Cryopreserved nanostructured fibrin-agarose hydrogels are efficient and safe hemostatic agents.

Uncontrolled bleeding during surgery is associated with high mortality and prolonged hospital stay, necessitating the use of hemostatic agents. Fibrin sealant patches offer an efficient solution to achieve hemostasis and improve patient outcomes in liver resection surgery. We have previously demonstrated the efficacy of a nanostructured fibrin-agarose hydrogel (NFAH). However, for the widespread distribution and commercialization of the product, it is necessary to develop an optimal preservation method that allows for prolonged stability and facilitates storage and distribution. We investigated cryopreservation as a potential method for preserving NFAH using trehalose. Structural changes in cryopreserved NFAH (Cryo-NFAH) were investigated and comparative in vitro and in vivo efficacy and safety studies were performed with freshly prepared NFAH. We also examined the long-term safety of Cryo-NFAH versus TachoSil in a rat partial hepatectomy model, including time to hemostasis, intra-abdominal adhesion, hepatic hematoma, inflammatory factors, histopathological variables, temperature and body weight, hemocompatibility and cytotoxicity. Structural analyses demonstrated that Cryo-NFAH retained most of its macro- and microscopic properties after cryopreservation. Likewise, hemostatic efficacy assays showed no significant differences with fresh NFAH. Safety evaluations indicated that Cryo-NFAH had a similar overall profile to TachoSil up to 40 days post-surgery in rats. In addition, Cryo-NFAH demonstrated superior hemostatic efficacy compared with TachoSil while also demonstrating lower levels of erythrolysis and cytotoxicity than both TachoSil and other commercially available hemostatic agents. These results indicate that Cryo-NFAH is highly effective hemostatic patch with a favorable safety and tolerability profile, supporting its potential for clinical use.

Long-term persistence of carrier-bound fibrin sealant (TachoSil®) following abdominal surgery: a decade-long follow-up study.

This study analyzed the long-term effects of carrier-bound fibrin sealant (CBFS) following abdominal surgery by tracking patients for years post-application. From 2006 to 2022, patients who underwent this procedure were contacted via telephone. Those who died due to underlying diseases, natural causes, or refused the check-up were excluded from the study. After 11 years of follow-up, CBFS was observed in different forms on computed tomography scans in four patients. Our findings indicate that CBFS can persist for years after the procedure. While we cannot confirm any secondary effects, it appears that CBFS sponges are not resorbed within 12 weeks and can remain for many years post-implantation.

Diaphragm reconstruction using a TachoSil patch as alternative to intrasellar packing for small focal diaphragm defects in pituitary surgery: a cohort study.

BACKGROUND: During pituitary surgery, CSF leaks are often treated by intrasellar packing, using muscle or fat grafts. However, this strategy may interfere with the interpretation of postoperative MRI and may impact the quality of resection in cases of second surgery, due to the existence of additional fibrous tissue. We present an alternative technique, using a diaphragm reconstruction with a heterologous sponge combining fibrinogen and thrombin (TachoSil), applied in selected patients with low-flow CSF leaks. This study investigates the surgical outcome of patients treated with this strategy. METHODS: From a cohort of 2231 patients treated from June 2011 to June 2023 by endoscopic endonasal approach for pituitary surgery, the surgical technique of diaphragm repair with TachoSil patch performed in 55 patients (2.6%) was detailed, and the rate of closure failure was analyzed at 6 months postoperatively. No intrasellar packing was used and sellar floor reconstruction was performed whenever possible. The rate of postoperative CSF leak was compared with that reported in three previous publications that also used the TachoSil patch technique. RESULTS: Patients were mostly women (F/M ratio: 1.2) with a median age of 53.6 years. Surgery was indicated for non-functioning adenomas, Cushing's disease, acromegaly, and Rathke's cleft cysts in 38/55 (69.1%), 6/55 (10.9%), 5/55 (9.1%) and 6/55 (10.9%) patients respectively. The rate of postoperative CSF leak was 1.8% (n = 1/55), which was not significantly different from that reported in the three cohorts from the literature (2.8%, p > 0.05). No postoperative meningitis was recorded. CONCLUSIONS: In highly selected patients with low-flow CSF leaks related to small focal diaphragm defects, diaphragm reconstruction using a TachoSil patch can be a safe and valuable alternative to intrasellar packing.

Thoracoscopic Management of Chylothorax by Application of a Fibrin Sealant Patch.

Thoracic duct ligation is a demanding procedure when the chyle leak and/or the duct itself are not identified. This report describes a new procedure using thoracoscopic closure of the chyle leak by application of a fibrin sealant patch. This strategy was successfully applied for closing (i) a small fistula due to a postoperative lesion of the lymphatic tributary vessels in one case, and (ii) a large fistula due to idiopathic rupture of the thoracic duct in another case.

NHS-POx-loaded patch versus fibrin sealant patch in a porcine robotic liver bleeding model.

BACKGROUND: The management of bleeding is paramount to any surgical procedure. With the increased use of less invasive laparoscopic and robotic methods, achieving hemostasis can be challenging since the surgeons cannot manually apply hemostatic agents directly onto bleeding tissue. In this study, we assessed the use of a pliable hemostatic sealant patch comprising fibrous gelatin carrier impregnated with poly(2-oxazoline) (NHS-POx) for hemostasis in robotic liver resection in a porcine bleeding model. METHODS: The NHS-POx-loaded patch (GATT-Patch), was first evaluated in a Feasibility Study to treat surgical bleeding in 10 lesions, followed by a Comparative Study in which the NHS-POx patch was compared to a standard-of-care fibrin sealant patch (TachoSil), in 36 lesions (superficial, resection, or deep injuries mimicking metastasectomies). For each lesion type, the NHS-POx and fibrin sealant patches were used in an alternating fashion with 18 lesions treated with NHS-POx and 18 with the fibrin patch. Animal preparation and surgical procedures were consistent across studies. The primary outcome was time to hemostasis (TTH) within 3 min for the Feasibility Study and within 5 min for the Comparative Study. RESULTS: In the Feasibility Study, 8 of the 10 NHS-POx-treated lesions achieved hemostasis at 30 s and 3 min. In the Comparative Study, all 18 NHS-POx patch-treated lesions and 9 of the 18 fibrin sealant patch-treated lesions achieved hemostasis at 5 min. Median TTH with NHS-POx vs fibrin sealant patch was 30 vs 300 s (P < 0.001). CONCLUSIONS: In this animal study, hemostasis during robotic liver surgery was achieved faster and more often with the NHS-POx loaded vs fibrin sealant patch.

Collagen fleece (Tachosil®) for treating testis torsion: A case report.

BACKGROUND: Testicular torsion is an emergent disease in urology, and there has been discussion of the treatment of testicular torsion. Testicular decompression has been established as a critical treatment for testicular compartment syndrome (TCS), which occurs after detorsion in a patient who is diagnosed with testis torsion. Until now, testicular fasciotomy and incision of tunica albuginea with tunica vaginalis flap (TVF) graft have been suggested for decompression, and some studies about the efficacy of TVF were reported. However, this method is time consuming and needs meticulous technique, so other methods such as orchio-septopexy are suggested. The objective of this clinical case report was to propose new surgical method using collagen fleece (Tachosil®) instead of tunica vagina flap. CASE SUMMARY: A 5-year-old boy with scrotal pain visited our hospital 24 h after symptom onset. After history taking, physical examination, and scrotum ultrasonography, he was diagnosed with testis torsion. Emergency surgery was performed after diagnosis. Following the incision of scrotum and fasciotomy, we covered his tunica albuginea with collagen fleece called Tachosil® instead of covering with TVF. CONCLUSION: Short-term follow-up showed normal blood flow in testis without a TCS. This is the first case report of using Tachosil® in testicular torsion surgery, and its advantages were already reported in other surgeries like Peyronie's disease. Our case suggests this new technique is an appropriate method because of its advantages including its cost-effective and time-saving characteristics. The main limitation is the short follow-up, so more studies are needed to provide a high level of evidence about its efficacy and safety.

Quick and Easy Application Method of TachoSil®ï¸ During Laparoscopic and Robotic Liver Resections.

TachoSil®ï¸, a fibrin sealant patch, is a sheet-type hemostatic agent. Therefore, it is technically demanding to put it on the target place especially in laparoscopic surgeries due to the motion restriction of straight-fixed instruments. This article describes a quick and easy technique of TachoSil application during laparoscopic liver surgeries, by sewing it to the laparoscopic gauze in advance. This method allows for one-handed operation and stress-free application even in the situation of active bleeding.

Efficacy of a novel polyoxazoline-based hemostatic patch in liver and spleen surgery.

BACKGROUND: A new hemostatic sealant based on a N-hydroxy-succinimide polyoxazoline (NHS-POx) polymer was evaluated to determine hemostatic efficacy and long-term wound healing and adverse effects in a large animal model of parenchymal organ surgical bleeds. METHODS: Experiment 1 included 20 pigs that were treated with two NHS-POx patch prototypes [a gelatin fibrous carrier (GFC) with NHS-POx and an oxidized regenerated cellulose (ORC) with poly(lactic-co-glycolic acid)-NHS-POx:NU-POx (nucleophilically activated polyoxazoline)], a blank gelatin patch (GFC Blank), TachoSil® and Veriset™ to stop moderate liver and spleen punch bleedings. After various survival periods (1-6 weeks), pigs were re-operated to evaluate patch degradation and parenchymal healing. During the re-operation, experiment 2 was performed: partial liver and spleen resections with severe bleeding, and hemostatic efficacy was evaluated under normal and heparinized conditions of the two previous prototypes and one additional NHS-POx patch. In the third experiment an improved NHS-POx patch (GATT-Patch; GFC-NHS-POx and added 20% as nucleophilically activated polyoxazoline; NU-POx) was compared with TachoSil®, Veriset™ and GFC Blank on punch bleedings and partial liver and spleen resections for rapid (10s) hemostatic efficacy. RESULTS: NHS-POx-based patches showed better (GFC-NHS-POx 83.1%, ORC-PLGA-NHS-POx: NU-POx 98.3%) hemostatic efficacy compared to TachoSil® (25.0%) and GFC Blank (43.3%), and comparable efficacy with Veriset™ (96.7%) on moderate standardized punch bleedings on liver and spleen. All patches demonstrated gradual degradation over 6 weeks with a reduced local inflammation rate and an improved wound healing. For severe bleedings under non-heparinized conditions, hemostasis was achieved in 100% for Veriset™, 40% for TachoSil and 80-100% for the three NHS-POx prototypes; similar differences between patches remained for heparinized conditions. In experiment 3, GATT-Patch, Veriset™, TachoSil and GFC Blank reached hemostasis after 10s in 100%, 42.8%, 7.1% and 14.3%, respectively, and at 3 min in 100%, 100%, 14.3% and 35.7%, respectively, on all liver and spleen punctures and resections. CONCLUSIONS: NHS-POx-based patches, and particularly the GATT-Patch, are fast in achieving effective hemostatic sealing on standardized moderate and severe bleedings without apparent long-term adverse events.

Use of tissue sealant patch (TachoSil) in the management of cerebrospinal fluid leaks after anterior cervical spine discectomy and fusion.

PURPOSE: The purpose of this study was to evaluate a fast, sutureless technique to repair anterior cervical dural tears. Anterior cervical discectomy and fusion (ACDF) is a commonly performed procedure for the treatment of cervical degenerative diseases. Although uncommon, incidental durotomy with cerebrospinal fluid (CSF) leak during ACDF is a potentially serious complication. Yet, its technical management for the prevention of CSF leak is controversial. METHODS: Between September 2012 and June 2018 we encountered seven cases (2 female/5 male) presenting with intraoperative CSF leaks secondary to incidental dural tears during ACDF surgery. All the cases were surgically treated using a topical fibrin sealant patch (TachoSil) with high adesive strength and fibrin glue (Tisseel). Intraoperative source of leakage, time to leakage control, quantity of Sealant Sponge used and postoperative complications were evaluated. RESULTS: Dural tears were tipically the result of dissection of adherent posterior longitudinal ligament and/or calcified disc from the cervical dural sac to allow full decompression of the spinal cord. Effective repair of dural tear defined as cessation of CSF leak after topical sealant agents application was achieved no later than one minute in all cases. Evident clinical and/or radiological postoperative CSF leak was used to determine the patient's postoperative result. Postoperative CSF leak was not evident during a minimum 6 months follow up. CONCLUSIONS: In the present study, we have reported our experience with a new sealing technique to manage CSF leaks from iatrogenic cervical dural lacerations. Tachosil tissue sealant patch is a rapid sutureless technique that may help in repairing introperatively incidental dural tears, thus reducing the risk of postoperative CSF leaks. To our knowledge, this is the first series to report the use of Tachosil adhesive sealant patch for the treatment of incidental dural tears during anterior cervical discectomy.

Validity of a novel ex vivo porcine liver perfusion model for studying haemostatic products.

INTRODUCTION: We developed a novel normothermic ex vivo porcine liver perfusion model with whole blood in order to have alternatives for animal experiments in the research and development of new local haemostatic agents. This study aims to assess the construct and content validity of this model. METHODS: In this study we performed two ex vivo experiments using nine livers and one in vivo experiment using six female Norsvin Topigs pigs: (1) ex vivo liver perfusion for establishing physiological blood parameters of the perfused liver and controlled heparinization, (2) ex vivo liver perfusion with a surgical injury and (3) a surgical liver injury in anaesthetized pigs with and without heparin. RESULTS: Ex vivo coagulation parameters were comparable to in vivo with heparin. Blood gas values and metabolic parameters were comparable between ex vivo and in vivo with heparin, but significantly different compared with in vivo baseline, with the exception of (partial pressure of oxygen (PO2). Activated clotting time (ACT) values significantly differed depending on the heparin doses. The coagulation parameters fibrinogen, activated partial thromboplastin time, prothrombin time and ACT were rather constant during the 4 h ex vivo perfusion. Haemostatic efficacy of commercially available products was comparable between in vivo with heparin and the ex vivo liver perfusion experiment. CONCLUSION: This novel ex vivo liver perfusion model demonstrates good construct and content validity for at least 4 h of perfusion. The model is an easily accessible, table-top, tunable and effective alternative for the in vivo testing of (new) haemostatic products on their haemostatic properties.Validité d'un nouveau modèle de perfusion hépatique porcin ex-vivo pour l'étude des produits hémostatiques Résumé.