Naofumi Hayabuchi

Lung adenocarcinoma with mixed bronchioloalveolar and invasive components: clinicopathological features, subclassification by extent of invasive foci, and immunohistochemical characterization.

A significant proportion of small lung adenocarcinomas consists of two components: bronchioloalveolar carcinoma (BAC) and invasive carcinoma. The purpose of this study was to compare their clinicopathologic features with those of BAC and those of invasive cancer without BAC, and to define “early invasive” lesions based on the extent of invasive foci. We reviewed 484 lesions of resected lung adenocarcinoma and classified them into three groups according to tumor growth pattern: group 1 (n = 102, BAC), group 2 (n = 216, adenocarcinoma consisting of BAC and invasive carcinoma), and group 3 (n = 166, invasive adenocarcinoma without BAC component). Group 2 was further subdivided according to the extent of the invasive area: group 2a (n = 54), BAC with invasive foci ≤5 mm; group 2b (n = 162), BAC with invasive foci >5 mm. These groups were compared with regard to their clinicopathologic features, expression of Ki-67 and p53, and expression of laminin-5, a putative marker for tumor invasion. The positivity rates of vascular, lymphatic, and pleural invasion in each group were as follows: 0%, 0%, and 0% in group 1; 5.5%, 14.8%, and 1.9% in group 2a; 45.7%, 41.4%, and 25.9% in group 2b; and 84.9%, 61.4%, and 60.8% in group 3. Notably, no lymph node metastasis occurred in either group 2a or group 1, but it was observed in 24.1% of group 2b and 47.0% of group 3. The mean Ki-67 labeling index, the frequency of p53 overexpression, and the frequency of laminin-5 overexpression increased from group 1 (11%, 4%, and 0%) to group 2a (16%, 20%, and 7%) to group 2b (24%, 41%, and 23%) to group 3 (35%, 38%, and 38%). In contrast, no clear differences were observed when lesions were subdivided according to size. Based on the distribution pattern of Ki-67-positive tumor cells, lesions were classified into two groups: marginal type (63%) and nonmarginal type (37%). The latter showed a significantly higher labeling index than the former. Moreover, the proportion of the marginal type clearly decreased from group 1 (85%) and group 2a (87%) to group 2b (55%) to group 3 (19%). Group 2 lesions showed characteristics intermediate between the BAC and invasive adenocarcinoma. According to the extent of the invasive area, we were able to define a subgroup of mixed-type adenocarcinomas (group 2a) that could be regarded as early invasive cancer because they showed low rates of vascular, lymphatic, and pleural invasion, and no nodal involvement.

Optimum Treatment Strategy for Superficial Esophageal Cancer: Endoscopic Mucosal Resection versus Radical Esophagectomy

This study was designed to determine the optimum treatment for a superficial esophageal cancer involving the mucosal or submucosal layer of the esophagus. The subjects were 150 patients with a superficial esophageal cancer who underwent endoscopic mucosal resection (EMR) or esophagectomy in Kurume University Hospital from 1981 to 1997. The mortality and morbidity rates, survival rate, and recurrence rate were retrospectively compared for (1) 35 patients who underwent EMR and 37 patients who underwent esophagectomy for a mucosal esophageal cancer and (2) 45 patients who underwent extended radical esophagectomy and 33 patients who underwent less radical esophagectomy for a submucosal esophageal cancer. Among the 72 patients with a mucosal cancer, lymph node metastasis/recurrence was observed in only one (1%); whereas of 78 patients with a submucosal cancer it was observed in 30 (38%). Among patients with a mucosal cancer the mortality and morbidity rates after EMR were lower than for those after esophagectomy. The survival rate after EMR was the same as that after esophagectomy. No recurrence was observed after either treatment modality. Among the patients with a submucosal cancer, the survival rate was higher and the recurrence rate lower after extended radical esophagectomy; than after less radical esophagectomy; the mortality and morbidity rates after extended radical esophagectomy were the same as those after less radical esophagectomy. Multivariate analysis demonstrated that the treatment modality (EMR versus esophagectomy) did not influence the survival of patients with a mucosal esophageal cancer, whereas it strongly influenced the survival of patients with a submucosal esophageal cancer. We concluded that EMR was the mainstay of treatment for a mucosal esophageal cancer, and extended radical esophagectomy was the mainstay of treatment for a submucosal esophageal cancer.

Lung Cyst Formation in Lymphocytic Interstitial Pneumonia: Ct Features

Objective We performed this study to identify and characterize the CT findings of lymphocytic interstitial pneumonia (LIP). Materials and Methods The CT findings of two patients with LIP were reviewed and correlated with their histologic specimens. Results Chest CT of the two patients showed areas of increased attenuation in both lung fields which were associated with nodular and cystic lesions surrounding the peribronchovascular bundles. The most characteristic abnormality identified on CT was the presence of multiple cysts throughout both lungs. Macroscopic findings of lung biopsy specimens included multiple nodular and cystic lesions. Conclusion This description of multiple pulmonary cysts formation in LIP is new.

Heterogeneous myocardial FDG uptake and the disease activity in cardiac sarcoidosis.

OBJECTIVES This study evaluated the usefulness of fasting (18)F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) in the diagnosis and management of cardiac sarcoidosis (CS) and compared it with FDG uptake in dilated cardiomyopathy (DCM). BACKGROUND Cardiac sarcoidosis may clinically present as DCM but is amenable to systemic corticosteroid therapy if disease activity is high. Although alterations of FDG uptake have been reported in CS, limited information is available on the quantitative estimates of FDG uptake. METHODS Fasting FDG-PET was performed in 24 systemic sarcoidosis patients and was compared with 8 age-matched DCM patients. FDG-PET was also performed in 15 age-matched healthy control subjects. Twelve of the 24 sarcoidosis patients had cardiac involvement based on criteria established by the Japanese Ministry of Health and Welfare; the remaining 12 of 24 patients revealed no evidence of cardiac involvement. The myocardial FDG uptake was quantified by measuring the standardized uptake value in 17 myocardial segments in each subject. Coefficient of variation (COV), which equals the standard deviation of uptake divided by the average uptake of 17 segments, was calculated as an index of heterogeneity in the heart. RESULTS The FDG uptake was distinctly heterogeneous in CS patients. The COV value was significantly greater in CS patients (0.25 ± 0.05) than control subjects (0.14 ± 0.03, p < 0.01), sarcoidosis patients without cardiac involvement (0.14 ± 0.03, p < 0.01), or DCM patients (0.15 ± 0.02, p < 0.01). The COV value in DCM patients was similar to control subjects or sarcoidosis patients without cardiac involvement. The cutoff COV value for the diagnosis of CS was 0.18 (sensitivity: 100%; specificity: 97%). After corticosteroid therapy in CS patients, the COV value was decreased to 0.14 ± 0.06 (p < 0.05) and became essentially similar to the other groups. CONCLUSIONS Heterogeneous myocardial FDG uptake may be a useful diagnostic marker of disease activity for CS.

Intrahepatic peripheral cholangiocarcinoma : Comparison of dynamic CT and dynamic MRI

PURPOSE The purpose of this work was to compare dynamic MRI (D-MRI) with dynamic CT (D-CT) for the diagnosis of peripheral cholangiocarcinoma (PCC) of the liver. METHOD Twenty patients with PCC underwent both D-CT and D-MRI during the early, middle, and delayed phase after contrast medium administration. The findings from D-MRI were compared with those from D-CT. RESULTS D-CT and D-MRI exhibited a similar tumoral enhancement pattern, and this enhancement was more conspicuous on D-MRI. A wedge-like enhancement area peripheral to the tumor was observed in 9 (45%) patients on D-CT and 11 (55%) patients on D-MRI. Ductal dilatation was found in 13 (65%) patients on both techniques. Vascular involvement and extrahepatic invasion were seen in nine (45%) and two (10%) patients, respectively. The relationship of the tumor to the vessels and surrounding organs was more easily evaluated on D-CT. CONCLUSION Both D-CT and D-MRI can provide important information for the diagnosis of PCC. D-CT is better than D-MRI for demonstrating vascular involvement and extrahepatic invasion. D-MRI gives more conspicuous enhancement.

Pioglitazone Attenuates Atherosclerotic Plaque Inflammation in Patients With Impaired Glucose Tolerance or Diabetes: A Prospective, Randomized, Comparator-Controlled Study Using Serial FDG PET/CT Imaging Study of Carotid Artery and Ascending Aorta

OBJECTIVES The aim of this study was to compare the effect of pioglitazone, an insulin sensitizer, with glimepiride, an insulin secretagogue, on atherosclerotic plaque inflammation by using serial (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) imaging. BACKGROUND Atherosclerosis is intrinsically an inflammatory disease. Although hyperglycemia is associated with an increased risk of atherosclerotic cardiovascular disease, there are no clinical data to show the preference of any specific oral hypoglycemic agents to prevent atherosclerotic plaque inflammation. METHODS A total of 56 impaired glucose tolerant or diabetic patients with carotid atherosclerosis underwent a complete history, determinations of blood chemistries, anthropometric variables, and FDG-PET. They were randomly assigned to receive either pioglitazone (15 to 30 mg) or glimepiride (0.5 to 4.0 mg) for 4 months with titration to optimal dosage. Effects of the drugs on atherosclerotic plaque inflammation were evaluated by FDG-PET at study completion. Plaque inflammation was measured by blood-normalized standardized uptake value, known as a target-to-background ratio. RESULTS The study was completed in 31 pioglitazone-treated patients and 21 glimepiride-treated patients. Although both treatments reduced fasting plasma glucose and hemoglobin A1c values comparably, pioglitazone, but not glimepiride, decreased atherosclerotic plaque inflammation. Compared with glimepiride, pioglitazone significantly increased high-density lipoprotein cholesterol level. High-sensitivity C-reactive protein was decreased by pioglitazone, whereas it was increased by glimepiride. Multiple stepwise regression analysis revealed that the increase in high-density lipoprotein cholesterol level was independently associated with the attenuation of plaque inflammation. CONCLUSIONS Our present study suggests that pioglitazone could attenuate atherosclerotic plaque inflammation in patients with impaired glucose tolerance or in diabetic patients independent of glucose lowering effect. Pioglitazone may be a promising strategy for the treatment of atherosclerotic plaque inflammation in impaired glucose tolerance or diabetic patients. (Detection of Plaque Inflammation and Visualization of Anti-Inflammatory Effects of Pioglitazone on Plaque Inflammation in Subjects With Impaired Glucose Tolerance and Type 2 Diabetes Mellitus by FDG-PET/CT; NCT00722631).

Diffusion-weighted imaging of soft tissue tumors: usefulness of the apparent diffusion coefficient for differential diagnosis.

PurposeWe evaluated the efficacy of using the apparent diffusion coefficient (ADC) to differentiate soft tissue tumors.Materials and methodsWe examined 88 histologically proven tumors (44 benign, 8 intermediate, 36 malignant) using diffusion-weighted magnetic resonance images. Images of the tumors were obtained using a single-shot, spin-echo type echo-planar imaging sequence. The tumors were classified histologically as myxoid or nonmyxoid. We then compared the ADC values of the myxoid and nonmyxoid tumors; the benign and malignant myxoid tumors; and the benign, intermediate, and malignant nonmyxoid tumors.ResultsThe mean ADC value of the myxoid tumors (2.08 ± 0.51 × 10−3 mm2/s) was significantly greater than that of the nonmyxoid tumors (1.13 ± 0.40 × 10−3 mm2/s) (P < 0.001). There was no significant difference in the mean ADC values between benign myxoid tumors (2.10 ± 0.50 × 10−3 mm2/s) and malignant myxoid tumors (2.05 ± 0.58 × 10−3 mm2/s). The mean ADC value of benign nonmyxoid tumors (1.31 ± 0.46 × 10−3 mm2/s) was significantly higher than that of malignant nonmyxoid tumors (0.94 ± 0.25 × 10−3 mm2/s) (P < 0.001).ConclusionThe ADC value might be useful for diagnosing the malignancy of nonmyxoid soft tissue tumors.

Dynamic MRI of Solitary Pulmonary Nodules: Comparison of Enhancement Patterns of Malignant and Benign Small Peripheral Lung Lesions

OBJECTIVE The purpose of this study was to compare the dynamic contrast-enhanced MRI enhancement characteristics of malignant and benign solitary pulmonary nodules. MATERIALS AND METHODS The characteristics of 202 solitary pulmonary nodules (diameter, 1-3 cm; 144 cases of primary lung cancer, 31 cases of focal organizing pneumonia, 15 tuberculomas, 12 hamartomas) were reviewed retrospectively. In all cases dynamic MR images were obtained before and 1, 2, 3, 4, 5, 6, and 8 minutes after bolus injection of gadopentetate dimeglumine. Maximum enhancement ratio, time at maximum enhancement ratio, slope of time-enhancement ratio curves, and washout ratio were assessed. Statistical analyses were performed with the Kruskal-Wallis test with Bonferroni correction, chi-square test, and receiver operating characteristic curves. RESULTS For 122 (85%) of 144 primary lung cancers, time at maximum enhancement ratio was 4 minutes or less. For all tuberculomas and hamartomas, time at maximum enhancement ratio was greater than 4 minutes or gradual enhancement occurred without a peak time (p < 0.0001). Lung cancers had different maximum enhancement ratios and slopes than benign lesions (all p < 0.005). With 110% or lower maximum enhancement ratio as a cutoff value, the positive predictive value for malignancy was 92%; sensitivity, 63%; and specificity, 74%. With 13.5%/min or greater slope as a cutoff value, sensitivity, specificity, positive predictive value, and negative predictive value for malignancy were 94%, 96%, 99%, and 74%, respectively. CONCLUSION Dynamic contrast-enhanced MRI is helpful in differentiating benign from malignant solitary pulmonary nodules. Absence of significant enhancement is a strong predictor that a lesion is benign.

Primary central nervous system lymphoma in Japan: a nationwide survey.

PURPOSE To analyze clinical features, treatment results, and prognostic factors of primary central nervous system lymphoma (PCNSL) in Japan, we conducted a nationwide survey. METHODS AND MATERIALS We analyzed 466 patients with histologically proven PCNSL treated between 1985 and 1994 at 62 institutions, including 56 medical schools. RESULTS Patient and tumor characteristics of the 466 patients were not greatly different from those reported previously, except for the relatively high proportion of T-cell lymphoma (8.5%). The median survival time of the 466 patients was 18 months, and the 5- and 10-year survival rates were 15.2% and 8.2%, respectively. Complete response was observed in 63% of evaluable patients, but 64% of the complete responders developed recurrence (77% within the irradiated volume). Among patient- or tumor-related factors, higher age, worse performance status, presence of B symptom, multiple lesions, presence of meningeal dissemination, and elevated lactate dehydrogenase (LDH) level were associated with poorer survival, whereas no significant difference was observed in prognosis with respect to sex, T/B phenotype, or histological subclassification. In 410 patients receiving at least 40 Gy to the tumor, there was no difference in survival with respect to total radiation dose or field. Patients receiving 2 or more cycles of systemic chemotherapy had a slightly longer median survival time (22 months) and higher 5-year survival rate (20%) than those receiving radiotherapy alone (18 months and 17%, respectively), but the difference was not significant (p = 0.13). No chemotherapy protocol appeared to be better than any other. CONCLUSIONS In addition to age and performance status, which are well-known prognostic factors, B symptom, tumor number, presence of meningeal dissemination, and serum LDH level also seemed to influence survival. Higher radiation dose was not associated with better prognosis. The role of chemotherapy could not be clarified because of the use of various protocols, but it seemed that the influence of various prognostic factors is greater than the effect of chemotherapy.

Evaluation of the mean and entropy of apparent diffusion coefficient values in chronic hepatitis C: Correlation with pathologic fibrosis stage and inflammatory activity grade

PURPOSE To determine whether mean and entropy apparent diffusion coefficient (ADC) values obtained at diffusion-weighted (DW) magnetic resonance (MR) imaging can help detect and stage histopathologic liver fibrosis and grade inflammation activity in patients with chronic hepatitis C. MATERIALS AND METHODS This retrospective study was approved by the institutional review board, and the requirement for informed consent was waived. The study included 55 patients with focal hepatic lesions and either chronic hepatitis C (n = 43) or normal hepatic function (control subjects) (n = 12). Mean and entropy of volume histograms were generated in four cubic regions of interest placed in the right hepatic lobe of ADC map images, which were obtained at echo-planar DW MR imaging (gradient factor b values of 0 and 1000 sec/mm(2)). These two parameters (mean and entropy ADC) were compared by using METAVIR histopathologic liver fibrosis and inflammatory activity scores. Statistical analysis was performed with the Kruskal-Wallis test and receiver operating characteristic curves. RESULTS The mean ADC decreased with an increase in the fibrosis stage or inflammatory activity grade, and the entropy ADC increased with an increase in the fibrosis stage or inflammatory activity grade (P < .001 for all comparisons, Kruskal-Wallis test). The area under the receiver operating characteristic curve (A(z)) for the mean ADC was statistically significant in the differentiation of fibrosis stage or inflammatory activity grade (A(z), 0.807-0.926; P < .001 for all comparisons). Entropy of ADC was helpful for classifying normal from abnormal fibrosis stage or inflammatory activity grade (A(z) for both parameters, 0.937; P < .001). CONCLUSION Assessment of a combination of mean ADC and entropy ADC in patients with chronic hepatitis C is more accurate for predicting pathologic hepatic fibrosis stage and inflammatory activity grade and helpful for detecting early fibrotic or inflammatory activity when compared with assessment of mean ADC alone.