Influence of Respiratory Motion on Dose Distribution in Gastric Mucosa-associated Lymphoid Tissue Lymphoma Radiotherapy.

BACKGROUND/AIM: The present study investigated the effect of respiratory motion on planned radiotherapy (RT) dose for gastric mucosa-associated lymphoid tissue (MALT) lymphoma using four-dimensional dose (4D-dose) accumulation. PATIENTS AND METHODS: 4D-computed tomography (4D-CT) images of 10 patients with gastric MALT lymphomas were divided into 10 respiratory phases. Further, the 3D-dose was calculated using 3D conformal RT (3D-CRT) and volumetric modulated arc therapy (VMAT) plans based on the average intensity projection (AIP) images. Then, both plans were recalculated according to each phase image. Moreover, the dose distributions in each phase were transferred to the AIP images using deformable image registration. The 4D-dose distribution was calculated by summing the doses of each phase, and it was compared with the dosimetric parameters of the 3D-dose distribution. RESULTS: For 3D-CRT, the D95 and D99 of the 4D-dose in the planning target volume (PTV) were significantly lower than those of the 3D-dose, with mean differences of 0.2 (p=0.009) and 0.1 Gy (p=0.021), respectively. There were no significant differences in the other PTV and organ-at-risk dosimetric parameters of 3D-CRT or in any dosimetric parameters of VMAT between the 3D- and 4D-dose distributions. CONCLUSION: The effect of respiratory motion on the planned 3D-CRT and VMAT dose distributions for gastric MALT lymphoma is minimal and clinically negligible.

Impact of metal artifact reduction algorithm on gross tumor volume delineation in tonsillar cancer: reducing the interobserver variation.

BACKGROUND: Patients with tonsillar cancer (TC) often have dental fillings that can significantly degrade the quality of computed tomography (CT) simulator images due to metal artifacts. We evaluated whether the use of the metal artifact reduction (MAR) algorithm reduced the interobserver variation in delineating gross tumor volume (GTV) of TC. METHODS: Eighteen patients with TC with dental fillings were enrolled in this study. Contrast-enhanced CT simulator images were reconstructed using the conventional (CTCONV) and MAR algorithm (CTMAR). Four board-certified radiation oncologists delineated the GTV of primary tumors using routine clinical data first on CTCONV image datasets (GTVCONV), followed by CTCONV and CTMAR fused image datasets (GTVMAR) at least 2 weeks apart. Intermodality differences in GTV values and Dice similarity coefficient (DSC) were compared using Wilcoxon's signed-rank test. RESULTS: GTVMAR was significantly smaller than GTVCONV for three observers. The other observer showed no significant difference between GTVCONV and GTVMAR values. For all four observers, the mean GTVCONV and GTVMAR values were 14.0 (standard deviation [SD]: 7.4) cm3 and 12.1 (SD: 6.4) cm3, respectively, with the latter significantly lower than the former (p < 0.001). The mean DSC of GTVCONV and GTVMAR was 0.74 (SD: 0.10) and 0.77 (SD: 0.10), respectively, with the latter significantly higher than that of the former (p < 0.001). CONCLUSIONS: The use of the MAR algorithm led to the delineation of smaller GTVs and reduced interobserver variations in delineating GTV of the primary tumors in patients with TC.

Implementation of 99mTc-GSA SPECT Image-guided Inverse Planning into Palliative Radiotherapy for Diffuse Liver Metastases: A Novel Approach.

BACKGROUND/AIM: This is a report of the first clinical implementation of 99mTc-labeled diethylene triamine pentaacetate-galactosyl human serum albumin (99mTc-GSA) single-photon emission computed tomography (SPECT) image-guided inverse planning into palliative radiotherapy (RT) for diffuse liver metastases. CASE REPORT: A 48-year-old man developed chemo-refractory diffuse liver metastases from thymic carcinoma characterized by abdominal pain and distension. Palliative RT was performed with a total dose of 20 Gy in five fractions using double arc volumetric modulated arc therapy to reduce the dose to functional liver defined by 99mTc-GSA SPECT images. His symptoms were immediately relieved after RT and did not experience radiation-induced liver disease. Both Functional Assessment of Cancer Therapy (FACT)-G and FACT-Hep total scores improved after 2 weeks of RT initiation and did not become worse than baseline scores. CONCLUSION: The 99mTc-GSA SPECT image-guided palliative RT is an effective and safe treatment for patients with diffuse liver metastases.

A prospective comparison of adaptive and fixed boost plans in radiotherapy for glioblastoma.

PURPOSE: To analyze the efficacy of adaptive radiotherapy (ART) for glioblastoma. METHODS: Sixty-one glioblastoma patients who received ART were prospectively evaluated. The initial clinical target volume (CTVinitial) was represented by T2 hyperintensity on postoperative MRIs (pre-RT MRI [MRIpre])plus 10 mm. The initial planning target volume (PTVinitial) was the CTVinitial plus a 5-mm margin. The PTVinitial received 40 Gy. An MRI and a second planning CT were performed during radiotherapy (MRImid). Two types of boost CTVs (the resection cavity and residual tumor on enhanced T1-weighted MRI plus 10 mm) were created based on the MRIpre and MRImid (CTVboost-pre and -mid). The boost PTV (PTVboost) was the CTVboost plus 5 mm. Two types of boost plans (fixed and adaptive boost plans in the first and second planning CT, respectively) of 20 Gy were created. The PTV based on the post-RT MRI (PTVboost-post) was created, and the dose-volume histograms of the PTVboost-post in the fixed and adaptive boost plans were compared. Additionally, the conformity indices (CIs) of the fixed and adaptive boost plans were compared. RESULTS: The median V95 of the PTVboost-post of the fixed and adaptive boost plans (V95pre and V95mid) were 95.6% and 98.3%, respectively (P < 0.01). The median V95pre and V95mid of patients after gross total resection (GTR) were 97.4% and 98.8%, respectively (P = 0.41); in contrast, the median values of patients after non-GTR were 91.9% and 98.2%, respectively (P < 0.01). The median CIs of the fixed and adaptive boost plans in all patients were 1.45 and 1.47, respectively (P = 0.31). The median CIs of the fixed and adaptive boost plans in patients after GTR were 1.61 and 1.48, respectively (P = 0.01); in contrast, those in patients after non-GTR were 1.36 and 1.44, respectively (P = 0.13). CONCLUSION: ART for glioblastoma improved the target coverage and dose reduction for the normal brain. By analyzing the results according to the resection rate, we can expect a decrease in normal brain dose in patients with GTR and an increase in coverage in those with partial resection or biopsy.

Prevalence and risk factors of retro-styloid lymph node metastasis in oropharyngeal carcinoma.

BACKGROUND: Supporting data defining the selection criteria of level VIIb for inclusion in the target volume in radiotherapy (RT) planning are insufficient. We evaluated the prevalence of level VIIb retro-styloid lymph node metastasis (RSLNM) and associated risk factors in patients with oropharyngeal carcinoma (OPC). MATERIALS AND METHODS: We retrospectively reviewed pre-treatment [18F]-fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography (CT) along with contrast-enhanced thin slice CT and magnetic resonance (MR) images of 137 patients pathologically confirmed as having OPC who underwent RT. The location of lymph nodes (LNs) was confirmed on the planning CT images. Fisher's exact test and logistic regression analyses were made to determine the risk factors of RSLNM. RESULTS: RSLNM was confirmed in 18 (13%) patients. All RSLNMs were located within level VIIb on the planning CT images. No patients exhibited LNM in contralateral level VIIb. Furthermore, no patients with negative or single ipsilateral cervical LNM had RSLNM. Fisher's exact test revealed that smoking status (p=.027), multiple ipsilateral cervical LNM (p=.045) and LN ≥15 mm in the upper limit of ipsilateral level II (p<.001) were significantly associated with RSLNM. Logistic regression analyses revealed that the presence of LNs ≥15 mm in upper limit of ipsilateral level II was significantly associated with RSLNM (odds ratio: 977.297; 95% confidence interval: 57.629-16573.308; p<.001). CONCLUSIONS: RSLNM is relatively common in patients with OPC with a prevalence rate of approximately 10%. The prevalence of RSLNM in patients with negative or single ipsilateral cervical LNM and contralateral RSLNM is extremely low; therefore, level VIIb can be excluded from the target volume in such patients. LN ≥15 mm in the upper limit of ipsilateral level II is a risk factor for RSLNM. Ipsilateral level VIIb should be included in the target volume for patients with this risk factor.KEY MESSAGERetro-styloid lymph node metastasis (RSLNM) prevalence is ∼10% in oropharyngeal carcinoma.Lymph node ≥15 mm in ipsilateral level II upper limit is a risk factor for RSLNM.

Plan Quality Comparisons Between 3D-CRT, IMRT, and VMAT Based on 4D-CT for Gastric MALT Lymphoma.

BACKGROUND/AIM: We compared three-dimensional conformal RT (3D-CRT), intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy (VMAT) for gastric mucosa-associated lymphoid tissue (MALT) lymphoma using four-dimensional computed tomography (4D-CT) images. PATIENTS AND METHODS: Three treatment plans of 3D-CRT, IMRT, and VMAT with 30 Gy were created based on 4D-CT images of seven patients. We calculated D95, homogeneity index (HI), and conformity index (CI) of planning target volume, and organs at risk doses. RESULTS: There was no significant difference among the three plans in D95. HI of the IMRT plan was significantly better than that of the VMAT (p=0.047) and 3D-CRT (p=0.047) plans. CIs of the IMRT and VMAT plans were significantly better than those of the 3D-CRT plan (p=0.047 and p=0.047, respectively). Dmean of the liver for 3D-CRT was significantly higher than that for the IMRT (p=0.047) and VMAT (p=0.047) plans. CONCLUSION: The IMRT plan yields the best plan quality for gastric MALT lymphoma.

Impact of four-dimensional cone-beam computed tomography on target localization for gastric mucosa-associated lymphoid tissue lymphoma radiotherapy: reducing planning target volume.

BACKGROUND: Radiotherapy of gastric mucosa-associated lymphoid tissue (MALT) lymphoma should be delivered to the entire stomach with planning target volume (PTV) that accounts for variations in stomach volume, respiratory movement, and patient set-up error. In this study, we evaluated whether the use of four-dimensional cone-beam computed tomography (4D-CBCT) reduces the PTV. METHODS: Eight patients underwent radiotherapy with 15 fractions of gastric MALT lymphoma using 4D-CBCT. PTV structures of 5-30 mm margins (5 mm intervals) from the clinical target volume (CTV) delineated based on the 4D-CT images (CTV-4D) were generated. For the target localization, we performed matching based on skin marking (skin matching), bone anatomy (bone matching), and stomach anatomy (4D soft-tissue matching) based on registration between planning CT and 4D-CBCT images from 10 phases. For each patient, we calculated the covering ratio (CR) of the stomach with variable PTV structures, based on the 4D-CBCT images, with a total of 150 phases [CR (%) = (number of covering phases/150 phases) × 100], for three target localization methods. We compared the CR values of the different target localization methods and defined the PTV with an average CR of ≥ 95% for all patients. RESULTS: The average CR for all patients increased from 17.9 to 100%, 19.6 to 99.8%, and 33.8 to 100%, in the skin, bone, and 4D soft-tissue matchings, respectively, as the PTV structures increased from 5 to 30 mm. The CR obtained by 4D soft-tissue matching was superior to that obtained by skin (P = 0.013) and bone matching (P = 0.008) for a PTV structure of 15 mm margin. The PTV required an additional margin of 20 mm (average CR: 95.2%), 25 mm (average CR: 99.1%), and 15 mm (average CR: 98.0%) to CTV-4D for the skin, bone, and 4D soft-tissue matchings, respectively. CONCLUSIONS: This study demonstrates that the use of 4D-CBCT reduces the PTV when applying 4D soft-tissue matching, compared to skin and bone matchings. Additionally, bone matching does not reduce the PTV as compared with traditional skin matching.

Hypofractionated palliative volumetric modulated arc radiotherapy with the Radiation Oncology Study Group 8502 "QUAD shot" regimen for incurable head and neck cancer.

BACKGROUND: To review a single institutional experience of the Radiation Therapy Oncology Group (RTOG) 8502 "QUAD shot" regimen using volumetric modulated arc radiotherapy (VMAT) for incurable head and neck cancer (HNC). METHODS: Thirty-four consecutive patients with HNC were treated with at least one cycle of the RTOG 8502 regimen. Treatment plans included the use of VMAT with 6 MV photons generated by a linear accelerator. Two daily fractions of 3.7 Gy were delivered with an interval of at least 6 h for 2 consecutive days, totaling 14.8 Gy over 4 fractions. This was repeated every 3-4 weeks for a total of three cycles. No concurrent systemic therapy was performed. RESULTS: The number of completed cycles was 1 in 6 (18%) patients, 2 in 5 (15%), and 3 in 23 (68%). Tumor response was achieved in 29 (85%) patients and symptom relief in 20 (77%) of 26 patients. Overall response (tumor response or symptom relief) was achieved in 32 (94%) patients. All patients who received 2 or more treatment cycles achieved overall response. Median overall survival (OS) was 5.7 months. Multivariate analysis revealed that completion of all three treatment cycles was significantly associated with better OS (P = 0.002). Grade 2 toxicity was observed in four (12%) patients, but no acute Grade ≥ 3 or late toxicity was observed. CONCLUSIONS: The RTOG 8502 "QUAD shot" regimen using VMAT is effective for incurable HNC with highly reduced toxicity. Treatment with multiple cycles is recommended for better treatment response and/or survival.

Correction to: Treatment of aggressive adult T-cell leukemia/lymphoma: a retrospective study in a hospital located in HTLV-1 highly endemic area.

In the original publication of the article, Table 5 was published with incorrect contents. The correct Table 5 is given in this correction.

Ectopic expression of a rice plasma membrane intrinsic protein (OsPIP1;3) promotes plant growth and water uptake.

Plasma membrane intrinsic proteins (PIPs) are known to be major facilitators of the movement of a number of substrates across cell membranes. From a drought-resistant cultivar of Oryza sativa (rice), we isolated an OsPIP1;3 gene single-nucleotide polymorphism (SNP) that is mostly expressed in rice roots and is strongly responsive to drought stress. Immunocytochemistry showed that OsPIP1;3 majorly accumulated on the proximal end of the endodermis and the cell surface around the xylem. Expression of GFP-OsPIP1;3 alone in Xenopus oocytes or rice protoplasts showed OsPIP1;3 mislocalization in the endoplasmic reticulum (ER)-like neighborhood, whereas co-expression of OsPIP2;2 recruited OsPIP1;3 to the plasma membrane and led to a significant enhancement of water permeability in oocytes. Moreover, reconstitution of 10×His-OsPIP1;3 in liposomes demonstrated water channel activity, as revealed by stopped-flow light scattering. Intriguingly, by patch-clamp technique, we detected significant NO3- conductance of OsPIP1;3 in mammalian cells. To investigate the physiological functions of OsPIP1;3, we ectopically expressed the OsPIP1;3 gene in Nicotiana benthamiana (tobacco). The transgenic tobacco plants exhibited higher photosynthesis rates, root hydraulic conductivity (Lpr ) and water-use efficiency, resulting in a greater biomass and a higher resistance to water deficit than the wild-type did. Further experiments suggested that heterologous expression of OsPIP1;3 in cyanobacterium altered bacterial growth under different conditions of CO2 gas supply. Overall, besides shedding light on the multiple functions played by OsPIP1;3, this work provides insights into the translational value of plant AQPs.

Treatment of aggressive adult T-cell leukemia/lymphoma: a retrospective study in a hospital located in HTLV-1 highly endemic area.

Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell neoplasm associated with the human T-cell leukemia virus type-I (HTLV-1); prognosis still remains very poor. We retrospectively reviewed the treatment of 198 patients with acute-, lymphoma- and unfavorable chronic-type ATL (aggressive ATL) diagnosed from 2005 to 2014 in a hospital located in an area of Japan in which HTLV-1 is highly endemic. One-hundred forty-three, and 35 patients were treated using OPEC/MPEC and VCAP-AMP-VECP, respectively. OPEC/MPEC was mainly used until around 2010, and gradually switched to VCAP-AMP-VECP, especially for younger patients. The 2-year overall survival for patients treated by VCAP-AMP-VECP was significantly higher than that using OPEC/MPEC for patients < 70 years old (y.o.), but not for patients ≥ 70 y.o. A less intensive chemotherapy OPEC/MPEC could be performed without reducing dose intensity, even in elderly patients, and its therapeutic outcome is not inferior to that of VCAP-AMP-VECP. It is difficult to draw definite conclusion from this small retrospective study; however, OPEC/MPEC may represent an alternative option for elderly patients with aggressive ATL.

Pentosan Polysulfate Demonstrates Anti-human T-Cell Leukemia Virus Type 1 Activities In Vitro and In Vivo.

Human T-cell leukemia virus type 1 (HTLV-1) infection causes T-cell leukemia and inflammatory diseases, most notably including HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The underlying mechanism for the pathogenesis of HAM/TSP remains unclear. According to a recent clinical trial, a humanized antibody that targets CCR4+ cells ameliorates inflammation by reducing the number of infected cells in the central nervous system; this result suggests that the transmigration of HTLV-1-infected cells plays a crucial role in HAM/TSP. Partly due to the blood-brain barrier, current treatments for HAM/TSP are mostly palliative. Pentosan polysulfate (PPS), a semisynthetic glycosaminoglycan, has recently been used to treat HAM/TSP and was found to alleviate the symptoms. In this study, we investigated the effect of PPS on HTLV-1-infected cells and provide evidence for its efficacy in HAM/TSP. PPS was cytotoxic to certain HTLV-1-infected cells and significantly suppressed HTLV-1 virion production. PPS also efficiently inhibited HTLV-1 cell-cell transmission in T cells. In addition, PPS blocked HTLV-1 infection of primary endothelial cells (human umbilical vascular endothelial cells) and suppressed the subsequent induction of proinflammatory cytokine expression. Furthermore, PPS was found to inhibit the adhesion and transmigration of HTLV-1-infected cells. We also confirmed the anti-HTLV-1 effect of PPS in vivo using two mouse models. PPS blocked HTLV-1 infection in a mouse model with peripheral blood mononuclear cell (PBMC)-humanized NOD-scid IL2Rgammanull (huPBMC NSG) mice. PPS was also found to suppress the development of dermatitis and lung damage in HTLV-1 bZIP factor (HBZ)-transgenic (HBZ-Tg) mice, an HTLV-1 transgenic mouse model in which the mice develop systemic inflammation.IMPORTANCE HTLV-1 is the first human retrovirus to have been identified and is endemic in certain areas worldwide. HTLV-1 infection leads to the development of an inflammatory disease called HAM/TSP, a myelopathy characterized by slowly progressive spastic paraparesis. There have been no effective therapeutics available for HAM/TSP, but recently, a semisynthetic glycosaminoglycan, named pentosan polysulfate (PPS), has been found to alleviate the symptoms of HAM/TSP. Here we conducted a comprehensive study on the effect of PPS both in vitro and in vivo PPS demonstrated anti-HTLV-1 potential in infected cell lines, as shown by its suppressive effects on HTLV-1 replication and transmission and on the transmigration of infected T cells. Moreover, results obtained from two HTLV-1 mouse models demonstrate that PPS inhibits HTLV-1 infection and inflammation development in vivo Our work offers insights into the treatment of HAM/TSP by PPS and also suggests its possible use for treating other HTLV-1-induced inflammatory diseases.

The neurorestorative effect of human amniotic fluid stem cells on the chronic phase of neonatal hypoxic-ischemic encephalopathy in mice.

BACKGROUND: Hypoxic-ischemic encephalopathy (HIE) remains a major cause of cerebral palsy. Increasing evidence has suggested that mesenchymal stem cells have a favorable effect on HIE. However, the efficacy of human amniotic fluid stem cells (hAFS) for HIE, especially in the chronic phase, remains unclear. The aim of this study was to determine the neurorestorative effect of hAFS on the chronic phase of HIE. METHODS: hAFS were isolated from AF cells as CD117-positive cells. HI was induced in 9-day-old mice. Animals intranasally received hAFS or phosphate-buffered saline at 10 days post HI and were harvested for histological analysis after functional tests at 21 days post HI. We also implanted PKH26-positive hAFS to assess their migration to the brain. Finally, we determined gene expressions of trophic factors in hAFS co-cultured with HI brain extract. RESULTS: hAFS improved sensorimotor deficits in HIE by gray and white matter restoration and neuroinflammation reduction followed by migration to the lesion. Brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), hepatocyte growth factor (HGF), and stromal cell-derived factor-1 (SDF-1) gene expressions in hAFS were elevated when exposed to HI-induced brain extract. CONCLUSION: hAFS induced functional recovery by exerting neurorestorative effects in HIE mice, suggesting that intranasal administration of hAFS could be a novel treatment for HIE, especially in the chronic phase.

Intravitreal bevacizumab treatment reduces ocular blood flow in retinopathy of prematurity: a four-case report.

PURPOSE: To evaluate the relationship between ocular blood flow, expressed as mean blur rate (MBR) by laser speckle flowgraphy, and intravitreal bevacizumab (IVB) therapy in neonates with retinopathy of prematurity (ROP). METHODS: This was a case series study of 4 neonates with ROP under sedation before and after IVB and evaluated 8 eyes, in which the circulation could be measured three times consecutively. We performed optic nerve head blood flow measurement and fluorescein angiography (FA) before and 1 week after treatment. Blood flow was analyzed separately for MBR-A (mean of all values), MBR-V (vessel mean), and MBR-T (tissue mean). Comparisons between the MBR (-A, -V, -T), body weight, and other systemic and ocular parameters before and after treatment were performed using a paired t test. RESULTS: The MBR values after IVB were lower than the pre-treatment values in all cases. All eyes showed leakage at neovascularization on FA before treatment. Although leakage improved 1 week after treatment, the neovascularization did not completely regress. CONCLUSIONS: IVB improves vein dilation and artery tortuosity, while reducing ocular blood flow in neonates with ROP. We suggest that neovascularization might not be involved in reducing ocular blood flow in the early stage of IVB treatment.

Human Amniotic Fluid Stem Cells: Therapeutic Potential for Perinatal Patients with Intractable Neurological Disease.

Mesenchymal stem cells (MSCs) have generated great interest in the fields of regenerative medicine and immunotherapy because of their unique biological properties. Among MSCs, amniotic fluid stem cells (AFS) have a number of characteristics that make them attractive candidates for tissue engineering and cell replacement strategies, particularly for perinatal medicine. If various neonatal conditions, including birth asphyxia, preterm birth, and congenital abnormalities, which result in long-lasting severe impairments, could be predicted during pregnancy, it would allow collection of small samples of amniotic fluid cells by amniocentesis. In vitro culture of these autologous AFS during pregnancy would make them available for use soon after birth. Hypoxic-ischemic encephalopathy (HIE) and myelomeningocele (MMC) are neonatal conditions that cause permanent neurological disability, for which the treatment options are extremely limited. Experiments using animal models of HIE and MMC and human clinical trials have demonstrated that MSCs, including AFS, have beneficial effects on the central nervous system through paracrine influences, indicating that autologous AFS treatment may be applicable for intractable neurological diseases, including HIE and MMC, during the perinatal period. In this review, we focus on recent research related to the therapeutic potential of AFS for perinatal neurological diseases such as HIE and MMC.

Double non-contiguous fractures in a patient with spondylo-epiphyseal dysplasia with spinal ankylosis treated with open and percutaneous spinal fixation technique: a case report.

BACKGROUND: Patients with ankylosing spines are susceptible to developing spinal fractures even with minor trauma and can develop early or late neurological injuries. These fractures require early and aggressive surgical management to enable spinal stability and/or neural decompression. Being highly unstable by nature, they require relatively long segment instrumentation and fusion, which can increase paravertebral soft tissue damage and perioperative bleeding. The purpose of this report is to describe a rare case of traumatic double fractures at the cervico-thoracic and thoraco-lumbar transition zones in ankylosing spine with spondylo-epiphyseal dysplasia (SED) of unknown cause, which were successfully treated with a combined open and percutaneous spinal fusion procedure. CASE PRESENTATION: A 46-year-old woman who was diagnosed with non-contiguous fractures in cervico-thoracic and thoraco-lumbar junction zones among multiple injuries sustained in a traffic accident was treated with hybrid techniques for posterior instrumentation with an open approach using a computed tomography (CT)-based navigation system and percutaneous pedicle-screwing method. She regained mobility to pre-admission levels and started walking on crutches 3 months postoperatively. Genetic testing for the cause of SED revealed no mutation in the COL2A1 or TRPVR4 genes. The union of fractured spine was confirmed on CT scan 1 year postoperatively. CONCLUSION: This is the first report of double spinal fractures in an ankylosing spine with genetically undetermined spondyloepiphyseal dysplasia. A long-segment posterior instrumentation procedure incorporating the invasive treatment of spinal fractures in ankylosing spondylitis or diffuse idiopathic hyperostosis was effective.