Real-world effects, safety, and predictors of the effectiveness of romosozumab in primary and secondary osteoporosis: An observational study.

Romosozumab is an anti-sclerostin antibody that increases bone formation and decreases bone resorption. It became available for patients at high risk of osteoporotic fractures in Japan in 2019. The aim of this study was to clarify the clinical effects, safety, and predictors of the effectiveness of 12 months of romosozumab therapy. The study had an observational pre-post design and included 460 patients. Romosozumab was administered at a dose of 210 mg subcutaneously every 4 weeks for 12 months. The incidence of new fractures, safety, and changes in bone mineral density (BMD) and bone turnover markers were recorded. New fractures occurred in 11 cases (3.0 %). Nine patients (2.0 %) experienced cardiovascular events, which were fatal in 3 (0.65 %). Percent changes in BMD at the spine and total hip at 12 months from baseline were +7.7 % and +1.8 %, respectively. Romosozumab had better effects in patients with good renal function, low spine BMD, and high TRACP-5b at baseline and low TRACP-5b or high P1NP after 1 month of treatment. The percent change in spine BMD at 12 months was significantly lower in patients transitioning from denosumab than in those not previously treated with other anti-osteoporosis agents. Romosozumab is considered to be relatively safe in patients with primary osteoporosis compared to those with secondary osteoporosis. Romosozumab resulted in larger increases in spine BMD in patients with primary osteoporosis who were not previously treated with other anti-osteoporosis therapies and those with low spine BMD at the start of treatment.

Republication of "Mucous Cyst at the Interphalangeal Joint of the First Toe Caused by Contact Pressure With the Second Toe due to Hallux Valgus: A Case Report".

A 77-year-old woman presented with a mucous cyst on the lateral aspect of the interphalangeal joint of the first toe caused by contact pressure with the second toe from hallux valgus. She complained of discomfort and discharge from the left first toe for approximately 4 months. Physical examination showed the second toe pressing strongly against the first toe due to hallux valgus and discharge from the skin on the lateral aspect of the interphalangeal joint of the first toe. Magnetic resonance imaging showed a cystic lesion at the same level. The patient underwent a modified scarf osteotomy of the first metatarsal for hallux valgus to resolve the contact pressure between the toes-considered the cause of the mucous cyst-and resection of mucous cyst. Forefoot weight bearing was allowed 6 weeks after surgery. As of 1 year after surgery, she has had no recurrence of the cyst. The score on the Japanese Society for Surgery of the Foot hallux metatarsophalangeal-interphalangeal scale improved from 59/100 points to 92/100. This outcome suggests that hallux valgus correction should be considered when a mucous cyst is associated with contact pressure due to a hallux valgus deformity. To the best of our knowledge, there are no previous reports of a mucous cyst caused by contact pressure between the first toe and second toe due to hallux valgus.

Atypical femoral fracture in a multiple myeloma patient undergoing treatment with denosumab: A case report and literature review.

INTRODUCTION AND IMPORTANCE: Denosumab is a new standard treatment for bone disease caused by multiple myeloma. There are a few reports of atypical femoral fracture in patients with multiple myeloma, all of which were associated with long-term use of bisphosphonate. Here, we report the first case of denosumab-induced atypical femoral fracture in a patient with multiple myeloma. CASE PRESENTATION: A 71-year-old woman with multiple myeloma developed dull pain in her right thigh 8 months after restarting high-dose denosumab following its initial administration for 4 months and subsequent withdrawal for 2 years. Fourteen months later, complete atypical femoral fracture occurred. Osteosynthesis was achieved using an intramedullary nail and she was switched to oral bisphosphonate 7 months after cessation of denosumab. There was no exacerbation of the multiple myeloma. Bone union was achieved and she recovered to her pre-injury level of activities. The oncological outcome was alive with disease at 2 years after surgery. CLINICAL DISCUSSION: Prodromal symptoms such as thigh pain and radiographical finding of thickening of the lateral cortex in the subtrochanteric region of the femur were attributed to denosumab-induced atypical femoral fracture in the case. A unique aspect of this case worth highlighting is that the fracture occurred after short-term denosumab use. This may be associated with multiple myeloma or other medication including dexamethasone and cyclophosphamide. CONCLUSION: Atypical femoral fracture may occur in patients with multiple myeloma who receive denosumab, even for a short period. Attending physicians should be cognizant of the early symptoms and signs of this fracture.

Blue light induces apoptosis and autophagy by promoting ROS-mediated mitochondrial dysfunction in synovial sarcoma.

BACKGROUND: Synovial sarcoma (SS) has limited treatment options and there is an urgent need to develop a novel therapeutic strategy to treat SS. Blue light (BL) has been shown to inhibit the growth of several cancer cells. However, the efficacy of BL in soft tissue sarcomas such as SS has not been demonstrated, and the detailed mechanism underlying the antitumor activity of BL is not fully understood. In this study, we investigated the antitumor effect of BL on SS. METHODS: Human SS cell lines were continuously irradiated with BL using light-emitting diodes (LEDs) in an incubator for in vitro analysis. The chicken chorioallantoic membrane (CAM) tumors and xenograft tumors in mice were subjected to daily BL irradiation with LEDs. RESULTS: BL caused growth inhibition of SS cells and histological changes in CAM tumors. BL also suppressed the migration and invasion abilities of SS cells. The type of cell death in SS cells was revealed to be apoptosis. Furthermore, BL induced excessive production of reactive oxygen species (ROS) in mitochondria, resulting in oxidative stress and malfunctioned mitochondria. Reducing the production of ROS using N-acetylcysteine (NAC), a ROS scavenger, attenuated the inhibitory effect of BL on SS cells and mitochondrial dysfunction. In addition, BL induced autophagy, which was suppressed by the administration of NAC. The autophagy inhibitor of 3-methyladenine and small interfering RNA against the autophagy marker light chain 3B facilitated apoptotic cell death. Moreover, BL suppressed tumor growth in a mouse xenograft model. CONCLUSION: Taken together, our results revealed that BL induced apoptosis via the ROS-mitochondrial signaling pathway, and autophagy was activated in response to the production of ROS, which protected SS cells from apoptosis. Therefore, BL is a promising candidate for the development of an antitumor therapeutic strategy targeting SS.

Dedifferentiated liposarcoma in the extremity and trunk wall: A multi-institutional study of 132 cases by the Japanese Musculoskeletal Oncology Group (JMOG).

BACKGROUND: Dedifferentiated liposarcoma occurs predominantly in the retroperitoneum. Given the paucity of cases, information on the clinical characteristics of this entity in the extremities and trunk wall is quite limited. In particular, the significance of preoperative evaluation and principles of intraoperative management of the different components, i.e., well-differentiated and dedifferentiated areas, are still to be defined. METHODS: Clinical characteristics, treatment outcomes, and risk factors for poor oncological outcomes in cases of dedifferentiated liposarcoma in the extremity or trunk wall were analyzed by a retrospective, multicentric study. RESULTS: A total of 132 patients were included. The mean duration from the initial presentation to dedifferentiation was 101 months in dedifferentiation-type cases. The 5-year local recurrence-free survival, metastasis-free survival, and disease-specific survival rates were 71.6%, 75.7%, and 84.7%, respectively. Among 32 patients with metastasis, 15 presented with extrapulmonary metastasis. A percentage of dedifferentiated area over 87.5%, marginal/intralesional margin, and R1/2 resection in the dedifferentiated area were independent risk factors for local recurrence. Dedifferentiated areas over 36 cm2, French Federation of Cancer Centers Sarcoma Group grade III, and intralesional or marginal resection were independent risk factors for metastasis. A dedifferentiated area over 77 cm2 and lung metastasis were independent risk factors for disease-specific mortality. CONCLUSIONS: The typical clinical characteristics of dedifferentiated liposarcoma in the extremity and trunk wall were reconfirmed in the largest cohort ever. The evaluation of the dedifferentiated area in terms of grade, extension, and pathological margin, together with securing adequate surgical margins, was critical in the management of this entity.

ZFTA::RELA fusion in a distinct liposarcoma morphologically overlapping with chondroid lipoma.

Chondroid lipoma is a rare benign adipose tumor characterized by a recurrent ZFTA::MRTFB fusion. Herein, we report an unusual liposarcoma that partly exhibited overlapping features with those of chondroid lipoma and harbored a ZFTA::RELA fusion. A 59-year-old man presented with a shoulder mass that had existed for approximately 8 years and with increasing pain due to a pelvic mass. The 5.8-cm resected shoulder tumor partly consisted of nests and strands of variably lipogenic epithelioid cells within a hyalinized or focally chondromyxoid stroma, indistinguishable from chondroid lipoma. The histological pattern gradually transitioned to highly cellular, stroma-poor, diffuse sheets of cells with greater nuclear atypia and mitotic activity. Vascular invasion and necrosis were present. The metastatic pelvic tumor revealed a similar histology. Despite multimodal treatment, the patient developed multiple bone metastases and succumbed to the disease 14 months after presentation. Targeted RNA sequencing identified an in-frame ZFTA (exon 3)::RELA (exon 2) fusion, which was confirmed by reverse transcription-polymerase chain reaction, Sanger sequencing, and break-apart fluorescent in situ hybridization assays. The tumor showed a different histology from that of ependymoma, no brain involvement, and no match with any sarcoma types or ZFTA::RELA-positive ependymomas according to DNA methylation analysis. p65 and L1CAM were diffusely expressed, and a CDKN2A/B deletion was present. This is the first report of an extra-central nervous system tumor with a ZFTA::RELA fusion. The tumor partly displayed an overlapping histology with that of chondroid lipoma, suggesting that it may represent a hitherto undescribed malignant chondroid lipoma with an alternative ZFTA fusion.

Combination chemotherapy of doxorubicin and ifosfamide with proton beam therapy for myoepithelial carcinoma originating in the paraspinal region: A case report and literature review.

Soft tissue myoepithelial carcinoma (MEC) is an extremely rare mesenchymal tumor that has a poor prognosis unless complete surgical resection is achieved. The present study reported a case of a 38-year-old woman with a tumor in the left paraspinal region at L2 to L3 with vertebral destruction. MEC was diagnosed based on molecular pathological examination of a biopsy specimen. Because curative surgery was expected to be difficult, a combination of chemotherapy with doxorubicin and ifosfamide and proton beam therapy as local therapy was performed, resulting in long-term survival for at least 7.8 years. To the best of our knowledge, this is the first case of soft tissue MEC for which classical cytotoxic chemotherapy and proton beam therapy were effective. Although surgical resection with negative margins is the mainstay of treatment for MEC, adequate doxorubicin-based systemic therapy and high-dose radiation therapy may be a feasible alternative in patients with unresectable or advanced MEC. Future studies on the relationship between molecular pathological features, including biomarkers, and the selection of therapeutic agents are warranted.

Hemangioblastoma of the Cauda Equina†:†A Case Report and Review of the Literature.

Introduction : Hemangioblastoma in the spine mainly occurs at the cervical and thoracic levels and is often associated with von Hippel-Lindau (VHL) syndrome. Here, we reported a quite rare case of spinal sporadic hemangioblastoma arising from the cauda equina. Case presentation : A 66-year-old woman presented with a 5-year history of low back and leg pain. Imaging revealed a hypervascular intradural extramedullary tumor in the lumbar region. Preoperative angiography helped to identify the feeding arteries and draining vein, and so facilitated subsequent tumor resection. The pain was dramatically improved but weakness of the left tibialis anterior and left extensor hallucis longus muscles persisted. Discussion : We reported a rare case of spinal hemangioblastoma arising from the cauda equina. Preoperative angiography may be useful for diagnosis and understanding of the anatomy of feeding veins. J. Med. Invest. 69 : 312-315, August, 2022.

Preoperative Planning Using Three-dimensional Printing for Full-endoscopic Spine Surgery: A Technical Note.

Transforaminal full-endoscopic spine surgery (TF-FESS) is a novel minimally invasive spine surgery that requires only an 8-mm skin incision and causes minimal damage to the paravertebral muscles. To perform TF-FESS safely and efficiently, preoperative planning is quite important as the intervention requires anatomical understanding and high technical skills. Recently, three-dimensional (3D) printing has become a useful tool in various surgeries, and several studies have addressed its efficacy; however, there are no reports on the application of 3D printing to FESS. In this study, we present two cases of severe lumbar deformities for which preoperative 3D printing was useful. The 3D printing enabled the surgeons to visualize and plan the drilling of the superior articular process for a successful foraminoplasty at a low cost. The manufacturing equipment cost about USD 900 and is able to produce an actual-size model at a cost of less than USD 10 per patient. In conclusion, preoperative planning using 3D printing should be adopted to safely perform FESS.

Image-guided core needle biopsy for musculoskeletal lesions.

BACKGROUND: Image-guided percutaneous core needle biopsy (CNB) has been an important diagnostic procedure for musculoskeletal lesions. Here we surveyed the variety of diagnostic strategies available and assessed the clinical usefulness and limitations of image-guided CNB carried out by a multidisciplinary team comprising specialists in various fields. METHODS: We conducted a retrospective study of 284 image-guided CNBs among 1899 consecutive biopsy procedures carried out at our institution for musculoskeletal tumorous conditions, focusing on their effectiveness including diagnostic accuracy and utility for classification of specimens according to malignant potential and histological subtype as well as their correlation with biopsy routes. RESULTS: Among the 284 studied biopsies, 252 (88.7%) were considered clinically "effective". The sensitivity for detection of malignancy was 94.0% (110/117) and the specificity was 95.3% (41/43). The diagnostic accuracy for detection of malignancy was 94.4% (151/160) and that for histological subtype was 92.3% (48/52). The clinical effectiveness of the procedure was correlated with the complexity of the biopsy route (P = 0.015); the trans-pedicular, trans-retroperitoneal and trans-sciatic foramen approaches tended to yield ineffective results. Repeat biopsy did not have a significant impact on the effectiveness of image-guided CNB (P = 0.536). CONCLUSIONS: The diagnostic accuracy rates of image-guided CNB performed at multidisciplinary sarcoma units were usable even for patients who have variety of diagnostic biopsy procedures. It is important to establish and implement diagnostic strategies based on an understanding that complicated routes, especially for spine and pelvic lesions, may be associated with ineffectiveness and/or complications.

Clinical application of dynamic 18F-fluorodeoxyglucose positron-emission tomography / computed tomography in the differential diagnoses of musculoskeletal lesions.

We aimed to assess the differential diagnostic efficacy of dynamic F-18 fluorodeoxyglucose (FDG) positron emission tomography / computed tomography (PET / CT) and to evaluate the appropriate scan timings for diagnosis of musculoskeletal lesions (MSLs). Dynamic scans (5-15 [phase 1], 15-25 [phase 2], and 25-35 [phase 3] min after F-18 FDG injection) and dual-time-point scans (1 and 2 h after injection) were acquired for 23 MSLs [4 benign MSLs (BMSLs). 10 primary malignant musculoskeletal tumors (PMMSTs), and 9 metastatic musculoskeletal tumors (MMSTs)]. We compared the maximum standardized uptake values (SUVmax) and corresponding retention indices for dynamic (RI-SUVdyn) and dual-time-point (RI-SUVdual) scans and evaluated diagnostic efficacy using receiver operating characteristic (ROC) curve analyses. The SUVmax gradually decreased or was almost identical with minimal fluctuation in 3 BMSLs and 1 PMMST. SUVmax increased over time after phase 2 in 18 malignant MSLs (MMSLs). There were significant differences in SUVmax (for all time phases) and RI-SUV dual between BMSLs and MMSLs and between PMMSTs and MMSTs. In the ROC analyses, the areas under the curve for SUV in phases 2 and 3 were highest for differentiating BMSLs from MMSLs and PMMSTs from MMSTs, respectively. Dynamic F-18 FDG PET / CT is valuable for diagnosis of musculoskeletal lesions. J. Med. Invest. 68 : 96-104, February, 2021.

Distribution of the Spinal Arteries in Adult Patients with Lumbar Spondylolysis.

INTRODUCTION : The pathology of lumbar spondylolysis is generally thought to begin with a stress fracture in adolescence. Stress fractures of the lower extremities occur in watershed areas with a poor vascular supply because of an inability to respond to stress and heal. This pathology has not been well researched in the lumbar spine. The aim of this study was to evaluate the distribution of the spinal arteries in patients with lumbar spondylolysis. METHODS : The extraosseous distribution of the arteries around the pars interarticularis was retrospectively investigated in 14 patients with colon cancer who underwent abdominal contrast-enhanced computed tomography (CE-CT) as part of a preoperative assessment at our hospital and were found to have spondylolysis at L5. RESULTS : All patients were found to have terminal-stage spondylolysis at L5 (1 unilateral, 13 bilateral). L5 segmental artery was absent in all cases. However, separate spinal arteries supplying the pars interarticularis at L5 were found above and below the transverse process at this level. CONCLUSION : All the patients had two separate arteries originating from the cranial and caudal sides that distributed to the superior and inferior articular processes, suggesting that the pars interarticularis is a posterior element containing a vascular watershed area. J. Med. Invest. 67 : 62-66, February, 2020.

Intracanalicular Osteochondroma in the Lumbar Spine.

Osteochondroma is a common benign bone tumor that is relatively rare in the spine. Here, we report two cases of symptomatic solitary osteochondroma of the lumbar spine. The first case was a 61-year-old man who presented with a 2-year history of right leg numbness. Imaging findings showed that the cause of the radiculopathy was osteochondroma of the right inferior articular process at L4. The tumor was removed en bloc, and the numbness resolved. The second case was a 62-year-old man with osteochondroma of the right superior articular process at L5 that caused pain and numbness in the right leg. En bloc resection of the osteochondroma with the ligamentum flavum relieved the symptoms. Spinal osteochondroma occurs relatively frequently in elderly individuals compared with peripheral lesions and mimics a degenerative spinal disorder. Careful physical examination and imaging evaluation can reveal this tumor and surgery is effective for relieving the symptoms.

Preliminary clinical assessment of dynamic carbon-11 methionine positron-emission tomography/computed tomography for the diagnosis of the pathologies in patients with musculoskeletal lesions: a prospective study.

BACKGROUND: This study prospectively assessed the diagnostic capacity of dynamic carbon-11 methionine (C-11 MET) positron-emission tomography (PET)/computed tomography for the diagnosis of pathologies in patients with primary unknown musculoskeletal lesions (MSLs). In total, 13 patients with MSLs underwent dynamic scans (5-10 [phase 1], 10-15 [phase 2], 15-20 [phase 3], 20-25 [phase 4], 25-30 [phase 5], and 30-35 [phase 6] min post-injection of C-11 MET). We statistically compared the maximum standardised uptake values (SUVmax) and corresponding retention index for dynamic scans (RI-SUV) for five benign MSLs (BMSLs), five primary malignant musculoskeletal tumours (PMMSTs), four metastatic musculoskeletal tumours (MMSTs), and three malignant lymphoma (ML) cases and explored their diagnostic capacities using receiver operating characteristic (ROC) curve analyses. RESULTS: SUVmax gradually decreased or remained similar with minimal fluctuations in all BMSL cases and four of five PMMST cases. In contrast, SUVmax increased over time in one case of PMMST and in all cases of MMST and ML. Significant differences were observed in SUVmax for all time phases and RI-SUV between BMSLs and MMSLs, in SUVmax for all time phases between PMMSTs and BMSLs, in SUVmax for all time phases and RI-SUV between non-PMMST-malignant tumours and BMSL, and in RI-SUV between non-PMMST-malignant tumours and PMMST. In ROC analyses, the areas under the curve yielded the highest values at 1.00 for differentiating most intergroup comparisons. CONCLUSIONS: Dynamic C-11 MET PET scans have the potential to be good predictors of discriminating MSLs in patients with primary unknown MSLs in clinical practice.

Osteolytic primary bone lymphoma in the multiple bones.

Primary non-Hodgkin bone lymphoma (PBL) can involve solitary or multiple destructive bone lesions such as those of the femur or pelvis humerus, and some cases have osteolytic lesions. PBL is a rare disease in adults. Thus, PBL is rarely considered a differential diagnosis of the osteolytic tumor. In addition, PBL can be underdiagnosed because patients do not experience symptoms or show objective abnormalities in the early stage. Here, we reported an elderly patient with PBL in multiple bones, including the cranial and femoral bones that were fractured due to falling. J. Med. Invest. 66 : 347-350, August, 2019.

A Rare Case of Acute-Onset Spastic Quadriparesis Caused by a Chondroma of the Cervical Spine.

Chondromas are benign cartilaginous tumors that occur very rarely in the spine. Moreover, chondromas of the extraskeletal origin are also very rare. In this case report, we describe an extremely rare case of chondroma arising from the ligamentum flavum in the cervical spine. A 67-year-old man presented to our clinic with acute-onset spastic quadriparesis. We performed emergent magnetic resonance imaging and found an epidural mass in the right ligamentum flavum at C4-C5. The acute-onset presentation was suspicious for intraligamentous hematoma in the ligamentum flavum at this level. We performed emergency decompression surgery and en bloc removal of the epidural mass with the right C4 and C5 lamina. The lesion had the appearance of cartilaginous tissue rather than hematoma. Based on the histological investigation, the final diagnosis was intraligamentous chondroma of the cervical spine. The quadriparesis improved postoperatively, as did the results of manual muscle testing in the affected area, and he was able to resume walking independently with a cane. At the one-year follow-up, the manual muscle testing results were almost normal. Surgeons should keep in mind the possibility of benign tumors including chondroma of the cervical spine when a patient presents with acute-onset quadriparesis.

Intimal sarcoma arising from the common iliac artery presenting with artery occlusion : a case report and literature review.

We present a rare case of intimal sarcoma arising from the common iliac artery in an 82-year-old man who presented with intermittent claudication. He had undergone endovascular therapy with self-expanding stents to both iliac arteries that had occluded soon after placement. After salvage bypass grafting, a diagnosis of intimal sarcoma with angiosarcoma phenotype from the iliac artery was made. Further bypass graft surgery relieved symptoms temporarily. However, the tumor progressed and the left limb became ischemic. The chemotherapy of eribulin did not prevent tumor progression. The patient died of the disease 20 months after the first surgery. J. Med. Invest. 66 : 205-208, February, 2019.

Symptomatic Os Intercuneiform: A Case Report.

We encountered a case of an accessory bone in the foot in the distal portion of the tarsal navicular and the proximal portion of the intermediate cuneiform, namely an os intercuneiform. The patient presented with a history of pain on the dorsal aspect of the left foot, with tenderness and swelling. Perioperative findings revealed a synfibrotic connection between the accessory bone and the navicular and intermediate cuneiform. After unsuccessful conservative treatment, the accessory bone was excised, leading to postoperative symptomatic relief.

Total calcanectomy for metastasis of renal cell carcinoma in the calcaneus: A case report.

We present a rare case of metastasis of renal cell carcinoma to the calcaneus in a 59-year-old man who presented with pain and inability to bear weight on the left foot 3 years after right nephrectomy for renal cell carcinoma. He successfully underwent en bloc resection of his right calcaneus with a limb salvage procedure, total calcanectomy without bony reconstruction. Histological findings identified the lesion as a metastasis originating from a renal cell carcinoma. Recent follow-up examination showed no recurrence. To the best of our knowledge, this is the first reported case to be treated with total calcanectomy for renal cell carcinoma metastasis.

Restoration of the Active Forearm Rotation Using Vascularized Free Fibular Graft and Radial Head Arthroplasty for a Wide Defect of the Proximal Radius.

In this report we present a case of re-stabilization of the proximal radius using vascularized free fibular graft combined with anconeus arthroplasty to stabilize the transplanted fibula in a patient with large loss of the proximal radius due to Ewing's sarcoma. A 20-year-old woman had Ewing's sarcoma in the proximal three-fourths of the radius. The resection of large part of the radius containing radial head were necessary for removal of the sarcoma. Reconstruction of the proximal radius was performed using vascularized free fibular graft and the transplanted fibula was stabilized by attaching the anconeus to the proximal edge of the fibula. 2 years after surgery, she had neither recurrence nor metastasis, and achieved functional recovery. The combination anconeus arthroplasty with vascularized free fibular graft can be a good technique for re-stabilization of the elbow and recovery of the forearm function.