Whole Blood Titanium Concentration after Limb Salvage Surgery with Three-Dimensional-Printed Ti6Al4V Implants

Background@#Three-dimensional (3D)-printed customized implants can be fabricated and utilized for all bones with massive bone defects. The main safety issues with 3D-printed implants made of Ti6Al4V alloy are related to the release of metal debris and residual powder. In this study, we investigated the perioperative titanium concentrations in whole blood and peri-implant fluid samples of patients who underwent limb salvage surgery with a 3D-printed Ti6Al4V implant. @*Methods@#Nineteen patients who underwent limb salvage surgery with 3D-printed Ti6Al4V implants were divided into two groups:the serial samples group and the follow-up group. To observe metal distribution and clearance in the body, serial samples of blood and peri-implant fluid from the surgical drain were prospectively collected for five patients in the serial samples group. For the remaining 14 patients who were followed up for more than a year, blood samples were collected only once. @*Results@#In the serial samples group, the mean baseline titanium concentration was 0.78 μg/L (range, 0.1–2.2 μg/L): 3 patients showed peak concentration before the third postoperative month, while 2 patients still showed an increasing pattern at this point.Total titanium mass in the surgical drain showed a wash-out phenomenon in a week, with a significant uniform decrease (p = 0.04).In 14 patients in the follow-up group, the mean titanium concentration in the whole blood was 10.8 μg/L (range, 0.3–36.6 μg/L). For the 14 patients with a long-term follow-up, the aluminum and vanadium concentrations were all negligible. @*Conclusions@#Whole blood titanium concentrations were higher after surgery using 3D-printed implants than after that using conventional orthopedic implants, but markedly lower than in patients with implant failure. None of the patients developed serious clinical adverse effects during follow-up.

Vincristine, Irinotecan, and Temozolomide as a Salvage Regimen for Relapsed or Refractory Sarcoma in Children and Young Adults / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#No standard salvage regimen is available for relapsed or refractory sarcoma. We investigated the efficacy and toxicity of the vincristine, irinotecan, and temozolomide combination (VIT) for relapsed or refractory sarcomas of variable histology in children and young adults. @*Materials and Methods@#We retrospectively reviewed data from the relapsed or refractory sarcoma patients who were treated with VIT. The VIT protocol was given every 3 weeks as follows: vincristine, 1.5 mg/m2 intravenously on day 1, irinotecan, 50 mg/m2/day intravenously on days 1-5, and temozolomide, 100 mg/m2/day orally on days 1-5. @*Results@#A total of 26 patients (12 males) with various sarcoma histology were included in the study. Most common diagnosis was rhabdomyosarcoma (n=8) followed by osteosarcoma (n=7). Median age at the start of VIT was 18.5 years (range, 2.0 to 39.9). VIT was delivered as 2nd to 7th line of treatment, with 4th line most common (9/26, 34.6%). Median number of VIT courses given was 3 (range, 1 to 18). Of the 25 evaluable patients, there was two partial response (PR) and 11 stable disease (SD) with an overall control rate (complete remission+PR+SD) of 52%. PR was seen in one (50%) of the two evaluable patients with Ewing sarcoma and one (14.3%) of the seven patients with osteosarcoma. Overall survival and progression-free survival rates were 79.3% and 33.9% at 1 year, and 45.5% and 25.4% at 2 years, respectively. There was no treatment-related mortality. @*Conclusion@#The VIT regimen was effective and relatively safe in our cohort of sarcoma patients.

Incidence Patterns and Outcomes of Ewing Sarcoma in South Korea (1999-2017): A Retrospective Analysis Using Korea Central Cancer Registry Data / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Due to low incidence, epidemiologic data of Ewing sarcoma in the Asian population are scarce. We aimed to examine the incidence pattern and outcome of patients with Ewing sarcoma in the Republic of Korea. @*Materials and Methods@#Data of patients with Ewing sarcoma diagnosed between 1999 and 2017 were obtained from the Korea Central Cancer Registry (KCCR). Incidence, clinical characteristics, and survival rates were analyzed and compared between different age groups. @*Results@#There were 788 cases (459 males, 329 females), with a median age at diagnosis of 20 years. The age-standardized rate of Ewing sarcoma was 1.01. The number of cases and incidence rates in each age group were as follows: children, 1.6; adolescents and young adults (AYA), 0.93; adults, 0.44; and elderly, 0.53. There were more male cases in children and the AYA group (p < 0.001). Extraskeletal tumors (p < 0.001), primary sites other than extremity (p=0.007), and presence of metastasis at diagnosis (p=0.031) were more frequent in the adults and elderly group. With a median survival time of 78 months, the 5-year overall survival (OS) rate of the entire cohort was 52%. Children fared best (5-year OS, 75%), and the 5-year OS of AYA patients (51%) approximated the OS of the entire cohort. A two-fold difference of 5-year OS was observed between adults and elderly patients (42% vs. 19%). On univariate and multivariate analyses, age ≥ 15 years and presence of metastasis were adverse prognostic factors. @*Conclusion@#This was the first epidemiologic study of Ewing sarcoma using the KCCR data. With a similar incidence to other Asian countries, the survival rate was slightly lower than that of Euro-American cases. Collaborative clinical studies are necessary to improve the outcome of Ewing sarcoma in low-incidence populations.

Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea / Journal of the Korean Cancer Association, 대한암학회지

At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.

Guidelines for Cancer Care during the COVID-19 Pandemic in South Korea / Journal of the Korean Cancer Association, 대한암학회지

At the end of 2019, the cause of pneumonia outbreaks in Wuhan, China, was identified as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In February 2020, the World Health Organization named the disease cause by SARS-CoV-2 as coronavirus disease 2019 (COVID-19). In response to the pandemic, the Korean Cancer Association formed the COVID-19 task force to develop practice guidelines. This special article introduces the clinical practice guidelines for cancer patients which will help oncologists best manage cancer patients during the COVID-19 pandemic.

A Metastatic Lung Adnocarcinoma Misdiagnosed as Trauma Induced Sternoclavicular Joint Arthrosis / 대한스포츠의학회지

The prevalence of metastatic tumorous lesion at medial clavicle or sternoclavicular joint is low. Herein, we presented a 45-year-old female patient with left sternoclavicular joint pain followed a weight-lifting exercise. The patient was initially diagnosed as traumatic sternoclavicular arthrosis, however, on later computed tomography scan demonstrated the bony destruction of medial clavicle which was diagnosed as metastasized non-small cell lung carcinoma after a fine needle biopsy.

Distinct Clinical Characteristics of Unplanned Excision in Synovial Sarcoma

BACKGROUND: We aimed to describe the clinical characteristics and outcomes of unplanned excisions of synovial sarcomas. METHODS: In total, 90 patients with synovial sarcomas in the extremities were retrospectively reviewed. Patients were divided into unplanned excision (n = 38) and planned excision (n = 52) groups. The average follow-up period was 6 years. The clinicopathological characteristics and oncologic outcomes were compared. RESULTS: The unplanned excision group showed longer duration of symptoms before diagnosis (p = 0.023), smaller lesion dimensions (p = 0.001), superficial location (p = 0.049), and predilection in the upper extremities (p = 0.037). Synovial sarcomas were most commonly misdiagnosed as neurogenic tumors (56%) in the upper extremities or as cystic masses (47%) in the lower extremities. Oncological outcomes, including disease-specific survival, metastasis-free survival, or local recurrence were not significantly different between the 2 groups (p = 0.159, p = 0.444, and p = 0.335, respectively). Repeated unplanned excision (p = 0.012) and delayed re-excision (p = 0.038) were significant risk factors for local recurrence in the unplanned excision group. CONCLUSIONS: Synovial sarcomas treated with unplanned excision had distinct characteristics. These findings are important for developing diagnostic and therapeutic strategies for synovial sarcoma.

Limb Salvage Surgery Using Whole Knee Joint Allograft Reconstruction in Osteosarcoma / 대한정형외과학회잡지

Limb salvage should be considered after complete remission in young and physically active patients with osteosarcoma. Herein we described a patient who was treated with whole knee allograft reconstruction for the clinical implications of biological reconstruction which can avoid the problems with several consecutive sessions of mega-prosthesis revision. The mid-term result of this whole knee joint allograft reconstruction showed that it provided optimal joint congruence with durable joint stability, well balanced mechanical axis without joint space narrowing, and satisfactory gait pattern.

Intercalary Allograft Reconstruction after Malignant Tumor Resection around the Knee / 대한정형외과학회잡지

PURPOSE: We aimed to assess the treatment outcomes and factors affecting bone union of intercalary allograft reconstruction after primary malignant bone tumor resection around the knee. MATERIALS AND METHODS: Twenty-one patients who underwent intercalary allograft reconstruction after resection of a malignant tumor of femur or tibia were retrospectively reviewed. The average follow-up period was 46.4 months. Location of the tumor was as follows: femur in 12 cases and tibia in 9. Osteosarcoma was the most common tumor (12 cases). Intercalary allograft was internally fixed with an intramedullary (IM) nail in 3 cases, with a plate in 12 cases and with an IM nail combined with a plate in 6 cases. The survival of the grafts and functional outcomes were evaluated. Factors affecting bone union and complications were assessed. RESULTS: All allografts survived without removal. The average Musculoskeletal Tumor Society functional score was 27. The mean length of the allograft was 16.7 cm and bony union took 10.9 months, in average. Nonunion occurred in 6 cases: at the diaphyseal side in 3, and the remaining 3 at the metaphyseal side. The graft length was shorter than average in all the diaphyseal side nonunion cases and longer than average in all the metaphyseal side nonunion cases. All cases of nonunion obtained bone union after additional operations (autologous bone graft alone: 1, bone graft with hardware change: 5). CONCLUSION: Survival and functional outcomes of intercalary allograft were satisfactory. Long allograft showed a tendency of fracture or nonunion at the metaphyseal side. Nonunion could be managed with additional operation without allograft removal.

Grafting Using Injectable Calcium Sulfate in Bone Tumor Surgery: Comparison with Demineralized Bone Matrix-based Grafting

BACKGROUND: Injectable calcium sulfate is a clinically proven osteoconductive biomaterial, and it is an injectable, resorbable and semi-structural bone graft material. The purpose of this study was to validate the clinical outcomes of injectable calcium sulfate (ICS) grafts as compared with those of a demineralized bone matrix (DBM)-based graft for filling in contained bony defects created by tumor surgery. METHODS: Fifty-six patients (41 males and 15 females) with various bone tumors and who were surgically treated between September 2003 and October 2007 were included for this study. The patients were randomly allocated into two groups, and either an ICS graft (28 patients) or a DBM-based graft (28 patients) was implanted into each contained defect that was developed by the surgery. The radiographic outcomes were compared between the two groups and various clinical factors were included for the statistical analysis. RESULTS: When one case with early postoperative pathologic fracture in the DBM group was excluded, the overall success rates of the ICS and DBM grafting were 85.7% (24/28) and 88.9% (24/27) (p > 0.05), respectively. The average time to complete healing was 17.3 weeks in the ICS group and 14.9 weeks in the DBM group (p > 0.05). Additionally, the ICS was completely resorbed within 3 months, except for one case. CONCLUSIONS: Although the rate of resorption of ICS is a concern, the injectable calcium sulfate appears to be a comparable bone graft substitute for a DBM-based graft, with a lower cost, for the treatment of the bone defects created during surgery for various bone tumors.

Soft Tissue Reconstruction of the Foot Using the Distally Based Island Pedicle Flap after Resection of Malignant Melanoma

BACKGROUND: We report on our experience with using a distally based island flap for soft tissue reconstruction of the foot in limb salvage surgery for malignant melanoma patients. METHODS: A distally based sural flap was used for 10 cases for the hindfoot reconstruction, and a lateral supramalleolar flap was used for 3 cases for the lateral arch reconstruction of the mid- and forefoot after wide excision of malignant melanomas. RESULTS: The length of the flap varied from 7.5 cm to 12 cm (mean, 9.6 cm) and the width varied from 6.5 cm to 12 cm (mean, 8.8 cm). Superficial necrosis developed in four flaps, but this was successfully treated by debridement and suture or a skin graft. All thirteen flaps survived completely and they provided good contour, stable and durable coverage for normal weight bearing. CONCLUSIONS: The distally based sural flap is considered to be useful for reconstructing the hindfoot, and the lateral supramalleolar flap is good for reconstructing the lateral archs of the mid- and forefoot after resection of malignant melanoma of the foot.

Aberrant CpG Island Hypermethylation of the RUNX3 Gene in Osteosarcoma / 대한정형외과학회잡지

PURPOSE: Transcriptional silencing of tumor suppressor genes by aberrant methylation of CpG islands plays a crucial role in the development of human cancers. We comprehensively examined the methylation status of several tumor suppressor genes in osteosarcoma with a special focus on the RUNX3 gene. MATERIALS AND METHODS: Methylation-specific polymerase chain reaction (MSP) was performed for osteosarcoma tissues and their cell lines. MSP and RT-PCR for the RUNX3 gene were performed in the tumor-derived cell lines and the immortalized cell lines. The demethylating agent 5-aza-2' deoxycytidine was used in the SaOS-2 cell line to reverse the methylation status. RESULTS: Hypermethylation of the RUNX3 gene was observed in 60% (24 of 40) of the osteosarcoma tissues, whereas other tumor suppressor genes showed very low methylation. Thirteen of 30 (43%) tumor-derived cell lines, and U-2OS and SaOS-2 showed hypermethylation of the RUNX3 gene on MSPCR. However, RUNX3 was expressed in the SaOS-2 cell line, as determined by RT-PCR, and the expression was augmented by treatment with 5-aza-2' deoxycytidine. CONCLUSION: Our study suggests that aberrant methylation is an important mechanism of RUNX3 down-regulation in osteosarcoma. This data may have potential significance in developing a potential therapeutic target for osteosarcoma.

Treatment of Simple Bone Cysts with Percutaneous Injection of Autogenous Bone Marrow with Crushed Cancellous Allograft / 대한정형외과학회잡지

PURPOSE: This study evaluated the feasibility and efficacy of a percutaneous injection of a mixture of autogenous bone marrow and crushed cancellous bone allografts for the treatment of simple bone cysts. MATERIALS AND METHODS: Fifteen patients with a simple bone cyst were enrolled in this study. The mean age was 13.5 years (range, 4-32 years), and the mean follow-up period was 13.2 months (range, 8-19 months). The radiographic signs of the resolution of the cyst were categorized as healed, healed with a defect, persistent and recurrent. The groups of healed and healed with a defect were designated the positive response groups. RESULTS: Fourteen patients responded to the treatment. Nine patients showed complete healing that was first seen radiographically at 3 months (range, 1-6 months). Five patients showed healing with a defect, but no patient required a second injection because the cysts were small and did not cause functional pain. There was no correlation between clinical responses and age, gender, location, cyst index and previous treatment modalities. One patient had a pathological fracture, which was treated successfully by open bone grafting with flexible intramedullary nailing. CONCLUSION: A percutaneous injection of a mixture of autogenous bone marrow and a crushed cancellous bone allograft may be an effective treatment for simple bone cysts.

Expression and Clinical Significance of Heparanasein Osteosarcoma / 대한정형외과학회잡지

PURPOSE: This study examined the expression of heparanase in osteosarcomas and evaluated its prognostic value. MATERIALS AND METHODS: The immunohistochemical expression of heparanase from 51 osteosarcoma tissues was examined, and the correlations between the heparanase expression level and the clinicopathological factors were evaluated. RESULTS: Heparanase over-expression was observed in 37 tissue samples. There was a correlation between the heparanase expression level and a poor chemotherapeutic response, metastasis and poor survival rate. Multivariate analyses revealed that heparanase over-expression was a significant independent risk factor for a distant metastasis of an osteosarcoma. Among the 46 patients who underwent an adequate wide resection, there was a correlation between the heparanase expression level and recurrence. The 5-year survival rate was 83.8% for patients with heparanase negative tumors, and 46.9% for those with heparanase over-expression. Multivariate analysis using the Cox regression model revealed the heparanase expression level to be an independent prognostic indicator. CONCLUSION: These results indicate that heparanase expression might play an important role in local recurrence and metastasis, and might be a biological marker of the prognostic significance in osteosarcoma patients.

Prosthetic Survival and Functional Evaluation in Prosthetic Reconstruction of Malignant Bone Tumors of the Proximal Tibia / 대한정형외과학회잡지

PURPOSE: This study retrospectively analyzed the prosthetic survival and functional results after a prosthetic reconstruction for malignant bone tumors of the proximal tibia. MATERIALS AND METHODS: Thirty-five patients (32 osteosarcomas and 3 chondrosarcomas) were followed up for an average 72 months (24-167 months). A gastrocnemius flap was transferred in 12 patients and cement fixation of the stem was performed in 10. More than 40% of the bone length was resected in 12 patients. RESULTS: Three patients had died of the disease at the time of the final follow-up. There were one local recurrence and five distant metastases. The major complications were infection (5), aseptic loosening (5) and periprosthetic fractures (1). Gastrocnemius flap affected the incidence of a deep infection in the proximal tibia (17.4% vs. 8.3%) but there were no statistical correlation. A resection of >40% of the involved tibia increased the incidence of aseptic loosening (p=0.002). The rate of prosthetic survival was 72% at 5 years and 58% at 10 years. The functional score at the final follow-up was 81% (43-93%). CONCLUSION: A prosthetic reconstruction in the proximal tibia showed acceptable oncologic and functional outcomes in patients at an intermediate term follow-up. Infection and loosening were the main factors threatening the survival of the prosthesis.

Significance of the Methylation of Cyclin-Dependent Kinase Inhibitor 2A gene in the Prognosis of Osteosarcoma / 대한정형외과학회잡지

PURPOSE: The methylation status of the CpG promoter regions of the p16INK4A and p14ARF genes, mutations of 4 exons of the CDKN2A gene, and the expression of the corresponding proteins were examined. Prognostic implications were assessed in osteosarcoma. MATERIALS AND METHODS: Methylation-specific PCR, sequence analysis, and immunohistochemical staining were performed upon 32 frozen osteosarcoma tissues. RESULTS: Methylation of p16INK4A was found in 16%, and methylation of p14ARF in 47%. Metastasis and poor survival was statistically related to the methylation of p14ARF. The methylation of p14ARF correlated with the repression of the corresponding protein, and repression of p14ARF with the repression of p21 and of wild type of p53. No sequence alterations were found in the four exons of the CDKN2A gene. Methylation of p14 showed highest hazard ratio by multivariate survival analysis. CONCLUSION: Our data suggest that methylation of the CDKN2A gene seems to be the main mechanism of protein repression. For p14ARF, the methylation of its promoter region was related to the repression of p21 and wild type p53, distant metastasis and a poor prognosis. Further study regarding cell cycle regulatory factors should shed light on oncogenesis and the possibility of a new treatment strategy for osteosarcoma.