Mouse Model of Residual Prostate Cancer

INTRODUCTION AND OBJECTIVE: Despite improved surgical techniques local tumor recurrence after radical prostatectomy is not uncommon. We previously reported that IL-12 gene modified macrophages (IL-12/M|[Phi]|) suppress tumor growth and metastasis in pre-clinical mouse models of prostate cancer (Satoh et al, Cancer Res., 63: 7853-7860, 2003).

GELATIN MATRIX TREATMENT OF COMPLEX RENAL INJURIES IN A PORCINE MODEL

We developed a complex porcine renal laceration model at our laboratory to test the efficacy of an abbreviated, sutureless treatment regimen using FloSeal gelatin matrix hemostatic sealant (Baxter Healthcare Corp., Fremont, California). We evaluated the influence of preliminary renal arterial occlusion on hemostatic efficacy and assessed the risk of delayed hematoma or urinoma formation after treatment. A total of 21 commercial swine underwent celiotomy with creation of a complex upper pole renal injury using a 4 x 4 cm cruciate press instrument. The injury was uniformly produced at the caudal extent of the upper third portion of the left kidney. Subjects were prospectively randomized into 3 treatment groups. Experimental animals were treated with the application of gelatin matrix with (7 in group 1) or without (7 in group 2) preliminary renal arterial occlusion. Control subjects (7 in group 3) were treated with conventional horizontal mattress sutured gelatin sponge bolsters over the capsular injury. Operative blood loss, time to hemostasis and volume of gelatin matrix required for hemostasis were compared among the groups. Abdominal computerized tomography with intravenous contrast medium was performed in each animal 7 days postoperatively. Gelatin matrix use resulted in significantly less mean blood loss (80.7 and 99.0 ml in groups 1 and 2, respectively) vs conventional suture treatment (191.8 ml in group 3, p = 0.036). Time to hemostasis was similarly decreased (1.1, 2 to 2.5 and 5.8 minutes in groups 1 to 3, respectively, p = 0.009). Followup abdominal computerized tomography with contrast medium revealed no clinically significant perinephric fluid collections (greater than 2 cm). FloSeal gelatin matrix hemostatic sealant provided effective hemostasis after complex renal injury with and without preliminary vascular control. No delayed bleeding or clinically significant urinoma formation was noted. These findings suggest a possible increased role for FloSeal gelatin matrix in renal salvage surgery.

What Happens to Hemostatic Agents in Contact with Urine? An in Vitro Study

As the indications for topical hemostatic agents increase in urology, the question arises: what happens to these agents when they enter the urinary collecting system? To answer this question, we performed a series of in-vitro experiments mixing three hemostatic agents with normal and sanguineous urine. Four commercially available topical hemostatic products: oxidized regenerated cellulose (Surgicel; Ethicon, Somerville, NJ), fibrin sealant (Tisseel VH Kit; Baxter Health Care Corporation, Irvine, CA), gelatin matrix hemostatic sealant (FloSeal; Baxter Health Care), and polyethylene glycol (CoSeal; Cohesion Technologies, Palo Alto, CA) were studied. Human urine (10 mL) was added to samples of each substance; this was done in triplicate. The 12 sample tubes were then capped and placed on a tube shaker at slow speed and 37 degrees C. Observations regarding consistency of the material were made at 6, 12, 24, 48, 72, 96, and 120 hours (5 days). Gelatin matrix hemostatic sealant was further tested in urine with various amounts of blood or blood clot; observations were again recorded out to 5 days. Surgicel maintained its solid form when it initially came in contact with urine, but over a period of 5 days, it transformed into a mucoid substance with visible free-floating fibers. It did not dissolve completely in urine within 5 days. Gelatin matrix was immediately transformed by urine into a fine colloidal suspension that did not change over the 5 days of the study. Fibrin glue, after mixing of the two components (fibrinogen and thrombin) directly in the urine, and polyethylene glycol immediately formed a solid clot at the bottom of the test tube on contact with the urine. When the mixture of fibrin sealant was allowed to form for 15 minutes and then added to urine, it again maintained a solid form. After 72 hours, the fibrin glue became a semisolid gelatinous plug. On analysis at 5 days, the fibrin sealant clot had transformed into a cohesive mucoid gel, and the polyethylene glycol clot had not changed. The gelatin matrix hemostatic sealant, when in contact with blood or blood clot, appeared to either become part of a clot or to remain in a colloidal suspension. At 5 days, all clots had dissolved to fine particulate suspensions, and the gelatin matrix appeared as a fine suspension. Fibrin glue and oxidized regenerated cellulose maintain a solid form when initially placed in direct contact with urine and then assume a semisolid gelatinous state, which is still present at 5 days. Polyethylene glycol forms a solid clot initially and does not change after 5 days. Only hemostatic gelatin matrix remained as a fine particulate suspension in both normal and sanguineous urine. The implications of these findings with regard to sealing the renal parenchyma or small violations of the collecting system after percutaneous or laparoscopic surgery await in-vivo testing.

Hand-Assisted Laparoscopic Partial Nephrectomy in the Porcine Model Using Gelatin Matrix Hemostatic Sealant Without Hilar Occlusion

Gelatin matrix hemostatic sealant (GMHS) has been used for hemostasis during partial nephrectomy with hilar clamping. The objective of this study was to determine the ability of GMHS to achieve hemostasis without hilar clamping in the porcine model. In this feasibility study, eight farm pigs underwent a left-hand-assisted laparoscopic partial nephrectomy (HALPN). The lower fourth of the kidney was removed with cold scissors, and GMHS was applied laparoscopically. Samples were collected for measurement of serum hemoglobin (Hb) and creatinine (Cr) prior to surgery and at 4 and 30 days after HALPN. The kidneys were harvested at 30 days, and retrograde pyelograms and pathologic analysis were performed. Application of GMHS achieved complete hemostasis in all eight animals. The mean estimated blood loss was 40 mL, and the operating time was short (mean 92.5 minutes). In three kidneys, a significant collecting system opening was noted but not repaired. At harvest, there were no hematomas, infections, or urine leaks in any animals. In one animal, a 2-cm contained fluid collection was identified. There was no difference in the preoperative and harvest Hb (9.63 v 9.21 g/dL; P = 0.49), but there was a slight increase in Cr (1.21 v 1.46 mg/dL; P = 0.01) possibly because of the decreased renal mass after partial nephrectomy. Even without hilar occlusion, GMHS was 100% safe and effective in controlling bleeding after HALPN in the porcine model. Avoidance of hilar occlusion may reduce the risk associated with warm renal ischemia and the extra dissection required to isolate the hilum in preparation for clamping.

Floseal gelatin matrix treatment of complex renal injuries in a porcine model

Abstract Introduction: We developed a complex porcine renal laceration model and tested the efficacy of a treatment regimen based on FLOSEAL gelatin matrix hemostatic sealant (Baxter Healthcare Corp, Fremont, CA). We evaluated the influence of preliminary renal vascular occlusion on hemostatic efficacy and the risk of urinoma formation after treatment. Methods: A total of 19 commercial swine a complex upper pole renal laceration via a 2 × 2 cm cruciate press instrument. The injury was uniformly produced on the left kidney. Subjects were randomized into 3 treatment groups. Experimental animals were treated with FLOSEAL gelatin matrix with (Group 1, n = 7) or without (Group 2, n = 6) preliminary renal vascular occlusion. Control subjects (Group 3, n = 6) were treated by a conventional sutured repair. Operative blood loss and time to hemostasis was compared between the groups. Abdominal CT scan was performed on each animal at 7 days. Results: Use of FLOSEAL gelatin matrix resulted in significantly less mean blood loss (Group 1—80.7 cc, Group 2—99.0 cc) versus conventional suture treatment (Group 3—191.8 cc, p = 0.036). Time to hemostasis was similarly reduced (Group 1—1.1 min, Group 2—2.5 min, Group 3—5.8 min, p = 0.009). Follow up CT scan revealed no evidence of significant perirenal fluid collections. Conclusions: FLOSEAL gelatin matrix hemostatic sealant provided effective hemostatic treatment after complex renal injury, both with and without preliminary vascular control. No delayed bleeding or urinoma formation was noted.

Sealing Percutaneous Nephrolithotomy Tracts With Gelatin Matrix Hemostatic Sealant: Initial Clinical Use

Tubeless percutaneous nephrolithotomy (PCNL) has been performed at several centers with good success. However, these cases have been carefully selected with regard to short duration and smaller stone burden to prevent complications associated with the loss of access to the collecting system. We describe the use of gelatin matrix hemostatic sealant (FloSeal Baxter Medical, Fremont, California) as an adjunct to tubeless percutaneous nephrolithotomy to help preclude bleeding complications. Two patients were treated with PCNL through a single nephrostomy tract. At the satisfactory conclusion of the cases the tract was occluded retrograde with an occlusion balloon catheter and gelatin matrix hemostatic sealant was injected down the nephrostomy tract. An indwelling stent and bladder catheter were placed following which all guidewires were removed and skin sutures were placed. The operative times were 75 and 180 minutes, respectively. Both patients had stable postoperative hemoglobin and no evidence of bleeding or obstruction on postoperative computerized tomography. Injection of gelatin matrix hemostatic sealant into the nephrostomy tract may be of value in preventing bleeding after PCNL. In this pilot experience it provided immediate and effective hemostasis.