Tomoyuki Akamaru

Surgical Strategy for Spinal Metastases

Study Design. A new surgical strategy for treatment of patients with spinal metastases was designed, and 61 patients were treated based on this strategy. Objectives. To propose a new surgical strategy for the treatment of patients with spinal metastases. Summary of Background Data. A preoperative score composed of six parameters has been proposed by Tokuhashi et al for the prognostic assessment of patients with metastases to the spine. Their scoring system was designed for deciding between excisional or palliative procedures. Recently, aggressive surgery, such as total en bloc spondylectomy for spinal metastases, has been advocated for selected patients. Surgical strategies should include various treatments ranging from wide or marginal excision to palliative treatment with hospice care. Methods. Sixty-seven patients with spinal metastases who had been treated from 1987–1991 were reviewed, and prognostic factors were evaluated retrospectively (phase 1). A new scoring system for spinal metastases that was designed based on these data consists of three prognostic factors: 1) grade of malignancy (slow growth, 1 point; moderate growth, 2 points; rapid growth, 4 points), 2) visceral metastases (no metastasis, 0 points; treatable, 2 points: untreatable, 4 points), and 3) bone metastases (solitary or isolated, 1 point; multiple, 2 points). These three factors were added together to give a prognostic score between 2–10. The treatment goal for each patient was set according to this prognostic score. The strategy for each patient was decided along with the treatment goal: a prognostic score of 2–3 points suggested a wide or marginal excision for long-term local control; 4–5 points indicated marginal or intralesional excision for middle-term local control; 6–7 points justified palliative surgery for short-term palliation; and 8–10 points indicated nonoperative supportive care. Sixty-one patients were treated prospectively according to this surgical strategy between 1993–1996 (phase 2). The extent of the spinal metastases was stratified using the surgical classification of spinal tumors, and technically appropriate and feasible surgery was performed, such as en bloc spondylectomy, piecemeal thorough excision, curettage, or palliative surgery. Results. The mean survival time of the 28 patients treated with wide or marginal excision was 38.2 months (26 had successful local control). The mean survival time of the 13 patients treated with intralesional excision was 21.5 months (nine had successful local control). The mean survival time of the 11 patients treated with palliative surgery and stabilization was 10.1 months (eight had successful local control). The mean survival time of the patients with terminal care was 5.3 months. Conclusions. A new surgical strategy for spinal metastases based on the prognostic scoring system is proposed. This strategy provides appropriate guidelines for treatment in all patients with spinal metastases.

Adjacent segment motion after a simulated lumbar fusion in different sagittal alignments: a biomechanical analysis.

Study Design. An in vitro biomechanical study of adjacent segment motion (at L3–L4 and L5–S1) after a simulated lumbar interbody fusion of L4–L5 in different sagittal alignments was carried out. Objectives. To test the hypothesis that an L4–L5 fixation in different sagittal alignments causes increased angular motion at the adjacent levels (L3–L4 and L5–S1) in comparison with the intact spine. Summary of Background Data. Clinical experience has suggested that lumbar fusion in a nonanatomic sagittal alignment can increase degeneration of the adjacent levels. It has been hypothesized that this is the result of increased motion at these levels; however, to the authors’ knowledge no mechanical studies have demonstrated this. Methods. Eight fresh human cadaveric lumbar spines (L3–S1) were biomechanically tested. Total angular motion at L3–L4 and L5–S1 under flexion-extension load conditions (7-Nm flexion and 7-Nm extension) was measured. Each specimen was tested intact, and then again after each of three different sagittal fixation angles (at L4–L5): (1) in situ (21°lordosis), (2) hyperlordotic (31°lordosis), and (3) hypolordotic (7°lordosis). The simulated anterior/posterior fusion was performed at L4–L5 with pedicle screws posteriorly, vertebral body screws anteriorly, and an interbody dowel. Results. The averaged values for flexion-extension motion at L3–L4 were as follows: intact specimen 2.0°, in situ fixation 4.0°, hyperlordotic fixation 1.7°, hypolordotic fixation 6.5°. The averaged values for flexion-extension motions at L5–S1 were as follows: intact specimen 2.3°, in situ fixation 2.6°, hyperlordotic fixation 3.6°, hypolordotic fixation 2.9°. Conclusion. Hypolordotic alignment at L4–L5 caused the greatest amount of flexion-extension motion at L3–L4, and the differences were statistically significant in comparison with intact specimen, in situ fixation, and hyperlordotic fixation. Hyperlordotic alignment at L4–L5 caused the greatest amount of flexion-extension motion at L5–S1, and the difference was statistically significant in comparison with intact specimen but not in situ fixation or hypolordotic fixation.

The Effect of Bone Morphogenetic Protein-2 on Rat Intervertebral Disc Cells in Vitro

Study Design. An in vitro experiment to determine the molecular and cellular effect of recombinant human bone morphogenetic protein-2 on cultured rat intervertebral disc cells was performed. Objectives. To determine the effect of recombinant human bone morphogenetic protein-2 on cell proliferation, production of sulfated-glycosaminoglycan, and the expression of genes specific for chondrocytes (Type II collagen, aggrecan, and Sox9) in cultured rat intervertebral disc cells. Summary of Background Data. Intervertebral disc degeneration is associated with cellular and biochemical changes, which include decreased synthesis of cartilage specific gene products such as Type II collagen and aggrecan. Although bone morphogenetic protein-2 is known to induce chondrogenesis during new bone formation, the effects on intervertebral disc cells have not been characterized. Method. Cells were isolated from the anulus fibrosus and transition zones of lumbar discs from Sprague-Dawley rats. The cells were grown in monolayer and treated with recombinant human bone morphogenetic protein-2 (0, 10, 100, 1000 ng/mL) in Dulbecco’s Modified Eagle Medium/F-12 with 1% fetal bovine serum (day 0). On days 2, 4, and 7 after recombinant human bone morphogenetic protein-2 treatment, sulfated-glycosaminoglycan content in the media was quantified using 1,9-dimethylmethylene blue staining. The results were normalized according to culture duration and cell number. On day 7, mRNA was extracted for reverse transcriptase-polymerase chain reaction and real-time polymerase chain reaction to quantitate mRNAs of Type I collagen, Type II collagen, aggrecan, Sox9, osteocalcin, and glyceraldehyde phosphate dehydrogenase. Cell number was determined with a hemocytometer. Results. Recombinant human bone morphogenetic protein-2 at 100 and 1000 ng/mL yielded a 17% and 42% increase in cell number on day 4, and a 59% and 79% on day 7, respectively. Recombinant human bone morphogenetic protein-2 at 10 ng/mL had no effect on cell number. Sulfated-glycosaminoglycan increase was greatest at day 7, increasing by 1.3-, 2.1-, and 3.6-fold with recombinant human bone morphogenetic protein-2 treatments of 10, 100, and 1000 ng/mL, respectively. Increases in mRNA levels of Type II collagen, aggrecan, Sox9, and osteocalcin were observed with recombinant human bone morphogenetic protein-2 concentrations of 100 and 1000 ng/mL on day 7 as determined by reverse transcriptase-polymerase chain reaction. No detectable increase in mRNA level of Type I collagen was observed with any levels of recombinant human bone morphogenetic protein-2. Real-time polymerase chain reaction showed the greatest effect at 1000 ng/mL recombinant human bone morphogenetic protein-2, leading to an 11.5-fold increase in aggrecan, a 4.6-fold increase in Type II collagen, a 5.3-fold increase in Sox9, and a 1.9-fold increase in osteocalcin mRNA above untreated controls at day 7. Conclusion. The results of this study show that recombinant human bone morphogenetic protein-2 enhances disc matrix production and chondrocytic phenotype of intervertebral disc cells. Recombinant human bone morphogenetic protein-2 increases cell proliferation and sulfated-glycosaminoglycan (proteoglycan) synthesis. It increases mRNA of Type II collagen, aggrecan, and Sox9 genes (chondrocyte specific genes), and osteocalcin, but not Type I collagen or glyceraldehyde phosphate dehydrogenase.

Simple carrier matrix modifications can enhance delivery of recombinant human bone morphogenetic protein-2 for posterolateral spine fusion

Study Design. A nonhuman primate lumbar intertransverse process arthrodesis model was used to evaluate modifications to a plain collagen sponge to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2). Objectives. To evaluate the feasibility of enhancing the delivery of rhBMP-2 with the established collagen sponge carrier by adding biphasic ceramic phosphate (BCP) granules (15% hydroxyapatite, 85% tricalcium phosphate) or allograft chips to provide compression resistance for posterolateral spine arthrodesis. Summary of Background Data. Recombinant human bone morphogenetic protein-2 was successfully delivered with a resorbable collagen sponge in a rabbit intertransverse process fusion model. Success in nonhuman primates required a higher dose (6–9 mg) of rhBMP-2 and a more compression-resistant matrix (ceramic) than plain collagen. The limitation of the ceramic carrier was its radiopacity, which made radiographic detection of new bone formation difficult. Methods. Nine adult rhesus monkeys underwent bilateral posterolateral intertransverse process arthrodesis at L4-L5. The animals were divided into three groups (n = 3 each) based on the graft material implanted: 1) autogenous iliac crest bone (5 cm3/side); 2) collagen sponge and 15:85 BCP granules loaded with rhBMP-2 (3 mg/side); and, 3) collagen sponge and allograft chips loaded with rhBMP-2 (3 mg/side). The monkeys were killed 24 weeks after surgery. Inspection, manual palpation, radiography, computed tomographic scans, and histology were used to assess fusion. Results. All six monkeys with rhBMP-2 delivered in the collagen/15:85 BCP carrier and the collagen/allograft chips carrier achieved solid spine fusions, whereas only one of three animals fused with autogenous bone graft. Histologic analysis of the bone induced by rhBMP-2 showed normal trabecular bone and bone marrow elements. Conclusions. The addition of either 15:85 BCP granules or allograft bone chips to the existing resorbable collagen sponge matrix enhanced delivery of rhBMP-2 in the posterolateral spine. The combination matrices were more compression resistant and had improved radiographic resorption properties that permitted easy radiographic visualization of new bone. In addition, a lower dose of rhBMP-2 (3 mg/side) was successful compared with the dose previously used with the plain collagen sponge (6 mg/side).

Influence of acute shortening on the spinal cord: an experimental study.

Study Design. Morphometric changes of the spinal cord and influence on spinal cord-evoked potentials and spinal cord blood flow and postoperative function of hind limbs were studied in various degrees of acute spinal column shortening in dogs. Objectives. To study the morphometric and physiologic effects of acute spinal column shortening on the spinal cord. Summary of Background Data. The technique of acute spinal column shortening is sometimes applied for correction of spinal deformity, total en bloc spondylectomy operation, or other diseases. However, safe limits and physiologic effects of acute spinal column shortening have not yet been described. Methods. Total spondylectomy of T13 was performed in dogs after spinal instrumentation placed 2 levels above and 2 levels below the spondylectomy level. Spinal column was gradually shortened until the lower endplate of T12 contacted the L1 upper endplate (maximum of 20 mm). When any morphologic change of the dural sac or the spinal cord was observed, the length of shortening was measured. Spinal cord-evoked potentials were recorded on the exposed dura mater following epidural stimulation at the C7 level in 8 dogs. Spinal cord blood flow was measured during shortening in 6 dogs. Hindlimb function was evaluated 2 weeks after operation in 10 dogs. Results. No morphometric changes occurred in the dural sac and the spinal cord until shortening of 7.2 ± 1.7 mm (n = 6). From 7.2 ± 1.7 to 12.5 ± 1.1 mm shortening, the dural sac was deformed, whereas the spinal cord maintained its shape. Shortening more than 12.5 ± 1.1 mm buckled the dural sac, and the spinal cord kinked itself and was compressed by the buckled dura in its concave side (n = 6). No changes could be detected in spinal cord-evoked potentials in 5 or 10 mm of shortening. Spinal cord-evoked potential changes were recorded in the 2 of 6 dogs with 15 mm of shortening. At 20 mm of shortening, spinal cord-evoked potential abnormality was observed in 4 of 6 dogs. At shortening of 5, 10, 15, and 20 mm, spinal cord blood flow was 146 ± 10%, 160 ± 21%, 102 ± 17%, and 93 ± 7% of the control (29.2 ± 7.9 mL/100 g/min, n = 6), respectively. All 3 dogs with 10 mm ofshortening had normal hindlimb function 2 weeks after operation. One of the 3 dogs with 15 mm of shortening had paraparesis. Three of the 4 dogs with 20 mm of shortening had also paraparesis after operation. Conclusions. Acute spinal column shortening can be characterized into 3 phases. Phase 1, safe range: occurred during shortening within one-third of the vertebral segment and is characterized by no deformity of the dural sac or the spinal cord. Phase 2, warning range: occurred during spinal shortening between one-third and two-thirds of the vertebral segment and is characterized by shrinking and buckling of the dural sac and no deformity of the spinal cord. Phase 3, dangerous range: occurred after shortening in excess of two-thirds of the vertebral segment and is characterized by spinal cord deformity and compression by the buckled dura. Spinal shortening within the safe range increases spinal cord blood flow.

Effect of tail suspension (or simulated weightlessness) on the lumbar intervertebral disc: study of proteoglycans and collagen.

Study Design. An experiment to measure the proteoglycan and collagen content of the lumbar intervertebral discs of rats that had been tail-suspended for up to 4 weeks. Objectives. To determine the effect of tensile force (or simulated weightlessness) on the intervertebral disc. Summary of Background Data. During space flight the intervertebral disc experiences low compressive force (because of so-called “weightlessness”), which, in turn, produces, among other things, low hydrostatic pressure acting on the disc cells. Although disc cells respond (in vitro) to changes in hydrostatic pressure, it is unclear what effect low levels of hydrostatic pressure have in vivo and whether they lead to a degenerative catabolic process. The rat tail-suspension model is appropriate for studying the effects of tensile force on the disc. The disc (especially the anulus) is subjected to tension during various body movements (e.g., bending stretches the posterior anulus, and twisting tensions the whole anulus). Methods. Thirty-two Sprague–Dawley rats were tail-suspended for either 2 weeks (16 rats) or 4 weeks (16 rats). Sixteen other rats were left unsuspended for 4 weeks; these were used as controls. At the end of 2 or 4 weeks, as appropriate, the rats were killed and their lumbar spines were removed. In each rat the six lumbar discs were bisected and the discs (anulus and nucleus together) were carefully removed. The six lumbar discs from one rat were pooled with the six lumbar discs of a second matching rat (i.e., from the same group) to give one sample. The disc samples were then assessed using enzyme-linked immunosorbent assays. Results. There was a 35% statistically significant decrease in proteoglycan content going from the control group down to the 4-week group, but no significant differences between the control group and the 2-week group or between the 2-week group and the 4-week group. There were no statistically significant differences between the three groups for collagen I or collagen II. Conclusions. These findings clearly establish a link between decreased proteoglycan content and tension on the disc, as modeled by the tail-suspended rat.

Transdiscal L5-S1 screws for the fixation of isthmic spondylolisthesis: a biomechanical evaluation.

The current study is a biomechanical study using a cadaveric model of L5–S1 spondylolisthesis. The purpose of the current study was to compare, in a cadaveric model of simulated L5–S1 spondylolisthesis, the biomechanical stiffness of transdiscal fixation with traditional pedicle screw fixation, and transdiscal fixation with combined interbody/pedicle screw fixation. The surgical management of L5–S1 spondylolisthesis is a challenge because of the difficulties in achieving a reliable arthrodesis in the face of high mechanical forces. A method of lumbosacral fixation that has been used successfully in moderate grades of spondylolisthesis at our institution involves the use of transdiscal S1 pedicle screws. With this technique, S1 pedicle screws are placed through the S1 pedicle, through the superior endplate of S1, through the inferior endplate of L5, to terminate in the L5 body. Eighteen fresh human cadaveric (age 59–88 years) L5–S1 motion segments were obtained. The end of each intact motion segment was potted up to its midbody in a 10-cm-diameter polyvinylchloride end-cap using dental cement. The intact specimen was then biomechanically tested as follows: 1) axial compression (500 N), 2) flexion (10 Nm), 3) extension (10 Nm), 4) right lateral bending (10 Nm), and 5) left lateral bending (10 Nm). Stiffness values were calculated from the load–deflection curves obtained. Spondylolisthesis was then simulated by displacing L5 on S1 (% slip average = 41.3%) after performing a radical L5–S1 discectomy, L5 laminectomy, and bilateral L5–S1 facetectomies. The 18 motion segments were divided into two groups. Group I (n = 10) was biomechanically tested (as above) after pedicle screw fixation and again after replacing the S1 pedicle screws with transdiscal screws. Group II (n = 8) was biomechanically tested (as above) after combined interbody/pedicle screw fixation and again after fixation with transdiscal screws. Load–deflection curves were obtained each time, and stiffness values were calculated from the curves. Transdiscal fixation was 1.6–1.8 times stiffer than pedicle screw fixation (p < 0.05) in all loading modes tested. There were no differences in stiffness between transdiscal fixation and combined interbody/pedicle screw fixation. In a cadaveric model of simulated L5–S1 spondylolisthesis, transdiscal L5–S1 fixation produced a 1.6–1.8 times stiffer construct than traditional pedicle screw fixation. Further, the stiffness of the transdiscal fixation was equal to that of a combined interbody/pedicle screw fixation.

Healing of autologous bone in a titanium mesh cage used in anterior column reconstruction after total spondylectomy.

Study Design. Autologous bone inside a titanium mesh cage, used as an anterior strut in a reconstruction after total spondylectomy, was histologically examined in a postmortem specimen. Objectives. To determine whether the autologous bone inside the titanium mesh cage attained fusion and remodeling in a combined reconstruction, consisting of an anterior titanium mesh cage with posterior multilevel instrumentation, after total spondylectomy. Summary of Background Data. There are few previous reports on the histologic analysis of the bone inside a titanium mesh cage when it is used clinically as an anterior column support in a spinal fusion. Attaining biologic bony fusion is desirable for long-term stability after total spondylectomy. Methods. A postmortem specimen from a 16-year-old boy with Ewing’s sarcoma at T6, who died of lung metastasis 16 months after total spondylectomy and combined reconstruction, was analyzed. Results. Histologic examination revealed many viable cells and normal lamella of trabecular bone formation in the grafted bone inside the mesh. Consecutive trabecular cancellous bony fusion between the grafted bone and the adjacent vertebral bodies was achieved. Conclusion. Remodeling and fusion of the grafted bone inside the titanium mesh cage was observed. Combined reconstruction using an anterior titanium mesh cage with posterior multilevel instrumentation after total spondylectomy makes it possible to achieve biologic fusion of the bone inside the mesh cage with the adjacent vertebral bodies.

The role of the sternum, costosternal articulations, intervertebral disc, and facets in thoracic sagittal plane biomechanics: a comparison of three different sequences of surgical release.

Study Design. Eighteen human torsos were used in three experiments (A, B, and C) to determine the changes in sagittal motion due to three different sequences of three surgical releases. Objectives. To investigate the relative effects of releasing the intervertebral disc, the costosternal joint, the sternum, and the facet joints on sagittal thoracic motion and the consequences of altering the sequence of the releases. Summary of Background Data. The biomechanics of the thoracic spine are different from the cervical and lumbar spine particularly due to the ribs and sternum, which contribute to stability and control motion. The role of the sternum and costosternal articulation in the biomechanics of thoracic sagittal motion has not been well studied. The effects of releasing each of these structures, whether alone or with discectomy and/or facetectomy, is potentially relevant in the surgical correction of thoracic deformities, such as severe kyphosis, and in the biomechanics of thoracic fracture. Methods. In Experiment A, the release sequence was back to front: total facetectomy (T4–T8), then radical discectomy (T4–T8), then costosternal release, then sternal osteotomy. In Experiment B, the release sequence was front to back: sternal osteotomy, then costosternal release, then radical discectomy, and finally total facetectomy. In Experiment C, the release sequence was: radical discectomy, then sternal osteotomy, then costosternal release, then total facetectomy. The different sequences allowed separate analysis of each component and the synergistic patterns. In each of the three experiments, the torso was flexed then extended each time by an applied force (25 N) before and after each release. The extent of flexion and the extent of extension were measured each time and compared with the intact condition, after each release. Results. The results obtained for sternal osteotomy were combined with the results obtained for costosternal release to give “sternal release.” Radical discectomy provided the greatest increase (P < 0.05) in range of motion (ROM) compared with the other two single releases, no matter what the sequence. For paired release combinations, the radical discectomy and sternal release (as in Experiments B and C) provided a significant (P < 0.05) increase in total sagittal ROM compared with the combination of radical discectomy and total facetectomy (Experiment A). In Experiment A, sternal release accounted for 42% of the total sagittal ROM compared with only 26% related to the total facetectomy (Experiment B). In general, all of the releases allowed more extension than flexion. Conclusions. Sagittal plane motion in the thoracic spine is influenced by all three structures tested in this experiment. Overall, the radical discectomy provides the greatest increase in total ROM and in extension compared with the other two releases. The second most influential release is the combination of sternal osteotomy plus costosternal release (i.e., sternal release), particularly in extension (correction of kyphosis). When two releases are done in sequence, radical discectomy plus sternal release provides the greatest increase in total ROM and in extension. Overall, total facetectomy is the least effective release. These data have relevance for surgical strategies in the correction of thoracic kyphosis or lordosis and suggest a potential role for sternal osteotomy and costosternal release in severe and rigid upper thoracic kyphosis.

The effect of blocking a nutritional pathway to the intervertebral disc in the dog model.

Background The hypothesis that injecting bone cement adjacent to one or both endplates would bring about degeneration in the intervening disc was tested. Methods In 11 dogs, bone cement was injected just below the superior endplates of L1, L2, and L3 to block the nutritional supply through these endplates to the three intervertebral discs T13–L1, L1–L2, and L2–L3. In one other dog, both the superior and the inferior endplates of the same discs (T13–L1, L1–L2, and L2–L3) were blocked with bone cement. All 12 dogs were euthanized between 31 and 70 weeks after the surgery. The three experimental discs (T13–L1, L1–L2, and L2–L3) and two control discs (T12–T13 and L4–L5) were excised and assessed using enzyme-linked immunosorbent assay (ELISA) and histology. Results Radiographs of the lumbar spine at the time of death did not show any signs of disc bulging, disc space narrowing, or peripheral osteophyte formation in any of the 12 dogs. The experimental discs as well as the control discs appeared normal in every dog. After the discs were bisected, they were carefully inspected for any visible signs of degeneration. The experimental discs showed no clear signs of disc degeneration and were not distinguishable from the control discs on a gross level. The numerical results from the ELISA showed that in the experimental discs as opposed to the control discs, there were significant increases in proteoglycan content in both the nucleus (P = 0.033) and annulus (P = 0.01) and clear histologic changes in some of the discs. Conclusion The results show that injecting bone cement adjacent to one or both endplates for up to 70 weeks does not produce degeneration in any visible form in the intervening disc. There were no disc bulging, no apparent annular fissures, and no disc spacing narrowing. There were, however, increases in protoglycan content in both the nucleus and the annulus and clear histologic changes in some of the discs.