Koji Uotani

Tumors of the spine and spinal cord, including primary and metastatic vertebral tumors, intramedullary gliomas, and refractory intradural lesions, are challenging to treat because curative local therapy is limited by the eloquent, nonregenerating neural tissue surrounding them. Oncolytic virotherapy may offer a rational alternative by combining tumor-selective oncolysis with the induction of systemic antitumor immunity, while sparing normal neural cells. This review summarizes the current field of oncolytic viruses, including adenovirus, herpes simplex virus, reovirus, and others, in the context of spinal and spinal cord tumors. Clinical data in the spine remain scarce; however, the rationale is based on histological evidence from sarcomas and other tumors, extensive glioma experience, including diffuse intrinsic pontine glioma, and preclinical activity in nerve sheath and meningioma models. We discuss the telomerase-specific oncolytic adenovirus OBP-301 and its derivatives, whose hTERT-driven replication provides histology-agnostic tumor selectivity, while sparing the telomerase-silent spinal cord. This telomerase dependence, however, limits activity against tumors that maintain telomeres through the alternative lengthening of telomeres (ALT) pathway, such as many osteosarcomas and some spinal cord astrocytomas. We also discuss delivery and safety within the confined spinal canal, combination strategies, and future directions, such as extracellular vesicle-mediated delivery and biomarker-guided patient selection. Although clinical translation to the spine will require dedicated preclinical and early-phase studies, virotherapy represents a promising, mechanistically grounded modality for these therapeutically challenging tumors.

A woman in her 20s presented with neck pain and was diagnosed with a primary giant cell tumour (GCT) involving the C5 vertebral body and encasing the left vertebral artery (VA). Denosumab therapy was initiated to reduce tumour vascularity and facilitate resection. After preoperative embolisation of the left VA, total en bloc resection of the tumour was performed. Postoperatively, the patient experienced transient left upper extremity weakness, which improved significantly over time. Follow-up imaging showed successful bony fusion and no recurrence. This case highlights the importance of multidisciplinary planning in managing cervical spine GCTs involving critical neurovascular structures. Combined denosumab therapy and VA embolisation can enable safe and complete tumour resection, potentially improving outcomes and reducing recurrence risk, especially in young patients.

Background/Objectives: Vertebral body stenting (VBS) and balloon kyphoplasty (BKP) are widely used for the treatment of osteoporotic vertebral fractures (OVFs). However, it remains unclear whether the theoretical biomechanical advantages of VBS translate to superior clinical or radiographic outcomes. This study aimed to compare VBS and BKP with respect to clinical outcomes, radiographic parameters, and complications. Methods: In this multicenter retrospective comparative cohort study, 123 patients with OVF treated with VBS (n = 24) or BKP (n = 99) were analyzed. VBS was indicated for complex fracture patterns, including severe endplate injury, split-type fractures, and absence of interbody sclerosis; other fractures were treated with BKP. Pain outcomes, operative parameters, cement volume and leakage, and radiographic measures of vertebral kyphosis angle (VKA) and local kyphosis angle (LKA) were assessed. For group comparisons, we used independent-samples t tests or Mann–Whitney U tests for continuous variables and chi-squared or Fisher’s exact tests for categorical variables. Results: Baseline demographics and bone mineral density were comparable between groups. Surgical time was longer for VBS (39 ± 6 vs. 35 ± 9 min, p = 0.007). Both procedures produced significant pain reductions (p < 0.001), and postoperative VAS did not differ between VBS and BKP (18 ± 11 vs. 13 ± 12 mm, p = 0.06). Although VKA immediately after surgery was lower for VBS (4.8 ± 4.4° vs. 7.0 ± 4.9°, p = 0.03), the magnitude of correction, VKA, and LKA at final follow-up were comparable. Cement volume was similar (6.4 ± 1.4 vs. 6.7 ± 1.9 mL, p = 0.45), but cement leakage occurred more frequently with VBS (54% vs. 24%, p = 0.005). Rates of adjacent vertebral fracture (13% vs. 26%, p = 0.12) and revision surgery (4% vs. 8%, p = 0.44) were comparable between groups. Conclusions: Despite VBS being reserved for more complex fracture morphologies with split-type fractures and severe endplate defects, while BKP was generally used for uncomplicated OVF cases, VBS provided pain relief and radiographic correction comparable to BKP.

Objective: Major cause of low‐back pain is intervertebral disc degeneration ( IVDD ), with mechanical stress playing a crucial role in its progression. A mechanosensitive ion channel, PIEZO1 , is involved in various musculoskeletal tissues, but its role in the annulus fibrosus ( AF ) remains unclear. This study aimed to elucidate the function of PIEZO1 in AF cells under mechanical stimulation. Methods: Primary rat AF cells were subjected to cyclic tensile strain ( CTS ) at low (2%) and high (12%) strain levels to investigate strain‐dependent effects on osteogenic gene expression. We evaluated the effects of Piezo1 , Piezo2 , and Trpv4 knockdown by RNA interference to identify the upstream mechanotransducer. Furthermore, PIEZO1 was activated using the agonist Yoda1, followed by RNA ‐sequencing analysis and evaluation of its effects on BMP2 ‐induced osteogenesis in rat AF cells. We also examined the effects of Yoda1 in primary human AF cells. Results: Low‐strain CTS significantly suppressed osteogenic marker expression, which was not observed with high strain. Piezo1 knockdown reversed this suppression, whereas Piezo2 and Trpv4 had no effect. Piezo1 activation by Yoda1 produced similar anti‐osteogenic effects in both rat and human AF cells. RNA sequencing revealed the enrichment of ossification and calcineurin signaling pathways in rat cells. Furthermore, Piezo1 activation inhibited BMP2 ‐induced osteogenesis and nuclear translocation of p‐Smad1/5/9. Conclusions: Piezo1 maintains AF cell homeostasis under mechanical stress by suppressing osteogenic changes via calcineurin‐mediated inhibition of BMP signaling, which may represent a novel therapeutic target for IVDD .

Background: Intraoperative neurophysiological monitoring (IONM) has become an invaluable tool for spinal deformity surgery. This study aims to present our experience of using transcranial motor evoked potential (Tc-MEP) as an IONM tool in adolescent idiopathic scoliosis patients undergoing navigation-assisted deformity correction and explore the potential risk factors associated with false-positive and true-positive IONM findings. Methods: A retrospective study was conducted in 103 patients (mean age 16.2 ± 4.0 years) undergoing corrective surgery for spinal deformity. All pediatric spinal deformity correction surgeries at the center were performed by a single senior spine surgeon, utilizing navigation and Tc-MEP to enhance the neurological safety profile. The sensitivity and the specificity of Tc-MEP were calculated. Results: Of the total cases, 87 patients (84.5%) exhibited no IONM signal alert and did not experience any postoperative neurological deficits, representing true negatives. There were no false-negative cases, which gives a negative predictive value of 100%. Significant IONM signal alerts were observed in 16 patients (15.5%), but only two patients (1.9%) experienced a postoperative motor deficit, representing true positives, which yielded a positive predictive value of 12.5%. Conclusions: This study demonstrated the sensitivity and specificity of Tc-MEP to be 100% and 86.3%, respectively, with a false-positive rate of 13.7%. Blood loss was the only factor significantly associated with IONM alerts, while age, gender, surgical duration, and anesthetic modality showed no significant differences.

Study Design: A retrospective multicenter cohort study.Purpose: We sought to determine whether occipitocervical (OC) fusion is followed by more postoperative complications and revision surgery than is atlantoaxial (AA) fusion. We aim to compare postoperative complications and revision surgery associated with OC fusion and AA fusion.Overview of Literature: OC and AA fusion are established techniques for restoring upper cervical stability. However, the outcomes of the two methods have not been compared.Methods: This study included 90 patients who underwent upper spinal fusion surgery for mechanical instability, performed by three surgeons in two hospitals from 2011 to 2023; OC fusion was indicated for irreducible AA subluxation, os odontoideum, and severe upper C1 fracture. Of the patients, 38 (mean age, 58.7 years) underwent OC fusion, and 52 (mean age, 62.8 years) underwent AA fusion. To evaluate surgical outcomes, we documented surgical time, intraoperative blood loss, postoperative complications, and the rate of revision surgery. Radiographs were obtained to identify screw malposition, rod breakage, and nonunion. To compare the outcomes of the two techniques, we used the Mann-Whitney U test for continuous variables and the chi-square or Fisher’s exact test for dichotomous variables.Results: OC fusion took significantly longer (175.4 minutes) than AA fusion (150.7 minutes, p=0.020) and had a higher complication rate (39.5% vs. 11.5%, p <0.0001). The reoperation rate was 23.7% (9/38) after OC fusion and 3.8% (2/52) after AA fusion; the difference was statistically significant (p=0.0073). Average amounts of blood loss were 224 mL during OC fusion and 224 mL during AA fusion; the difference was not significant (p=0.947).Conclusions: Although OC fusion is indispensable for certain conditions, particularly basilar invagination, it entails more risk than dose AA fusion; the choice of technique thus warrants careful consideration.

Meticulous clinical examination is essential for spinal disorders to utilize the diagnostic methods and technologies that strongly support physicians and enhance clinical practice. A significant change in the approach to diagnosing spinal disorders has occurred in the last three decades, which has enhanced a more nuanced understanding of spine pathology. Traditional radiographic methods such as conventional and functional X-rays and CT scans are still the first line in the diagnosis of spinal disorders due to their low cost and accessibility. As more advanced imaging technologies become increasingly available worldwide, there is a constantly increasing trend in MRI scans for detecting spinal pathologies and making treatment decisions. Not only do MRI scans have superior diagnostic capabilities, but they also assist surgeons in performing meticulous preoperative planning, making them currently the most widely used diagnostic tool for spinal disorders. Positron Emission Tomography (PET) can help detect inflammatory lesions, infections, and tumors. Other advanced diagnostic tools such as CT/MRI fusion image, Functional Magnetic Resonance Imaging (fMRI), Upright and Kinetic MRI, magnetic resonance spectroscopy (MRS), diffusion-weighted imaging (DWI), and diffusion tensor imaging (DTI) could play an important role when it comes to detecting more special pathologies. However, some technical difficulties in the daily praxis and their high costs act as obstacles to their further spread. Integrating artificial intelligence and advancements in data analytics and virtual reality promises to enhance spinal procedures’ precision, safety, and efficacy. As these technologies continue to develop, they will play a critical role in transforming spinal surgery. This paradigm shift emphasizes the importance of continuous innovation and adaptability in improving the diagnosis and treatment of spinal disorders.

Objective: Postoperative lymphopenia is reported as an excellent indicator to predict surgical-site infection (SSI) after spine surgery. However, there is still controversy concerning which serological markers can predict spinal SSI. This study aims to evaluate excellent and early indicators for detecting SSI, focusing on spine instrumented surgery. Materials and Methods: This study included 268 patients who underwent spinal instrumented surgery from January 2022 to December 2023 (159 female and 109 male, average 62.9 years). The SSI group included 20 patients, and the non-SSI group comprised 248 patients. Surgical time, intraoperative blood loss, and glycemic levels were measured in both groups. The complete blood cell counts, differential counts, albumin, and C-reactive protein (CRP) levels were measured pre-surgery and postoperative on Days 1, 3, and 7. In comparing the groups, the Mann–Whitney U test analysis was used for continuous variables, while the chi-squared test and Fisher’s exact test were used for dichotomous variables. Results: The incidence of SSI after spinal instrumentation was 7.46% and was relatively higher in scoliosis surgery. The SSI group had significantly longer surgical times (248 min vs. 180 min, p = 0.0004) and a higher intraoperative blood loss (772 mL vs. 372 mL, p < 0.0001) than the non-SSI group. In the SSI group, the Day 3 (10.5 ± 6.2% vs. 13.8 ± 6.0%, p = 0.012) and Day 7 (14.4 ± 4.8% vs. 18.8 ± 7.1%, p = 0.012) lymphocyte ratios were lower than the non-SSI group. Albumin levels on Day 1 in the SSI group were lower than in the non-SSI group (2.94 ± 0.30 mg/dL vs. 3.09 ± 0.38 mg/dL, p = 0.045). There is no difference in CRP and lymphocyte count between the two groups. Conclusions: SSI patients had lower lymphocyte percentages than non-SSI patients, which was a risk factor for SSI, with constant high inflammation. The Day 3 lymphocyte percentage may predict SSI after spinal instrumented surgery.

The lack of circulating biomarkers for tumor monitoring is a major problem in Ewing sarcoma management. The development of methods for accurate tumor monitoring is required, considering the high recurrence rate of drug‐resistant Ewing sarcoma. Here, we describe a sensitive analytical technique for tumor monitoring of Ewing sarcoma by detecting circulating extracellular vesicles secreted from Ewing sarcoma cells. Proteomic analysis of Ewing sarcoma cell‐derived extracellular vesicles identified 564 proteins prominently observed in extracellular vesicles from three Ewing sarcoma cell lines. Among these, CD99, SLC1A5, and ENO‐1 were identified on extracellular vesicles purified from sera of patients with Ewing sarcoma before treatment but not on extracellular vesicles from those after treatment and healthy individuals. Notably, not only Ewing sarcoma‐derived extracellular vesicles but also Ewing sarcoma cells demonstrated proteomic expression of CD99 and ENO‐1 on their surface membranes. ENO‐1⁺CD63⁺ extracellular vesicle detection was reduced after tumor resection while both CD99⁺CD63⁺ and ENO‐1⁺CD63⁺ extracellular vesicles were detected in serum from Ewing sarcoma‐bearing mice. Finally, the accuracy of liquid biopsy targeting these candidates was assessed using extracellular vesicles from the sera of patients with Ewing sarcoma. Elevated ENO‐1⁺CD81⁺ extracellular vesicles in the serum of patients before treatments distinguished patients with Ewing sarcoma from healthy individuals with an area under the curve value of 0.92 (P < 0.001) and reflected the tumor burden in patients with Ewing sarcoma during multidisciplinary treatments. Collectively, circulating ENO‐1⁺CD81⁺ extracellular vesicle detection could represent a novel tool for tumor monitoring of Ewing sarcoma.

Purpose: The increasing elderly patient population is contributing to the rising worldwide load of cervical spinal disorders, which is expected to result in a global increase in the number of surgical procedures in the foreseeable future. Cervical rehabilitation plays a crucial role in optimal recovery after cervical spine surgeries. Nevertheless, there is no agreement in the existing research regarding the most suitable postsurgical rehabilitation program. Consequently, this review assesses the ideal rehabilitation approach for adult patients following cervical spine operations. Materials and Methods: This review covers activities of daily living and encompasses diverse treatment methods, including physiotherapy, specialized tools, and guidance for everyday activities. The review is organized under three headings: (1) historical perspectives, (2) patient-reported functional outcomes, and (3) general and disease-specific rehabilitation. Results: Rehabilitation programs are determined on the basis of patient-reported outcomes, performance tests, and disease prognosis. CSM requires strengthening of the neck and shoulder muscles that have been surgically invaded. In contrast, the CCI requires mobility according to the severity of the spinal cord injury and functional prognosis. The goal of rehabilitation for CCTs, as for CCIs, is to achieve ambulation, but the prognosis and impact of cancer treatment must be considered. Conclusions: Rehabilitation of the cervical spine after surgery is essential for improving physical function and the ability to perform daily activities and enhancing overall quality of life. The rehabilitation process should encompass general as well as disease-specific exercises. While current rehabilitation protocols heavily focus on strengthening muscles, they often neglect the crucial aspect of spinal balance. Therefore, giving equal attention to muscle reinforcement and the enhancement of spinal balance following surgery on the cervical spine is vital.