Osteosarcoma is the most common primary malignancy of bone. Although outcomes of patients with osteosarcoma have improved since the introduction of chemotherapy, outcomes of metastatic or unresectable osteosarcomas are still unsatisfactory. To improve osteosarcoma outcomes, the development of novel systemic therapies for osteosarcoma is needed. Since the 1880s, various immunotherapies have been utilized in patients with osteosarcoma and some patients have shown response to the treatment. Based on recent studies about the role of the immune system in malignancies, immunotherapies including immune modulators such as interleukin-2 and muramyl tripeptide, dendritic cells, immune checkpoint inhibitors, and engineered T cells have been utilized in patients with malignancies. Although there are limited reports of immunotherapies for osteosarcoma, immunotherapy is thought to be a promising treatment option for treating osteosarcomas. In this review, an overview of various immunotherapies for osteosarcoma is provided and their potential as adjuvant therapies is discussed.

Use of an implant is one of the risk factors for surgical site infection (SSI) after malignant bone tumor resection. We developed a new technique of coating titanium implant surfaces with iodine to prevent infection. In this retrospective study, we investigated the risk factors for SSI after malignant bone tumor resection and to evaluate the efficacy of iodine-coated implants for preventing SSI. Data from 302 patients with malignant bone tumors who underwent malignant bone tumor resection and reconstruction were reviewed. Univariate analyses were performed, followed by multivariate analysis to identify risk factors for SSI based on the treatment and clinical characteristics. The frequency of SSI was 10.9% (33/302 tumors). Pelvic bone tumor (OR: 4.8, 95% CI: 1.8–13.4) and an operative time ≥ 5 h (OR: 3.4, 95% CI: 1.2–9.6) were independent risk factors for SSI. An iodine-coated implant significantly decreased the risk of SSI (OR: 0.3, 95% CI: 0.1–0.9). The present data indicate that pelvic bone tumor and long operative time are risk factors for SSI after malignant bone tumor resection and reconstruction, and that iodine coating may be a promising technique for preventing SSI.

Purpose: CD81 is a member of the tetraspanin family of membrane proteins. Recently, it has been shown that CD81 may be involved in cancer cell proliferation and metastasis. As yet, however, there have been few reports on the expression and role of CD81 in osteosarcoma. Methods: The expression of CD81 was investigated in human osteoblast cell line hFOB1.19 and in human osteosarcoma cell lines Saos2, MG63 and 143B. The expression of CD81 was inhibited in osteosarcoma cells using siRNA after which cell proliferation, migration and invasion were assessed. We also used Western blotting to investigate the phosphorylation status of Akt, Erk, JNK and p38, and measured the expression of MMP-2, MMP-9 and MT1-MMP. In addition, we used a CRISPR/Cas9 system to stably knock out CD81 expression in 143B cells, transplanted the cells into mice, and assessed tumor formation and lung metastasis in these mice compared to those in the control group. Results: We found that CD81 was expressed in the human osteoblast cell line and in all osteosarcoma cell lines tested. The osteosarcoma cell line 143B exhibited a particularly high level of expression. In addition, we found that osteosarcoma cell proliferation, migration and invasion were decreased after CD81 inhibition, and that the phosphorylation of Akt and Erk was suppressed. Also, the expression levels of MMP-2, MMP-9 and MT1-MMP were found to be suppressed, with MMP-9 showing the greatest suppression. In vivo, we found that mice transplanted with CD81 knockout 143B cells exhibited significantly less tumor formation and lung metastasis than mice in the control group. Conclusion: Based on our findings we conclude that inhibition of CD81 suppresses intracellular signaling and reduces tumorigenesis and lung metastasis in osteosarcoma cells.

Postoperative infection is one of the most serious complications in orthopedic surgery. We have developed and use iodine-coated implants to prevent and treat postoperative infection in compromised hosts. This study evaluated outcomes using iodine-coated implants for postoperative infections. We treated 72 postoperative infected patients using iodine-coated implants. Of these, 38 were males and 34 were females, with a mean age of 59.3 years. The mean follow-up period was 5.6 years. The patients included 23 with an infection following total knee arthroplasty, 20 following total hip arthroplasty, 11 following osteosynthesis, 11 following spine surgery, 6 following tumor excision, and 1 following osteotomy. Of these, 37 underwent single-stage surgery and 35 underwent staged revision surgery. We performed staged surgery in any case with active infection. The survival of iodine-coated implants was determined using Kaplan-Meier analysis. White blood cell (WBC) and C-reactive protein (CRP) levels were measured pre- and postoperatively. To evaluate the systemic effects of iodine, serum thyroid hormone levels were examined. Five patients underwent re-revision surgery. In 3 patients, periprosthetic infection recurred at an average of 18 months after surgery. The reinfection rate was 4.2%. These patients recovered following reimplantation of iodine-coated prostheses. No patients required amputation. The survival rate of iodine-coated implants was 91%. There were no signs of infection at the latest follow-up. The median WBC level was nearly in the normal range, and CRP levels returned to normal within 4 weeks after surgery. No abnormalities of thyroid gland function were detected. Iodine-coated titanium implants can be very effective in the treatment of postoperative infections. An iodine coating can be safely applied to infected regions.

Background: Surgical site infection (SSI) is a common complication following orthopedic implantation. We developed an iodine coating for titanium implants to reduce implant-related infections and conducted a prospective clinical study to evaluate the efficacy and potential drawbacks of iodine-supported implants. Patients and methods: Between July 2008 and July 2017, 653 patients (377 male and 27 female patients; mean age, 48.6) with postoperative infection or a compromised status were treated using iodine-loaded titanium implants. The mean follow-up period was 41.7 months. In 477 patients, iodine-supported implants were used to prevent infection and in 176 patients, to treat active infection (one-stage surgery, 89 patients; two-stage surgery, 87 patients). In the limbs and pelvis, the primary diagnoses included the following: 161 tumors, 92 deformities/shortening, 47 pseudarthrosis, 42 fractures, 32 infected TKA, 25 osteoarthritis, 21 pyogenic arthritis, 20 infected THA, and 6 osteomyelitis. In the spinal cases, there were 136 cases of tumors, 36 cases of pyogenic spondylitis, and 35 cases of degeneration. Five modes of implant failure were identified and classified as follows: soft tissue failure (type 1), aseptic loosening (type 2), structural failure (type 3), infection (type 4), and tumor progression (type 5). Results: The overall failure rate in our series was 26.3% (172/653). There were 101 mechanical failures, including 22 type 1, 20 type 2, and 59 type 3 failures. Non-mechanical causes accounted for 71 failures, including 45 type 4 and 26 type 5 failures. The overall incidence of infections was 6.8%. The mean time to the onset of infection after implantation was 9.1 months. The overall infection rate was 3.7% in the prevention cases and 15.3% in the treatment cases. There was no difference between one-stage replacement (14.6%) and two-stage replacement (16.0%). There were 11 cases of treatment for SSI of spine surgery, and the re-infection rate was 0% using iodine-coated instruments. Conclusions: The five modes of failure of the iodine-supported implant were satisfactory compared with previous reports. In particular, because the infection rate of iodine-coated implants used for compromised hosts is low compared with other methods, postoperative infection is more easily controlled. It can be considered highly effective for spinal infections that require one-stage revision surgery. Level of evidence IV. Trial registration Prospective, Observation study.