Analysis of the Relationship between Hypertrophy of the Ligamentum Flavum and Lumbar Segmental Motion with Aging Process

Study DesignRetrospective cross-sectional study.PurposeTo investigate the relationship between ligamentum flavum (LF) hypertrophy and lumbar segmental motion.Overview of LiteratureThe pathogenesis of LF thickening is unclear and whether the thickening results from tissue hypertrophy or buckling remains controversial.Methods296 consecutive patients underwent assessment of the lumbar spine by radiographic and magnetic resonance imaging (MRI). Of these patients, 39 with normal L4–L5 disc height were selected to exclude LF buckling as one component of LF hypertrophy. The study group included 27 men and 12 women, with an average age of 61.2 years (range, 23–81 years). Disc degeneration and LF thickness were quantified on MRI. Lumbar segmental spine instability and presence of a vacuum phenomenon were identified on radiographic images.ResultsThe distribution of disc degeneration and LF thickness included grade II degeneration in 4 patients, with a mean LF thickness of 2.43±0.20 mm; grade III in 10 patients, 3.01±0.41 mm; and grade IV in 25 patients, 4.16±1.12 mm. LF thickness significantly increased with grade of disc degeneration and was significantly correlated with age (r=0.55, p<0.01). Logistic regression analysis identified predictive effects of segmental angulation (odds ratio [OR]=1.55, p=0.014) and age (OR=1.16, p=0.008).ConclusionsAge-related increases in disc degeneration, combined with continuous lumbar segmental flexion-extension motion, leads to the development of LF hypertrophy

Predictable Imaging Signs of Cauda Equina Entrapment in Thoracolumbar and Lumbar Burst Fractures with Greenstick Lamina Fractures

Study DesignA retrospective study.PurposeThe aim of present study was to investigate imaging findings suggestive of cauda equina entrapment in thoracolumbar and lumbar burst fractures.Overview of LiteratureBurst fractures with cauda equina entrapment can cause neurologic deterioration during surgery. However, dural tears and cauda equina entrapment are very difficult to diagnose clinically or radiographically before surgery.MethodsTwenty-three patients who underwent spinal surgery for thoracolumbar or lumbar burst fractures were enrolled in this study. In magnetic resonance imaging T2-weighted images of the transverse plane, we defined cauda equina notch sign (CENS) as a v-shaped image that entrapped cauda equina gathers between lamina fractures. We evaluated the fractured spine by using CENS and lamina fractures and the rate of available space for the spinal canal at the narrowest portion of the burst fracture level. We classified patients into entrapment group or non-entrapment group, based on whether cauda equina entrapment existed.ResultsLamina fractures were detected in 18 (78.3%) and CENS were detected in 6 (26.1%) of 23 burst-fracture patients. Cauda equina entrapment existed in all the patients with CENS. In addition, the rate of available space for the spinal canal increased according to logistic regression. The size of the retropulsed fragment in the spinal canal was the most reliable of all the factors, suggesting cauda equina entrapment.ConclusionsCENS was the most predictable sign of cauda equina entrapment associated with burst fractures

Analysis of the Prevalence and Distribution of Cervical and Thoracic Compressive Lesions of the Spinal Cord in Lumbar Degenerative Disease

Study DesignRetrospective study.PurposeThe aim of the present study is to analyze the prevalence and distribution of cervical and thoracic compressive lesions of the spinal cord in lumbar degenerative disease, using whole-spine postmyelographic computed tomography.Overview of LiteratureOf the various complications resulting from spinal surgery, unexpected neurological deterioration is the most undesired. There are reports of missed compressive lesions of the spinal cord at the cervical or thoracic level in lumbar degenerative disease.MethodsThere were 145 consecutive patients with symptomatic lumbar degenerative disease evaluated. Before the lumbar surgery, image data were obtained. The following parameters at the cervical and thoracic levels were analyzed: compressive lesions from the anterior parts; compressive lesions from the anterior and posterior parts; ossification of the ligamentum flavum; ossification of the posterior longitudinal ligament; and spinal cord tumor.ResultsCompressive lesions from the anterior parts were observed in 34 cases (23.4%). Compressive lesions from the anterior and posterior parts were observed in 34 cases (23.4%). Lesions of ossification of the ligamentum flavum were observed in 45 cases (31.0%). Lesions of ossification of the posterior longitudinal ligament were observed in 15 cases (10.3%). Spinal cord tumor was not observed.ConclusionsA survey of compressive lesions at the cervical or thoracic level in lumbar degenerative disease is important in preventing unexpected neurological deterioration after the lumbar surgery

Prevalence and Distribution of Thoracic and Lumbar Compressive Lesions in Cervical Spondylotic Myelopathy

Study DesignRetrospective cross-sectional study.PurposeThis study analyzed the prevalence and distribution of horacic and lumbar compressive lesions in cervical spondylotic myelopathy as well as their relationships with cervical developmental spinal canal stenosis (DCS) by using whole-spine postmyelographic computed tomography.Overview of LiteratureThere are few studies on missed compressive lesions of the spinal cord or cauda equina at the thoracolumbar level in cervical spondylotic myelopathy. Furthermore, the relationships between DCS, and the prevalence and distribution of thoracic and lumbar compressive lesions are unknown.MethodsEighty patients with symptomatic cervical spondylotic myelopathy were evaluated. Preoperative image data were obtained. Patients were classified as DCS or non-DCS (n=40 each) if their spinal canal longitudinal diameter was <12 mm at any level or ≥12 mm at all levels, respectively. Compressive lesions in the anterior and anteroposterior parts, ligamentum flavum ossification, posterior longitudinal ligament ossification, and spinal cord tumors at the thoracolumbar levels were analyzed.ResultsCompressive lesions in the anterior and anteroposterior parts were observed in 13 (16.3%) and 45 (56.3%) patients, respectively. Ligamentum flavum and posterior longitudinal ligament ossification were observed in 19 (23.8%) and 3 (3.8%) patients, respectively. No spinal cord tumors were observed. Thoracic and lumbar compressive lesions of various causes tended to be more common in DCS patients than non-DCS patients, although the difference was statistically insignificant.ConclusionsSurveying compressive lesions and considering the thoracic and lumbar level in cervical spondylotic myelopathy in DCS patients are important for preventing unexpected neurological deterioration and predicting accurate neurological condition after cervical surgery

Analysis of the Relationship between Ligamentum Flavum Thickening and Lumbar Segmental Instability, Disc Degeneration, and Facet Joint Osteoarthritis in Lumbar Spinal Stenosis

Study DesignCross-sectional study.PurposeTo investigate the relationship between ligamentum flavum (LF) thickening and lumbar segmental instability and disc degeneration and facet joint osteoarthritis.Overview of LiteraturePosterior spinal structures, including LF thickness, play a major role in lumbar spinal canal stenosis pathogenesis. The cause of LF thickening is multifactorial and includes activity level, age, and mechanical stress. LF thickening pathogenesis is unknown.MethodsWe examined 419 patients who underwent computed tomography (CT) myelography and magnetic resonance imaging after complaints of clinical symptoms. To investigate LF hypertrophy, 57 patients whose lumbar vertebra had normal disc heights at L4–5 were selected to exclude LF buckling as a hypertrophy component. LF thickness, disc space widening angulation in flexion, segmental angulation, presence of a vacuum phenomenon, and lumbar lordosis at T12–S1 were investigated. Disc and facet degeneration were also evaluated. Facet joint orientation was measured via an axial CT scan.ResultsThe mean LF thickness in all patients was 4.4±1.0 mm at L4–5. There was a significant correlation between LF thickness and disc degeneration; LF thickness significantly increased with severe disc degeneration and facet joint osteoarthritis. There was a tendency toward increased LF thickness in more sagittalized facet joints than in coronalized facet joints. Logistic regression analysis showed that LF thickening was influenced by segmental angulation and facet joint osteoarthritis. Patient age was associated with LF thickening.ConclusionsLF hypertrophy development was associated with segmental instability and severe disc degeneration, severe facet joint osteoarthritis, and a sagittalized facet joint orientation

Local oncolytic adenovirotherapy produces an abscopal effect via tumor-derived extracellular vesicles

Extracellular vesicles (EVs) play important roles in various intercellular communication processes. The abscopal effect is an interesting phenomenon in cancer treatment, in which immune activation is generally considered a main factor. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), and occasionally observed therapeutic effects on distal tumors after local treatment in immunodeficient mice. In this study, we hypothesized that EVs may be involved in the abscopal effect of OBP-301. EVs isolated from the supernatant of HCT116 human colon carcinoma cells treated with OBP-301 were confirmed to contain OBP-301, and they showed cytotoxic activity (apoptosis and autophagy) similar to OBP-301. In bilateral subcutaneous HCT116 and CT26 tumor models, intratumoral administration of OBP-301 produced potent antitumor effects on tumors that were not directly treated with OBP-301, involving direct mediation by tumor-derived EVs containing OBP-301. This indicates that immune activation is not the main factor in this abscopal effect. Moreover, tumor-derived EVs exhibited high tumor tropism in orthotopic HCT116 rectal tumors, in which adenovirus E1A and adenovirus type 5 proteins were observed in metastatic liver tumors after localized rectal tumor treatment. In conclusion, local treatment with OBP-301 has the potential to produce abscopal effects via tumor-derived EVs

Immune Modulation by Telomerase-Specific Oncolytic Adenovirus Synergistically Enhances Antitumor Efficacy with Anti-PD1 Antibody

The clinical benefit of monotherapy involving immune checkpoint inhibitors (ICIs) such as anti-programmed death-1 antibody (PD-1 Ab) is limited to small populations. We previously developed a telomerase-specific oncolytic adenovirus, Telomelysin (OBP-301), the safety of which was confirmed in a phase I clinical study. Here, we examined the potential of OBP-502, an OBP-301 variant, as an agent for inducing immunogenic cell death (ICD) and synergistically enhancing the efficacy of OBP-502 with PD-1 Ab using CT26 murine colon cancer and PAN02 murine pancreatic cancer cell lines. OBP-502 induced the release of ICD molecules such as adenosine triphosphate (ATP) and high-mobility group box protein 1 (HMGB1) from CT26 and PAN02 cells, leading to recruitment of CD8-positive lymphocytes and inhibition of Foxp3-positive lymphocyte infiltration into tumors. Combination therapy involving OBP-502 intratumoral administration and PD-1 Ab systemic administration significantly suppressed the growth of not only OBP-502-treated tumors but also tumors not treated with OBP-502 (so-called abscopal effect) in CT26 and PAN02 bilateral subcutaneous tumor models, in which active recruitment of CD8-positve lymphocytes was observed even in tumors not treated with OBP-502. This combined efficacy was similar to that observed in a CT26 rectal orthotopic tumor model involving liver metastases. In conclusion, telomerase-specific oncolytic adenoviruses are promising candidates for combined therapies with ICIs