The association between the immune status within the tumor microenvironment and prognosis in synovial sarcoma is not well understood. We aimed to investigate the tumor immune microenvironment and ...analyze its prognostic impact for patients with synovial sarcoma. A total of 36 primary patients who were treated in our institution were retrospectively evaluated. Infiltration of lymphocytes (CD4+, CD8+, and FOXP3+), CD163+ macrophages, and expression of human leukocyte antigen (HLA) class I and programmed death ligand 1 (PD‐L1) were evaluated by immunohistochemistry. Moreover, we investigated PD‐L1 and programmed death ligand 2 (PD‐L2) mRNA expression in 19 of the 36 cases, using real‐time PCR. The Kaplan‐Meier method was used to estimate overall survival and progression‐free survival. Infiltration of lymphocytes and macrophages varied among the patients. Furthermore, the expression of HLA class I was negative or downregulated in 11 specimens. No PD‐L1 expression was observed using immunohistochemistry. Moreover, although PD‐L1 mRNA expression was observed in 18 of 19 specimens, the expression level was low. A higher infiltration of CD8+ or FOXP3+ lymphocytes in patients was associated with a favorable overall survival. In addition, a higher infiltration of CD163+ macrophages indicated a significantly worse overall and progression‐free survival. Infiltration of CD4+ lymphocytes, HLA class I, PD‐L1, and PD‐L2 expression were not associated with patient prognosis. This represents the first report investigating the tumor immune microenvironment as a prognostic factor in synovial sarcoma, indicating that CD163+ macrophages are associated with tumor progression. Our results underscore the clinical significance of the tumor immune microenvironment in synovial sarcoma.
We are the first to investigate the tumor immune environment of primary non‐treated patients with synovial sarcoma and analyze its clinical significance in synovial sarcoma. We showed that the infiltration of CD163+ macrophages plays an important role in disease progression in patients with synovial sarcoma.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Introduction
Polypharmacy is associated with an increased risk of fracture in aging populations, but no study has accounted for the impact of kidney function on this association. This study aimed to ...examine the association between polypharmacy and incident fragility fracture based on chronic kidney disease (CKD) status.
Materials and methods
Participants were 2023 patients (55% men; mean age, 69 years) of Sado General Hospital enrolled in the Project in Sado for Total Health (PROST) between June 2008 and December 2016. Among these, 65%, 28%, and 7% had non-CKD, non-dialysis-dependent CKD, and dialysis-dependent CKD, respectively. Multivariable Cox proportional hazards analysis was conducted with adjustments for potential confounders.
Results
Prevalences of polypharmacy (≥ 5 medications) and hyperpolypharmacy (≥ 10 medications) among participants were 43% and 9% for non-CKD, 62% and 23% for non-dialysis-dependent CKD, and 85% and 34% for dialysis-dependent CKD, respectively. During a median follow-up of 5.6 years, 256 fractures occurred. More medications were associated with a higher risk of fractures. Specifically, compared to participants without polypharmacy, adjusted hazard ratios were 1.32 (95% CI 0.96–1.79) and 1.99 (1.35–2.92) for those with polypharmacy and hyperpolypharmacy, respectively, after adjusting for osteoporosis risk factors, CKD status, and comorbidities. No effect modification by CKD status was observed (interaction
P
= 0.51). Population-attributable fractions of hyperpolypharmacy for fracture were 9.9% in the total cohort and 42.1% in dialysis-dependent CKD patients.
Conclusion
Hyperpolypharmacy is associated with an increased risk of fragility fracture regardless of CKD status, and has a strong impact on incident fragility fractures in dialysis-dependent CKD patients.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Chondrosarcoma is the second most common primary malignant bone tumor. In this multicenter study, we sought to evaluate the disease‐specific survival (DSS) and disease‐free survival (DFS), and ...prognostic factors in patients with dedifferentiated chondrosarcoma (DDCS) or grade 3 chondrosarcoma (G3CS) in Japan. We retrospectively investigated the treatment outcomes and prognostic factors in 62 patients with DDCS and 19 patients with G3CS at 15 institutions participating in the Japanese Musculoskeletal Oncology Group. We also clarified significant clinicopathological factors for oncological outcomes. In surgery for primary lesions aimed at cure, a histologically negative margin (R0) was obtained in 93% (14/15) of patients with G3CS and 100% (49/49) of patients with DDCS. The 5‐year DSS was 18.5% in patients with DDCS and 41.7% in patients with G3CS (p = 0.13). Local control was obtained in 80% (12/15) and 79.6% (39/49) of patients with G3CS and DDCS in the primary lesion after surgery with a wide surgical margin, respectively. In multivariate analysis, stage and no treatment/palliative treatment for the primary lesion were independent prognostic factors for DSS of DDCS, and age and no treatment/palliative treatment for DSS of G3CS. The 5‐year DFS rate was 22.8% in 26 patients with DDCS who did not receive adjuvant chemotherapy, and 21.4% in 14 patients who received adjuvant chemotherapy. The prognosis of DDCS remains poor, although R0 resection was carried out in most cases. Effective and/or intensive chemotherapeutic regimens or agents should be considered or developed for patients with high‐grade chondrosarcoma, particularly for those with DDCS.
This study clarified the clinical outcomes of dedifferentiated chondrosarcoma (DDCS) and grade 3 chondrosarcoma (G3CS) by a nationwide multicenter study in Japan, which is the largest research report from Asian countries. Although all cases (100%) of DDCS and 93% of G3CS underwent surgery with a negative margin (R0), the 5‐year disease‐specific survival was 18.5% in DDCS and 41.7% in G3CS patients.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
The regioselective halogenation of porphyrinoids is critical for their selective functionalization, which enables the fine tuning of their electronic and optical properties. Here we report the ...synthesis of two regioisomeric Ni(II) bromonorcorroles on the basis of the acid-induced migration of the bromo substituent. Treatment of Ni(II) dimesitylnorcorrole with N-bromosuccinimide (NBS) selectively afforded Ni(II) 3-bromonorcorrole, which was further converted into Ni(II) 2-bromonorcorrole upon treatment with hydrogen bromide. In addition, the reaction of Ni(II) dimesitylnorcorrole with an excess amount of NBS afforded the octabrominated product. The reaction mechanism of the bromination reaction of Ni(II) dimesitylnorcorrole was investigated by theoretical calculations.
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IJS, KILJ, NUK, PNG, UL, UM
Global femoral offset (GFO) and femoral offset (FO) reportedly affect outcomes following total hip arthroplasty (THA). However, FO assessed using plain radiography is affected by internal and ...external rotations of the hip joint. We investigated the relationship between leg length discrepancy and Harris hip score (HHS), and their influence on acetabular offset (AO), FO, GFO, anterior femoral offset, and outcomes after THA. We retrospectively evaluated 140 patients with hip osteoarthritis who underwent THA. A three-dimensional (3D) pelvis and femur model created from computed tomography (data using ZedHip software was used to investigate these parameters. The modified (m)HHS scores were significantly improved from 49.0 to 88.8 in total mHHS, 20.0-44.5 in pain, and 28.9-44.4 points in function. Significant correlations were found between the differences in AO, FO, GFO, and pain score in binominal, with maximum values of - 1.24, + 1.54, and + 0.90 mm/100 cm body height, respectively. The maximum value of GFO and mHHS in binominal was + 1.17 mm/100 cm body height (BH). The optimal range of difference of GFO was - 1.75 to 4.09 mm/100 cm BH. This is the first report using a 3D method for assessing FO. Preoperative planning using the system could improve postoperative function.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Teriparatide (TPTD) administration has a potent osteogenic action and promotes the healing of osteoporotic vertebral fractures (OVFs). We aimed to investigate the outcomes of vertebroplasty with ...posterior spinal fusion (VP + PSF) and determine the impact of perioperative TPTD administration. We included 73 patients (18 male and 55 female patients; mean age: 78 years) with thoracolumbar OVFs who underwent VP + PSF and were followed-up for at least 2 years. Twenty-three patients who received TPTD perioperatively for > 3 months were included in the TPTD group, and the remaining 50 patients were included in the non-TPTD group. Radiographic findings regarding sagittal alignment and clinical outcomes in both groups were compared. The mean duration of TPTD administration was 17.5 ± 5.0 months (range 4-24 months). The mean loss of correction of local kyphosis angle in the TPTD group (4.0°) was lesser than that in the non-TPTD group (7.5°; p < 0.05); however, no significant differences were observed between the groups regarding global sagittal alignment, the occurrence of subsequent vertebral fractures, pedicle screw loosening and treatment-efficacy rates of clinical outcomes. Local kyphosis correction in patients who underwent VP + PSF for OVFs could be maintained through perioperative TPTD administration; however, TPTD administration had little effect on clinical outcomes.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The synthesis and properties of a 2-to-2′ 18-to-18′ doubly linked Ni(
ii
) norcorrole dimer are described. It adopts a highly planar structure, resulting in effective electronic interactions between ...the constituent norcorrole units. Nevertheless, each norcorrole unit exhibits substantial antiaromaticity, which stands in sharp contrast to stacked norcorrole dimers.
A fused norcorrole dimer has been synthesized in which each norcorrole unit exhibited distinct antiaromaticity.
Purpose
Whether the inclined articular surface on the medial proximal tibia and the external knee adduction moment (KAM) correlate remains unclear. The hypothesis was that a steeper inclined ...articular surface correlated with a larger KAM in advanced knee osteoarthritis (OA).
Methods
A total of 44 females (non-OA, 9 knees; early OA, 14 knees; advanced OA, 21 knees; mean age, 58 ± 16 years) were examined. Three-dimensional (3D) assessment was used on biplanar long-leg radiographs and 3D bone models using a 3D to 2D image registration technique. The approximation plane in the proximal tibia was determined using the least-square method. The joint moments were mathematically calculated in a gait analysis, applying a motion capture system and force plates. The main evaluation parameters were the femorotibial angle (FTA), the coronal inclination of the approximation plane in the medial proximal tibia (coronal inclination), and internal knee joint moments. The KAM means the external moments balanced with the internal knee abduction moments.
Results
The advanced OA showed a larger internal abduction moment (
p
= 0.017) at the loading response than the other groups. The larger FTA and steeper coronal inclination correlated with the larger internal abduction moment (FTA,
p
< 0.001; coronal inclination,
p
= 0.003) at the loading response.
Conclusions
As the clinical relevance, the association among the coronal inclination of the medial proximal tibia, lower extremity alignment, and KAM is one of the key factors to help better understand the etiology of knee OA.
Level of evidence
III.
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EMUNI, FSPLJ, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Clear cell chondrosarcoma is an extremely rare chondrosarcoma subtype; thus, its treatment outcomes and associated factors have not been widely studied. Knowing more about it is potentially important ...because clear cell chondrosarcomas are often misdiagnosed as other benign lesions and subsequently treated and followed inappropriately.
(1) What are the patient- and tumor-related characteristics of clear cell chondrosarcoma? (2) What proportion of patients with clear cell chondrosarcoma initially had a misdiagnosis or a misleading initial biopsy result? (3) What is the survivorship of patients with clear cell chondrosarcoma free from death, local recurrence, and distant metastasis, and what factors are associated with greater survivorship or a reduced risk of local recurrence?
Between 1985 and 2018, 12 Japanese Musculoskeletal Oncology Group (JMOG) hospitals treated 42 patients with a diagnosis of clear cell chondrosarcoma. All 42 patients had complete medical records at a minimum of 1 year or death, and were included in this multicenter, retrospective, observational study. No patients were lost to follow-up within 5 years of treatment but four were lost to follow-up greater than 5 years after treatment because their physicians thought their follow-up was sufficient. Clinical data were collected by chart review. The median (range) follow-up period was 69 months (2 to 392). In general, when a possibly malignant bone tumor was found on imaging studies, the histological diagnosis was made by biopsy before initiating treatment. Once the diagnosis had been made, the patients were treated by surgery only, complete resection if technically possible, because chondrosarcomas are known to be resistant to chemotherapy and radiotherapy. Unresectable tumors were treated with particle-beam radiation therapy. When patients with chondrosarcoma were referred after unplanned surgical procedures with inadequate surgical margins, immediate additional wide resection was considered before local recurrence developed. This diagnostic and treatment strategy is common to all JMOG hospitals and did not change during the study period. Primary wide resection was performed in 79% (33 of 42) patients, additional wide resection after initial inadequate surgery in 12% (five of 42), curettage and bone grafting in 5% (two of 42) patients, and radiotherapy was administered to 5% (two of 42). Surgical margins among the 40 patients who underwent surgery at JMOG hospitals were no residual tumor in 93% (37 of 42) of patients, microscopic residual tumor in 2% (one of 42), and macroscopic residual tumor or state after curettage or intralesional excision in 5% (two of 42). The oncological endpoints of interest were 5- and 10- year overall survival, disease-free survival, survival free of local recurrence, and survival free of distant metastases; these were calculated using the Kaplan-Meier method and compared using the log-rank test. Risk ratios with their respective 95% confidence intervals (CIs) were estimated in a Cox regression model. The Bonferroni adjustment was used for multiple testing correction.
The sex distribution was 74% men and 26% women (31 and 11 of 42, respectively), with a mean age of 47 ± 17 years. Eighty one percent (34 of 42) of tumors occurred at the ends of long bones, and the proximal femur was the most common site accounting for 60% (25 of 42). The mean size of the primary tumors was 6.3 ± 2.7 cm. Definite pathologic fractures were present in 26% (10 of 42) and another 26% (10 of 42) had extraskeletal involvement. None had metastases at presentation. Twenty four percent (six of 25) tumors in the proximal femur were misdiagnosed as benign lesions and treated inadequately without biopsy. Twenty nine percent (10 of 35) patients had initial misdiagnoses by biopsy and core needle biopsies had a greater risk of resulting in inaccurate histological diagnoses. The study patients' 5- and 10-year overall survival rates were 89% (95% CI 74 to 96) and 89% (95% CI 74 to 96), respectively; 5- and 10- year disease-free survival rates 77% (95% CI 58 to 89) and 57% (95% CI 36 to 75), respectively; 5- and 10-year local recurrence-free survival rates 86% (95% CI 68 to 95) and 71% (95% CI 49 to 86), respectively; and 5- and 10-year distant metastasis-free survival rates 84% (95% CI 67 to 93) and 74% (95% CI 53 to 88), respectively. Notably, bone metastases (17%, seven of 42) were as common as pulmonary metastases (14%, six of 42); four patients developed both bone and pulmonary metastases. The difference between 10-year overall survival rates and 10-year disease-free survival indicated very late recurrence more than 5 years after the initial treatment. After controlling for multiple comparisons, the only factor we found that was associated with local recurrence-free survival was initial treatment (positive margin versus primary wide resection) (risk ratio 8.83 95% CI 1.47 to 53.1; p = 0.022 after the Bonferroni adjustment). Additional wide resection reduced the risk of local recurrence.
The femoral head was the most common location of clear cell chondrosarcoma and had a high risk of misdiagnosis as common benign lesions that resulted in initial inadequate surgery and a consequent high risk of local recurrence. Immediate additional wide resection should be considered in patients who had initial inadequate surgery to reduce the risk of local recurrence. Because clear cell chondrosarcoma can recur locally or distantly in the bones and lungs in the long term, patients should be informed of the risk of very late recurrence and the necessity of decades-long with surveillance for local recurrence and lung and bone metastases.
Level IV, therapeutic study.
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