Faculty Profiles - OZAKI Toshifumi

Papers - OZAKI Toshifumi

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Diagnostic performance of open MRI in the flexed knee position for the detection of medial meniscus ramp lesions. International journal

Yuki Okazaki, Takayuki Furumatsu, Soichiro Okamoto, Takaaki Hiranaka, Keisuke Kintaka, Shinichi Miyazawa, Toshifumi Ozaki

Skeletal radiology 49 ( 11 ) 1781 - 1788 2020.11

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

OBJECTIVES: To identify the diagnostic performance of magnetic resonance imaging (MRI) in the knee-flexed position for the detection of meniscal ramp lesions in patients with anterior cruciate ligament tears. MATERIALS AND METHODS: Forty-three patients (mean age 24.5 ± 9.5 years; 21 males, 22 females) with an arthroscopically proven anterior cruciate ligament tear were included in this retrospective study. The presence of the following two important features on MRI was recorded: irregularity of the medial meniscus at the posterior margin, and complete fluid filling between the posterior horn of the medial meniscus and the capsule margin. Findings obtained in arthroscopy served as the reference standard. The diagnostic sensitivity, specificity, and inter-observer agreement were calculated. RESULTS: Sixteen ramp lesions were noted on arthroscopy (37.2%). With an irregularity of the medial meniscus at the posterior margin on MRI, the sensitivity and specificity were 87.5 and 59.3% at 10° knee flexion and 93.8 and 85.2% at 90° flexion, respectively. The complete fluid filling sign on MRI showed sensitivity and specificity of 31.3 and 100% at 10° knee flexion and 87.5 and 100% at 90° flexion, respectively. The concordance between the two observers for the two MRI features was very good (k = 0.70-0.88). CONCLUSION: MRI with the knee in the flexed position improves the diagnostic performance of the detection of meniscal ramp lesions compared with MRI with the knee in the extended position.

DOI： 10.1007/s00256-020-03480-2

A histological study of the medial meniscus posterior root tibial insertion. International journal

Tomohito Hino, Takayuki Furumatsu, Shinichi Miyazawa, Masataka Fujii, Yuya Kodama, Yusuke Kamatsuki, Yoshiki Okazaki, Shin Masuda, Yuki Okazaki, Toshifumi Ozaki

Connective tissue research 61 ( 6 ) 546 - 553 2020.11

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Purpose/Aim of the study: Posterior root injury of the medial meniscus often leads to articular cartilage degeneration due to altered biomechanics. To avoid dysfunction, the attachment must be repaired using the transtibial pullout technique. To guide appropriate placement of the tibial tunnel, additional details on the normal anatomy of the meniscus insertion are needed. Therefore, we performed a histological analysis of a tibial bone slice with the medial meniscus posterior insertion obtained during total knee arthroplasty surgery. Materials and methods: Horizontal slices of the proximal tibia were obtained from 7 patients with osteoarthritis who underwent total knee arthroplasty. After decalcification, the region of the posterior horn was cut out and segmented into four pieces (2.0 mm thickness; medial to lateral). Sagittal sections were evaluated by safranin O staining or immunohistochemistry with anti-type collagen antibody. Results: Safranin O staining showed that the insertion of the posterior root consisted primarily of fibrocartilaginous layers in segment 2. Anatomically, segment 2 corresponded to the sagittal plane passing through the peak of the medial intercondylar tubercle. In this section, safranin O staining and immunohistochemistry revealed that the anterior one-third of the posterior root insertion was richer in proteoglycans and type II collagen than the central and posterior one-third. Conclusions: Anatomical insertion of the posterior root of the medial meniscus was located at the sagittal plane passing through the peak of the medial intercondylar tubercle. The structure of the medial meniscus posterior insertion was mainly localized in the anterior one-third.

DOI： 10.1080/03008207.2019.1631298

Medial meniscus posterior root tear causes swelling of the medial meniscus and expansion of the extruded meniscus: a comparative analysis between 2D and 3D MRI. International journal

Yoshiki Okazaki, Takayuki Furumatsu, Takuya Yamaguchi, Yuya Kodama, Yusuke Kamatsuki, Shin Masuda, Yuki Okazaki, Takaaki Hiranaka, Ximing Zhang, Toshifumi Ozaki

Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 28 ( 11 ) 3405 - 3415 2020.11

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: This study aimed to clarify the advantages of three-dimensional (3D) magnetic resonance imaging (MRI) over two-dimensional (2D) MRI in measuring the size of the medial meniscus (MM) and to analyse the volumes of MM and the extruded meniscus in patients with MM posterior root tear (MMPRT), at 10° and 90° knee flexion. METHODS: This study included 17 patients with MMPRTs and 15 volunteers with uninjured knees. The MMs were manually segmented for 3D reconstruction; thereafter, the extruded part separated from the tibial edge was determined. The length, width, height, and extrusion of MM were measured by the 2D and 3D methods, and compared. The MM volume, extruded meniscus volume, and their ratio were also calculated using 3D analysis software in the two groups. RESULTS: The estimated length and posterior height of MM were larger with 3D MRI than with 2D MRI measurements. The MM volume was significantly greater in MMPRT knees than in normal knees, with increasing MM height. In MMPRT knees, the mean volume of the extruded meniscus and its ratio significantly increased by 304 mm3 (p = 0.02) and 9.1% (p < 0.01), respectively, during knee flexion. CONCLUSIONS: This study demonstrated that 3D MRI could estimate the precise MM size and that MMPRT caused swelling of the meniscus due to the increased thickness in the posteromedial part. The clinical significance of this study lies in its 3D evaluation of MM volume, which should help the surgeon understand the biomechanical failure of MM function and improve MMPRT repair technique. LEVEL OF EVIDENCE: III.

DOI： 10.1007/s00167-019-05580-6

Transtibial fixation for medial meniscus posterior root tear reduces posterior extrusion and physiological translation of the medial meniscus in middle-aged and elderly patients. International journal

Yuya Kodama, Takayuki Furumatsu, Shin Masuda, Yoshiki Okazaki, Yusuke Kamatsuki, Yuki Okazaki, Takaaki Hiranaka, Shinichi Miyazawa, Masaharu Yasumitsu, Toshifumi Ozaki

Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 28 ( 11 ) 3416 - 3425 2020.11

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: To investigate changes in meniscal extrusion during knee flexion before and after pullout fixation for medial meniscus posterior root tear (MMPRT) and determine whether these changes correlate with articular cartilage degeneration and short-term clinical outcomes. METHODS: Twenty-two patients (mean age 58.4 ± 8.2 years) diagnosed with type II MMPRT underwent open magnetic resonance imaging preoperatively, 3 months after transtibial fixation and at 12 months after surgery, when second-look arthroscopy was also performed. The medial meniscus medial extrusion (MMME) and the medial meniscus posterior extrusion (MMPE) were measured at knee 10° and 90° flexion at which medial meniscus (MM) posterior translation was also calculated. Articular cartilage degeneration was assessed using International Cartilage Research Society grade at primary surgery and second-look arthroscopy. Clinical evaluations included Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee subjective knee evaluation form, Lysholm score, Tegner activity level scale, and pain visual analogue scale. RESULTS: MMPE at 10° knee flexion was higher 12 months postoperatively than preoperatively (4.8 ± 1.5 vs. 3.5 ± 1.2, p = 0.01). MMPE at 90° knee flexion and MM posterior translation were smaller 12 months postoperatively than preoperatively (3.5 ± 1.1 vs. 4.6 ± 1.3, 7.2 ± 1.7 vs. 8.9 ± 2.0, p < 0.01). Articular cartilage degeneration of medial femoral condyle correlated with MMME in knee extension (r = 0.5, p = 0.04). All clinical scores significantly improved 12 months postoperatively. However, correlations of all clinical scores against decreased MMPE and increased MMME were not detected. CONCLUSIONS: MMPRT transtibial fixation suppressed the progression of MMPE and cartilage degeneration and progressed MMME minimally in knee flexion position at 1 year. However, in the knee extension position, MMME progressed and correlated with cartilage degeneration of medial femoral condyle. MMPRT transtibial fixation contributes to the dynamic stability of the MM in the knee flexion position. LEVEL OF EVIDENCE: IV.

DOI： 10.1007/s00167-019-05810-x

Medial meniscus posterior root repair restores the intra-articular volume of the medial meniscus by decreasing posteromedial extrusion at knee flexion. International journal

Yoshiki Okazaki, Takayuki Furumatsu, Takatsugu Yamauchi, Yuki Okazaki, Yusuke Kamatsuki, Takaaki Hiranaka, Yuya Kajiki, Ximing Zhang, Toshifumi Ozaki

Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 28 ( 11 ) 3435 - 3442 2020.11

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

PURPOSE: Transtibial repair of a medial meniscus posterior root tear (MMPRT) can improve clinical outcomes, although meniscal extrusion remains. However, few studies have investigated the volume of meniscal extrusion. This study aimed to evaluate the effect of transtibial repair in reducing the volume using three-dimensional (3D) magnetic resonance imaging, at 10° and 90° knee flexion. METHODS: Twenty patients with MMPRTs and 16 volunteers with normal knees participated. The 3D models of meniscus were constructed using SYNAPSE VINCENT®. The meniscal extrusion and its volume were measured at 10° and 90° knee flexion. Differences between the pre- and postoperative examinations were assessed using the Wilcoxon signed-rank test. The postoperative parameters were compared to those in patients with normal knees. RESULTS: There were no significant pre- and postoperative differences in any parameter at 10° knee flexion. At 90° knee flexion, the posterior extrusion and its meniscal volume were decreased significantly after transtibial repair (p < 0.05), even though these parameters were larger than in the normal knees. On the other hand, intra-articular meniscal volume calculated by the extrusion volume was increased to the level of the normal knee. CONCLUSIONS: This study demonstrated that transtibial repairs improved the intra-articular/intra-tibial surface volume of the medial meniscus by reducing the posteromedial extrusion during knee flexion. This 3D analysis is clinically relevant in evaluating that, while transtibial root repair has a limited ability to reduce meniscal extrusion, it can restore the functional volume of the medial meniscus which contributes to the shock absorber postoperatively. LEVEL OF EVIDENCE: IV.

DOI： 10.1007/s00167-020-05953-2

What Factors Are Associated with Treatment Outcomes of Japanese Patients with Clear Cell Chondrosarcoma? International journal

Robert Nakayama, Keiko Hayakawa, Eisuke Kobayashi, Makoto Endo, Naofumi Asano, Tsukasa Yonemoto, Hiroyuki Kawashima, Kenichiro Hamada, Itsuo Watanabe, Hiroyuki Futani, Takahiro Goto, Yoshihiro Nishida, Toshifumi Ozaki

Clinical orthopaedics and related research 478 ( 11 ) 2537 - 2547 2020.11

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Clear cell chondrosarcoma is an extremely rare chondrosarcoma subtype; thus, its treatment outcomes and associated factors have not been widely studied. Knowing more about it is potentially important because clear cell chondrosarcomas are often misdiagnosed as other benign lesions and subsequently treated and followed inappropriately. QUESTIONS/PURPOSES: (1) What are the patient- and tumor-related characteristics of clear cell chondrosarcoma? (2) What proportion of patients with clear cell chondrosarcoma initially had a misdiagnosis or a misleading initial biopsy result? (3) What is the survivorship of patients with clear cell chondrosarcoma free from death, local recurrence, and distant metastasis, and what factors are associated with greater survivorship or a reduced risk of local recurrence? METHODS: Between 1985 and 2018, 12 Japanese Musculoskeletal Oncology Group (JMOG) hospitals treated 42 patients with a diagnosis of clear cell chondrosarcoma. All 42 patients had complete medical records at a minimum of 1 year or death, and were included in this multicenter, retrospective, observational study. No patients were lost to follow-up within 5 years of treatment but four were lost to follow-up greater than 5 years after treatment because their physicians thought their follow-up was sufficient. Clinical data were collected by chart review. The median (range) follow-up period was 69 months (2 to 392). In general, when a possibly malignant bone tumor was found on imaging studies, the histological diagnosis was made by biopsy before initiating treatment. Once the diagnosis had been made, the patients were treated by surgery only, complete resection if technically possible, because chondrosarcomas are known to be resistant to chemotherapy and radiotherapy. Unresectable tumors were treated with particle-beam radiation therapy. When patients with chondrosarcoma were referred after unplanned surgical procedures with inadequate surgical margins, immediate additional wide resection was considered before local recurrence developed. This diagnostic and treatment strategy is common to all JMOG hospitals and did not change during the study period. Primary wide resection was performed in 79% (33 of 42) patients, additional wide resection after initial inadequate surgery in 12% (five of 42), curettage and bone grafting in 5% (two of 42) patients, and radiotherapy was administered to 5% (two of 42). Surgical margins among the 40 patients who underwent surgery at JMOG hospitals were no residual tumor in 93% (37 of 42) of patients, microscopic residual tumor in 2% (one of 42), and macroscopic residual tumor or state after curettage or intralesional excision in 5% (two of 42). The oncological endpoints of interest were 5- and 10- year overall survival, disease-free survival, survival free of local recurrence, and survival free of distant metastases; these were calculated using the Kaplan-Meier method and compared using the log-rank test. Risk ratios with their respective 95% confidence intervals (CIs) were estimated in a Cox regression model. The Bonferroni adjustment was used for multiple testing correction. RESULTS: The sex distribution was 74% men and 26% women (31 and 11 of 42, respectively), with a mean age of 47 ± 17 years. Eighty one percent (34 of 42) of tumors occurred at the ends of long bones, and the proximal femur was the most common site accounting for 60% (25 of 42). The mean size of the primary tumors was 6.3 ± 2.7 cm. Definite pathologic fractures were present in 26% (10 of 42) and another 26% (10 of 42) had extraskeletal involvement. None had metastases at presentation. Twenty four percent (six of 25) tumors in the proximal femur were misdiagnosed as benign lesions and treated inadequately without biopsy. Twenty nine percent (10 of 35) patients had initial misdiagnoses by biopsy and core needle biopsies had a greater risk of resulting in inaccurate histological diagnoses. The study patients' 5- and 10-year overall survival rates were 89% (95% CI 74 to 96) and 89% (95% CI 74 to 96), respectively; 5- and 10- year disease-free survival rates 77% (95% CI 58 to 89) and 57% (95% CI 36 to 75), respectively; 5- and 10-year local recurrence-free survival rates 86% (95% CI 68 to 95) and 71% (95% CI 49 to 86), respectively; and 5- and 10-year distant metastasis-free survival rates 84% (95% CI 67 to 93) and 74% (95% CI 53 to 88), respectively. Notably, bone metastases (17%, seven of 42) were as common as pulmonary metastases (14%, six of 42); four patients developed both bone and pulmonary metastases. The difference between 10-year overall survival rates and 10-year disease-free survival indicated very late recurrence more than 5 years after the initial treatment. After controlling for multiple comparisons, the only factor we found that was associated with local recurrence-free survival was initial treatment (positive margin versus primary wide resection) (risk ratio 8.83 [95% CI 1.47 to 53.1]; p = 0.022 after the Bonferroni adjustment). Additional wide resection reduced the risk of local recurrence. CONCLUSIONS: The femoral head was the most common location of clear cell chondrosarcoma and had a high risk of misdiagnosis as common benign lesions that resulted in initial inadequate surgery and a consequent high risk of local recurrence. Immediate additional wide resection should be considered in patients who had initial inadequate surgery to reduce the risk of local recurrence. Because clear cell chondrosarcoma can recur locally or distantly in the bones and lungs in the long term, patients should be informed of the risk of very late recurrence and the necessity of decades-long with surveillance for local recurrence and lung and bone metastases. LEVEL OF EVIDENCE: Level IV, therapeutic study.

DOI： 10.1097/CORR.0000000000001266

What Are the Results of Resection of Localized Dedifferentiated Liposarcomas in the Extremities? International journal

Eiji Nakata, Toshiyuki Kunisada, Joe Hasei, Ryuichi Nakahara, Hiroyuki Yanai, Tomohiro Toji, Hirofumi Inoue Ct, Toshifumi Ozaki

Clinical orthopaedics and related research 478 ( 11 ) 2550 - 2561 2020.11

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Dedifferentiated liposarcoma (DDLPS) is a rare malignancy that transitions from an atypical lipomatous tumor to a sarcoma with a variable morphologic appearance. The behavior of this tumor in the retroperitoneum is aggressive, but the behavior of DDLPS in the extremities is less well-defined because it is rare. Few reports have assessed the imaging features and clinical outcomes of primary DDLPS in the extremities. QUESTIONS/PURPOSES: In patients with primary DDLPS of the extremity, we asked the following questions: (1) How frequently do additional primary malignancies occur in patients with DDLPS? (2) What is the rate of overall survival, metastases, and local recurrence in DDLPS? (3) What factors are associated with metastasis-free survival and local recurrence in DDLPS? METHODS: We defined DDLPS as a biphasic neoplasm that transitions from an atypical lipomatous tumor (ALT) to a sarcoma of variable morphologic appearance and histologic grades. We retrospectively evaluated the medical records of patients with DDLPS of the extremities who underwent surgery in our institution between 2003 and 2017. During that time, 16 patients were treated for this diagnosis; one was excluded from this study because the patient did not have an MRI, leaving 15 patients (nine men, six women; their median [range] age was 67 years [42 to 87]) for evaluation. All had a minimum of 2 years follow-up (median [range] 54 months [25 to 136]); 14 of 15 have been seen in the last 5 years (one patient, who was doing well at the time, was lost after 9 years of follow-up). In 11 patients, MRI demonstrated two components: an ALT component with high intensity on both T1-weighed and T2-weighted sequences and a dedifferentiated component low-to-intermediate intensity on T1-weighed and heterogeneous hyperintensity on T2-weighted sequence. Nine patients were evaluated using 2-deoxy-2-18F-fluoro-D-glucose positron emission tomography (FDG-PET) combined with CT (PET/CT). PET/CT showed a biphasic pattern with a close relationship to MRI findings. The dedifferentiated component presented with high FDG uptake (median [range] maximum standardized uptake value 5.1 [1.9 to 22.6]), while the atypical lipomatous tumor component showed almost no FDG uptake. In all patients, immunohistochemical studies of p16 and cyclin-dependent kinase-4 (CDK4) were investigated. Positive staining for both p16 and CDK4 were seen in 13 of 15 patients.We retrospectively evaluated the electronic medical records of all patients in our institution for the presence of additional primary malignancies, local recurrence-free survival, metastasis-free survival, and overall survival. The survival rate was estimated using the Kaplan-Meier method. The Wilcoxon exact test was used to determine the prognostic importance of the following survival variables: age, sex, maximum tumor size, radiotherapy, and surgical margin. RESULTS: Seven additional primary malignancies developed in five of 15 patients (two lung cancers, two sarcomas, one renal cell cancer, one uterine cancer, and one non-Hodgkin lymphoma). The 3- and 5-year metastasis-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. With the numbers available, we found no factors associated with metastasis-free survival. The 3- and 5-year overall survival rates were 100% (95% CI 1.00 to 1.00) and 88% (95% CI 0.65 to 1.00), respectively. Three of 15 patients had local recurrence. The 3- and 5-year local recurrence-free survival rates were 86% (95% CI 0.67 to 1.00) and 75% (95% CI 0.49 to 1.00), respectively. Large (> 15 cm) tumors were more likely to have a local recurrence (p = 0.04). CONCLUSIONS: In this small series, we found that the extremities are a favorable site for DDLPS compared with the retroperitoneum, although we did not directly compare the two sites. This rare tumor has a relatively high likelihood of being associated with other malignancies. We believe patients should be assessed and monitored carefully for this possibility. In the future, larger studies are needed to better define predictors of local recurrence, although the tumor's size may be associated with a greater propensity for local recurrence. LEVEL OF EVIDENCE: Level II, prognostic study.

DOI： 10.1097/CORR.0000000000001338

Letter regarding "Comparing the usefulness of a fluoroscopic navigation system in femoral trochanteric fracture for orthopaedic residents with the conventional method". International journal

Norio Yamamoto, Yosuke Tomita, Keisuke Kawasaki, Toshifumi Ozaki

Injury 51 ( 10 ) 2348 - 2348 2020.10

Cognitive factors associated with locomotive syndrome in chronic pain patients: A retrospective study.

Hironori Tsuji, Tomoko Tetsunaga, Tomonori Tetsunaga, Haruo Misawa, Keiichiro Nishida, Toshifumi Ozaki

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 26 ( 5 ) 896 - 901 2020.9

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Prevention and treatment for locomotive syndrome (LS) are important for extending healthy life expectancy. The 25-question geriatric locomotive function scale (GLFS-25) was developed to diagnose LS. The Fear-Avoidance model was proposed to explain pain chronicity. LS and chronic pain decrease activities of daily living; however, the relationships between LS and factors related to chronic pain in the Fear-Avoidance model are unknown. Objective of the current study was to assess the prevalence of LS and examine the factors of the Fear-Avoidance model and the GLFS-25 that affect the prevalence of LS in patients with chronic pain. METHODS: Participants included 281 patients (99 men, 182 women) aged over 40 years with chronic pain who visited our outpatient clinic for chronic pain. All participants completed the GLFS-25, numeric rating scale (NRS), pain catastrophizing scale (PCS), hospital anxiety and depression scale (HADS), and Athene insomnia scale (AIS). According to a GLFS-25 cutoff point, participants were divided into three groups (LS-2; GLFS-25 ≥ 16, LS-1; 7 ≤ GLFS-25 < 16, and non-LS; GLFS-25 < 7 points) and each parameter was compared among the groups, followed by multiple logistic regression analysis. Next, multiple linear regression analysis was performed to determine the factors associated with the GLFS-25. RESULTS: Of all 281 patients, 241 (85.8%) patients were diagnosed with LS-2. Univariate analysis revealed there were significant differences in NRS, PCS, HADS anxiety, HADS depression, and AIS among groups. Multiple logistic regression analyses showed PCS was significantly associated with LS-2 prevalence. The GLFS-25 was positively correlated with NRS, HADS depression, AIS in multiple linear regression analysis. CONCLUSIONS: We found that patients with chronic pain in our outpatient clinic had a significant rate of LS-2. The prevalence of LS-2 was significantly correlate with pain catastrophizing, and the GLFS-25 was significantly correlated with higher pain intensity, depression, and insomnia.

DOI： 10.1016/j.jos.2020.08.007

Early response of bone metastases can predict tumor response in patients with non-small-cell lung cancer with bone metastases in the treatment with nivolumab. International journal

Eiji Nakata, Shinsuke Sugihara, Yoshifumi Sugawara, Toshiyuki Kozuki, Daijiro Harada, Naoyuki Nogami, Ryuichi Nakahara, Takayuki Furumatsu, Tomonori Tetsunaga, Toshiyuki Kunisada, Toshifumi Ozaki

Oncology letters 20 ( 3 ) 2977 - 2986 2020.9

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

The effect of nivolumab and the relation between bone response and tumor control in patients with non-small-cell lung cancer (NSCLC) with bone metastases are not clear. The outcome of nivolumab monotherapy was investigated, and whether the response of bone metastases is useful as an early predictor of tumor control in patients with NSCLC with bone metastases was examined. The participants included 15 patients who received nivolumab monotherapy for NSCLC with bone metastases in our institution between 2015 and 2017. Tumor control was defined using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST1.1). Response of bone metastases was assessed by the MD Anderson response criteria (MDA criteria). Responses according to RECIST1.1 and the MDA criteria were classified as responder (complete response or partial response) and non-responder [progressive disease (PD) or stable disease]. Progression-free survival (PFS) was investigated using the Kaplan-Meier method. With RECIST1.1, the overall response rate was 20%. Multivariate analysis showed that the MDA criteria were the only risk factor for patients with PD (RECIST1.1). Median PFS was 1.9 months, with PFS of 20% at 6 months. Univariate analysis showed that being a non-responder according to the MDA criteria was the only risk factor for PFS. In patients who were responders (MDA criteria) within 3 months, PFS was 83 and 50% at 3 and 6 months, respectively, though all non-responder (MDA criteria) patients converted to PD (RECIST1.1) within 3 months. Response according to RECIST1.1 was significantly correlated with response according to the MDA criteria (P<0.05). In patients who were both responders according to RECIST1.1 and the MDA criteria, time to response with the MDA criteria (1.4-2.0 months) was earlier than with RECIST1.1 (2.8-3.0 months) in all patients. In conclusion, application of the MDA criteria within 2 months of nivolumab monotherapy is useful for early prediction of response and prognosis in patients with NSCLC with bone metastases.

DOI： 10.3892/ol.2020.11856

Phase II trial of pazopanib in patients with metastatic or unresectable chemoresistant sarcomas: A Japanese Musculoskeletal Oncology Group study. International journal

Hiroshi Urakawa, Akira Kawai, Takahiro Goto, Hiroaki Hiraga, Toshifumi Ozaki, Hiroyuki Tsuchiya, Robert Nakayama, Norifumi Naka, Yoshihiro Matsumoto, Eisuke Kobayashi, Tomotake Okuma, Toshiyuki Kunisada, Masahiko Ando, Takafumi Ueda, Yoshihiro Nishida

Cancer science 111 ( 9 ) 3303 - 3312 2020.9

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

Alveolar soft part sarcoma (ASPS), epithelioid sarcoma (ES), and clear cell sarcoma (CCS) are known to be chemoresistant tumors. The aim of this study was to investigate the effect of pazopanib on these chemoresistant tumors. This study is designed as a single-arm, multicenter, investigator-initiated phase II trial. Patient enrollment was undertaken between July 2016 and August 2018 at 10 hospitals participating in the Japanese Musculoskeletal Oncology Group. The primary end-point is the CBR (CBR, including complete or partial response and stable disease) at 12 weeks after treatment with pazopanib according to RECIST. Eight patients were enrolled within the period. The histological subtypes were 5 ASPS, 2 ES, and 1 CCS. The median follow-up period was 22.2 (range, 4.9-24.9) months. All patients initially received pazopanib 800 mg once daily. The CBRs were 87.5% (7 of 8) and 75.0% (6 of 8) according to RECIST and Choi criteria at 12 weeks after pazopanib treatment, respectively. The CBRs at 12 weeks according to RECIST were 80.0%, 100.0%, and 100.0% in ASPS, ES, and CCS, respectively. Partial response was observed in 1 ASPS according to RECIST and 3 ASPS and 1 ES according to Choi criteria at 12 weeks after pazopanib treatment. This study documented antitumor activity of pazopanib, especially in ASPS. These results support the frontline use of pazopanib for ASPS. Prospective data collection is desired using both RECIST and Choi criteria for these rare chemoresistant tumors.

DOI： 10.1111/cas.14542

Acetabular depth, an early predictive factor of acetabular development: MRI in patients with developmental dysplasia of the hip after open reduction. International journal

Yoshi Kawamura, Tomonori Tetsunaga, Hirofumi Akazawa, Kazuki Yamada, Tomoaki Sanki, Yoshihiro Sato, Eiji Nakata, Toshifumi Ozaki

Journal of pediatric orthopedics. Part B 30 ( 6 ) 509 - 514 2020.8

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Early prediction of future acetabular development is important to determine an additional surgery for developmental dysplasia of the hip (DDH). The purpose of this study was to investigate the predictive factors of acetabular development using MRI. We retrospectively investigated dislocated 40 hips and 34 normal hips in 37 pediatric patients (9 males and 28 females) with DDH who underwent open reduction after walking age. We evaluated the cartilaginous acetabulum and labrum of the patients using coronal MRI T2*-weighted images at 5 years of age. The mean age at the time of surgery was 22 months, and the mean age at the final survey was 19 years. We divided patients into two groups in accordance with the Severin classification at the final follow-up. Groups with good outcomes (affected 26 hips and unaffected 27 hips) and poor outcomes (14 hips and 7 hips) were compared using the MRI parameters on each side. Predictive factors of acetabular development were identified using univariate and multiple logistic regression analyses. Using multiple logistic regression analysis, labral acetabular roof depth and labral hip center distance at 5 years of age represented predictors after open reduction (odds ratio 0.27, P = 0.035; odds ratio 3.4, P = 0.028, respectively) on the affected side, and bony hip center distance represented a predictor on the unaffected side (odds ratio 2.6, P = 0.049). Acetabular development in the unaffected side could be predicted by bony assessment, while acetabular development in the affected side had to be assessed by labrum using MRI.

DOI： 10.1097/BPB.0000000000000799

Tibial Tunnel Positioning Using the Posterolateral (PL) Divergence Guide in Anterior Cruciate Ligament Reconstruction.

Takaaki Tanaka, Takayuki Furumatsu, Takaaki Hiranaka, Yuki Okazaki, Kenji Masuda, Noritaka Seno, Toshifumi Ozaki

Acta medica Okayama 74 ( 4 ) 345 - 350 2020.8

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

The aim of this study was to evaluate tunnel coalition and inter-tunnel distance by comparing the tibial tunnel position in double-bundle anterior cruciate ligament (ACL) reconstruction performed with a conventional guide versus a posterolateral (PL) divergence (PLD) guide. Subjects were 43 patients (ACL tip aimer: 20 knees; PLD guide: 23 knees) who underwent double-bundle ACL reconstruction between September 2014 and December 2017. In all cases, the tibial tunnel position, tunnel edge distance and tunnel angles were evaluated based on CT images. Clinical outcome was evaluated using the Lachman test, pivot-shift test, and Lysholm score. Tibial tunnel positions were similar between the conventional and PLD guide groups, while tibial tunnel edge distance was significantly less in the conventional group. Tunnel coalition was observed in 5 knees in the conventional and no knees in the PLD guide group. Distance between two tibial tunnel centers was 9.1 mm for the tip aimer, and 10.5 mm for the PLD guide. Creation of the PL tunnel tended to involve insertion from a more medial aspect for the PLD guide group than the conventional guide group. No differences in clinical outcomes were noted. The PLD guide can be used to create anatomically-positioned PL tunnels, and reduce the probability of occurrence of tunnel coalition.

DOI： 10.18926/AMO/60373

Risk factors of local recurrence after surgery in extraabdominal desmoid-type fibromatosis: A multicenter study in Japan. International journal

Yoshihiro Nishida, Shunsuke Hamada, Akira Kawai, Toshiyuki Kunisada, Akira Ogose, Yoshihiro Matsumoto, Keisuke Ae, Junya Toguchida, Toshifumi Ozaki, Akihiro Hirakawa, Toru Motoi, Tomohisa Sakai, Eisuke Kobayashi, Tabu Gokita, Takeshi Okamoto, Tomoya Matsunobu, Koki Shimizu, Hiroshi Koike

Cancer science 111 ( 8 ) 2935 - 2942 2020.8

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

This study was undertaken to clarify the risk factors, including the mutation status of CTNNB1, for the local recurrence after surgery of the rare disease desmoid-type fibromatosis. It was designed as a multiinstitutional joint research project with 7 major centers in Japan participating. The committee members of 7 major medical centers specializing in bone and soft tissue tumors formed this study group to develop clinical care guidelines. Of 196 cases with specimens and medical records collected from the 7 institutions, 88 surgically treated ones were analyzed regarding clinicopathologic prognostic factors including CTNNB1 mutation status. Excluding R2 cases (n = 3), 5-year local recurrence-free survival (LRFS) was 52.9%. No case had received pre- or postoperative radiotherapy. Univariate analysis revealed that extremity location (P < .001) and larger size (8 cm or more, P = .036) were significant adverse risk factors for LRFS. Multivariate analysis indicated that extremity location (P < .001) was a significantly adverse factor in addition to recurrent tumor (P = .041), S45F mutation (P = .028), and R1 surgical margin (P = .039). Preoperative drug treatment, including nonsteroidal antiinflammatory drugs, did not reduce the incidence of local recurrence (P = .199). This is the first study to analyze the factors correlating with outcomes of surgical treatment, including CTNNB1 mutation status, in a relatively large number of cases from an Asian country. Tumor location was found to be the most influential prognostic factor for local recurrence, similar to the results from Europe and North America. The development of more sensitive method(s) for determination of CTNNB1 mutation is a priority for future study.

DOI： 10.1111/cas.14528

股関節の関節裂隙開大距離と関節弛緩性およびX線学的指標についての検討

山田和希, 遠藤裕介, 鉄永智紀, 三喜知明, 河村涌志, 佐藤嘉洋, 尾崎敏文

Hip Joint 46 ( 1 ) 566 - 570 2020.8

Cam type FAIに対する骨軟骨形成術においてcam切除量を定量化した1例

佐藤嘉洋, 鉄永智紀, 山田和希, 三喜知明, 河村涌志, 尾崎敏文

Hip Joint 46 ( 1 ) 428 - 430 2020.8

寛骨臼形成不全股における骨頭被覆とX線学的指標の比較検討

三喜知明, 鉄永智紀, 遠藤裕介, 山田和希, 河村涌志, 佐藤嘉洋, 尾崎敏文

Hip Joint 46 ( 2 ) 1031 - 1034 2020.8

A repair technique using two simple stitches reduces the short-term postoperative medial meniscus extrusion after pullout repair for medial meniscus posterior root tear. International journal

Takaaki Hiranaka, Takayuki Furumatsu, Shin Masuda, Yoshiki Okazaki, Yuki Okazaki, Yuya Kodama, Yusuke Kamatsuki, Yuya Kajiki, Ximing Zhang, Toshifumi Ozaki

European journal of orthopaedic surgery & traumatology : orthopedie traumatologie 30 ( 5 ) 901 - 908 2020.7

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Two types of repair techniques, FasT-Fix modified Mason-Allen (F-MMA) and two simple stitches (TSS), for the treatment of a medial meniscus posterior root tear (MMPRT) were previously reported. However, whether these techniques could prevent postoperative medial meniscus extrusion (MME) progression is unknown. This study investigated and compared postoperative MME of the two repair techniques. METHODS: Forty-seven knees that had undergone pullout repair for MMPRT were retrospectively reviewed. These knees were divided into two groups as follows: In 26 knees, MMPRT was treated using the F-MMA technique and fixed with the knee flexed at 45° and 20 N of tension [F-MMA (45°-20 N) group], and in 21 knees, MMPRT was treated using the TSS technique and fixed with the knee flexed at 20° and 30 N of tension [TSS (20°-30 N) group]. The medial meniscus body width (MMBW), absolute MME (aMME), and relative MME (rMME = absolute MME/MMBW) were measured and compared using magnetic resonance imaging 3 months postoperatively. The Knee Injury and Osteoarthritis Outcome Score (KOOS) subscales for clinical outcomes were compared between the two groups at 6 months postoperatively. RESULTS: At 3 months postoperatively, the aMME and rMME significantly decreased in the TSS (20°-30 N) compared to the F-MMA (45°-20 N) group. The TSS (20°-30 N) group had better KOOS subscale scores than the F-MMA (45°-20 N) group at 6 months postoperatively. CONCLUSIONS: The TSS technique with appropriate tibial fixation can decrease MME soon after surgery. This may prevent osteoarthritis progression and improve clinical outcomes.

DOI： 10.1007/s00590-020-02647-w

Vacuum phenomenon in pelvic fractures. International journal

Norio Yamamoto, Tomoyuki Noda, Shintaro Sukegawa, Tomohiro Inoue, Keisuke Kawasaki, Toshifumi Ozaki

Injury 51 ( 7 ) 1618 - 1621 2020.7

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Vacuum phenomenon (VP) in closed pelvic fracture is a rare disorder. This study aimed to examine the prevalence and clinical findings of VP in closed pelvic fracture. METHODS: We retrospectively reviewed 197 patients with closed pelvic fracture who presented to our institution from January 2012 to December 2018. Pelvic fractures were diagnosed by plain radiography and computed tomography (CT). First, we investigated the prevalence and clinical findings of VP in pelvic fractures. Second, we compared the clinical findings between pelvic fracture with and without VP. Finally, VP in pelvic fracture was evaluated clinically and radiologically. RESULTS: VP in pelvic fractures was detected by CT in 9 (3.6%) of the 197 patients with pelvic fractures. Patients with VP had a significantly greater proportion of fracture progression than those without VP (42.9% vs. 11.3%, P = 0.02). Patients with VP had a greater proportion of fragility fractures of the pelvis (FFP), and a lesser proportion of bone union than those without VP, although the differences were not significant. In nine pelvic fractures with VP, all sacral fractures were classified as type 1 according to the Denis classification, and all pubic fractures were classified as type 1 according to the Nakatani classification. Two (22.2%) nonunion in nine pelvic fractures with VP occurred at the pubic fracture site alone. CONCLUSIONS: Orthopedic clinicians should be aware of the potential of CT for detecting VP in pelvic fractures, especially in the course of FFP progression.

DOI： 10.1016/j.injury.2020.03.051

Clinical relevance and functional significance of cell-free microRNA-1260b expression profiles in infiltrative myxofibrosarcoma. International journal

Takuya Morita, Tomohiro Fujiwara, Aki Yoshida, Koji Uotani, Masahiro Kiyono, Suguru Yokoo, Joe Hasei, Toshiyuki Kunisada, Toshifumi Ozaki

Scientific reports 10 ( 1 ) 9414 - 9414 2020.6

Authorship：Last author Language：English Publishing type：Research paper (scientific journal)

Infiltrative tumor growth into adjacent soft tissues is a major cause of the frequent recurrence and tumor-related death of myxofibrosarcoma (MFS), but no useful biomarkers reflecting tumor burden and infiltrative growth are available. While emerging evidence suggests a diagnostic and functional role of extracellular/circulating microRNA (miRNA) in various malignant diseases, their significance in MFS patients remains unknown. Global miRNA profiling identified four upregulated miRNAs in MFS patient sera and culture media of MFS cells. Among these, serum miR-1260b level was significantly upregulated in patient serum discriminating from healthy individuals and closely correlated with clinical status and tumor dynamics in MFS-bearing mice. In addition, high miR-1260b expression in serum was correlated with radiological tail-like patterns, characteristic of the infiltrative MFS. The extracellular miR-1260b was embedded in tumor-derived extracellular vesicles (EVs) and promoted cellular invasion of MFS through the downregulation of PCDH9 in the adjacent normal fibroblasts. Collectively, circulating miR-1260b expression may represent a novel diagnostic target for tumor monitoring of this highly aggressive sarcoma. Moreover, EV-miR-1260b could act as a transfer messenger to adjacent cells and mediate the infiltrative growth of MFS, providing new insights into the mechanism of infiltrative nature via crosstalk between tumor cells and their microenvironment.

DOI： 10.1038/s41598-020-66120-8

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