ABSTRACT
The ultimate goal of regenerative medicine is to regain or restore the damaged or lost function of tissues and organs. Several therapeutic strategies are currently being explored to achieve this goal. From the point of view of regenerative medicine, extracellular vesicles (EVs) are exceptionally attractive due to the fact that they can overcome the limitations faced by many cell therapies and can be engineered according to their purpose through various technical modifications. EVs are biological nanoscale vesicles naturally secreted by all forms of living organisms, including prokaryotes and eukaryotes, and act as vehicles of communication between cells and their surrounding environment. Over the past decade, EVs have emerged as a new therapeutic agent for various diseases and conditions owing to their multifaceted biological functions. This is reflected by the number of publications on this subject found in the Web of Science database, which currently exceeds 12,300, over 85% of which were published within the last decade, demonstrating the increasing global trends of this innovative field. The reviews collected in this special issue provide an overview of the different approaches being explored in the use of EVs for regenerative medicine.
ABSTRACT
The ultimate goal of regenerative medicine is to regain or restore the damaged or lost function of tissues and organs. Several therapeutic strategies are currently being explored to achieve this goal. From the point of view of regenerative medicine, extracellular vesicles (EVs) are exceptionally attractive due to the fact that they can overcome the limitations faced by many cell therapies and can be engineered according to their purpose through various technical modifications. EVs are biological nanoscale vesicles naturally secreted by all forms of living organisms, including prokaryotes and eukaryotes, and act as vehicles of communication between cells and their surrounding environment. Over the past decade, EVs have emerged as a new therapeutic agent for various diseases and conditions owing to their multifaceted biological functions. This is reflected by the number of publications on this subject found in the Web of Science database, which currently exceeds 12,300, over 85% of which were published within the last decade, demonstrating the increasing global trends of this innovative field. The reviews collected in this special issue provide an overview of the different approaches being explored in the use of EVs for regenerative medicine.
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Purpose@#To identify the clinical usefulness of serum M protein and to establish a rationale for regular follow-up with serum protein electrophoresis in solitary plasmacytoma. @*Materials and Methods@#Sixty-nine patients with solitary plasmacytoma and solitary plasmacytoma with minimal marrow involvement according to the International Myeloma Working Group criteria were retrospectively reviewed. @*Results@#At a median follow-up of 6.2 years, 5-year local control (LC), 5-year multiple myeloma-free survival (MMFS), 5-year failure-free survival (FFS), and 5-year overall survival (OS) were 82.6%, 44.1%, 41.8%, and 85.1%, respectively. Among the patients whose initial serum M protein was present or not evaluated, 37.3% of patients showed disappearance of serum M protein after various treatment. MMFS of these patients were comparable to non-secretory plasmacytoma with undetectable levels of M protein, and significantly better than patients with persistent M protein. Increase of serum M protein ≥0.1 g/dL was most predictive of treatment failure with area under the curve of 0.731. @*Conclusion@#Patients who eventually showed persistence of serum M protein after treatment showed worse MMFS and FFS compared to those whose serum M protein disappeared or who had initially non-secretory disease. The increase of serum M protein level ≥0.1 g/dL from current nadir was predictive of treatment failure. Therefore, regular follow-up with serum M protein is highly recommended especially unless the patient had initially non-secretory disease.
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Background@#Cancer stem cells (CSCs) are cells characterized by their self-renewal and tumorigenic potential. The purpose of this study was to discover the role of the delta-like factor 1 (DLK1) in sarcoma. @*Methods@#mRNA expression of DLK1 from 13 sarcoma cell lines was examined. Isolated CSCs from the tumors were examined using fluorescence-activated cell sorting (FACS) with CD133, the CSC marker, or sphere-forming assay. The relationship between DLK1 and CSCs in sarcoma was examined using cell proliferation and cell invasion assays after they were treated with DLK1 short interfering RNA (siRNA). @*Results@#A high expression of DLK1 mRNA was observed in all sarcoma cell lines. However, CSCs were isolated from over expressed sarcomas of the DLK1 gene, and they have shown to be expressed lower than the wild type. The anti-cancer effects of DLK1 siRNA inhibited cell proliferation and invasion in U2OS, A204, and sw872. In addition, treatment with DLK1 siRNA inhibited cell invasion in sw872 CSCs. DLK1 gene induces tumorigenesis in various sarcoma cells and regulates the invasiveness of liposarcoma. These results suggest that DLK1 could serve as a possible therapeutic target for sarcoma. @*Conclusions@#Our study showed that the DLK1 gene induces tumorigenesis in various sarcomas and is associated with invasive mechanism in sarcoma. These results suggest DLK1 could serve as a possible therapeutic target in a variety of sarcomas.
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Background@#Repetitive transcranial magnetic stimulation (rTMS) has been in use for the treatment of various neurological diseases, including depression, anxiety, stroke and Parkinson’s disease (PD), while its underlying mechanism is stills unclear. This study was undertaken to evaluate the potential synergism of rTMS treatment to the beneficial effect of human mesenchymal stem cells (hMSCs) administration for PD and to clarify the mechanism of action of this therapeutic approach. @*Methods@#The neuroprotective effect in nigral dopamine neurons, neurotrophic/growth factors and anti-/pro-inflammatory cytokine regulation, and functional recovery were assessed in the rat 6-hydroxydopamine (6-OHDA) model of PD upon administration of hMSCs and rTMS. @*Results@#Transplanted hMSCs were identified in the substantia nigra, and striatum. Enhancement of the survival of SN dopamine neurons and the expression of the tyrosine hydroxylase protein were observed in the hMSCs + rTMS compared to that of controls. Combination therapy significantly elevated the expression of several key neurotrophic factors, of which the highest expression was recorded in the rTMS + hMSC group. In addition, the combination therapy significantly upregulated IL-10 expression while decreased IFN-γ and TNF-α production in a synergistic manner. The treadmill locomotion test (TLT) revealed that motor function was improved in the rTMS + hMSC treatment with synergy. @*Conclusion@#Our findings demonstrate that rTMS treatment and hMSC transplantation could synergistically create a favorable microenvironment for cell survival within the PD rat brain, through alteration of soluble factors such as neurotrophic/growth factors and anti-/pro-inflammatory cytokines related to neuronal protection or repair, with preservation of DA neurons and improvement of motor functions.
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Background@#Repetitive transcranial magnetic stimulation (rTMS) has been in use for the treatment of various neurological diseases, including depression, anxiety, stroke and Parkinson’s disease (PD), while its underlying mechanism is stills unclear. This study was undertaken to evaluate the potential synergism of rTMS treatment to the beneficial effect of human mesenchymal stem cells (hMSCs) administration for PD and to clarify the mechanism of action of this therapeutic approach. @*Methods@#The neuroprotective effect in nigral dopamine neurons, neurotrophic/growth factors and anti-/pro-inflammatory cytokine regulation, and functional recovery were assessed in the rat 6-hydroxydopamine (6-OHDA) model of PD upon administration of hMSCs and rTMS. @*Results@#Transplanted hMSCs were identified in the substantia nigra, and striatum. Enhancement of the survival of SN dopamine neurons and the expression of the tyrosine hydroxylase protein were observed in the hMSCs + rTMS compared to that of controls. Combination therapy significantly elevated the expression of several key neurotrophic factors, of which the highest expression was recorded in the rTMS + hMSC group. In addition, the combination therapy significantly upregulated IL-10 expression while decreased IFN-γ and TNF-α production in a synergistic manner. The treadmill locomotion test (TLT) revealed that motor function was improved in the rTMS + hMSC treatment with synergy. @*Conclusion@#Our findings demonstrate that rTMS treatment and hMSC transplantation could synergistically create a favorable microenvironment for cell survival within the PD rat brain, through alteration of soluble factors such as neurotrophic/growth factors and anti-/pro-inflammatory cytokines related to neuronal protection or repair, with preservation of DA neurons and improvement of motor functions.
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BACKGROUND: Exosomes are membrane-enclosed extracellular vesicles implicated in cell-cell communication. Exosomes contain proteins, mRNAs, non-coding RNAs (miRNAs and lncRNAs) and lipids that are derived from producing cells. These nano-sized vesicles are present in biofluids including blood, urine, saliva, amniotic fluid, semen and conditioned media of cultured cells. METHODS: This review summarizes current progress on the strategies of development of diagnostic biomarkers and drug loading onto exosomes for overcoming cancer progression. RESULTS: A number of studies indicate that the exosome appears to be a key player in tissue repair and regeneration of in a number of animal disease models. In addition, alterations of the molecular profiles in exosomes are known to be correlated with the disease progression including cancer, suggesting their usefulness in disease diagnosis and prognosis. Studies utilizing engineered exosomes either by chemical or biological methods have demonstrated promising results in a number of animal models with cancer. CONCLUSION: Understanding the molecular and cellular properties of exosomes offer benefits for cancer diagnosis by liquid biopsy and for their application in therapeutic drug delivery systems. Studies have shown that genetic or molecular engineering of exosomes augmented their target specificity and anticancer activity with less toxicity. Thus, deeper understanding of exosome biology will facilitate their therapeutic potential as an innovative drug delivery system for cancer.
Subject(s)
Female , Amniotic Fluid , Biology , Biomarkers , Biopsy , Cells, Cultured , Culture Media, Conditioned , Diagnosis , Disease Models, Animal , Disease Progression , Drug Delivery Systems , Exosomes , Extracellular Vesicles , Models, Animal , Prognosis , Regeneration , RNA, Messenger , RNA, Untranslated , Saliva , Semen , Sensitivity and SpecificityABSTRACT
PURPOSE: To identify prognostic factors influencing progression-free survival (PFS) of aggressive fibromatosis (AF) after postoperative radiotherapy (PORT) and assess correlations between immunohistochemistry (IHC) features of β-catenin/smooth muscle actin (SMA) and PFS. MATERIALS AND METHODS: Records of 37 patients with AF treated by PORT from 1984 to 2015 were retrospectively reviewed. Fifteen patients underwent wide excision for AF and 22 patients received debulking operation. The median total dose of PORT was 59.4 Gy. IHC staining results of β-catenin and SMA were available for 11 and 12 patients, respectively. RESULTS: The median follow-up duration was 105.9 months. Five-year PFS rate was 70.9%. Tumor size or margin status was not related to PFS in univariate analysis (p = 0.197 and p = 0.716, respectively). Multivariate analysis showed that increased interval from surgery to PORT (>5.7 weeks) was a marginal risk factor for PFS (p = 0.054). Administration of PORT at the initial diagnosis resulted in significantly improved PFS compared to deferring PORT after recurrence (p = 0.045). Patient with both risk factors of deferring PORT after recurrence and interval from surgery to PORT >5.7 weeks had significantly lower 5-year PFS than patients without risk factor (34.1% vs. 100.0%; p = 0.012). Nuclear β-catenin intensity tended to inversely correlate with 5-year PFS, although it did not reach statistical significance (62.5% at low vs. 100.0% at high; p = 0.260). SMA intensity was not related to PFS (p = 0.700). CONCLUSION: PORT should be performed immediately after surgery irrespective of margin status or tumor size especially in recurrent case. Nuclear β-catenin staining intensity of IHC might correlate with local recurrence.
Subject(s)
Humans , Actins , beta Catenin , Diagnosis , Disease-Free Survival , Fibromatosis, Aggressive , Follow-Up Studies , Immunohistochemistry , Multivariate Analysis , Radiotherapy , Radiotherapy, Adjuvant , Recurrence , Retrospective Studies , Risk FactorsABSTRACT
OBJECTIVES: This study was conducted to examine the association of serum Vitamin D with insulin resistance and β-cell function in Korean health checkup examinees. METHODS: This study subjects were 374 healthy adults (199 males, 175 females) over the age of 20, who visited a general hospital medical center located in Haenam-gun, Jeollanam-do. To find the association of Vitamin D with HOMA-IR and HOMA-β, the used statistical analysis were ANOVA and ANCOVA. RESULTS: Of the study subjects, the level of serum Vitamin D defined by deficient group, insufficient group and sufficient group was 38.5%, 48.1% and 13.4%, respectively. According to the level of serum Vitamin D, the mean values of HOMA-IR were 1.92±1.08 in sufficient group, 1.99±1.04 in the insufficient group and 2.91±1.05 in deficient group and there were statistically significant different(p<0.001). The mean values of HOMA-β were 84.69±1.07 in sufficient group, 78.41±1.04 in the insufficient group and 80.48±1.04 in deficient group, and there were not significant. As a result of ANCOVA, adjusted mean of HOMA-IR were statistically significant different (p<0.001), but those of HOMA-β were not statistically significant according to the level of serum Vitamin D. CONCLUSIONS: The insufficient level of serum Vitamin D was relatively high in healthy adults who live in rural area, and it was found that HOMA-IR significantly increased when Vitamin D was deficient. To prevent insulin resistance or diabetes, it is necessary to provide sufficient information related to sufficient production of Vitamin D such as Vitamin D supplement, sun exposure, food intake and etc.
Subject(s)
Adult , Humans , Male , Eating , Hospitals, General , Insulin Resistance , Insulin , Solar System , Vitamin D , VitaminsABSTRACT
BACKGROUND: We retrospectively reviewed the outcomes of patients who had been treated with meloxicam for the extra-abdominal desmoid tumors and evaluated the correlation between clinical outcome and clinic pathological variables. METHODS: Twenty patients treated with meloxicam were followed up every 3 to 6 months. Meloxicam administration was planned at 15 mg/day orally for 6 months. RESULTS: Of the 20 patients evaluated, according to Response Evaluation Criteria in Solid Tumors criteria, there were five patients with partial response (25.0%), eight with stable disease (40.0%), and seven with tumor progression (35.0%). The cumulative probability of dropping out from our nonsurgical strategy using meloxicam was 35.0% at 1 year and 35.0% at 5 years. CONCLUSIONS: The present study suggests that conservative treatment would be a primary treatment option for this perplexing disease even though we were not able to determine that the use of a cyclooxygenase-2 inhibitor would have an additional influence on the natural course of a desmoid tumor.
Subject(s)
Humans , Cyclooxygenase 2 , Fibromatosis, Aggressive , Response Evaluation Criteria in Solid Tumors , Retrospective StudiesABSTRACT
Unfortunately, Acknowledgements section was missing in the originally published article.
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BACKGROUND: Soft tissue clear cell sarcoma is a rare tumor which originates from neural crest cells. Due to its rarity and lack of established treatment, the prognosis of clear cell sarcoma is poor. Here, we reviewed the clinical data and outcome of patients diagnosed with soft tissue clear cell sarcoma in our institution.METHODS: A retrospective study was conducted on pediatric patients who were treated for pathologically confirmed soft tissue clear cell sarcoma at the Seoul National University Hospital, between January 2000 and July 2017.RESULTS: Six patients (3 boys and 3 girls) were diagnosed with soft tissue clear cell sarcoma at a median age of 14 years 4 months (range 11 years 7 months - 19 years 3 months). The median size of the tumor was 5.6 cm (range, 0.6 cm to 7.9 cm). The most frequent symptom was pain (67%), and the most common primary site was the lower limb (67%). Three patients (50%) presented with metastases at diagnosis. Four patients underwent chemotherapy with various therapeutic combinations. Four patients received surgical resection. Only one patient received local radiotherapy. One patient died of primary refractory disease, three patients relapsed, while the remaining two survive event-free.CONCLUSION: Soft tissue clear cell sarcoma is a rare and highly aggressive tumor, for which there is no established treatment. All surviving patients received surgery, indicating that surgery is a key treatment modality. Further genetic studies of soft tissue clear cell sarcoma are needed to find a better treatment strategy.
Subject(s)
Humans , Diagnosis , Drug Therapy , Korea , Lower Extremity , Neoplasm Metastasis , Neural Crest , Pediatrics , Prognosis , Radiotherapy , Retrospective Studies , Sarcoma, Clear Cell , Seoul , Treatment OutcomeABSTRACT
PURPOSE: Rearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes. MATERIALS AND METHODS: The effects of EGF and HGF on the susceptibility of a CCDC6-RET lung cancer cell line to RET inhibitors (sunitinib, E7080, vandetanib, and sorafenib) were examined. RESULTS: CCDC6-RET lung cancer cells were highly sensitive to RET inhibitors. EGF activated epidermal growth factor receptor (EGFR) and triggered resistance to sunitinib, E7080, vandetanib, and sorafenib by transducing bypass survival signaling through ERK and AKT. Reversible EGFR-TKI (gefitinib) resensitized cancer cells to RET inhibitors, even in the presence of EGF. Endothelial cells, which are known to produce EGF, decreased the sensitivity of CCDC6-RET lung cancer cells to RET inhibitors, an effect that was inhibited by EGFR small interfering RNA (siRNA), anti-EGFR antibody (cetuximab), and EGFR-TKI (Iressa). HGF had relatively little effect on the sensitivity to RET inhibitors. CONCLUSION: EGF could trigger resistance to RET inhibition in CCDC6-RET lung cancer cells, and endothelial cells may confer resistance to RET inhibitors by EGF. E7080 and other RET inhibitors may provide therapeutic benefits in the treatment of RET-positive lung cancer patients.
Subject(s)
Humans , Adenocarcinoma/drug therapy , Cell Line, Tumor , Cetuximab/pharmacology , Drug Resistance, Neoplasm/drug effects , Epidermal Growth Factor/metabolism , Gene Rearrangement , Hepatocyte Growth Factor/pharmacology , Indoles/pharmacology , Lung Neoplasms/drug therapy , MAP Kinase Signaling System , Mutation , Niacinamide/analogs & derivatives , Phenylurea Compounds/pharmacology , Piperidines/pharmacology , Protein Kinase Inhibitors/therapeutic use , Proto-Oncogene Proteins c-ret/antagonists & inhibitors , Pyrroles/pharmacology , Quinazolines/pharmacology , RNA, Small Interfering/pharmacology , ErbB Receptors/genetics , Signal Transduction/drug effects , fms-Like Tyrosine Kinase 3/metabolismABSTRACT
Extracellular vesicles (EVs), a heterogenous group of membrane-bound particles, are virtually secreted by all cells and play important roles in cell-cell communication. Loaded with proteins, mRNAs, non-coding RNAs and membrane lipids from their donor cells, these vesicles participate in normal physiological and pathogenic processes. In addition, these subcellular vesicles are implicated in the progression of neurodegenerative disorders. Accumulating evidence suggests that intercellular communication via EVs is responsible for the propagation of key pathogenic proteins involved in the pathogenesis of amyotrophic lateral sclerosis, Parkinson's diseases, Alzheimer's diseases and other neurodegenerative disorders. For therapeutic perspective, EVs present advantage over other synthetic drug delivery systems or cell therapy; ability to cross biological barriers including blood brain barrier (BBB), ability to modulate inflammation and immune responses, stability and longer biodistribution with lack of tumorigenicity. In this review, we summarized the current state of EV research in central nervous system in terms of their values in diagnosis, disease pathology and therapeutic applications.
Subject(s)
Humans , Amyotrophic Lateral Sclerosis , Blood-Brain Barrier , Cell- and Tissue-Based Therapy , Central Nervous System , Diagnosis , Drug Delivery Systems , Extracellular Vesicles , Inflammation , Membrane Lipids , Neurodegenerative Diseases , Pathology , RNA, Messenger , RNA, Untranslated , Tissue DonorsABSTRACT
PURPOSE: CD74 (cluster of differentiation 74) is a type II transmembrane protein that associates with MHC-II (major histocompatibility complex-II) molecules and binds with the macrophage migration inhibitory factor (MIF), which is known to be associated with tumorigenesis. The purpose of this study was to examine the relationship between CD74 with MIF and the role of CD74 in osteosarcoma tumorigenesis. MATERIALS AND METHODS: A correlation between CD74 with MIF was examined using immunohistochemistry (IHC) of tissues from patients with osteosarcoma (n=45). The mRNA expression of CD74 from patient-derived primary cells of osteosarcoma (n=22) was examined by a real-time polymerase chain reaction. The role of CD74 and in cisplatin-resistance of osteosarcoma was examined using WST-1 and colony forming assay. RESULTS: Of the 45 patients, 25 patients (55.6%) had a high level of expression in both CD74 and MIF by IHC. High level of MIF expression was observed in 40 patients (88.9%). We detected that mRNA expression of CD74 was higher in cells of all osteosarcoma patients (n=22) examined than in the control cells (hFOb 1.19). After cisplatin treatment, the inhibition of cell proliferation and suppression of colony formation were reduced in osteosarcoma cells expressing CD74. Interestingly, the effect of inhibiting anchorage independent growth was activated after cisplatin treatment in the cells with very high expression CD74 mRNA. CONCLUSION: This study suggests that the level of CD74 expression correlates with that of MIF expression. Moreover, CD74 might have a role in cisplatin resistance of osteosarcoma.
Subject(s)
Humans , Carcinogenesis , Cell Proliferation , Cisplatin , Drug Resistance , Histocompatibility , Immunohistochemistry , Macrophages , Osteosarcoma , Real-Time Polymerase Chain Reaction , RNA, MessengerABSTRACT
There are few reports on the surgical treatment of secondary malignancy arising from an osteochondroma on the lateral side of the proximal tibia. From March 2008 to December 2011, 3 patients were treated for a secondary chondrosarcoma from an osteochondroma of the proximal tibia involving the fibula. The operative procedure can be summed up as follows: (1) resection of the tumor including the fibula; (2) preservation of the peroneal nerve and the fibular head; and (3) arthrodesis of the proximal tibiofibular joint. Serial radiological studies showed successful fusion in the proximal tibiofibular joint in all patients. The Musculoskeletal Tumor Society functional scores were excellent in all 3 patients. No patients showed instability of the ipsilateral knee joint in any direction. All 3 patients could return to sports activities. Until the last follow-up, there was no evidence of disease recurrence. We suggest that the operative procedure described in this article would provide satisfactory oncological and functional outcomes.
Subject(s)
Humans , Arthrodesis , Chondrosarcoma , Fibula , Follow-Up Studies , Head , Joints , Knee Joint , Osteochondroma , Peroneal Nerve , Recurrence , Return to Sport , Surgical Procedures, Operative , TibiaABSTRACT
BACKGROUND: Soft tissue clear cell sarcoma is a rare tumor which originates from neural crest cells. Due to its rarity and lack of established treatment, the prognosis of clear cell sarcoma is poor. Here, we reviewed the clinical data and outcome of patients diagnosed with soft tissue clear cell sarcoma in our institution. METHODS: A retrospective study was conducted on pediatric patients who were treated for pathologically confirmed soft tissue clear cell sarcoma at the Seoul National University Hospital, between January 2000 and July 2017. RESULTS: Six patients (3 boys and 3 girls) were diagnosed with soft tissue clear cell sarcoma at a median age of 14 years 4 months (range 11 years 7 months - 19 years 3 months). The median size of the tumor was 5.6 cm (range, 0.6 cm to 7.9 cm). The most frequent symptom was pain (67%), and the most common primary site was the lower limb (67%). Three patients (50%) presented with metastases at diagnosis. Four patients underwent chemotherapy with various therapeutic combinations. Four patients received surgical resection. Only one patient received local radiotherapy. One patient died of primary refractory disease, three patients relapsed, while the remaining two survive event-free. CONCLUSION: Soft tissue clear cell sarcoma is a rare and highly aggressive tumor, for which there is no established treatment. All surviving patients received surgery, indicating that surgery is a key treatment modality. Further genetic studies of soft tissue clear cell sarcoma are needed to find a better treatment strategy.
Subject(s)
Humans , Diagnosis , Drug Therapy , Korea , Lower Extremity , Neoplasm Metastasis , Neural Crest , Pediatrics , Prognosis , Radiotherapy , Retrospective Studies , Sarcoma, Clear Cell , Seoul , Treatment OutcomeABSTRACT
BACKGROUND: The pelvic bone is the most common site of bone metastases following the axial skeleton. Surgery on the pelvic bone is a demanding procedure. Few studies have been published on the surgical outcomes of metastasis to the pelvic bone with only small numbers of patients involved. This study sought to analyze the complications, local progression and survival after surgery for metastasis to the pelvic bone on a larger cohort of patients. METHODS: We analyzed 83 patients who underwent surgery for metastases to the pelvic bone between the years 2000 and 2015. There were 41 men and 42 women with a mean age of 55 years. Possible factors that might be associated with complications, local progression and survival were investigated with regard to patient demographics and disease-related and treatment-related variables. RESULTS: The overall complication rate was 16% (13/83). Advanced age (> 55 years, p = 0.034) and low preoperative serum albumin levels (≤ 39 g/L, p = 0.001) were associated with increased complication rates. In patients with periacetabular disease, the complication rate was higher in those who underwent total hip replacement arthroplasty (THR) than those who did not (p = 0.030). Local progression rate was 46% (37/83). The overall median time to local progression was 26 ± 14.3 months. The median time from local progression to death was 13 months (range, 0 to 81 months). The local progression-free survival was 52.6% ± 6.4% at 2 years and 36.4%± 7.6% at 5 years, respectively. Presence of skip lesions (p = 0.017) and presence of visceral metastasis (p = 0.027) were found to be significantly associated with local progression. The median survival of all patients was 24 months. The 2-year and 3-year survival rates were 52.5% ± 5.9% and 35.6% ± 6%, respectively. Metastasis from the kidney, breast, or thyroid or of hematolymphoid origin (p = 0.014), absence of visceral metastasis (p = 0.017) and higher preoperative serum albumin levels (p = 0.009) were associated with a prolonged survival. CONCLUSIONS: Advanced age and low serum albumin levels were associated with high complication rates. Local progression after surgery for metastases to the pelvic bone was affected by the presence of skip lesions, not by surgical margins. Primary cancer type, serum albumin level and visceral metastasis influenced survival.
Subject(s)
Female , Humans , Male , Arthroplasty , Arthroplasty, Replacement, Hip , Bone Neoplasms , Breast , Cohort Studies , Demography , Disease Progression , Disease-Free Survival , Kidney , Neoplasm Metastasis , Pelvic Bones , Serum Albumin , Skeleton , Survival Rate , Thyroid GlandABSTRACT
BACKGROUND: Endoprosthetic reconstruction is widely applied for pathological fractures of the proximal humerus; however, functional impairment is usually unsatisfactory. The aims of the current study are to evaluate the reliability of interlocking intramedullary (IM) nailing with cement augmentation as a fixation method in proximal humeral lesions and to assess functional outcomes. METHODS: We reviewed 32 patients with pathological fractures of the proximal humerus who underwent interlocking IM nailing and cement augmentation. Functional scores and pain relief were assessed as outcomes. RESULTS: The mean follow-up period was 14.2 months. The mean Musculoskeletal Tumor Society functional score and Karnofsky performance status scale score were 27.7 and 75.6, respectively. Improvement of pain assessed using the visual analogue scale was 6.2 on average. Thirty-one patients (97%) experienced no pain after surgery. The mean ranges of forward flexion and abduction were 115° and 112.6°, respectively. All patients achieved stability and had no local recurrence without failure of fixation until the last follow-up. CONCLUSIONS: Proximal interlocking IM nailing with cement augmentation appears to be a reliable treatment option for pathological or impending fractures of the proximal humerus in selected patients with metastatic tumors, even with extensive bone destruction.
Subject(s)
Humans , Follow-Up Studies , Fracture Fixation, Intramedullary , Fractures, Spontaneous , Humerus , Karnofsky Performance Status , Methods , Neoplasm Metastasis , RecurrenceABSTRACT
PURPOSE: The purpose of this study is to report on the incidence and the experience in management of radiation-induced sarcoma (RIS) at a large single center in Korea for 15 years. MATERIALS AND METHODS: We retrospectively reviewed the sarcoma registry of a large institution from January 2000 to April 2014. RESULTS: Out of the 3,674 patients listed in the registry, 33 patients (0.9%) diagnosed with RIS were identified. The median latency of RIS was 12.1 years. The number of cases of RIS increased from four cases in the years 2000-2003 to 14 cases in the years 2012-2014. The most common histology was osteosarcoma (36.4%). The median follow-up period was 23.1 months, the median overall survival (OS) of all patients was 2.9 years, and their 5-year survival rate was 44.7%. Univariate and multivariate analyses showed association of the age at diagnosis (p=0.01) and the treatment aim (p=0.001) with the OS. The median OS and the 5-year survival rate of patients treated with curative surgery (n=19) were 9.6 years and 65%, respectively, and of the conservatively treated patients, 0.7 years and 0% (n=14). Re-irradiation was delivered to nine patients, and radiation toxicity was observed in five patients. CONCLUSION: In this study, RIS accounted for 0.9% of the cases of sarcoma, with increasing incidence. Despite the association of curative resection with increased survival, it could be applied to only 58% of the patients. Considering the limited treatment options for RIS, conduct of a genetic study to identify the underlying mechanism of RIS is needed.