Motoyasu Sagawa

Diffusion-Weighted Imaging Is Superior to Positron Emission Tomography in the Detection and Nodal Assessment of Lung Cancers

BACKGROUNDnDiffusion-weighted magnetic resonance imaging (DWI) makes it possible to detect malignant tumors based on the difference in the diffusion of water molecules among tissues. The aims of this study are to examine the usefulness of DWI compared with positron emission tomography-computed tomography (PET-CT) in the assessment of lung cancer, and the relationships between the apparent diffusion coefficient (ADC) value and several pathologic factors.nnnMETHODSnSixty-three patients with primary non-small cell lung cancer were enrolled in this study. The DWI and PET-CT were performed before surgery. There were 42 adenocarcinomas, 19 squamous cell carcinomas, and 2 other cell types.nnnRESULTSnSixty-one lung cancers (97%) were detected visually with DWI. This was significantly higher than 54 lung cancers (86%) with PET-CT. The accuracy for N staging by DWI was 0.81 (51 of 63), which was not significantly higher than 0.71 (45 of 63) by PET-CT. The sensitivity (0.75) for individual metastatic lymph node stations by DWI was significantly higher than that (0.48) by PET-CT. The specificity for individual nonmetastatic lymph node stations was 0.99 by DWI and 0.97 by PET-CT, respectively. The accuracy (0.95) for the diagnosis of lymph node stations by DWI was significantly higher than that (0.90) by PET-CT. There was a weak reverse relationship (correlation coefficient: 0.286) between the ADC value and the maximum standardized uptake value, but no relationship between ADC value and tumor size. The ADC values increased while the cell differentiation increased.nnnCONCLUSIONSnDiffusion-weighted magnetic resonance imaging is superior to PET-CT in the detection of primary lesions and nodal assessment of non-small cell lung cancers.

Relationship of aquaporin 1, 3, and 5 expression in lung cancer cells to cellular differentiation, invasive growth, and metastasis potential

An oncogenic capacity of aquaporins, transmembrane channels for water, was recently proposed. This study seeks to elucidate the involvement of aquaporin 1, 3, and 5 in the development and progression of lung cancer. Expression of aquaporin 1, 3, and 5 was examined by immunohistochemistry, Western blot, and laser-captured microdissection/real-time reverse transcription polymerase chain reaction in 160 lung cancers of various histologic subtypes; and its correlation with clinicopathological factors and survival was analyzed. Aquaporin 1, 3, and 5 were expressed in tumor cells in 71%, 40%, and 56% of lung cancers, respectively. Aquaporin expressions were frequent in adenocarcinomas, whereas aquaporin 1 and 5 were negative in squamous cell carcinomas. Bronchioloalveolar carcinoma cells exhibited an apicolateral aquaporin 1 and apicolateral or basolateral aquaporin 3 localization in nonmucinous type, and apical aquaporin 1 and 5 and basolateral aquaporin 3 expression in mucinous type, which corresponded to aquaporins expression of nonneoplastic lung tissue. Basolateral aquaporin 5 expression was acquired during tumorigenesis of nonmucinous bronchioloalveolar carcinoma. In contrast, invasive adenocarcinoma tumor cells overexpressed aquaporin 1 and 5 with loss of subcellular polarization and with an intracytoplasmic distribution. Overexpression of aquaporin 1 correlated with high postoperative adenocarcinoma metastasis ratios and unfavorable disease-free survival rates (P = .031). We conclude that expression patterns of aquaporin 1, 3, and 5 in lung cancer cells are mostly associated with cellular differentiation. However, the expression of aquaporin 1 and 5 is up-regulated in invading lung cancer cells, particularly in adenocarcinomas; and the overexpression of aquaporin 1 with loss of subcellular polarization is suggested to be involved in their invasive and metastatic potential.

Advantages of Diffusion-Weighted Imaging Over Positron Emission Tomography-Computed Tomography in Assessment of Hilar and Mediastinal Lymph Node in Lung Cancer

BackgroundThe significance of diffusion-weighted imaging (DWI) is uncertain for the diagnosis of nodal involvement. The purpose of this study was to examine diagnostic capability of DWI compared with PET-CT for nodal involvement of lung cancer.MethodsA total of 160 lung cancers (114 adenocarcinomas, 36 squamous cell carcinomas, and 10 other cell types) were analyzed in this study. DWI and PET-CT were performed preoperatively.ResultsThe optimal cutoff values to diagnose metastatic lymph nodes were 1.70xa0×xa010−3xa0mm2/s for ADC value and 4.45 for SUVmax. DWI correctly diagnosed N staging in 144 carcinomas (90xa0%) but incorrectly diagnosed N staging in 16 (10xa0%) [3 (1.9xa0%) had overstaging, 13 (8.1xa0%) had understaging]. PET-CT correctly diagnosed N staging in 133 carcinomas (83.1xa0%) but incorrectly diagnosed N staging in 27 (16.8xa0%) [4 (2.5xa0%) had overstaging, 23 (14.4xa0%) had understaging]. Sensitivity, accuracy, and negative predictive value for N staging by DWI were significantly higher than those by PET-CT. Of the 705 lymph node stations examined, 61 had metastases, and 644 did not. The maximum diameter of metastatic lesions in lymph nodes were 3.0xa0±xa00.9xa0mm in 21 lymph node stations not detected by either DWI or PET-CT: 7.2xa0±xa04.1xa0mm in 39 detected by DWI, and 11.9xa0±xa04.1xa0mm in 24 detected by PET-CT. There were significant differences among them. The sensitivity (63.9xa0%) for metastatic lymph node stations by DWI was significantly higher than that (39.3xa0%) by PET-CT. The accuracy (96.2xa0%) for all lymph node stations by DWI was significantly higher than that (94.3xa0%) by PET-CT.ConclusionsDWI has advantages over PET-CT in diagnosing malignant from benign lymph nodes of lung cancers.

Comparative Immunohistochemical Analysis of IMP3, GLUT1, EMA, CD146, and Desmin for Distinguishing Malignant Mesothelioma From Reactive Mesothelial Cells

OBJECTIVESnTo identify useful biomarkers for differentiating between malignant mesothelioma (MM) and reactive mesothelial cells (RMCs).nnnMETHODSnFormalin-fixed, paraffin-embedded (FFPE) tissues from 34 MM and 40 RMC samples were analyzed using immunohistochemistry, and the findings were compared.nnnRESULTSnPositive markers for MM included insulin-like growth factor 2 messenger RNA binding protein 3 (IMP3), glucose transporter 1 (GLUT1), epithelial membrane antigen (EMA), and CD146, which showed sensitivities of 94%, 85%, 79%, and 71% and specificities of 78%, 100%, 88%, and 98%, respectively. In sarcomatoid MM, EMA had significantly lower expression than did IMP3, GLUT1, and CD146 (P < .001). The areas under receiver operating characteristic curves were the highest for IMP3 (0.95), followed by GLUT1 (0.93). When the optimal cutoff points for IMP3 (30%) and GLUT1 (10%) were used, the sensitivity of IMP3 and GLUT1 for MM was 100%, and the specificity of both for MM was 95%.nnnCONCLUSIONSnThe combination of IMP3 and GLUT1 is most appropriate for distinguishing MM from RMC using FFPE sections.

Relationships between EGFR mutation status of lung cancer and preoperative factors - are they predictive?

BACKGROUNDnThe epidermal growth factor receptor (EGFR) mutation status of lung cancer is important because it means that EGFR-tyrosine kinase inhibitor treatment is indicated. The purpose of this prospective study is to determine whether EGFR mutation status could be identified with reference to preoperative factors.nnnMATERIALS AND METHODSnOne hundred-forty eight patients with lung cancer (111 adenocarcinomas, 25 squamous cell carcinomas and 12 other cell types) were enrolled in this study. The EGFR mutation status of each lung cancer was analyzed postoperatively.nnnRESULTSnThere were 58 patients with mutant EGFR lung cancers (mutant LC) and 90 patients with wild-type EGFR lung cancers (wild-type LC). There were significant differences in gender, smoking status, maximum tumor diameter in chest CT, type of tumor shadow, clinical stage between mutant LC and wild-type LC. EGFR mutations were detected only in adenocarcinomas. Maximum standardized uptake value (SUVmax:3.66±4.53) in positron emission tomography-computed tomography of mutant LC was significantly lower than that (8.26±6.11) of wild-type LC (p<0.0001). Concerning type of tumor shadow, the percentage of mutant LC was 85.7% (6/7) in lung cancers with pure ground glass opacity (GGO), 65.3%(32/49) in lung cancers with mixed GGO and 21.7%(20/92) in lung cancers with solid shadow (p<0.0001). For the results of discriminant analysis, type of tumor shadow (p=0.00036) was most significantly associated with mutant EGFR. Tumor histology (p=0.0028), smoking status (p=0.0051) and maximum diameter of tumor shadow in chest CT (p=0.047) were also significantly associated with mutant EGFR. The accuracy for evaluating EGFR mutation status by discriminant analysis was 77.0% (114/148).nnnCONCLUSIONSnMutant EGFR is significantly associated with lung cancer with pure or mixed GGO, adenocarcinoma, never-smoker, smaller tumor diameter in chest CT. Preoperatively, EGFR mutation status can be identified correctly in about 77 % of lung cancers.

Diagnostic Performance of Diffusion Weighted Imaging of Malignant and Benign Pulmonary Nodules and Masses: Comparison with Positron Emission Tomography

BACKGROUNDnDiffusion-weighted imaging (DWI) makes it possible to detect malignant tumors based on the diffusion of water molecules. However, it is uncertain whether DWI has advantages over FDG-PET for distinguishing malignant from benign pulmonary nodules and masses.nnnMATERIALS AND METHODSnOne hundred- forty-three lung cancers, 17 metastatic lung tumors, and 29 benign pulmonary nodules and masses were assessed in this study. DWI and FDG-PET were performed.nnnRESULTSnThe apparent diffusion coefficient (ADC) value (1.27 ± 0.35 ?10-3 mm2/sec) of malignant pulmonary nodules and masses was significantly lower than that (1.66 ± 0.58 ?10-3 mm2/sec) of benign pulmonary nodules and masses. The maximum standardized uptake value (SUV max: 7.47 ± 6.10) of malignant pulmonary nodules and masses were also significantly higher than that (3.89 ± 4.04) of benign nodules and masses. By using optimal cutoff values for ADC (1.44?10-3 mm2/sec) and for SUV max (3.43), which were determined with receiver operating characteristics curves (ROC curves), the sensitivity (80.0%) of DWI was significantly higher than that (70.0%) of FDG-PET. The specificity (65.5%) of DWI was equal to that (65.5%) of FDG-PET. The accuracy (77.8%) of DWI was not significantly higher than that (69.3%) of FDG- PET for pulmonary nodules and masses. As the percentage of bronchioloalveolar carcinoma (BAC) component in adenocarcinoma increased, the sensitivity of FDG-PET decreased. DWI could not help in the diagnosis of mucinous adenocarcinomas as malignant, and FDG-PET could help in the correct diagnosis of 5 out of 6 mucinous adenocarcinomas as malignant.nnnCONCLUSIONSnDWI has higher potential than PET in assessing pulmonary nodules and masses. Both diagnostic approaches have their specific strengths and weaknesses which are determined by the underlying pathology of pulmonary nodules and masses.

Diagnostic Performance of Diffusion-Weighted Imaging for Multiple Hilar and Mediastinal Lymph Nodes with FDG Accumulation.

BACKGROUNDnIt is sometimes difficult to assess patients who have multiple hilar and mediastinal lymph nodes (MHMLN) with FDG accumulation in PET-CT. Since it is uncertain whether diffusion-weighted magnetic resonance imaging (DWI) is useful in the assessment of such patients, its diagnostic performance was assessed.nnnMATERIALS AND METHODSnTwenty-three patients who had three or more stations of hilar and mediastinal lymph nodes with SUVmax of 3 or more in PET-CT were included in this study.nnnRESULTSnFor diagnosis of disease, there were 20 malignancies (lung cancers 17, malignant lymphomas 2 and metastatic lung tumor 1), and 3 benign cases (sarcoidosis 2 and benign disease 1). For diagnosis of lymph nodes, there were 7 malignancies (metastasis of lung cancer 7 and malignant lymphoma 1) and 16 benign lymphadenopathies (pneumoconiosis/silicosis 7, sarcoidosis 4, benign disease 4, and atypical lymphocyte infiltration 1). The ADC value (1.57±0.29x10(-3) mm2/sec) of malignant MHMLN was significantly lower than that (1.99±0.24x10(-3) mm2/sec) of benign MHMLN (P=0.0437). However, the SUVmax was not significantly higher (10.0±7.34 as compared to 6.38±4.31) (P=0.15). The sensitivity (86%) by PET-CT was not significantly higher than that (71%) by DWI for malignant MHMLN (P=1.0). The specificity (100%) by DWI was significantly higher than that (31%) for benign MHMLN (P=0.0098). Furthermore, the accuracy (91%) with DWI was significantly higher than that (48%) with PET-CT for MHMLN (P=0.0129).nnnCONCLUSIONSnEvaluation by DWI for patients with MHMLN with FDG accumulation is useful for distinguishing benign from malignant conditions.

Diffusion-weighted imaging (DWI) signal intensity and distribution represent the amount of cancer cells and their distribution in primary lung cancer

The aim of this study was to interpret diffusion-weighted imaging (DWI) signals in lung cancers. They were converted into several three-dimensional DWI signals patterns, which represent the degree of DWI signal intensity by height and the degree of distribution by area: flat, low elevation, irregular elevation, single-peak elevation, multiple-peak elevation, and nodular elevation. There were 39 adenocarcinomas and 21 squamous cell carcinomas. Three-dimensional DWI signals decreased significantly in order of cell differentiation. Tumor cellular densities were increased according to the increase in three-dimensional DWI signals. DWI signal intensity and distribution can represent the amount of cancer cells and their distribution in the carcinoma.

A phantom study investigating the relationship between ground‐glass opacity visibility and physical detectability index in low‐dose chest computed tomography

In this study, the relationship between ground‐glass opacity (GGO) visibility and physical detectability index in low‐dose computed tomography (LDCT) for lung cancer screening was investigated. An anthropomorphic chest phantom that included synthetic GGOs with CT numbers of ‐630 Hounsfield units (HU; high attenuation GGO: HGGO) and ‐800 HU (low attenuation GGO: LGGO), and three phantoms for physical measurements were employed. The phantoms were scanned using 12 CT systems located in 11 screening centers in Japan. The slice thicknesses and CT dose indices (CTDIvol) varied over 1.0–5.0 mm and 0.85–3.30 mGy, respectively, and several reconstruction kernels were used. Physical detectability index values were calculated from measurements of resolution, noise, and slice thickness properties for all image sets. Five radiologists and one thoracic surgeon, blind to one anothers observations, evaluated GGO visibility using a five‐point scoring system. The physical detectability index correlated reasonably well with the GGO visibility (R2=0.709,p<0.01 for 6 mm HGGO and R2=0.646,p<0.01 for 10 mm LGGO), and was nearly proportional to the CTDIvol. Consequently, the CTDIvol also correlated reasonably well with the GGO visibility (R2=0.701,p<0.01 for 6 mm HGGO and R2=0.680,p<0.01 for 10 mm LGGO). As a result, the CTDIvol was nearly dominant in the GGO visibility for image sets with different reconstruction kernels and slice thicknesses, used in this study. PACS numbers: 81.70.Tx, 87.57.Q‐In this study, the relationship between ground-glass opacity (GGO) visibility and physical detectability index in low-dose computed tomography (LDCT) for lung cancer screening was investigated. An anthropomorphic chest phantom that included synthetic GGOs with CT numbers of -630 Hounsfield units (HU; high attenuation GGO: HGGO) and -800 HU (low attenuation GGO: LGGO), and three phantoms for physical measurements were employed. The phantoms were scanned using 12 CT systems located in 11 screening centers in Japan. The slice thicknesses and CT dose indices (CTDIvol) varied over 1.0-5.0 mm and 0.85-3.30 mGy, respectively, and several reconstruction kernels were used. Physical detectability index values were calculated from measurements of resolution, noise, and slice thickness properties for all image sets. Five radiologists and one thoracic surgeon, blind to one anothers observations, evaluated GGO visibility using a five-point scoring system. The physical detectability index correlated reasonably well with the GGO visibility (R2=0.709,p<0.01 for 6 mm HGGO and R2=0.646,p<0.01 for 10 mm LGGO), and was nearly proportional to the CTDIvol . Consequently, the CTDIvol also correlated reasonably well with the GGO visibility (R2=0.701,p<0.01 for 6 mm HGGO and R2=0.680,p<0.01 for 10 mm LGGO). As a result, the CTDIvol was nearly dominant in the GGO visibility for image sets with different reconstruction kernels and slice thicknesses, used in this study. PACS numbers: 81.70.Tx, 87.57.Q.

Thymic lymphoid hyperplasia with multilocular thymic cysts diagnosed before the Sjögren syndrome diagnosis

BackgroundThymic lymphoid hyperplasia is often present with myasthenia gravis as well as other autoimmune diseases such as systemic lupus erythematosus and rheumatoid arthritis. Of the 4 cases of thymic lymphoid hyperplasia associated with Sjögren syndrome that have been reported, no case with a thymic lesion diagnosis that led to the diagnosis of Sjögren syndrome has been reported. We herein report a case of thymic lymphoid hyperplasia with multilocular thymic cysts, diagnosed before Sjögren syndrome.Case presentationA 37-year-old Japanese woman had an approximate 5-cm anterior mediastinal mass detected by chest imaging. The resected lesion revealed multilocular thymic cysts that were filled with colloid-like material. Histology showed lymph follicular hyperplasia with many epithelial cysts. The epithelium consisted of thymic medullary epithelium, and no epithelial proliferation was seen in the lymphoid tissue. Lymphocytes were composed of an organized mixed population of mature T and B cells without significant atypia. The infiltrated B cells did not reveal light chain restriction or immunoglobulin heavy chain gene rearrangement. After the pathological diagnosis of thymic lesion, tests for the presence of autoantibodies were positive for antinuclear antibodies, rheumatic factor, and anti-SSA/Ro antibodies. The Schirmer’s, chewing gum, and Saxon tests showed decreased salivary and lacrimal secretion. Lip biopsy showed focal lymphocytic sialadenitis. The signs and symptoms of Sjögren syndrome had not resolved, without aggravation, 1xa0year after the thymectomy.ConclusionWhen a case with thymic lymphoid hyperplasia without myasthenia gravis is encountered, it is essential to consider the presence of another autoimmune disease including Sjögren syndrome.