Ability of the prognostic model of J-ACCESS study to predict cardiac events in a clinical setting: The APPROACH study.

BACKGROUND: In patients with coronary artery disease (CAD), one of the risk models available in Japan was a multivariate risk prediction model based on a Japanese multicenter database: the Japanese Assessment of Cardiac Events and Survival Study by Quantitative Gated SPECT (J-ACCESS). The aim of this study was to clinically validate the accuracy of this risk model. METHODS: We evaluated the performance of the J-ACCESS model using data derived from the Assessment of the Predicted value of PROgnosis of cArdiaC events in Hokuriku (APPROACH) registry. Variables of age, summed stress score (SSS), left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), and diabetes mellitus were included. The major cardiac events were defined as cardiac death, non-fatal myocardial infarction, and heart failure that required hospitalization. The patients were followed up for three years to compare between predicted risk and actual events. RESULTS: We evaluated 283 patients with suspected or confirmed CAD receiving myocardial perfusion imaging using 99mTc-tetrofosmin between March 2009 and August 2011. Mean age was 68.9±10.1 years, mean eGFR 67.4±24.3mL/min/1.73m2, mean SSS 5.2±7.2, and mean LVEF 65.4±14.0%. Fourteen (4.9%) patients experienced major cardiac events including cardiac death in 4 patients (1.4%), non-fatal myocardial infarction in 1 patient (0.3%), and severe heart failure in 9 patients (3.2%), respectively. While SSS≥8, LVEF<50%, eGFR<45mL/min/1.73m2, and event risk≥10% were significant variables in survival analysis, multivariate proportional hazard analysis showed that only LVEF and eGFR were significant. The event rate estimated from the J-ACCESS model was comparable to the actual number of major cardiac events (9 and 6, respectively, p=0.58 by Chi-square test). CONCLUSIONS: The predictive ability of the J-ACCESS risk model is clinically valid among patients with CAD and could be applicable in clinical practice.

Dual-energy bone removal computed tomography (BRCT): preliminary report of efficacy of acute intracranial hemorrhage detection.

PURPOSE: One of the major applications of dual-energy computed tomography (DECT) is automated bone removal (BR). We hypothesized that the visualization of acute intracranial hemorrhage could be improved on BRCT by removing bone as it has the highest density tissue in the head. This preliminary study evaluated the efficacy of a DE BR algorithm for the head CT of trauma patients. METHODS: Sixteen patients with acute intracranial hemorrhage within 1 day after head trauma were enrolled in this study. All CT examinations were performed on a dual-source dual-energy CT scanner. BRCT images were generated using the Bone Removal Application. Simulated standard CT and BRCT images were visually reviewed in terms of detectability (presence or absence) of acute hemorrhagic lesions. RESULTS: DECT depicted 28 epidural/subdural hemorrhages, 17 contusional hemorrhages, and 7 subarachnoid hemorrhages. In detecting epidural/subdural hemorrhage, BRCT [28/28 (100%)] was significantly superior to simulated standard CT [17/28 (61%)] (p = .001). In detecting contusional hemorrhage, BRCT [17/17 (100%)] was also significantly superior to simulated standard CT [11/17 (65%)] (p = .0092). CONCLUSION: BRCT was superior to simulated standard CT in detecting acute intracranial hemorrhage. BRCT could improve the detection of small intracranial hemorrhages, particularly those adjacent to bone, by removing bone that can interfere with the visualization of small acute hemorrhage. In an emergency such as head trauma, BRCT can be used as support imaging in combination with simulated standard CT and bone scale CT, although BRCT cannot replace a simulated standard CT.

Thyroglobulin gene mutation with cold nodule on thyroid scintigraphy.

Thyroglobulin gene mutation is a rare cause of congenital hypothyroidism, but thyroglobulin gene mutations are thought to be associated with thyroid cancer development. A 21-year-old Japanese man treated with levothyroxine for congenital hypothyroidism had an enlarged thyroid gland with undetectable serum thyroglobulin despite elevated serum TSH level. The patient was diagnosed with thyroglobulin gene mutation, with compound heterozygosity for Gly304Cys missense mutation and Arg432X nonsense mutation. Ultrasonography showed a hypovascular large tumor in the left lobe that appeared as a cold nodule on thyroid scintigraphy. He underwent total thyroidectomy, but pathological study did not reveal findings of thyroid carcinoma, but rather a hyperplastic nodule with hemorrhage. Strong cytoplasmic thyroglobulin immunostaining was observed, but sodium iodide symporter immunostaining was hardly detected in the hyperplastic nodule. The clinical characteristics of patients with thyroglobulin gene mutations are diverse, and some patients are diagnosed by chance on examination of goiter in adults. The presence of thyroid tumors that appear as cold nodules on thyroid scintigraphy should consider the potential for thyroid carcinoma, if the patient has relatively low serum thyroglobulin concentration in relation to the degree of TSH without thyroglobulin autoantibody.

Thallium-201 scintigraphy for the assessment of long-term prognosis in patients with osteosarcoma.

OBJECTIVE: The aim of this study was to confirm the prognostic value of (201)Tl scintigraphy in the midcourse of preoperative chemotherapy in patients with osteosarcoma. METHODS: The 28 patients with biopsy-proven osteosarcoma were enrolled retrospectively in this study. Planar scintigraphy was performed 15 min after injection of 111 MBq (201)Tl before preoperative chemotherapy and after third course (midcourse) of chemotherapy in all patients. The (201)Tl uptake ratio was calculated by dividing the count density of the lesion by that of the contralateral normal area. The percentage reduction of the (201)Tl uptake ratio calculated by 100 × [(pre-chemotherapy ratio - mid-chemotherapy ratio)/pre-chemotherapy ratio] was compared with the histopathological response and long-term survival rate. RESULTS: Good histopathological response was observed in 16 patients. Mean follow-up period was 58.0 ± 41 months. Both overall and event-free survival rates of histopathologically good responders were significantly higher than that of poor responders (P = 0.018 and P = 0.0076). There was also significant correlation between pre-chemotherapeutic effect evaluated with (201)Tl scintigraphy and overall and event-free survival rate in all patients (P = 0.045 and P = 0.017, respectively), and in patients without metastasis at initial diagnosis (P = 0.043 and P = 0.031, respectively). CONCLUSION: (201)Tl scintigraphy performed in the middle of neoadjuvant chemotherapy can predict overall survival and event-free survival in patients with osteosarcoma.

Assessment of doxorubicin cardiac toxicity using gated 99mTc-hexakis-2-methoxyisobutylisonitrile myocardial single photon emission computed tomography: wall thickening and motion abnormalities can be an early sign of cardiac involvement.

BACKGROUND: Advancement in chemotherapy has significantly improved the prognosis of cancer patients. However, many anticancer drugs have serious cardiovascular side effects. We assessed doxorubicin-induced cardiac toxicity (DCT) during and after preoperative chemotherapy using gated (99m)Tc-hexakis-2-methoxyisobutylisonitrile (MIBI) single photon emission computed tomography (SPECT) in patients with malignant bone and soft tissue tumors. METHODS AND RESULTS: Gated (99m)Tc-MIBI SPECT was performed before, and after the middle and final courses of preoperative chemotherapy. Gated (99m)Tc-MIBI SPECT was quantitatively analyzed with QGS/QPS software. We also assessed the reproducibility of measurements of global and regional functions from gated SPECT images. Twenty-eight patients (19 males and 9 females), eligible for preoperative chemotherapy, were included. All patients had normal myocardial perfusion images based on QPS during preoperative chemotherapy. Wall thickening (WT) and motion (WM) decreased after the middle course of preoperative chemotherapy compared to baseline. After the final course of preoperative chemotherapy, significant decreases of ejection fraction, WT and WM, and one-third mean filling rate were observed compared to baseline. By regression analysis, correlation coefficients of inter- and intra-observer reproducibility of global and regional functions were excellent (r ≥ 0.95). CONCLUSIONS: Gated (99m)Tc-MIBI SPECT can monitor the deterioration of cardiac function in asymptomatic patients with possible DCT. WT and WM might be useful as early markers of ventricular dysfunction due to DCT.

Prognostic value of Tc-99m-MIBI performed during middle course of preoperative chemotherapy in patients with malignant bone and soft-tissue tumors.

PURPOSE: This study was aimed to determine whether Tc-99m-hexakis-2-methoxyisobutylisonitrile (MIBI) scintigraphy performed in the middle of preoperative chemotherapy has a prognostic value in patients with malignant bone and soft tissue tumors (MBST). MATERIALS AND METHODS: In 90 patients with MBST, Tc-99m-MIBI scintigraphy was performed 15 minutes after tracer injection before the first and after the third chemotherapy cycles. After 5 cycles of chemotherapy and tumor resection, therapeutic effect was assessed by histopathology. The percent reduction of uptake ratio (ΔUR) was calculated according to the following equation: 100 × ([prechemotherapy UR - post-middle course of chemotherapy UR]/prechemotherapy UR). RESULTS: The average follow-up for the entire population was 52 months. Twenty-one patients had clinically detectable metastases at initial presentation (primary metastasis). Kaplan-Meier analysis demonstrated that absence of metastasis was associated with good survival in all patients, in patients with bone tumor, and those with soft tissue tumor (P < 0.0001, P < 0.0001, and P = 0.0003, respectively), and ΔUR ≧30% was also associated with survival in all patients and patients with bone tumor (P = 0.011 and P = 0.047, respectively), but was marginal in those with soft tissue tumor (P = 0.091). Multivariate analysis showed that primary metastasis was the most powerful independent predictor of a lethal clinical outcome in all patients, in both patients with bone and soft tissue tumors (hazard ratio [HR]: 4.9, 95% confidence interval [CI]: 2.61-9.08, P < 0.0001; HR: 15.1, CI: 4.86-52.7, P < 0.0001; HR: 3.7, CI: 1.45-8.94, P = 0.0069, respectively) and showed that Tc-99m-MIBI scintigraphy had a good independent long-term prognostic value in all patients and patients with bone tumor (HR: 2.2, CI: 1.14-4.43, P = 0.017; HR: 6.0, CI: 2.01-21.6, P = 0.0009, respectively) but not in those with soft tissue tumor (HR: 1.5, CI: 0.61-4.09, P = 0.38). Good disease-free survival was associated with ΔUR ≧30% in all patients and patients with soft tissue tumor (P = 0.0093 and P = 0.017, respectively) but not in those with bone tumor (P = 0.19). CONCLUSIONS: Tc-99m-MIBI scintigraphy at the middle course of preoperative chemotherapy could be used as a prognostic indicator in patients with MBST.

Toxic multinodular goiter with low radioactive iodine uptake.

A 74-year-old woman was referred to our hospital for goiter and persistent thyrotoxicosis. She had no signs of ophthalmopathy. She was not taking thyroid hormone. Thyroid CT revealed multiple nodules. The thyroid gland was not detected on (99m)Tc scintigraphy, (123)I uptake rate was 4.5% at 24 hours without hot nodules, and aberrant goiter was negative. After partial thyroidectomy, she was treated with levothyroxine. TRAb was undetectable during the disease course, and focal destructive change or chronic lymphocytic thyroiditis on the pathological specimens was not evident. We report a rare case of toxic multinodular goiter with low radioactive iodine uptake.

Use of 99mTc-MIBI scintigraphy in the evaluation of the response to chemotherapy for osteosarcoma: comparison with 201Tl scintigraphy and angiography.

BACKGROUND: In the treatment of osteosarcoma, the chemotherapeutic effect influences decisions regarding the surgical margin, continuation of chemotherapy, and choice of anticancer drugs for further chemotherapy. Therefore, it is necessary to evaluate the response to chemotherapy in the middle of the chemotherapy course. In this study, we investigated the use of (99m)Tc-hexakis-2-methoxyisobutyl-isonitrile ((99m)Tc-MIBI) scintigraphy in evaluating the response to chemotherapy of patients with osteosarcoma in comparison with (201)Tl scintigraphy and angiography. METHODS: A total 45 patients with osteosarcoma were examined using (99m)Tc-MIBI scintigraphy, (201)Tl scintigraphy, and angiography to evaluate their response to chemotherapy. The percentage reduction in the uptake ratios (ΔUR) calculated as 100 × [(prechemotherapy value - postchemotherapy value)/prechemotherapy value] were compared with histological assessments. Similarly, changes in tumor vascularity assessed by angiograms were compared with histological assessments. On the angiographic findings, the results were classified as complete response (CR), partial response (PR), no change (NC), or progressive disease (PD). On the images, ΔUR in (99m)Tc-MIBI ≥ 30% and ΔUR in (201)Tl ≥ 30% were classified as responder, as were CR and PR in angiograms. The therapeutic effect was assessed by histopathological examination of the resected specimens. The tumors of poor responders showed less than 90% necrosis, whereas the tumors of good responders showed 90% or more necrosis. RESULTS: Sensitivity, specificity, and accuracy were 73.9, 84.2, and 78.6%, respectively, for (99m)Tc-MIBI (κ = 0.57); 80.0, 61.1, and 72.1%, respectively, for (201)Tl (κ = 0.42); and 91.7, 35.0, and 65.9%, respectively for angiography (κ = 0.28). CONCLUSION: (99m)Tc-MIBI could be effectively used to predict the final response to chemotherapy of osteosarcoma.

Early prediction of histopathological tumor response to preoperative chemotherapy by Tc-99m MIBI imaging in bone and soft tissue sarcomas.

PURPOSE: Tc-99m-methoxyisobutylisonitrile (MIBI) accumulates in only viable cells. In patients with bone and soft tissue sarcomas, preoperative chemotherapy is essential and the early prediction of the tumor response to chemotherapy would be beneficial for the planning of treatment strategy. The purpose of this study was to assess whether the change of Tc-99m-MIBI images from the prechemotherapy state to the early to midportion of chemotherapy can predict the final histopathological tumor response as accurately as the change of imaging after completion of chemotherapy. METHODS: Seventy-three patients with bone and soft tissue sarcomas underwent Tc-99m-MIBI scintigraphy before chemotherapy and at least 2 times after the second or third or fifth course of chemotherapy. The changes of the tracer uptake (DeltaUR) and perfusion (DeltaPI) from prechemotherapy to postchemotherapy were compared with histologic response. RESULTS: The sensitivity, specificity, and accuracy for the prediction of effective chemotherapy in DeltaPI were 88%, 83%, 85% after second, 85%, 72%, 78% after third, and 81%, 71%, 76% after 5th chemotherapy, and those in DeltaUR were 88%, 83%, 85% after 2nd, 85%, 92%, 89% after 3rd, and 94%, 77%, 85% after fifth chemotherapy, respectively. The area under the receiver operator characteristic curve of the DeltaPI after second, third, and fifth chemotherapy were similarly good (0.842, 0.858, 0.811, respectively) and those of DeltaUR were similarly excellent (0.915, 0.936, 0.931, respectively). CONCLUSION: In patients with bone and soft tissue sarcomas, the change of Tc-99m-MIBI images from prechemotherapy to early to middle of chemotherapy can predict the final histopathological tumor response to chemotherapy as accurately as the change of Tc-99m-MIBI images from prechemotherapy to the completion of the preoperative chemotherapy.

Detection of Lewy body disease in patients with late-onset depression, anxiety and psychotic disorder with myocardial meta-iodobenzylguanidine scintigraphy.

PURPOSE: Lewy body disease (LBD) is comprised of a spectrum of diseases that includes Parkinson's disease (PD), PD dementia (PDD) and dementia with LBD (DLBD), an array of dementia, and motor symptoms. Low uptake of myocardial meta-iodobenzylguanidine (MIBG) validates diagnosis of LBD. Psychiatric symptoms sometimes precede atypical Parkinsonian syndromes in LBD. Of 34 patients with low MIBG uptake, late-onset depressive, anxiety, or psychotic symptoms were analyzed in term of clinical profiles. METHOD: Thirty-four patients were classed into three groups according to three main symptoms, 11 patients with visual hallucination (VH), 13 with depression-anxiety (DA), and 10 with psychosis with cognitive disturbance (PCD). Cutoff values of heart-to-mediastinum (HM) ratio of MIBG were set at 1.78 in early phase or 1.68 in late phase. RESULTS: Group VH patients showed a trend toward higher age at onset and occipital lobe hypoperfusion. Group DA patients lacked central and core features of DLBD and five of them showed frontal lobe hypoperfusion. Group PCD patients had the highest frequencies of suggestive symptoms and UPDRS scores and showed temporal lobe hypoperfusion. HM ratio was not associated with clinical profiles of three groups. Cognitive function was more severely disturbed in atypical Parkinsonian syndrome cases at an initial visit. CONCLUSION: Group VH was considered to DLBD, and Group PCD was regarded as PDD or DLBD with early psychotic presentation. Group DA has a possibility of early depression or anxiety disorder of LBD although it lacked DLBD criteria. Atypical Parkinsonian syndromes are associated with cognitive disturbance irrespective of psychiatric profiles.

Prediction of final tumor response to preoperative chemotherapy by Tc-99m MIBI imaging at the middle of chemotherapy in malignant bone and soft tissue tumors: comparison with Tl-201 imaging.

The aim of this study was to assess the predictive power of 99mTc-MIBI scintigraphy performed in the middle of chemotherapy, for the final tumor response to chemotherapy, and compare it to that of (201)Tl in malignant bone and soft tissue tumors (MBST). Sixty-eight patients with MBST underwent 99mTc-MIBI and 201Tl scintigraphies at 15 min after tracer injection before the first, and after the third, chemotherapy cycles. After five cycles of chemotherapy and tumor resection, therapeutic effect was assessed by histopathology. Less than 90% and > or =90% necrosis were judged as poor and good response to chemotherapy, respectively. Tracers uptake ratios were calculated by dividing the lesion count density by that of the background. 99mTc-MIBI perfusion index was also calculated. The % reduction of the perfusion index (DeltaPI) and uptake ratios (DeltaUR) calculated by 100 x [(prechemotherapy value--postchemotherapy value)/prechemotherapy value] were compared with histologic response. The sensitivity, specificity, and accuracy for the prediction of effective chemotherapy in 99mTc-MIBI imaging were 80%, 95%, 88% in DeltaUR, and 74%, 74%, 74% in DeltaPI, respectively. The area under the receiver operator characteristic curve (A(z)) of the 99mTc-MIBI-DeltaUR (0.923) was significantly higher than that of DeltaPI (0.809, p = 0.025) but only marginally higher than that of the 201Tl-DeltaUR (0.865, p = 0.079). A(z) in 201Tl (0.865) was not significantly different from that of DeltaPI (0.809, p = 0.35). 99mTc-MIBI imaging performed in the middle of chemotherapy well predicts the final tumor response to chemotherapy in patients with malignant bone and soft tissue tumors.

Skeletal recurrences and metastases of extraskeletal myxoid chondrosarcoma.

OBJECTIVE: The objective was to elucidate clinical and imaging features of skeletal involvement, recurrences, and metastases of extraskeletal myxoid chondrosarcoma. MATERIALS AND METHODS: Included in this series are 4 patients, aged 44 to 65 years, 3 of whom were men and 1 a woman. RESULTS: The primary lesions were in the thigh (n = 3) and the upper arm (n = 1). Three patients with multiple metastases died of the disease, 2 were considered to have local recurrence in the adjacent bone. Skeletal metastases occurred after lung metastases in 2 cases, and before lung metastases in 1 case. Typical imaging findings are well-defined lesions with no sclerotic margin or matrix mineralization. A slow, but persistent growth is noted on the imaging features. CONCLUSION: Although skeletal metastases of chondrosarcoma of bone and soft tissue are rare, myxoid chondrosarcomas, currently classified tumors of uncertain differentiation, rarely metastasize and/or recur in the bones. The imaging features are typically of a localized lesion with cortical disruption or expansion.

Characterization of cartilaginous tumors with 201Tl scintigraphy.

UNLABELLED: Histological diagnosis and grading of cartilaginous tumors are closely correlated with patient prognosis; consequently, they are essential elements. We attempted to clarify the characteristics of 201Tl uptake in various histological types of cartilaginous tumors and to assess its clinical value. METHODS: Twenty-two cases with histologically proven cartilaginous tumors (3 enchondromas, 15 conventional chondrosarcomas (grade I = 9, II = 5, III = 1), 3 mesenchymal chondrosarcomas, and 1 de-differentiated chondrosarcoma) were examined retrospectively. Planar 201Tl images were recorded 15 min following intravenous injection of 201Tl (111 MBq). 201Tl uptake in the tumor was evaluated visually employing a five-grade scoring system: 0 = no appreciable uptake, 1 = faint uptake above the background level, 2 = moderate uptake, 3 = intense uptake but lower than heart uptake and 4 = uptake higher than heart uptake. RESULTS: 201Tl uptake scores were 0 in 3 of 3 enchondromas, 9 of 9 grade I, and 4 of 5 grade II conventional chondrosarcomas. 201Tl uptake scores were 1 among 1 of 5 grades II and a grade III conventional chondrosarcoma. Mesenchymal chondrosarcoma and de-differentiated chondrosarcoma displayed 201Tl uptake scores of 2 or 3. CONCLUSIONS: Absence of elevated 201Tl uptake in cartilaginous tumors was indicative of enchondroma or low-grade conventional chondrosarcoma. However, in instances in which 201Tl uptake is obvious, high-grade chondrosarcoma or variant types should be considered.

Histological and radiological analysis of autoclaved bone 2 years after extirpation.

We examined grafted distal femoral autoclaved bone radiologically and histologically 24 months after surgery. The patient was a 16-year-old boy with osteoblastic-type osteosarcoma in the distal part of the left femur. The patient received pre- and postoperative chemotherapy and underwent limb reconstruction surgery using an autoclaved autograft. He was forced to undergo hip disarticulation because of local recurrence in the soft tissue. Radiologically and histologically, we were able to detect newly formed bone at the site of the distal junction and surrounding the autoclaved autograft, although most of the autoclaved bone remained without substitution even 24 months after implantation. The layer of newly formed bone surrounding the autoclaved autograft was so thin that it seemed to be ineffective for weight-bearing. Drilling into the autoclaved autograft appeared to promote little bone regeneration inside the autoclaved autograft. A bone scintigram showed newly formed bone around the autoclaved autograft, but the scan tended to exaggerate such bone formation beyond that actually confirmed by histological examination. We should be careful when applying autoclaved bone for weight-bearing parts.

Prediction of myocutaneous adverse side effect due to intra-arterial chemotherapy by intra-arterial (99m)Tc-macroaggregated albumin administration in patients with bone and soft-tissue tumors.

UNLABELLED: In malignant bone and soft-tissue tumors, intra-arterial chemotherapy and limb-saving surgery have become popular. Myocutaneous inflammatory change and necrosis are the major local side effects of intra-arterial chemotherapy. (99m)Tc-macroaggregated albumin (MAA) imaging with intra-arterial tracer administration was performed to evaluate drug distribution, and the ability of (99m)Tc-MAA imaging to predict local side effects was assessed. METHODS: In 24 patients, 42 (99m)Tc-MAA images were obtained with tracer injection through an intra-arterial catheter that was inserted into the proximal portion of the tumor-feeding artery. Abnormal uptake other than by tumor was assessed visually and quantitatively. RESULTS: In visual analysis, abnormal (99m)Tc-MAA accumulation was observed in 21 of 42 images. In the first consecutive 13 of these 21 images, intra-arterial chemotherapy with cisplatin, doxorubicin, and caffeine was administered, and myocutaneous inflammation or necrosis in the area corresponding to the abnormal (99m)Tc-MAA uptake was observed in 11. In contrast, none of the 21 images without abnormal (99m)Tc-MAA uptake demonstrated any local adverse effect from intra-arterial chemotherapy. In the last consecutive 8 images with abnormal (99m)Tc-MAA uptake, intra-arterial chemotherapy was initiated with only cisplatin, and doxorubicin and caffeine administration was changed to the intravenous route. In all 8 of these images, no local adverse effects from chemotherapy were observed. Overall, the sensitivity, specificity, and accuracy of (99m)Tc-MAA imaging for the detection of myocutaneous damage were 100% (11/11), 91% (21/23), and 94% (32/34), respectively, and positive and negative predictive values were 85% (11/13) and 100% (21/21), respectively. In quantitative analysis, when the diagnostic threshold of the uptake ratio was set at 2.5, sensitivity, specificity, and accuracy for the detection of myocutaneous complications were 91% (10/11), 96% (22/23), and 94% (32/34), respectively, and positive and negative predictive values were 91% (10/11) and 96% (22/23), respectively. CONCLUSION: (99m)Tc-MAA imaging with intra-arterial infusion before intra-arterial chemotherapy for bone and soft-tissue tumors can facilitate prediction of local myocutaneous adverse effects due to chemotherapy.