Risk factor analysis for progressive spinal deformity after resection of spinal cord tumors─a retrospective study of 272 cases

OBJECTIVE: Progressive spinal deformity has become a well-recognized complication of spinal cord tumors (SCTs)resection. However, the factors affecting post-operative spinal stability remain to be further research. Here, we described the current largest series of risk factors analysis for progressive spinal deformity following resection of SCTs. METHODS: We retrospectively analyzed the medical records of the patients with resection of SCTs between January 2009 and December 2018.All patients who underwent resection of spinal cord tumors performed regular postoperative follow-up were identified and included in the study. Clinical, radiological, surgical, histopathological, and follow-up data were collected. The incidence of postoperative progressive kyphosis or scoliosis was calculated. The statistical relationship between postoperative progressive spinal deformity and radiographic, clinical, and surgical variables was assessed by using univariate tests and multivariate logistic regression analysis. RESULTS: Two hundred seventy-two patients (mean age 42.56 ± 16.18 years)with median preoperative modified McCormick score of 3 met the inclusion criteria. Among them, 72.6%patients were found to have spinal deformity preoperatively, and the extent of spinal deformity in these 7 patients deteriorated after surgery. 36 (13.2%) were new cases of postoperative progressive deformity. The mean duration of follow-up was 21.8 months (median 14 months, range 6– 114 months). In subsequent multivariate logistic regression analysis, age≤18 years(p=0.027), extent of tumor involvement(p = 0.019)and preoperative spinal deformity(p=0.008)was the independent risk factors (p < 0.05), increasing the odds of postoperative progressive spinal deformity by 3.94- , 0.69- and 27.11-fold, respectively. CONCLUSIONS: The incidence of postoperative progressive spinal deformity was 15.8%, mostly in these patients who had younger age (≤18 years), tumors involved in multiple segments and preoperative spinal deformity. The risk factors of postoperative progressive


Introduction
Primary spinal cord tumors are rare, with an incidence of 0.76 per100,000 in the United States [1]. Advances in intraoperative neuroelectrophysiological monitoring and microsurgical techniques have contributed to the success rate of SCTs resection, which increases long-term survival and improves the quality of life of patients with spinal cord tumors [2,3].However, with improved survival and longer follow-up times, patients often develop progressive spinal deformity postoperatively in the years after surgery, and which cause postoperative pain, reoperation and neurologic compromise in patients. It is reported that incidence of spinal deformity following intradural spinal tumor resection up to 10% in adults and rates ranging from 16% to 100% in pediatric patients [4][5][6][7]. Some repotes suggested that laminoplasty resulted in less spinal deformity for the partial restoration of the posterior tension band [4]. But recent studies indicated that the incidence of postoperative spinal deformity associated with laminoplasty is close to laminectomy [8][9][10]. In fact, the study about risk factors for progressive spinal deformity after SCTs resection using the laminoplasty or laminectomy has been conducted. However, limited by small samples and absence of multivariate analysis in previous studies, the convincing risk factors are still unclear. We undertook this larger retrospective study to furthermore determine the risk factors which may result in the higher incidence of progressive spinal deformity after surgical treatment of SCTs. preoperatively and at the last follow-up [11].

Patients And Methods
The key endpoint of this study was the occurrence of progressive spinal deformity ( Figure   1). Progressive spinal deformity was defined as the progression of kyphotic or scoliotic curves by at least10°on 2 or more consecutive radiographs. Preoperative coronal Cobb angles > 10°, less of cervical/lumbar lordosis and kyphosis of the cervical/thoracic/ lumbar spine before SCTs resection were classified as preoperative spinal deformity. Progressive spinal deformity was first treated conservatively, followed by two more consecutive radiographic studies.

Surgical Technique
Laminoplasty or laminectomy were used in the period of this study, and most of the surgical procedures were similar in the two operation. Firstly, the lamina was exposed by dissecting the subperiosteal paraspinal muscle. The facet joint capsules were maintained.
The interspinous and supraspinal ligaments between the levels of rostral and caudal were resected. To protect the ligamentum flavum and interspinous ligaments, the spinous processes of the planned laminoplasty segment were left intact. A purchase grove for the osteotome footplate and identification of the dura before drilling was made by small interlaminar fenestrations and partial laminotomies using a 2-mm Kerrison punch at the caudal edge of the caudal-most lamina. Bilateral laminotomies that spanned the entire laminoplasty segment were performed in a caudal-to-rostral direction. The ligamentum flavum was removed with a Kerrison laminectomy rongeur. Secondly, to expose and remove the tumor, the midline dural spanning the entire length of the tumor was incised.
After resection of the tumors, careful hemostasis and closure of the primary dural, the laminae were restored together and then connected with titanium microplates. Lastly, the paraspinal muscles that were reapproximated to the laminae were sutured to the deep interspinous ligaments. For these patients who underwent laminectomy the entire length of the tumor laminae was removed. Facetectomy was not performed in any patients who underwent laminectomy in this study. Sensory-evoked and motor-evoked potentials were continuously detected during surgery in all cases.
In most cases, gross-total resection of the tumor, defined as excision of ≥95% of the tumor or absence of residual enhancement on postoperative MRI, was performed. In other cases, subtotal resection (80%-95% resection) were made when the tumors invaded some more important tissues. Meanwhile, immediate postoperative MRI may detect retained fragment. Partial resection (removal of < 80% of the tumor) only occurred rarely when the tumor margin could not be clearly defined during surgery.

Statistical Analysis
For intergroup comparison, the Student t test was used for parametric data and the Mann-Whitney U test for nonparametric data. Percentages were compared via the chi-square test or the Fisher exact test. In univariate analysis, variables with p 0.2 entried into subsequent multivariate logistic regression analysis to determine the more important risk factors. Differences were considered significant with p < 0.05. The results are presented as odds ratio (OR) and 95% confidence intervals. Analyses were performed using IBM SPSS Statistics 20 (IBM Corp., Armonk, New York, USA).

Patient Characteristics
Two hundred and seventy-two patients underwent SCTs resection were reviewed in this study. Demographic, clinical, and surgical features are summarized in Table 1 One patient underwent chemotherapy before surgery.

Surgical and tumor characteristics
The extent of surgical resection was depended on the extent of tumor involvement.

Risk Factors for Progressive Spinal Deformity
In the univariate analysis, age (p = 0.000),sex(p=0. Papagelopoulos et al. [13,14] reported that the incidence of spinal column deformity was 33% in children and adolescents while 8% in young adults. Recently, Wei Shi et al. [14] reported that patient age ≤ 25 was the main significant predictive risk factor for postoperative spinal deformity. These data were consistent with our results that pediatric patients (≤ 18 years of age) were more likely to suffer from postoperative progressive spinal deformity than the older adults (> 18 years of age). We speculated that the pediatric patient's immature skeletal system as well as surgery itself may change the mechanics of the spine, contributing to this phenomenon. In additionbecause the growth rate of bone growth in children was greater than the spinal cord, adhesions in the postoperative area may cause a phenomenon similar with tethered cord syndrome, which caused related muscle neurotrophic decline that contributed to the development of spinal deformity.
Many previous studies demonstrated that extent of surgery resection (no. of spinal levels) was related to progressive spinal deformity. Katsumi et al. [15]revealed that age at operation, preoperative curvature in neutral position, number of removed laminas, C2 laminectomy, and destruction of facet joints are the risk factors that are involved in the pathogenetic mechanism of cervical instability. However, in our research, our data showed that not the extent of surgery resection, but the extent of tumor involvement may cause instability of the spine. The study revealed the average level of tumor involvement was 3.4 in patients who had progressive spinal deformity, comparing with 2 who had not. The risk factor of the extent of tumor involvement increased the odds of postoperative progressive spinal deformity by 0.69-fold. The more levels of tumor involvement, the more severe compression of the spinal cord, which may led to neurotrophic decline that aggravated the occurrence of spinal deformity.
Preoperative spinal deformity was independently associated with development of postoperative spinal deformity [16]. Similarly, Kaptain GJ et al. [14,17] reported that the presence of preoperative spinal deformity was the factor most significantly related to the risk of developing progressive spinal deformity. Our research drawed the same conclusion.
Preoperative spinal deformity even increased the odds of postoperative progressive spinal deformity by 27.11-fold, and it was the biggest risk factor in the occurrence of postoperative spinal deformity. We speculated that it may result from the spinal cord compression of spinal cord from by the spinal cord tumors, which in turn led to neurotrophic disorders of the paravertebral muscles of at the corresponding segments.
The imbalance of paravertebral muscle strength eventually caused a decrease in the stability of the spine.
Riseborough et al. [18] reported that the greater amount of irradiation could lead to more severe deformity of the spine. Although the prior radiotherapy was not analyzed because of few relevant cases in our study, we found the patients with spinal deformity were more likely to suffer from preoperative puncture or biopsy, which might destroy the stability of the spine to some extent. Moreover, in the univariate analysis, extent of surgery resection involvement was also significantly higher in patients with spinal deformity than that without spinal deformity. However, in subsequent multivariate analysis, we found that  [16,19]. Our research also showed this trend (pathology, p=0.085; surgeon, p= 0.078), but they did not reach statistical significance. In addition, our study showed that methods(laminectomy or laminoplasty, p= 0.746) didn't affect the occurrence of postoperative progressive spinal deformity.

Conclusions
We found that the patients who had younger age (< 18 years), tumors involved in multiple

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