Diagnosis and treatment of bone metastasis: comprehensive guideline of the Japanese Society of Medical Oncology, Japanese Orthopedic Association, Japanese Urological Association, and Japanese Society for Radiation Oncology.

Diagnosis and treatment of bone metastasis requires various types of measures, specialists and caregivers. To provide better diagnosis and treatment, a multidisciplinary team approach is required. The members of this multidisciplinary team include doctors of primary cancers, radiologists, pathologists, orthopaedists, radiotherapists, clinical oncologists, palliative caregivers, rehabilitation doctors, dentists, nurses, pharmacists, physical therapists, occupational therapists, medical social workers, etc. Medical evidence was extracted from published articles describing meta-analyses or randomised controlled trials concerning patients with bone metastases mainly from 2003 to 2013, and a guideline was developed according to the Medical Information Network Distribution Service Handbook for Clinical Practice Guideline Development 2014. Multidisciplinary team meetings are helpful in diagnosis and treatment. Clinical benefits such as physical or psychological palliation obtained using the multidisciplinary team approaches are apparent. We established a guideline describing each specialty field, to improve understanding of the different fields among the specialists, who can further provide appropriate treatment, and to improve patients' outcomes.

(62)Cu-diacetyl-bis (N(4)-methylthiosemicarbazone) PET in human gliomas: comparative study with [(18)F]fluorodeoxyglucose and L-methyl-[(11)C]methionine PET.

BACKGROUND AND PURPOSE: (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) was developed as a hypoxic radiotracer in PET. We compared imaging features among MR imaging and (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone)-PET, FDG-PET, and L-methyl-[(11)C]methionine)-PET in gliomas. MATERIALS AND METHODS: We enrolled 23 patients who underwent (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone)-PET and FDG-PET and 19 (82.6%) who underwent L-methyl-[(11)C]methionine)-PET, with all 23 patients undergoing surgery and their diagnosis being then confirmed by histologic examination as a glioma. Semiquantitative and volumetric analysis were used for the comparison. RESULTS: There were 10 newly diagnosed glioblastoma multiforme and 13 nonglioblastoma multiforme (grades II and III), including 4 recurrences without any adjuvant treatment. The maximum standardized uptake value and tumor/background ratios of (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone), as well as L-methyl-[(11)C]methionine, were significantly higher in glioblastoma multiforme than in nonglioblastoma multiforme (P = .03 and P = .03, respectively); no significant differences were observed on FDG. At a tumor/background ratio cutoff threshold of 1.9, (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) was most predictive of glioblastoma multiforme, with 90.0% sensitivity and 76.9% specificity. The positive and negative predictive values, respectively, for glioblastoma multiforme were 75.0% and 85.7% on (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone), 83.3% and 60.0% on L-methyl-[(11)C]methionine, and 72.7% and 75.0% on MR imaging. In glioblastoma multiforme, volumetric analysis demonstrated that (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) uptake had significant correlations with FDG (r = 0.68, P = .03) and L-methyl-[(11)C]methionine (r = 0.87, P = .03). However, the (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone)-active region was heterogeneously distributed in 50.0% (5/10) of FDG-active and 0% (0/6) of L-methyl-[(11)C]methionine)-active regions. CONCLUSIONS: (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone) may be a practical radiotracer in the prediction of glioblastoma multiforme. In addition to FDG-PET, L-methyl-[(11)C]methionine)-PET, and MR imaging, (62)Cu-diacetyl-bis(N(4)-methylthiosemicarbazone)-PET may provide intratumoral hypoxic information useful in establishing targeted therapeutic strategies for patients with glioblastoma multiforme.

Application of 62Cu-diacetyl-bis (N4-methylthiosemicarbazone) PET imaging to predict highly malignant tumor grades and hypoxia-inducible factor-1α expression in patients with glioma.

BACKGROUND AND PURPOSE: Hypoxic tissue evaluation in glioma is important for predicting treatment response and establishing antihypoxia therapy. In this preliminary study, (62)Cu-ATSM PET was used to determine its validity as a biomarker for distinguishing tumor grade and tissue hypoxia. MATERIALS AND METHODS: (62)Cu-ATSM PET was performed in 22 patients with glioma, and the (62)Cu-ATSM SUV(max) and T/B ratio were semiquantitatively evaluated. (62)Cu-ATSM uptake distribution was qualitatively evaluated and compared with MR imaging findings. HIF-1α expression, a hypoxia marker, was compared with (62)Cu-ATSM uptake values. RESULTS: The (62)Cu-ATSM SUV(max) and T/B ratio were significantly higher in grade IV than in grade III gliomas (P = .014 and .018, respectively), whereas no significant differences were found between grade III and grade II gliomas. At a T/B ratio cutoff threshold of 1.8, (62)Cu-ATSM uptake was predictive of HIF-1α expression, with 92.3% sensitivity and 88.9% specificity. The mean T/B ratio was also significantly higher in HIF-1α-positive glioma tissue than in HIF-1α-negative tissue (P = .001). Using this optimal threshold of T/B ratio, (62)Cu-ATSM PET showed regional uptake in 61.9% (13/21) of tumors within the contrast-enhanced region on MR imaging, which was significantly correlated with presence of a necrotic component (P = .002). CONCLUSIONS: Our results demonstrated that (62)Cu-ATSM uptake is relatively high in grade IV gliomas and correlates with the MR imaging findings of necrosis. Moreover, the (62)Cu-ATSM T/B ratio showed significant correlation with HIF-1α expression. Thus, (62)Cu-ATSM appears to be a suitable biomarker for predicting highly malignant grades and tissue hypoxia in patients with glioma.

Radiolabeled RGD peptides as integrin alpha(v)beta3-targeted PET tracers.

Imaging techniques targeting tumor angiogenesis have been investigated for past decade. Of these, the radiolabeled Arg-Gly- Asp (RGD) peptide has been focused because it has high affinity and selectivity for integrin alpha(v)beta3. Integrin alpha(v)beta3 is expressed on the plasma membrane in an active status in which it binds its ligands and transduce signals when exposed activating external stimuli of tumor angiogenesis such as vascular endothelial growth factor (VEGF). Many linear or cyclic RGD peptides were developed for positron emission tomography (PET). In this review, we focused on currently developed RGD peptides as PET probes for non-invasive detection of integrin alpha(v)beta3 expression.

Simultaneous evaluation of long-lasting knee synovitis in patients undergoing arthroplasty by power Doppler ultrasonography and contrast-enhanced MRI in comparison with histopathology.

OBJECTIVES: We simultaneously assessed ultrasonography (US) and magnetic resonance imaging (MRI) in comparison with histopathological changes in the knee joints of long-lasting arthritis patients. METHODS: We studied 15 patients with rheumatoid arthritis and 5 patients with osteoarthritis, who underwent total knee arthroplasty. On the day before surgery, the joints were examined by US and contrast-enhanced MRI. In US, synovitis was graded with 0-3 grey scale (GSUS) and power Doppler (PDUS). In MRI, synovitis was graded according to OMERACT-RAMRIS (grade 0-3). Synovial tissue samples were obtained during arthroplasty and evaluated on the basis of inflammatory cell infiltrates (grade 0-3), synovial lining layer thickness (grade 0-3) and vascularity (grade 0-3). RESULTS: Positive findings of PDUS and contrast-enhanced MRI were 45% and 85% of 20 operated joints, respectively. GSUS, PDUS and MRI synovitis were well correlated with overall histopathological grades of synovitis (Spearman correlation coefficients 0.48, 0.84 and 0.48, p<0.05, p<0.01 and p<0.05, respectively). Moreover, positive PDUS findings were closely associated with all pathological comportments of synovitis including inflammatory cell infiltrates, synovial lining layer thickness and vascularity. CONCLUSIONS: The present study revealed that positive PDUS findings more faithfully illustrated active synovitis than MRI, whereas contrast-enhanced MRI was more sensitive in detecting synovitis in patients with long-lasting arthritis. It is important to understand distinct features of the both modalities for clinical assessment of chronic joint diseases.

Solitary pulmonary granuloma caused by Mycobacterium avium-intracellulare complex.

OBJECTIVES: To analyse the clinical features and high resolution computed tomography (HRCT) findings of solitary pulmonary granulomas caused by the Mycobacterium avium-intracellulare (MAI) complex. METHODS: We retrospectively analysed a series of 73 consecutive patients with solitary pulmonary granuloma and negative sputum smear and culture results, in whom the diagnosis was established by histological examination of specimens obtained by partial pulmonary resection or lobectomy. We compared the clinical features and HRCT findings of the solitary pulmonary granulomas definitively diagnosed to be caused by the MAI complex with those of granulomas of other causes by univariate and multivariate analyses. RESULTS: In this study series of 24 patients with solitary pulmonary granuloma, the aetiological agent was established as being the MAI complex. According to the results of the multivariate analysis, 'female sex', 'pleural indentation' and 'lobulation' on the HRCT images were significantly associated with solitary pulmonary granuloma caused by the MAI complex. CONCLUSION: This study demonstrated several characteristics of solitary pulmonary granulomas caused by the MAI complex, and suggested that it might be a subtype of pulmonary MAI complex infection without the typical radiographic features of the infection.

Dedifferentiated chondrosarcoma with telangiectatic osteosarcoma-like features.

A 35-year-old Japanese man was admitted to the National Cancer Center, Tokyo, Japan, in December 2000, with a 2-month history of pain around the left thigh. Radiographs showed a poorly demarcated osteolytic lesion with focal mineralisation and endosteal scalloping in the left proximal femur. Biopsy showed a proliferation of highly anaplastic cells without any cartilaginous component. A wide excision of the left proximal femur with a replacement by endoprosthesis was carried out in February 2001 after treatment with methotrexate and 20 Gy radiation therapy. Pathological examination of the surgical specimen showed a focus of low-grade chondrosarcoma and the coexistence of telangiectatic osteosarcoma-like features. The patient was diagnosed with dedifferentiated chondrosarcoma with telangiectatic osteosarcoma-like features. Lung metastasis appeared in July 2001 despite an adjuvant chemotherapy including methotrexate, cis-platinum and doxorubicin. The latest follow-up study in June 2004 showed multiple lung metastases. Establishing a definitive diagnosis of dedifferentiated chondrosarcoma may be difficult with limited small biopsy specimens. Dedifferentiated chondrosarcoma should be included in the differential diagnosis of osteolytic tumours with focal calcification and endosteal scalloping even if an extraosseous tumour component is not identified.

Diagnostic accuracy of CT-guided percutaneous cutting needle biopsy for thymic tumours.

AIM: To determine the diagnostic accuracy of computed tomography (CT)-guided percutaneous cutting needle biopsy (PCNB) for thymic tumours in accordance with the World Health Organization (WHO) classification. MATERIAL AND METHODS: We retrospectively analysed a consecutive series of 138 cases in which CT-guided PCNB had been performed for an anterior mediastinal tumour. Its sensitivity and specificity for thymic epithelial tumours were evaluated, and the concordance between the histopathological diagnosis according to the WHO classification of thymic tumours based on PCNB and the diagnosis is based on the surgical specimens was assessed by Kappa statistic. RESULTS: The diagnostic sensitivity and specificity of CT-guided PCNB for thymic tumours were 93.3 and 100%, respectively. The overall concordance between the diagnosis according to the WHO classification established by PCNB specimen and by the surgical specimen was 79.4% (weighted kappa=0.79). CONCLUSION: CT-guided PCNB is a reliable method of diagnosing thymic tumours, and there was good concordance for the WHO classification between the diagnosis based on CT-guided PCNB specimen and that based on the surgical specimen.

Percutaneous transhepatic portal vein embolization: effectiveness of absolute ethanol infusion with balloon catheter in a pig model.

PURPOSE: To evaluate the effectiveness of portal vein embolization (PVE) with absolute ethanol using multidetector-row computed tomography (CT) angiography in a pig model. MATERIAL AND METHODS: Percutaneous transhepatic PVE with 10 ml absolute ethanol was performed in liver segments (n = 5) or subsegments (n = 5) in 10 pigs. CT images and volumetric data were qualitatively and quantitatively assessed to determine future liver remnant (FLR) hypertrophy and to correlate with histopathologic changes 2-6 weeks after PVE. Effectiveness evaluation was based on changes in absolute FLR size and ratio of FLR to total estimated liver volume (TELV). RESULTS: Occlusion of the embolized vessel was achieved immediately after injecting absolute ethanol within a range of 0.25-0.33 ml/kg. The TELV prior to PVE was 660.49 +/- 103.66 cm3 (range 527.22 to 833.70 cm3) and after PVE 769.51 +/- 29.36 cm3 (range 685.95 to 887.34 cm3). The mean FLR/TELV ratio increase after PVE was 14.2%. No statistically significant difference was found in the increase of TELV between segmental or subsegmental PVE. On microscopic observation, atrophy of the embolized liver was noted in all animals and was seen distinctly at 3 weeks after PVE in 2 animals. CONCLUSION: Both regenerative response and histopathologic changes of the liver were seen after PVE with absolute ethanol with a mean FLR/TELV ratio of 14.2%.

A practical approach to the clinical diagnosis of Ewing's sarcoma/primitive neuroectodermal tumour and other small round cell tumours sharing EWS rearrangement using new fluorescence in situ hybridisation probes for EWSR1 on formalin fixed, paraffin wax embedded tissue.

BACKGROUND: Over 90% of Ewing's sarcoma/primitive neuroectodermal tumour (ES/PNET) cases have the t(11;22) chromosomal rearrangement, which is also found in other small round cell tumours, including desmoplastic small round cell tumour (DSRCT) and clear cell sarcoma (CCS). Although this rearrangement can be analysed by fluorescence in situ hybridisation (FISH) using routinely formalin fixed, paraffin wax embedded (FFPE) tissues when fresh or frozen tissues are not available, a sensitive and convenient detection method is needed for routine clinical diagnosis. AIMS: To investigate the usefulness of newly developed probes for detecting EWS rearrangement resulting from chromosomal translocations using FISH and FFPE tissue in the clinical diagnosis of ES/PNET, DSRCT, and CCS. METHODS: Sixteen ES/PNETs, six DSRCTs, and six CCSs were studied. Three poorly differentiated synovial sarcomas, three alveolar rhabdomyosarcomas, and three neuroblastomas served as negative controls. Interphase FISH analysis was performed on FFPE tissue sections with a commercially available EWSR1 (22q12) dual colour, breakapart rearrangement probe. RESULTS: One fused signal and one split signal of orange and green, demonstrating rearrangement of the EWS gene, was detected in 14 of 16 ES/PNETs, all six DRSCTs, and five of six CCSs, but not in the negative controls. CONCLUSIONS: Interphase FISH using this newly developed probe is sensitive and specific for detecting the EWS gene on FFPE tissues and is of value in the routine clinical diagnosis of ES/PNET, DSRCT, and CCS.

Lower incidence of Bronchiolitis obliterans in allogeneic hematopoietic stem cell transplantation with reduced-intensity conditioning compared with myeloablative conditioning.

Bronchiolitis obliterans (BO) is one of the most devastating complications after allogeneic stem cell transplantation (HSCT). However, its true pathogenesis is still to be elucidated. We conducted this study to find whether tissue damage due to high-dose chemo-radiotherapy is related to its pathogenesis. In all, 144 patients who received allogeneic HSCT between May 1999 and October 2001, and survived more than 80 days after transplant, were analyzed. Clinical course, pulmonary function tests, imaging studies including CT scan, and pathology results were reviewed. The overall incidence of BO was 9.7% (14/144). The cumulative incidence of BO at 2 years after transplant was 17% with myeloablative conditioning, and 2.3% with reduced intensity conditioning (P=0.024). Multivariate analysis showed that myeloablative conditioning was the only factor which affected the incidence of BO. Development of BO did not significantly affect the overall survival of patients. However, if they developed BO earlier than 200 days post transplant, the prognosis was significantly worse than if they developed it later than 200 days post transplant (P=0.003) or if they did not develop BO (P=0.002). Our results imply that tissue damage secondary to intensive chemo-radiotherapy may contribute to the pathogenesis of BO.

Hepatic metastases of soft tissue angiosarcoma: CT and MR imaging findings.

BACKGROUND: We describe the computed tomographic (CT) and magnetic resonance imaging (MRI) findings of hepatic metastases caused by soft tissue angiosarcomas to clarify the relation between radiologic appearances and clinicopathologic features. METHODS: CT and MR examinations of 13 patients with hepatic metastases of soft tissue angiosarcoma were retrospectively analyzed. RESULTS: Contrast-enhanced CT images showed multiple hypoattenuating lesions relative to the adjacent liver parenchyma. Lesions contained peripheral areas of enhancement in eight patients (62%). Tumors showed cystic attenuation with fluid-fluid levels, which were suggestive of hemorrhage in five patients (38%). In one patient (8%) with cystic attenuation and fluid-fluid levels, lesions also contained marked enhanced nodular portions located centrally or peripherally. On T1-weighted MR images, all four liver tumors appeared heterogeneous and hypointense relative to adjacent liver parenchyma. Fluid-fluid levels were identified on T2-weighted MR images in five patients (38%). After an intravenous bolus of gadolinium-based contrast material was administered, slight peripheral enhancement was seen in three patients (75%). CONCLUSION: The common CT findings of metastatic angiosarcoma in our series were multiple hypoattenuating lesions often associated with nodular enhancement and cystic lesions with hemorrhagic change.

Prognostic significance of grading (MIB-1 system) in patients with myxoid liposarcoma.

AIMS: To determine the relation between clinical outcome and tumour grade defined by a MIB-1 (Ki-67) score based grading system. METHOD: The clinical and pathological features of 50 patients with myxoid liposarcoma were evaluated, and MIB-1 immunostaining was performed to grade these patients' tumours. Univariate and multivariate analyses were conducted to evaluate survival. Clinical follow up details were available for all patients (median, 46.5 months; range, 9-408). RESULTS: Univariate analysis revealed that the tumour site (p < 0.05), round cell component content (p < 0.01), necrosis (p < 0.01), mitosis (p < 0.01), MIB-1 labelling index (p < 0.001), and tumour grade (p < 0.001) had a significant impact on overall survival. Multivariate analysis showed that, of the variables evaluated, the tumour grade defined by a MIB-1 score based grading system was the most significant adverse prognostic factor. CONCLUSION: Tumour grade determined by the grading system using the MIB-1 score (MIB-1 system) is a very strong prognostic factor in patients with myxoid liposarcoma.

MR imaging of the brain in lymphomatoid granulomatosis.

BACKGROUND AND PURPOSE: Clinical diagnosis of lymphomatoid granulomatosis (LG) of the brain, in patients without skin or chest lesions, usually is difficult because of the nonspecific neurologic manifestations, laboratory data, and CT appearance. Our aim was to characterize the MR appearance of LG of the brain. METHODS: We retrospectively reviewed the MR images in four patients (35 to 72 years old) with histologically confirmed LG of the brain. RESULTS: On T2-weighted images, we noted diffuse hyperintense lesions in the cerebral white matter bilaterally (n = 3), in the brain stem and cerebellar hemisphere (n = 1), and patchy hyperintense lesions the brain stem (n = 2). On contrast-enhanced T1-weighted images, we observed multiple punctate or linear enhancements residing along the perivascular space (n = 4), nodular enhancements (n = 2), ringlike enhancements (n = 1), and a large, enhanced mass (n = 1). All patients had multifocal lesions. CONCLUSION: Although the MR appearance of LG of the brain varies, multiple punctate or linear enhancements that reside along the perivascular space suggest LG.

HTLV-1-associated bronchopneumonopathy (HAB): CT-pathological correlation.

We describe the thin-section CT appearances of HTLV-1-associated bronchopneumonopathy, with histopathological correlation, in two biopsy proven cases.

Tumor angiogenesis and dynamic CT in lung adenocarcinoma: radiologic-pathologic correlation.

PURPOSE: The purpose of this work was to evaluate the correlation of tumor angiogenesis and dynamic CT in lung adenocarcinoma. METHOD: Thirty-five consecutive patients with lung adenocarcinoma underwent dynamic chest CT. Maximum attenuation of dynamic CT was compared with microvessel densities (MVDs) and vascular endothelial growth factor (VEGF) expression by immunohistochemistry. RESULTS: The mean peak attenuation (A(PA)) of lung adenocarcinoma correlated with MVD (r = 0.689, p < 0.0001). VEGF positiveness of lung adenocarcinoma was 63%. There was a significant difference in A(PA) between VEGF-positive and -negative lung adenocarcinomas (39.9 +/- 3.9 and 24.3 +/- 2.3; p < 0.05). The mean MVDs of VEGF-positive adenocarcinomas were significantly higher than those of negative ones (82.5 +/- 5.9 and 49.2 +/- 7.1; p < 0.05). The mean A(PA) of VEGF-positive lung adenocarcinomas correlated positively with MVD (r = 0.707, p < 0.0001). CONCLUSION: The A(PA) value of dynamic CT reflects MVD in lung adenocarcinoma. The A(PA) value of dynamic CT might be an index for VEGF-related tumor angiogenesis.

High-resolution CT findings of macrophage activation syndrome: a case report.

Macrophage activation syndrome (MAS) is a rare disorder characterised by benign, reactive, excessive, well-differentiated macrophage proliferation, secondary to an immune dysregulation in response to some triggering agents such as viral infection. We report a 3-year-old girl with MAS and pulmonary involvement. This is the first radiographic description of MAS on high-resolution CT.