Hiroyuki Inatani

Risk factors of recurrent lumbar disk herniation: A single center study and review of the literature

Background: The recurrence of lumbar disk herniation (LDH) is a major problem in the treatment of LDH. The purpose of this study was to investigate the risk factors for recurrent LDH. Methods: Between April 2005 and March 2008, 298 patients with LDH, who underwent surgical treatment, were enrolled in this study. The patients were divided into a nonrecurrent group (N group) and a recurrent group (R group). We compared their clinical parameters including age, sex, body mass index, smoking, alcohol, sports activity, occupational lifting, and occupational driving. The relationships between the variables and recurrent LDH were evaluated by univariate analysis and multiple logistic regression analysis. Results: The N group had 266 patients (89.3%) and the R group had 32 patients (10.7%). Univariate analysis showed that current smoking (P<0.001) and occupational lifting (P=0.02) significantly correlated with recurrent LDH. Multivariate analysis showed that current smoking significantly related with recurrent LDH (OR, 3.47; 95% CI, 1.55–7.80; P=0.003). Conclusions: Our study suggests that smoking cessation and restraining from lifting may significantly decrease the incidence of recurrent LDH.

Diagnosis and treatment of low-grade osteosarcoma: experience with nine cases

BackgroundLow-grade osteosarcoma, including low-grade central osteosarcoma and parosteal osteosarcoma, is an extremely rare variant, and the diagnosis is occasionally difficult. In this article we present cases of low-grade osteosarcomas that should be reviewed by a clinical oncologist.Patients and methodsNine cases of histologically diagnosed Broder grade 1 osteosarcoma were retrospectively reviewed. The pathological diagnoses included parosteal osteosarcoma, low-grade central osteosarcoma, and low-grade chondroblastic osteosarcoma in four, four, and one cases, respectively.ResultsDuration from initial surgical intervention including biopsy to final diagnosis as low-grade osteosarcoma was a mean of 9.4 months. The initial benign diagnoses on biopsy specimens included fibrous dysplasia in three cases, chondroblastoma in one case, and a giant cell tumor in one case. The average number of histological examinations was 1.8. Low-grade osteosarcomas are well suited for biological reconstruction: seven cases were reconstructed by frozen autografts, distraction osteogenesis, or vascularized bone grafts.ConclusionLow-grade osteosarcomas can be misdiagnosed as benign lesions, especially fibrous dysplasia. If the diagnosis of a low-grade osteosarcoma is not established on the basis of radiologic findings, care should be exercised, even when a biopsy suggests a benign lesion. Low-grade osteosarcomas should be treated with wide excision, even after an intralesional excision. Biological reconstruction might be a better option for low-grade osteosarcomas.

Knee joint preservation surgery in osteosarcoma using tumour-bearing bone treated with liquid nitrogen

PurposeTo preserve the joint structure in order to maintain good limb function in patients with osteosarcoma, we perform epiphyseal or metaphyseal osteotomy and reconstruction using frozen autografts that contain a tumour treated with liquid nitrogen. There are two methods of using liquid nitrogen-treated autografts: the free-freezing method and the pedicle-freezing method. The purpose of this study was to evaluate the results of intentional joint-preserving reconstruction using the free-freezing method and the pedicle-freezing method in patients with osteosarcoma.MethodsBetween 2006 and 2014, we performed joint-preserving surgery (12 with the free-freezing method and six with the pedicle freezing method) to treat 18 cases of osteosarcoma (12 distal femurs and six proximal tibias) in patients who had achieved a good response to neoadjuvant chemotherapy.ResultsAmong the 18 patients (nine boys and nine girls) who had a mean age of 11.6 years, 13 remained continuously disease-free, three showed no evidence of disease, one was alive with the disease, and one died from the disease. Functional outcomes were assessed as excellent in 15 patients and poor in three, with a mean follow-up period of 46.1 months. The mean Musculoskeletal Tumour Society (MSTS) score was 90.2%. Except for one patient who underwent amputation, all patients could bend their knee through >90° flexion, and nine achieved full ROM. All but two patients could walk without aid, and 11 were able to run normally throughout the follow-up period. No intraoperative complications were observed, such as surrounding soft-tissue damage, neurovascular injury, or recurrence from frozen bone.ConclusionsJoint-preserving reconstruction using frozen autografts yielded excellent function in patients with osteosarcoma.

Do Mesenchymal Stem Cells Derived From Atypical Lipomatous Tumors Have Greater Differentiation Potency Than Cells From Normal Adipose Tissues

BackgroundThe p53 protein in mesenchymal stem cells (MSCs) regulates differentiation to osteogenic or adipogenic lineage. Because p53 function is depressed in most malignancies, if MSCs in malignancy also have p53 hypofunction, differentiation therapy to osteogenic or adipogenic lineage may be an effective treatment. We therefore wished to begin to explore this idea by evaluating atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) cells, because murine double minute 2 (MDM2) gene amplification, which leads to p53 hypofunction, is found in almost all ALT/WDLs.Questions/purposesWe compared osteogenic and adipogenic differentiation potency between MSCs isolated and cultured from normal adipose tissues and ALT/WDLs from the same patients.MethodsDuring tumor resections in six patients with ALT/WDL, we analyzed 3 mL of tumor, and for comparison, we harvested a similar amount of normal-appearing subcutaneous adipose tissue from an area remote from the tumor for comparison. Adipogenic differentiation potency was quantitatively assessed using spectrometry after oil red O staining. Osteogenic differentiation potency was semiquantitatively assessed by measuring a specific colored area after alkaline phosphatase (ALP) and alizarin red S staining. ALP is related to preosseous cellular metabolism, and alizarin red is related to calcium deposits in cell culture. There were three observers for each assessment, and each assessment (including induced-differentiation and histologic analysis) was performed in duplicate. We then analyzed the mechanism of the difference of osteogenic differentiation potency using the MDM2-specific inhibitor Nutlin-3 at various concentrations.ResultsIn terms of adipogenic differentiation potency, contrary to our expectations, more fatty acid droplets were observed in MSCs derived from normal fat than in MSCs derived from ALT/WDL, although we found no significant difference between MSCs derived from ALT/WDL and MSCs derived from normal fat; the mean differentiation potency values (normal adipose tissue versus ALT/WDL) (± SD) were 0.34 (SD, ± 0.13; 95% CI, 0.24–0.44) versus 0.25 (SD, ± 0.10; 95% CI, 0.18–0.33; p = 0.22). By contrast, we found greater osteogenic differentiation potency in MSCs derived from ALT/WDL than in MSCs derived from normal fat. The mean differentiation potency values (normal adipose tissue versus ALT/WDL) (±SD) based on ALP staining was 1.0 versus 17 (SD, ± 36; 95% CI, −2.8 to 38; p = 0.04). However, we found no differences based on alizarin red S staining; mean differentiation potency value (normal adipose tissue versus ALT/WDL) (± SD) was 1.0 versus 4.2 (SD, ± 4.8; 95% CI, 1.3–7.2; p = 0.58). The gap of osteogenic differentiation potency between MSCs from normal adipose tissue and ALT/WDL was decreased as MDM2-inhibitor Nutlin-3 concentration increased.ConclusionsMSCs derived from ALT/WDL had higher osteogenic differentiation potency based on ALP staining, which disappeared as Nutlin-3 concentration increased, suggesting that could be caused by amplified MDM2 in ALT/WDL. Future laboratory studies might mechanistically confirm the gene and protein expression, and based on the mechanism of the gap of differentiation potency, if p53 contrast between MSCs in tumor and normal tissue could be stimulated, less-toxic and more-effective differentiation therapy to MSCs in malignancies might be developed.

Surgical management of proximal fibular tumors: A report of 12 cases

Background/aim Aggressive benign or malignant tumors in the proximal fibula may require en bloc resection of the fibular head, including the peroneal nerve and lateral collateral ligament. Here, we report the treatment outcomes of 12 patients with aggressive benign or malignant proximal fibula tumors. Patients and methods Four patients with osteosarcoma and 1 patient with Ewings sarcoma were treated with intentional marginal resections after effective chemotherapy, and 4 patients underwent fibular head resections without ligamentous reconstruction. Clinical outcomes were investigated. Results The mean Musculoskeletal Tumor Society scores were 96% and 65% in patients without peroneal nerve resection and those with nerve resection, respectively. No patients complained of knee instability. Conclusion Functional outcomes after resection of the fibular head were primarily influenced by peroneal nerve preservation. If patients are good responders to preoperative chemotherapy, malignant tumors may be treated with marginal excision, resulting in peroneal nerve preservation and good function.

Anti-tumor effects of a nonsteroidal anti-inflammatory drug zaltoprofen on chondrosarcoma via activating peroxisome proliferator-activated receptor gamma and suppressing matrix metalloproteinase-2 expression

Surgical resection is the only treatment for chondrosarcomas, because of their resistance to chemotherapy and radiotherapy; therefore, additional strategies are crucial to treat chondrosarcomas. Peroxisome proliferator‐activated receptor gamma (PPARγ) is a ligand‐activated transcription factor, which has been reported as a possible therapeutic target in certain malignancies including chondrosarcomas. In this study, we demonstrated that a nonsteroidal anti‐inflammatory drug, zaltoprofen, could induce PPARγ activation and elicit anti‐tumor effects in chondrosarcoma cells. Zaltoprofen was found to induce expressions of PPARγ mRNA and protein in human chondrosarcoma SW1353 and OUMS27 cells, and induce PPARγ‐responsible promoter reporter activities. Inhibitory effects of zaltoprofen were observed on cell viability, proliferation, migration, and invasion, and the activity of matrix metalloproteinase‐2 (MMP2); these effects were dependent on PPARγ activation and evidenced by silencing PPARγ. Moreover, we showed a case of a patient with cervical chondrosarcoma (grade 2), who was treated with zaltoprofen and has been free from disease progression for more than 2 years. Histopathological findings revealed enhanced expression of PPARγ and reduced expression of MMP2 after administration of zaltoprofen. These findings demonstrate that zaltoprofen could be a promising drug against the malignant phenotypes in chondrosarcomas via activation of PPARγ and inhibition of MMP2 activity.

The usefulness of wide excision assisted by a computer navigation system and reconstruction using a frozen bone autograft for malignant acetabular bone tumors: a report of two cases

BackgroundDifficult resection of tumors from regions with complex local anatomy, such as the pelvis and sacrum, is likely to result in inadequate surgical margins (intralesional or marginal); this is because three-dimensional osteotomy is difficult particularly around the acetabulum. Additionally, removal of the joint makes reconstruction very difficult; thus, retention of good function also becomes difficult. In musculoskeletal oncology, computer navigation systems are still not widely used to prevent tumor-positive margins. We performed wide excision with guidance from a computer navigation system and reconstruction using frozen bone autografts for malignant pelvic bone tumors in two patients, and we obtained excellent functional and oncological outcomes. Here we present these patients and discuss our approach.Case presentationCase 1: A 12-year-old girl presented with Ewing sarcoma of the left pelvis (PI-II). We performed wide excision assisted by a computer navigation system with the osteotomy of the load surface of acetabulum and reconstruction using a frozen bone autograft. At the final follow-up, she showed excellent function and was alive without the disease. Moreover, she did not have osteoarthritis of the left hip joint.Case 2: A 71-year-old woman presented with dedifferentiated chondrosarcoma of the right pelvis (PII-III). We performed wide excision assisted by a computer navigation system with osteotomy avoiding load surface of the acetabulum and reconstruction using a frozen bone autograft; there was no tumor at the load surface. At the final follow-up, she showed good function, was alive without the disease, and did not have osteoarthritis of the left hip joint.ConclusionsWide excision assisted by a computer navigation system and reconstruction using a frozen bone autograft are very useful for the management/treatment of extremely difficult cases such as malignant pelvic bone tumors, particularly those including the acetabulum.

Efficacy and Limitations of F-18-fluoro-2-deoxy-D-glucose Positron Emission Tomography to Differentiate Between Malignant and Benign Bone and Soft Tissue Tumors

Background/Aim: Positron emission tomography (PET) using 18fluorine-labelled fluorodeoxyglucose (FDG), is the most widely applied molecular imaging technique in oncology. The present study assessed the efficacy and limitations of FDG-PET by comparing FDG accumulation in bone and soft tissue lesions, as well as histopathological features. Patients and Methods: The study included 122 patients with 165 lesions, as assessed by histopathological examinations. The maximum standardized uptake values (SUVmax) of benign lesions were compared to those of primary, recurrent, or metastatic sarcomas, as well as those of other malignancies. Results: The sensitivity, specificity, and accuracy of SUVmax for differentiation between benign lesions and primary sarcomas were 67.9%, 92.9%, and 80.4%, respectively. There were no significant differences between benign lesions and recurrent or metastatic sarcomas. Conclusion: Although FDG-PET is a useful imaging modality to differentiate primary sarcomas from benign lesions, it is difficult to differentiate residual or metastatic sarcomas from benign lesions.

Risk factors for postoperative deep infection in bone tumors

Background Postoperative deep infection after bone tumor surgery remains a serious complication. Although there are numerous reports about risk factors for postoperative deep infection in general surgery, there is only a small number of reports about those for bone tumor surgery. This retrospective study aimed to identify risk factors for postoperative deep infection after bone tumor resection. Methods We reviewed data of 681 patients (844 bone tumors) who underwent surgery. Associations between variables, including age, recurrent tumor, pathological fracture, surgical site (pelvis/other), chemotherapy, biological reconstruction, augmentation of artificial bone or bone cement, the use of an implant, intraoperative blood loss, operative time, additional surgery for complications, and postoperative deep infection were evaluated. Results The rate of postoperative deep infection was 3.2% (27/844 tumors). A pelvic tumor (odds ratio [OR]: 3.4, 95% confidence interval [CI]: 1.0–11.3) and use of an implant (OR: 9.3, 95% CI: 1.9–45.5) were associated with an increased risk of deep infection. Conclusions This retrospective study showed that pelvic tumor and use of an implant were independent risk factors for deep infection. This information will help surgeons prepare an adequate surgical plan for patients with bone tumors.

A case of infected schwannoma mimicking malignant tumor

BackgroundInfected schwannoma has been reported, this being one of the four cases published in the literature. Infected schwannoma has proven to be a tough diagnostic challenge to the treating tumor surgeon, mimicking infectious entities and most essentially, a malignant tumor.Case presentationThe authors report the case of a 64-year-old male with a soft tissue mass in his right gluteal area that presented initially with right leg pain, then later with signs of inflammation on the tumor area. Magnetic resonance imaging (MRI), computed tomography (CT), and thallium-201 scintigraphy studies confirm the presence of soft tissue mass which had continuity with sciatic nerve, with subsequent serial MRI findings suggesting tumor enlargement with cystic degeneration. Increased level of C-reactive protein (CRP) was observed before surgery. During an open biopsy upon tissue sampling, exudates with necrotic tissue were seen. Increased level of CRP and necrotic change suggested the possibility of malignant tumor. Histopathological diagnosis was schwannoma, and group B Streptococcus was detected by culture. After the confirmation of infected schwannoma, enucleation of the tumor was performed.ConclusionsThe report concludes that establishment of a benign pathology is essential when presented with similar clinical findings prior to definitive enucleation of an infected schwannoma.