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BACKGROUND: Several studies have reported surgical techniques and favorable postoperative outcomes of post-axial polydactyly of the foot; however, few studies have investigated the long-term postoperative outcomes. The aim of this study was to evaluate long-term results of our surgical treatment, which emphasized the alignment between the distal and proximal phalanges, and the ligamentous stability. METHODS: This is a retrospective chart review of patients who underwent surgery for post-axial polydactyly and were followed up until epiphyseal closure of the foot. The study included 13 feet from 12 patients with a mean age at initial surgery of 22 months and postoperative follow-up of 161 months. The surgical method emphasized phalangeal alignment during resection of excess bones and collateral ligament reconstruction to obtain joint stability. Postoperative outcomes included functional problems, varus or valgus deformities, thickening of the reconstructed toe, postoperative complications, additional surgery, esthetic appearance evaluated using the scoring system, and subjective evaluation by patients and the parents. RESULTS: At the latest evaluation after epiphyseal closure of the foot, there were no cases with functional problem or valgus deformities based on morphologic findings. The esthetic appearance of the reconstructed toes was favorable in all but 1 case. Subjective evaluation was more than "satisfied" in 12 toes. In one case, additional surgery to excise scar and excessive soft tissue was performed due to pain. Visible thickening was found in 5 toes, although subjective evaluation by patients and their parents was more than "satisfied." CONCLUSION: We have demonstrated the long-term postoperative outcomes in post-axial polydactyly of the foot with an emphasis on the phalangeal alignment and ligamentous stability until epiphyseal closure as a sign of skeletal maturity. We obtained favorable long-term postoperative outcomes of the reconstructed toes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

DOI： 10.1016/j.jos.2025.10.009

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PURPOSE: Surgical management of lumbar degenerative spondylolisthesis-whether decompression alone or combined with fusion-often relies on instability assessment with standing flexion-extension radiographs. However, these evaluations are influenced by low back pain and other factors, introducing variability into instability determination and surgical planning. Despite widespread use, the reproducibility of quantitative parameters remains unclear. This study evaluated the reproducibility of commonly used quantitative indicators from lumbar functional imaging. METHODS: We retrospectively analyzed 112 patients with L4-5 degenerative spondylolisthesis who underwent two sets of standing flexion-extension radiographs within six months. Five parameters were measured: Changes in lumbar lordosis during flexion [ΔLL(flex)], changes during extension [ΔLL(ext)], sagittal translation (ST), posterior opening (PO), and segmental angulation (SA). Instability was defined as ST ≥ 3 mm or ≥ 8% of the upper vertebral body width, PO ≥ 5°, or SA ≥ 20°, and diagnostic consistency was examined. Two raters independently assessed all radiographs. Test-retest, intra-rater, and inter-rater reliabilities were determined using intraclass correlation coefficients (ICC [1, 1] ICC [1, 2]). Bland-Altman analysis tested fixed and proportional bias. RESULTS: Diagnostic discrepancies between imaging sessions occurred in 25.0-27.7%. ΔLL(flex) showed poor test-retest reliability (ICC = 0.23, 0.32), whereas ΔLL(ext) and PO demonstrated higher reliability. ST and SA yielded low ICC values. Intra-rater and inter-rater reliability was consistently good (ICC > 0.75), and no fixed or proportional bias was detected. CONCLUSION: Variability in flexion influenced ST and SA, potentially affecting instability diagnosis. Standardized imaging protocols and clearer patient instructions are essential to improve diagnostic accuracy and reliability.

DOI： 10.1007/s00586-025-09539-9

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PURPOSE: The effect of the knee flexion angle on the direction and magnitude of tensile force on the meniscus during flexion and extension under a load is unknown. This study aimed to clarify this effect on repair sutures in a lateral meniscus radial tear of the midbody under knee-joint conditions during flexion and extension. METHODS: This study was performed using 10 porcine knees, a robotic system with six degrees of freedom and a load cell. Meniscal repairs were performed using horizontal sutures, with a single stitch between the central and peripheral regions at (1) the inner third position and (2) the outer third position, each meniscus sequentially. The suture of the posterior segment was drawn tangentially anteriorly, whereas the suture of the anterior segment was drawn tangentially posteriorly. The suture of the posterior segment was connected to an anterior load cell to measure the tensile force applied to the suture in the posterior direction. Subsequently, the suture of the anterior segment was connected to a posterior load cell to measure the tensile force applied in the anterior direction. A valgus load of 5 N m was applied for three cycles at 30°, 60° and 90° flexion. RESULTS: The tensile forces exerted anteriorly on the repair sutures at the inner and outer sides in the anterior segment at 30°, 60° and 90° flexions were 13.7/13.3 N (inner/outer), 7.6/7.3 N and 3.4/3.5 N, respectively. The tensile forces exerted posteriorly on the repair sutures in the posterior segment at 30°, 60° and 90° flexions were 1.8/1.5, 10.6/9.7 and 16.2/16.4 N, respectively. CONCLUSIONS: Tensile force was exerted on the repair sutures of complete lateral meniscus radial tears of the midbody, anteriorly in the anterior segment at 30° flexion and posteriorly in the posterior segment at 90° flexion. LEVEL OF EVIDENCE: N/A.

DOI： 10.1002/jeo2.70465

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PURPOSE: This study was performed to compare clinical outcomes of medial opening-wedge high tibial osteotomy (MOWHTO) with individualised alignment and medial meniscus centralisation versus conventional alignment targeting the Fujisawa point without centralisation using propensity score matching. It was hypothesised that the individualised approach with centralisation would not be inferior to conventional HTO targeting the Fujisawa point. METHODS: This retrospective matched case-control study analysed 161 consecutive knees treated with MOWHTO. After applying uniform exclusion criteria and 1:1 propensity score matching for demographic, radiographic, and meniscal factors, 24 knees with HTO and centralisation and 24 control knees were compared. The centralisation group received individualised alignment based on patient characteristics, targeting a weight-bearing line (WBL) ratio of 57.0%-62.5%, whereas the control group followed the standard 62.5% WBL target. The primary outcome was the Knee Injury and Osteoarthritis Outcome Score (KOOS). The secondary outcomes were radiographic alignment and International Cartilage Repair Society (ICRS) cartilage grade on second-look arthroscopy. RESULTS: The mean follow-up duration was 2.5 ± 0.4 years in the centralisation group and 2.5 ± 0.5 years in the control group. Both groups showed significant improvements in all KOOS subscales from preoperative to final follow-up (all p < 0.01). Final KOOS values were comparable, except for a higher Sports and Recreation score in the centralisation group (72.8 ± 21.1 vs. 56.1 ± 27.5; p = 0.039). Postoperative alignment was more neutral in the centralisation group (WBL ratio 51.9% ± 8.7% vs. 61.4% ± 7.6%; p < 0.001). Improvement in the ICRS grade of the medial femoral condyle was observed in 54.2% of knees in the centralisation group compared with 12.5% in the control group (p = 0.001). CONCLUSION: MOWHTO with individualised alignment and medial meniscus centralisation achieved clinical outcomes not inferior to conventional alignment targeting the Fujisawa point without centralisation. LEVEL OF EVIDENCE: Level III, retrospective cohort study.

DOI： 10.1002/jeo2.70594

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INTRODUCTION: Fracture Liaison Service (FLS) programs are beneficial for reducing the frequency of subsequent fractures and mortality in post-hip fracture patients. The aim of this study was to investigate recent changes in the rate of pharmaceutical treatment for osteoporosis in post-hip fracture surgery patients in the absence of FLS programs compared to the previous 10 and 20 years, and whether introduction of a new reimbursement scheme in hip fracture care, launched in 2022 by the Japanese government, improved the pharmaceutical treatment rate after surgical intervention. MATERIALS AND METHODS: Study 1 included 1490 post-hip fracture patients in seven hospitals without an FLS program. Study 2 included 396 osteoporosis patients who were covered by the new reimbursement scheme at five of the seven hospitals. Treatment-related variables and the number of patients who received the different pharmaceutical treatments at 0, 3, 6 and 12 months after discharge from the hospital were examined. RESULTS: Two hundred and thirty-two of 1474 patients received anti-osteoporotic medication at hospital discharge, which was not a significant improvement in the rate of pharmaceutical treatment in comparison with that in our previous studies over 20 years. On the other hand, introduction of the new reimbursement scheme at hospitals significantly improved the rate of pharmaceutical treatment, with 263 of the 391 patients receiving anti-osteoporotic medication at discharge, as well as a significant improvement. CONCLUSION: We demonstrated a significant improvement in the pharmaceutical treatment rate for osteoporosis in post-hip fracture surgery patients after introduction of the new reimbursement scheme launched by the Japanese government.

DOI： 10.1007/s00774-025-01613-y

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Background: Post-hamstring-injury residual pain may persist despite muscle-tissue healing and impairs athletes seeking early full recovery. Given their unclear cause, recent attention has focused on the role of fascial dysfunction and a method to restore fascial mobility, namely, hydrorelease (HR), involving the ultrasound (US)-guided injection of saline. We evaluated the clinical efficacy of HR for treating residual pain and ascertained the underlying pathological mechanisms. Methods: Seven patients (aged 17-49 years) with residual pain ≥8 weeks after hamstring injury were included. All exhibited localized tenderness and US findings of fascial thickening around the aponeurotic fascia (APF). HR with 6.0 mL saline-lidocaine solution (0.17% lidocaine) was performed and targeted the peri-APF loose connective tissues. Pain was evaluated using a numerical rating scale (NRS) before and after HR. Passive straight leg raise (SLR) was used to assess tightness. Results: Post-HR, the mean NRS score significantly decreased from 10 to 0.86 (p = 0.017). Four patients required a single HR session; three required two-four sessions. Post-HR, the tightness of all patients improved. Short-axis US of the posterior thigh revealed APF fascial thickening in the area of tenderness, including the posterior femoral cutaneous nerve (PFCN). No adverse events or recurrence occurred during the follow-up (mean: 6.6 months). Conclusions: HR targeting the peri-PFCN-APF effectively reduced residual pain following hamstring injury. These findings support the concept of "Perineural fascial pain"-a pathology wherein persistent pain originates not from direct nerve damage or classical myofascial pain syndrome but rather from the dysfunction of the surrounding fascia.

DOI： 10.3390/jfmk10030318

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BACKGROUND: Evaluation of medial meniscal extrusion (MME) under physiological loads is crucial because of the influence of MME on meniscal function. Reducing the MME is essential for meniscal function. Few studies have compared the extent of MME in cases of complete radial tears of the posterior segment of the medial meniscus (MM) treated using basic meniscal repair techniques: the inside-out and all-inside techniques. PURPOSE: To compare the extent of MME after the treatment of complete radial tears of the posterior segment using inside-out and all-inside meniscal repair techniques in a cadaveric model. STUDY DESIGN: Controlled laboratory study. METHODS: Six fresh-frozen human cadaveric knees were subjected to a compression load of 250 N using a 6 degrees of freedom robotic system under ultrasound evaluation. The MME was evaluated at 30° and 90° knee flexion in 4 meniscal conditions: (1) intact; (2) complete radial tear in the posterior segment of the MM; (3) inside-out repair technique; and (4) all-inside repair technique using 1 horizontal suture. Conditions 3 and 4 were performed on the same knee in a randomized order. Measurements were obtained at the center of the superficial medial collateral ligament (MCL) (central image) and 1 cm posterior to the superficial MCL (posterior image). Statistical analysis was conducted using a 2-factor repeated-measures analysis of variance with Bonferroni post-hoc correction, with significance level set at P < .05. RESULTS: The amount of MME under compression load after inside-out repair was significantly lower than that after all-inside repair (mean ± SD values for the central image: 30°, 1.93 ± 0.26 mm vs 2.45 ± 0.34 mm; 90°, 2.02 ± 0.29 mm vs 2.53 ± 0.42 mm; for the posterior image: 30°, 1.98 ± 0.30 mm vs 2.43 ± 0.35 mm; 90°, 2.45 ± 0.26 mm vs 3 ± 0.42 mm; P < .001 for all comparisons). CONCLUSION: Although the inside-out repair technique reduced the amount of MME to a greater extent than the all-inside repair technique using a single horizontal stitch for MM posterior segment tears, neither technique was able to reduce MME to the same level as that of the intact state; furthermore, the change in MME was relatively small. CLINICAL RELEVANCE: The findings indicate that the inside-out repair technique should be used to repair complete radial tears in the posterior segment of the MM.

DOI： 10.1177/23259671251356695

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Pleomorphic rhabdomyosarcoma (pRMS) is a rare and highly malignant mesenchymal tumor. Complete resection is the only curative treatment available, owing to the limited efficacy of chemotherapy and radiotherapy. Therefore, developing novel therapies for pRMS is important for improving clinical outcomes. Herein, a novel pRMS cell line, SMU-pRMS, was established for a detailed understanding of the biological characteristics of pRMS, thereby developing new therapies. A tissue sample from a surgically resected tumor of a 69-year-old patient was subjected to primary culture. The cell line was established and authenticated by evaluating the short tandem repeats of DNA microsatellites. Monolayer cultures of SMU-pRMS cells exhibited constant growth, spheroid formation, and invasiveness. These cells exhibited high chemosensitivity to eribulin. In addition, mice inoculated with SMU-pRMS cells developed tumors after 4 weeks. Therefore, the SMU-pRMS cell line is a useful tool for investigating pRMS development and evaluating novel therapeutic agents.

DOI： 10.1007/s13577-025-01263-2

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BACKGROUND: The mainstay of treatment for soft-tissue sarcomas is complete resection with negative surgical margins. However, treatment strategies for local control including the frequency of adjuvant radiotherapy (RT) and surgical margin differ greatly between Japan and other countries, and the optimal strategy of local control remains controversial. METHODS: A total of 70 patients with high-grade sarcoma who underwent surgery of the 72 patients enrolled in JCOG0304, were included. The primary endpoint was the proportion of local recurrence, and we investigated the clinicopathological background of local recurrence cases, including the surgical margins according to the Japanese Orthopedic Association (JOA) margin classification or histological margin, and use of adjuvant RT. RESULTS: Local recurrence occurred in five patients, with a 5-year local recurrence proportion of 7.1% (95% confidence interval, 2.6%-14.8%) in 70 patients. The histological subtype were four cases of undifferentiated pleomorphic sarcoma (UPS) and 1 case of liposarcoma. The 5-year local recurrence proportions for UPS and non-UPS were 19.0% and 2.0%, respectively. Two of the five recurrent cases (40%) had adjuvant RT. The recurrent cases were four males and one female, median age 54 years (range: 33-66), JOA margin classification showed wide resection in four cases and marginal resection in one case, and histological margin showed negative in all five cases. CONCLUSION: Despite the low proportion of adjuvant RT, local control of high-grade soft tissue sarcoma with preoperative chemotherapy in JCOG0304 was good. However, more detailed surgical margin evaluation and the use of adjuvant RT should be further investigated in the future for UPS.

DOI： 10.1093/jjco/hyaf027

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Purpose In anterior cruciate ligament (ACL) injury among young patients, non-operative treatments are the common approach. However, meniscal and cartilage damage have been associated with this treatment, highlighting the need to explore surgical procedures for treating pediatric ACL injuries. We employed a modification of the hybrid physeal-sparing and anatomical double-bundle ACL reconstruction (ACLR) in skeletally immature patients. Here, we aimed to compare the clinical and radiographic outcomes, including International Knee Documentation Committee (IKDC) scores and growth disturbances, between early ACLR (ER) and delayed ACLR (DR) using our modified hybrid physeal-sparing anatomical double-bundle ACL reconstruction technique in skeletally immature patients. Methods Patients with an ACL injury with open physes following two techniques, were retrospectively included. The patients decided whether to select ER or DR. Patients who selected ER underwent surgery as early as possible. Patients who chose DR underwent conservative treatment and anatomical double-bundle ACLR after skeletal maturation. Clinical outcomes were described using the International Knee Documentation Committee Subjective Knee Form, the Tegner activity scale, and the Lysholm score. Using bilateral standing long-leg radiographs after skeletal maturation, growth disturbance was defined as a leg length discrepancy of >10 mm or varus or valgus angular deformity of >3° compared to the other leg. For the femur, three out of 10 patients (30%) had an angle deformity of >3°. For the tibia, one in 10 patients (10%) had an angle deformity of >3°. Results Sixteen patients, 10 (five boys and five girls) treated with ER and six (four boys and two girls) with DR, were analyzed. Clinical outcomes of both groups were good, and there were no significant differences. None of the patients had a leg length discrepancy of >10 mm. Four of the 10 patients (40%) had angle deformity of >3°. Conclusions Anatomical double-bundle ACLR using a hybrid physeal-sparing technique for skeletally immature patients revealed good clinical outcomes. Even though it was not associated with any symptoms, a relatively high rate of angle deformity was observed with ER.

DOI： 10.7759/cureus.85464

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PURPOSE: Our previous NECO phase II studies on high-grade osteosarcoma suggested that administering ifosfamide (IF; 16 g/m2 [4g/m2 once on day 1, then 2g/m2 once on days 2-7] × six) to patients showing a poor response (PrRsp) to preoperative chemotherapy with methotrexate, doxorubicin, and cisplatin (MAP) improves their prognoses. In this Japan Clinical Oncology Group (JCOG) study, JCOG0905, we aimed to investigate the efficacy and safety of IF in patients with PrRsp. METHODS: JCOG0905 is a multicenter, open-label, multi-institutional, randomized trial. Eligible patients (50 years and younger) had resectable, high-grade osteosarcoma (stage II or III, Union for International Cancer Control TNM) of the extremities, limb girdles, and thoracic wall. After two MAP cycles and tumor resection, patients with PrRsp were randomly assigned to either the MAP or MAP plus 15 g/m2 (3g/m2 once daily on days 1-5) × six IF (MAP + IF [MAPIF]) group. The primary end point was disease-free survival (DFS); secondary end points were overall survival (OS) and safety. The planned sample size was 100 patients with a one-sided α of .1 and a power of 0.7, assuming a 3-year DFS of 50% and 65% for MAP and MAPIF, respectively. This trial is registered with the Japan Registry of Clinical Trials (jRCT; jRCTs031180126). RESULTS: Of the 287 patients registered between February 2010 and August 2020, 51 and 52 patients with PrRsp were assigned to the MAP and MAPIF groups, respectively. As of March 2022, DFS did not differ between groups (hazard ratio [HR], 1.05 [95% CI, 0.55 to 1.98]) and OS was numerically inferior in the MAPIF group (HR, 1.48 [95% CI, 0.68 to 3.22]). Nine and zero patients in the MAPIF and MAP groups discontinued treatment because of adverse events, respectively. CONCLUSION: Evidence from JCOG0905 does not support the addition of IF for patients with PrRsp.

DOI： 10.1200/JCO-24-01281

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BACKGROUND: Each band of the deltoid ligament cooperatively contributes to stability of the medial side of the ankle joint. Investigating the function of each band of the deltoid ligament is essential to assess abnormalities and develop treatment options. PURPOSE: To evaluate the changes in ankle kinematics when each band of the deltoid ligament is injured and to measure the in situ force of each ligamentous band in intact ankle kinematics. STUDY DESIGN: Descriptive laboratory study. METHODS: A total of 8 healthy fresh-frozen cadaveric legs were examined by applying forces through eversion and external rotation of the ankle joint using a 6 degrees of freedom robotic system. The deltoid ligament was separated into 6 discrete bands: tibionavicular ligament, tibiospring ligament, tibiocalcaneal ligament (TCL), anterior tibiotalar ligament, superficial posterior tibiotalar ligament (sPTTL), and deep posterior tibiotalar ligament; the bands were then sequentially transected. A loading test was performed in each model, and the changes in ankle motion and in situ force of each ligamentous band were measured using the robotic system. RESULTS: When an eversion force was applied to the intact ankle, the in situ force of the sPTTL was 21.6 N in dorsiflexion and that of the TCL was 19.4 N in plantarflexion, both of which were significantly greater than those of the other ligamentous bands. Additionally, the amount of eversion under eversion loading increased significantly by 3.3° with sPTTL resection in dorsiflexion and by 4.2° with TCL resection in plantarflexion. CONCLUSION: The TCL and sPTTL play important roles among the ligamentous bands of the deltoid ligament. The sPTTL played a more significant role in ankle dorsiflexion, whereas the TCL played a more significant role in ankle plantarflexion. CLINICAL RELEVANCE: The TCL and sPTTL should receive attention in the treatment of deltoid ligamentous injuries.

DOI： 10.1177/23259671251327406

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UNLABELLED: <p>Objectives: Unplanned excision (UE) of soft tissue sarcoma (STS) impacts recurrence and prognosis, influenced by various factors. However, few studies have thoroughly analyzed these patients. This study aimed to comprehensively evaluate prognostic factors in patients with STS who underwent UE. SUBJECT AND METHODS: We retrospectively identified 62 patients with STS who underwent UE. Data on clinical information and detailed assessment were collected. Clinical data were evaluated as risk factors for overall survival, local recurrence, and distant metastases. Furthermore, associations of influencing factors and survival outcomes were analyzed. RESULTS: Multivariate analysis identified consultation after local recurrence following previous surgery and histological high grade as significant predictors of poor prognosis (p = 0.0390 and p = 0.0282, respectively). Histological high grade was the only risk factor for distant metastasis (p = 0.0173). Kaplan-Meier curves demonstrated significant differences in overall survival based on the presence or absence of local recurrence at referral after UE (p = 0.0476, p = 0.0022). The use of local anesthetics in previous surgeries was the only risk factor for consultation after local recurrence. CONCLUSION: Referral after local recurrence after UE and histological high grade were poor prognostic factors. Physicians must be aware that patients with UE should be referred to specialists promptly. </p>.

DOI： 10.1159/000547333

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BACKGROUND/AIM: The incidence of soft tissue sarcomas (STSs) among older patients is increasing. Although it has been reported that surgical treatment of elderly patients with STS improves prognosis, most of these studies included patients aged <85 years. This study aimed to analyze the clinical features and prognostic factors of STS in excessively elderly patients aged ≥85 or ≥90 years. PATIENTS AND METHODS: We retrospectively identified 398 patients with STS who were treated at our two hospitals between 1994 and 2022. Only histological types that existed in ≥20 cases were included. Data on clinical information and detailed assessments were collected. We divided the patients into two subgroups according to 85 or 90 years of age and compared the groups within each subgroup. Furthermore, we examined the factors affecting the prognosis of all and older patients. RESULTS: Patients ≥85 or ≥90 years old comprised 12.1% and 4.0% of the study population, respectively. In all patients, Kaplan-Meier curves for overall survival demonstrated a significantly poorer prognosis in elderly patients with STS aged ≥85 years (p=0.0476) and ≥90 years (p=0.0164). However, no significant differences were observed when analyzing only patients who underwent surgical treatment without distant metastasis at diagnosis. In the multivariate analyses, surgical treatment for the primary tumor improved prognosis exclusively in patients ≥85 years old (p =0.0300). CONCLUSION: Surgical treatment improves the prognosis in elderly STS patients aged ≥85 years and possibly among those aged ≥90 years.

DOI： 10.21873/invivo.13967

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Other Link： https://link.springer.com/article/10.1007/s13577-024-01157-9/fulltext.html

DOI： 10.1007/s13577-024-01157-9

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ABSTRACT

Background

Radiotherapy is considered an alternative treatment for unresectable or pharmacologically resistant desmoid‐type fibromatosis. While it results in relatively good local control, the risk of secondary malignancy remains a concern.

Case

We present a case of secondary osteosarcoma after carbon‐ion radiation therapy (CIRT). A 31‐year‐old male patient presented with left thigh pain. The tumor was located between the left gluteus maximus and gluteus medius and extended to the vastus lateralis and biceps femoris. It was diagnosed as desmoid‐type fibromatosis after needle biopsy. The patient was treated with several medications, including a cyclooxygenase 2 inhibitor and tamoxifen; however, his left thigh pain did not improve. He was treated with CIRT 1 year after diagnosis (67.2 Gy [relative biological effectiveness] 16fr/4wks). He developed osteosarcoma of the left femur 8 years later. He underwent chemotherapy and tumor excision with disarticulation of the left hip. Pulmonary metastasis was detected 6 and 17 months after the definitive surgery and excised using metastasectomy. However, he died due to the recurrence of multiple pulmonary metastases 29 months after the definitive surgery.

Conclusions

In this case, we believe that the low radiation dose to the femur may have caused secondary malignancy.

DOI： 10.1002/cnr2.70062

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Recently, arthroscopic anterior talofibular ligament (ATFL) repair has become popular, and favorable outcomes have been reported. In general, ATFL injuries are often caused by fibular attachment, and there are no reports of arthroscopic ligament repair of talar attachment injuries. We present a surgical technique for arthroscopic ligament repair via the anterolateral portal, accessory anterolateral portal, and far accessory anterolateral portal for ATFL injuries on the talar side. Ligament plication is performed using a suture anchor at the talar footprint of the ATFL after the small bone fragments are removed under arthroscopy. Arthroscopic surgery may lead to less postoperative swelling and pain than open surgery, allowing for early exercise and return to activity.

DOI： 10.1016/j.eats.2024.103098

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A 26-year-old man presented with a tumor in the left soleus muscle. The tumor was diagnosed as a locally advanced leiomyosarcoma. The patient was treated with irradiation followed by wide resection. One year after surgery, the patient presented with multiple lung metastases. Despite aggressive sequential chemotherapy, systemic metastatic tumors continued to develop. To explore therapeutic options for the patient, we performed DNA-based CGP with FoundationOne® CDx (F1). F1 identified an out-of-strand rearrangement of the NOS1AP::NTRK1 gene, which has not been previously reported. In contrast, RNA sequencing revealed an in-frame LMNA::NTRK1 gene, which is an oncogenic fusion gene.

DOI： 10.2169/internalmedicine.2879-23

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DOI： 10.1002/pbc.31148

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We previously identified papillomavirus binding factor (PBF) as an osteosarcoma antigen recognized by an autologous cytotoxic T lymphocyte clone. Vaccination with PBF-derived peptide presented by HLA-A24 (PBF peptide) elicited strong immune responses. In the present study, we generated T cell receptor-engineered T cells (TCR-T cells) directed against the PBF peptide (PBF TCR-T cells). PBF TCR was successfully transduced into T cells and detected using HLA-A*24:02/PBF peptide tetramer. PBF TCR-T cells generated from a healthy donor were highly expanded and recognized T2-A24 cells pulsed with PBF peptide, HLA-A24+ 293T cells transfected with PBF cDNA, and sarcoma cell lines. To establish an adoptive cell therapy model, we modified the PBF TCR by replacing both α and β constant regions with those of mice (hybrid PBF TCR). Hybrid PBF TCR-T cells also showed reactivity against T2-A24 cells pulsed with PBF peptide and to HLA-A24+ 293T cells transfected with various lengths of PBF cDNA including the PBF peptide sequence. Subsequently, we generated target cell lines highly expressing PBF (MFH03-PBF [short] epitope [+]) containing PBF peptide with in vivo tumorigenicity. Hybrid PBF TCR-T cells exhibited antitumor effects compared with mock T cells in NSG mice xenografted with MFH03-PBF (short) epitope (+) cells. CD45+ T cells significantly infiltrated xenografted tumors only in the hybrid PBF TCR T cell group and most of these cells were CD8-positive. CD8+ T cells also showed Ki-67 expression and surrounded the CD8-negative tumor cells expressing Ki-67. These findings suggest that PBF TCR-T cell therapy might be a candidate immunotherapy for sarcoma highly expressing PBF.

DOI： 10.1111/cas.15967

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Painful sensitivity of the hand or foot are the most common and debilitating symptoms of complex regional pain syndrome (CRPS). Physical therapy is standard treatment for CRPS, but evidence supporting its efficacy is minimal and it can be essentially impossible for CRPS patients to actively exercise the painful limb. Using the well-characterized distal tibial fracture CRPS mouse model, we compared the therapeutic effects of several weeks of daily hindlimb loading versus rotarod walking exercise. The effects of loading and exercise were evaluated by weekly testing of hind-paw withdrawal thresholds to von Frey fibers and radiant heat, as well as measurements of paw and ankle edema. At 6 weeks after fracture, the mice were killed and the ipsilateral femur, spinal cord and L4/5 dorsal root ganglia, and hind-paw skin collected for PCR assays and paw skin Immunohistochemistry evaluation. Hindlimb loading reduced hind-paw von Frey allodynia and heat hyperalgesia and edema within a week and these effects persisted for at least a week after discontinuing treatment. These therapeutic effects of loading exceeded the beneficial effects observed with rotarod walking exercise in fracture mice. Levels of nerve growth factor and transient receptor potential vanilloid 1 (TRPV1) immunostaining in the hind-paw skin were increased at 6 weeks after fracture, and both loading and exercise treatment reduced increases. Collectively, these results suggest that loading may be an effective and possibly curative treatment in CRPS patients with sensitivity in the affected limb.

DOI： 10.1002/jor.25750

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DOI： 10.1016/j.annonc.2023.09.142

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PURPOSE: To determine, for patients with advanced or recurrent synovial sarcoma not suitable for surgical resection and resistant to anthracycline, the safety and efficacy of the infusion of autologous T lymphocytes expressing NY-ESO-1 antigen-specific T-cell receptor gene and siRNAs to inhibit the expression of endogenous T-cell receptors (product code: TBI-1301). PATIENTS AND METHODS: Eligible Japanese patients (HLA-A*02:01 or *02:06, NY-ESO-1-positive tumor expression) received cyclophosphamide 750 mg/m2 on days -3 and -2 (induction period) followed by a single dose of 5 x 109 (±30%) TBI-1301 cells as a divided infusion on days 0 and 1 (treatment period). Primary endpoints were safety-related (phase I part) and efficacy-related (objective response rate [ORR] by RECIST v1.1/irRECIST; phase II part). Safety- and efficacy-related secondary endpoints were considered in both phase I/II parts. RESULTS: For the full analysis set (N=8; phase I, n=3; phase II, n=5), the ORR was 50.0% (95%CI: 15.7-84.3) with best overall partial response in 4 of 8 patients according to RECIST v1.1/irRECIST. All patients experienced adverse events and 7 of 8 patients (87.5%) had adverse drug reactions but no deaths were attributed to adverse events. Cytokine release syndrome occurred in 4 of 8 patients (50.0%) but all cases recovered with prespecified treatment. Immune effector cell-associated neurotoxicity syndrome, replication competent retrovirus, and lymphocyte clonality were absent. CONCLUSIONS: Adoptive immunotherapy with TBI-1301 to selectively target NY-ESO-1 positive tumor cells appears to be a promising strategy for the treatment of advanced or recurrent synovial sarcoma with acceptable toxicity.

DOI： 10.1158/1078-0432.CCR-23-1456

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Other Link： https://link.springer.com/article/10.1007/s00256-023-04457-7/fulltext.html

DOI： 10.1007/s00256-023-04457-7

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Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory spondyloarthropathy characterized by ectopic calcification of spinal cord tissue. Its etiology is possibly polygenic. However, its pathogenesis and systemic effects remain unclear. Recent studies have reported a high prevalence of DISH in heart failure patients. The authors investigated how the incidence and severity of DISH are associated with vascular calcification and the occurrence of cardiovascular events. In this retrospective chart review study, 500 patients with cardiovascular disease who underwent surgery (cardiovascular events group) and 500 patients with non-cardiovascular disease who underwent computed tomography scans (non-cardiovascular events group) were randomly selected to investigate the degree of ossification of the anterior longitudinal ligament and the incidence of DISH. We found that the incidence of DISH was higher in patients with cardiovascular events and that patients with DISH had more calcification of the coronary arteries and aorta. Next, we examined the relationship between the degree of coronary and aortic calcification, the incidence of DISH, and the degree of ossification of the anterior longitudinal ligament in the non-cardiovascular event group. The prevalence of DISH in the cardiovascular and non-cardiovascular groups was 31.4% and 16.5%, respectively (p = 0.007). Aortic calcification and a predominant degree of vascular calcification with a certain level of ossification of the anterior longitudinal ligament suggest some correlation between DISH and cardiovascular events. This study is important in understanding the pathophysiology and pathogenesis of DISH.

DOI： 10.3390/jcm12165412

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BACKGROUND: Limb immobilization is considered to contribute to limb pain including hyperalgesia. Approximately 50% of patients with such chronic limb pain complain that their abnormal pain worsens after exposure to cold. However, there have been few studies on the relationship between limb immobilization and cold hypersensitivity. The aim of this study was to examine whether limb immobilization induces cold hypersensitivity, and whether physical exercise such as ankle stretching prevents its induction in model mice. METHOD: We used forty-four 8-week-old male C57Bl/6J mice, consisting of 32 immobilized mice and 12 control mice. The bilateral hind limbs of the mice were immobilized by a thermoplastic cast. After limb-immobilization for 1 week, changes in mechanical, thermal and cold hypersensitivity, and the expression levels of TRPV1, TRPA1, TRPM8, IL-1β, IL-6, and TNFα in the spinal cord, dorsal root ganglia and the affected hind paw were evaluated in comparison with those in the control mice. In addition, we examined the effect of ankle stretching on the hypersensitivity and expression levels in the limb-immobilized mice. RESULTS: Mechanical, thermal and cold hypersensitivity were significantly increased in the limb-immobilized mice. In addition, ankle stretching during the immobilization period significantly prevented the increases in those hypersensitivities. There were no significant differences in the expression levels of TRPV1, TRPA1 and TRPM8 among the control, and limb-immobilized mice with and without ankle stretching. The expression levels of IL-1 and IL-6 were significantly increased in the immobilized hind limb paw. Furthermore, ankle stretching significantly prevented the increases in their expression levels. CONCLUSION: Limb-immobilization induced cold hypersensitivity as well as mechanical and thermal hypersensitivity, and ankle stretching significantly prevented the hypersensitivity induction in the model mice. It would be of great interest to clarify whether a patient with limb-immobilization experiences cold hypersensitivity and whether ankle stretching might prevent hypersensitivity induction in the future.

DOI： 10.1016/j.jos.2023.08.007

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Other Link： https://link.springer.com/article/10.1007/s13577-023-00944-0/fulltext.html

DOI： 10.1007/s13577-023-00944-0

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The efficacy of immune checkpoint inhibitors is limited in refractory solid tumors. T-cell receptor gene-modified T (TCR-T)-cell therapy has attracted attention as a new immunotherapy for refractory cold tumors. We first investigated the preclinical efficacy and mode of action of TCR-T cells combined with the pullulan nanogel:long peptide antigen (LPA) vaccine in a mouse sarcoma model that is resistant to immune checkpoint inhibition. Without lymphodepletion, the pullulan nanogel:LPA vaccine markedly increased the number of TCR-T cells in the draining lymph node and tumor tissue. This change was associated with enhanced CXCR3 expression in TCR-T cells in the draining lymph node. In the phase 1 trial, autologous New York esophageal squamous cell carcinoma 1 (NY-ESO-1)-specific TCR-T cells were infused twice into HLA-matched patients with NY-ESO-1+ soft tissue sarcoma (STS). The pullulan nanogel:LPA vaccine contains an epitope recognized by TCR-T cells, and it was subcutaneously injected 1 day before and 7 days after the infusion of TCR-T cells. Lymphodepletion was not performed. Three patients with refractory synovial sarcoma (SS) were treated. Two out of the three patients developed cytokine release syndrome (CRS) with low-to-moderate cytokine level elevation. We found obvious tumor shrinkage lasting for more than 2 years by tumor imaging and long-term persistence of TCR-T cells in one patient. In conclusion, NY-ESO-1-specific TCR-T-cell therapy plus vaccination with the pullulan nanogel carrying an LPA containing the NY-ESO-1 epitope without lymphodepletion is feasible and can induce promising long-lasting therapeutic effects in refractory SS (Registration ID: JMA-IIA00346).

DOI： 10.1002/ijc.34453

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BACKGROUND: As therapy for solid tumours, various tumour antigens have been selected as targets, but CAR-T cells targeting these antigens have shown limited efficacy, in contrast to the effectiveness of CAR-T cells targeting haematological malignancies. In a previous report, we identified a cancer-testis antigen, DNAJB8. DNAJB8 plays a major role in tumorigenicity in cancer stem-like cells/cancer-initiating cells (CSCs/CICs). Here, we report a DNAJB8-reactive CAR yielding anti-tumour effects against renal cell carcinoma (RCC) and osteosarcoma. METHODS: We constructed a second-generation chimeric antigen receptor (CAR) against HLA-A*24:02/DNAJB8-derived peptide (DNAJB_143) complex (B10 CAR). The reactivity of B10-CAR T cells against T2-A24 cells pulsed with the cognate peptide and an RCC and osteosarcoma cell lines were quantified. The effects of adoptive cell transfer (ACT) therapy were assessed using in vivo xenografted mice models. RESULTS: B10 CAR-T cells recognised DNAJB8_143-pulsed T2-A24 cells and HLA-A*24:02(+)/DNAJB8(+) renal cell carcinoma and osteosarcoma cell lines. Moreover, ACT using B10 CAR-T cells showed anti-tumour effects against RCC and osteosarcoma cells. CONCLUSION: B10 CAR-T cells could show specific cytotoxicity against RCC and osteosarcoma cells in vitro and in vivo. B10 CAR-T cells targeting the CSC/CIC antigen DNAJB8 might be a candidate immunotherapy for carcinoma and sarcoma.

DOI： 10.1038/s41416-022-02100-1

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BACKGROUND: Accuracy of current standard radiographic measurement of the critical shoulder angle (CSA) is not well established. This study analyzed the reliability and accuracy of the CSA measurements obtained via anteroposterior (AP) radiographs, using a digitally reconstructed radiograph (true AP view) generated from a computed tomography image as the gold standard. METHODS: The CSA was measured on the radiographs and true AP views of 88 consecutive patients who had undergone shoulder arthroscopy for rotator cuff tears. Intraobserver and interobserver reliabilities of the CSA, measured by 2 orthopedic surgeons, were evaluated, and the average deviation of the CSA between radiographs and true AP views was calculated. Moreover, we compared the deviation of CSA between standard AP films (types A1 and C1) and nonstandard AP films (other types) against the Suter-Henninger criteria. RESULTS: Intraobserver and interobserver reliabilities were almost perfect on radiographs (0.96, 0.86) and true AP views (0.93, 0.85). The average deviation of CSA was 2.1° ± 1.6° for observer 1 and 2.2° ± 1.9° for observer 2. The percentage of cases with deviations of 2° or more when compared with the true AP view was 42% (37 of 88) for observer 1 and 53% (47 of 88) for observer 2. Only 22% (19 of 88) of films were standard AP films. The average deviation of CSA was not significantly different between standard and nonstandard AP films for observer 1 (standard 1.9° ± 1.3°; nonstandard 2.1° ± 1.7°; P = .76) and observer 2 (standard 1.6° ± 1.5°; nonstandard 2.4° ± 1.9°; P = .09). CONCLUSION: The CSA measurements using radiography were highly congruent, but a large measurement deviation occurred between radiographs and true AP views. The clinical usefulness and role of CSA in diagnosis require careful consideration.

DOI： 10.1016/j.jse.2022.07.017

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BACKGROUND: Direct and quantitative measurement of median nerve strain within the carpal tunnel has been difficult because of the technical limitations associated with conventional devices. We used capacitive sensors (C-stretch), which are thin and flexible, to measure the median nerve strain within the carpal tunnel. METHODS: We used 12 fresh frozen upper extremity specimens. The transverse carpal ligament was left in situ, and we attached the sensor to the palmar surface of the median nerve to measure the nerve strain at 60 degrees of wrist extension. The sensor measured the median nerve strain at both the carpal tunnel site and the proximal to the carpal tunnel site before and after the carpal tunnel release. The amount of nerve excursion during wrist extension was also measured with the length change of the attached suture by a digital caliper. FINDINGS: The mean median nerve strain within the carpal tunnel [8.07% (95 %CI:7.17-8.97)] was significantly higher than that proximal to the carpal tunnel [5.21% (95 %CI:4.46-5.97)] at the wrist extension. There was no significant difference of the mean nerve excursion within and proximal to the carpal tunnel. The mean nerve strain and excursion were unaffected by carpal tunnel release. INTERPRETATION: These results indicated that wrist extension position might lead to increased strain on the median nerve within the carpal tunnel compared with at the proximal to the carpal tunnel. We believe that the current study might provide new information and help us understand the pathogenesis of carpal tunnel syndrome.

DOI： 10.1016/j.clinbiomech.2023.105894

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<title>Abstract</title><sec>
<title>Background</title>
Predicting the prognosis of patients with solitary fibrous tumor (SFT) is often difficult. The prognostic risk models developed by Demicco et al. are now the standard for evaluating the risk of SFT metastasis in the current World Health Organization classification of soft tissue and bone tumors.


</sec><sec>
<title>Methods</title>
In this study, we examined the prognostic usefulness of a modified version of the Demicco risk models that replaces the mitotic count with the Ki-67 labeling index. We compared the three-variable and four-variable Demicco risk models with our modified risk models using Kaplan–Meier curves based on data for 43 patients with SFT.


</sec><sec>
<title>Results</title>
We found a significant difference in metastasis-free survival when patients were classified into low-risk and intermediate/high-risk groups using the three-variable (<italic>P</italic> = 0.022) and four-variable (<italic>P</italic> = 0.046) Demicco models. There was also a significant difference in metastasis-free survival between the low-risk and intermediate/high-risk groups when the modified three-variable (<italic>P</italic> = 0.006) and four-variable (<italic>P</italic> = 0.022) models were used.


</sec><sec>
<title>Conclusion</title>
Modified risk models that include the Ki-67 labeling index are effective for prediction of the prognosis in patients with SFT.


</sec>

Other Link： https://link.springer.com/article/10.1186/s12957-022-02497-2/fulltext.html

DOI： 10.1186/s12957-022-02497-2

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Abstract

Background

Tenosynovial giant cell tumor (TSGCT) is a benign fibrohistiocytic tumor that affects the synovium of joints, bursa, and tendon sheaths and is categorized into localized TSGCT (LTSGCT) and diffuse TSGCT (DTSGCT). LTSGCT and DTSGCT are characterized by recurrent fusions involving the colony-stimulating factor 1 (CSF1) gene and its translocation partner collagen type VI alpha 3 chain. The fusion gene induces intratumoral overexpression of CSF1 mRNA and CSF1 protein. CSF1 expression is a characteristic finding of TSGCT and detection of CSF1 mRNA and CSF1 protein may be useful for the pathological diagnosis. Although there have been no effective anti-CSF1 antibodies to date, in situ hybridization (ISH) for CSF1 mRNA has been performed to detect CSF1 expression in TSGCT. We performed CSF1 immunohistochemistry (IHC) using anti-CSF1 antibody (clone 2D10) in cases of TSGCT, giant cell-rich tumor (GCRT), and GCRT-like lesion and verified its utility for the pathological diagnosis of TSGCT.

Methods

We performed CSF1 IHC in 110 cases including 44 LTSGCTs, 20 DTSGCTs, 1 malignant TSGCT (MTSGCT), 10 giant cell tumors of bone, 2 giant cell reparative granulomas, 3 aneurysmal bone cysts, 10 undifferentiated pleomorphic sarcomas, 10 leiomyosarcomas, and 10 myxofibrosarcomas. We performed fluorescence ISH (FISH) for CSF1 rearrangement to confirm CSF1 expression on IHC in TSGCTs. We considered the specimens to have CSF1 rearrangement if a split signal was observed in greater than 2% of the tumor cells.

Results

Overall, 50 of 65 TSGCT cases, including 35 of the 44 LTSGCTs and 15 of the 20 DTSGCTs, showed distinct scattered expression of CSF1 in the majority of mononuclear tumor cells. MTSGCT showed no CSF1 expression. Non-TSGCT cases were negative for CSF1. FISH revealed CSF1 rearrangement in 6 of 7 CSF1-positive cases on IHC. On the other hand, FISH detected no CSF1 rearrangement in all CSF1-negative cases on IHC. Thus, the results of IHC corresponded to those of FISH.

Conclusion

We revealed characteristic CSF1 expression on IHC in cases of TSGCT, whereas the cases of non-TSGCT exhibited no CSF1 expression. CSF1 IHC may be useful for differentiating TSGCTs from histologically mimicking GCRTs and GCRT-like lesions.

Other Link： https://link.springer.com/article/10.1186/s13000-022-01266-9/fulltext.html

DOI： 10.1186/s13000-022-01266-9

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DOI： 10.1097/BRS.0000000000004377

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Language：Japanese   Publisher：日本股関節学会  

43歳男性。左大腿骨頭内の悪性腫瘍に対する広範切除術+腫瘍用THA術から1年後、X線像で左坐骨カップ辺縁の骨透亮像が認められた。慎重に経過観察したが、徐々に拡大し、術後4年時に精査入院となった。所見では坐位時に軽度の疼痛が認められたが、歩行時痛はなかった。単純X線およびCTを行ったところ、左坐骨部臼蓋コンポーネント下方に骨溶解像が認められた。MRIにて腫瘍の再発または感染を疑い、切開生検術を施行した結果、病理所見より腫瘍用THA後メタローシスと診断された。治療は摺動面交換術を施行し、骨溶解部は掻爬して人工骨を充填した。再手術から4年経過現在、独歩可能であり、骨溶解像の進行はみられていない。

Ichushi

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Other Link： https://link.springer.com/article/10.1007/s00795-022-00327-8/fulltext.html

DOI： 10.1007/s00795-022-00327-8

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BACKGROUND: Low back pain (LBP) is a major symptom of symptomatic lumbar spinal stenosis (SLSS). It is important to assess LBP in patients with SLSS to develop better treatment. This study aimed to analyse the factors associated with LBP in patients with SLSS. METHODS: This cross-sectional study included consecutive patients with SLSS aged between 51 and 79 years who had symptoms in one or both the legs, with and without LBP. The participants were classified into two groups: the high group (LBP visual analogue scale [VAS] score ≥ 30 mm) and the low group (LBP VAS score < 30 mm). We performed multiple logistic regression analysis with the high and low groups as dependent variables, and a receiver operating characteristic (ROC) analysis. RESULTS: A total of 80 patients with LSS were included (35 men and 45 women; mean age 64.5 years), with 47 and 30 patients in the high and low groups, respectively. Multivariate logistic regression analysis revealed that the sagittal vertical axis (SVA; + 10 mm; odds ratio, 1.331; 95% confidence interval, 1.051 - 1.660) and pelvic incidence-lumbar lordosis (PI-LL; + 1°; odds ratio, 1.065; 95% confidence interval, 1.019-1.168) were significantly associated with LBP. A receiver operating characteristic analysis revealed cut-off values of 47.0 mm of SVA and 30.5° of PI-LL, respectively. CONCLUSION: Our results indicated that SVA and PI-LL were significant predictors for LBP in SLSS. It is suggested that these parameters should be taken into consideration when assessing LBP in patients with SLSS.

DOI： 10.1186/s12891-022-05483-7

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Background and Objectives: Percutaneous pedicle screws were first introduced in 2001, soon becoming the cornerstone of minimally invasive spinal stabilization. Use of the procedure allowed adequate reduction and stabilization of spinal injuries, even in severely injured patients. This decreased bleeding and shortened surgical time, thereby optimizing outcomes; however, postoperative correction loss and kyphosis still occurred in some cases. Thus, we investigated cases of percutaneous posterior fixation for thoracolumbar injury and examined the factors affecting the loss of correction. Materials and Methods: Sixty-seven patients who had undergone percutaneous posterior fixation for thoracolumbar injury (AO classifications A3, A4, B, and C) between 2009 and 2016 were included. Patients with a local kyphosis angle difference ≥10° on computed tomography at the postoperative follow-up (over 12 months after surgery) or those requiring additional surgery for interbody fusion were included in the correction loss group (n = 23); the no-loss group (n = 44) served as the control. The degree of injury (injury level, AO classification, load-sharing score, local kyphosis angle, cuneiform deformity angle, and cranial and caudal disc injury) and surgical content (number of fixed intervertebral vertebrae, type of screw used, presence/absence of screw insertion into the injured vertebrae, and presence/absence of vertebral formation) were evaluated as factors of correctional loss and compared between the two groups. Results: Comparison between each group revealed that differences in the wedge-shaped deformation angle, load-sharing score, degree of cranial disc damage, AO classification at the time of injury, and use of polyaxial screws were statistically significant. Logistic regression analysis showed that the differences in wedge-shaped deformation angle, AO classification, and cranial disc injury were statistically significant; no other factors with statistically significant differences were found. Conclusion: Correction loss was seen in cases with damage to the cranial intervertebral disc as well as the vertebral body.

DOI： 10.3390/medicina58050583

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BACKGROUND: The aim of the present study was to evaluate the prevalence of non-ossifying fibroma (NOF) and fibrous cortical defect (FCD) in a Japanese pediatric population and the association between the lesion size and pain. METHODS: This retrospective study, conducted across 10 Japanese institutions, included patients aged 5-15 years who had undergone standard antero-posterior and lateral view radiography of the knee. Using these radiographs, we diagnosed the lesion as a NOF or FCD. Patient demographics, including age, sex, the size and location of the NOF, and chief complaint were recorded. The lesion size was determined using radiographs. Student's t-test was used to compare the associations between the lesion size and spontaneous pain. RESULTS: A total of 6222 subjects (3567 boys and 2455 girls) were included in this study. The number of NOF and FCD cases was 143 and 437, respectively, and the prevalence of NOF and FCD was 2.3% and 7.0%, respectively. The average size of NOF and FCD was 22.1 mm (range: 4-102 mm) and 13.2 mm (range: 5-21 mm), respectively. Three patients (2.1%) had pathological fractures due to NOF. Of the 140 NOFs and 437 FCDs, we obtained complaints from the medical records of 126 and 393 patients, respectively. The number of patients with spontaneous pain or other problems with NOF was 68 (54%) and 58 (46%), respectively, that of patients with FCD was 195 (50%) and 198 (50%) patients, respectively. The lesion size was not associated with spontaneous pain in either lesion (p = 0.67 and p = 0.27, respectively). CONCLUSION: The prevalence of NOF and FCD around the knee was lower than that reported in previous studies. The prevalence of NOF increased and that of FCD decreased with advancing age. In both lesions, the lesion size may not be associated with pain.

DOI： 10.1186/s12891-022-05330-9

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STUDY DESIGN: Retrospective analysis of prospectively collected observational data. OBJECTIVE: This study aimed to evaluate the slippage, sagittal alignment, and range of motion (ROM) after selective laminectomy (SL) in patients who had cervical spondylotic myelopathy (CSM) with degenerative spondylolisthesis (DS). SUMMARY OF BACKGROUND DATA: Clinical outcomes have been reported for both decompression and fusion surgeries for DS of the lumbar spine. However, only a few reports have examined cervical spine spondylolisthesis. MATERIALS AND METHODS: This study included 178 patients who underwent SL for CSM. Those with ossification of the posterior longitudinal ligament were excluded. Slippage >2 mm was defined as spondylolisthesis, and spondylolisthesis progression was defined as an additional displacement >2 mm on a neutral radiograph. The slippage, translational motion, C2-C7 angle, local kyphosis, and ROM were examined before and ≥2 years after surgery. Radiologic parameters were evaluated according to the slip direction and the number of laminae removed. RESULTS: DS was observed in 29 patients (16.3%); 24 patients, comprising 9 and 15 in the anterolisthesis and retrolisthesis groups, respectively, were successfully followed up for more than 2 years. Preoperative and postoperative radiologic changes in slippage, translational motion, C2-C7 angle, local kyphosis, and ROM were not remarkable in either group regardless of the number of laminae removed. Revision surgery for the progression of DS and alignment deterioration was not required in any patient of either group. CONCLUSIONS: SL does not affect DS, sagittal alignment, or ROM irrespective of the slip direction and the number of laminae removed, even after >2 years after surgery. Given the preservation of the posterior elements, SL may be an effective treatment for CSM with DS. LEVEL OF EVIDENCE: Level IV.

DOI： 10.1097/BSD.0000000000001161

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DOI： 10.1097/BSD.0000000000001161

Web of Science

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Publishing type：Research paper (scientific journal)   Publisher：AME Publishing Company  

DOI： 10.21037/apm-22-536

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Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Internal Medicine  

DOI： 10.2169/internalmedicine.9423-22

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BACKGROUND: The differential diagnosis of fibroma of tendon sheath (FTS) and giant cell tumor of tendon sheath (GCTTS) on the basis of clinical and radiographic characteristics remains difficult. PURPOSE: To evaluate the quantitative measurement of signal intensity (SI) obtained by magnetic resonance imaging (MRI) for the differential diagnosis of FTS and GCTTS in just the finger. MATERIAL AND METHODS: We retrospectively identified patients with FTS (n = 6) and GCTTS (n = 22) of the finger who were treated at our hospitals between April 2011 and August 2019. Two researchers independently reviewed the MRIs and measured the regions of interest (ROIs) in the tumor and flexor tendon from the same image. The SI ratio obtained for the tumor and tendon ROIs was measured and compared using receiver-operating characteristic curve analyses. Sensitivity and specificity analyses were performed. RESULTS: The SI ratios (mean ± SD) of FTS and GCTTS were 1.83 ± 0.64 and 6.34 ± 3.16 for researcher 1 and 1.82 ± 0.60 and 6.10 ± 3.22 for researcher 2, respectively. The areas under the curve were 0.970 and 0.970 for researchers 1 and 2, respectively. The cut-off values of the SI ratio as determined by researchers 1 and 2 for differentiating FTS from GCTTS were 3.00 and 3.00, respectively (sensitivity = 95.5%, specificity = 100%). CONCLUSIONS: The SI ratio is useful for differentiating FTS from GCTTS independent of a combination of tumor signal and shape.

DOI： 10.1177/0284185120976915

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OBJECTIVE: Soft tissue sarcomas in the elbow are extremely rare, and they have primarily been described in case series. Definitive concerning the prevalence and prognostic factors of elbow soft tissue sarcomas remain unknown. We examined the outcome of patients with elbow soft tissue sarcomas and identified the relevant prognostic factors. METHODS: In total, 219 patients with elbow soft tissue sarcomas were identified using data from the bone and soft tissue tumor registry in Japan. Differences in demographics, disease characteristics, treatment and survival were compared among the patients. Survival analyses including local recurrence-free survival, distant metastasis-free survival, and overall survival were performed using the Kaplan-Meier method with log-rank tests and the Cox proportional hazards model. RESULTS: Two hundred nineteen patients with elbow soft tissue sarcomas were identified, including 119 males (54.3%) and 100 females (45.7%). In total, 189 patients (86.3%) underwent surgery including re-excision. Of the surgically treated patients, 180 (95.2%) underwent limb salvage surgery, and nine patients (4.8%) underwent amputation. The 5-year overall survival, local recurrence-free survival, and distant metastasis-free survival rates for the entire patient cohort were 76.3, 70.1, and 69.3%, respectively. After adjusting for clinically relevant factors, overall survival was significantly worse among patients with tumors: >10 cm (hazard ratio = 4.34; 95% confidence interval = 1.03-18.2) and metastatic disease (hazard ratio = 6.94; 95% confidence interval = 1.55-31.0). CONCLUSIONS: Tumor size was identified as an independent risk factor for poor prognosis.

DOI： 10.1093/jjco/hyab119

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The efficacy and safety of cyclooxygenase 2 (COX2) inhibitors for the treatment of desmoid-type fibromatosis (DF) are unclear. Therefore, we systematically reviewed related literature to assess the efficacy and safety of COX2 inhibitors for DF treatment. We searched pertinent literature between January 1999 and August 2017 to identify relevant studies using the keywords "Fibromatosis, aggressive" and "Cyclooxygenase inhibitors." Thereafter, we screened and determined the quality of the studies using the Grading of Recommendations Assessment, Development, and Evaluation system and extracted the article data. The critical outcomes selected were the efficacy and adverse effects of COX2 inhibitors. Efficacy was evaluated in terms of clinical benefit when patients showed complete response, partial response, and stable disease. Thirty-one articles were identified from the database search, and one was identified through the reviewers' manual search. Finally, we retrieved six studies, including three case reports, comprising 89 patients after the first and second screenings. Fifty-three patients were excluded because three studies were reported from the same institution; hence, in total, 36 patients were included. Clinical benefit was noted in 64% of the patients. Three adverse effects were identified from the records of the six extracted studies. The strategy of watchful waiting using COX2 inhibitors with few side effects is weakly recommended for DF, especially DF patients with pain.

DOI： 10.18999/nagjms.83.4.673

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Academic Press Inc.  

DOI： 10.1053/j.jfas.2021.04.011

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BACKGROUND: The malignant potential of the musculoskeletal tumors of the foot and ankle has often been underestimated because of their rarity. The current study reviewed the clinical features of the tumors of the foot and ankle, and evaluated the tumor size via imaging-based analysis to distinguish between benign and malignant lesions. METHODS: A retrospective review was performed using the clinical records of all patients with histologically confirmed musculoskeletal tumors of the foot and ankle, treated between 1998 and 2020 at our institution. We examined the distribution of tumors, rate of unplanned excision for primary surgery, and subsequent outcomes. In addition, the tumor size was examined via magnetic resonance imaging, and the cut-off value was determined via receiver operating characteristic (ROC) curve. RESULTS: A total of 103 bone and soft tissue tumors of the foot and ankle were included, of which 78 were soft tissue tumors and 25 were bone tumors. Of the 14 cases of malignant bone and soft tissue tumors, 6 (42.9%) received unplanned excision in the primary surgery, followed by amputation in 3 cases. Tumor size of malignant soft tissue tumors was significantly larger than that of benign soft tissue tumors (47.6 mm vs. 31.0 mm, respectively, P < .001). However, the difference between benign and malignant bone tumors was not statistically significant with the numbers available. ROC curve determined that the optimum diagnostic cutoff value for soft tissue tumor size was 40 mm, with a high area under the ROC curve 0.816 (95% CI: 0.711-0.921, sensitivity 91.7%, specificity 70.5%) CONCLUSIONS: We highlighted that bone and soft tissue tumors of the foot and ankle were often misdiagnosed and initially inadequately treated. We suggest that a cutoff value of 40 mm may be a useful index for prediction of malignancy in soft tissue tumors of the foot and ankle. LEVEL OF EVIDENCE: Ⅲ.

DOI： 10.1016/j.jos.2020.08.016

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DOI： 10.1016/j.jos.2018.11.002

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BACKGROUND: A definitive diagnosis of malignant peripheral nerve sheath tumor (MPNST) is challenging, especially in cases without neurofibromatosis 1 (NF1), because MPNST lacks specific markers on immunohistochemistry (IHC). METHODS: We performed IHC for histone 3 trimethylated on lysine 27 (H3K27me3) and evaluated the percentage of cells with H3K27me3 loss using measured values at 10% intervals, categorized as complete loss (100% of tumor cells lost staining), partial loss (10% to 90% of tumor cells lost staining), and intact (no tumor cells lost staining). We conducted fluorescence in situ hybridization (FISH) for NF1 and p16 deletions comparing 55 MPNSTs and 35 non-MPNSTs, consisting of 9 synovial sarcomas (SSs), 8 leiomyosarcomas (LMSs), 10 myxofibrosarcomas (MFSs), and 8 undifferentiated pleomorphic sarcomas (UPSs). We assessed the percentage of cells with homozygous and heterozygous deletions and defined "deletion" if the percentage of either the NF1 or p16 deletion signals was greater than 50% of tumor cells. RESULTS: Among the 55 MPNSTs, 23 (42%) showed complete H3K27me3 loss and 32 (58%) exhibited partial loss or intact. One each of the 9 SSs (11%), 8 LMSs (12%), and 8 UPSs (12%) showed complete H3K27me3 loss and many non-MPNSTs exhibited intact or partial H3K27me3 loss. Among the 55 MPNSTs, 33 (60%) and 44 (80%) showed NF1 or p16 deletion, respectively. Co-deletion of NF1 and p16 was observed in 29 (53%) MPNSTs. Among the 23 MPNTSs showing H3K27me3 complete loss, 18 (78%) and 20 (87%) exhibited NF1 or p16 deletion, respectively. Among the 32 MPNSTs with H3K27me3 partial loss or intact, 15 (47%) and 24 (75%) exhibited NF1 or p16 deletion, respectively. The frequency of NF1 and/or p16 deletion tended to be lower in non-MPNSTs than in MPNSTs. Approximately 90% of MPNSTs included cases with H3K27me3 complete loss and cases showing H3K27me3 partial loss or intact with NF1 and/or p16 deletion. Approximately 50% of MPNSTs showed co-deletion of NF1 and p16 regardless of H3K27me3 loss. CONCLUSIONS: FISH for NF1 and p16 deletions, frequently observed in high-grade MPNSTs, might be a useful ancillary diagnostic tool for differentiating MPNST from other mimicking spindle cell and pleomorphic sarcomas.

DOI： 10.1186/s13000-021-01140-0

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Language：Japanese   Publisher：東日本整形災害外科学会  

Ichushi

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STUDY DESIGN: Cross-sectional study. PURPOSE: This study aimed to analyze the differences in the lipid contents in chronic low back pain (CLBP) patients with nociceptive pain (NocP) and neuropathic pain (NeP) using magnetic resonance spectroscopy (MRS) of the multifidus muscle (Mm). OVERVIEW OF LITERATURE: Early identification of the pain characteristics with CLBP is important because specific treatment approaches are required, depending on NocP and NeP. METHODS: The participants were 50 patients with CLBP (23 men and 27 women; mean age, 63.1±17.8 years; range, 41-79 years). We compared the Visual Analog Scale (VAS) scores, intramyocellular lipids (IMCLs) and extramyocellular lipids (EMCLs) of the Mm in NocP and NeP groups, as evaluated with the Japanese NeP screening questionnaire. RESULTS: The patients were categorized into the NocP (n=32) and NeP (n=18) groups. The mean VAS score of the NocP group was 59.3±3.1 mm and that of the NeP group was 73.6±4.6 mm. The mean VAS score was significantly higher in the NeP group as compared to that in the NocP group (p<0.01). As per the analysis of covariance for the VAS score, the mean IMCL levels of the Mm in the NocP and NeP groups were 722.3 mmol/L (95% confidence interval [CI], 611.4-833.1) and 484.8 mmol/L (95% CI, 381.1-588.5), respectively. The mean IMCL level was significantly higher in the NocP group than in the NeP group (p<0.05). The mean EMCL levels of the Mm for the NocP and NeP groups were 6,022.9 mmol/L (95% CI, 4,510.6-7,535.2) and 5,558.1 mmol/L (95% CI, 4,298.3-6,817.9), respectively; however, the difference was not significant (p=0.72). CONCLUSIONS: The results indicated an association between the IMCL level of the Mm and NocP. Our results suggest that MRS of the Mm might be beneficial for the assessment of CLBP as well as appropriate targeted analgesic therapies.

DOI： 10.31616/asj.2020.0247

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Language：Japanese   Publisher：(公社)日本整形外科学会  

Ichushi

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BACKGROUND: Pain sensitization may be one of the mechanisms contributing to chronic low back pain (CLBP). OBJECTIVE: To evaluate the association between visceral fat, CLBP, and central sensitization (CS); describe the relationship between low back pain (LBP) intensity and CS; and identify possible correlation between visceral fat and LBP intensity. METHODS: Patients with CLBP were divided using their CS inventory (CSI) scores into low- (CSI < 40) and high-CSI (CSI ⩾ 40) subgroups. We compared computed tomography (CT) measurements and scores for association with pain according to the visual analogue scale (VAS) between the two groups. RESULTS: The low-CSI and the high-CSI groups had 47 patients (67.1%; 21 men, 26 women) and 23 patients (32.9%; 11 men and 12 women), respectively. The high-CSI group had a significantly higher mean VAS score (p< 0.01) and estimated mean visceral fat area (p< 0.05) than the low-CSI group. There was a moderate positive correlation between VAS score and visceral fat (standardised partial regression coefficient: 0.659, p< 0.01) in the high-CSI group according to multiple linear regression analysis adjusted for age and sex. CONCLUSIONS: Visceral fat is associated with CLBP, regardless of sex or age, and may be a potential therapeutic target for CLBP with CS.

DOI： 10.3233/BMR-210124

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BACKGROUND: Tetranectin, a plasminogen-binding protein, is present in human serum and has a role in tissue remodeling. The wound healing process is established and follows a similar cascade in tendon tissue as in other tissues. In this study, we investigated whether tetranectin has a role in regulating tissue formation of injured tendon. METHODS: Using the patella tendon injury model in the tetranectin-null mice, healing processes of the injured tendon were evaluated by histological and immunohistochemical analyses, and measurement of the expression of tetranectin, type 1 collagen (Col 1), tenomodulin, scleraxis, TGFβ, IL-1β, IL-6 and TNF-α. RESULTS: At the inflammatory phase within 7 days after the injury, involvement of inflammatory cells and the expressions of IL-1β, IL-6 and TNF-α were significantly decreased in tetranectin-null mice. Tetranectin expression increased at 1 day and peaked at 3 days, and finally disappeared at 7 days after the injury in wild-type mice. The tendon healing period and maturity were significantly delayed in the tetranectin-null mice. Expression levels of type 1 collagen and tenomodulin in tetranectin-null mice were significantly lower than those in the wild-type mice until 70 days after injury. With regard to the long-term processes, the healing and maturation of the injured tendon in tetranectin-null mice were eventually completed. CONCLUSION: We believe that tetranectin might have a potential role in enhancing tissue formation of healing tendon at the inflammatory phase after injuries. The characteristics of tetranectin as a purified protein from human serum could be interested in an attractive candidate as a potential agent to enhance tendon healing after injury.

DOI： 10.1016/j.jos.2020.12.011

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BACKGROUND: Pathological conditions after skeletal tissue injury such as trauma and surgical intervention are often accompanied with regional osteoporotic changes, which are recognized to be mainly caused by limb immobility after injury. However, the mechanisms for the progression of regional osteoporotic changes related to the injury remains unknown. Previous studies reported that the pathophysiological conditions related to tissue injury include the acidic micro-environment formation and increased ATP levels. In addition, we previously demonstrated that those changes in the micro-environment induced a high bone turnover state through the activation of TRPV1, ASICs and P2X expressed in bone cells. We, therefore, hypothesized that tissue injury could enhance a high bone turnover state due to those pathophysiological changes in soft tissue in the injured limb. The aim of this study was to examine whether soft tissue injury associated with cutaneous incisions in a limb affects regional bone turnover. METHODS: Eight-week-old male C57BL/6 J mice underwent soft tissue injury associated with cutaneous incisions in the right femoral skin. During the 14 days after the incision, changes in the expression of osteoblast and osteoclast differentiation regulators and ATP were evaluated in comparison with those in uninjured mice. The pain-like behaviors and the expression of those differentiation regulators with and without treatment with bisphosphonate and Cox2 inhibitor were assessed in the injured limb. RESULTS: Consistent with the wound healing process, the expression levels of Osterix, osteocalcin and RANKL in the femur of the incised limb were significantly increased up to 7 days, and then decreased to the same level as those in the control limbs by 14 days after the incisions. The levels of TRAP 5b and ATP were initially significantly increased, and then decreased to the same level as before injury by day 14. Bisphosphonate significantly improved the pain-like behaviors in the injured limb associated with the inhibition of osteoblast and osteoclast differentiation regulators. CONCLUSION: We believe that the pathophysiological changes in soft tissue resulting from cutaneous incisions could be related to the induction of osteoblast and osteoclast differentiation regulators.

DOI： 10.1016/j.injury.2020.12.019

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：S. Karger AG  

DOI： 10.1159/000513117

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Spine Surgery and Related Research  

DOI： 10.22603/SSRR.2020-0165

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Publishing type：Research paper (scientific journal)   Publisher：Anticancer Research USA Inc.  

DOI： 10.21873/invivo.12647

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Taylor and Francis Ltd.  

DOI： 10.1080/2000656X.2021.1873795

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Language：Japanese   Publisher：北海道整形災害外科学会  

Ichushi

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OBJECTIVES: It is challenging to know at the first which patients with desmoid fibromatosis (DF) are better suited to conservative or aggressive treatment. To investigate whether the low signal intensity bundles on T1- or T2-weighted images (WI), termed the "black fiber sign (BFS)," can predict non-progressive behavior in the conservative approach. METHODS: This retrospective study included 59 patients with primary DF managed with wait-and-see approach from 2005 to 2018 and serial MR images were analyzed. Three observers blinded to the patient information verified the presence or absence of BFS on baseline T1 or T2WI. The likelihood of progression-free survival (PFS) after ascertaining the presence or absence of the BFS was estimated using the Kaplan-Meier method and analyzed with the log-rank test. RESULTS: PFS was significantly higher in cases with BFS than without BFS on T1WI (p < 0.01), but there was no significant difference in PFS between cases with and without BFS on T2WI. Multivariable Cox proportional hazards analysis revealed that the absence of BFS on T1WI was a high-risk factor for progression (hazard ratio, 14.9; p < 0.01). Drastic tumor regression was apparent with significantly increased low-signal area in cases with BFS on T1WI. Intra- and interobserver reliabilities of BFS on T1WI were in almost-perfect agreement (κ > 0.8). CONCLUSION: Our retrospective observational data support that presence of BFS in baseline MRI may be a predictor for progression-free survival of DF. BFS on T1WI is easily identifiable and can be utilized clinically in patients with DF. KEY POINTS: • We proposed a new imaging marker for prediction of desmoid fibromatosis progression. • The absence of black fiber sign predicted a high risk of disease progression.

DOI： 10.1007/s00330-020-06953-z

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DOI： 10.21873/invivo.12097

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BACKGROUND: Morphologically, osteofibrous dysplasia-like adamantinoma is thought to be intermediate between osteofibrous dysplasia and adamantinoma. Its treatment is not well established owing to its rarity. CASE PRESENTATION: We report about of a 10-year-old girl with osteofibrous dysplasia-like adamantinoma initially diagnosed as osteofibrous dysplasia and treated via intercalary segmental resection with partial cortex preservation using a pedicled vascularized fibula graft for reconstruction. Bone union was observed 9 weeks after surgery. Twenty-two months after the definitive surgery, no recurrence was observed. CONCLUSION: This case illustrates the upgrade from osteofibrous dysplasia to osteofibrous dysplasia-like adamantinoma. The surgical method may aid the treatment of osteofibrous dysplasia-like adamantinoma with incomplete cortex involvement of the tumor.

DOI： 10.1186/s12957-020-01983-9

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DOI： 10.1016/j.mri.2020.07.004

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DOI： 10.1007/s00774-020-01124-y

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.21873/invivo.11994

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Language：Japanese   Publisher：(公社)日本整形外科学会  

Ichushi

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Language：Japanese   Publisher：(公社)日本整形外科学会  

Ichushi

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DOI： 10.1007/s00774-020-01086-1

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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The aim of the present study was to evaluate the survival impact of surgical resection among patients with pulmonary metastases from bone and soft tissue sarcomas. A total of 34 consecutive patients with ≤5 pulmonary metastases from bone and soft tissue sarcomas were retrospectively reviewed. The patients included 19 men and 15 women, with a median age of 64.0 years and a median follow-up of 14.5 months. The oncological outcome was compared between patients who underwent surgical and non-surgical treatment. A total of 22 patients underwent surgery and 12 patients did not undergo surgery. The surgery group had 3- and 5 year overall survival rates of 62 and 53%, respectively. None of the patients in the non-surgery group survived to 3 years. Compared with the non-surgery group, surgery achieved significantly better 3- and 5 year overall survival rates. Pulmonary metastasectomy was associated with significantly improved survival among patients who were aged <64 years (P=0.0155), as well as those who were aged ≥64 years (P=0.0444), which indicated that age was not associated with a difference in survival between the two groups. Therefore, pulmonary metastasectomy may improve the prognosis of patients with pulmonary metastases from bone and soft tissue sarcomas.

DOI： 10.3892/mco.2020.2009

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Study Design: Cross-sectional study. Purpose: The purpose of this study was to elucidate the relevance among Schmorl's node (SN), chronic low back pain (CLBP), and intervertebral disc degeneration (IVDD) with the use of magnetic resonance imaging T2 mapping. Overview of Literature: SN may be combined with CLBP and/or IVDD; however, their relationship has not been determined to date. Methods: A total of 105 subjects were included (48 men and 57 women; mean age, 63.2±2.7 years; range, 22-84 years). We analyzed five functional spinal unit levels (L1-S1) and evaluated the T2 values of the anterior annulus fibrosus (AF), nucleus pulposus, and posterior AF. We compared the low back pain (LBP) Visual Analog Scale (VAS) scores and the T2 values in each decade with or without SN. Results: There were no remarkable differences in SN prevalence rate regarding age decade or gender. SNs were more prevalent in the upper 2 levels (70.3%). LBP VAS scores with and without SN were 64.7±4.3 mm and 61.9±2.8 mm, respectively, with no significant differences between the groups (p =0.62). The T2 values of anterior AF with SN were significantly lower than those without SN in patients in their 50s, 60s, 70s, and 80s (p <0.01). Conclusions: SN presence is not itself a risk factor for CLBP; however, it indicates IVDD of the anterior AF in subjects with SN who are ≥50 years old.

DOI： 10.31616/asj.2019.0231

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Language：Japanese   Publisher：(公社)日本整形外科学会  

Ichushi

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DOI： 10.1097/BRS.0000000000003203

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Osteosarcoma (OS) is a highly malignant bone tumor and the prognosis for non-responders to chemotherapy remains poor. Previous studies have shown that human sarcomas contain sarcoma-initiating cells (SIC), which have the characteristics of high tumorigenesis and resistance to chemotherapy. In the present study, we characterized SIC of a novel OS cell line, screened for SIC-related genes, and tried to regulate the proliferation of OS by metabolic interference. Initially, we established a new human OS cell line (OS13) and isolated clones showing higher tumorigenesis as SIC (OSHIGH ) and counterpart clones. OSHIGH cells showed chemoresistance and their metabolism highly depended on aerobic glycolysis and suppressed oxidative phosphorylation. Using RNA-sequencing, we identified LIN28B as a SIC-related gene highly expressed in OSHIGH cells. mRNA of LIN28B was expressed in sarcoma cell lines including OS13, but its expression was not detectable in normal organs other than the testis and placenta. LIN28B protein was also detected in various sarcoma tissues. Knockdown of LIN28B in OS13 cells reduced tumorigenesis, decreased chemoresistance, and reversed oxidative phosphorylation function. Combination therapy consisting of a glycolysis inhibitor and low-dose chemotherapy had antitumor effects. In conclusion, manipulation of glycolysis combined with chemotherapy might be a good adjuvant treatment for OS. Development of immunotherapy targeting LIN28B, a so-called cancer/testis antigen, might be a good approach.

DOI： 10.1111/cas.14229

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A 50-year-old man presented to the clinic with severe neck pain, fever, and difficulty breathing and was subsequently admitted to the local orthopedics department with possible retropharyngeal abscess and pyogenic spondylitis. Antibiotic therapy was initiated; however, due to poor oxygenation, he was referred and transferred to our department and admitted. Magnetic resonance imaging showed signal changes at the left C1/2 lateral atlantoaxial joint, posterior pharynx, longus colli muscle, carotid space, and medial deep cervical region, predominantly on the left side. In addition, despite lymph node enlargement from the posterior pharynx to the deep cervical region, there was no abscess formation. There were no signs of a space-occupying lesion or signal changes in the jugular foramen. One day postadmission, the patient's temperature had risen to 39.1°C and his SpO2 had fallen. His neck pain had also worsened, and emergency surgery was decided. Preoperatively, we suspected retropharyngeal abscess and pyogenic spondylitis. On day 13 postadmission, the patient exhibited dysphagia, deviated tongue protrusion, and the curtain sign. Glossopharyngeal and hypoglossal nerve paralysis were diagnosed. The patient's swallowing functions recovered and he was discharged on day 36. We experienced a case of glossopharyngeal and hypoglossal nerve paralysis secondary to pyogenic cervical facet joint arthritis.

DOI： 10.1155/2020/3795035

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OBJECTIVES: Soft tissue metastasis (STM) is an uncommon condition in carcinoma. Although various case series related to STM have been reported, few reports have examined prognostic factors. This study aimed to evaluate the characteristics of STM and the factors affecting its prognosis. MATERIALS AND METHODS: Patients with STM from carcinoma were retrospectively studied. The patients' information, including age, sex, primary tumor, metastasis location, size of the metastatic tumor, presence of pain, histological classification, history of primary tumor treatment, and other metastasis at diagnosis of STM were collected and associated with prognosis. RESULTS: Overall, 16 patients with a mean age of 68.7 years were evaluated. The overall survival rate was not significantly different between lung cancer and non-lung cancer patients. The overall survival rate was significantly better in patients undergoing definitive treatment for the primary tumor than in those without history of treatment (p = 0.046). The overall survival rate of STM patients with no metastasis was significantly better than those with other metastasis at the diagnosis of STM (p = 0.041). On multivariate analysis, no history of primary tumor treatment and STM without pain were risk factors for prognosis (p = 0.0340 and 0.0474, respectively). None of the patients who developed STM under the skin experienced pain, while 92.3% of the patients who developed STM in the deep layer had pain. CONCLUSION: The risk factors for poor diagnosis of STM were no past treatment of the primary tumor and absence of pain. STM in the deep layer is prone to pain.

DOI： 10.1159/000508463

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Language：Japanese   Publisher：北海道整形災害外科学会  

Ichushi

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Language：Japanese   Publisher：北海道整形災害外科学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Wiley  

BACKGROUND: Primary soft tissue sarcomas (STSs) involving the chest wall are uncommon. The aim of this study was to identify factors that influence the prognosis of patients with primary chest wall STS. METHODS: The records of 38 patients (23 men and 15 women) who were treated at our institutions during 2002 to 2018 were reviewed. The following variables were evaluated as potential prognostic factors: sex, tumor size, chemotherapy, and completeness of surgical margins. Multivariate analysis was conducted to identify predictors of overall survival (OS) and disease-free survival (DFS). RESULTS: Of the 38 included patients, 5 had low-grade tumors and 33 had high-grade tumors. Five patients required chest wall reconstruction including rib resection. Thirty patients (79%) underwent R0 resection. The 5-year OS and DFS rates were 45% and 27%, respectively. Local recurrence developed in 7 patients. Multivariate analysis identified tumor size (hazard ratio [HR]: 4.13; 95% confidence interval [CI]: 1.05-16.24; P = .04) and R1/2 resection (HR: 3.92; 95% CI: 1.12-13.66; P = .03) as predictors of OS. CONCLUSIONS: Prognostic factors for survival included tumor size and completeness of surgical margins. Complete tumor excision is desirable, particularly in cases of early detection.

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/jso.25708

DOI： 10.1002/jso.25708

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SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a new clinical entity characterized by SMARCA4 inactivation and has a dismal prognosis because of rapid growth. Effective treatments for SMARCA4-DTS have not yet been developed. Most recently, anti-programmed cell death 1 receptor (PD-1) blockade has been effective for SMARCA4-deficient lung cancer and malignant rhabdoid tumor-like tumors. Here, we describe a patient with SMARCA4-DTC who experienced a marked response to the administration of pembrolizumab. A 70-year-old female was referred to our department for treatment of SMARCA4-DTC. Positron emission tomography-computed tomography had revealed a left mediastinal tumor, peritoneal dissemination and multiple cutaneous metastases at diagnosis. Immunohistochemical analyses revealed 60% of tumor cells expressed programmed cell death ligand 1 (PD-L1). The patient was given pembrolizumab as first-line treatment. Pembrolizumab suppressed tumor growth dramatically, with only one dose leading to a partial response. Our case suggests the immunohistochemical analysis of PD-L1 expression be undertaken for patients with SMARCA4-DTS and that pembrolizumab treatment may be a promising strategy for PD-L1-positive SMARCA4-DTS.

DOI： 10.1111/1759-7714.13215

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BACKGROUND/AIM: Although few studies have shown the effectiveness of adjuvant therapy with acridine orange (AO) for soft tissue sarcoma (STS) patients, no study has investigated this among cases with marginal resection. The aim of the study was to evaluate the effectiveness of AO therapy directly by comparing it to marginal resection cases that did not receive AO. PATIENTS AND METHODS: This retrospective study included 19 and 33 patients with STS who received AO therapy (AO group) and marginal resection without AO therapy (non-AO group), respectively. The patients' clinical information was collected, and the clinical courses were compared. RESULTS: The local recurrence rate in the AO group was significantly lower than that in the non-AO group (p<0.05). The local recurrence-free survival curves significantly differed between the two groups (p<0.05). High grade malignancy and no treatment with AO were identified as risk factors for local recurrence (p<0.05). CONCLUSION: AO therapy strongly suppressed local recurrence after marginal resection of STS.

DOI： 10.21873/anticanres.13849

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Pneumothorax has been reported as a pazopanib-associated adverse event in patients with lung metastases of soft tissue sarcoma (STS). However, pneumothorax triggered by eribulin treatment has never been reported. We herein report two cases of spontaneous pneumothorax in patients with STS treated with eribulin. Both patients experienced pneumothorax accompanied by sudden dyspnea on day 9 or 10 of eribulin treatment. These two cases suggest that spontaneous pneumothorax may occur as an adverse event of eribulin treatment in such patients. We should therefore be alert for the potential development of pneumothorax during eribulin treatment of patients with STS and lung metastases.

DOI： 10.2169/internalmedicine.2790-19

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A 70-year-old woman developed severe buttock pain that progressed to a walking disturbance. Radiographs and computed tomography scans revealed an osteolytic lesion with osteosclerosis extending from the body to the arch of the fifth lumbar vertebra. Magnetic resonance imaging showed multinodular masses in the fifth lumbar vertebral body extending into the spinous processes and right transverse process. The masses were hypointense to isointense on T1-weighted images and hypointense to hyperintense on T2-weighted images. Histologic examination of biopsy specimens showed destruction of the trabecula of the vertebral bone by a fascicular and solid proliferation of spindle tumor cells and scattered rhabdomyoblasts, in a fibrotic background. The tumor cells were immunoreactive for keratins, vimentin, desmin, MyoD1, myogenin, and anaplastic lymphoma kinase. Fluorescence in situ hybridization detected split signals for FUS and TFCP2 in 80% and 64% of the tumor cells, respectively, suggesting FUS-TFCP2 fusion. Reverse transcription-polymerase chain reaction revealed a FUS-TFCP2 fusion. The final diagnosis was spindle cell rhabdomyosarcoma of a lumbar vertebra with a FUS-TFCP2 fusion. A spindle cell rhabdomyosarcoma with a FUS-TFCP2 fusion in a vertebral bone is rare and should be differentiated from metastatic carcinoma, particularly in the elderly.

DOI： 10.1016/j.prp.2019.03.027

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Language：Japanese   Publisher：東日本整形災害外科学会  

Ichushi

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Language：Japanese   Publisher：(公社)日本整形外科学会  

Ichushi

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Language：Japanese   Publisher：(公社)日本整形外科学会  

Ichushi

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Language：Japanese   Publisher：(公社)日本整形外科学会  

Ichushi

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Recent technical improvements in both mass spectrometry and protein extraction have made it possible to use formalin-fixed, paraffin-embedded (FFPE) tissues for proteome analysis. In this study, comparable proteome analysis of FFPE tissues revealed multiple candidate marker molecules for differentiating atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) from lipoma. A total of 181 unique proteins were identified for ALT/WDL. Of the identified proteins, coiled-coil domain-containing protein 180 (CCDC180) and leucine-rich repeat-containing protein 4 (LRRC4) were studied as candidate markers of ALT/WDL. CCDC180 and LRRC4 immunohistochemistry clearly stained tumor cells of ALT/WDL and dedifferentiated liposarcoma and could differentiate them from lipoma with high accuracy. Cell biological methods were used to further examine the expression of the candidate marker molecules in liposarcoma cells. In liposarcoma cells, knockdown of CCDC180 and LRRC4 inhibited cell proliferation. CCDC180 inhibited cell migration, invasion, and apoptosis resistance in WDL cells. Adipogenic differentiation suppressed the expression of CCDC180 and LRRC4 in WDL cells. These results indicated that LRRC4 and CCDC180 are novel immunohistochemical markers for differentiating ALT/WDLs. Their expression was associated with adipocyte differentiation and contributed to malignant potentials of WDL cells. Proteome analysis using a standard stock of FFPE tissues can reveal novel biomarkers for various diseases, which contributes to the progress of molecular pathology.

DOI： 10.1016/j.ajpath.2019.01.013

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DOI： 10.22603/ssrr.2018-0064

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An activated AKT pathway underlies the pathogenesis of soft tissue sarcoma (STS), with over-expressed phosphorylated AKT (p-AKT) correlating with a poor prognosis in a subset of STS cases. Recently, eribulin, a microtubule dynamics inhibitor, has demonstrated efficacy and is approved in patients with advanced/metastatic liposarcoma and breast cancer. However, mechanisms of eribulin resistance and/or insensitivity remain largely unknown. In this study, we demonstrated that an increased p-AKT level was associated with eribulin resistance in STS cells. We found a combination of eribulin with the AKT inhibitor, MK-2206, synergistically inhibited STS cell growth in vivo as well as in vitro. Mechanistically, eribulin plus MK-2206 induced G1 or G2/M arrest by down-regulating cyclin-dependent kinases, cyclins and cdc2, followed by caspase-dependent apoptosis in STS cells. Our findings demonstrate the significance of p-AKT signaling for eribulin-resistance in STS cells and provide a rationale for the development of an AKT inhibitor in combination with eribulin to treat patients with STS.

DOI： 10.1038/s41598-019-42300-z

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Ichushi

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DOI： 10.1159/000500404

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BACKGROUND: Lymph node metastasis (LNM) is a relatively rare event in soft tissue sarcoma. An association between the timing of LNM detection and patient prognosis is presently unknown. PATIENTS AND METHODS: We retrospectively analyzed the clinicopathological features of 33 patients with LNM between 2001 and 2015. Analysis of the timing of LNM diagnosis was grouped according to patients presenting LNM in either <8 months (the median time from primary tumor diagnosis to LNM) or ≥8 months after primary tumor diagnosis. RESULTS: A relationship between the primary tumor size and the timing of the LNM was not significantly found (Rs = 0.0088, p=0.96). Sixteen patients had an LNM detection duration of <8 months, and 17 patients had a duration of ≥8 months. The 5-year survival for patients with an LNM detection duration of <8 months and ≥8 months was 19% and 71%, respectively (p=0.0016). There were 19 patients with pulmonary metastases. Among them, there were 13 patients with a duration of primary tumor diagnosis to LNM of <8 months and 6 with a duration of ≥8 months (p=0.01). CONCLUSION: Early LNM (<8 months) may predict poor prognosis in soft tissue sarcoma.

DOI： 10.1155/2019/6708474

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：International Institute of Anticancer Research  

DOI： 10.21873/invivo.11709

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DOI： 10.22603/ssrr.2018-0076

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DOI： 10.22603/ssrr.2018-0049

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BACKGROUND: Clear cell sarcoma of soft tissue (CCSST) and clear cell sarcoma-like gastrointestinal tumor (CCSLGT) are malignant mesenchymal tumors that share some pathological features, but they also have several different characteristics. They are well known to express chimeric fusions of Ewing sarcoma breakpoint region 1 (EWSR1) and cAMP response element-binding protein (CREB) family members; namely, EWSR1-activating transcription factor 1 (ATF1) and EWSR1-CREB1. In addition, recent studies have suggested the presence of other fusions. METHODS: We used fluorescence in situ hybridization to detect specific rearrangements including EWSR1, ATF1, CREB1, and cAMP response element modulator (CREM) in 16 CCSST and 6 CCSLGT cases. We also used reverse transcription polymerase chain reaction (RT-PCR) to detect specific chimeric fusions of EWSR1-ATF1 and EWSR1-CREB1 using fresh tumor samples in available cases. RESULTS: A total of 15 of 16 CCSST cases (93.8%) had EWSR1 rearrangement, of which 11 (68.8%) also had ATF1 rearrangement, suggestive of the presence of EWSR1-ATF1 fusions. One CCSST case (6.3%) was found to have EWSR1 and CREM rearrangements, and 4 of 6 CCSLGT cases (66.7%) had EWSR1 rearrangement, of which 2 (33.3%) showed ATF1 rearrangement and the other 2 cases (33.3%) showed CREB1 rearrangement. These cases most likely had EWSR1-ATF1 and EWSR1-CREB1 fusions, respectively. RT-PCR was performed in 8 available cases, including 6 CCSSTs and 2 CCSLGTs. All CCSSTs showed EWSR1-ATF1 fusions. Among the 2 CCSLGT cases, one had EWSR1-ATF1 fusion and the other had EWSR1-CREB1 fusion. CONCLUSIONS: Rearrangements of EWSR1 and ATF1 or EWSR1-ATF1 fusion were predominantly found in CCSST, whereas those of EWSR1 and CREB1 or EWSR1-CREB1 tended to be detected in CCSLGT. A novel CREM fusion was also detected in a few cases of CCSST and CCSLGT. The cases in which EWSR1 rearrangement was detected without definitive partner genes should be considered for the presence of CREM rearrangement.

DOI： 10.1186/s13000-018-0752-6

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BACKGROUND: Soft tissue sarcomas (STS) are rare malignant tumors. The efficacy of preoperative chemotherapy for STS is evaluated using various tumor size-based radiological response criteria. However, it is still unclear which set of criteria would show the best association with pathological response and survival of the patients with STS. METHODS: We compared radiological responses to preoperative chemotherapy for operable STS by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST, World Health Organization criteria, Japanese Orthopaedic Association criteria, and modified Choi criteria and analyzed the association with pathological response and survival using the data from the Japan Clinical Oncology Group (JCOG) study JCOG0304, a phase II clinical trial evaluating the efficacy of perioperative chemotherapy for STS in the extremities. RESULTS: Seventy eligible patients in JCOG0304 were analyzed. The results demonstrated that none of the size-based radiological response criteria showed significant association with pathological response to preoperative chemotherapy for STS. The difference between overall survival of the patients assessed as partial response and stable disease/progressive disease by RECIST was not significant (hazard ratio 1.37, p = 0.63), and calculated C-index was 0.50. All other response criteria also could not exhibit significant association between radiological responses and survival. CONCLUSION: In the present study, none of the radiological response criteria analyzed demonstrated association of response to preoperative chemotherapy with pathological response or survival of the patients with operable STS. Further prospective investigation is required to develop criteria to evaluate not only tumor shrinkage but biological effects of preoperative chemotherapy for the patients with localized STS. TRIAL REGISTRATION: UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

DOI： 10.1186/s12957-018-1462-y

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BACKGROUND: Giant cell tumor of bone (GCTB) is an intermediate tumor known to be locally aggressive, but rarely metastasizing. To plan a prospective study of GCTB, we performed a questionnaire survey for institutions participating in the Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical Oncology Group (JCOG) in 2015. METHODS: We reviewed 158 consecutive patients with primary GCTB treated with curettage without perioperative denosumab from 2008 to 2010 in Japan. We investigated local and distant recurrence rates after definitive curettage. We also investigated the recurrence rate after treatment with preoperative and/or postoperative denosumab with curettage in recent years. There were 40 patients treated with perioperative denosumab, and the factors affecting recurrence in them were investigated. RESULTS: Answers were available from 24 of 30 institutions (80.0%) participating in JCOG BSTTSG. Thirty (19.0%) and 4 (2.5%) of 158 patients developed local and distant recurrence after curettage without perioperative denosumab from 2008 to 2010, respectively. Campanacci grade and embolization before surgery were significantly associated with increasing incidence of local recurrence after curettage (p = 0.034 and p = 0.022, respectively). In patients treated with perioperative desnosumab, 120 mg denosumab was administered subcutaneously for a median 6 (2-41) and 6 (1-14) times in preoperative and postoperative settings, respectively. The recurrence rates were 6 of 21 (28.6%), 2 of 9 (22.2%), and 0 of 10 (0.0%) in the preoperative, postoperative, and both pre- and postoperative denosumab treatment groups, respectively. With all of the preoperative treatments, administration exceeding five times was significantly associated with a decreased incidence of local recurrence after curettage (p < 0.001). CONCLUSION: The recurrence rate of GCTB was still high after curettage, especially in Campanacci grade III, and improvements in the therapeutic strategy are needed in this cohort. There is a possibility that a sufficient dose of preoperative denosumab can reduce recurrence after curettage. Recently, we have started a clinical trial, JCOG1610, to investigate the efficacy of preoperative denosumab in patients who can be treated with curettage in GCTB.

DOI： 10.1186/s12957-018-1459-6

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Nodular fasciitis (NF) is a self-limiting fibrous neoplasm that can be mistaken for a soft tissue sarcoma. It is characterised by rapid growth, slight pain and local tenderness. Although it is frequently found in the forearm, a lesion distal to the wrist is quite rare. We present two unusual cases of NF involving the palm, supported by detecting ubiquitin specific protease 6 gene rearrangement. The first patient had non-intraneural NF presenting as peripheral neuropathy affecting the digital nerve while the second patient suffered from painless, non-tender NF in the palm, which had not regressed spontaneously during the five months prior to surgery.

DOI： 10.1308/rcsann.2018.0061

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DOI： 10.1111/pin.12650

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Tokyo  

DOI： 10.1007/s10147-018-1255-x

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AIMS: The aims of this study were to analyse the long-term outcome of vascularised fibular graft (VFG) reconstruction after tumour resection and to evaluate the usefulness of the method. PATIENTS AND METHODS: We retrospectively reviewed 49 patients who had undergone resection of a sarcoma and reconstruction using a VFG between 1988 and 2015. Their mean follow-up was 98 months (5 to 317). Reconstruction was with an osteochondral graft (n = 13), intercalary graft (n = 12), inlay graft (n = 4), or resection arthrodesis (n = 20). We analysed the oncological and functional outcome, and the rate of bony union and complications. RESULTS: Five- and ten-year overall survival rates were 89% and 86%, respectively. Local recurrence occurred in two patients. Eight patients developed pulmonary metastases. Bone union was achieved in 44 patients (90%). Fracture occurred in six patients (12%), infection in three (6%), and nonunion in five (10%). The mean Musculoskeletal Tumor Society (MSTS) scores were as follows: osteochondral graft 70%; intercalary graft 73%; inlay graft 89%; and resection arthrodesis 83%. CONCLUSION: Although associated with a relatively high rate of complications, each reconstruction method is useful, with a high rate of successful limb salvage and a good long-term functional outcome. Cite this article: Bone Joint J 2017;99-B:1237-43.

DOI： 10.1302/0301-620X.99B9.BJJ-2017-0219.R1

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Chemotherapy has improved the prognosis of patients with sarcomas. However, it may suppress anti-tumor immunity. Recently, we reported a novel CD8+ memory T cell population with a chemo-resistance property, "young memory" T (TYM ) cells. In this study, we investigated the proportion and function of TYM cells in peripheral blood of healthy donors and sarcoma patients who received chemotherapy and those who did not. The proportion of TYM cells was significantly decreased in patients compared with that in healthy donors. In healthy donors, anti-EBV CTLs were induced using mixed lymphocyte peptide culture, from not only TYM cells but also TCM and TEM cells. No CTLs directed to tumor-associated antigens were induced. In sarcoma patients who did not receive chemotherapy, in addition to anti-EBV CTLs, CTLs directed to the tumor-associated antigen PBF were induced from TYM , TCM and TEM cells. In sarcoma patients who received chemotherapy, EBV-specific CTLs were induced from TYM cells but were hardly induced from TEM cells. Interestingly, CTLs directed to the anti-tumor-associated antigen PBF were induced from TYM cells but not from the TCM and TEM cells in sarcoma patients who received chemotherapy. The findings suggest that TYM cells are resistant to chemotherapy and can firstly recover from the nadir. TYM cells might be important for immunological memory, especially in sarcoma patients receiving chemotherapy.

DOI： 10.1111/cas.13319

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Language：Japanese   Publisher：北海道整形災害外科学会  

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CIC-rearranged sarcoma is a new entity of undifferentiated small round cell sarcoma characterized by chimeric fusions with CIC rearrangement. We report a NUTM2A-CIC fusion sarcoma in a 43-year-old woman who died of rapidly progressive disease. Histologic analysis revealed multinodular proliferation of small round tumor cells with mild nuclear pleomorphism. The sclerotic fibrous septa separated the tumor into multiple nodules. Immunohistochemistry showed that the tumor cells were diffusely positive for vimentin, focally positive for cytokeratin, and negative for CD99 and NKX2.2. Tumor cells were also negative for ETV4, which was recently identified as a specific marker for CIC-rearranged sarcoma. High-throughput RNA sequencing of a formalin-fixed, paraffin-embedded clinical sample unveiled a novel NUTM2A-CIC fusion between NUTM2A exon 7 and CIC exon 12, and fluorescence in situ hybridization identified CIC and NUTM2A split signals. This case shared several clinicopathological findings with previously reported CIC-rearranged cases. We recognized the tumor as a genetically distinct variant of CIC-rearranged sarcomas with a novel NUTM2A-CIC fusion.

DOI： 10.1016/j.humpath.2017.01.012

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DOI： 10.1111/pin.12503

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BACKGROUND: Uterine sarcoma is a rare tumor that is often difficult to classify based on morphological and immunohistochemical analysis alone. Limited access to molecular biological analysis in routine practice would hinder making a definitive diagnosis. CASE PRESENTATION: In this report, we describe a case of a mesenchymal tumor arising from the uterine cervix in a 52-year-old woman. From microscopic morphology of the resected specimen, epithelioid leiomyosarcoma, high-grade endometrial stromal sarcoma, or uterine gastrointestinal stromal tumor (GIST) were considered as differential diagnoses. The immunophenotype of the tumor featured smooth muscle differentiation and hormone receptor expression. The cell membrane and cytoplasm were positive for c-kit, although no mutation was found in the c-kit or PDGFRA gene. Fluorescence in situ hybridization (FISH) analysis revealed a relatively low frequency of YWHAE rearrangement, whereas there were few NUTM2A and NUTM2B split signals. CONCLUSIONS: In this case, the tumor was not typical of any three of the differential diagnoses mentioned above. However, insufficient frequency of YWHAE, NUTM2A, and NUTM2B gene rearrangement and absence of mutation in both the c-kit and PDGFRA genes suggested that this tumor should be categorized as epithelioid leiomyosarcoma. This is an instructive case showing a potential diagnostic pitfall of uterine sarcoma. Comprehensive approaches including molecular biological techniques are required for definitive diagnosis.

DOI： 10.1186/s13000-017-0615-6

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DOI： 10.1080/03009734.2017.1356404

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BACKGROUND: Pseudomyogenic hemangioendothelioma (PHE) is an unusual vascular tumor of intermediate malignancy that rarely metastasizes and tends to arise in the lower limbs of young adults and children. Histologically, PHE shows fascicular proliferation of eosinophilic spindle cells and/or epithelioid cells showing "pseudomyogenic" morphology. Immunohistochemically, PHE is usually positive for vimentin, cytokeratin, CD31 and ERG. METHOD: We examined FOSB immunohistochemistry (IHC) in 27 cases consisting of 4 PHE and its histologic mimics including 6 epithelioid hemangioendotheliomas (EHE), 8 angiosarcomas (AS), 4 Kaposi sarcomas (KS) and 5 epithelioid sarcomas (ES). In addition, we performed IHC of CAMTA1 which has recently been established as a useful marker of EHE. We elucidated the diagnostic utility of FOSB IHC in the differential diagnosis of PHE and its histological mimics and also examined the usefulness of FOSB and CAMTA1 IHC combination in the differential diagnosis of the tumors. RESULTS: IHC revealed diffuse and strong FOSB expression in all PHE cases, while the other tumor types demonstrated limited, weak or no FOSB expression. All EHE cases exhibited diffuse and moderate to strong expression of CAMTA1. All tumor types except for EHE showed limited, weak or no CAMTA1 reactivity. CONCLUSIONS: Diffuse and strong FOSB expression was specific for PHE in the current series and FOSB IHC is an effective tool for differentiating between PHE and its histological mimics. Moreover, the combination of FOSB and CAMTA1 IHC is useful for distinguishing PHE from EHE.

DOI： 10.1186/s13000-016-0530-2

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UNLABELLED: We report the treatment outcomes of 5 cases of adult-onset Ewing sarcoma(ES)managed between 2011 and 2014. We examined prognostic factors including the primary lesion, tumor size, metastatic status, and serum LDH levels. RESULTS: The locations of the primary lesions included the limbs in 1 case and the trunk in 4; the cases in the trunk had a worse prognosis than that in the limbs. Tumor size was greater than 8 cm in only 1 patient, who also displayed evidence of metastases at presentation and high LDH levels. All the patients received chemotherapy consisting of alternating vincristine, doxorubicin, and cyclophosphamide(VDC)and etoposide and ifosfamide(IE). Surgery was selected for the treatment of 4 patients, and radiotherapy was administered to 1 patient for local treatment of the tumor. A median follow-up duration of 31.6 months revealed the 2-year overall survival rate and progression-free survival rate to be 80.0%. CONCLUSIONS: The prognosis of patients with adult-onset ES is poor; however, combined modality therapy, including VDC-IE, was demonstrated to improve the outcome of patients in the present study. Nevertheless, the patient with tumor size exceeding 8 cm, metastasis, and high LDH levels, relapsed 1 year after treatment, as reported previously. Further investigation is required to clarify the factors affecting prognosis in adults, and to develop effective therapies for patients with a poor prognosis.

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INTRODUCTION: The use of immunotherapeutic challenges for sarcoma has a long history. Despite the existence of objective responses, immunotherapy has been overshadowed by the results of chemotherapy, especially for osteosarcoma. However, the prognosis for non-responders to chemotherapy is still poor and immunotherapy is now focused on again. AREAS COVERED: We reviewed the following types of clinical trials of immunotherapy for sarcoma: (i) vaccination with autologous tumor cells, (ii) vaccination with peptides derived from tumor-associated antigens, (iii) adoptive cell transfer using engineered T cells expressing T cell receptor directed at NY-ESO-1 and (iv) immune checkpoint inhibitors targeting CTLA-4 and PD1/PDL1. EXPERT OPINION: The immunogenicity of sarcoma might be lower than that of melanoma. Patients with small lesions who have not received any chemotherapy are good candidates for peptide-based immunotherapy. Combining peptide vaccination and immune checkpoint inhibitors is an attractive option, and long-lived memory T cells are attracting attention. Memory T stem cells defined by CD95+ are long-lived and have the capacity for self-renewal and multidifferentiation. We also identified a novel memory T cell population, young memory T cells defined by CD73+CXCR3+. Regulation of such memory T stem cells will be useful for peptide vaccination and adoptive cell transfer.

DOI： 10.1080/14712598.2016.1188075

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Language：Japanese   Publisher：(公社)日本整形外科学会  

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High-dose chemotherapy may kill not only tumor cells but also immunocytes, and frequently induces severe lymphocytopenia. On the other hand, patients who recover from the nadir maintain immunity against infection, suggesting the existence of an unknown memory T-cell population with stress resistance, long-living capacity, proliferation and differentiation. Recently, the differentiation system of T-cell memory has been clarified using mouse models. However, the human T-cell memory system has great diversity induced by natural antigens derived from many pathogens and tumor cells throughout life, and profoundly differs from the mouse memory system constructed using artificial antigens and transgenic T cells. Here we report a novel human T-cell memory population, "young memory" T (TYM) cells. TYM cells are defined by positive expression of CD73, which represents high aldehyde dehydrogenase 1 (ALDH1) activity and CXCR3 among CD8(+)CD45RA(+)CD62L(+) T cells. TYM proliferate upon TCR stimulation, with differentiation capacity into TCM and TEM and drug resistance. Moreover, TYM are involved in memory function for viral and tumor-associated antigens in healthy donors and cancer patients, respectively. Regulation of TYM might be very attractive for peptide vaccination, adoptive cell-transfer therapy and hematopoietic stem cell transplantation.

DOI： 10.1080/2162402X.2016.1165376

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BACKGROUND: CD109, a TGF-β co-receptor, is reported to be preferentially expressed during the early stages of tumorigenesis in several carcinoma types. Myxofibrosarcoma is one of the most common soft-tissue sarcomas found in elderly patients. This study aimed to elucidate the impact of CD109 expression in myxofibrosarcoma on prognosis and recurrence. METHODS: Immunohistochemical staining for CD109 was performed on archival specimens from 37 patients. The Fisher exact test was used to evaluate association between CD109 expression and other clinicopathological features. Survival analysis was performed using Kaplan-Meier curves, and the prognostic significance was evaluated using the log-rank test. Multivariate analysis of factors was performed using Cox regression analysis. RESULTS: CD109 overexpression was significantly associated with surgical stage and distant metastasis (P = 0.00499, and 0.011, respectively). The frequency of CD109 overexpression was approximately 10% and CD109 overexpression was significantly associated with decreased overall survival (P = 0.004). Five-year overall survival rates 77% and 0% for CD109-negative and CD109-positive patients, respectively. In multivariate analysis, CD109 overexpression was the only independent risk factor for poor outcome (P = 0.02; hazard ratio, 10.64; 95% confidence interval, 1.47-76.91). CONCLUSIONS: Immunohistochemical CD109 expression in myxofibrosarcoma was associated with poor prognosis.

DOI： 10.1002/jso.23934

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Language：Japanese   Publisher：The Japan Society for Clinical Immunology  

骨肉腫に代表される高悪性度骨軟部肉腫は予後不良であり，新しい治療法が求められている．我々は骨肉腫の免疫制御を目指し，自家の骨肉腫細胞株とCTLクローンを用いたcDNAライブラリ発現クローニングで世界で初めて骨肉腫抗原PBFを同定した．PBFは転写調節因子であり，骨肉腫のアポトーシスを制御している．PBF蛋白は骨肉腫組織の92％で，骨軟部肉腫全体では87％に発現が見られた．またPBF陽性の骨肉腫患者の予後は不良であり，PBFは予後不良骨肉腫の標的分子となり得る．そこで我々はHLA-A24/A2拘束性PBFペプチドを設計して骨肉腫患者のペプチド特異的CTL応答を解析し，まず骨肉腫患者に対するペプチドワクチン臨床試験を10例に行った．臨床効果は不変3例，増悪6例で，9例でペプチドに対する免疫応答が検出された．多発肺転移および皮下転移をもつ1例で，ペプチドワクチンに対する高い免疫応答がELISPOTで観察された．また局所再発巣に骨化とCD8陽性細胞浸潤を認めた．この症例はペプチドワクチン療法のみで加療され，合計31か月生存した．そして試験的に実施した再発粘液線維肉腫1例においてPBFペプチドに対する極めて高い免疫応答が誘導され，病勢にも相関した．これらの2症例はいずれも化学療法未施行例であり，病巣が小さかった（2 cm以下）．これらの知見は今後のペプチドワクチン療法のさらなる実効化に大変重要と考えている

Other Link： http://search.jamas.or.jp/link/ui/2016051690

DOI： 10.2177/jsci.38.286b

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DOI： 10.1038/labinvest.2014.122

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Chordomas are rare, low grade, malignant tumours derived from the ectopic remnants of the notochord that line the axial skeleton. They are characterised by their slow growth, long disease course and propensity for local relapse. Furthermore, up to 40% of non-cranial chordomas metastasise. We describe the first reported case of a hand metastasis arising from a conventional sacral chordoma after carbon ion radiotherapy. The common occurrence of distant metastasis with chordomas makes it important to perform a systemic examination, in part because their resection might improve patient prognosis.

DOI： 10.1308/003588414X13946184902686

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Osteosarcoma is a rare but highly malignant tumor occurring most frequently in adolescents. The prognosis of non-responders to chemotherapy is still poor, and new treatment modalities are needed. To develop peptide-based immunotherapy, we previously identified autologous cytotoxic T lymphocyte-defined osteosarcoma antigen papillomavirus binding factor (PBF) in the context of HLA-B55 and the cytotoxic T lymphocyte epitope (PBF A2.2) presented by HLA-A2. PBF and HLA class I are expressed in ∼90 and 70% of various sarcomas, respectively. However, the expression status of peptide PBF A2.2 presented by HLA-A2 on osteosarcoma cells has remained unknown because it is difficult to generate a specific probe that reacts with the HLA·peptide complex. For detection and qualification of the HLA-A*02:01·PBF A2.2 peptide complex on osteosarcoma cells, we tried to isolate a single chain variable fragment (scFv) antibody directed to the HLA-*A0201·PBF A2.2 complex using a naïve scFv phage display library. As a result, scFv clone D12 with high affinity (KD = 1.53 × 10(-9) M) was isolated. D12 could react with PBF A2.2 peptide-pulsed T2 cells and HLA-A2+PBF+ osteosarcoma cell lines and simultaneously demonstrated that the HLA·peptide complex was expressed on osteosarcoma cells. In conclusion, scFv clone D12 might be useful to select candidate patients for PBF A2.2 peptide-based immunotherapy and develop antibody-based immunotherapy.

DOI： 10.1074/jbc.M114.568725

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Soft tissue angiofibroma (STA), a recently suggested new histologic entity, is a benign fibrovascular soft tissue tumor composed of bland spindle-shaped tumor cells with abundant collagenous to myxoid stroma and branching small vessels. The lesion has a characteristic AHRR-NCOA2 fusion gene derived from chromosomal translocation of t(5;8)(p15;q13). However, morphologically similar tumors containing abundant fibrovascular and myxoid stroma can complicate diagnosis. We designed an original DNA probe for detecting NCOA2 split signals on fluorescence in situ hybridization (FISH) and estimated its utility with 20 fibrovascular tumors: 4 each of STAs, solitary fibrous tumors (SFTs), and cellular angiofibromas and 3 each of low-grade myxofibrosarcomas, myxoid liposarcomas, and low-grade fibromyxoid sarcomas. We also performed FISH for 13q14 deletion and immunohistochemistry (IHC) staining for estrogen receptor, progesterone receptor, retinoblastoma protein, and MUC-4 expression. Furthermore, IHC for Stat6 was conducted in the 20 cases analyzed by FISH and in an additional 26 SFTs. We found moderate to strong nuclear Stat6 expression in all SFTs but no expression in the other tumors. Both estrogen receptor and progesterone receptor expressions were observed in STAs, SFTs, and cellular angiofibromas. Expression of retinoblastoma protein was found in less than 10% of cells in all tumor types except myxoid liposarcoma. The low-grade fibromyxoid sarcomas were strongly positive for MUC-4. All STAs showed NCOA2 split signals on FISH. All tumors, regardless of histologic type, had 13q14 deletion. The NCOA2 FISH technique is a practical method for confirming STA diagnosis. The combination of NCOA2 FISH and Stat6 IHC proved effective for the differential diagnosis of STA, even when using small biopsy specimens.

DOI： 10.1016/j.humpath.2013.12.022

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BACKGROUND: This study aimed to investigate the expression profile of cyclooxygenase-2 (COX-2) in desmoid tumor specimens and to evaluate the correlation of intratumoral COX-2 expression with pain status. METHODS: Sixteen patients with histologically proven desmoid tumors who attended our institution between 2003 and 2010 were enrolled in this study. COX-2 protein expression in desmoid tumors was determined by immunohistochemistry. COX-2 - positive cells had similar morphology to that of mast cells, and therefore, immunohistochemical staining for tryptase was performed in co-localized sections. The number of COX-2 -positive cells in 10 consecutive fields was counted at 400× magnification. Patients were stratified into 2 groups according to the number of COX-2- positive cells, the COX-2 -positive group (≧10 COX-2 -positive cells) and the COX-2 -negative group (<10 COX-2 -positive cells). The prevalence of painful tumors was compared between the 2 groups. RESULTS: COX-2 was expressed in 9 patients (56%). COX-2 proteins were expressed not in tumor cells but in tryptase-positive mast cells in the stroma of desmoid tumors. 6 of 9 patients in COX-2 -positive group had painful tumors. This difference was statistically significant according to the chi-squared test (p = 0 .036), suggesting a positive correlation between COX-2 expression and tumor-associated pain. CONCLUSIONS: Our results indicated that COX-2 secretion from mast cells modulates desmoid tumor-associated pain. In addition, mast cells may at least in part contribute to the pathogenesis of desmoid tumors. VIRTUAL SLIDE: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1490389349103056.

DOI： 10.1186/1746-1596-9-14

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Verlag  

DOI： 10.1007/s12570-013-0236-9

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BACKGROUND CONTEXT: Essential thrombocythemia (ET) is a chronic myeloproliferative disorder characterized by a relatively benign clinical course that may be complicated by conflicting thrombosis and bleeding. Postoperative spinal epidural hematoma is an uncommon, but well-known, complication after spinal surgery. PURPOSE: To describe a patient with ET who underwent surgery for lumbar spinal canal stenosis resulting in leg paraplegia and discuss the perioperative management for ET. STUDY DESIGN: Case report. RESULTS: The patient with ET underwent laminoplasty and posterolateral fusion for degenerative spondylolisthesis and spinal stenosis at L4-L5. A hematoma was observed in the epidural cavity after surgery, and emergency surgical evacuation was performed. After revision surgery, bleeding from the wound continued for 2 months, despite transfusions of platelets and coagulation factors, and right unilateral leg paralysis developed. CONCLUSIONS: This case presentation increases the awareness of this disorder to the spinal community and the need to establish guidelines for the perioperative management of patients who require surgery in similar settings.

DOI： 10.1016/j.spinee.2013.06.018

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Language：English   Publisher：(一社)日本癌学会  

Ichushi

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Ichushi

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Language：Japanese   Publisher：(公社)日本整形外科学会  

Ichushi

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Language：Japanese   Publisher：(一社)日本病理学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

Epithelioid sarcoma (ES) is a relatively rare, highly malignant soft tissue sarcoma. The mainstay of treatment is resection or amputation. Currently other therapeutic options available for this disease are limited. Therefore, a novel therapeutic option needs to be developed. In the present study, we established a new human ES cell line (ESX) and analyzed the characteristics of its cancer stem-like cells/cancer-initiating cells (CSCs/CICs) based on ALDH1 activity. We demonstrated that a subpopulation of ESX cells with high ALDH1 activity (ALDH(high) cells) correlated with enhanced clonogenic ability, sphere-formation ability, and invasiveness in vitro and showed higher tumorigenicity in vivo. Next, using gene expression profiling, we identified CD109, a GPI-anchored protein upregulated in the ALDH(high) cells. CD109 mRNA was highly expressed in various sarcoma cell lines, but weakly expressed in normal adult tissues. CD109-positive cells in ESX predominantly formed spheres in culture, whereas siCD109 reduced ALDH1 expression and inhibited the cell proliferation in vitro. Subsequently, we evaluated the expression of CD109 protein in 80 clinical specimens of soft tissue sarcoma. We found a strong correlation between CD109 protein expression and the prognosis (P = 0.009). In conclusion, CD109 might be a CSC/CIC marker in epithelioid sarcoma. Moreover, CD109 is a promising prognostic biomarker and a molecular target of cancer therapy for sarcomas including ES.

DOI： 10.1371/journal.pone.0084187

PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Verlag  

DOI： 10.1007/s12570-012-0138-2

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1349-7006.2012.02370.x

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Web of Science

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Language：English   Publishing type：Research paper (scientific journal)  

The management of giant cell tumor of the proximal humerus that extends to the joint is challenging. Here, we report a case of proximal humerus giant cell tumor with cortical bone destruction extending to the shoulder joint. Pre-operative selective arterial embolization induced peripheral tumor ossification. Subsequently, the lesion was removed by intralesional curettage, and the cavity was filled with cement. Macroscopically, the inner wall of the cavity was found to be lined with a thick fibrous membrane. Histologically, massive fibrosis and resultant remodeling of the destroyed cortical bone were induced, which was consistent with the peripheral ossification on the plain radiograph. We believe that selective arterial embolization can be an effective neoadjuvant therapy for giant cell tumors of the extremities, especially for tumors with large cortical defects or joint involvement.

DOI： 10.1093/jjco/hys090

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Language：Japanese   Publisher：(公社)日本整形外科学会  

Ichushi

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Treatment of soft-tissue sarcomas involving the inguinal region remains challenging because of difficulties in achieving wide surgical margins due to anatomical features. The study aimed to analyze the oncologic and functional outcomes of wide resection with vascular reconstruction for inguinal soft-tissue sarcomas. METHODS: Three men and seven women were treated for inguinal soft-tissue sarcomas by wide surgical resection with vascular reconstruction. RESULTS: Arteries and veins were replaced in nine patients, and artery replacement alone was carried out in one patient. Femoral nerve resections were performed in six patients. One patient and five patients developed local recurrence and distant metastases, respectively. Limb salvage was achieved in 9 of 10 patients (90%). Six patients and one patient developed vascular (arterial graft occlusion [n = 1], lymphedema [n = 5]) and nonvascular (hematoma [n = 1]) complications, respectively. Five-year arterial primary patency was 77%. Five-year disease-free and overall survival rates were 45% and 77%, respectively. Functional outcome scores at latest follow-up averaged 87.5% for Musculoskeletal Tumor Society 1993. CONCLUSIONS: En-bloc resection of major critical structures along with tumor and vascular reconstructions using synthetic grafts is a feasible option in limb salvage surgery for inguinal soft-tissue sarcomas.

DOI： 10.1016/j.avsg.2011.12.003

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Language：Japanese   Publisher：The Japan Society for Clinical Immunology  

骨肉腫患者の予後は化学療法の導入により5年生存率約70%に向上した．しかし化学療法不応性の骨肉腫患者の予後はいまだに不良である．また上皮系癌と比べて若年発症例が多く，骨肉腫に対するペプチドワクチン療法に対する期待は大きい．我々は1999年より骨肉腫に対するペプチドワクチンの開発を始め，世界で初めて自家CTLクローンに認識されるヒト骨肉腫抗原PBFをcDNAライブラリ発現クローニング法により同定した．PBF蛋白全長よりHLA-A24拘束性ペプチド（PBF A24.2）およびHLA-A2拘束性ペプチド（PBF A2.2）を設計し，これらの免疫原性を検討した．そしてPBFペプチドを用いた末期骨肉腫患者に対するペプチドワクチンの第1相臨床試験を2009年より開始した．これまでにPBFA24.2ペプチド+IFAを5例に，PBFA2.2ペプチド+IFAを2例に接種した．PBF A24.2ペプチド症例の5/6例で，PBF A2.2ペプチド症例の1/2例でペプチド特異的免疫応答がテトラマーまたはELISPOTで検出された．臨床効果は全例PDであったが，PBF A2.2ペプチドを接種した1例で皮下転移巣の石灰化がみられ，切除標本において腫瘍の部分壊死とCD8陽性T細胞の浸潤が認められた．ペプチドワクチンによる効果が示唆された．有害事象としてアドリアマイシン心筋症によると考えられるCPAが1例でみられた．他に重篤な有害事象はみられなかった．今後さらに症例を重ねて，ペプチドワクチンの免疫応答，臨床効果と安全性を検討していく．<br>

Other Link： http://search.jamas.or.jp/link/ui/2012350636

DOI： 10.2177/jsci.35.323b

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1111/j.1349-7006.2011.01962.x

PubMed

Web of Science

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Language：English   Publishing type：Research paper (scientific journal)  

Chondrosarcomas are the most frequently occurring primary malignant chest wall tumors. Furthermore, the lungs serve as the most frequent sites for metastases. Pulmonary metastases from sarcomas usually appear as round nodules of varying sizes on roentgenograms. Here, we report an unusual clinical and radiographic presentation of pulmonary metastasis from a costal chondrosarcoma. Bilateral pulmonary metastases developed soon after wide surgical resection. Thoracic computed tomography revealed unusual radiological findings: consolidation accompanied with ground-glass opacity. To confirm the metastasis, we recommend a transbronchial biopsy in cases where unusual pulmonary findings are detected.

DOI： 10.1186/1477-7819-9-50

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Language：English   Publishing type：Research paper (scientific journal)  

The proximal tibia is a common site for primary bone tumors. Proximal tibial tumors may invade the adjacent soft-tissue by destroying the cortex and may further invade neurovascular bundles. We treated a patient with primary bone tumor of the proximal tibia with neurovascular invasion by extracorporeally irradiated autograft-prosthetic composite arthroplasty with vascular reconstruction. In cases of concomitant allograft arthroplasty and vascular reconstruction, we recommend that vascular reconstruction be performed before arthroplasty to minimize ischemia time. Good oncological and functional outcomes were achieved 75 months after surgery. Therefore, this reconstruction technique can be considered as a good treatment option.

DOI： 10.1016/j.avsg.2010.07.008

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Language：English   Publishing type：Research paper (scientific journal)  

Swelling, pain, and discoloration in the affected extremities are classic symptoms of deep vein thrombosis (DVT), although these symptoms are often unreliable for diagnosis, and wide differential diagnoses exist. Soft-tissue sarcomas arising in the inguinal region may encompass or be adjacent to femoral vessels and result in venous obstruction, mimicking symptoms of DVT. We present two cases of soft-tissue sarcomas in the inguinal region that were initially misdiagnosed as spontaneous DVT and administered unnecessary long-term anticoagulation therapy. In patients diagnosed with unprovoked DVT, especially young patients aged <45 years, we recommend a careful physical examination and ultrasonography in the inguinal region to prevent overlooking possible underlying malignancy, as delays in diagnosis may affect prognosis.

DOI： 10.1016/j.avsg.2010.03.001

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.foot.2010.06.001

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Language：English   Publishing type：Research paper (scientific journal)  

Vascular lesions associated with neurofibromatosis type 1 (NF1) are rare but can lead to catastrophic complications if disrupted. Ruptured aneurysms in NF1 patients are difficult to treat surgically because of vascular wall fragility. We describe a female NF1 patient with a ruptured aneurysm of her brachial artery. This is the first published case of successful reconstruction of a ruptured brachial aneurysm associated with NF1, using a saphenous vein graft.

DOI： 10.1016/j.jvs.2009.11.040

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/RLU.0b013e3181cc62ad

PubMed

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Language：English  

DOI： 10.1177/1753193408093561

PubMed

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Language：Japanese   Publisher：北海道整形災害外科学会  

Ichushi

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Language：Japanese   Publisher：東日本整形災害外科学会  

Ichushi

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