Shuhei Sato

Intracoronary Autologous Cardiac Progenitor Cell Transfer in Patients With Hypoplastic Left Heart Syndrome The TICAP Prospective Phase 1 Controlled Trial

Rationale: Hypoplastic left heart syndrome (HLHS) remains a lethal congenital cardiac defect. Recent studies have suggested that intracoronary administration of autologous cardiosphere-derived cells (CDCs) may improve ventricular function. Objective: The aim of this study was to test whether intracoronary delivery of CDCs is feasible and safe in patients with hypoplastic left heart syndrome. Methods and Results: Between January 5, 2011, and January 16, 2012, 14 patients (1.8±1.5 years) were prospectively assigned to receive intracoronary infusion of autologous CDCs 33.4±8.1 days after staged procedures (n=7), followed by 7 controls with standard palliation alone. The primary end point was to assess the safety, and the secondary end point included the preliminary efficacy to verify the right ventricular ejection fraction improvements between baseline and 3 months. Manufacturing and intracoronary delivery of CDCs were feasible, and no serious adverse events were reported within the 18-month follow-up. Patients treated with CDCs showed right ventricular ejection fraction improvement from baseline to 3-month follow-up (46.9%±4.6% to 52.1%±2.4%; P=0.008). Compared with controls at 18 months, cardiac MRI analysis of CDC-treated patients showed a higher right ventricular ejection fraction (31.5%±6.8% versus 40.4%±7.6%; P=0.049), improved somatic growth (P=0.0005), reduced heart failure status (P=0.003), and lower incidence of coil occlusion for collaterals (P=0.007). Conclusions: Intracoronary infusion of autologous CDCs seems to be feasible and safe in children with hypoplastic left heart syndrome after staged surgery. Large phase 2 trials are warranted to examine the potential effects of cardiac function improvements and the long-term benefits of clinical outcomes. Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01273857.

Dual-Time-Point F-18 FDG PET/CT for Evaluation of Intrathoracic Lymph Nodes in Patients with Non-Small Cell Lung Cancer

Purpose: The aim of this study was to evaluate the diagnostic capacity of F-18 fluorodeoxyglucose dual-time-point (DTP) positron emission tomography (PET)/computed tomography (CT) for intrathoracic lymph node (LN) metastases in patients with nonsmall cell lung cancer (NSCLC). Materials and Methods: Thirty-four patients had DTP PET/CT, with 60 minutes and 2-hour scans (n = 19, NSCLC; n = 15, benign pulmonary disease). LN diagnoses were confirmed by surgery or clinical follow-up (n = 14, metastatic LNs; n = 45, nonmetastatic LNs; n = 39, inflammatory LNs). Results: The maximum standardized uptake value (SUVmax) in the metastatic group was significantly higher than those in the nonmetastatic and inflammatory groups on both early- and delayed-phase imaging (each P < 0.0001). The retention index (RI) of SUVmax (RI-SUVmax) in the metastatic group was significantly higher than in the nonmetastatic (P = 0.0008) and inflammatory groups (P = 0.0074). No significant difference was found between SUVmax values of the nonmetastatic and inflammatory groups on early- (P = 0.6461) or delayed-phase (P = 0.6913), or between RI-SUVmax values of the nonmetastatic and inflammatory groups (P = 0.5717). For early-phase SUVmax, the cut-off value for highest accuracy with metastatic LNs was 3.61, yielding a sensitivity of 86.67% and a specificity of 88.00%. For delayed-phase SUVmax, the cut-off value was 4.00, yielding a sensitivity of 91.6% and specificity of 92.9%. For RI-SUVmax, the cut-off value was 20.91%, yielding a sensitivity of 73.6% and specificity of 75.9%. Conclusions: DTP PET/CT with a semiquantitative technique may improve diagnostic capacity for nodal staging of NSCLC.

Analysis of factors associated with radiation-induced bronchiolitis obliterans organizing pneumonia syndrome after breast-conserving therapy.

PURPOSE To evaluate factors associated with radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome after breast-conserving therapy. METHODS AND MATERIALS A total of 702 women with breast cancer who received radiotherapy after breast-conserving surgery at seven institutions between July 1995 and December 2006 were analyzed. In all patients, the whole breast was irradiated with two tangential photon beams. The criteria used for the diagnosis of radiation-induced BOOP syndrome were as follows: (1) radiotherapy to the breast within 12 months, (2) general and/or respiratory symptoms lasting for >or=2 weeks, (3) radiographs showing lung infiltration outside the radiation port, and (4) no evidence of a specific cause. RESULTS Radiation-induced BOOP syndrome was seen in 16 patients (2.3%). Eleven patients (68.8%) were administered steroids. The duration of steroid administration ranged from 1 week to 3.7 years (median, 1.1 years). Multivariate analysis revealed that age (>or=50 years; odds ratio [OR] 8.88; 95% confidence interval [CI] 1.16-67.76; p = 0.04) and concurrent endocrine therapy (OR 3.05; 95% CI 1.09-8.54; p = 0.03) were significantly associated with BOOP syndrome. Of the 161 patients whose age was >or=50 years and who received concurrent endocrine therapy, 10 (6.2%) developed BOOP syndrome. CONCLUSIONS Age (>or=50 years) and concurrent endocrine therapy can promote the development of radiation-induced BOOP syndrome after breast-conserving therapy. Physicians should carefully follow patients who received breast-conserving therapy, especially those who are older than 50 years and received concurrent endocrine therapy during radiotherapy.

Preliminary retrospective investigation of FDG-PET/CT timing in follow-up of ablated lung tumor

ObjectiveThe aim of this study was to clarify the most appropriate follow-up initiation time point for positron emission tomography (PET)/computed tomography (CT) following radio frequency ablation (RFA) of lung tumors, and the cutoff values of maximum standard uptake value (SUVmax) to evaluate local tumor progression.MethodsWe enrolled 15 patients (8 men, median age 62 years) with 60 tumors, who were treated with RFA of lung tumors and underwent fluorodeoxyglucose (FDG)-PET/CT following RFA. Local tumor progression was assessed by periodic chest CT images prior to and following intravenous administration of a contrast medium. The SUVmax of three periods, namely, 0–3 months, 3–6 months, and 6–9 months after RFA, was evaluated. The appropriate time point for follow-up initiation and the cutoff value of SUVmax were determined using receiver-operating characteristic (ROC) analysis.ResultsThe median follow-up period was 357 days. Of 60 tumors, 10 showed local progression. The area under the ROC curve (Az) for the 6–9 months (P = 0.044) was the largest and almost equal to that of the 3–6 months (P = 0.024). Az for the 0–3 months was the smallest and statistically insignificant (P = 0.705). The cutoff value of 1.5 of SUVmax at 3–9 months after RFA showed 77.8% sensitivity and 85.7–90.5% specificity.ConclusionsThe appropriate follow-up initiation time point is at least 3 months following RFA. Thus, SUVmax is a useful and reliable predictive indicator.

Additional diagnostic value of first-pass myocardial perfusion imaging without stress when combined with 64-row detector coronary CT angiography in patients with coronary artery disease

Objective Multi-detector coronary CT angiography (CCTA) can detect coronary stenosis, but it has a limited ability to evaluate myocardial perfusion. We evaluated the usefulness of first-pass CT-myocardial perfusion imaging (MPI) in combination with CCTA for diagnosing coronary artery disease (CAD). Methods A total of 145 patients with suspected CAD were enrolled. We used 64-row multi-detector CT (Definition Flash, Siemens). The same coronary CCTA data were used for first-pass CT-MPI without drug loading. Images were reconstructed by examining the signal densities at diastole as colour maps. Diagnostic accuracy was assessed by comparison with invasive coronary angiography. Results First-pass CT-MPI in combination with CCTA significantly improved diagnostic performance compared with CCTA alone. With per-vessel analysis, the sensitivity, specificity, positive predictive value and negative predictive value increased from 81% to 85%, 87% to 94%, 63% to 79% and 95% to 96%, respectively. The area under the receiver operating characteristic curve for detecting CAD also increased from 0.84 to 0.89 (p=0.02). First-pass CT-MPI was particularly useful for assessing segments that could not be directly evaluated due to severe calcification and motion artefacts. Conclusions First-pass CT-MPI has an additional diagnostic value for detecting coronary stenosis, in particular in patients with severe calcification.

Frontal Assessment Battery and Brain Perfusion Imaging in Early Dementia

Background/Aims: The frontal assessment battery (FAB) is reported to be a useful tool for screening frontal function. However, the neural substrates involved remain to be elucidated. The aim of the present study was to identify the brain regions responsible for FAB performance in patients with early dementia. We sought a correlation between FAB scores and brain perfusion. Methods: A total of 117 subjects participated in this study (Alzheimer’s disease = 51, frontotemporal dementia = 14, vascular dementia = 13, dementia with Lewy bodies = 7, psychiatric disease = 7, mild cognitive impairment = 11, controls = 14). They underwent brain single photon emission computed tomography with 99mTc-ethylcisteinate dimer, and we analyzed the data, using a regional cerebral blood flow (rCBF) quantification software program, 3DSRT (3-dimensional stereotaxic region of interest template). Results: FAB scores had a moderately positive correlation with left callosomarginal and precentral rCBF. Comparison of rCBF between high- and low-scoring FAB groups revealed that the latter showed significantly lower rCBF in the bilateral callosomarginal and left precentral regions. Conclusion: The results in this study suggest that the FAB mainly reflects the function of the callosomarginal and precentral segments, especially the left side, and that it might be a valid frontal lobe function test.

Clinical Significance of Preoperative Lymphoscintigraphy for Sentinel Lymph Node Biopsy in Breast Cancer

BACKGROUND Lymphoscintigraphy (LSG) has been widely used as an additional modality to sentinel lymph node biopsy (SLNB) using isotope. However, the significance of the number of LSG-visualized axillary nodes has not been fully understood. We analyzed this and discussed its potential as a modality to complement SLNB. METHODS Ninety-one breasts and axillary lymph nodal status were evaluated retrospectively. All patients were examined by LSG using isotope and subsequently by SLNB. RESULTS Nine patients (9.9%) had no LSG-visualized axillary node, while 61 patients (67.0%) had only 1 node, and 21 patients (23.1%) had multiple nodes. Overall, sentinel lymph node (SLN) identification rate was 96.7%, and the mean number of removed SLNs was 1.5 nodes per patient. In patients with nonvisualized nodes, 66.7% of SLNs were successfully identified, while 100% of SLNs were identified in those with LSG-visualized nodes. Compared with patients with less than one visualized node, significantly more SLNs were removed in patients with multiple visualized nodes. The number of LSG-visualized nodes correlated with that of metastatic nodes. CONCLUSIONS Preoperative LSG is effective in evaluating SLN status, and the LSG status could be associated with the number of dissected SLN. Moreover, the results of LSG potentially reflect the histological nodal status.

Hepatectomy simulation discrepancy between radionuclide receptor imaging and CT volumetry: influence of decreased unilateral portal venous flow.

Background: Regional dysfunction demonstrated by Tc-99m-diethylenetriamine-penta-acetic acid-galactosyl human serum albumin (GSA) scintigraphy due to regional decrease in the portal venous flow has previously been reported. In this study, we call attention to the significance of unilateral portal venous flow decrease for preoperative hepatectomy simulation, and evaluate the hepatectomy simulation discrepancy between Tc-99m-GSA single-photon emission computed tomography (SPECT) and CT volumetry.Methods: Twenty-four hepatectomy candidates underwent preoperative hepatectomy simulation by both Tc-99m-GSA SPECT and CT volumetry. Both anatomical and functional resection ratios were calculated by means of CT volumetry and Tc-99m-GSA SPECT, respectively. The differences and ratios between anatomical and functional resection ratios were calculated in all patients, and compared in patients with and without unilateral portal venous flow decrease.Results: Anatomical resection ratios were 28.0±11.7 (mean±standard deviation) in patients with unilateral portal venous flow decrease, and 42.1±15.7 in patients without unilateral portal venous flow decrease (p=0.0127). Functional resection ratios were 14.7±12.8 in patients with unilateral portal venous flow decrease and 40.5±14.6 in patients without (p=0.0004). The differences between anatomical and functional resection ratios were 13.0±7.9 in patients with unilateral portal venous flow decrease and 5.6±3.1 in patients without (p=0.0009). The ratios between anatomical and functional resection ratios were 0.48±0.29 in patients with unilateral portal venous flow decrease and 0.86±0.10 in patients without (p=0.0018). In 12 of the 13 patients with unilateral portal venous flow decrease, anatomical resection ratios were found to be larger than functional resection ratios, whereas this happened in only 6 of 11 patients without unilateral portal venous flow decrease (p=0.0063).Conclusion: Unilateral portal venous flow decrease is suspected to be a major factor in the discreapancy between hepatectomy simulations with radionuclide receptor imaging and CT volumetry.

Trail making test B and brain perfusion imaging in mild cognitive impairment and mild Alzheimer's disease.

The trail making test (TMT) has long been used to investigate deficits in cognitive processing speed and executive function in humans. However, there are few studies that elucidate the neural substrates of the TMT. The aim of the present study was to identify the brain regional perfusion patterns associated with performance on TMT part B (TMT-B) in patients with amnestic mild cognitive impairment (aMCI) or mild Alzheimers disease (AD). Twenty-one patients with good TMT-B scores and 21 age- and sex-matched patients with poor TMT-B scores were selected. All 42 subjects underwent brain single photon emission computed tomography (SPECT), and the SPECT images were analyzed by statistical parametric mapping. No significant differences between good- and poor-scoring groups were found with respect to years of education, Addenbrookes Cognitive Examination scores, and scores on TMT-A. Compared to patients with good scores on TMT-B, patients with poor scores showed significant hypoperfusion in the bilateral anterior cingulate extending to the posterior region on the right side, bilateral caudate nucleus and putamen, and bilateral thalamus. Analysis of 63 AD or aMCI subjects revealed significant correlation a between regional cerebral blood flow in the right cingulate cortex and TMT-B scores. Our results suggest that functional activity of the anterior cingulate, striatum and thalamus is closely related to performance time on TMT-B. The performance time on the TMT-B score might be a promising index of dysfunction of the anterior cingulate, striatum, and thalamus among patients with aMCI or mild AD.

Frontal assessment battery and brain perfusion imaging in Alzheimer's disease

BACKGROUND The frontal assessment battery (FAB) is reported to be a useful tool for assessing frontal dysfunction. However, the neural substrates involved in patients with Alzheimers disease (AD) remain to be elucidated. The aim of the present study was to identify the regional perfusion patterns of the brain associated with performance scores on the FAB of patients with AD using brain perfusion assessed by single photon emission computed tomography (SPECT). METHODS Twenty-four AD patients with high scores and 24 age- and sex-matched AD patients with low scores on the FAB were selected from 470 consecutive Japanese patients of the Memory Clinic of Okayama University Hospital. All 48 participants underwent brain SPECT with 99mTc-ethylcysteinate dimer, and the SPECT images were analyzed by statistical parametric mapping. RESULTS No significant differences were found between high and low FAB scoring groups with respect to Addenbrookes Cognitive Examination scores, Mini-Mental State Examination scores, or the depression score of the Neuropsychiatric Inventory subscale. Compared with patients with high scores on the FAB, AD patients with low scores showed significant hypoperfusion in the left middle frontal gyrus (MFG) and the right superior frontal gyrus (SFG) extending to the left SFG. CONCLUSION Our results suggest that functional activity of the SFG and MFG is closely related to the FAB score. The FAB might be a promising strategy to detect early stages of AD with low SFG and MFG function.