Improved outcomes utilizing a novel pectin-based pleural sealant following acute lung injury.

BACKGROUND: Persistent air leaks after thoracic trauma are associated with significant morbidity. To evaluate a novel pectin sealant in a swine model of traumatic air leaks, we compared a pectin biopolymer with standard surgical and fibrin-based interventions. METHODS: A standardized lung injury was created in male Yorkshire swine. Interventions were randomized to stapled wedge resection (n = 5), topical fibrin glue (n = 5), fibrin patch (n = 5), and a pectin sealant (n = 6). Baseline, preintervention and postintervention tidal volumes (TV) were recorded. Early success was defined as the return to near-normal TV (>95% of baseline). Late success was defined as no detectable air leak in the chest tube after chest closure. RESULTS: There were no differences in injury severity between groups (mean TV loss, 62 ± 17 mL, p = 0.2). Early success was appreciated in 100% (n = 6) of the pectin interventions which was significantly better than the fibrin sealant (20%, n = 1), fibrin patch (20%, n = 1), and stapled groups (80%, n = 4, p = 0.01). The percent of return to baseline TV after sealant intervention was significantly increased in the pectin (98%) and staple arms (97%) compared with the fibrin sealant (91%) and fibrin patch arms (90%) (p = 0.02; p = 0.03). Late success was also improved with the pectin sealant: no air leak was detected in 83% of the pectin group compared with 40% in the stapled group (p = 0.008)-90% of the fibrin-based interventions resulted in continuous air leaks (p = 0.001). CONCLUSION: Pectin-based bioadhesives effectively seal traumatic air leaks upon application in a porcine model. Further testing is warranted as they may provide a superior parenchymal-sparing treatment option for traumatic air leaks.

A Novel Technique in the Treatment of Lymphoceles After Renal Transplantation: C-Arm Cone Beam CT-Guided Percutaneous Embolization of Lymphatic Leakage After Lymphangiography.

BACKGROUND: We aimed to evaluate the efficacy of percutaneous embolization after lymphangiography using C-arm cone-beam computed tomography (CBCT) performed at the site of lymphatic leakage in patients with postrenal transplant lymphocele. METHODS: Between July 2014 and August 2017, 13 patients not responding to percutaneous ethanol sclerotherapy and conservative treatment for recurrent lymphocele after renal transplant were included. The mean age of the patients was 56.38 ± 9.91 (range, 36-70) years, and it comprised 9 men and 4 women. All patients underwent intranodal lymphangiography. C-arm CBCT-guided percutaneous embolization was performed in patients with confirmed lymphatic leakage. Patients who had no lymphatic leakage underwent drainage with fibrin glue injection. RESULTS: Lymphatic leakage was observed in 9 patients after lymphangiography, and they underwent CBCT-guided percutaneous N-butyl-2-cyanoacrylate embolization. The volume of lymphatic drainage reduced to less than 10 mL in 8 patients. One patient who was not responding to embolization was treated surgically, after percutaneous drainage and fibrin glue injection. Lymphatic leakage was not observed in 4 patients after lymphangiography. Of these, 3 patients showed a reduction in the amount of lymphatic drainage after lymphangiography. All 4 patients underwent percutaneous drainage and fibrin glue injection. One patient did not respond to the treatment and was treated surgically. Prelymphangiography and postlymphangiography and embolization, the volume of lymphatic drainage was 113.07 ± 21.75 mL, and 53.84 ± 30.96 mL, respectively, and statistically significant decrease was detected (P < 0.005). CONCLUSIONS: Lymphangiography and CBCT-guided percutaneous embolization procedures might be an effective treatment method for patients with lymphocele refractory to treatment.

Successful Treatment of Postdural Puncture Headache Using Epidural Fibrin Glue Patch after Persistent Failure of Epidural Blood Patches.

OBJECTIVES: Epidural blood patch is the gold standard for the treatment of postdural puncture headache (PDPH) when conservative treatments have failed to provide any relief. However, alternative therapies are lacking when epidural blood patch persistently fails to improve symptoms. Failure to treat PDPH may lead to significant functional impairment of daily living. Alternative therapies should be sought to accelerate recovery from PDPH. CASE REPORT: This case describes a woman who developed PDPH secondary to accidental dural puncture during a spinal cord stimulator trial. She was successfully treated with epidural fibrin glue patch after multiple trials of epidural blood patches. CONCLUSION: Percutaneous injection of fibrin glue to seal the dural defect demonstrated promising outcomes for both immediate and long-lasting resolution of persistent PDPH in our patient. In the event of epidural blood patch failure, epidural fibrin glue patch may be a reasonable alternative for the treatment of persistent PDPH.

Low cost biological lung volume reduction therapy for advanced emphysema.

BACKGROUND: Bronchoscopic lung volume reduction (BLVR), using biological agents, is one of the new alternatives to lung volume reduction surgery. OBJECTIVES: To evaluate efficacy and safety of biological BLVR using low cost agents including autologous blood and fibrin glue. METHODS: Enrolled patients were divided into two groups: group A (seven patients) in which autologous blood was used and group B (eight patients) in which fibrin glue was used. The agents were injected through a triple lumen balloon catheter via fiberoptic bronchoscope. Changes in high resolution computerized tomography (HRCT) volumetry, pulmonary function tests, symptoms, and exercise capacity were evaluated at 12 weeks postprocedure as well as for complications. RESULTS: In group A, at 12 weeks postprocedure, there was significant improvement in the mean value of HRCT volumetry and residual volume/total lung capacity (% predicted) (P-value: <0.001 and 0.038, respectively). In group B, there was significant improvement in the mean value of HRCT volumetry and (residual volume/total lung capacity % predicted) (P-value: 0.005 and 0.004, respectively). All patients tolerated the procedure with no mortality. CONCLUSION: BLVR using autologous blood and locally prepared fibrin glue is a promising method for therapy of advanced emphysema in term of efficacy, safety as well as cost effectiveness.

Fibrin-sealant-delivered cisplatin chemotherapy versus cisplatin hyperthermic intraperitoneal perfusion chemotherapy for locally advanced gastric cancer without peritoneal metastases: a randomized phase-II clinical trial with a 40-month follow-up.

A new intraoperative cisplatin administration method for patients with locally advanced gastric cancer (AGC) and without peritoneal metastasis, fibrin-sealant-delivered cisplatin chemotherapy, was reported, and its safety, pharmacokinetics, and efficacy were compared with cisplatin hyperthermic intraperitoneal perfusion chemotherapy. Forty-two AGC patients were randomly divided into 2 groups: fibrin-sealant-delivered cisplatin chemotherapy (FS) (n = 21) and cisplatin hyperthermic intraperitoneal perfusion chemotherapy (CHIC) (n = 21). Both groups received 120 mg cisplatin after complete cytoreductive surgery. At different time points, cisplatin concentrations in patients' sera and urine samples were measured to determine time-dependent maximal concentration (Cmax) and the area under the curve (AUC). The primary and secondary end-points were overall survival (OS) and safety profiling, respectively. Occurrence of grade-3 to grade-4 liver or kidney dysfunction was less frequent in the FS group than in the CHIC group (28.6 % vs 47.6 %). Cisplatin Cmax and AUC for the serum and urine of the FS patients were significantly lower than that of the CHIC patients. Elimination half-life of cisplatin in the FS group was significantly longer than in the CHIC group (24.1 h vs 14.2 h). After a median follow-up of 40 months, 1-, 2-, and 3-years OS were 90.5 %, 71.4 %, and 61.9 % in the FS group, and 61.9 %, 47.6 %, and 42.8 % in the CHIC group, respectively. The median OS was 35.9 months in the FS group and 29.1 months in the CHIC group. Fibrin-sealant-delivered cisplatin chemotherapy was as effective and had a favorable pharmacokinetic profile with similar survival outcomes as cisplatin hyperthermic intraperitoneal perfusion chemotherapy following complete cytoreductive surgery of locally advanced GC without peritoneal metastases.

Lower reoperation rates with the use of fibrin sealant versus tacks for mesh fixation.

BACKGROUND: Groin hernia repair may be associated with long-term complications such as chronic pain, believed to result from damage to regional nerves by tissue penetrating mesh fixation. Studies have shown that mesh fixation with fibrin sealant reduces the risk of these long-term complications, but data on recurrence and reoperation rates after the use of fibrin sealant compared with tacks are not available. This study aimed to determine whether fibrin sealant is a safe and feasible alternative to tacks with regard to reoperation rates after laparoscopic groin hernia repair. METHODS: The current study compared reoperation rates after laparoscopic groin hernia repair between fibrin sealant and tacks used for mesh fixation. The study used data collected prospectively from The National Danish Hernia Database and analyzed 8,314 laparoscopic groin hernia repairs for reoperation rates. Mesh fixation was performed with fibrin sealant (n = 784) or tacks (n = 7,530). RESULTS: The findings showed a significantly lower reoperation rate for the fibrin sealant than for the tacks (0.89 vs 2.94 %, p = 0.031). The median follow-up period was 17 months (range, 0-44 months) for the fibrin sealant group and 21 months (range, 0-44 months) for the tacks group. CONCLUSIONS: Fibrin sealant was superior to tacks for mesh fixation in laparoscopic groin hernia repair with regard to reoperation rates. The study could not differentiate between different hernia defect sizes, and future studies should therefore explore whether the superior effect of fibrin sealant applies for all hernia types and sizes.

Cystoscopic injection of N-butyl-2-cyanoacrylate followed by fibrin glue for the treatment of persistent or massive vesicourethral anastomotic urine leak after radical prostatectomy.

OBJECTIVES: Vesicourethral anastomotic urine leak is a common postoperative complication of radical prostatectomy. Herein we describe a novel method for the treatment of this complication. METHODS: Intervention for a prolonged or massive anastomotic urine leak was required in 10 out of 1828 patients (0.5%) submitted to radical prostatectomy between 2007 and 2011. N-butyl-2-cyanoacrylate (Histoacryl) followed by fibrin glue (Greenplast) were injected under local anesthesia into vesicourethral anastomotic gaps under fluoroscopic guidance using a 20-Fr rigid cystoscope. Cystograms were taken in all patients to confirm complete urine leak resolution before the removal of the urethral catheter. RESULTS: Cystoscopic injection of Histoacryl followed by fibrin glue was technically successful and well tolerated in all patients. The mean time from radical prostatectomy to glue injection was 16.0 days (range 12-27 days). Urethral catheterization was required for an average of 7.7 days after cystoscopic injection of fibrin glue (range 3-13 days). These measures ultimately enabled complete resolution of the urine leak in all cases. At a mean follow up of 23.3 months, all 10 patients were fully continent. The mean time to recovery of urinary continence was 20.4 weeks (range 3.9-60.0 weeks). CONCLUSIONS: Cystoscopic injection of N-butyl-2-cyanoacrylate followed by fibrin glue into the anastomotic gap is both a feasible and effective solution in patients with a persistent or massive vesicourethral anastomotic urine leak after radical prostatectomy.

All-arthroscopic technique of biological meniscal tear therapy with collagen matrix.

PURPOSE: The number of meniscus surgeries, including partial or complete meniscectomy, has increased considerably with the progress in knee arthroscopy. An analysis of treatment results, carried out at several centres by numerous study groups, showed a development of early degenerative changes in the knees of treated patients. METHODS: This study is aimed at developing a fully arthroscopic technique to treat meniscal tears by suturing and wrapping them in collagen matrix, followed by injection of liquid bone-marrow collected from the tibial proximal epiphysis, into the area of meniscal lesion. RESULTS: In this paper, we presented arthroscopic technique for wrapping meniscal tears using the collagen matrix sutured with the Fast-Fix sutures. CONCLUSIONS: Proposed surgical technique is not straightforward to perform, but can be learned by adhering to strict arthroscopic principles. The use of collagen matrix and bone marrow aspirate from bone-marrow blood, including stem cells, creates favourable biological conditions for meniscus healing, which may increase the rate of healing.

A new approach to percutaneous transhepatic portal embolization using ethanolamine oleate iopamidol.

PURPOSE: We aimed to examine the therapeutic efficacy of ethanolamine oleate iopamidol (EOI) as an embolic material for percutaneous transhepatic portal embolization (PTPE). METHODS: Eighty-two patients with liver tumors were treated with PTPE. Fifty-eight patients had hepatocellular carcinomas, 11 had liver metastases, and 13 had other liver tumors. A total of 55 patients (group E) were treated with 5% ethanolamine oleate after gelatin sponge administration. As a control, we evaluated 27 patients (group F) who were treated with fibrin glue and iodized oil. PTPE was mainly indicated before hepatic resection, for patients with high nontumorous volumetric resection ratios (the nontumorous volumetric resection ratio was estimated to be greater than 65% in patients with an indocyanine green retention ratio of 15 min (ICG R15) of 10% or less, and the nontumorous volumetric resection ratio was estimated to be greater than 40% in the patients with an ICG R15 of 10-20%). RESULTS: All patients were successfully treated percutaneously under local anesthesia. Balloon-occluded and ipsilateral approaches were used in 81 patients (99%) and 62 (75%) patients, respectively. The rate of insufficient embolization or recanalization was significantly lower in group E (7.3%) in comparison to group F (25.9%; p < 0.05). The volumetric resection ratios, before and after PTPE, decreased from 60 to 45% in group E and from 63 to 55% in group F. The post-PTPE resection ratio was significantly decreased in group E. Before and after PTPE, average ICG R15 values changed from 17 to 27% in group E and from 18 to 26% in group F. The complication rates in groups E and F were similar (7.3 vs. 7.4%). CONCLUSION: EOI is a safe embolic material that can be used to induce greater liver hypertrophy, in comparison to fibrin glue, in PTPE for liver tumors.

Healing of full-thickness defects of the articular cartilage in rabbits using fibroblast growth factor-2 and a fibrin sealant.

We have investigated in vitro the release kinetics and bioactivity of fibroblast growth factor-2 (FGF-2) released from a carrier of fibrin sealant. In order to evaluate the effects of the FGF-2 delivery mechanism on the repair of articular cartilage, full-thickness cylindrical defects, 5 mm in diameter and 4 mm in depth, which were too large to undergo spontaneous repair, were created in the femoral trochlea of rabbit knees. These defects were then filled with the sealant. Approximately 50% of the FGF-2 was released from the sealant within 24 hours while its original bioactivity was maintained. The implantation of the fibrin sealant incorporating FGF-2 successfully induced healing of the surface with hyaline cartilage and concomitant repair of the subchondral bone at eight weeks after the creation of the defect. Our findings suggest that this delivery method for FGF-2 may be useful for promoting regenerative repair of full-thickness defects of articular cartilage in humans.

Validity of microporous polysaccharide hemispheres as a hemostatic agent in hepatic injuries: an experimental study in rats.

INTRODUCTION: In the treatment of hepatic injuries, there is not always adequate and secure hemostasis. A hepatic biopsy is indispensable in the evolution of focal or diffuse liver cell disease, being necessary for candidates for liver transplant and post-transplant treatment. Many patients suffer blood clotting that increases the risk of bleeding. For this reason, it is necessary to seek for substances capable of bringing about hemostasis quickly and effectively. PURPOSE: The aim of this study was to recognize the validity of the use of microporous polysaccharide hemispheres (MPH) as a hemostatic agent for hepatic injuries. METHODS: Thirty Wistar rats were used, split into three groups. Under anaesthetic, a laparotomy was done and resulted in a standard liver injury that was treated in Group A with MPH, in Group B with n-butyl-2-cyanoacrylate and in Group C with fibrin adhesive. Immediate hemostasis, delayed bleeding and histological evolution were timed. RESULTS: The MPH took on average six minutes to promote hemostasis and also resulted in re-bleeding, which required reapplication; the n-butyl-2-cyanoacrylate took twenty seconds and the fibrin adhesive took one minute. The cyanoacrylate resulted in more intense adherence. The three adhesives mainly showed a chronic inflammatory reaction. The injuries treated with cyanoacrylate showed a larger area of injury (p=0,0164). The density of the collagen was similar in all groups. CONCLUSION: The MPH, despite achieving hemostasis, proved to be no more favorable than n-butyl-cyanoacrylate and the fibrin adhesive, the latter resulting in the lowest tissue reaction.

Validity of microporous polysaccharide hemispheres as a hemostatic agent in hepatic injuries: an experimental study in rats

INTRODUCTION: In the treatment of hepatic injuries, there is not always adequate and secure hemostasis. A hepatic biopsy is indispensable in the evolution of focal or diffuse liver cell disease, being necessary for candidates for liver transplant and post-transplant treatment. Many patients suffer blood clotting that increases the risk of bleeding. For this reason, it is necessary to seek for substances capable of bringing about hemostasis quickly and effectively. PURPOSE: The aim of this study was to recognize the validity of the use of microporous polysaccharide hemispheres (MPH) as a hemostatic agent for hepatic injuries. METHODS: Thirty Wistar rats were used, split into three groups. Under anaesthetic, a laparoptomy was done and resulted in a standard liver injury that was treated in Group A with MPH, in Group B with n-butyl-2-cyanoacrylate and in Group C with fibrin adhesive. Immediate hemostasis, delayed bleeding and histological evolution were timed. RESULTS: The MPH took on average six minutes to promote hemostasis and also resulted in re-bleeding, which required reapplication; the n-butyl-2-cyanoacrylate took twenty seconds and the fibrin adhesive took one minute. The cyanoacrylate resulted in more intense adherence. The three adhesives mainly showed a chronic inflammatory reaction. The injuries treated with cyanoacrylate showed a larger area of injury (p=0,0164). The density of the collagen was similar in all groups. CONCLUSION: The MPH, despite achieving hemostasis, proved to be no more favorable than n-butyl-cyanoacrylate and the fibrin adhesive, the latter resulting in the lowest tissue reaction.

INTRODUÇÃO: No tratamento de lesões hepáticas nem sempre se tem hemostasia adequada e segura. Biópsia hepática é indispensável na evolução de doença hepato-celular difusa ou focal sendo necessária para candidatos à transplante hepático e para acompanhamento pós-transplante. Muitos doentes apresentam coagulopatias que aumentam os riscos de sangramento. Daí a necessidade de se procurar substâncias capazes de promover a hemostasia de forma rápida e efetiva. OBJETIVO: O objetivo deste estudo foi reconhecer a validade do uso de hemosferas microporosas de polissacarídeos (MPH) como agente hemostático para lesões hepáticas. MÉTODOS: Utilizaram-se 30 ratos Wistar distribuídos em três grupos. Sob anestesia, fez-se uma laparotomia e produziu-se um ferimento hepático padrão que foi tratado no grupo A com MPH, no grupo B, com n-butil-2-cianoacrilato e no grupo C com adesivo de fibrina. Cronometrou-se o tempo para a obtenção da hemostasia imediata, a existência de sangramento tardio e a evolução histológica. RESULTADOS: O MPH levou, em média, seis minutos para promover a hemostasia e apresentou re-sangramento exigindo reaplicação, o n-butil-2-cianoacrlato, 20 segundos e o adesivo de fibrina, um minuto. O cianoacrilato promoveu aderências mais intensas. Os três adesivos determinaram principalmente reação inflamatória do tipo crônico. As feridas tratadas com cianoacrilato apresentaram maior área de lesão (p=0,0164). A densidade do colágeno foi semelhante entre os grupos. CONCLUSÃO: O MPH, embora tenha conseguido hemostasia, não se mostrou mais favorável do que o n-butil-2-cianoacrilato e o adesivo de fibrina sendo que este último promoveu a menor reação tecidual.

[A mixture of antimicrobial peptides and fibrin glue in treatment of partial-thickness burn wounds]. / Antimikrobielle Peptide und Fibrinkleber in Verbrennungen. Biologische Potenz gegen multiresistente Pseudomonas-aeruginosa-Bakterien in Verbrennungen der Tiefe IIb.

BACKGROUND: Antimicrobial peptides are naturally occurring cationic peptides. The first-line of defense in infected burns is the innate immune system, of which antimicrobial peptides are essential parts. To facilitate their topical use in infected partial-thickness burns, the efficacy of a mixture with fibrin glue in vitro and in vivo was tested. METHODS: After in vitro tests, 15 male Sprague-Dawley rats received partial-thickness burns. Afterwards, the wounds were infected with multiresistant Pseudomonas aeruginosa. The animals received PG-1 (100 microg/ml, n=5), fibrin glue (n=5), or a mixture of both (n=5) topically. The efficacy of the materials was previously proven by radial diffusion assay. After 24 h, the infected and burned skin was harvested and quantitative bacterial counts per gram of skin performed. RESULTS: The biologic effect of the peptides was confirmed in vitro. The PG-1 and fibrin glue groups did not show significant differences in bacterial numbers, whereas the mixture group showed significant reduction in Pseudomonas in vivo (P<0.04 and P<0.01). CONCLUSION: A mixture of an antimicrobial peptide and commercially available fibrin glue is capable of significantly reducing bacteria in infected partial thickness burns in vivo compared to controls.

Novel PCL-based honeycomb scaffolds as drug delivery systems for rhBMP-2.

This study investigated a novel drug delivery system (DDS), consisting of polycaprolactone (PCL) or polycaprolactone 20% tricalcium phosphate (PCL-TCP) biodegradable scaffolds, fibrin Tisseel sealant and recombinant bone morphogenetic protein-2 (rhBMP-2) for bone regeneration. PCL and PCL-TCP-fibrin composites displayed a loading efficiency of 70% and 43%, respectively. Fluorescence and scanning electron microscopy revealed sparse clumps of rhBMP-2 particles, non-uniformly distributed on the rods' surface of PCL-fibrin composites. In contrast, individual rhBMP-2 particles were evident and uniformly distributed on the rods' surface of the PCL-TCP-fibrin composites. PCL-fibrin composites loaded with 10 and 20 microg/ml rhBMP-2 demonstrated a triphasic release profile as quantified by an enzyme-linked immunosorbent assay (ELISA). This consisted of burst releases at 2 h, and days 7 and 16. A biphasic release profile was observed for PCL-TCP-fibrin composites loaded with 10 microg/ml rhBMP-2, consisting of burst releases at 2 h and day 14. PCL-TCP-fibrin composites loaded with 20 microg/ml rhBMP-2 showed a tri-phasic release profile, consisting of burst releases at 2 h, and days 10 and 21. We conclude that the addition of TCP caused a delay in rhBMP-2 release. Sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE) and alkaline phosphatase assay verified the stability and bioactivity of eluted rhBMP-2 at all time points.

Treatment of experimental osteomyelitis with a fibrin sealant antibiotic implant.

Two methods currently are available for the delivery of antibiotics: intravenous injection with a long-term indwelling catheter and local implant of antibiotic-containing polymethylmethacrylate beads. Both of these methods have significant disadvantages. A fibrin sealant implant, impregnated with tobramycin, was evaluated in a rabbit model of osteomyelitis to determine whether it has the potential of supplying a basis for bone reconstruction and providing an improved treatment method for the delivery of antibiotics to orthopaedic infections. Localized tibial osteomyelitis, with methicillin-sensitive Staphylococcus aureus, was developed surgically in female New Zealand White rabbits. After 2 weeks, rabbits with evidence of osteomyelitis were treated with debridement alone, debridement plus systemic tobramycin, debridement plus fibrin sealant, debridement plus fibrin sealant loaded with tobramycin, polymethylmethacrylate beads loaded with tobramycin, or not treated at all (control). After 4 weeks of therapy, the rabbits were sacrificed and the involved bones were cultured for concentrations of methicillin-sensitive Staphylococcus aureus per gram of bone and marrow. Preliminary data (N = 14) indicate fibrin sealant plus tobramycin may be as effective as polymethylmethacrylate beads plus tobramycin against methicillin-sensitive Staphylococcus aureus osteomyelitis in a rabbit model.

The inhibitory effect of simvastatin on growth in malignant gliomas--with special reference to its local application with fibrin glue spray in vivo.

Simvastatin is one of the competitive inhibitors of HMG-CoA reductase. During clinical trials, it has shown the ability to lower serum cholesterol. We investigated the effect of simvastatin on the growth of malignant gliomas in vitro, semi-in vivo, and in vivo. An in-vitro MTT assay revealed that human malignant glioma cell lines: U-251MG, U-373MG, and U-87MG, and rat malignant glioma cell line C6 were well inhibited in growth in a dose-dependent fashion. An anchorage-independent growth assay showed that the number of colonies (more than 100 microM in size) of human (U-373MG) and rat malignant gliomas (C6) was markedly reduced in a dose-dependent fashion. A flow cytometry analysis revealed that simvastatin treatment led U-251MG cells to accumulate in sub G0-G1. Immunostaining by TUNEL method showed that most glioma cells treated by 10 microM simvastatin had nuclear immunostaining, suggesting apoptotic changes of the treated cells. The human umbilical vein endothelial cells and human lung fibroblasts were inhibited in growth by no more than 20% of controls even with a high dose (10 microM) of simvastatin. In the semi-in vivo model, using newborn rat brain slice cultures, the rhodamine-labeled glioma cells were abolished after 7 days of local simvastatin treatment with fibrin glue probably suggesting that simvastatin led the cells to apoptosis. In rat models using subcutaneously inoculated C6, the local application of simvastatin combined with fibrin glue (spray method) was quite effective in inhibiting the growth of the tumor. These data suggest that simvastatin may be a novel anti-glioma drug, and the local application of simvastatin combined with fibrin glue (by spray method) may be a crucial new clinical strategy against glioma growth.

An evaluation of fibrin tissue adhesive concentration and application thickness on skin graft survival.

OBJECTIVES: To examine the effects of fibrinogen concentration and application thickness of fibrin tissue adhesive on skin graft survival. STUDY DESIGN: Prospective controlled study. METHODS: Ten domestic pigs were included in the study. A 20 x 5-cm area of skin was harvested bilaterally along the flanks of the animals using a Padgett dermatome. The harvested grafts were trimmed into four 4 x 4-cm squares. Donor sites were treated according to group assignment and the non-meshed grafts were placed on the side opposite their initial orientation and secured with staples. Both single- and multiple-donor human fibrin tissue adhesive preparations, with low and high average fibrinogen concentrations of 30 mg/mL and 60 mg/ mL, were used. Adhesive preparations were applied in either a thin layer (0.015 mL/cm2) or a thick layer (0.06 mL/cm2) using a spray applicator. A constant thrombin concentration of 10 U/mL was used in the study. No adhesive was used in the control group and grafts were stabilized with staples. No topical dressings were applied to any of the treatment sites. Animals were sacrificed 4 weeks after graft application. RESULTS: Based on statistical analysis, thickness of adhesive application had a significant effect on skin graft survival. Percent mean graft survival in the control and thin application groups was found to be 92% and 97.8% respectively; the mean survival rate in the thick application group was 63.1%. Fibrinogen concentration, when evaluated independently within the thin and thick application groups, was found to have no significant effect on graft survival. CONCLUSION: Independent of fibrinogen concentration, a thin layer of fibrin tissue adhesive, when applied between two opposing surfaces, does not interfere with and may support the healing process, whereas a thick layer of adhesive inhibits skin graft healing.

Selective percutaneous transhepatic embolization of the portal vein in preparation for extensive liver resection: the ipsilateral approach.

The ipsilateral approach was used at preoperative portal vein embolization in 38 patients with hepatobiliary malignancy. The right anterior portal branch was punctured. Two different 5.5-F triple-lumen balloon catheters were used, and fibrin glue and iodized oil were injected. Portal vein embolization was successful in all cases (right lobe, 24 patients; left lobe and right anterior segment, six; right lobe and left medial segment, three; right posterior segment, two; right anterior segment, one; left lobe, one; and right and caudate lobes, one).

Efficacy of slow-releasing anticancer drug delivery systems on transplantable osteosarcomas in rats.

New drug delivery systems for cis-diamminedichloroplatinum (CDDP) incorporated into vehicles, such as polymethylmethacrylate (PMMA), fibrin glue (F.G.), alpha-tricalciumphosphate (TCP) and ethylenevinyleacetate copolymer (Polymer) were examined using a rat osteosarcoma model. The materials containing CDDP were directly implanted into the tumors or subcutaneous tissue of rats, and the inhibitory effects on tumor growth and lung metastasis were evaluated. Data on in vitro kinetics of CDDP release revealed good results for both TCP and F.G., and the release pattern from TCP to be most appropriate for a slow-releasing drug delivery system. This was supported by the results of the implantation experiments, whereby the direct implantation of TCP containing CDDP (CDDP-TCP) into tumors, gave significantly better inhibitions of tumor growth and metastasis than either non-treatment (P < 0.01) or subcutaneous implantation (P < 0.05). In a second experiment, using different administration procedures, different inhibitory effects on tumor growth and lung metastatic potency were observed with intra-arterial and intravenous CDDP administration, as well as with CDDP-TCP implanted subcutaneously. Suppression effects of CDDP (10 mg/kg)-TCP directly implanted into tumors were equal to those of intra-arterial (2.5 mg/kg) and intravenous (5.0 mg/kg) administrations. The present results suggest CDDP-TCP implantation to be effective as a slow-release drug delivery system for inhibiting tumor growth and metastasis, and that it should be a useful adjuvant to conventional i.v. or i.a. chemotherapy.

[Local chemotherapy by a sustained-release preparation with fibrin seal against the operative wound in head and neck cancer].

Fibrin seal has been used for hemostasis and sealing in operative field of tumors in the head and neck. The authors applied it for drug preparation and tried a local chemotherapy to treat residual and disseminated tumors of cellular level in the operative wound using 5-FU. The drug release rate in this therapy in vitro study was 50% after 24 hrs. When injected to rats bearing Yoshida sarcoma, it exhibited a marked antitumor effect compared to the control group given 5-FU alone. This therapy is easy to make the dosage adjustment and can apply drugs directly to the tumor residue at the high concentration. It will be clinically a useful adjuvant therapy for radiotherapy, surgery or chemotherapy.