研究者詳細 - 藤原　智洋

論文 - 藤原　智洋

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Operative management of metastatic disease of the acetabulum: review of the literature and prevailing concepts. 国際誌

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

Hip international : the journal of clinical and experimental research on hip pathology and therapy 33 ( 2 ) 11207000221130270 - 11207000221130270 2022年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

Metastatic disease of the periacetabular region is a common problem in orthopaedic oncology, associated with severe pain, decreased mobility, and substantial decline of the quality of life. Conservative management includes optimisation of pain management, activity modification, and radiation therapy. However, patients with destructive lesions affecting the weight-bearing portion of the acetabulum often require reconstructive surgery to decrease pain and restore mobility. The goal of surgery is to provide an immediately stable and durable construct, allowing immediate postoperative weight-bearing and maintaining functional independence for the remaining lifetime of the patient. A variety of surgical techniques have been reported, most of which are based upon cemented total hip arthroplasty, but also include porous tantalum implants and percutaneous cementoplasty. This review discusses the various reconstructive concepts and options, including their respective indications and outcome. A reconstructive algorithm incorporating different techniques and strategies based upon location and quality of remaining bone is also presented.

DOI： 10.1177/11207000221130270

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軟部肉腫に対する薬物療法がん遺伝子パネルに基づく肉腫診療

中田英二, 藤原智洋, 国定俊之, 平沢晃, 遠西大輔, 尾崎敏文

中部日本整形外科災害外科学会雑誌 65 ( 秋季学会 ) 77 - 77 2022年10月

がん遺伝子パネルに基づく肉腫診療

中田英二, 藤原智洋, 平沢晃, 二川摩周, 遠西大輔, 山本英喜, 冨田秀太, 久保寿夫, 田端雅弘, 国定俊之, 豊岡伸一, 尾崎敏文

日本癌治療学会学術集会抄録集 60回 O49 - 4 2022年10月

がん遺伝子パネルに基づく肉腫診療

中田英二, 藤原智洋, 平沢晃, 二川摩周, 遠西大輔, 山本英喜, 冨田秀太, 久保寿夫, 田端雅弘, 国定俊之, 豊岡伸一, 尾崎敏文

日本癌治療学会学術集会抄録集 60回 O49 - 4 2022年10月

Clinicopathological and histological analysis of secondary malignant giant cell tumors of bone without radiotherapy. 国際誌

Eiji Nakata, Hotaka Kawai, Tomohiro Fujiwara, Toshiyuki Kunisada, Hirofumi Inoue, Mashu Futagawa, Haruyoshi Katayama, Takuto Itano, Toshifumi Ozaki

Oncology letters 24 ( 3 ) 319 - 319 2022年9月

記述言語：英語掲載種別：研究論文（学術雑誌）

Giant cell tumor of bone (GCTB) is an intermediate bone tumor that rarely undergoes malignant transformation. Secondary malignant GCTB (SMGCTB) is defined as a lesion in which high-grade sarcoma occurs at the site of previously treated GCTB. The present study retrospectively reviewed the medical records of patients with GCTB treated at Okayama University Hospital between April 1986 and April 2020. The clinicopathological and histological features of patients with SMGCTB without prior radiotherapy were investigated. A total of three patients (4%) with SMGCTB were detected, and the tumor sites were the distal ulna, distal femur and sacrum. Two of the patients had been treated with curettage and bone graft, and one had been treated with denosumab. In all cases, the lesions were made up of two components, the conventional GCTB component and the malignant component. The Ki67 labeling index was higher in the malignant components of SMGCTB and metastatic lesions compared with that in primary and recurrent conventional GCTB, or the conventional GCTB component of SMGCTB. Moreover, p53 expression was higher in these same components in patients who underwent curettage and bone grafting; however, there was no difference in the patient that received denosumab treatment. In this patient, clinical cancer genomic profiling revealed loss of CDKN2A, CDKN2B and MTAP expression. All three patients developed distant metastasis. The patients with SMGCTB in the ulna and femur died 13 and 54 months after detection of malignant transformation, respectively. The patient with SMGCTB in the sacrum received carbon-ion radiotherapy to the sacrum and pazopanib; the treatment was effective and the patient was alive at the last follow-up 3 years later. In conclusion, p53 may be associated with malignant transformation in GCTB. Future studies should investigate the association of between denosumab treatment and malignant transformation, as well as molecular targeted therapy to improve the clinical outcomes of SMGCTB.

DOI： 10.3892/ol.2022.13439

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がんゲノム医療において遺伝性骨・軟部肉腫を同定する臨床的意義(Clinical significance of identifying hereditary bone and soft tissue sarcomas in precision medicine)

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 植野さやか, 山本英喜, 藤原智洋, 国定俊之, 尾崎敏文, 平沢晃

日本癌学会総会記事 81回 P - 3121 2022年9月

骨・軟部腫瘍の基礎科学のトピックスクリニカルシークエンスによる肉腫のゲノム医療

中田英二, 藤原智洋, 国定俊之, 二川摩周, 遠西大輔, 久保寿夫, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1533 - S1533 2022年9月

骨・軟部肉腫に対するがんゲノムプロファイリング検査から検出されるpresumed germline pathogenic variantsの意義

二川摩周, 中田英二, 十川麗美, 加藤芙美乃, 浦川優作, 河内麻里子, 山本英喜, 藤原智洋, 国定俊之, 平沢晃, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1770 - S1770 2022年9月

骨・軟部腫瘍の基礎科学のトピックス転移性骨肉腫は臓器指向性サイトカインの分泌を介して微小環境を変化させ前転移ニッチを形成する

近藤宏也, 田澤大, 藤原智洋, 近藤彩奈, 片山晴喜, 佐藤浩平, 畑利彰, 中田英二, 国定俊之, 藤原俊義, 尾崎敏文

日本整形外科学会雑誌 96 ( 8 ) S1532 - S1532 2022年9月

悪性軟部腫瘍に対する抗CSF-1R阻害薬の有効性抗腫瘍効果と微小環境へ与える影響(Antitumor effect of CSF-1/CSF-1R blockade in soft-tissue sarcomas)

近藤彩奈, 藤原智洋, 吉田晶, 畑利彰, 近藤宏也, 国定俊之, 尾崎敏文

日本癌学会総会記事 81回 J - 1062 2022年9月

転移性骨肉腫細胞はCCL2によるM2マクロファージの腫瘍内浸潤を誘導して肺転移を促進する(Metastatic osteosarcoma cells facilitate lung metastasis by inducing CCL2-mediated tumor infiltration of M2 macrophages)

近藤宏也, 田澤大, 久禮美穂, 藤原智洋, 国定俊之, 尾崎敏文, 藤原俊義

日本癌学会総会記事 81回 J - 2087 2022年9月

Geographic Access to High-Volume Care Providers and Survival in Patients with Bone Sarcomas: Nationwide Patterns in the United States. 国際誌

Tomohiro Fujiwara, Koichi Ogura, Motaz Alaqeel, John H Healey

The Journal of bone and joint surgery. American volume 104 ( 16 ) 1426 - 1437 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Clinical practice guidelines recommend centralized care for patients with bone sarcoma. However, the relationship between the distance that patients travel to obtain care, institutional treatment volume, and survival is unknown. METHODS: We used the National Cancer Database to examine associations between travel distance and survival among 8,432 patients with bone sarcoma diagnosed from 2004 to 2015. Associations were identified using multivariable Cox regression analyses that controlled for sociodemographic, clinical, and hospital-level factors; subgroup analyses stratified patients by histological diagnosis, tumor stage, and pediatric or adult status. RESULTS: Mortality risk was lower among patients who traveled ≥50 miles (≥80.5 km) than among patients who traveled ≤10 miles (≤16.1 km) (hazard ratio [HR], 0.69 [95% confidence interval (CI), 0.63 to 0.76]). Among hospital-level factors, facility volume independently affected survival: mortality risk was lower among patients at high-volume facilities (≥20 cases per year) than at low-volume facilities (≤5 cases per year), with an HR of 0.72 (95% CI, 0.66 to 0.80). The proportion of patients who received care at high-volume facilities varied by distance traveled (p < 0.001); it was highest among patients who traveled ≥50 miles (53%) and lower among those who traveled 11 to 49 miles (17.7 to 78.9 km) (32%) or ≤10 miles (18%). Patients who traveled ≥50 miles to a high-volume facility had a lower risk of mortality (HR, 0.65 [95% CI, 0.56 to 0.77]) than those who traveled ≤10 miles to a low-volume facility. In subgroup analyses, this association was evident among patients with all 3 major histological subtypes; those with stage-I, II, and IV tumors; and adults. CONCLUSIONS: This national study showed that greater travel burden was associated with higher survival rates in adults, a finding attributable to patients traveling to receive care at high-volume facilities. Despite the burdens associated with travel, modification of referral pathways to specialized centers may improve survival for patients with bone sarcoma. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

DOI： 10.2106/JBJS.21.01140

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Effect of bacterium in the malignant wounds of soft tissue sarcoma 国際誌

Eiji Nakata, Tomohiro Fujiwara, Haruyoshi Katayama, Takuto Itano, Toshiyuki Kunisada, Toshifumi Ozaki

Oncology Letters 24 ( 4 ) 345 - 345 2022年8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：Spandidos Publications

Malignant wounds (MWs) are rare skin lesions, which accompany ulceration, necrosis and infection caused by infiltration or damage by malignant tumor. The present study aimed to investigate the bacterial etiology implicated in MW in soft tissue sarcoma (STS), and the effectiveness of culture-guided perioperative antibacterial administration. A retrospective evaluation was conducted on medical records of patients who presented with MW between 2006 and 2020. A total of seven patients were included in the present study, in whom all tumors were relatively large (>5 cm) and high-grade. Subsequently, five patients underwent limb-sparing surgery, and three patients had distant metastases with a 5-year overall survival of 71%. Preoperative microbiological sampling from the wound identified 11 different bacterial strains in five patients. The infections were polymicrobial with an average of 2.6 strains isolated per patient (1 aerobic, 1.6 anaerobic bacteria). They were predominantly methicillin-sensitive Staphylococcus aureus. Patients with MWs from STS reported symptoms, including bleeding (71%), exudation (71%) and malodorous wound (43%) at the initial presentation; these completely resolved after surgery. All but one patient reported pain at the MW site with an average numeric rating scale of 4.4 at presentation that decreased to 1.4 (P=0.14) and 0.6 (P=0.04) one and two weeks after surgery, respectively. The patients had elevated C-reactive protein (71%), anemia (57%), low albumin (86%) and renal/liver dysfunction (14-29%). One patient was diagnosed with sepsis. Surgical resection afforded symptomatic relief and resolution of abnormal laboratory values. Although selected antibiotics were administered in four patients based on the preoperative antibiotic sensitivity test, surgical site infection (SSI) occurred in three patients. Therefore, the effectiveness of the selected antibiotics based on the results of the preoperative culture in preventing SSI needs to be investigated in the future. In conclusion, physicians should keep in mind that although surgical resection can improve the symptoms and abnormal values in laboratory examination form MW, it is accompanied with a high rate of SSI and poor prognosis.

DOI： 10.3892/ol.2022.13465

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Alveolar soft part sarcoma: progress toward improvement in survival? A population-based study. 国際誌

Tomohiro Fujiwara, Eiji Nakata, Toshiyuki Kunisada, Toshifumi Ozaki, Akira Kawai

BMC cancer 22 ( 1 ) 891 - 891 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Alveolar soft part sarcoma (ASPS) is a rare histological subtype of soft-tissue sarcoma, which remains refractory to conventional cytotoxic chemotherapy. We aimed to characterize ASPS and investigate whether the oncological outcome has improved over the past decade. METHODS: One hundred and twenty patients with newly diagnosed ASPS from 2006 to 2017, identified from the Bone and Soft-Tissue Tumor Registry in Japan, were analyzed retrospectively. RESULTS: The study cohort comprised 34 (28%) patients with localized ASPS and 86 (72%) with metastatic disease at presentation. The 5-year disease-specific survival (DSS) was 68% for all patients and 86% and 62% for localized and metastatic disease, respectively (p = 0.019). Metastasis at presentation was the only adverse prognostic factor for DSS (hazard ratio [HR]: 7.65; p = 0.048). Patients who were > 25 years (80%; p = 0.023), had deep-seated tumors (75%; p = 0.002), and tumors > 5 cm (5-10 cm, 81%; > 10 cm, 81%; p < 0.001) were more likely to have metastases at presentation. In patients with localized ASPS, adjuvant chemotherapy or radiotherapy did not affect survival, and 13 patients (45%) developed distant metastases in the lung (n = 12, 92%) and brain (n = 2, 15%). In patients with metastatic ASPS (lung, n = 85 [99%]; bone, n = 12 [14%]; and brain n = 9 [11%]), surgery for the primary or metastatic site did not affect survival. Prolonged survival was seen in patients who received pazopanib treatment (p = 0.045), but not in those who received doxorubicin-based cytotoxic chemotherapy. Overall, improved DSS for metastatic ASPS has been observed since 2012 (5-year DSS, from 58 to 65%) when pazopanib was approved for advanced diseases, although without a statistically significant difference (p = 0.117). CONCLUSION: The national study confirmed a unique feature of ASPS with frequent metastasis to the lung and brain but an indolent clinical course. An overall trend toward prolonged survival after the introduction of targeted therapy encourages continuous efforts to develop novel therapeutic options for this therapeutically resistant soft-tissue sarcoma.

DOI： 10.1186/s12885-022-09968-5

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Neoplastic synovial lining cells that coexpress podoplanin and CD90 overproduce CSF-1, driving tenosynovial giant cell tumor. 国際誌

Andrew C Chandler, Mohamed Yakoub, Tomohiro Fujiwara, Laura T Donlin, Paul Edward Purdue, John H Healey

Journal of orthopaedic research : official publication of the Orthopaedic Research Society 40 ( 8 ) 1918 - 1925 2022年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Tenosynovial giant cell tumor (TCGT) is a rare neoplasm affecting the synovium of joints, bursae, and tendon sheaths. The overproduction of colony-stimulating factor-1 (CSF-1) by a minority of the tumor population works in a paracrine fashion to drive tumor growth. Pathology of the reactive, monocytic component has been well elucidated, whereas the populations of neoplastic cells and all the sources of CSF-1 overproduction are incompletely characterized. Podoplanin (PDPN), or gp38, is a cell surface glycoprotein that is expressed on fibroblast-like synovial cells and upregulated in rheumatoid arthritis and many cancers; it governs cell mobility, epithelial-mesenchymal transition, and other functions and is associated with lymphangiogenesis and poor prognosis in many solid tumors, which underscores its local and possible systemic effects. We found higher PDPN expression in TGCT than in internal controls of patients' healthy synovium. Flow cytometry partitioned PDPNhigh cells into PDPNhigh CD90+ and PDPNhigh CD14+ populations. Quantitative real-time polymerase chain reaction analysis of the PDPNhigh CD90+ cells revealed that CSF-1 expression was 10-fold higher than in PDPNhigh CD14+ cells. Therefore, we conclude that the lining fibroblast-like synovial cells, which express PDPNhigh CD90+ , are responsible for the overproduction of CSF-1 and for driving tumor growth.

DOI： 10.1002/jor.25216

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Impact of racial disparities and insurance status in patients with bone sarcomas in the USA : a population-based cohort study. 国際誌

Xianglin Hu, Tomohiro Fujiwara, Matthew T Houdek, Lingxiao Chen, Wending Huang, Zhengwang Sun, Yangbai Sun, Wangjun Yan

Bone & joint research 11 ( 5 ) 278 - 291 2022年5月

記述言語：英語掲載種別：研究論文（学術雑誌）

AIMS: Socioeconomic and racial disparities have been recognized as impacting the care of patients with cancer, however there are a lack of data examining the impact of these disparities on patients with bone sarcoma. The purpose of this study was to examine socioeconomic and racial disparities that impact the oncological outcomes of patients with bone sarcoma. METHODS: We reviewed 4,739 patients diagnosed with primary bone sarcomas from the Surveillance, Epidemiology and End Results (SEER) registry between 2007 and 2015. We examined the impact of race and insurance status associated with the presence of metastatic disease at diagnosis, treatment outcome, and overall survival (OS). RESULTS: Patients with Medicaid (odds ratio (OR) 1.41; 95% confidence interval (CI) 1.15 to 1.72) and uninsured patients (OR 1.90; 95% CI 1.26 to 2.86) had higher risks of metastatic disease at diagnosis compared to patients with health insurance. Compared to White patients, Black (OR 0.63, 95% CI 0.47 to 0.85) and Asian/Pacific Islander (OR 0.65, 95% CI 0.46 to 0.91) were less likely to undergo surgery. In addition, Black patients were less likely to receive chemotherapy (OR 0.67, 95% CI 0.49 to 0.91) compared to White patients. In patients with chondrosarcoma, those with Medicaid had worse OS compared to patients with insurance (hazard ratio (HR) 1.65, 95% CI 1.06 to 2.56). CONCLUSION: In patients with a bone sarcoma, the cancer stage at diagnosis varied based on insurance status, and racial disparities were identified in treatment. Further studies are needed to identify modifiable factors which can mitigate socioeconomic and racial disparities found in patients with bone sarcomas. Cite this article: Bone Joint Res 2022;11(5):278-291.

DOI： 10.1302/2046-3758.115.BJR-2021-0258.R2

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Impact of the national sarcoma guidelines on the prevalence and outcome of inadvertent excisions of soft tissue sarcomas: An observational study from a UK tertiary referral centre. 国際誌

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

European journal of surgical oncology : the journal of the European Society of Surgical Oncology and the British Association of Surgical Oncology 48 ( 3 ) 533 - 540 2022年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: This study aims to investigate the impact of the national guideline on the prevalence and outcome in patients with soft-tissue sarcoma (STS) who had undergone inadvertent excisions. METHODS: A total of 2336 patients were referred to a tertiary sarcoma centre from six regions (North East, North West, East Midlands, West Midlands, Wales, and South West) in the United Kingdom with a diagnosis of STS between 1996 and 2016, of whom 561 patients (24.0%) had undergone inadvertent excisions. Patients were categorised into two groups of 10-year periods pre and post the National Institute for Health and Clinical Excellence (NICE) guideline implementation in 2006. RESULTS: The proportion of inadvertent excisions decreased after the NICE guideline implementation: 27.2% (pre-NICE) versus 19.8% (post-NICE) (p = 0.001). A substantial regional variation (17.4%-34.5%) in the proportion of inadvertent excisions in the pre-NICE era was reduced in the post-NICE era (14.3%-22.4%). The 5-year disease-specific survival was 77.7% (pre-NICE) versus 75.6% (post-NICE) (p = 0.961) and there was a trend toward lower incidence of local recurrence in the post-NICE era; 13.5% (pre-NICE) versus 10.5% (post-NICE) (p = 0.522). Multivariate analyses revealed that residual tumours in re-resection specimens were independently associated with an increased risk of disease-specific mortality (HR, 3.35; p < 0.001) and local recurrence (HR, 1.99; p = 0.017), which was significantly reduced after the NICE guideline implementation (53.2% versus 42.0%; p = 0.022). CONCLUSIONS: The NICE guideline implementation reduced the proportion of patients with STS who had undergone inadvertent excisions and residual tumour in re-resection specimens, indicating an improved pre-referral management of STSs.

DOI： 10.1016/j.ejso.2021.11.013

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Long-Term Results of Kyocera Modular Limb Salvage System after Resection of Tumors in the Distal Part of the Femur: Report from Japanese Musculoskeletal Oncology Group Study. 国際誌

Tomoki Nakamura, Akihiko Matsumine, Yu Toda, Satoshi Takenaka, Hidetatsu Outani, Tomohiro Fujiwara, Yoshihiro Nishida, Satoshi Tsukushi, Yasunori Tome, Teruya Kawamoto, Munehisa Kito, Naohiro Shinohara, Masato Tomita, Tomoaki Torigoe, Akihiro Sudo, Hirotaka Kawano

Cancers 14 ( 4 ) 2022年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The distal femur is a common site of bone tumors. After surgical resection, prosthetic replacement is a major reconstruction method. We aimed to elucidate the long-term outcomes of the Kyocera Modular Limb Salvage (KMLS) systems after resection of tumors in the distal part of the femur. METHODS: Between 1998 and 2014, 125 patients were treated at 14 institutions. There were 59 males and 66 females, with a mean age of 35 years. The mean follow-up period was 132 months. RESULTS: There had been 65 additional surgeries, including 56 revisions and 9 amputations: 15 for aseptic loosening, 14 for stem breakage, 13 for deep infection, 13 for rotator-hinge bushing failure, 5 for local recurrence, and 5 for others. Implant survival rates at 10 and 15 years were 58.5% and 39.4%. The cumulative incidence of 15-year revision for femoral stem breakage was 31.7% in patients with cementless fixation. The 15-year cumulative incidence of revision for aseptic loosening was 19.8% in patients with cement fixation. CONCLUSIONS: KMLS systems represent a reliable system with long-term results. Stem breakage should be considered in patients with cementless and/or smaller femoral stem sizes. Aseptic loosening should be considered in patients with cement systems after 10 years.

DOI： 10.3390/cancers14040870

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Soft-tissue sarcoma in adolescents and young adults

Toshiyuki Kunisada, Eiji Nakata, Tomohiro Fujiwara, Ako Hosono, Shota Takihira, Hiroya Kondo, Toshifumi Ozaki

International Journal of Clinical Oncology 28 ( 1 ) 1 - 11 2022年1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：Springer Science and Business Media LLC

Soft-tissue sarcoma is a rare cancer that accounts for approximately 1% of all malignant tumors. Although they occur in various age groups, soft-tissue sarcomas account for 8% of all malignant tumors developing in adolescents and young adults, suggesting that they are not rare in this age group. This study aimed to evaluate the clinical and pathological characteristics of soft-tissue sarcoma in adolescents and young adults. According to the Bone and Soft-Tissue Tumor Registry in Japan, myxoid liposarcoma is the most common type of soft-tissue sarcoma found in adolescents and young adults; alveolar soft part sarcoma, extraskeletal Ewing sarcoma, epithelioid sarcoma, clear cell sarcoma and synovial sarcoma occur predominantly in this age group among soft-tissue sarcomas. The analysis based on this registry demonstrated that age was not a prognostic factor for poor survival of soft-tissue sarcoma, although the prognosis in adolescents and young adults was better than that in older patients in the US and Scandinavia. Adolescent and young adult patients with soft-tissue sarcoma have age-specific problems, and a multidisciplinary approach to physical, psychological, and social issues is necessary to improve the management of these young patients both during and after treatment.

DOI： 10.1007/s10147-022-02119-7

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その他リンク： https://link.springer.com/article/10.1007/s10147-022-02119-7/fulltext.html

The Role of Imaging in Computer-Assisted Tumor Surgery of the Sacrum and Pelvis. 国際誌

Andrea Sambri, Tomohiro Fujiwara, Michele Fiore, Claudio Giannini, Riccardo Zucchini, Luca Cevolani, Davide Maria Donati, Massimiliano De Paolis

Current medical imaging 18 ( 2 ) 137 - 141 2022年

記述言語：英語掲載種別：研究論文（学術雑誌）

The use of a navigation system allows precise resection of a tumor and accurate reconstruction of the resultant defect thereby sparing important anatomical structures and preserving function. It is an "image-based" system where the imaging (computed tomography and magnetic resonance imaging) is required to supply the software with data. The fusion of the preoperative imaging provides pre-operative information about local anatomy and extent of the tumor, so that it allows an accurate preoperative planning. Accurate pre-operative imaging is mandatory in order to minimize CATS errors, thus performing accurate tumor resections.

DOI： 10.2174/1573405617666210303105735

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