Hemostatic Effect and Mechanism of Epidermal Growth Factor-Hemostatic Powder after Endoscopic Submucosal Dissection in a Porcine Model

Background/Aims@#Among several methods used to prevent endoscopic submucosal dissection (ESD) bleeding, the recently developed hemostatic powder (HP) has few technical limitations and is relatively easy-to-use. This study aimed to analyze the hemostatic effects and mechanisms of two HPs using a porcine upper gastrointestinal hemorrhage model. @*Methods@#We evaluated HPs (Endospray and epidermal growth factor [EGF]-endospray) for adhesion, waterproofing ability, permeability, and absorption in vitro. ESD was performed to induce bleeding ulcers in the porcine stomachs. In a total of three pigs, three bleeding ulcers per animal were generated. Hemostasis and rebleeding were evaluated endoscopically. After 72 hours, the animals were sacrificed, and histologically analyzed. @*Results@#The water absorption of HPs was over 20 times the initial value within 30 minutes. The gelated HPs completely blocked water penetration into the applied site within 5 minutes and strongly adhered to the Petri-dish surface for up to 6 hours. The initial hemostasis rates within 5 minutes were 33.3%, 100.0%, and 66.7%, and the rebleeding rates at 6 to 72 hours after HP application were 33.3%, 16.7%, and 33.3% (control, Endospray, and EGF-endospray groups, respectively). Histological analysis revealed the thickness of the regenerated mucosa (522.1, 514.5, and 680.3 µm) and the submucosal layer (1,510.3, 2,848.2, and 3,062.3 µm) and the number of newly formed blood vessels (15.3, 17.9, and 20.5) in the control, Endospray, and EGFendospray groups, respectively. @*Conclusions@#The endoscopic HPs demonstrated the ability to elicit effective initial hemostasis and the histological ulcer-healing effect of EGF in an animal model of hemorrhagic gastric ulcers.

Recurred Intracranial Meningioma: A Retrospective Analysis for Treatment Outcome and Prognostic Factor

BACKGROUND: In this study, we aimed to compare repeated resection and radiation treatment, such as Gamma knife radiosurgery (GKRS) or conventional radiotherapy (RT), and investigate the factors influencing treatment outcome, including overall survival (OS), progression-free survival (PFS), and complication rates. METHODS: We retrospectively reviewed 67 cases of recurred intracranial meningiomas (repeated resection: 36 cases, radiation treatment: 31 cases) with 56 months of the median follow-up duration (range, 13–294 months). RESULTS: The incidence of death rate was 29.9% over follow-up period after treatment for recurred meningiomas (20/67). As independent predictable factors for OS, benign pathology [hazard ratio (HR) 0.132, 95% confidence interval (CI) 0.048–0.362, p<0.001] and tumor size <3 cm (HR 0.167, 95% CI 0.061–0.452, p<0.001) were significantly associated with a longer OS. The incidence of progression rate was 23.9% (16/67). Only treatment modality was important for PFS as an independent predictable factor (GKRS/RT vs. open resection; HR 0.117, 95% CI 0.027–0.518, p<0.005). The complication rate was 14.9% in our study (10/67). Larger tumor size (≥3 cm, HR 0.060, 95% CI 0.007–0.509, p=0.010) was significant as an independent prognostic factor for development of complications. Although treatment modality was not included for multivariate analysis, it should be considered as a predictable factor for complications (p=0.001 in univariate analysis). CONCLUSION: The role of repeated resection is questionable for recurred intracranial meningiomas, considering high progression and complication rates. Frequent and regular imaging follow-up is required to detect recurred tumor sized as small as possible, and radiation treatment can be a preferred treatment.

Negative Effect of Rapidly Resorbing Properties of Bioactive Glass-Ceramics as Bone Graft Substitute in a Rabbit Lumbar Fusion Model

BACKGROUND: Bioactive glass-ceramics have the ability to directly bind to bones and have been widely used as bone graft substitutes due to their high osteoconductivity and biocompatibility. CaO-SiO2-P2O5-B2O3 glass-ceramics are known to have good osteoconductivity and are used as bone graft extenders. METHODS: This study aimed to evaluate the effects of the resorbing properties of glass-ceramics in bone fusion after producing and analyzing three types of CaO-SiO2-P2O5-B2O3 glass-ceramics with high osteoconductivity that had enhanced resorption by having an increased B2O3 content. The three types of CaO-SiO2-P2O5-B2O3 glass-ceramics with B2O3 contents of 8.0, 9.0, and 9.5 weight % were designated and grouped as P20B80, P10B90, and P5B95, respectively. Glass-ceramic types were tested for fusion rates and bone formation by employing the lumbar 5-6 intertransverse process fusion model in 51 New Zealand male rabbits. Bioactivity was assessed by soaking in simulated body fluid (SBF). RESULTS: In vitro study results showed sufficient hydroxycarbonate apatite layer formation occurred for P20B80 in1 day, for P10B90 in 3 days, and for P5B95 in 5 days after soaking in SBF. For the rabbit lumbar spine posterolateral fusion model, the autograft group recorded a 100% fusion rate with levels significantly higher than those of P20B80 (29.4%), P10B90 (0%), and P5B95 (14.3%), with high resorbing properties. Resorbing property differences among the three glass-ceramic groups were not significant. Histological results showed new bone formation confirming osteoconductivity in all three types of glass-ceramics. Radiomorphometric results also confirmed the resorbing properties of the three glass-ceramic types. CONCLUSIONS: The high resorbing properties and osteoconductivity of porous glass-ceramics can be advantageous as no glass-ceramics remain in the body. However, their relatively fast rate of resorption in the body negatively affects their role as an osteoconductive scaffold as glass-ceramics are resorbed before bony fusion.

Evaluation of Osteosynthesis in CaO-SiO2-P2O5-B2O3 Glass-ceramics by Posterolateral Fusion of Rabbit Lumbar vertebrae / 대한척추외과학회지

STUDY DESIGN: A comparative in vivo study between ceramics with different compositions. OBJECTIVES: To compare the biodegradation and osteoconduction properties of CaO-SiO2- P2O5- B2O3 glass-ceramics and Cerabone(R)-AW. Summary of Literature Review: Bioglass ceramics can be used as bone graft substitutes. However, no study has been undertaken to investigate the possibility of CaO-S i O2-P2O5-B2O3 glass-ceramics as a bone graft substitute. MATERIALS AND METHODS: Porous CSPB2 implants (44.07% CaO, 40.28% SiO2, 8.1% P2O5 and 5.0% B2O3), porous CSPB3 implants (43.76% CaO, 43.41% SiO2, 4.05% P2O5 and 7.5% B2O3) and porous Cerabone(R)-AW were prepared by the polymer sponge method. Single-level posterolateral spinal fusions were performed on sixty New Zealand white male rabbits. The animals were divided into four groups (9 of autograft, 17 per 3 kind of porous implant group) according to the implant material used: autograft, CSPB2, CSPB3 and Cerabone(R)-AW. Radiographs were performed every two weeks. All animals were sacrificed 12 weeks after surgery. Manual palpation and uniaxial tensile strength were determined. The proportion of the area occupied by the ceramics in the final compared to the initial radiographs was calculated. Decalcified and undecalcified histological sections were evaluated by light microscopy. RESULTS: Fifty one rabbits were evaluated. The union rates were 100 (9 out of 9), 80 (8 out of 8), 81.1 (9 out of 11) and 90.9% (10 out of 11) in the autograft, Cerabone(R)-AW, CSPB2 and CSPB3 groups, respectively. The proportion of the area occupied by Cerabone(R)-AW (90.8 % +/- 14.0) was significantly higher than for CSPB2 (73.1% +/- 11.5) and CSPB3 (73.5% +/- 10.0)(p=0.0011). The mean values of the tensile strengths of Cerabone(R)-AW (214. +/- 57.3N), CSPB2 (214. +/- 57.3 N) and CSPB3 (217 +/- 70.1 N) were not significantly different (p>0.05). CONCLUSION: CSPB2 and CSPB3 had similar tensile strengths and fusion rates of the fusion masses as those of Cerabone(R)-AW; however, they degraded more rapidly than Cerabone(R)-AW. These findings suggest that CSPB2 and CSPB3 grafts can be used as a more ideal new bone graft substitutes than Cerabone(R)-AW.

Evaluation of Biodegradation and Osteosynthesis in CaO-SiO2-B2O3 Glass-ceramics by Posterolateral Fusion of Rabbit Lumbar vertebrae / 대한정형외과학회잡지

PURPOSE: To compare the biodegradation and osteoconduction properties of CaO-SiO2-B2O3 glass-ceramics (CS10B), hydroxyapatite(HA), and tricalcium phosphate (TCP). MATERIALS AND METHODS: Porous CS10B implants were prepared by the polymer sponge method. Single-level posterolateral spinal fusions were performed on thirty rabbits. The animals were divided into three groups by implant material: HA, TCP and CS10B. Radiographs were performed every two weeks. All animals were sacrificed 12 weeks after surgery. The proportion of the area occupied by the ceramicsin the final over the initial radiographs was calculated. Uniaxial tensile strength was determined from 7 cases in each group. RESULTS: The proportion of the area occupied by HA (88.7+/-16.1%) was significantly higher than the others (p<0.05), and the proportion of the area occupied by CS10B (28.2+/-9.3%) was significantly lower than those of HA and TCP (37+/-9.6%) (p<0.05). The mean values of the tensile strengths of HA (191.4+/-33.5 N) and CS10B (182.7+/-19.9 N) were significantly higher (p<0.05) than those of TCP (141.1+/-28.2 N). CONCLUSION: CS10B had similar tensile strengths of the fusion masses as HA, however, it degraded more rapidly than HA or TCP. These findings suggest CS10B grafts as possible bone replacement materials.

Evaluation of Osseointegration in Dense Ceramics Using Rabbit's External Fixation Model / 대한정형외과연구학회지

PURPOSE: To evaluate the osseointegration of different dense ceramics. MATERIALS AND METHODS: Twenty-eight New Zealand white male rabbits were divided into 4 groups by implant materials: Cerabone(R)-AW, CaO-SiO2- B2O3 glass ceramics (CS10B), CaO-SiO2- B2O3 glass (CS5B glass) and Cerabone(R)- A W + A l2O3 glass ceramics. We implanted the dense ceramics into the tibia of rabbits with external fixator and checked the radiographs every 4 weeks. The union rate, histology and SEM were evaluated 8 weeks after surgery. RESULTS: The union rates were 85.7% (6 of 7) in Cerabone(R)-AW, 85.7% (6 of 7) in CS10B, 71.4% (5 of 7) in CS5B glass and 28.6% (2 of 7) in Cerabone(R)-AW+Al2O3 by simple radiographs. The union rates of Cerabone (R)-AW and CS10B were statistically higher than that of Cerabone(R)-AW+Al2O3 (p=0.031). Histologically, the Cerabone(R)-AW had fused with tibia without biodegradation, CS10B, CS5B glass had fused with tibia in some portion but resorbed in others. Cerabone(R)-AW+Al2O3 had not fused with bony tissue. CONCLUSION: We confirmed the osseointegration and insolubility of Cerabone(R)-AW. We also confirmed the osseointegration and partial solubility of CaO-SiO2-B2O3 glass ceramics. These findings suggest that Cerabone (R)-AW can be used as an insoluble artificial bone and CaO-SiO2-B2O3 glass ceramics as biodegradable bone replacement materials.

Porous Beta-Calcium Pyrophosphate as a Bone Graft Substitute in a Canine Bone Defect Model / 대한정형외과학회잡지

PURPOSE: To evaluate the possibility of using porous beta-calcium pyrophosphate (beta-CPP) as a bone graft substitute by comparing its osteoconduction and degradation with porous hydroxyapatite (HA). MATERIALS AND METHODS: Porous HA and porous beta-CPP were implanted in the proximal tibia of 7 dogs. Two animals were sacrificed at 8weeks and 5 animals were sacrificed at 20 weeks after surgery. Radiographs and histologic sections were evaluated. RESULTS: The mean period required for the radiolucent zone to disappear was 7.1+/-1.1 weeks in HA and 6.4+/-1.1 weeks in beta-CPP. By serial radiography, resorption was more prominent in porous beta-CPP than in porous HA at 8 weeks (p=0.04) and at 20 weeks. The proportion of bony tissue in the pore was 16.8% in HA and 29.7% in -CPP. The proportion of pores with bony tissue was 70.2% in HA and 62.5% in beta-CPP at 8 weeks. CONCLUSION: In beta-CPP, the new bone growth was as vigorous as in HA, but the degradation was more rapid than in HA. These results suggest that beta-CPP is a more ideal new bone graft substitute.

Comparison of Osteosyntheses in Various Types of Porous Calcium Phosphate Compounds: An Experimental Study by Posterolateral Fusion of Rabbits' Lumbar Vertebrae / 대한척추외과학회지

PURPOSE: The purpose of the present study was to compare the osteoconduction in porous bodies made of various compositions of calcium phosphate compounds and other porous artificial bones. MATERIALS AND METHODS: Single-level posterolateral spinal fusions were performed on ninety rabbits. The animals were divided into nine groups by graft materials: autograft (positive control), implantation of HA, TCP, CPP, HA/TCP composite, TCP/CPP composite, Lubboc(R) and Calcium sulfate pellet (CSP), no-graft after decortication (negative control). Serial radiography, serum calcium and phosphorus levels were checked. All animals were sacrificed 12 weeks after surgery and the fusion masses were compared by manual palpation, uniaxial tensile strength measurement and histological evaluation. RESULTS: Autografted and CPP implanted groups showed significantly higher fusion ratio than TCP, TCP/CPP composite, and no-graft groups. Meanwhile, HA and HA/TCP groups showed no significant difference with other groups in fusion ratio. From the radiological examination, TCP and CPP groups seemed to show more rapid absorption of implant than HA group. The mean values of tensile strength of autografted and CPP group were significantly larger than those of TCP, TCP/CPP composite, and no-graft groups. The result of direct inspection and microscopic examination showed the TCP-contained implants lost their porous structure, whereas the other implants did not. On the light microscopy, both HA and CPP groups showed more abundant new bone growth into the pores than TCP-contained groups, but the pore size of CPP became larger than that of the HA, which manifested more rapid absorption of CPP in the living body. CONCLUSION: The porous CPP implant is considered to be more desirable bone graft substitute because it has satisfactory osteoconductive ablility and better biodegradation than porous HA. And the maintenance of porous structure is considered to be indispensable for osteoconduction.

Effects of Pore Size on Osteoconduction at the Porous Hydroxyapatite / 대한정형외과학회잡지

PURPOSE: Porous hydroxyapatite is resorbable and osteoconductive, so it is slowly replaced by ingrowing new bone. Optimal pore geometry for osteoconduction, however, has not been determined yet. The objective of this investigation was to assess both the histological response and the reinforcing effects of bone ingrowth within the porous hydroxyapatite implants depending on pore size. MATERIALS AND METHODS: Four kinds of cylindrical types (50, 100, 300, 500 micrometer) of porous hydrox-yapatite were prepared. Fifty-six white rabbits were divided into 4 groups and porous hydroxyapatite block was inserted through the medial cortical window of a proximal tibia. Histomorphological changes were examined using light microscopy and scanning electron microscopy. Biomechanical compression test was performed using a material test machine. RESULTS: Hydroxyapatite implants appeared to have no early adverse effects, such as inflammation and foreign body reaction. Osteoconduction through the pores was found in all four implants and new bone was found on the surface of pores with no histologically demonstrable intervening nonosseous tissue. At four weeks after implantation, new bone was arranged in a concentric pattern around the vessel, similar to osteon. New bone formation through pores was most evident at 300 micrometer-sized type. At 8 weeks, active osteoconduction was also found at 50 micrometer-sized type. Evidence of bone marrow formation within porous hydroxyapatite was found. In a biomechanical study, ultimate compression strength significantly increased in the 300 micrometer-sized type, after 8 weeks implantation compared to preimplantation. CONCLUSIONS: Porous hydroxyapatite implanted into rabbit tibia showed biological fixation and osteointegration. A pore size of 300 micrometer was most effective for bone ingrowth. Osteoconduction also took place in 50 micrometer-sized cylindrical pores.