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Although hematological toxicities (HT) are the leading adverse events of systemic chemotherapy, the estimation of severe HT is challenging. Recently, 3′-deoxy-3′-[18F]-fluorothymidine (18F-FLT) accumulation with PET has been considered a biomarker of the cell proliferation. This study aims to elucidate whether the vertebral accumulation of 18F-FLT could estimate severe HT during platinum-doublet chemotherapy. In this Institutional Review Board–approved retrospective study, 50 patients with primary lung cancer underwent 18F-FLT PET scan before platinum-doublet chemotherapy. We evaluated the standardized uptake value, total vertebral proliferation (TVP), and TVP/body surface area (TVP/BSA) of the vertebral body (Th4, Th8, Th12, and L4), and then the associations between those parameters and frequency of severe HT during platinum-doublet chemotherapy were assessed. Severe HT (grade 3/4) was observed in 40.0% of patients during the first cycle. The ROC curve analyses revealed that the TVP/BSA of L4 was the most discriminative parameter among PET parameters for the prediction of severe HT. The multivariate logistic regression analysis revealed the TVP/BSA of L4 (odds ratio [OR], 0.94; p = 0.0036) and the frequency of the grade 3/4 hematological toxicity in previous clinical trials (OR, 1.03; p = 0.023) were independent predictors. Furthermore, the sensitivity, specificity, and accuracy of the TVP/BSA of L4 cut-off of 68.7 to predict grade 3/4 HT were 80.0%, 86.7%, and 84.0%, respectively. A low TVP/BSA of L4 (

BackgroundThe early response to treatment with immune-checkpoint inhibitors is difficult to evaluate. We determined whether changes in integrated [18F]-fluoro-2-deoxy-D-glucose positron emission tomography/MRI (18F-FDG PET/MRI) parameters after the first 2 weeks of antiprogrammed death-1 antibody nivolumab therapy could predict the response of patients with non-small cell lung cancer (NSCLC).MethodsTwenty-five patients with previously treated NSCLC were enrolled prospectively and underwent18F-FDG PET/MRI before and at 2 weeks after nivolumab therapy. Changes in maximal standardized uptake value, total lesion glycolysis (ΔTLG) and apparent diffusion coefficient (ΔADC) between the two scans were calculated and evaluated for their associations with the clinical response to therapy.ResultsThe disease control rate was 64%. Patients with non-progressive disease (non-PD) had significantly decreased TLG, increased ADCmean(ie, negative ΔADCmean) and lower ΔTLG+ΔADCmeanthan patients with PD. Among the parameters tested, receiver operating characteristic curve analysis revealed that a cut-off value of 16.5 for ΔTLG+ΔADCmeanhad the highest accuracy (92%) for distinguishing between patients with non-PD and PD. A ΔTLG+ΔADCmeanvalue meanvalue ≥16.5. A multivariate Cox model revealed that ≥16.5 ΔTLG+ΔADCmeanwas an independent predictor of shorter progression-free survival (HR 37.7) and overall survival (HR 9.29).ConclusionsA combination of ΔTLG and ΔADCmeanmeasured by integrated18F-FDG PET/MRI may have value as a predictor of the response and survival of patients with NSCLC following nivolumab therapy.Trial registration numberUMIN 000020707.

Although hematological toxicities (HT) are the leading adverse events of systemic chemotherapy, the estimation of severe HT is challenging. Recently, 3'-deoxy-3'-[In this Institutional Review Board-approved retrospective study, 50 patients with primary lung cancer underwentSevere HT (grade 3/4) was observed in 40.0% of patients during the first cycle. The ROC curve analyses revealed that the TVP/BSA of L4 was the most discriminative parameter among PET parameters for the prediction of severe HT. The multivariate logistic regression analysis revealed the TVP/BSA of L4 (odds ratio [OR], 0.94; p = 0.0036) and the frequency of the grade 3/4 hematological toxicity in previous clinical trials (OR, 1.03; p = 0.023) were independent predictors. Furthermore, the sensitivity, specificity, and accuracy of the TVP/BSA of L4 cut-off of 68.7 to predict grade 3/4 HT were 80.0%, 86.7%, and 84.0%, respectively. A low TVP/BSA of L4 ( 68.7) as a binary variable was a significant indicator of severe HT (OR, 26.0; p = 0.000026).The lowTrial registration: UMIN000027540 KEY POINTS: • The vertebral

A 62-year-old man was admitted to our hospital because of wheezing and dyspnea. Chest computed tomography showed ground-glass opacity and some centrilobular nodules. Chronic eosinophilic pneumonia complicated with Mycoplasma pneumoniae infection was diagnosed on the basis of bronchoalveolar lavage eosinophilia and blood findings. However, based on the clinical course, the patient was suspected to have eosinophilic bronchiolitis. This case suggests the possibility that eosinophilic inflammation can occur concomitantly in the central airway and distal airway.

The present study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced non-small cell lung cancer who responded well to initial gefitinib, followed by cytotoxic chemotherapy. Twenty subjects were enrolled, and 3 and 6 patients achieved partial response and stable disease, respectively. These findings provide valuable information for the management of previous gefitinib responders. Introduction: Salvage treatment for acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitor in patients with non-small-cell lung cancer is a matter of clinical concern. Several retrospective reports have indicated the usefulness of epidermal growth factor receptor tyrosine kinase inhibitor readministration; however, there have been few prospective studies. Materials and Methods: This study was designed to prospectively evaluate the clinical efficacy of gefitinib readministration in patients with advanced or metastatic non-small-cell lung cancer who responded well to initial gefitinib treatment. The subjects received at least 1 regimen of cytotoxic chemotherapy after progressive disease with the initial gefitinib therapy. Gefitinib administration (250 mg/d, orally) was started after progressive disease with the previous chemotherapeutic regimen. The primary endpoint in the present study was the response rate. Results: Twenty patients were enrolled between April 2007 and May 2011. Three patients achieved partial response, and 6 showed stable disease. Thus, the overall response rate and disease control rate of gefitinib readministration were 15% (95% Cl, 3.21-37.9) and 45% (95% Cl, 23.1-68.5), respectively. Median progression-free survival and overall survival from the start of gefitinib readministration were 2.0 months (95% Cl, 0.9-3.1 months) and 12.0 months (95% Cl, 8.0-16.0 months), respectively. Conclusion: These results suggest that gefitinib readministration may be an option, albeit with a low response rate and short progression-free survival, for patients who responded well to initial gefitinib followed by systemic chemotherapy. These findings provide valuable information for the management of previous gefitinib responders., Article, CLINICAL LUNG CANCER. 13(6):458-463 (2012)

Efficacy of first-line gefitinib for elderly epidermal growth factor receptor mutated patients with lung adenocarcinoma is uncertain. This study was aimed to investigate efficacy of gefitinib for such population. The primary endpoint was response rate (RR) and at least 12 cases were needed. Overall RR was 59% (95% confidence interval, 33%-81%) and first-line gefitinib was effective for elderly patients.Feasibility of gefitinib therapy in elderly patients with non-small-cell lung cancer is uncertain. This phase II study aimed to investigate the efficacy and usefulness of gefitinib therapy as a first-line treatment for elderly patients who have advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) mutations.We enrolled chemotherapy-naïve advanced lung adenocarcinoma patients aged 75 years or older. Patients were administered gefitinib (250 mg) once daily until progression or unacceptable toxicity. The primary endpoint was response rate (RR), and secondary endpoints were disease control rate (DCR; defined as complete response [CR] plus partial response [PR] plus stable disease [SD]), progression-free survival (PFS), overall survival (OS), and toxicity profile.Between April 2008 and November 2009, 17 lung adenocarcinoma patients were enrolled. Overall RR was 59% (95% confidence interval [CI]: 33% to 81%), with 2 patients achieving CR and 8 PR. SD was noted in 5 patients, and DCR was 88% (95% CI: 62% to 98%). Median PFS was 12.9 months (95% CI: 2.2 to 23.6 months), and median OS had not yet been reached. Major grade 3 toxicities were skin rash (12%) and increased levels of aspartate aminotransferase or alanine aminotransferase (18%).First-line treatment with gefitinib was effective and well-tolerated in elderly patients with EGFR mutations.

Background and objective: The value of dual-time- point 18F-FDG PET was investigated to predict the prognosis of patients with pulmonary sarcoidosis. Methods: Twenty-one patients with pulmonary sarcoidosis underwent 18F-FDG PET examinations at two time points: an early scan at 60 min and a delayed scan at 180 min after injection of 18F-FDG. Standardized uptake values (SUVs) at the two time points and the retention index (RI-SUV) calculated from these were evaluated. To evaluate disease progression, all patients underwent chest CT 1 year after 18F-FDG PET. Using these results, the accuracy of 18F-FDG PET parameters and 67Ga uptake for predicting disease persistence were compared, and the correlations between those parameters and serum markers were assessed. Results: RI-SUV was significantly higher in patients with increased or unchanged pulmonary lesions at follow-up CT (persistent group; 21.3 ± 9.6%) than in patients with improved pulmonary lesions (improved group; −9.2 ± 28.6%, P = 0.0075). The diagnostic accuracy of RI-SUV in the persistent group was significantly greater than that of early SUV or 67Ga uptake, and serum soluble IL-2 receptor showed a significant correlation with RI-SUV. Conclusions: RI-SUV showed better diagnostic accuracy compared with early SUV or 67Ga uptake, in patients with persistent lung involvement at 1 year. It may be a useful measure of persistent inflammation in patients with pulmonary sarcoidosis.

We report a case of acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) after pandemic influenza (H1N1) vaccination. A 57-year-old man, who had been diagnosed with IPF in September 2008, was admitted to our hospital in December 2009 because of aggravation of dyspnea and fever two days after H1N1 vaccination. Chest computed tomography showed diffuse bilateral ground-glass opacities superimposed on preceding reticular opacities. We diagnosed AE-IPF. Corticosteroid and cyclophosphamide were effective. Although the efficacy of influenza vaccination in patients with chronic lung diseases is well established, physicians should keep in mind that influenza vaccination has the potential to cause AE-IPF.

Background: Nanoparticle albumin-bound paclitaxel (nab-PTX), which avoids toxicities associated with a vehicle used in solvent-based PTX, has already shown safety and efficacy in patients with non-small cell lung cancer (NSCLC). Methods: A phase II study was performed to assess the safety and efficacy of nab-PTX monotherapy as second-line chemotherapy after cytotoxic anticancer drugs for previously treated advanced NSCLC. Thirty-two patients with advanced NSCLC who had previously undergone 1 regimen of cytotoxic anticancer drugs were enrolled. Nab-PTX was administered intravenously at a dose of 100 mg/m2 on days 1, 8, and 15 of a 28-day cycle. The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and toxicity profile were evaluated. Results: The ORR was 28.1%, the DCR was 71.9%, median PFS was 3.9 months (95% confidence interval [CI] 2.7–5.1 months), and median OS was 10.9 months (95% CI 9.5–12.3 months). The mean relative dose intensity of nab-PTX was 77%. Grade 3 or 4 neutropenia, and grade 3 febrile neutropenia were observed in 11 and 1 of 32 patients, respectively. As nonhematologic toxicities, grade 3 peripheral sensory neuropathy and pneumonitis were each observed in 2 of 32 patients. Conclusion: Nab-PTX is an active and well-tolerated regimen in patients with previously treated NSCLC.

Individual clinical courses of idiopathic interstitial pneumonia (IIP) are variable and difficult to predict because the pathology and disease activity are contingent, and chest computed tomography (CT) provides little information about disease activity. In this study, we applied dual-time-point [(18)F]-fluoro-2-deoxy-D-glucose ((18)F-FDG) positron emission tomography (PET), commonly used for diagnosis of malignant tumours, to the differential diagnosis and prediction of disease progression in IIP patients.Fifty patients with IIP, including idiopathic pulmonary fibrosis (IPF, n = 21), non-specific interstitial pneumonia (NSIP, n = 18) and cryptogenic organizing pneumonia (COP, n = 11), underwent (18)F-FDG PET examinations at two time points: scan 1 at 60 min (early imaging) and scan 2 at 180 min (delayed imaging) after (18)F-FDG injection. The standardized uptake values (SUV) at the two points and the retention index (RI-SUV) calculated from them were evaluated and compared with chest CT findings, disease progression and disease types. To evaluate short-term disease progression, all patients were examined by pulmonary function test every 3 months for 1 year after (18)F-FDG PET scanning.The early SUV for COP (2.47 +/- 0.74) was significantly higher than that for IPF (0.99 +/- 0.29, p = 0.0002) or NSIP (1.22 +/- 0.44, p= 0.0025). When an early SUV cut-off value of 1.5 and greater was used to distinguish COP from IPF and NSIP, the sensitivity, specificity and accuracy were 90.9, 94.3 and 93.5%, respectively. The RI-SUV for IPF and NSIP lesions was significantly greater in patients with deteriorated pulmonary function after 1 year of follow-up (progressive group, 13.0 +/- 8.9%) than in cases without deterioration during the 1-year observation period (stable group, -16.8 +/- 5.9%, p0.0001). However, the early SUV for all IIP types provided no additional information of disease progression. When an RI-SUV cut-off value of 0% and greater was used to distinguish progressive IIPs from stable IIPs, the sensitivity, specificity and accuracy were 95.5, 100 and 97.8%, respectively.Early SUV and RI-SUV obtained from dual-time-point (18)F-FDG PET are useful parameters for the differential diagnosis and prediction of disease progression in patients with IIP.

To evaluate the usefulness of 18F-FDG PET in the imaging of pulmonary lesions related to disease activity and in monitoring responses to treatment in patients with pulmonary mycobacteriosis (PM). We used high-resolution computed tomography (HRCT) and 18F-FDG PET to evaluate 47 consecutive untreated patients with PM, 25 with tuberculosis (TB) and 22 with Mycobacterium avium-intracellulare complex (MAC), who presented with small peripheral pulmonary nodules ≤3 cm, and compared the findings. The diagnosis of mycobacteriosis was confirmed by bacteriological examinations of bronchoscopic or surgically resected specimens. PET scans were visually and quantitatively analysed using SUVmax. In addition, 14 patients with PM underwent repeat PET scanning during antimycobacterial therapy, and changes in 18F-FDG uptake were clinically evaluated (6 during treatment and 12 after treatment). Of all the lesions, 87.2% had SUVmax levels ranging from 3 to 7 (5.05 ± 1.56, range 2.5–7.6, n = 47). Further, SUV levels in patients with PM reflected disease activity as estimated by HRCT, but did not differ significantly between those with TB (4.96 ± 1.61, n = 25) and MAC (5.15 ± 1.53, n = 22). 18F-FDG uptake was significantly decreased in all 14 patients who received chemotherapy, indicating a positive response to treatment. 18F-FDG PET is considered to be useful for the diagnosis and evaluation of disease activity along with HRCT findings, and in monitoring response to chemotherapy in patients with PM.

Several studies have reported the findings of fluorine-18-labeled fluoro-2-deoxy-D: -glucose positron emission tomography (FDG-PET) in benign lung disease with diffuse pulmonary injury; however, the characteristics and effectiveness of FDG-PET imaging for interstitial pneumonitis have not been substantiated. We report two cases of drug-induced pneumonitis in two patients treated for breast cancer who were diagnosed by FDG-PET examination. Both the cases showed diffuse interstitial infiltration in the bilateral lungs on computed tomography, but the degree of FDG accumulation was different. It is probable that the degree of FDG accumulation reflected the activity of the drug-induced pneumonitis. The present cases show very interesting FDG-PET imaging findings of diffuse lung disease.

Arterial infusion chemotherapy is considered to be a treatment option for lung cancer patients who are intolerant of systemic chemotherapy because of an increased risk of severe toxicity. However, a number of major studies regarding arterial infusion chemotherapy for lung cancer have reported disappointing results. We performed arterial infusion chemotherapy for four patients with advanced NSCLC who were unable to receive systemic chemotherapy or radiotherapy. After detecting the feeding arteries precisely by angiography, low-dose chemotherapeutic agents were administrated into the corresponding arteries. In each case, multiple feeding arteries including main feeding arteries other than the bronchial artery were detected and a partial response (PR) was obtained without severe toxicity in all. We consider that the present method is an effective treatment option for lung cancer patients who are restricted from undergoing standard systemic chemotherapy or radiotherapy.

The aim of this prospective study was to clarify whether dual-time-point 18F-FDG PET imaging results are useful to predict long-term survival of idiopathic pulmonary fibrosis (IPF) patients. Methods: Fifty IPF patients underwent 18F-FDG PET examinations at 2 time points: 60 min (early imaging) and 180 min (delayed imaging) after 18F-FDG injection. The standardized uptake value (SUV) at each point and retention index value (RI-SUV) calculated from those were evaluated, and then the results were compared with overall and progression-free survival. Results: A multivariate Cox proportional hazards model showed higher RI-SUV and higher extent of fibrosis score as independent predictors of shorter progression-free survival. The median progression-free survival for patients with negative RI-SUV was better than that for those with positive RI-SUV (27.9 vs. 13.3 mo, P = 0.0002). On the other hand, multivariate Cox analysis showed higher RI-SUV and lower forced vital capacity to be independent predictors of shorter overall survival. The 5-y survival rate for patients with negative RI-SUV was better than that for those with positive RI-SUV (76.8% vs. 14.3%, P = 0.00001). In addition, a univariate Cox model showed that positive RI-SUV as a binary variable was a significant indicator of mortality (hazard ratio, 7.31; 95% confidence interval, 2.64–20.3; P = 0.0001). Conclusion: Our results demonstrate that positive RI-SUV is strongly predictive of earlier deterioration of pulmonary function and higher mortality in patients with IPF.

Background As the number of elderly people has increased in Japan, the occurrence of aspiration pneumonia has also increased. Guidelines for the treatment of pneumonia have been proposed, in which the use of antibiotics, such as β-lactam plus β-lactamase inhibitor, clindamycin, and carbapenem, has been recommended as effective against anaerobic bacteria in the treatment of aspiration pneumonia. However, to our knowledge, a prospective comparison of these antibiotics regarding their clinical efficacy in aspiration pneumonia has not been performed Study objectives We compared the effects of IV administration of a half dose of ampicillin/sulbactam (SBT/ABPC), normal dose of SBT/ABPC, IV clindamycin, and IV panipenem/betamiprom (PAPM/BP) for treatment of mild-to-moderate aspiration pneumonia in elderly patients Design Randomized prospective study Patients One hundred adult patients with compatible signs and symptoms of aspiration pneumonia Assessments Patients were assessed before, during, and after treatment regarding symptoms, as well as results of laboratory values, chest radiograph examinations, and sputum bacterial cultures Results We found few differences between the groups regarding cure rate, duration of IV medication, and occurrence of adverse effects with the tested therapies. However, clindamycin therapy was less expensive and was associated with a lower rate of posttreatment occurrence of methicillin-resistant Staphylococcus aureus Conclusions Clindamycin therapy for mild-to-moderate aspiration pneumonia is clinically effective, and provides economic advantages as compared to SBT/ABPC or PAPM/BP therapy

Although nitric oxide (NO) is known to inhibit vascular smooth muscle cell proliferation, the subcellular molecular mechanisms involved with the inhibitory signal transduction pathways are uncertain. We investigated the effect of exogenous NO on cell proliferation and the expression of p53, p21, and phosphorylated p42/44 mitogen-activated protein kinase (MAPK) in human pulmonary arterial smooth muscle cells (HPASMC). Both S-nitroso-N-acetyl penicillamine and diethylenetriaminelNONOate dose-dependently suppressed [3H]-thymidine incorporation in cultured HPASMC, and induced the expression of p53 and p21 protein. Further, the NO donors transiently increased the phosphorylation of p42/44 MAPK and then suppressed it. Although MAPK kinase inhibitors suppressed [3H]-thymidine incorporation by the cells, no significant change was observed in the expression of p53 and p21. The NO donors also suppressed the activation of p42/44 MAPK evoked by transient transfection of the wild-type p53 gene; however, they failed to suppress the activation of p42/44 MAPK in constitutive-active mutations of the Ras or Raf genes trasnsfected from HPASMC. These results indicate that exogenous NO is able to transiently activate p42/44 MAPK via the induction of p53, and then suppress it via inactivation of the Ras and Raf cascades.

Osteogenesis Imperfecta Associated with Dendriform Pulmonary Ossification Miwa Morikawa, Yuh Fukuda, Yasuhiro Terasaki, Harumi Itoh, Yoshiki Demura, Masato Sasaki, Yoshiaki Imamura, Chisato Honjo, Yukihiro Umeda, Masaki Anzai, Shingo Ameshima, Takeshi Ishizaki, and Tamotsu Ishizuka Third Department of Internal Medicine and Department of Radiology, University of Fukui Faculty of Medical Sciences, Fukui, Japan; Department of Diagnostic Pathology, Itabashi Chuo Medical Center, Tokyo, Japan; Department of Analytic Human Pathology, Nippon Medical School, Tokyo, Japan; Department of Respiratory Medicine, Japanese Red Cross Fukui Hospital, Fukui, Japan; Division of Thoracic Surgery and Division of Surgical Pathology, University of Fukui Hospital, Fukui, Japan; and Department of Respiratory Medicine, Kanazawa Medical University, Ishikawa, Japan

PPARgamma is a member of a family of nuclear receptors/ligand-dependent transcription factors, which bind to hormone response elements on target gene promoters. An antiproliferative and proapoptotic action profile of PPARgamma has been described and PPARgamma may function as a tumor suppressor gene, but little is known about the role of PPARgamma in vascular remodeling. One group of human diseases that shows impressive vascular remodeling exclusively in the lungs is the group of severe pulmonary hypertensive disorders, which is characterized by complex, endothelial cell-proliferative lesions of lung precapillary arterioles composed of clusters of phenotypically altered endothelial cells that occlude the vessel lumen and contribute to the elevation of the pulmonary arterial pressure and reduce local lung tissue blood flow. In the present study, we report the ubiquitous PPARgamma expression in normal lungs, and in contrast, a reduced lung tissue PPARgamma gene and protein expression in the lungs from patients with severe PH and loss of PPARgamma expression in their complex vascular lesions. We show that fluid shear stress reduces PPARgamma expression in ECV304 endothelial cells, that ECV304 cells that stably express dominant-negative PPARgamma (DN-PPARgamma ECV304) form sprouts when placed in matrigel and that DN-PPARgamma ECV304 cells, after tail vein injection in nude mice, form lumen-obliterating lung vascular lesions. We conclude that fluid shear stress decreases the expression of PPARgamma in endothelial cells and that loss of PPARgamma expression characterizes an abnormal, proliferating, apoptosis-resistant endothelial cell phenotype.

To investigate the effect of extracellular pH on endothelial nitric oxide synthase (eNOS) in human pulmonary arteries, we measured eNOS activity and expression as well as some ion channels in human pulmonary arterial endothelial cells (HPAEC) exposed to various pH levels (6.6–8.0). eNOS activity was found to increase with alkalization and decrease with acidification, while Ca2+ uptake into HPAEC increased with alkalization. The addition of 3′,4′-dichlorobenzamil hydrochloride, an inhibitor of the Na+/Ca2+ exchanger (NCX), prevented the increase of eNOS activity with alkalosis. Exposure to alkalosis and acidosis increased eNOS and NCX mRNA levels. These results suggest that an elevation of extracellular pH activates eNOS via the influx of extracellular Ca2+ and that NCX also regulates eNOS activity during alkalosis. Furthermore, NCX may have a tight interaction with eNOS at the level of transcription and might affect pulmonary circulation during alkalosis and acidosis.

胸部異常陰影精査目的に施行した全身FDG-PETの他臓器悪性腫瘍診断に対する有用性について検討した. 1997年から2000年7月までに肺癌を疑われ, 全身FDG-PETを施行した79例中, 他臓器悪性腫瘍を確認されたものは8例 (約10%) 存在した. 8例の内訳は, 胃癌1例, 大腸癌2例, 甲状腺癌2例, 喉頭癌1例, 膵癌1例, 脾原発悪性リンパ腫1例であった. FDG-PETは全例において病変を検出し, 発見動機となった. 全例に通常の肺癌病期診断のための検査が行われたが, 他臓器病変は指摘されなかった. 全身FDG-PETによる胸部異常陰影精査は, 通常見逃されやすい消化管や頭頸部の病変も鋭敏に検出し, 総合的な診断能の向上と治療方針の決定に役立つものと考えられた

BACKGROUND It is well known that acute pulmonary inflammation, such as that observed in pneumonia, elevates secretory leukoprotease inhibitor (SLPI) levels in serum. A previous report indicated that serum SLPI levels in lung carcinoma patients with concurrent pneumonia were significantly higher than in those in patients whose disease was unaccompanied by pneumonia or in healthy subjects. The authors hypothesized that serum SLPI may increase in patients with lung carcinoma, even carcinoma occurring without pneumonia, and that cells in lung carcinoma might produce SLPI. METHODS Serum SLPI levels in 58 patients with primary lung carcinoma unaccompanied by pneumonia and in 42 healthy subjects were measured by an enzyme immunoassay. Twenty-four specimens from 24 of the patients with primary lung carcinoma also were examined immunohistochemically using the rabbit antihuman SLPI antibody. RESULTS The results of the current study confirmed that the serum levels of SLPI in patients with primary lung carcinoma were higher than those in healthy subjects, and further found there was no significant correlation between serum SLPI levels and C-reactive protein in lung carcinoma patients without pneumonia. When classifying primary lung carcinoma by its histology, SLPI levels in patients with adenocarcinoma and squamous cell carcinoma were significantly higher than in those in patients with small cell lung carcinoma (SCLC). In patients with nonsmall cell lung carcinoma (NSCLC), the SLPI levels in the advanced group (International Union Against Cancer Stages III and IV disease; n = 35) were significantly elevated compared with the nonadvanced group (Stages I and II disease; n = 12), and such elevated SLPI levels were reduced in some cases by an efficient response to surgical therapy or chemotherapy. Immunohistochemical studies showed that all the NSCLC tissues were stained with anti-human SLPI antibody, whereas staining was not noted in any of the SCLC tissues. CONCLUSIONS The authors believe that the findings of the current study demonstrate that cells of NSCLC produce SLPI. Furthermore, they suggest that serum SLPI levels in serum may be a helpful marker in patients with NSCLC unaccompanied by pneumonia, and that SLPI also could be used as an immunohistochemical marker to distinguish between NSCLC and SCLC. Cancer 2000;89:1448–56. © 2000 American Cancer Society.

48歳女性.全身の多発関節痛を認め近医受診し, 胸部異常陰影を指摘され, 経皮肺生検にて腺癌と診断.精査加療目的にて当院紹介入院となった.全身検索の結果, 原発性肺腺癌と考えられた.ばち状指とともに増悪する多発関節痛を認め, 腫瘍随伴症候群が疑われたこと, 重複癌の可能性等を考慮し外科的に腫瘍切除が行われた.術後病理よりp-T4N0M1 (対側肺内転移) と診断された.術前の骨X線写真上は明らかな異常が認められなかったが, 骨シンチグラムでは全身の関節に異常集積を認め, 両手のサーモグラフィーにて手指の血流増加が指摘された.術後, 関節症状とともに骨シンチグラム, サーモグラフィー上の異常所見は次第に改善した.サーモグラフィーは非侵?的に反復可能であり, 本症例のように骨X線写真上異常所見に乏しい肺性肥大性骨関節症では, 骨シンチグラムとともに診断及び治療効果判定に有用な方法と考えられた.

The aim of the study was to elucidate the vasodilatory mechanism due to Cu2+ by assessing nitric oxide (NO) production as determined by NOx (NO, NO2-, and NO3-) that is released from human pulmonary arterial endothelial cell (HPAEC) monolayers using a NO chemiluminescence analyzer, and also to assess Ca2+ movement using 45Ca and fura 2 in HPAEC. Cu2+ (10(-6)-10(-4) M) significantly increased NO production in a dose-dependent manner when extracellular Ca2+ was present. 45Ca influx into the adherent cells was dose-dependently enhanced by Cu(2+) (10(-6)-10(-4) M), but not by Mn(2+), Zn(2+) or Fe(2+). [Ca2+]i, measured by monitoring the fluorescence changes of fura 2, was significantly elevated in the presence of Cu2+. The increase in [Ca2+]i induced by Cu2+ was inhibited by either diethyldithiocarbamate (DDC) or the depletion of extracellular Ca2+. The dihydropyridine receptor agonist, BayK8644, significantly attenuated the Cu2+-induced increase in [Ca2+]i in a dose dependent manner and nitrendipine or nifedipine, the dihydropyridine receptor antagonists, dose-dependently inhibited a Cu2+-induced increase in [Ca2+]i. These results suggest that Cu2+ activates eNOS through the mechanism of [Ca2+]i elevation due to Ca2+ influx into HPAEC and that the Cu2+-induced [Ca2+]i elevation in HPAEC is likely due to activation of the dihydropyridine-like receptors.

68歳男性, 下腿浮腫・頸部及び縦隔に多発性リンパ節腫張を指摘され当院受診.頸部リンパ節生検にて小細胞癌と診断された.全身検索の結果, 肝・副腎に血行性転移と思われる病変を認めたが, 消化管・骨盤腔など胸部以外に原発巣と思われるところがなく, 肺小細胞癌ED症例と考えられた.肝・副腎腫瘍及び下大静脈内腫瘍塞栓により肝部下大静脈閉塞を生じており, 下腿浮腫, 表在静脈怒張, 肝腫大の急速な進行を認め急性型Budd-Chiari症候群を来たしたと考えられた.化学療法が一旦は効果を示したが, 最終的には急性型Budd-Chiari症候群の再発にて約半年の経過で亡くなった.肺癌のBudd-Chiari症候群合併例は稀であり, 本症例の様に小細胞癌でBudd-Chiari症候群を来たした報告は我々の検索した限りではみられず, 貴重な症例と考え報告した.

In the current study, Cu2+ was tested for its ability to relax vessels and to accumulate cyclic GMP (cGMP) in rat pulmonary artery employing rat extrapulmonary arterial rings. Cu(2+)-induced relaxation was endothelium and concentration (in the range from 10(-7) to 10(-4) M) dependent. The content of cGMP in the rings was increased 1.7-fold with 10(-4) M Cu2+. NG-Monomethyl-L-arginine abolished both the copper-induced relaxation and the increase in cGMP of rings. Cu2+ and zaprinast, which inhibits phosphodiesterase activity, caused a synergistic increase in cGMP level in the rings, suggesting that Cu2+ enhanced cGMP level through a mechanism different from that of zaprinast, probably as a consequence of elevated accumulation of nitric oxide (NO). The magnitude of vasorelaxation observed due to simultaneous addition of Cu2+ and acetylcholine was additive, not synergistic. Cu2+ did not augment relaxation induced by exogenously added NO donor. These results suggest that Cu2+ elevates NO level in the rings not by prolonging the half-life of NO, but by activation of endothelial nitric oxide synthase and subsequently potentiating the action of NO on vascular tone.

Recent advances in endobronchial ultrasonography with a guide sheath (EBUS-GS) have enabled better visualization of distal airways, while virtual bronchoscopic navigation (VBN) has been shown useful as a guide to navigate the bronchoscope. However, indications for utilizing VBN and EBUS-GS are not always clear. To clarify indications for a bronchoscopic examination using VBN and EBUS-GS, we evaluated factors that predict the diagnostic yield of a transbronchial biopsy (TBB) procedure for peripheral lung cancer (PLC) lesions.We retrospectively reviewed the charts of 194 patients with 201 PLC lesions (≤3cm mean diameter), and analyzed the association of diagnostic yield of TBB with [(18)F]-fluoro-2-deoxy-d-glucose ((18)F-FDG) positron emission tomography and chest computed tomography (CT) findings.The diagnostic yield of TBB using VBN and EBUS-GS was 66.7%. High maximum standardized uptake value (SUVmax), positive bronchus sign, and ground-glass opacity component shown on CT were all significant predictors of diagnostic yield, while multivariate analysis showed only high (18)F-FDG uptake (SUVmax ≥2.8) and positive bronchus sign as significant predictors. Diagnostic yield was higher for PLC lesions with high (18)F-FDG uptake (SUVmax ≥2.8) and positive bronchus sign (84.6%) than for those with SUVmax2.8 and negative bronchus sign (33.3%). High (18)F-FDG uptake was also correlated with tumor invasiveness.High (18)F-FDG uptake predicted the diagnostic yield of TBB using VBN and EBUS-GS for PLC lesions. (18)F-FDG uptake and bronchus sign may indicate for the accurate application of bronchoscopy with those modalities for diagnosing PLC.

The value of dual-time- point (18) F-FDG PET was investigated to predict the prognosis of patients with pulmonary sarcoidosis.Twenty-one patients with pulmonary sarcoidosis underwent (18) F-FDG PET examinations at two time points: an early scan at 60min and a delayed scan at 180min after injection of (18) F-FDG. Standardized uptake values (SUVs) at the two time points and the retention index (RI-SUV) calculated from these were evaluated. To evaluate disease progression, all patients underwent chest CT 1year after (18) F-FDG PET. Using these results, the accuracy of (18) F-FDG PET parameters and (67) Ga uptake for predicting disease persistence were compared, and the correlations between those parameters and serum markers were assessed. RI-SUV was significantly higher in patients with increased or unchanged pulmonary lesions at follow-up CT (persistent group; 21.3±9.6%) than in patients with improved pulmonary lesions (improved group; -9.2±28.6%, P=0.0075). The diagnostic accuracy of RI-SUV in the persistent group was significantly greater than that of early SUV or (67) Ga uptake, and serum soluble IL-2 receptor showed a significant correlation with RI-SUV.RI-SUV showed better diagnostic accuracy compared with early SUV or (67) Ga uptake, in patients with persistent lung involvement at 1year. It may be a useful measure of persistent inflammation in patients with pulmonary sarcoidosis.

金沢大学医薬保健研究域医学系, In humans, aromatase (CYP19) gene expression is regulated via alternative promoters. Activation of each promoter gives rise to a CYP19 mRNA species with a unique 5′-untranslated region. Inhibition of aromatase has been reported to downregulate lung tumor growth. The genetic basis for CYP19 gene expression and aromatase activity in lung cancer remains poorly understood. We analyzed tissues from 15 patients with non-small cell lung cancer (NSCLC) to evaluate CYP19 promoter usage and promoter-specific aromatase mRNA levels in NSCLC tumor tissues and adjacent non-malignant tissues. CYP19 promoter usage was determined by multiplex RT-PCR and aromatase mRNA levels were measured with real-time RT-PCR. In non-malignant tissues, aromatase mRNA was primarily derived from activation of CYP19 promoter I.4. Although promoter I.4 usage was also dominant in tumor tissues, I.4 activation was significantly lower compared with adjacent non-malignant tissues. Activity of promoters I.3, I.1 and I.7 was significantly higher in tumor tissues compared with non-malignant tissues. In 4 of 15 cases of non-small cell lung cancer, switching from CYP19 promoter I.4 to the alternative promoters II, I.1 or I.7 was observed. In 9 cases, there were significantly higher levels of aromatase mRNA in lung tumor tissues compared with adjacent non-malignant tissues. These findings suggest aberrant activation of alternative CYP19 promoters that may lead to upregulation of local aromatase expression in some cases of NSCLC. Further studies are needed to examine the impact of alternative CYP19 promoter usage on local estrogen levels and lung tumor growth. © 2011 Elsevier Ireland Ltd. All rights reserved.

1) 進行肺癌症例に対する化学療法施行時にOK-432・5KE皮内投与 (週2～3回) を併用し, 骨髄抑制に対する効果を検討した.2) OK-432投与群では末梢血の白血球および顆粒球のNadirが非投与群と比較して有意に高かった.3) 小細胞肺癌例では化学療法施行後の血小板のNadirも非投与群と比較して有意に高かった.4) 白血球数2000/mm3未満, あるいは血小板数50000/mm3未1黄を示す症例はOK-432投与群で明らかに少なく, 更にその期間は短かった.5) 白血球のNadirから正常白血球数 (4000/mm3以上) に復するまでの期間はOK-432投与群が有意に短かった.

Background Hypoxia induces the proliferation of lung fibroblasts in vivo and in vitro. However, the subcellular interactions between hypoxia and expression of tumor suppressor p53 and cyclin-dependent kinase inhibitors p21 and p27 remain unclear. Methods Normal human lung fibroblasts (NHLF) were cultured in a hypoxic chamber or exposed to desferroxamine (DFX). DNA synthesis was measured using bromodeoxyuridine incorporation, and expression of p53, p21 and p27 was measured using real-time RT-PCR and Western blot analysis. Results DNA synthesis was increased by moderate hypoxia (2% oxygen) but was decreased by severe hypoxia (0.1% oxygen) and DFX. Moderate hypoxia decreased p21 synthesis without affecting p53 synthesis, whereas severe hypoxia and DFX increased synthesis of both p21 and p53. p27 protein expression was decreased by severe hypoxia and DFX. Gene silencing of p21 and p27 promoted DNA synthesis at ambient oxygen concentrations. p21 and p53 gene silencing lessened the decrease in DNA synthesis due to severe hypoxia or DFX exposure. p21 gene silencing prevented increased DNA synthesis in moderate hypoxia. p27 protein expression was significantly increased by p53 gene silencing, and was decreased by wild-type p53 gene transfection. Conclusion These results indicate that in NHLF, severe hypoxia leads to cell cycle arrest via the p53-p21 pathway, but that moderate hypoxia enhances cell proliferation via the p21 pathway in a p53-independent manner. In addition, our results suggest that p27 may be involved in compensating for p53 in cultured NHLF proliferation.

The purpose of this study was to compare the efficacy of short-τ inversion-recovery (STIR) MRI and 18F-FDG PET/CT for the detection of metastasis in mediastinal and hilar lymph nodes in patients with lung cancer. Methods: Ninety-three patients with known or suspected lung cancer with mediastinal and hilar lymph node swelling underwent STIR MRI and 18F-FDG PET/CT examinations. STIR MRI scans were obtained with a 2% copper sulfate phantom placed along the back of each patient, with the lymph node–to–phantom ratio calculated for quantitative analysis. For qualitative analysis, the results of all STIR MRI scans were evaluated using a 5-point visual scoring system. To evaluate the diagnostic capabilities of STIR MRI and 18F-FDG PET/CT, we used receiver-operating-characteristic curve analysis to determine the optimal thresholds for the lymph node–to–phantom ratio, visual score, and maximal standardized uptake value. Further, the capability of each to determine N-stage was compared in each patient using the McNemar test. Results: A total of 137 lymph nodes (82 malignant lesions, 55 benign lesions) were analyzed. When optimal threshold values were adopted, the quantitative and qualitative sensitivity, specificity, and accuracy of STIR MRI were not significantly different from those of 18F-FDG PET/CT. However, 18F-FDG PET/CT in combination with qualitative STIR MRI analysis had a significantly higher capability to detect nodal involvement on an individual-patient basis (96.9% specificity, 90.3% accuracy) than did 18F-FDG PET/CT alone (65.6% specificity, 81.7% accuracy). Conclusion: We found that the diagnostic capability of STIR MRI was not significantly different from that of 18F-FDG PET/CT. However, when those methods were combined, the diagnostic capability for N-staging was significantly improved.

PPARgamma is a member of a family of nuclear receptors/ligand-dependent transcription factors, which bind to hormone response elements on target gene promoters. An antiproliferative and proapoptotic action profile of PPARgamma has been described, but little is known about the role of PPARgamma in vascular remodeling. We reported a reduced PPARgamma gene and protein expression in the lungs from patients with severe pulmonary hypertension and loss of PPARgamma expression in their complex vascular lesion. We showed that fluid shear stress reduces PPARgamma expression in ECV304 endothelial cells and that ECV304 cells that stably express dominant-negative PPARgamma form lumen-obliterating lung vascular lesion in the artificial capillaries under fluid shear stress and in the intrapulmonary arteries after tail vein injection in nude mice. Recently, there are some evidences that PPARgamma may represent a novel therapeutic target in pulmonary hypertension.

Background To diagnose sputum smear-negative pulmonary tuberculosis (PTB) is difficult and the ability of high-resolution computed tomography (HRCT) for diagnosing PTB has remained unclear in the sputum smear-negative setting. We retrospectively investigated whether or not this imaging modality can predict risk for sputum smear-negative PTB. Methods We used HRCT to examine the findings of 116 patients with suspected PTB despite negative sputum smears for acid-fast bacilli (AFB). We investigated their clinical features and HRCT-findings to predict the risk for PTB by multivariate analysis and a combination of HRCT findings by stepwise regression analysis. We then designed provisional HRCT diagnostic criteria based on these results to rank the risk of PTB and blinded observers assessed the validity and reliability of these criteria. Results A positive tuberculin skin test alone among clinical laboratory findings was significantly associated with an increase of risk of PTB. Multivariate regression analysis showed that large nodules, tree-in-bud appearance, lobular consolidation and the main lesion being located in S1, S2, and S6 were significantly associated with an increased risk of PTB. Stepwise regression analysis showed that coexistence of the above 4 factors was most significantly associated with an increase in the risk for PTB. Ranking of the results using our HRCT diagnostic criteria by blinded observers revealed good utility and agreement for predicting PTB risk. Conclusions Even in the sputum smear-negative setting, HRCT can predict the risk of PTB with good reproducibility and can select patients having a high probability of PTB.

18F-FDG PET is increasingly used for lung cancer; however, some insufficient results have been reported. The purpose of this study was to evaluate the efficacy of dual–time-point 18F-FDG PET for staging lung cancer and for differentiating metastatic from nonmetastatic lung cancer lesions. Methods: One hundred fifty-five lung cancer patients with known or suspected mediastinal and hilar lymph node involvement or distant metastases underwent whole-body 18F-FDG PET at 2 time points: scan 1 at 60 min (early imaging) and scan 2 at 180 min (delayed imaging) after 18F-FDG injection. 18F-FDG PET findings of nodal and distant metastases were evaluated using conventional imaging, clinical follow-up findings, and the results of autopsy or biopsy. Results: A total of 580 lesions (155 primary lesions, 315 metastatic lesions, and 110 nonmetastatic lesions) were used for analysis. A closer correlation between the primary lesions and metastases was observed for the retention index (RI) standardized uptake value (SUV) than for early and delayed SUV. There was no relationship between the RI SUV results of primary lesions and those of nonmetastatic lesions. The RI SUV of metastatic lesions was approximately 0.5–2 times the RI SUV of primary tumors. We found that the accuracy of 18F-FDG PET was improved when RI SUV was used for detecting lymph node and distant metastases, because of the significant improvement in specificity relative to early and delayed SUV. Conclusion: RI SUV raised the accuracy for diagnosis of metastases and was superior to early and delayed imaging in terms of differentiating malignancy from nonmetastatic uptake.

The present study examines the significance of defining feeding arteries to arterial infusion chemotherapy for patients with non-small cell lung carcinoma. We retrospectively studied feeding arteries and findings from 32 patients treated by arterial infusion chemotherapy. We graded tumor staining by angiography and compared grade in the bronchial artery with that of total staining in all detected feeding arteries, and investigated the relationship between grade and treatment response. One patient achieved a complete response and 16 achieved a partial response with no serious adverse effects. Many feeding arteries were detected and the grade of total tumor staining in these patients was significantly higher than that of tumor staining in the bronchial artery. The number of lesions that responded was significantly increased among those with a higher grade of total tumor staining. Precise definition of feeding arteries and sufficient tumor staining are vital to ensure a successful outcome of arterial infusion chemotherapy for patients with NSCLC.

A 60-year-old woman was referred to our hospital because of an abnormal chest radiograph in May, 2000. She was found to have rheumatoid arthritis in March, 1998, and pharmacologic therapy with anti-rheumatic drug was started. The chest CT scan revealed bilateral multiple lung nodular lesions of various sizes up to 30 mm. F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) demonstrated a lesion with intense FDG activity in the right lung with a standardized uptake value (SUV) of 10.1. Fiberoptic bronchoscopy revealed no endobronchial lesions. Video-assisted thoracoscopic surgery was done to ascertain the pathological diagnosis. Histological examination showed that the pulmonary nodules were composed of amyloid A (AA) protein. Secondary Sjögren syndrome was subsequently diagnosed. A diagnosis of localized nodular pulmonary amyloidosis with AA type amyloid protein was made, and therapy with anti-rheumatic drugs was continued. After six years of therapy, the size of pulmonary amyloidoma was reduced, and the accumulation of FDG returned to normal. We reported this interesting case in which FDG-PET apparently reflected the disease activity of pulmonary amyloidosis.

This study evaluated 18F-FDG-PET imaging for the detection of gastrointestinal tract cancer in patients with suspected lung cancer. A total of 351 patients who had abnormal lung shadows and who underwent whole-body FDG-PET between June 1998 and January 2006 were retrospectively entered for analysis. Gastrointestinal tract cancers were subsequently found in 15 patients (4.3%) who had been found to have lung diseases consisting of 7 inflammatory changes, 6 lung cancers, and 2 metastatic lung carcinomas, 9 colon cancers, 4 gastric cancers, and 2 esophageal cancers. Five patients (2 colon cancers, 2 gastric cancers, and 1 esophageal cancer) had early stage carcinoma. In this study, FDG-PET was useful not only for the diagnosis and staging of lung cancer, but also for the detection of unexpected gastrointestinal tract cancers. FDG-PET may be most suitable for cancer screening.

High-resolution computed tomography (HRCT) findings in patients with respiratory bronchiolitis-associated interstitial lung disease (RB-ILD) are varied and nonspecific. There is no known report of changes in HRCT findings and respiratory function test results for RB-ILD patients following the cessation of smoking. Five patients with RB-ILD, confirmed by surgical lung biopsy, were retrospectively studied. Each stopped cigarette smoking and did not receive corticosteroid therapy after diagnosis. The clinical symptoms, respiratory function test results and HRCT findings obtained at the final observation were compared with those from the time of diagnosis. Ground-glass opacity and centrilobular nodules corresponding to pathological respiratory bronchiolitis, as well as intralobular fine linear-reticular opacity corresponding to fibrosis involving the subpleural alveolar septa, showed computed tomography-pathological correlations. Both clinical symptoms and the diffusing capacity of the lungs for carbon monoxide improved significantly following smoking cessation, as did ground-glass opacity and centrilobular nodules seen during the initial HRCT examination. Centrilobular nodules and ground-glass opacity, which are the main features of high-resolution computed tomography of respiratory bronchiolitis-associated interstitial lung disease patients and represent pathological respiratory bronchiolitis, can be improved by smoking cessation. The diffusing capacity of the lung for carbon monoxide in respiratory function tests can be also improved.

A 55-year-old man complained of acute onset of shoulder pain and dyspnea in the supine position. A diagnosis of bilateral diaphragmatic paralysis was made based on clinical inspection of his breathing pattern, radiographic appearance, and pulmonary function tests. He had had no traumatic or thoracic surgery or inflammatory episode. He did not suffer from diabetes, other central neural diseases, or any neoplastic disease. From the clinical feature and electromyographic findings, phrenic nerve involvement of brachial neuritis without any other muscle involvement was considered as a causative disease. When he received non-invasive intermittent positive-pressure ventilation by nasal mask in a supine position, his dyspnea was substantially attenuated and Carbon dioxide retention was lessened. After 1 year, his shoulder pain is still persisting and radiographic findings are not remarkably improved.

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the nuclear hormone receptor superfamily, which regulates transcription of target genes in a ligand-dependent manner. Ligands for PPARgamma have been shown to attenuate proliferation of vascular smooth muscle cells, and to induce apoptosis in several cell lines in vitro. Since monocrotaline (MCT)-induced pulmonary hypertension in rats is characterized by proliferation of pulmonary vascular smooth muscle cells, we hypothesized that PPARgamma ligands may reduce MCT-induced pulmonary hypertension. To test this hypothesis, we treated MCT-injected rats with pioglitazone and troglitazone, synthetic ligands for PPARgamma, for three weeks and measured pulmonary artery pressure and pulmonary vessel wall thickness. TdT-mediated dUTP-biotin nick end labeling (TUNEL) and immunostaining for proliferating cell nuclear antigen (PCNA) were utilized to assess apoptosis and cell proliferation in the pulmonary arterial walls of pioglitazone-treated rats. MCT with pioglitazone or troglitazone treatment significantly reduced pulmonary hypertension and wall thickening of the pulmonary arteries. TUNEL-positive apoptotic cells were not seen in the pulmonary arterial walls of either MCT-injected or control rats with or without pioglitazone. PCNA-positive cells were only seen in the thickened pulmonary arterial walls of MCT rats, but not in the pulmonary arterial walls of controls and of pioglitazone-treated MCT rats. We conclude that PPARgamma ligands reduce MCT-induced pulmonary hypertension and pulmonary vascular wall thickening in rats. Inhibition of MCT-induced cell proliferation in the pulmonary arterial walls may account for this effect

We encountered a case of small-cell lung cancer with paraneoplastic neurologic syndrome in a 68-year old man. Progressive dysesthesia had developed in his hands and legs over a period of 4 months. Chest radiography and chest CT scanning on admission showed a mass in the hilum of the left lung. Anti-Hu antibody was found in his serum and the subsequent histopathological diagnosis by TBLB was small cell lung cancer. The patient underwent complete remission, in terms of tumor size, as a result of concurrent chemoradiotherapy (cisplatin, etoposid) and the dysesthesia in his legs was alleviated.

Recent reports have indicated the value and limitations of (18)F-FDG PET and (201)Tl SPECT for determination of malignancy. We prospectively assessed and compared the usefulness of these scintigraphic examinations as well as (18)F-FDG PET delayed imaging for the evaluation of thoracic abnormalities.Eighty patients with thoracic nodular lesions seen on chest CT images were examined using early and delayed (18)F-FDG PET and (201)Tl-SPECT imaging within 1 wk of each study. The results of (18)F-FDG PET and (201)Tl SPECT were evaluated and compared with the histopathologic diagnosis.Fifty of the lesions were histologically confirmed to be malignant, whereas 30 were benign. On (18)F-FDG PET, all malignant lesions showed higher standardized uptake value (SUV) levels at 3 than at 1 h, and benign lesions revealed the opposite results. Correlations were seen between (18)F-FDG PET imaging and the degree of cell differentiation in malignant tumors. No significant difference in accuracy was found between (18)F-FDG PET single-time-point imaging and (201)Tl SPECT for the differentiation of malignant and benign thoracic lesions. However, the retention index (RI) of (18)F-FDG PET (RI-SUV) significantly improved the accuracy of thoracic lesion diagnosis. Furthermore, (18)F-FDG PET delayed imaging measuring RI-SUV metastasis was useful for diagnosing nodal involvement and it improved the specificity of mediastinal staging.No significant difference was found between (18)F-FDG PET single-time-point imaging and (201)Tl SPECT for the differentiation of malignant and benign thoracic lesions. The RI calculated by (18)F-FDG PET delayed imaging provided more accurate diagnoses of lung cancer.