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PURPOSE: Total knee arthroplasty (TKA), which has medial pivot and mobile-bearing mechanisms, has been developed and clinically used. However, the in vivo dynamic kinematics of the mobile medial pivot-type TKA (MMPTKA) is unclear. This study analysed the in vivo kinematics of MMPTKA in weight-bearing and nonweight-bearing conditions. METHODS: The study included 10 knees that underwent primary TKA using MMPTKA. After TKA, lateral view radiographs of the knee in full extension, 90° of flexion and passive full flexion were taken under general anaesthesia in the nonweight-bearing condition. At least 6 months postoperatively, knee motion during squatting from a weight-bearing standing position was observed using a flat-panel detector and analysed using the three-dimensional-to-two-dimensional image registration technique. RESULTS: Under anaesthesia: in passive full flexion, the anteroposterior (AP) locations of the femoral component's medial and lateral distal points were 10.2 and 16.0 mm posterior, and the rotational angles of the femoral component's X-axis (FCX) and insert were 8.1° external rotation and 18.5° internal rotation to full extension, respectively. Squatting: the AP translations of the femoral component's medial and lateral most distal points were 2.2 and 6.4 mm, and the rotational angles of the FCX and insert were 5.7° and 1.6° external rotation, respectively. Significant differences were observed in the AP translation of the femoral component's medial and lateral most distal points and changes in the insert's rotational angle when comparing under anaesthesia and squatting. CONCLUSIONS: The kinematics of the insert in MMPTKA was significantly influenced by loading and muscle contraction. The femoral component exhibited substantial external rotation and posterior translation under anaesthesia, which may contribute to achieving an optimal range of motion. The insert remained relatively stable during squatting and minimal rotation was observed, indicating good stability. MMPTKA was expected to demonstrate rational kinematics by incorporating mobile and medial pivot mechanisms. LEVEL OF EVIDENCE: Level IV, prospective biomechanical case series study.

DOI： 10.1002/ksa.12147

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Background: This retrospective cross-sectional study investigated the cutoff values (COVs) for developmental dysplasia of the hip (DDH) using a three-dimensional (3D) pelvic model reconstructed using computed tomography (CT). We included 107 healthy Japanese participants and 73 patients who had undergone curved periacetabular osteotomy (CPO) for DDH between 2012 and 2017. Methods: The hip CT images were adjusted to the anterior pelvic plane (APP), functional pelvic plane (FPP), sagittal anterior center-edge angle (ACEA), and sagittal posterior center-edge angle (PCEA). The lateral center-edge angle (LCEA), acetabular roof obliquity (ARO), anterior acetabular sector angle (AASA), and posterior acetabular sector angle (PASA) were measured. Receiver operating characteristic (ROC) curves were used to calculate the COVs, and the association between the parameters was analyzed using multiple logistic regression. Results: The ARO (≥10.2°) and LCEA (≤22.2°) were independent influencing factors for the APP, whereas the AASA (≤53.1°) and LCEA (≤24.5°) were independent influencing factors for the FPP. Conclusions: The 3D criteria for the diagnosis of DDH in Japanese individuals can identify DDH with insufficient anterior coverage, which anteroposterior plain radiographs cannot visualize, and can help determine indications for acetabular osteotomy.

DOI： 10.3390/jcm13092536

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INTRODUCTION: Although multimodal intraoperative neuromonitoring (IONM), which has high sensitivity and specificity, is typically performed during spinal deformity surgery, neurological status may deteriorate with delay after surgical maneuvers. Here, we report a rare case of delayed postoperative neurological deficit (DPND) that was not detected by IONM during posterior spinal fusion (PSF) for congenital scoliosis. CASE PRESENTATION: A 14-year-old male presented with congenital scoliosis associated with T3 and T10 hemivertebrae. Preoperative Cobb angle of proximal thoracic (PT) and main thoracic (MT) curves were 50° and 41°, respectively. PSF (T1-L1) without hemivertebrectomy was performed, and the curves were corrected to 31° and 21° in the PT and MT curves, respectively, without any abnormal findings in IONM, blood pressure, or hemoglobin level. However, postoperative neurological examination revealed complete loss of motor function. A revision surgery, release of the curve correction by removing the rods, was immediately performed and muscle strength completely recovered on the first postoperative day. Five days postoperatively, PSF was achieved with less curve correction (36° in the PT curve and 26° in the MT curve), without postoperative neurological deficits. DISCUSSION: Possible mechanisms of DPND in our patient are spinal cord ischemia due to spinal cord traction caused by scoliosis correction and spinal cord kinking by the pedicle at the concave side. Understanding the possible mechanisms of intra- and postoperative neural injury is essential for appropriate intervention in each situation. Additionally, IONM should be continued to at least skin closure to detect DPND observed in our patient.

DOI： 10.1038/s41394-024-00639-0

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PURPOSE: We aimed to determine the clinical significance of neck and shoulder pain (NSP) 10 years after posterior spinal fusion (PSF) for thoracic adolescent idiopathic scoliosis (AIS) and the relationship between radiographic parameters and NSP. METHODS: Of 72 patients who underwent PSF for thoracic AIS (Lenke 1 or 2) between 2000 and 2013, we included 52 (46 females; Lenke type 1 in 34 patients and type 2 in 18; mean age, 25.6 years) who underwent NSP evaluation using visual analog scale (VAS, 10 cm) 10 years postoperatively (follow-up rate, 72.2%). Correlation analyses were performed using Spearman's rank correlation coefficient (r). RESULTS: The VAS for NSP was 2.6 cm in median and 3.4 cm in mean at 10 years. The VAS had significant negative correlations with several SRS-22 domain scores (rs = - 0.348 for pain, - 0.347 for function,  -  0.308 for mental health, and - 0.372 for total) (p < 0.05). In addition, the VAS score was significantly correlated with cervical lordosis (CL) (rs = 0.296), lumbar lordosis (rs = - 0.299), and sacral slope (rs = 0.362) (p < 0.05). Furthermore, at the 10-year follow-up, CL was significantly negatively correlated with T1 slope (rs = - 0.763) and thoracic kyphosis (TK) (- 0.554 for T1-12 and - 0.344 for T5-12) (p < 0.02). CONCLUSION: NSP was associated with deterioration in SRS-22 scores, indicating that NSP is a clinically significant long-term issue in PSF for thoracic AIS. Restoring or maintaining the TK and T1 slopes, which are controllable factors during PSF, may improve cervical lordosis and alleviate NSP at 10-year follow-up.

DOI： 10.1007/s00586-024-08233-6

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Background and objectives Mixed reality (MR) is one of the image processing technologies that allows the user to manipulate three-dimensional (3D) virtual images (hologram). The aim of this study was to evaluate the accuracy of MR-based pedicle screw (PS) placement using 3D spine models. Materials and methods Using the preoperative CT data of a patient with adolescent idiopathic scoliosis (AIS) who had undergone posterior spinal fusion in our hospital, a 3D-printed spine model was created. On the other hand, a 3D hologram of the same patient was automatically created using the preoperative CT data uploaded to the Holoeyes MD service website (Holoeyes Inc., Tokyo, Japan). Using a Magic Leap One® headset (Magic Leap Inc., Plantation, FL), the 3D hologram with lines of predetermined PS trajectories was superimposed onto the 3D-printed spine model and PS were inserted bilaterally along with the trajectory lines from T5 to L3. As a control, we used a readymade 3D spine model of AIS and inserted PS bilaterally with a freehand technique from T4 to L3. The rate of pedicle violation was compared between the MR-based and freehand techniques. Results A total of 22 and 24 PS were placed into the 3D-printed spine model of our patient and the readymade 3D spine model, respectively. The rate of pedicle violation was 4.5% (1/22 screws) in the MR-based technique and 29.2% (7/24 screws) in the freehand technique (P = 0.049). Conclusions We demonstrated a significantly lower rate of PS misplacement in the MR-based technique than in the freehand technique. Therefore, an MR-assisted system is a promising tool for PS placement in terms of feasibility, safety, and accuracy, warranting further studies including cadaveric and clinical studies.

DOI： 10.7759/cureus.59240

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Background and Objectives: The incidence of osteoporotic hip fractures in Niigata Prefecture, Japan, has been studied approximately every 5 years since 1985. In 2020, as in previous surveys, a prefecture-wide survey was initiated as planned; however, the global outbreak of the coronavirus disease 2019 (COVID-19) began simultaneously. This study aimed to compare the results of the 2015 and 2020 Niigata Prefecture Fragility Hip Fracture Surveys to determine whether the COVID-19 pandemic affected the occurrence and treatment of proximal femoral fractures throughout Niigata Prefecture. Materials and Methods: In this study, data from the 2015 and 2020 Niigata Prefecture Fragility Hip Fracture Surveys were used. Data were obtained from registration forms returned by hospitals and clinics in Niigata Prefecture for patients living therein who were diagnosed with osteoporotic hip fractures over a 1-year period in 2015 and 2020. Results: In Niigata Prefecture, the total annual number of fractures increased from 3181 in 2015 to 3369 in 2020, whereas the age-adjusted fracture rate decreased. Regarding the location of the fractures, the proportion of outdoor fractures was lower than that of indoor fractures. The proportion of outdoor fractures decreased over the year as a whole, but in particular, the proportion of outdoor fractures decreased significantly under the issued emergency declarations. The most common reasons for delayed surgery related to COVID-19 were "waiting for PCR results" and "quarantine for fever," accounting for approximately 1.9% of all causes. Conclusions: In Niigata Prefecture, Japan, the effect of the COVID-19 pandemic on the number and rate of fractures was minuscule. The proportion of indoor fractures to outdoor fractures increased during the emergency declaration period. Considering that the number of fragility fractures remains the same during an infectious disease pandemic such as COVID-19, it is necessary to ensure that healthcare resources are available to deal with them.

DOI： 10.3390/medicina60040573

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Background/Objectives: Global femoral offset (GFO) and leg length discrepancy (LLD) affect outcomes after total hip arthroplasty (THA). Moreover, the sum of the difference in GFO between the THA and non-surgical sides and LLD (SGL) reportedly affects the outcomes in a two-dimensional evaluation. We examined the association of the GFO, LLD, and SGL with the Harris Hip Score (HHS) using a three-dimensional (3D) evaluation. Methods: We retrospectively surveyed 172 patients with hemilateral hip osteoarthritis who underwent THA. The GFO, LLD, and SGL were measured using the 3D pelvis and femur models; these models were adjusted for the pelvis and femur, and the coordinate systems were parallelized. Furthermore, their relationship with the modified HHS (mHHS) 1 year after THA was determined. Results: Significant correlations were found among mHHS, GFO, and SGL in the binomial group, whereas LLD was not significantly correlated. The optimal values of GFO and SGL were 1.01 mm and 0.18 mm/100 cm body height, respectively, which were considered optimal when the SGL values were approximately equal to those of the non-operative side. The optimal ranges for GFO and SGL were -1.65 to 3.67 mm and -4.78 to 5.14 mm/100 cm, respectively. Conclusions: Our findings were obtained after adjusting the pelvis and femur to a unified coordinate system. Therefore, the results of this study can be directly applied to 3D planning.

DOI： 10.3390/jcm13061698

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INTRODUCTION: Vitamin D deficiency causes osteoporosis, bone mineralization disorders, and osteomalacia. Osteomalacia is diagnosed using blood biochemical tests, clinical symptoms, and imaging; however, accurate detection of mineralization disorders requires tissue observation. We investigated the prevalence of bone mineralization disorders and their relationship with serum 25-hydroxyvitamin D (25OHD) levels in patients with untreated osteoporosis with femoral neck fractures. MATERIALS AND METHODS: A non-demineralized specimen was prepared from the femoral head removed during surgery in 65 patients. Bone histomorphometry of cancerous bone in the femoral head center was conducted. Osteoid volume per bone volume (OV/BV) and osteoid thickness (O.Th) were measured as indicators of mineralization disorder. RESULTS: The mean serum 25OHD level (11.9 ± 5.7 ng/mL) was in the deficiency range (< 12 ng/mL). There were no clinically diagnosed cases of osteomalacia (OV/BV > 10% and O.Th > 12.5 µm); however, one case of mineralization disorder, considered histologically pre-osteomalacia (OV/BV > 5% and O.Th < 12.5 µm), was observed (OB/BV, 17.6%; O.Th, 12.3 µm). Excluding this case, those with severe (25OHD < 12 ng/mL, at risk of osteomalacia; n = 39) and non-severe deficiency (25OHD ≥ 12 ng/mL; n = 25) did not significantly differ in OV/BV (%; 0.77 ± 0.54 vs. 0.69 ± 0.38, p = 0.484) or O.Th (µm; 5.32 ± 1.04 vs. 5.13 ± 0.78, p = 0.410). Further, 25OHD and OV/BV were not significantly correlated (R = - 0.124, p = 0.327). CONCLUSION: This is the first study in the twenty-first century to examine serum 25OHD concentrations and bone mineralization disorders in Japanese patients with osteoporosis. The results indicate that vitamin D deficiency does not necessarily cause bone mineralization disorders and rarely leads to osteomalacia.

DOI： 10.1007/s00774-024-01495-6

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UNLABELLED: Backgroumd: There have been few reports on the long-term survival of computed tomography (CT)-navigated total hip arthroplasty (THA), which should lead to a lower incidence of dislocation and loosening. In this study, we examined survivorship, dislocation, and loosening incidence using plain radiographs over a minimum 15-year follow-up after CT-navigated THA. METHODS: We retrospectively reviewed 145 consecutive CT-navigated THAs for >15 years. We surveyed the angles placed in both the acetabular and femoral components, survivorship, the occurrence of dislocation, the revision rate, and the fixation grade of the acetabular component. RESULTS: The mean follow-up duration was 18.4 years. Overall, 73.8% of THAs were within the safe zone of Lewinnek. There were four dislocations (2.8%), with three occurring within 1 month after surgery and the other within 7 years after surgery. Revision THA was performed in one case (0.69%); consequently, the survival rate was 99.3%. The fixation grade was evaluated in 144 hips, and those were evaluated as having "no loosening". CONCLUSIONS: CT-navigated THA was speculated to contribute to long-term survivorship, with a low rate of loosening, even after 18 years of follow-up. It was speculated that the acetabular component was placed at an acceptable insertion angle and a suitable position for stable initial fixation.

DOI： 10.3390/jcm13051374

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A 15-year-old girl had experienced hip pain at 11 years of age. At 15 years of age, the patient complained of persistent generalised pain. Her rheumatoid factor and serum matrix metalloproteinase-3 levels were below standard values; there were no inflammatory responses, and the human leukocyte antigen test was negative for B27 and positive for B52 and B62. The bath ankylosing spondylitis disease activity index (BASDAI) value was 8.0 at the time of induction and 3.1 at 6 months after the introduction of adalimumab (at a dose of 40 mg). The BASDAI value improved with an increase in the dose of adalimumab to 80 mg at 8 months after the initial introduction of adalimumab (at 40 mg), although it remained at 4.8 at 16 months after the dose increase. The BASDAI value was 2.6 at 6 months, 2.7 at 1 year, and 1.8 at 1.5 years after the introduction of infliximab, indicating that the patient had progressed well without any adverse events. Based on this case, juvenile ankylosing spondylitis is a differential diagnosis for low back pain and generalised pain since childhood. Tumour necrosis factor (TNF) inhibitors were promptly introduced in this case, although it took 4 years from the initial presentation. TNF inhibitors were effective in treating juvenile ankylosing spondylitis in the present case without any adverse events. This case is notable because juvenile onset ankylosing spondylitis is one of the reasons for severe lumbago since childhood and because TNF inhibitors were administered promptly after diagnosis.

DOI： 10.1093/mrcr/rxae006

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Language：Japanese   Publisher：克誠堂出版(株)  

症例は29歳女性で、右胸壁の腫瘤と疼痛を主訴とした。22歳時に胸壁動静脈奇形(AVM)の診断を受け、3回の経動脈的塞栓術の既往があるが、腫瘤はその後も増大し14×10cmとなった。3D-CT画像とMRIからAVMの主体は肋骨より浅層に存在し、肋骨への強い癒着はないと推察された。全身麻酔下で手術を施行し、周囲二重結紮法で周囲からの流入流出血管を止血しつつ切除を進めた。肋骨とAVMの接する部分からの出血が多かったため、肋骨周囲の出血点に繰り返し縫合結紮を行い、濃厚赤血球4単位の輸血を要したが、肋骨より浅層の腫瘤を一塊として摘出できた。術後15年経過して腫瘤や疼痛の再発は見られない。

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Deep dermatophytosis is an invasive and sometimes life-threatening fungal infection mainly reported in immunocompromised patients. However, a caspase recruitment domain-containing protein 9 (CARD9) deficiency has recently been reported to cause deep dermatophytosis. Herein, we report the first Japanese case of deep dermatophytosis associated with CARD9 deficiency. An 80-year-old Japanese man with tinea corporis presented with subcutaneous nodules on his left sole. Histopathological findings revealed marked epithelioid cell granulomas with filamentous fungal structures in the deep dermis and subcutis, and the patient was diagnosed with deep dermatophytosis. Despite antifungal therapy, the subcutaneous nodule on his left sole gradually enlarged, his left calcaneal bone was invaded, and the patient finally underwent amputation of his left leg. Genetic analysis revealed a homozygous CARD9 c.586 A > G (p. Lys196Glu) variant, suggesting a CARD9 deficiency. Here, we discuss the clinical features of CARD9 deficiency-associated deep dermatophytosis with a case report and review of the literature.

DOI： 10.1111/1346-8138.16995

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BACKGROUND: The postoperative varus/valgus stability assessment in stress X-rays has been established as an evaluation index. However, it is performed by the two-dimensional (2D) method rather than the three-dimensional (3D) method. OBJECTIVE: This study aimed to identify the precision and reproducibility of measuring varus/valgus stress X-rays three-dimensionally and to examine varus/valgus stability under anesthesia in imageless robotic assisted total knee arthroplasty (rTKA). METHODS: This prospective study analyzed 52 consecutive rTKAs (five males, 67 ± 5.3 years; 47 females, 74 ± 5.9 years). Postoperative varus/valgus stress X-rays in knee extension under anesthesia at manual maximum stress were three-dimensionally assessed by 2D-3D image matching technique using the 3D bone and component models. Varus/valgus angle between components (VV angle) in no stress, valgus stress, varus stress, medial joint opening (MJO), and lateral joint opening (LJO) were evaluated, clarifying this method's precision and reproducibility and valgus/varus stability. RESULTS: All parameters' precision and reproducibility had <1° mean differences and high intra- and inter-class correlation coefficients. Bland-Altman plots showed no fixed and proportional bias. Non-stress VV angle, valgus VV angle, varus VV angle, MJO, and LJO were 3.6 ± 1.2°, 1.0 ± 1.4°, 7.1 ± 1.9°, 1.5 ± 1.0 mm, and 2.8 ± 2.7 mm, respectively. CONCLUSION: This prospective study demonstrated that (1) the three-dimensional measurement method provided sufficient precision and reproducibility, and (2) the rTKAs could achieve good postoperative varus/valgus stability with a small standard deviation.

DOI： 10.3233/BME-230146

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BACKGROUND: Opioids often need to be discontinued because they cause nausea, whereas the administration of intravenous acetaminophen (APAP) causes less nausea and vomiting. This study aimed to compare the effects of fentanyl-based intravenous patient-controlled analgesia (IV-PCA) and intravenous APAP on pain and nausea after total hip arthroplasty (THA). METHODS: We prospectively investigated primary THA patients who underwent the anterolateral supine approach at four centers between October 2021 and October 2022. The patients (n = 178) were divided randomly into IV-PCA (n = 88) and APAP groups (n = 90). Rest pain, motion pain, and nausea were assessed using NRS scores. RESULTS: Compared with the APAP group, the IV-PCA group experienced significantly greater resting pain and nausea on postoperative day 1. A correlation was found between preoperative and postoperative pain. Postoperative nausea at 8 h was significantly correlated with pain at rest at 4 h (r = 0.193), 8 h (r = 0.194), day 1 (r = 0.245), and day 2 (r = 0.188) after surgery. Early postoperative pain and nausea correlated with subsequent pain and nausea. CONCLUSIONS: Intravenous APAP is associated with less pain and nausea and is superior to IV-PCA.

DOI： 10.3390/jcm12237445

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INTRODUCTION: Gait disturbance due to compressive cervical myelopathy has been previously described. However, data on how gait disturbance varies with the degree of lower extremity motor impairment are limited. Therefore, we investigated the characteristics of gait analysis based on severity and determined how gait disturbance progresses in compressive cervical myelopathy. METHODS: We enrolled 44 patients (32 men and 12 women; mean age, 65.0 years) out of 108 consecutive patients with compressive cervical myelopathy who underwent spinal cord decompression surgery in our hospital. The exclusion criteria were inability to gait and complications affecting gait. Twenty-two patients with Japanese Orthopaedic Association scores 1 or 2 for lower extremity motor functions were assigned to the severe group, and 22 patients who scored 3 or 4 were assigned to the moderate group. Gait analysis was performed preoperatively using a long thin-type sensor sheet, and 25 healthy volunteers were assigned to the control group. RESULTS: Stride length, swing phase, and gait speed decreased whereas step angle, stance phase, and double support duration increased as myelopathy progressed. Step width was significantly larger in the severe group than in the moderate and control groups. The cutoff values based on severe myelopathy with the inability to ascend or descend stairs without support were 60% for the stride length percentage of body height and 100 cm/s for gait speed. CONCLUSIONS: Decreases in stride length, swing phase, and gait speed and increases in step angle, stance phase, and double support duration are compensatory changes as cervical myelopathy progresses. Step width is a compensatory change that is not significantly altered in moderate myelopathy but increases when gait becomes affected, such that the patient cannot ascend or descend stairs without support.

DOI： 10.22603/ssrr.2023-0104

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PURPOSE: The purpose of this study was to identify factors related to the external rotation of the femur during knee flexion. METHODS: Three-dimensional (3D) digital models of the femur and tibia were reconstructed from computed tomography images of 41 healthy Japanese subjects. Thirteen parameters related to femoral and tibial morphology and alignment of the lower extremities were evaluated, including the inclination angle of the posterior lateral and medial femoral condyles, the ratio of the medial and lateral posterior condyle radii approximated as spheres, the spherical condylar angle, the posterior condylar angle, the medial and lateral posterior tibial slope, the difference of medial and lateral posterior tibial slope, the tibiofemoral rotation angle, the 3D femorotibial angle, the 3D hip-knee-ankle angle, and the passing point of the weight-bearing line (medial-lateral and anterior-posterior). The rotation angle of the femur relative to the tibia during squatting was investigated using a 3D to 2D image matching technique and the relationships with the13 parameters were determined. RESULTS: The femur externally rotated substantially up to 20° of knee flexion (9.2° ± 3.7°) and gently rotated after 20° of knee flexion (12.8° ± 6.2°). The external rotation angle at 20°-120° of knee flexion correlated with the spherical condylar angle, the tibiofemoral rotation angle and the inclination angle of the posterior medial condyles (correlation coefficient; 0.506, 0.364, 0.337, respectively). CONCLUSION: The parameter that was most related to the external rotation of the femur during knee flexion was the spherical condylar angle. LEVEL OF EVIDENCE: IV.

DOI： 10.1186/s40634-023-00686-w

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BACKGROUND: The examination of femoral cortical bone thickness in patients with rheumatoid arthritis (RA) has been notably limited in prior research. We aimed to compare femoral cortical thickness in patients with rheumatoid arthritis (RA) and healthy controls and to investigate the association between femoral cortical thickness and clinical parameters within the RA group. METHODS: Forty-four patients (58 limbs) with RA who underwent total knee arthroplasty were enrolled. Preoperative computed tomography images of the lower limbs were analyzed. The femoral cortex was divided into the proximal, central, and distal diaphysis regions and further into the anterior, posterior, medial, and lateral regions. The divisions were measured using Stradwin® software and standardized by femoral length. Femoral cortical thickness was compared between RA and healthy control (n = 25) groups. Correlation analyses between standardized cortical thickness and disease parameters were performed in the RA group. RESULTS: The RA group had significantly lower standardized femoral cortical thickness at the anterior and medial distal diaphysis than healthy controls. Standardized proximal lateral and central lateral in the RA group were significantly larger than those in the healthy control groups. Standardized femoral cortical thickness was significantly correlated with bone mineral density (BMD) in 11 areas, except the posterior central diaphysis, and with body mass index in 8 areas, except the central posterior, distal lateral, distal anterior, and distal medial diaphysis. CONCLUSIONS: Femoral cortical thinning was noted in patients with RA complicated with destructive knee, particularly at the anterior and medial distal diaphysis. Femoral cortical thickness was significantly correlated with BMD and body mass index (BMI); thus, patients with RA and low BMD and BMI should be cared for to prevent fragility fractures.

DOI： 10.1186/s13018-023-04340-0

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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.

DOI： 10.1097/CORR.0000000000002720

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PURPOSE: The longitudinal changes in alignment and structure, including the joint line and cortical bone thickness (CBT) of the femur and tibia, and knee phenotype in patients with knee osteoarthritis (OA) remain unknown. The aim of this retrospective study was to clarify the longitudinal changes in matched healthy subjects. METHODS: The follow-up Matsudai Knee Osteoarthritis Survey was administered between 23 and 28 years. This study included 285 healthy knees from 235 females with an average age of 53 ± 6 years at baseline. The non-OA individuals, with an average age of 79 ± 4 years, were divided into three groups at baseline according to their follow-up radiographic results [the non-OA (n = 52), early OA (n = 131), and advanced OA groups (n = 102)]. Changes in alignment, joint line, CBT, and knee phenotype were assessed at baseline and at follow-up using standing anteroposterior radiographs. RESULTS: This study showed significant varus changes in the alignment (p < 0.001) and tibial and femoral joint line parameters (p < 0.05) in the OA group. Decreased CBT and increased mediolateral CBT ratios were observed in all groups (p < 0.001). The knee phenotypes in the OA groups were changed to varus angles, especially in the alignment and tibial joint line. CONCLUSIONS: The longitudinal changes of knee phenotypes in alignment and structure (CBT and joint line) from baseline to follow-up were shown in the OA groups. In addition, alignment and tibial structural factors at baseline are useful in predicting the incidence of knee OA in daily practice. LEVELS OF EVIDENCE: III.

DOI： 10.1007/s00167-023-07554-1

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BACKGROUND: Intraoperative pathological diagnosis has a major influence on the intra- and postoperative management of spinal cord tumors. Thus, the aim of this study was to assess the reliability of intraoperative pathological diagnosis for spinal cord lesions by comparing it with the final pathological diagnosis and to determine its usefulness and limitations. METHOD: Three-hundred and three consecutive patients (mean age, 53.9 years) with neoplastic spinal cord lesions who underwent initial surgery between 2000 and 2021 were included. The anatomical locations of the spinal cord tumors and the implementation rate of intraoperative pathological diagnosis in each tumor type were evaluated. As the primary outcome, we determined the concordance rates between the intraoperative pathological diagnosis and the final diagnosis. When the intraoperative pathological diagnosis and final diagnosis were the same, the diagnosis was defined as a "match." Otherwise, the diagnosis was defined as a "mismatch." RESULTS: The overall implementation rate of intraoperative pathological diagnosis was 53%, with implementation rates of 71%, 45%, 47%, and 50% for intramedullary, intradural extramedullary, extradural, and dumbbell tumors, respectively. The overall concordance rate was 87.6%, with concordance rates of 80%, 95%, 75%, and 90% for intramedullary, intradural extramedullary, extradural, and dumbbell tumors, respectively (p < 0.05). The diagnoses of ependymomas, low-grade astrocytomas, and high-grade astrocytomas was occasionally difficult among intramedullary tumors. Among intradural extramedullary tumors, differentiation between grade 1 meningioma and high-grade meningioma was difficult using intraoperative pathological diagnosis. CONCLUSIONS: Surgeons must recognize the lower accuracy of intraoperative pathological diagnosis for intramedullary and extradural lesions and make a final decision by considering the intraoperative gross findings, preoperative clinical course, and imaging.

DOI： 10.1016/j.jos.2023.08.011

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BACKGROUND: Adult spinal deformity has a substantially debilitating effect on older people's physical and mental health. However, the impact of sagittal malalignment on locomotive syndrome (LS), sarcopenia, and physical function in community-dwelling older women has not yet been clarified. This study aimed to investigate the association between these factors in community-dwelling middle aged and older women. METHODS: A total of 361 women were recruited from participants performing aquatic exercises in a rural area of Japan. The body mass index, skeletal muscle mass index, trunk muscle mass, spinal inclination angle (SIA), grip strength, timed up-and-go test (TUG), maximum stride of the participants, and one-leg standing time were measured. Low back pain (LBP)- and health-related quality of life (HRQOL) were evaluated using the Oswestry Disability Index (ODI) and the Short-Form 8 questionnaire. Associations between the global sagittal alignment using SIA and investigating parameters were analyzed. RESULTS: The prevalence of sarcopenia was 3.6%. The prevalence of LS (stages 1, 2, and 3) was 43.8% (158 of 361), and the number of participants in each LS stage was 203 (stage 0), 95 (stage 1), 28 (stage 2), and 35 (stage 3). The SIA was significantly correlated with the 25-question geriatric locomotive function scale (r' = 0.292, p < 0.001), ODI (r' = 0.267, p < 0.001), and TUG (r' = 0.453, p < 0.001) after adjusting for age. In the receiver-operating characteristic curve analysis, the cutoff values of SIA for LS ≥ stage 2 and ODI ≥ 20% were 5°. CONCLUSIONS: LBP-related QOL and physical performance were significantly associated with global sagittal alignment. Global sagittal alignment was correlated with the three-stage category of LS. The spinal inclination of 5° was a cutoff value to predict exacerbation of mobility function and HRQOL status.

DOI： 10.1186/s12891-023-06686-2

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OBJECTIVE: Patients with advanced chronic kidney disease (CKD) are generally discouraged from consuming high amounts of vegetables and fruits given the potential risk of hyperkalemia. In the general population, however, lower vegetable and fruit intake is associated with higher mortality. This Japanese hospital-based prospective cohort study including non-CKD and CKD participants examined whether the frequency of vegetable and fruit intake is associated with mortality, and whether the presence of CKD modifies this association. METHODS: Participants were 2,006 patients who visited the outpatient department of a general hospital between June 2008 and December 2016 (55% men; mean age, 69 years). Among these participants, 902 (45%) and 131 (7%) were non-dialysis-dependent patients with CKD and hemodialysis patients, respectively. The frequency of vegetable and fruit intake was determined by a self-report questionnaire using an ordinal scale, "never or rarely," "sometimes," and "every day." Multivariable Cox proportional hazards analysis was conducted, adjusting for potential confounders. RESULTS: Vegetable and fruit intake frequency decreased with worsening CKD stage (P for trend < .001). Baseline serum potassium levels stratified by CKD stage were similar across the three vegetable and fruit intake frequency groups. During a median follow-up of 5.7 years, 561 participants died (47.1/1,000 person-years). Adjusted hazard ratios relative to the "every day" group were 1.25 (95% confidence interval, 1.04-1.52) and 1.60 (95% confidence interval, 1.23-2.08) for the "sometimes" and "never or rarely" groups, respectively, after adjusting for demographic factors, comorbidities, and CKD status. When stratified by CKD status, a similar, albeit non-significant, dose-dependent relationship was observed between vegetable and fruit intake frequency and all-cause mortality irrespective of CKD status, with no effect modification by CKD status (Pinteraction = .69). CONCLUSION: A lower frequency of vegetable and fruit intake is significantly associated with a higher risk of death regardless of CKD status.

DOI： 10.1053/j.jrn.2023.01.011

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BACKGROUND: Surgical smoke is a vaporous by-product generated during tissue incision and cauterization with an electric scalpel. This smoke contains tissue- and blood/vascular-derived substances, bacteria, viruses, and chemical substances. Among them, it contains many fine particles called particulate matter (PM) 2.5, which are harmful and hazardous to the human body. We aimed to investigate the occurrence of PM2.5 in surgical smoke produced during spinal surgery and to evaluate the efficacy of an electric scalpel with a smoke evacuation pencil. METHODS: In this retrospective observational study, 89 patients who underwent spinal surgery between June 2019 and May 2021 were included. A dust monitor was installed in the operating room to measure the PM2.5 air concentration during the surgery. During each surgery, the total amount of PM2.5, the maximum PM2.5 air concentration, the exposure time to PM2.5, and the average value of PM2.5 air concentration from the start to the end of the surgery were calculated. RESULTS: We found that in 29 of the 89 cases (32.6%), the air concentration of PM2.5 increased to a level that could cause health damage during the surgery. Twelve cases (13.4%) reached the level that could cause serious health damage, and 8 cases (9%) reached an emergency warning level. The total amount and the maximum and average levels of PM2.5 were significantly suppressed in the surgery with a smoke evacuation pencil group than in the surgery without a smoke evacuation pencil group. CONCLUSION: We detected hazardous levels of PM2.5 in the air during spinal surgery, highlighting the importance of considering smoke control or reduction during spinal surgery. We recommend using an electric scalpel with a smoke evacuation pencil for regulating PM2.5 levels in the operating room.

DOI： 10.1016/j.jos.2022.04.010

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INTRODUCTION: A 2015 study showed a decreasing trend in the incidence of osteoporotic hip fractures in Niigata Prefecture, Japan, which had been increasing. This study aimed to investigate the incidence of osteoporotic hip fractures in 2020, determine the long-term change in the incidence of hip fractures from 1985 to 2020, and assess whether the decline in fracture incidence since 2010 has continued. MATERIALS AND METHODS: We obtained data from the registration forms submitted by hospitals and clinics of patients who lived in Niigata Prefecture and were diagnosed with osteoporotic hip fracture through a survey conducted from January 1, 2020 to December 31, 2020. RESULTS: In 2020, 3,369 hip fractures were recorded in Niigata Prefecture. Although the overall incidence of age-specific hip fractures decreased, it increased in patients aged ≥ 90 years, regardless of sex. The proportion of patients receiving anti-osteoporosis drugs prior to hip fracture increased from 7.6% in 2004 to 17.3% in 2020. Notably, surgical treatment should be performed as early as possible, and the preoperative waiting time was 2.9 days, which was mainly due to holidays. CONCLUSION: The incidence of hip fractures in Niigata Prefecture has gradually increased over the past 35 years, with an increasing change observed in the very elderly recently in 2020. Although the treatment of osteoporotic hip fractures in Niigata Prefecture is adequate, improvements may include increasing the rate of adoption of osteoporosis treatment further and decreasing the number of days of preoperative waiting.

DOI： 10.1007/s00774-023-01421-2

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Language：Japanese   Publisher：東北整形災害外科学会  

2000～2019年に単一施設で腎癌脊椎転移に対して姑息的手術が行われた22例のうち、術後1年以上あるいは死亡まで追跡可能であった19例を対象とし、術後生存期間が1年以上であった群(12例)と1年未満群(7例)に分け、「手術時年齢」「性別」「術前の徳橋スコア」「術前の血液検査値」「主要臓器転移の合併率」などについて比較検討した。血液検査値の調査項目は「Alb」「LDH」「T-Bil」「補正Ca」「WBC」「Hb」「Plt」「好中球/リンパ球比(NLR)」「CRP」とした。検討の結果、術後生存期間が1年以上の群は1年未満群に比べて、術前の「徳橋スコア」が有意に高く、血液検査では「Alb値」が有意に高く、「NLR」が有意に低かった。術後生命予後不良のカットオフ値として、過去の報告から「徳橋スコア12点未満」「Alb<3.7g/dl」「NLR>3」を採用し、術後生命予後1年未満の予測について感度と特異度を算出した。結果、「徳橋スコア」単独では、感度は100%であったものの特異度は50%にとどまった。「徳橋スコア」に「Alb<3.7g/dlあるいはNLR>3のいずれかを満たす」を加えると、感度は100%のままで特異度は75%に上昇した。「Alb<3.7g/dlおよびNLR>3を満たす」を加えた場合には、感度は85.7%に低下したものの特異度は91.7%に上昇した。

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BACKGROUND: A significant increase in the older adult population in Japan will significantly increase healthcare costs. This study aimed to examine the risk factors contributing to robustness transitioning to frailty in older residents. METHODS: Participants were aged 70 in 2016 and 76 in 2022. Participants were evaluated using the Kihon Checklist (KCL). RESULTS: Participants for this longitudinal study included 444 older persons who completed the KCL surveys in 2016 and 2022. The follow-up rate was 80.6%; therefore, 358 participants were included in the analysis. The median KCL score increased significantly from 2 to 2016 to 3 in 2022 (p < 0.001). The prevalence of robustness significantly decreased from 60.9 to 48.6% (p = 0.042). In a stepwise logistic regression analysis, robustness was independently associated with regular continuous walks for 15 min and a body mass index of above 18.5%. The following variables were associated with the transition to prefrailty: experiencing a fall in the past year and not going out at least once a week. For the transition to frailty, the variables were turned to family or friends for advice, experienced a fall in the past year, and felt helpless in the last two weeks. The independent factor for the transition from prefrailty to frailty was having a BMI of less than 18.5. In contrast, the independent factor for improving from frailty to robustness or prefrailty was going out at least once a week. CONCLUSIONS: We recommend maintaining continuous walking for more than 15 min, maintaining a BMI of at least 18.5, and going out more than once a week to improve being house-bounded and depressive mood, not only to prevent the transition to prefrailty or frailty but also to improve frailty.

DOI： 10.1186/s12877-023-04055-1

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Background and Objectives: In the field of orthopedic surgery, novel techniques of three-dimensional shape modeling using two-dimensional tomographic images are used for bone-shape measurements, preoperative planning in joint-replacement surgery, and postoperative evaluation. ZedView® (three-dimensional measurement instrument and preoperative-planning software) had previously been developed. Our group is also using ZedView® for preoperative planning and postoperative evaluation for more accurate implant placement and osteotomy. This study aimed to evaluate the measurement error in this software in comparison to a three-dimensional measuring instrument (3DMI) using human bones. Materials and Methods: The study was conducted using three bones from cadavers: the pelvic bone, femur, and tibia. Three markers were attached to each bone. Study 1: The bones with markers were fixed on the 3DMI. For each bone, the coordinates of the center point of the markers were measured, and the distances and angles between these three points were calculated and defined as "true values." Study 2: The posterior surface of the femur was placed face down on the 3DMI, and the distances from the table to the center of each marker were measured and defined as "true values." In each study, the same bone was imaged using computed tomography, measured with this software, and the measurement error from the corresponding "true values" was calculated. Results: Study 1: The mean diameter of the same marker using the 3DMI was 23.951 ± 0.055 mm. Comparisons between measurements using the 3DMI and this software revealed that the mean error in length was <0.3 mm, and the error in angle was <0.25°. Study 2: In the bones adjusted to the retrocondylar plane with the 3DMI and this software, the average error in the distance from the planes to each marker was 0.43 (0.32-0.58) mm. Conclusion: This surgical planning software could measure the distance and angle between the centers of the markers with high accuracy; therefore, this is very useful for pre- and postoperative evaluation.

DOI： 10.3390/medicina59061030

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BACKGROUND: The Japanese Orthopaedic Association (JOA) introduced the concept of locomotive syndrome (LS), which indicates a decline in mobility function by musculoskeletal disorders with new 3-staged category. Additionally, sarcopenia indicates a decline in the quantity and/or quality of skeletal muscle. However, the relationship between low back pain (LBP) and LS or sarcopenia in older people has not been sufficiently understood. This study aimed to investigate the association between them through a cross-sectional locomotorium survey. METHODS: A total of 302 participants were drawn from the aquatic exercise participants in a rural area of Japan. The body mass index, body fat percentage, skeletal muscle mass index (SMI), spinal inclination angle (SIA), grip strength, timed up-and-go test (TUG), and maximum stride of the participants were measured. LBP and LBP-related quality of life (QOL) were evaluated using the Oswestry Disability Index (ODI), visual analogue scale (VAS) of LBP, and the Short-Form 8 (SF-8). Associations between the investigating parameters and sarcopenia or LS were analyzed. RESULTS: There were no significant differences in the findings except grip strength between the non-sarcopenia and sarcopenia groups. However, the LS group showed significantly larger SIA, higher ODI, higher VAS of LBP, lower physical component score (PCS) of the SF-8, longer time in TUG, and lower value in maximum stride than the non-LS group. In addition, the ODI and PCS of the SF-8 significantly deteriorated as the LS stage progressed, and the GLFS-25 score was significantly correlated with ODI (r = 0.706, p < 0.001) and PCS (r = -0.643, p < 0.001) scores. CONCLUSIONS: LBP, LBP-related QOL, and physical performance were found to be significantly associated with LS, not sarcopenia, with LBP-related QOL and physical function being closely correlated with 3-stage categories of LS. Thus, these results suggested that LBP is a key factor for LS prevalence.

DOI： 10.1016/j.jos.2022.03.004

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PURPOSE: We aimed to investigate the marital status and childbirth in adolescent idiopathic scoliosis (AIS) patients. METHODS: This study included women who were treated surgically or non-surgically for AIS with a scoliosis magnitude ≥ 30° before surgery or at skeletal maturity and were followed up until age 30 years or older. Patients were divided into surgically treated (S-AIS, n = 55) and non-surgically treated AIS groups (N-AIS, n = 86). Data from the national fertility survey were used as control values. RESULTS: There were no significant differences in age at the final follow-up between the S- (40.7 years) and N-AIS (42.1 years) groups. The unmarried rate among all women and the nulliparous rate among married women in the S-AIS group (29.1% and 18.4%, respectively) were similar to those in the N-AIS group (26.7% and 16.1%, respectively). The mean number of children per married woman also did not differ between the S- and N-AIS groups (1.5 vs 1.4). Compared to the control group, after adjusting for age, the common odds ratio in the AIS group was 1.56 (p = 0.031) for unmarried status and 1.88 (p = 0.026) for nulliparity among married women. Moreover, the mean number of children per married woman was significantly lower in the AIS group than in the control group (1.3 vs 1.7, p < 0.001). CONCLUSION: Surgically and non-surgically treated women with AIS had a similar status with regard to marriage and childbirth, while women with AIS were more likely to be unmarried and nulliparous and to have fewer children compared to the nationwide population.

DOI： 10.1007/s43390-023-00648-3

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PURPOSE: New concept of functional knee phenotypes in Caucasians demonstrated the variability of coronal alignment in knee osteoarthritis (OA), but it remains unclear in Japanese. This study aims to analyze the knee phenotype in advanced varus knee OA for Japanese. In addition, the ethnical difference is discussed. METHODS: This study analyzed 879 knees involving 186 males (74 years) and 693 females (74 years). The knee phenotypes were assessed by the definition in Hirschmann's group. The hip-knee-ankle angle (HKA), femoral mechanical angle (FMA) and tibial mechanical angle (TMA) were assessed in CT data according to the coordinate system. The neutral angle was 180° in HKA, 93° in FMA and 87° in TMA. The smaller angle means larger varus angles. RESULTS: The average angle (males, females) of the HKA (170.9 ± 4.3°, 169.4 ± 5.0°), FMA (91.5 ± 2.7°, 90.6 ± 3.0°), and TMA (82.4 ± 3.6°, 82.7 ± 3.7°) demonstrated varus angles with the sex difference (HKA, p < 0.001; FMA, p = 0.001). The phenotypes were 73 types in males and 150 types in females with a mild correlation between the HKA and the FMA or TMA. In 61.3% of males and 52.2% of females, the TMA was greater than the FMA, while the FMA was greater in 16.7% of males and 23.1% of females. CONCLUSION: There were many functional knee phenotypes with sex differences for advanced varus knee OA in Japanese, showing ethnical differences of larger varus angles compared to those for Caucasians in the previous report. LEVEL OF EVIDENCE: IV.

DOI： 10.1007/s00167-022-07248-0

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PURPOSE: This study aimed to establish biomarkers to predict the progression of ossification by examining ossification volume and bone metabolism dynamics in patients with ossification of the posterior longitudinal ligament (OPLL). METHODS: We assessed OPLL progression using computed tomography-based three-dimensional (3D) image analysis and examined bone metabolism dynamics in 107 patients with OPLL (men, 72; women, 35; mean age, 63.6 years). The volume of OPLL was calculated twice during the follow-up period, and OPLL progression was evaluated by the annual rate of ossification increase. Bone metabolism dynamics were assessed by routine blood tests and analysis of various serum biomarkers (including 25-hydroxyvitamin D, intact parathyroid hormone, fibroblast growth factor 23, intact N-terminal propeptide of type 1, tartrate-resistant acid phosphatase isoform 5b, sclerostin, and Dickkopf-1) and bone mineral density (BMD). Patients were classified into the progression (P) or non-progression (NP) group according to the annual rate of increase in previous 3D image analyses, and associated factors between these groups were compared. RESULTS: The P and NP groups consisted of 29 patients (23 men and 6 women) and 78 patients (49 men and 29 women), respectively. Univariate analysis revealed significant differences in terms of age, body mass index, serum phosphorus, serum sclerostin, and BMD. In multivariate analysis, age, serum phosphorus, and serum sclerostin were identified as independent factors associated with OPLL progression. CONCLUSION: Younger age, hypophosphatemia, and high serum sclerostin are risk factors for OPLL progression. Serum phosphorus and sclerostin could serve as important biomarkers for predicting ossification progression.

DOI： 10.1007/s00586-023-07565-z

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

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

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Malignant peripheral nerve sheath tumors (MPNSTs) are soft-tissue sarcomas of the peripheral nervous system that develop either sporadically or in the context of neurofibromatosis type 1 (NF1). MPNST diagnosis can be challenging and treatment outcomes are poor. We present here a resource consisting of the genomic characterization of 9 widely used human MPNST cell lines for their use in translational research. NF1-related cell lines recapitulated primary MPNST copy number profiles, exhibited NF1, CDKN2A, and SUZ12/EED tumor suppressor gene (TSG) inactivation, and presented no gain-of-function mutations. In contrast, sporadic cell lines collectively displayed different TSG inactivation patterns and presented kinase-activating mutations, fusion genes, altered mutational frequencies and COSMIC signatures, and different methylome-based classifications. Cell lines re-classified as melanomas and other sarcomas exhibited a different drug-treatment response. Deep genomic analysis, methylome-based classification, and cell-identity marker expression, challenged the identity of common MPNST cell lines, opening an opportunity to revise MPNST differential diagnosis.

DOI： 10.1016/j.isci.2023.106096

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Language：Japanese   Publisher：日本レックリングハウゼン病学会  

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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.

DOI： 10.1038/s41598-023-28863-y

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Multiple subcutaneous extensor tendon ruptures in more than the ulnar three fingers sometimes occur in patients with rheumatoid arthritis accompanied by wrist deformity. In these situations, the flexor digitorum superficialis tendon of the middle finger (the FDS3 tendon) and that of the ring finger (the FDS4 tendon) are used for the transferred tendon (modified Boyes' procedure). Here, we treated two patients with rheumatoid arthritis, whose extensor tendons of more than three fingers were ruptured, using the modified Boyes' procedure. Case 1 had ruptures in four fingers (index through little), and Case 2 had ruptures in three fingers (middle through little). The FDS3 and FDS4 tendons were passed subcutaneously around the radial side of the wrist to the extensor sides and interlaced with the distal stump of the ruptured tendons. Switching of the finger movement was achieved smoothly in both cases. The post-operative evaluation showed an extension lag of -15° for the index finger 0° for the middle through the little fingers in Case 1, and 0° for the middle finger and -5° for the ring and little fingers in Case 2. The average post-operative extension lag was -3.5°. However, median nerve palsy occurred in both cases, and it gradually recovered. Stretching of the nerve by the correction of the wrist deformity and increased pressure in the carpal tunnel were supposed to be causes of this palsy. Modified Boyes' procedure is a useful method for more than three ulnar finger extensor tendon ruptures; however, post-operative median nerve palsy should be considered.

DOI： 10.1093/mrcr/rxac050

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BACKGROUND: Closed-wedge high tibial osteotomy (CWHTO) with a fibular osteotomy (FO) causes medial joint space widening in the knee. However, the effect of FO on the joint space width remains unclear. OBJECTIVE: This study aimed to examine the effect of FO on the knee in HTO. METHODS: A compression load test was performed on two amputated human limbs under four conditions: (1) normal (without any osteotomy), (2) open-wedge HTO (OWHTO), (3) OWHTO with FO, and (4) CWHTO. The contact area of the femoral and tibial cartilages and the medial and lateral joint space widths in each condition were evaluated using a motion capture system with computed tomography (CT) and magnetic resonance imaging (MRI) data. RESULTS: The contact area increased on the lateral side after OWHTO, which increased more on the lateral side with a concomitant decrease on the medial side in both subjects when FO was added to OWHTO. An increase in the medial joint space width and a decrease on the lateral side were seen in both OWHTO with FO and CWHTO. CONCLUSIONS: The contact area and joint space widths are affected by the FO, and the effect is more pronounced than the way of HTO (OWHTO or CWHTO).

DOI： 10.3233/BME-221395

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BACKGROUND: During gait, healthy knee coronal kinematics of each bony axis and lower extremity alignment are important because they could be useful as reference data for several surgeries and provide clarification of the etiology of diseases around the knee in healthy participants; however, it remains unknown. OBJECTIVE: The objective of this study was to clarify the kinematics of lower extremity alignment and the bony axes relative to the ground during gait, focused on the coronal plane, in healthy individuals by applying our unique three-dimensional (3D) motion analysis. METHODS: The study included 21 healthy individuals, including 9 healthy females and 12 healthy males with an average age of 36 ± 17 years. Knee kinematics were calculated in a gait analysis by combining the data from a motion-capture system and a 3D lower-extremity alignment assessment system on biplanar long-leg radiographs by using a 3D-2D registration technique. The main kinematic parameters were the dynamic position change relative to the ground, applying the femoral anatomical axis (FAA), tibial anatomical axis (TAA), and dynamic alignment in the coronal plane during the stance phase of gait. RESULTS: The average changes in FAA, TAA, and dynamic varus alignment were 3.7° ± 1.2°, 3.5° ± 0.8°, and 3.0° ± 1.2°, respectively. The TAA tilted laterally during the loading response and a plateau area appeared afterwards; the FAA gradually inclined laterally until the terminal stance phase, and the dynamic alignment showed varus angular change during the loading response. CONCLUSIONS: The tibia and femur were found to change approximately 2-5° of the position of the bony axes relative to the ground. In terms of clinical relevance, our findings can be used to clarify the etiology of diseases around the knee joint and as reference data for surgeries.

DOI： 10.3233/BME-211383

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PURPOSE: The purpose of this study was to analyze the dynamic kinematics of the mobile medial pivot-type total knee arthroplasty (MMPTKA) using the three-dimensional (3D)-to-2D registration technique. METHODS: Cadaveric knees from five humans were used. Computed tomography of the lower limb and preoperative 3D planning for MMPTKA were performed. After performing TKA, passive motion of the knee was observed from a fully extended position to maximum flexion using a flat panel detector. The following parameters were determined: (1) anteroposterior (AP) translations of the medial and lateral most distal points (estimated contact point) of the femoral component, (2) rotational femoral component's X-axis (FCX) angle, and (3) rotational insert angle. Paired t-tests were used to analyze differences in the AP translation between the medial and lateral most distal points of the femoral component as well as differences in the changes in the rotational angle between the FCX and X-axis of the insert on the tibial component's axial plane. RESULTS: The AP translations of the femoral component's medial and lateral most distal points were 8.4 ± 2.5 and 13.6 ± 3.3 mm, respectively (p = 0.001). The rotational angles of the FCX and insert were 10.7° ± 4.9° external rotation and 8.9° ± 4.1° internal rotation, respectively (p = 0.004). CONCLUSIONS: The posterior translation of the lateral side of the femoral component was greater than that of the medial in all cases. Hence, a medial pivot pattern was identified. The femoral component exhibited external rotation throughout knee flexion in all subjects, whereas the mobile insert exhibited internal rotation (opposite pattern relative to the femoral component). This study provides valuable kinematical information of MMPTKA that has not been clear yet.

DOI： 10.1186/s40634-022-00558-9

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PURPOSE: This study aims to (1) measure the kinematics of lower extremity alignment and the bony position relative to the ground during walking, focusing on the coronal plane, and (2) determine the correlation between the kinematics and coronal inclination of the medial tibial plateau (coronal inclination) for healthy and varus knee osteoarthritis (OA). METHODS: In this study, 43 women (non-OA, 9 knees; early OA, 13 knees; advanced OA, 21 knees; mean age 58 ± 17 years) were examined. The knee phenotypes in varus knee OA were varied. Three-dimensional (3D) knee kinematics were calculated in gait analysis by combining the motion capture system and the 3D lower extremity alignment assessment system via biplanar long-leg X-rays, applying the 3D-2D registration technique. The main parameters were the kinematics of the bony axes relative to the ground in the coronal plane during the stance phase of the gait. The differences in overall kinematics were assessed using repeated measures ANOVA with Tukey's post hoc test. The association between kinematic parameters and coronal inclination was evaluated by multiple linear regression after univariate analysis. RESULTS: The tibia tilted laterally during the loading response, and a plateau area subsequently appeared until the terminal stance phase, whereas the femur slowly tilted laterally until the terminal stance phase. The dynamic alignment showed a relatively large varus angular change during the loading response in all groups. The trend of motion was similar among all groups (p = n.s.), although to varying degrees. The coronal inclination was the more dominant factor than the Kellgren-Lawrence (K-L) grades (β =  - 0.423, p = 0.005) when the change in dynamic alignment was determined. CONCLUSIONS: The TAA plateau area after the loading response implies that the tibial articular surface may become horizontal. The femur slowly tilted laterally until the terminal stance phase in response to the tibial motion. Consequently, the dynamic alignment showed a varus angular change, in which coronal MCT was more involved than K-L grades.

DOI： 10.1007/s00167-022-07019-x

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Language：Japanese   Publisher：新潟整形外科研究会  

脊椎後方固定術(PSF)を行った10歳以上の特発性側彎症48例を対象としてPSF術後の理学療法が術後回復過程に及ぼす効果について検討した。理学療法導入の有無により理学療法群24例(R群)と対照群24例(C群)に分け、患者背景、術式、画像所見、術中・術後の鎮痛剤使用量、術後回復過程を比較した。その結果、R群ではPonte骨切りの併用率が高い傾向にあり、術後の主カーブCobb角が有意に小さく、側彎矯正率が有意に大きかった。R群では手術翌日から経口摂取が可能で、鎮痛薬内服への早期切り替えと麻薬使用量の減少が得られており、尿道カテーテル留置期間と歩行開始までの期間は有意に短かったが、術後入院期間に有意差はなかった。

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Language：Japanese   Publisher：新潟整形外科研究会  

症例は78歳女性で、上腕、大腿部を中心とした筋痛、左膝関節周囲痛、手指のこわばりを主訴とした。1994年に第12胸椎椎体骨折を受傷し、脆弱性骨折として骨粗鬆症治療薬が開始されるも効果は乏しかった。重症骨粗鬆症と判断してロモソズマブ210mg皮下注を開始した。その結果、投与翌日から両大腿部、腰部の筋痛、3時間以上続くこわばりが出現し、血液検査でCRPの上昇を認めた。膝などの関節に化膿性関節炎を示唆する所見はなく、アセトアミノフェン投与で経過を観察したが、両大腿部、腰部の筋痛は改善せず、両上肢の筋痛や体重減少が生じたため、ACR/EULAR基準に準じてリウマチ性多発筋痛症と診断した。NSAIDsとプレドニゾロンの投与により症状とCRPは速やかに改善し、リウマチ性多発筋痛症として典型的な経過であった。

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

BACKGROUND: T-cell receptor-engineered T-cell therapies have achieved promising response rates against synovial sarcoma in clinical trials, but their applicability is limited owing to the HLA matching requirement. Chimeric antigen receptor (CAR) can redirect primary T cells to tumor-associated antigens without requiring HLA matching. However, various obstacles, including the paucity of targetable antigens, must be addressed for synovial sarcoma. Ligands for natural killer (NK) cell-activating receptors are highly expressed by tumor cells. METHODS: The surface expression of ligands for NK cell-activating receptors in synovial sarcoma cell lines was analyzed. We analyzed RNA sequencing data deposited in a public database to evaluate NKp44-ligand expression. Primary T cells retrovirally transduced with CAR targeting NKp44 ligands were evaluated for their functions in synovial sarcoma cells. Alterations induced by various stimuli, including a histone deacetylase inhibitor, a hypomethylating agent, inflammatory cytokines, and ionizing radiation, in the expression levels of NKp44 ligands were investigated. RESULTS: Ligands for NKp44 and NKp30 were expressed in all cell lines. NKG2D ligands were barely expressed in a single cell line. None of the cell lines expressed NKp46 ligand. Primary synovial sarcoma cells expressed the mRNA of the truncated isoform of MLL5, a known cellular ligand for NKp44. NKp44-based CAR T cells specifically recognize synovial sarcoma cells, secrete interferon-γ, and exert suppressive effects on tumor cell growth. No stimulus altered the expression of NKp44 ligands. CONCLUSION: NKp44-based CAR T cells can redirect primary human T cells to synovial sarcoma cells. CAR-based cell therapies may be an option for treating synovial sarcomas.

DOI： 10.1016/j.tranon.2022.101521

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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

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BACKGROUND: This randomised phase II/III trial aimed to determine whether perioperative chemotherapy with gemcitabine plus docetaxel (GD) is non-inferior to the standard Adriamycin plus ifosfamide (AI) in terms of overall survival (OS) in patients with soft tissue sarcoma (STS). METHODS: Patients with localised high-risk STS in the extremities or trunk were randomised to receive AI or GD. The treatments were repeated for three preoperative and two postoperative courses. The primary endpoint was OS. RESULTS: Among 143 enrolled patients who received AI (70 patients) compared to GD (73 patients), the estimated 3-year OS was 91.4% for AI and 79.2% for GD (hazard ratio 2.55, 95% confidence interval: 0.80-8.14, P = 0.78), exceeding the prespecified non-inferiority margin in the second interim analysis. The estimated 3-year progression-free survival was 79.1% for AI and 59.1% for GD. The most common Grade 3-4 adverse events in the preoperative period were neutropenia (88.4%), anaemia (49.3%), and febrile neutropenia (36.2%) for AI and neutropenia (79.5%) and febrile neutropenia (17.8%) for GD. CONCLUSIONS: Although GD had relatively mild toxicity, the regimen-as administered in this study-should not be considered a standard treatment of perioperative chemotherapy for high-risk STS in the extremities and trunk. CLINICAL TRIAL REGISTRATION: jRCTs031180003.

DOI： 10.1038/s41416-022-01912-5

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Language：Japanese   Publisher：(株)南江堂  

当院で人工股関節置換術(THA)を行った患者のうち、CT-based navigation下にセメントカップを設置した28例28関節(男性7例、女性21例、平均年齢69.2±12.4歳)のカップ設置角精度について検討した。その結果、セメントカップの絶対値誤差はRI 2.6±2.4°、RA 2.9±2.3°であった。また、BMIと誤差に相関はなく、初回THAと再置換、Paprosky分類において誤差に有意差はみられなかった。本法の結果はCT-based navigationを使用して設置したセメンレスカップに近い設置精度であることが示唆された。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00764&link_issn=&doc_id=20221111070004&doc_link_id=issn%3D0030-5901%26volume%3D73%26issue%3D11%26spage%3D1139&url=http%3A%2F%2Fwww.pieronline.jp%2Fopenurl%3Fissn%3D0030-5901%26volume%3D73%26issue%3D11%26spage%3D1139&type=PierOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00005_2.gif

Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞関節リウマチ(RA)は原因不明の滑膜炎症が体内に生じ,全身の関節,骨を破壊しさらに日常生活動作障害をきたす自己免疫性疾患である.診療ガイドラインが整備され,最新のものは2020年であるが,まずは薬物治療が提示される.メトトレキサートが第一選択薬であり,phase 2以降でbiological disease-modifying antirheumatic drugs(bDMARDs)やtargeted synthetic disease-modifying antirheumatic drugs(tsDMARDs)が使用される.このように関節リウマチの薬物治療は進歩しているが,手指や手関節病変は70%もの患者でみられ,進行する関節破壊は時に生じ,手術にいたるような手関節病変は依然として存在する.特に伸筋腱皮下断裂を合併するような場合は手術適応となる.小指,環指の順に腱断裂が生じやすく,中指あるいは示指まで皮下断裂が及ぶような症例では腱の再建に難渋する.本稿では,関節リウマチの手関節病変および手指伸筋腱断裂に対する当科が行ってきた治療方針を概説する.多数指伸筋腱断裂に対する治療法としてmodified Boyes法があげられるが,本術式についても述べる.

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J04037&link_issn=&doc_id=20221027340025&doc_link_id=10.15106%2Fj_besei82_128&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_besei82_128&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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BACKGROUND: Near-falls should be detected to prevent falls related to the earlier ambulation after Total knee arthroplasty (TKA). The quadriceps weakness with femoral nerve block (FNB) has led to a focus on adductor canal block (ACB). We purposed to examine the risk of falls and the earlier ambulation in each continuous infusion nerve block. METHODS: Continuous infusion nerve block (FNB or ACB) was performed until postoperative day (POD) 2 or 3. Pain levels and falls/near-falls with knee-buckling were monitored from POD 1 to POD 3. The score on the manual muscle test, MMT (0 to 5, 5 being normal), of the patients who could ambulate on POD 1, was investigated. RESULTS: A total of 73 TKA cases, 36 FNB and 37 ACB, met the inclusion criteria. No falls were noted. But episodes of near-falls with knee-buckling were witnessed in 14 (39%) cases in the FNB group and in 4 (11%) in the ACB group (p = 0.0068). In the ACB group, 81.1% of patients could ambulate with parallel bars on POD 1, while only 44.4% of FNB patients could do so (p = 0.0019). The quadriceps MMT values in the ACB group was 2.82, significantly higher than 1.97 in the FNB group (p = 0.0035). There were no significant differences in pain as measured with a numerical rating scale (NRS) and rescue analgesia through POD 3. CONCLUSION: ACB was associated with significantly less knee-buckling and earlier ambulation post-TKA, with better quadriceps strength. Our study indicated the incidence of falls and near-falls with continuous infusion nerve blocks, and support the use of ACB to reduce the risk of falls after TKA. It is suggested that a certain number of the patients even with continuous ACB infusion should be considered with the effect of motor branch to prevent falls.

DOI： 10.1186/s12891-022-05735-6

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

INTRODUCTION: Fine needle aspiration cytology (FNAC) and core needle biopsy (CNB) can provide tissue samples for the diagnoses of bone and soft tissue tumors. We evaluated the diagnostic accuracy of FNAC and CNB, the usefulness of the image-guided needle procedures, and assessed whether a discordance can influence the prognosis. PATIENTS AND METHODS: We retrospectively examined the accuracy rates of FNAC and CNB procedures by analyzing results of 405 specimens of 389 patients. We evaluated the diagnostic accuracy of FNAC and CNB, compared the clinical effectiveness between the image-guided procedures and the blind procedures, and also compared survival rates between the true positive and the false negative cases for patients with high-grade malignant tumors. RESULTS: The accuracy rates of FNAC were 86.6% and 93.8% for CNB. In cases with non-palpable masses, there were significantly low sampling error rates in the image-guided procedure. There were no significant differences in progression-free-survival and overall survival rates in patients between the false negative and true positive cases. CONCLUSION: Both FNAC and CNB procedures had high accuracy rates. Limited to cases with no palpable masses, the image-guided procedure had a low sampling error rate and was an effective method for obtaining tissue samples.

DOI： 10.1016/j.anndiagpath.2022.151936

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Language：Japanese   Publisher：(一社)日本骨粗鬆症学会  

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AIM: This prospective cohort study aimed to (i) examine stroke incidence and stroke subtypes by chronic kidney disease (CKD) stage, (ii) examine whether CKD patients with or without proteinuria have a high risk of stroke independent of traditional cardiovascular risk factors, and (iii) determine precise estimates of stroke risk by CKD stage while accounting for competing mortality risk. METHODS: Participants were 2023 patients enrolled in the Project in Sado for Total Health between June 2008 and December 2016 (55% men; mean age, 69 years), of whom 52% had CKD (stage 1-2, 10%; G3a, 48%; G3b, 17%; G4-5, 11% and G5D, 14%). RESULTS: During a median follow-up of 5.7 years, 157 participants developed stroke and 448 died without developing stroke. Most stroke cases were ischaemic among non-dialysis-dependent CKD participants, but the relative frequency of ischaemic stroke was near that of intracerebral haemorrhage among dialysis-dependent CKD participants. After adjustment, stage 1-2 (hazard ratio [HR], 2.97; 95% confidence interval [CI], 1.60-5.51) and stage G3-5 participants with proteinuria (HR, 2.50; 95% CI, 1.56-4.02), but not stage G3-5 participants without proteinuria (HR, 0.64; 95% CI, 0.38-1.08), had a higher stroke risk compared to non-CKD participants. In competing risk analyses, the association was attenuated but remained significant. CONCLUSION: Although the distribution of stroke subtypes differed, CKD participants with proteinuria and those with CKD stage 5D had a 2- and 4-times higher risk of stroke, respectively, than that of non-CKD participants, after accounting for competing mortality risk and traditional risk factors.

DOI： 10.1111/nep.14049

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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.

DOI： 10.1111/cas.15382

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

This study aimed to retrospectively analyze the clinical outcomes of patients with pelvic and retroperitoneal bone and soft tissue sarcoma (BSTS). Overall, 187 patients with BSTS in the pelvis and retroperitoneal region treated at 19 specialized sarcoma centers in Japan were included. The prognostic factors related to overall survival (OS), local control (LC), and progression-free survival (PFS) were evaluated. The 3-year OS and LC rates in the 187 patients were 71.7% and 79.1%, respectively. The 3-year PFS in 166 patients without any distant metastases at the time of primary tumor diagnosis was 48.6%. Osteosarcoma showed significantly worse OS and PFS than other sarcomas of the pelvis and retroperitoneum. In the univariate analyses, larger primary tumor size, soft tissue tumor, distant metastasis at the time of primary tumor diagnosis, P2 location, chemotherapy, and osteosarcoma were poor prognostic factors correlated with OS. Larger primary tumor size, higher age, soft tissue tumor, chemotherapy, and osteosarcoma were poor prognostic factors correlated with PFS in patients without any metastasis at the initial presentation. Larger primary tumor size was the only poor prognostic factor correlation with LC. This study has clarified the epidemiology and prognosis of patients with pelvic and retroperitoneal BSTS in Japan.

DOI： 10.3390/cancers14123023

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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.

DOI： 10.1038/s41598-022-12655-x

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DOI： 10.1007/s00774-022-01315-9

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OBJECTIVES: To investigate the outcomes of the modified Thompson-Littler (m-TL) method, a corrective surgical method utilising a dynamic tenodesis, in patients with rheumatoid swan-neck deformity. METHODS: Twenty-seven fingers in 10 patients with rheumatoid arthritis (RA) underwent surgical correction. The mean age at the time of surgery was 60.3 (45-77) years, the mean duration of RA was 19.3 (4-34) years, and the mean postoperative follow-up period was 2.4 (0.5-6) years. RESULTS: The deformity was corrected and the proximal interphalangeal (PIP) joint pain disappeared in all operated fingers. The mean pinch power between the thumb and the operated finger increased. The active extension decreased, the active flexion increased, and the total arc of motion decreased. Comparing the range of motion by Nalebuff's type classification, the postoperative arc of motion decreased as the type advanced. CONCLUSIONS: The m-TL method provided a favourable outcome in cases of Type ≤III rheumatoid swan-neck deformity without severe joint deterioration at the PIP joint. Aesthetic and functional improvements were observed and the patients were satisfied with the operation.

DOI： 10.1093/mr/roab015

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OBJECTIVE: Teriparatide (TPTD) is a potent promoter of early-stage osteogenesis and may be a useful adjuvant therapy to reduce complications related to bone fragility in spinal surgery patients with osteoporosis. However, effective neoadjuvant TPTD therapy regimens remain poorly understood. This study aimed to examine the effect of preoperative TPTD administration on cancellous bone with bone histomorphometry and to clarify the timing of preoperative TPTD administration for patients with spinal fusion and osteoporosis. METHODS: In this longitudinal multicenter study, 57 patients with spinal fusion and osteoporosis, who consented to undergo iliac biopsy, were allocated to the following treatment groups: neoadjuvant TPTD therapy group (n = 42) and no neoadjuvant therapy (NTC) group (n = 15). Patients in the TPTD group were categorized into subgroups on the basis of duration of preoperative TPTD administration, as follows: 1 month (n = 9), 2 months (n = 8), 3 months (n = 9), 4 months (n = 7), and 6 months (n = 9). All patient samples were preoperatively double labeled with tetracycline, and iliac biopsies were performed during spinal fusion surgery. Histomorphometric analyses were performed on nondecalcified, thin-sliced specimens. Specimens were classified on the basis of TPTD administration duration and subsequently compared with those of the NTC group. Postoperative complications and Oswestry Disability Index scores were evaluated at 1 and 2 years after surgery. RESULTS: There were no demographic differences between groups. Mineralizing surface/bone surface, a key parameter of dynamic bone formation, started to increase after 1 month of TPTD administration; this increase became significant after 3 months of administration and peaked at 4 months, with a 6-fold increase relative to that of the NTC group. The patients who received preoperative TPTD for 3 months or more had superior clinical results in terms of the osteoporotic complication rate and Oswestry Disability Index scores, except for bisphosphonate-pretreated patients. CONCLUSIONS: When considering neoadjuvant TPTD therapy, the authors recommend at least 3 months of preoperative administration to provide a more substantial anabolic effect from the early postoperative stage.

DOI： 10.3171/2021.5.SPINE202003

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Language：Japanese   Publisher：東日本整形災害外科学会  

仰臥位アプローチで行う人工股関節置換術において術中ステム前捻角を計測し,術後CTで計測したステム前捻角との差を算出した.術中計測は最終ラスプが固定された際に患肢を胡坐位としてラスプホルダーの傾きを計測した.差は7.7±6.2度であり身長と下肢長に弱い相関を認めた.本方法での計測では約8度過小評価する傾向にあり,高身長例,下肢の長い例ではより過小に評価する傾向にあった.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J03098&link_issn=&doc_id=20220425530007&doc_link_id=%2Fdx3eastj%2F2022%2F003401%2F008%2F0033-0036%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdx3eastj%2F2022%2F003401%2F008%2F0033-0036%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：(株)南江堂  

症例は60歳女性で、左大腿部の腫瘤を主訴に、前医を経て当科紹介となった。初診時画像所見・開放生検で多形型平滑筋肉腫と診断し、ゲムシタビン塩酸塩・ドセタキセル水和物療法を3コース施行するもSD判定であったため、広範切除術を行った。術後ゲムシタビン塩酸塩・ドセタキセル水和物療法を2コース行った。その後、両側の多発肺転移を生じたが、アドリアマイシン単剤療法を7コース施行し消失が得られた。さらに脳転移を生じたため全脳照射を開始したが、Trousseau症候群を発症しヘパリン持続静注を開始するも、発症約2ヵ月で死亡した。

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Herein, we present two cases of older adult patients with highly destructive changes in ankle joints (Larsen grade IV) who underwent retrograde intramedullary ankle nail fixation with fins. In both patients, bony union was achieved, and full weight-bearing was attained at 3 months after surgery.

DOI： 10.1002/ccr3.5348

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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.

DOI： 10.1007/s00167-020-06323-8

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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

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PURPOSE: To evaluate the impact of the flexibility of thoracolumbar or lumbar (TL/L) curves on low back pain (LBP) and disc degeneration in adult patients nonoperatively treated for adolescent idiopathic scoliosis (AIS). METHODS: Forty-seven adult patients (46 women; mean age, 40.5 years) nonoperatively treated for AIS with TL/L curves were included. The patients completed radiological examinations, magnetic resonance imaging, and a questionnaire survey for LBP evaluation. The flexibility of the spinal deformity was evaluated using supine side-bending radiographs. Radiographic measurements were correlated with scores for LBP and disc degeneration. RESULTS: The average magnitude and flexibility of the TL/L curve were 49.0° and 56%, respectively. The magnitudes of the TL/L curve and disc wedging were significantly correlated with LBP (|r|= 0.3-0.4). The flexibility of the TL/L curve and disc wedging, and the lumbar lateral range of motion (ROM) were significantly correlated with LBP and disc degeneration (|r|= 0.3-0.5). After controlling for the magnitudes of the TL/L curve and disc wedging, the flexibility of L4/5 disc wedging and the lumbar lateral ROM remained significantly correlated with the Scoliosis Research Society-22 pain score (partial correlation coefficient [r'] = 0.5 and 0.3), Oswestry Disability Index (- 0.3 and - 0.3), and disc degeneration (- 0.4 and 0.3). CONCLUSION: In AIS patients with TL/L curves, the flexibility of L4/5 disc wedging and the lumbar lateral ROM were significantly correlated with LBP and disc degeneration, independent of the magnitudes of the coronal deformities. Our findings indicate that maintaining or improving lumbar flexibility may be beneficial for preventing or treating LBP.

DOI： 10.1007/s43390-021-00402-7

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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.

DOI： 10.1007/s00774-021-01272-9

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Language：Japanese   Publisher：新潟県医師会  

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The characteristics of the tumor immune microenvironment remains unclear in liposarcomas, and here we aimed to determine the prognostic impact of the tumor immune microenvironment across separate liposarcomas subtypes. A total of 70 liposarcoma patients with three subtypes: myxoid liposarcoma (n = 45), dedifferentiated liposarcoma (n = 17), and pleomorphic liposarcoma (n = 8) were enrolled. The presence of tumor infiltrating lymphocytes (CD4+ , CD8+ , FOXP3+ lymphocytes) and CD163+ macrophages and expression of HLA class I and PD-L1 were assessed by immunohistochemistry in the diagnostic samples; overall survival and progression-free survival were estimated from outcome data. For infiltrating lymphocytes and macrophages, dedifferentiated liposarcoma and pleomorphic liposarcoma patients had a significantly higher number than myxoid liposarcoma patients. While myxoid liposarcoma patients with a high number of macrophages were associated with worse overall and progression-free survival, dedifferentiated liposarcoma patients with high macrophage numbers showed a trend toward favorable prognosis. Expression of HLA class I was negative in 35 of 45 (77.8%) myxoid liposarcoma tumors, whereas all dedifferentiated liposarcoma and pleomorphic liposarcoma tumors expressed HLA class I. The subset of myxoid liposarcoma patients with high HLA class I expression had significantly poor overall and progression-free survival, while dedifferentiated liposarcoma patients with high HLA class I expression tended to have favorable outcomes. Only four of 17 (23.5%) dedifferentiated liposarcomas, two of eight (25%) pleomorphic liposarcomas, and no myxoid liposarcoma tumors expressed PD-L1. Our results demonstrate the unique immune microenvironment of myxoid liposarcomas compared to other subtypes of liposarcomas, suggesting that the approach for immunotherapy in liposarcomas should be based on subtype.

DOI： 10.1007/s00262-021-02928-1

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BACKGROUND: Synovial sarcoma is a rare malignant soft-tissue tumor that is prevalent in adolescents and young adults, and poor prognosis has been reported in patients with metastatic lesions. Chimeric antigen receptor (CAR) T-cell therapy is an emerging novel therapy for solid tumors; however, its application in synovial sarcoma has not yet been explored. METHODS: A novel human epidermal growth factor receptor 2 (HER2)-targeted CAR containing scFv-FRP5, CD8α hinge and transmembrane domains as well as 4-1BB costimulatory and CD3ζ signaling domains was developed. Three synovial sarcoma cell lines that expressed the fusion transcript SS18-SSX1/2/4 were used in the study. Cytokine secretion assay, cytotoxicity assay, and real-time cell analysis experiments were conducted to confirm the function of T cells transduced with the CAR gene. RESULTS: High cell-surface expression of HER2 was observed in all the cell lines. HER2-targeted/4-1BB-costimulated CAR T cells specifically recognized the synovial sarcoma cells, secreted interferon gamma and tumor necrosis factor alpha, and exerted cytotoxic effects in these cells. CONCLUSION: To the best of our knowledge, this is the first study to indicate that HER2-targeted CAR T cells are directly effective against molecularly defined synovial sarcoma cells. Furthermore, our findings might set the basis for developing improved CAR T cell-based therapies for chemo-refractory or relapsed synovial sarcoma.

DOI： 10.1016/j.tranon.2021.101227

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Language：Japanese   Publisher：新潟整形外科研究会  

新潟県立中央病院の外来に通院中のRA患者のうち、2010年4月～2018年3月にアバタセプトが導入された33例を対象とし、導入時年齢が65歳未満の群(18例)と65歳以上群(15例)に分け、導入後2年間の「CRP」「ESR」「DAS28-ESR」「MTX使用量」「PSL使用量」の経時的変化について群間ごとに調査した。結果、「CRP」は65歳未満群では導入時に比べて導入後3ヵ月以降に有意に改善し、65歳以上群では導入時に比べて導入後1ヵ月以降に有意に改善していた。「ESR」は65歳未満群では導入時に比べて導入後3ヵ月以降に有意に改善し、65歳以上群では導入後6ヵ月以降に有意に改善していた。「DAS28-ESR」は両群とも導入後3ヵ月以降に有意に改善していた。「MTX使用量」は65歳未満群では有意な変化なく、65歳以上群では導入後6ヵ月以降に有意に減少していた。「PSL使用量」は両群とも有意な変化はみられなかった。アバタセプトの継続率について調査した結果、1年継続率は65歳未満群72.2%、65歳以上群86.7%、2年継続率はそれぞれ72.2%、78.8%であり、1年・2年とも有意な群間差はみられなかった。

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Language：Japanese   Publisher：新潟整形外科研究会  

THA周術期のDVT予防方法として弾性包帯(EB)法は下腿マッサージ(CaM)法等に比べて簡便な方法であり、米国胸部外科学会ガイドラインではEB法において足関節圧30～40mmHgで圧迫することを推奨している。当科でもEB法を導入したが、その手順は術前にEBを患肢に巻いた後に足関節圧を計測し、圧計測器は術前に抜去しているため、術中の足関節圧は不明である。そこで今回、術前にどれくらいの圧でEBを巻けば術中に30～40mmHgとなるのか明らかにするため、健常人4名を対象とし、EBを巻いた後に二つの体圧計で足関節圧を計測し、計測後に一つを除去し、その後、もう一つで再度計測を行い、初回計測値との差を調べた。その結果、二つ装着しているときに比べて一つ除去すると足関節圧は平均8%減少していたことから、EBを巻く圧は34～43mmHgと定めた。EB法の効果について検討するため、2018～2021年に初回THAを施行した患者163例を対象とし、DVT予防法別にCaM群(149例)とEB群(14例)に分け、VTE発生率やPTE発生率を比較した。結果、VTE発生率はCaM群5.0%、EB群7.1%で、EB群のほうが若干高かったが統計学的有意差はなく、PTEの発生は両群ともなかった。

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Language：Japanese   Publisher：新潟整形外科研究会  

当院で2007～2013年に初回THAを施行した症例のうち、術前と術後1・3・5年時に腰椎の臥位側面X線と立位側面X線を撮影した50例(片側28例、両側22例)を対象に検討した。結果、立位での骨盤傾斜の変化は、片側例・両側例とも経年的に後傾していた。臥位での骨盤傾斜も経年的に後傾する傾向にあったが、術前に比べて有意差を認めたのは片側例では術後5年時のみであり、両側例では2回目術前と術後3年時のみであった。術前臥位での仙骨傾斜角(SS)に比べて術後5年時の立位SSが15°以上後傾していた群では、そうでない群に比べて、術前立位での前骨盤平面角(APPA)が有意に後傾していた。そこで、SSが術後15°以上後傾する術前APPA後傾のカットオフ値をROC解析により求めたところ、「11.5°後傾」と算出された。

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BACKGROUND: The quadriceps femoris may be a reliable reference to proper alignment in total knee arthroplasty (TKA). We previously showed the quadriceps vector (QV) to be the most parallel to the spherical axis (SA-center hip to center medial condyle) for healthy knees. The purpose of this study was to determine whether the QV is the most parallel to the SA in knees with varus osteoarthritis (OA). METHODS: CT imaging for 35 varus OA and 40 healthy Japanese knees was used to construct 3D models of the femur, patella and each quadriceps component for each subject. The QV was calculated using principal component analysis for direction and was compared with the relationship of the QV to the measurement axes of the lower extremity, including the anatomical, mechanical and spherical axes. RESULTS: The direction of the QV for the OA knee group was different from that for the healthy knee group in 3D space (medio-lateral direction: women, p = 0.532, men, p = 0.540; antero-posterior direction: women, p = 0.141, men, p < 0.001). However, the angle of the QV in relation to measurement axes in the coronal plane was closest to the SA in both groups (around 1°), with no difference between the groups (women, p = 0.382, men, p = 0.943). CONCLUSION: In the coronal plane, the SA most closely approximates the QV for both healthy and OA knees. The more posterior QV position in the 3D space may affect the patellofemoral joint.

DOI： 10.1016/j.knee.2021.09.002

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The main function of skeletal muscles is to generate force. The force developed by myofiber contraction is transmitted to the tendon. There are two pathways of force transmission from myofibers to tendons: longitudinal transmission that depends on tension elicited via the myotendinous junction and lateral transmission that depends on shear elicited via the interface between the myofiber surface and surrounding connective tissue. Experiments using animal muscle and mathematical models indicated that lateral transmission is the dominant pathway in muscle force transmission. Studies using rat muscle showed that the efficiency of lateral force transmission declines with age. Here, the lateral transmission of force was measured using the extensor digitorum longus muscle from young and old mice. Dependence on longitudinal transmission increased in the old muscle, and there was a trend for lower efficiency of lateral force transmission in the old muscle compared to the young muscle. There was a noticeable increase in the connective tissue volume in the old muscle; however, there was no significant change in the expression of dystrophin, a critical molecule for the link between the myofiber cytoskeleton and extracellular matrix. This study demonstrates the measurement of lateral force transmission in mouse muscles and that alteration in force transmission property may underlie age-related muscle weakness.

DOI： 10.3390/ijms222212356

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Language：Japanese   Publisher：(株)医学書院  

＜文献概要＞背景:がんとロコモティブシンドローム(がんロコモ)の概念が提唱されているが,一般病院の整形外科におけるがん診療の実情は明らかでない.対象と方法:2015年6月～2020年5月までの5年間に受診したがん患者の原発疾患,整形外科受診歴,受診要因,予後について診療録を用いて後ろ向きに調査した.当院では骨転移患者を整形外科で診療した場合,極力経過観察を整形外科でも継続する対応をしてきた.結果:3,679人のがん患者のうち642人(17.5%)が整形外科を受診しており,これは整形外科受診者全体18,347人の3.5%であった.がんそのものの症状のための受診者は228例であり,死亡・転院患者83例中72例は整形外科での経過観察が終末期まで継続されていた.整形外科で施行した非腫瘍性疾患のCT検査3,946件中31例(0.8%)で偶発がんが発見されていた.まとめ:一般病院のがん患者の17.5%が整形外科を受診し,これは整形外科受診者の3.5%であった.骨転移患者を診療した場合,整形外科医の経過観察を極力終了しない方針で対応することががんロコモの1つの実践法と思われる.整形外科医が内臓がんの発見者になることも少なくない.

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PURPOSE: It has been reported that C7 and C8 nerve root impairment can cause drop finger; however, the clinical characteristics of each injured nerve root and post-operative outcomes remain unclear. This study aimed to investigate the detailed features and surgery-related prognostic factors of drop finger caused by cervical radiculopathy. METHODS: We retrospectively investigated the clinical characteristics, paralysis patterns and surgery-related prognostic factors of 23 patients with drop finger caused by cervical radiculopathy who underwent posterior cervical foraminotomy. We classified paralysis into three patterns based on the fingers predominantly exhibiting extensor digitorum communis (EDC) muscle weakness: index finger side-dominant, middle and ring fingers-dominant and little finger side-dominant. RESULTS: The aetiologies were cervical disc hernia (CDH) in ten patients, cervical spondylotic radiculopathy (CSR) in eight and both CDH and CSR in five. The levels of the decompressed root were C7 in one patient, C8 in 11 and both C7 and C8 in 11. Scapular pain was frequently observed as the initial symptom (78%), especially in patients with only C8 nerve root disorder (91%). Drop finger recovered to a score of ≥ 3 on manual muscle testing in 17 patients; patients with the little finger side-dominant pattern tended to have poor recoveries. Patients with CDH improved significantly than those with CSR or both CDH and CSR (p < 0.05). CONCLUSIONS: Good surgical recovery of drop finger can be expected in patients with CDH and in those with index fingers-dominant and middle and ring fingers-dominant patterns.

DOI： 10.1007/s00264-021-05197-w

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Pustulotic arthro-osteitis (PAO) is a major complication of palmoplantar pustulosis (PPP). In orthopedic surgery outpatient clinics, PPP patients with osteoarticular symptoms are seen frequently, but PAO's clinical features remain not well known. To determine Japanese patients' clinical features and treatment status with PAO, we conducted a single-center retrospective epidemiologic survey. Clinical features, including gender, age, smoking habit, the onset pattern, interval between skin manifestation and osteoarticular symptoms, and the incidence of sternoclavicular joint lesions, axial and peripheral joint lesions, were examined. The association between physical status and image findings by X-ray, computed tomography, bone scintigraphy with Technetium99 , or magnetic resonance imaging was evaluated. The distribution pattern of peripheral joint lesions and the treatment status were evaluated. We identified 51 patients, 10 men and 41 women, with PAO. The average age was 48 years and 59% were smokers. The frequency of onset patterns was skin-leading type (63%), simultaneous onset (18%), and osteoarticular leading type (16%). The average interval between skin involvement and osteoarticular involvement in skin-leading type was significantly longer than that in osteoarticular leading type (7.1 years vs. 2.0 years). A sternoclavicular joint (SCJ) lesion was detected in 65% cases, and the physical findings of SCJ were significantly related to the image findings. Axial and peripheral joint lesions were detected in the same ratio (23 cases, 45%). In the peripheral joints, the finger joint was the most common (26%), followed by the shoulder joint (21%). Patients were treated with nonsteroidal anti-inflammatory drugs (76%), followed by conventional synthetic disease-modifying antirheumatic drugs (DMARDs) (29%) and biological DMARDs (9.8%). Tonsillectomy was performed in 11 cases. In conclusion, PAO more frequently involves SCJ in middle-aged women who smoke. Given that osteoarticular leading type was detected in 16% cases, seronegative oligoarthritis patients should be monitored for PPP, leading to a diagnosis of PAO.

DOI： 10.1111/1346-8138.16107

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Language：Japanese   Publisher：(株)北隆館  

骨軟部腫瘍における免疫環境の研究は未開拓分野である。筆者らは肉腫の一部に自然寛解がみられることより、骨軟部腫瘍においても免疫環境が予後に影響を持つものと考え研究を続けている。これまでHLA class Iの腫瘍細胞おける発現、CD8陽性リンパ球、CD163陽性マクロファージ浸潤を解析してきたが、組織型ごとに特徴や予後に関する影響も異なっていた。今後はCAR-T細胞を用いた細胞療法等が新たな治療戦略になることを期待し研究を続けている。(著者抄録)

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Language：Japanese   Publisher：(一社)日本臨床バイオメカニクス学会  

本研究の目的は踏み出し脚の前足底接地からボールリリース区間の踏み出し脚の膝・股関節・骨盤の運動が投球リリースポイント(RP)ばらつきに与える影響を検討することである。高校野球部の投手10名を対象に、マウンドプレートから12m先、右打者の外角と内角低めを的として10球ごとに休息し、合計20球を全力投球して3次元測定を行い、20球の平均値を各選手の投球動作結果とした。RPばらつきと投球動作の膝・股関節・骨盤の運動量との関係性をSpearmanの順位相関係数で検討した。前後方向ばらつきは膝関節屈伸量(r=0.68、p=0.03)と骨盤回旋量(r=0.73、p=0.02)に、側方方向ばらつきは股関節内外転量(r=-0.69、p=0.003)に有意な相関を示した。前足底接地からボールリリース区間で膝関節屈伸量と骨盤回旋量はRP前後方向のばらつきに影響し、股関節内外転量はRP側方のばらつきに影響することが示唆された。(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J05471&link_issn=&doc_id=20211007090001&doc_link_id=%2Fcx9biomc%2F2021%2F004200%2F002%2F0001-0007%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fcx9biomc%2F2021%2F004200%2F002%2F0001-0007%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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

DOI： 10.1016/j.jos.2018.09.009

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A 21-year-old man consulted our hospital for treatment of a spinal giant cell tumor (GCT) of Enneking stage III. Lower lumbar-spine tumors and severe spinal canal stenosis are associated with high risk for surgical mor-bidity. Stability was temporarily secured with a percutaneous pedicle screw fixation in combination with deno-sumab, which shrank the tumor. Total en bloc spondylectomy was then performed 6 months after initiation of denosumab, and the patient was followed for 3 years. There was no local recurrence, and bony fusion was obtained. Minimally invasive surgery and denosumab allowed safer and easier treatment of a collapsing lower lumbar extra-compartmental GCT.

DOI： 10.18926/AMO/61442

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BACKGROUND: Assessment of three-dimensional (3D) femorotibial alignment is essential for successful knee osteoarthritis treatment in the elderly. The complex morphology of the posterior tibial slope (PTS) might have an influence on sagittal and rotational alignment and the positional relationship between the femur and tibia in the anterior-posterior (AP) direction under weight-bearing conditions. OBJECTIVE: This study aimed to clarify the association between the PTS and 3D femorotibial alignment under weight-bearing conditions in healthy Japanese elderly individuals. METHODS: We investigated the 3D femorotibial alignment of 110 lower extremities of 55 healthy individuals (26 women, 29 men, mean age: 70 ± 6 years). Using our previously reported 3D-to-2D image registration technique, we evaluated the 3D hip-knee-ankle angle (3DHKA) in the sagittal plane, rotational alignment, and the distance between the femoral and tibial origins in the AP direction (tibial AP position) as femorotibial alignment parameters under weight-bearing conditions. We assessed the medial and lateral PTS and their angular difference (PTS difference) as PTS parameters. Stepwise multiple linear regression analysis was performed using PTS parameters and other possible confounders (age, sex, height, and weight) as the independent variables and femorotibial alignment parameters as the dependent variable. RESULTS: Weight (𝛽 = 0.393, p < 0.001) and lateral PTS (𝛽 = 0.298, p < 0.001) were the predictors associated with 3DHKA in the sagittal plane. Lateral PTS (𝛽 = 0.304, p = 0.001) was the only predictor associated with the tibial AP position. Sex (𝛽 = -0.282, p = 0.002) and PTS difference (𝛽 = -0.231, p = 0.012) were associated with rotational alignment. CONCLUSIONS: We found that a steeper lateral PTS resulted in a more flexed knee and anterior tibia. The PTS difference was positively correlated with tibial external rotation. Our data could be used as the standard reference for realignment surgery to ensure PTS is appropriately maintained.

DOI： 10.3233/BME-201209

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Language：Japanese   Publisher：新潟整形外科研究会  

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Language：Japanese   Publisher：新潟整形外科研究会  

過去10年3ヵ月間の特発性側彎症に対する椎弓根スクリューによる後方矯正固定術(PSF)症例172例(男性16例、女性156例、手術時年齢10～20歳、平均15.2±2.0歳)を対象に、周術期疼痛管理および術後回復過程について後方視的に検討した。その結果、術後疼痛管理は平均4.1日間のフェンタニル持続静注(平均17.6μg/kg/日)で行われ、自立歩行は術後平均6.2日で開始、退院は術後平均11.0日であった。

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BACKGROUND: 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. QUESTIONS/PURPOSES: (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? METHODS: 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. RESULTS: 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. CONCLUSIONS: 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 OF EVIDENCE: Level IV, therapeutic study.

DOI： 10.1097/CORR.0000000000001266

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OBJECTIVE: The treatment modality for desmoid-type fibromatosis has shifted from surgery to conservative treatment. The guideline committee for clinical care of extra-abdominal desmoid-type fibromatosis in Japan conducted a systematic review of treatment with doxorubicin-based chemotherapy for desmoid-type fibromatosis. METHODS: We searched the pertinent literature. Two reviewers evaluated and screened it independently for eligibility and extracted data. They rated each report according to the grading of recommendations development and evaluation methodology. Based on the 'body of evidence', which the reviewers created, the clinical guideline committee decided a recommendation for the clinical question, 'Is doxorubicin-based chemotherapy effective for patients with extra-abdominal desmoid-type fibromatosis?' RESULTS: Fifty-three articles were extracted by the literature search, and one from hand search. After the first and second screenings, five articles were subjected to the final evaluation. There were no randomized controlled trials. According to response evaluation criteria in solid tumors criteria, the response rates of doxorubicin-based regimens and liposomal doxorubicin were 44% (28.6-54) and 33.3% (0-75) on average, respectively. In two reports, the response rates of doxorubicin-based regimens were higher than those of non-doxorubicin-based ones; 54% vs 12%, 40% vs 11%, respectively. The rates of G3 or G4 complications according to common terminology criteria for adverse events were 28% and 13% with doxorubicin-based and liposomal doxorubicin chemotherapy, respectively, including neutropenia or cardiac dysfunction. None of the reports addressed the issue of QOL. CONCLUSION: Although the evidence level was low in the evaluated studies, doxorubicin-based and liposomal doxorubicin chemotherapy was observed to be effective. However, doxorubicin-based chemotherapy is associated with non-ignorable adverse events, and is not covered by insurance in Japan. We weakly recommend doxorubicin-based chemotherapy for patients with extra-abdominal desmoid-type fibromatosis in cases resistant to other treatments.

DOI： 10.1093/jjco/hyaa125

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PURPOSE: This study aimed to evaluate the age- and sex-related characteristics in cortical thickness of the tibial diaphysis between non-obese healthy young and elderly subjects as reference data. METHODS: The study investigated 31 young subjects (12 men and 19 women; mean age, 25 ± 8 years) and 54 elderly subjects (29 men and 25 women; mean age, 70 ± 6 years). Three-dimensional estimated cortical thickness of the tibial diaphysis was automatically calculated for 5000-9000 measurement points using the high-resolution cortical thickness measurement from clinical computed tomography data. In 12 assessment regions created by combining three heights (proximal, central, and distal diaphysis) and four areas of the axial plane at 90° (medial, anterior, lateral, and posterior areas) in the tibial coordinate system, the standardized thickness was assessed using the tibial length. RESULTS: As structural characteristics, there were no differences in the medial and lateral thicknesses, while the anterior thickness was greater than the posterior thickness in all groups. The sex-related difference was not shown. As an age-related difference, elderly subjects showed greater or lesser cortical thickness than the young subjects, depending on the regions of the tibia. CONCLUSIONS: Cortical thickness was different depending on sex, age, and regions in the tibia. The results of this study are of clinical relevance as reference points to clarify the causes of various pathological conditions for diseases. LEVEL OF EVIDENCE: Level 3.

DOI： 10.1186/s40634-020-00297-9

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DOI： 10.1016/j.jtcvs.2019.04.015

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BACKGROUND AND AIM: The pathophysiology of rheumatoid arthritis (RA) is characterized by excess production of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) by neutrophils and macrophages in synovium. Additionally, these cytokines promote the production of reactive oxygen species (ROS), and increased production of matrix metalloproteinases (MMPs), including MMP-3, in synoviocytes that result in joint destruction. There is limited information on how proteolytic enzymes such as MMP-3 can be regulated. We evaluated the effect of the antioxidant N-acetylcysteine (NAC) on RA and identified the relationship between the c-Jun N terminal kinase (JNK) pathway and MMP-3. We hypothesized that elucidating this relationship would lead to novel therapeutic approaches to RA treatment and management. METHODS: We investigated the effect of administering a low dose (1000 μM or less) of an antioxidant (NAC) to human rheumatoid fibroblast-like synoviocytes (MH7A cells). We also investigated the response of antioxidant genes such as nuclear factor erythroid -derived 2-related factor 2 (Nrf2) and Sequestosome 1 (p62). The influence of MMP-3 expression on the JNK pathway leading to joint destruction and the mechanisms underlying this relationship were investigated through primary dispersion culture cells collected from the synovial membranes of RA patients, consisting of rheumatoid arthritis-fibroblast-like synoviocytes (RA-FLS). RESULTS: Low-dose NAC (1000 μM) increased the expression of Nrf2 and phospho-p62 in MH7A cells, activating antioxidant genes, suppressing the expression of MMP-3, and inhibiting the phosphorylation of JNK. ROS, MMP-3 expression, and IL-6 was suppressed by administering 30 μM of SP600125 (a JNK inhibitor) in MH7A cells. Furthermore, the administration of SP600125 (30 μM) to RA-FLS suppressed MMP-3. CONCLUSIONS: We demonstrated the existence of an MMP-3 suppression mechanism that utilizes the JNK pathway in RA-FLS. We consider that the JNK pathway could be a target for future RA therapies.

DOI： 10.1186/s13018-020-01595-9

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BACKGROUND: Primary osteosarcoma in elderly patients are rare malignant tumors. Its optimal treatment has not yet been determined. METHODS: This retrospective study included 104 patients aged >50 years with resectable, non-metastatic osteosarcoma treated by the members of the Bone and Soft Tissue Tumor Study Group of the Japan Clinical Oncology Group. The effects of adjuvant chemotherapy were estimated by comparing outcomes in patients who received surgery plus chemotherapy with those who underwent surgery alone. RESULTS: Median age at presentation was 59 years. Neoadjuvant and adjuvant chemotherapy was administered to 83 (79.8%) patients. Patients who underwent surgery plus chemotherapy and those who underwent surgery alone had 5-year overall survival (OS) rates of 68.6% and 71.7%, respectively (p = 0.780), and 5-year relapse free survival (RFS) rates of 48.2% and 43.6%, respectively (p = 0.64). Univariate analysis showed that resection with wide margins was significantly correlated with better prognosis. CONCLUSIONS: The addition of chemotherapy to surgery did not improve OS or RFS in patients aged >50 years with resectable, non-metastatic osteosarcoma. Surgery with wide margins was only significantly prognostic of improved survival. The effect of chemotherapy in elderly osteosarcoma patients was unclear.

DOI： 10.1016/j.jos.2019.04.008

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Stanniocalcin-1 (STC1) is a glycoprotein that was originally identified as a calcium-regulating hormone in bony fish, and that has been shown to also critically mediate cell growth, proliferation and differentiation, etc. in humans. Increased STC1 expression levels have been previously detected in different human cancer samples, such as those isolated from lung, breast, ovary, colon, pancreas, and liver tumors; thus, the present study evaluated STC1 expression in various soft-tissue tumors. STC1 mRNA isolated from 16 cell lines and 186 clinical soft-tissue tumor specimens were analyzed via quantitative real-time PCR, and the calculated expression levels were normalized to those exhibited by STC1-expressing MDA-MB-231 cells. The results of these analyses did not reveal any specific histological tumor types that displayed significantly increased STC1 expression; however, they did not indicate that STC1 expression was significantly higher in malignant compared to benign soft-tissue tumors. Furthermore, in adipocytic tumors, STC1 expression in dedifferentiated liposarcomas was found to be highest and lowest in lipoma tissues, respectively, suggesting that adipocytic tumors may express increasely high levels of STC1 mRNA as they become histologically more advanced. STC1 expression correlates with the malignancy grade in soft-tissue tumors.

DOI： 10.18999/nagjms.82.1.85

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NAGOYA UNIV, SCH MED  

Stanniocalcin-1 (STC1) is a glycoprotein that was originally identified as a calcium-regulating hormone in bony fish, and that has been shown to also critically mediate cell growth, proliferation and differentiation, etc. in humans. Increased STC1 expression levels have been previously detected in different human cancer samples, such as those isolated from lung, breast, ovary, colon, pancreas. and liver tumors; thus, the present study evaluated STC1 expression in various soft-tissue tumors. STC1 mRNA isolated from 16 cell lines and 186 clinical soft-tissue tumor specimens were analyzed via quantitative real-time PCR, and the calculated expression levels were normalized to those exhibited by STC1-expressing MDA-MB-231 cells. The results of these analyses did not reveal any specific histological tumor types that displayed significantly increased STC1 expression; however, they did not indicate that STC1 expression was significantly higher in malignant compared to benign soft-tissue tumors. Furthermore, in adipocytic tumors, STC1 expression in dedifferentiated liposarcomas was found to be highest and lowest in lipoma tissues, respectively, suggesting that adipocytic tumors may express increasely high levels of STC1 mRNA as they become histologically more advanced. STC1 expression correlates with the malignancy grade in soft-tissue tumors.

DOI： 10.18999/nagjms.82.1.85

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BACKGROUND: Patellar tendon autograft after intraoperative extracorporeal radiotherapy has been used for reconstruction of the extensor mechanism following limb-sparing wide tumor resection around the knee. The purpose of this study was to determine the clinical outcome of this reconstruction technique. METHODS: We retrospectively reviewed six consecutive patients with peripatellar tendon and proximal tibial sarcoma who underwent reconstruction of the knee extensor mechanism. The resection area was planned to be contained with the patellar tendon in order to obtain a wide margin. First, the patella was osteotomized at the midline, and the inferior half of patella, patellar tendon, and tibial tuberosity were excised en bloc. The resected segments were devitalized with intraoperative extracorporeal radiotherapy and reimplanted into the original site. A follow-up evaluation included an assessment of the range of motion, extensor lag, the International Society of Limb Salvage score, and complications. RESULTS: Six patients were followed up for 121-270 months. One patient underwent an additional reconstruction with total knee arthroplasty due to a collapse of the tibial subchondral bone. A supracondylar fracture of the femur occurred in two patients, and a delayed union of the osteosynthesis site of the tibial shaft was observed in one patient. At the latest follow up, extensor lag had a median of five degrees, and International Society of Limb Salvage scores had a median of 83%. No local recurrence or rupture of the patellar tendon was observed. CONCLUSIONS: Reconstruction of the knee extensor mechanism using a patellar tendon treated with intraoperative radiotherapy is a reliable and successful method.

DOI： 10.1016/j.knee.2019.10.008

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BACKGROUND: The outcomes of unplanned surgery for bone sarcomas have not been frequently discussed. However, it is important to recognize patterns, treatment, and clinical outcomes of unplanned surgeries for patients with bone sarcomas. This multicenter study aimed to characterize the clinical outcomes of patients with bone sarcomas who underwent unplanned surgeries. PATIENTS AND METHODS: Data of 43 patients with bone sarcomas who underwent unplanned surgery between 2006 and 2017 were obtained from 23 hospitals in Japan. These included 18 cases of osteosarcoma, 9 of Ewing sarcoma, 8 of chondrosarcoma, and 6 of undifferentiated pleomorphic sarcoma. The study included 28 men and 15 women, with a mean age of 46 years. The mean follow-up duration was 59 months. RESULTS: The main primary tumor sites were the femur (n = 19), spine (n = 6), pelvis (n = 5), tibia (n = 3), and humerus (n = 3). The primary diagnoses were benign bone tumor (n = 24), trauma (n = 7), bone metastasis (n = 5), osteomyelitis (n = 4), degeneration (n=2), and unknown (n = 1). As unplanned surgeries, curettage, with or without bone graft, was performed in 26 patients; internal fixation was performed in 7; spinal surgery in 5; arthroplasty in 4; and arthroscopy in one. Thirty-eight patients received additional standard treatments. Thirty-four of these patients underwent surgical tumor resections, including amputation (n = 10), and the remaining 4 received radiotherapy or carbon ion radiotherapy as additional standard treatments. The 5-year disease-specific survival (DSS) rates in patients with osteosarcoma, Ewing sarcoma, and chondrosarcoma were 65.5%, 58.3%, and 72.9%, respectively. Twelve (27.9%) patients developed local recurrences (LR); among the total 43 patients studied, the 5-year DSS rates were significantly worse for those who developed LR compared to those who did not (p = 0.03). The 5-year DSS rates in patients with and without LR were 44% and 73.8%, respectively. CONCLUSION: We recommend that patients who have undergone unplanned surgery be administered standard treatment, including the option of amputation because herein, LR was shown to be a risk factor for decreased DSS.

DOI： 10.2147/CMAR.S270178

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Porphyromonas gingivalis infection can lead to periodontitis and dysbiosis, which are known risk factors for rheumatoid arthritis (RA). We investigated whether P. gingivalis administration affected bone regeneration in mice with or without arthritis. We administered P. gingivalis to male DBA/1 J mice that were or were not sensitised to type II collagen-induced arthritis (CIA). All mice underwent drilling of bilateral femurs. We histologically evaluated new bone regeneration (bone volume of the defect [BVd]/tissue volume of the defect [TVd]) using micro-computed tomography (micro-CT), osteoclast number/bone area, and active osteoblast surface/bone surface (Ob.S/BS). We measured serum cytokine levels and bone mineral density of the proximal tibia using micro-CT. CIA resulted in significantly reduced bone regeneration (BVd/TVd) at all time-points, whereas P. gingivalis administration showed similar effects at 2 weeks postoperatively. CIA resulted in higher osteoclast number/bone area and lower Ob.S/BS at 2 and 3 weeks postoperatively, respectively. However, P. gingivalis administration resulted in lower Ob.S/BS only at 2 weeks postoperatively. During later-stage bone regeneration, CIA and P. gingivalis administration synergistically decreased BVd/TVd, increased serum tumour necrosis factor-α, and resulted in the lowest bone mineral density. Therefore, RA and dysbiosis could be risk factors for prolonged fracture healing.

DOI： 10.1038/s41598-019-56265-6

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Language：Japanese   Publisher：(株)南江堂  

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2019&ichushi_jid=J00764&link_issn=&doc_id=20191129240016&doc_link_id=10.15106%2Fj_seikei70_1385&url=https%3A%2F%2Fdoi.org%2F10.15106%2Fj_seikei70_1385&type=%E5%8C%BB%E6%9B%B8.jp_%E3%82%AA%E3%83%BC%E3%83%AB%E3%82%A2%E3%82%AF%E3%82%BB%E3%82%B9&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00024_2.gif

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Background: Musculoskeletal sarcomas (MSSs) are rare cancers and often aggressive tumors that originate from mesenchymal tissue. Patients with advanced MSS often report difficulties with symptom burden, which can reduce their health-related quality-of-life. Objective: The aim of this study was to describe the patterns of the physical symptoms of MSS patients in the palliative setting and to detail the palliative treatment used in the last two weeks of life. Design: Retrospective study using the electronic patient records from a single institution. Setting/Subjects: A retrospective study was carried out in a sample of 46 consecutive MSS patients with locally advanced/metastatic disease, who were hospitalized and died in our department. The median age of these patients was 56 years at death. Measurements: Symptom burden and medical intervention during the last two weeks of life were collected. Results: The most frequent physical symptoms were pain and dyspnea in 93% and 78% of patients, respectively, while only 17% of patients suffered from nausea. A total of 98% of patients required opioids, and most patients were treated with morphine through either subcutaneous or intravenous continuous injection. Nonsteroidal anti-inflammatory drugs and acetaminophen were administered to 79% of patients. Corticosteroids were administered for the relief of dyspnea to 83% of patients. Of the patients, 46% received palliative chemotherapy within the last two weeks of life, and the oral treatment was continued until a median of 5.6 days before death. In addition, 39% of patients received a sedative treatment during the last two weeks of life for uncontrolled refractory symptoms. Conclusions: The symptom burden experienced by advanced MSS patients is profound at the end of life for all palliative approaches. Therefore, palliative medicine is an important and even crucial component of the continuum of care, allowing for aggressive symptom management with a variety of medical interventions, including palliative sedation.

DOI： 10.1089/jpm.2018.0415

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Tohoku University Medical Press  

Bone and soft tissue tumors are derived from mesenchymal cells, and they are hard to treat. Receptor-activator of nuclear factor-kappa B ligand (RANKL) is an essential cytokine for osteoclast differentiation and activation and is expressed on the surface of osteoblasts or stromal cells. In this study, to explore the potential of denosumab treatment for soft tissue tumors, we analyzed the expression profiles of RANKL mRNA in 425 tumor specimens of 33 histological types by real-time RT-PCR. Denosumab is a monoclonal antibody that prevents the binding of RANKL to receptor-activator of nuclear factor-kappa B (RANK). For comparison, the relative expression levels of RANK and osteoprotegerin (OPG) mRNAs were also measured. OPG functions as a soluble decoy receptor for RANKL. Higher expression levels of RANKL mRNA were detected in calcifying aponeurotic fibroma, fibrosarcoma, calcifying epithelioma, myositis ossificans, heterotopic calcification, giant cell tumor of the tendon sheath (GCTTS), and pigmented villonodular synovitis (PVNS), compared with the levels of other tumor types. Moreover, the expression levels of RANK mRNA were highest in GCTTS, followed by myositis ossificans and PVNS, whereas the expression levels of OPG mRNA were greatly varied among these histological types. We then analyzed RANKL protein expression by immunohistochemistry in 57 tumor specimens with higher expression levels of RANKL mRNA. RANKL-positive cells were detected in GCTTS, PVNS, myositis ossificans, heterotopic calcification, and calcifying aponeurotic fibroma. In conclusion, RANKL is expressed in subsets of soft tissue tumors with calcification, and denosumab is a potential therapeutic option for soft tissue tumors expressing RANKL.

DOI： 10.1620/tjem.248.87

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Language：Japanese   Publisher：日本手術医学会  

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Language：Japanese   Publisher：新潟整形外科研究会  

症例1は14歳女性で、左大腿骨転子下骨折を繰り返し、10歳時に大腿骨の矯正外反骨切り術とプレート固定術を施行した。13歳時にプレートを抜去したが2週間で同部骨折を生じ、矯正外反骨切り術と髄内釘固定を行った。術後4ヵ月で遠位横止めスクリューを抜去して骨癒合が得られた。症例2は30歳女性で、12歳時に右大腿骨転子下矯正外反骨切り術とA-O condylar angle plate固定を行った。13歳時からパミドロン酸3日間連続点滴投与を半年に一度2年間継続し、その後は内反変形の進行なく自立歩行可能である。症例3は87歳女性で、38歳時にMcLanghling nail固定と遊離腓骨柱移植で内固定を行い、術後32年でMcLanghling nail固定を抜去し、A-O dynamic condylar screw plate固定を行った。71歳時より疼痛コントロール目的にアレドロン酸の連日内服を開始し、軽度内反進行は認めるが掴まり歩行にて自宅で生活している。

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The natural history of asymptomatic retroperitoneal schwannomas is poorly understood. This study aimed at investigating the natural history of incidental retroperitoneal schwannomas. The medical charts and imaging studies of 22 asymptomatic patients under observation for at least 12 months for retroperitoneal schwannomas were reviewed. The duration of follow-up ranged between 13 and 176 months (mean 48 months). In the 22 patients managed by the "wait and see" approach, the average tumor size at initial presentation was 51 mm, which increased to 57 mm at final follow-up. During the final follow-up, 2 patients required surgical treatment for tumor enlargement, while the remaining patients remained asymptomatic without surgery. The average growth rate of the tumors was 1.9 mm/year (range: -1.9 to 8.7 mm/year). The majority of asymptomatic retroperitoneal schwannomas demonstrate minimal growth and may be suitable for management with the "wait and see" approach.

DOI： 10.1371/journal.pone.0215336

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Language：English  

A 34-year-old woman was diagnosed with acute promyelocytic leukemia. Chemotherapy was administered following the JALSG APL204 protocol. Induction therapy with all-trans retinoic acid resulted in complete remission on day 49. She developed coccygeal pain from day 18, which spread to the spine and cheekbones and lasted 5 weeks. She had similar bone pain on days 7-10 of the first consolidation therapy and on days 4-12 of the second consolidation therapy. Oral loxoprofen was prescribed for pain relief. On day 33 of the third consolidation, white blood cell and neutrophil counts were 320/μL and 20/μL, respectively. After she developed epigastralgia and hematemesis, she developed septic shock. Gastroendoscopy revealed markedly thickened folds and diffusely damaged mucosa with blood oozing. Computed tomography revealed thickened walls of the antrum and the pylorus. Despite emergency treatments, she died. Bacterial culture of the gastric fluid yielded Enterobacter cloacae and enterococci growth. Collectively, she was diagnosed with phlegmonous gastritis. Retrospective examination of serial bone marrow biopsy specimens demonstrated progressive bone marrow fibrosis, which may have caused prolonged myelosuppression. Thus, evaluation of bone marrow fibrosis by bone marrow biopsy after each treatment cycle might serve as a predictor of persistent myelosuppression induced by chemotherapy.

DOI： 10.1155/2019/1616237

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Erdheim-Chester disease is a rare histiocytosis with insufficient clinical data. To clarify the clinical features and prognostic factors of Erdheim-Chester disease, we conducted a nationwide survey to collect the detailed data of 44 patients with Erdheim-Chester disease in Japan. The median age of onset of the participants was 51 (range: 23-76) years, and the median number of involved organs per patient was 4 (range: 1-11). The existence of central nervous system disease was correlated with older age (P=0.033), the presence of cardiovascular lesions (P=0.015), and an increased number of involved organs (P=0.0042). The median survival from the onset was 10.4 years, and >3.0 mg/dL C-reactive protein level at onset was associated with worse outcome (median survival, 14.6 vs. 7.4 years; P=0.0016). In a multivariate analysis, age >60 years (hazard ratio, 25.9; 95% confidence interval, 2.82-237; P=0.0040) and the presence of digestive organ involvement (hazard ratio, 4.74; 95% confidence interval, 1.05-21.4; P=0.043) were correlated with worse survival. Fourteen patients had available histological samples of Erdheim- Chester disease lesions. BRAFV600E mutation was detected in 11 patients (78%) by Sanger sequencing. A correlation between BRAF mutation status and clinical factors was not observed. Our study revealed that age and digestive organ involvement influence the outcome of Erdheim-Chester disease patients, and an inflammatory marker, such as C-reactive protein, might reflect the activity of this inflammatory myeloid neoplasm.

DOI： 10.3324/haematol.2018.190728

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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.

DOI： 10.1111/cas.13769

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Bone leiomyosarcoma is a rare primary osseous malignant tumor with a high metastatic potential. Similar to other bone sarcomas, high histological grade and tumor stage are predictive of a poor outcome. We herein present our experience with treating a 64-year-old woman with bone leiomyosarcoma accompanied by multiple bone metastases. A biopsy revealed occasional osteoclast-like giant cells. In addition to radiation therapy, the osteoclastogenesis inhibitor denosumab was administered but the patient did not undergo adjuvant chemotherapy or surgery. Good clinical and short-term radiological responses to denosumab have been observed for 2 years. Therefore, denosumab may represent a viable treatment option without the need for adjuvant chemotherapy.

DOI： 10.3892/mco.2017.1489

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Histiocytic sarcoma, a rare hematopoietic neoplasm with evidence of histiocytic differentiation, is often refractory to conventional chemotherapy and radiotherapy, and its prognosis is generally dismal. The optimal management of this malignancy has not been established. We report a case of 8-year-old girl with histiocytic sarcoma involving the left femur. The tumor rapidly responded to a combination of cladribine and high-dose cytosine arabinoside, an aggressive salvage regimen for refractory Langerhans cell histiocytosis, and became impalpable during the first cycle. The patient has remained in complete remission more than 7 years from diagnosis.

DOI： 10.1007/s12185-017-2202-8

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

2005〜2015年までに、無治療のまま1ヵ月以上の間隔で複数回の画像評価を行った骨・軟部肉腫症例20例(男性14例、女性6例、年齢14〜85歳)を対象に、CTあるいはMRIのDICOMで腫瘍倍加時間を測定した。その結果、組織診断は未分化多型肉腫4例、高分化型脂肪肉腫、悪性末梢神経鞘腫瘍、平滑筋肉腫が各2例、その他10例で、骨腫瘍3例、軟部腫瘍17例であった。倍加時間は23〜858日、推定腫瘍発生時期は2.4〜84.7年前、推定腫瘍発生年齢は-8〜79歳であった。4例は先天性発生と推定され(生下時3例、-8歳1例)、そのうち2例は高齢者であった。最終転帰は腫瘍死9例、有病生存4例、無病生存7例で、腫瘍倍加時間が100日以内の6例は腫瘍死5例、多発転移1例で予後不良であった。

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Other Link： http://search.jamas.or.jp/link/ui/2017355781

Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE BV  

Background: Reconstruction of the extensor mechanism after resection of the proximal tibia is challenging, and several surgical procedures are available. The purpose of this study was to determine the outcome of the fibular transposition technique for reconstruction of the extensor mechanism of the knee after proximal tibial resection.
Methods: We retrospectively reviewed five consecutive patients who underwent resection of the proximal tibia with prosthetic reconstruction and reconstruction of the extensor using fibular transposition between 1997 and 2011. There were two female and three male patients with a mean age of 50 years (range, 27 to 76 years). A follow-up evaluation included both passive and active range of motion, extensor lag, the MSTS score and complications.
Results: Patients were followed up for 93 months (range, 44 to 160 months). The mean extensor lag and active flexion were four degrees (range, 0 to 10 degrees) and 103 degrees (range, 85 to 110 degrees), respectively. The mean MSTS score was 80% (range, 73 to 90%). All patients were able to ambulate without crutches at the latest follow-up.
Conclusions: The utilization of the fibular transposition technique is a simple, reliable, and successful procedure for extensor reconstruction after proximal tibial resection. (C) 2016 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.knee.2016.11.005

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Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

ランゲルハンス細胞組織球症(LCH)は、ランゲルハンス細胞様細胞(LCH細胞)のモノクローナルな腫瘍性増殖をきたす疾患である。骨病変の頻度が最も高く、軟部組織単独病変は稀である。今回我々は、胸椎の骨融解病変、胸膜病変、および骨病変に連続しない後頸部の軟部組織病変を伴う多臓器型LCHの5歳女児例を経験した。本例は当初、後頸部皮下膿瘍および化膿性脊椎炎の疑いで抗菌薬が投与され、解熱し病変部位の腫脹が軽減消失したことから、結果的に化学療法の同意が得られず経過観察の方針となった。約9ヵ月間で2回の再燃を観察し、いずれも抗菌薬投与のみで解熱し、局所症状も軽減消失した。最終的に多剤併用化学療法を導入したところ、速やかに寛解が得られ、4年間再発なく経過良好である。本例はLCHでは稀な軟部組織病変を伴うのみならず、抗菌薬による一時的効果が観察された点で、LCHの複雑な病態を考察する上で貴重と思われる。(著者抄録)

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Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J06030&link_issn=&doc_id=20170907100013&doc_link_id=%2Fex9syoga%2F2017%2F005402%2F013%2F0157-0160%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fex9syoga%2F2017%2F005402%2F013%2F0157-0160%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese   Publisher：東北整形災害外科学会  

小児骨肉腫治療を行った51例(男児24例、女児27例、初診時平均年齢12.1歳)を対象に、二次がん(SMN)発生状況とその特徴について検討した。平均観察期間13.2年の結果、SMNの発生率は7.8%(4例)であった。SMN発生例は全て女児であり、女児はリスク因子と考えられた。また、全例で疾患特異的な融合遺伝子や染色体転座を認め、化学療法の影響が示唆された。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: A solitary fibrous tumour (SFT) is an unusual neoplasm typically found in soft tissues. Although SFTs can arise in the bones, they very rarely arise in the vertebral arch. Here, we describe a case of a SFT that arose in the vertebral arch of the first lumbar (L1) spinal vertebrae and mimicked osteosarcoma.
Case presentation: A 49-year-old woman presented with a 2-month history of lower back pain and a lumbar region mass. Magnetic resonance imaging demonstrated a heterogeneously enhanced mass in the L1 vertebral arch. The patient received neoadjuvant chemotherapy, followed by a surgical procedure comprising an anterior spinal fusion and en bloc resection. Histologically, our initial diagnosis was osteosarcoma. The postoperative course was uneventful, and the patient received adjuvant chemotherapy. However, the tumour metastasised to the lung 5 years after the first surgery, and a second surgery was performed for lung tumour resection. The histology of the metastatic lung tumour appeared similar to that of the malignant SFT, and the specimen from the first surgery was re-examined. Immunohistochemically, the tumour was positive for STAT6. Reverse transcription-polymerase chain reaction revealed a NAB2-STAT6 fusion gene, thus confirming our final diagnosis of malignant SFT. The patient died of disease progression 8 years after the first surgery; however, there was no evidence of local recurrence.
Conclusions: Malignant SFT in the vertebral arch is extremely rare and very difficult to distinguish histologically an osteoid from lace-like collagen. STAT6 immunostaining is useful for distinguishing malignant SFTs from other neoplasms. Although it is difficult to completely resect a SFT arising from the spine, we demonstrated the feasibility of an en bloc resection of spinal tumours arising from posterior elements, without local recurrence.

DOI： 10.1186/s12957-017-1161-0

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

The prognosis of alveolar soft part sarcoma is poor, despite the slow growth of the tumor. A number of cases with spontaneous regression of this rare tumor have been reported. Although the mechanisms underlying spontaneous regression remain uncertain, local immune reaction may be a possible contributing factor. Immunohistochemical expression of human leukocyte antigen (HLA) class I, cluster of differentiation (CD) 3, CD4, CD8, CD20, CD45, CD56, CD68, CD138 and CD163 were assessed in a series of 10 alveolar soft part sarcomas, and the expression profiles were associated with patients' clinicopathological parameters. Expression of HLA class I was observed in almost all the tumor cells of all cases. CD8(+) cells were identified in all tumors with varying densities. Moderate infiltration of CD8(+) cells was detected in three patients; one of these patients survived with long-term tumor remission. Infiltration of CD10(+), CD20(+), CD56(+) or CD138(+) cells was not revealed in all tumors. Moderate-diffuse infiltration of CD163(+) cells was observed in all tumors. To the best of our knowledge, the present study represents the first report of intratumoral immune cells in alveolar soft part sarcoma. Frequent expression of HLA class I in tumor cells was observed. CD8(+) cells were identified at various densi-sarcoma. Moderate infiltration of CD8(+) cells in patients with a good prognosis may indicate the antitumor effects of immune cells in alveolar soft part sarcoma.

DOI： 10.3892/ol.2017.5696

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

Intravertebral cleft (IVC) is a common finding in osteoporotic compression fracture. However, since the vertebral collapse attributable to cancer metastasis is rarely associated with IVC, the phenomenon is generally considered as a sign of a benign lesion. In this study, we retrospectively reviewed the radiographs, computed tomography scans, and magnetic resonance images of 111 patients with spinal metastasis. Three cases (2.7 %) had IVC in the collapsed thoracic vertebral bodies (T7, T8, and T11) attributable to cancer metastasis. IVC alone is not necessarily an indicator of a benign vertebral collapse.

DOI： 10.1007/s00256-016-2505-5

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Language：English   Publisher：SPRINGER JAPAN KK  

DOI： 10.1007/s10147-016-1051-4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Myoepithelial carcinoma of the breast is an extremely rare tumor composed entirely of malignant spindle cells with myoepithelial differentiation. The majority of previously reported cases have mainly described the clinicopathological features of the disease, and few have presented cytogenetic data. We herein present the case of a 48-year-old woman who was admitted with a left sided breast lump in the inner upper quadrant that was initially diagnosed as a myoepithelioma with potentially malignant disorder. At 12 months after resection, she complained about a newly developed solid mass in the subareolar region of the ipsilateral breast that was diagnosed as an invasive ductal carcinoma. In addition, 16 months after the initial admission, a re-growing remnant lesion recurred in the inner upper quadrant and was ultimately diagnosed as a myoepithelial carcinoma. Lymph node metastasis of the myoepithelial carcinoma was also observed in her left axillary region 11 months after local recurrence. A cytogenetic analysis showed recurring specific chromosomal alterations both in the locally recurrent and in the lymph-node metastatic lesion: 48, XX, t(5;18)(q13;q23),del(6)(q?),+14. + marl. To our knowledge, this is the first published report of clonal chromosomal rearrangements in myoepithelial carcinoma of the breast that presented as metachronic double cancer with invasive ductal carcinoma in the ipsilateral breast.

DOI： 10.1016/j.cancergen.2016.10.005

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

1988年〜2014年の間に施行された腫瘍用下肢人工関節151例中、20年以上にわたり経過観察が可能であった12例を対象に治療成績について検討した。その結果、12例中、7例(58.3%)で平均1.4回の再置換があった。様々な合併症により再置換の必要な場合があったが、歩行機能をはじめとする患肢機能は良好で、患者の満足度も高かった。就業調査では軽作業への配置転換や定年退職があったものの、失業中の症例はなく、社会復帰は順調であった。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER JAPAN KK  

Malignant granular cell tumors (MGCTs) are extremely rare neoplasms with only a limited number of studies published to date. The aim of this study is to elucidate the clinicopathological characteristics and prognostic factors of MGCTs.
This is a multi-institutional retrospective study of MGCTs with a central pathological review. A total of 18 cases were retrieved. Specimens were blindly reviewed by two pathologists based on the diagnostic criteria by Fanburg-Smith et al. Kaplan-Meier survival probabilities were calculated, and risk factors for poor prognosis were evaluated.
Three and fifteen cases were diagnosed as atypical GCTs (AGCTs) and mGCTs according to the Fanburg-Smith et al. classification, respectively. Four (one atypical and three malignant) cases had metastasis at the first presentation, including lymph node metastasis. Three out of ten cases treated with wide resection developed local recurrence. Although prolonged static disease periods of a parts per thousand yen1 year were observed in four cases receiving chemotherapy, all cases with local recurrence or metastasis, including two atypical cases, eventually died of disease. The 5- and 10-year overall survival rates for localized MGCTs were 69.2 and 34.6 %, respectively. The presence of necrosis was revealed as a risk factor associated with adverse clinical outcomes.
MGCTs have high rates of recurrence and metastasis including lymph node metastasis. As histologically atypical cases also have metastatic potential, close attention should be paid to AGCTs. The combination of histological evaluation and tumor size may lead to more accurate diagnosis of this rare neoplasm.

DOI： 10.1007/s10147-016-0949-1

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Background
Bedridden patients are at risk of osteoporosis and fractures, although the long-term bone metabolic processes in these patients are poorly understood. Therefore, we aimed to determine how long-term bed confinement affects bone metabolism.
Methods
This study included 36 patients who had been bedridden from birth due to severe immobility. Bone mineral density and bone metabolism markers were compared to the bedridden period in all study patients. Changes in the bone metabolism markers during a follow-up of 12 years were studied in 17 patients aged &lt;30 years at baseline.
Results
The bone mineral density was reduced (0.58 +/- 0.19g/cm(3)), and the osteocalcin (13.9 +/- 12.4 ng/mL) and urine N-terminal telopeptide (NTX) levels (146.9 +/- 134.0 mM BCE/mM creatinine) were greater than the cutoff value for predicting fracture. Among the bone metabolism markers studied, osteocalcin and NTX were negatively associated with the bedridden period. During the follow-up, osteocalcin and parathyroid hormone were decreased, and the 25(OH) vitamin D was increased. NTX at baseline was negatively associated with bone mineral density after 12 years.
Conclusions
Unique bone metabolic abnormalities were found in patients who had been bedridden for long periods, and these metabolic abnormalities were altered by further bed confinement. Appropriate treatment based on the unique bone metabolic changes may be important in long-term bedridden patients.

DOI： 10.1371/journal.pone.0156991

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Language：Japanese   Publisher：東北整形災害外科学会  

骨芽細胞様細胞である骨肉腫細胞株由来Saos-2とNOS-1を使用し、これまで癌骨転移などで報告されているインターロイキン-6(IL-6)/IL-6受容体(gp130)/STAT経路の活性化によるκ-Bリガンド核内転写因子受容体活性化因子(RANKL)産生のメカニズムが、Saos-2とNOS-1においても同様に作用しているか検討した。Saos-2、NOS-1の両細胞株においてIL-6受容体(gp130)が発現していることは定量的RT-PCR法によって確認できた。細胞培養液へのIL-6添加によりRANKLの発現量はSaos-2とNOS-1の両細胞株において経時的に増加し、特に72時間後には非添加群に比べSaos-2においては約2倍、NOS-1においては約2.5倍高値を示し、IL-6によるRANKLの発現増強効果が認められた。リン酸化特異的な抗体を用いたウエスタンブロット法により、細胞内におけるIL-6受容体の下流シグナルの変化について検討した。IL-6受容体添加後にSaos-2とNOS-1の両細胞株においてリン酸化STAT3の発現が高くなっていることが確認された。しかし、リン酸化AktとERK1/2の発現に大きな変化はみられなかった。Saos-2、NOS-1において、細胞はIL-6受容体を発現し、培養液にIL-6を添加することによりRANKL産生が促進され、そのメカニズムとしてSTAT3の活性化に伴う細胞内シグナルの関与が示唆された。

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The receptor-activator of nuclear kappaB ligand (RANKL) signaling pathway plays an important role in the regulation of bone growth and mediates the formation and activation of osteoclasts. Osteoclasts are involved in significant bone resorption and destruction. Denosumab is a fully human monoclonal antibody against RANKL that specifically inhibits osteoclast differentiation and bone resorption. It has been approved for use for multiple myeloma and bone metastases, as well as for giant cell tumor of bone. However, there is no previous report quantitatively, comparing RANKL expression in histologically varied bone tumors. Therefore, we analyzed the mRNA level of various bone tumors and investigated the possibility of these tumors as a new therapeutic target for denosumab. We examined RANKL mRNA expression in 135 clinical specimens of primary and metastatic bone tumors using real-time PCR. The relative quantification of mRNA expression levels was performed via normalization with RPMI8226, a human multiple myeloma cell line that is recognized to express RANKL. Of 135 cases, 64 were also evaluated for RANKL expression by using immunohistochemistry. Among all of the tumors investigated, RANKL expression and the RANKL/osteoprotegerin ratio were highest in giant cell tumor of bone. High RANKL mRNA expression was observed in cases of aneurysmal bone cyst, fibrous dysplasia, osteosarcoma, chondrosarcoma, and enchondroma, as compared to cases of multiple myeloma and bone lesions from metastatic carcinoma. RANKL-positive stromal cells were detected in six cases: five cases of GCTB and one case of fibrous dysplasia. The current study findings indicate that some primary bone tumors present new therapeutic targets for denosumab, particularly those tumors expressing RANKL and those involving bone resorption by osteoclasts.

DOI： 10.1371/journal.pone.0154680

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The Akt/mTOR and MAPK pathways play important roles in modulating cellular function in response to extracellular signals, and they are known to be activated in certain kinds of sarcomas. Few investigations have examined these pathways in dedifferentiated liposarcoma (DDLS), in relation to clinicopathological features. Clinicopathological and immunohistochemical analyses were conducted using 99 DDLS specimens. An in vitro study was also conducted to examine the antitumor effects of an mTOR inhibitor and a MEK inhibitor on two DDLS cell lines. The clinicopathological analyses revealed that the AJCC staging was a significant prognostic factor for overall survival and that the tumor size, depth, and location were significant prognostic factors for event-free survival. Phosphorylated Akt (pAkt), pmTOR, pS6RP, p4E-BP1, pMEK, and pERK expressions were positive in 57.4, 52.4, 71.4, 57.1, 84.1, and 50.8 % of the dedifferentiated component of the 63 primary DDLSs. Positive staining for pmTOR was significantly more frequent in the dedifferentiated component than the well-differentiated component. A univariate prognostic analysis revealed that pmTOR expression was associated with poor prognosis in the tumors in the retroperitoneum/ventral body cavity. The mTOR and MEK inhibitors dose-dependently inhibited the cell proliferation of both DDLS cell lines and decreased the expression of downstream pS6RP and pERK, respectively. The combined use of the two inhibitors enhanced antiproliferative activity. In conclusion, the Akt/mTOR and MAPK pathways were activated in DDLS specimens, and the inhibition of these pathways decreased cell proliferation in DDLS cell lines. Our findings suggest that these pathways could be a therapeutic target for patients with DDLS.

DOI： 10.1007/s13277-015-4232-2

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A giant-cell tumor of the bone (GCTB) is a benign but locally aggressive bone tumor. Recently, the receptor activator of nuclear factor kappa B (RANK) ligand inhibitor, denosumab, has demonstrated activity against giant-cell tumors. The current study reports a case of a sacral GCTB with lung metastasis. A 19-year-old male patient presented with right buttock pain and right lower leg pain, and a sacral GCTB was diagnosed based on the histological analysis of a biopsy specimen. The patient was successfully treated with neoadjuvant denosumab therapy, which allowed curettage. In addition, the pulmonary nodule reduced in size following denosumab administration, and surgical resection was performed. Since the operation, the patient has been managed with the continued use of denosumab with no sign of recurrence. Microscopic findings from the surgical specimen following denosumab treatment revealed that the giant cells had disappeared and woven bone had formed. The specimen from the pulmonary nodule exhibited similar findings to the surgical specimen. It was reported that denosumab treatment was able to reduce the number of giant cells and RANK-positive stromal cells, and cause the formation of new bone in the primary lesion. The present study reports the first case to demonstrate the efficiency of denosumab in treating pulmonary metastasis of GCTB.

DOI： 10.3892/ol.2015.3858

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Musculoskeletal sarcomas (MSS) are a heterogeneous group of malignancies with relatively high mortality rates. The prognosis for patients with MSS is poor, with few drugs inducing measurable activity. Alkylating agents, namely ifosfamide and dacarbazine, which act nonspecifically on proliferating cells, are the typical therapy prescribed for advanced MSS. A novel alkylating agent, temozolomide (TMZ), has several advantages over existing alkylating agents. TMZ induces the formation of O-6-methylguanine in DNA, thereby inducing mismatches during DNA replication and the subsequent activation of apoptotic pathways. However, due to conflicting data in the literature, the mechanism of TMZ action has remained elusive. Therefore, the present study aimed to evaluate apoptosis in MSS cells treated with TMZ, and to evaluate the correlation between TMZ action and survival pathways, including the phosphoinositide 3-kinase (PI3K)/Akt and extracellular signal-regulated kinase (ERK)1/2 mitogen activated protein kinase (MAPK) pathways. Cell proliferation was evaluated by performing an XTT (sodium 3'-[1-(phenylaminocarbony1)-3,4-tetrazolium] -bis (4-methoxy-6-nitro) benzene sulfonic acid hydrate) assay. Apoptotic morphological changes, for example chromatin condensation, were evaluated by fluorescence confocal microscopy. The expression of the apoptosis-associated proteins caspase-3, poly adenosine diphosphate ribose polymerase (PARP), Akt and ERK1/2, was determined by western blotting. The results of the present study indicated that, in certain MSS cells, the IC50 value was lower than that in TMZ-sensitive U-87 MG cells. Furthermore, TMZ treatment was associated with apoptotic morphological changes and the expression levels of pro-apoptotic cleaved caspase-3 and PARP were also increased in TMZ-treated MSS cells. In addition, the result indicated that PI3K/Akt and ERK1/2 MAPK were constitutively phosphorylated in MSS cells, and phosphorylation of PI3K/Akt was suppressed in certain cells, and maintained in other cells, by TMZ. These observations emphasized the plasticity of MSS cells, and suggested that this plasticity may contribute to the variance in cell sensitivity to TMZ and TMZ-resistance in MSS.

DOI： 10.3892/ol.2015.3506

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Language：Japanese   Publisher：(株)医学書院  

1999年から2012年までにβ-リン酸3カルシウム(β-TCP)を使用した整形外科手術714例に対し,合併症を含め後ろ向きに調査した.骨腫瘍(263例)に対して使用した症例では術後早期の骨折が3例にみられたが,遅発性の骨折や変形,術後深部感染は生じず良好な成績が得られていた.β-TCP移植を行った脊椎手術(350例)では3例に術後感染が生じ,5例に再固定手術が施行された.関節疾患,骨折に対して移植を行った101例では深部感染は生じなかった.画像判断の可能な例ではいずれも移植β-TCPと周囲骨とは連続性がみられ,症例によっては継時的にほぼすべてが吸収され新生骨に置き換わっていた.β-TCPは吸収されつつ自家骨形成が生じる優れた骨補填材料であり,整形外科手術に用いた場合,感染率の上昇などの危険性は少ないと考えられた.(著者抄録)

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Other Link： http://search.jamas.or.jp/link/ui/2015404646

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

The present study reports the first case of malignant transformation to osteosarcoma arising from osteochondroma following childhood total-body irradiation (TBI). The association between TBI and later development of osteochondroma is well-known; however, malignant degeneration arising from radiation-induced osteochondroma is rare. The current study describes the case of a 17-year-old boy with osteosarcoma arising from osteochondroma of the left distal humerus, which developed following TBI. TBI was administered as part of a conditioning regimen received prior to autologous peripheral hematopoietic stem cell transplantation (HSCT) at the age of 6 years, following an initial diagnosis of neuroblastoma at the age of 5 years. The patient subsequently underwent preoperative chemotherapy followed by wide local excision and reconstruction with an extracorporeally irradiated autograft. Postoperative chemotherapy was administered, and the patient demonstrated no clinical or radiographic evidence of recurrence after 40 months of follow-up. To the best of our knowledge, this is only the second reported case of malignant degeneration of osteochondroma following childhood TBI, and the first reported case of transformation to osteosarcoma. The current case highlights the importance of close observation for secondary malignancies in this patient population.

DOI： 10.3892/ol.2015.3257

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Language：Japanese   Publisher：新潟整形外科研究会  

16歳男性。誘因なく労作時左股関節痛が出現した。今回、徐々に増悪し、安静時痛や歩行困難が生じたため近医を受診、単純X線にて骨腫瘍を疑われ、著者らの施設へ紹介となった。臨床症状および画像所見より類骨骨腫と診断され、保存療法を行うも改善が得られず、約半年経過後、CTガイド下にてnidus摘出術と焼灼術を施行した。その結果、術後22日目に患肢部分荷重を開始し、術後83日目の最終観察時には患肢全荷重で日常生活に支障なく、歩行時痛も再発もみられなかった。

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Expression of the tumor suppressor gene TUSC2 is reduced or absent in most lung cancers and is associated with worse overall survival. In this study, we restored TUSC2 gene expression in several wild type EGFR non-small cell lung cancer (NSCLC) cell lines resistant to the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib and analyzed their sensitivity to erlotinib in vitro and in vivo. A significant inhibition of cell growth and colony formation was observed with TUSC2 transient and stable expression. TUSC2-erlotinib cooperativity in vitro could be reproduced in vivo in subcutaneous tumor growth and lung metastasis formation lung cancer xenograft mouse models. Combination treatment with intravenous TUSC2 nanovesicles and erlotinib synergistically inhibited tumor growth and metastasis, and increased apoptotic activity. High-throughput qRT-PCR array analysis enabling multi-parallel expression profile analysis of eighty six receptor and non-receptor tyrosine kinase genes revealed a significant decrease of FGFR2 expression level, suggesting a potential role of FGFR2 in TUSC2-enhanced sensitivity to erlotinib. Western blots showed inhibition of FGFR2 by TUSC2 transient transfection, and marked increase of PARP, an apoptotic marker, cleavage level after TUSC2-erlotinb combined treatment. Suppression of FGFR2 by AZD4547 or gene knockdown enhanced sensitivity to erlotinib in some but not all tested cell lines. TUSC2 inhibits mTOR activation and the latter cell lines were responsive to the mTOR inhibitor rapamycin combined with erlotinib. These results suggest that TUSC2 restoration in wild type EGFR NSCLC may overcome erlotinib resistance, and identify FGFR2 and mTOR as critical regulators of this activity in varying cellular contexts. The therapeutic activity of TUSC2 could extend the use of erlotinib to lung cancer patients with wildtype EGFR.

DOI： 10.1371/journal.pone.0123967

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

Soft tissue tumors arising in deep veins of the extremities are uncommon, although a few cases of synovial sarcoma or leiomyosarcoma arising in the femoral vein have been documented. However, to the best of our knowledge, an extraskeletal myxoid chondrosarcoma (EMC) arising in the femoral vein has not been reported in the English literature. We report a case of EMC arising in the femoral vein of a 70-year-old man who presented with right leg edema and was diagnosed with a deep venous thrombosis (DVT) by computed tomography (CT). Magnetic resonance imaging (MRI) revealed a mass in the right proximal thigh that was diagnosed as myxomatous sarcoma by aspiration cytology, and anticoagulant therapy was initiated. The mass was surgically resected en bloc, including the femoral vein and surrounding soft tissue, and the femoral artery was preserved. The femoral vein was not reconstructed. The histologic diagnosis was an extraskeletal myxoid chondrosarcoma. The patient received postoperative local radiation treatment, with a total dose of 60 Gy, and is currently doing well with no evidence of local recurrence or metastasis at 8 months after surgery. In summary, this case report shows that EMC can arise in the femoral vein, and that reconstruction of the femoral vein is not always necessary during surgery for soft tissue tumors.

DOI： 10.1007/s00256-014-1897-3

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Language：English   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

DOI： 10.1212/WNL.0000000000000714

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

Secondary osteosarcoma from fibrous dysplasia (FD) is very rare. The etiology of FD is linked to activating missense mutations of the guanine nucleotide-binding protein alpha-subunit (GNAS) gene, which encodes the stimulatory alpha subunit of the G protein (G(s)alpha) and is located at chromosome 20q13. These mutations are central to the pathogenesis of FD; however, it is not known whether G(s)alpha mutations are retained following malignant transformation in FD. In addition, to the best of our knowledge, no studies have been performed on chromosomal analysis of secondary osteosarcoma from FD. The present study presents a case of secondary osteosarcoma arising from polyostotic FD in a 72-year-old male. Chromosomal analysis showed 44, X, -Y, add(4)(p11), add(5)(p15), der(11)add(11)(p15) t(1;11)(q21;q23), add(12)(q11), -13, der(22)t(12;22)(q11;p12). Reverse transcription-polymerase chain reaction (RT-PCR) analysis demonstrated the presence of a G(s)alpha mutation in both the primary tumor cells and secondary osteosarcoma cells. There was no alteration in this mutation in the region of malignant transformation, which suggests that this mutation may be a useful clinical marker for distinguishing de novo osteosarcoma (primary osteosarcoma) from secondary osteosarcoma arising from FD.

DOI： 10.3892/ol.2014.2082

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Language：Japanese   Publisher：新潟整形外科研究会  

2006年〜2012年に骨腫瘍の疑いで受診し、最終診断が骨髄炎であった6例(男児3例、女児3例、9〜17歳)を対象に、骨腫瘍と骨髄炎の鑑別について検討した。骨髄炎は高熱や局所の腫脹疼痛、血液検査でのWBC、CRP上昇といった強い炎症反応を伴うものから、これらがほとんどみられないものまで臨床症状は多彩である。炎症反応を伴わないあるいは軽微な場合に骨腫瘍との鑑別にしばしば苦労する。鑑別点は好発部位は骨髄炎は長管骨骨幹端、骨腫瘍は症例により多彩、MRIで骨髄炎は周囲のT2高信号、変化が強い、骨腫瘍は骨内外に腫瘤性病変を形成しやすい等である。いずれも迅速な診断が必須で、開放生検、細菌培養を速やかに施行することが重要である。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Diagnosing adipocytic tumors can be challenging because it is often difficult to morphologically distinguish between benign, intermediate and malignant adipocytic tumors, and other sarcomas that are histologically similar. Recently, a number of tumor-specific chromosome translocations and associated fusion genes have been identified in adipocytic tumors and atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL), which have a supernumerary ring and/or giant chromosome marker with amplified sequences of the MDM2 and CDK4 genes. The purpose of this study was to investigate whether quantitative real-time polymerase chain reaction (PCR) could be used to amplify MDM2 and CDK4 from total RNA samples obtained from core-needle biopsy sections for the diagnosis of ALT/WDL.
Methods: A series of lipoma (n = 124) and ALT/WDL (n = 44) cases were analyzed for cytogenetic analysis and lipoma fusion genes, as well as for MDM2 and CDK4 expression by real-time PCR. Moreover, the expression of MDM2 and CDK4 in whole tissue sections was compared with that in core-needle biopsy sections of the same tumor in order to determine whether real-time PCR could be used to distinguish ALT/WDL from lipoma at the preoperative stage.
Results: In whole tissue sections, the medians for MDM2 and CDK4 expression in ALT/WDL were higher than those in the lipomas (P &lt; 0.05). Moreover, karyotype subdivisions with rings and/or giant chromosomes had higher MDM2 and CDK4 expression levels compared to karyotypes with 12q13-15 rearrangements, other abnormal karyotypes, and normal karyotypes (P &lt; 0.05). On the other hand, MDM2 and CDK4 expression levels in core-needle biopsy sections were similar to those in whole-tissue sections (MDM2: P = 0.6, CDK4: P = 0.8, Wilcoxon signed-rank test).
Conclusion: Quantitative real-time PCR of total RNA can be used to evaluate the MDM2 and CDK4 expression levels in core-needle biopsies and may be useful for distinguishing ALT/WDL from adipocytic tumors. Thus, total RNA from core-needle biopsy sections may have potential as a routine diagnostic tool for other tumors where gene overexpression is a feature of the tumor.

DOI： 10.1186/1471-2407-14-468

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

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Language：Japanese   Publisher：日本レックリングハウゼン病学会  

神経線維腫症1型(NF1)に発症した悪性末梢神経鞘腫瘍MPNSTは予後不良の疾患でしばしば全身性に転移を生じ、抗がん剤抵抗性であるといわれている。我々の施設において治療を行ったNF1に合併したMPNSTの23症例に対して診療録を利用した後ろ向き調査を行った。症例は男13例、女10例、治療開始年齢は15から81歳(平均38歳)、腫瘍径は2-25cm(平均13cm)、症状発生から治療開始までは1-144ヵ月(平均30ヵ月)であった。初回外科治療として広範切除がなされた10例には局所再発がなく、辺縁切除となった(前医を含む)9例のうち8例に局所再発がみられた。抗がん剤治療は13例に対して施行され、効果判定可能であった11例では最高効果時の評価で、部分寛解3例、不変1例、進行7例であった。不変以上の効果が得られたものはいずれも大量イホマイドを主体とするレジメンであったが、いずれも再増悪が生じた。最終転帰は腫瘍死14、持続的無病生存6、有病生存2、他因死1でカプランマイヤー法による累積5年生存率は35%であった。大量イホマイドを主体とする化学療法は至適投与量を維持できれば腫瘍の縮小効果が得られる場合があり、多発肺転移の一時的消失や大幅な縮小がみられる症例も存在する。しかし経過とともに抗がん剤不応性になり、転移巣の長期間コントロールを得ることは極めて困難である。(著者抄録)

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Other Link： http://search.jamas.or.jp/link/ui/2014244734

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

This study investigated the pathway underlying the antitumor activity of telomelysin, a telomerase-dependent, replication-selective oncolytic adenovirus, in soft tissue sarcoma cells. Treatment with telomelysin alone resulted in simultaneous induction of apoptosis and autophagy, whereas cotreatment with telomelysin and 3-methyladenine significantly reduced cell viability and increased apoptosis and the cellular ATP level compared to treatment with telomelysin alone, indicating that telomelysin-mediated autophagy is a death-protective but not death-promoting process. Cotreatment with Z-Val-Ala-Asp-CH2F significantly increased cellular ATP depletion compared to telomelysin-alone treatment while inhibiting telomelysin-induced apoptosis and having no significant effect on cell viability, indicating that it promotes transition from apoptotic to necrotic cell death. © 2013 Japanese Cancer Association.

DOI： 10.1111/cas.12208

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Language：Japanese   Publisher：東北整形災害外科学会  

尖足拘縮を生じた腓腹筋内血管腫1例と膝屈曲制限を生じた大腿四頭筋内血管腫1例について報告した。症例1は11歳男で、左腓腹部筋外側頭の圧痛と硬結を認め、膝伸展位での左足関節可動域は-45°であった。MRIでは左腓腹筋外側頭にT1強調画像で筋肉と等信号と高信号が混在し、T2強調画像では高信号と低信号が混在する腫瘍があり、管腔構造の造影効果を認めた。症例2は37歳男で、右大腿前面の硬結と圧痛、右膝関節可動域制限があり、MRIでは中間広筋内にT1強調画像で等信号、T2強調画像で高信号、内部に管腔構造の造影効果を伴う腫瘍を認めた。いずれも周囲筋肉と血管腫の切除により関節可動域は改善し、病理組織所見では周囲筋組織の線維化を認め、筋肉内血管腫と診断された。

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Language：Japanese   Publisher：新潟整形外科研究会  

37歳男性。左鼠径部から臀部側腹部にかけて18×9×2cm大の可動性不良な軟腫瘤を皮下に認め、軟部肉腫と診断され、広範切除術が施行された。その際、鼠径部は大腿動静脈神経の露出および24×17cmの皮膚軟部組織欠損を生じたため、有茎腹直筋皮弁を挙上移行し、左下腹部から左鼠径部の欠損を被覆した。また、左側腹部の腹膜露出部に対しては左大腿直筋弁、左大腿筋膜、左大腿筋膜張筋を左外側大腿回旋動静脈を茎とし、一塊として挙上後、腹膜側が筋膜側に接するように翻転し、欠損部を被覆補強した。更に大腿直筋は筋膜とともに腹膜露出部に縫合固定後、筋・筋膜弁上に左大腿からの分層植皮を施行した。その結果、病理診断では粘液線維肉腫もしくは粘液型悪性線維性組織球腫と診断された。術後は再発はなかったが、腹直筋採取部と植皮部の肥厚性瘢痕および下腹部のbulgingが認められた。尚、目下は膝の伸展・歩行に関しては日常生活に不自由を感じていないが、階段の昇りにやや困難を感じている。

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

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Other Link： http://search.jamas.or.jp/link/ui/2012372566

Language：Japanese   Publisher：(一社)日本皮膚悪性腫瘍学会  

20歳、男性。2008年5月頃より頭頂部に腫瘤が出現し、近医で切開・吸引されたが、短期間で腫瘤が再増大した。同年8月20日に当科を初診した。表面に凹凸のある約15cm×10cmの腫瘤が頭頂部にあり、血痂や潰瘍を伴い、易出血性であった。病理組織学的に、真皮、皮下組織に小型円形で均一なCD99陽性の腫瘍細胞がシート状に増殖し、RT-PCRでEWS-FLI1、EWS-ERGは陰性であった。免疫学的検索、FISHの結果よりEwing肉腫と診断した。原発巣と所属リンパ節に対する放射線照射と化学療法を行ったが、無効であった。腫瘍の重さ、悪臭と外観が患者のQOLを損なっていたため、Mohs軟膏を用いた腫瘍の硬化療法と、腫瘍減量術を施行した。その結果、手術時の出血量を少量に抑え、腫瘍を約半分の大きさに減量することができ、患者のQOLの改善をみた。Mohs軟膏は根治不能な皮膚悪性腫瘍の姑息治療に有用である。(著者抄録)

DOI： 10.5227/skincancer.26.311

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

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Other Link： http://search.jamas.or.jp/link/ui/2012161645

Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

Polyostotic fibrous dysplasia (PFD) is a high-turnover bone disease that frequently entails chronic bone pain, pathological fractures and severe deformities. Recently, bisphosphonates have shown effective antiresorptive properties in the treatment of children or adults with PFD. We report on a 79-year-old female with PR), who had severe lower limb deformity and chronic bone pain in multiple sites of her extremities for more than 55 years. The patient experienced significant decrease in bone pain and bone turnover markers following long-term (8.5 years) treatment with a low-dose oral alendronate treatment (5 mg/day). To the best of our knowledge, this is the first report of a long-term follow-up of a postmenopausal elderly patient with long-standing symptomatic PFD following continuous low-dose oral alendronate therapy. This case report indicates that long-term daily administration of low-dose alendronate alone is a potential treatment option for elderly patients with PFD, particularly those with long-standing bone pain.

DOI： 10.3892/ol.2011.369

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

We established a dedifferentiated liposarcoma cell line (NDDLS-1) that produces interleukin-6 (IL-6) and granulocyte-colony stimulating factor (G-CSF). The parental tumor showed high leukemoid reactions. The NDDLS-1 cell line was established from a pleural effusion associated with a lung metastasis. Pleomorphic tumor cells arranged in a haphazard growth pattern were seen in xenograft tumors. Numerous inflammatory cells including neutrophils or eosinophils were present throughout the tumor cells. This finding resembled the dedifferentiated area of the parental tumor. The mice bearing NDDLS-1 showed marked leukocytosis. In addition, the NDDLS-1 cells expressed IL-6 and G-CSF at both the mRNA and protein levels, while the NDDLS-1 cells produced near normal levels of tumor necrosis factor alpha (TNF-alpha). In the cytogenetic analysis, both the parental tumor and the NDDLS-1 cells showed a ring or giant marker chromosomes. The NDDLS-1 cell line demonstrated the amplification and expression of both MDM2 and CDK4 by fluorescence in situ hybridization and immunohistochemical analysis. The NDDLS-1 cell line is consistent with the parental dedifferentiated liposarcoma, and it should therefore be useful for further investigations of human dedifferentiated liposarcomas.

DOI： 10.1111/j.1440-1827.2011.02683.x

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

A telomerase-specific oncolytic adenovirus, Telomelysin, can selectively kill cancer cells, and be attenuated in normal cells. We herein describe the oncolytic effect of Telomelysin on human osteosarcoma both in vitro and in vivo.
The anti-tumor effects of Telomelysin were evaluated on human osteosarcoma cell lines in vitro and in a mouse xenograft model of human osteosarcoma in vivo. The replication efficiencies of Telomelysin in human osteosarcoma cell lines and normal cell lines and in osteosarcoma xenografts were determined by the expression levels of E1 mRNA and E1A protein using real-time quantitative PCR, Western blot analysis and immunohistochemistry. The in vitro telomerase-specific replication and the viral infection rate were also confirmed by TelomeScan (Telomelysin-GFP), using fluorescent microscopy and flow cytometry, respectively. The cell viabilities were examined by XTT assay, and the tumor volumes were measured every 2 days. The induction of apoptosis was assessed by Western blot analysis, as well as by TUNEL assay.
TelomeScan and Telomelysin were efficiently replicated in human osteosarcoma cell lines and led to a dose- and time-dependent expression of GFP, E1 mRNA and E1A protein. Telomelysin infection induced marked cytolysis and apoptosis in osteosarcoma cell lines in vitro. Neither cytotoxicity nor apoptosis were induced in normal human cell lines. In the human osteosarcoma cell xenograft model, intratumoral injection of Telomelysin resulted in increased viral replication, significant tumor growth suppression and distinct apoptotic cell death.
This study indicated that virotherapy with Telomelysin may provide a promising strategy for the treatment of human osteosarcoma.

DOI： 10.1007/s00432-010-0969-6

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Language：Japanese   Publisher：東日本整形災害外科学会  

鎖骨周囲に発生した骨軟部腫瘍に対し鎖骨切除術を行った6例について、肩関節自動可動域が正常になるまでの期間とEnnekingの上肢機能評価法による成績を評価した。6例の内5例で8週間以内に関節自動可動域は正常範囲となり、Ennekingの上肢機能評価法でも100%となった。また、6例とも患者満足度は高く、鎖骨切除術の術後成績は良好であった。(著者抄録)

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Language：Japanese   Publisher：東北整形災害外科学会  

膝関節荷重部に発生した骨巨細胞腫26例(男13例・女13例・平均38歳)の治療成績を検討した。初回手術として腫瘍切除または掻爬後に再建術を行い、再発などに対する追加手術を含め最終手術は人工骨充填術13例、セメント充填術8例、固定術3例、腫瘍型人工関節置換術2例であった。観察期間2〜280ヵ月で、再建術後の新たなX線学的関節症性変化の出現は人工骨群1例、セメント群3例に認めた。International Society of Limb Salvage(ISOLS)患肢機能評価で平均点が他の群より低かったのは、painではセメント群4点、functionでは人工関節群3点、emotional acceptanceでは関節固定群1.3点、supportでは人工関節群4点、walkingでは人工関節群3.5点、gaitでは人工関節群3点であった。ISOLS患肢機能評価の総合平均は89%で、人工骨群97%、セメント群85%、関節固定群71%、人工関節群73%であった。人工骨群では、12例中10例が総合100%と良好であった。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

Podoplanin is a 38 kDa mucin-type transmembrane glycoprotein that was first identified in rat glomerular epithelial cells (podocytes). It is expressed in normal lymphatic endothelium, but is absent from vascular endothelial cells. D2-40 is a commercially available mouse monoclonal antibody which binds to an epitope on human podoplanin. D2-40 immunoreactivity is therefore highly sensitive and specific for lymphatic endothelium. Recent investigations have shown widespread applications of immunohistochemical staining with D2-40 in evaluating podoplanin expression as an immunohistochemical marker for diagnosis and prognosis in various tumors. To determine whether the podoplanin (D2-40) antibody may be useful for the diagnosis of soft tissue tumors, 125 cases, including 4 kinds of benign tumors, 15 kinds of malignant tumors and 3 kinds of tumor-like lesions were immunostained using the D2-40 antibody. Total RNA was extracted from frozen tumor tissue obtained from 41 corresponding soft tissue tumor patients and 12 kinds of soft tissue tumor cell lines. Quantitative real-time PCR reactions were performed. Immunohistochemical and quantitative real-time RT-PCR analyses demonstrated the expression of the podoplanin protein and mRNA in the majority of benign and malignant soft tissue tumors and tumor-like lesions examined, with the exception of alveolar soft part sarcoma, embryonal and alveolar rhabdomyosarcoma, extraskeletal Ewing&apos;s sarcoma/peripheral primitive neuro-ectodermal tumor and lipoma, which were completely negative for podoplanin. Since it is widely and highly expressed in nearly all kinds of soft tissue tumors, especially in spindle cell sarcoma, myxoid type soft tissue tumors and soft tissue tumors of the nervous system, podoplanin is considered to have little value in the differential diagnosis of soft tissue tumors.

DOI： 10.3892/or.2011.1141

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Ewing sarcoma/primitive neuroectodermal tumors (ES/PNETs) may arise in bone or soft tissue; however, these tumors rarely originate in the stomach. To the best of our knowledge, only four cases have previously been reported in the English-language literature. A 41-year-old Japanese woman was admitted with abdominal pain and underwent gastrectomy to remove the primary tumor. Immunohistochemistry, chromosomal karyotype and molecular analysis using reverse transcription-polymerase chain reaction were performed in the tumor specimens obtained. Tumor cells showed positive immunoreactivity for CD99, vimentin, CD117 (c-kit), S100, chromogranin A and synaptophysin. The tumor was a gastric ES/PNET with the EWS-FLII fusion gene translocation t(11;22)(q24;q12). Multiple repeat metastasectomies, as well as multi-agent chemotherapy and radiotherapy were performed for recurrent disease. Despite treatment, the patient succumbed due to progressive disease 110 months after the initial surgery for gastric ES/PNET. A review of the reported cases suggests that patients with gastric ES/PNETs have an unfavorable prognosis following resection due to the high propensity of these tumors to metastasize. Thus, multimodal treatment approaches including surgery, as well as multi-agent chemotherapy and radiotherapy may provide a survival benefit for patients with gastric ES/PNETs.

DOI： 10.3892/ol.2011.246

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

Background: FUS1 is a tumor suppressor gene located on human chromosome 3p21.3. Frequent loss of FUS1 protein expression is associated with lung cancer development. This study examined FUS1 expression and its possible tumor-suppressive role in bone and soft tissue sarcomas. Materials and Methods: The expressions of FUS1 mRNA and FUS1 protein were assessed in sarcoma cell lines, sarcoma tissues, benign bone and soft-tissue tumor (BST) tissues, and healthy tissues. Exogenous FUS1 gene transfection was performed on sarcoma cell lines. Results: FUS1 mRNA expression was detected in all sarcoma cell lines, all benign BSTs and healthy tissues, and almost all sarcoma tissues. In contrast, FUS1 protein expression was frequently lost in sarcoma cells and sarcoma tissues. The exogenous PUS1 gene delivery induced strong FUS1 protein expression, inhibition of cell viability and apoptosis in sarcoma cells. Conclusion: PUS1 may act as a tumor suppressor in bone and soft-tissue sarcomas.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER TOKYO  

DOI： 10.1007/s00776-010-0001-7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY-ELSEVIER  

DOI： 10.1016/j.jse.2010.05.017

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

表在性の軟部腫瘍や骨外性病変が触知できる骨腫瘍では触診しながら腫瘍または骨外病変を直接穿刺し、通常の骨腫瘍はX線透視下に穿刺を行った。深部の骨・軟部腫瘍に対してはCTガイド下に穿刺を行った。骨腫瘍および軟部腫瘍に対して行われた針生検983例のうち、最終的に切除材料または開放生検で確認ができた穿刺吸引細胞診(FNAC)359例(骨腫瘍90例、軟部腫瘍269例)、針組織生検(CNB)127例(骨腫瘍40例、軟部腫瘍87例)を対象とした。FNACでは、誤診はすべて偽陰性で3例に認めた。感度、特異度、偽陽性率、偽陰性率はそれぞれび94.3%、100%、0%、5%で、正診率は96.7%であった。CNBでは、臨床所見より判定が正しいものと判断された。誤診例はなかった。感度、特異度、偽陽性率、偽陰性率はそれぞれ100%、100%、0%、0%であり、正診率は100%であった。

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Language：Japanese   Publisher：新潟整形外科研究会  

症例1は30歳女性で、左膝痛が出現し徐々に増悪していたが原因がはっきりしなかった。症状が改善しないため5年後受診し、MRIで血管腫が疑われ受診した。左大腿遠位前面に疼痛・圧痛を認めたが明らかな腫瘤は触知せず、皮膚所見、左膝関節可動域は正常であった。単純X線で特記すべき所見はなく、MRIで左内側広筋内にT1、T2共に筋肉と比べ高信号と低信号が混在する造影効果のある腫瘤を認めた。血管腫を疑い辺縁切除術を施行した。病理診断は筋肉内血管腫で、術後、症状は消失し、3年経過時点で症状の再燃を認めていない。症例2は28歳男性で、左大腿痛が出現し、受診したが原因が分からず、症状は消失と出現を繰り返した。4年後、症状が強くなり、MRIで血管腫を疑われ受診した。左大腿遠位前面に圧痛を認めたが明らかな腫瘤は触知せず、皮膚所見、左膝関節可動域は正常であった。単純X線で特記すべき所見はなく、MRIで左内側広筋内にT1で筋肉と比べやや高信号、T2で筋肉と比べ高信号を呈する造影効果のある内部不均一な腫瘤を認めた。血管腫を疑い辺縁切除術を施行した。病理診断は静脈型血管腫で、術後、症状は消失した。

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

We report here, our experience of seven patients with epithelioid sarcomas and their serum CA 125 levels, as well as the results of an in vitro and in vivo study of CA 125 expression in epithelioid sarcoma cells and xenografts using three epithelioid sarcoma cell lines.
In the clinical study, the serum CA 125 levels of seven epithelioid sarcoma patients were examined at multiple time points. Expression of the MUC16 gene that encodes the CA 125 sequence was examined using RT-PCR methods in three epithelioid sarcoma cell lines, FU-EPS-1, SFT-8606 and NEPS, and the CA 125 protein in each cell lysate was examined by Western blot using anti-CA 125 clone OC125 antibody. The concentration of CA 125 in the conditioned medium of each cell line was also measured.
In five of the seven epithelioid sarcoma patients, CA 125 levels reflected regression and progression of their disease. The CA 125 concentrations in the conditioned medium of FU-EPS-1, SFT-8606 and NEPS cells were 259, 252, and 6 U/ml, respectively. Strong expression of MUC16 mRNA was shown in FU-EPS-1 and SFT-8606 cells: correspondingly, a thick band was observed by Western blot analysis in only FU-EPS-1 and SFT-8606 cells.
We concluded that epithelioid sarcoma cells produce and secrete CA 125 into the blood serum and that the elevation of serum CA 125 correlates with disease progression. Therefore, measuring the serum CA 125 level should provide an useful index for diagnosing and monitoring the course of epithelioid sarcoma.

DOI： 10.1007/s00432-009-0678-1

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL PUBLISHING, INC  

Podoplanin is known as a lymphatic marker because its expression is detected in lymphatic but not vascular endothelium. Podoplanin is also expressed in several normal tissues including osteocytes or osteoblasts. A systematic examination of the podoplanin expression was conducted in normal skeletal tissues and some bone tumor cell lines, and the diagnostic value determined in primary bone tumors. Podoplanin mRNA was expressed at a high level in bone marrow tissue and cartilage, and was upregulated with differentiation to osteoblasts in bone marrow cells. Strong podoplanin expression was seen in osteocytes, chondrocytes, and osteoblasts on immunohistochemistry. Podoplanin mRNA was expressed at a high level in several osteosarcoma and chondrosarcoma cell lines, whereas podoplanin was expressed at a low level in a Ewing&apos;s/primitive neuroectodermal tumor cell line. In the clinical samples, osteosarcomas (22/26) expressed podoplanin at various levels. In small cell osteosarcomas (2/2), podoplanin was expressed strongly, although the tissue samples included few diagnostic osteoids. Chondrosarcomas (10/10) expressed podoplanin strongly, and chondroblastomas (5/5) expressed podoplanin moderately, while podoplanin was absent or expressed at low levels in Ewing&apos;s sarcomas (0/5), chordomas (0/6) and giant cell tumors of bone (1/7). Therefore, podoplanin may be a sensitive immunohistochemical marker of osteogenic and chondrogenic bone tumors.

DOI： 10.1111/j.1440-1827.2009.02510.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPANDIDOS PUBL LTD  

The elbow is an uncommon site for malignant bone tumors Surgical options for the reconstruction of the elbow Joint are limited and technically challenging In this study, we describe a patient with osteosarcoma of the proximal ulna treated by wide resection and reconstruction with a combined use of free vascularised fibula graft and extracorporeally irradiated osteochondral graft Ten years after the surgery, the patient is alive, without disease and is able to play golf with no lateral instability or pain of the elbow joint A vascularised fibula, combined with extracorporeally irradiated osteochondral graft with ligamentous repair is one of the options for the treatment of malignant bone tumor of the proximal ulna

DOI： 10.3892/ol_00000024

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Language：Japanese   Publisher：東日本整形災害外科学会  

ゲムシタビンを中心とした化学療法を行った悪性顆粒細胞腫2例を経験したので報告する。症例1:62歳男性。右鼠径部に腫瘤出現。切除後照射施行するも4年後遠隔転移を認め、ゲムシタビン、パクリタキセルの併用療法を開始した。3ヵ月間はSDであった。症例2:49歳女性。頸髄腫瘍にて発症し切除術施行するも、1年後に再発、転移した。再度切除術を施行し、術後照射後にゲムシタビンを中心とした化学療法を開始した。12ヵ月間SDである。(著者抄録)

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Language：Japanese   Publisher：整形外科バイオマテリアル研究会  

下肢骨端の良性腫瘍に対する掻爬とβ-リン酸三カルシウム(β-TCP)移植の効果を後ろ向きに調べた。患者10名(男7名、女3名、手術時平均29歳)を対象とした。組織型は骨巨細胞腫が7名、軟骨芽細胞腫が3名であった。まず病巣に大きな開窓を施し、病巣を掻爬後、アルゴンビームレーザーと電気メスで掻爬壁を焼灼した。その後骨髄液を添加したβ-TCPを移植した。大腿骨頭例には血管付腸骨移植を、骨皮質の欠損した膝関節症例には遊離腸骨移植を実施した。手術後に再発を認めず、いずれも術後平均3ヵ月目には移植β-TCPと周囲正常骨の境界が不明瞭となり、移植β-TCPは自家骨へと置換されていた。関節可動域は健側と同程度に回復し、両側変形性膝関節症の既往を有する1名以外は疼痛もなく日常生活を送っている。以上より、下肢関節周辺に発生した骨腫瘍に対するβ-TCP移植は長期に安定した成績を期待できる治療法である。

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Language：Japanese   Publisher：新潟整形外科研究会  

歩行中に右股関節痛が出現した44歳女性症例について検討した。26歳時にIgM型骨髄腫、41歳時にマクログロブリン血症とそれに伴うアミロイドーシスの既往歴があった。単純X線像では右大腿骨頸部骨折および両側大腿骨頸部骨透亮像を認めた。MRI T1強調像では、両側大腿骨頸部および周囲筋内の低信号病変を認めた。画像所見、既往歴からアミロイド沈着による病的骨折の可能性が疑われ、両側大腿骨に人工骨頭置換術、経皮的ピンニング術を行った。摘出標本はアミロイド沈着陽性であった。M蛋白血症を合併する全身性アミロイドーシス患者の骨折は、アミロイド沈着による病的骨折の可能性を考慮すべきであると思われた。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Pleomorphic rhabdomyosarcoma (PRMS) is a rare variant of rhabdomyosarcoma that occurs mostly in adults. A few cytogenetic studies of PRMS have been reported, but no consistent specific chromosome aberrations were detected. We herein report a cytogenetic study of three cases of pleomorphic rhabdomyosarcoma using a conventional G-banded karyotyping analysis. The three cases appeared to exhibit an extremely complex karyotype with numeric and structural rearrangements. Although the three cases displayed several common aberrations, including -2, -4, -9, -13, -14, -15, -19, -2 1, add(X)(p11), add(1)(q11), add(7)(p11), and add(13)(p11), no recurrent characteristic chromosomal aberrations could be detected. In addition, among these cases and seven other cases of previously reported PRMS, the most frequent chromosomal alterations were -2, -13, -14, -15, -16, and -19. No obviously consistent structural alterations can be found in these 10 PRMS cases, however, thereby suggesting that it is difficult to confirm whether these complex karyotypes correlated with the diagnosis or clinical outcome in PRMS. In this study, we detected MyoDt and myogenin gene transcripts at the mRNA level in four cases of PRMS together with other soft-tissue sarcomas, including seven cases of malignant fibrous hitiocytoma, five cases of liposacroma, and three cases of leiomyosacroma using a real-time quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) analysis. High-level expressions of MyoD1 and myogenin gene transcripts were determined in all cases of PRMS. In contrast, the other non-PRMS sarcomas showed either no expression or extremely weak expressions for both genes. Our findings suggest that the detections of MyoD1 and myogenin transcripts using real-time quantitative RT-PCR, combined with immunohistochemical stains, are extremely sensitive and useful for the diagnosis of PRMS. (C) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cancergencyto.2009.02.011

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

Background: A giant cell tumor (GCT) of bone is a locally aggressive tumor with a propensity for local recurrence. A characteristic pattern of peripheral bone formation has been described in GCT recurrence in soft tissue, and in some pulmonary metastases from benign GCT. Although the bone formation in GCT in supposedly due to bone morphogenetic proteins (BMPs), the expression pattern of BMPs in GCT has not been well investigated. Materials and Methods: The expression of BMPs in GCT tissues, cultured stromal cells from GCT and osteoclast-like giant cells harvested by laser microdissection (LM), as well as from control osteosarcoma (NOS-1) cells was analyzed using reverse transcriptional-semiquantitative PCR. Results: BMP 2, 3, 4, 5 and 6 were expressed in the GCT tissue. The cultured GCT cells expressed BMP 2, 4, 5 and 6. The osteoclast-like giant cells expressed BMP 2, 3, 5 and 6 and BMP 5 was expressed at the highest level. Conclusion: Both stromal cells and osteoclast-like cells in GCT expressed several kinds of BMPs.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Chondromodulin-1 (ChM1), an endogenous anti-angiogenic factor expressed in cartilage, has been suggested to inhibit invasion of endothelial cells into cartilage. In addition, the ectopic administration of ChM1 has been reported to suppress tumorigenesis in vivo. However, it is unclear whether the anti-tumor effect is due to not only the anti-vascularization effect of ChM1, but also its direct action against oncocytes. In the present study, we sought to determine whether ChM1 has a direct action on tumor cells.
Methods: BrdU incorporation assay was performed on human umbilical vein endothelial cells (HUVECs), normal human dermal fibroblasts (NHDFs), HepG2 cells and HeLa cells in the presence or absence of recombinant human ChM1 (rhChM1). An adenovirus that expresses ChM1, Ad-ChM1, was established and applied to the tumor xenografted in vivo, and to in vitro tumor cells cultured on plates or in soft agar. Cell cycle-related proteins and the phosphorylation of Erk, Akt, and GSK3 beta, the downstream molecules of the extracellular matrix-integrin signaling pathways, in HepG2 cells treated with or without Ad-ChM1 were detected by western blot analysis. Luciferase reporter assays of STAT, GAS, and ISRE, which participate in another cytokine signaling pathway, ware performed in HepG2, HeLa, and HUVEC cells.
Results: ChM1 suppressed BrdU incorporation in HUVECs and in HepG2 cells dose-dependently, but did not suppress BrdU incorporation in NHDFs and HeLa cells cultured on plates. In soft agar, however, ChM1 suppressed the growth of HeLa cells, as well as HepG2 cells. Western blot analyses demonstrated that ChM1 decreased the levels of cyclin D1, cyclin D3, and cdk6 and increased those of p21(cip1) without affecting the phosphorylation levels of Erk, Akt, and GSK3 beta in HepG2 cells. The luciferase reporter assay demonstrated that ChM1 suppressed the transcriptional activities of STAT and GAS but not of ISRE.
Conclusion: ChM1 directly suppressed the proliferation of tumor cells in an anchorage- independent manner. However, ChM1 did not alter the phosphorylation of downstream molecules, at which the signaling pathways through growth factor and cytokine receptors converge with the anchorage-dependent pathway. Our results show that ChM1 has a direct anti-tumor effect; moreover, this effect occurs by inhibiting the STAT signaling pathway.

DOI： 10.1186/1471-2407-9-166

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Alveolar soft part sarcoma (ASPS) is a distinct, rare soft tissue tumor with an unknown histogenesis and a tendency for late widespread metastases to lung, bone, and brain. It is now clear that they are caused by a specific unbalanced translocation, der(17)t(X;17)(p11;q25), which results in the formation of all ASPSCR1-TFE3 (alias ASPL-TFE3) fusion gene. The rearrangement results; ill the expression of chimeric transcripts, which can be identified by means of reverse transcriptase-polymerase chain reaction (RT-PCR). We investigated the histogenesis of ASPS and attempted to detect Circulating ASPS tumor cells in peripheral blood. The immunohistochemical and genetic details of four cases and one cell title of ASPS were examined. An immunohistochemical analysis and RT-PCR did not detect myogenic differentiation gene MYOD1. The sensitivity of nested RT-PCR for detection of circulating ASPS cells was assessed by demonstrating that the tumor cell-associated gene translocation could be detected in 50 tumor cells/2 mL of blood. Clinically, it was detectable in a peripheral blood sample (2 mL) of ASPS patient with distant metastases. The findings suggest that ASPS is not of skeletal muscle origin. ASPS tumor cells in the peripheral blood could be monitored by RT-PCR. (c) 2009 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cancergencyto.2008.11.014

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Multinucleated cells are frequently seen in association with a malignant neoplasm. Some of these multinucleated cells are considered to be neoplastic. The mechanism of neoplastic multinucleation remains unknown, but is considered to be induced by either cell-cell fusion or acytokinetic cell division. Myxofibrosarcoma consists of spindled and pleomorphic tumor cells and bizarre multinucleated giant cells. Some of these multinucleated cells are considered to be neoplastic.
Methods: We studied the mitotic activity of the multinucleated cells by Ki-67 immunohistochemistry, and the dynamics and differentiation by live-cell video microscopy in the two myxofibrosarcoma cell lines to determine whether the mechanism of multinucleation is cell-cell fusion or acytokinetic cell division
Results: A Ki-67 immunohistochemical analysis revealed a high positive rate of multinucleated cells, as well as mononuclear cells, and mitotic ability was shown in the multinucleated cells. In live-cell video microscopy, most of the multinucleated cells were induced via the process of acytokinetic cell division.
Conclusion: The current study indicates that a vulnerability of the cytoskeleton components, such as the contractile ring, causes multinucleation to occur from the telophase to the cytokinesis of the cell cycle.

DOI： 10.1186/1756-9966-28-44

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DOI： 10.1186/1756-9966-28-44

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

切除不能な再発あるいは転移を有する骨・軟部腫瘍症例で、同意が得られた8症例に対しシクロスファミド(CPM)100mgの内服を中心とした外来化学療法を施行しており、その短期成績を報告した。症例により、ドキソルビジン(DOX)の静注を月一回施行した。DOX投与後2、3日は食欲不振を来たすことがあり、吐き気や不快感がある場合は、QOLの維持に主眼を置くためDOX静注は早めに中止した。高齢者の1例、長期の入院抗癌剤治療後の2例は好中球減少が生じてCPMを減量したが、血液毒性は軽度であり、連日投与が可能であった。薬剤投与に関しては外来で十分管理可能であった。投与2ヵ月後では部分奏功1例、安定5例、進行2例であった。部分奏功例では施行後1年間は腫瘍の十分な抑制効果がみられたが、DOXが極量となり、CPM内服単独となって再増悪した。腫瘍進行までの期間は1〜11ヵ月で、最終追跡時3例が有病生存で内服を継続中であり、5例が腫瘍死した。

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Language：Japanese   Publisher：新潟整形外科研究会  

症例1:49歳男。18歳時に第5頸髄を損傷し、完全四肢麻痺、不全呼吸麻痺となり、気管切開され人工呼吸器管理となった。受傷直後より仙骨部褥瘡を認めており、3年前に褥瘡部に隆起性腫瘤が出現し、徐々に増大した。入院時、仙骨部褥瘡に径約20cmの隆起した腫瘤があり、大量の排膿があった。CTにて右臀部から腸骨、仙骨まで浸潤する腫瘍、両肺に転移巣を認めた。右鼠径リンパ節の吸引細胞診にてリンパ節転移と診断され、腫瘍切除および右股関節離断、右大腿部筋皮弁を用いた欠損部再建を行った。病理診断は扁平上皮癌であった。術後肺転移が増大、呼吸状態悪化し、術後35日に死亡した。症例2:55歳男。21歳時に第4胸髄を損傷し、完全対麻痺となった。受傷直後より仙骨部褥瘡があり、約2年前に褥瘡内左半分に腫瘤性病変を認め、fibrous polyposisの診断で腫瘤切除された。その後、再び褥瘡内に腫瘤が出現し、急激に増大し、CTにて右臀部から骨盤内にかけて巨大な腫瘍性病変を認めた。入院時、仙骨部の褥瘡内部に易出血性の腫瘤があり、大量出血と排膿があった。生検で卵円形、紡錘形の細胞を認め、悪性線維性組織球腫と診断され、腫瘍切除および右半骨盤切除を施行し、大腿部筋皮弁を用いて再建した。術後1ヵ月に肺転移、局所再発を認め、化学療法を行ったが腫瘍は皮膚へ浸潤し、全身状態が悪化して術後56日に死亡した。

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Language：Japanese   Publisher：(株)医学書院  

胞巣状構造を呈するが特異的遺伝子転座を認めない横紋筋肉腫1例を経験したので報告する.症例は1歳2ヵ月の女児で,針細胞診で横紋筋肉腫と診断し,広範切除を行った.術後組織病理学所見では,胎児型の部分と胞巣状構造が混じったパターンであった.典型的胞巣型と異なり,線維性間質に乏しく,大量の横紋筋芽細胞が混在するのが特徴であった.胞巣型に特異的なt(2;13)またはt(1;13)の転座を認めなかった.術後6年9ヵ月の現在,多発性転移を認め,再発と軽快を繰り返し,現在化学療法中である.(著者抄録)

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Other Link： http://search.jamas.or.jp/link/ui/2008306918

Language：Japanese   Publisher：東北整形災害外科学会  

1988〜2006年にかけ著者らにより仙骨切断術が施行され、温存できた神経が術中において肉眼で確認できた仙骨脊索腫6症例を対象に、仙髄神経根と膀胱直腸機能の関係を検討した。その結果、1)S3神経根が膀胱直腸機能の維持に重要であることが確認された。2)両側S2神経根を温存した4例すべてに膀胱直腸障害が認められた。3)尿路変更、人工肛門例を除いた5例の自覚症状は、排尿している時の感覚の減弱、尿意の減弱、夜間の失禁、便秘が多かった。4)膀胱と直腸の知覚が低下し、膀胱収縮が減弱した状態であったことから、主に骨盤神経の障害によるものと考えられた。5)これらのことは骨盤神経障害が陰部神経障害より優位に出現していると考えられる傾向であり、過去に指摘されていない事実であった。6)脊索腫に限らず、腫瘍高位によってS3神経根の温存不可能な場合、術後の膀胱直腸機能障害は必発と考えられ、温存不可能な場合は術前に十分な説明が必要であると思われた。

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

We report a case of cystic teratoma of the diaphragm that was considered to be a soft tissue lipoma by the preoperative examination. A magnetic resonance imaging revealed an 8x8 cm well-demarcated, homogeneous mass. On T1- and T2-weighted imaging, the mass was isointense to fat. On the fat-suppressed imaging, the signal from the mass was reduced to the same degree as subcutaneous fat. We performed marginal excision. The tumor contained a large number of hairs and oily liquid; and it was connected to the diaphragm.

DOI： 10.1007/s00256-007-0318-2

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

Dedifferentiated chondrosarcoma is a rare, highly malignant variant of chondrosarcoma in which a high-grade sarcoma coexists with a low-grade chondroid tumor. We herein review a case of dedifferentiated chondrosarcoma with an osteosarcoma omit component that occurred in the distal femur of a 38-year-old man. We established the cell line (NDCS-1) from a pleural effusion of the metastatic lung tumor. The cell line was characterized by a the G-banded karyotype, polymerase chain reaction (PCR) single-strand conformation polymorphism analysis, spectral karyotyping, and reverse transcriptase PCR (RT-PCR). The tumor exhibited complex karyotypes and a high frequency of chromosomal amplication with p53 mutation. This tumor revealed an osteoblastic and chondroblastic character in vitro and in severe combined immunodeficiency mice. The expression and phosphorylation of platelet-derived growth factor receptor-beta, which seemed to play a major role in the malignant phenotype of chondrosarcoma, was confirmed by RT-PCR and Western blotting. To our knowledge, this is the first report of the establishment of a human dedifferentiated chondrosarcoma.

DOI： 10.1007/s00428-007-0426-3

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

We report on a case of a solitary fibrous tumor that developed in the thigh of an 82-year-old woman. The tumor was composed of areas of high-grade sarcoma and typical solitary fibrous tumor. Its karyotype was: 70,XXX, +X [4],+1 [2],add(1) (p3 6) [4], add( 1) [2],+2 [4],-3 [4],+ 6 [4], add(6) (p11) x 2[4],+7[4],+9[3],-11[4],-12[4],-13[4],add(13)(p11)x2[4],-14[4],+15[4],-16[3],-17[4],-19[4],+ 20,[4],+21[4],+22 [2], +mar 1x2[4][cp4]. (c) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cancergencyto.2007.04.016

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

Despite its benign nature, a ganglion can be problematic. We successfully treated a patient with large painful ganglion in his ankle by OK-432 (lyophilized incubation mixture of group A Streptococcus pyogenes of human origin) injection. OK-432 injection seems to be a safe, convenient, and effective alternative to surgical treatment for either symptomatic or recurrent ganglia. © Japan College of Rheumatology 2007.

DOI： 10.1007/s10165-007-0597-4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Ossifying fibromyxoid tumor (OFMT) is a rare but morphologically distinctive soft-tissue tumor. The histologic origin of this tumor is not clearly known, but its various features suggest a schwannian, neuronal, or chondroid origin. We herein report a case of a typical OFMT that occurred in the shoulder of a 65-year-old man. The karyotype exhibited the following complex numeric and structural aberrations: 42 similar to 46, XY, -Y, add(1)(q42),add(6) (p21),t(10;18)(q26;q11),der(11)t(11; 15) (q23;q15),add(12)(q13),ins(14;?)(q13;?),-15, +mar. Combined with several previously reported studies, these aberrations could not identify a common cytogenetic, abnormality in OFMT. (C) 2007 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cancergencyto.2007.04.009

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Language：Japanese   Publisher：新潟整形外科研究会  

40歳男。3歳時よりネフローゼ症候群のため内科で加療中であった。38歳時の胸部X線で右第5肋骨と左第6肋骨に骨硬化性の結節影を指摘され、骨島の疑いで経過観察されたが、40歳時に同結節影に増大傾向があり、当科紹介受診した。胸部X線像の経過をみると、17歳時には結節影を認めなかったが、38歳時では右第5肋骨と左第6肋骨に骨硬化性の結節影を認め、40歳時にはそれらが増大していた。骨盤部X線検査では両腸骨・右仙腸関節部、両恥骨、両坐骨、両大腿骨頸部、右大腿骨転子部に小斑状〜結節状の多発性骨硬化像を認め、胸部CT検査では肋骨・胸椎椎体の骨髄内に散在する結節性骨硬化像を認めた。血液検査ではネフローゼ症候群によると思われる低蛋白血症と軽度低リン血症を認めた。左腸骨の開放生検を行い、病理組織学的に海綿骨内に緻密骨を認め、骨島の所見であった。

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC CANCER RESEARCH  

NPRL2 is one of the novel candidate tumor suppressor genes identified in the human chromosome 3p21.3 region. The NPRL2 has shown potent tumor suppression activity in vitro and in vivo and has been suggested to he involved in DNA mismatch repair, cell cycle checkpoint signaling, and regulation of the apoptotic pathway. In this study, we analyzed the endogenous expression of the NPRL2 protein and the cellular response to cisplatin in 40 non-small-cell lung cancer cell lines and found that expression of NPRL2 was significantly and reciprocally correlated to cisplatin sensitivity, with a Spearman correlation coefficient of -0.677 (P &lt; 0.00001). Exogenously introduced expression of NPRL2 by N-[1-(2,3-dioleoyloxyl)propyl]-NNN-trimethylammoniummethyl sulfate: cholesterol nanoparticle-mediated gene transfer significantly resensitized the response to cisplatin, yielding a 40% greater inhibition of tumor cell viability and resulting in a 2- to 3-fold increase in induction of apoptosis by activation of multiple caspases in NPRL2-transfected cells compared with untransfected cells at an equal dose of cisplatin. Furthermore, a systemic treatment with a combination of NPRL2 nano-particles and cisplatin in a human H322 lung cancer orthotopic mouse model significantly enhanced the therapeutic efficacy of cisplatin and overcame cisplatin-induced resistance (P &lt; 0.005). These findings implicate the potential of NPRL2 as a biomarker for predicting cisplatin response in lung cancer patients and as a molecular therapeutic agent for enhancing response and resensitizing nonresponders to cisplatin treatment.

DOI： 10.1158/0008-5472.CAN-06-1483

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

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

Background: Activating Gs a mutations have been identified in most instances of fibrous dysplasia (FD). This mutation leads to consistently elevated intracellular cyclic adenosine monophosphate (cAMP) levels, with various biological consequences. The development of secondary sarcoma in FD is a rare but well-established phenomenon. This finding raised the possibility that a common gene mutation exists in these tumors. Materials and Methods: The expression of the Gs a mutation was examined in 16 cell lines and 173 musculoskeletal tumor tissues, including 13 cases of FD, via RT-PCR and sequence analysis. Results: No expression of a Gs a mutation was detected in any cell line or clinical tissue sample, excluding FD tissues. Direct sequence analysis demonstrated results identical to those of RT-PCR. Conclusion: Activating Gs a mutation rarely occurs in musculoskeletal tumors other than FD. The occurrence of most sarcomas displays no correlation with Gs a mutations.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Prominent osteoconductive activity and the biodegradable nature of commercially available beta-tricalcium phosphate (beta-TCP, OSferion (R)) have been documented in animal experiments. We analyzed four cases of involving grafted OSferion (R) in human bone with respect to histological features by routine hematoxylin and eosin staining, silver impregnation, immunohistochemistry and in situ hybridization. OSferion (R) affords early bioresorption by osteoclasts, vascular invasion of macropores and osteoblastic cell attachment on the surface on the ceramic surface 14 days after grafting. Prominent bone formation and direct bone connection between preexisting bone and OSferion (R) were evident 28 days after grafting. Nearly the entire TCP surface was covered by lamellar bone; additionally, active osteoblastic lining and attachment of the osteoclast-like giant cells were not observed 72 weeks after grafting. Silver impregnation revealed the presence of collagen fibrils within probable micropores of OSferion (R). (c) 2005 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.biomaterials.2005.08.034

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：APSIT ASSOC PROM STUD IMMUNOL TUMOR  

The present investigation examined the effect of bisphosphonates on six mesenchymal tumor cell lines and the mechanisms of inhibition of tumor cell proliferation. HT-1080, a fibrosarcoma cell line that exhibits increased Ras activity due to a mutation of the Ras gene, demonstrated significantly reduced tumor cell proliferation upon treatment with incadronate. The other cell lines, however, which lack mutation of the Ras gene, showed no influence upon treatment with incadronate. Autoradiography demonstrated no difference in the uptake of 3 H-labelled incadronate between susceptible and unaffected cells. The anti-proliferation of HT-1080 was reversed by the addition of geranylgeranyl pyrophosphate. Etidronate exhibited no influence on all tested cell lines. On the basis of these data, we hypothesized that incadronate inhibits the mevalonate pathway and blocks oncogenic Ras signaling. In an effort to confirm this hypothesis, the influence of incadronate on an oncogenic Ras transfected BALB/3T3 cell line (Bhas 42) and a parental BALB/3T3 cell line were compared. The parental BALB/3T3 cells showed slight inhibition upon treatment with incadronate, however, the proliferation of Bhas 42 cells was significantly reduced. These results suggest that incadronate suppresses oncogenic Ras-activated mesenchymal tumors through the inhibition of Ras signaling pathways.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS  

We report a case of successful control of the infection of megaprosthesis in the distal femur. Deep infection occurred 5 years after the resection of the osteosarcoma and reconstruction with cernentless megaprosthesis. Multiple debridement and intravenous administration of antibiotics did not eradicate the infection. He developed aortitis syndrome (Takayasu's arteritis) and needed to undergo steroid therapy. Total removal of the prosthesis achieved good control of the infection, and the patient had started prednisolone therapy. The patient can walk alone with an ischial weight-bearing brace. Removal of the endoprosthesis and application of ischial weight-bearing brace may be a possible option for the treatment of infected megaprosthesis.

DOI： 10.1016/j.arth.2005.07.004

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：B M J PUBLISHING GROUP  

This report describes a case of congenital dermatofibrosarcoma protuberans (DFSP) with fibrosarcomatous (FS) and myxoid areas. Immunohistochemical results showed that tumour cells in ordinary DFSP areas were diffusely positive for CD34, whereas in the FS and myxoid areas, few tumour cells were positive for this antigen. Ki-67 positive tumour cell numbers were greater in the FS (11.8%) and myxoid areas (19.8%) relative to ordinary DFSP areas (2.2%). Reverse transcription polymerase chain reaction and sequence analysis showed the presence of an identical COL1A1-PDGFB fusion transcript in ordinary DFSP ( plaque-like area), FS, and myxoid areas of DFSP. These results indicate that the three components of DFSP have a common histogenesis. This study documents the first application of gene analysis involving the myxoid area of DFSP.

DOI： 10.1136/jcp.2004.024430

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

We established a novel human myxofibrosarcoma cell line NMFH-1 and analyzed it with spectral karyotyping and comparative genomic hybridization (CGH). NMFH-1 cells are composed of two different types of cells, small, spindle-shaped mononuclear cells and bizarre multinucleated giant cells, which were maintained in vitro over 200 passages. Xenografted tumor showed typical features of myxofibrosarcoma, which included bizarre multinucleated giant cells. Cytogenetic analyses revealed complex abnormalities, including a t(17;22)(q2?2;q13), which has been found in dermatofibrosarcoma protuberans. Subsequent reverse-transcription polymerase chain reaction revealed that the cell line did not have the COL1A1-PDGFB gene fusion. Significant gains of the 1q12 similar to q23 and 8q13-qter regions and loss of the 9p21-pter and 13q12 regions often found in MFH were observed by CGH analysis. We investigated the origin of multinucleated giant cells in xenografted tumor through DNA in situ hybridization. In this system, the human-specific Alu sequence and the mouse L1 sequence were used as specific cell markers of identity. In situ hybridization revealed neoplastic proliferation of the multinucleated giant cells of human origin. (c) 2005 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cancergencyto.2005.02.003

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Language：Japanese   Publisher：東北整形災害外科学会  

症例1:16歳男.右大腿部腫脹があり,血腫除去術を施行された.術後創部からの出血が持続し,病理検査にて血腫は肉腫と多量の壊死組織であることが判明し,この時点で骨盤内腫瘤は転移巣であり,かつ多発肺転移の存在が判明した.アドリアシン,イフォマイドを施行したが,呼吸不全のため死亡した.最終的に骨外性Ewing肉腫と診断した.症例2:26歳女.後腹膜巨大嚢腫の診断で嚢腫除去術を施行し,術後Ewing肉腫と判明したため多剤併用化学療法を開始した.8年経過し無病生存中である.症例3:34歳男.左胸部皮下腫瘤があり,針生検でEwing肉腫が疑われたため多剤併用化学療法を開始した.1サイクル終了後に広範切除術を行い,現在無病生存中である.症例4:78歳女.左大腿軟部腫瘤があり,大腿動静脈温存腫瘍内切除術を行った.術後Ewing肉腫と判明したが,肺転移による呼吸不全のため死亡した

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC CLINICAL ONCOLOGY  

DOI： 10.1200/JCO.2005.05.042

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Germline mutation and functional loss of EXT1 or EXT2 are commonly found in multiple osteochondrornas and predispose to the development of chondrosarcoma. Mutations of EXT1 and EXT2 have rarely been detected in sporadic secondary chondrosarcomas from osteochondrorna; these frequently display loss of heterozygosity at the EXT1 and EXT2 loci, but primary chondrosarcomas typically do not. To evaluate promoter methylation (which is an epigenetic gene silencing mechanism) of EXT1 and EXT2, we performed methylation-specific polymerase chain reaction (PCR) for 20 chondrosarcoma cases (12 primary, 3 secondary to osteochondroma, 2 secondary to enchondromatosis, 2 extraskeletal ordinary. and I clear cell) and in five cell lines. In addition, mutation analysis of the EXT1 and EXT2 coding regions was performed using PCR-single-strand conformation polymorphism and sequencing analysis for 12 of the 20 chondrosarcoma cases (8 primary, I secondary to enchondromatosis, I secondary to osteochondroma, and 2 extraskeletal ordinary) and five cell lines. Promoter methylation of EXT1 and EXT2 was not detected in any of the cases, and both EXT1 and EXT2 were expressed in all cell lines. Two missense mutations in EXT2 (D227E and R299H) were detected among the chondrosarcoma cases. When considering tumor development in primary chondrosarcoma, we should include mutations in EXT2, along with the status of other members of the EXT gene family. (c) 2005 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cancergentyto.2004.08.031

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BRITISH EDITORIAL SOC BONE JOINT SURGERY  

We describe two patients with a diffuse haemangioma of the lower limb complicated by pathological fracture of the femoral shaft, one of whom was treated by a bone graft and immobilisation in a cast, and the other by external fixation and injection of bone marrow. A review of the literature identified difficulty in control of bleeding and obtaining bony union.

DOI： 10.1302/0301-620X.87B3

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Long-term results are reported in 23 patients and short-term results in 30 patients presenting with bone tumors treated by curettage or resection followed by implantation of hydroxyapatite (HA) or highly purified beta-tricalcium phosphate (β-TCP), respectively. Mean follow-up was 97 and 26 months in cases involving HA implantation and β-TCP implantation, respectively. Radiographs revealed HA incorporation into host bone in all but two cases
moreover, no obvious evidence of HA biodegradation was observed. A single patient exhibited late deformity following implantation of HA. All grafted β-TCP was, at least partially, absorbed and replaced by newly formed bone. The mean period required for the disappearance of radiolucent zones between the ceramics and host bone was 17 weeks in HA and 9.7 weeks in β-TCP. Highly purified β-TCP appears to be advantageous relative to HA for surgical intervention in bone tumors consequent to the nature of remodeling and superior osteoconductivity. © 2004 Wiley Periodicals, Inc.

DOI： 10.1002/jbm.b.30136

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-LISS  

Long-term results are reported in 23 patients and short-term results in 30 patients presenting with bone tumors treated by curettage or resection followed by implantation of hydroxyapatite (HA) or highly purified beta-tricalcium phosphate (beta-TCP), respectively. Mean follow-up was 97 and 26 months in cases involving HA implantation and beta-TCP implantation, respectively. Radiographs revealed HA incorporation into host bone in all but two cases; moreover, no obvious evidence of HA biodegradation was observed. A single patient exhibited late deformity following implantation of HA. All grafted beta-TCP was, at least partially, absorbed and replaced by newly formed bone. The mean period required for the disappearance of radiolucent zones between the ceramics and host bone was 17 weeks in HA and 9.7 weeks in beta-TCP. Highly purified beta-TCP appears to be advantageous relative to HA for surgical intervention in bone tumors consequent to the nature of remodeling and superior osteoconductivity. (C) 2004 Wiley Periodicals, Inc.

DOI： 10.1002/jbm.b.30136

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Study Design. Case report.
Objectives. To report primary angiosarcoma of the T8 vertebra, which was successfully managed with en bloc spondylectomy and postoperative chemotherapy.
Summary of Background Data. To the best of our knowledge, the present case is the first documented example of successful treatment of angiosarcoma of the spine.
Methods. Angiosarcoma of the eighth thoracic vertebra was diagnosed in a 48-year-old man with impending neurologic deficit. Imaging findings revealed a nonspecific high-grade lesion. A total spondylectomy of T8 by en bloc resection was performed. The defect of the vertebral body was reconstructed with a apatite-wollastonite glass ceramic prosthesis; moreover, the T6 - T10 vertebrae were instrumented by the pedicle screw, hook and rod system. The histologic diagnosis of the excised specimen was high-grade angiosarcoma. Postoperative chemotherapy was implemented to prevent local recurrence and distant metastasis.
Results. No sign of local recurrence or metastasis was evident 5 years after surgery.
Conclusion. This case is the first documented example of successful treatment of angiosarcoma of the thoracic spine. Radiologic findings were nonspecific; consequently, correct diagnosis was established by pathologic examination. Immediate, aggressive operative treatment and postoperative adjuvant chemotherapy afforded a satisfactory outcome.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Objective: To distinguish between benign and malignant peripheral nerve sheath tumors around the pelvis.
Methods: A retrospective study of 30 patients with benign and malignant peripheral nerve sheath tumors located around the pelvis was performed. Clinical, imaging and histological features of 19 benign and 11 malignant peripheral nerve sheath tumors around the pelvis were reviewed retrospectively.
Results: Nearly all patients exhibited pain at presentation in cases involving both benign and malignant tumors. Although tumor size, duration of symptoms and presence of sensory disturbance possessed little value in differential diagnosis, severe motor weakness was observed exclusively in patients presenting with malignant tumors. On CT or MRI, central enhancement was apparent in 11 of the 19 benign tumors; in contrast, central enhancement was evident in one of the 11 malignant tumors. Fine needle aspiration cytology was performed in 11 tumors; correct diagnosis was achieved in four tumors. Core needle biopsy was performed in five tumors, all of which were correctly diagnosed with no neurological deficits. Immunohistochemically, all benign tumors were diffusely positive for S-100 protein, whereas malignant tumors were negative or focally positive for S-100 protein. Ki-67 index was less than 4% in all benign tumors; additionally, this index was 7-36% in malignant tumors.
Conclusion: Central enhancement pattern on imaging studies strongly suggests a benign tumor; in contrast, severe motor weakness suggests malignant lesions. Core needle biopsy was reliable with respect to preoperative diagnosis.

DOI： 10.1093/jjco/hyh072

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Sclerosing epithelioid fibrosarcoma is a recently described, rare mesenchymal neoplasm. We report a case of sclerosing epithelioid fibrosarcoma that occurred in the lower leg of a 48-year-old man. The karyotype of the tumor exhibited der(1)t(1; 10)(p31; p11), der(10)t(10; 17)(p11; q11), and der(17) t(11; 17)(?; q11). Rearrangement of 10p11 was also found in one previous reported case of this uncommon tumor. (C) 2004 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.cancergenyto.2003.11.007

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Language：Japanese   Publisher：新潟整形外科研究会  

78歳女.左大腿骨骨幹部骨折を受傷し,観血的骨接合術が施行された.しかし皮膚と筋膜の切開のみで3000mlの出血があり,臀部から下肢全体に広がる血管腫と判明した.X線所見で大腿骨骨幹部に横骨折を認め,骨折部周囲の皮下組織内に小さな石灰化を数個認めた.側面像では大腿骨の横径が小さく,骨硬化像を伴っていた.MRI-T2強調画像にて骨を含む大腿部全体に,高信号領域と低信号領域が混在し,血管腫と考えられる病変を認めた.創外固定術を施行し,術中出血は20mlであったが,術後も筋層内への出血と考えられる大腿軟部の腫脹を認めた.濃厚赤血球と新鮮凍結血漿を4単位ずつ輸血したが,術後1週で貧血が残存し,濃厚赤血球と新鮮凍結血漿を2単位ずつ更に輸血した.骨折受傷から約2年後に抜釘術を行い,再骨折防止目的で大ギプスを装着した.抜釘後8ヵ月現在も骨癒合良好で,膝の可動域は伸展0°,屈曲50°で疼痛もなく日常生活を送っている

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Language：Japanese   Publisher：東北整形災害外科学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER ASSOC CANCER RESEARCH  

Purpose: The sensitivity of human tumor tissues to infection with recombinant adenoviruses correlates with the expression of the coxsackievirus and adenovirus receptor (CAR). CAR has been shown to function as the primary receptor for adenoviruses and to play a critical role in adenovirus entry into host cells. It is important for clinical gene therapy to determine the expression level of CAR in tumor tissues.
Experimental Design: We analyzed the expression of CAR mRNA in 154 musculoskeletal tumor tissues from 154 patients and, 10 normal mesenchymal tissues from 3 patients using reverse transcription-PCR and real-time quantitative PCR. An adenovirus infection assay was performed in two cell lines that were established from CAR-positive osteosarcoma tissue and CAR-negative malignant fibrous histiocytoma tissue.
Results: Ninety-nine of 154 tumors were detected as CAR positive by reverse transcription-PCR. We found that the expression levels of CAR mRNA varied markedly between different tumors as determined by real-time quantitative PCR. CAR mRNA was expressed at high levels in osteosarcoma, Ewing's sarcoma, neurofibroma, and schwannoma; at intermediate levels in exostosis, giant cell tumor, liposarcoma, synovial sarcoma, malignant peripheral nerve sheath tumor, and hemangioma; and at low levels in alveolar soft part sarcoma and desmoid. Whereas the osteosarcoma cell line that expressed a high level of CAR mRNA, like its parent tumor, had a high efficiency of adenovirus infection, the malignant fibrous histiocytoma cell line with. almost undetectable expression of CAR mRNA, like its parent tumor, had a low efficiency of infection.
Conclusions: Our data showed the great variations in CAR mRNA expression among human musculoskeletal tumors and mesenchymal tissues and implicated the potential usefulness of adenoviral vectors in gene therapy for osteosarcoma, Ewing's sarcoma, neurofibroma, and schwannoma. Efficient transduction with adenovirus for gene therapy could be realized in appropriate, sensitive tumor types.

DOI： 10.1158/1078-0432.CCR-03-0345

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER SOC MICROBIOLOGY  

Ligaments and tendons are comprised of tough yet flexible connective tissue. Little is known, however, about the precise characteristics of the cells in ligaments and tendons due to the absence of specific markers and cell lines. We recently reported a periodontal ligament cell line, PDL-L2, with suppressed Runx2/Osf2 transcriptional activity and an inability to form mineralized nodules. The present study demonstrates that the homeobox protein Msx2 is a key factor in suppressing those two functions. Msx2 colocalizes with Runx2/Osf2 and suppresses its activity cooperatively, acting with another corepressor, TLE1, as a complex to recruit histone deacetylase 1 activity. Reverse transcription-PCR and in situ hybridization demonstrated that Msx2 expression is higher in periodontal ligament and tendon cells than in osteoblasts. Stable reduction of Msx2 expression in PDL-L2 cells induces osteoblastic differentiation, thereby causing matrix mineralization. Conversely, stable, forced Msx2 expression in MC3T3-E1 cells prevented osteoblast differentiation and matrix mineralization. Msx2-induced suppression of osteoblast differentiation was repressed by bone morphogenetic protein 2. In addition, Msx2 was downregulated in a symptom- and calcification-dependent manner at the affected region in patients with ossification of the posterior longitudinal ligament. Our findings indicate that Msx2 plays a central role in preventing ligaments and tendons from mineralizing.

DOI： 10.1128/MCB.24.8.3460-3472.2004

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

We report a case of plexiform schwannoma located in the flexor muscles of the forearm in the absence of other signs of neurofibromatosis or schwannomatosis. Magnetic resonance examination revealed a multinodular irregular inhomogeneous mass. Some nodules displayed a peripheral, high intensity rim and a central low intensity (target sign) on T2-weighted images. Pre-operative diagnosis of the rare plexiform schwannoma may be possible with careful imaging examination for the target sign.

DOI： 10.1007/s00256-003-0701-6

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：W B SAUNDERS CO  

Liposclerosing myxofibrous tumor (LSMFT) is a benign fibroosseous lesion that is characterized by mixture of histologic elements including lipoma, fibroxanthoma, myxoma, ischemic ossification, and fibrous dysplasia (FD)-like features. These tissue components are seen in the original reports of FD; however, the relationship between LSMFT and FD is not clear. Point mutation of the a subunit of G protein (Gs alpha), which increases cyclic adenosine monophosphate formation, has been recognized as the cause of McCune-Albright syndrome as well as polyostotic and monostotic FD of bone. Gs alpha mutation at the Arg(201) codon in 2 patients of LSMFT was demonstrated in the present study. Although direct sequencing analysis using the fresh-frozen materials could not detect the mutation, the polymerase chain reaction fragmentation length polymorphism (PCR-RFLP) disclosed the missense point mutation Gs a at the Arg201 codon in 2 cases involving LSMFT. This result strongly suggests that a subset of LSMFT is a variant form of FD. (C) 2003 Elsevier Inc. All rights reserved.

DOI： 10.1016/S0046-8177(03)00430-1

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Language：Japanese   Publisher：新潟整形外科研究会  

症例1:51歳男.主訴は右腋窩部腫瘤.MRIでは尺骨神経と思われる部位にT1強調で筋肉と比し等〜高輝度,T2強調で辺縁が著明に高輝度で,内部がやや低輝度ないわゆるTarget signを呈する多房性の腫瘤が認められた.多発性神経鞘腫を疑い腫瘍核出術を施行した.大小6個の黄白色を呈する腫瘤が摘出され,病理組織診断は良性神経鞘腫であった.腫瘍は紡錘形細胞が密に存在し,充実性のAntoni Aと細胞密度が疎で粘液状のAntoni Bが混在してみられた.症例2:37歳女.主訴は左上肢腫瘤,疼痛.左前腕部のMRIではT1強調で筋肉に比し低輝度,T2強調でTarget sign陽性,T1〜Gdにてよく造影される多房性の腫瘤がみられた.多発性神経鞘腫を疑い腫瘍核出術を施行した.大小6個の黄白色を呈する腫瘤が摘出され,病理組織診断は神経鞘腫であった.本例もAntoni AとAntoni Bが混在してみられた.術後,橈骨神経領域にMMT1〜3程度の筋力低下が出現した.術後1年半経過した現在,筋力はほぼ回復しADL上不自由なくなっている

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Language：Japanese   Publisher：(NPO)日本小児がん学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Study Design. Case report. The authors documented a patient presenting with multiple cellular schwannomas along the sciatic nerve. The patient had no stigmas of neurofibromatosis. Thirteen tumors were resected via both anterior and posterior approaches.
Objectives. To point out that presacral cellular schwannoma can display multiple occurrences.
Summary of Background Data. Cellular schwannoma, which is a well-recognized variant of benign schwannoma, is often misdiagnosed as sarcoma. The tumor is usually a solitary lesion.
Materials and Methods. Medical history, physical findings, imaging features, and histologic findings were reviewed in a case of multiple cellular schwannomas in the presacral regions.
Results. A 39-year-old woman without any evidence of neurofibromatosis underwent removal of presacral multiple tumors along the sacral nerve root. Nineteen years after the surgery, the tumors recurred with multiple fashion. Thirteen tumors were resected via both anterior and posterior approaches. Immunohistochemical analysis of S-100 protein and Ki-67 were beneficial with respect to differentiation of cellular schwannoma from malignant peripheral nerve sheath tumor.
Conclusions. The present case illustrated that multiple cellular schwannomas can develop in nonneurofibromatosis patients.

DOI： 10.1097/01.BRS.0000092344.14376.D9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Adenovirus vectors are expected to be a powerful tool for gene therapy to treat severe fractures. Adenovirus invades cells through binding to the coxsackievirus and adenovirus receptor (CAR) on the cell membrane. CAR expression is low in normal adult animals, but it is induced on regenerating cells in some experimental models. We made a rib fracture model in mice and evaluated the histological changes and CAR mRNA expression by RT-PCR 1, 5,10,14, and 21 days after the fracture. CAR mRNA was expressed exclusively in the fractured ribs at each time point, but not in the normal ribs. We detected the CAR protein immunohistochemically in fibroblast-like cells in the fracture callus on days 10 and 14 after fracture. In situ hybridization showed that these fibroblast-like cells expressed mRNA of type I collagen and osteppontin, but not osteocalcin, defining the cells as immature osteoblasts. We then transferred small doses (10(4)-10(8) PFU) of lacZ-expressing adenovirus vector into immature osteoblasts on day 14. beta-galactosidase was detected only on the immature osteoblasts at every dose. Immature osteoblasts play an important role in the matrix replacement step in fracture healing. CAR-mediated gene transfer into immature osteoblasts can be reasonable for adenovirus-mediated treatment of fracture healing.

DOI： 10.1038/sj.gt.3302060

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

Local recurrence free survival rate for myxoid liposarcoma (MLS) is related to negative surgical margins. The goal of surgery in the treatment of MLS is to obtain tumor free surgical margins. When a tumor is adjacent to critical structures, wider resection, which can result in amputation, would be selected for local control. While recognizing that marginal or intralesional resection is associated with high risk of recurrence, circumstances occur that lead surgeons to conduct conservative surgery. To determine whether marginal or intralesional resection combined with radiotherapy can achieve local control, 10 cases (12 tumors) were reviewed involving MLS treated with marginal (8 tumors) or intralesional resection (4 tumors) followed by postoperative radiotherapy (50-70 Gy, average 59.2 Gy). No recurrences of MLS were observed locally at the mean follow-up of 58.1 months. The development of severe radiation-related complications was not detected. This medium follow-up study suggested that this method can achieve a high rate of local control.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BRITISH MED JOURNAL PUBL GROUP  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Recombinant adenovirus is used as a competent vector in a wide spectrum of cancer gene therapies. Adenovirus infection depends on coxsackievirus and adenovirus receptor (CAR)-mediated virus attachment to the cell surface. However, the expression levels of CAR and the efficiency of adenoviral gene transduction in musculoskeletal tumors have not been systematically investigated. To study the feasibility of gene therapy in musculoskeletal tumors, the expression levels of CAR and the antiproliferative effect of an adenovirally transduced wild-type p53 tumor suppressor gene were examined in 15 distinct musculoskeletal tumor cell lines, 19 tumor tissue samples, and the corresponding pathologically unremarkable mesenchymal tissues. The expression levels of the CAR gene were significantly higher in six of seven osteosarcoma cell lines and two of five osteosarcoma tissue samples than in the other cell lines, musculoskeletal tumors, and mesenchymal tissues. CAR expression levels were closely correlated with adenoviral gene transduction efficiency and the antiproliferative effect of a transduced adenoviral p53 gene in the tested cell lines. In addition, an immunocytochemical study confirmed that transfected green fluorescent protein (GFP) borne by Ad-CAG-GFP was expressed at the cell surface of CAR-positive cells. These results indicate that CAR expression is a critical determinant of transduction efficiency in adenovirus-based gene therapy. Most osteosarcomas appeared to express high levels of CAR, and thus adenovirus-mediated p53 gene therapy is likely to be suitable for the treatment of such tumors.

DOI： 10.1111/j.1349-7006.2003.tb01354.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Japan  

The effect of dexamethasone, a synthetic glucocorticoid, on in vitro and in vivo growth and differentiation of the human chondrosarcoma cell line (OUMS-27) was studied. Cells were treated with various doses of dexamethasone, and increasing doses produced an inhibitory effect on OUMS-27 tumor cell proliferation and induced maturation. Cell counts for OUMS-27 on day 9 ranged from 59% of the control at 10-8 M to 45% of the control at 10-5 M dexamethasone. Northern blot analysis revealed that the type II collagen mRNA level in cells given dexamethasone was lower than that in the controls, and the type X collagen mRNA level was higher than that in the controls. Phase-contrast microscopy revealed that cells grown in control medium formed monolayers consisting of small, polygonal cells, whereas dexamethasone-treated cells became larger and more irregular in shape. In the in vivo study the growth rate of masses in nude mice indused by inoculating OUMS-27 cells was also reduced in a dosedependent manner with dexamethasone administration. These results suggest that dexamethasone caused growth inhibition and induced chondrogenic maturation of human chondrosarcoma cells.

DOI： 10.1007/s10776-003-0650-y

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

Objective: The clinical features and the management of alveolar soft part sarcoma (ASPS) are not well known. The efficacy of chemotherapy for soft tissue sarcoma, including high-dose ifosfamide and cisplatin, has not been established yet. Some reports suggest ASPS may occur primarily in bone. Methods: We report on a series of 57 patients with ASPS over 20 years. Their ages ranged from 7 to 75 years (mean 25). Results:There were 37 females and 20 males. Thirteen lesions (23%) showed bone involvement at the primary site, and 6 of them were diagnosed as bone tumors at presentation. Thirty-seven patients had distant metastases at presentation. Tumor size, bone involvement at the primary site and the presence of metastases at presentation were prognostic indicators (p &lt; 0.05). Marginal exicision with radiotherapy or wide excision without radiotherapy achieved good local control. Chemotherapy was performed in 47 patients with different regimens. Two patients treated with intraarterial chemotherapy regimens responded partially, but intravenous chemotherapy with high-dose ifosfamide or cisplatin failed. Conclusions: ASPS can present primarily as a bone tumor. No advantage of chemotherapy with high-dose ifosfamide or cisplatin could be demonstrated. Copyright (C) 2003 S. Karger AG, Basel.

DOI： 10.1159/000071199

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Language：Japanese   Publisher：東北整形災害外科学会  

上肢悪性腫瘍に対する三角筋筋膜皮弁を用いた肩甲帯離断術を行った3例を経験した.症例1は61歳男性.右環指爪下部原発の悪性黒色腫で,腫瘍は尺骨,正中,筋皮神経内に浸潤していた.リンパ節以外の転移を認めず,三角筋筋膜皮弁で断端被覆を行う肩甲帯離断術を施行した.しかし,術後8年後に後腹膜腔への転移で死亡した.症例2は54歳男性.小児期の前腕部火傷瘢痕部に生じた扁平上皮癌で,前医に広範切除・脇窩リンパ節郭清を施行されたが,腋窩部で再発を来して受診した.症例1と同様に腋窩部切除の皮切デザインで手術を行ったが,術後約11ヵ月後に多発肺転移にて死亡した.症例3は76歳女性.乳癌切除後の左上肢リンパ血管肉腫で,左上腕内側の紫斑が上肢全体に拡大し,潰瘍も形成され受診した.腫瘍は上肢全体に進展し,左上背部,左前胸部までの浸潤を疑い,本術式を行った.術後約11ヵ月経過で再発,転移はない

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Language：Japanese   Publisher：東北整形災害外科学会  

足部に原発し悪性化した多発性内軟骨腫症の2例を経験した.症例1は初診時17歳男性.左足部痛が持続,内軟骨腫症の診断で左脛骨遠位部,母趾基節に掻爬骨移植施行した.31歳時に脛骨に再発し,舟状骨の腫瘍出現で掻爬骨移植を施行したが,32歳時に舟状骨部の疼痛出現,X線,CTで舟状骨外への浸潤を認め,悪性化と判断して左下腿切断を施行した.術後9年経過で再発,転移はない.症例2は初診時52歳男性で,左足部痛で受診し,X線で左第4,5趾,第5中足骨,踵骨,立方骨に透亮像を認め,多発性内軟骨腫症の診断で第4,5趾はMTP関節離断,第5中足骨と踵骨は掻爬骨移植を行った.組織診断は内軟骨腫であった.その後,69歳時に左足部の持続疼痛出現し,X線で立方骨の透亮像増大,骨皮骨の破壊と踵骨再発を認め,左下腿切断を施行した.術後半年経過で再発,転移はない.両症例とも下腿切断時の組織診断は軟骨肉腫であった

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：JOHN WILEY & SONS INC  

Prominent osteoconductive activity and the biodegradable nature of beta tricalcium phosphate (beta-TCP) for bone grafts in animal experiments has been reported. A new type of beta-TCP has been manufactured at extraordinarily high purity and has been available as potent bone grafting substitute for clinical use. The histological features of grafted beta-TCP in human bone have been analyzed. A 33-year-old female with a bone tumor of the proximal femur underwent curettage and beta-TCP graft under the diagnosis of probable benign fibrous dysplasia. Four weeks later, the proximal femur, including the grafted beta-TCP was resected because of the final diagnosis of the curettaged materials was osteosarcoma. The resected specimen revealed abundant direct new bone apposition on beta-TCP. There was no cartilaginous tissue or enchondral ossification. Bone formation was more prominent in the periphery of the grafted area than in the center. There was a considerable number of osteoclast-like giant cells surrounding the beta-TCP. This case illustrated that highly purified beta-TCP had prominent osteoconductive activity and biodegradable nature in human bone. (C) 2002 Wiley Periodicals, Inc.

DOI： 10.1002/jbm.10380

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Language：Japanese   Publisher：東北整形災害外科学会  

21歳女の第1子である女児.妊娠25週,妊婦検診時の超音波検査で左下腿腫瘤を指摘された.妊娠29週より心不全徴候が出現したため経母体的投与によるジギタリス療法を開始し,妊娠31週,胎児仮死のため帝王切開で出生した.出生時,左下肢に径15×16cmの巨大な充実性腫瘤を認めた.腫瘍への血流の供給によると思われる心不全が出現した.針生検を行い,左下肢腫瘤を線維肉腫と診断した.心不全に加え,腫瘍そのものの増大と腫瘍上の皮膚の壊死傾向を認め,全身状態のすみやかな改善が必要と判断し,大腿切断術を施行した.術後よりすみやかに心不全は改善した.現在,術後112日の時点で局所再発,遠隔転移を疑わせる所見は認めていない

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Language：Japanese   Publisher：(一社)日本皮膚悪性腫瘍学会  

75歳男.左母指背側に隆起性腫瘤が出現した.左母指DIP関節背側の3.5×3.2cm大の暗紫紅色の腫瘤は,類円形で表面平滑,一部血痂を付着し,弾性軟,脆弱で易出血性,疼痛を伴っていた.胸部X線,CTで右上肺葉に径10cmを越える腫瘤陰影を認めた.強い疼痛と腫瘤の急速な増大で左母指切断術を施行した.病理組織では,腫瘍は核の濃染した小型な類円形細胞を主体とし,一部管腔様構造も認めた.また,組織の一部に腺腔様構造を取り囲む様に,または数珠状に配列する大型の上皮様細胞や,柵状に配列する紡錘形細胞を認め,二相性構造であった.免疫組織では,小型および紡錘形細胞はビメンチン陽性,上皮様細胞はCAM5.2陽性で,左母指の腫瘤は低分化型滑膜肉腫と診断し,肺腫瘤はその転移と考えた.全身状態より手術適応がないと判断し,肺腫瘤には放射線療法を開始したが,発症後6ヵ月で呼吸不全のため永眠した

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：INT INST ANTICANCER RESEARCH  

Background: Clear cell chondrosarcoma is a rate bone tumor, which is sometimes misdiagnosed as a different bone neoplasm. Materials and Methods: The files of 6 patients with clear cell chondrosarcomas were reviewed. Histological slides, radiographic studies, and pre- and post-operative serum alkaline phosphatase (ALP) levels were evaluated. Molecular and histochemical analyses of ALP were documented in one case of clear cell chondrosarcoma. Results: Pre-operative serum ALP levels were elevated in 3 patients, and were normal in another 3 patients. After removal of the tumors, the enzyme levels decreased in all patients and returned to normal in 3 patients, who had pre-operative high ALP levels. Enzyme histochemical and molecular analyses demonstrated that the tumor produced ALP. Conclusion: Clear cell chondrosarcoma produces ALP, which can be used as a tumor marker in diagnosis and follow-up.

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Springer Japan  

Circulating tumor cells in the blood play a central role in the metastatic process. There have been no reports describing the relationship between lung metastasis and circulating osteosarcoma cells. We developed a system with a polymerase chain reaction assay based on an enzyme-linked immunosorbent assay (PCR-ELISA) to detect circulating osteosarcoma cells in a mouse metastatic model. Osf2/Cbfal, hereafter called Osf2, a member of the runt family of transcription factors, was used as a target gene. One splicing variant of Osf2 mRNA was identified and its expression was restricted to the bones and osteosarcomas. The amount of the splicing variant of Osf2 mRNA was significantly higher in the blood of mice with metastasis than in the blood of the control group. The PCR-ELISA using Osf2 mRNA is a potential method to detect circulating osteosarcoma cells in peripheral blood.

DOI： 10.1007/s007760100046

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Language：Japanese   Publisher：新潟整形外科研究会  

症例は76歳の男性で主訴は多関節痛,両下腿紅斑,腫脹である.入院時,MRI所見は左膝T1強調像では脛骨で虫食い状の高低輝度混在,T2強調像でも同様で,一部低輝度に変化した部分が認められた.また右手のMRI T1強調像では,中指,環指,小指に低輝度陰影がみられた.入院時,アミラーゼ,リパーゼが異常高値で非定型的膵炎と考えメチル酸ガベキサート(FOY)を投与し,関節痛は膵炎合併骨内脂肪壊死と判断した.その後FOYによる膵炎治療の結果徐徐に疼痛が軽減し,アミラーゼ,リパーゼの正常化と共に疼痛消滅,独歩可能となった

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Language：Japanese   Publisher：新潟整形外科研究会  

30歳女.嚢腫を基部で切離し,嚢腫壁を縫縮することにより良好な結果を得た

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Language：Japanese   Publisher：東北整形災害外科学会  

坐骨腫瘍3例(外骨腫,血管腫,動脈瘤様骨嚢腫),恥骨腫瘍6例(軟骨肉腫3例,骨肉腫1例,Ewing肉腫1例,外骨腫1例)の治療成績を報告した.いずれも局所再発は無く,機能も極めて良好であった.Ewing肉腫の1例のみ腫瘍死したが,他の悪性腫瘍4例は無病生存していた.恥骨の一期的再建は不要と思われた

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Language：Japanese   Publisher：東北整形災害外科学会  

1)片麻痺を合併した大腿骨頸部骨折症例について検討した. 2)臨床像としては,麻痺側の骨折率は80%と高く,性別では健常群に比べ男性の割合が高いという特徴があった. 3)麻痺合併症例は入院日数が長期化する傾向があり,退院時歩行再獲得率も低いことから,リハビリ病院等の中間施設の整備の必要性が示唆された

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Language：Japanese   Publisher：東北整形災害外科学会  

1)外傷性骨折後偽関節に対し,手術治療を行った20例を検討した. 2)初回偽関節手術で骨癒合が得られたのは,人工骨頭置換術2例を除く18例中15例. 3)偽関節手術として,骨移植+圧迫プレート法は,確実性のある術式である. 4)感染を伴わない難治性の偽関節に対しては,血管柄付き腓骨移植を行うことにより,ほぼ良好な経過を得た

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Language：Japanese   Publisher：東北整形災害外科学会  

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Language：Japanese   Publisher：新潟整形外科研究会  

1)性別では麻痺側群は男性の割合が高いのに対し,健側群は全例女性であり有意差を認めた.この要因の一つとして,それぞれ麻痺側の易骨折性の関与,骨粗鬆症の関与が考えられた. 2)麻痺側群は歩行能力再獲得率に差はないものの,入院日数が長期化する傾向があった.これは麻痺と同一側に骨折が加わることにより,歩行機能を回復する迄に長い期間を要したためと考えられた

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Language：Japanese

＜文献概要＞股関節固定術後人工股関節全置換術(total hip arthroplasty;THA)は概ね成績良好であると報告されているが,手術手技そのものの困難さがあり,通常のTHAよりも神経損傷・弛み・異所性骨化・脱臼などの術後合併症リスクが高く,また,THA後のインプラントの生存率も,通常の初回THAと比較すると若干劣る。そのため,高い専門的技術が必要であること,通常のTHAよりも合併症率が高いことなどを十分に理解したうえで慎重に行う必要がある。

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J00282&link_issn=&doc_id=20220126080015&doc_link_id=%2Fap4kange%2F2022%2F004102%2F014%2F0189-0194%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fap4kange%2F2022%2F004102%2F014%2F0189-0194%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Language：Japanese

肺がん,大腸がん,乳がん,胃がん,肝がんを指して「5大がん」という.肺がんは,死亡率が1位のがんであり,喫煙との関連が非常に高いとされている.骨転移の頻度は高く,骨病変による疼痛を初発症状として発見される例もある.大腸がんは,女性における死亡率1位のがんであり,食事スタイルの欧米化に伴って患者数は増加し続けており,飲酒との関連も指摘されている.乳がんは女性で罹患数が1位である一方で,5年生存率は90%以上と高く,早期発見が重要ながんである.骨転移が多いことも特徴であり,骨病変に対しても適切な対応が求められる.胃がんは日本人に多く,食塩摂取量など食生活に関連するとされ,骨髄癌腫症を呈することもある.肝がんは,肝炎ウイルス感染が原因の肝細胞がんが90%を占めていたが,近年は非ウイルス性肝細胞がんが増加している.肝がんの骨転移は多血性であり,手術治療を選択するにあたっては慎重な対応が必要となる.(著者抄録)

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Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J01133&link_issn=&doc_id=20220208130009&doc_link_id=%2Ffj2ortho%2F2022%2F009601%2F010%2F0053-0062%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Ffj2ortho%2F2022%2F009601%2F010%2F0053-0062%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

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Language：Japanese

骨軟部腫瘍における免疫環境の研究は未開拓分野である。筆者らは肉腫の一部に自然寛解がみられることより、骨軟部腫瘍においても免疫環境が予後に影響を持つものと考え研究を続けている。これまでHLA class Iの腫瘍細胞おける発現、CD8陽性リンパ球、CD163陽性マクロファージ浸潤を解析してきたが、組織型ごとに特徴や予後に関する影響も異なっていた。今後はCAR-T細胞を用いた細胞療法等が新たな治療戦略になることを期待し研究を続けている。(著者抄録)

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Language：Japanese   Publisher：新潟整形外科研究会  

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Language：Japanese   Publisher：新潟整形外科研究会  

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Language：Japanese   Publisher：新潟整形外科研究会  

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Language：Japanese   Publisher：東北整形災害外科学会  

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Language：Japanese   Publisher：東北整形災害外科学会  

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

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

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

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Language：Japanese   Publisher：東北整形災害外科学会  

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Language：Japanese   Publisher：東北整形災害外科学会  

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

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

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Language：Japanese   Publisher：(株)南江堂  

＜文献概要＞はじめに 運動器に発生する腫瘍は,一般に骨・軟部腫瘍と称され,骨腫瘍は骨から発生し,軟部腫瘍は軟部組織から発生する腫瘍の総称である.全身のあらゆる部位に発生し,骨・軟骨・皮下・筋肉・脂肪・血管・腱・滑膜などに由来する間葉系腫瘍に末梢神経系腫瘍を加えたものと考えることができる.しかし,由来細胞がはっきりしない腫瘍も含まれ,これらの病理組織学的な分類は非常に多岐にわたる.腫瘍性疾患の診断は最終的には病理診断に頼ることになるが,診断する多くの病理医にとっても経験することが少ない疾患が多く,整形外科医との協働は重要である.そこで本稿では,小児の運動器に発生し,日常診療で遭遇する頻度の高い疾患を対象として解説する.

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

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

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

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Language：Japanese   Publisher：日本レックリングハウゼン病学会  

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Language：Japanese   Publisher：東日本整形災害外科学会  

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

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

J-GLOBAL

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

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

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

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

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

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

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

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

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

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Language：Japanese   Publisher：東北整形災害外科学会  

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Language：Japanese   Publisher：東北整形災害外科学会  

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Language：Japanese   Publisher：東北整形災害外科学会  

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Language：Japanese   Publisher：(NPO)日本緩和医療学会  

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

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

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

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Language：Japanese   Publisher：新潟整形外科研究会  

症例は6歳男児で、2歳時に多発性軟骨性外骨腫症と診断され、自覚症状なく経過観察した。3ヵ月前に家族が歩行時の躓きと右下垂足に気づいた。X線検査にて右腓骨頭部に骨軟骨腫増大を認めた。単純X線で右腓骨頭に骨髄腔と連続した腫瘤を認め、初診時と比較し増大していた。右脛腓骨遠位にも腫瘤を認めたが、足関節の内外反変形は認めなかった。単純CTで右腓骨頭前方外側に隆起性病変を認め、MRI造影T1強調脂肪抑制像およびT2強調脂肪抑制像で同部位に骨と同信号の腫瘤を認め、T2強調脂肪抑制像で腫瘤辺縁に軟骨帽と思われる約2mmの高信号域を認めた。右下垂足の原因として腓骨神経領域に一致した筋力低下と右腓骨頭部の骨軟骨腫増大を認めたことより、腓骨頭骨軟骨腫による腓骨神経圧迫を疑い、手術を施行した。腫瘍上に神経が多数分枝し、腫瘍の一塊での摘出は囲難と考え、断片的に腫瘤を摘出して神経の圧迫を解除した。腫瘤の病理診断は、骨軟骨腫であった。術後2ヵ月迄に下肢筋力は徐々に回復し、術後4ヵ月で走行も可能となった。

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

軟部腫瘍の診断は、問診、視診、触診といった基本的な診察を行ったあとに、MRIを中心とした画像検査を行い、最終的には組織生検により病理学的な診断を確定していく。しかし、疾患そのものに多様性があり、希少なものが多いため、これらの検査を行っても特徴的な所見が得られず、診断に難渋することもしばしばである。一方で、日常診療で目にすることが多い、脂肪腫やガングリオン、類上皮嚢胞(粉瘤)、神経鞘腫などにおいては、比較的特徴的な所見がみられる。よって、これらの良性腫瘍を診断する際に、自信を持ってしっかりと診断できることが重要であり、そうでないものは常に悪性の可能性を考慮して、早めに専門医へ相談するという姿勢が必要だろう。本稿では、良性軟部腫瘍診断においてピットフォールに陥らないための基本的なポイントを中心に解説する。(著者抄録)

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

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

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Language：Japanese   Publisher：東北整形災害外科学会  

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Language：Japanese   Publisher：東北整形災害外科学会  

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

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

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

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Language：Japanese   Publisher：(NPO)日本緩和医療学会  

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

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

膝痛は、極めて頻度の高い病態であるが、その原因は多岐にわたる。整形外科医が得意とする骨関節の損傷、変性、炎症による疾患だけでなく、血管性疾患や悪性疾患による膝痛、あるいは全身疾患の随伴症状の一つとして膝痛が生じることもある。このような疾患では膝の局所所見のみならず、全身的な病変や症状の確認、詳細な病歴の聴取が診断上の重要な手掛かりになる。本稿では膝痛をきたす疾患のうち、日常診療で見落としがちな「整形外科疾患以外の疾患」について取り挙げ、疾患の特徴について概説する。(著者抄録)

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

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

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