Using Patient-Specific Contrast Enhancement Optimizer Simulation Software During the Transcatheter Aortic Valve Implantation-Computed Tomography Angiography in Patients With Aortic Stenosis.

OBJECTIVES: This study assessed whether patient-specific contrast enhancement optimizer simulation software (p-COP) can reduce the contrast material (CM) dose compared with the conventional body weight (BW)-tailored scan protocol during transcatheter aortic valve implantation-computed tomography angiography (TAVI-CTA) in patients with aortic stenosis. METHODS: We used the CM injection protocol selected by the p-COP in group A (n = 30). p-COP uses an algorithm that concerns data on an individual patient's cardiac output. Group B (n = 30) was assigned to the conventional BW-tailored CM injection protocol group. We compared the CM dose, CM amount, injection rate, and computed tomography (CT) values in the abdominal aorta between the 2 groups and classified them as acceptable (>280 Hounsfield units (HU)) or unacceptable (<279 HU) based on the optimal CT value and visualization scores for TAVI-CTA. We used the Mann-Whitney U test to compare patient characteristics and assess the interpatient variability of subjects in both groups. RESULTS: Group A received 56.2 mL CM and 2.6 mL/s of injection, whereas group B received 76.9 mL CM and 3.4 mL/s of injection ( P < 0.01). The CT value for the abdominal aorta at the celiac level was 287.0 HU in group A and 301.7HU in group B ( P = 0.46). The acceptable (>280 HU) and unacceptable (<280 HU) CT value rates were 22 and 8 patients in group A and 24 and 6 patients in group B, respectively ( P = 0.76). We observed no significant differences in the visualization scores between groups A and B (visualization score = 3, P = 0.71). CONCLUSION: The utilization of p-COP may decrease the CM dosage and injection rate by approximately 30% in individuals with aortic stenosis compared with the body-weight-tailored scan protocol during TAVI-CTA.

Can Machine Learning Identify the Intravenous Contrast Dose and Injection Rate Needed for Optimal Enhancement on Dynamic Liver Computed Tomography?

OBJECTIVES: This study aimed to investigate whether machine learning (ML) is useful for predicting the contrast material (CM) dose required to obtain a clinically optimal contrast enhancement in hepatic dynamic computed tomography (CT). METHODS: We trained and evaluated ensemble ML regressors to predict the CM doses needed for optimal enhancement in hepatic dynamic CT using 236 patients for a training data set and 94 patients for a test data set. After the ML training, we randomly divided using the ML-based (n = 100) and the body weight (BW)-based protocols (n = 100) by the prospective trial. The BW protocol was performed using routine protocol (600 mg/kg of iodine) by the prospective trial. The CT numbers of the abdominal aorta and hepatic parenchyma, CM dose, and injection rate were compared between each protocol using the paired t test. Equivalence tests were performed with equivalent margins of 100 and 20 Hounsfield units for the aorta and liver, respectively. RESULTS: The CM dose and injection rate for the ML and BW protocols were 112.3 mL and 3.7 mL/s, and 118.0 mL and 3.9 mL/s ( P < 0.05). There were no significant differences in the CT numbers of the abdominal aorta and hepatic parenchyma between the 2 protocols ( P = 0.20 and 0.45). The 95% confidence interval for the difference in the CT number of the abdominal aorta and hepatic parenchyma between 2 protocols was within the range of predetermined equivalence margins. CONCLUSIONS: Machine learning is useful for predicting the CM dose and injection rate required to obtain the optimal clinical contrast enhancement for hepatic dynamic CT without reducing the CT number of the abdominal aorta and hepatic parenchyma.

Prediction of Aortic Contrast Enhancement on Dynamic Hepatic Computed Tomography-Performance Comparison of Machine Learning Methods and Simulation Software.

OBJECTIVES: The aim of this study was to compare prediction ability between ensemble machine learning (ML) methods and simulation software for aortic contrast enhancement on dynamic hepatic computed tomography. METHODS: We divided 339 human hepatic dynamic computed tomography scans into 2 groups. One group consisted of 279 scans used to create cross-validation data sets, the other group of 60 scans were used as test data sets. To evaluate the effect of the patient characteristics on enhancement, we calculated changes in the contrast medium dose per enhancement of the abdominal aorta in the hepatic arterial phase. The parameters for ML were the patient sex, age, height, body weight, body mass index, and cardiac output. We trained 9 ML regressors by applying 5-fold cross-validation, integrated the predictions of all ML regressors for ensemble learning and the simulations, and used the training and test data to compare their Pearson correlation coefficients. RESULTS: Comparison of different ML methods showed that the Pearson correlation coefficient for the real and predicted contrast medium dose per enhancement of the abdominal aorta was highest with ensemble ML (r = 0.786). It was higher than that obtained with the simulation software (r = 0.350). With ensemble ML, the Bland-Altman limit of agreement [mean difference, 5.26 Hounsfield units (HU); 95% limit of agreement, -112.88 to 123.40 HU] was narrower than that obtained with the simulation software (mean difference, 11.70 HU; 95% limit of agreement, -164.71 to 188.11 HU). CONCLUSION: The performance for predicting contrast enhancement of the abdominal aorta in the hepatic arterial phase was higher with ensemble ML than with the simulation software.

Usefulness of the patient-specific contrast enhancement optimizer simulation software during the whole-body computed tomography angiography.

To evaluate whether the patient-specific contrast enhancement optimizer simulation software (p-COP) is useful for predicting contrast enhancement during whole-body computed tomography angiography (WBCTA). We randomly divided the patients into two groups using a random number table. We used the contrast material (CM) injection protocol selected by p-COP in group A (n = 52). The p-COP used an algorithm including data on the individual patient's cardiac output. Group B (n = 50) was assigned to the conventional CM injection protocol based on body weight. We compared the CT number in the abdominal aorta at the celiac artery level between the two groups and classified them as acceptable (> 280 HU) and unacceptable (< 279 HU) based on the optimal CT number for the WBCTA scans. To evaluate the difference in both injection protocols, we compared the visual inspection of the images of the artery of Adamkiewicz in both protocols. The CM dosage and injection rate in group A were significantly lower than those in group B (480.8 vs. 501.1 mg I/kg and 3.1 vs. 3.3 ml/s, p < 0.05). The CT number of the abdominal aorta at the celiac level was 382.4 ± 62.3 HU in group A and 363.8 ± 71.3 HU in group B (p = 0.23). CM dosage and injection rate were positively correlated to cardiac output for group A (r = 0.80, p < 0.05) and group B (r = 0.16, p < 0.05). The number of patients with an acceptable CT number was higher in group A [46/6 (86.7%)] than in group B [43/7 (71.4%)], but not significant (p = 0.71). The visualization rate for the Adamkiewicz artery was not significantly different between groups A and B (p = 0.89). The p-COP was useful for predicting contrast enhancement during WBCTA with a lower CM dosage and a lower contrast injection rate than that based on the body weight protocol. In patients with lower cardiac output a reduction in contrast injection rate and CM dosage did not lead to a reduced imaging quality, thus particularly in this group CM dosage can be reduced by p-COP.

Retrospective analysis of definitive radiotherapy for neck node metastasis from unknown primary tumor: Japanese Radiation Oncology Study Group study.

OBJECTIVE: To investigate the optimal treatment method and risk factor of neck node metastasis from unknown primary tumors (NUP) treated by radiotherapy. METHODS: Retrospective case study based on a multi-institutional survey was conducted by the Japanese Radiation Oncology Study Group. Patients pathologically diagnosed as having NUP from 1998 to 2007 were identified. Univariate and multivariate analyses of overall survival (OS), progression free survival (PFS), neck progression free survival (NPFS) and mucosal progression free survival (MPFS) were evaluated. RESULTS: In total, 130 patients with median age of 65 years were included. Nodal stages N1, N2a, N2b and N2c were observed for 10, 26, 43, 12 and 39 patients, respectively. All the patients received radiotherapy (RT) with neck dissection in 60 and with chemotherapy in 67 cases. The median doses to the metastatic nodes, prophylactic neck and prophylactic mucosal sites were 60.0, 50.4 and 50.4 Gy, respectively. The median follow-up period for surviving patients was 42 months. Among 12 patients, occult primary tumors in the neck region developed after radiotherapy. The 5-year OS, PFS, NPFS and MPFS were 58.1%, 42.4%, 47.3% and 54.9%, respectively. Univariate analysis showed that lower N stage (N1-2b), non-bulky node (<6 cm) and negative extracapsular extension (ECE) status were the factors associated with favorable OS, PFS, NPFS and MPFS. Radical surgery proved to be a favorable factor of OS, NPFS and MPFS. On multivariate analysis, lower N stage and negative ECE status were correlated with improved survival. CONCLUSIONS: Lower nodal stage and negative ECE status showed a favorable impact on survival and disease control in patients with NUP treated by radiotherapy.

A phase I/II clinical trial for the hybrid of intracavitary and interstitial brachytherapy for locally advanced cervical cancer.

BACKGROUND: This paper describes about a study protocol of phase I/II multicenter prospective clinical trial evaluating the feasibility and efficacy of the hybrid of intracavitary and interstitial brachytherapy (HBT) for locally advanced uterine cervical cancer patients. METHODS AND DESIGN: Patients with histologically confirmed FIGO stage IB2, IIA2, IIB, and IIIB uterine cervical carcinoma width of which is larger than 5 cm assessed by MRI will be entered to this clinical trial. Protocol therapy is 30-30.6 Gy in 15-17 fractions of whole pelvic radiotherapy concurrent with weekly CDDP (40 mg/m(2)), followed by 24 Gy in 4 fractions of HBT and central shield EBRT up to 50-50.4 Gy in 25-28 fractions. Tumor width is assessed again within one week before the first HBT and if the tumor width is larger than 4 cm, patients proceed to the secondary registration. In phase I section, feasibility of this will be investigated. If less than 10 % out of 20 patients experienced greater than grade 3 acute non-hematologic adverse effects, the study proceeds to phase II part. In phase II part a total of 55 patients will be accrued and the efficacy of the HBT will be investigated comparing with historical control data. If the lower margin of 90 % confidence interval of the 2-year pelvic progression-free survival of the HBT trial is higher than 64 %, the HBT is considered to be more effective than conventional ICBT. DISCUSSION: The aim of this study is to demonstrate the feasibility and efficacy of the HBT for locally advanced cervical cancer. This trial will clarify the indication, feasibility, and efficacy of this new technique. TRIAL REGISTRATION: UMIN000019081 ; Registration date: 2015/9/30.

Boron neutron capture therapy for advanced salivary gland carcinoma in head and neck.

PURPOSE: Boron neutron capture therapy (BNCT) is among the radiation treatments known to have a selective lethal effect on tumor cells. This study summarizes the tumor responses and the acute and late adverse effects of BNCT in the treatment of patients with both recurrent and newly diagnosed T4 salivary gland carcinoma. METHODS: Two patients with recurrent cancer and 3 with newly diagnosed T4 advanced malignancy were registered between October 2003 and September 2007, with the approval of the medical ethics committees of Kawasaki Medical School and Kyoto University. BNCT was performed, in a single fraction using an epithermal beam, at Japan Research Reactor 4. RESULTS: All patients achieved a complete response within 6 months of treatment. The median duration of the complete response was 24.0 months; the median overall survival time was 32.0 months. Three of the 5 patients are still alive; the other 2 died of distant metastatic disease. Open biopsy of the parotid gland after BNCT was performed in 1 patient and revealed no residual viable cancer cells and no serious damage to the normal glandular system. Although mild alopecia, xerostomia, and fatigue occurred in all patients, there were no severe adverse effects of grade 3 or greater. CONCLUSIONS: Our preliminary results demonstrate that BNCT is a potential curative therapy for patients with salivary gland carcinoma. The treatment does not cause any serious adverse effects, and may be used regardless of whether the primary tumor has been previously treated.

Prediction of endovascular leaks after thoracic endovascular aneurysm repair though machine learning applied to pre-procedural computed tomography angiographs.

To predict endoleaks after thoracic endovascular aneurysm repair (TEVAR) we submitted patient characteristics and vessel features observed on pre- operative computed tomography angiography (CTA) to machine-learning. We evaluated 1-year follow-up CT scans (arterial and delayed phases) in patients who underwent TEVAR for the presence or absence of an endoleak. We evaluated the effect of machine learning of the patient age, sex, weight, and height, plus 22 vascular features on the ability to predict post-TEVAR endoleaks. The extreme Gradient Boosting (XGBoost) for ML system was trained on 14 patients with- and 131 without endoleaks. We calculated their importance by applying XGBoost to machine learning and compared our findings between with those of conventional vessel measurement-based methods such as the 22 vascular features by using the Pearson correlation coefficients. Pearson correlation coefficient and 95% confidence interval (CI) were r = 0.86 and 0.75 to 0.92 for the machine learning, r = - 0.44 and - 0.56 to - 0.29 for the vascular angle, and r = - 0.19 and - 0.34 to - 0.02 for the diameter between the subclavian artery and the aneurysm (Fig. 3a-c, all: p < 0.05). With machine-learning, the univariate analysis was significant higher compared with the vascular angle and in the diameter between the subclavian artery and the aneurysm such as the conventional methods (p < 0.05). To predict the risk for post-TEVAR endoleaks, machine learning was superior to the conventional vessel measurement method when factors such as patient characteristics, and vascular features (vessel length, diameter, and angle) were evaluated on pre-TEVAR thoracic CTA images.

Effect of asbestos exposure on differentiation of cytotoxic T lymphocytes in mixed lymphocyte reaction of human peripheral blood mononuclear cells.

Asbestos fibers are associated with tumorigenicity, and are thought to cause mesothelioma. However, their effect on immune response remains unclear. We examined the effect of asbestos exposure on differentiation of cytotoxic T lymphocytes (CTLs) in mixed lymphocyte reactions (MLR) of human peripheral blood mononuclear cells (PBMCs) upon exposure to chrysotile B (CB) or crocidolite (CR) asbestos at 5 µg/ml for 7 days. Exposure to CB during MLR suppressed increases in the percentage and number of CD8⁺ T cells in response to allogenic cells. The cytotoxicity for allogenic targets decreased in PBMCs exposed to CB, but not CR, when compared with PBMCs without any exposure during MLR. Exposure to CB during MLR resulted in suppression of increases in granzyme B⁺ cells and IFN-γ⁺ cells. CB exposure also resulted in suppression of increases in CD45RO⁺ effector/memory cells and CD25⁺-activated cells in CD8⁺ lymphocytes, and a decrease in CD45RA⁺ cells. CB exposure suppressed the proliferation of CD8⁺ lymphocytes without an increase in annexin V⁺ apoptotic cells in CD8⁺ lymphocytes. Moreover, the production of IL-10, IFN-γ, and TNF-α, but not IL-2, decreased in the presence of CB. These results suggest that exposure to asbestos potentially suppresses the differentiation of cytotoxic T lymphocyte, accompanied by decreases in IFN-γ and TNF-α.

COMPARISON OF THE 64- AND 80-DETECTOR ROW COMPUTED TOMOGRAPHY AMONG THE CT NUMBER AND RADIATION DOSE DURING LOWER EXTREMITY COMPUTED TOMOGRAPHY ANGIOGRAPHY.

To compare the computed tomography (CT) number and the radiation dose between the 64 (group A) and 80-detector row (group B) during lower extremity computed tomography angiography (LE-CTA). We enrolled 144 patients underwent LE-CTA and compared the CT number for the popliteal arteries, radiation dose and the rate of the optimal CT number during the LE-CTA exceeding 200 HU between the two groups. The CT number for the popliteal arteries and mean dose-length product was significantly higher in Group A than in Group B (P < 0.01). The rate of the optimal CT number for the popliteal arteries was 23.6% with Group B scanner and 56.9% with Group A (P < 0.05). The 64-detector row CT was significantly higher in the CT number for the popliteal arteries, radiation dose and rate of the optimal CT number during the LE-CTA than the 80-detector row. Depiction ability did not improve by using a high CT scanner with a wider detector during LE-CTA.

Usefulness of large beam-shaping filters at different tube voltages of newborn chest CT.

BACKGROUND: To investigate optimizing the use of different beam shaping filters (viz. small, medium and large) when using different tube voltages during the newborn chest computed tomography (CT) on a GE Lightspeed VCT scanner. METHODS: We used pediatric anthropomorphic phantoms with a 64 detector-row CT scanner while scanning the chest. A real-time skin dosimeter (RD - 1000; Trek Corporation, Kanagawa, Japan) was positioned into the phantom center of the body, the surface of the body back, and the right and left mammary glands. We performed and compared six scan protocols using small, medium, and large beam shaping filters at 80 and 120 kVp protocols. RESULT: There were no significant differences in the image noise for the chest scan among the different beam shaping filters. By using the large beam shaping filter at 80 kVp, it was possible to reduce the exposure dose by 5% in comparison with the small beam shaping filter, and by 10% in comparison with the medium beam shaping filter. By using the large beam shaping filter at 120 kVp, it was possible to reduce the exposure dose by 15% in comparison with the small beam shaping filter and by 20% in comparison with the medium beam shaping filter (p < 0.01). CONCLUSION: The large beam shaping filter had the most dose reduction effect during newborn chest CT on a GE Lightspeed VCT scanner. The additional copper filtration being present in the large bowtie filter of the GE Lightspeed CT scanner when using different tube voltages is more effective in reducing radiation exposure in children.

RADIATION DOSE REDUCTION AT LOW TUBE VOLTAGE WITH CORONARY ARTERY BYPASS GRAFT COMPUTED TOMOGRAPHY ANGIOGRAPHY BASED ON THE CONTRAST NOISE RATIO INDEX.

To compare the radiation dose and diagnostic ability of the 100-kVp protocol, based on the contrast noise ratio (CNR) index, during coronary artery bypass graft (CABG) vessels with those of the 120-kVp protocol. For the 120-kVp scans (150 patients), the targeted image level was set at 25 Hounsfield units (HU) (CNR120 = iodine contrast/25 HU). For the 100-kVp scans (150 patients), the targeted noise level was set at 30 HU to obtain the same CNR as in the 120-kVp scans (i.e. using 1.2-fold higher iodine contrast, CNR100 = 1.2 × iodine contrast/(1.2 × 25 HU) = CNR120). We compared the CNRs, radiation doses, detection of CABG vessels and visualisation scores of the scans acquired at 120 and 100 kVp, respectively. At the same CNR, the 100-kVp protocol may help reduce the radiation dose by ⁓30% compared with the 120-kVp protocol, without degradation of diagnostic ability during CABG.

Usefulness of electrocardiogram mA modulation during the electrocardiogram-gated CT scan in paediatrics with high heart rate for different helical pitch: a phantom-based assessment study.

We investigated the effect of electrocardiographic (ECG) mA-modulation of ECG-gated scans of computed tomography (CTA) on radiation dose and image noise at high heart rates (HR) above 100 bpm between helical pitches (HP) 0.16 and 0.24. ECG mA-modulation range during ECG-gated CTA is 50-100 mA, the phase setting is 40-60% and the scan range is 90 mm for clinical data during HR for 90, 120 and 150 bpm. Radiation dose and image noise in Housfield units are measured for CT equipment during HR for 90, 120 and 150 bpm between HP 0.16 and 0.24. ECG mA-modulation, dose reduction ratio for HR 90, 120 and 150 bpm are 19.1, 13.4 and 8.7% at HP 0.16 and 17.1, 13.3 and 7.7% at HP 0.24, respectively. No significant differences were observed in image noise between both HP. Dose reductions of 8-24% are achieved with ECG mA-modulation during ECG-gated CCTA scan, which is beneficial even in high HR more than 100 bpm.

Effect of patient characteristics on vessel enhancement on arterio-venous fistula CT angiography in a retrospective cohort study.

To evaluate the effects of various patient characteristics on vessel enhancement on arterio-venous fistula (AVF) computed tomography (CT) angiography (AVF-CT angiography). A total of 127 patients with suspected or confirmed shunt stenosis and internal AVF complications were considered for inclusion in a retrospective cohort study. The tube voltage was 120 kVp, and the tube current was changed from 300 to 770 mA to maintain the image quality (noise index: 14) using automatic tube current modulation. To evaluate the effects of age, sex, body size, and scan delay on the CT number of the brachial artery or vein, we used correlation coefficients and multivariate regression analyses. There was a significant positive correlation between the CT number of the brachial artery or vein and age (R = 0.21 or 0.23, P < .01). The correlations were inverse with the height (r = -0.45 or -0.42), total body weight (r = -0.52 or -0.50), body mass index (r = -0.21 or -0.23), body surface area (body surface area [BSA]; r = -0.56 or -0.54), and lean body weight (r = -0.55 or -0.53) in linear regression analysis (P < .01 for all). There was a significant correlation between the CT number of the brachial artery or vein and scan delay (R = 0.19 or 01.9, P < .01). Only the BSA had significant effects on the CT number in multivariate regression analysis (P < .01). The BSA was significantly correlated with the CT number of the brachial artery or vein on AVF-CT angiography.

Asbestos-induced cellular and molecular alteration of immunocompetent cells and their relationship with chronic inflammation and carcinogenesis.

Asbestos causes lung fibrosis known as asbestosis as well as cancers such as malignant mesothelioma and lung cancer. Asbestos is a mineral silicate containing iron, magnesium, and calcium with a core of SiO(2). The immunological effect of silica, SiO(2), involves the dysregulation of autoimmunity because of the complications of autoimmune diseases found in silicosis. Asbestos can therefore cause alteration of immunocompetent cells to result in a decline of tumor immunity. Additionally, due to its physical characteristics, asbestos fibers remain in the lung, regional lymph nodes, and the pleural cavity, particularly at the opening sites of lymphatic vessels. Asbestos can induce chronic inflammation in these areas due to the production of reactive oxygen/nitrogen species. As a consequence, immunocompetent cells can have their cellular and molecular features altered by chronic and recurrent encounters with asbestos fibers, and there may be modification by the surrounding inflammation, all of which eventually lead to decreased tumor immunity. In this paper, the brief results of our investigation regarding reduction of tumor immunity of immunocompetent cells exposed to asbestos in vitro are discussed, as are our findings concerned with an investigation of chronic inflammation and analyses of peripheral blood samples derived from patients with pleural plaque and mesothelioma that have been exposed to asbestos.

Salvage high-dose-rate brachytherapy for local prostate cancer recurrence after radiotherapy - preliminary results.

OBJECTIVE: To assess the preliminary clinical results of salvage high-dose-rate brachytherapy (HDR-BT) applied in cases of suspected local recurrence or of residual tumour after radiotherapy. PATIENTS AND METHODS: The subjects were 11 patients who met the above conditions and underwent salvage HDR-BT between December 2006 and January 2009. The T stage at the initial treatment was T1c in three patients, T2 in three patients and T3 in five patients. Ten patients received HDR-BT ± electron beam radiation therapy and one patient received proton beam irradiation. Follow-up after the completion of salvage HDR-BT lasted 18-41 months (mean 29 months). A dose of 11.0 Gy radiation was delivered twice (22.0Gy in total), separated by a 6-h interval, on the day the applicators were inserted. RESULTS: Seven of the 11 cases remained in a biochemical non-evidence of disease state. The prostate-specific antigen (PSA) level continuously rose after salvage HDR-BT in three of the four other cases. Hormone administration was initiated in the four cases of PSA recurrence. No G3 or more severe events occurred, and the incidence of G2 was low during this study period. CONCLUSION: Of the 11 cases treated with salvage HDR-BT, PSA levels remained low in seven cases and the incidence of complications was also low. This suggests that salvage HDR-BT is effective as an option for treatment of local prostate cancer recurrence after radiotherapy.

COMPARISON OF PEDIATRIC LENS DOSE MEASUREMENTS BETWEEN AXIAL SCAN MODE WITHOUT ACTIVE COLLIMATOR AND HELICAL SCAN MODE WITH ACTIVE COLLIMATOR BY USING A 64 DETECTOR-ROW COMPUTED TOMOGRAPHY SCANNER.

To investigate the pediatric eye lens entrance surface dose for both axial scan modes without an active collimator and helical scan modes with an active collimator on 64 detector-row computed tomography (CT) scanner. We used three pediatric anthropomorphic phantoms with axial and helical scan modes from the superior orbitomeatal line to the crown of the head. We compared the measured dose values of the real-time skin dosemeter at the surfaces of the lens and the image noise at different scan modes. The median measured dose values for the lens of newborn, 1-year-old and the 5-year-old phantom were 31.3, 0.97 and 0.65 mGy, respectively, in the axial scan mode and 0.89, 1.21 and 0.71 mGy, respectively, in the helical scan mode. Compared with helical scans with an active collimators, axial scans can reduce the lens dose by ∼10% during head CT on 64 detector-row CT scanner without deterioration of image noise.

Decreased CXCR3 expression in CD4+ T cells exposed to asbestos or derived from asbestos-exposed patients.

Asbestos causes malignant tumors such as lung cancer and malignant mesothelioma (MM). To determine whether asbestos exposure causes reduction of antitumor immunity, we established an in vitro T-cell line model of low-dose and continuous exposure to asbestos using an human adult T-cell leukemia virus-1 immortalized human polyclonal T-cell line, MT-2, and revealed that MT-2 cells exposed continuously to asbestos showed resistance to asbestos-induced apoptosis. In addition, the cells presented reduction of surface CXCR3 chemokine receptor expression and IFN-γ production. In this study, to confirm that these findings are suitable for clinical translation, surface CXCR3 and IFN-γ expression were analyzed using freshly isolated human CD4(+) T cells derived from healthy donors and patients with pleural plaque (PP) or MM. The results revealed that CXCR3 and IFN-γ expression in the ex vivo model were reduced in some cases. Additionally, CXCR3 expression in CD4(+) T cells from PPs and MMs was significantly reduced compared with that from healthy donors, and CD4(+) T cells from patients with MMs exhibited a marked reduction in IFN-γ mRNA levels after stimulation in vitro. Moreover, CD4(+)CXCR3(+) T cells in lymphocytes from MMs showed a tendency for an inverse correlation with its ligand CXCL10/IP10 in plasma. These findings show reduction of antitumor immune function in asbestos-exposed patients and indicate that CXCR3, IFN-γ, and CXCL10/IP10 may be candidates to detect and monitor disease status.

Reduction of CXC chemokine receptor 3 in an in vitro model of continuous exposure to asbestos in a human T-cell line, MT-2.

Because patients with silicosis who are chronically exposed to silica particles develop not only pulmonary fibrosis, but also complications involving autoimmune diseases such as rheumatoid arthritis and systemic sclerosis, exposure to asbestos may affect the human immune system. This immunologic effect may impair antitumor immune function because cancer complications such as lung cancer and malignant mesothelioma are found in patients exposed to asbestos. To elucidate the antitumor immune status caused by CD4(+) T cells exposed to asbestos, an in vitro T-cell model of long-term and low-level exposure to chrysotile asbestos was established from a human adult T-cell leukemia virus-1-immortalized human polyclonal T cell line, MT-2, and the resulting six sublines showed resistance to asbestos-induced apoptosis after more than 8 months of continuous exposure. The results of DNA microarray analysis showed that the expression of 139 genes was altered by long-term and low-level exposure to asbestos, and the profile was almost similar among the six sublines when compared with the original MT-2 cells that had never been exposed to asbestos. Pathway and network analysis indicated a down-regulation of IFN-γ signaling and expression of CXC chemokine receptor 3 (CXCR3) in the sublines, whereas ELISA and flow cytometry analysis demonstrated a reduction in Th1-related IFN-γ production and cell-surface CXCR3 expression. These findings suggest that chronic exposure to asbestos may reduce antitumor immune status in CD4(+) T cells, and that an in vitro T-cell model may be useful in identifying molecules related to the impairment of antitumor immune function.

Locally recurrent prostate cancer after high-dose-rate brachytherapy: the value of diffusion-weighted imaging, dynamic contrast-enhanced MRI, and T2-weighted imaging in localizing tumors.

OBJECTIVE: The purpose of this article is to retrospectively evaluate the utility of prostate MRI for detecting locally recurrent prostate cancer after high-dose-rate (HDR) brachytherapy. MATERIALS AND METHODS: Sixteen men with biochemical failure after HDR brachytherapy for prostate cancer underwent prostate MRI, including T2-weighted imaging, dynamic contrast-enhanced MRI (DCE-MRI), and diffusion-weighted imaging (DWI), using a 1.5-T MRI unit before 12-core-specimen biopsy. Two radiologists in consensus assessed the presence of tumor on each sequence within eight regions of the prostate (six from the peripheral zone [PZ] and two from the transition zone [TZ]) on the basis of biopsy. RESULTS: Biopsy revealed locally recurrent prostate cancer in 22 (17 in PZ and five in TZ) of 128 regions (17.2%). The sensitivity, specificity, and accuracy of each MRI method in the detection of recurrent tumor were 27%, 99%, and 87%, respectively, for T2-weighted imaging; 50%, 98%, and 90%, respectively, for DCE-MRI; and 68%, 95%, and 91%, respectively, for DWI. The sensitivity of DWI in detecting recurrent tumor was significantly higher than that of T2-weighted imaging (p = 0.004). Multiparametric MRI achieved the highest sensitivity (77%) but with slightly decreased specificity (92%). CONCLUSION: These results indicate that a multiparametric MRI protocol that includes DWI provides a sensitive method to detect local recurrence after HDR brachytherapy.