Allografts with titanium cage in the treatment of tuberculous spondylitis: at least 3-year follow-up study

Background Anterior radical debridement and spinal fusion with instrumentation have been advocated in treating the spinal tuberculosis patients. But there are few long-term studies on the ecacy of fresh-frozen allografts with titanium cage in reconstruction of the anterior spinal column after debridement and decompression for tuberculosis. The purpose of this study was to evaluate the ecacy of anterior allografts with titanium cage which were stabilized with anterior or posterior instrumentation at least 3-year follow-up study. Methods A retrospective analysis of 133 patients were treated between January 2002 and December 2012. There were 71 men and 62 women. Those patients were evaluated according to clinical and radiographical record for a minimum of 3 year, including deformity correction, pain and neurologic status. The kyphosis deformity was measured on lateral radiographs according the angle between the superior endplate of the rst upper uninvolved vertebra and the rst lower uninvolved vertebra. In the lumbosacral region, the kyphosis angle was measured by two lines along the posterior border of the rst normal vertebra above the level of the lesion and posterior margin of sacrum on lateral radiographs. Clinical evaluation of back pain was evaluated and documented according to VAS pain score. Patients with neural decits were graded according to the ASIA scale. all earliest fusion follow-up. forward our last follow-up. 49 patients; 73 patients; 11 patients; patient. 3 vs. initial). Of the 44 patients who developed neural decits before their operations, 41 patients improved according to the ASIA AIS. 3 patients did not have substantial improvement and remained Grade AIS B. Conclusions Radical debridement followed by allograft with titanium cage in reconstruction of the anterior spinal column offers very satisfactory results in patients with tuberculous spondylitis. It provides immediate stability, offers lasting kyphosis correction, bypasses the donor site morbidity and diculties involved in obtaining structural autograft. plate to the adjacent unaffected which may lead to more complications or infection spread. In the current series, about 60 percent of the patients (80 of 133) had destruction of two or more vertebral bodies. And combined anterior and posterior procedure was performed for these patients. This study identied a correction of kyphosis in these patients from preoperative 23.3° to immediate postoperative 3.9°, and a nal kyphosis of 4.5°, which corresponded to a mean loss of correction of 0.8°, resulted from subsidence of titanium cage. This has shown that although the combined anterior and posterior procedure was related with prolonged operating time, more blood loss, and increased postoperative complications [40], posterior stabilization with instrumentation after anterior spinal debridement and fusion is effective in maintaining sagittal alignment over a long postoperative period.

Preoperatively, all patients were evaluated with radiographic examination and computed tomography (CT) and most of the patients were evaluated magnetic resonance imaging (MRI). Radiographic examination revealed vertebral destruction/collapse, kyphotic deformities and paravertebral abscess. CT scans mostly revealed the extent of bony destruction and location of abscess. MRI revealed vertebral destruction, collapse, paravertebral and/or psoas abscess, and spinal cord compression. The kyphosis deformity was measured on lateral radiographs according the angle between the superior endplate of the rst upper uninvolved vertebra and the rst lower uninvolved vertebra. In the lumbosacral region, the kyphosis angle was measured by two lines along the posterior border of the rst normal vertebra above the level of the lesion and posterior margin of sacrum on lateral radiographs.
All patients underwent antituberculous chemotherapy (Rifampicin, 450 mg/d; Isoniazid, 300 mg/d; Ethambutol 750 mg/d)) before surgery for 3 weeks, except those who need urgent decompression for recently developed progressive neurologic de cits. All procedures were preformed by the same surgeon (YM.L). A transpleural or retroperitoneal approach was used according to the location of infection. Perioperatively, frozen-section histopathological examination was performed to con rm the diagnose of tuberculosis, according to the presence of Langerhans giant cells, granuloma, and caseating necrosis on the histopathological sections. After radical debridement and decompression, we used titanium cages lled with crushed cancellous allograft for anterior column reconstruction. Structural stability was secured with the anterior instrumentation when one vertebra has been removed or posterior instrumentation when two or more vertebrae have been removed resulted from radical debridement. Postoperatively, patients were mobilized for six weeks with the aid of a molded Boston type brace. Postoperatively, histopathological examination and cultures of material obtained from the debridement con rmed the diagnosis of tuberculosis. All patients received antituberculous chemotherapy up to 12 months postoperatively. Liver and renal functions were monitored regularly throughout this period. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also monitored regularly to exclude the presence of infection activity.
Anteroposterior (AP) and lateral radiographs were taken immediately after surgery, 3 months, 6 months, and 12 months postoperatively, and subsequently at yearly intervals. All radiographs were evaluated by the same observer (X.W), who was blinded to the clinical outcome. The presence of allograft incorporation was determined by plain radiographs and was further veri ed by CT scans in some patients.
Clinical evaluation was done by another observer (HC.C), who was blinded to the radiographic outcome. The patients' preoperative and postoperative neurologic status was evaluated and documented according to the American Spinal Injury Association (ASIA) Impairment Scale (AIS) [15]. Clinical evaluation of back pain was evaluated and documented according to VAS pain score [16].
Descriptive statistics were used for all variables with distributions assessed for normality. The paired t-tests were conducted to compare preoperative and post-operative changes of kyphosis and VAS pain score. The Statistical Package for the Social Sciences (version 17.0 for Windows; SPSS Inc, Chicago, IL) was used for statistical analysis. The difference was considered to be statistically signi cant at the p < 0.05 level.
Of the 44 patients who developed neural de cits before their operations, 41 patients improved according to the ASIA AIS. Three patients did not have substantial improvement and remained Grade AIS B.
There were no major complications, such as implant failure, wound infection and iatrogenic neurovascular injuries. Infection control was achieved in all patients except for tuberculosis recurrence in one patient.

Discussion
The present study suggests that radical debridement followed by allograft with titanium cage in reconstruction of the anterior spinal column offers very satisfactory results in patients with tuberculous spondylitis who need for surgical intervention. It provides immediate sagittal stability, offers lasting kyphosis correction, bypasses the donor site morbidity and di culties involved in obtaining structural autograft.
Early initiation of the proper antituberculous chemotherapy coupled with immobilization leads to a favorable outcome in most patients with spinal tuberculosis [5]. Failure of nonsurgical treatment, abscess formation, neurological deterioration and progressive kyphotic deformity or instability are all indications for surgical intervention [2,6]. Goals of surgical intervention for spinal tuberculosis include alleviation of pain, spinal cord decompression, prevention and correction of deformity with spinal stabilization, and resection of the infectious paraspinal component to allow antituberculous chemotherapy to work more effectively [18].
Anterior radical debridement and fusion has been advocated for the treatment of patients with tuberculous spondylitis since 1960 [13,19,20].
Surgical debridement of the compromised anterior column results in a further loss of structural integrity that requires anterior reconstruction.
Structural autograft continues to be the historical standard in anterior reconstruction [21]. However, there may be substantial morbidity associated with the harvest of large structural autografts, such as infection, pain, and loss of structural support at the harvest site, in addition to the limited supply of structural autograft that makes it di cult or impractical in many patients with tuberculous spondylitis who require surgical treatment [22]. Other options available for anterior column reconstruction include structural allograft or titanium cages lled with crushed cancellous allograft and autograft [14,23]. Titanium cages have been shown to be effective for anterior column reconstruction of spine in traumatic, pathologic and infection [23][24][25][26]. The titanium cage can be lled with autograft in addition to crushed cancellous allograft that can allow rapid incorporation of the graft. The cage with bone grafts allows for a more solid xation construct and minimizes the risk of graft dislodgement or subsidence that are well documented complications when structural bone graft alone is used [11,12,[27][28][29]. It also provides safer stability than structural bone graft alone in the infection region that allows tissue rest and earlier mobilization [12,27]. Our consideration for using titanium cages lled with crushed cancellous allograft/and autograft was to overcome the morbidity associated with structural autograft and the slow rate of graft incorporation associated with structural allograft. This study identi ed a correction of kyphosis from preoperative 20.8° to immediate postoperative 3.9°, and a nal kyphosis of 4.7°, which corresponded to a mean loss of correction of 0.8°, resulted from subsidence of titanium cage. This has shown that the titanium cage is effective in maintaining sagittal alignment over a long postoperative period.
The criteria described by Bridwell et al is probably the gold standard in assessing the completeness of bony fusion for the high intraobserver and interobserver agreement [17,30]. As the Bridwell criteria were initially described to identify bony fusion in cases of strut allograft rather than titanium cages, we modi ed it in this study considering that the achievement of bony healing of compromised vertebra despite the presence of remodeling may be the more important factor for the ultimate outcome of spinal tuberculosis. The duration of biologic incorporation of allografts is of clinical importance because it may be slow and unpredictable, resulted from immunological responses to donor antigens [31,32]. This study identi ed a Grade 1 or 2 allograft incorporation in 92% of the patients, suggesting that immunological responses does not hinder the development of solid bony fusion, and that the achievement of this solid bony fusion despite the duration of allograft incorporation may be the more important factor for the ultimate outcome of spinal tuberculosis.
Implantation of metallic instrumentation into the infected region, however, is a matter of debate because although implants help provide structural stability, the presence of foreign material in an area of mycobacterial infection may interfere with successful eradication of infection [12,27,28]. There were experimental studies suggest that Mycobacterium tuberculosis, unlike pyogenic bacteria, has low adherence to metal and forms less polysaccharide bio lm [33,34]. Therefore, the use of metal implants in the region of mycobacterial infection may be relatively safe [9]. This study identi ed tuberculosis recurrence only in one of 133 patients, suggesting that implantation of titanium cages into the region of mycobacterial infection have lower infection risk. Furthermore, we believe that the reconstruction of unstable spinal segments offered by this method may resulted in a more favorable environment for control of infection, graft incorporation, and solid bony fusion.
Although the anterior instrumentation offers more reliable restoration of structural stability compared with posterior instrumentation [35], in patients with two or more severe vertebral destruction that may lead to signi cant kyphotic deformity [36], either the anterior or posterior instrumentation alone may be insu cient theoretically, and a combined anterior and posterior instrumentation should be more reliable in preventing the development of kyphotic deformity [20,37,38]. There were researches suggest that when two or more vertebrae have been removed resulted from radical debridement, the grafts are prone to failure or resorption [12], and supplemental posterior fusion and instrumentation is an reinforcement to anterior instrumentation and helpful to arrest the infection, correct the kyphosis, prevent progression of kyphosis and promote early fusion [37][38][39]. Furthermore, the surgical dissection should be wider to x the anterior plate to the adjacent unaffected vertebrae, which may lead to more complications or infection spread. In the current series, about 60 percent of the patients (80 of 133) had destruction of two or more vertebral bodies. And combined anterior and posterior procedure was performed for these patients. This study identi ed a correction of kyphosis in these patients from preoperative 23.3° to immediate postoperative 3.9°, and a nal kyphosis of 4.5°, which corresponded to a mean loss of correction of 0.8°, resulted from subsidence of titanium cage. This has shown that although the combined anterior and posterior procedure was related with prolonged operating time, more blood loss, and increased postoperative complications [40], posterior stabilization with instrumentation after anterior spinal debridement and fusion is effective in maintaining sagittal alignment over a long postoperative period.
Our study is mainly limited by the retrospective study and the absence of a control group. As the result of infrequent condition of spinal tuberculosis, it is nearly impossible to conduct a prospective study with a rational timepoint for completion. The fact that all patients were operated on by the same surgeon and were observed for a mean > 3 years by two blinded independent observers may allow us to draw meaningful conclusions.

Conclusion
Radical debridement followed by allograft with titanium cage in reconstruction of the anterior spinal column offers very satisfactory results in patients with tuberculous spondylitis. It provides immediate stability, offers lasting kyphosis correction, bypasses the donor site morbidity and   Graft intact with no lucencies at the top or bottom, but without full healing of compromised vertebra.

Figure 3
Fusion, graft intact but de nite lucency at bottom of the titanium cage.