Quality of life and cost-utility of surgical treatment for patients with spinal metastases: prospective cohort study.

PURPOSE: Palliative surgery for patients with spinal metastasis provides good clinical outcomes. However, there have been few studies on quality of life (QOL) and cost-utility of this surgery. We aimed to elucidate QOL and cost-utility of surgical treatment for spinal metastasis. METHODS: We prospectively analyzed 47 patients with spinal metastasis from 2010 to 2014 who had a surgical indication. Thirty-one patients who desired surgery underwent spinal surgery (surgery group). Sixteen patients who did not want to undergo spinal surgery (non-surgery group). The EuroQol 5D (EQ-5D) and relevant costs were measured at one, three, six, and 12 months after study enrollment. Health state values were obtained by Japanese EQ-5D scoring and quality-adjusted life years (QALY) gained were calculated for each group. Cost-utility was expressed as the incremental cost-utility ratio (ICUR). RESULTS: Health state values improved from 0.036 at study enrollment to 0.448 at 12 months in the surgery group, but deteriorated from 0.056 to 0.019 in the non-surgery group, with a significant difference between groups (P < 0.05). The mean QALY gained at 12 months were 0.433 in the surgery group and 0.024 in the non-surgery group. The mean total cost per patient in the surgery group was $25,770 compared with $8615 in the non-surgery group. The ICUR using oneyear follow-up data was $42,003/QALY gained. CONCLUSIONS: Surgical treatment for spinal metastases is associated with significant improvement in health state value. In orthopaedic surgery, an ICUR less than $50,000/QALY gained is considered acceptable cost-effectiveness. Our results indicate that surgical treatment could be cost-effective.

Surgical debridement with retention of spinal instrumentation and long-term antimicrobial therapy for multidrug-resistant surgical site infections after spinal surgery: a case series.

PURPOSE: Post-operative surgical site infection (SSI) is one of the most significant complications after instrumented spinal surgery. However, implant retention feasibility for early-onset multidrug-resistant SSI is still controversial. We aimed to verify our therapeutic strategy, surgical debridement with implant retention and long-term antimicrobial therapy for post-operative early-onset multidrug-resistant SSI. METHODS: We retrospectively analyzed the clinical course of 11 cases [eight men and three women, with a mean age of 70.4 (54-82) years] with early-onset multidrug-resistant SSI out of 409 consecutive cases of spinal instrumentation surgery performed between 2007 and 2013 at our institution. RESULTS: The median duration of follow-up was 868 (178-1,922) days. All SSIs were controlled, without recurrence during follow-up. The microbial pathogens were methicillin-resistant Staphylococcus aureus (seven cases), multidrug-resistant Corynebacterium (two cases), methicillin-resistant Staphylococcus epidermidis (one case), and methicillin-resistant coagulase-negative Staphylococcus aureus (one case). The mean duration from SSI diagnosis to surgery was 2.9 (1-6) days. Ten patients underwent surgical debridement with implant retention. No patients required multiple operations. All patients were given antimicrobial treatments. Mean duration of intravenous antimicrobials (vancomycin, vancomycin+ piperacillin/tazobactam, or gentamicin) was 66.5 (12-352) days and 336 (89-1,673) days for oral antimicrobials (rifampicin + sulfamethoxazole/trimethoprim, sulfamethoxazole/trimethoprim, or minomycin). The mean duration of clinical signs and symptom recovery was 31.0 (7-73) days, and the mean time for normalization of C-reactive protein was 54.5 (7-105) days. CONCLUSIONS: Early-onset multidrug-resistant SSI was successfully treated by surgical debridement with implant retention and long-term antimicrobial therapy.

A case of parathyroid adenoma adjacent to the thoracic spine in a hemodialysis patient.

Ectopic parathyroid glands are detected occasionally, especially in cases of recurrent hyperparathyroidism after initial parathyroidectomy. Their ectopic locations usually result from faulty migration during embryogenesis. Ectopic parathyroid glands can be found within the thyroid gland, thymus, mediastinum, carotid sheath, or retropharynx, which lie along the path of their normal migration. Here we report a rare case of parathyroid adenoma adjacent to the thoracic spine in a hemodialysis patient who had undergone parathyroidectomy previously. A 67-year-old woman on maintenance hemodialysis since 1993 developed hyperparathyroidism. She underwent total parathyroidectomy with autotransplantation in 2007. Histological examination of the parathyroid glands showed hyperplasia in three glands and adenoma in one. Serum parathyroid hormone levels gradually increased after a year. Ultrasonography of the neck and upper limbs was negative, but technetium-99-sestamibi scanning showed focal uptake in the posterior mediastinum. Computed tomography and magnetic resonance imaging confirmed a tumor adjacent to the left costovertebral junction of the third thoracic vertebra. A tumor resection was performed in 2010, and histopathological examination showed a parathyroid adenoma. Parathyroid adenoma adjacent to the thoracic spine has not been reported previously, and our case suggests that technetium-9-sestamibi scanning is useful for the correct preoperative diagnosis of such rare cases of ectopic parathyroid glands.

Symptomatic perineural cyst: report of two cases treated with cyst-subarachnoid shunts.

INTRODUCTION: Symptomatic perineural cysts are rare. Resection and closure of such cysts sometimes results in postoperative neurological deficits and they can recur. We report two cases of symptomatic perineural cysts treated with subarachnoid shunts. MATERIALS AND METHODS: Case 1: A 62-year-old woman presented with bladder dysfunction. We identified a cyst communicating with the subarachnoid space adjacent to the S2 nerve root and implanted a subarachnoid shunt. Seven years after this surgery, her bladder dysfunction had not recurred. Case 2: A 35-year-old woman had low back pain, radiculopathy and bladder dysfunction. We identified a cyst adjacent to the S1 nerve root and implanted a subarachnoid shunt. Her low back pain and radiculopathy improved immediately and she experienced neither postoperative neurological deficits nor recurrence. CONCLUSION: Cyst-subarachnoid shunts are a useful treatment option for symptomatic perineural cysts.

Outcomes of surgical intervention for cervical spondylotic myelopathy accompanying local kyphosis (comparison between laminoplasty alone and posterior reconstruction surgery using the screw-rod system).

PURPOSE: The surgical strategy for cervical spondylotic myelopathy (CSM) accompanying local kyphosis is controversial. The purpose of the present study was to compare and evaluate the outcomes of two types of surgery for CSM accompanying local kyphosis: (1) laminoplasty alone (LP) and (2) posterior reconstruction surgery (PR) in which we corrected the local kyphosis using a pedicle screw or lateral mass screw. METHODS: Sixty patients who presented with local kyphosis exceeding 5° were enrolled. LP and PR were each performed on a group of 30 of these patients; 30 CSM patients without local kyphosis, who had undergone LP, were used as controls. The follow-up period was 2 years or longer. Preoperative local kyphosis angles in LP and PR were 8.3° ± 4.4° and 8.8° ± 5.7°, respectively. Preoperative C2-7 angles in LP, PR and controls were -1.7° ± 9.6°, -0.4° ± 7.2° and -12.0° ± 5.6°, respectively. The recovery rate of the JOA score, local kyphosis angle and C2-7 angle at post-op and follow-up were compared between the groups. RESULTS: The recovery rate of the JOA score in the LP group (32.6 %) was significantly worse than that in the PR group (44.5 %) and that of controls (53.8 %). Local kyphosis angles in the PR and LP groups at follow-up were 4.0° ± 8.6° and 8.0° ± 6.0°, respectively. However, although the C2-7 angle at follow-up was improved to -11.1° ± 12.7° in PR, and maintained at -11.6° ± 6.2° in controls, it deteriorated to 0.5° ± 12.7° in LP. CONCLUSIONS: The present study is the first to compare the outcomes between LP alone and PR for CSM accompanying local kyphosis. It revealed that PR resulted in a better clinical outcome than did LP alone. This result may be due to reduction of local kyphosis, stabilization of the unstable segment, and/or the maintenance of C2-7 angle until follow-up in the PR group.

Intervertebral disc and macrophage interaction induces mechanical hyperalgesia and cytokine production in a herniated disc model in rats.

OBJECTIVE: The expression of proinflammatory factors such as tumor necrosis factor α (TNFα), interleukin-6 (IL-6), IL-8, and prostaglandin E(2) (PGE(2) ) is significantly correlated with the symptoms of herniated disc disease. Among the different types of immune cells, macrophages are frequently noted in the herniated disc tissue. We undertook this study to clarify the interaction of the intervertebral disc (IVD) and macrophages with regard to the production of TNFα, IL-6, IL-8, and PGE(2) . METHODS: We developed 2 animal models to assess the interactions of IVDs with macrophages in terms of TNFα, IL-6, IL-8, and PGE(2) production and pain-related behavior. We also cocultured IVDs and macrophages to assess the role of TNFα in IL-6, IL-8, and PGE(2) production. RESULTS: IVD autografts induced TNFα, IL-6, IL-8, and cyclooxygenase 2 (COX-2) messenger RNA (mRNA) up-regulation; macrophage infiltration was seen shortly after the autograft was implanted. A significant decrease was noted in the mechanical threshold of the ipsilateral paw following the up-regulation of TNFα, IL-6, IL-8, and COX-2 mRNA. Only IVD and macrophage cocultures resulted in IL-8 and PGE(2) up-regulation. TNFα up-regulation was maximized before that of IL-6 and IL-8. TNFα neutralization attenuated production of IL-6 and PGE(2) , but not that of IL-8. Neutralization of TNFα and IL-8 significantly increased the paw withdrawal mechanical threshold in the IVD autograft and spinal nerve ligation model. CONCLUSION: IVD-macrophage interaction plays a major role in sciatica and in the production of TNFα, IL-6, IL-8, and PGE(2) . TNFα is required for IL-6 and PGE(2) production, but not for IL-8 production, during IVD-macrophage interaction. Neutralization of TNFα and IL-8 can be a valuable therapy for herniated disc disease.

C1 laminectomy for retro-odontoid pseudotumor without atlantoaxial subluxation: review of seven consecutive cases.

PURPOSE: A retro-odontoid pseudotumor is usually a reactive fibrocartilaginous mass associated with atlantoaxial subluxation (AAS). However, a retro-odontoid pseudotumor not associated with AAS, which undergoes spontaneous regression following C1 laminoplasty, has been reported. The purpose of this study was to report surgical outcomes of C1 laminectomy for retro-odontoid pseudotumor without AAS. MATERIALS AND METHODS: The cases of seven patients (mean age 75.6 ± 7.6 years-old) with retro-odontoid pseudotumor without AAS were reviewed. The mean follow up time was 52.3 ± 25.5 months. Each patient underwent a C1 laminectomy with an additional C3-6 expansion laminoplasty in three patients. The Japanese Orthopaedic Association score (JOA score) was used for neurological assessment. Pseudotumor size and additional AAS were analyzed using MRI and radiography. RESULTS: All patients exhibited neurological improvement following surgery, the JOA score improved from 7.2 ± 3.2 to 14.1 ± 2.6. The mean O-C2 and C2-7 angle decreased from -3.2 ± 2.1° to -3.9 ± 1.7°, showing a slight kyphotic change. Postoperative AAS was not observed. All pseudotumors spontaneously resolved, and recurrence and regrowth were not observed. Five patients had MRIs after gadolinium administration; four patients who showed enhancement of the pseudotumor had almost complete reduction within 1 year following surgery. DISCUSSION: Our study, assessing the outcome of C1 laminectomy for retro-odontoid pseudotumor, found neurological improvement in all cases. Since all pseudotumors were reduced and additional AAS was not observed, C1 laminectomy for retro-odontoid pseudotumor, in the absence of AAS, is recommended as a therapeutic strategy.

Efficacy of hemostasis for epidural venous plexus and safety for neural structure using soft coagulation system in spinal surgery: a laboratory investigation using a porcine model.

STUDY DESIGN: A laboratory investigation using porcine model. OBJECTIVE: To clarify the effectiveness of the soft coagulation system for stopping bleeding from the epidural vein using different outputs and the safety in terms of tissue damage including spinal cord injury. SUMMARY OF BACKGROUND DATA: Problems associated with coagulation using an electrosurgical device, such as carbonization of tissue or adhesion to the electrode, have been highlighted. So called "soft coagulation" has been developed to solve these problems. Its' utility as well as the safety of the neural structure in spine surgery has never been reported. METHODS: A total of 3 animals and 45 spinal segments were used. Total laminectomy was performed to expose the dural tube and epidural venous plexus. Stable bleeding was induced by a 22 G needle puncture. Soft coagulation monopolar output (SCM), soft coagulation bipolar output (SCB), and conventional bipolar output (CB) were used as the coagulators. Valid hemostasis was defined as macroscopically complete bleeding stoppage by coagulation within 3 minutes. The neurological assessment was evaluated by somatosensory evoked potential. Histologic analysis was performed to determine the area of thermal damage. RESULTS: Valid hemostasis ratio was 75.0% of SCM group, 68.8% of SCB group, and 30.8% of CB group. Somatosensory evoked potential monitoring revealed that spinal cord injury was observed in 4 lesions (25%) of the SCM group. Neither bipolar groups (SCB and CB) showed any changes in waveform pattern. Histologic analysis revealed that severe thermal damages were observed in the epidural space of the SCM group. CONCLUSIONS: The usefulness of soft coagulation is revealed in terms of bleeding stoppage from epidural vessels and reduced soft-tissue damage compared with the conventional electric device. However, assessing the potential risk of severe neural tissue damage including spinal cord injury, a bipolar soft coagulation is strongly recommended for use in spine surgery.

Development of percutaneously insertable/removable interspinous process spacer for treatment of posture-dependent lumbar spinal-canal stenosis: preclinical feasibility study using porcine model.

PURPOSE: A procedure using an interspinous process spacer (IPS) was recently developed for the treatment of posture-dependent lumbar spinal-canal stenosis (LSS) patients. We developed a novel IPS which can be inserted with simpler procedures and removed percutaneously. The objectives of this study were: (1) to evaluate the feasibility and safety of this novel technique, and (2) to assess the effectiveness of this spacer in terms of preventing an increase of epidural pressure in lumbar extension using a porcine model. METHODS: Eight young pigs were used. Under general anesthesia and image guidance, the spacers were inserted. Three months after operation, MR images were taken and all spacers were removed. Blood samples were obtained before and 1, 3, 7 days after surgery. After killing the animals, the lumbar spines were observed macroscopically. Another six animals were used. Under general anesthesia and image guidance, a flexible pressure transducer was inserted into the epidural space and epidural pressure was measured in neutral and at maximum extension with and without spacer insertion. RESULTS: Percutaneous insertion and removal of the spacer was successful for all animals through small skin incisions. MR images showed minimal damage to the muscle. No significant up-regulation of Interleukin-6 (IL-6) and CRP was detected. Macroscopic observation of the lumbar spine 3 months after the operation revealed that the area of the interspinous process contacting with the inserted spacer showed some bone erosion/remodeling. Insertion of the spacer did not affect the epidural pressure in neutral but significantly prevented an increase of epidural pressure in lumber extension. CONCLUSIONS: This study demonstrated that the percutaneous insertion and removal of a novel IPS was feasible and safe using a simple technique. Furthermore, this procedure can be recognized as minimally invasive surgery from the viewpoint of skin incision, short insertion track, inflammatory mediators, and muscle damage. Improvements should be attempted in future studies using softer or more elastic materials for the spacer to lessen bone erosion/remodeling at contacting area of the inserted spacer.

Improved bone bonding of hydroxyapatite spacers with a high porosity in a quantitative computed tomography-image pixel analysis: A prospective 1-year comparative study of the consecutive cohort undergoing double-door cervical laminoplasty.

Laminoplasty using hydroxyapatite (HA) spacers is widely performed in patients with cervical myelopathy. However, spacer dislocation is a critical complication caused by bone absorption and inadequate bone conductivity, and can result in dural damage and restenosis. We thus designed a prospective cohort study to clarify the feasibility of increased porosity HA spacers for double-door laminoplasty by analyzing computed tomography (CT) images. Forty-seven patients underwent cervical laminoplasty. Two different types of CERATITE HA spacer were used, either high porosity (50%) or low porosity (35%). These HA spacers were placed in an alternating manner into the laminae in each patient. In total, 85 high-porosity (50%) HA spacers and 84 low-porosity (35%) HA spacers were implanted. At postoperative 2 weeks, 3 months, 6 months, and 1 year, CT images were obtained. In both groups, the percentage of bone-bonding boundary area of the HA spacer in contact with laminae and bone volume of the spinous process relative to the 2-week value were calculated by a 3D and 2D CT-image pixel analysis. The bone-bonding ratio was significantly higher in high-porosity (50%) than low-porosity (35%) HA spacers at 3 months and thereafter (1 year, 69.3 ± 27.8% and 49.7 ± 32.9% respectively, P < .01). The bone volume in both groups significantly decreased with time (1 year, 73.2 ± 29.8% and 69.0 ± 30.4% respectively, P < .01), indicating bone absorption. This showed no significant difference between the HA spacers (P = .15) but was higher in high-porosity (50%) than low-porosity (35%) HA spacers throughout the study period. Meanwhile, spacer breakage was found in 4.7% of high-porosity (50%) HA spacers and 1.2% of low-porosity (35%) HA spacers (P = .37). In summary, high-porosity (50%) HA spacers have the advantages of accelerated bone bonding and relatively decelerated bone absorption compared to low-porosity (35%) HA spacers; however, possibly more frequent breakage of HA spacers with a high porosity (50%) requires careful, extended postoperative follow-up.

Sustained long-term RNA interference in nucleus pulposus cells in vivo mediated by unmodified small interfering RNA.

RNA interference (RNAi) technology has recently emerged as an important biological strategy for gene silencing. Previously, the efficacies of RNAi in cultured nucleus pulposus cells in vitro have been reported. However, RNAi in the disc in vivo has never been reported. Therefore, the aims of the present study were to establish a method for RNAi in the disc in vivo and to evaluate the applicability of this technique for endogenous genes in the intervertebral discs using Fas Ligand (FasL) as a representative endogenous gene. To evaluate the efficacy of RNAi in vivo, two reporter luciferase plasmids (Firefly and Renilla) were used. These plasmids and unmodified short interference RNA (siRNA) duplex for targeting Firefly luciferase were co-transfected into coccygeal intervertebral disc of Sprague-Dawley rats in vivo using the ultrasound gene transfer technique. To evaluate the RNAi of the endogenous gene in vivo, siRNAs targeting rat FasL were transfected with the same technique. Non-specific siRNA was used as the negative control. The discs receiving no siRNAs were used as the control. The inhibitory effect of Firefly luciferase against Renilla luciferase was obtained using the results of dual-luciferase assay. Down-regulation of endogenous FasL was calculated by the data from real-time PCR. Our results showed that siRNA for Firefly luciferase can dramatically down-regulate the Firefly luciferase gene expression in vivo compared with Renilla luciferase. The inhibitory effects were maintained for at least 24 weeks and at 24 weeks post transfection, the inhibitory rate was 80% compared with the control group. Furthermore, the siRNA co-transfection group inhibited endogenous FasL expression by 53% compared with the control group. The present study demonstrates long-term down-regulation mediated by unmodified siRNA is possible not only for the exogenous reporter gene, but also for endogenous FasL expression in rat discs in vivo. This application of RNAi might be promising as a local therapy for disc degeneration and associated disorders by down-regulating some of the genes that are harmful for the normal physiology of the disc and may cause disc degeneration.

Gene therapy approach for disc degeneration and associated spinal disorders.

Disc degeneration is deeply associated with many spinal disorders and thus has a significant clinical impact on society. The currently available surgical treatment often necessitates removing a pathological disc and spinal fusion. However, it is also well known that these surgical treatments have many potential problems including invasion and cost. Therefore, biological approaches for regenerating these pathological discs have received much attention. Gene therapy is one of these biological approaches. Gene therapy involves the transfer of genes to cells so the recipient cells express these genes and thereby synthesize the RNA and protein they encode in a continuous fashion. One of the significant advantages of gene therapy is that we can expect a lasting duration of biological effect which is potentially beneficial for most disc degeneration associated disorders, as they are, by nature, chronic conditions. Originally, gene therapy was mediated by viral vectors, but recent technological progress has enabled us to opt for non-virus-mediated gene therapy for the disc. Furthermore, the development of the RNA interference technique has enabled us to down-regulate a specific gene expression in the disc opening the door for a new generation of intradiscal gene therapy.

Two-stage decompression, reduction, and interbody fusion for lumbosacral spondyloptosis through a posterior approach using Ilizarov external fixation.

The suggested methods of treatment for spondyloptosis have included benign neglect, in situ fusion and variations, decompression and fusion, and vertebrectomy (the Gaines procedure). On review of the literature, the authors found no previous report in the English-language literature in which external fixation was used in the treatment of spondyloptosis. This 33-year-old woman with spondyloptosis underwent a 2-stage operation involving decompression, reduction, and posterior fusion in which an Ilizarov external fixator and transpedicular fixation system were used. Spondylolisthesis with a slippage of angle 78 degrees and > 100% slippage was partially reduced to 30 degrees and 60% without neurological alterations and without complications. The postoperative follow-up showed marked improvement in her symptoms and a good cosmetic result. Reconstructed computed tomography scanning at 18 months demonstrated complete fusion. The use of external fixation in the treatment of spondyloptosis may be preferable because of its neurological safety, despite the longer duration of treatment, than single-stage operation. The authors believe posterior decompression of the cauda equina, partial reduction of the spondylolisthetic deformity, interbody fusion, and stabilization with an external fixator and transpedicular fixation system can be successfully and safely used as a 2-stage treatment for adult high-grade spondyloptosis.

Bilateral pedicle stress fracture in a patient with lumbar spinal stenosis: a case report.

STUDY DESIGN: A case of bilateral pedicle stress fracture in a patient with lumbar spinal stenosis is reported, and the literature is reviewed. OBJECTIVES: To report a rare case of bilateral pedicle stress fracture without a history of major trauma or surgery. SUMMARY OF BACKGROUND DATA: Bilateral pedicle fracture is a rare entity and few cases have been reported in the literature. All the reported cases had some underlying causative factors like previous spine surgery or stress-related activities. To the best of the authors' knowledge, only 1 case of bilateral pedicle stress fracture without a history of trauma, previous spine surgery, or stress-related activities has been reported. METHOD: A 57-year-old man presented with low back pain and radiating pain in left leg that was exacerbated after walking. Plain radiograph showed severe degenerative changes at L4-5 level. Magnetic resonance imaging revealed lumbar spinal stenosis at L2-3, 3-4, and 4-5 levels. A computed tomography demonstrated bilateral L4 pedicle stress fracture. The patient was treated with decompressive laminectomies of L3-5, followed by posterior spinal fusion with rigid pedicle screw fixation and autogenous bone graft mixed with hydroxyapatite. RESULTS: The patient achieved pain relief and returned to normal activity. CONCLUSIONS: Stress fracture of the pedicle within the proximal vertebra of a severely degenerated lumbar spine is an uncommon entity. It may, however, be an additional source of symptoms in patients with lumbar spinal stenosis who present with further back pain. Surgeons caring for this group of patients should be aware of this condition.

Activation of Syk protein tyrosine kinase in response to osmotic stress requires interaction with p21-activated protein kinase Pak2/gamma-PAK.

The p21-activated serine/threonine protein kinase Pak2/gamma-PAK and the nonreceptor type of protein tyrosine kinase Syk are known to be activated when the cells are exposed to osmotic stress. The purpose of the present study was to examine whether Pak2 and Syk functionally cooperate in cellular signaling. Cotransfection studies revealed that Pak2 associates with Syk in COS cells. The constitutively active form of Cdc42 increases the association of Pak2 with Syk. Pak2 coexpressed with an inactive form of Cdc42 or kinase-inactive Pak2 interacts to a lesser extent with Syk, suggesting that Pak2-Syk association is enhanced by Pak2 activation. Interaction with Pak2 enhances the intrinsic kinase activity of Syk. This is supported by in vitro studies showing that Pak2 phosphorylates and activates Syk. Treatment of cells with sorbitol to induce hyperosmolarity results in the translocation of Pak2 and Syk to the region surrounding the nucleus and in dramatic enhancement of their association. Furthermore, cotransfection of Pak2 and Syk leads to the activation of c-Jun N-terminal kinase (JNK) under hyperosmotic conditions. Pak2 short interfering RNA suppresses sorbitol-mediated activation of endogenous Syk and JNK, thus identifying a novel pathway for JNK activation by Cdc42. These results demonstrate that Pak2 and Syk positively cooperate to regulate cellular responses to stress.

Lumbar spondylolysis: A report of four cases from two generations of a family.

Spondylolysis is a major cause of back pain in children and adolescents. The prevalence of spondylolysis depends on the sex, race, and congenital abnormality. These biases suggest hereditary predisposition as an etiology of spondylolysis. However, no conclusive evidence still exists regarding the inheritance for spondylolysis. Herein, we report rare cases with familial occurrence of lumbar spondylolysis. In two generations of a Japanese family, three brothers including identical twins complained of back pain related to sports activities. Clinical, radiographic, and computed tomographic examinations identified spondylolysis at L4 and L5 in all these boys. The father experienced long-term back pain and had spondylolisthesis at L4-L5 and healed spondylolysis at L5. The daughter and mother did not show any lumbar spondylolysis. The frequent development of spondylolysis at L4, a rarely affected segment, in four of six family members (66.7%) support that lumbar spondylolysis has an underlying genetic etiology, primarily autosomal dominant inheritance.

Thoracic compression myelopathy due to the progression of dystrophic scoliosis, the presence of a paraspinal tumor, and high and excessive amplitude movement of the shoulder.

The authors present a case of 45-year-old man with neurofibromatosis type 1 (NF-1) and thoracic scoliosis, previously undergoing fusion surgery, who developed myelopathy. This patient further complained of lightning pain when he extended and horizontally abducted the convex-side shoulder. Radiological examination revealed the progression of dystrophic scoliosis with opened spinal canals and the presence of a neurofibroma behind the spinal cord at the apical levels. Delayed development of spinal instability can occur due to dystrophy even postoperatively in patients with NF-1. After tumor resection, he had rapid recovery from myelopathy and no recurrence of radiating pain despite shoulder movement. These findings provide a speculation that high, intense amplitude movement of the shoulder toward the spinal canal causes the impingement on the neurofibroma, resulting in indirect compression of the exposed spinal cord. This is the first report describing thoracic compression myelopathy associated with paraspinal displacement of the scapula.

Prospective Cohort Study of Performance Status and Activities of Daily Living After Surgery for Spinal Metastasis.

STUDY DESIGN: A prospective cohort study of performance status (PS) and activities of daily living (ADL) in patients with spinal metastasis. OBJECTIVE: To identify the effect of spinal surgery on PS and ADL in patients with spinal metastasis. SUMMARY OF BACKGROUND DATA: Spinal metastasis causes severe neurological deficits, resulting in drastic loss of patients' PS and ADL. However, the effect of spine surgery on PS and ADL is not well known. MATERIALS AND METHODS: Seventy patients with spinal metastasis were enrolled in this study. Forty-six patients desired and underwent spine surgery ("surgery" group) and 24 patients did not desire surgery ("nonsurgery" group). Both groups received optimal treatments, including radiation, chemotherapy, and palliative care services. Evaluation was performed at 1, 3, and 6 months after study enrollment using the Eastern Cooperative Oncology Group PS, the Barthel index (BI) for ADL, and Frankel classification for neurological status. RESULTS: There was no significant difference in baseline PS, the BI, or Frankel classification between the groups. The surgery group showed significant improvement in PS, maintaining grade 2 or less throughout the duration of the study, as well as in ADL, exceeding 70 points of the BI, compared with the nonsurgery group (P<0.05). Significantly improved neurological condition was also observed in the surgery group over the following 6 months. More than 95% of patients who underwent surgery improved their PS, the BI, and neurological status. Furthermore, >80% of these patients maintained improvement in PS, the BI, and neurological status for at least 6 months. In contrast, PS, the BI, and neurological status of patients in the "nonsurgery" group deteriorated throughout the study period. CONCLUSIONS: Spine surgery improves PS, ADL, and neurological status in patients with spinal metastasis for a minimum 6 months. This indicates that these patients can acquire an independent daily life.

Prolonged down regulation of specific gene expression in nucleus pulposus cell mediated by RNA interference in vitro.

To investigate the efficacies and the longevity of RNA interference in nucleus pulposus cells from rat and human, two reporter luciferase plasmids (Firefly and Renilla) were used. These plasmids were cotransfected with siRNA targeting Firefly luciferase to the nucleus pulposus cells extracted from Sprague Dawley rats and scoliosis patients. The inhibitory effects were evaluated by dual luciferase assay for 3 weeks. Proliferation activity of fibroblast-like cells extracted from the subcutaneous tissue of Sprague Dawley rats and the nucleus pulposus cells were measured by proliferation assay (WST-8 assay) every 2 days after plating. The expression of Firefly luciferase was drastically inhibited both in rats (94.7%) and in humans (93.7%). The inhibitory effects were maintained for 2 weeks and had disappeared completely by 3 weeks. The proliferation activity of nucleus pulposus cells was significantly lower than fibroblast-like cells. We have shown, for the first time, siRNA-mediated gene silencing in rat and human disc cells for a relatively sustained period, probably due to the stability of the nucleus pulposus cells in terms of cell proliferation. The demonstration of this study may allow further exploration of the use of siRNA for scientific research and the treatment of disc degenerative diseases.

Expression of adiponectin receptors in human and rat intervertebral disc cells and changes in receptor expression during disc degeneration using a rat tail temporary static compression model.

BACKGROUND: Adipose tissue is a large endocrine organ known to secret adiponectin, which has anti-diabetic, anti-atherogenic, and anti-inflammatory properties. Adiponectin is widely involved in systemic disease, diabetes mellitus, and cardiac infraction. This study aimed to investigate the involvement of adiponectin in intervertebral disc (IVD) degeneration. METHODS: Adipose and IVD tissues were obtained from human patients undergoing surgery (n = 4) and from skeletally mature Sprague-Dawley rats (n = 21). Tissues were stained immunohistochemically for adiponectin and adiponectin receptors AdipoR1 and AdipoR2. Changes in adiponectin receptor expression with IVD degeneration severity were then investigated using a rat tail temporary compression model. Rat IVD tissues were stained immunohistochemically with AdipoR1 or AdipoR2, and immunopositive cell percentages were calculated. Rat nucleus pulposus (NP) and annulus fibrosus (AF) tissues were isolated separately and treated with recombinant adiponectin (Ad 0.1 or 1.0 µg/ml) and/or interleukin-1 beta (IL-1ß) (0.2 µg/ml) for 24 h. The four groups were as follows: control group (no treatment), IL-1ß group (IL-1ß-only treatment), IL-1ß+Ad (0.1) group (IL-1ß and adiponectin [0.1 µg/ml] treatment), and IL-1ß+Ad (1.0) group (IL-1ß and adiponectin [1.0 µg/ml]). Real-time reverse transcription-polymerase chain reaction was performed to evaluate messenger-RNA (mRNA) expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6). RESULTS: Adiponectin was widely expressed in human subcutaneous and epidural adipose tissue. In rat IVD tissue, adiponectin was not observed in NP and AF. However, both AdipoR1 and AdipoR2 were widely expressed in both human and rat IVD tissues, with no significant differences in expression levels between receptors. Furthermore, expression levels of AdipoR1 and AdipoR2 were gradually decreased with increased IVD degeneration severity. Interestingly, mRNA expression levels of TNF-α and IL-6 were significantly upregulated by IL-1ß stimulation. TNF-α expression in the IL-1ß+Ad 1.0 group was significantly lower than that in the IL-1ß group in both NP and AF cells (P < 0.05). Finally, IL-6 expression was not affected by adiponectin treatment in IVD cells. CONCLUSIONS: This study investigated for the first time the expression of adiponectin receptors in human and rat IVD cells. The findings indicate that adiponectin produced by the systemic or epidural adipose tissue may be involved in the pathomechanism of IVD degeneration.