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Background: Recently, the T2 alpha nailing system (Stryker, Inc.), which has advanced locking screws that can attach a screw to a rod, has been used worldwide and is expected to improve fracture fixation. We analyzed two cases of supracondylar femoral fractures in older adult patients, in which intraoperative fractures occurred during the insertion of advanced locking screws of the T2 alpha femur retrograde intramedullary nail. Case presentation: A 93-year-old and an 82-year-old woman each underwent T2 alpha femur retrograde nail fixation for supracondylar femur fractures at separate hospitals, and advanced locking screws were used as the proximal transverse locking screws. In both patients, a fracture line was observed at the proximal screw postoperatively, and the fractures were refixed with distal cable wiring and/or femoral distal plates. The patients were subsequently discharged from the same facility with no remarkable pain. Conclusions: When inserting advanced locking screws, it is necessary to enlarge the screw hole in the near-bone cortex with a counterbore drill, which might add torque to the bone cortex that could result in fractures. If the sleeve is distant from the bone, the counterbore drill will not reach the bone, the screw hole will not expand, and the insertion of advanced locking screws will apply a strong torque to the bone cortex and may result in fracture. Moreover, it is important to confirm that the counterbore drill is securely inserted under fluoroscopy and to carefully enlarge the bony foramen manually to prevent fractures during screw insertion. [ABSTRACT FROM AUTHOR]

Simple Summary: In this retrospective cohort study, predictive factors for graft survival were investigated in 123 patients who underwent reconstructions using a tumor-bearing frozen autograft after bone tumor resection of the extremities. The graft survival rates were 83.2% at 5 years and 70.2% at 10 years. Multivariate analysis using the Cox proportional hazards regression model revealed that BMI of ≥23.6 (HR, 3.4; p = 0.005), tibia (HR, 2.3; p = 0.047), and freezing procedure (HR, 0.3; p = 0.016) were independently associated with graft survival. Based on the results, pedicle or hemicortical freezing techniques are recommended in cases where these techniques can be applied. Tumor-bearing frozen autografts have been widely used for reconstruction of bone defects caused by tumor resection. However, some patients undergo removal of the grafted bone due to surgical site infection, tumor recurrence, or fractures of the grafted bone. In this retrospective cohort study, predictive factors for graft survival were investigated in 123 patients who underwent reconstructions using a tumor-bearing frozen autograft after bone tumor resection of the extremities. To determine the independent predictors of graft survival, the association between various parameters and graft survival was investigated. The graft survival rates were 83.2% at 5 years and 70.2% at 10 years. Among the 123 frozen autografts, 25 (20.3%) were removed because of complications. In univariate analyses, male sex, BMI of ≥23.6, tibia, and chemotherapy were significantly associated with poor graft survival, whereas the pedicle/hemicortical freezing procedure was significantly associated with better graft survival. Multivariate analysis using the Cox proportional hazards regression model revealed that BMI of ≥23.6 (HR, 3.4; p = 0.005), tibia (HR, 2.3; p = 0.047), and freezing procedure (HR, 0.3; p = 0.016) were independently associated with graft survival. Based on the results, pedicle or hemicortical freezing techniques are recommended in cases where these techniques can be applied. [ABSTRACT FROM AUTHOR]

Adipose-derived stem cells (ADSCs) have been studied for many years as a therapeutic option for osteoarthritis (OA); however, their efficacy remains insufficient. Since platelet-rich plasma (PRP) induces chondrogenic differentiation in ADSCs and the formation of a sheet structure by ascorbic acid can increase the number of viable cells, we hypothesized that the injection of chondrogenic cell sheets combined with the effects of PRP and ascorbic acid may hinder the progression of OA. The effects of induction of differentiation by PRP and formation of sheet structure by ascorbic acid on changes in chondrocyte markers (collagen II, aggrecan, Sox9) in ADSCs were evaluated. Changes in mucopolysaccharide and VEGF-A secretion from cells injected intra-articularly in a rabbit OA model were also evaluated. ADSCs treated by PRP strongly chondrocyte markers, including type II collagen, Sox9, and aggrecan, and their gene expression was maintained even after sheet-like structure formation induced by ascorbic acid. In this rabbit OA model study, the inhibition of OA progression by intra-articular injection was improved by inducing chondrocyte differentiation with PRP and sheet structure formation with ascorbic acid in ADSCs. [ABSTRACT FROM AUTHOR]

We aimed to retrospectively investigate the demographic characteristics and short-term outcomes of traumatic cervical spine injuries in patients with dementia. We enrolled 1512 patients aged ≥ 65 years with traumatic cervical injuries registered in a multicenter study database. Patients were divided into two groups according to the presence of dementia, and 95 patients (6.3%) had dementia. Univariate analysis revealed that the dementia group comprised patients who were older and predominantly female and had lower body mass index, higher modified 5-item frailty index (mFI-5), lower pre-injury activities of daily living (ADLs), and a larger number of comorbidities than patients without dementia. Furthermore, 61 patient pairs were selected through propensity score matching with adjustments for age, sex, pre-injury ADLs, American Spinal Injury Association Impairment Scale score at the time of injury, and the administration of surgical treatment. In the univariate analysis of the matched groups, patients with dementia had significantly lower ADLs at 6 months and a higher incidence of dysphagia up to 6 months than patients without dementia. Kaplan–Meier analysis revealed that patients with dementia had a higher mortality than those without dementia until the last follow-up. Dementia was associated with poor ADLs and higher mortality rates after traumatic cervical spine injuries in elderly patients. [ABSTRACT FROM AUTHOR]

For older patients with decreased reserve function, traumatic cervical spine injuries frequently lead to early mortality. However, the prognostic factors for early mortality remain unclear. This study included patients aged ≥65 years and hospitalized for treatment of traumatic cervical spine injuries in 78 hospitals between 2010 and 2020. Early mortality was defined as death within 90 days after injury. We evaluated the relationship between early mortality and the following factors: age, sex, body mass index, history of drinking and smoking, injury mechanisms, presence of a cervical spine fracture and dislocation, cervical ossification of the posterior longitudinal ligament, diffuse idiopathic skeletal hyperostosis, American Spinal Injury Association Impairment Scale, concomitant injury, pre-existing comorbidities, steroid administration, and treatment plan. Overall, 1512 patients (mean age, 75.8 ± 6.9 years) were included in the study. The early mortality rate was 4.0%. Multivariate analysis identified older age (OR = 1.1, p < 0.001), male sex (OR = 3.7, p = 0.009), cervical spine fracture (OR = 4.2, p < 0.001), complete motor paralysis (OR = 8.4, p < 0.001), and chronic kidney disease (OR = 5.3, p < 0.001) as risk factors for early mortality. Older age, male sex, cervical spine fracture, complete motor paralysis, and chronic kidney disease are prognostic factors for early mortality in older patients with traumatic cervical spine injuries. [ABSTRACT FROM AUTHOR]

A long noncoding RNA, nuclear paraspeckle assembly transcript 1 (NEAT1) variant 1 (NEAT1v1), confers radioresistance to hepatocellular carcinoma (HCC) cells by inducing autophagy via γ-aminobutyric acid A receptor-associated protein (GABARAP). Radiation induces oxidative stress to damage cellular components and organelles, but it remains unclear how NEAT1v1 protects HCC cells from radiation-induced oxidative stress via autophagy. To address this, we precisely investigated NEAT1v1-induced autophagy in irradiated HCC cell lines. X-ray irradiation significantly increased cellular and mitochondrial oxidative stress and mitochondrial DNA content in HCC cells while NEAT1v1 suppressed them. NEAT1v1 concomitantly induced the phosphatase and tensin homolog-induced kinase 1 (PINK1)/parkin-mediated mitophagy. Interestingly, parkin expression was constitutively upregulated in NEAT1v1-overexpressing HCC cells, leading to increased mitochondrial parkin levels. Superoxide dismutase 2 (SOD2) was also upregulated by NEAT1v1, and GABARAP or SOD2 knockdown in NEAT1v1-overexpressing cells increased mitochondrial oxidative stress and mitochondrial DNA content after irradiation. Moreover, it was suggested that SOD2 was involved in NEAT1v1-induced parkin expression, and that GABARAP promoted parkin degradation via mitophagy. This study highlights the unprecedented roles of NEAT1v1 in connecting radioresistance and mitophagy in HCC. [ABSTRACT FROM AUTHOR]

Total hip arthroplasty (THA) for patients with hip osteoarthritis improves hip flexion contracture, subsequently improving spinal sagittal balance. However, in some cases, spinal sagittal imbalance develops in the course after THA, and its risk factors remain unknown. We aimed to investigate the risk factors of progressive spinal sagittal imbalance after THA. This retrospective cohort study of a prospectively maintained database included female patients aged ≥50 years who underwent THA. Before performing THA, we obtained each patient's anthropometric and muscle strength measurements and whole-spine radiographs. Three years postoperatively, patients underwent whole-spine radiography to examine changes in the spinal sagittal balance. Patients were assigned into groups on the basis of their preoperative and 3 year postoperative sagittal vertical axis (SVA) values. Patients with 3 year postoperative SVA values ≥40 mm with an increase ≥30 mm were categorized into the imbalance group; the other patients were categorized into the non-imbalance group. Of 103 patients, 11 (10.7%) were in the imbalance group. In multiple logistic regression analysis, preoperative weak abdominal trunk muscle strength (ATMS) (p = 0.007) and small sacral slope (SS) (p = 0.005) were significant risk factors for progressive spinal sagittal imbalance. In conclusion, risk factors for progressive spinal sagittal imbalance after THA were weak preoperative ATMS and small SS. [ABSTRACT FROM AUTHOR]

We investigated the abscopal effect after cryoablation (CA) on bone metastasis using a mouse model. Breast cancer cells were implanted in the bilateral tibiae of mice. The left tumor was treated locally with CA, and the right abscopal tumor (AT) was left untreated. The mice were divided into four groups based on the combination of CA and intraperitoneal administration of anti-PD-1 antibody (PD) as treatment interventions (Control, CA, PD, and CA + PD). The reduction ratio of the size of AT, the quantitative immune effects at enzyme-linked immunospot (ELISPOT) assay, and the intensity of infiltration of immune-related cells to AT were compared among the groups. CA alone showed a significant immunoenhancing effect on the volume change ratio of AT from day 0 to day 14 (Control-CA: p < 0.05), ELISPOT assay (Control-CA: p < 0.01), and CD4+ cell count in immunostaining (Control-CA: p < 0.05). CA alone showed no significant immunoenhancing effect on CD8+ and Foxp3+ cell counts in immunostaining, but the combination of CA and PD showed a significant immunoenhancing effect (Control-CA + PD: p < 0.01 [CD8, Foxp3]). The results suggested that the abscopal effect associated with the local cryotherapy of metastatic bone tumors was activated by CA and enhanced by its combination with PD. [ABSTRACT FROM AUTHOR]

Potential risk factors associated with future osteoporotic vertebral fracture (OVF) were prospectively investigated in middle-aged and older adult women. We enrolled 197 female patients aged ≥50 years who were scheduled to undergo surgery for lower-extremity degenerative diseases. Patient anthropometric and muscle strength measurements, a bone mineral density measurement of the lumbar spine (L-BMD), and full-spine standing radiographs to examine the presence of old OVFs and spinopelvic sagittal parameters were obtained preoperatively. We evaluated 141 patients who underwent full-spine standing radiographs three years postoperatively to identify new OVFs. We excluded 54 patients who did not undergo a second radiographic examination and 2 with new traumatic OVFs. Univariate and multivariate analyses were performed to identify risk factors associated with new non-traumatic OVF occurrence. Ten (7.1%) patients developed new non-traumatic OVFs during the study period (fracture group). The fracture group had less abdominal trunk muscle strength, lower L-BMD, smaller sacral slopes, and larger pelvic tilt than the non-fracture group. The fracture group showed a higher prevalence of old OVFs preoperatively than the non-fracture group. Abdominal trunk muscle weakness, low L-BMD, and the presence of old OVFs were identified as significant risk factors for OVF occurrence. In middle-aged or older adult women, abdominal trunk muscle weakness, low L-BMD, and old OVFs were associated with future OVF. [ABSTRACT FROM AUTHOR]

Although there are limited treatment options for sarcoma patients, recent studies have demonstrated promising therapeutic targets, anticancer agents, and combinations of these treatments. Although the incidence of sarcomas accounts for less than 1% of all malignancies, they are classified into more than 50 different subtypes with different biological behaviours. Chondrosarcoma, the second most common primary bone sarcoma, is characterised by the production of cartilaginous matrix and accounts for approximately 30% of malignant bone tumours. [Extracted from the article]

Simple Summary: With the prolonged survival of metastatic cancer patients, medium to long-term outcomes of local therapy for oligometastases are important and should be discussed. Metastasectomy is a reasonable treatment for isolated lesions when feasible. This retrospective study aimed to examine the medium to long-term outcomes of spinal metastasectomy in 124 patients with isolated spinal metastases who underwent metastasectomy. The primary malignancy was renal cell carcinoma in 51 patients, thyroid carcinoma in 14 patients, low-grade sarcoma in 13 patients, lung cancer in 13 patients, breast cancer in 12 patients, and other malignancies in 21 patients. The 3-year and 5-year survival rates were 70% and 60%, respectively. Patients with thyroid cancer had the best survival results. The occurrence rates for the local recurrence of the operated spinal lesion and instrumentation failure were 10% and 22%, respectively. For certain patients with isolated and removable spine metastases, metastasectomy can be a useful treatment option. The prolonged survival of metastatic cancer patients highlights the importance of the local control of spinal metastases, which reduce patient performance status. This retrospective study examined the medium to long-term outcomes of spinal metastasectomy by evaluating 124 patients who underwent metastasectomy for isolated spinal metastases (2006–2018) with a postoperative follow-up for a minimum of 3 years. The findings present information on patient demographics (i.e., performance status, location of non-spinal metastases, and history of systemic therapy) and postoperative outcomes, including perioperative complications, disease progression of non-operated metastases, and additional excisional surgeries. Additionally, postoperative survival, local tumor control in the operated spine, and maintenance of spinal reconstruction without instrumentation failure were determined using Kaplan–Meier analyses. The primary malignancy was kidney and thyroid cancer in 51 and 14 patients, respectively, low-grade sarcoma and lung cancer in 13 patients, breast cancer in 12 patients, and other malignancies in 21 patients. The 3-year and 5-year survival rates were 70% and 60%, respectively. We found that patients with thyroid cancer had the best survival results, with local tumor recurrence and instrumentation failure at 10% and 22%, respectively. These findings suggest that for certain patients with isolated and removable spine metastases, metastasectomy can improve function and survival. [ABSTRACT FROM AUTHOR]

Simple Summary: Chondrosarcomas develop chemoresistance to standard anticancer drugs, making it difficult to control unresectable or metastatic chondrosarcomas. To improve the clinical outcomes of chondrosarcoma, new treatment approaches, such as molecule-targeting agents and immunotherapy, are needed. Recent research has revealed promising biomarkers and therapeutic targets for chondrosarcoma. In addition, several molecule-targeting agents have shown favorable antitumor activities in several clinical studies in patients with advanced sarcomas, including chondrosarcoma. This review summarizes recent basic studies on biomarkers and therapeutic targets and recent clinical studies on treating chondrosarcomas. Due to resistance to standard anticancer agents, it is difficult to control the disease progression in patients with metastatic or unresectable chondrosarcoma. Novel therapeutic approaches, such as molecule-targeting drugs and immunotherapy, are required to improve clinical outcomes in patients with advanced chondrosarcoma. Recent studies have suggested several promising biomarkers and therapeutic targets for chondrosarcoma, including IDH1/2 and COL2A1. Several molecule-targeting agents and immunotherapies have shown favorable antitumor activity in clinical studies in patients with advanced chondrosarcomas. This review summarizes recent basic studies on biomarkers and molecular targets and recent clinical studies on the treatment of chondrosarcomas. [ABSTRACT FROM AUTHOR]

A long noncoding RNA (lncRNA), nuclear enriched abundant transcript 1 (NEAT1) variant 1 (NEAT1v1), is involved in the maintenance of cancer stem cells (CSCs) in hepatocellular carcinoma (HCC). CSCs are suggested to play important roles in therapeutic resistance. Therefore, we investigated whether NEAT1v1 is involved in the sensitivity to radiation therapy in HCC. Gene knockdown was performed using short hairpin RNAs, and NEAT1v1-overexpressing HCC cell lines were generated by stable transfection with a NEAT1v1-expressing plasmid DNA. Cells were irradiated using an X-ray generator. We found that NEAT1 knockdown enhanced the radiosensitivity of HCC cell lines and concomitantly inhibited autophagy. NEAT1v1 overexpression enhanced autophagy in the irradiated cells and conferred radioresistance. Gamma-aminobutyric acid receptor-associated protein (GABARAP) expression was downregulated by NEAT1 knockdown, whereas it was upregulated in NEAT1v1-overexpressing cells. Moreover, GABARAP was required for NEAT1v1-induced autophagy and radioresistance as its knockdown significantly inhibited autophagy and sensitized the cells to radiation. Since GABARAP is a crucial protein for the autophagosome-lysosome fusion, our results suggest that NEAT1v1 confers radioresistance to HCC by promoting autophagy through GABARAP. [ABSTRACT FROM AUTHOR]

Simple Summary: Patients with bone metastases (BMs) from differentiated thyroid carcinoma (DTC) can live longer than those with BMs from other cancers. BMs from DTC create destructive lesions and easily cause intractable pain and neurological symptoms, including paralysis. These symptoms related to BMs affect mortality directly and indirectly by hampering the application of systemic therapies. Therefore, long-term local control of BMs in patients with DTC is desired, especially in patients with single or a small number of metastases. Local treatments for BMs have recently become advanced and sophisticated in surgery, radiotherapy, and percutaneous procedures. These therapies, either alone or in combination with other treatments, can effectively improve, or prevent the deterioration of, the performance status and quality of life of patients with DTC-BM. Among local therapies, complete surgical resection and stereotactic radiosurgery are the mainstay for achieving long-term control of DTC-BM. After the lung, the skeleton is the second most common site of distant metastases in differentiated thyroid carcinoma (DTC). Patients with osteolytic bone metastases (BMs) from thyroid carcinoma often have significantly reduced performance status and quality of life. Recent advancements in cancer therapy have improved overall survival in multiple cancer subtypes, including thyroid cancer. Therefore, long-term local control of thyroid BMs is desired, especially in patients with a single metastasis or oligometastases. Here, we reviewed the current management options for DTC-BMs and especially focused on local treatments for long-term local tumor control from an orthopedic tumor surgeon's point of view. Metastasectomy and stereotactic radiosurgery can be performed either alone or in combination with radioiodine therapy and kinase inhibitors to cure skeletal lesions in selected patients. Percutaneous procedures have been developed in recent years, and they can also have a curative role in small BMs. Recent advancements in local therapies have the potential to provide not only long-term local tumor control but also a better prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Background: It is challenging to differentiate between enchondromas and atypical cartilaginous tumors (ACTs)/chondrosarcomas. Methods: To evaluate the diagnostic usefulness of radiological findings for differentiation between enchondromas and chondrosarcomas, correlations between various radiological findings and final diagnoses were investigated. Based on the correlations, a scoring system combining these findings was developed. Results: In a cohort of 81 patients, periosteal reaction on X-ray, endosteal scalloping and cortical defect on CT, extraskeletal mass, multilobular lesion, abnormal signal in adjacent tissue on MRI, and increased uptake in bone scan and thallium scan was significantly correlated with final diagnoses. Based on the correlations, a radiological scoring system combining radiological findings was developed. In another cohort of 17 patients, the sensitivity, specificity, and accuracy of the radiological score rates for differentiation between enchondromas and chondrosarcomas were 88%, 89%, and 88%, respectively. Conclusion: Comprehensive assessment combining radiological findings is recommended to differentiate between enchondromas and ACTs/chondrosarcomas. Background: It is challenging to differentiate between enchondromas and atypical cartilaginous tumors (ACTs)/chondrosarcomas. In this study, correlations between radiological findings and final diagnosis were investigated in patients with central cartilaginous tumors. Methods: To evaluate the diagnostic usefulness of radiological findings, correlations between various radiological findings and final diagnoses were investigated in a cohort of 81 patients. Furthermore, a new radiological scoring system was developed by combining radiological findings. Results: Periosteal reaction on X-ray (p = 0.025), endosteal scalloping (p = 0.010) and cortical defect (p = 0.002) on CT, extraskeletal mass (p < 0.001), multilobular lesion (p < 0.001), abnormal signal in adjacent tissue (p = 0.004) on MRI, and increased uptake in bone scan (p = 0.002) and thallium scan (p = 0.027) was significantly correlated with final diagnoses. Based on the correlations between each radiological finding and postoperative histological diagnosis, a radiological scoring system combining these findings was developed. In another cohort of 17 patients, the sensitivity, specificity, and accuracy of the radiological score rates for differentiation between enchondromas and ACTs/chondrosarcomas were 88%, 89%, and 88%, respectively (p = 0.003). Conclusion: Radiological assessment with combined radiological findings is recommended to differentiate between enchondromas and ACT/chondrosarcomas. [ABSTRACT FROM AUTHOR]

We evaluated the abscopal effect of re-implantation of liquid nitrogen-treated tumor-bearing bone grafts and the synergistic effect of anti-PD-1 (programmed death-1) therapy using a bone metastasis model, created by injecting MMT-060562 cells into the bilateral tibiae of 6–8-week-old female C3H mice. After 2 weeks, the lateral tumors were treated by excision, cryotreatment using liquid nitrogen, excision with anti-PD-1 treatment, and cryotreatment with anti-PD-1 treatment. Anti-mouse PD-1 4H2 was injected on days 1, 6, 12, and 18 post-treatment. The mice were euthanized after 3 weeks; the abscopal effect was evaluated by focusing on growth inhibition of the abscopal tumor. The re-implantation of frozen autografts significantly inhibited the growth of the remaining abscopal tumors. However, a more potent abscopal effect was observed in the anti-PD-1 antibody group. The number of CD8+ T cells infiltrating the abscopal tumor and tumor-specific interferon-γ (IFN-γ)-producing spleen cells increased in the liquid nitrogen-treated group compared with those in the excision group, with no significant difference. The number was significantly higher in the anti-PD-1 antibody-treated group than in the non-treated group. Overall, re-implantation of tumor-bearing frozen autograft has an abscopal effect on abscopal tumor growth, although re-implantation of liquid nitrogen-treated bone grafts did not induce a strong T-cell response or tumor-suppressive effect. [ABSTRACT FROM AUTHOR]

Sports activity has many benefits in cancer survivors. A key one is having sport activity contribute to the well-being of the individual. However, there are no guidelines about the intensity and kind of postoperative mobility workouts after hip or knee megaprosthetic treatment. Opinion research about sports after modular bone and joint replacement may provide an understanding of surgeons' attitudes on sports activity after megaprostheses of the hip and knee joint. A web survey with members of three international professional organizations of orthopedic tumor reconstructive surgeons was conducted between September 2016 and January 2018. Members were invited via personalized emails by the European Musculoskeletal Oncology Society (EMSOS), the International Society of Limb Salvage (ISOLS), and the Musculoskeletal Tumor Society (MSTS). The questionnaire included 26 questions. A total of 149 surgeons started the survey, and 76 finished the entire survey (American Association for Public Opinion Research (AAPOR) second response rate (RR2) EMSOS: 12.3%; ISOLS: 21.9%; MSTS: n/a). More than half of the respondents encourage sarcoma survivors after megaprosthetic treatment to reach an activity level that would allow them to regularly participate in active sporting events of University of California, Los Angeles (UCLA) activity level 7 and higher. Orthopedic tumor reconstructive surgeons do fear a number of complications (periprosthetic fracture, allograft failure/fracture, loosening, prosthetic or bearing failure, and early polyethylene wear) due to sports activity after modular bone–joint replacement, but they actually witness fewer complications than they conceptually anticipated. According to the surgeons' opinions, between four to seven types of sports after surgery could reasonably be recommended depending on the type of hip or knee procedures. This survey provides insights into opinions on what could be recommended, what could be allowed if surgeons and their patients agree on the potential negative outcome, and which sports should definitely not be allowed after hip and knee megaprostheses. [ABSTRACT FROM AUTHOR]

Rhabdomyosarcoma, the most common soft tissue sarcoma noted in childhood, requires multimodality treatment, including chemotherapy, surgical resection, and/or radiation therapy. The majority of the patients with localized rhabdomyosarcoma can be cured; however, the long-term outcomes in patients with metastatic rhabdomyosarcoma remain poor. The standard chemotherapy regimen for patients with rhabdomyosarcoma is the combination of vincristine, actinomycin, and cyclophosphamide/ifosfamide. In recent clinical trials, modifications of the standard chemotherapy protocol have shown improvements in the outcomes in patients with rhabdomyosarcoma. In various type of malignancies, new treatments, such as molecular targeted drugs and immunotherapies, have shown superior clinical outcomes compared to those of standard treatments. Therefore, it is necessary to assess the benefits of these treatments in patients with rhabdomyosarcoma. Moreover, recent basic and clinical studies on rhabdomyosarcoma have reported promising therapeutic targets and novel therapeutic approaches. This article reviews the recent challenges and advances in the management of rhabdomyosarcoma. [ABSTRACT FROM AUTHOR]

Peri-prosthetic joint infection (PJI) definition plays an important role in diagnostic and therapeutic decisions. However, while several criteria have been proposed by eminent institutions to define a PJI in the last decade, their clinical validation has been rarely performed. Aim of the present multicenter, international, retrospective study was to validate the World Association against Infection in Orthopedics and Trauma (WAIOT) pre/intra-operative PJI definition with post-operative confirmatory tests. A total of 210 patients, undergoing hip (n = 86) or knee (n = 124) revision surgery for any reason in six orthopedic centers in Africa, Asia, Europe and South America, were retrospectively evaluated at a two years minimum follow-up after surgery. All the available pre-, intra- and post-operative findings were collected and analyzed according to the WAIOT criteria, which include a set of tests to confirm (Rule In) or to exclude (Rule Out) a PJI. On average, patients were investigated pre/intra-operatively with 3.1 ± 1.1 rule out and 2.7 ± 0.9 rule in tests; the presence of a fistula or exposed implant was reported in 37 patients (17.6%). According to pre/intraoperative findings, 36.2% of the patients were defined as affected by high-grade PJI (n = 76; average score: 2.3 ± 0.8), 21.9% by low-grade PJI (n = 46; average score: 0.8 ± 0.8), 10.5% by biofilm-related implant malfunction (n = 22; average score: –1.6 ± 0.8), 2.9% as contamination (n = 6; average score: –3.5 ± 1.0), and 28.6% as no infection (n = 60; average score: –3.0 ± 1.4). Pre/intra-operative PJI definitions matched post-operative confirmatory tests, in 97.1% of the patients. This is, to our knowledge, one of the largest study ever conducted to validate a PJI definition The retrospective analysis in different centers was greatly facilitated by the structure of the WAIOT definition, that allows to include different tests on the basis of their sensitivity/specificity, while the comparison between pre/intra-operative and post-operative findings offered the internal validation of the scoring system. Our results authenticate the WAIOT definition as a reliable, simple tool to identify patients affected by PJI prior to joint revision surgery. [ABSTRACT FROM AUTHOR]

CD44, a cancer stem cell (CSC) marker, is required for maintaining CSC properties in hepatocellular carcinoma (HCC). Nuclear enriched abundant transcript 1 (NEAT1), a long noncoding RNA (lncRNA), is an oncogenic driver in HCC. In the present study, we investigated the significance of the NEAT1 gene in association with CD44 expression in liver CSCs of human HCC cell lines. The CSC properties were evaluated by spheroid culture, CSC marker expression, and sensitivity to anti-cancer drugs. The expression of both NEAT1 variant 1 (NEAT1v1) and variant 2 (NEAT1v2) as well as CD44 was significantly increased in the spheroid culture, compared with that in monolayer culture. Overexpression of Neat1v1, but not Neat1v2, enhanced the CSC properties, while knockout of the NEAT1 gene suppressed them. CD44 expression was increased by the overexpression of Neat1v1 and abrogated by NEAT1 knockout. The overexpression of NEAT1v1 restored the CSC properties and CD44 expression in NEAT1-knockout cells. NEAT1v1 expression in HCC tissues was correlated with poor prognosis and CD44 expression. These results suggest that NEAT1v1 is required for CD44 expression. To our surprise, NEAT1v1 also restored the CSC properties even in CD44-deficient cells, suggesting that NEAT1v1 maintains the properties of CSCs in a CD44-independent manner. [ABSTRACT FROM AUTHOR]

Unconventional prefoldin RNA polymerase II subunit 5 interactor (URI1) has emerged as an oncogenic driver in hepatocellular carcinoma (HCC). Although the hepatitis B virus (HBV) represents the most common etiology of HCC worldwide, it is unknown whether URI1 plays a role in HBV-related HCC (HCC-B). In the present study, we investigated URI1 expression and its underlying mechanism in HCC-B tissues and cell lines. URI1 gene-promoter activity was determined by a luciferase assay. Human HCC-B samples were used for a chromatin immunoprecipitation assay. We found that c-MYC induced URI1 expression and activated the URI1 promoter through the E-box in the promoter region while the HBx protein significantly enhanced it. The positivity of URI1 expression was significantly higher in HCC-B tumor tissues than in non-HBV-related HCC tumor tissues, suggesting that a specific mechanism underlies URI1 expression in HCC-B. In tumor tissues from HCC-B patients, a significantly higher level of c-MYC was recruited to the E-box than in non-tumor tissues. These results suggest that HBx and c-MYC are involved in URI1 expression in HCC-B. URI1 expression may play important roles in the development and progression of HCC-B because HBx and c-MYC are well-known oncogenic factors in the virus and host, respectively. [ABSTRACT FROM AUTHOR]

Due to the rarity and heterogeneity of bone and soft-tissue sarcomas, investigation into molecular targets and new treatments has been particularly challenging. Although intensive chemotherapy and establishment of surgical procedures have improved the outcomes of patients with sarcoma, the curative rate of recurrent and metastatic sarcomas is still not satisfactory. Recent basic science research has revealed some of the mechanisms of progression and metastasis of malignancies including proliferation, apoptosis, angiogenesis, tumor microenvironment, migration, invasion, and regulation of antitumor immune systems. Based on these basic studies, new anticancer drugs, including pazopanib, trabectedin, eribulin, and immune checkpoint inhibitors have been developed and the efficacies and safety of the new drugs have been assessed by clinical trials. This review summarizes new molecular therapeutic targets and advances in the treatment for bone and soft tissue sarcomas. [ABSTRACT FROM AUTHOR]

Retinoids exert antitumor effects through the retinoic acid receptor α (RARα). In the present study, we sought to identify the factors involved in the RARα-mediated transcriptional regulation of the tumor suppressor gene and the tissue factor pathway inhibitor 2 (TFPI2) in hepatocellular carcinoma (HCC). All-trans-retinoic acid (ATRA) was used in the in vitro experiments. Cell invasiveness was measured using trans-well invasion assay. ATRA significantly increased TFPI2 expression through RARα in a human HCC cell line known as HuH7. TFPI2 was vital in the ATRA-mediated suppression of HuH7 cell invasion. The musculo-aponeurotic fibrosarcoma oncogene homolog B (MAFB) significantly enhanced the activation of the TFPI2 promoter via RARα while MAFF inhibited it. The knockdown of RARα or MAFB counteracted the ATRA-mediated suppression of HuH7 cell invasion while the knockdown of MAFF inhibited the invasion. TFPI2 expression in HCC tissues was significantly downregulated possibly due to the decreased expression of RARβ and MAFB. Patients with HCC expressing low MAFB and high MAFF levels showed the shortest disease-free survival time. These results suggest that MAFB and MAFF play critical roles in the antitumor effects of retinoids by regulating the expression of retinoid target genes such as TFPI2 and can be promising for developing therapies to combat HCC invasion. [ABSTRACT FROM AUTHOR]

This study investigated the effects of a long noncoding RNA, nuclear paraspeckle assembly transcript 1 (NEAT1) variant 1 (NEAT1v1) on drug resistance in liver cancer cell lines. NEAT1 knockdown activated mitogen-activated protein kinase (MAPK) signaling pathways, including MAPK kinase (MEK)/extracellular signal-regulated kinase (ERK), but suppressed AKT. Moreover, NEAT1 knockdown sensitized liver cancer cells to sorafenib and lenvatinib, both clinically used for treating hepatocellular carcinoma, whereas it conferred resistance to an AKT-targeted drug, capivasertib. NEAT1v1 overexpression suppressed MEK/ERK and activated AKT, resulting in resistance to sorafenib and lenvatinib and sensitization to capivasertib. Superoxide dismutase 2 (SOD2) knockdown reverted the effects of NEAT1v1 overexpression on the sensitivity to the molecular-targeted drugs. Although NEAT1 or SOD2 knockdown enhanced endoplasmic reticulum (ER) stress, concomitant with the suppression of AKT, taurodeoxycholate, an ER stress suppressor, did not restore AKT activity. Although further in vivo and clinical studies are needed, these results suggested that NEAT1v1 switches the growth modality of liver cancer cell lines from MEK/ERK-dependent to AKT-dependent mode via SOD2 and regulates sensitivity to the molecular-targeted drugs independent of ER stress.