EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: This paper aimed to study the feasibility, the surgical methodology, and technique for reconstruction using allogeneic sternal graft after sternum tumor resection.

Materials and Methods: Three patients (2 men and 1 woman, aged 19, 44, and 52) with primary sternum malignant tumor were admitted from January 2008 to December 2010 to the Second Hospital of Shandong University, Jinan, China. We conducted subtotal resection of the sternum and simultaneous reconstruction with allogeneic sternal graft. Allogeneic sternum was frozen beforehand; the scope of removal was 2 cm away from the lesion. Transplanted allogeneic sternum was fixed using steel wire and residual cavity was filled with the greater omentum.

Results: Three patients recovered without major complication and were discharged from the hospital with successful operation and satisfactory results. They were followed-up for 6 months to 2 years, no tumor relapse or any obvious rejection were found.

Conclusions: The freezing allogeneic sternum can be used as a substitute for reconstruction after sternum tumor resection.

Key words : Freezing allogeneic sternum, Transplant, Surgical resection

Primary malignant tumors of the sternum are rare, accounting for only 9 of 2004 (0.45%) primary bone tumors in the Leeds Bone Tumor Registy.¹ Most sternum tumor cases, benign or malignant, surgical resection seems to be the most common form of treatment when possible. The goal of surgery is to ressect the tumor with a wide margin of normal tissue, ensuring that all tumor cells have been excised and resulting in local disease control. Removal of the sternum for a malignant tumor results in a large defects in bone and soft tissue, causing deformity and paradoxical movement of the chest wall, so reconstruction was done at the same time. However, there is figurative literature about reconstruction methods after sternum resection. Some artificial materials, such as organic glass plate, steel plate, titanium mesh, and autologous tissue (autologous bone and muscle flap) were used as alternative material,^2-5 each has advantages and disadvantages. In this study, 3 patients underwent sternum resection and reconstruction using allogeneic graft, which produced satisfactory clinical results.

Materials and Methods

All clinical trials involving human subjects were approved by the ethics committee of the institution before the study began, and that the protocols conformed to the ethical guidelines of the 1975 Helsinki Declaration. Written informed consent was obtained from patients.

Three patients with 2 to 4 months’ history, including 2 men and 1 woman and aged 19, 44, and 52, were admitted from January 2008 to December 2010 to the Second Hospital of Shandong University, Jinan, China. On physical examination an anterior sternal mass whose maximum diameter was 8 to 10 cm was found and tenderness was obvious. Routine blood test and urinalysis were unremarkable, and alpha-fetoprotein levels were normal. Radiograph, chest computed tomography (CT) scan, 3-dimensional reconstruction of sternum CT and Emission Computed Tomography electroconvulsive therapy examinations were given. Osteolytic and destructive lesion, expansive growth of tumor and discontinuity of bone cortex could be seen clearly (Figures 1 and 2). Based on clinical findings and imaging characteristics, the tumors were diagnosed as primary bone tumor arising from the body of the sternum.

The allogeneic sternum, donated by the accidental death, was from our hospital cryogenic laboratory, the sternums were chemically sterilized and cryopreserved and transported with liquid nitrogen tank (Figure 3). The desired size of the donor sternum was chosen by them according to the patient`s gender, age, and height. All the programs comply with medical ethics standards.

The patients underwent a mid-sternal thoracotomy and received subtotal sternum. The skin and subcutaneous tissue were cut, free to both sides along the sternum film to expose rib cartilage and costal arch, the rib cartilage, costal arch and intercostal muscle, and internal thoracic arteries and veins were ligated. At the same time, refrigerated homograft sternum was taken out of nitrogen canister storage and rewarmed under room temperature. Soft tissues and anadems attached to the bone were cleared with a periosteal elevator or knife blade to minimize immunologic rejection. The homograft sternum was washed with sterile saline and anilin repeatedly, trimmed properly to match the defect of chest and sutured with steel-wire, clavicle to manubrium sterni, costal cartilage to costal cartilage and costal arch to lower body of sternum (Figure 4). The greater omentum was freed and moved up to fill the space around sternum. A drainage tube with porosity was placed in the rear of homograft sternum.

No immunosuppressive agent was used in these patients. Two patients recovered smoothly and were discharged from the hospital within 2 weeks. A small range of effusion was found under subcutaneous in another patient, no sign of infection was detected. The patient was completely cured and released from the hospital after incision dressing. Pathologic examination showed plasma cell myeloma and giant cell tumor. Chest CT examination was given after 3 to 5 months after operation, the bone graft healed well without sequestrum, decalcification, and significant rejection. We conducted follow-up observation for 6 months to 2 years, and the patients lived a tumor-free life without relapse. At present, 2 patients have been lost to follow-up and 1 patient with giant cell tumor is still alive, whose CT scan represents a satisfactory result (Figures 5 and 6).

Sternum tumor is rare, the incidence rate of the chest wall bone tumors accounts for about 2% to 10% of the whole body bone tumors, of which 80% are located in the caste and coastal cartilage, and 20% in the sternum. With complex tissue origins and multiple pathological types, sternum tumors are mostly malignant, approximately 60% of primary malignant ones and 40% for metastatic ones. Sternal tumors generally have the typical symptoms and signs. Sternum lumps and subsequent chest pain are found on physical examination. The diagnosis depends on biopsy, and chest CT and radiograph can confirm the diagnosis. Although with postoperative recurrence, surgical excision is the preferred treatment options. Although radiotherapy was found as an effective treatment in some cases,6 chemotherapy and radiotherapy have not been shown effective.^7-10 In surgeries, tumor tissues should be resected as complete as possible, and adjacent normal tissue be removed as well. Surgical margin should be 2 to 5 cm away from the tumor.^11,12 Generally, extended resection is needed to avoid relapse of tumor, including removal of total or partly sternum, normal tissue around the tumor such as cartilage, rib, clavicular head and pectoralis major, even some benign tumors such as enchondrosis and fibroma, which have invasive growth characteristics should be resected extensively.

Reconstruction is very important after sternal resection. The patients’ respiratory and circulatory function are affected adversely after the sternum tumor was completely or subtotally removed due to the destruction of the integrity of the thorax. For those who have smaller damaged area, pectoralis, or pedicled muscle flap, Marlex mesh, PROLENE mesh, or polyester fabric are available, but if a patient’s sternal damage covers more than half of sternum, especially for those whose sternum requires full resection, or chest wall defects ranged over 6 × 6 cm and more than 3 neighboring costae are damaged, hard materials for reconstruction should be used¹⁰ to protect the lungs, heart, and main vessels, and to restore functional thoracic movement to prevent paradoxical respiration.^13,14

The ideal reconstruction materials should meet the following requirements: (1) hardness and stability to prevent floating chest wall, (2) good histocompatibility and can stay in the body for a long time, (3) easy to be cut, and fixed, (4) can be disinfected, and (5) can penetrate retrograph. Materials of reconstruction mainly include autologous and allogeneic tissues or artificial materials. In the literature, hard materials such as allogeneic sternum, autologous iliac bone or rib, titanium steel plate, organic glass plate and artificial biomimetic bone have been reported. Although with no rejection and best performance in matching with human’s physiology, disadvantages of autologous tissues such as increasing trauma, prolonging surgical time, and having limited availability of alternative materials are difficult to solve. The allogeneic sternum, fully comply with the above 5 conditions, not only ensure maximum removal of lesions of the sternum, but also is closer to the physiological state without increasing trauma.

The fresh allogeneic sternum contains more surviving cells of presenting antigen directly, which can induce strong immune rejection of host. While the allogeneic sternum, after chemical sterilization, was frozen to -70°C, so that its plasmin activity was lost and immune activity was significantly reduced with good histocompatibily.¹⁵ Deep hypothermia does not change the mechanical properties of the allograft bone, the damage the osteoinductive activity, and the integration with the host bone. Without own osteogenic ability, allogeneic sternum healing relies mainly on the role of bone conduction and bone induction.¹⁶ Bone conduction is that host bone tissue grow along the implantation of allogeneic sternum in bone repair, while allogeneic one was gradually absorbed by osteoclasts, thereby new bone tissue of specific shape appear in the region of the original frame, instead of the allogeneic one healing with host one, this is the theory of creeping substitution. Bone induction is that mesenchymal tissue in transplant sternum parts differentiate and proliferate to new bone by inducible factor. Numerous studies confirmed that bone morphogenetic proteins factor have a strong bone-inducing activity. Bone morphogenetic proteins in matrix can induce host mesenchymal cells into osteogenic factor and formation of new bone tissue in absorbed parts. Chronic rejection of frozen allogenic sternum immune response is through T-cell–mediated immunity. Rejection of allogenic sternum is reduced primarily by the following 3 ways: (1) transplant sternum antigen, we chose the deep-frozen bone, and try to remove periosteum and soft tissue of allogeneic sternum to reduce its antigenicity; (2) donor and host tissue matching, this is not feasible in clinic; and (3) apply immuno-suppressants. The immune activity was significantly reduced with good histocompatibility, deep hypothermia does not cause significant change in the mechanical properties of allogeneic bone, nor adversely affects the bone inducing activity of transplant sternum with the host bone integration.

With satisfactory short-term effect, our experiences are that the surgical method is easy without obvious rejection (no immunosuppressive agent was used in these 3 patients), greater omentum can be pulled upward to rear of allogeneic sternum to fill the residual cavity that can eradicate dead space and avoid partial effusion and infection.

We have obtained some preliminary experience in clinical practice using allogeneic sternal graft for sternum reconstruction and our surgeries turned out to be successful. However, long-term effect needs to be followed-up, and more clinical cases should be assessed, and few studies report on experiments and clinical researches of allogeneic sternal graft are available, studied in future should be done in biological, immunological changes and other basic issues after operation.

Volume: 14 Issue: 3 June 2016

FULL TEXT