Perioperative Adriamycin plus ifosfamide vs. gemcitabine plus docetaxel for high-risk soft tissue sarcomas: randomised, phase II/III study JCOG1306.

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.

Standardization of evaluation method and prognostic significance of histological response to preoperative chemotherapy in high-grade non-round cell soft tissue sarcomas.

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).

Definitive radiation therapy in patients with unresectable desmoid tumors: a systematic review.

BACKGROUND: Desmoid tumors are rare soft tissue tumors. Wide local excision has been the standard surgical treatment for desmoid tumors. However, this procedure results in high local recurrence rates, so non-surgical treatments should be considered. The aim of this systematic review was to evaluate the effect of radiation therapy on patients with desmoid tumors, especially those with unresectable disease. METHODS: We evaluated studies published between 1 January 1990 and 31 August 2017 and cited in PubMed and Ichushi (in Japanese). All studies evaluating the effect of radiation therapy on desmoid tumors were included. Data regarding radiation dose, recurrence and adverse events were recorded. RESULTS: Among 218 identified studies, only 6 were finally included in this review. Local control was achieved in 253 of 317 patients with unresectable or unresected tumors who underwent definitive radiation therapy (the crude rate of local control was 79.8%). Toxicity was evaluated in patients who underwent definitive radiation therapy or surgery plus radiation therapy. One of the most common acute complications was skin toxicity. Frequent late complications of radiation therapy included fibrosis/contracture/joint stiffness, skin disorders, lymphedema and pain. Six patients developed secondary malignancies in the radiation field. CONCLUSIONS: In patients treated unsuccessfully with surgery, watchful waiting and pharmacotherapy, radiation therapy may be an option as salvage therapy because of the high rate of local control. Because desmoid tumors frequently develop in young individuals, children and young patients who receive radiation therapy for the treatment of desmoid tumors should be followed up on a long-term basis with periodic monitoring for late radiation toxicities.

Meniscal ramp lesions should be considered in anterior cruciate ligament-injured knees, especially with larger instability or longer delay before surgery.

PURPOSE: To determine the incidence of meniscal ramp lesions in an anterior cruciate ligament (ACL) injured knees and to clarify whether ramp lesions are related to chronic ACL deficiency and increased knee instability. METHODS: Consecutive ACL injured patients were evaluated arthroscopically for a ramp lesion via a trans-notch view and evidence of menisco-capsular injury was recorded. Other concomitant injuries to the knee were also noted. Incidence of meniscal ramp lesions, delay before surgery, and anterior-posterior stability was analyzed. All patients underwent bilateral KT-2000 evaluation. RESULTS: One hundred and three consecutive ACL injured patients with a mean age of 24 years were included in this study. In total, a ramp lesion was found in 10 knees (9.7%) via a trans-notch view. None of these lesions could be identified by the standard view from the anterolateral portal. Other medial meniscal lesions were found in 26 knees (25.2%) by standard arthroscopic viewing. The ramp lesion group had significantly longer delay before surgery with a median of 191 days (p < 0.01) as well as a larger side-to-side difference of KT-2000 measurement (7.3 ± 1.8 mm; p < 0.01), compared with the intact medial meniscus group (53 days and 5.5 ± 1.5 mm, respectively). CONCLUSION: Ramp lesions that were identified using a trans-notch view were not visualized with standard arthroscopic views. Increased anterior tibial translation and longer delay before surgery were seen in knees with ramp lesions. Careful inspection of the posteromedial menisco-capsular region is required as hidden menisco-capsular lesions may occur which may result in residual knee instability. LEVEL OF EVIDENCE: Level II.

Osteosarcoma in patients over 50 years of age: Multi-institutional retrospective analysis of 104 patients.

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.

Ten-year follow-up results of perioperative chemotherapy with doxorubicin and ifosfamide for high-grade soft-tissue sarcoma of the extremities: Japan Clinical Oncology Group study JCOG0304.

BACKGROUND: Soft-tissue sarcomas (STS) are rare malignant tumors those are resistant to chemotherapy. We have previously reported the 3-year follow-up result on the efficacy of perioperative chemotherapy with doxorubicin (DXR) and ifosfamide (IFM) for high-risk STS of the extremities (JCOG0304). In the present study, we analyzed the 10-year follow-up results of JCOG0304. METHODS: Patients with operable, high-risk STS (T2bN0M0, AJCC 6th edition) of the extremities were treated with 3 courses of preoperative and 2 courses of postoperative chemotherapy, which consisted of 60 mg/m2 of DXR plus 10 g/m2 of IFM over a 3-week interval. The primary study endpoint was progression-free survival (PFS) estimated by Kaplan-Meier methods. Prognostic factors were evaluated by univariable and multivariable Cox proportional hazards model. RESULTS: A total of 72 patients were enrolled between March 2004 and September 2008, with 70 of these patients being eligible. The median follow-up period was 10.0 years for all eligible patients. Local recurrence and distant metastasis were observed in 5 and 19 patients, respectively. The 10-year PFS was 65.7% (95% CI: 53.4-75.5%) with no PFS events being detected during the last 5 years of follow-up. The 10-year overall survival was 78.1% (95% CI: 66.3-86.2%). Secondary malignancy was detected in 6 patients. The subgroup analysis demonstrated that there was significant difference in survival with regard to primary tumor size. CONCLUSIONS: Only a few long-term results of clinical trials for perioperative chemotherapy treatment of STS have been reported. Our results demonstrate that the 10-year outcome of JCOG0304 for patients with operable, high-risk STS of the extremities was stable and remained favorable during the last 5 years of follow-up. TRIAL REGISTRATION: This trial was registered at the UMIN Clinical Trials Registry as C000000096 on August 30, 2005.

A randomized phase III trial of denosumab before curettage for giant cell tumor of bone: Japan Clinical Oncology Group Study JCOG1610.

A randomized phase III trial was planned to commence in October 2017. Resectable giant cell tumor of bone (GCTB) without possible postoperative large bone defect has been treated by curettage with local adjuvant treatment, with the local recurrence rate found to be as high as 24.6-30.8%. The aim of this study is to confirm the superiority of preoperative denosumab for patients with GCTB without possible postoperative large bone defect. A total of 106 patients will be accrued from 34 Japanese institutions over 5 years. The primary endpoint is relapse-free survival (RFS). Secondary endpoints include overall survival, joint-preserved survival, local RFS, metastasis-free survival, adverse events, serious adverse events, surgical and postoperative complications, and discontinuation of denosumab. This trial is conducted by the Bone and Soft Tissue Tumor Study Group in the Japan Clinical Oncology Group and has been registered in the UMIN Clinical Trials Registry as UMIN000029451 [http://www.umin.ac.jp/ctr/index.htm].

Periostin Promotes Scar Formation through the Interaction between Pericytes and Infiltrating Monocytes/Macrophages after Spinal Cord Injury.

Scar formation is a prominent pathological feature of traumatic central nervous system (CNS) injury, which has long been implicated as a major impediment to the CNS regeneration. However, the factors affecting such scar formation remain to be elucidated. We herein demonstrate that the extracellular matrix protein periostin (POSTN) is a key player in scar formation after traumatic spinal cord injury (SCI). Using high-throughput RNA sequencing data sets, we found that the genes involved in the extracellular region, such as POSTN, were significantly expressed in the injured spinal cord. The expression of POSTN peaked at 7 days after SCI, predominantly in the scar-forming pericytes. Notably, we found that genetic deletion of POSTN in mice reduced scar formation at the lesion site by suppressing the proliferation of the pericytes. Conversely, we found that recombinant POSTN promoted the migration capacity of the monocytes/macrophages and increased the expression of tumor necrosis factor-α from the monocytes/macrophages in vitro, which facilitated the proliferation of pericytes. Furthermore, we revealed that the pharmacological blockade of POSTN suppressed scar formation and improved the long-term functional outcome after SCI. Our findings suggest a potential mechanism whereby POSTN regulates the scar formation after SCI and provide significant evidence that POSTN is a promising therapeutic target for CNS injury.

Characteristics of patients with fragility hip fractures in the northern Kyushu district in Japan: a multicenter prospective registry based on an electronic data capture system.

Osteoporosis has become a worldwide public health problem, in part due to the fact that it increases the risk of fragility hip fractures (FHFs). The epidemiological assessment of FHFs is critical for their prevention; however, datasets for FHFs in Japan remain scarce. This was a multicenter, prospective, observational study in the northern district of Kyushu Island. Inclusion criteria were age > 60 years with a diagnosis of FHF and acquisition of clinical data by an electronic data capture system. Of 1294 registered patients, 1146 enrolled in the study. Nearly one third of patients (31.8%) had a history of previous fragility fractures. The percentage of patients receiving osteoporosis treatment on admission was 21.5%. Almost all patients underwent surgical treatment (99.1%), though fewer than 30% had surgery within 48 h after hospitalization. Bone mineral density (BMD) was evaluated during hospitalization in only 50.4% of patients. The rate of osteoporosis treatment increased from 21.5% on admission to 39.3% during hospitalization. The main reasons that prescribers did not administer osteoporosis treatment during hospitalization were forgetfulness (28.4%) and clinical judgment (13.6%). Age and female ratio were significantly higher in patients with previous FHFs than in those without. There was a significant difference in the rate of osteoporosis treatment or L-spine BMD values in patients with or without previous FHFs on admission. In conclusion, this study confirmed that the evaluation and treatment of osteoporosis and FHFs is still suboptimal in Japan, even in urban districts.

Prospective comparison of various radiological response criteria and pathological response to preoperative chemotherapy and survival in operable high-grade soft tissue sarcomas in the Japan Clinical Oncology Group study JCOG0304.

BACKGROUND: Soft tissue sarcomas (STS) are rare malignant tumors. The efficacy of preoperative chemotherapy for STS is evaluated using various tumor size-based radiological response criteria. However, it is still unclear which set of criteria would show the best association with pathological response and survival of the patients with STS. METHODS: We compared radiological responses to preoperative chemotherapy for operable STS by the Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST, World Health Organization criteria, Japanese Orthopaedic Association criteria, and modified Choi criteria and analyzed the association with pathological response and survival using the data from the Japan Clinical Oncology Group (JCOG) study JCOG0304, a phase II clinical trial evaluating the efficacy of perioperative chemotherapy for STS in the extremities. RESULTS: Seventy eligible patients in JCOG0304 were analyzed. The results demonstrated that none of the size-based radiological response criteria showed significant association with pathological response to preoperative chemotherapy for STS. The difference between overall survival of the patients assessed as partial response and stable disease/progressive disease by RECIST was not significant (hazard ratio 1.37, p = 0.63), and calculated C-index was 0.50. All other response criteria also could not exhibit significant association between radiological responses and survival. CONCLUSION: In the present study, none of the radiological response criteria analyzed demonstrated association of response to preoperative chemotherapy with pathological response or survival of the patients with operable STS. Further prospective investigation is required to develop criteria to evaluate not only tumor shrinkage but biological effects of preoperative chemotherapy for the patients with localized STS. TRIAL REGISTRATION: UMIN Clinical Trials Registry C000000096. Registered 30 August, 2005 (retrospectively registered).

Clinical outcome of primary giant cell tumor of bone after curettage with or without perioperative denosumab in Japan: from a questionnaire for JCOG 1610 study.

BACKGROUND: Giant cell tumor of bone (GCTB) is an intermediate tumor known to be locally aggressive, but rarely metastasizing. To plan a prospective study of GCTB, we performed a questionnaire survey for institutions participating in the Bone and Soft Tissue Tumor Study Group (BSTTSG) in the Japan Clinical Oncology Group (JCOG) in 2015. METHODS: We reviewed 158 consecutive patients with primary GCTB treated with curettage without perioperative denosumab from 2008 to 2010 in Japan. We investigated local and distant recurrence rates after definitive curettage. We also investigated the recurrence rate after treatment with preoperative and/or postoperative denosumab with curettage in recent years. There were 40 patients treated with perioperative denosumab, and the factors affecting recurrence in them were investigated. RESULTS: Answers were available from 24 of 30 institutions (80.0%) participating in JCOG BSTTSG. Thirty (19.0%) and 4 (2.5%) of 158 patients developed local and distant recurrence after curettage without perioperative denosumab from 2008 to 2010, respectively. Campanacci grade and embolization before surgery were significantly associated with increasing incidence of local recurrence after curettage (p = 0.034 and p = 0.022, respectively). In patients treated with perioperative desnosumab, 120 mg denosumab was administered subcutaneously for a median 6 (2-41) and 6 (1-14) times in preoperative and postoperative settings, respectively. The recurrence rates were 6 of 21 (28.6%), 2 of 9 (22.2%), and 0 of 10 (0.0%) in the preoperative, postoperative, and both pre- and postoperative denosumab treatment groups, respectively. With all of the preoperative treatments, administration exceeding five times was significantly associated with a decreased incidence of local recurrence after curettage (p < 0.001). CONCLUSION: The recurrence rate of GCTB was still high after curettage, especially in Campanacci grade III, and improvements in the therapeutic strategy are needed in this cohort. There is a possibility that a sufficient dose of preoperative denosumab can reduce recurrence after curettage. Recently, we have started a clinical trial, JCOG1610, to investigate the efficacy of preoperative denosumab in patients who can be treated with curettage in GCTB.

Nationwide multicenter follow-up cohort study of hip arthroplasties performed for osteonecrosis of the femoral head.

PURPOSE: To identify modifiable factors related to post-operative dislocation and reoperation in patients with osteonecrosis of the femoral head (ONFH) in a large cohort. METHODS: We studied 4995 hip arthroplasties: total hip arthroplasty (THA) was performed in 79% of patients; bipolar hemiarthroplasty (BP), 17%; total resurfacing arthroplasty (tRS), 3%; and hemi-resurfacing arthroplasty (hRS), 1%. A new type of BP (accounting for 49% of BPs) comprised a femoral component with a polished or smooth, small-diameter (approximately 10 mm) neck with a round or oval axial cut surface and no sharp corners. RESULTS: The infection rate was relatively low (0.56%) even though 58% of cases of ONFH were associated with systemic steroid use, a known risk factor for infection. Post-operative dislocation occurred in 4.3% of cases, with re-operation needed in 3.9%. The dislocation rate was related to surgery type: 5.2% in THA, 0.9% in BP, and 0% in tRS and hRS. Among total arthroplasties with six month or longer follow-up (3670 THAs and 159 tRSs), the risk factors for post-operative dislocation were younger (≤ 40 years) or older (≥ 62 years) age, higher body weight, posterolateral approach, and smaller prosthetic head diameter. Regarding the need for re-operation, higher body weight and surgery type were identified as risk factors. CONCLUSIONS: The relatively high dislocation rate of 5.2% in THA is a cause for concern. The identified risk factors for dislocation should be considered when selecting THA for treatment. Prosthesis survivorship in hRSs was inferior to that in BPs or THAs. Body weight also affected the survivorship of hip arthroplasties.

Tumor-induced osteomalacia caused by a massive phosphaturic mesenchymal tumor of the acetabulum: A case report.

We report a case of tumor-induced osteomalacia (TIO) caused by a massive phosphaturic mesenchymal tumor (PMT) of the acetabulum. A 68-year-old woman presented with progressive bone pain of the rib cage, and polyarthralgia and back pain for 3 years. She was diagnosed with hypophosphatemic osteomalacia because laboratory testing was remarkable for low serum phosphorus and a low level of 1,25(OH)2 vitamin D. Three years later, her hip radiograph revealed an osteolytic lesion of the acetabulum. Magnetic resonance imaging of the acetabulum showed a massive lesion. Laboratory data showed hypophosphatemia and an elevated serum level of fibroblast growth factor 23 (FGF-23). Samples obtained with open biopsy showed a low-grade spindle cell neoplasm with FGF-23 positivity, identified by using immunohistochemical staining, confirming the diagnosis of a PMT mixed connective tissue variant. Curettage of the tumor was performed, and the defects were filled with bone allografts. The hip joint was reconstructed with total hip arthroplasty using a Muller support ring. To our knowledge, this report represents the first documented case of massive PMT of the acetabulum causing TIO.

Phosphorylation of STAT3 in Undifferentiated Pleomorphic Sarcoma Is Correlated with a Favorable Prognosis.

OBJECTIVE: The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays a role in various biological processes. Phosphorylated STAT3 (p-STAT3) functions as a transcriptional factor, and suppressor of cytokine signaling 3 (SOCS3) is a potential inhibitor of STAT3. Here, we analyzed the status of the JAK-STAT pathway in undifferentiated pleomorphic sarcoma (UPS). METHODS: We performed immunohistochemistry in 79 samples of UPS and Western blotting in 10 frozen samples. We also examined alterations in protein expression in the JAK-STAT pathway after the inhibition of phosphorylated Akt (p-Akt) or extracellular signal-regulated kinase (p-Erk) in vitro. RESULTS: Immunohistochemically, p-STAT3 and SOCS3 were positive in 59.7 and 55.8%, respectively. Positivity for p-STAT3 was significantly correlated with a better prognosis (p = 0.0006) and negatively with SOCS3 expression (p = 0.0223). Positivity for SOCS3 was significantly correlated with a worse prognosis (p = 0.0001). Western blotting analysis revealed that p-STAT3 expression was lower in tumor than in normal tissue. In vitro results demonstrated that there was no detectable change in the expression of p-STAT3 regardless of the status of p-Akt or p-Erk. CONCLUSION: p-STAT3 may be a useful prognostic factor for UPS.

Comparison of graft bending angle during knee motion after outside-in, trans-portal and trans-tibial anterior cruciate ligament reconstruction.

PURPOSE: To determine graft bending angle (GBA) during knee motion after anatomic anterior cruciate ligament (ACL) reconstruction and to clarify whether surgical techniques affect GBA. Our hypotheses were that the graft bending angle would be highest at knee extension and the difference of surgical techniques would affect the bending steepness. METHODS: Eight healthy volunteers with a mean age of 29.3 ± 3.0 years were recruited and 3D MRI knee models were created at three flexion angles (0°, 90° and 130°). Surgical simulation of the tunnel drilling was performed with anatomic tunnel position using each outside-in (OI), trans-portal (TP) and trans-tibial (TT) techniques on the identical cases. The models were matched to other knee positions and the GBA in 3D was measured using computational software. Double-bundle ACL reconstruction was analysed first, and single-bundle reconstruction was also analysed to evaluate its effect to reduce GBA. A repeated-measures ANOVA was used to compare GBA difference at three flexion angles, by three techniques or of three bundles. RESULTS: GBA changed substantially with knee motion, and it was highest at full extension (p < 0.001) in each surgical technique. OI technique exhibited highest GBA for anteromedial bundle (94.3° ± 5.2°) at extension, followed by TP (83.1° ± 6.5°) and TT (70.0° ± 5.2°) techniques (p < 0.01). GBA for posterolateral bundle at extension were also high in OI (84.6° ± 7.4°), TP (83.0° ± 6.3°) and TT (77.2° ± 7.0°) techniques (n.s.). Single-bundle grafts did not decrease GBA compared with double-bundle grafts. In OI technique, a more proximal location of the femoral exit reduced GBA of each bundle at extension and 90° flexion. CONCLUSION: A significant GBA change with knee motion and considerably steep bending at full extension, especially with OI and TP techniques, were simulated. Although single-bundle technique did not reduce GBA as seen in double-bundle technique, proximal location of femoral exits by OI technique, with tunnels kept in anatomic position, was effective in decreasing GBA at knee extension and flexion. For clinical relevance, high stress on graft and bone interface has been suggested by steep GBA at full extension after anatomic ACL reconstruction. LEVEL OF EVIDENCE: Therapeutic study (prospective comparative study), Level II.

Comparison of the impact of closing wedge versus opening wedge high tibial osteotomy on proximal tibial deformity and subsequent revision to total knee arthroplasty.

PURPOSE: The purpose of this study was to assess the differences in proximal tibial deformity between closing wedge (CW) and opening wedge (OW) high tibial osteotomy (HTO) and their effects on the difficulty of total knee arthroplasty (TKA) conversion. METHODS: Surgical simulations of CW-HTO and OW-HTO were performed on the same 3D computer-aided design knee models reconstructed from computed tomographic datasets of patients (median age 77 years; range 55-87 years; 40 knees) with medial osteoarthritis or osteonecrosis, and proximal tibial deformities were analysed. Subsequent TKA conversion was simulated in both CW and OW models, and the interference between the tibial implant and endosteal cortex was assessed. RESULTS: The difference in the metaphyseal-diaphyseal angle in the CW-HTO and OW-HTO groups was 0.3° ± 0.2° (p < 0.001). The mechanical axis in the CW-HTO group was shifted laterally by 1.8 ± 1.1 mm relative to that in the OW-HTO group (p < 0.001) on the resection surface in TKA. Finally, the TKA tibial implant was substantially closer to the endosteal cortex in the CW-HTO group (mean 5.6 ± 1.6 mm) than to that in the OW-HTO group (mean 7.3 ± 1.6 mm) (p < 0.001). CONCLUSION: The difference in the post-operative angular deformities of the proximal tibia between CW-HTO and OW-HTO was considered to be clinically irrelevant. The risk of interference between TKA tibial implant and endosteal bone was greater after CW-HTO than after OW-HTO. For clinical relevance, the difference between the two techniques has little influence on subsequent TKA difficulty regarding the proximal tibial deformity, although preoperative planning is obligatory, particularly after CW-HTO, to prevent interference with the tibial implant. LEVEL OF EVIDENCE: II.

In vivo kinematic analysis of the glenohumeral joint during dynamic full axial rotation and scapular plane full abduction in healthy shoulders.

PURPOSE: The purpose of this study was to evaluate the kinematics of healthy shoulders during dynamic full axial rotation and scapular plane full abduction using three-dimensional (3D)-to-two-dimensional (2D) model-to-image registration techniques. METHODS: Dynamic glenohumeral kinematics during axial rotation and scapular plane abduction were analysed in 10 healthy participants. Continuous radiographic images of axial rotation and scapular plane abduction were taken using a flat panel radiographic detector. The participants received a computed tomography scan to generate virtual digitally reconstructed radiographs. The density-based digitally reconstructed radiographs were then compared with the serial radiographic images acquired using image correlations. These 3D-to-2D model-to-image registration techniques determined the 3D positions and orientations of the humerus and scapula during dynamic full axial rotation and scapular plane full abduction. RESULTS: The humeral head centre translated an average of 2.5 ± 3.1 mm posteriorly, and 1.4 ± 1.0 mm superiorly in the early phase, then an average of 2.0 ± 0.8 mm inferiorly in the late phase during external rotation motion. The glenohumeral external rotation angle had a significant effect on the anterior/posterior (A/P) and superior/inferior (S/I) translation of the humeral head centre (both p < 0.05). 33.6 ± 15.6° of glenohumeral external rotation occurred during scapular plane abduction. The humeral head centre translated an average of 0.6 ± 0.9 mm superiorly in the early phase, then 1.7 ± 2.6 mm inferiorly in the late phase, and translated an average of 0.4 ± 0.5 mm medially in the early phase, then 1.6 ± 1.0 mm laterally in the late phase during scapular plane abduction. The humeral abduction angle had a significant effect on the S/I and lateral/medial (L/M) translation of the humeral head centre (both p < 0.05). CONCLUSION: This study investigated 3D translations of the humerus relative to the scapula: during scapular plane full abduction, the humerus rotated 33.6° externally relative to the scapula, and during external rotation motion in the adducted position, the humeral head centre translated an average of 2.5 mm posteriorly. Kinematic data will provide important insights into evaluating the kinematics of pathological shoulders. For clinical relevance, quantitative assessment of dynamic healthy shoulder kinematics might be a physiological indicator for the assessment of pathological shoulders.

The Anteroposterior Axis of the Proximal Tibia Can Change After Tibial Resection in Total Knee Arthroplasty: Computer Simulation Using Asian Osteoarthritis Knees.

BACKGROUND: We evaluated the effect of cutting surface on the anteroposterior (AP) axis of the proximal tibia using a 3-dimensional (3D) bone model to ensure proper tibial rotational alignment in total knee arthroplasty. METHODS: 3D bone models were reconstructed from the preoperative computed tomography data of 93 Japanese osteoarthritis knees with varus deformity. The AP axis was defined as the perpendicular bisector of the medial and lateral condylar centers in a 3D coordinate system. Bone cutting of the proximal tibia was performed with various tibial posterior slopes (0°, 3°, 7°) to the mechanical axis, and we compared the AP axes before and after bone cutting. RESULTS: The AP axis before bone cutting crossed a point at about 16% (one-sixth) of the distance from the medial edge of the patellar tendon at its tibial attachment. The AP axis after bone cutting was significantly internally rotated at all posterior slopes: 4.1° at slope 0°, 3.0° at slope 3°, and 2.1° at slope 7°. The percentages of cases with differences of more than 3° or 5° were 66.7% and 34.4% at slope 0°, 53.8% and 24.7% at slope 3°, and 38.3% and 11.8% at slope 7°, respectively. CONCLUSION: The AP axis of the proximal tibia may be rotated internally after resection of the proximal tibia in total knee arthroplasty. Hence, surgeons should recognize the effect of changes in the cutting surface on rotational alignment of the proximal tibia.

Radiological morphology variances of transient osteoporosis of the hip.

BACKGROUND: Although several morphological abnormalities or variances of the hip joint have been proposed to be associated with hip joint degeneration, few studies have investigated any radiological features in patients with transient osteoporosis of the hip (TOH). The purpose of this study is to evaluate the morphological variances of the hip joint in TOH patients radiographically. METHODS: The TOH group consisted of 31 hips in 31 patients. Age- and gender-matched asymptomatic hips in patients with unilateral osteonecrosis of the femoral head were served as controls. Radiographs and MRI were utilized to examine the following parameters: acetabular dysplasia, acetabular overcoverage, acetabular retroversion, and asphericity of the femoral head-neck junction. Also, localization of the main bone marrow edema (BME) lesion was investigated. RESULTS: TOH patients had a significantly higher incidence of acetabular retroversion (52% with a positive cross-over sign and 29% with posterior wall deficiency) than the controls (13%, P = 0.0023; 6%, P = 0.043, respectively), which was also confirmed by smaller acetabular anteversion angles on axial MRI. In addition, TOH patients tended to show asphericity of the anterior femoral head-neck junction compared to controls (39% vs. 13%, P = 0.040). In 90% of the TOH patients, the main BME lesion was located in the subchondral area of the superior portion of the femoral head, and 77% of the lesion were recognized as a band-like pattern in MRI. CONCLUSIONS: Acetabular retroversion and asphericity of the femoral head-neck junction were more commonly observed in TOH patients compared to controls. The main BME lesion was most frequently located in the superior portion of the femoral head.

Is the timing of surgery associated with avascular necrosis after unstable slipped capital femoral epiphysis? A multicenter study.

BACKGROUND: An unstable slipped capital femoral epiphysis (SCFE) is associated with a high rate of avascular necrosis (AVN). The etiology of AVN seems to be multifactorial, although it is not thoroughly known. The aims of our study were to determine the rate of AVN after an unstable SCFE and to investigate the risk factors for AVN, specifically evaluating the notion of an "unsafe window", during which medical interventions would increase the risk for AVN. METHODS: This retrospective multicenter study included 60 patients with an unstable SCFE diagnosed between 1985 and 2014. Timing of surgery was evaluated for three time periods, from acute onset of symptoms to surgery: period I, <24 h; period II, between 24 h and 7 days; and period III, >7 days. Multivariate logistic regression analysis was used to identify risk factors for AVN. RESULTS: Closed reduction and pinning was performed in 43 patients and in situ pinning in 17. Among these cases, 16 patients (27%) developed AVN. The rate of AVN was significantly higher in patients treated by closed reduction and pinning (15/43, 35%) than in those treated by in situ pinning (1/17, 5.9%) (p = 0.022). In patients treated by closed reduction and pinning, the incidence of AVN was 2/11 (18%) in period I, 10/13 (77%) in period II and 3/15 (20%) in period III, showing the significantly higher rate in period II (p = 0.002). The surgery provided in period II was identified as an independent risk factor for the development of AVN. CONCLUSIONS: Our rate of AVN was 27% using two classical treatment methods. Time-to-surgery, between 24 h and 7 days, was independently associated with AVN, supporting the possible existence of an "unsafe window" in patients with unstable SCFE treated by closed reduction and pinning.