Benefits of Collaboration Between the Wound, Ostomy, and Continence Nurse and Orthopedic Surgeon When Treating Skin Defects After Soft Tissue Sarcoma Resection: A Retrospective Case-Control Study.

PURPOSE: The purpose of this study was to evaluate the benefits of collaborative management between orthopedic surgery and WOC nurses in patients undergoing resection of subcutaneous sarcomas. DESIGN: Retrospective case-control study. SUBJECTS AND SETTING: The sample comprised 25 patients who underwent wide resection for soft tissue sarcoma, followed by 2-stage split-thickness skin grafting. Data collection occurred between January 2015 and April 2021 in a university hospital based in Kagoshima, Japan. For comparison, we categorized these patients into 2 groups: intervention group participants were managed by an orthopedic surgeon and a WOC nurse; nonintervention group members were managed without WOC nurse participation. METHODS: Patient background and treatment-related information was retrospectively collected from medical records and compared between the WOC nurse intervention group and the nonintervention group, including maximum tumor diameter, surgical time, maximum skin defect diameter, length of hospital stay, and time from surgery to complete wound healing. RESULTS: The average length of hospital stay was significantly shorter in the WOC nurse intervention group compared with the nonintervention group (38.3 days, SD = 8.0 vs 47.1 days, SD = 10.2; P = .023). CONCLUSION: Collaborative wound management with a WOC nurse resulted in a shorter hospital length of stay when compared to traditional management with WOC nurse involvement. Based on these findings, we assert that WOC nurses provide an important bridge between postoperative wound management in patients undergoing resection of subcutaneous sarcomas.

Low-grade Fibromyxoid Sarcoma With Massive Degeneration: A Case of Unusual Gross and Histological Features.

BACKGROUND: Low-grade fibromyxoid sarcoma (LGFMS) is a rare type of sarcoma which is observed in the soft tissue of proximal extremities, typically in young and middle-aged adults. It consists of a solid proliferation of bland spindle cells within collagenous and myxoid stroma. CASE REPORT: Herein, we report a case of LGFMS with massive degeneration and hyalinization. A 30-year-old man presented with a well-circumscribed mass measuring 15 cm in diameter in his left biceps femoris muscle. Marginal tumor resection was performed under the clinical diagnosis of an ancient schwannoma or chronic expanding hematoma (CEH). The resected tissue revealed a well-demarcated tumor mass with massive degeneration and hyalinization with focal calcification. Proliferation of spindle tumor cells with abundant collagenous stroma, which resembled the fibrous capsule of CEH, was observed exclusively in a small area of the periphery of the tumor. No nuclear palisading, myxoid stroma, or collagen rosettes were identified. Immunohistochemical analysis demonstrated that the spindle tumor cells expressed mucin 4 and epithelial membrane antigen. Reverse transcriptase-polymerase chain reaction analysis detected mRNA expression of fused in sarcoma::CAMP-responsive element binding protein 3-like protein 2 (FUS::CREB3L2) fusion gene. Thus, a final diagnosis of LGFMS with massive degeneration and FUS::CREB3L2 fusion was made. CONCLUSION: The recognition of massive degeneration and hyalinization as unusual features of LGFMS might be helpful to differentiate it from CEH and other benign spindle-cell tumors.

Liposarcoma of the pleural cavity.

Liposarcoma rarely occurs in the pleura or thoracic cavity, and few reports appear in the literature. We hypothesized that combining clinicopathologic, immunohistochemical, and fluorescence in situ hybridization methods would allow definite diagnoses. Using formalin-fixed, paraffin-embedded blocks, we examined 6 atypical lipomatous tumor/well-differentiated liposarcomas (ALT/WDLPS), 5 dedifferentiated liposarcomas (DDLPSs), 2 pleomorphic liposarcomas, and 1 myxoid liposarcoma (MLPS). We used the Kaplan-Meier method and the Wilcoxon test for survival analysis for prognostic factor evaluation. Histologically, ALT/WDLPS was composed of a relatively mature adipocytic proliferation, accompanied by some lipoblasts. DDLPS exhibited round-to-oval tumor cells with a high nucleus-to-cytoplasm ratio that had proliferated in nests, accompanied in case 10 by some giant cells but no fatty cells. The pleomorphic type contained a varying proportion of pleomorphic lipoblasts. MLPS displayed uniform round- to oval-shaped cells and small signet-ring lipoblasts in a myxoid stroma. Immunohistochemically, 11 (79%), 11 (79%), and 10 (71%) of 14 cases were positive for S-100, p16, and CDK4, respectively. Six of the 14 cases (43%) were positive for MDM2 and adipophilin. One case of ALT/WDLPS and 3 cases of DDLPS exhibited MDM2 amplification by fluorescence in situ hybridization (Vysis LSI MDM2 SpectrumGreen Probe plus Vysis CEP 12 SpectrumOrange probe). ALT/WDLPS was the most favorable type for survival, while adipophilin tended to be a negative prognostic factor for pleural liposarcoma. For a firm diagnosis of liposarcoma in the pleura, immunohistochemistry for CDK4, MDM2, and adipophilin together with MDM2 gene amplification by fluorescence in situ hybridization may be an important diagnostic tool.

Long-Term Results of Kyocera Modular Limb Salvage System after Resection of Tumors in the Distal Part of the Femur: Report from Japanese Musculoskeletal Oncology Group Study.

BACKGROUND: The distal femur is a common site of bone tumors. After surgical resection, prosthetic replacement is a major reconstruction method. We aimed to elucidate the long-term outcomes of the Kyocera Modular Limb Salvage (KMLS) systems after resection of tumors in the distal part of the femur. METHODS: Between 1998 and 2014, 125 patients were treated at 14 institutions. There were 59 males and 66 females, with a mean age of 35 years. The mean follow-up period was 132 months. RESULTS: There had been 65 additional surgeries, including 56 revisions and 9 amputations: 15 for aseptic loosening, 14 for stem breakage, 13 for deep infection, 13 for rotator-hinge bushing failure, 5 for local recurrence, and 5 for others. Implant survival rates at 10 and 15 years were 58.5% and 39.4%. The cumulative incidence of 15-year revision for femoral stem breakage was 31.7% in patients with cementless fixation. The 15-year cumulative incidence of revision for aseptic loosening was 19.8% in patients with cement fixation. CONCLUSIONS: KMLS systems represent a reliable system with long-term results. Stem breakage should be considered in patients with cementless and/or smaller femoral stem sizes. Aseptic loosening should be considered in patients with cement systems after 10 years.

18F-FDG PET/CT Imaging of G-CSF-Producing Dedifferentiated Liposarcoma.

ABSTRACT: Granulocyte colony-stimulating factor (G-CSF)-producing tumors are malignant tumors associated with a poor prognosis, and G-CSF-producing liposarcoma is particularly rare. We report a case of G-CSF-producing dedifferentiated liposarcoma. 18F-FDG PET/CT showed abnormal 18F-FDG uptake throughout the bone marrow and in the primary site. When a diffuse bone marrow 18F-FDG uptake was observed on 18F-FDG PET/CT, G-CSF-producing dedifferentiated liposarcoma should be included in the differential diagnosis.

PEG10 counteracts signaling pathways of TGF-ß and BMP to regulate growth, motility and invasion of SW1353 chondrosarcoma cells.

Recently, we reported highly active transforming growth factor (TGF)-ß and bone morphogenetic protein (BMP) signaling in human chondrosarcoma samples and concurrent downregulation of paternally expressed gene 10 (PEG10). PEG10 expression was suppressed by TGF-ß signaling, and PEG10 interfered with the TGF-ß and BMP-SMAD pathways in chondrosarcoma cells. However, the roles of PEG10 in bone tumors, including chondrosarcoma, remain unknown. Here, we report that PEG10 promotes SW1353 chondrosarcoma cell growth by preventing TGF-ß1-mediated suppression. In contrast, PEG10 knockdown augments the TGF-ß1-induced motility of SW1353 cells. Individually, TGF-ß1 and PEG10 siRNA increase AKT phosphorylation, whereas an AKT inhibitor, MK2206, mitigates the effect of PEG10 silencing on cell migration. SW1353 cell invasion was enhanced by BMP-6, which was further increased by PEG10 silencing. The effect of siPEG10 was suppressed by inhibitors of matrix metalloproteinase (MMP). BMP-6 induced expression of MMP-1, -3, and -13, and PEG10 lentivirus or PEG10 siRNA downregulated or further upregulated these MMPs, respectively. PEG10 siRNA increased BMP-6-induced phosphorylation of p38 MAPK and AKT, whereas the p38 inhibitor SB203580 and MK2206 diminished SW1353 cell invasion by PEG10 siRNA. SB203580 and MK2206 impeded the enhancing effect of PEG10 siRNA on the BMP-6-induced expression of MMP-1, -3, and -13. Our findings suggest dual functions for PEG10: accelerating cell growth by suppressing TGF-ß signaling and inhibiting cell motility and invasion by interfering with TGF-ß and BMP signaling via the AKT and p38 pathways, respectively. Thus, PEG10 might be a molecular target for suppressing the aggressive phenotypes of chondrosarcoma cells.

TGF-ß signalling and PEG10 are mutually exclusive and inhibitory in chondrosarcoma cells.

Histological distinction between enchondroma and chondrosarcoma is difficult because of a lack of definitive biomarkers. Here, we found highly active transforming growth factor-ß (TGF-ß) and bone morphogenetic protein (BMP) signalling in human chondrosarcomas compared with enchondromas by immunohistochemistry of phosphorylated SMAD3 and SMAD1/5. In contrast, the chondrogenic master regulator SOX9 was dramatically down-regulated in grade 1 chondrosarcoma. Paternally expressed gene 10 (PEG10) was identified by microarray analysis as a gene overexpressed in chondrosarcoma SW1353 and Hs 819.T cells compared with C28/I2 normal chondrocytes, while TGF-ß1 treatment, mimicking higher grade tumour conditions, suppressed PEG10 expression. Enchondroma samples exhibited stronger expression of PEG10 compared with chondrosarcomas, suggesting a negative association of PEG10 with malignant cartilage tumours. In chondrosarcoma cell lines, application of the TGF-ß signalling inhibitor, SB431542, increased the protein level of PEG10. Reporter assays revealed that PEG10 repressed TGF-ß and BMP signalling, which are both SMAD pathways, whereas PEG10 knockdown increased the level of phosphorylated SMAD3 and SMAD1/5/9. Our results indicate that mutually exclusive expression of PEG10 and phosphorylated SMADs in combination with differentially expressed SOX9 is an index to distinguish between enchondroma and chondrosarcoma, while PEG10 and TGF-ß signalling are mutually inhibitory in chondrosarcoma cells.

Human immunodeficiency virus type 1 enhancer-binding protein 3 is essential for the expression of asparagine-linked glycosylation 2 in the regulation of osteoblast and chondrocyte differentiation.

Human immunodeficiency virus type 1 enhancer-binding protein 3 (Hivep3) suppresses osteoblast differentiation by inducing proteasomal degradation of the osteogenesis master regulator Runx2. In this study, we tested the possibility of cooperation of Hivep1, Hivep2, and Hivep3 in osteoblast and/or chondrocyte differentiation. Microarray analyses with ST-2 bone stroma cells demonstrated that expression of any known osteochondrogenesis-related genes was not commonly affected by the three Hivep siRNAs. Only Hivep3 siRNA promoted osteoblast differentiation in ST-2 cells, whereas all three siRNAs cooperatively suppressed differentiation in ATDC5 chondrocytes. We further used microarray analysis to identify genes commonly down-regulated in both MC3T3-E1 osteoblasts and ST-2 cells upon knockdown of Hivep3 and identified asparagine-linked glycosylation 2 (Alg2), which encodes a mannosyltransferase residing on the endoplasmic reticulum. The Hivep3 siRNA-mediated promotion of osteoblast differentiation was negated by forced Alg2 expression. Alg2 suppressed osteoblast differentiation and bone formation in cultured calvarial bone. Alg2 was immunoprecipitated with Runx2, whereas the combined transfection of Runx2 and Alg2 interfered with Runx2 nuclear localization, which resulted in suppression of Runx2 activity. Chondrocyte differentiation was promoted by Hivep3 overexpression, in concert with increased expression of Creb3l2, whose gene product is the endoplasmic reticulum stress transducer crucial for chondrogenesis. Alg2 silencing suppressed Creb3l2 expression and chondrogenesis of ATDC5 cells, whereas infection of Alg2-expressing virus promoted chondrocyte maturation in cultured cartilage rudiments. Thus, Alg2, as a downstream mediator of Hivep3, suppresses osteogenesis, whereas it promotes chondrogenesis. To our knowledge, this study is the first to link a mannosyltransferase gene to osteochondrogenesis.

Bone morphogenic protein (BMP) signaling up-regulates neutral sphingomyelinase 2 to suppress chondrocyte maturation via the Akt protein signaling pathway as a negative feedback mechanism.

Although bone morphogenic protein (BMP) signaling promotes chondrogenesis, it is not clear whether BMP-induced chondrocyte maturation is cell-autonomously terminated. Loss of function of Smpd3 in mice results in an increase in mature hypertrophic chondrocytes. Here, we report that in chondrocytes the Runx2-dependent expression of Smpd3 was increased by BMP-2 stimulation. Neutral sphingomyelinase 2 (nSMase2), encoded by the Smpd3 gene, was detected both in prehypertrophic and hypertrophic chondrocytes of mouse embryo bone cartilage. An siRNA for Smpd3, as well as the nSMase inhibitor GW4869, significantly enhanced BMP-2-induced differentiation and maturation of chondrocytes. Conversely, overexpression of Smpd3 or C2-ceramide, which mimics the function of nSMase2, inhibited chondrogenesis. Upon induction of Smpd3 siRNA or GW4869, phosphorylation of both Akt and S6 proteins was increased. The accelerated chondrogenesis induced by Smpd3 silencing was negated by application of the Akt inhibitor MK2206 or the mammalian target of rapamycin inhibitor rapamycin. Importantly, in mouse bone culture, GW4869 treatment significantly promoted BMP-2-induced hypertrophic maturation and calcification of chondrocytes, which subsequently was eliminated by C2-ceramide. Smpd3 knockdown decreased the apoptosis of terminally matured ATDC5 chondrocytes, probably as a result of decreased ceramide production. In addition, we found that expression of hyaluronan synthase 2 (Has2) was elevated by a loss of Smpd3, which was restored by MK2206. Indeed, expression of Has2 protein decreased in nSMase2-positive hypertrophic chondrocytes in the bones of mouse embryos. Our data suggest that the Smpd3/nSMase2-ceramide-Akt signaling axis negatively regulates BMP-induced chondrocyte maturation and Has2 expression to control the rate of endochondral ossification as a negative feedback mechanism.

[Emergency surgery for coronary ostial occlusion and aortic root aneurysm associated with Takayasu's arteritis; report of a case].

We report a case of Takayasu's arteritis who underwent emergency surgery. A 39-year-old female presented with severe back pain. Electrocardiogram demonstrated complete atrio-ventricular (AV) block and acute inferior myocardial infarction. Coronary angiography revealed ostial occlusion of the right coronary artery. Aortography and contrast-enhanced computed tomography revealed dilated and bizarre-shaped aortic root. The remainder of the aorta and its branches appeared normal. She underwent emergency aortic root replacement with valved conduit. Coronary artery bypass grafting to right coronary artery( RCA) using saphenous vein graft was performed concomitantly. Histologic findings of the aortic root were compatible with Takayasu's arteritis. Postoperative angiography showed graft patency. Takayasu arteritis should be considered for differential diagnosis of acute myocardial infarction in young woman.

Bilobular calcifying fibrous pseudotumor in soleus muscle: a case report.

INTRODUCTION: Calcifying fibrous pseudotumor is a rare benign soft-tissue lesion composed of fibrous tissue with abundant hyalinized collagen and dystrophic and often psammomatous calcifications. The cause of the disease is unclear but, usually, complete resection of the well-circumscribed tumor is sufficient to avoid recurrence of the disease. Here, we report an unusual case of this rare tumor that presented as two lobulated lesions in the calf muscle. CASE PRESENTATION: The patient was a 17-year-old Japanese girl who noted a hard mass in her left calf. Magnetic resonance imaging revealed two well-demarcated lobular masses in the soleus muscle, and the tumor was significantly enhanced by contrast medium. Preoperative differential diagnoses included soft-part tumors composed of fibrous tissue. However, making a definite diagnosis was impossible because a lobulated shape is rare for fibrous tumors. Biopsy demonstrated that the mass was a benign tumor composed of collagen-rich, hyalinized fibrosclerotic tissue. We performed marginal resection of the two nodules, including the fibrous tissue that connected them. Immunohistochemistry was positive for factor XIIIa and negative for anaplastic lymphoma kinase-1. These findings were helpful to distinguish calcifying fibrous pseudotumor from inflammatory myofibroblastic tumor. There was no sign of recurrence at 30 months after surgery. CONCLUSION: To the best of our knowledge, this is the first case of bilobular calcifying fibrous pseudotumor that developed in an extremity. As described in the previous literature, simple excision was sufficient for the treatment of calcifying fibrous pseudotumor with two lobules.

Rapid recurrence of cystic adventitial disease in femoral artery and an etiologic consideration for the cyst.

A 53-year-old man, complaining of left calf and hip claudication, was treated with surgery of the occluded common femoral artery. After incision in the artery, gelatinous material came out from the intramural cavity. All the contained material was evacuated, and definitive diagnosis of cystic adventitial disease was confirmed postoperatively. Twenty days later, he complained of identical claudication again. Follow-up study suggested the recurrence. Therefore, the artery replacement with polytetrafluoroethylene graft was performed. Pathologic examinations showed that the adventitial cyst lining cells expressed macrophage markers (CD68 and CD14), while fibroblast-like cells were not found on the lining. Cystic adventitial disease was not derived from synovium in this case.

[A case of primary pulmonary leiomyosarcoma showing rapid growth and fatal outcome].

An 80-year-old man was admitted to our hospital with a 4.0 x 2.0 cm shadow accompanied by calcification, found on chest CT scans on a health check. The shadow was located in the left lower lobe (S10), and was attached to the pleura. A transbronchial biopsy did not yield a definitive diagnosis. A percutaneous needle biopsy yielded a diagnosis of leiomyosarcoma. A general examination did not show any metastatic lesions in other areas. However, the tumor grew rapidly, with pleural effusion, and therefore he was treated only by palliative therapy. He died from respiratory failure 90 days after onset. The primary site of the tumor was determined to be intrapulmonary area by radiographic and autopsy findings. We report a rare primary pulmonary leiomyosarcoma showing rapid growth and fatal outcome.