遺伝性疾患に好発する骨軟部腫瘍の腫瘍発生・悪性化メカニズムの解明と新規治療ターゲットの探索

Language：English   Publisher：International Journal of Clinical Oncology  

Introduction: Chemotherapy for breast cancer can cause neutropenia, increasing the risk of febrile neutropenia (FN) and serious infections. The use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis has been explored to mitigate these risks. To evaluate the efficacy and safety of primary G-CSF prophylaxis in patients with invasive breast cancer undergoing chemotherapy. Methods: A systematic literature review was conducted according to the “Minds Handbook for Clinical Practice Guideline Development” using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing using G-CSF as primary prophylaxis in invasive breast cancer were included. The primary outcomes were overall survival (OS) and FN incidence. Meta-analyses were performed for outcomes with sufficient data. Results: Eight RCTs were included in the qualitative analysis, and five RCTs were meta-analyzed for FN incidence. The meta-analysis showed a significant reduction in FN incidence with primary G-CSF prophylaxis (risk difference [RD] = 0.22, 95% CI: 0.01–0.43, p = 0.04). Evidence for improvement in OS with G-CSF was inconclusive. Four RCTs suggested a tendency for increased pain with G-CSF, but statistical significance was not reported. Conclusions: Primary prophylactic use of G-CSF is strongly recommended for breast cancer patients undergoing chemotherapy, as it has been shown to reduce the incidence of FN. While the impact on OS is unclear, the benefits of reducing FN are considered to outweigh the potential harm of increased pain.

DOI： 10.1007/s10147-024-02570-8

Web of Science

Scopus

PubMed

Language：English  

DOI： 10.1093/jjco/hyae095

Web of Science

PubMed

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

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：International Journal of Clinical Oncology  

Background: Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, “Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?” and CQ #2, “Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?”. Methods: A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain. Results: Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval. Conclusion: This review indicated that G-CSF’s efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma.

DOI： 10.1007/s10147-024-02572-6

Web of Science

Scopus

PubMed

Language：English   Publisher：International Journal of Clinical Oncology  

Background: Granulocyte colony-stimulating factor (G-CSF) is an essential supportive agent for chemotherapy-induced severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, “Does primary prophylaxis with G-CSF benefit chemotherapy for non-round cell soft tissue sarcoma (NRC-STS)?” and CQ #2, “Does G-CSF-based intensified chemotherapy improve NRC-STS treatment outcomes?” for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology. Methods: A literature search was performed on the primary prophylactic use of G-CSF for NRC-STSs. Two reviewers assessed the extracted papers and analyzed overall survival, incidence of febrile neutropenia, infection-related mortality, quality of life, and pain. Results: Eighty-one and 154 articles were extracted from the literature search for CQs #1 and #2, respectively. After the first and second screening, one and two articles were included in the final evaluation, respectively. Only some studies have addressed these two clinical questions through a literature review. Conclusion: The clinical questions were converted to future research questions because of insufficient available data. The statements were proposed: “The benefit of primary G-CSF prophylaxis is not clear in NRC-STS” and “The benefit of intensified chemotherapy with primary G-CSF prophylaxis is not clear in NRC-STSs.” G-CSF is often administered as primary prophylaxis when chemotherapy with severe myelosuppression is administered. However, its effectiveness and safety are yet to be scientifically proven.

DOI： 10.1007/s10147-024-02569-1

Web of Science

Scopus

PubMed

Web of Science

Web of Science

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：International Journal of Clinical Oncology  

Background: Febrile neutropenia represents a critical oncologic emergency, and its management is pivotal in cancer therapy. In several guidelines, the use of granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapy-induced febrile neutropenia is not routinely recommended except in high-risk cases. The Japan Society of Clinical Oncology has updated its clinical practice guidelines for the use of G-CSF, incorporating a systematic review to address this clinical question. Methods: The systematic review was conducted by performing a comprehensive literature search across PubMed, the Cochrane Library, and Ichushi-Web, focusing on publications from January 1990 to December 2019. Selected studies included randomized controlled trials (RCTs), non-RCTs, and cohort and case–control studies. Evaluated outcomes included overall survival, infection-related mortality, hospitalization duration, quality of life, and pain. Results: The initial search yielded 332 records. Following two rounds of screening, two records were selected for both qualitative and quantitative synthesis including meta-analysis. Regarding infection-related mortality, the event to case ratio was 5:134 (3.73%) in the G-CSF group versus 6:129 (4.65%) in the non-G-CSF group, resulting in a relative risk of 0.83 (95% confidence interval, 0.27–2.58; p = 0.54), which was not statistically significant. Only median values for hospitalization duration were available from the two RCTs, precluding a meta-analysis. For overall survival, quality of life, and pain, no suitable studies were found for analysis, rendering their assessment unfeasible. Conclusion: A weak recommendation is made that G-CSF treatment not be administered to patients with febrile neutropenia during cancer chemotherapy. G-CSF treatment can be considered for patients at high risk.

DOI： 10.1007/s10147-024-02541-z

Web of Science

Scopus

PubMed

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：International Journal of Clinical Oncology  

Background: Granulocyte colony-stimulating factor (G-CSF) reportedly reduces the risk of neutropenia and subsequent infections caused by cancer chemotherapy. Although several guidelines recommend using G-CSF in primary prophylaxis according to the incidence rate of chemotherapy-induced febrile neutropenia (FN), the effectiveness of G-CSF in digestive system tumor chemotherapy remains unclear. To address these clinical questions, we conducted a systematic review as part of revising the Clinical Practice Guidelines for the Use of G-CSF 2022 published by the Japan Society of Clinical Oncology. Methods: This systematic review addressed two main clinical questions (CQ): CQ1: “Is primary prophylaxis with G-CSF effective in chemotherapy?”, and CQ2: “Is increasing the intensity of chemotherapy with G-CSF effective?” We reviewed different types of digestive system tumors, including esophageal, gastric, pancreatic, biliary tract, colorectal, and neuroendocrine carcinomas. PubMed, Cochrane Library, and Ichushi-Web databases were searched for information sources. Independent systematic reviewers conducted two rounds of screening and selected relevant records for each CQ. Finally, the working group members synthesized the strength of evidence and recommendations. Results: After two rounds of screening, 5/0/3/0/2/0 records were extracted for CQ1 of esophageal/gastric/pancreatic/biliary tract/colorectal/ and neuroendocrine carcinoma, respectively. Additionally, a total of 2/6/1 records were extracted for CQ2 of esophageal/pancreatic/colorectal cancer, respectively. The strength of evidence and recommendations were evaluated for CQ1 of colorectal cancer; however, we could not synthesize recommendations for other CQs owing to the lack of records. Conclusion: The use of G-CSF for primary prophylaxis in chemotherapy for colorectal cancer is inappropriate.

DOI： 10.1007/s10147-024-02502-6

Web of Science

Scopus

PubMed

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：International Journal of Clinical Oncology  

Backgroud: Granulocyte colony-stimulating factor (G-CSF) is widely used for the primary prophylaxis of febrile neutropenia (FN). Two types of G-CSF are available in Japan, namely G-CSF chemically bound to polyethylene glycol (PEG G-CSF), which provides long-lasting effects with a single dose, and non-polyethylene glycol-bound G-CSF (non-PEG G-CSF), which must be sequentially administrated for several days. Methods: This current study investigated the utility of these treatments for the primary prophylaxis of FN through a systematic review of the literature. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis or meta-analysis was conducted to evaluate six outcomes. Results: Through the first and second screenings, 23 and 18 articles were extracted for qualitative synthesis and meta-analysis, respectively. The incidence of FN was significantly lower in the PEG G-CSF group than in the non-PEG G-CSF group with a strong quality/certainty of evidence. The differences in other outcomes, such as overall survival, infection-related mortality, the duration of neutropenia (less than 500/μL), quality of life, and pain, were not apparent. Conclusions: A single dose of PEG G-CSF is strongly recommended over multiple-dose non-PEG G-CSF therapy for the primary prophylaxis of FN.

DOI： 10.1007/s10147-024-02504-4

Web of Science

Scopus

PubMed

Language：English   Publisher：International Journal of Clinical Oncology  

Background: The outcomes of relapsed or refractory acute myeloid leukemia (AML) remain poor. Although the concomitant use of granulocyte colony-stimulating factor (G-CSF) and anti-chemotherapeutic agents has been investigated to improve the antileukemic effect on AML, its usefulness remains controversial. This study aimed to investigate the effects of G-CSF priming as a remission induction therapy or salvage chemotherapy. Methods: We performed a thorough literature search for studies related to the priming effect of G-CSF using PubMed, Ichushi-Web, and the Cochrane Library. A qualitative analysis of the pooled data was performed, and risk ratios (RRs) with confidence intervals (CIs) were calculated and summarized. Results: Two reviewers independently extracted and accessed the 278 records identified during the initial screening, and 62 full-text articles were assessed for eligibility in second screening. Eleven studies were included in the qualitative analysis and 10 in the meta-analysis. A systematic review revealed that priming with G-CSF did not correlate with an improvement in response rate and overall survival (OS). The result of the meta-analysis revealed the tendency for lower relapse rate in the G-CSF priming groups without inter-study heterogeneity [RR, 0.91 (95% CI 0.82–1.01), p = 0.08; I2 = 4%, p = 0.35]. In specific populations, including patients with intermediate cytogenetic risk and those receiving high-dose cytarabine, the G-CSF priming regimen prolonged OS. Conclusions: G-CSF priming in combination with intensive remission induction treatment is not universally effective in patients with AML. Further studies are required to identify the patient cohort for which G-CSF priming is recommended.

DOI： 10.1007/s10147-023-02461-4

Web of Science

Scopus

PubMed

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

DOI： 10.1302/0301-620X.106B5.BJJ-2023-1381

PubMed

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：International Journal of Clinical Oncology  

Background: Docetaxel (DTX) is commonly used as a primary chemotherapy, and cabazitaxel (CBZ) has shown efficacy in patients who are DTX resistant. Primary prophylactic granulocyte colony stimulating factor (G-CSF) therapy is currently used with CBZ treatment in routine clinical care in Japan. Methods: In this study, we performed a systematic review following the Minds guidelines to investigate the effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for prostate cancer and to construct G-CSF guidelines for primary prophylaxis use during chemotherapy. A comprehensive literature search of various electronic databases (PubMed, Cochrane Library, and Ichushi) was performed on January 10, 2020, to identify studies published between January 1990 and December 31, 2019 that investigate the impact of primary prophylaxis with G-CSF during CBZ administration on clinical outcomes. Results: Ultimately, nine articles were included in the qualitative systematic review. Primary G-CSF prophylaxis during CBZ administration for metastatic castration-resistant prostate cancer was difficult to assess in terms of correlation with overall survival, mortality from infection, and patients’ quality of life. These difficulties were owing to the lack of randomized controlled trials comparing patients with and without primary prophylaxis of G-CSF during CBZ administration. However, some retrospective studies have suggested that it may reduce the incidence of febrile neutropenia. Conclusion: G-CSF may be beneficial as primary prophylaxis during CBZ administration for metastatic castration resistant prostate cancer, and we made a “weak recommendation to perform” with an annotation of the relevant regimen.

DOI： 10.1007/s10147-024-02501-7

Web of Science

Scopus

PubMed

Language：English   Publisher：シュプリンガー・ジャパン(株)  

Language：English   Publisher：International Journal of Clinical Oncology  

Introduction: The timing of prophylactic pegylated granulocyte colony-stimulating factor (G-CSF) administration during cancer chemotherapy varies, with Day 2 and Days 3–5 being the most common schedules. Optimal timing remains uncertain, affecting efficacy and adverse events. This systematic review sought to evaluate the available evidence on the timing of prophylactic pegylated G-CSF administration. Methods: Based on the Minds Handbook for Clinical Practice Guideline Development, we searched the PubMed, Ichushi-Web, and Cochrane Library databases for literature published from January 1990 to December 2019. The inclusion criteria included studies among the adult population using pegfilgrastim. The search strategy focused on timing-related keywords. Two reviewers independently extracted and assessed the data. Results: Among 300 initial search results, only four articles met the inclusion criteria. A meta-analysis for febrile neutropenia incidence suggested a potential higher incidence when pegylated G-CSF was administered on Days 3–5 than on Day 2 (odds ratio: 1.27, 95% CI 0.66–2.46, p = 0.47), with a moderate certainty of evidence. No significant difference in overall survival or mortality due to infections was observed. The trend of severe adverse events was lower on Days 3–5, without statistical significance (odds ratio: 0.72, 95% CI 0.14–3.67, p = 0.69) and with a moderate certainty of evidence. Data on pain were inconclusive. Conclusions: Both Day 2 and Days 3–5 were weakly recommended for pegylated G-CSF administration post-chemotherapy in patients with cancer. The limited evidence highlights the need for further research to refine recommendations.

DOI： 10.1007/s10147-024-02499-y

Web of Science

Scopus

PubMed

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Although granulocyte colony-stimulating factor (G-CSF) reduces the incidence, duration, and severity of neutropenia, its prophylactic use for acute myeloid leukemia (AML) remains controversial due to a theoretically increased risk of relapse. The present study investigated the effects of G-CSF as primary prophylaxis for AML with remission induction therapy. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis of pooled data was conducted, and the risk ratio with corresponding confidence intervals was calculated in the meta-analysis and summarized. Sixteen studies were included in the qualitative analysis, nine of which were examined in the meta-analysis. Although G-CSF significantly shortened the duration of neutropenia, primary prophylaxis with G-CSF did not correlate with infection-related mortality. Moreover, primary prophylaxis with G-CSF did not affect disease progression/recurrence, overall survival, or adverse events, such as musculoskeletal pain. However, evidence to support or discourage the use of G-CSF as primary prophylaxis for adult AML patients with induction therapy remains limited. Therefore, the use of G-CSF as primary prophylaxis can be considered for adult AML patients with remission induction therapy who are at a high risk of infectious complications.

DOI： 10.1007/s10147-023-02465-0

Web of Science

Scopus

PubMed

researchmap

Other Link： https://link.springer.com/article/10.1007/s10147-023-02465-0/fulltext.html

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

Currently, it is difficult to predict the prognosis of myxoid liposarcoma (MLS) in biopsy specimens. In this study, we determined whether nuclear morphology may be used to predict the prognosis of MLS in primary biopsy specimens. Two pathologists evaluated nuclear morphology using the modified WHO/ISUP and Fuhrman grades. Survival analyses were performed by grouping nuclear high- and low-grades. We examined 53 MLS cases, which included 29 (54.7%) male and 24 (45.3%) female patients with a median age of 46 years (interquartile range, 37 - 60). In total, 7 (13.2%) and 16 (30.2%) cases were assigned to the high nuclear grade group based on the modified WHO/ISUP and Fuhrman gradings, respectively. Survival analyses revealed a significantly worse disease-free survival in the high-grade group (hazard ratio (HR), 7.51; 95% confidence interval (CI), 2.67-21.1, p < 0.001 by the modified WHO/ISUP grading; HR, 4.45; 95% CI, 1.63-12.1, p = 0.001 by the modified Fuhrman grading). Moreover, the modified WHO/ISUP grade showed a significantly worse overall survival in the high-grade group (HR, 4.39; 95% CI, 1.04-18.6, p = 0.028), and the modified Fuhrman grade exhibited a similar, but not significant, trend. Our results indicate that nuclear morphology grading is a good predictor of patient prognosis at the time of biopsy in MLS. Even when cell density is sparse, treatment strategies should be carefully considered when individual tumor cells exhibit atypical nuclei.

DOI： 10.1007/s00428-024-03796-7

Web of Science

Scopus

PubMed

researchmap

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

Low-grade central osteosarcoma (LGCOS), which arises from the intramedullary cavity of the metaphysis of long bones, occasionally exhibits extraosseous spread. Approximately 10-30% of patients with LGCOS exhibit dedifferentiation, but it is rare to experience a primary tumor with a dedifferentiated component. A 38-year-old female patient presented with right knee pain for two months. Imaging studies revealed a bone mass with extraosseous involvement. Wide resection was performed, and pathologic examination led to the diagnosis of LGCOS with a dedifferentiated extraosseous lesion. A single defect in the bone cortex constituted the boundary between the low- and high-grade components. The extraosseous high-grade component included more tumor cells with p53 overexpression and more murine double minute 2 (MDM2) copies compared with the low-grade component. These genetic mutations and copy number alterations can be associated with malignant transformation of LGCOS.

DOI： 10.1007/s00256-024-04647-x

Web of Science

Scopus

PubMed

researchmap

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s10147-024-02491-6

Web of Science

Scopus

PubMed

researchmap

Other Link： https://link.springer.com/article/10.1007/s10147-024-02491-6/fulltext.html

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s10147-024-02469-4

Web of Science

Scopus

PubMed

researchmap

Other Link： https://link.springer.com/article/10.1007/s10147-024-02469-4/fulltext.html

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

A glomus tumor is a benign mesenchymal tumor comprised of cells that resemble the perivascular modified smooth muscle cells of the glomus body. Glomus tumors typically appear in the superficial lesions of the soft tissue in the extremities, such as the subungual region. However, their occurrence in the bone is rare, with only about 30 cases reported to date. Half of these cases involved the distal phalanges of the fingers or toes, with only three reported cases involving the long bones. Here, we present the first case, a primary glomus tumor in the humerus of a 14-year-old female. An osteolytic and cystic lesion was detected after a pathological fracture occurred during exercise. Despite the tumor's large size, no pathological findings indicated malignancy. The fracture healed through conservative treatment, while the tumor was effectively managed with curettage. Appropriate medical care can be provided to patients by focusing on pathological findings.

DOI： 10.1007/s00256-024-04604-8

Web of Science

Scopus

PubMed

researchmap

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s42399-024-01648-8

researchmap

Other Link： https://link.springer.com/article/10.1007/s42399-024-01648-8/fulltext.html

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

BACKGROUND: Leiomyosarcomas are among the most common histological types of soft tissue sarcoma (STS), with no effective treatment available for advanced patients. Lung metastasis, the most common site of distant metastasis, is the primary prognostic factor. We analysed the immune environment targeting lung metastasis of STS to explore new targets for immunotherapy. METHODS: We analysed the immune environment of primary and lung metastases in 38 patients with STS using immunohistochemistry. Next, we performed gene expression analyses on primary and lung metastatic tissues from six patients with leiomyosarcoma. Using human leiomyosarcoma cell lines, the effects of the identified genes on immune cells were assessed in vitro. RESULTS: Immunohistochemistry showed a significant decrease in CD8+ cells in the lung metastases of leiomyosarcoma. Among the genes upregulated in lung metastases, epithelial cellular adhesion molecule (EPCAM) showed the strongest negative correlation with the number of CD8+ cells. Transwell assay results showed that the migration of CD8+ T cells was significantly increased in the conditioned media obtained after inhibition or knock down of EPCAM. CONCLUSIONS: EPCAM was upregulated in lung metastases of leiomyosarcoma, suggesting inhibition of CD8+ T cell migration. Our findings suggest that EPCAM could serve as a potential novel therapeutic target for leiomyosarcoma.

DOI： 10.1038/s41416-024-02576-z

Web of Science

Scopus

PubMed

researchmap

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

Prognosis after neoadjuvant chemotherapy (NAC) for osteosarcoma is generally predicted using manual necrosis-rate assessments; however, necrosis rates obtained in these assessments are not reproducible and do not adequately reflect individual cell responses. We aimed to investigate whether viable tumor cell density assessed using a deep-learning model (DLM) reflects the prognosis of osteosarcoma. Seventy-one patients were included in this study. Initially, the DLM was trained to detect viable tumor cells, following which it calculated their density. Patients were stratified into high and low-viable tumor cell density groups based on DLM measurements, and survival analysis was performed to evaluate disease-specific survival and metastasis-free survival (DSS and MFS). The high viable tumor cell density group exhibited worse DSS (p = 0.023) and MFS (p = 0.033). DLM-evaluated viable density showed correct stratification of prognosis groups. Therefore, this evaluation method may enable precise stratification of the prognosis in osteosarcoma patients treated with NAC.

DOI： 10.1038/s41698-024-00515-y

Web of Science

Scopus

PubMed

researchmap

Language：English   Publisher：Microsurgery  

Background: Concomitant resection of the sciatic nerve along with a malignant tumor is no longer a contraindication for limb-sparing surgery, as most of these patients remain ambulatory. However, sciatic nerve reconstruction after sarcoma resection is not commonly performed. Restoration of nerve function can improve patient quality of life. We describe our experience with four patients who underwent sciatic nerve reconstruction using an ipsilateral common peroneal nerve graft at the time of sarcoma resection. Methods: Because of the low chance of peroneal nerve recovery, the ipsilateral peroneal trunk was used as a graft to reconstruct the tibial trunk of the sciatic nerve. Two patients were men and two were women. Mean age was 45.3 years (range, 15–62). Mean sciatic nerve defect length was 9.4 cm (range, 8.5–12.0). Proximal thigh defects (three patients) were reconstructed with a double cable; the one patient with a distal thigh defect underwent single cable reconstruction. Mean operation time was 492 min (range, 428–682). Results: Mean length of the harvested peroneal trunks was 21 cm (range, 11–26). Mean graft length was 11.9 cm (range, 11–13). Postoperative course was uneventful in all four patients. One patient died of sarcoma lung metastasis and could not be evaluated. Three patients were followed for more than 2 years. Two patients achieved British Medical Research Council grade 4 plantar flexion; the remaining patient achieved grade 5 plantar flexion and grade 4 toe flexion. Semmes–Weinstein monofilament sensory testing showed loss of protective sensation on the plantar surface in all three. Musculoskeletal Tumor Society scores at last follow-up were 60.0%, 70.0%, and 43.3%, respectively. Conclusions: Immediate sciatic nerve reconstruction using an ipsilateral common peroneal nerve graft avoids reconstruction delay and scar tissue formation, which is advantageous for nerve recovery. This technique may be considered when sciatic nerve resection is anticipated during sarcoma resection.

DOI： 10.1002/micr.31034

Web of Science

Scopus

PubMed

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

AIMS: To evaluate mid-to long-term patient-reported outcome measures (PROMs) of endoprosthetic reconstruction after resection of malignant tumours arising around the knee, and to investigate the risk factors for unfavourable PROMs. METHODS: The medical records of 75 patients who underwent surgery between 2000 and 2020 were retrospectively reviewed, and 44 patients who were alive and available for follow-up (at a mean of 9.7 years postoperatively) were included in the study. Leg length discrepancy was measured on whole-leg radiographs, and functional assessment was performed with PROMs (Toronto Extremity Salvage Score (TESS) and Comprehensive Outcome Measure for Musculoskeletal Oncology Lower Extremity (COMMON-LE)) with two different aspects. The thresholds for unfavourable PROMs were determined using anchor questions regarding satisfaction, and the risk factors for unfavourable PROMs were investigated. RESULTS: The thresholds for favourable TESS and COMMON were 64.8 and 70.4 points, respectively. Multivariate analysis showed that age at surgery (p = 0.004) and postoperative leg length discrepancy (p = 0.043) were significant risk factors for unfavourable TESS results, while age at surgery (p < 0.001) was a significant risk factor for unfavourable COMMON-LE results. Following receiver operating characteristic analysis, the threshold for both TESS and COMMON-LE was 29 years of age at surgery. Additionally, a leg length discrepancy of 8.2 mm was the threshold for unfavourable TESS. CONCLUSION: Patients aged > 29 years at the time of surgery require appropriate preoperative counselling and adequate postoperative physical and socioemotional support. Reconstruction equivalent to the length of the resected bone can reduce the risk of functional disabilities in daily living.

DOI： 10.1302/2633-1462.412.BJO-2023-0125.R1

Web of Science

PubMed

researchmap

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.annonc.2023.09.142

Web of Science

researchmap

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Kurume University School of Medicine  

<p><b>Summary:</b> <i><b>Background</b></i><b>:</b> Small-sized tumors tend to be resected without thorough assessment and are often managed in a sarcoma center after a malignancy is diagnosed. The lack of knowledge about the features of smallsized sarcomas may lead to unplanned resection. The features of small-sized soft tissue sarcomas were investigated by comparing them with those of small benign soft tissue tumors. </p><p><i><b>Methods</b></i><b>:</b> We included 17 soft tissue sarcoma cases (7 on the hands and feet and 10 on the limbs and trunk) with a diameter of under 2 cm. The features of small-sized sarcomas were compared to those of 39 benign soft tissue tumors with a diameter of under 2 cm and non-specific imaging findings (30 on the hands and feet and 9 on the limbs and trunk). The investigated features were age, sex, presence of pain, subjective increasing tumor size, and duration of observation. </p><p><i><b>Results</b></i><b>:</b> When we compared the tumors in the hands and feet, those <40 years of age (5/7 [71%] vs. 8/30 [27%], p=0.03) experiencing pain (7/7 [100%] vs. 13/30 [43%], p=0.007) were more common in patients with sarcomas than in patients with benign tumors. When we compared the tumors in the limbs and trunk, there was no significant difference in all investigated features. </p><p><i><b>Conclusion</b></i><b>:</b> Although clinical features were ineffective in distinguishing malignancy in most small-sized soft tissue tumors, we should pay attention to painful tumors of the hands and feet in younger patients.</p>

DOI： 10.2739/kurumemedj.MS69120015

Scopus

PubMed

CiNii Research

researchmap

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

BACKGROUND: Approximately 1% of clinically treatable tyrosine kinase fusions, including anaplastic lymphoma kinase, neurotrophic tyrosine receptor kinase, RET proto-oncogene, and ROS proto-oncogene 1, have been identified in soft tissue sarcomas via comprehensive genome profiling based on DNA sequencing. Histologic tumor-specific fusion genes have been reported in approximately 20% of soft tissue sarcomas; however, unlike tyrosine kinase fusion genes, these fusions cannot be directly targeted in therapy. Approximately 80% of tumor-specific fusion-negative sarcomas, including myxofibrosarcoma and leiomyosarcoma, that are defined in complex karyotype sarcomas remain genetically uncharacterized; this mutually exclusive pattern of mutations suggests that other mutually exclusive driver oncogenes are yet to be discovered. Tumor-specific, fusion-negative sarcomas may be associated with unique translocations, and oncogenic fusion genes, including tyrosine kinase fusions, may have been overlooked in these sarcomas. QUESTIONS/PURPOSES: (1) Can DNA- or RNA-based analysis reveal any characteristic gene alterations in bone and soft tissue sarcomas? (2) Can useful and potential tyrosine kinase fusions in tumors from tumor-specific, fusion-negative sarcomas be detected using an RNA-based screening system? (3) Do the identified potential fusion tumors, especially in neurotrophic tyrosine receptor kinase gene fusions in bone sarcoma, transform cells and respond to targeted drug treatment in in vitro assays? (4) Can the identified tyrosine kinase fusion genes in sarcomas be useful therapeutic targets? METHODS: Between 2017 and 2020, we treated 100 patients for bone and soft tissue sarcomas at five institutions. Any biopsy or surgery from which a specimen could be obtained was included as potentially eligible. Ninety percent (90 patients) of patients were eligible; a further 8% (8 patients) were excluded because they were either lost to follow-up or their diagnosis was changed, leaving 82% (82 patients) for analysis here. To answer our first and second questions regarding gene alterations and potential tyrosine kinase fusions in eight bone and 74 soft tissue sarcomas, we used the TruSight Tumor 170 assay to detect mutations, copy number variations, and gene fusions in the samples. To answer our third question, we performed functional analyses involving in vitro assays to determine whether the identified tyrosine kinase fusions were associated with oncogenic abilities and drug responses. Finally, to determine usefulness as therapeutic targets, two pediatric patients harboring an NTRK fusion and an ALK fusion were treated with tyrosine kinase inhibitors in clinical trials. RESULTS: DNA/RNA-based analysis demonstrated characteristic alterations in bone and soft tissue sarcomas; DNA-based analyses detected TP53 and copy number alterations of MDM2 and CDK4. These single-nucleotide variants and copy number variations were enriched in specific fusion-negative sarcomas. RNA-based screening detected fusion genes in 24% (20 of 82) of patients. Useful potential fusions were detected in 19% (11 of 58) of tumor-specific fusion-negative sarcomas, with nine of these patients harboring tyrosine kinase fusion genes; five of these patients had in-frame tyrosine kinase fusion genes (STRN3-NTRK3, VWC2-EGFR, ICK-KDR, FOXP2-MET, and CEP290-MET) with unknown pathologic significance. The functional analysis revealed that STRN3-NTRK3 rearrangement that was identified in bone had a strong transforming potential in 3T3 cells, and that STRN3-NTRK3-positive cells were sensitive to larotrectinib in vitro. To confirm the usefulness of identified tyrosine kinase fusion genes as therapeutic targets, patients with well-characterized LMNA-NTRK1 and CLTC-ALK fusions were treated with tyrosine kinase inhibitors in clinical trials, and a complete response was achieved. CONCLUSION: We identified useful potential therapeutic targets for tyrosine kinase fusions in bone and soft tissue sarcomas using RNA-based analysis. We successfully identified STRN3-NTRK3 fusion in a patient with leiomyosarcoma of bone and determined the malignant potential of this fusion gene via functional analyses and drug effects. In light of these discoveries, comprehensive genome profiling should be considered even if the sarcoma is a bone sarcoma. There seem to be some limitations regarding current DNA-based comprehensive genome profiling tests, and it is important to use RNA testing for proper diagnosis and accurate identification of fusion genes. Studies on more patients, validation of results, and further functional analysis of unknown tyrosine kinase fusion genes are required to establish future treatments. CLINICAL RELEVANCE: DNA- and RNA-based screening systems may be useful for detecting tyrosine kinase fusion genes in specific fusion-negative sarcomas and identifying key therapeutic targets, leading to possible breakthroughs in the treatment of bone and soft tissue sarcomas. Given that current DNA sequencing misses fusion genes, RNA-based screening systems should be widely considered as a worldwide test for sarcoma. If standard treatments such as chemotherapy are not effective, or even if the sarcoma is of bone, RNA sequencing should be considered to identify as many therapeutic targets as possible.

DOI： 10.1097/CORR.0000000000002901

Web of Science

Scopus

PubMed

researchmap

Language：Japanese  

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

BACKGROUND: Patients undergoing massive tumor resection and total femur replacement (TFR) face a substantial risk of hip dislocation and infection, often resulting in multiple implant revisions or hip disarticulation. These complications can impact their independence and prognosis. Additionally, their shorter life expectancy is influenced by challenges in achieving local radical resection and controlling metastases. Identifying suitable candidates for TFR is vital, necessitating investigations into dislocation, infection, implant failure rates, local recurrence, overall survival, and associated factors. QUESTIONS/PURPOSES: (1) What is the postsurgical complication (hip dislocation and infection) rate and factors associated with postsurgical complications in patients who underwent TFR after tumor resection? (2) What is the local recurrence rate, implant failure rate, overall survival rate, and factors associated with local recurrence and implant failure? METHODS: We retrospectively evaluated 42 patients (median [range] age 47 years [10 to 79 years]) who underwent TFR and tumor resection at the time of the same surgical procedure between 1990 and 2020 at 12 registered institutions that specialized in tumor treatment in Japan. A total of 55% (23) of the patients were men, and 79% (33) had bone sarcoma. The median (range) follow-up period was 36.5 months (2 to 327 months). Of the 42 patients, 12% (5) were lost to follow-up before 2 years without meeting a study endpoint (postsurgical complications, revision, or amputation), and another 19% (8) died before 2 years with implants intact, leaving 69% (29) of the original group who had either follow-up of at least 2 years or met a study endpoint before the minimum surveillance duration. Another 10% (4) had a minimum of 2 years of follow-up but had not been seen in the past 5 years. Infection was defined as deep-seated infection involving soft tissues, bones, joints, and the area around the implant. We did not consider superficial infections. Implant failure was defined when a patient underwent reimplantation or amputation. The complication and implant failure rates were assessed by the cumulative incidence function method, considering competing events. The Kaplan-Meier method was used to estimate the overall survival rate. RESULTS: The 1-month, 6-month, 1-year, and 2-year dislocation rates were 5%, 12%, 14%, and 14%, respectively. The 1-month, 6-month, 1-year, and 2-year infection rates were 5%, 7%, 10%, and 15%, respectively. Multivariable analyses for hip dislocation and infection revealed that resection of the abductor muscles and large tumor size were positively associated with hip dislocation. The 6-month, 1-year, and 2-year local recurrence rates were 5%, 15%, and 15%, respectively. The 6-month, 1-year, 2-year, and 5-year implant failure rates were 5% (95% confidence interval 1% to 15%), 7% (95% CI 2% to 18%), 16% (95% CI 6% to 29%), and 16% (95% CI 6% to 29%), respectively. Multivariable analyses of local recurrence and implant failure that led to reimplantation or amputation revealed that a positive surgical margin was positively associated with local recurrence. The 1-year, 2-year, and 5-year overall patient survival rates were 95% (95% CI 87% to 102%), 77% (95% CI 64% to 91%), and 64% (95% CI 48% to 81%), respectively. CONCLUSION: Hip dislocation, infection, and local recurrence were frequently observed in patients who received massive tumor resection and TFR in our study, eventually leading to reimplantation or amputation. Preserving the abductor muscles and resecting the tumor with a wide margin can prevent postoperative dislocation and local recurrence. Future research should focus on patient selection criteria, prevention of hip dislocation, and innovative treatments. LEVEL OF EVIDENCE: Level IV, therapeutic study.

DOI： 10.1097/CORR.0000000000002874

Web of Science

Scopus

PubMed

researchmap

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

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

DOI： 10.1158/1078-0432.CCR-23-1456

Web of Science

Scopus

PubMed

researchmap

Language：English  

Mesenchymal chondrosarcoma is a rare subset of sarcomas accounting for 3%-10% of all cases of chondrosarcomas. Radical resection is the only curative strategy, even in patients with metastatic tumors. However, data regarding treatment strategies remain limited owing to the small number of cases. Herein, we report a patient who underwent repeated robotic pancreatectomy for recurrent pancreatic metastasis originating from extraskeletal mesenchymal chondrosarcoma of the pelvis. First, robotic pancreaticoduodenectomy with a reconstruction of pancreaticogastrostomy was performed for synchronous pancreatic metastasis 5 months after the primary resection of mesenchymal chondrosarcoma. Ten months after robotic pancreaticoduodenectomy, tumor recurrence was observed at the tail end of the pancreas, which was removed by reperforming robotic distal pancreatectomy. Given the precise tissue manipulation that can be achieved with robotic articulated forceps, the peripheral splenic artery and pancreas were easily isolated and divided in close proximity to the tumor. The central part of the pancreas was preserved. Robotic surgery allowed safe and effective resection of the reconstructed remnant pancreas. The patient survived for 28 months after primary tumor resection. Repeated pancreatectomy with minimally invasive techniques is a feasible and curative treatment for metastatic mesenchymal chondrosarcoma.

DOI： 10.1111/ases.13240

Web of Science

Scopus

PubMed

researchmap

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

Sarcomas are malignant mesenchymal tumors that are extremely rare and divergent. Fusion genes are involved in approximately 30% of sarcomas as driver oncogenes; however, their detailed functions are not fully understood. In this study, we determined the functional significance of 59 sarcoma-related fusion genes. The transforming potential and drug sensitivities of these fusion genes were evaluated using a focus formation assay (FFA) and the mixed-all-nominated-in-one (MANO) method, respectively. The transcriptome was also examined using RNA sequencing of 3T3 cells transduced with each fusion gene. Approximately half (28/59, 47%) of the fusion genes exhibited transformation in the FFA assay, which was classified into five types based on the resulting phenotype. The sensitivity to 12 drugs including multityrosine kinase inhibitors was assessed using the MANO method and pazopanib was found to be more effective against cells expressing the COL1A1-PDGFB fusion gene compared with the others. The downstream MAPK/AKT pathway was suppressed at the protein level following pazopanib treatment. The fusion genes were classified into four subgroups by cluster analysis of the gene expression data and gene set enrichment analysis. In summary, the oncogenicity and drug sensitivity of 59 fusion genes were simultaneously evaluated using a high-throughput strategy. Pazopanib was selected as a candidate drug for sarcomas harboring the COL1A1-PDGFB fusion gene. This assessment could be useful as a screening platform and provides a database to evaluate customized therapy for fusion gene-associated sarcomas.

DOI： 10.1111/cas.15915

Web of Science

Scopus

PubMed

researchmap

Language：Japanese  

Language：Japanese  

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

症例は45歳女性。2年前からの左股間痛を主訴に来院した。特記すべき既往や家族歴はなかった。腹部造影CTで、左外閉鎖筋に内部が不均一で、粗大石灰化像を伴う径70mmの腫瘍病変を認めた。また膵体部に径22mmの嚢胞性腫瘍を認めた。全身CTを施行したが、骨盤と膵臓以外に腫瘍は検出されなかった。CTガイド下生検で骨盤内腫瘍は軟骨性腫瘍と診断され、外科的切除術を施行した。切除標本の病理組織学的検査で濃染性の腫大した核を有する紡錘形細胞と腫瘍性軟骨細胞の増殖を認めた。免疫組織化学染色でCD99、BCOR、NKX2.2に陽性を呈し、間葉型軟骨肉腫と診断した。術後に超音波内視鏡下穿刺吸引法を施行し、膵癌は間葉型軟骨肉腫の膵転移と診断した。5ヵ月後にロボット支援下に膵頭十二指腸切除術を施行した。10ヵ月後のCTで膵尾部に石灰化を伴う低吸収腫瘤を認めた。間葉型軟骨肉腫の膵転移再発と診断し、ロボット支援下膵切除術を施行した。手術時間は315分、術中出血量は170mLであった。8ヵ月後に骨盤内腫瘍の再発を認め、切除術を施行した。初回のロボット支援下手術から28ヵ月後の現在も無再発生存中である。

Language：Japanese   Publisher：西日本整形・災害外科学会  

researchmap

Language：Japanese   Publisher：西日本整形・災害外科学会  

researchmap

Language：English   Publisher：John Wiley & Sons Australia, Ltd  

肉腫に関連している59種の融合遺伝子を対象に、それらの機能的意義を決定した。フォーカス形成アッセイで形質転換能を示した融合遺伝子は28種(47%)あり、それらは生じさせた形質によって5種類に分類された。マルチチロシンキナーゼ阻害剤を含む12種の薬剤への感受性をmixed-all-nominated-in-one(MANO)法で評価した。その結果、COL1A1-PDGFB融合遺伝子を発現している細胞に対してはパゾパニブがより効果的であることが判明した。パゾパニブで処理すると下流のMAPK/AKT経路は蛋白質レベルで抑制された。遺伝子発現データによるクラスター分析および遺伝子セットエンリッチメント解析の結果、融合遺伝子類は4種類の亜集団に分類された。本研究により、59種の融合遺伝子の発癌性と薬剤感受性が、ハイスループット的な方策を用いて同時評価され、COL1A1-PDGFB融合遺伝子を持つ肉腫への薬剤候補としてパゾパニブが選出された。

Language：Japanese   Publisher：西日本整形・災害外科学会  

researchmap

Language：Japanese   Publisher：西日本整形・災害外科学会  

<p>Klippel-Trenaunay-Weber症候群（以下KTW症候群）は先天性の脈管異常と四肢肥大を来す疾患であるが，長管骨内に腫瘍性病変を生じることは稀である．今回，大腿骨に浸潤性の血管腫を生じたKTW症候群症例を経験したので報告する．症例は7歳男児．出生直後より両下肢に脈管異常が認められ，KTW症候群，両巨趾症と診断されていた．6歳時に単純X線にて右大腿骨遠位に骨透亮像が認められ次第に拡大してきた．MRIでは不均一に造影される腫瘤性病変による骨浸潤像が認められ，CTでは骨皮質が欠損していた．腫瘍動脈塞栓術を施行した上で，腫瘍切除および人工骨移植術を施行した．皮下組織には易出血性の脈管が多数認められた．病変部位には厚い骨膜に連続した柔らかい血管性病変が認められ，小さな骨孔から大腿骨内に連続していた．病理組織診断は血管腫であり，骨内流入血管の血管腫性変化による骨浸潤と考えられた．</p>

DOI： 10.5035/nishiseisai.72.841

CiNii Research

Language：Japanese  

Klippel-Trenaunay-Weber症候群(以下KTW症候群)は先天性の脈管異常と四肢肥大を来す疾患であるが,長管骨内に腫瘍性病変を生じることは稀である.今回,大腿骨に浸潤性の血管腫を生じたKTW症候群症例を経験したので報告する.症例は7歳男児.出生直後より両下肢に脈管異常が認められ,KTW症候群,両巨趾症と診断されていた.6歳時に単純X線にて右大腿骨遠位に骨透亮像が認められ次第に拡大してきた.MRIでは不均一に造影される腫瘤性病変による骨浸潤像が認められ,CTでは骨皮質が欠損していた.腫瘍動脈塞栓術を施行した上で,腫瘍切除および人工骨移植術を施行した.皮下組織には易出血性の脈管が多数認められた.病変部位には厚い骨膜に連続した柔らかい血管性病変が認められ,小さな骨孔から大腿骨内に連続していた.病理組織診断は血管腫であり,骨内流入血管の血管腫性変化による骨浸潤と考えられた.(著者抄録)

Language：Japanese   Publisher：西日本整形・災害外科学会  

Klippel-Trenaunay-Weber症候群(以下KTW症候群)は先天性の脈管異常と四肢肥大を来す疾患であるが,長管骨内に腫瘍性病変を生じることは稀である.今回,大腿骨に浸潤性の血管腫を生じたKTW症候群症例を経験したので報告する.症例は7歳男児.出生直後より両下肢に脈管異常が認められ,KTW症候群,両巨趾症と診断されていた.6歳時に単純X線にて右大腿骨遠位に骨透亮像が認められ次第に拡大してきた.MRIでは不均一に造影される腫瘤性病変による骨浸潤像が認められ,CTでは骨皮質が欠損していた.腫瘍動脈塞栓術を施行した上で,腫瘍切除および人工骨移植術を施行した.皮下組織には易出血性の脈管が多数認められた.病変部位には厚い骨膜に連続した柔らかい血管性病変が認められ,小さな骨孔から大腿骨内に連続していた.病理組織診断は血管腫であり,骨内流入血管の血管腫性変化による骨浸潤と考えられた.(著者抄録)

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J00766&link_issn=&doc_id=20231208120063&doc_link_id=10.5035%2Fnishiseisai.72.841&url=https%3A%2F%2Fdoi.org%2F10.5035%2Fnishiseisai.72.841&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：西日本整形・災害外科学会  

Klippel-Trenaunay-Weber症候群(以下KTW症候群)は先天性の脈管異常と四肢肥大を来す疾患であるが,長管骨内に腫瘍性病変を生じることは稀である.今回,大腿骨に浸潤性の血管腫を生じたKTW症候群症例を経験したので報告する.症例は7歳男児.出生直後より両下肢に脈管異常が認められ,KTW症候群,両巨趾症と診断されていた.6歳時に単純X線にて右大腿骨遠位に骨透亮像が認められ次第に拡大してきた.MRIでは不均一に造影される腫瘤性病変による骨浸潤像が認められ,CTでは骨皮質が欠損していた.腫瘍動脈塞栓術を施行した上で,腫瘍切除および人工骨移植術を施行した.皮下組織には易出血性の脈管が多数認められた.病変部位には厚い骨膜に連続した柔らかい血管性病変が認められ,小さな骨孔から大腿骨内に連続していた.病理組織診断は血管腫であり,骨内流入血管の血管腫性変化による骨浸潤と考えられた.(著者抄録)

Web of Science

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

Language：Japanese   Publisher：(一社)日本骨・関節感染症学会  

researchmap

Language：Japanese   Publisher：(一社)日本骨・関節感染症学会  

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

Language：Japanese   Publisher：The Japanese Society of Clinical Pharmacology and Therapeutics  

DOI： 10.3999/jscpt.54.3_135

CiNii Research

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

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

AIMS: Liposarcoma is a malignant soft tissue tumour with adipocytic differentiation. Dedifferentiated liposarcoma (DDLS) and myxoid liposarcoma (MLS) are classified as high-grade liposarcomas. Lipid droplet-associated protein (also known as perilipin 1 (PLIN1)) is the predominant perilipin and has utility as a specific marker of adipogenic differentiation. Adipose differentiation-related protein (also known as adipophilin (ADRP)) is ubiquitously expressed in a range of tissues. High ADRP expression is reportedly a poor prognostic factor in several cancer types. However, no previous studies have examined the association between PLIN1 or ADRP expression and prognosis in sarcoma. This study therefore aimed to evaluate the association between PLIN1 or ADRP expression and prognosis in liposarcoma. METHODS: In total, 97 primary resection specimens (53 MLS and 44 DDLS) were examined in this study. PLIN1 and ADRP expression was evaluated by immunohistochemistry. Survival analyses were performed for MLS and DDLS. RESULTS: Of the 53 MLS specimens, 15 (28.3%) exhibited high PLIN1 expression. PLIN1 expression was not observed in DDLS specimens. High PLIN1 expression was significantly associated with increased disease-free survival (DFS) among patients with MLS (p=0.045). Distinct ADRP expression was observed in 13 of 53 (24.5%) MLS specimens and 5 of 44 (11.4%) DDLS specimens. High ADRP expression was associated with shorter overall survival (OS) in MLS (p=0.042) and DFS and shorter OS in DDLS (p=0.024 and p<0.001, respectively). CONCLUSIONS: PLIN1 and ADRP expression is associated with poor prognosis in high-grade liposarcoma.

DOI： 10.1136/jcp-2023-208814

Web of Science

Scopus

PubMed

researchmap

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

Publishing type：Research paper (scientific journal)  

Web of Science

researchmap

Publishing type：Research paper (scientific journal)  

Web of Science

researchmap

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

This retrospective multicenter study aimed to analyze the clinical features and prognosis of 24 patients diagnosed with LGMS between 2002 and 2019 in the Japanese sarcoma network. Twenty-two cases were surgically treated and two cases were treated with radical radiotherapy (RT). The pathological margin was R0 in 14 cases, R1 in 7 cases, and R2 in 1 case. The best overall response in the two patients who underwent radical RT was one complete response and one partial response. Local relapse occurred in 20.8% of patients. Local relapse-free survival (LRFS) was 91.3% at 2 years and 75.4% at 5 years. In univariate analysis, tumors of 5 cm or more were significantly more likely to cause local relapse (p < 0.01). In terms of the treatment of relapsed tumors, surgery was performed in two cases and radical RT was performed in three cases. None of the patients experienced a second local relapse. Disease-specific survival was 100% at 5 years. A wide excision aimed at the microscopically R0 margin is considered the standard treatment for LGMS. However, RT may be a viable option in unresectable cases or in cases where surgery is expected to cause significant functional impairment.

DOI： 10.3390/cancers15082314

Web of Science

Scopus

PubMed

researchmap

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

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

BACKGROUND: Soft tissue sarcomas (STS) are a rare type of malignancy comprising a variety of histological diagnoses. Chemotherapy constitutes the standard treatment for advanced STS. Doxorubicin-based regimens, which include the administration of doxorubicin alone or in combination with ifosfamide or dacarbazine, are widely accepted as first-line chemotherapy for advanced STS. Trabectedin, eribulin, pazopanib, and gemcitabine plus docetaxel (GD), which is the empirical standard therapy in Japan, are major candidates for second-line chemotherapy for advanced STS, although clear evidence of the superiority of any one regimen is lacking. The Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group (JCOG) conducts this trial to select the most promising regimen among trabectedin, eribulin, and pazopanib for comparison with GD as the test arm regimen in a future phase III trial of second-line treatment for patients with advanced STS. METHODS: The JCOG1802 study is a multicenter, selection design, randomized phase II trial comparing trabectedin (1.2 mg/m2 intravenously, every 3 weeks), eribulin (1.4 mg/m2 intravenously, days 1 and 8, every 3 weeks), and pazopanib (800 mg orally, every day) in patients with unresectable or metastatic STS refractory to doxorubicin-based first-line chemotherapy. The principal eligibility criteria are patients aged 16 years or above; unresectable and/or metastatic STS; exacerbation within 6 months prior to registration; histopathological diagnosis of STS other than Ewing sarcoma, embryonal/alveolar rhabdomyosarcoma, well-differentiated liposarcoma and myxoid liposarcoma; prior doxorubicin-based chemotherapy for STS, and Eastern Cooperative Oncology Group performance status 0 to 2. The primary endpoint is progression-free survival, and the secondary endpoints include overall survival, disease-control rate, response rate, and adverse events. The total planned sample size to correctly select the most promising regimen with a probability of > 80% is 120. Thirty-seven institutions in Japan will participate at the start of this trial. DISCUSSION: This is the first randomized trial to evaluate trabectedin, eribulin, and pazopanib as second-line therapies for advanced STS. We endeavor to perform a subsequent phase III trial comparing the best regimen selected by this study (JCOG1802) with GD. TRIAL REGISTRATION: This study was registered with the Japan Registry of Clinical Trials ( jRCTs031190152 ) on December 5, 2019.

DOI： 10.1186/s12885-023-10693-w

Web of Science

Scopus

PubMed

researchmap

Language：Japanese  

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

Language：Japanese   Publisher：The Japanese Society for Spine Surgery and Related Research  

<p><b>Introduction: </b>The spinal instability neoplastic score (SINS) is a classification system used to diagnose neoplastic spinal instability. Several reports have also described its use as a screening tool to identify patients at risk of skeletal-related events. We investigated the efficacy of SINS to detect the risk of neurological deficit in patients with spinal metastases by assessing spinal metastatic instability before the onset of myelopathy.</p><p><b>Methods: </b>We performed surgery on 81 patients with cervical or thoracic lesions classified as metastatic spine disease between 2004 and 2019. In this cohort, spinal instability was assessed in 29/81 patients before the occurrence of myelopathy. Spinal instability was evaluated by SINS with computed tomography (CT) performed within 6 months of the neurological deficit. We defined patients with a score of 7 or higher as at-risk patients.</p><p><b>Results: </b>CT was performed at an average of 72 days before the onset of neurological deficits. The SINS were 2 no-metastases cases, 4 of less than 7 (stability), 15 of 7-12 (indeterminate instability), and 8 of 13-18 (instability). We were unable to detect 21% (6/29) patients at risk of SINS.</p><p><b>Conclusions: </b>We may not be able to detect approximately 20% at-risk patients with neurological deficits by SINS before myelopathy presents.</p>

DOI： 10.34371/jspineres.2022-0021

CiNii Research

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

Abstract

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

DOI： 10.1002/ijc.34453

Web of Science

Scopus

PubMed

researchmap

Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/ijc.34453

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

INTRODUCTION: In patients with chronic pain, oral analgesics are essential treatment options to manage pain appropriately, improve activities of daily living abilities and achieve a higher quality of life (QOL). It is desirable to select analgesics for elderly patients based on comparative data on analgesic effect and risk of adverse events; however, there are few comparative studies so far. The purpose of this study is to determine whether the efficacy and safety of acetaminophen are non-inferior to non-steroidal anti-inflammatory drugs (NSAIDs) in the treatment of chronic pain associated with osteoarthritis of the hip and knee in elderly patients. METHODS AND ANALYSIS: This study is a multicentre, randomised controlled, double-blind, parallel-group study to compare the analgesic effect and adverse events between acetaminophen or NSAIDs (loxoprofen or celecoxib). A total of 400 elderly patients with osteoarthritis of the hip and knee will be recruited from five institutions in Japan. Patients of 65 years or older with osteoarthritis-related pain will be registered and randomly assigned to acetaminophen, loxoprofen or celecoxib with 2:1:1 allocation. The primary endpoint is change in the Brief Pain Inventory (BPI) item 3 (worst pain) score from baseline to week 8. The secondary endpoints are BPI item 3 score change from baseline to week 4, health-related QOL measured by Short Form-8 Health Survey, and occurrence of adverse events including gastrointestinal disorders and abnormal liver function. Data will be analysed in accordance with a predefined statistical analysis plan. ETHICS AND DISSEMINATION: This study protocol was approved by the Kyushu University Hospital Certified Institutional Review Board for Clinical Trials on 28 January 2021 (KD2020004) and the chief executive of each participating hospital. The results of the study will be submitted to international peer-reviewed journals, and the main findings will be presented at international scientific conferences. TRIAL REGISTRATION NUMBER: jRCTs071200112.

DOI： 10.1136/bmjopen-2022-068220

Web of Science

Scopus

PubMed

researchmap

Language：Japanese  

はじめに:Spinal Instability Neoplastic Score(SINS)は転移性脊椎腫瘍の不安定性評価法であるが,骨有害事象リスク患者を検出する際のスクリーニング手段としても使用が報告されている.転移性脊椎腫瘍による脊髄症状発症例から,脊髄症状発症前のSINSを測定することにより,SINSによるリスク患者検出の有効性について検証した.対象と方法:2004年から2019年,頸胸椎部の転移性脊椎腫瘍に対する手術例81例から,脊髄症状発症前の画像評価が可能であった29例について調査した.脊髄症状発症半年以内に撮影されたCTからSINSを測定し,SINS7以上をリスク患者とした.結果:CT撮影時期は脊髄症状発症の平均72日前であった.SINSは転移なし2例,7未満(stability)4例,7以上～13未満(indeterminate instability)15例,13以上(instability)8例であり,21%(6/29)はリスク患者とならなかった.結語:脊髄症状発症前のSINSによる評価では約20%で脊髄症状発症の危険性を検出できない可能性が示唆された.(著者抄録)

Language：Japanese  

はじめに:Spinal Instability Neoplastic Score(SINS)は転移性脊椎腫瘍の不安定性評価法であるが,骨有害事象リスク患者を検出する際のスクリーニング手段としても使用が報告されている.転移性脊椎腫瘍による脊髄症状発症例から,脊髄症状発症前のSINSを測定することにより,SINSによるリスク患者検出の有効性について検証した.対象と方法:2004年から2019年,頸胸椎部の転移性脊椎腫瘍に対する手術例81例から,脊髄症状発症前の画像評価が可能であった29例について調査した.脊髄症状発症半年以内に撮影されたCTからSINSを測定し,SINS7以上をリスク患者とした.結果:CT撮影時期は脊髄症状発症の平均72日前であった.SINSは転移なし2例,7未満(stability)4例,7以上～13未満(indeterminate instability)15例,13以上(instability)8例であり,21%(6/29)はリスク患者とならなかった.結語:脊髄症状発症前のSINSによる評価では約20%で脊髄症状発症の危険性を検出できない可能性が示唆された.(著者抄録)

Web of Science

Language：Japanese   Publisher：(一社)日本脊椎脊髄病学会  

はじめに:Spinal Instability Neoplastic Score(SINS)は転移性脊椎腫瘍の不安定性評価法であるが,骨有害事象リスク患者を検出する際のスクリーニング手段としても使用が報告されている.転移性脊椎腫瘍による脊髄症状発症例から,脊髄症状発症前のSINSを測定することにより,SINSによるリスク患者検出の有効性について検証した.対象と方法:2004年から2019年,頸胸椎部の転移性脊椎腫瘍に対する手術例81例から,脊髄症状発症前の画像評価が可能であった29例について調査した.脊髄症状発症半年以内に撮影されたCTからSINSを測定し,SINS7以上をリスク患者とした.結果:CT撮影時期は脊髄症状発症の平均72日前であった.SINSは転移なし2例,7未満(stability)4例,7以上～13未満(indeterminate instability)15例,13以上(instability)8例であり,21%(6/29)はリスク患者とならなかった.結語:脊髄症状発症前のSINSによる評価では約20%で脊髄症状発症の危険性を検出できない可能性が示唆された.(著者抄録)

Language：Japanese   Publisher：(一社)日本脊椎脊髄病学会  

はじめに:Spinal Instability Neoplastic Score(SINS)は転移性脊椎腫瘍の不安定性評価法であるが,骨有害事象リスク患者を検出する際のスクリーニング手段としても使用が報告されている.転移性脊椎腫瘍による脊髄症状発症例から,脊髄症状発症前のSINSを測定することにより,SINSによるリスク患者検出の有効性について検証した.対象と方法:2004年から2019年,頸胸椎部の転移性脊椎腫瘍に対する手術例81例から,脊髄症状発症前の画像評価が可能であった29例について調査した.脊髄症状発症半年以内に撮影されたCTからSINSを測定し,SINS7以上をリスク患者とした.結果:CT撮影時期は脊髄症状発症の平均72日前であった.SINSは転移なし2例,7未満(stability)4例,7以上～13未満(indeterminate instability)15例,13以上(instability)8例であり,21%(6/29)はリスク患者とならなかった.結語:脊髄症状発症前のSINSによる評価では約20%で脊髄症状発症の危険性を検出できない可能性が示唆された.(著者抄録)

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J05510&link_issn=&doc_id=20230227380004&doc_link_id=%2Ffg7spine%2F2023%2F001402%2F005%2F0082-0087%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Ffg7spine%2F2023%2F001402%2F005%2F0082-0087%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(一社)日本脊椎脊髄病学会  

はじめに:Spinal Instability Neoplastic Score(SINS)は転移性脊椎腫瘍の不安定性評価法であるが,骨有害事象リスク患者を検出する際のスクリーニング手段としても使用が報告されている.転移性脊椎腫瘍による脊髄症状発症例から,脊髄症状発症前のSINSを測定することにより,SINSによるリスク患者検出の有効性について検証した.対象と方法:2004年から2019年,頸胸椎部の転移性脊椎腫瘍に対する手術例81例から,脊髄症状発症前の画像評価が可能であった29例について調査した.脊髄症状発症半年以内に撮影されたCTからSINSを測定し,SINS7以上をリスク患者とした.結果:CT撮影時期は脊髄症状発症の平均72日前であった.SINSは転移なし2例,7未満(stability)4例,7以上～13未満(indeterminate instability)15例,13以上(instability)8例であり,21%(6/29)はリスク患者とならなかった.結語:脊髄症状発症前のSINSによる評価では約20%で脊髄症状発症の危険性を検出できない可能性が示唆された.(著者抄録)

researchmap

Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J05510&link_issn=&doc_id=20230227380004&doc_link_id=10.34371%2Fjspineres.2022-0021&url=https%3A%2F%2Fdoi.org%2F10.34371%2Fjspineres.2022-0021&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：BMJ  

Introduction

Adoptive cell transfer of genetically engineered T cells is a promising treatment for malignancies; however, there are few ideal cancer antigens expressed on the cell surface, and the development of chimeric antigen receptor T cells (CAR-T cells) for solid tumour treatment has been slow. CAR-T cells, which recognise major histocompatibility complex and peptide complexes presented on the cell surface, can be used to target not only cell surface antigens but also intracellular antigens. We have developed a CAR-T-cell product that recognises the complex of HLA-A*02:01 and an epitope of the MAGE-A4 antigen equipped with a novel signalling domain of human GITR (investigational product code: MU-MA402C) based on preclinical studies.

Methods and analysis

This is a dose-escalation, multi-institutional, phase 1 study to evaluate the tolerability and safety of MU-MA402C for patients with MAGE A4-positive and HLA-A*02:01-positive unresectable advanced or recurrent solid cancer. Two dose cohorts are planned: cohort 1, MU-MA402C 2×10⁸/person; cohort 2, MU-MA402C 2×10⁹/person. Prior to CAR-T-cell infusion, cyclophosphamide (CPA) and fludarabine (FLU) will be administered as preconditioning chemotherapy. Three evaluable subjects per cohort, for a total of 6 subjects (maximum of 12 subjects), will be recruited for this clinical trial. The primary endpoints are safety and tolerability. The severity of each adverse event will be evaluated in accordance with Common Terminology Criteria for Adverse Events V.5.0. The secondary endpoint is efficacy. Antitumour response will be evaluated according to Response Evaluation Criteria in Solid Tumours V.1.1.

Ethics and dissemination

This clinical trial will be conducted in accordance with the current version of Good Clinical Practice. The protocol was approved by the Clinical Research Ethics Review Committee of Mie University Hospital (approval number F-2021-017). The trial results will be published in peer-reviewed journals and/or disseminated through international conferences.

Trial registration number

jRCT2043210077.

DOI： 10.1136/bmjopen-2022-065109

Web of Science

Scopus

PubMed

researchmap

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

Chondroblastoma (CB) is histologically characterized by oval to polygonal-shaped mononuclear neoplastic cells, multinucleated osteoclastic giant cells, and eosinophilic matrix with occasional calcification. Genetically, the majority of CBs harbor H3F3B p.K36M mutation. Despite the historical nomenclature, it has been reported that the matrix of CB is similar to osteoid rather than true cartilage; however, it remains unclear whether neoplastic cells in CB have the potential for osteoblastic differentiation. To clarify this issue, we immunohistochemically examined the expression of osteogenic and chondrogenic markers (SATB2, RUNX2, p63, and SOX9) as well as H3K36M mutant protein in 33 cases of CB. All 33 cases of CB were positive for H3K36M, while SATB2, RUNX2, p63, and SOX9 were expressed in 30/33 (91%), 33/33 (100%), 29/33 (88%), and 31/32 (97%) CB cases, respectively. Our immunohistochemical results suggest that neoplastic cells in CB frequently express both osteogenic and chondrogenic markers and may have an intermediate feature of osteoblastic and chondroblastic nature.

DOI： 10.1016/j.prp.2022.154239

Web of Science

Scopus

PubMed

researchmap

Language：English   Publisher：シュプリンガー・ジャパン(株)  

低悪性度骨肉腫における脱分化(DLOS)の臨床的特徴および転帰、化学療法の有効性を明らかにするため、多施設共同後方視的研究を実施した。DLOS患者33例(年齢中央値36歳)を対象とした。その内訳は、低悪性度中心性骨肉腫(LGCOS)10例(30.3%)、傍骨性骨肉腫(POS)23例(69.7%)であり、LGCOSの方が腫瘍の亜型が多かった。脱分化の時期は同時性25例(75.8%)、異時性8例(24.2%)であった。DLOSの術前診断率は、コアニードル生検で40.0%、切開生検で65.4%であった。全例に手術が行われ、25例に周術期化学療法が施行された。術前補助化学療法を受けた13例のうち、11例は組織学的奏効が不良であった。5年全生存率(OS)と無転移生存率(MFS)はそれぞれ88.1%と77.7%であった。単変量解析により、局所再発はOS(P<0.01)およびMFS(P<0.01)の不良と関連していることが示された。周術期化学療法はOSとMFSに影響を与えなかった。以上より、DLOSの腫瘍生検の診断精度は、骨肉腫の診断精度に比べて低かった。通常型骨肉腫は化学療法への感受性が高かったが、DLOSに対する化学療法の有効性は低いことが明らかとなった。

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

イソクエン酸脱水素酵素(IDH)遺伝子変異が軟骨肉腫の臨床的アウトカムに及ぼす影響について検討した。生検または手術時に凍結腫瘍サンプルを採取した軟骨肉腫患者38例を対象に、IDH遺伝子変異の有無と臨床病理学的データとの関係を評価した。ヘテロ接合型IDH1変異を15例(40%)、ヘテロ接合型IDH2変異を5例(13%)に認め、その他の18例はIDH野生型であった。IDH変異は上肢の軟骨肉腫、IDH野生型は体幹に生じた軟骨肉腫に多くみられ、IDH野生型とIDH1変異との間に組織学的グレードに有意差はなかったが、IDH2変異では80%が脱分化型軟骨肉腫に分類された。患者予後に関して、椎骨軟骨肉腫が最も予後不良であり、組織学的グレードが高くなるにつれて予後が悪くなる傾向にあった。IDH変異群の方がIDH野生型群より全生存率が悪化しており、脱分化型軟骨肉腫を呈するIDH2変異群の無転移生存率と全生存率は有意に不良であった。Cox解析ではIDH変異、組織学的グレード、腫瘍転移が予後不良と有意に関連しており、年齢、性別、腫瘍の局在、腫瘍容積、局所再発と予後との関連はみられず、多変量解析でもIDH変異と組織学的グレードが予後に有意に影響を及ぼしていた。次世代シークエンス解析によって、IDH変異群においてTP53変異やCOL2A1変異といった特徴が認められた。IDH変異を有する軟骨肉腫患者では予後不良となる可能性が示唆された。

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

Sarcoma is a rare cancer, and little is known about the etiology, lifestyle epidemiology, and actual circumstances of treatment in hospitals in Japan. Understanding these issues is essential for the effective prevention and treatment of sarcoma. We therefore investigated the incidence of a personal and family cancer history in a total of 1320 sarcoma patients at the National Cancer Center Hospital. In addition, obesity, hypertension, dyslipidemia, diabetes mellitus, drinking, smoking, age and sex were compared in a descriptive study of 1159 of these sarcoma patients who were ≥ 20 years of age, and 7738 controls derived from the National Health and Nutrition Examination Survey in Japan. A total of 8% of sarcoma patients had a personal history of another cancer, and 30% of soft tissue sarcoma patients had a family cancer history in a first-degree relative (malignant peripheral nerve sheath tumor, 52%; leiomyosarcoma, 46%). A smoking habit was associated with the development of sarcoma (odds ratio [OR], 2.05; 95% confidence interval, 1.78-2.37; p < 0.01). According to the histology, the ORs for undifferentiated pleomorphic sarcoma (UPS) of bone, UPS of soft tissue, and liposarcoma were 5.71, 3.04, and 2.92, respectively. A family cancer history may be associated with certain soft tissue sarcomas, and a smoking habit was significantly associated with the development of sarcomas; however, further studies are necessary.

DOI： 10.1038/s41598-022-21500-0

Web of Science

Scopus

PubMed

researchmap

Language：English  

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

BACKGROUND: Tumors and tumor-like lesions of the foot and ankle are relatively rare and their postoperative clinical outcome has not been well reported. METHODS: This study retrospectively reviewed medical records of all patients who underwent excision of tumors and tumor-like lesions of the foot and ankle from 2008 to 2020. Preoperative and postoperative clinical outcomes were evaluated by the Japanese Society for Surgery of the Foot (JSSF) scales (pain, function, and alignment). RESULTS: A total of 117 consecutive patients were analyzed in this study. Bone lesions accounted for 51 patients (benign: 45, intermediate malignancy: 1, malignant: 5), and soft tissue lesions accounted for 66 patients (benign: 57, intermediate malignancy: 2, malignant: 7). Four patients (8%) presenting with bone tumor and six (9%) soft tissue tumors resulted in recurrence. Eight (67%) patients with malignant lesions were alive continuously disease free and followed for a median of 50.5 (range: 18 to 82) months. Amputation at the first operation was done for five cases (33%) of malignant or intermediate malignancy (below-knee amputation: 1, Chopart disarticulation: 1, forefoot amputation: 3). Postoperative JSSF scores resulted in a significant 'positive' increase (bone lesion, 75.9 ± 13.7 to 91.4 ± 14.9, p < 0.001; soft tissue lesion, 84.7 ± 14.8 to 91.9 ± 12.5, p < 0.001). The score improvement in bone lesions was significantly higher than in soft tissue lesions (p = 0.003). CONCLUSION: The surgical management of tumors and tumor-like lesions of the foot and ankle showed good post-operative functional outcomes with bone lesions exhibiting better results when compared to soft-tissue lesions.

DOI： 10.1186/s13047-022-00582-z

Web of Science

Scopus

PubMed

researchmap

Language：English   Publisher：(一社)日本癌治療学会  

researchmap

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media SA  

Background

A tenosynovial giant cell tumor (TGCT) is a locally aggressive benign neoplasm arising from intra- or extra-articular tissue, categorized as localized (L-TGCT, solitary lesion) and diffuse (D-TGCT, multiple lesions) TGCT. Surgical excision is the mainstay of the treatment, and a high local recurrence rate of approximately 50% has been reported. We focused on zaltoprofen, a nonsteroidal anti-inflammatory drug that can activate peroxisome proliferator-activated receptor gamma (PPARγ) and inhibit the proliferation of TGCT stromal cells. Therefore, we conducted a randomized trial to evaluate the safety and effectiveness of zaltoprofen in patients with D-TGCTs or unresectable L-TGCTs.

Methods

This randomized, placebo-controlled, double-blind, multicenter trial evaluated the safety and efficacy of zaltoprofen. In the treatment group, zaltoprofen (480 mg/day) was administered for 48 weeks; the placebo group received similar dosages without zaltoprofen. The primary outcome was progression-free rate (PFR) 48 weeks after treatment administration. Disease progression was defined as the following conditions requiring surgical intervention: 1) repetitive joint swelling due to hemorrhage, 2) joint range of motion limitation, 3) invasion of the adjacent cartilage or bone, 4) severe joint space narrowing, and 5) increased tumor size (target lesion).

Results

Forty-one patients were allocated to the zaltoprofen (n=21) or placebo (n=20) groups. The PFR was not significant between the zaltoprofen group and the placebo group at 48 weeks (84.0% and 90.0%, respectively; p=0.619). The mean Japanese Orthopedic Association knee score significantly improved from baseline to week 48 in the zaltoprofen group (85.38 versus 93.75, p=0.027). There was a significant difference between the values at 48 weeks of placebo and zaltoprofen group (p=0.014). One severe adverse event (grade 3 hypertension) was observed in the zaltoprofen group.

Discussion

This is the first study to evaluate the efficacy and safety of zaltoprofen in patients with TGCT. No significant differences in PFR were observed between the groups at 48 weeks. Physical function significantly improved after zaltoprofen treatment. The safety profile of zaltoprofen was acceptable. This less invasive and safer treatment with zaltoprofen, compared to surgical removal, could be justified as a novel approach to treating TGCT. Further analysis of long-term administration of zaltoprofen should be considered in future studies.

Clinical Trial Registration

University Hospital Medical Information Network Clinical Trials Registry, identifier (UMIN000025901).

DOI： 10.3389/fonc.2022.900010

Web of Science

Scopus

PubMed

researchmap

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

<sec><title>Study Design:</title> Retrospective diagnostic analysis.

</sec><sec><title>Objectives:</title> To establish a new predictor of surgical outcome after surgery for intradural extramedullary spinal tumor (IDEMT) in the thoracic spine, we introduced shape factor (SF), a mathematical description of the morphology of the spinal cord. SF was calculated by dividing object area by the square of perimeter.

</sec><sec><title>Materials and Methods:</title> Forty-three consecutive patients with IDEMT, detected by magnetic resonance imaging at the thoracic level with myelopathic signs, were included. Preoperative transverse cross-sectional area (CSA) and perimeter of the spinal cord (perimeter) at the level of maximal compression were measured. SF was calculated as 4π × CSA/(perimeter)². The association between clinicoradiological factors and surgical outcome of IDEMT was statistically analyzed.

</sec><sec><title>Results:</title> Mean CSA, perimeter, and SF were 27.8 ± 15.8 mm², 28.8 ± 6.1 mm, and 0.385 ± 0.14, respectively. A histogram distribution revealed that perimeter and SF, but not CSA, fit the normal distribution. The patients were subdivided into 2 groups according to postoperative modified Japanese Orthopedic Association Score (mJOA). [group F (favorable): n = 32, mJOA ≥ 9; group UF (unfavorable): n = 11, mJOA &lt; 9). Group UF had significantly lower mean CSA and SF. In univariate analysis of possible predictive factors for IDEMT surgery, greater age, lower preoperative mJOA, and lower SF were significantly associated with unfavorable outcome. In multivariate analysis, lower SF was the only significant predictor of postoperative outcome (odds ratio = 2.66, 95% CI 1.10–6.39, p = 0.0115).

</sec><sec><title>Conclusion:</title> Measurements of CSA and perimeter, followed by calculation of SF, may provide valuable quantitative information for the outcome of surgery for IDEMT.

</sec>

DOI： 10.1177/2192568220982571

Web of Science

Scopus

PubMed

researchmap

Other Link： http://journals.sagepub.com/doi/full-xml/10.1177/2192568220982571

Language：Japanese  

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

BACKGROUND: Dedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Given the paucity of cases, information on the clinical characteristics of this entity in the extremities and trunk wall is quite limited. In particular, the significance of preoperative evaluation and principles of intraoperative management of the different components, i.e., well-differentiated and dedifferentiated areas, are still to be defined. METHODS: Clinical characteristics, treatment outcomes, and risk factors for poor oncological outcomes in cases of dedifferentiated liposarcoma in the extremity or trunk wall were analyzed by a retrospective, multicentric study. RESULTS: A total of 132 patients were included. The mean duration from the initial presentation to dedifferentiation was 101 months in dedifferentiation-type cases. The 5-year local recurrence-free survival, metastasis-free survival, and disease-specific survival rates were 71.6%, 75.7%, and 84.7%, respectively. Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. A percentage of dedifferentiated area over 87.5%, marginal/intralesional margin, and R1/2 resection in the dedifferentiated area were independent risk factors for local recurrence. Dedifferentiated areas over 36 cm2, French Federation of Cancer Centers Sarcoma Group grade III, and intralesional or marginal resection were independent risk factors for metastasis. A dedifferentiated area over 77 cm2 and lung metastasis were independent risk factors for disease-specific mortality. CONCLUSIONS: The typical clinical characteristics of dedifferentiated liposarcoma in the extremity and trunk wall were reconfirmed in the largest cohort ever. The evaluation of the dedifferentiated area in terms of grade, extension, and pathological margin, together with securing adequate surgical margins, was critical in the management of this entity.

DOI： 10.1016/j.ejso.2022.08.024

Web of Science

Scopus

PubMed

researchmap

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

researchmap

Language：English   Publisher：Oxford University Press  

骨軟部腫瘍の手術を受ける患者を対象に、止血作用や抗炎症作用などを有するトラネキサム酸(TXA)投与の有効性と安全性を検討するため、後方視的な傾向スコアマッチング解析を行った。2017年1月から2018年12月までに切開生検、辺縁切除、掻爬、広範切除を受けた骨軟部腫瘍の患者連続454例を対象とした。TXA投与の有無によってTXA投与群211例(平均47.6±20.7歳)とTXA非投与群243例(平均45.1±22.1歳)に分けた。患者454例のうち、切開生検は102例、辺縁切除は175例、掻爬は54例、広範切除は123例で行われた。術中出血量は、辺縁切除、広範切除ともにTXA投与群がTXA非投与群に比べて有意に少なかった(辺縁切除:17.3g vs.70.3g、P=0.045;広範切除:128.8g vs.273.1g、P=0.023)。周術期出血量および推定出血量も、広範切除ではTXA投与群でTXA非投与群に比べて有意に少なかった(周術期出血量:341.5g vs.686.5g、P=0.0039;推定出血量:320.7mL vs.550.6mL、P=0.030)。静脈血栓塞栓症は両群とも発生しなかった。以上より、TXA投与は、有害事象の発生率を上昇させずに、特に広範な切除術において安全かつ効果的に出血量を減少させることが示唆された。

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

BACKGROUND: Low-grade osteosarcomas, namely parosteal osteosarcoma (POS) and low-grade central osteosarcoma (LGCOS), occasionally dedifferentiate into high-grade malignancy, referred to as dedifferentiation in low-grade osteosarcoma (DLOS). This study aimed to elucidate the clinicopathologic features of DLOS, which are poorly described to date due to the extreme rarity of the disease. METHODS: A total of 33 patients with DLOS were included. Clinical characteristics, including the diagnostic accuracy of tumor biopsy, multimodal treatments, and clinical course, were retrospectively reviewed. Univariate analysis was performed to identify prognostic factors associated with overall survival (OS) and metastasis-free survival (MFS). RESULTS: The tumor subtypes comprised 10 cases (30.3%) of LGCOS and 23 cases (69.7%) of POS. The timing of dedifferentiation was synchronous in 25 (75.8%) and metachronous in 8 (24.2%) patients. The rates of preoperative diagnosis of DLOS were 40.0% and 65.4% for core needle biopsy and incisional biopsy, respectively. All patients underwent surgery and 25 patients received perioperative chemotherapy. Of the 13 patients who received neoadjuvant chemotherapy, 11 exhibited a poor histological response. The 5-year OS and MFS rates were 88.1% and 77.7%, respectively. Univariate analysis revealed that local recurrence was associated with poor OS (P < 0.01) and MFS (P < 0.01). Perioperative chemotherapy did not affect OS or MFS. CONCLUSIONS: The diagnostic accuracy of tumor biopsy for DLOS was lower than that for bone sarcomas, as reported previously. In contrast to conventional osteosarcomas with high chemosensitivity, both histological responses and survival analysis revealed low efficacy of chemotherapy for DLOS.

DOI： 10.1007/s10147-022-02223-8

Web of Science

Scopus

PubMed

researchmap

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

Denosumab is a game-changing drug for giant cell tumor of bone (GCTB); however, its clinical biomarker regarding tumor ossification of GCTB has not been elucidated. In this study, we investigated the relationship between Wnt/β-catenin signaling and the ossification of GCTB and evaluated whether endogenous nuclear β-catenin expression predicted denosumab-induced bone formation in GCTB. Genuine patient-derived primary GCTB tumor stromal cells exhibited osteoblastic characteristics. Identified osteoblastic markers and nuclear β-catenin translocation were significantly upregulated via differentiation induction and were inhibited by treating with Wnt signaling inhibitor, GGTI-286, or selective Rac1-LEF inhibitor, NSC23766. Furthermore, we reviewed the endogenous ossification and nuclear β-catenin translocation of 86 GCTB clinical samples and elucidated that intra-tumoral ossification was significantly associated with the nuclear translocation. Three-dimensional quantitative analyses (n = 13) of tumoral CT images have revealed that the nuclear β-catenin translocation of naïve GCTB samples was significantly involved with the denosumab-induced tumor ossification. Our findings suggest a close relationship between the nuclear β-catenin translocation and the osteoblastic differentiation of GCTB. Investigations of the nuclear β-catenin in naïve GCTB samples may provide a promising biomarker for predicting the ossification of GCTB following denosumab treatment.

DOI： 10.1038/s41598-022-17728-5

Web of Science

Scopus

PubMed

researchmap

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/J.JBO.2022.100430

Web of Science

Scopus

PubMed

researchmap

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

PURPOSE: Undifferentiated pleomorphic sarcoma (UPS) is associated with poor prognosis. Recently, signal regulatory protein alpha (SIRPα), which is the immune checkpoint of macrophages, and T cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domains (TIGIT), which is the immune checkpoint of T cells and natural killer cells, have been considered as potential targets for cancer immunotherapy. This study aimed to assess the value of SIRPα and TIGIT as prognostic factors of UPS. MATERIALS AND METHODS: The cBio Cancer Genomics Portal was used to analyze mRNA expression data of 50 UPS cases in the Cancer Genome Atlas. We retrieved 49 UPS cases and performed immunohistochemistry (IHC) to detect programmed death ligand 1 (PD-L1), SIRPα, CD68, CD163, TIGIT, CD155, and CD8. RESULTS: SIRPα was positively associated with CD163 (Pearson's r = 0.51, p = 0.0002) as per open access data and IHC of the cohort (p = 0.002), which revealed that SIRPα-positive macrophage infiltration was higher in UPS cells with ≥ 1% PD-L1 expression than that in UPS cells with < 1% PD-L1 expression (p = 0.047). TIGIT was positively correlated with PD-L1 (r = 0.54, p < 0.0001) and CD8A (r = 0.98, p < 0.0001). In 35 of 49 cases, IHC revealed high levels of TIGIT expression on tumor cells. Furthermore, TIGIT expression on tumor cells was negatively correlated with CD155-positive (p = 0.0144) and CD8-positive (p = 0.0487) cell infiltration. Survival analysis showed that the high degree of SIRPα-positive macrophage infiltration was associated with poor overall survival and metastasis (p < 0.0001, p = 0.0006, respectively). CONCLUSION: SIRPα-positive macrophages infiltrated UPS cells, which predicted poor prognosis. High TIGIT expression on tumor cells was associated with decreased levels of tumor-infiltrating macrophages in UPS.

DOI： 10.1007/s00432-022-04078-y

Web of Science

Scopus

PubMed

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

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

researchmap

Language：English   Publisher：久留米大学医学部  

小型軟部肉腫の臨床的特徴を小型良性軟部腫瘍と比較する後ろ向き研究を行った。2006～2019年に当院で手術が施行された直径2cm以下の軟部肉腫患者17例と、直径2cm以下で非特異的な画像所見を示す良性軟部組織腫瘍患者39例を対象とした。病変部位が手足の患者は軟部肉腫群7例(40歳未満71%、男性43%)、良性軟部組織腫瘍群30例(同27%、27%)、病変部位が四肢・体幹の患者はそれぞれ10例(同30%、30%)と9例(同44%、33%)であった。手足の腫瘍を比較した結果、40歳未満の患者と疼痛を経験した患者は軟部肉腫群が良性軟部組織腫瘍群よりも有意に多かった。四肢・体幹の腫瘍を比較した結果、調査したすべての特徴に有意差はみられなかった。以上から、大半の小型軟部腫瘍において臨床的特徴は悪性の鑑別に有効ではなかったが、若年患者における手足の有痛性腫瘍には注意を払う必要があることが示唆された。

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

researchmap

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

OBJECTIVE: The aim of this study was to investigate the efficacy and safety of tranexamic acid in patients undergoing surgery for bone and soft tissue tumors. METHODS: Data were retrospectively collected from 454 consecutive patients with bone and soft tissue tumors who underwent open biopsy, marginal resection, curettage or wide resection between January 2017 and December 2018. We performed propensity score matching of patients who received tranexamic acid with those who did not. The primary outcome variables were intra-operative, peri-operative and estimated blood loss (IBL, PBL and EBL, respectively). RESULTS: Tranexamic acid (+) and tranexamic acid (-) groups were defined according to whether patients received tranexamic acid or not. Among the 454 patients, open biopsy was performed in 102, marginal resection in 175, curettage in 54 and wide resection in 123. Intra-operative blood loss was significantly lower in the tranexamic acid (+) group than in the tranexamic acid (-) group for both marginal and wide resection (marginal resection: 17.3 vs. 70.3 g, respectively, P = 0.045; wide resection: 128.8 vs. 273.1 g, respectively, P = 0.023). Peri-operative blood loss and estimated blood loss were also significantly lower in the tranexamic acid (+) group for wide resection (peri-operative blood loss: 341.5 vs. 686.5 g, respectively, P = 0.0039; estimated blood loss: 320.7 vs. 550.6 ml, respectively, P = 0.030). No venous thromboembolism occurred in either group. CONCLUSION: This study suggests that TXA administration safely and effectively reduces blood loss, in particular for wide resection, with no increase in the rate of adverse events.

DOI： 10.1093/jjco/hyac078

Web of Science

Scopus

PubMed

researchmap

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

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

In rare cases, giant cell tumor of bone (GCTB) can undergo primary or secondary malignant transformation to malignant giant cell tumor of bone (MGCTB), but the details of the molecular alterations are still unclear. The present study aimed to elucidate the clinicopathologic and molecular features of MGCTBs based on immunohistochemistry, fluorescence in situ hybridization (FISH) and next generation sequencing (NGS) of nine MGCTBs (five primary and four secondary). Seven (78%) of 9 MGCTBs were immunohistochemically positive for H3.3 G34W. In two (22%) patients, although GCTB components were focally or diffusely positive for H3.3 G34W, their malignant components were entirely negative for H3.3 G34W, which was associated with heterozygous loss of H3F3A by FISH. NGS on four MGCTBs revealed pathogenic mutations in TP53 (n = 3), EZH2 (n = 1) and several other genes. Immunohistochemical analysis of the nine MGCTBs confirmed the p53 nuclear accumulation (n = 5) and loss of H3K27me3 expression (n = 3) and showed that they were mutually exclusive. In addition, four (80%) of five cases of pleomorphic or epithelioid cell-predominant MGCTBs were positive for p53, while three (75%) of four cases of spindle cell-predominant MGCTBs were negative for trimethylation at lysine 27 of histone 3 (H3K27me3). The results suggested that p53 alteration and dysfunction of histone methylation as evidenced by H3K27me3 loss may play an important role in the malignant progression of GCTB, and might contribute to the phenotype-genotype correlation in MGCTB. The combined histologic, immunohistochemical and molecular information may be helpful in part for the diagnosis of challenging cases.

DOI： 10.1038/s41379-021-00972-x

Web of Science

Scopus

PubMed

researchmap

Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

researchmap

Language：Japanese   Publisher：西日本整形・災害外科学会  

researchmap

Language：Japanese   Publisher：西日本整形・災害外科学会  

researchmap

Language：Japanese   Publisher：(公社)日本リハビリテーション医学会  

researchmap

Language：Japanese   Publisher：西日本整形・災害外科学会  

researchmap

Language：Japanese   Publisher：西日本整形・災害外科学会  

researchmap

Language：Japanese  

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Periosteal chondrosarcoma is an extremely rare malignant cartilage-forming tumour that originates from the periosteum and occurs on the surface of bone. Often, it is difficult to distinguish periosteal chondrosarcoma from other tumours, and reports in the literature are scarce. This study aims to investigate the characteristics of periosteal chondrosarcoma, focusing particularly on medullary invasion. Among 33 periosteal cartilaginous tumours, seven patients with pathologically proven periosteal chondrosarcoma were identified retrospectively. The average tumour size was 5.4 cm in the long axis; two tumours were smaller than 3.0 cm. Six tumours were resected with a wide margin, and the remaining tumour had a marginal margin. Histology revealed that six tumours (85.7%) had invaded the medullary cavity; three of these did not show invasion into the medullary cavity on MRI evaluation. Neither local recurrence nor metastasis was observed among these patients. The frequency of invasion of the medullary cavity was higher than that reported previously. The recommended treatment for periosteal chondrosarcoma is resection with an adequate margin. Therefore, surgeons should consider the possibility of medullary invasion when attempting to achieve a histologically negative margin, even if the tumour does not show invasion into the medullary cavity on MRI.

DOI： 10.3390/jcm11072062

Web of Science

Scopus

PubMed

researchmap

Language：Japanese  

Language：Japanese   Publisher：(一社)日本手外科学会  

researchmap

Language：Japanese   Publisher：(一社)日本手外科学会  

researchmap

Publisher：Gan to kagaku ryoho. Cancer &amp; chemotherapy  

Scopus

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Others   Publisher：金原出版  

DOI： 10.18888/se.0000002057

CiNii Research

researchmap

Language：Japanese  

Language：Japanese  

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

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

researchmap

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

researchmap

Language：Japanese   Publisher：(株)癌と化学療法社  

researchmap

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J00296&link_issn=&doc_id=20220324350008&doc_link_id=issn%3D0385-0684%26volume%3D49%26issue%3D3%26spage%3D273&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0385-0684%26volume%3D49%26issue%3D3%26spage%3D273&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

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

PubMed

researchmap

Language：Japanese  

PubMed

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

researchmap

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

researchmap

Language：Japanese   Publisher：(一社)日本脊椎脊髄病学会  

researchmap

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

researchmap

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

researchmap

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1007/s10147-022-02137-5

Web of Science

Scopus

PubMed

researchmap

Other Link： https://link.springer.com/article/10.1007/s10147-022-02137-5/fulltext.html

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

The Japan Society of Clinical Oncology (JSCO) published the “JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients” in 2017. This was the first guideline in cancer reproductive medicine in Japan. In the field of cancer reproductive medicine, close cooperation between an oncologist and a physician for reproductive medicine is important from before treatment initiation until long after treatment. The guideline takes into consideration disease specificity and provides opinions from the perspective of oncologists and specialists in reproductive medicine that are in line with the current state of the Japanese medical system. It is intended to serve as a reference for medical staff in both fields regarding the availability of fertility preservation therapy before the start of cancer treatment. Appropriate use of this guideline makes it easier to determine whether fertility preservation therapy is feasible and, ultimately, to improve survivorship in childhood, adolescent, and young adult cancer patients. In this article (Part 2), we describe details by organ/system and also for pediatric cancer.

DOI： 10.1007/s10147-021-02076-7

Web of Science

Scopus

PubMed

researchmap

Other Link： https://link.springer.com/article/10.1007/s10147-021-02076-7/fulltext.html

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

In 2017, the Japan Society of Clinical Oncology (JSCO) published the JSCO Clinical Practice Guidelines 2017 for Fertility Preservation in Childhood, Adolescent, and Young Adult Cancer Patients. These were the first Japanese guidelines to address issues of oncofertility. In this field of medicine, sustained close cooperation between oncologists and reproductive specialists is essential from the diagnosis of cancer until many years after completion of cancer treatment. These JSCO guidelines were intended to guide multidisciplinary medical staff in considering the availability of fertility preservation options and to help them decide whether to provide fertility preservation to childhood, adolescent, and young adult cancer patients before treatment starts, with the ultimate goal of improving patient survivorship. The guidelines are presented as Parts 1 and 2. This article (Part 1) summarizes the goals of the guidelines and the methods used to develop them and provides an overview of fertility preservation across all oncology areas. It includes general remarks on the basic concepts surrounding fertility preservation and explanations of the impacts of cancer treatment on gonadal function by sex and treatment modality and of the options for protecting/preserving gonadal function and makes recommendations based on 4 clinical questions. Part 2 of these guidelines provides specific recommendations on fertility preservation in 8 types of cancer (gynecologic, breast, urologic, pediatric, hematologic, bone and soft tissue, brain, and digestive).

DOI： 10.1007/s10147-021-02081-w

Web of Science

Scopus

PubMed

researchmap

Other Link： https://link.springer.com/article/10.1007/s10147-021-02081-w/fulltext.html

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

BACKGROUND: Preoperative chemotherapy is widely applied to high-grade localized soft tissue sarcomas (STSs); however, the prognostic significance of histological response to chemotherapy remains controversial. This study aimed to standardize evaluation method of histological response to chemotherapy with high agreement score among pathologists, and to establish a cut-off value closely related to prognosis. METHODS: Using data and specimens from the patients who had registered in the Japan Clinical Oncology Group study, JCOG0304, a phase II trial evaluating the efficacy of perioperative chemotherapy with doxorubicin (DOX) and ifosfamide (IFO), we evaluated histological response to preoperative chemotherapy at the central review board. RESULTS: A total of 64 patients were eligible for this study. The percentage of viable tumor area ranged from 0.1% to 97.0%, with median value of 35.7%. Regarding concordance proportion between pathologists, the weighted kappa coefficient (κ) score in all patients was 0.71, indicating that the established evaluation method achieved substantial agreement score. When the cut-off value of the percentage of the residual tumor area was set as 25%, the p-value for the difference in overall survival showed the minimum value. Hazard ratio of the non-responder with percentage of the residual tumor < 25%, to the responder was 4.029 (95% confidence interval 0.893-18.188, p = 0.070). CONCLUSION: The standardized evaluation method of pathological response to preoperative chemotherapy showed a substantial agreement in the weighted κ score. The evaluation method established here was useful for estimating of the prognosis in STS patients who were administered perioperative chemotherapy with DOX and IFO. TRIAL REGISTRATION: UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

DOI： 10.1186/s12885-022-09195-y

Web of Science

Scopus

PubMed

researchmap

Language：Japanese  

軟部腫瘍、軟部肉腫の組織型は極めて多彩であり、2020年に改訂されたWHO診断基準では、100種を超える組織診断が分類されている。本稿では、その他の軟部腫瘍、軟部肉腫ということで、他稿で取り上げられていない組織型である分化方向不明の腫瘍や骨や軟部に発生する未分化小円形細胞肉腫の中から、しばしば皮下腫瘍として発生し、臨床上重要と思われる、滑膜肉腫、類上皮肉腫、骨外性粘液型軟骨肉腫、骨化性線維粘液性腫瘍、骨外性ユーイング肉腫や、近年新しく疾患が定義され、注目されている腫瘍としてNTRK遺伝子再構成紡錘形細胞腫瘍を取り上げ、その診断、治療計画、手術方法等について解説する。(著者抄録)

Language：Others   Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

DOI： 10.1038/s41416-021-01695-1

Web of Science

Scopus

PubMed

researchmap

Other Link： https://www.nature.com/articles/s41416-021-01695-1

Language：Japanese   Publisher：(株)全日本病院出版会  

軟部腫瘍、軟部肉腫の組織型は極めて多彩であり、2020年に改訂されたWHO診断基準では、100種を超える組織診断が分類されている。本稿では、その他の軟部腫瘍、軟部肉腫ということで、他稿で取り上げられていない組織型である分化方向不明の腫瘍や骨や軟部に発生する未分化小円形細胞肉腫の中から、しばしば皮下腫瘍として発生し、臨床上重要と思われる、滑膜肉腫、類上皮肉腫、骨外性粘液型軟骨肉腫、骨化性線維粘液性腫瘍、骨外性ユーイング肉腫や、近年新しく疾患が定義され、注目されている腫瘍としてNTRK遺伝子再構成紡錘形細胞腫瘍を取り上げ、その診断、治療計画、手術方法等について解説する。(著者抄録)

researchmap

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

DOI： 10.1159/000521504

Scopus

PubMed

Language：Japanese  

Language：Japanese  

Language：Japanese  

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

DOI： 10.3390/jcm10214972

Language：Japanese  

Language：Japanese  

Language：Japanese  

＜文献概要＞はじめに がんの骨転移に対する薬物療法は,破骨細胞に作用して骨吸収を阻害する骨修飾薬(BMA),がん細胞そのものをおさえる化学療法やホルモン療法,放射性医薬品の三つに大別される.化学療法やホルモン療法,放射性医薬品の適応ががんの種類や抗悪性腫瘍薬感受性に左右されるのに対し,BMAはほぼすべての転移性骨腫瘍に適応がある.BMAにはビスホスホネート製剤(BP)と抗receptor activator of NF-κB ligand(RANKL)抗体であるデノスマブの2種類があるが,いずれも骨粗鬆症の治療にも用いられており,整形外科医にとって馴染みのある薬剤である.転移性骨腫瘍に対応するがん診療チームのなかで整形外科医がはたすべき役割には手術的治療をはじめとしてさまざまなものがあるが,BMAについてもその作用機序や合併症に習熟した整形外科医が積極的に助言をすべきである.本稿では薬物治療のなかでも主にBMAについて概説し,特にその合併症への対策を紹介する.

Language：Japanese  

＜文献概要＞はじめに がんの骨転移に対する薬物療法は,破骨細胞に作用して骨吸収を阻害する骨修飾薬(BMA),がん細胞そのものをおさえる化学療法やホルモン療法,放射性医薬品の三つに大別される.化学療法やホルモン療法,放射性医薬品の適応ががんの種類や抗悪性腫瘍薬感受性に左右されるのに対し,BMAはほぼすべての転移性骨腫瘍に適応がある.BMAにはビスホスホネート製剤(BP)と抗receptor activator of NF-κB ligand(RANKL)抗体であるデノスマブの2種類があるが,いずれも骨粗鬆症の治療にも用いられており,整形外科医にとって馴染みのある薬剤である.転移性骨腫瘍に対応するがん診療チームのなかで整形外科医がはたすべき役割には手術的治療をはじめとしてさまざまなものがあるが,BMAについてもその作用機序や合併症に習熟した整形外科医が積極的に助言をすべきである.本稿では薬物治療のなかでも主にBMAについて概説し,特にその合併症への対策を紹介する.

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

DOI： 10.1016/j.prp.2021.153668

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

DOI： 10.1016/j.jos.2021.07.024

Web of Science

Scopus

PubMed

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

<title>Abstract</title>
<sec>
<title>Background</title>
Soft tissue sarcomas arise in the deep sites of the buttocks and lower extremities. Since a tourniquet is not applied during surgery for soft tissue sarcomas at such sites, excessive intraoperative blood loss may occur. Various devices, including LigaSure™ (Medtronic, Dublin, Ireland), are used as electrothermal bipolar vessel sealers. However, its clinical relevance in soft tissue sarcomas surgery remains unclear. This study aimed to assess the effectiveness of LigaSure™ in soft tissue sarcomas surgery.


</sec>
<sec>
<title>Methods</title>
This study included 168 patients who underwent surgeries for soft tissue sarcomas in the deep sites in the buttocks and lower extremities between January 2004 and March 2018. The primary outcome was intraoperative blood loss, and secondary outcomes were surgery duration, wound complications, perioperative haemoglobin concentrations and intraoperative blood transfusion. To reduce selection biases, propensity score matching was applied. We defined the matched cases wherein LigaSure™ was used as the ‘using group’ and the other matched cases as the ‘non-using group’. Outcomes were compared between both groups.


</sec>
<sec>
<title>Results</title>
From each group, 35 cases were selected using propensity score matching. The intraoperative blood loss was significantly smaller statistically in the using group (181.5 ± 240.4 ml vs. 394.7 ± 547.3 ml, respectively; P = 0.041). The duration of operation was longer in the using group (189.9 ± 97.6 min vs. 140.6 ± 75.7 min, respectively; P = 0.007). There were no significant differences in other outcomes.


</sec>
<sec>
<title>Conclusion</title>
By using LigaSure™ for soft tissue sarcomas occurring in the buttocks and lower extremities, we observed a trade-off between reduced intraoperative blood loss and longer operative time.


</sec>

DOI： 10.1093/jjco/hyab083

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

DOI： 10.1007/s42399-021-00860-0

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

DOI： 10.1007/s00428-021-03189-0

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

DOI： 10.1245/s10434-020-09306-8

Language：Japanese  

重粒子線治療(CIRT)を行った原発性悪性骨・軟部腫瘍(PMST)30症例(男性18人、女性12人、年齢中央値55.9歳)を対象として、照射後の圧迫骨折(VCF)の発生率とspinal instability neoplastic score(SINS)の有用性について検討した。照射後VCFは10例(33.3%)に認め、いずれも照射野内に生じており、CIRTから発症までの期間は平均8.4ヵ月で、発症前や発症時に局所再発は認めなかった。照射後VCFの累積発生率は6ヵ月で15%、2年では29%であり、SINSの評価は平均6.2であった。また、受信機動作特性曲線を用いた解析にて、SINSカットオフスコアを6とした場合の照射後VCFの予測感度は90%、特異度は85%であった。

Language：Japanese  

Language：Japanese  

Language：Japanese  

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

DOI： 10.1200/jco.2021.39.15_suppl.tps11580

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

DOI： 10.1007/s00432-021-03616-4

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

DOI： 10.1111/cas.14793

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

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

DOI： 10.1016/j.lungcan.2020.12.023

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

DOI： 10.3892/ol.2021.12473

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

DOI： 10.1038/s41598-020-77898-y

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

DOI： 10.1097/CORR.0000000000001266

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

DOI： 10.3390/jcm9103133

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

【目的】軟部肉腫の根治的治療の原則は広範切除であるが，部位や進展の程度によって骨切除も考慮しなければならない．今回，対側からの椎弓根骨切り術Contralateral osteotomy of the pedicle and posterolateral elements for en bloc resection（COPPER）法により背部の軟部肉腫の広範切除を行ったので報告する．【症例】症例は57歳男性，5ヶ月ほど前に左背部に腫瘤を自覚，長径10 cm大に増大した．切開生検にて脱分化型脂肪肉腫と診断された．腫瘍は左T12-3椎弓に広く接し，横突起の間から一部椎間孔へ進展していた．塞栓術後，対側からのT12-L3椎弓根骨切り術を併用し広範切除術を行った．T10-L4脊椎固定と横隔膜再建も併せて行い，手術時間は812分，出血量1000 mlであった．【考察】COPPER法は脊椎後外側に発生した骨腫瘍の切除法として報告されているが，椎弓からの剥離が困難と思われる傍脊柱筋の軟部腫瘍にも応用可能である．

DOI： 10.5035/nishiseisai.69.948

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

DOI： 10.1080/14737140.2020.1814150

Language：Japanese  

Language：Japanese  

Language：Japanese  

【背景】腫瘍用人工膝関節置換術の術後成績と患肢機能に影響する因子を検討した．【方法】2000年から2017年に腫瘍用人工膝関節置換を行った56例のうちフォロー中断した3例を除く53例（大腿骨遠位38例，脛骨近位15例）を対象とした．平均年齢38.7歳，男性27例，女性26例で，平均経過観察期間は5年4ヶ月であった．治療予後，インプラント生存率，合併症，最終評価時のMSTS Scoreと骨・筋切除量の関連を調査した．【結果】5年生存率は77％，10年生存率は66％で，インプラント10年生存率は90％であった．合併症は計5例に生じ，うち3例に深部感染を生じていた．MSTS Scoreは平均23点と良好で，14㎝以上骨切りした例で有意に歩行と歩容が悪化しており，大腿四頭筋を2筋以上切除した例で有意に歩容が悪化していた．【結論】術後患肢機能温存の為に広範切除は必要最低限にすべきである．

DOI： 10.5035/nishiseisai.69.461

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

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

Language：Others  

DOI： 10.15106/j_seikei71_811

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

DOI： 10.1097/ij9.0000000000000089

Language：English  

DOI： 10.1007/s00262-020-02508-9

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

【背景】良性骨病変の診断で病巣掻爬後に悪性骨腫瘍と分かる場合が稀にあり，追加治療が必要となる．今回我々は当科で経験した5例を報告する．【対象・方法】2011～18年に針生検にて良性骨病変の診断で，病巣掻爬後に悪性骨腫瘍と診断された症例を対象とした．症例数は男性2例，女性3例，診断時平均年齢は29歳で，術前・術後の病理診断，腫瘍の発生部位，治療内容，Follow up期間，転移の有無，最終転帰などを調べた．【結果】発生部位は脛骨2例・上腕骨2例・大腿骨1例と全て長管骨で，全例掻爬前に切開生検を行っており，術前（術後）診断は骨髄炎2例（Ewing肉腫・小円型細胞肉腫），良性骨腫瘍1例（平滑筋肉腫），骨芽細胞腫1例・骨巨細胞腫1例（骨肉腫）であった．4例に追加化学療法，4例に追加広範切除を行った．当科初診日から1例は0.3年でDOD，4例は平均2.7年経過し，CDFであった．【考察】悪性と診断後，早急に適切な追加治療を行うことで根治の可能性がある．

DOI： 10.5035/nishiseisai.69.68

Language：Japanese  

【背景】Chronic Expanding Hematoma（CEH）はしばしば悪性腫瘍との鑑別が困難となる．今回悪性腫瘍を疑い広範切除術を施行したCEHの一例を経験したので報告する．【症例】50歳男性で，既往歴に特記事項なく，3年前より右大腿外側の腫瘤を自覚した．徐々に増大し，自壊・出血をきたしたため近医を受診し，右大腿部悪性軟部腫瘍が疑われ，当科紹介となった．MRIでT1・2共に低～高信号が混在し，辺縁が不均一に造影されていた．FDG-PETでは辺縁にのみ軽度集積していた．針生検で壊死組織のみを認めたが，経過より悪性腫瘍を疑い広範切除術を行った．切除により広範な皮膚欠損を生じたため，人工真皮で被覆し，術後5週で分層植皮を行った．病理診断はCEHであった．【考察】悪性腫瘍の中には血腫を伴うものも存在し，CEHとの鑑別が困難となる場合が多い．病歴と画像所見をもとに総合的に判断する必要がある．

DOI： 10.5035/nishiseisai.69.30

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

DOI： 10.1007/s13577-019-00291-z

Language：English  

DOI： 10.1002/cam4.2991

Language：English  

DOI： 10.1007/s10147-019-01505-y

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：English  

DOI： 10.1093/jjco/hyz096

Language：English  

DOI： 10.1038/s41388-019-0929-9

Language：Japanese  

Language：Japanese  

【はじめに】大腿近位部悪性腫瘍治療後に大腿骨頭すべり症を発生した症例を2例経験したので報告する.【症例1】4歳時に右大腿骨骨幹部Ewing肉腫に対し,化学療法,自己末梢血幹細胞移植,放射線治療(40Gy)を受け,寛解した.9歳時に右大腿骨頭すべり症(後方すべり角70度)を生じ,大腿骨頭前方回転骨切り術を施行した.脚長不等に対し,13歳及び20歳時に仮骨延長を行った.【症例2】1歳時に左大腿部横紋筋肉腫に対し,術前後化学療法,広汎切除術,放射線治療(36Gy)を受け,寛解した.7歳時に左大腿骨転子下病的骨折を受傷し,骨接合術,腸骨骨移植を施行した.9歳時に左大腿骨頭すべり症(後方すべり角30度)を生じ,in situ pinningを施行した.術後半年ですべりの増悪を認め,抜釘,大腿骨転子間屈曲外反骨切り術を施行した.【考察】小児悪性腫瘍に対する放射線照射の晩期合併症として,成長障害,病的骨折に加えて,大腿骨頭すべり症が知られる.当科で経験した2例について,文献的考察を加えて報告する.(著者抄録)

Language：English  

DOI： 10.1007/s11864-019-0656-z

Language：Japanese  

Language：Others  

DOI： 10.11477/mf.1408201414

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：English  

DOI： 10.1016/j.jos.2018.10.020

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：English  

DOI： 10.1016/j.isci.2019.02.008

Language：Japanese  

【目的】悪性骨軟部腫瘍の不適切切除例に対する追加手術は高侵襲となり、特に上肢では追加広範切除による機能損失が大きい。当科で追加治療を施行した上肢の不適切切除例について検討した。【対象】2011～2017年に当科紹介された上肢発生骨軟部腫瘍815例のうち不適切切除例と判断された9例を対象とした。【結果】男性7例、女性2例、平均年齢69.3歳であった。全例が浅在性軟部腫瘍であり、病理診断は粘液線維肉腫6例、隆起性皮膚線維肉腫、骨外性Ewing肉腫、CIC遺伝子再構成肉腫各1例であった。初回術前にMRIを施行されたのは3例のみで、生検は全例未施行であった。初回手術時の手技上の問題点として横皮切、被膜損傷や掻爬による腫瘍播種などがあった。当院での追加手術7例のうち4例で再建を要した。【考察】上肢発生軟部腫瘍では、浅在性腫瘍であっても一期的な切除生検は適応を限定して施行することが望ましいと思われた。(著者抄録)

DOI： 10.5035/nishiseisai.68.177

Language：English  

DOI： 10.1186/s12891-019-2453-z

Language：English  

DOI： 10.1016/j.jos.2019.03.022

Language：Japanese  

Language：Japanese  

＜文献概要＞骨髄腫およびリンパ腫はいずれも血液系悪性腫瘍であり,頻繁に骨病変を有することから,整形外科医が接する機会が多い腫瘍である.両者ともに化学療法および放射線治療に対する感受性に優れ,原疾患治療における手術の必要性は低い.しかし,いずれの腫瘍も骨脆弱性や病的骨折の原因となり得るため,しばしば整形外科医による介入が必要となる.いずれの腫瘍も診断のポイントがあり,その知識があれば,適切に早期診断することはさほど難しくない.本稿では,整形外科医として最低限知っておくべき基礎知識を概説するとともに,整形外科医が果たす役割について解説する.

Language：Japanese  

Language：Japanese  

Language：Japanese  

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

DOI： 10.21037/cco.2018.08.10

Language：Japanese  

Language：English  

DOI： 10.1007/s11626-018-0258-2

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

【はじめに】骨シンチグラフィで乳がん骨転移として長期間経過観察が行われた大腿骨非定型骨折(atypical femoral fracture;AFF)の1例を経験したので報告する。【症例】75歳、女性。乳がん(45歳時乳房切断)。60歳時に左大腿骨転子部に骨転移が出現し、ホルモン療法およびビスホスホネートを開始。64歳時、骨シンチグラフィで左大腿骨骨幹部外側皮質に集積出現。66歳時、左股部痛が出現。左大腿骨転子部病変の増大と判断され、放射線治療を受けた。単純X線写真では骨幹部外側皮質の肥厚を認めた。その後、左大腿骨頸部骨折を生じ人工骨頭置換を受けた。75歳時、転倒し骨皮質肥厚部に一致した横骨折を生じAFFと診断した。人工骨頭の緩みはなく内固定術を行い骨癒合を得た。【考察・結論】がん骨転移は生命予後には影響しないもののADL、QOLに大きくかかわる因子である。骨転移のマネジメントには整形外科医の関与も必要であり、主診療科を含めたチームとして診療にあたることが望まれる。(著者抄録)

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：English  

DOI： 10.1007/s11626-018-0237-7

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

DOI： 10.1371/journal.pone.0194508

Language：Japanese  

Language：Japanese  

Language：English  

DOI： 10.1007/s11626-017-0207-5

Language：English  

Eribulin is a new drug to treat soft tissue sarcoma (STS) that exerts antitumor activity by binding to microtubules. The prognosis of STS is poor, and eribulin is expected to improve the treatment outcome. We observed several cases that exhibited resistance to eribulin and developed an eribulin-resistant leiomyosarcoma cell line to investigate the mechanism of resistance. The IC50 of eribulin was 125 times higher in the resistant cell line than in the parental cell line, and eribulin did not induce G2/M arrest in resistant cells. The resistant cell line showed increased expression of MDR1 transcript, but protein levels and functional analysis results were similar to the parental cell line. We found that class III β-tubulin (TUBB3) was overexpressed in the resistant cell line, and siRNA knockdown of TUBB3 partially recovered sensitivity to eribulin. TUBB3 expression in clinical samples varied, suggesting that TUBB3 has the potential to be a biomarker for selection of anticancer drugs and may be a target for overcoming resistance to eribulin.

DOI： 10.1155/2018/8987568

Language：English  

DOI： 10.2106/JBJS.CC.17.00061

Language：English  

DOI： 10.22603/ssrr.2018-0004

Language：English  

DOI： 10.1093/jjco/hyx096

Language：Japanese  

Language：English  

Dermatofibrosarcoma protuberans (DFSP) is a cutaneous mesenchymal tumor of intermediate malignancy and fibroblastic/myofibroblastic differentiation. Fibrosarcomatous (FS) component is a high-grade component of DFSP. The detailed oncogenic difference between DFSP and FS components is not clear. We thus investigated the Akt-mTOR pathway in both components. We used 65 tumor samples obtained from 65 patients. The phosphorylation of Akt-mTOR pathway proteins (Akt, mTOR, 4EBP1, and S6RP) and PDGFRα/β was assessed by immunohistochemical staining, the results of which were confirmed by Western blotting. The immunohistochemical results were as follows: in ordinary DFSP components, p-PDGFRα–positive tumors were 41.9&#37; (18/43 cases), p-PDGFRβ 55.8&#37; (24/43 cases), p-Akt 51.2&#37; (22/43 cases), p-mTOR 39.5&#37; (17/43 cases), p-4EBP1 46.5&#37; (20/43 cases), and p-S6RP 41.8&#37; (18/43 cases); in DFSP components of FS-DFSP, 52.6&#37; (10/19 cases), 47.4&#37; (9/19 cases), 52.6&#37; (10/19 cases), 36.8&#37; (7/19 cases), 52.6&#37; (10/19 cases), and 52.6&#37; (10/19 cases); and in FS components, 45.5&#37; (10/22 cases), 36.4&#37; (8/22 cases), 72.7&#37; (16/22 cases), 54.5&#37; (12/22 cases), 72.7&#37; (16/22 cases), and 68.2&#37; (15/22 cases), respectively. There were significant positive correlations of the phosphorylation of most of the Akt-mTOR pathway proteins (p-Akt, p-mTOR, p-4EBP1, and p-S6RP) with each other (P <.05). Phospho-PDGFRβ was well correlated with the phosphorylation of Akt-mTOR pathway proteins in DFSP components of ordinary and FS-DFSPs, but these correlations were weaker in FS components. This study suggested the association of activation of Akt-mTOR pathway proteins and PDGFR with the progression of DFSP to FS. The Akt-mTOR pathway is thus a potential therapeutic target in imatinib-resistant DFSP/FS.

DOI： 10.1016/j.humpath.2017.07.001

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

DOI： 10.1111/1346-8138.13876

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

DOI： 10.1155/2017/8132676

Language：English  

DOI： 10.1038/s41598-017-04967-0

Language：Japanese  

Language：Japanese  

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

DOI： 10.1155/2017/9467402

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：Japanese  

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

DOI： 10.1371/journal.pone.0178064

Language：English  

DOI： 10.1038/srep45332

Language：Japanese  

Language：Japanese  

Language：Japanese  

Language：English  

DOI： 10.2106/JBJS.CC.17.00002

Language：Japanese