Differential Diagnosis of Lipomatous Tumors Using 18F-Fluorodeoxygulcose Positron Emission Tomography/Computed Tomography: A Retrospective Observational Study.

Background/Aim: Lipomatous tumors, including lipomas, atypical lipomatous tumors (ALTs), myxoid liposarcomas (MLs), and dedifferentiated liposarcomas (DLs), are often diagnosed using magnetic resonance imaging (MRI). Differential diagnosis of lipomas and ALTs by MRI is often challenging. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) has recently been used for the diagnosis and evaluation of tumor staging and recurrence of soft tissue tumors. The maximum standardized uptake value (SUVmax) is positively associated with malignant grade in several cancers. This study aimed to evaluate SUVmax of 18F-FDG PET/CT in the differential diagnosis of lipomatous tumors. Patients and Methods: Patients who underwent 18F-FDG PET/CT for the diagnosis of lipomatous tumors between January 2013 and September 2021 were included in the study. Patients with lipomatous tumors, confirmed by pathological diagnosis or surgical specimens, were evaluated for lipomatous tumor SUVmax. Results: This study included 44 patients with lipomas (n=19), ALTs (n=12), MLs (n=9), and DLs (n=4). The mean SUVmax of lipomas, ALTs, MLs, and DLs was 0.99±1.41, 1.92±0.95, 5.21±4.94, and 9.29±1.43, respectively. Lipomas showed a significantly lower SUVmax than did ALTs, MLs, and DLs (p<0.05). ALTs demonstrated a significantly lower SUVmax than did MLs and DLs (p<0.05). No significant differences were observed between MLs and DLs. Conclusion: Lipomas or ALTs had a significantly lower SUVmax than lipomatous sarcomas. Lipomas had a significantly lower SUVmax than ALTs, aiding in their preoperative differentiation. 18F-FDG-PET/CT could serve as a potent tool for the differential diagnosis of lipomatous tumors.

Rare coexistence of multiple osteochondromas and solitary osteoid osteoma: A case report.

Multiple osteochondromas (MOs) are inherited in an autosomal-dominant manner, with a penetrance of ~96 and 100% in female and male patients, respectively. Osteochondromas primarily involve the metaphyses and diaphyses of long bones, including the ribs. Osteoid osteomas account for ~3 and 11% of all bone tumors and benign bone tumors, respectively. Furthermore,1 the male-to-female ratio is 2-3:1, and they generally occur in the long bones of the lower extremities, with the femoral neck being the most frequent site. The present study describes the case of a 16-year-old male patient with a bony mass around the left knee joint and pain in the left calf. Radiography revealed MOs in the upper and lower extremities, while computed tomography showed a nidus in the cortex of the tibial shaft. The patient's family history included the presence of MOs, and the patient was diagnosed with MOs and a solitary osteoid osteoma. Surgical excision of the osteochondroma and curettage of the osteoid osteoma in the proximal tibia and tibial shaft, respectively, were performed simultaneously. Postoperative pathological examination revealed osteochondroma and osteoid osteoma. Furthermore, the pain resolved, and no recurrence was observed 7 months post-operation. To the best of our knowledge, no reports exist on coexisting MOs and osteoid osteoma; therefore, the present study describes the first case of such a condition. Marginal excision for osteochondroma and curettage for osteoid osteoma effectively improved the symptoms.

Oncological and functional outcomes of modified arthroscopic resection for intra-articular tenosynovial giant cell tumor of the knee using multiple portals.

BACKGROUND: Arthroscopic resection of tenosynovial giant cell tumor (TS-GCT) presents favorable outcomes. However, there are reportedly higher recurrence rates in patients who had incomplete resection. To minimize incomplete resection, we established a multiple portal approach depending on the location of the disease. In this study, we aimed to retrospectively evaluate the clinical outcomes of arthroscopic resection for both localized and diffuse types of TS-GCT of the knee. METHODS: From 2009 to 2019, 13 patients who underwent arthroscopic synovectomy of the knee and were histologically diagnosed with TS-GCT were included in this study. The pre- and postoperative range of motion (ROM) of the knee was measured. The Japanese Orthopaedic Association (JOA) score and the Knee Injury and Osteoarthritis Outcome Score (KOOS) were assessed at the final follow-up examination. Magnetic resonance imaging was performed to detect incomplete resection or local recurrence. RESULTS: Among the 13 patients, seven and six had localized and diffuse type TS-GCT, respectively. Regarding the knee ROM, preoperative knee flexion in patients with the localized type was limited compared with that in those with the diffuse type. However, the ROM was significantly improved in patients with both types postoperatively. The JOA score and KOOS of patients with both types at the final follow-up were favorable, and there were no significant differences between both types. There was neither recurrence nor incomplete resection in any patient for both types. CONCLUSION: All patients, regardless of the TS-GCT type, achieved favorable outcomes after arthroscopic surgery; especially, the failure rate was 0%.

Intraoperative cone-beam computed tomography-guided curettage for osteoid osteoma.

Recently, cone-beam computed tomography (CBCT)-guided surgeries have been developed for bone and soft tissue tumors. The present study aimed to evaluate the efficacy of CBCT-guided curettage for osteoid osteoma. Our study population included 13 patients who underwent primary curettage for osteoid osteoma using intraoperative CBCT in a hybrid operating room between April 2019 and November 2022. We collected the following data: sex, age, follow-up period, symptom onset to time of surgery, tumor size and location, length of skin incision, operating time, radiation dose, recurrence, postoperative complications, and visual analog scale for pain during the last follow-up. There were 10 male and 3 female patients, and the mean age was 25.0 years (range, 9-49 years). The mean follow-up period was 10.6 months (range, 0.4-24.0 months). The locations of the tumors were the proximal femur in 6 patients, the acetabular region in 2 patients, and the ilium, tibial shaft, calcaneus, cuboid, and talus in 1 patient each. The mean time of symptoms onset to surgery was 18.7 months (range, 2.3-69.9 months). The mean maximum diameter of the tumor was 5.9 mm (range, 3.5-10.0 mm). The mean length of the skin incision was 2.2 cm (range, 1.5-3.5 cm). The mean operating time was 96.9 minutes (range, 64-157 minutes). The mean dose of radiation was 193.2 mGy (range, 16.3-484.0 mGy). No recurrences, postoperative complications, and reoperation were observed in this study. All the patients reported 0 mm on the visual analogue scale for pain on the last follow-up. CBCT-guided curettage for osteoid osteoma was minimally invasive and reliable. This procedure can be effective for the treatment of lesions found in deep locations such as the pelvic bone and proximal femur or an invisible lesion that cannot be detected by regular fluoroscopy.

The Combination of Methioninase and Ethionine Exploits Methionine Addiction to Selectively Eradicate Osteosarcoma Cells and Not Normal Cells and Synergistically Down-regulates the Expression of C-MYC.

BACKGROUND/AIM: The fundamental and general hallmark of cancer cells, methionine addiction, termed the Hoffman effect, is due to overuse of methionine for highly-increased transmethylation reactions. In the present study, we tested if the combination efficacy of recombinant methioninase (rMETase) and a methionine analogue, ethionine, could eradicate osteosarcoma cells and down-regulate the expression of c-MYC. MATERIALS AND METHODS: 143B osteosarcoma cells and Hs27 normal human fibroblasts were tested. The efficacy of rMETase alone and ethionine, alone and in their combination, on cell viability was determined with the WST-8 assay on 143B cells and Hs27 cells. c-MYC expression was examined with western immunoblotting and compared in 143B cells treated with/without rMETase, ethionine, or the combination of both rMETase and ethionine. RESULTS: 143B cells were more sensitive to both rMETase and ethionine than Hs 27 cells, with the following IC50s: rMETase (143B: 0.22 U/ml; Hs27: 0.82 U/ml); ethionine (143B: 0.24 mg/ml; Hs27: 0.42 mg/ml). The combination of rMETase and ethionine synergistically eradicated 143B cells, lowering the IC50 for ethionine 14-fold compared to ethionine alone (p<0.001). In contrast, Hs27 fibroblasts were relatively resistant to the combination. The expression of c-MYC was significantly down-regulated only by the combination of rMETase and ethionine in 143B cells (p<0.001). CONCLUSION: In the present study, we showed, for the first time, the synergistic combination efficacy of rMETase and ethionine on osteosarcoma cells in contrast to normal fibroblasts, which were relatively resistant. The combination of rMETase and ethionine down-regulated c-MYC expression in the cancer cells. The present results indicate the combination of rMETase and ethionine may reduce the malignancy of osteosarcoma cells and can be a potential future clinical strategy.

Denosumab administration for bone metastases from solid tumors: a retrospective cross-sectional study.

BACKGROUND: Little is known on how denosumab reduces skeletal-related events (SREs) by bone metastases from solid tumors. We sought to evaluate the effect of denosumab administration in patients with bone metastases from solid tumors. METHODS: Data of patients treated with denosumab were collected from electronic medical charts (n = 496). Eligible participants in this study were adult patients (age ≥ 18 years) with metastatic bone lesions from solid tumors treated with denosumab. SREs, surgical interventions, the spinal instability neoplastic score (SINS) for spinal region, and Mirels' score for the appendicular region were evaluated. To assess whether denosumab could prevent SREs and associated surgery, the SINS and Mirels' score were compared between patients with and without SREs. RESULTS: A total of 247 patients (median age, 65.5 years old; median follow-up period, 13 months) treated with denosumab for metastatic bone lesions from solid tumors were enrolled in this study. SREs occurred in 19 patients (7.7%). SREs occurred in 2 patients (0.8%) who took denosumab administration before SREs. Surgical interventions were undertaken in 14 patients (5.7%) (spinal and intradural lesions in five patients and appendicular lesions in nine patients). The mean SINS of patients without SREs compared to those with SREs were 7.5 points and 10.2 points, respectively. The mean Mirels' scores of non-SREs patients and those with SREs were 8.07 points and 10.7 points, respectively. Patients with SREs had significantly higher Mirels' score than non-SREs patients (p < 0.01). Patients with SREs had higher SINS than non-SREs patients (p = 0.09). CONCLUSIONS: SREs occurred in patients with higher SINS or Mirels' scores. Two patients suffered from SREs though they took denosumab administration before SREs. Appropriate management of denosumab for patients with bone metastasis is significant. Surgical interventions may be needed for patients who with higher SINS or Mirel's scores.

The influence of COVID-19 epidemic on the number of orthopaedic surgeries in Japan.

BACKGROUND: There is limited data on the impact of COVID-19 epidemic on the number of orthopaedic surgeries in Japan. METHODS: We conducted a nationwide hospital survey asking for the monthly number of orthopaedic surgeries performed at each facility from January 2019 to June 2021. Those facilities that had performed at least 100 surgeries in 2019 were included for analyses. The facilities were further grouped by prefecture and by hospital characteristics. A brief health economic evaluation was also performed. Risk ratios were compared using univariate analyses with P < 0.05 considered statistically significant. RESULTS: Questionnaire was sent to 1988 hospitals with 1671 hospitals (84%) responding. The survey data indicated a total number of orthopaedic surgeries decreased in 2020 compared to 2019 (1,061,541 vs 1,119,955 P < 0.01), and also for the first six months of 2021 compared to the same period in 2019 (530,388 vs 550,378 P < 0.01). In 2020, over 50% of all facilities in nearly all of the prefectures saw a decline in surgical procedures. The risk of incurring more than a 25% decease in the number of surgeries was significantly higher in 2020 for class I designated medical institutions compared to those that were not designated for any types of infectious diseases among the institutions with a tertiary emergency medical center in 2020 (crude risk ratio 2.9: 95% CI 1.2-7.4, p = 0.02) and in 2021 (crude risk ratio 4.7: 95% CI 1 0.9-12.1, p < 0.01). The estimated total nationwide decrease of revenue were in the range of approximately ¥29.2 to ¥116.8 billion per year for orthopaedic surgeries alone. CONCLUSION: There was a statistically significant decrease in the number of orthopaedic surgeries in Japan. The magnitude of the decline varied by prefectures and hospital characteristics, with the greater impact imposed on medical institutions with higher classification functions. The estimated immediate health economic impact was sizable.

Long-lasting Limb Salvage After Malignant Femoral-Bone Tumor Resection Reconstructed With a Thin-mantle Titanium Stem Fixated With Cement.

BACKGROUND/AIM: The purpose of the present study was to review and report clinical outcomes of the Kyocera Modular Limb Salvage System (KMLS) using a thin-mantle titanium stem fixated with cement, for reconstruction after resection of malignant femoral-bone tumors. PATIENTS AND METHODS: Twenty consecutive patients who had undergone reconstruction using the KMLS with cemented thin-mantle titanium stem fixation between July 2010 and December 2019 at Ryukyu University Hospital were included. We retrospectively collected the following data: age, sex, follow-up period, tumor location, histological diagnosis, stem size, overall implant survival, radiolucency, postoperative complications, overall survival, and oncological survival. RESULTS: The median follow-up period was 63 months (range=10.7-261 months). The bone tumors were in the proximal part of the femur in 9 patients and in the distal part of the femur in 11 patients. The 5-year overall implant survival rate was 90.9% among surviving patients. A revision surgery was required for only one patient (5%), due to infection. Radiolucency, due to an instability of the implant, was observed in 7 out of 20 patients: 6 patients with distal femoral reconstruction, and 1 patient with proximal femoral reconstruction. However, none of the patients complained of any symptoms or required revision surgeries at the last follow-up. The 5-year overall patient-survival rate was 67.6%. CONCLUSION: The KMLS with cemented thin-mantle titanium stem fixation for femoral bone reconstruction after resection for bone malignancy resulted in long-term patient benefit.

Imaging characteristics of tenosynovial giant cell tumors on 18F-fluorodeoxyglucose positron emission tomography/computed tomography: a retrospective observational study.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) is useful for assessing location, metastasis, staging, and recurrence of malignant tumors. Tenosynovial giant cell tumor (TSGCT) is a benign tumor; however, some studies have reported that TSGCTs have a high uptake of FDG. Few studies have reported on the detailed evaluation of TSGCT using 18F-FDG-PET/CT. The purpose of the current study is to evaluate the image characteristics and locations, particularly where possible, with or without, extra-articular invasion from TSGCT of the knee in 18F-FDG-PET/CT could occur. METHODS: We retrospectively reviewed the patients with TSGCT who were diagnosed pathologically either by biopsy or surgical specimen. Furthermore, we evaluated the difference of the maximum standardized uptake value (SUVmax) between diffused TSGCT with extra-articular invasion and TSGCT with intra-articular localization in the knee. RESULTS: The study consisted of 20 patients with TSGCT. The mean SUVmax of TSGCT was 12.0 ± 6.50. There were five patients with TSGCT arising in the knee with extra-articular invasion and six with TSGCT with intra-articular localization. The mean SUVmax of TSGCT with extra-articular invasion and those with intra-articular localization were 14.3 ± 6.00 and 5.94 ± 3.89, respectively. TSGCT with extra-articular invasion had significantly higher SUVmax than TSGCT with intra-articular localization (p < 0.05). CONCLUSIONS: TSGCT revealed high FDG uptake. Furthermore, SUVmax was higher in diffused TSGCT with extra-articular invasion than in intra-articular localized TSGCT; this may reflect its local aggressiveness.

Precise and Facile Endotracheal Lung-tumor-implantation Mouse Model Visualized by GFP Expression.

BACKGROUND/AIM: In osteosarcoma, lung metastasis is a major cause of cancer-related death, as the 5-year survival rate for patients with metastases is approximately only 20-30%. To develop improved therapeutic strategies against lung-metastatic osteosarcoma, an experimental lung-tumor-implantation mouse model is needed for basic research. In the present study, we developed a precise and facile endotracheal lung-tumor-implantation technique. MATERIALS AND METHODS: For establishment of the lung-tumor-implantation mouse model of metastatic osteosarcoma, 5 mice were used. A 15-mm longitudinal incision was made in the center of the neck to expose the salivary glands. The salivary glands were then split, exposing the trachea covered by the sternohyoid muscles. The trachea was then clearly exposed by cutting the sternohyoid muscles longitudinally. A 22 G gavage needle was tilted slightly toward the left side of the mouse and inserted from the oral cavity into the bronchus, with confirmation of the position of the tip of the gavage needle visualized through the tracheal wall, followed by injection of 0.5% crystal violet to first confirm the accuracy of endotracheal injection in the lung. A 143B-GFP cell suspension (2.0×106 cells/50 µl PBS) was then injected endotracheally in other mice. RESULTS: The procedure, including anesthesia and suturing, took approximately 10 minutes. The left lobe of the lung, in which crystal violet was injected endotracheally, was stained in 3 out of 3 mice (100%). 143B-GFP-osteosarcoma tumors were detected with GFP fluorescence in the left lobe of the lung in 3 out of 4 mice (75%), 5 weeks after endotracheal injection. One mouse died 4 weeks after 143B-GFP-cell implantation. CONCLUSION: This novel technique of establishing tumors in the lung via endotracheal injection of cancer cells is precise and facile and can be used widely, since neither a surgical microscope nor X-ray imaging are needed.

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

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

Reconstructed bone fracture 28 years after hip rotationplasty for Ewing sarcoma: A case report.

Hip rotationplasty is a surgical method used to treat malignant tumors of the proximal femur. A 52-year-old woman, who underwent hip rotationplasty for Ewing sarcoma of the proximal left femur at the age of 24, fell and hit the left buttock. The patient was then admitted to the Department of Orthopedic Surgery, Graduate School of Medicine, University of the Ryukyus. Radiography and computed tomography (CT) revealed a comminuted fracture of the reconstructed bone distally. The patient underwent open reduction and internal fixation (ORIF) and external fixator. External fixation was removed 1 month after the surgery. At two years after surgery, at the latest follow-up, bone union was confirmed by 3-dimensional CT. The combination of ORIF and temporal external fixation was effective for the reconstructed bone fractures after hip rotationplasty.

Relationship between the morphology of osteophytes and cartilage lesions in anterior ankle impingement in athletes: a cross-sectional study.

BACKGROUND: The present study aimed to describe the frequency and severity of tram-track lesions in anterior ankle impingement in athletes and to evaluate the association between osteophyte morphology and severity of tram-track lesions, the distinctive cartilage lesions associated with tibial osteophytes in anterior ankle impingement syndrome. METHODS: We evaluated 34 athletes who underwent arthroscopic osteophyte resection for anterior ankle impingement between January 2017 and March 2021. RESULTS: We found tram-track lesions in 26 athletes (76.5%). Arthroscopic findings revealed the distribution of the International Cartilage Repair Society grades of tram-track lesions (grade 0, eight; grade 1, seven; grade 2, ten; grade 3, nine; grade 4, zero). These findings indicate that athletes with anterior ankle impingement syndrome may have more severe cartilage lesions than non-athletes. There was a positive correlation between the International Cartilage Repair Society grade and osteophyte size (r = 0.393, p = 0.021). We divided athletes into two groups according to the presence or absence of osteophyte protrusion into the joint space. Osteophyte protrusion was present in 14 athletes (41.2%). All athletes in the protrusion-type group had tram-track lesions; seven (50%) had International Cartilage Repair Society grade 3. The protrusion-type group's International Cartilage Repair Society grade was significantly higher than that of the non-protrusion-type group (p = 0.008). The osteophyte sizes in the two groups were not significantly different (p = 0.341). CONCLUSIONS: Based on these findings, osteophyte protrusion should be assessed when an indication of arthroscopic treatment for anterior ankle impingement syndrome is considered, particularly in athletes.

Progressive scoliosis associated with microphthalmia with limb anomalies: A case report.

RATIONALE: Microphthalmia with limb anomalies is a rare, autosomal recessive, multiple congenital anomaly syndrome. Patients with this syndrome particularly present with monocular or bilateral anophthalmia/microphthalmia and distal limb anomalies. However, details regarding associated spinal deformities have not been fully elucidated. PATIENT CONCERNS: A 12-year-old girl initially presented with progressive scoliosis, who was previously diagnosed with microphthalmia with limb anomalies. However, 4 years after the initial visit, the scoliosis deformity gradually progressed. The patient and family requested the surgical treatment to preserve standing/sitting balance. DIAGNOSES: She was diagnosed with microphthalmia with limb anomalies and progressive scoliosis. INTERVENTIONS: A posterior corrective fusion surgery (including a pelvic fusion) was performed to prevent future standing/sitting imbalance. OUTCOMES: Significant improvement of spinal deformity was observed, with no adverse events. LESSONS: This report demonstrated a case of progressive scoliosis associated with microphthalmia with limb anomalies. A posterior corrective spinal fusion was effective to preserve standing/sitting balance. To the best of our knowledge, this is the first report of surgical treatment of progressive scoliosis associated with microphthalmia with limb anomalies.

Oncogenes and Methionine Addiction of Cancer: Role of c-MYC.

BACKGROUND/AIM: Methionine addiction is a general and fundamental hallmark of cancer cells, termed the Hoffman effect. Previously Vanhamme and Szpirer showed that methionine addiction could be induced by transfection of the activated HRAS1 gene to a normal cell line. In the present study, we investigated the role of the c-MYC oncogene in methionine addiction of cancer, by comparison of c-Myc expression and malignancy of methionine-addicted osteosarcoma cells and rare methionine-independent revertants, derived from the methionine-addicted cells. MATERIALS AND METHODS: Methionine-independent revertant 143B osteosarcoma cells (143B-R) were derived from methionine-addicted parental 143B osteosarcoma cells (143B-P), by continuous culture in medium depleted of methionine by recombinant methioninase. To compare in vitro malignancy of methionine-addicted parental cells and methionine-independent revertant cells, the following experiments were performed: for 143B-P and 143B-R cells, cell proliferation capacity was measured with a cell-counting assay, and colony-formation capacity was determined on plastic and in soft agar, all in methionine-containing Dulbecco's Modified Eagle's Medium (DMEM). Tumor growth was measured in orthotopic xenograft nude-mouse models, to compare in vivo malignancy of 143B-P and 143B-R cells. c-MYC expression was examined with western immunoblotting and compared in 143B-P and 143B-R cells. RESULTS: 143B-R cells had reduced cell proliferation capacity, compared to 143B-P cells, in methionine-containing medium (p=0.003). 143B-R cells had reduced colony formation capacity on plastic (p=0.003) and in soft agar, compared to 143B-P cells in methionine-containing medium. 143B-R cells had reduced tumor growth in orthotopic xenograft nude-mouse models, compared to 143B-P cells, (p=0.002). These results demonstrate that 143B-R methionine-independent revertant cells lost malignancy. Expression of c-MYC was reduced in 143B-R methionine-independent revertant osteosarcoma cells, compared to 143B-P cells, (p=0.0007). CONCLUSION: The present study demonstrated that c-MYC expression is linked to malignancy and methionine addiction of cancer cells. The present study on c-MYC, and the previous study on HRAS1, suggest that oncogenes may play a role in methionine addiction, which is a hallmark of all cancers, as well as in malignancy.

Reconstruction of the lateral collateral ligament using the plantaris tendon after wide excision of soft tissue sarcoma of the knee: A case report.

An 83-year-old woman presented with a 1-year history of a growing mass on the lateral surface of the right knee. Magnetic resonance imaging revealed a large soft tissue tumor in the subcutis of the right knee. The mass in the right knee rapidly increased, due to hemorrhage from the tumor. A needle biopsy revealed that the diagnosis was synovial sarcoma. The patient underwent wide excision and lateral collateral ligament reconstruction using the plantaris tendon. The patient had a Musculoskeletal Tumor Society Score of 86% at the lateset follow-up. In conclusion, reconstruction of the lateral collateral ligament using the plantaris tendon may be useful for preserving the function of the knee joint after resection of the soft tissue due to sarcoma of the knee.

Reversion of methionine addiction of osteosarcoma cells to methionine independence results in loss of malignancy, modulation of the epithelial-mesenchymal phenotype and alteration of histone-H3 lysine-methylation.

Methionine addiction, a fundamental and general hallmark of cancer, known as the Hoffman Effect, is due to altered use of methionine for increased and aberrant transmethylation reactions. However, the linkage of methionine addiction and malignancy of cancer cells is incompletely understood. An isogenic pair of methionine-addicted parental osteosarcoma cells and their rare methionine-independent revertant cells enabled us to compare them for malignancy, their epithelial-mesenchymal phenotype, and pattern of histone-H3 lysine-methylation. Methionine-independent revertant 143B osteosarcoma cells (143B-R) were selected from methionine-addicted parental cells (143B-P) by their chronic growth in low-methionine culture medium for 4 passages, which was depleted of methionine by recombinant methioninase (rMETase). Cell-migration capacity was compared with a wound-healing assay and invasion capability was compared with a transwell assay in 143B-P and 143B-R cells in vitro. Tumor growth and metastatic potential were compared after orthotopic cell-injection into the tibia bone of nude mice in vivo. Epithelial-mesenchymal phenotypic expression and the status of H3 lysine-methylation were determined with western immunoblotting. 143B-P cells had an IC50 of 0.20 U/ml and 143B-R cells had an IC50 of 0.68 U/ml for treatment with rMETase, demonstrating that 143B-R cells had regained the ability to grow in low methionine conditions. 143B-R cells had reduced cell migration and invasion capability in vitro, formed much smaller tumors than 143B-P cells and lost metastatic potential in vivo, indicating loss of malignancy in 143B-R cells. 143B-R cells showed gain of the epithelial marker, ZO-1 and loss of mesenchymal markers, vimentin, Snail, and Slug and, an increase of histone H3K9me3 and H3K27me3 methylation and a decrease of H3K4me3, H3K36me3, and H3K79me3 methylation, along with their loss of malignancy. These results suggest that shifting the balance in histone methylases might be a way to decrease the malignant potential of cells. The present results demonstrate the rationale to target methionine addiction for improved sarcoma therapy.

Wide excision alone for elderly patients aged > 70 years old with soft tissue sarcomas.

The purpose of the present study was to clarify clinical outcomes of elderly patients with soft tissue sarcoma who underwent surgery neither with neoadjuvant nor adjuvant chemotherapy. The median follow-up period was 46.3 (range 6.7-99.0) months. All patients underwent surgical resections. R0 margins were achieved in 24 cases (92.3%) and R1 margins in 2 cases (7.7%). The 1-, 2-, and 5-year sarcoma-specific survival (SSS) rates were 92.3%, 88.5%, and 83.8%, respectively. Multivariate analysis showed no significant risk factors for SSS. No significant relationship of histological grades and local recurrences (P = .56) or distant metastases (P = .54) was shown. In the current study, we observed a comparable survival ratio, despite no neoadjuvant or adjuvant chemotherapies performed. Tumor resections with adequate margins might, at least in part, have contributed to the decent survival ratio regardless of histological grade. Twenty-six consecutive patients aged ≥ 70 years, who underwent surgical resections of soft tissue sarcoma between January 2013 and December 2019, were included. SSS were analyzed by the Kaplan-Meier method, and the relationships between SSS and clinical parameters were evaluated by Cox proportional hazards analysis.

Non-invasively Imageable Tibia-tumor-fragment Implantation Experimental-bone-metastasis Mouse Model of GFP-expressing Prostate Cancer.

BACKGROUND/AIM: Although the 5-year survival rate for localized prostate cancer is nearly 100%, prognosis for patients with metastases, of which the bone is the most common site, is poor. In order to evaluate efficacy of treatments against metastatic prostate cancer, experimental tibia-bone-metastasis mouse models of prostate cancer have been previously established. In the present study, we used a novel procedure for establishment of an experimental tibiabone metastasis mouse model, with human PC-3 prostate cancer expressing green fluorescent protein (GFP), that more closely matches prostate cancer growing in the bone. MATERIALS AND METHODS: PC-3 human prostate cancer cells, labeled with GFP, were initially subcutaneously injected into the flank of five male nude mice to obtain tumor tissues. Once the tumor tissue grew larger than 10 mm in diameter, the tumor tissue was harvested and minced into fragments of 1 mm3 A 1-mm hole was made in the proximal left tibia of eight male nude mice, using the tip of a 5-mm blade, and a tumor fragment was implanted into the hole for an exact fit. Tumor size was measured once a week, by non-invasive imaging of GFP fluorescence. The mice were sacrificed four weeks after tumor implantation. RESULTS: Tumors grew in 8 out of 8 mice (100%). All tumors were non-invasively detectable with GFP fluorescence, through the skin. Increased tumor growth in the tibia was observed every week. CONCLUSION: The establishment in the tibia of the novel experimental bone-metastatic mouse model of human prostate cancer enables facile screening, in a clinically-relevant system, of improved therapeutics for this recalcitrant disease.