Tsuneo Matsumoto

Prognostic potential of FOXP3 expression in non-small cell lung cancer cells combined with tumor-infiltrating regulatory T cells

Expression of the transcription factor FOXP3 characterizes regulatory T cells (Tregs) that engage in the maintenance of immunological self-tolerance and immune homeostasis. Intra-tumoral accumulation of Tregs is associated with unfavorable prognosis in several kinds of cancers. Recently, expression of FOXP3 and its association with prognosis have also been shown in some cancer cells in clinical studies. For non-small cell lung cancer (NSCLC), however, prognostic significance of tumor FOXP3 expression and its relationship with Tregs remain unknown. FOXP3 expression in cancer cells and tumor-infiltrating lymphocytes was examined by immunohistochemical staining of surgical specimens from 87 patients with NSCLC. Prognostic values of the tumor-infiltrating Treg count and tumor FOXP3 expression status were evaluated retrospectively. FOXP3-positive cancer cells were observed in 27 of 87 (31.0%) patients. There was no significant relationship between Treg count and tumor FOXP3 status. Increased Treg counts were associated with worse overall and relapse-free survival whereas the influence of tumor FOXP3 status on survival was not significant. However, when FOXP3-positive cancer cells were present, the relationship between Treg accumulation and worse prognosis was attenuated. In contrast, patients without tumor FOXP3 expression and high Treg count had significantly worse overall and relapse-free survival (hazard ratio: 3.118 and 3.325, p=0.028 and 0.024, respectively) than other groups. These results suggest that tumor FOXP3 expression has a better prognostic potential in NSCLC and that in combination with tumor-infiltrating Treg count the absence of tumor FOXP3 allows the selection of high-risk patients.

High resolution CT findings in community-acquired pneumonia

PURPOSE Our goal was to clarify the high resolution CT (HRCT) findings of community-acquired pneumonia based on pathologic findings and to make a differential diagnosis between bacterial and atypical pneumonias. METHOD This study evaluated 32 cases with community-acquired pneumonia, including 18 cases with bacterial pneumonia and 14 cases with atypical pneumonia [mycoplasma pneumonia (n = 12), chlamydia pneumonia (n = 1), and influenza viral pneumonia (n = 1)]. HRCT images in these cases were space consolidation, ground-glass attenuation, thickening of the bronchovascular bundle, and distribution of abnormal attenuation. RESULTS Bacterial pneumonia frequently showed air space consolidation with segmental distribution (72.2%) that tended to locate at the middle and outer zones of the lung. Atypical pneumonia frequently showed centrilobular shadow (64.3%), acinar shadow (71.4%), air space consolidation and ground-glass attenuation with lobular distribution (57.1 and 85.7%, respectively), and tendency of the lesions to distribute at the inner layer of the lung in addition to the middle and outer layers (85.7%). CONCLUSION Characteristic HRCT findings of both bacterial and atypical pneumonia were demonstrated. These HRCT features seemed to reflect pathologic findings and the manner of lesional progression. This information may support the appropriate antibiotic therapy in medical practice.

IMAGE FEATURE ANALYSIS OF FALSE-POSITIVE DIAGNOSES PRODUCED BY AUTOMATED DETECTION OF LUNG NODULES

RATIONALE AND OBJECTIVES To reduce the number of false-negative diagnoses by radiologists, the authors are developing a computer-aided diagnosis scheme for detection of lung nodules in digital chest images. In this study, the authors attempted to reduce the number of false-positive diagnoses obtained with a previous computer scheme by incorporating additional knowledge from experienced chest radiologists into the computer scheme. METHODS The authors applied their previous computer scheme, using less-strict criteria, to 60 clinical chest radiographs; this yielded 735 candidate nodules (23 true nodules and 712 false-positive diagnoses). These candidates were analyzed using region-growing, trend-correction, and edge-gradient techniques to determine measures by which to quantify image features of candidate nodules. RESULTS The 712 false-positive diagnoses represented various anatomic structures that were located throughout the chest image. From this analysis, we were able to decrease the number of false-positive errors from an average of 12 to approximately 5 per image without eliminating any true nodules. CONCLUSION Our results show that incorporating knowledge from experienced chest radiologists into the computer algorithm will play an important role in the development of computerized schemes for the detection of pulmonary nodules.

Assessing myometrial invasion by endometrial carcinoma with dynamic MRI.

Objective Dynamic MRI was used to analyze patterns of contrast enhancement in muscle layers in the normal uterine body and to evaluate the depth of myometrial invasion by endometrial carcinoma. Materials and Methods Dynamic MRI was performed in 18 normal volunteers and 22 patients with endometrial carcinoma. Eight of the 18 normal volunteers were of reproductive age, and 10 were postmenopausal. The dynamic study was performed immediately after the bolus administration of gadopentetate dimeglumine. Twelve consecutive images, including the early phase images, were obtained during the first 2 min. The delayed phase image was obtained subsequently. Results An early enhancement zone of the inner muscle layer was demonstrated in 15 normal volunteers. In all patients in whom this early enhancement zone was preserved, the tumor was confined to <50% of the muscle layer. In the evaluation of myometrial invasion, the accuracy of dynamic MRI was 91% compared with 77% on T2-weighted images. This improvement may be attributed to greater contrast and clearer demonstration of the border between tumor and myometrium in the early phase. Conclusion We consider the disruption of the early enhancement zone of the inner muscle layer to be an important indicator of myometrial invasion.

Therapeutic efficacy of transcatheter arterial chemoembolization for hepatocellular carcinoma: MRI and pathology.

Objective Our goal was to evaluate the usefulness of multisection dynamic MRI with gadopentetate dimeglumine in the assessment of the therapeutic efficacy of transcatheter arterial chemoembolization (TAE) with iodized oil for hepatocellular carcinomas (HCCs). Materials and Methods Findings on multisection dynatnic MR images were compared with gross appearance and histologic findings in 13 patients with HCCs after TAE with iodized oil. Arterial dominant phase images of the entire liver were obtained 20 s after the start of administration of gadopentetate dimeglumine. Results In 3 of the 13 patients, no enhancing areas within the tumors were detected. In the retnaining 10 patients, enhancing portions were detected within the tumor on arterial dominant phase images. Histologically, viable tumor cells were present in the rapidly enhancing portions, while necrotic tissues were present in nonenhancing areas, irrespective of the accumulation of iodized oil on CT scans. However, in one patient in whotn no enhancing portion was seen in the tumor, a small number of viable tumor cells within the capsule were identified on pathologic examination. Conclusion Multisection dynamic MRI is helpful for evaluating the therapeutic efficacy of TAE with iodized oil for HCCs by revealing the hemodynamics of the tumor irrespective of accumulation of iodized oil. Index Terms Liver neoplasms—Contrast media—Magnetic resonance imaging.

Potential usefulness of computerized nodule detection in screening programs for lung cancer.

RATIONALE AND OBJECTIVE To alert radiologists to possible nodule locations and subsequently to reduce the number of false-negative diagnoses, the authors are developing a computer-aided diagnostic (CAD) scheme for the detection of lung nodules in digital chest images. METHODS A computer-vision scheme was applied to photofluorographic films obtained in a mass survey for detection of asymptomatic lung cancer in Japan. Ninety-five patients with abnormal test results who had primary and metastatic lung cancers and 103 patients with normal test results were included. RESULTS The sensitivity of the computer output was comparable with that of physicians in this mass survey (62%). The computer detected approximately 40% of all nodules missed in the mass survey, but missed 17 true-positive results identified in the mass survey. The CAD scheme produced an average of 15 false-positive findings per image. CONCLUSION If the number of false-positive results can be significantly reduced, computer-vision schemes such as this may have a role in lung cancer screening programs.

Association between cytokine removal by polymyxin B hemoperfusion and improved pulmonary oxygenation in patients with acute exacerbation of idiopathic pulmonary fibrosis

Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is characterized by severe worsening dyspnea of unknown etiology and high mortality without effective treatment. Recently, direct hemoperfusion with polymyxin B (PMX)-immobilized fiber cartridge (PMX-DHP) has been reported to improve pulmonary oxygenation and survival in patients with AE-IPF although its mechanism of action remains unknown. To gain insights into the pathobiology of AE-IPF through the beneficial effects of PMX-DHP, we analyzed the profile of cytokines adsorbed onto PMX-fibers used in 9 AE-IPF patients. In addition, the sera of these AE-IPF patients collected immediately before and after PMX-DHP, 9 stable IPF patients and 8 healthy individuals were also analyzed. The serum levels of cytokines including IL-9, IL-12, IL-17, PDGF and VEGF were significantly decreased immediately after PMX-DHP (P<0.02), and VEGF and IL-12 were most prominently reduced. In addition to PDGF and VEGF, IL-1β, IL-1ra, IL-8, IL-23, FGF basic, GM-CSF, IP-10, RANTES and TGF-β were eluted from used PMX-fibers. Interestingly, improved pulmonary oxygenation after PMX-DHP was correlated well with the quantities of eluted VEGF. These results suggest that adsorption of proinflammatory, profibrotic and proangiogenic cytokines onto PMX-fibers is one of the mechanisms of action of PMX-DHP in AE-IPF. Notably, removal of VEGF by PMX-DHP may contribute to the rapid improvement in oxygenation by suppressing vascular permeability in the lung.

CT findings of leukemic pulmonary infiltration with pathologic correlation

The aim of this study was to demonstrate the characteristic CT findings of leukemic pulmonary infiltration based on the pathologic findings. The CT findings of 11 leukemic patients with leukemic pulmonary infiltration were compared with those of 22 leukemic patients with other diseases as a control group. Evaluated pulmonary parenchymal CT findings included thickening of bronchovascular bundles and interlobular septa, prominence of peripheral pulmonary arteries, ground-glass opacities, air-space consolidation, and nodules. The CT-pathologic correlations for leukemic infiltration were evaluated in 7 patients. Frequent parenchymal CT findings were thickening of bronchovascular bundles (81.8%), prominence of peripheral pulmonary arteries (81.8%), and non-lobular and non-segmental ground-glass opacities (90.9%). The first two findings were significantly more frequently observed in leukemic infiltration than in the control group, had good interobserver agreement, and corresponded pathologically to leukemic cell infiltration around the pulmonary arteries, bronchi, or bronchioles. Non-lobular and non-segmental ground-glass opacity corresponded to leukemic cell infiltration within alveolar spaces and septa adjacent to the pulmonary arteries or bronchi and also corresponded to hemorrhage, edema, or diffuse alveolar damage. Thickening of bronchovascular bundles and prominence of peripheral pulmonary arteries are CT findings suggestive for leukemic infiltration and correspond to peribronchovascular tumor extension.

Detection of hepatocellular carcinoma: comparison of T2-weighted breath-hold fast spin-echo sequences and high-resolution dynamic MR imaging with a phased-array body coil.

The purpose of our study was to compare T2‐weighted breath‐hold fast spin‐echo sequence (BHFSE) and high‐resolution dynamic MR imaging (HR‐DMRI) in the detection of hepatocellular carcinoma (HCC). Short and long T2‐weighted BHFSE sequences and biphasic HR‐DMRI including arterial‐dominant and delayed phase images with a phased‐array body coil were performed in 30 consecutive patients with 37 HCCs. The lesion‐to‐liver contrast‐to‐noise ratio (CNR) was quantitatively measured. The lesion conspicuity and delineation was qualitatively rated according to a four‐point scale. The lesion‐to‐liver CNR was highest with the arterial‐dominant phase HR‐DMRI and was significantly higher than those obtained with both short and long T2‐weighted BHFSE and those obtained with unenhanced and delayed HR‐DMRI. The CNR obtained with short T2‐weighted BHFSE was significantly higher than those obtained with long T2‐weighted BHFSE and with unenhanced and delayed HR‐DMRI. The sensitivity for the sequences was 78.4% (29/37) for short T2‐weighted BHFSE, 67.6% (25/37) for long T2‐weighted BHFSE, 37.8% (14/37) for unenhanced HR‐DMRI, 97.3% (36/37) for arterial‐dominant phase HR‐DMRI, and 43.2% (16/37) for delayed HR‐DMRI. The sensitivity of serial dynamic MR imaging combined with unenhanced, arterial‐dominant phase imaging and delayed phase imaging was 100% (37/37). The score in the qualitative analysis of the lesion conspicuity and delineation was highest for the arterial‐dominant phase HR‐DMRI and was significantly higher than that for the short T2‐weighted BHFSE. The score for the short T2‐weighted BHFSE was significantly higher than that for the long T2‐weighted BHFSE and that for the unenhanced HR‐DMRI. Arterial‐dominant phase HR‐DMRI is superior to the T2‐weighted BHFSE technique, and also HR‐DMRI combined with unenhanced, arterial‐dominant and delayed phases is the most sensitive technique in the detection of HCC. J. Magn. Reson. Imaging 1999;9:274–279.

Difference in 201Tl accumulation on single photon emission computed tomography in benign and malignant thoracic lesions.

The difference in 201Tl-chloride (201Tl) accumulation on single photon emission computed tomography (SPECT) between 58 benign (58 cases) and 48 malignant (46 cases) thoracic lesions, each of more than 20 mm in diameter was investigated. In the 34 benign and 48 malignant lesions depicted in both early (15 min) and delayed (3 h) images there was no significant difference in the mean early and delayed uptake ratios of lesion to normal contralateral lung between benign and malignant. However, the retention index in the lesion derived from (delayed ratio — early ratio)/(early ratio) ± 100% showed a significant difference (benign −4.30 ± 13.6% versus malignant 23.3 + 18.9%, P < 0.01), indicating the poor 201Tl retention in the benign lesions. Using the criteria of nondepiction in the delayed image or a negative retention index, 81.1% accuracy and 95.2% predictive value for diagnosis of benign lesions were obtained. Thus, 201Tl SPECT appears to have potential usefulness in the diagnosis of benign thoracic lesions.