Establishment and characterization of NCC-LMS3-C1: a novel patient-derived cell line of leiomyosarcoma.

Leiomyosarcoma (LMS) is an aggressive mesenchymal malignancy, which originates from the smooth muscle cells or from the precursor mesenchymal stem cells that potentially differentiate into smooth muscle cells. LMS is one of the most common sarcomas. LMS has genomic instability, reflecting complex and unbalanced karyotypes, and the cytogenetic and molecular changes in LMS are not consistent. The standard treatment of the primary LMS is complete resection, and the metastasis is often observed even after curative surgery. Patient-derived cancer models are a key bioresource to develop a novel therapy, and we aimed to establish and characterize a novel cell line for LMS. We established a cell line from tumor tissues of the patient with LMS and named it NCC-LMS3-C1. We maintained NCC-LMS3-C1 cells for 12 months and passed them more than 30 times. Genome-wide copy number analysis demonstrated that NCC-LMS3-C1 cells harbored genetic abnormalities. NCC-LMS3-C1 cells exhibited aggressive phenotypes such as continuous growth, spheroid formation, and invasion in the tissue culture condition, which may reflect the clinical behaviors of LMS. We performed a drug screening using NCC-LMS3-C1 cells and found that four anti-cancer agents, such as bortezomib, dasatinib, mitoxantrone, and romidepsin, had remarkable anti-proliferative effects on NCC-LMS3-C1 cells. We conclude that NCC-LMS3-C1 cells will be a useful resource for the study of LMS.

Comparison of the clinical outcomes of intramedullary nailing between impending and completed pathological fractures caused by metastatic femoral tumors from solid cancers.

BACKGROUND: We examined the treatment outcomes following intramedullary nailing in patients with metastatic femoral tumors, excluding those from hematological malignancies. METHODS: We retrospectively evaluated treatment outcomes following intramedullary nailing between patients who underwent preventative surgery compared with those who had surgery following pathological fracture. Patients who underwent preventative surgery (Mirels' score ≥8) were allocated to the impending fracture group (n = 11) and those who underwent surgery after pathological fracture were allocated to the completed fracture group (n = 20). RESULTS: Duration of surgery was significantly shorter in the impending fracture group than in the completed fracture group. Median blood loss was significantly less, and the median duration of hospital stay was significantly shorter in the impending fracture group than in the completed fracture group. Among patients who died following surgery, the median postoperative survival duration was significantly longer in the impending fracture group than in the completed fracture group. Significantly more patients regained walking function in the impending fracture group than in the completed fracture group. Regarding complications, infection occurred in one patient in the completed fracture group. No implant damage was observed in either group. CONCLUSIONS: Patients with metastatic femoral tumors who underwent intramedullary nailing in the impending fracture group had better postoperative survival and gait function, less blood loss, and shorter durations of surgery and hospital stay than those in the completed fracture group. These findings indicate the importance of early diagnosis and treatment and value of treatment prior to fracture occurrence.

Perivascular epithelioid cell tumors (PEComas) of the bone and soft tissue: a Japanese Musculoskeletal Oncology Group (JMOG) multi-institutional study.

PURPOSE: Perivascular epithelioid cell tumors (PEComas) of the bone and soft tissues are rare mesenchymal neoplasms, some of which are malignant. However, their clinical and pathological characteristics remain unclear. This study was performed to investigate the clinical and pathological characteristics of PEComas in bone and soft tissues by leveraging information from the Japanese Musculoskeletal Oncology Group. METHODS: Nine patients, including four male and five female patients with a median age of 50 years, were retrospectively reviewed. PEComas of the visceral organs, including the uterus and retroperitoneum, were excluded. RESULTS: Eight tumors arose in the soft tissue and one in the bone, with a mean size of 8.8 cm. Four patients showed local recurrence or distant metastasis. The 1-year survival rate was 78%. Pathologically, eight tumors were classified as malignant and one as having uncertain malignancy potential. Half of the tumors showed high MIB-1 index values of > 30%. Immunohistochemically, the melanocyte marker HMB45 was expressed in 89% of the cases, and muscle-specific markers were expressed only in 30-50% of the cases. Transcription factor binding to IGHM enhancer 3 (TFE3) expression was positive in 100% of the patients. Tumors with high expression of TFE3 were classified as PEComas with malignant potential according to Folpe's classification. CONCLUSIONS: Bone and soft tissue PEComas may have a higher malignancy potential than other visceral PEComas and are more likely to develop as TFE3-rearranged PEComas.

What Are the Complications, Function, and Survival of Tumor-devitalized Autografts Used in Patients With Limb-sparing Surgery for Bone and Soft Tissue Tumors? A Japanese Musculoskeletal Oncology Group Multi-institutional Study.

BACKGROUND: Tumor-devitalized autografts treated with deep freezing, pasteurization, and irradiation are biological reconstruction methods after tumor excision for aggressive or malignant bone or soft tissue tumors that involve a major long bone. Tumor-devitalized autografts do not require a bone bank, they carry no risk of viral or bacterial disease transmission, they are associated with a smaller immunologic response, and they have a better shape and size match to the site in which they are implanted. However, they are associated with disadvantages as well; it is not possible to assess margins and tumor necrosis, the devitalized bone is not normal and has limited healing potential, and the biomechanical strength is decreased owing to processing and tumor-related bone loss. Because this technique is not used in many countries, there are few reports on the results of this procedure such as complications, graft survival, and limb function. QUESTIONS/PURPOSES: (1) What was the rate of complications such as fracture, nonunion, infection, or recurrence in a tumor-devitalized autograft treated with deep freezing, pasteurization, and irradiation, and what factors were associated with the complication? (2) What were the 5-year and 10-year grafted bone survival (free from graft bone removal) of the three methods used to devitalize a tumor-containing autograft, and what factors were associated with grafted bone survival? (3) What was the proportion of patients with union of the tumor-devitalized autograft and what factors were associated with union of the graft-host bone junction? (4) What was the limb function after the tumor-devitalized autograft, and what factors were related to favorable limb function? METHODS: This was a retrospective, multicenter, observational study that included data from 26 tertiary sarcoma centers affiliated with the Japanese Musculoskeletal Oncology Group. From January 1993 to December 2018, 494 patients with benign or malignant tumors of the long bones were treated with tumor-devitalized autografts (using deep freezing, pasteurization, or irradiation techniques). Patients who were treated with intercalary or composite (an osteoarticular autograft with a total joint arthroplasty) tumor-devitalized autografts and followed for at least 2 years were considered eligible for inclusion. Accordingly, 7% (37 of 494) of the patients were excluded because they died within 2 years; in 19% (96), an osteoarticular graft was used, and another 10% (51) were lost to follow-up or had incomplete datasets. We did not collect information on those who died or were lost to follow-up. Considering this, 63% of the patients (310 of 494) were included in the analysis. The median follow-up was 92 months (range 24 to 348 months), the median age was 27 years (range 4 to 84), and 48% (148 of 310) were female; freezing was performed for 47% (147) of patients, pasteurization for 29% (89), and irradiation for 24% (74). The primary endpoints of this study were the cumulative incidence rate of complications and the cumulative survival of grafted bone, assessed by the Kaplan-Meier method. We used the classification of complications and graft failures proposed by the International Society of Limb Salvage. Factors relating to complications and grafted autograft removal were analyzed. The secondary endpoints were the proportion of bony union and better limb function, evaluated by the Musculoskeletal Tumor Society score. Factors relating to bony union and limb function were also analyzed. Data were investigated in each center by a record review and transferred to Kanazawa University. RESULTS: The cumulative incidence rate of any complication was 42% at 5 years and 51% at 10 years. The most frequent complications were nonunion in 36 patients and infection in 34 patients. Long resection (≥ 15 cm) was associated with an increased risk of any complication based on the multivariate analyses (RR 1.8 [95% CI 1.3 to 2.5]; p < 0.01). There was no difference in the rate of complications among the three devitalizing methods. The cumulative graft survival rates were 87% at 5 years and 81% at 10 years. After controlling for potential confounding variables including sex, resection length, reconstruction type, procedure type, and chemotherapy, we found that long resection (≥ 15 cm) and composite reconstruction were associated with an increased risk of grafted autograft removal (RR 2.5 [95% CI 1.4 to 4.5]; p < 0.01 and RR 2.3 [95% CI 1.3 to 4.1]; p < 0.01). The pedicle freezing procedure showed better graft survival than the extracorporeal devitalizing procedures (94% versus 85% in 5 years; RR 3.1 [95% CI 1.1 to 9.0]; p = 0.03). No difference was observed in graft survival among the three devitalizing methods. Further, 78% (156 of 200 patients) of patients in the intercalary group and 87% (39 of 45 patients) of those in the composite group achieved primary union within 2 years. Male sex and the use of nonvascularized grafts were associated with an increased risk of nonunion (RR 2.8 [95% CI 1.3 to 6.1]; p < 0.01 and 0.28 [95% CI 0.1 to 1.0]; p = 0.04, respectively) in the intercalary group after controlling for confounding variables, including sex, site, chemotherapy, resection length, graft type, operation time, and fixation type. The median Musculoskeletal Tumor Society score was 83% (range 12% to 100%). After controlling for confounding variables including age, site, resection length, event occurrence, and graft removal, age younger than 40 years (RR 2.0 [95% CI 1.1 to 3.7]; p = 0.03), tibia (RR 6.9 [95% CI 2.7 to 17.5]; p < 0.01), femur (RR 4.8 [95% CI 1.9 to 11.7]; p < 0.01), no event (RR 2.2 [95% CI 1.1 to 4.5]; p = 0.03), and no graft removal (RR 2.9 [95% CI 1.2 to 7.3]; p = 0.03) were associated with an increased limb function. The composite graft was associated with decreased limb function (RR 0.4 [95% CI 0.2 to 0.7]; p < 0.01). CONCLUSION: This multicenter study revealed that frozen, irradiated, and pasteurized tumor-bearing autografts had similar rates of complications and graft survival and all resulted in similar limb function. The recurrence rate was 10%; however, no tumor recurred with the devitalized autograft. The pedicle freezing procedure reduces the osteotomy site, which may contribute to better graft survival. Furthermore, tumor-devitalized autografts had reasonable survival and favorable limb function, which are comparable to findings reported for bone allografts. Overall, tumor-devitalized autografts are a useful option for biological reconstruction and are suitable for osteoblastic tumors or osteolytic tumors without severe loss of mechanical bone strength. Tumor-devitalized autografts could be considered when obtaining allografts is difficult and when a patient is unwilling to have a tumor prosthesis and allograft for various reasons such as cost or socioreligious reasons. LEVEL OF EVIDENCE: Level III, therapeutic study.

Family cancer history and smoking habit associated with sarcoma in a Japanese population study.

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.

Dedifferentiation in low-grade osteosarcoma: a Japanese Musculoskeletal Oncology Group (JMOG) study.

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.

Immunological status of peripheral blood is associated with prognosis in patients with bone and soft-tissue sarcoma.

Immune-checkpoint inhibitors have shown promising antitumor effects against certain types of cancer. However, specific immune-checkpoint inhibitors for patients with sarcoma have yet to be identified, whereas the immunological status of peripheral blood in patients with bone sarcoma and soft-tissue sarcoma (STS) remains unknown. In addition, it is unclear whether the immunological status from the peripheral blood could be used as a prognostic indicator. Therefore, the present study aimed to clarify the immunological status of peripheral blood samples derived from patients with bone sarcoma and STS. Immune monitoring was performed using the peripheral blood samples of 61 patients with no metastasis of high-grade sarcoma. A total of 25 patients with metastatic sarcoma were used for comparison. A total of 41 immune cell subsets were analyzed using multicolor-flow cytometry. The patients that did not have metastasis demonstrated higher quantities of monocytic myeloid-derived suppressor cells (M-MDSCs) and T cell immunoglobulin and mucin domain-3 (Tim-3)+ CD8+ T cells, which were significantly associated with poor disease-free survival (DFS) time, while higher quantities of NKG2D+ CD8+ T cells were significantly associated with improved DFS time. Multivariate Cox regression analysis demonstrated that the number of Tim-3+ CD8+ T cells was associated with lower DFS time. A significant association was also found between the number of M-MDSCs and progression-free survival (PFS) time in patients with metastasis. The results suggested the occurrence of immune surveillance, which indicated that the host immune reaction against cancer existed in patients with bone sarcoma and STS. Notably, a high number of M-MDSCs was associated with both DFS and PFS time, suggesting a strong prognostic value. The data suggested that the immune status of peripheral blood was associated with the prognosis in patients with sarcoma, as previously reported in patients with other cancer types. In summary, the results may assist with the development of novel strategies for sarcoma treatment, based on the use of biomarkers or immunotherapy.

Establishment and characterization of patient-derived cancer models of malignant peripheral nerve sheath tumors.

BACKGROUND: Malignant peripheral nerve sheath tumors (MPNSTs) are a rare subtype of soft-tissue sarcoma, derived from a peripheral branch or the sheath of the sciatic nerve, brachial plexus, or sacral plexus. The clinical outcomes for MPNST patients with unresectable or metastatic tumors are dismal, and novel therapeutic strategies are required. Although patient-derived cancer cell lines are vital for basic research and preclinical studies, few MPNST cell lines are available from public cell banks. Therefore, the aim of this study was to establish cancer cell lines derived from MPNST patients. METHODS: We used tumor tissues from five patients with MPNSTs, including one derived from a rare bone tissue MPNST. The tumor tissues were obtained at the time of surgery and were immediately processed to establish cell lines. A patient-derived xenograft was also established when a sufficient amount of tumor tissue was available. The characterization of established cells was performed with respect to cell proliferation, spheroid formation, and invasion. The mutation status of actionable genes was monitored by NCC Oncopanel, by which the mutation of 114 genes was assessed by next-generation sequencing. The response to anti-cancer agents, including anti-cancer drugs approved for the treatment of other malignancies was investigated in the established cell lines. RESULTS: We established five cell lines (NCC-MPNST1-C1, NCC-MPNST2-C1, NCC-MPNST3-C1, NCC-MPNST4-C1, and NCC-MPNST5-C1) from the original tumors, and also established patient-derived xenografts (PDXs) from which one cell line (NCC-MPNST3-X2-C1) was produced. The established MPNST cell lines proliferated continuously and formed spheroids while exhibiting distinct invasion abilities. The cell lines had typical mutations in the actionable genes, and the mutation profiles differed among the cell lines. The responsiveness to examined anti-cancer agents differed among cell lines; while the presence of an actionable gene mutation did not correspond with the response to the anticipated anti-cancer agents. CONCLUSION: The established cell lines exhibit various characteristics, including proliferation and invasion potential. In addition, they had different mutation profiles and response to the anti-cancer agents. These observations suggest that the established cell lines will be useful for future research on MPNSTs.

Minimal clinically important differences in Toronto Extremity Salvage Score for patients with lower extremity sarcoma.

BACKGROUND: The Toronto Extremity Salvage Score (TESS) is the most widely used patient-reported outcome measure for orthopaedic oncology patients. However, minimal clinically important differences (MCIDs) in the TESS have not been analyzed. The aim of this study was to define the MCIDs of TESS in patients with lower extremity sarcoma. METHODS: A total of 85 patients were investigated to calculate the MCIDs for TESS. Three different methods were used: 1) distribution-based methods based on one-half of the standard deviation and standard error of measurement (SEM) at the baseline, 2) anchor-based and receiver operating characteristic (ROC) analysis, and 3) anchor-based using Akaike's Information Criterion (AIC) analysis. RESULTS: The MCIDs at 6 months were 4.9-7.8 by distribution-based methods and 4.3-4.4 by anchor-based methods. The MCIDs at 12 months were 4.0-6.9 by distribution-based methods and 10.6-11.6 by anchor-based methods. CONCLUSIONS: We calculated MCID values for the TESS based on distribution- and anchor-based approaches. Our results seem reasonable since MCIDs calculated by the different approaches had similar values. This knowledge will enable clinicians to identify meaningful functional improvements in sarcoma patients.

KMT2A (MLL) fusions in aggressive sarcomas in young adults.

AIM: To characterise unclassifiable sarcomas by use of a combined histological and molecular approach. METHODS AND RESULTS: Using RNA sequencing, we identified in-frame fusions involving KMT2A (MLL) in two cases. Case 1 was a 20-year-old woman with a deep soft tissue mass in the thigh. The tumour consisted of monomorphic round, epithelioid and spindle cells in a highly sclerotic background that were focally immunopositive for CD34, CD31, and ERG. Case 2 was a 30-year-old woman with a tumour that affected the femur and surrounding soft tissue. The tumour consisted of monomorphic round to spindle cells that were immunopositive for BCOR, Wilms tumour 1, and NKX2-2. Both tumours were aggressive and had metastasised to the lung; both patients died within a few years. RNA sequencing identified a YAP1 (exon 5)-KMT2A (exon 4) fusion in case 1 and a VIM (exon 4)-KMT2A (exon 2) fusion in case 2, both of which were confirmed by reverse transcription polymerase chain reaction, Sanger sequencing, and fluorescence in-situ hybridisation. The fusion protein structure was different from that in acute leukaemia, suggesting a novel oncogenic mechanism. CONCLUSIONS: KMT2A fusions account for a subset of aggressive unclassifiable sarcomas in young adults. Although it is presently unclear whether these sarcomas belong to a single group, the well-established role of KMT2A fusions as drivers of acute leukaemia and a recent publication regarding identification of YAP1-KMT2A in one unclassifiable sarcoma support the significance of these fusions. Further studies on additional cases are necessary to fully understand the clinicopathological and molecular aspects of KMT2A-rearranged sarcomas.

A serum microRNA classifier for the diagnosis of sarcomas of various histological subtypes.

Due to their rarity and diversity, sarcomas are difficult to diagnose. Consequently, there is an urgent demand for a novel diagnostic test for these cancers. In this study, we investigated serum miRNA profiles from 1002 patients with bone and soft tissue tumors representing more than 43 histological subtypes, including sarcomas, intermediate tumors, and benign tumors, to determine whether serum miRNA profiles could be used to specifically detect sarcomas. Circulating serum miRNA profiles in sarcoma patients were clearly distinct from those in patients with other types of tumors. Using the serum levels of seven miRNAs, we developed a molecular detector, Index VI, that could distinguish sarcoma patients from benign and healthy controls with remarkably high sensitivity (90%) and specificity (95%), regardless of histological subtype. Index VI provides an approach to the early and precise detection of sarcomas, potentially leading to curative treatment and longer survival.

Development of a patient-oriented disease specific outcome measure of health-related quality of life (HRQOL) for musculoskeletal oncology patients.

BACKGROUND: According to improved functional outcome and life expectancy in orthopaedic oncology patients, there has been a growing interest in not only oncologic and functional outcomes but also health-related quality of life (HRQOL), including body image, mental status, or social activities, after surgery. However, there has been a lack of disease-specific measures focusing on the ability of orthopaedic oncology patients to evaluate their HRQOL comprehensively. Therefore, our aims in the present study were 1) to develop a patient-oriented disease-specific outcome measure of HRQOL for musculoskeletal oncology patients (COMMON-LE), and 2) to examine the practical applicability, reliability and validity of the COMMON-LE for patients with musculoskeletal tumors in the lower extremity. METHODS: The COMMON-LE was developed by expert committee of orthopaedic oncology and rehabilitation. A total of 101 patients were surveyed using the COMMON-LE, as well as the TESS, the MSTS score, and the SF-36, to assess their psychometric characteristics, including reliability, validity, and responsiveness. RESULTS: The COMMON-LE showed no marked floor and ceiling effects. Test-retest reliability and internal consistency determined using the intraclass correlation coefficient (0.928) and Cronbach's alpha (0.948-0.968), respectively, were excellent. Each domain of the COMMON-LE (pain, ADL, socioemotional condition and general health) was well correlated with the scores of the standard measures (SF-36, TESS, MSTS score). Factor analysis and the AIC network showed the questionnaire items of the COMMON-LE were clearly separable into three clusters according to their content, corresponding to each domain of the questionnaire. CONCLUSIONS: We have successfully developed and validated a disease-specific measure, the COMMON-LE, to evaluate not only physical function, but also various aspects of HRQOL in patients with musculoskeletal tumors. The COMMON-LE has sufficient reliability and internal consistency, and good validity, and appears to be practically applicable to this group of patients.

Establishment of a novel patient-derived Ewing's sarcoma cell line, NCC-ES1-C1.

Ewing's sarcoma is an aggressive mesenchymal tumor characterized by the presence of a unique EWSR1-FLI1 translocation. Ewing's sarcoma primarily occurs in the bone and soft tissues. Cell lines enable researchers to investigate the molecular backgrounds of disease and the significance of genetic alterations in relevant cellular contexts. Here, we report the establishment and characterization of a novel Ewing's sarcoma cell line following primary Ewing's sarcoma tumor tissue culture. The established cell line was authenticated by DNA microsatellite short tandem repeat analysis, characterized by in vitro assays, and named NCC-ES1-C1. The NCC-ES1-C1 cell line grew well for 15 mo and was subcultured more than 50 times during this period. Characterization of the cells revealed that they were not adherent and showed floating features. In conclusion, we successfully established a novel Ewing's sarcoma cell line, NCC-ES1-C1, from primary tumor tissue. The cell line has the characteristic EWSR1-FLI1 gene fusion and exhibits aggressive growth in vitro. Thus, the NCC-ES1-C1 cell line will be a useful tool for investigating the mechanisms of disease and the biological role of the EWSR1-FLI1 fusion gene.

Reconstruction of the Shoulder Joint with a Custom-Made Ceramic Implant After a Total Scapulectomy: A Case Report.

CASE: We describe a 22-year-old woman who underwent total scapulectomy and shoulder joint reconstruction with use of a custom-made ceramic implant composed of hydroxyapatite and beta-tricalcium phosphate (ß-TCP) for a recurrent atypical perineurioma that had arisen from the scapula. CONCLUSION: To our knowledge, there have been no previous reports of shoulder joint reconstruction with use of a custom-made ceramic implant after a total scapulectomy. The patient showed excellent function of the new shoulder joint and good range of motion without pain or dislocation at 18 months postsurgery. This new method of reconstructing the shoulder joint after a total scapulectomy appears useful and promising.

Reliability and Validity of the Musculoskeletal Tumor Society Scoring System for the Upper Extremity in Japanese Patients.

BACKGROUND: The Musculoskeletal Tumor Society (MSTS) scoring system developed in 1993 is a widely used disease-specific evaluation tool for assessment of physical function in patients with musculoskeletal tumors; however, only a few studies have confirmed its reliability and validity. QUESTIONS/PURPOSES: The aim of this study was to validate the MSTS scoring system for the upper extremity (MSTS-UE) in Japanese patients with musculoskeletal tumors for use by others in research. Does the MSTS-UE have: (1) sufficient reliability and internal consistency; (2) adequate construct validity; and (3) reasonable criterion validity in comparison to the Toronto Extremity Salvage Score (TESS) or SF-36? METHODS: Reliability was performed using test-retest analysis, and internal consistency was evaluated with Cronbach's alpha coefficient. Construct validity was evaluated using a scree plot to confirm the construct number and the Akaike information criterion network. Criterion validity was evaluated by comparing the MSTS-UE with the TESS and SF-36. RESULTS: The test-retest reliability with intraclass correlation coefficient (0.95; 95% CI, 0.91-0.97) was excellent, and internal consistency with Cronbach's α (0.7; 95% CI, 0.53-0.81) was acceptable. There were no ceiling and floor effects. The Akaike Information Criterion network showed that lifting ability, pain, and dexterity played central roles among the components. The MSTS-UE showed substantial correlation with the TESS scoring scale (r = 0.75; p < 0.001) and fair correlation with the SF-36 physical component summary (r = 0.37; p = 0.007). Although the MSTS-UE showed slight correlation with the SF-36 mental component summary, the emotional acceptance component of the MSTS-UE showed fair correlation (r = 0.29; p = 0.039). CONCLUSIONS: We can conclude that the MSTS is not an adequate measure of general health-related quality of life; however, this system was designed mainly to be a simple measure of function in a single extremity. To evaluate the mental state of patients with musculoskeletal tumors in the upper extremity, further study is needed.

Phase 1/2 study of immunotherapy with dendritic cells pulsed with autologous tumor lysate in patients with refractory bone and soft tissue sarcoma.

BACKGROUND: There are limited options for the curative treatment of refractory bone and soft tissue sarcomas. The purpose of this phase 1/2 study was to assess the immunological and clinical effects of dendritic cells (DCs) pulsed with autologous tumor lysate (TL) in patients with advanced bone and soft tissue sarcomas. METHODS: Thirty-seven patients with metastatic or recurrent sarcomas were enrolled in this study. Peripheral blood mononuclear cells obtained from the patients were suspended in media containing interleukin 4 (IL-4) and granulocyte-macrophage colony-stimulating factor. Subsequently, these cells were treated with TL, tumor necrosis factor α, and OK-432. The DCs were injected into the inguinal or axillary region. One treatment course comprised 6 weekly DC injections. The toxicity, clinical response (tumor volume, serum interferon-γ [IFN-γ], and serum IL-12), and oncological outcomes were observed. RESULTS: In total, 47 courses of DC therapy were performed in 37 patients. No severe adverse events or deaths associated with the DC injections were observed in the study patients. Increased serum IFN-γ and IL-12 levels were observed 1 month after the DC injection. Among the 37 patients, 35 patients were assessed for clinical responses: 28 patients showed tumor progression, 6 patients had stable disease, and 1 patient showed a partial response 8 weeks after the DC injection. The 3-year overall and progression-free survival rates of the patients were 42.3% and 2.9%, respectively. CONCLUSIONS: Although DC therapy appears safe and resulted in an immunological response in patients with refractory sarcoma, it resulted in an improvement of the clinical outcome in only a small number of patients. Cancer 2017;123:1576-1584. © 2017 American Cancer Society.

Pathogenesis of Osteosclerotic Change Following Treatment with an Antibody Against RANKL for Giant Cell Tumour of the Bone.

BACKGROUND: Giant cell tumours (GCTs) of the bone are intermediate tumours that are locally aggressive. Denosumab, an antibody against receptor activator of nuclear factor kappa-B ligand (RANKL), was recently developed; however, it induces osteosclerotic change through an unknown mechanism. We determined whether osteosclerotic change could be induced by neoplastic stromal cells of giant cell tumours (GCTs). PATIENTS AND METHODS: Participants included four patients with GCT of the bone who were treated with neoadjuvant denosumab. Expression of alkaline phosphatase (ALP), osteocalcin (OCN), RANKL and histone H3K36 trimethylation were assessed through immunohistochemistry of biopsy and surgical specimens. RESULTS: OCN expression was significantly elevated after denosumab treatment, whereas ALP and RANKL expressions were not significantly elevated. Immunofluorescence staining revealed OCN expression and H3K36 trimethylation while their co-localisation was confirmed in the surgical specimens. CONCLUSION: Denosumab promoted OCN expression and might induce the osteogenic differentiation of GCT stromal cells.

Angiomatoid fibrous histiocytoma: a series of seven cases including genetically confirmed aggressive cases and a literature review.

BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor of intermediate biologic potential. Because of its rarity and nonspecific radiological and diverse pathological findings, AFH is often clinically misdiagnosed. However, few clinical reports have described this tumor. As reported herein, we analyzed the clinical and radiological features and clinical outcomes of AFH. METHODS: We retrospectively reviewed the medical records of seven cases histopathologically diagnosed as AFH. We examined clinical features, MRI findings, histopathological diagnoses, treatments, and outcomes. RESULTS: These seven cases comprised five male and two female patients with ages ranging from 8 to 50 years old. The primary locations included upper extremities in 2, lower extremities in 4, and the inguinal region in one patient. Of the tumors, 4 occurred in subcutaneous tissues and 3 occurred in deep tissues. No cases were diagnosed as AFH from MRI and needle biopsy results. All cases were diagnosed histopathologically after excision. After treatment, 2 patients (29%) had tumor recurrence and metastasis, one of whom died from disease progression. These 2 aggressive cases involved both EWSR1 and CREB1 gene rearrangements as determined by FISH. The other patients were alive and well without recurrence or metastasis. CONCLUSION: AFH is a rare tumor that is difficult to diagnose. Therefore, it tends to be misdiagnosed and to be treated inadequately by referring physicians. Surgeons must therefore be mindful of the presence of AFH, learn about appropriate treatment necessary for this tumor, and conduct careful follow-up because AFH can engender poor outcomes.