The decline in cellular iron is crucial for differentiation in keratinocytes.

Iron is a vital metal for most biological functions in tissues, and its concentration is exquisitely regulated at the cellular level. During the process of differentiation, keratinocytes in the epidermis undergo a noticeable reduction in iron content. Conversely, psoriatic lesions, characterized by disruptions in epidermal differentiation, frequently reveal an excessive accumulation of iron within keratinocytes that have undergone differentiation. In this study, we clarified the significance of attenuated cellular iron content in the intricate course of epidermal differentiation. We illustrated this phenomenon through the utilization of hinokitiol, an iron chelator derived from the heartwood of Taiwanese hinoki, which forcibly delivers iron into cells independent of the intrinsic iron-regulation systems. While primary cultured keratinocytes readily succumbed to necrotic cell death by this iron chelator, mild administration of the hinokitiol-iron complex modestly disrupts the process of differentiation in these cells. Notably, keratinocyte model cells HaCaT and anaplastic skin rudiments exhibit remarkable resilience against the cytotoxic impact of hinokitiol, and the potent artificial influx of iron explains a suppressive effect selectively on epidermal differentiation. Moreover, the augmentation of iron content induced by the overexpression of divalent metal transporter 1 culminates in the inhibition of differentiation in HaCaT cells. Consequently, the diminution in cellular iron content emerges as an important determinant influencing the trajectory of keratinocyte differentiation.

Gap analysis between trainees' subjective competencies and the competencies expected by instructors in urology: A need assessment survey in Japan.

OBJECTIVE: According to the rapid progress in surgical techniques, a growing number of procedures should be learned during postgraduate training periods. This study aimed to clarify the current situation regarding urological surgical training and identify the perception gap between trainees' competency and the competency expected by instructors in Japan. METHODS: Regarding the 40 urological surgical procedures selected via the Delphi method, we collected data on previous caseloads, current subjective autonomy, and confidence for future skill acquisition from trainees (<15 post-graduate years [PGY]), and the competencies when trainees became attending doctors expected by instructors (>15 PGY), according to a 5-point Likert scale. In total, 174 urologists in Hokkaido Prefecture, Japan were enrolled in this study. RESULTS: The response rate was 96% (165/174). In a large proportion of the procedures, caseloads grew with accumulation of years of clinical practice. However, trainees had limited caseloads of robotic and reconstructive surgeries even after 15 PGY. Trainees showed low subjective competencies at present and low confidence for future skill acquisition in several procedures, such as open cystectomy, ureteroureterostomy, and ureterocystostomy, while instructors expected trainees to be able to perform these procedures independently when they became attending doctors. CONCLUSION: Trainees showed low subjective competencies and low confidence for future skill acquisition in several open and reconstructive procedures, while instructors considered that these procedures should be independently performable by attending doctors. We believe that knowledge of these perception gaps is helpful to develop a practical training program.

CAMSAP3, a microtubule orientation regulator, plays a vital role in manifesting differentiation-dependent characteristics in keratinocytes.

Microtubules constitute pivotal structural elements integral to cellular architecture and physiological functionality. Within the epidermis of the skin, microtubules undergo a noteworthy transition in orientation, shifting from centrosomal to non-centrosomal configurations during the processes of differentiation and stratification. This transition aligns with a discernible increase in the expression of CAMSAP3, a protein that binds to the minus end of microtubules, thereby regulating their orientation. In this study, we identified microtubule-bound CAMSAP3 within HaCaT keratinocytes, revealing an upregulation during the mitotic phase and accumulation at the intercellular bridge during cytokinesis. Building upon this observation, we scrutinized cellular responses upon a tetracycline/doxycycline-inducible CAMSAP3 expression in CAMSAP3-deficient HaCaT cells. Remarkably, CAMSAP3 deficiency induced shifts in microtubule orientation, resulting in cell cycle exit and delayed cytokinesis in a subset of the cells. Furthermore, our inquiry unveiled that CAMSAP3 deficiency adversely impacted the formation and stability of Adherens Junctions and Tight Junctions. In contrast, these perturbations were rectified upon the re-expression of CAMSAP3, underscoring the pivotal role of CAMSAP3 in manifesting differentiation-dependent characteristics in stratified keratinocytes. These observations emphasize the significance of CAMSAP3 in maintaining epidermal homeostasis.

Annual (2023) taxonomic update of RNA-directed RNA polymerase-encoding negative-sense RNA viruses (realm Riboviria: kingdom Orthornavirae: phylum Negarnaviricota).

In April 2023, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by one new family, 14 new genera, and 140 new species. Two genera and 538 species were renamed. One species was moved, and four were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.

Extracellular epimorphin impairs expression and processing of profilaggrin in HaCaT keratinocytes.

The expression and processing of filaggrin, a filament-associated protein in the skin epidermis, is closely associated with keratinocyte cornification. The large precursor profilaggrin (Pro-FLG) is initially detected at the granular layer in keratohyalin granules, subsequently processed into 10 to 12 filaggrin monomers (mFLGs) for keratin assembly, and ultimately degraded into smaller peptides that behave as natural moisturizing factor (NMF) at the outermost epidermis. We previously reported that epimorphin (EPM) extruded upon external stimuli severely perturbs epidermal terminal differentiation. Using HaCaT keratinocytes with inducible expression and recombinant EPM and FLG, we investigated the effect of extracellular EPM on the expression profile of filaggrin. As expression and processing of Pro-FLG in primary keratinocytes are accompanied with apoptotic cell death, we employed HaCaT keratinocytes that grow and express filaggrin mRNA in standard culture medium. In response to ectopic stimulation with extracellular EPM, Pro-FLG expression decreased with elimination of keratohyalin granules in the cells, with filaggrin mRNA remained constant and profilaggrin processing was not accelerated. Additionally, using a recombinant form of mFLG engineered for intracellular localization, we found that extracellular EPM hindered proteolytic cleavage of mFLG for production of NMF. Taken together, extracellularly extruded EPM, an epidermal cornification blocker, not only decreases Pro-FLG expression but also reduces the production of NMF in HaCaT keratinocytes. Supplementary Information: The online version contains supplementary material available at 10.1007/s10616-022-00566-8.

Suppression of P-cadherin expression as a key regulatory element for embryonic stem cell stemness.

In embryonic stem (ES) cell colonies, a small subpopulation that changes cell shape and loses pluripotency often appears in two-dimensional (2D) cultures, even in the presence of a stemness factor. We have previously shown that membrane translocation of the syntaxin4, t-SNARE protein contributes to this phenomenon. Here, we show that ES cells in three-dimensional (3D) aggregates do not succumb to extruded syntaxin4 owing to suppressed expression of P-cadherin protein. While extracellular expression of syntaxin4 led to the striking upregulation of P-cadherin mRNA in both 2D and 3D-ES cells, morphological changes and appreciable expression of P-cadherin protein were detected only in 2D-ES cells. Importantly, the introduction of an expression cassette for P-cadherin practically reproduced the effects induced by extracellular syntaxin4, where the transgene product was clearly detected in 2D-, but not 3D-ES cells. An expression construct for P-cadherin-Venus harboring an in-frame insertion of the P2A sequence at the joint region gave fluorescent signals only in the cytoplasm of 2D-ES cells, demonstrating translational regulation of P-cadherin. These results provide the mechanistic insight into the uncontrollable differentiation in 2D-ES cells and shed light on the validity of the "embryoid body protocol commonly used for ES cell handling" for directional differentiation.Key words: differentiation, embryoid body, ES cells, P-cadherin, syntaxin4.

Assessment of type I interferon signatures in undifferentiated inflammatory diseases: A Japanese multicenter experience.

Purpose: Upregulation of type I interferon (IFN) signaling has been increasingly detected in inflammatory diseases. Recently, upregulation of the IFN signature has been suggested as a potential biomarker of IFN-driven inflammatory diseases. Yet, it remains unclear to what extent type I IFN is involved in the pathogenesis of undifferentiated inflammatory diseases. This study aimed to quantify the type I IFN signature in clinically undiagnosed patients and assess clinical characteristics in those with a high IFN signature. Methods: The type I IFN signature was measured in patients' whole blood cells. Clinical and biological data were collected retrospectively, and an intensive genetic analysis was performed in undiagnosed patients with a high IFN signature. Results: A total of 117 samples from 94 patients with inflammatory diseases, including 37 undiagnosed cases, were analyzed. Increased IFN signaling was observed in 19 undiagnosed patients, with 10 exhibiting clinical features commonly found in type I interferonopathies. Skin manifestations, observed in eight patients, were macroscopically and histologically similar to those found in proteasome-associated autoinflammatory syndrome. Genetic analysis identified novel mutations in the PSMB8 gene of one patient, and rare variants of unknown significance in genes linked to type I IFN signaling in four patients. A JAK inhibitor effectively treated the patient with the PSMB8 mutations. Patients with clinically quiescent idiopathic pulmonary hemosiderosis and A20 haploinsufficiency showed enhanced IFN signaling. Conclusions: Half of the patients examined in this study, with undifferentiated inflammatory diseases, clinically quiescent A20 haploinsufficiency, or idiopathic pulmonary hemosiderosis, had an elevated type I IFN signature.

High-Throughput Sequencing Indicates Novel Varicosavirus, Emaravirus, and Deltapartitivirus Infections in Vitis coignetiae.

Vitis coignetiae samples were collected from several locations in the northern area of Japan, and virome analysis using a high-throughput sequencing technique was performed. The data indicated that some of the collected samples were in mixed infections by various RNA viruses. Among these viruses, three were identified as newly recognized species with support of sequence identity and phylogenetic analysis. The viruses have been provisionally named the Vitis varicosavirus, Vitis emaravirus, and Vitis crypticvirus, and were assigned to the genus Varicosavirus, Emaravirus, and Deltapartitivirus, respectively.

Acute Coronary Syndrome in Acute Myeloid Leukemia with Maturation Accompanying Megakaryocytic Differentiation.

An autopsy case (85-year-old Japanese male) of myeloperoxidase- (MPO-) positive acute myeloid leukemia with maturation (M1) accompanying megakaryocytic differentiation is presented. The patient manifested acute coronary syndrome. Even after emergent percutaneous coronary intervention, his performance status remained poor, so no chemotherapy against leukemia was given. The final white blood cell count reached 291,700/µL, and the platelet count was elevated to 510,000/µL. No cytogenetic studies were performed. He died at the 25th day of hospitalization. Autopsy revealed marked leukemic infiltration to the endocardium and subendocardial myocardium. Subendocardial myonecrosis was surrounded or replaced by the leukemic blasts, and neither granulation tissue reaction nor fibrosis was observed. In the cardiovascular lumen, lard-like blood clots were formed and microscopically consisted of leukemic blasts and platelets (leukemic thrombi). Infiltration of leukemic blasts was seen in the body cavities and systemic organs including the lung. The MPO-positive blasts lacked azurophilic granules and expressed the stem cell markers, CD34 and CD117 (c-kit). No features of myelofibrosis were seen in the 100% cellular marrow. In the endocardium, liver, lymph nodes, and bone marrow, megakaryocytic cells (CD42b/CD61+, MPO-) were distributed, while the small-sized blastic cells in the blood and tissues predominantly expressed MPO. The blasts lacked expression of CD42b/CD61. Megakaryocytic differentiation might be stimulated by certain tissue factors. AML accompanying megakaryocytic differentiation in certain tissues and organs should be distinguished from acute megakaryoblastic leukemia. The mechanisms provoking acute coronary syndrome in acute myeloid leukemia are discussed.

[Xanthogranulomatous Pyelonephritis after Partial Nephrectomy Mimicking the Local Recurrence of Papillary Renal Cell Carcinoma].

A 55-year-old man underwent right partial nephrectomy and was diagnosed with papillary type 1 renal cell carcinoma (RCC), pT1a. The surgical margin was negative. Six months later, a follow-up computed tomography scan revealed that a mass appeared adjacent to the location of resection. There were no symptoms nor abnormal blood chemistry results at that time. The possibility of local recurrence of RCC could not be ruled out with by magnetic resonance imaging. Radical nephrectomy was performed for suspected rapid recurrence of RCC. Pathological diagnosis was xanthogranulomatous pyelonephritis but not malignancy.

Recessive Resistance Governed by a Major Quantitative Trait Locus Restricts Clover Yellow Vein Virus in Mechanically but Not Graft-Inoculated Cultivated Soybeans.

Clover yellow vein virus (ClYVV) infects and causes disease in legume plants. However, here, we found that ClYVV isolate No. 30 (ClYVV-No.30) inefficiently multiplied or spread via cell-to-cell movement in mechanically inoculated leaves of a dozen soybean (Glycine max) cultivars and resulted in failure to spread systemically. Soybean plants also had a similar resistance phenotype against additional ClYVV isolates. In contrast, all but one of 24 tested accessions of wild soybeans (G. soja) were susceptible to ClYVV-No.30. Graft inoculation of cultivated soybean TK780 with ClYVV-No.30-infected wild soybean B01167 scion resulted in systemic infection of the cultivated soybean rootstock. This suggests that, upon mechanical inoculation, the cultivated soybean inhibits ClYVV-No.30, at infection steps prior to the systemic spread of the virus, via vascular systems. Systemic infection of all F1 plants from crossing between TK780 and B01167 and of 68 of 76 F2 plants with ClYVV-No.30 indicated recessive inheritance of the resistance. Further genetic analysis using 64 recombinant inbred lines between TK780 and B01167 detected one major quantitative trait locus, designated d-cv, for the resistance that was positioned in the linkage group D1b (chromosome 2). The mapped region on soybean genome suggests that d-cv is not an allele of the known resistance genes against soybean mosaic virus.

National survey of Japanese patients with mevalonate kinase deficiency reveals distinctive genetic and clinical characteristics.

OBJECTIVES: Mevalonate kinase deficiency (MKD), a rare autosomal recessive autoinflammatory syndrome, is caused by disease-causing variants of the mevalonate kinase (MVK) gene. A national survey was undertaken to investigate clinical and genetic features of MKD patients in Japan. METHODS: The survey identified ten patients with MKD. Clinical information and laboratory data were collected from medical records and by direct interviews with patients, their families, and their attending physicians. Genetic analysis and measurement of MVK activity and urinary excretion of mevalonic acid were performed. RESULTS: None of the 10 patients harbored MVK disease-causing variants that are common in European patients. However, overall symptoms were in line with previous European reports. Continuous fever was observed in half of the patients. Elevated transaminase was observed in four of the 10 patients, two of whom fulfilled the diagnostic criteria for hemophagocytic lymphohistiocytosis. About half of the patients responded to temporary administration of glucocorticoids and NSAIDs; the others required biologics such as anti-IL-1 drugs. CONCLUSION: This is the first national survey of MKD patients in a non-European country. Although clinical symptoms were similar to those reported in Europe, the incidence of continuous fever and elevated transaminase was higher, probably due to differences in disease-causing variants.

P3N-PIPO, a Frameshift Product from the P3 Gene, Pleiotropically Determines the Virulence of Clover Yellow Vein Virus in both Resistant and Susceptible Peas.

UNLABELLED: Peas carrying the cyv1 recessive resistance gene are resistant to clover yellow vein virus (ClYVV) isolates No.30 (Cl-No.30) and 90-1 (Cl-90-1) but can be infected by a derivative of Cl-90-1 (Cl-90-1 Br2). The main determinant for the breaking of cyv1 resistance by Cl-90-1 Br2 is P3N-PIPO produced from the P3 gene via transcriptional slippage, and the higher level of P3N-PIPO produced by Cl-90-1 Br2 than by Cl-No.30 contributes to the breaking of resistance. Here we show that P3N-PIPO is also a major virulence determinant in susceptible peas that possess another resistance gene, Cyn1, which does not inhibit systemic infection with ClYVV but causes hypersensitive reaction-like lethal systemic cell death. We previously assumed that the susceptible pea cultivar PI 226564 has a weak allele of Cyn1 Cl-No.30 did not induce cell death, but Cl-90-1 Br2 killed the plants. Our results suggest that P3N-PIPO is recognized by Cyn1 and induces cell death. Unexpectedly, heterologously strongly expressed P3N-PIPO of Cl-No.30 appears to be recognized by Cyn1 in PI 226564. The level of P3N-PIPO accumulation from the P3 gene of Cl-No.30 was significantly lower than that of Cl-90-1 Br2 in a Nicotiana benthamiana transient assay. Therefore, Cyn1-mediated cell death also appears to be determined by the level of P3N-PIPO. The more efficiently a ClYVV isolate broke cyv1 resistance, the more it induced cell death systemically (resulting in a loss of the environment for virus accumulation) in susceptible peas carrying Cyn1, suggesting that antagonistic pleiotropy of P3N-PIPO controls the resistance breaking of ClYVV. IMPORTANCE: Control of plant viral disease has relied on the use of resistant cultivars; however, emerging mutant viruses have broken many types of resistance. Recently, we revealed that Cl-90-1 Br2 breaks the recessive resistance conferred by cyv1, mainly by accumulating a higher level of P3N-PIPO than that of the nonbreaking isolate Cl-No.30. Here we show that a susceptible pea line recognized the increased amount of P3N-PIPO produced by Cl-90-1 Br2 and activated the salicylic acid-mediated defense pathway, inducing lethal systemic cell death. We found a gradation of virulence among ClYVV isolates in a cyv1-carrying pea line and two susceptible pea lines. This study suggests a trade-off between breaking of recessive resistance (cyv1) and host viability; the latter is presumably regulated by the dominant Cyn1 gene, which may impose evolutionary constraints upon P3N-PIPO for overcoming resistance. We propose a working model of the host strategy to sustain the durability of resistance and control fast-evolving viruses.

Image-guided Spine Stabilization for Traumatic Or Osteoporotic Spine Injury: Radiological Accuracy and Neurological Outcome.

Significant progress has been made in image-guided surgery (IGS) over the last few decades. IGS can be effectively applied to spinal instrumentation surgery. In the present study, we focused our attention on the feasibility and safety of image-guided spine stabilization for traumatic or osteoporotic spine injury. The IGS spine fixation with or without minimally invasive surgery (MIS) techniques such as percutaneous screw placement, balloon kyphoplasty (BKP), or vertebroplasty (VP) were accomplished in 80 patients with traumatic or osteoprotic spine injury between 2007 and 2015. The injured vertebral levels included the following: cervical spine, 41; thoracic spine, 22; and lumbar spine, 17. Neurological condition before and after surgery was assessed using the American Spinal Injury Association Impairment Scale (AIS). A total of 419 pedicle, lateral mass, or laminar screws were placed, and 399 screws (95.2%) were found to be placed correctly based on postoperative computed tomography scan. Although 20 screws (4.8%) were found to be unexpectedly placed incorrectly, no neural or vascular complications closely associated with screw placement were encountered. Neurological outcomes appeared to be acceptable or successful based on AIS. The IGS is a promising technique that can improve the accuracy of screw placement and reduce potential injury to critical neurovascular structures. The integration of MIS and IGS has proved feasible and safe in the treatment of traumatic or osteoporotic spine injury, although a thorough knowledge of surgical anatomy, spine biomechanics, and basic technique remain the most essential aspects for a successful surgery.

Truncated yet functional viral protein produced via RNA polymerase slippage implies underestimated coding capacity of RNA viruses.

RNA viruses use various strategies to condense their genetic information into small genomes. Potyviruses not only use the polyprotein strategy, but also embed an open reading frame, pipo, in the P3 cistron in the -1 reading frame. PIPO is expressed as a fusion protein with the N-terminal half of P3 (P3N-PIPO) via transcriptional slippage of viral RNA-dependent RNA polymerase (RdRp). We herein show that clover yellow vein virus (ClYVV) produces a previously unidentified factor, P3N-ALT, in the +1 reading frame via transcriptional slippage at a conserved G(1-2)A(6-7) motif, as is the case for P3N-PIPO. The translation of P3N-ALT terminates soon, and it is considered to be a C-terminal truncated form of P3. In planta experiments indicate that P3N-ALT functions in cell-to-cell movement along with P3N-PIPO. Hence, all three reading frames are used to produce functional proteins. Deep sequencing of ClYVV RNA from infected plants endorses the slippage by viral RdRp. Our findings unveil a virus strategy that optimizes the coding capacity.

Glioblastoma in long-term survivors of acute lymphoblastic leukemia: Report of two cases.

Acute lymphoblastic leukemia (ALL) is the most common form of cancer in children. Second neoplasms as late effects of therapy for ALL have been recognized as a significant clinical issue given the increasing number of long-term survivors of ALL, because they can be the cause of death in such cases. In contrast, glioblastoma (GBM) is the most common primary brain tumor in adults. It is a malignant brain tumor that most often occurs in elderly patients, and GBM in young adults or adolescents appears to be rare. Here, we describe our experience of two cases of GBM in young long-term survivors of ALL, and emphasize the necessity of careful follow up of patients treated for ALL for the potential occurrence of central nervous system second neoplasms, especially when the patients have previously undergone cranial radiotherapy.

Qualitative analysis of spinal intramedullary lesions using PET/CT.

OBJECT Although the usefulness of PET for brain lesions has been established, few reports have examined the use of PET for spinal intramedullary lesions. This study investigated the diagnostic utility of PET/CT for spinal intramedullary lesions. METHODS l-[methyl-11C]-methionine (MET)- or [18F]-fluorodeoxyglucose (FDG)-PET/CT was performed in 26 patients with spinal intramedullary lesions. The region of interest (ROI) within the spinal cord parenchyma was placed manually in the axial plane. Maximum pixel counts in the ROIs were normalized to the maximum standardized uptake value (SUVmax) using subject body weight. For FDG-PET the SUVmax was corrected for lean body mass (SULmax) to exclude any influence of the patient's body shape. Each SUV was analyzed based on histopathological results after surgery. The diagnostic validity of the SUV was further compared with the tumor proliferation index using the MIB-1 monoclonal antibody (MIB-1 index). RESULTS A total of 16 patients underwent both FDG-PET and MET-PET, and the remaining 10 patients underwent either FDG-PET or MET-PET. Pathological diagnoses included high-grade malignancy such as glioblastoma multiforme, anaplastic astrocytoma, or anaplastic ependymoma in 5 patients; low-grade malignancy such as hemangioblastoma, diffuse astrocytoma, or ependymoma in 12 patients; and nonneoplastic lesion including cavernous malformation in 9 patients. Both FDG and MET accumulated significantly in high-grade malignancy, and the SULmax and SUVmax correlated with the tumor proliferation index. Therapeutic response after chemotherapy or radiation in high-grade malignancy was well monitored. However, a significant difference in SULmax and SUVmax for FDG-PET and MET-PET was not evident between low-grade malignancy and nonneoplastic lesions. CONCLUSIONS Spinal PET/CT using FDG or MET for spinal intramedullary lesions appears useful and practical, particularly for tumors with high-grade malignancy. Differentiation of tumors with low-grade malignancy from nonneoplastic lesions may still prove difficult. Further technological refinement, including the selection of radiotracer or analysis evaluation methods, is needed.

Efficacy of arachnoid plasty with collagen sheets and fibrin glue: An in vitro experiment and a case review.

BACKGROUND: Postoperative subdural fluid collection sometimes occurs after clipping of cerebral aneurysms. Arachnoid plasty is used to prevent such postoperative complications; however, the optimal materials for arachnoid plasty remain unclear. In this study, we aimed to clarify the optimal materials for arachnoid plasty and report our experience of arachnoid plasty after clipping of unruptured aneurysms. METHODS: In an in vitro experiment, adhesive strengths of three materials permitted for use in the intradural space, such as collagen sheets, gelatin sponge, and oxidized cellulose sheets, were measured by assessing their water pressure resistance. Then, 80 consecutive cases surgically treated unruptured cerebral aneurysms were retrospectively reviewed to examine the occurrence rate of postoperative subdural fluid collection. RESULTS: The collagen sheet exhibited the greatest adhesive strength, so we used collagen sheets for the arachnoid plasty procedures. In all of these cases, arachnoid plasty was performed with fibrin glue-soaked collagen sheets. No postoperative subdural fluid collection, inflammation, or allergic reactions occurred in any case. CONCLUSIONS: The present study suggests that collagen sheet might be one of the optimal materials for arachnoid plasty. This technique is simple and may be effective to prevent subdural fluid collection after clipping.

Surgical management of solitary nerve sheath tumors of the cervical spine: a retrospective case analysis based on tumor location and extension.

Complete resection of spinal nerve sheath tumors (NSTs) does not always result in significant neurological deficit. The purpose of this retrospective case analysis was to discuss the optimal surgical strategy for spinal NST of the cervical spine. Twenty-four patients who underwent surgery for solitary cervical NST over the past decade were included in this retrospective study. Patients with neurofibromatosis or schwannomatosis were excluded. Seventeen of the 24 cases (70.8%) showed extradural dumbbell extension, most frequently at the C1 or C2 vertebral level. Neurological condition was assessed using the modified McCormick functional schema and sensory pain scale. Total removal of the tumor was achieved in 20 of 24 cases (83.3%). Staged surgery using combined anterior and posterior approaches was applied for 2 of 17 cases with extradural dumbbell extension. Tumor involvement with nerve root fibers critical for upper extremity function (C5-C8) was recognized in 6 of 24 cases (25.0%), with complete resection in all 6 cases. Final assessment of neurological function revealed satisfactory or acceptable recovery in all 6 patients. Spinal NSTs with extradural dumbbell extension are a common condition in the cervical spine. Complete removal of spinal NST of the cervical spine may carry a risk of permanent neurological deficit, but such sequelae appeared to be the exception in the present case analysis. A radical and safe surgical strategy, including staged surgery combining anterior and posterior approaches, should be tailored to the individual case.