Toshitake Yakushiji

Monitoring therapeutic responses of primary bone tumors by diffusion-weighted image: Initial results.

The purpose of our study was to investigate whether quantitative diffusion-weighted images (DWI) were useful for monitoring the therapeutic response of primary bone tumors. We encountered 18 osteogenic and Ewing sarcomas. Magnetic resonance (MR) images were performed in all patients before and after therapy. We measured the apparent diffusion coefficient (ADC) values, contrast-to-noise ratio (CNR), and tumor volume of the bone tumors pre- and posttreatment. We determined change in ADC value, change in CNR on T2-weighted images (T2WI), change in CNR on gadopentetate dimeglumine (Gd)-T1-weighted images (Gd-T1WI), and change in tumor volume. The bone tumors were divided into two groups: group A was comprised of tumors with less than 90% necrosis after treatment and group B of tumors at least with 90%. Changes in ADC value, tumor volume, and CNR were compared between the groups. Change in the ADC value was statistically greater in group B than that in the group A (p=0.003). There was no significant difference in the changes in CNR on T2WI (p=0.683), in CNR on Gd-T1WI (p=0.763), and tumor volume (p=0.065). The ADC value on DWI is a promising tool for monitoring the therapeutic response of primary bone sarcomas.

The value of diffusion-weighted imaging for monitoring the chemotherapeutic response of osteosarcoma: a comparison between average apparent diffusion coefficient and minimum apparent diffusion coefficient.

ObjectiveThe objective of this study was to evaluate whether the average apparent diffusion coefficient (ADC) or the minimum ADC is more useful for evaluating the chemotherapeutic response of osteosarcoma.Materials and methodsTwenty-two patients with osteosarcoma were examined in this study. Diffusion-weighted (DW) and magnetic resonance (MR) images were performed for all patients before and after chemotherapy. The pre- and post-chemotherapy values were obtained both in the average and minimum ADC. The pre-chemotherapy values of the average ADC and minimum ADC respectively were compared with the post-chemotherapy values. In addition, the ADC ratios ([ADCpost - ADCpre] / ADCpre) were calculated using the average ADC and the minimum ADC. Twenty-two patients with osteosarcomas were divided into two groups, those with a good response to chemotherapy (≥ 90% tumor necrosis, n = 7) and those with a poor response (< 90% tumor necrosis, n = 15). The average ADC ratio and the minimum ADC ratio of the two groups were compared.ResultsWith both the average ADC and the minimum ADC, post-chemotherapy values were significantly higher than pre-chemotherapy values (P < 0.05). The patients with a good response had a significantly higher minimum ADC ratio than those with a poor response (1.01 ± 0.22 and 0.55 ± 0.29 respectively, P < 0.05). However, with regard to the average ADC ratio, no significant difference was observed between the two groups (0.66 ± 0.18 and 0.46 ± 0.31 respectively, P = 0.19).ConclusionThe minimum ADC is useful for evaluating the chemotherapeutic response of osteosarcoma.

Ability of diffusion-weighted imaging for the differential diagnosis between chronic expanding hematomas and malignant soft tissue tumors.

To evaluate the potential of diffusion‐weighted imaging (DWI) in distinguishing chronic expanding hematomas (CEHs) from malignant soft tissue tumors.

The Secreted Protein ANGPTL2 Promotes Metastasis of Osteosarcoma Cells Through Integrin α5β1, p38 MAPK, and Matrix Metalloproteinases

Preventing signaling by ANGPTL2, which is stimulated by the tumor microenvironment, could inhibit metastasis. Microenvironment Drives Osteosarcoma Metastasis The selective pressures of the tumor microenvironment alter the behavior of cancer cells. Odagiri et al. found that the expression of ANGPTL2, encoding the secreted angiopoietin-like protein 2, increased in osteosarcoma cells grown in xenografts in mice or cultured in conditions that mimic the tumor microenvironment. Silencing ANGPTL2 or overexpressing a proteolytically cleaved form decreased matrix metalloproteinase-9 (MMP-9) activity, delayed the onset of metastasis from xenografts, and prolonged survival in mice. The abundance of ANGPTL2 correlated with that of MMP-9 in patient samples, and both inversely correlated with metastasis-free survival in patients. The findings highlight the influence of the tumor microenvironment and implicate ANGPTL2 as a target to hinder metastasis in osteosarcoma. The tumor microenvironment can enhance the invasive capacity of tumor cells. We showed that expression of angiopoietin-like protein 2 (ANGPTL2) in osteosarcoma (OS) cell lines increased and the methylation of its promoter decreased with time when grown as xenografts in mice compared with culture. Compared with cells grown in normal culture conditions, the expression of genes encoding DNA demethylation–related enzymes increased in tumor cells implanted into mice or grown in hypoxic, serum-starved culture conditions. ANGPTL2 expression in OS cell lines correlated with increased tumor metastasis and decreased animal survival by promoting tumor cell intravasation mediated by the integrin α5β1, p38 mitogen-activated protein kinase, and matrix metalloproteinases. The tolloid-like 1 (TLL1) protease cleaved ANGPTL2 into fragments in vitro that did not enhance tumor progression when overexpressed in xenografts. Expression of TLL1 was weak in OS patient tumors, suggesting that ANGPTL2 may not be efficiently cleaved upon secretion from OS cells. These findings demonstrate that preventing ANGPTL2 signaling stimulated by the tumor microenvironment could inhibit tumor cell migration and metastasis.

Evaluation of diffusion‐weighted imaging for the differential diagnosis of poorly contrast‐enhanced and T2‐prolonged bone masses: Initial experience

To determine whether quantitative diffusion‐weighted imaging (DWI) is useful for characterizing poorly contrast‐enhanced and T2‐prolonged bone masses.

Usefulness of diffusion-weighted imaging for differentiating between desmoid tumors and malignant soft tissue tumors

To evaluate the usefulness of diffusion‐weighted imaging (DWI) for differentiating between desmoid tumors and malignant soft tissue tumors.

Characterization of chondroblastic osteosarcoma: gadolinium-enhanced versus diffusion-weighted MR imaging.

To detect differences in magnetic resonance imaging (MRI) between chondroblastic osteosarcoma and the other types of osteosarcomas or chondrosarcomas using gadolinium‐enhanced versus diffusion‐weighted sequences.

Therapeutic approaches targeting midkine suppress tumor growth and lung metastasis in osteosarcoma.

Midkine (MK) plays important roles in tumorigenesis, however, the biological function of MK and whether MK can be a therapeutic target in osteosarcoma are unclear. Here, we found that osteosarcoma tissues showed high MK expression. MK knockdown by small interfering RNA significantly induced apoptosis in osteosarcoma cells, whereas recombinant MK increased cell proliferation. Inhibition of MK signaling by anti-MK monoclonal antibody (anti-MK mAb) suppressed growth of osteosarcoma cells both in vitro and in vivo. Moreover, inhibition of MK function significantly suppressed lung metastasis in xenograft transplantation model. Targeting MK by anti-MK mAb may have value in the treatment of osteosarcoma.

Clinical outcomes of the KYOCERA Physio Hinge Total Knee System Type III after the resection of a bone and soft tissue tumor of the distal part of the femur

The KYOCERA Physio Hinge Total Knee System Type III (PHKIII) was developed to reconstruct bony defects of the distal femur. The PHKIII is originative in that the metallic parts are fully made of titanium alloy, and this prosthesis has a unique semi‐rotating hinge joint and was designed especially for people with the Asian physical body‐type. The clinical outcomes of the PHKIII after the resection of musculoskeletal tumors of the distal femur were evaluated.

PAINFUL HETEROTOPIC PACINIAN CORPUSCLE IN THE HAND: A REPORT OF THREE CASES

Severe pain in the finger caused by an abnormal Pacinian corpuscle is a rare condition. We have recently encountered three patients diagnosed with a heterotopic Pacinian corpuscle, based on histopathological findings. When making a differential diagnosis of unexplained severe pain in the finger, abnormal Pacinian corpuscles must be taken into account in addition to glomus tumour and other types of painful soft-tissue tumour.