Faculty Profiles - OZAKI Toshifumi

Papers - OZAKI Toshifumi

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Adjuvant and neoadjuvant chemotherapy for soft tissue sarcomas: JCOG Bone and Soft Tissue Tumor Study Group. International journal

Kazuhiro Tanaka, Toshifumi Ozaki

Japanese journal of clinical oncology 51 ( 2 ) 180 - 184 2021.2

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

The standard therapy for all localized soft tissue sarcomas is surgical resection of the tumor. For patients with soft tissue sarcomas who are at high risk for recurrence and/or metastasis, perioperative chemotherapy is a potential treatment option. Adriamycin plus ifosfamide is currently the most promising chemotherapy regimen for localized soft tissue sarcomas. Randomized controlled trials and meta-analyses of adjuvant postoperative chemotherapy for soft tissue sarcomas have suggested that adjuvant chemotherapy may provide an advantage, however small, compared with surgery alone. On the other hand, recent randomized trials have demonstrated the efficacy of neoadjuvant preoperative chemotherapy using full-dose anthracycline plus ifosfamide for high-risk soft tissue sarcomas and showed survival benefits in patients with large, deep-seated and high-grade soft tissue sarcomas of the trunk and extremities. In this review, adjuvant and neoadjuvant chemotherapies for soft tissue sarcomas and future perspectives are discussed.

DOI： 10.1093/jjco/hyaa231

Bipolar Hip Arthroplasty Using a Conjoined Tendon-preserving Posterior Approach in Geriatric Patients.

Tomonori Tetsunaga, Tomoko Tetsunaga, Kazuki Yamada, Tomoaki Sanki, Yoshi Kawamura, Toshifumi Ozaki

Acta medica Okayama 75 ( 1 ) 25 - 30 2021.2

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

In bipolar hemiarthroplasty (BHA), it is important to preserve soft tissue to reduce the risk of postoperative dislocation. A variety of surgical approaches for BHA are available, but extra care is needed with muscle- and tendon-preserving approaches in geriatric patients. We investigated the usefulness of BHA using a conjoined tendon-preserving posterior (CPP) approach, in which only the external obturator muscle is dissected, in geri-atric patients. We retrospectively analyzed the cases of 40 femoral neck fracture patients (10 men, 30 women) aged ≥ 80 years who underwent BHA using the CPP approach. The patients' average age was 85.8 years (80-94 years). We examined the operation time, bleeding, preservation of short external rotator muscles, complica-tions, and stem alignment and subsidence from postoperative radiographs. Although gemellus inferior muscle injury was detected in 4 patients (10%), the hip joint stability was very excellent in all cases. There was no intraoperative fracture or postoperative dislocation. On postoperative radiographs, all femoral stems were in a neutral position. There was no stem subsidence in all 40 patients. BHA using the CPP approach appeared to be useful even in geriatric patients.

DOI： 10.18926/AMO/61430

The Thickness of the Medial Wall of the Acetabulum Prevents Acetabular Fracture during the Insertion of a Cementless Cup in Total Hip Arthroplasty: A Biomechanical Study.

Tomoaki Sanki, Tomonori Tetsunaga, Takayuki Furumatsu, Kazuki Yamada, Yoshi Kawamura, Toshifumi Ozaki

Acta medica Okayama 75 ( 1 ) 71 - 77 2021.2

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

Intra-operative acetabular fracture is a total hip arthroplasty complication that can occur during cementless cup insertion, especially in osteoporotic patients. We conducted this biomechanical study to investigate the impact resistance of the acetabulum with simulated bones of different density by drop-weight impact testing. Low- and high-density polyurethane foam blocks were used as osteoporotic and healthy bone models, respectively. Polyurethane blocks were used as the acetabular cancellous bone. Composite sheets were used as the acetabu-lum's medial cortex. The testing revealed that the osteoporotic bone model's impact resistance was significantly lower than that the healthy bone model'. In the healthy bone model, even thin acetabular cancellous bone with ≥ 1 mm acetabulum medial cortex was less likely to fracture. In the osteoporotic bone model, fracture was pos-sible without ≥ 1 mm medial cortex of the acetabulum and thick acetabular cancellous bone. Although impac-tion resistance differs due to bone quality, the impaction resistance in this osteoporotic bone model was equiv-alent to that healthy bone model's when a thick medial wall was present. To avoid intra-operative acetabulum fracture, surgeons should consider both the bone quality and the thicknesses of the medial cortex and acetabu-lar cancellous bone.

DOI： 10.18926/AMO/61437

Quantification of patellar tendon reflex using portable mechanomyography and electromyography devices. International journal

Hironori Tsuji, Haruo Misawa, Tomoyuki Takigawa, Tomoko Tetsunaga, Kentaro Yamane, Yoshiaki Oda, Toshifumi Ozaki

Scientific reports 11 ( 1 ) 2284 - 2284 2021.1

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

Deep tendon reflexes are one of the main components of the clinical nervous system examinations. These assessments are inexpensive and quick. However, evaluation can be subjective and qualitative. This study aimed to objectively evaluate hyperreflexia of the patellar tendon reflex using portable mechanomyography (MMG) and electromyography (EMG) devices. This study included 10 preoperative patients (20 legs) who had a pathology that could cause bilateral patellar tendon hyperreflexia and 12 healthy volunteers (24 legs) with no prior history of neurological disorders. We attached MMG/EMG sensors onto the quadriceps and tapped the patellar tendon with maximal and constant force. Our results showed a significantly high amplitude of the root mean square (RMS) and low frequency of the mean power frequency (MPF) in the rectus femoris, vastus medialis, and vastus lateralis muscles in both EMG and MMG with both maximal and constant force. Especially in the patients with cervical and thoracic myelopathy, the receiver operating characteristic (ROC) curve for diagnosing hyperreflexia of the patellar tendon showed a moderate to very high area under the curve for all EMG-RMS, EMG-MPF, MMG-RMS, and MMG-MPF values. The use of EMG and MMG for objectively quantifying the patellar tendon reflex is simple and desirable for future clinical applications and could help diagnose neurological disorders.

DOI： 10.1038/s41598-021-81874-5

Chronic Pain Has Little Effect on Physical Condition During the COVID-19 Pandemic in Japan: A Web-based Cross-Sectional Survey

Tomoko Tetsunaga, Tomonori Tetsunaga, Haruo Misawa, Hironori Tsuji, Toshifumi Ozaki, Takahiro Tabuchi

2021.1

Publisher：Research Square Platform LLC

<title>Abstract</title>
<bold><italic>Background</italic></bold> Chronic pain affects people negatively, both mentally and physically. It is unclear how chronic pain affects people during social isolation and remote work due to the COVID-19 pandemic. The aim of this study was to analyze the effect of chronic pain on life during the COVID-19 pandemic.<bold><italic>Methods</italic></bold> This retrospective study included 4,972 matched-participants with or without chronic pain (2,311 males, 2,661 females; mean age, 53.8 years). The participants were divided into a chronic pain group (<italic>n</italic>=2,486) and a control group (<italic>n</italic>=2,486). Participants with chronic pain for three months or more were classified into the chronic pain group. All participants completed self-reported questionnaires. Factors related to physical condition during the COVID-19 pandemic were identified by univariate and multivariate analyses.<bold><italic>Results</italic></bold> Significant differences were found between participants with and without chronic pain for the pain that developed during the COVID-19 pandemic, lifestyle, interpersonal relationships, psychological factors related to COVID-19, and deterioration of physical condition. Multiple logistic regression analysis identified insomnia, poor work/study/housework performance, and anxiety/depression as factors related to deterioration of physical condition. Chronic pain was not identified as factor related to deterioration of physical condition.<bold><italic>Conclusions </italic></bold>The effect of chronic pain on lifestyle and physical condition during the COVID-19 pandemic was limited. The factors related to deterioration of the physical condition were insomnia, poor work/study/housework performance, and anxiety/depression.

DOI： 10.21203/rs.3.rs-138931/v1

Other Link： https://www.researchsquare.com/article/rs-138931/v1.html

Accurate placement of a tibial tunnel significantly improves meniscal healing and clinical outcomes at 1 year after medial meniscus posterior root repair. International journal

Yusuke Kamatsuki, Takayuki Furumatsu, Takaaki Hiranaka, Yuki Okazaki, Yuya Kodama, Keisuke Kintaka, Toshifumi Ozaki

Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 2021.1

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

PURPOSE: A medial meniscus posterior root tear results in the loss of meniscal circumferential hoop stress and causes a pathological posteromedial extrusion of the medial meniscus. Although creating a tibial tunnel in the anatomic place improves postoperative medial meniscus posterior extrusion, no studies have evaluated the relationship between tibial tunnel position and clinical outcomes. This study aimed to evaluate how tibial tunnel positioning of medial meniscus posterior root pullout repair affects meniscal healing status and clinical outcomes. METHODS: Sixty-two patients with 64 medial meniscus posterior root tears (mean age 62.8 ± 7.9 years) who had undergone pullout repairs and second-look arthroscopies were included. All 62 patients were Lachman test negative. Three-dimensional computed tomography images of the tibial surface were evaluated using a rectangular measurement grid to assess the tibial tunnel centre and medial meniscus posterior root attachment centre. Spearman's rank correlation analysis was undertaken to determine displacement distance from the medial meniscus posterior root attachment centre to the tibial tunnel centre and a meniscal healing score, as well as clinical outcomes at 1 year post-repair. RESULTS: Tibial tunnel centres were located more anteriorly and medially than the medial meniscus posterior root attachment centre (mean distance 5.0 ± 2.2 mm). The mean meniscal healing score was 6.7 ± 1.8 of 10 possible points. The 1-year postoperative clinical scores showed significant improvement compared with preoperative scores for all the items. There was a significant negative correlation in the absolute distance between the medial meniscus posterior root attachment centre and the tibial tunnel centre with the meniscal healing score (ρ = - 0.39, p = 0.002). Furthermore, there were significant positive correlations between the distance between the medial meniscus posterior root attachment centre and the tibial tunnel centre in the mediolateral direction and patient-based clinical outcomes (ρ = 0.25-0.43, p < 0.05). CONCLUSION: Accurate placement of a tibial tunnel, especially in the mediolateral direction, significantly improved meniscal healing and clinical outcomes at 1 year following medial meniscus posterior root repair. Surgeons should create a medial meniscus posterior root tibial tunnel at the anatomic attachment with particular attention to the mediolateral position. LEVEL OF EVIDENCE: Level IV.

DOI： 10.1007/s00167-020-06376-9

Phase II clinical trial of pazopanib for patients with unresectable or metastatic malignant peripheral nerve sheath tumors. International journal

Yoshihiro Nishida, Hiroshi Urakawa, Robert Nakayama, Eisuke Kobayashi, Toshifumi Ozaki, Keisuke Ae, Yoshihiro Matsumoto, Hiroyuki Tsuchiya, Takahiro Goto, Hiroaki Hiraga, Norifumi Naka, Shunji Takahashi, Yuichi Ando, Masahiko Ando, Yachiyo Kuwatsuka, Shunsuke Hamada, Takafumi Ueda, Akira Kawai

International journal of cancer 148 ( 1 ) 140 - 149 2021.1

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

Malignant peripheral nerve sheath tumor (MPNST) often does not respond well to chemotherapy and develops against a background of NF1. The purpose of our study was to examine the efficacy of pazopanib against MPNST. Our study was designed as a physician-initiated phase II clinical trial in patients with advanced MPNST. Patients were registered from 11 large hospitals. The primary endpoint was set to clarify the clinical benefit rate (CBR) at 12 weeks according to response evaluation criteria in solid tumors (RECIST). Progression-free survival (PFS), overall survival (OS) and the CBR based on modified Choi evaluation at week 12 were set as secondary endpoints along with treatment-related safety. The study enrolled 12 patients. Median age was 49 years. Seven had Grade 2 and five Grade 3 according to the FNCLCC evaluation. Median follow-up period was 10.6 months. CBR at 12 weeks was both 50.0% (RECIST and Choi). The median PFS was 5.4 months for both RECIST and Choi, and the median OS was 10.6 months. Of special interest, the median PFS was 2.9 months for patients with FNCLCC Grade 2 and 10.2 months for Grade 3 (both RECIST and Choi). Grade 4 adverse events of neutropenia and lipase elevation were noted in one patient each. The results of this pazopanib therapy were generally better than those of any of the other single molecular targeted therapies reported previously. Although accumulation of more cases remains necessary, we conclude pazopanib treatment for MPNST to be a safe and promising treatment after doxorubicin-based chemotherapy.

DOI： 10.1002/ijc.33201

Steep posterior slope and shallow concave shape of the medial tibial plateau are risk factors for medial meniscus posterior root tears. International journal

Yuki Okazaki, Takayuki Furumatsu, Yuya Kodama, Yusuke Kamatsuki, Yoshiki Okazaki, Takaaki Hiranaka, Shota Takihira, Tomonori Tetsunaga, Kenta Saiga, Toshifumi Ozaki

Knee surgery, sports traumatology, arthroscopy : official journal of the ESSKA 29 ( 1 ) 44 - 50 2021.1

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

PURPOSE: Bone morphological factors are important for menisci. Their association with medial meniscus posterior root tears, however, has not yet been studied. This study aimed to compare sagittal medial tibial slope and medial tibial plateau depth between knees with and without medial meniscus posterior root tears. METHODS: Nine healthy volunteers, 24 patients who underwent anterior cruciate ligament reconstruction, and 36 patients who underwent medial meniscus posterior root pullout repair were included. Magnetic resonance imaging examinations were performed in the 10°-knee-flexed position. The medial tibial slope and medial tibial plateau depth were compared among the groups. RESULTS: In healthy volunteers, the anterior cruciate ligament reconstruction group, and the medial meniscus posterior root tear group, the medial tibial slopes were 3.5° ± 1.4°, 4.0° ± 1.9°, and 7.2° ± 1.9°, respectively, and the medial tibial plateau depths were 2.1 ± 0.7 mm, 2.2 ± 0.6 mm, and 1.2 ± 0.5 mm, respectively. Patients with medial meniscus posterior root tears had a significantly steep medial tibial slope and shallow medial tibial plateau concavity compared to those of healthy volunteers (P < 0.01) and the anterior cruciate ligament group (P < 0.01). In the multivariate logistic regression analysis, body mass index, medial tibial slope, and medial tibial plateau depth were significantly associated with medial meniscus posterior root tears. CONCLUSIONS: A steep posterior slope and a shallow concave shape of the medial tibial plateau are risk factors for medial meniscus posterior root tear. LEVEL OF EVIDENCE: Level III: Case-control study.

DOI： 10.1007/s00167-019-05590-4

PRRX1 promotes malignant properties in human osteosarcoma. International journal

Ryoji Joko, Daisuke Yamada, Masahiro Nakamura, Aki Yoshida, Shota Takihira, Tomoka Takao, Ming Lu, Kohei Sato, Tatsuo Ito, Toshiyuki Kunisada, Eiji Nakata, Toshifumi Ozaki, Takeshi Takarada

Translational oncology 14 ( 1 ) 100960 - 100960 2021.1

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

Paired related homeobox 1 (PRRX1) is a marker of limb bud mesenchymal cells, and deficiency of p53 or Rb in Prrx1-positive cells induces osteosarcoma in several mouse models. However, the regulatory roles of PRRX1 in human osteosarcoma have not been defined. In this study, we performed PRRX1 immunostaining on 35 human osteosarcoma specimens to assess the correlation between PRRX1 level and overall survival. In patients with osteosarcoma, the expression level of PRRX1 positively correlated with poor prognosis or the ratio of lung metastasis. Additionally, we found PRRX1 expression on in 143B cells, a human osteosarcoma line with a high metastatic capacity. Downregulation of PRRX1 not only suppressed proliferation and invasion but also increased the sensitivity to cisplatin and doxorubicin. When 143B cells were subcutaneously transplanted into nude mice, PRRX1 knockdown decreased tumor sizes and rates of lung metastasis. Interestingly, forskolin, a chemical compound identified by Connectivity Map analysis using RNA expression signatures during PRRX1 knockdown, decreased tumor proliferation and cell migration to the same degree as PRRX1 knockdown. These results demonstrate that PRRX1 promotes tumor malignancy in human osteosarcoma.

DOI： 10.1016/j.tranon.2020.100960

Preoperative morphologic changes of the medial meniscus correlate with suture translations during knee flexion in pullout repair of medial meniscus posterior root tear. International journal

Takaaki Hiranaka, Takayuki Furumatsu, Yuki Okazaki, Yuya Kodama, Yusuke Kamatsuki, Toshifumi Ozaki

The Knee 28 346 - 353 2021.1

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

BACKGROUND: Medial meniscus (MM) translates and extrudes posteriorly during knee flexion in MM posterior root tear (MMPRT) knees, and transtibial pullout repair of MMPRT has been performed to regulate the MM extrusion. This study aimed to calculate each suture translation during knee flexion in transtibial pullout repair of MMPRT, and to investigate the morphologic features of the MM that lead to longer suture translations during knee flexion. METHODS: Thirty patients with MMPRT who met the operative indication of pullout repair were enrolled and investigated prospectively. Pullout repair was performed by using two simple stitches (outer and inner sutures) and an all-inside suture in the posteromedial part of the MM. Each suture's translation from 0° to 90° of knee flexion was measured intraoperatively. The MM morphologic features, including MM medial extrusion (MMME) and MM posterior height (MMPH), were measured using preoperative magnetic resonance imaging, and the correlation between these values and each suture translation was evaluated. RESULTS: The average outer, inner, and all-inside suture translations were 4.8 mm, 3.9 mm, and 1.3 mm, respectively. Significant correlations were observed between the outer suture translation and MMME, and MMPH (p < 0.001 and <0.01, respectively). The thresholds for preoperative MMME and MMPH for longer outer suture translations (≥6 mm) were 2.1 mm and 5.4 mm, respectively. CONCLUSIONS: Preoperative longer MMME and higher MMPH were associated with longer meniscus translations during knee flexion during MMPRT repair.

DOI： 10.1016/j.knee.2020.12.020

RANKL expression in chondrocytes and its promotion by lymphotoxin-α in the course of cartilage destruction during rheumatoid arthritis. International journal

Ayumu Takeshita, Keiichiro Nishida, Aki Yoshida, Yoshihisa Nasu, Ryuichi Nakahara, Daisuke Kaneda, Hideki Ohashi, Toshifumi Ozaki

PloS one 16 ( 7 ) e0254268 2021

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

We investigated the expression and localization of the receptor activator nuclear factor κB ligand (RANKL) in cartilage from patients with rheumatoid arthritis (RA) of relevance to cartilage degeneration. We also examined the role of exogenous lymphotoxin (LT)-α on RANKL expression in human chondrocytes and its effect on in vitro osteoclast differentiation. Cartilage and synovial fluid samples were obtained from 45 patients undergoing total joint replacement surgery or joint puncture, including 24 patients with osteoarthritis (OA) and 21 patients with RA. RANKL expression in articular cartilage was examined by immunohistochemistry. LT-α concentrations in synovial fluid were measured using an enzyme-linked immunosorbent assay (ELISA). Normal human chondrocytes were stimulated with LT-α, and the relative mRNA levels of RANKL, osteoprotegerin (OPG), matrix metalloproteinase-9, and vascular endothelial growth factor were examined by real-time polymerase chain reaction. Soluble RANKL protein in culture media was measured using ELISA, and membrane-bound RANKL protein in cells was examined by western blotting. Co-cultures of human chondrocytes with peripheral blood mononuclear cells (PBMCs) were stimulated with macrophage-colony stimulating factor and LT-α, and osteoclast differentiation was evaluated by staining for tartrate-resistant acid phosphatase. LT-α concentrations were higher in RA synovial fluid than in OA samples. The population of RANKL-positive chondrocytes of RA cartilage was higher than that of OA cartilage, and correlated with cartilage degeneration. Stimulation of cultured human chondrocytes by LT-α increased RANKL expression, the RANKL/OPG ratio, and angiogenic factors. Membrane-bound RANKL in chondrocytes was up-regulated after stimulation of LT-α, whereas soluble RANKL in culture medium did not increase. Co-cultures of human chondrocytes and PBMCs demonstrated that LT-α stimulated human chondrocytes to produce RANKL and induced osteoclastic differentiation of PBMCs. RANKL produced by chondrocytes may contribute to cartilage destruction during RA and LT-α could promote the expression of RANKL in human chondrocytes.

DOI： 10.1371/journal.pone.0254268

BAPGAN: GAN-based Bone Age Progression of Femur and Phalange X-ray Images.

Shinji Nakazawa, Changhee Han, Joe Hasei, Ryuichi Nakahara, Toshifumi Ozaki

CoRR abs/2110.08509 2021

Radiographic and clinical assessment of unidirectional porous hydroxyapatite to treat benign bone tumors. International journal

Toshiyuki Kunisada, Joe Hasei, Tomohiro Fujiwara, Eiji Nakata, Suguru Yokoo, Koji Demiya, Toshifumi Ozaki

Scientific reports 10 ( 1 ) 21578 - 21578 2020.12

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

Unidirectional porous hydroxyapatite (UDPHAp) was developed as an excellent scaffold with unidirectional pores oriented in the horizontal direction with interpore connections. The purpose of this study was to assess radiographic changes and clinical outcomes and complications following UDPHAp implantation to treat benign bone tumors. We retrospectively analyzed 44 patients treated with intralesional resection and UDPHAp implantation for benign bone tumors between 2010 and 2015. Clinical and radiographic findings were evaluated postoperatively at regular follow-up visits. The mean follow-up was 49 months. Radiographic changes were classified into five stages based on bone formation in the implanted UDPHAp according to Tamai's classification. All patients showed excellent bone formation inside and around implanted UDPHAp. Absorption of UDPHAp and bone marrow cavity remodeling was identified in 20 patients at a mean of 17 months postoperatively, and was significantly more common in young patients. Preoperative cortical thinning was completely regenerated in 26 of 31 patients on average 10 months after surgery. There were no cases of delayed wound healing, postoperative infection, or allergic reaction related to implanted UDPHAp. UDPHAp is a useful bone-filling substitute for treating benign bone tumor, and the use of this material has a low complication rate.

DOI： 10.1038/s41598-020-78409-9

Clinical Outcome of Patients with Recurrent/Refractory Localized Ewing's Sarcoma Family of Tumors: A Retrospective Report From the JESS Group

Katsutsugu Umeda, Takako Miyamura, Kenji Yamada, Ako Hosono, Hideki Sano, Minako Sumi, Hajime Okita, Yosuke Hosoya, Motoaki Chin, Toshifumi Ozaki

PEDIATRIC BLOOD & CANCER 67 2020.12

Clinical Outcome of Patients with Metastatic Ewing's Sarcoma Family of Tumors: A Retrospective Report From the JESS Group

Katsutsugu Umeda, Takako Miyamura, Ako Hosono, Hideki Sano, Minako Sumi, Hajime Okita, Yosuke Hosoya, Daiichiro Hasegawa, Motoaki Chin, Toshifumi Ozaki

PEDIATRIC BLOOD & CANCER 67 2020.12

Deep Learning for Osteoporosis Classification Using Hip Radiographs and Patient Clinical Covariates. International journal

Norio Yamamoto, Shintaro Sukegawa, Akira Kitamura, Ryosuke Goto, Tomoyuki Noda, Keisuke Nakano, Kiyofumi Takabatake, Hotaka Kawai, Hitoshi Nagatsuka, Keisuke Kawasaki, Yoshihiko Furuki, Toshifumi Ozaki

Biomolecules 10 ( 11 ) 2020.11

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

This study considers the use of deep learning to diagnose osteoporosis from hip radiographs, and whether adding clinical data improves diagnostic performance over the image mode alone. For objective labeling, we collected a dataset containing 1131 images from patients who underwent both skeletal bone mineral density measurement and hip radiography at a single general hospital between 2014 and 2019. Osteoporosis was assessed from the hip radiographs using five convolutional neural network (CNN) models. We also investigated ensemble models with clinical covariates added to each CNN. The accuracy, precision, recall, specificity, negative predictive value (npv), F1 score, and area under the curve (AUC) score were calculated for each network. In the evaluation of the five CNN models using only hip radiographs, GoogleNet and EfficientNet b3 exhibited the best accuracy, precision, and specificity. Among the five ensemble models, EfficientNet b3 exhibited the best accuracy, recall, npv, F1 score, and AUC score when patient variables were included. The CNN models diagnosed osteoporosis from hip radiographs with high accuracy, and their performance improved further with the addition of clinical covariates from patient records.

DOI： 10.3390/biom10111534

Medial meniscus posterior root repair prevents the progression of subchondral insufficiency fracture of the knee.

Yuki Okazaki, Takayuki Furumatsu, Takaaki Hiranaka, Keisuke Kintaka, Shota Takihira, Yusuke Kamatsuki, Tomonori Tetsunaga, Toshifumi Ozaki

Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association 26 ( 6 ) 1051 - 1055 2020.11

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

BACKGROUND: Medial meniscus posterior root tear (MMPRT) causes medial meniscus extrusion (MME) and leads to subchondral insufficiency fracture of the knee (SIFK). However, the progression of SIFK after MMPRT pullout repair remains unknown. This study aimed to investigate the progression of SIFK and compare clinical outcomes in patients with SIFK to those without SIFK after MMPRT pullout repair. We hypothesized that the progression of SIFK would be prevented by MMPRT pullout repair, and clinical outcomes would improve in all patients. METHODS: The SIFK grade (1-4) was evaluated using T2-fat suppression magnetic resonance imaging. Thirty-eight patients without SIFK (n = 22) and with low-grade SIFK (1 and 2; n = 16) who underwent MMPRT pullout repair were included. Preoperative factors, such as the duration from injury to the time of magnetic resonance imaging/surgery (weeks), femorotibial angle (degree), MME (mm), and clinical outcomes were evaluated, as well as the progression of SIFK. RESULTS: SIFK was identified in only 9 patients (grade 1) postoperatively. Significantly improved clinical outcomes were observed in all patients. Preoperative femorotibial angle, MME, and duration from injury to the time of magnetic resonance imaging/surgery were 177.1 ± 1.5°, 3.2 ± 1.6 mm, and 6.4 ± 7.0/10.1 ± 7.5 weeks, respectively. No significant difference in preoperative factors and clinical outcomes was observed between patients with SIFK and those without SIFK. CONCLUSIONS: MMPRT pullout repair prevented the progression of low-grade SIFK and improved clinical outcomes in all patients, although bone contusions (grade 1 SIFK) were not completely healed within 1 year. MMPRT pullout repair could be a good treatment option for optimizing clinical outcomes in patients with low-grade SIFK.

DOI： 10.1016/j.jos.2020.10.008

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 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

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

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