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Background: The purpose of this study was to prospectively observe the trends of ultrashort echo time (UTE)-T2* values for the intraarticular and intraosseous regions of reconstructed anterior cruciate ligaments from 6 to 12 months after anterior cruciate ligament reconstruction by using UTE-T2* mapping, and to investigate the changes and differences over time in each region. Methods: Ten patients underwent UTE-T2* mapping of the operated knee at 6, 9, and 12 months after anterior cruciate ligament reconstruction. The UTE-T2* values of intraarticular and intraosseous regions of reconstructed anterior cruciate ligaments at 6, 9, and 12 months postoperatively were statistically compared. Results: The UTE-T2* values of the intraarticular region at 6 months postoperatively were significantly higher than those at 9 and 12 months. There were no significant differences in the UTE-T2* values at 6, 9, and 12 months postoperatively in the intraosseous region. At 6 months postoperatively, the UTE-T2* values of the intraarticular region were significantly higher than those of the intraosseous region. The UTE-T2* values of the intraosseous region at the tibia were significantly lower than those of the other sites at any postoperative time point. Conclusions: According to UTE-T2*mapping-based findings, histological maturation of reconstructed ACLs is faster in the intraosseous region than in the intraarticular region. In particular, the intraarticular region is still undergoing rapid histologic changes at 6 months postoperatively, and its tissue structure is less substantial than normal. The findings of this study may provide clues to determine the optimal timing for safe return to sports in terms of ligamentaization of reconstructed ACLs. [ABSTRACT FROM AUTHOR]

This study was conducted to investigate the incidence of lumbar degeneration findings and low back pain (LBP) in children and adolescent weightlifters using magnetic resonance imaging (MRI) and medical questionnaires over a 5-year period. Moreover, we aimed to reveal the temporal changes in the lumbar vertebrae caused by long-term weightlifting training during the growth period. Twelve children and adolescent weightlifters who participated in weightlifting for >2 years (six boys, six girls, 11.4±2.0 years) were enrolled. Participants underwent annual medical questionnaire surveys, including data on practice frequency, competition history, presence of LBP, and lumbar examinations using MRI during the 5-year follow-up. Lumbar disc degeneration was detected in all the participants after 4 years, and lumbar disc herniation findings were detected in 33% of participants after 5 years; one underwent herniotomy during the follow-up period. Lumbar spondylolysis was detected in 58% of patients at 5 years. Although there were three participants who had LBP in the final year, none had LBP that prevented them from returning to weightlifting. This 5-year cohort study of 12 children and adolescent weightlifters detected lumbar degeneration in all participants. High frequency weightlifting training over a long period during the growth period may increase the risk of developing current and future LBP. [ABSTRACT FROM AUTHOR]

Background: Low back pain (LBP) and decreased mobility function are common problem among older people. Muscle weakness has been reported as a risk factor for these conditions, and exercise therapy can improve them. We created a novel exercise device that also measures abdominal trunk muscle strength. Malnutrition has also emerged as a major problem among older people. Muscle is a direct key linking decreased mobility function and malnutrition. This study aimed to examine the associations of LBP with not only decreased physical function and muscle weakness but also nutritional status of older people. Methods: We examined the associations of LBP with muscle weakness, decreased mobility function (locomotive syndrome [LS]), and malnutrition among older women. The study included 101 female patients aged 60 years or older scheduled to undergo surgery for degenerative lower extremity diseases. Preoperatively, physical tests including abdominal trunk muscle strength assessment using the device and laboratory tests were conducted. Subjects with LBP (numerical rating scale ≥2; range, 0–4) during the preceding month were allocated to the LBP group (n = 36). Other subjects were allocated to the non-LBP group (n = 65). Results: The LBP group had lower abdominal trunk and knee extensor muscle strength, lower serum albumin, and hemoglobin levels as blood biomarkers associated with malnutrition risk, and higher LS test scores than the non-LBP group. A multivariate analysis showed that abdominal trunk muscle weakness and advanced LS were associated with LBP. LBP intensity was negatively correlated with abdominal trunk and knee extensor muscle strength and positively correlated with the LS test score. The serum hemoglobin level was negatively correlated with the LS test score. Conclusion: Abdominal trunk muscle weakness and decreased mobility function were associated with LBP among older women. [ABSTRACT FROM AUTHOR]

Objectives: Soft tissue wounds with exposed bone often require extended healing times and can be associated with severe complications. We describe the ability of artificial dermis with autogenic adipose-derived stem cells (ADSCs) to promote the healing of wounds with exposed bone in a rat model. Methods: Adipose tissues harvested from the bilateral inguinal regions of Wistar rats were used as ADSCs. Rats were randomly divided into control and ADSC groups to investigate the efficacy of ADSC transplantation for wound healing (n = 20 per group). Soft tissue defects were created on the heads of the rats and were covered with artificial dermis with or without the seeded ADSCs. Specimens from these rats were evaluated using digital image analysis, histology, immunohistochemistry, cell labeling, and real-time reverse-transcription polymerase chain reaction (real-time RT-PCR). Results: The average global wound area was significantly smaller in the ADSC group than in the control group on days 3, 7, and 14 after surgery (p<0.05). After 14 days, the blood vessel density in the wound increased by 1.6-fold in the ADSC group compared with that in the control group (p<0.01). Real-time RT-PCR results showed higher Fgfb and Vegf expression levels at all time points, and higher Tgfb1 and Tgfb3 expression levels until 14 days after surgery in the ADSC group than in the control group (p<0.05). Conclusions: In wounds with exposed bone, autogenic ADSCs can promote vascularization and wound healing. Use of this cell source has multiple benefits, including convenient clinical application and lack of ethical concerns. [ABSTRACT FROM AUTHOR]

In the present study, we investigated whether both adipose-derived stem cell (ADSC) and osteogenic-induced ADSC sheets could promote bone healing in a rat distal femoral metaphysis bone defect model. A through-hole defect of 1 mm diameter was drilled into each distal femur of 12 week old rats. Forty-five rats were randomly assigned to three groups: (1) control group; (2) ADSC sheet group; or (3) osteogenic-induced ADSC sheet group. We evaluated each group by analysis of computerized tomography scans every week after the surgery, histological analysis, and DiI labeling (a method of membrane staining for post implant cell tracing). Radiological and histological evaluations showed that a part of the hole persisted in the control group at four weeks after surgery, whereas the hole was restored almost completely by new bone formation in both sheet groups. The mean value of bone density (in Houndsfield units) for the bone defect area was significantly higher in both sheet groups than that in the control group (p = 0.05) at four weeks postoperative. A large number of osteocalcin positive osteoblasts were observed at the area of bone defect, especially in the osteogenic-induced ADCS sheet group. DiI labeling in the newly formed bone showed that each sheet had differentiated into bone tissue at four weeks after surgery. The ADSC and the osteogenic-induced ADSC sheets promoted significantly quicker bone healing in the bone defect. Moreover, the osteogenic-induced ADSC sheet may be more advantageous for bone healing than the ADSC sheet because of the higher number of osteocalcin positive osteoblasts via the transplantation. [ABSTRACT FROM AUTHOR]

Purpose: During total knee arthroplasty, few rotating reference axes can be reliably used after tibial resection. We speculated that a line that passes through the lateral edge of the posterior cruciate ligament (PCL) at its tibial attachment after resection and the most prominent point of the tibial tubercle [after-tibial resection (ATR) line] will provide a good reference axis. In this study, we aimed to evaluate the association between ATR and Akagi’s lines. Materials and methods: In this case–control simulation study, we retrospectively evaluated 38 patients with varus knee and 28 patients with valgus knee. We defined the reference cutting plane as 10 mm distal from the lateral articular surface of the tibia in varus group and as 7 mm distal from the medial articular surface in the valgus group. We measured angles between Akagi’s line and the ATR line (ATR line angle) as well as between Akagi’s line and 1/3 Akagi’s line (1/3 Akagi’s line angle), which passes through the midpoint of PCL and the medial third of the patellar tendon. We used paired t-tests to determine the significance of differences between these angles, with p < 0.05 indicating statistical significance. Intra- and interclass correlation coefficients for the reproducibility of 1/3 Akagi’s line angle and ATR line angle were analyzed by two surgeons. Results: We found that 1/3 Akagi’s line angle was 10.2° ± 1.3° in the varus group and 10.9° ± 1.3° in the valgus group (p = 0.017). The ATR line was positioned externally compared with Akagi’s line in all patients. Mean ATR line angles at 0°, 3° and 7° posterior slopes were 6.1° ± 1.9°, 5.8° ± 2.0° and 6.0° ± 1.7° in the varus group and 6.3° ± 2.3°, 6.2° ± 2.3° and 5.4° ± 2.1° in the valgus group, respectively. There were no significant differences in the ATR line angle between the varus and valgus groups. (p = 0.34–0.67) Intra- and interclass correlation coefficients for the reproducibility of 1/3 Akagi’s line angle were 0.936 and 0.986 and those for the reproducibility of ATR line angle were 0.811 and 0.839. Conclusions: The ATR line was positioned between Akagi’s line and 1/3 Akagi’s line in all patients and was a valid option for evaluating rotational tibial alignment after tibial resection. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this three-year cohort study was to assess the incidence rates and characteristics of abnormal lumbar findings and low back pain (LBP) in child and adolescent weightlifting athletes using magnetic resonance imaging (MRI) and medical questionnaires. This study evaluated subclinical sports injuries, which in turn may help prevent competition-specific injuries and improve performance levels. Materials and methods: Between 2014 and 2016, twelve participants who had been competing in weightlifting events for at least 2 years were enrolled in this study. The mean age of the participants at the start of this study was 11.4 ± 2.0 years, and there were 6 boys and 6 girls. Annual medical questionnaire surveys and lumbar examinations using MRI were performed during the 3-year follow-up. The incidence rates and variations of LBP and abnormal MRI findings were evaluated. Results: At the start of this study, there were no positive findings of LBP, and abnormal lumbar findings on MRI were observed in only 2 participants. At the 2-year follow-up, 1 participant had LBP, and 8 of 12 participants had abnormal lumbar findings. In the final year, only 3 participants had LBP; however, abnormal lumbar findings were observed on MRI in 11 participants. Among these, lumbar spondylolysis was observed in 4 participants, lumbar disc protrusion or extrusion in 2 participants, and lumbar disc degeneration in 9 participants. Conclusion: This prospective 3-year cohort study of 12 child and adolescent weightlifters revealed abnormal lumbar findings in 11 participants at a high rate on MRI examination. Children and adolescents undergoing resistance training at the competition level could potentially have irreversible changes in the lumbar vertebra without symptoms. [ABSTRACT FROM AUTHOR]

Purpose: Radio-hyperthermo-chemo (RHC) therapy, which combines radiotherapy, hyperthermia, and chemotherapy, for malignant soft tissue tumors has been introduced with the aim of decreasing the possibility of local recurrence after surgery. To avoid unnecessary neoadjuvant therapy and to plan the appropriate surgical treatment, surveillance of RHC therapeutic efficacy during treatment is necessary. In this study, we determined the optimal response criteria to evaluate the efficacy of RHC by comparing preoperative images before and after RHC with pathological evaluation of necrosis in the resected tumor. Patients and methods: From 2004 to 2014, 20 patients were enrolled into this study. Needle biopsy revealed 6 cases of myxoid liposarcoma, 6 cases of undifferentiated pleomorphic sarcoma, 4 cases of myxofibrosarcoma, and 4 cases of synovial sarcoma. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST, we calculated the responses to RHC therapy by comparing pre- and post-RHC therapy images. In addition, resected specimens underwent pathological analysis to evaluate response based on tumor necrosis. The correlation between assessment based on preoperative images and resected tumors were evaluated by the Spearman’s rank-order correlation coefficient. Result: From the surgical specimens, pathological assessment of necrosis in resected tumor were assessed as less than 50% (2 cases), 50–90% (9 cases), 90–99% (6 cases), and total necrosis (3 cases). Use of the RECIST 1.1 underestimated good responders as stable disease (SD) or progressive disease (PD) in 5 out of 15 cases; on the other hand, use of the modified RECIST did not underestimate the pathological assessment of necrosis. The correlations between responses based on preoperative images and those based on histological assessments were 0.23 (RECIST 1.1) and 0.76 (modified RECIST). Conclusion: Because pathological responses can be underestimated using the RECIST 1.1, the modified RECIST, which take into consideration tumor viability, as assessed by contrast MRI, should also be considered when evaluating the efficacy of RHC. [ABSTRACT FROM AUTHOR]

Our aim was to compare the process of bone formation after reconstruction of the vertebral body using a titanium cage with either a liquid nitrogen-treated (frozen) bone autograft or non-treated fresh bone autograft. Twelve canine beagles underwent anterior reconstruction of the 5th lumbar vertebrae using a titanium cage and bone autograft. Bone formation was compared across four experimental groups: fresh bone autograft groups, with animals sacrificed at either 8 or 16 weeks post-reconstruction, and liquid nitrogen-treated (frozen) bone autograft groups, with animals again sacrificed at either 8 or 16 weeks post-reconstruction. Bone formation was evaluated histologically by calculating the proportion of ‘reaction’ and ‘mature bone’ regions at the ends of the cage, its center, and ventral/dorsal sides. The reaction region contained osteocytes with a nucleus and osteoblasts accumulated on the surface of an osteoid, while a laminar structure was visible for mature bone regions. For fresh bone autografts, the reaction and mature bone regions significantly increased from 8 to 16 weeks post-reconstruction. By comparison, for frozen autografts, the reaction bone region did not significantly increase from 8 to 16 weeks post-reconstruction, while the mature bone region did increase over this time period. The proportion of reaction bone was higher at the ends and dorsal side of the cage at 8 weeks, for both graft types, with greater bone formation at the center of the cage at 16 weeks only for the fresh bone autograft. Therefore, bone formation in the anterior spinal reconstruction site tended to be delayed when using a frozen bone autograft compared to a fresh bone autograft. The bone formation process, however, was similar for both groups, beginning at the ends and dorsal side of the cage adjacent to the surrounding vertebral bone. [ABSTRACT FROM AUTHOR]

Background: Postoperative deep infection after bone tumor surgery remains a serious complication. Although there are numerous reports about risk factors for postoperative deep infection in general surgery, there is only a small number of reports about those for bone tumor surgery. This retrospective study aimed to identify risk factors for postoperative deep infection after bone tumor resection. Methods: We reviewed data of 681 patients (844 bone tumors) who underwent surgery. Associations between variables, including age, recurrent tumor, pathological fracture, surgical site (pelvis/other), chemotherapy, biological reconstruction, augmentation of artificial bone or bone cement, the use of an implant, intraoperative blood loss, operative time, additional surgery for complications, and postoperative deep infection were evaluated. Results: The rate of postoperative deep infection was 3.2% (27/844 tumors). A pelvic tumor (odds ratio [OR]: 3.4, 95% confidence interval [CI]: 1.0–11.3) and use of an implant (OR: 9.3, 95% CI: 1.9–45.5) were associated with an increased risk of deep infection. Conclusions: This retrospective study showed that pelvic tumor and use of an implant were independent risk factors for deep infection. This information will help surgeons prepare an adequate surgical plan for patients with bone tumors. [ABSTRACT FROM AUTHOR]

Background: Exercise is one of the few treatments that provide significant improvements in chronic low back pain (CLBP). We developed an innovative exercise device for abdominal trunk muscles. This device can be used in a sitting or standing position and contains a built-in system to measure abdominal trunk muscle strength. We examined whether subjects can adequately use the device to perform the exercises and measure their abdominal trunk muscle strength. Methods: We collected data on the body height, body weight, body mass index, and girth of 30 healthy male volunteers, and measured their grip power and trunk extensor muscle strength using a dynamometer. The volunteers performed a sit-up test as an indicator of trunk flexor muscle strength, and we measured their abdominal muscle strength using the device. We then evaluated the correlations between abdominal trunk muscle strength and anthropometric parameters as well as the strength of other muscles. In subsequent tests, 5 of the 30 subjects participated in two positron emission tomography (PET) series consisting of examinations after a resting period (control study) and during exercise (exercise study). For the exercise study, the subjects performed 2 sets of exercises for 20 minutes using the device before and after an injection of 18F-fluorodeoxyglucose (FDG). PET-computed tomography images were obtained 60 minutes after FDG injection in each study. We compared the skeletal muscle metabolism of the participants in both studies using the standardized uptake value. Results: The muscle strength measured by the device and the 30-second sit-up frequency were correlated. FDG accumulation within the diaphragm and abdominal rectus muscles was significantly higher in the exercise study. Conclusion: Our innovative exercise device facilitates a coordinated contraction of the abdominal trunk muscles at the anterior aspect and the roof of the core, and enables subjects to measure the strength of these muscles. [ABSTRACT FROM AUTHOR]

Purpose: Spinal surgery in a previously irradiated field carries increased risk of perioperative complications, such as delayed wound healing or wound infection. In addition, adhesion around the dura mater is often observed clinically. Therefore, similar to radiation-induced fibrosis—a major late-stage radiation injury in other tissue—epidural fibrosis is anticipated to occur after spinal radiation. In this study, we performed histopathologic assessment of postirradiation changes in the spinal dura mater and peridural tissue in mice. Materials and Methods: The thoracolumbar transition of ddY mice was irradiated with a single dose of 10 or 20 Gy. After resection of the irradiated spine, occurrence of epidural fibrosis and expression of transforming growth factor beta 1 in the spinal dura mater were evaluated. In addition, microstructures in the spinal dura mater and peridural tissue were assessed using an electron microscope. Results: In the 20-Gy irradiated mice, epidural fibrosis first occurred around 12 weeks postirradiation, and was observed in all cases from 16 weeks postirradiation. In contrast, epidural fibrosis was not observed in the nonirradiated mice. Compared with the nonirradiated mice, the 10- and 20-Gy irradiated mice had significantly more overexpression of transforming growth factor beta 1 at 1 week postirradiation and in the late stages after irradiation. In microstructural assessment, the arachnoid barrier cell layer was thinned at 12 and 24 weeks postirradiation compared with that in the nonirradiated mice. Conclusion: In mice, spinal epidural fibrosis develops in the late stages after high-dose irradiation, and overexpression of transforming growth factor beta 1 occurs in a manner similar to that seen in radiation-induced fibrosis in other tissue. Additionally, thinning of the arachnoid barrier cell layer was observed in the late stages after irradiation. Thus, consideration should be given to the possibility that these phenomena can occur as radiation-induced injuries of the spine. [ABSTRACT FROM AUTHOR]

It is important to differentially diagnose thigh pain from lumbar spinal stenosis (particularly lumbar fourth nerve root radiculopathy) and osteoarthritis of the hip. In this study, using a treadmill and a motion analysis method, gait characteristics were compared between these conditions. Patients with lumbar fourth nerve root radiculopathy had increased physiological knee flexion immediately after foot-ground contact, possibly owing to a slight decrease in the muscle strength of the quadriceps femoris muscle. Patients with osteoarthritis of the hip had decreased range of motion of the hip joint probably due to anatomically limited mobility as well as gait strategy to avoid pain resulting from increased internal pressure on the hip joint during its extension. Our facile and noninvasive method can be useful for the differential diagnosis of lumbar spinal canal stenosis from osteoarthritis of the hip. [ABSTRACT FROM AUTHOR]

Background: In total en bloc spondylectomy (TES) of upper thoracic spine including the second thoracic (T2) vertebra, T2 nerve roots are usually transected. In this study, we examined the association between transection of the T2 nerve roots and upper-extremity motor function in patients with upper thoracic TES. Methods: We assessed 16 patients who underwent upper thoracic TES with bilateral transection of the T2 nerve roots. Patients were divided into three groups: 3 patients without any processing of T1 and upper nerve roots (T2 group), 7 with extensive dissection of T1 nerve roots (T1–2 group), and 6 with extensive dissection of T1 and upper nerve roots (C–T2 group). Postoperative upper-extremity motor function was compared between the groups. Results: Postoperative deterioration of upper-extremity motor function was observed in 9 of the 16 patients (56.3%). Three of the 7 patients in the T1–2 group and all 6 patients in the C–T2 group showed deterioration of upper-extremity motor function, but there was no deterioration in the T2 group. In the T1–2 group, 3 patients showed mild deterioration that did not affect their activities of daily living and they achieved complete recovery at the latest follow-up examination. In contrast, severe dysfunction occurred frequently in the C–T2 group, without recovery at the latest follow-up. Conclusions: The transection of the T2 nerve roots alone did not result in upper-extremity motor dysfunction; rather, the dysfunction is caused by the extensive dissection of the T1 and upper nerve roots. Therefore, transection of the T2 nerve roots in upper thoracic TES seems to be an acceptable procedure with satisfactory outcomes. [ABSTRACT FROM AUTHOR]

Background: Scapulectomy requires not only joint resection but also wide resection of the shoulder girdle muscles. Even the significance of reconstruction has not yet been determined because of the difficulties in comparing the different conditions. The purpose of this study was to investigate factors that influence functional outcomes after scapulectomy in a multicenter study. Methods: This retrospective study comprised 48 patients who underwent total or subtotal scapulectomy and were followed for at least one year after surgery. Patients were registered at the Japanese Musculoskeletal Oncology Group affiliated hospitals. Soft tissue reconstruction for joint stabilization was performed when there was enough remaining tissue for reconstruction of the rotator cuff and tendons. In 23 cases, humeral suspension was performed. The average follow-up period was 61.9 months. Multivariate analysis was performed using the patient’s background to determine which factors influence the Enneking functional score or active range of motion. Results: The average functional score was 21.1 out of 30. Active shoulder range of motion was 42.7 degree in flexion, 39.7 degree in abduction, 49.6 degree of internal rotation and 16.8 degree of external rotation. The amount of remaining bone influenced functional outcome, which means that preserving the glenoid or the acromion lead to better function compared to total scapulectomy (p<0.01). Factors that influenced each functional measure include the amount of remaining bone, soft tissue reconstruction, the length of the resected humerus and nerve resection (p<0.05). Conclusion: Although shoulder function was almost eliminated following total or subtotal scapulectomy, minimal resection of bone, and soft tissue reconstruction should lead to better function. [ABSTRACT FROM AUTHOR]

Background: Total en bloc spondylectomy (TES) is associated with a high complication rate because it is technically demanding and involves patients compromised by cancer. Specifically, perioperative complications are more likely to occur in patients receiving preoperative irradiation. We examined the perioperative complications associated with TES in patients receiving preoperative irradiation. Methods: Seventy-seven patients underwent TES between May 2010 and April 2013. We performed a retrospective review of prospectively collected data for 50 patients with metastatic tumors of the thoracic spine, excluding patients with primary spinal tumors, lumbar spinal metastasis, and combined anterior and posterior approach TES. Patients were divided into 2 groups: those with preoperative irradiation (RT-TES group, 18 patients) and those without preoperative irradiation (TES group, 32 patients). The following perioperative complications, occurring within 2 months of surgery, were compared between the groups: intraoperative dural injuries, epidural hematomas, deep surgical-site infections, postoperative cerebrospinal fluid leakage, wound dehiscence, pleural effusions, and neurological deficits. Results: Significant differences in patient characteristics were not observed between the RT-TES and TES groups. Perioperative TES complications occurred in 20/50 patients (40.0%). The complication rate in the RT-TES group was 77.8% (14 out of 18), threefold higher than the 18.8% (6 out of 32) in the TES group (P<0.01). The incidence of complications, including intraoperative dural injuries, postoperative cerebrospinal fluid leakage, wound dehiscence, and pleural effusions, was significantly higher in the RT-TES group (P<0.01). Conclusion: The perioperative complication rate associated with TES for spinal metastasis was significantly higher among patients receiving preoperative irradiation than among those not receiving preoperative irradiation. [ABSTRACT FROM AUTHOR]

Background: A number of publications have reported that adipose derived stem cells (ADSCs) have the capacity to be induced to differentiate into osteoblasts both in vitro and in vivo. However, it has been difficult to use separate ADSCs for cortical bone regeneration and bone reconstruction so far. Inspired by the research around stromal stem cells and cell sheets, we developed a new method to fabricate ADSCs sheets to accelerate and enhance the bone regeneration and bone reconstruction. Purpose: To fabricate ADSCs sheets and evaluate their capacity to be induced to differentiate to osteoblasts in vitro. Methods: Human adipose derived stem cells (hADSCs) were employed in this research. The fabricating medium containing 50 µM ascorbate-2-phosphate was used to enhance the secretion of collagen protein by the ADSCs and thus to make the cell sheets of ADSCs. As the separate ADSCs were divided into osteo-induction group and control group, the ADSCs sheets were also divided into two groups depending on induction by osteogenesis medium or no induction. The osteogenic capacity of each group was evaluated by ALP staining, Alizarin Red staining and ALP activity. Results: The ADSCs sheets were fabricated after one-week culture in the fabricating medium. The ALP staining of ADSCs sheets showed positive results after 5 days osteo-induction and the Alizarin Red staining of ADSCs sheets showed positive results after 1 week osteo-induction. The ALP activity showed significant differences between these four groups. The ALP activity of ADSCs sheets groups showed higher value than that of separate ADSCs. Conclusion: The experiments demonstrated that ADSCs sheets have better capacity than separate ADSCs to be induced to differentiate into osteoblasts. This indicates that it is possible to use the ADSCs sheets as a source of mesenchymal stem cells for bone regeneration and bone reconstruction. [ABSTRACT FROM AUTHOR]

Purpose: This study investigated the effect of the FIFA 11+ warm-up program on whole body muscle activity using positron emission tomography. Methods: Ten healthy male volunteers were divided into a control group and a group that performed injury prevention exercises (The 11+). The subjects of the control group were placed in a sitting position for 20 min and 37 MBq of 18F-fluorodeoxyglucose (FDG) was injected intravenously. The subjects then remained seated for 45 min. The subjects of the exercise group performed part 2 of the 11+for 20 min, after which FDG was injected. They then performed part 2 of the 11+for 20 min, and rested for 25 min in a sitting position. Positron emission tomography-computed tomography images were obtained 50 min after FDG injection in each group. Regions of interest were defined within 30 muscles. The standardized uptake value was calculated to examine the FDG uptake of muscle tissue per unit volume. Results: FDG accumulation within the abdominal rectus, gluteus medius and minimus were significantly higher in the exercise group than in the control group (P<0.05). Conclusion: The hip abductor muscles and abdominal rectus were active during part 2 of the FIFA 11+ program. [ABSTRACT FROM AUTHOR]

Background: A variety of surgical procedures are now available for tissue reconstruction after osteosarcoma excision, and an important prognostic factor is the evaluation of response to chemotherapy using histology. Although tumor-bearing autografts are useful tools for reconstruction, re-use of the primary tumor may make it difficult to assess the histological response to chemotherapy, since the entire tumor cannot be analyzed. Here, we analyzed the prognostic value of the histological response in the patients who received frozen tumor-bearing autografts for reconstruction. Method: Retrospective analysis of the medical records of 51 patients with high-grade osteosarcoma of the extremities was performed. All patients received reconstruction using frozen tumor-bearing autografts. Tumor necrosis was evaluated in extraskeletal masses and cancellous bone. Results: Five-year overall survival of patients with good and poor response to chemotherapy was 82.9% and 46.4%, respectively (P = 0.044), and 5-year event-free survival was 57.7% and 36.0%, respectively (P = 0.329). Multivariate analysis revealed that a poor histological response to chemotherapy was a significant prognostic factor for overall survival (P = 0.033). Conclusion: Histological response is an important and reliable prognostic factor in patients undergoing reconstruction using frozen tumor-bearing autografts. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy is essential to improve the prognosis of the patients with osteosarcoma, and the response to chemotherapy is an important prognostic factor. In this study, the impact of various radiological examinations on overall survival (OS) and event-free survival (EFS) was evaluated. Method: Eighty-two patients with high-grade osteosarcoma were included in this study, and we evaluated the following factors for prognostic significance: age (≥40 years), gender (male), tumor location (truncal site), metastatic disease, histological response to chemotherapy, radiological response to chemotherapy assessed using X-ray, angiography, CT, MRI, 201Tl scintigraphy, and 99mTc-MIBI scintigraphy (99mTc-MIBI), and combined radiological score (CRS). Results: Univariate analyses revealed that metastatic disease, histological response, 99mTc-MIBI, and CRS were significantly correlated with OS. Multivariate analyses showed that metastatic disease (OS: HR 35.9, P<0.001; EFS: HR 17.32, P<0.001) was an independent predictor of OS and EFS. Tumor location (HR 36.1, P = 0.003), histological response (HR 31.1, P = 0.036), and 99mTc-MIBI (HR 18.4, P = 0.038) were significant prognostic factors for OS. Moreover, CRS was a marginally significant predictor of OS and EFS. Conclusion: The chemotherapeutic effects evaluated by 99mTc-MIBI and CRS could be considered as prognostic factors in osteosarcoma. [ABSTRACT FROM AUTHOR]

Background: Total en bloc spondylectomy (TES) is a surgery designed to achieve complete resection of a malignant spinal tumor such as spinal metastasis. Although this procedure decreases the rate of local recurrence, it is questionable whether local control prolongs patient’s survival. We developed a “second-generation TES” that brings about TES enhancing antitumor immunity to prolong patient’s survival. Our purpose is to present a second-generation TES applied tumor-induced cryoimmunology and assess the immunity-enhancing effect after implementing this surgery. Methods: We performed a retrospective review of prospectively collected data in second-generation TES as carried out in 56 cases. In second-generation TES, instead of harvesting autograft from the ilium or fibula, the resected lamina and vertebral body from TES are frozen using liquid nitrogen and used as grafted bone for spinal reconstruction. In recent 26 of the 56 cases, in addition to the TES procedure, a small amount of the tumor tissue from the resected tumor-bearing vertebra was also placed into liquid nitrogen. This small amount of tumor tissue was then implanted subcutaneously on one side of the axilla. In 52 of 56 cases, measurement of interleukin 12 (IL-12) was performed before surgery and at both 1 and 3 months after surgery. Results: IL-12 increased after TES surgery in 38 of 52 cases (73.1%). The mean IL-12 relative concentrations at both 1 and 3 months after surgery, as compared to before surgery, were significantly higher (121±89 and 149±111%: P<0.05 and P<0.01). Conclusions: Our results show that second-generation TES may provide not only a local radical cure but also a systemic immunological enhancement. Further prolonged survival in patients with a malignant spinal tumor is promising by second-generation TES. [ABSTRACT FROM AUTHOR]

The incidence of advanced hepatocellular carcinoma (HCC) is increasing worldwide, and its prognosis is extremely poor. Interferon-alpha (IFN-α)/5-fluorouracil (5-FU) therapy is reportedly effective in some HCC patients. In the present study, to improve HCC prognosis, we identified the genes that are sensitizing to these agents. The screening strategy was dependent on the concentration of ribozymes that rendered HepG2 cells resistant to 5-FU by the repeated transfection of ribozymes into the cells. After 10 cycles of transfection, which was initiated by 5,902,875 sequences of a ribozyme library, three genes including protein kinase, adenosine monophosphate (AMP)-activated, gamma 2 non-catalytic subunit (PRKAG2); transforming growth factor-beta receptor II (TGFBR2); and exostosin 1 (EXT1) were identified as 5-FU-sensitizing genes. Adenovirus-mediated transfer of TGFBR2 and EXT1 enhanced IFN-α/5-FU-induced cytotoxicity as well as 5-FU, although the overexpression of these genes in the absence of IFN-α/5-FU did not induce cell death. This effect was also observed in a tumor xenograft model. The mechanisms of TGFBR2 and EXT1 include activation of the TGF-β signal and induction of endoplasmic reticulum stress, resulting in apoptosis. In HCC patients treated with IFN-α/5-FU therapy, the PRKAG2 mRNA level in HCC tissues was positively correlated with survival period, suggesting that PRKAG2 enhances the effect of IFN-α/5-FU and serves as a prognostic marker for IFN-α/5-FU therapy. In conclusion, we identified three genes that chemosensitize the effects of 5-FU and IFN-α/5-FU on HCC cells and demonstrated that PRKAG2 mRNA can serve as a prognostic marker for IFN-α/5-FU therapy. [ABSTRACT FROM AUTHOR]

Background: Dendritic cells (DCs) play a pivotal role in the immune system. There are many reports concerning DC-based immunotherapy. The differentiation and maturation of DCs is a critical part of DC-based immunotherapy. We investigated the differentiation and maturation of DCs in response to various stimuli. Methods: Thirty-one patients with malignant bone and soft tissue tumors were enrolled in this study. All the patients had metastatic tumors and/or recurrent tumors. Peripheral blood mononuclear cells (PBMCs) were suspended in media containing interleukin-4 (IL-4) and granulocyte-macrophage colony stimulating factor (GM-CSF). These cells were then treated with or without 1) tumor lysate (TL), 2) TL + TNF-α, 3) OK-432. The generated DCs were mixed and injected in the inguinal or axillary region. Treatment courses were performed every week and repeated 6 times. A portion of the cells were analyzed by flow cytometry to determine the degree of differentiation and maturation of the DCs. Serum IFN-c and serum IL-12 were measured in order to determine the immune response following the DC-based immunotherapy. Results: Approximately 50% of PBMCs differentiated into DCs. Maturation of the lysate-pulsed DCs was slightly increased. Maturation of the TL/TNF-α-pulsed DCs was increased, commensurate with OK-432-pulsed DCs. Serum IFN-γ and serum IL- 12 showed significant elevation at one and three months after DC-based immunotherapy. Conclusions: Although TL-pulsed DCs exhibit tumor specific immunity, TL-pulsed cells showed low levels of maturation. Conversely, the TL/TNF-α-pulsed DCs showed remarkable maturation. The combination of IL-4/GM-CSF/TL/TNF-α resulted in the greatest differentiation and maturation for DC-based immunotherapy for patients with bone and soft tissue tumors. [ABSTRACT FROM AUTHOR]