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Experimental And Clinical Research Of Using Flap And Vancomycin Loaded Calcium Sulfate And Autogenous Bone To Treat Traumatic Osteomyelitis In One Stage

Posted on:2016-06-15Degree:DoctorType:Dissertation
Country:ChinaCandidate:L F ShenFull Text:PDF
GTID:1224330482456722Subject:Human Anatomy and Embryology
Abstract/Summary:PDF Full Text Request
BackgroundWith an increasingly high incidence, traumatic osteomyelitis has been the major type of osteomyelitis in recent years. Traumatic osteomyelitis is complex and has long disease course, various pathogens and even mixed infection; meanwhile its treatment is involved in many aspects, such as the repair and reconstruction of soft tissue, bone defect and nonunion, and infection control. Besides, this disease presents a high recurrence and disability rate. Therefore, traumatic osteomyelitis is an intractable disease which needs to be treated urgently in orthopaedics. It proves that traumatic osteomyelitis occurs most frequently in tibia. Owing to the thin coverage of soft tissue in front of tibia, the infection of the disease after high energy injury or trauma often results in soft tissue defect. In the condition, flap repair is necessary, which brings difficulty to the treatment of traumatic osteomyelitis.The treatment principles of traumatic osteomyelitis include sufficient debridement and drainage, controlling infection through effective antibiotic treatment, fracture treatment, closing the dead cavity, and improving local blood circulation by establishing normal coverage of soft tissue.Most traumatic osteomyelitis always combines with soft tissue defection, while some cases without soft tissue defection will need soft tissue reparation after sufficient debridement because of the long disease course and local sinus. With the development of microsurgical technique, the popularization and application of various pedicle and free flaps has basically satisfied the demands for the repair and reconstruction of limb soft tissue. Currently, one of the major research focus is to realize satisfied repair effect through an operation as simple as possible and reduce the complications after flap operation. Since propeller flap was put forward and applied, it has been acknowledged by clinicians soon and popularized in many fields. The repair of soft tissue defect in the leg by using propeller flap has also been reported widely. However, there are rare basic researches on the anatomical characteristics of the perforating branches of posterior tibial artery and peroneal artery based on propeller flap, especially distal perforating branch. Venous drainage is still a major complication of propeller flap operation and requires to be further investigated.The existing methods for the repair and reconstruction of infective bone defect consist of the phase-two bone graft, phase-one open bone graft, free vascularized bone graft and bone transport. Traditional method is stage treatment or open bone graft based on Orr’s treatment. Even a satisfactory clinical effect can be achieved for segmental bone defect over 4 cm through bone transport or free vascularized bone graft. However, traditional methods present the shortfalls of long treatment cycle, frequent operations, high technic difficulty and no early functional rehabilitation training for the affected limb. Owing to the local drug delivery system significantly improves the local anti-infective ability of lesion, the infection control rate of osteomyelitis has increased remarkably to bring great progress for the treatment of osteomyelitis. Especially, due to the application of absorbable carriers, such as calcium sulfate, it is unnecessary to carry out a second operation to remove drug carrier. And the related clinical application has been popularized gradually. However, to improve the clinical effect and promote the development of the treatment of osteomyelitis, the main complications, including the recurrence of osteomyelitis due to infection after operation, bone nonunion and reactive exudation, need to be cured through further basic and clinical research.This paper mainly conducted a basic and clinical research on the phase-one treatment scheme for the traumatic osteomyelitis in tibia by combining tissue flap, vancomycin-loaded calcium sulfate, and autogenous bone. The scheme consists of three parts. First, based on the repair of soft tissue defect of the osteomyelitis in tibia, the gross anatomical study of the perforating branches of posterior tibial artery and peroneal artery was performed. This research attempts to guide the design of propeller flap in leg, apply the design to clinic and discuss the method for venous drainage disturbance after operation by observing the anatomical characteristics of both perforating artery and its concomitant veins. Second, an animal experiment was carried out to study the security and effectiveness of the treatment method of bone graft for infective bone defect based on a rabbit model of osteomyelitis. The method of bone graft combined vancomycin-loaded calcium sulfate and autogenous bone. Third, clinical practice was undertaken. The phase-one treatment scheme for the traumatic osteomyelitis in tibia by combining tissue flap, vancomycin-loaded calcium sulfate, and autogenous iliac bone was carried out. The cases of the treatment of the disease through bone graft by merely using tissue flap and vancomycin-loaded calcium sulfate were analyzed retrospectively. And by comparing the clinical effects of the two methods, the clinical effect and advantage of the optimized scheme were evaluated.Objective1. The research expects to investigate the gross anatomical characteristics of the perforating branches of posterior tibial artery and peroneal artery and repair the soft tissue defect in distal termination of leg and around the foot and ankle by using the perforator pedicled propeller flap of the two arteries. The prevention measures for the complications are also explored.2. The research aims to analyze the security of bone graft in treating infective bone defect by integrating vancomycin-loaded calcium sulfate and autogenous bone based on the rabbit model of osteomyelitis. Besides, the influences on the repair of bone defect resulting from the graft of autogenous bone are explored as well.3. Another goal of the paper is to discuss the clinical effect of the phase-one treatment scheme for traumatic osteomyelitis in tibia by combining tissue flap, vancomycin-loaded calcium sulfate and autogenous iliac bone.Materials and methods1. Concerning the specimens of 10 sides of 5 fresh cadavers, red latex was perfused into the popliteal arteries while blue latex was perfused into the veins. Then, after anatomization, the indexes, including the number, length, orientation angles, vessel diameter and the concomitant relationship between the artery and vein, of the perforating branches of posterior tibial artery and peroneal artery were recorded. And the constant site of perforating branch was investigated to guide the design of clinical flap. From June 2011 to June 2013,47 cases with soft tissue defect in distal termination of leg and around the foot and ankle were treated by repairing the perforator pedicled propeller flap. On this basis, the clinical effect was observed and the complication rate was calculated so as to study the prevention methods for the complications.2. Rabbit model of osteomyelitis was established by randomly dividing 40 rabbits into four groups:model group and treatment groups A, B, and C, with 10 rabbits in each group. For the model group, lesion was not removed and calcium sulfate and autogenous bone were not implanted. While regarding treatment group A, antibiotic-loaded calcium sulfate was implanted in bone defect site. Concerning treatment group B, calcium sulfate and autogenous bone were implanted in bone defect site in a ratio of 1:1. And for treatment group C, the ratio of calcium sulfate and autogenous bone implanted in bone defect site was 1:2. Afterwards, CT scan was conducted and the blood routine, CRP and ALP were measured at the lesion location in the four groups on the 1st,30th and 60th days after operation. Besides,30 and 60 days after operation, pathological sections were stained with HE reagent; under light microscope, the following conditions were observed, such as the abscess of tissue sections, necrotic bones, subperiosteal new bone, the infiltration of multinuclear giant cells, and the vascularization in bone defect site; the expression of osteocalcin in bone defect site was shown by using an immunohistochemical method; and the expression level of OC of bone tissue was analyzed through an image-analysis software Image-Pro Plus (IPP6.0). Based on the variance analysis method, statistical test was performed for the experimental results in each group, and P< 0.05 represented that the difference had statistical significance.3. From January 2013 to July 2014,58 patients which had traumatic osteomyelitis in tibia and met the inclusive criteria were investigated and treated. By taking these patients as treatment group A, they were treated by adopting the phase-one treatment scheme of combing tissue flap, vancomycin-loaded calcium sulfate and autogenous iliac bone. According to the different implantation amounts of calcium sulfate, these patients were divided into three subgroups Al, A2 and A3. The calcium sulfate containing 200 mg of vancomycin was implanted to the first subgroup, while 500 mg and over 1000 mg of vancomycin for the second and third subgroups respectively.300 patients with osteomyelitis who were treated from January 2009 to December 2012 were retrospectively analyzed. In which,15 patients who satisfied the inclusive criteria and were treated by using the phase-one treatment scheme, namely, removing the lesion, implanting vancomycin-loaded calcium sulfate and repairing the defect by means of tissue flap, were chosen as control group B. Concerning treatment group A, drainage fluid was collected after operation every day to measure the concentration of vancomycin until drainage tube was removed.1,3,6, 9 and 12 months after operation, X-ray examination was conducted for all the patients to evaluate the healing condition of fracture. All the patients were followed up to study the following indexes:the standing time of drainage tube, the healing time of fracture, infection control rate, bone nonunion rate and other complications. Based on a paired T test, the differences of the standing time of drainage tube and the healing time of fracture between groups A and B were analyzed. And P< 0.05 showed significant difference. In addition, through single factor analysis of variance, the differences of the standing time of drainage tube and the healing time of fracture among the three subgroups Al, A2 and A3 were discussed. Likewise, P< 0.05 presented remarkable difference.Results1. The perforating branch occurred in 92 posterior tibial and peroneal arteries. Among them, each of 52 arteries had 2 concomitant veins,37 presented 1 concomitant vein, and 1 had no concomitant vein; the perforating branches of 2 peroneal arteries entered into the skin by sharing 1 concomitant vein after perforating deep fascia. On fibular side, at (3.0±1.0) cm, (8.0±2.0) cm and (19.5±0.5) cm from lateral malleolus, constant perforating vessels of peroneal artery went into the skin after perforating deep fascia. Among them, perforating branch was found in 7 cases at (3.0±1.0) cm site and in 10 cases at (8.0±2.0) cm location. At (5.0±1.0) cm and (8.0±1.0) cm from medial malleolus on tibial side, it was observed that constant perforating vessels entered into the skin after perforating deep fascia. And among them, perforating branch was shown in 8 cases at (5.0±1.0) cm site and 9 cases at (8.0±1.0) cm site. Concerning the perforator pedicled propeller flaps of 36 peroneal arteries, the perforating branches were 6 to 18 cm and 10.1 cm on average to the lateral malleolus after perforating deep fascia. Among them, the perforating branch of 24 cases located in the range of (8.0±2.0) cm to the lateral malleolus; the perforating branches of 11 posterior tibial arteries were 6 to 18 cm with an average of 9.5 cm to the medial malleolus, after perforating deep fascia; the perforating branches of 6 cases were in the site (8.0±1.0) cm from the medial malleolus. The complications included 1 case of hematocele under flap,1 case of infection,1 case of necrosis of skin graft of donor site, and 13 cases (9 peroneal arteries and 4 posterior tibial arteries with perforating branch) of venous drainage disturbance, among which,4 cases were suffered with distal flap necrosis.2. Comparing with the model group, the Alkaline Phosphatase (ALP), white blood cell count (WBC) and high-sensitivity C-reactive protein (CRP) of treatment groups A, B and C were significantly lower (F=541.444, P=0.000; F=61.310, P=0.000; F=11.317, P=0.000).30 days after operation, the bone defect area at the lesion location in each group was reduced and bone callus began to be formed (P<0.05).60 days after operation, the bone defect area in the model group was greater (P<0.05). It was remarkably different from that in the treatment groups A, B and C, among which, the group B presented the smallest bone defect area and was almost in the healing state.30 days after operation, analysis of HE staining showed that, for the model group, obvious bone resorption and supurative lesion which was formed by necrotic bones were observed. However, concerning the treatment groups A, B and C, trabecular increased and normal osteocytes were formed constantly while inflammatory cells greatly decreased and surrounding necrotic bones were reduced gradually. While 60 days after operation, analysis of HE staining demonstrated that, many necrotic bones were observed besides the infiltration of inflammatory granulation tissue surrounding necrotic bones in the model group. However, numerous new bones were formed in the treatment groups A, B and C; besides, few osteoprogenitor cells and osteoclasts concurrently occurred around the grafted bone; therefore, osteogenesis and osteolysis underwent simultaneously.30 and 60 days after operation, the deposition of OC of varying degrees, was found in these groups.30 and 60 days after operation, the positive staining rate in the treatment groups A, B and C increased significantly and demonstrated remarkable difference compared with the model group (P<0.05).3. All cases were followed up during 6 to 30 months after operation and no amputation was conducted for the affected limb. To repair soft tissue defect, the lateral gastrocnemius muscle flap, medial gastrocnemius muscle flap, free anterolateral thigh flap, perforator pedicled propeller flap, adjacent fascia flap, and direct suture were adopted for 2,7,3,7,6, and 9 cases respectively in group A; results indicated that all flaps survived, the poor healing of flap defect was observed for 2 cases which were healed after dressing change. However, to repair soft tissue defect, group B used the lateral gastrocnemius muscle flap for 2 cases, medial gastrocnemius muscle flap for 5 cases, free anterolateral thigh flap for 2 cases, neurocutaneous vascular flap for 3 cases, perforating flap for 1 case, and adjacent fascia flap for 2 cases; results revealed that distal flap necrosis was found in 2 cases applying neurocutaneous vascular flap,,with defect exudation and infection while the 2 cases were cured after debridement and dressing change without performing a second flap operation. In group A,3 cases recurred during 5 months to 2 years after operation; among which 2 cases were healed by implanting vancomycin-loaded calcium sulfate and autogenous iliac bone after re-debridement and 1 case was cured through bone transport after re-debridement; other complications included 1 case of bone nonunion and 2 cases of pin-tract infection; regarding bone nonunion, the infection was controlled and healed after a second bone graft; concerning pin-tract infection, the 2 cases were cured through expectant treatment of pin-track and intravenous antibiotic. The complication of numbness of anterolateral thigh was observed in 10 cases after removing iliac bone; about 3 to 6 months later, the symptom was relieved; hematocele in iliac bone region was found for 2 cases, among which 1 case was infected by staphylococcus aureus and was cured by means of drainage and dressing change. For B group,8 months after operation, osteomyelitis recurred for 1 case which was healed by implanting vancomycin-loaded calcium sulfate and autogenous iliac bone after re-debridement; refracture occurred for 2 cases at the original lesion location 18 and 25 months after healing and was cured after plate refixation and the graft of autogenous iliac bone; intraoperative pathology validated no recurrence of osteomyelitis; the exudation and infection of pin-tract were observed in 1 case while the symptoms were disappeared after expectant treatment. The standing time of drainage tube was (12.53±4.56) days on average for group A while (17.07±3.87) days for group B; P< 0.01 indicated the significant difference between them. The healing time of fracture was (6.20±2.16) months on average for group A while (8.36±2.84) months for group B; likewise, P<0.01 revealed the significant difference between them. For the subgroups A1, A2 and A3, there was no significant difference between subgroups A2 and A3 in the standing time of drainage tube and among the three groups in the healing time except the remarkable difference between subgroup A1 and subgroups A2 and A3 in the standing time of drainage tube. By collecting drainage fluid, it was observed that the local concentration of vancomycin reached the peak on the third day after operation; the high concentration of vancomycin continued from the second to fifth day after operation; since the fifth day, the concentration had decreased gradually while it still maintained a higher level.Conclusions1. The texture and color of propeller flap with a beautiful surface were similar to the recipient area. Besides, there was a good compatibility between propeller flap and the recipient area. The resection of flap was simple to perform without the necessity to match the vessel. Propeller flap presents satisfied clinical effect and is one of the preferred alternatives for repairing the defect in distal termination of leg and around the foot and ankle. However, venous drainage disturbance is still the major complication after propeller flap operation. It can be effectively prevented through accurate preoperative design, the inverse-rotation of flap, delayed suture and blood dropping. In the range (8.0±2.0) cm from lateral malleolus, the perforating branch of peroneal artery was constant after perforating deep fascia with suitable length and vessel diameter. Therefore, peroneal artery is the optimal choice for designing pedicled propeller flap.2. The implantation of both vancomycin-loaded calcium sulfate and autogenous bone into the lesion location of infective bone defect did not influence the control of the infection. Besides, it promoted the healing of fracture and shortened the repair time of bone defect.3. In one stage treatment of localized and diffused traumatic osteomyelitis, the scheme of combining tissue flap, vancomycin-loaded calcium sulfate and autogenous iliac bone effectively shortened the healing time of fracture, increased the healing strength, and reduced the exudation after operation, without increasing infection recurrence rate. The scheme was superior to merely implanting vancomycin-loaded calcium sulfate. Additionally, the implantation amount of calcium sulfate presented a positive correlation with reactive exudation time after operation. And the minimum amount of calcium sulfate implanted was required to containing 200 mg of vancomycm.
Keywords/Search Tags:Propeller flap, Microsurgery anatomize, Complications, Osteomyelitis, Calcium sulfate, Drug delivery system
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