研究者詳細 - 藤原　智洋

論文 - 藤原　智洋

分割表示 200 件中 81 - 100 件目／全件表示 >>

Periacetabular reconstruction following limb-salvage surgery for pelvic sarcomas. 国際誌

Tomohiro Fujiwara, Koichi Ogura, Alexander Christ, Meredith Bartelstein, Shachar Kenan, Nicola Fabbri, John Healey

Journal of bone oncology 31 100396 - 100396 2021年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Limb-salvage surgery for pelvic sarcomas remains one of the most challenging surgical procedures for musculoskeletal oncologists. In the past several decades, various surgical techniques have been developed for periacetabular reconstruction following pelvic tumor resection. These methods include endoprosthetic reconstruction, allograft or autograft reconstruction, arthrodesis, and hip transposition. Each of these procedures has its own advantages and disadvantages, and there is no consensus or gold standard for periacetabular reconstruction. Consequently, this review provides an overview of the clinical outcomes for each of these reconstructive options following pelvic tumor resections. Overall, high complication rates are associated with the use of massive implants/grafts, and deep infection is generally the most common cause of reconstruction failure. Functional outcomes decline with the occurrence of severe complications. Further efforts to avoid complications using innovative techniques, such as antibiotic-laden devices, computer navigation, custom cutting jigs, and reduced use of implants/grafts, are crucial to improve outcomes, especially in patients at a high risk of complications.

DOI： 10.1016/j.jbo.2021.100396

Extra-articular resection of the hip joint for pelvic sarcomas: Are there any oncological and functional risks compared with intra-articular resection? 国際誌

Tomohiro Fujiwara, Yusuke Tsuda, Jonathan Stevenson, Michael Parry, Lee Jeys

Journal of bone oncology 31 100401 - 100401 2021年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

Background: While extra-articular resection (EAR) of the knee and shoulder joint is associated with poorer clinical outcomes, the oncological and functional risks of EAR of the hip joint are unknown. We aimed to compare these risks between EAR of the hip joint and intra-articular resection (IAR). Methods: We conducted a comparative study of 75 patients who underwent en-bloc tumour resection and limb-salvage reconstruction for bone sarcomas of the peri-acetabulum between 1996 and 2016. We divided patients into two groups for analyses; EAR (n = 21) and IAR (n = 54). Results: There was no statistical difference in oncological outcomes; the 5-year cumulative incidence of disease-specific death was 34% and 35% in the EAR and IAR groups, respectively (p = 0.943), and the 5-year cumulative incidence of LR was 26% and 34%, respectively (p = 0.482). The most common complications were dislocation (28%) and deep infection (28%); there was equally no difference between the groups. The mean Musculoskeletal Tumour Society score was 66% and 65% in the EAR and IAR groups, respectively (p = 0.795), and were significantly lower in patients with deep infection (52% vs. 69%; p = 0.013). In a sub-analysis on the outcomes in patients who underwent PI-uninvolved PII-resection for chondrosarcoma, no major differences in oncologic and functional outcomes were confirmed. Conclusion: Patients undergoing EAR and limb-salvage reconstructions of the hip joint have undistinguishable oncological, clinical and functional outcomes compared to those undergoing IAR and reconstructions. If preoperative imaging suggests articular tumour involvement, there appears to be no detrimental effect of undertaking EAR to optimise local control.

DOI： 10.1016/j.jbo.2021.100401

What are the Results of Resection of Forearm Soft Tissue Sarcoma? 国際誌

Eiji Nakata, Tomohiro Fujiwara, Toshiyuki Kunisada, Ryuichi Nakahara, Toshiyuki Watanabe, Toshifumi Ozaki

Journal of orthopaedic surgery and research 18 ( 1 ) 599 - 599 2021年11月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：Research Square Platform LLC

Abstract

Only few reports have assessed the characteristics and oncological and functional outcomes of forearm soft tissue sarcomas (STS). Then, we aimed to investigate the clinical features and survival-related factors for forearm STS who underwent surgical excision at our institution. There were 38 patients. Fourteen patients (41%) were referred to our institution after an unplanned excision and tumor size and grade were significantly associated with the receipt of it. The postoperative median Musculoskeletal Tumor Society rating scale (MSTS) score was 28. Bone resection or major nerve palsy was the only factor influencing the postoperative MSTS score (P < 0.001). There was no significant difference in MSTS scores according to the reconstruction procedures (the use of flap or tendon reconstruction). The 5-year local recurrence-free survival (LRFS) rate was 86%. Univariate analysis revealed that the histological diagnosis of myxofibrosarcoma was the only factor that influenced LRFS (P = 0.047). The 5-year metastasis-free survival rate was 77%. The 5-year overall survival (OS) rate was 94%. Age was the only factor that influenced OS (P = 0.01). In conclusion, reconstruction of the skin and tendon can compensate for function. Careful follow-up is important, especially in patients with myxofibrosarcoma, due to its likelihood of local recurrence.

DOI： 10.21203/rs.3.rs-1028963/v1

その他リンク： https://www.researchsquare.com/article/rs-1028963/v1.html

Surgical outcomes of bone sarcoma of the foot. 国際誌

Yusuke Tsuda, Tomohiro Fujiwara, Jonathan D Stevenson, Adesegun Abudu

Japanese journal of clinical oncology 51 ( 10 ) 1541 - 1546 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: Limb-salvage following resection of bone sarcomas of the foot are challenging due to the complicated anatomy, adjacent neurovascular structures and few durable reconstruction options. METHODS: We retrospectively analysed 50 patients with primary malignant bone sarcoma of the foot who underwent surgery including chondrosarcoma (n = 23), Ewing's sarcoma (n = 14) and osteosarcoma (n = 13). RESULTS: Median follow-up was 68 months. The primary sites were metatarsal (n = 18), phalanges (n = 15), calcaneus (n = 13) and others (n = 4). The 5-year disease-specific survivals were 100, 83 and 83% in chondrosarcoma, Ewing's sarcoma and osteosarcoma, respectively. Below knee amputation, ray/toe amputation, excision and curettage were performed in 21, 24, 2 and 3 patients, respectively. Below knee amputation was performed in 94% of mid/hindfoot tumours. Surgical margins were wide/radical, marginal and intralesional margin in 42, 5 and 3 patients. Three patients (6%) developed local recurrence, whereas, local recurrence was not observed in patients with wide/radical margins. Postoperative complications occurred in 3 patients (6%; surgical site infection n = 2 and delayed wound healing n = 1). Mean MSTS functional score was 26 points (range, 19-30). CONCLUSIONS: Good local control was achieved with acceptable functional outcomes and post-operative complications; almost all mid/hindfoot tumours required below knee amputation achieving wide/radical margins without local recurrence.

DOI： 10.1093/jjco/hyab118

Pelvic Ewing sarcoma: Should all patients receive pre-operative radiotherapy, or should it be delivered selectively? 国際誌

Johnathan R Lex, Vineet Kurisunkal, Yoichi Kaneuchi, Tomohiro Fujiwara, Jenny Sherriff, Catrin Wigley, Jonathan D Stevenson, Michael C Parry, Lee M Jeys

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 47 ( 10 ) 2618 - 2626 2021年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Locally recurrent disease following surgical resection of Ewing sarcoma (ES) confers a poor prognosis. Limited evidence is available evaluating non-selective use of pre-operative radiotherapy (RT) for patients with pelvic ES and its effect on local control and survival. PATIENTS AND METHODS: 49 consecutive patients with pelvic ES were identified retrospectively from a prospectively collated database. Patients either received non-selective pre-operative RT and surgery (n = 27), or selective post-operative RT (n = 22) (surgery alone (n = 11) or surgery and post-operative RT (n = 11)). RESULTS: Patients who had non-selective pre-operative radiotherapy appeared to have a higher LRFS, 88.0% compared to 66.5% in the selective RT group (p = 0.096, Kaplan Meier; p = 0.028, Chi-squared). Administration of non-selective, pre-operative RT to all patients with pelvic ES elevates the LFRS to that of the good responder group (≥90% tumour necrosis and margins, p = 0.880). There was no difference in metastasis-free survival, 60.0% and 54.5% (p = 0.728) and overall survival (OS), 57.7% and 63.6% (p = 0.893). The majority of pre-operative RT patients had both good necrosis (≥90%) (p = 0.003) and widely excised tumours, 81.5% vs 59.1% (p = 0.080). Tumour volume ≥250 ml was associated with worse LRFS (p = 0.045) and post-operative complications (p = 0.017). There may be improved LRFS (p = 0.057) with pre-operative proton-beam RT compared to surgery and selective post-operative RT. CONCLUSION: Pre-operative photon or proton-beam RT to all pelvic ES may improve LRFS compared to the selective delivery of post-operative RT. Radiotherapy delivered to all patients results in a greater percentage of highly necrotic tumours at surgical excision, enabling a greater proportion of patients with wide resection margins.

DOI： 10.1016/j.ejso.2021.05.027

The critical difference in the DASH (Disabilities of the Arm, Shoulder, and Hand) outcome measure after essential upper extremity tumor surgery. 国際誌

Koichi Ogura, Mohamed A Yakoub, Alexander B Christ, Tomohiro Fujiwara, Zarko Nikolic, Patrick J Boland, Edward A Athanasian, John H Healey

Journal of shoulder and elbow surgery 30 ( 9 ) e602-e609 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The DASH (Disabilities of the Arm, Shoulder, and Hand) is a scored questionnaire that is widely used to evaluate the health-related quality of life of patients with upper limb musculoskeletal disorders. However, numerical changes in the measure scores lack clinical significance without meaningful threshold change values of outcome measures that are diagnostically specific. The minimal clinically important difference (MCID) is useful for the interpretation of scores by defining the smallest change that a patient would perceive. However, the MCIDs of the scores in orthopedic oncology patients has not been reported. We aimed to determine the MCIDs of the measure in orthopedic oncology patients. METHODS: Data from our health-related quality of life database from 1999 to 2005 were retrospectively reviewed after institutional review board approval. Seventy-eight patients who underwent surgery and completed 2 surveys during postoperative follow-up were evaluated. Two different methods were used to estimate the MCIDs: distribution-based and anchor-based approaches (the latter used receiver operating characteristic analysis). RESULTS: Using distribution-based methods, the MCIDs of the DASH questionnaire were 7.4 and 8.3 by half standard deviation and the 90% interval of minimal detectable change, respectively. By anchor-based method (receiver operating characteristic analysis), the MCID was 8.3. CONCLUSION: The MCID values calculated by each method validates that the results for upper extremity oncology patients were similar to those reported in other orthopedic conditions. These results identify the threshold for meaningful improvements in DASH scores in orthopedic oncology patients and establish the reference to evaluate health-related quality of life and the outcomes of upper extremity oncology surgery. These data should be further refined for disease- and reconstruction-specific analyses.

DOI： 10.1016/j.jse.2020.11.027

Regional variation in the survival of patients with a soft-tissue sarcoma of the extremity and trunk wall under a centralized care system : what has been the impact of national policies in the UK? 国際誌

Tomohiro Fujiwara, Scott Evans, Jonathan Stevenson, Yusuke Tsuda, Jonathan Gregory, Robert J Grimer, Seggy Abudu

The bone & joint journal 103-B ( 9 ) 1541 - 1549 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: While a centralized system for the care of patients with a sarcoma has been advocated for decades, regional variations in survival remain unclear. The aim of this study was to investigate regional variations in survival and the impact of national policies in patients with a soft-tissue sarcoma (STS) in the UK. METHODS: The study included 1,775 patients with a STS who were referred to a tertiary sarcoma centre. The geographical variations in survival were evaluated according to the periods before and after the issue of guidance by the National Institute for Health and Care Excellence (NICE) in 2006 and the relevant evolution of regional management. RESULTS: There had been a significant difference in survival between patients referred from the North East, North West, East Midlands, West Midlands, South West, and Wales in the pre-NICE era (five-year disease-specific survival (DSS); South West, 74% vs North East, 47% (p = 0.045) or West Midlands, 54% (p = 0.049)), which was most evident for patients with a high-grade STS. However, this variation disappeared in the post-NICE era, in which the overall DSS for high-grade STS improved from 47% to 68% at five years (p < 0.001). Variation in the size of the tumour closely correlated with the variation in DSS, and the overall size of the tumour and incidence of metastasis at the time of diagnosis also decreased after the national policies were issued. CONCLUSION: The survival of patients with a STS improved and regional variation corrected after the introduction of national policies, as a result of a decreasing size of tumour and incidence of metastasis at the time of diagnosis, particularly in patients with a high-grade STS. This highlights the positive impact of national guidelines on regional variation in the presentation, management, and outcome in patients with a STS. Cite this article: Bone Joint J 2021;103-B(9):1541-1549.

DOI： 10.1302/0301-620X.103B9.BJJ-2020-2554.R1

Oncolytic virotherapy reverses chemoresistance in osteosarcoma by suppressing MDR1 expression. 国際誌

Kazuhisa Sugiu, Hiroshi Tazawa, Joe Hasei, Yasuaki Yamakawa, Toshinori Omori, Tadashi Komatsubara, Yusuke Mochizuki, Hiroya Kondo, Shuhei Osaki, Tomohiro Fujiwara, Aki Yoshida, Toshiyuki Kunisada, Koji Ueda, Yasuo Urata, Shunsuke Kagawa, Toshifumi Ozaki, Toshiyoshi Fujiwara

Cancer chemotherapy and pharmacology 88 ( 3 ) 513 - 524 2021年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Osteosarcoma (OS) is a malignant bone tumor primarily affecting children and adolescents. The prognosis of chemotherapy-refractory OS patients is poor. We developed a tumor suppressor p53-expressing oncolytic adenovirus (OBP-702) that exhibits antitumor effects against human OS cells. Here, we demonstrate the chemosensitizing effect of OBP-702 in human OS cells. MATERIALS AND METHODS: The in vitro and in vivo antitumor activities of doxorubicin (DOX) and OBP-702 were assessed using parental and DOX-resistant OS cells (U2OS, MNNG/HOS) and a DOX-resistant MNNG/HOS xenograft tumor model. RESULTS: DOX-resistant OS cells exhibited high multidrug resistant 1 (MDR1) expression, which was suppressed by OBP-702 or MDR1 siRNA, resulting in enhanced DOX-induced apoptosis. Compared to monotherapy, OBP-702 and DOX combination therapy significantly suppressed tumor growth in the DOX-resistant MNNG/HOS xenograft tumor model. CONCLUSION: Our results suggest that MDR1 is an attractive therapeutic target for chemoresistant OS. Tumor-specific virotherapy is thus a promising strategy for reversing chemoresistance in OS patients via suppression of MDR1 expression.

DOI： 10.1007/s00280-021-04310-5

Long-term competing risks for overall and cause-specific failure of rotating-hinge distal femoral arthroplasty for tumour reconstruction. 国際誌

Koichi Ogura, Tomohiro Fujiwara, Carol D Morris, Patrick J Boland, John H Healey

The bone & joint journal 103-B ( 8 ) 1405 - 1413 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: Rotating-hinge knee prostheses are commonly used to reconstruct the distal femur after resection of a tumour, despite the projected long-term burden of reoperation due to complications. Few studies have examined the factors that influence their failure and none, to our knowledge, have used competing risk models to do so. The purpose of this study was to determine the risk factors for failure of a rotating-hinge knee distal femoral arthroplasty using the Fine-Gray competing risk model. METHODS: We retrospectively reviewed 209 consecutive patients who, between 1991 and 2016, had undergone resection of the distal femur for tumour and reconstruction using a rotating-hinge knee prosthesis. The study endpoint was failure of the prosthesis, defined as removal of the femoral component, the tibial component, or the bone-implant fixation; major revision (exchange of the femoral component, tibial component, or the bone-implant fixation); or amputation. RESULTS: Multivariate Fine-Gray regression analyses revealed different hazards for each Henderson failure mode: percentage of femoral resection (p = 0.001) and extent of quadriceps muscle resection (p = 0.005) for overall prosthetic failure; extent of quadriceps muscle resection (p = 0.002) and fixation of femoral component (p = 0.011) for type 2 failure (aseptic loosening); age (p = 0.009) and percentage of femoral resection (p = 0.019) for type 3 failure (mechanical failure); and type of joint resection (p = 0.037) for type 4 (infection) were independent predictors. A bone stem ratio of > 2.5 reliably predicted aseptic loosening. CONCLUSION: We identified independent risk factors for overall and cause-specific prosthetic failure after rotating-hinge knee distal femoral arthroplasty using a competing risk Fine-Gray model. A bone stem ratio > 2.5 reliably predicts aseptic loosening. An accurate knowledge of the risks of distal femoral arthroplasty after resection for tumour assists surgical planning and managing patient expectations. Cite this article: Bone Joint J 2021;103-B(8):1405-1413.

DOI： 10.1302/0301-620X.103B8.BJJ-2020-2323.R1

CSF1/CSF1R Signaling Inhibitor Pexidartinib (PLX3397) Reprograms Tumor-Associated Macrophages and Stimulates T-cell Infiltration in the Sarcoma Microenvironment. 国際誌

Tomohiro Fujiwara, Mohamed A Yakoub, Andrew Chandler, Alexander B Christ, Guangli Yang, Ouathek Ouerfelli, Vinagolu K Rajasekhar, Aki Yoshida, Hiroya Kondo, Toshiaki Hata, Hiroshi Tazawa, Yildirim Dogan, Malcolm A S Moore, Toshiyoshi Fujiwara, Toshifumi Ozaki, Ed Purdue, John H Healey

Molecular cancer therapeutics 20 ( 8 ) 1388 - 1399 2021年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Colony-stimulating factor 1 (CSF1) is a primary regulator of the survival, proliferation, and differentiation of monocyte/macrophage that sustains the protumorigenic functions of tumor-associated macrophages (TAMs). Considering current advances in understanding the role of the inflammatory tumor microenvironment, targeting the components of the sarcoma microenvironment, such as TAMs, is a viable strategy. Here, we investigated the effect of PLX3397 (pexidartinib) as a potent inhibitor of the CSF1 receptor (CSF1R). PLX3397 was recently approved by the Food and Drug Administration (FDA) to treat tenosynovial giant cell tumor and reprogram TAMs whose infiltration correlates with unfavorable prognosis of sarcomas. First, we confirmed by cytokine arrays of tumor-conditioned media (TCM) that cytokines including CSF1 are secreted from LM8 osteosarcoma cells and NFSa fibrosarcoma cells. The TCM, like CSF1, stimulated ERK1/2 phosphorylation in bone marrow-derived macrophages (BMDMs), polarized BMDMs toward an M2 (TAM-like) phenotype, and strikingly promoted BMDM chemotaxis. In vitro administration of PLX3397 suppressed pERK1/2 stimulation by CSF1 or TCM, and reduced M2 polarization, survival, and chemotaxis in BMDMs. Systemic administration of PLX3397 to the osteosarcoma orthotopic xenograft model significantly suppressed the primary tumor growth and lung metastasis, and thus improved metastasis-free survival. PLX3397 treatment concurrently depleted TAMs and FOXP3+ regulatory T cells and, surprisingly, enhanced infiltration of CD8+ T cells into the microenvironments of both primary and metastatic osteosarcoma sites. Our preclinical results show that PLX3397 has strong macrophage- and T-cell-modulating effects that may translate into cancer immunotherapy for bone and soft-tissue sarcomas.

DOI： 10.1158/1535-7163.MCT-20-0591

Compliant Compression Reconstruction of the Proximal Femur Is Durable Despite Minimal Bone Formation in the Compression Segment. 国際誌

Alexander B Christ, Tomohiro Fujiwara, Nicola Fabbri, John H Healey

Clinical orthopaedics and related research 479 ( 7 ) 1577 - 1585 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Compliant compression fixation was developed to promote permanent bone-prosthesis osteointegration while preserving bone stock in patients needing endoprosthetic reconstructions. This has demonstrated durability in the distal femur, with reliable cortical hypertrophy adjacent to the implant. However, the extent of bone formation and prosthetic survivorship of proximal femoral replacements with compliant compression fixation has not been established. QUESTIONS/PURPOSES: (1) How much bone formation occurs across the compression segment in patients treated with a proximal femoral replacement implant using compliant compression fixation? (2) What were the Musculoskeletal Tumor Society (MSTS) scores at minimum 24-month follow-up of patients who received this reconstruction? (3) What is the implant survivorship free from implant removal or revision for any reason at final follow-up? METHODS: From 2006 to 2018, we performed 213 proximal femoral replacements in patients with oncologic conditions of the proximal femur where the trochanters could not be preserved. Of these, 6% (12 of 213) were performed with an implant that used compliant compression fixation. We used this device in primary oncologic reconstructions in patients younger than 65 years of age without metastases who had nonirradiated bone with the requisite ≥ 2.5 mm of cortical thickness in the hope that it would provide more durable fixation and bone stock preservation than conventional reconstructions. All patients were followed for longer than 2 years except one who died in that interval. Median (range) follow-up was 6 years (2 to 10 years). Seven patients received diagnosis-specific chemotherapy in a consistent manner based on Children's Oncology Group chemotherapy protocols. Using the NIH-developed ImageJ open-access software, we measured the area of bone under compression on 3-, 6-, 9-, 12-, 18-, and 24-month radiographs and the length of the traction bar potential-compression distance, reconciling independent measures from two investigators using the identical method as published for the distal femur with compression fixation. The duration of prosthesis retention was evaluated using a competing risk analysis for the 11 surviving patients. RESULTS: Bone hypertrophy in the compression segment was scant. At the final analysis, cortical bone formation was a median (range) of 4 (-7 to 14) above baseline. The median (range) MSTS score was 27 (19 to 30). One implant failed after trauma, and the patient underwent revision of the implant. CONCLUSION: Despite scant bone formation across the compression segment and drastically less formation than reported for distal femoral replacements, compliant compression fixation of the proximal femur demonstrated good survivorship in patients 65 years or younger with localized sarcoma and nonirradiated, adequate bone stock in this small, retrospective series. Patients achieved good functional outcomes at final follow-up. The potential benefit of this reconstruction method should be weighed against the initial period of limited weightbearing and the life expectancy of the patient. LEVEL OF EVIDENCE: Level IV, cohort study.

DOI： 10.1097/CORR.0000000000001663

The role of surgical margin quality in myxofibrosarcoma and undifferentiated pleomorphic sarcoma. 国際誌

Tomohiro Fujiwara, Vaiyapuri Sumathi, Michael Parry, Jonathan Stevenson, Yusuke Tsuda, Yoichi Kaneuchi, Lee Jeys

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 47 ( 7 ) 1756 - 1762 2021年7月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: The effect of margin quality as a barrier against infiltration of soft-tissue sarcomas (STSs) has been unclear. We aimed to investigate the effect of margin quantity and quality on local control for myxofibrosarcoma (MFS) and undifferentiated pleomorphic sarcoma (UPS). METHODS: 278 patients with a localised MFS and UPS were studied. Margin quality was categorized into five types; type 1, pseudocapsule/reactive zone; type 2, fat/fibrofatty tissue; type 3, muscle; type 4, fascia; type 5, periosteum. RESULTS: The 5-year cumulative LR incidence was 22% and 13% in patients with positive and 0.1-9.9 mm margins, respectively, but decreased to 3% with ≥10.0 mm margins (p = 0.009); the cumulative LR incidence was significantly lower in patients with ≥10.0 mm margins than those with positive margins (p = 0.033) but was not significantly different in those with 0.1-9.9 mm margins (p = 0.183). In patients with 0.1-9.9 mm margins, the cumulative LR incidence was affected by margin quality; type 4 and 5 provided an LR risk less than 5% (p < 0.001), which was similar to those with margins ≥10.0 mm. Combining these two factors together, the LR risk in patients with positive or 0.1-9.9 mm margins without fascia/periosteum was approximately 11 × higher than patients with 0.1-9.9 mm margins with fascia/periosteum or margins ≥10.0 mm (p = 0.002). CONCLUSIONS: A resection margin of 0.1-9.9 mm with fascia or periosteum provided a similar LR risk profile to ≥10 mm margins with any margin quality, which provided the lowest LR risk. The quality of fascial or periosteal tissue margins may be equivalent to a margin quantity of 10 mm as a barrier to LR.

DOI： 10.1016/j.ejso.2020.11.144

Pelvic reconstruction using an ice-cream cone prosthesis: correlation between the inserted length of the coned stem and surgical outcome.

Tomohiro Fujiwara, Jonathan Stevenson, Michael Parry, Louis-Romée Le Nail, Yusuke Tsuda, Robert Grimer, Lee Jeys

International journal of clinical oncology 26 ( 6 ) 1139 - 1146 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Acetabular reconstruction using an ice-cream cone prosthesis has been a reliable reconstruction option following pelvic tumour resection. However, it remains unknown which factor determines the success of this procedure. We aimed to determine risk factors for complications and functional loss in acetabular reconstruction using an ice-cream cone prosthesis. PATIENTS AND METHODS: Fifty-four patients with malignant bone tumours who underwent acetabular reconstruction using an ice-cream cone prosthesis between 2004 and 2016 were studied. The bone-stem ratio was calculated as the ratio of the inserted length into the bone per the entire stem length. RESULTS: A total of 26 (48%) patients had at least one complication and 11 patients (20%) required surgical interventions. The complication rates were 71% and 40% with a bone-stem ratio ≤ 50% and > 50%, respectively (p = 0.026), and the bone-stem ratio significantly stratified the risk of complications (≤ 50%: OR, 4.67 versus > 50%; p = 0.048). The mean MSTS score at the final follow-up was 60% (range 23-97%): the scores were significantly lower in patients with complications/leg-length discrepancy (52%) than in those without (79%; p = 0.002). The mean score with a bone-stem ratio ≤ 50% was significantly lower than the score with a ratio > 50%, especially in patients who underwent non-navigated reconstructions (33% versus 64%; p = 0.001). CONCLUSION: The inserted length of the coned stem into residual bone was predictive of complications and functional outcome. Surgical indication for this procedure should be considered with the size of the remaining ilium to stabilise the prosthesis with a coned stem longer than half length.

DOI： 10.1007/s10147-021-01882-3

Is 2 mm a wide margin in high-grade conventional chondrosarcomas of the pelvis? 国際誌

Vineet Kurisunkal, Minna K Laitinen, Yoichi Kaneuchi, Bilal Kapanci, Jonathan Stevenson, Michael C Parry, Aleksi Reito, Tomohiro Fujiwara, Lee M Jeys

The bone & joint journal 103-B ( 6 ) 1150 - 1154 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: Controversy exists as to what should be considered a safe resection margin to minimize local recurrence in high-grade pelvic chondrosarcomas (CS). The aim of this study is to quantify what is a safe margin of resection for high-grade CS of the pelvis. METHODS: We retrospectively identified 105 non-metastatic patients with high-grade pelvic CS of bone who underwent surgery (limb salvage/amputations) between 2000 and 2018. There were 82 (78%) male and 23 (22%) female patients with a mean age of 55 years (26 to 84). The majority of the patients underwent limb salvage surgery (n = 82; 78%) compared to 23 (22%) who had amputation. In total, 66 (64%) patients were grade 2 CS compared to 38 (36%) grade 3 CS. All patients were assessed for stage, pelvic anatomical classification, type of resection and reconstruction, margin status, local recurrence, distant recurrence, and overall survival. Surgical margins were stratified into millimetres: < 1 mm; > 1 mm but < 2 mm; and > 2 mm. RESULTS: The disease--specific survival (DSS) at five years was 69% (95% confidence interval (CI) 56% to 81%) and 51% (95% CI 31% to 70%) for grade 2 and 3 CS, respectively (p = 0.092). The local recurrence-free survival (LRFS) at five years was 59% (95% CI 45% to 72%) for grade 2 CS and 42% (95% CI 21% to 63%) for grade 3 CS (p = 0.318). A margin of more than 2 mm was a significant predictor of increased LRFS (p = 0.001). There was a tendency, but without statistical significance, for a > 2 mm margin to be a predictor of improved DSS. Local recurrence (LR) was a highly significant predictor of DSS, analyzed in a competing risk model (p = 0.001). CONCLUSION: Obtaining wide margins in the pelvis remains challenging for high-grade pelvic CS. On the basis of our study, we conclude that it is necessary to achieve at least a 2 mm margin for optimal oncological outcomes in patients with high-grade CS of the pelvis. Cite this article: Bone Joint J 2021;103-B(6):1150-1154.

DOI： 10.1302/0301-620X.103B6.BJJ-2020-1869.R1

Patients with an increased time to treatment initiation have a poorer overall survival after definitive surgery for localized high-grade soft-tissue sarcoma in the extremity or trunk : report from the National Cancer Database. 国際誌

Koichi Ogura, Tomohiro Fujiwara, John H Healey

The bone & joint journal 103-B ( 6 ) 1142 - 1149 2021年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: Time to treatment initiation (TTI) is generally defined as the time from the histological diagnosis of malignancy to the initiation of first definitive treatment. There is no consensus on the impact of TTI on the overall survival in patients with a soft-tissue sarcoma. The purpose of this study was to determine if an increased TTI is associated with overall survival in patients with a soft-tissue sarcoma, and to identify the factors associated with a prolonged TTI. METHODS: We identified 23,786 patients from the National Cancer Database who had undergone definitive surgery between 2004 and 2015 for a localized high-grade soft-tissue sarcoma of the limbs or trunk. A Cox proportional hazards model was used to examine the relationship between a number of factors and overall survival. We calculated the incidence rate ratio (IRR) using negative binomial regression models to identify the factors that affected TTI. RESULTS: Patients in whom the time to treatment initiation was prolonged had poorer overall survival than those with a TTI of 0 to 30 days. These were: 31 to 60 days (hazard ratio (HR) 1.08, p = 0.011); 61 to 90 days (HR 1.11, p = 0.044); and 91 days (HR 1.22; p = 0.003). The restricted cubic spline showed that the hazard ratio increased substantially with a TTI longer than 50 days. Non-academic centres (vs academic centres; IRR ranging from 0.64 to 0.86; p < 0.001) had a shorter TTI. Those insured by Medicaid (vs private insurance; IRR 1.34), were uninsured (vs private insurance; IRR 1.17), or underwent a transition in care (IRR 1.62) had a longer TTI. CONCLUSION: A time to treatment initiation of more than 30 days after diagnosis was independently associated with poorer survival. The hazard ratio showed linear increase, especially if the TTI was more than 50 days. We recommend starting treatment within 30 days of diagnosis to achieve the highest likelihood of cure for localized high-grade soft-tissue sarcomas in the limbs and trunk, even when a patient needs to be referred to a specialist centre. Cite this article: Bone Joint J 2021;103-B(6):1142-1149.

DOI： 10.1302/0301-620X.103B6.BJJ-2020-2087.R1

Prevalence of Psychological Distress and Its Risk Factors in Patients with Primary Bone and Soft Tissue Tumors. 国際誌

Masato Ise, Eiji Nakata, Yoshimi Katayama, Masanori Hamada, Toshiyuki Kunisada, Tomohiro Fujiwara, Ryuichi Nakahara, Shouta Takihira, Kohei Sato, Yoshiteru Akezaki, Masuo Senda, Toshifumi Ozaki

Healthcare (Basel, Switzerland) 9 ( 5 ) 2021年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

Psychological distress is common in patients with soft tissue and bone tumors. We first investigated its frequency and the associated risk factors in patients with pre-operative bone and soft tissue tumors. Participants included 298 patients with bone and soft tissue tumors who underwent surgery in our institution between 2015 and 2020. Psychological distress was evaluated by the Distress and Impact Thermometer (DIT) that consists of two types of questions (questions about the severity of the patient's distress (DIT-D) and its impact (DIT-I)). We used a cut-off point of 4 on the DIT-D and 3 on the DIT-I for screening patients with psychological distress. We therefore investigated: (1) the prevalence of psychological distress as assessed with DIT or distress thermometer (DT), which can be decided by DIT-D ≥ 4, (2) what are the risk factors for the prevalence of psychological distress, and (3) what is the number of patients who consulted a psychiatrist for psychological distress in patients with pre-operative bone and soft tissue tumors. With DIT and DT, we identified 64 patients (21%) and 95 patients (32%), respectively, with psychological distress. Multivariate logistic regression revealed that older age, sex (female), malignancy (malignant or intermediate tumor), a lower Barthel Index, and higher numeric rating scale were risk factors for psychological distress. Two patients (3%) consulted a psychiatrist after surgery. In conclusion, careful attention to psychological distress is needed, especially for female patients, older patients, and those with malignant soft or bone tissue tumors who have more than moderate pain.

DOI： 10.3390/healthcare9050566

Liquid Biopsy Targeting Monocarboxylate Transporter 1 on the Surface Membrane of Tumor-Derived Extracellular Vesicles from Synovial Sarcoma. 国際誌

Suguru Yokoo, Tomohiro Fujiwara, Aki Yoshida, Koji Uotani, Takuya Morita, Masahiro Kiyono, Joe Hasei, Eiji Nakata, Toshiyuki Kunisada, Shintaro Iwata, Tsukasa Yonemoto, Koji Ueda, Toshifumi Ozaki

Cancers 13 ( 8 ) 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

The lack of noninvasive biomarkers that can be used for tumor monitoring is a major problem for soft-tissue sarcomas. Here we describe a sensitive analytical technique for tumor monitoring by detecting circulating extracellular vesicles (EVs) of patients with synovial sarcoma (SS). The proteomic analysis of purified EVs from SYO-1, HS-SY-II, and YaFuSS identified 199 common proteins. DAVID GO analysis identified monocarboxylate transporter 1 (MCT1) as a surface marker of SS-derived EVs, which was also highly expressed in SS patient-derived EVs compared with healthy individuals. MCT1+CD9+ EVs were also detected from SS-bearing mice and their expression levels were significantly correlated with tumor volume (p = 0.003). Furthermore, serum levels of MCT1+CD9+ EVs reflected tumor burden in SS patients. Immunohistochemistry revealed that MCT1 was positive in 96.7% of SS specimens and its expression on the cytoplasm/plasma membrane was significantly associated with worse overall survival (p = 0.002). Silencing of MCT1 reduced the cellular viability, and migration and invasion capability of SS cells. This work describes a new liquid biopsy technique to sensitively monitor SS using circulating MCT1+CD9+ EVs and indicates the therapeutic potential of MCT1 in SS.

DOI： 10.3390/cancers13081823

Immunotherapy for sarcomas. 国際誌

Eiji Nakata, Tomohiro Fujiwara, Toshiyuki Kunisada, Tastuo Ito, Shota Takihira, Toshifumi Ozaki

Japanese journal of clinical oncology 51 ( 4 ) 523 - 537 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Sarcomas are a heterogeneous group of malignancies of mesenchymal origin; their molecular and genomic mechanisms differ with regard to histology. These characteristics lead to the presentation of varied immunological profiles based on the tumor microenvironment. Various immunotherapies are considered for the treatment of sarcoma. These treatments are performed either in isolation or in combination with other methods such as cytotoxic chemotherapy or the use of molecular target agents. Among these, two recently emerging immunotherapies include T-cell receptor gene therapy and immune checkpoint inhibitor therapy, which are expected to be effective for many types of sarcoma. A sarcoma with a disease-specific translocation and a limited number of mutations, such as synovial sarcoma, expresses high levels of self-antigens, like the New York esophageal squamous cell carcinoma 1, which has been targeted in T-cell receptor gene therapy. On the other hand, sarcomas with a greater number of mutations, such as undifferentiated pleomorphic sarcomas, myxofibrosarcoma and dedifferentiated liposarcomas, can be good candidates for immune checkpoint inhibitors. Among immune checkpoint inhibitor therapies, programmed cell death-1 blockade (nivolumab and pembrolizumab) and cytotoxic T-lymphocyte-associated antigen 4 blockade (ipilimumab) have been investigated most often in sarcoma. Although the sole use of immune checkpoint inhibitors provides limited efficacy, combined immunotherapy with immune checkpoint inhibitors or molecular target agents, especially antiangiogenic agents, has shown moderate results against some types of sarcoma, such as the alveolar soft part sarcoma. Several clinical trials utilizing immunotherapy, including T-cell receptor gene therapy and immune checkpoint inhibitors, in sarcomas are under progress. By clarifying the tumor microenvironment and biomarker-predictive capacity of immunotherapy in sarcomas, better clinical trials can be designed; this could lead to improved outcomes for immunotherapy in sarcoma.

DOI： 10.1093/jjco/hyab005

Anti-IL17 antibody Secukinumab therapy is associated with ossification in giant cell tumor of bone: a case report of pathologic similarities and therapeutic potential similar to Denosumab. 国際誌

Andrew Chandler, Meredith K Bartelstein, Tomohiro Fujiwara, Cristina R Antonescu, John H Healey, Max Vaynrub

BMC musculoskeletal disorders 22 ( 1 ) 320 - 320 2021年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Giant cell tumor of bone is a benign, locally aggressive neoplasm. Surgical resection is the preferred treatment method. However, for cases in which resection poses an increased risk to the patient, denosumab (anti-RANKL monoclonal antibody) is considered. Secukinumab is an anti-IL-17 antibody that is used in psoriatic arthritis to reduce bone resorption and articular damage. CASE PRESENTATION: One case of giant cell tumor of bone (GCTB) in a patient treated with secukinumab for psoriatic arthritis demonstrated findings significant for intra-lesional calcifications. Histologic examination showed ossification, new bone formation, and remodeling. A paucity of osteoclast type giant cells was noted. Real-time quantitative polymerase-chain-reaction (qRT-PCR) analysis revealed decreased osteoclast function compared to treatment-naive GCTB. CONCLUSIONS: Secukinumab may play a role in bone remodeling for GCTB. Radiologists, surgeons, and pathologists should be aware of this interaction, which can cause lesional ossification. Further research is required to define the therapeutic potential of this drug for GCTB and osteolytic disease.

DOI： 10.1186/s12891-021-04182-z

【骨・軟部腫瘍のマネジメント(その1)】総論診療体制サルコーマセンター設立と腫瘍内科医との連携集約化と地域連携

国定俊之, 中田英二, 藤原智洋, 久保寿夫, 西森久和, 田端雅弘, 尾崎敏文

別冊整形外科 ( 79 ) 7 - 12 2021年4月

記述言語：日本語出版者・発行元：(株)南江堂

＜文献概要＞はじめにわが国では歴史的に整形外科が中心となって肉腫(サルコーマ)の治療方針を決め,主に手術と化学療法を担当してきた.一方,欧米では腫瘍内科が肉腫の化学療法を担当することが一般的であり,わが国の治療状況とは大きく異なる.肉腫治療例の増加とともに進行例が増加し,新規治療薬も開発され,整形外科医のみで治療していくことがむずかしくなってきた.また,化学療法以外にも,肉腫の診断,手術には多くの診療科の協力が必要で,多職種による集学的医療チームによる治療が重要である.当院では肉腫患者によりよい治療を提供する目的で,2014年4月に大学病院の診療部門としては日本ではじめてサルコーマセンターを設立した.本稿では,当院サルコーマセンターの活動を紹介する.

その他リンク： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2021&ichushi_jid=J04037&link_issn=&doc_id=20210514600002&doc_link_id=10.15106%2Fj_besei79_7&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_besei79_7&type=%88%E3%8F%91.jp_%83I%81%5B%83%8B%83A%83N%83Z%83X&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

　前のページ - 次のページ　

1
2
3
4
5
6
7
8
9
10