Surgical Site Infection after Bone Tumor Surgery: Risk Factors and New Preventive Techniques.

The management of malignant bone tumors requires multidisciplinary interventions including chemotherapy, radiation therapy, and surgical tumor resection and reconstruction. Surgical site infection (SSI) is a serious complication in the treatment of malignant bone tumors. Compared to other orthopedic surgeries, the surgical treatment of malignant bone tumors is associated with higher rates of SSIs. In patients with SSIs, additional surgeries, long-term administrations of antibiotics, extended hospital stays, and the postponement of scheduled adjuvant treatments are required. Therefore, SSI may adversely affect functional and oncological outcomes. To improve surgical outcomes in patients with malignant bone tumors, preoperative risk assessments for SSIs, new preventive techniques against SSIs, and the optimal use of prophylactic antibiotics are often required. Previous reports have demonstrated that age, tumor site (pelvis and tibia), extended operative time, implant use, body mass index, leukocytopenia, and reconstruction procedures are associated with an increased risk for SSIs. Furthermore, prophylactic techniques, such as silver and iodine coatings on implants, have been developed and proven to be efficacious and safe in clinical studies. In this review, predictive factors of SSIs and new prophylactic techniques are discussed.

Reconstruction using a frozen autograft for a skull and humeral lesion of synchronous multicentric osteosarcoma after undergoing successful neoadjuvant chemotherapy: a case report and review of the literature.

BACKGROUND: Synchronous multicentric osteosarcoma (SMOS) is a rare disease characterized by simultaneous multicentricity of intraosseous osteosarcoma without visceral involvement. SMOS, including a skull lesion, which occurs relatively rarely, and reconstruction using a frozen autograft after the excision of a lesion of SMOS has been infrequently reported previously. CASE PRESENTATION: We report an 18-year-old girl with SMOS, with lesions located in the left distal femur, right proximal humerus, and left occipital bone. Her major complaint was pain and swelling around the left knee joint. Asymptomatic lesions of the humerus and skull bone were detected on a systemic bone scan. No visceral organ metastasis was observed. A biopsy of the distal femoral lesion revealed osteosarcoma. Based on the histological findings, multiple bone lesions, and absence of visceral lesion, the clinical diagnosis of SMOS was made. After five courses of neoadjuvant chemotherapy with a regimen of doxorubicin and cisplatin, reconstruction using a tumor prosthesis following wide excision of the left distal femur was performed, and total necrosis was histologically observed in the retracted specimen. Following three cycles of adjuvant chemotherapy, tumor excision and reconstruction with a frozen autograft treated with liquid nitrogen was conducted for both lesions of the humerus and skull, rather than tumor prosthesis or synthetics, in order to retain a normal shoulder function, and to obtain a good cosmetic and functional outcome after treatment of the skull lesion. Further adjuvant chemotherapy could not be administered after the completion of the surgical treatment for all lesions because the adverse events due to chemotherapy were observed. At over 5 years after the diagnosis, she remains clinically disease-free. CONCLUSIONS: An early correct diagnosis, the proper management of chemotherapy, and surgical treatment for all lesions are essential for achieving a good clinical outcome, even in SMOS including a skull lesion. By performing reconstruction using a frozen autograft for a proximal humeral lesion and a skull lesion after confirming the good histological efficacy of neoadjuvant chemotherapy for the primary lesion, the excellent function of the shoulder joint and a good cosmetic outcome at the site of the skull lesion was acquired without complications or recurrence.

Secondary Osteoarthritis After Curettage and Calcium Phosphate Cementing for Giant-Cell Tumor of Bone Around the Knee Joint: Long-Term Follow-up.

Giant-cell tumor of bone (GCTB) is a locally aggressive intermediate bone tumor with a rarely metastasizing disposition. Standard surgical treatment consists of curettage, adjuvant treatment, and augmentation with allograft, autograft, or synthetics. Polymethylmethacrylate (PMMA) has been widely used for augmentation of the bone defect; however, the hyperthermic polymerization of PMMA may cause damage to articular cartilage, and the stiffness of the material may decrease the ability of the joint to absorb shock. These properties were reported to result in secondary osteoarthritis. Calcium phosphate cement has a low degree of thermal reaction and a strength that is similar to cortical bone. The aim of the present study was to investigate the incidence of secondary osteoarthritis around the knee joint following augmentation with calcium phosphate cement. METHODS: We retrospectively evaluated 19 patients with primary GCTB from 2003 to 2012. Curettage, high-speed burring, phenolization, and filling with calcium phosphate cement were performed in all patients. Radiographic evidence of osteoarthritis progression was evaluated with use of the Kellgren-Lawrence grade; the postoperative grade was compared with both the preoperative grade and the grade of the nonoperative contralateral knee at the time of the latest follow-up. The Musculoskeletal Tumor Society score and oncological outcomes at the time of the latest follow-up were evaluated. RESULTS: At a median follow-up period of 131 months, osteoarthritic progression was observed in 5 patients (26%), of which 2 were classified as Kellgren-Lawrence grade 3 and 1 was classified as Kellgren-Lawrence grade 4. The patient with grade-4 osteoarthritis underwent total knee arthroplasty, and 1 of the patients with grade-3 osteoarthritis underwent open-wedge high tibial osteotomy. The 10-year survival rate of joint cartilage with a Kellgren-Lawrence grade of <3 was 83%. The average Musculoskeletal Tumor Society score was 29 points. GCTB recurred in 2 patients, and 1 of these patients developed pulmonary metastasis. CONCLUSIONS: The incidence of secondary osteoarthritis was low, despite the long follow-up period. Prospective investigation comparing PMMA and calcium phosphate cement is warranted to determine the relative rate of secondary osteoarthritis and the outcomes associated with the 2 different types of augmentation. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Local dissemination of osteosarcoma observed after massage therapy: a case report.

BACKGROUND: Limited evidence is available regarding the dissemination of tumor tissues due to compression during massage therapy, a routine procedure in patients with various symptoms in Asian countries. CASE PRESENTATION: A 12-year-old male presented at a massage clinic with pain and swelling of his left knee, which worsened the same night. Consistent with conventional osteosarcoma, radiography revealed cortical bone destruction, osteoblastic changes, and periosteal reactions. Magnetic resonance imaging revealed a tumor in the distal femur, an extraskeletal mass, and an infiltrative lesion in the intramuscular and neurovascular areas surrounding the distal femur; this was considered as hemorrhage and dissemination of the tumor tissue. 18Fluorine-labelled fluorodeoxyglucose-positron emission tomography and computed tomography revealed multiple metastases in the spine, liver, and lung. Consistent with osteosarcoma, histopathological examination revealed tumor cell proliferation with extensive pleomorphism and mitoses. Despite undergoing chemotherapy, radiation therapy, and hip disarticulation, the patient died due to multiple metastases 13 months after the initial diagnosis. CONCLUSIONS: The present case suggests association of massage therapy with the local dissemination of tumor tissues, although influence of massage therapy on metastatic lesions remains unclear. Massage therapists should be aware of the possibility for dissemination of hidden malignancies due to the procedure.

Combination Treatment With Sorafenib and Everolimus Regresses a Doxorubicin-resistant Osteosarcoma in a PDOX Mouse Model.

BACKGROUND/AIM: Osteosarcoma is a rare but recalcitrant type of bone cancer. To discover an effective therapy for osteosarcoma, we used a patient-derived orthotopic xenograft (PDOX) mouse model. A PDOX mouse model has been established for all major cancer types. Strong synergistic efficacy of sorafenib (SFN) and everolimus (EVL) has been demonstrated in several cancers. In the present study, we examined the efficacy of a SFN and EVL combination on a doxorubicin (DOX)-resistant osteosarcoma PDOX. MATERIALS AND METHODS: The osteosarcoma PDOX models were randomly divided into five treatment groups, each containing six mice: Control; DOX; SFN; EVL; and a combination of SFN and EVL. Mice were treated for 14 days. To observe the efficacy of these treatments, tumor size and body weight were measured, and histological sections were analyzed. RESULTS: Tumor growth regression was observed only in the mice treated with the combination of SFN-EVL. Histological analysis revealed necrosis with degenerative changes in tumors treated with a combination of SFN-EVL. CONCLUSION: A SFN-EVL combination could be a novel effective treatment option for osteosarcoma.

Therapeutic Targets for Bone and Soft-Tissue Sarcomas.

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.

Calcium Phosphate Cement in the Surgical Management of Benign Bone Tumors.

BACKGROUND/AIM: This study assessed the mid- to long-term outcomes of calcium phosphate cement (CPC) implantation in benign bone tumor surgery. PATIENTS AND METHODS: Between 2000 and 2015, 130 patients underwent CPC implantation in benign bone tumor surgery. Radiographic findings and clinical outcomes were retrospectively evaluated. RESULTS: The mean follow-up period was 52 months. CPC filling immediately after surgery was sufficient, regardless of the amount of CPC used and the usage of adjuvant substances, which resulted in 92% of the patients' radiological results being classified as good or excellent. Significantly more patients had better CPC filling among patients with less hemorrhage and patients with tourniquet. The number of patients with good or excellent CPC filling had significantly increased by the final follow-up. CONCLUSION: CPC is a useful bone substitute for benign bone tumor surgery providing excellent osteoconductivity and long-lasting stability without internal fixation.

Preoperative evaluation of the efficacy of radio-hyperthermo-chemotherapy for soft tissue sarcoma in a case series.

PURPOSE: Radio-hyperthermo-chemo (RHC) therapy, which combines radiotherapy, hyperthermia, and chemotherapy, for malignant soft tissue tumors has been introduced with the aim of decreasing the possibility of local recurrence after surgery. To avoid unnecessary neoadjuvant therapy and to plan the appropriate surgical treatment, surveillance of RHC therapeutic efficacy during treatment is necessary. In this study, we determined the optimal response criteria to evaluate the efficacy of RHC by comparing preoperative images before and after RHC with pathological evaluation of necrosis in the resected tumor. PATIENTS AND METHODS: From 2004 to 2014, 20 patients were enrolled into this study. Needle biopsy revealed 6 cases of myxoid liposarcoma, 6 cases of undifferentiated pleomorphic sarcoma, 4 cases of myxofibrosarcoma, and 4 cases of synovial sarcoma. Based on the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 or modified RECIST, we calculated the responses to RHC therapy by comparing pre- and post-RHC therapy images. In addition, resected specimens underwent pathological analysis to evaluate response based on tumor necrosis. The correlation between assessment based on preoperative images and resected tumors were evaluated by the Spearman's rank-order correlation coefficient. RESULT: From the surgical specimens, pathological assessment of necrosis in resected tumor were assessed as less than 50% (2 cases), 50-90% (9 cases), 90-99% (6 cases), and total necrosis (3 cases). Use of the RECIST 1.1 underestimated good responders as stable disease (SD) or progressive disease (PD) in 5 out of 15 cases; on the other hand, use of the modified RECIST did not underestimate the pathological assessment of necrosis. The correlations between responses based on preoperative images and those based on histological assessments were 0.23 (RECIST 1.1) and 0.76 (modified RECIST). CONCLUSION: Because pathological responses can be underestimated using the RECIST 1.1, the modified RECIST, which take into consideration tumor viability, as assessed by contrast MRI, should also be considered when evaluating the efficacy of RHC.

Clinical outcomes of radio-hyperthermo-chemotherapy for soft tissue sarcoma compared to a soft tissue sarcoma registry in Japan: a retrospective matched-pair cohort study.

Regional hyperthermia is considered to enhance the antitumor effects of chemotherapy and radiotherapy. In this study, we confirmed the efficacy of concomitant radiotherapy, hyperthermia, and chemotherapy (RHC) for neoadjuvant treatment of malignant soft tissue sarcoma (STS). From 1994 to 2013, we performed RHC in 150 patients. This study was limited to 60 patients using the following exclusion criteria: salvage for recurrence or unplanned excision, trunk location, metastasis at initiation, non-STS, and no definitive surgery. As a control group, we collected data from 11,031 patients in the Bone and Soft Tissue Tumor Registry in Japan (BSTT). We performed multivariate logistic regression analysis, and propensity scores were created for comparisons between groups. The primary outcome of this study was to compare oncologic outcomes (5-year local control rate [LC] and overall survival rate [OS]). In the RHC group, two local recurrences (3.3%) occurred, and no patients underwent amputation. Margins of definitive surgery were not identical between groups [wide margins (60.0% vs. 85.3%), marginal margins (28.3% vs. 10.5%), and intralesional margins (7.4% vs. 4.2%), RHC and BSTT groups, respectively, P < 0.001]. After adjustment, the difference in OS was not significant between groups (HR = 1.26, P = 0.532); however, a statistically significant difference in LC was observed (HR = 4.82, P = 0.037). RHC resulted in a high LC at 5 years compared to the BSTT group, and amputation was averted in the RHC group, despite the wider margins in the BSTT group. This indicates that less invasive surgery might be achieved with effective neoadjuvant therapy.

Tumor-targeting Salmonella typhimurium A1-R inhibits human prostate cancer experimental bone metastasis in mouse models.

Bone metastasis is a frequent occurrence in prostate cancer patients and often is lethal. Zoledronic acid (ZOL) is often used for bone metastasis with limited efficacy. More effective models and treatment methods are required to improve the outcome of prostate cancer patients. In the present study, the effects of tumor-targeting Salmonella typhimurium A1-R were analyzed in vitro and in vivo on prostate cancer cells and experimental bone metastasis. Both ZOL and S. typhimurium A1-R inhibited the growth of PC-3 cells expressing red fluorescent protien in vitro. To investigate the efficacy of S. typhimurium A1-R on prostate cancer experimental bone metastasis, we established models of both early and advanced stage bone metastasis. The mice were treated with ZOL, S. typhimurium A1-R, and combination therapy of both ZOL and S. typhimurium A1-R. ZOL and S. typhimurium A1-R inhibited the growth of solitary bone metastases. S. typhimurium A1-R treatment significantly decreased bone metastasis and delayed the appearance of PC-3 bone metastases of multiple mouse models. Additionally, S. typhimurium A1-R treatment significantly improved the overall survival of the mice with multiple bone metastases. The results of the present study indicate that S. typhimurium A1-R is useful to prevent and inhibit prostate cancer bone metastasis and has potential for future clinical use in the adjuvant setting.

Intraperitoneal administration of tumor-targeting Salmonella typhimurium A1-R inhibits disseminated human ovarian cancer and extends survival in nude mice.

UNLABELLED: Peritoneal disseminated cancer is highly treatment resistant. We here report the efficacy of intraperitoneal (i.p.) administration of tumor-targeting Salmonella typhimurium A1-R in a nude mouse model of disseminated human ovarian cancer. The mouse model was established by intraperitoneal injection of the human ovarian cancer cell line SKOV3-GFP. Seven days after implantation, mice were treated with S. typhimurium A1-R via intravenous (i.v.) or i.p. administration at the same dose, 5 × 10(7) CFU, once per week. Both i.v. and i.p. treatments effected prolonged survival compared with the untreated control group (P=0.025 and P<0.001, respectively). However, i.p. treatment was less toxic than i.v. TREATMENT: Tumor-specific targeting of S. typhimurium A1-R was confirmed with bacterial culture from tumors and various organs and tumor or organ colony formation after i.v. or i.p. injection. Selective tumor targeting was most effective with i.p. administration. The results of the present study show S. typhimurium A1-R has promising clinical potential for disseminated ovarian cancer, especially via i.p. administration.