A quantitative analysis of progressive fibrosing interstitial lung disease on computed tomography for the assessment of decreased vital capacity.

BACKGROUND: The results of a quantitative analysis of computed tomography (CT) of interstitial lung disease (ILD) using a computer-aided detection (CAD) technique were correlated with the results of pulmonary function tests. PURPOSE: To evaluate the correlation between a quantitative analysis of CT of progressive fibrosing interstitial lung disease (PF-ILD) including idiopathic pulmonary fibrosis (IPF) and non-IPF, which can manifest progressive pulmonary fibrosis and the vital capacity (VC), and to identify indicators for the assessment of a decreased VC. MATERIAL AND METHODS: A total of 73 patients (46 patients with IPF and 27 patients with non-IPF) were included in this study. Associations between the quantitative analysis of CT and the %VC using a CAD software program were investigated using Spearman's rank correlation and a logistic regression analysis. The appropriate cutoff vale for predicting a decreased VC was determined (%VC <80) and the area under the curve (AUC) was calculated. RESULTS: A multiple logistic regression analysis showed that the total extent of interstitial pneumonia on CT was a significant indicator of a decreased VC (P = 0.0001; odds ratio [OR]=1.15; 95% confidence interval [CI]=1.06-1.27 in IPF and P = 0.0025; OR=1.16; 95% CI=1.03-1.30 in non-IPF). The cutoff values of the total extent of interstitial pneumonia in IPF and non-IPF for predicting a decreased VC were determined to be 23.3% and 21.5%, and the AUCs were 0.83 and 0.91, respectively. CONCLUSION: A quantitative analysis of CT of PF-ILD using a CAD software program could be useful for predicting a decreased VC.

A quantitative analysis of long-term follow-up computed tomography of idiopathic pulmonary fibrosis: the correlation with the progression and prognosis.

BACKGROUND: Quantitative analyses of computed tomography (CT) images using computer-aided detection (CAD) are correlated with visual assessments and pulmonary function test findings and might be useful for predicting the prognosis of patients with idiopathic pulmonary fibrosis (IPF). PURPOSE: To evaluate the association between the quantitative analysis of long-term follow-up CT of IPF and the progression and prognosis. MATERIAL AND METHODS: A total of 48 patients with IPF who received over one year of follow-up CT were included in this study. The results of quantitative analyses (emphysema, ground-glass attenuation [GGA], consolidation, reticulation, and honeycombing) using a CAD software program of initial and follow-up CT findings were evaluated, and the association with the progression of the total lesion of IPF and prognosis using Spearman's rank correlation and Cox regression analyses was considered. RESULTS: Results of quantitative analyses of consolidation, reticulation, honeycombing, and the total lesion on initial CT were correlated with progressive changes in the total lesion of IPF per year (r = 0.4375, 0.4128, 0.4649, and 0.4095, respectively). The results of quantitative analyses of honeycombing (hazard ratio [HR] = 1.40, 95% confidence interval [CI] = 1.03-1.89, P = 0.0314) and GGA (HR = 0.85, 95% CI = 0.72-0.99, P = 0.0384) at initial CT were prognostic factors according to a multivariate Cox regression analysis. CONCLUSION: The quantitative analysis of honeycombing using a CAD software program of CT findings may be useful for predicting the progression and prognosis of patients with IPF.

Differential diagnosis of infectious diseases, drug-induced lung injury, and pulmonary infiltration due to underlying malignancy in patients with hematological malignancy using HRCT.

PURPOSE: To differentiate among infectious diseases, drug-induced lung injury (DILI) and pulmonary infiltration due to underlying malignancy (PIUM) based on high-resolution computed tomographic (HRCT) findings from patients with hematological malignancies who underwent chemotherapy or hematopoietic stem cell transplantation. MATERIALS AND METHODS: A total of 221 immunocompromised patients with hematological malignancies who had proven chest complications (141 patients with infectious diseases, 24 with DILI and 56 with PIUM) were included. Two chest radiologists evaluated the HRCT findings, including ground-glass opacity, consolidation, nodules, and thickening of bronchovascular bundles (BVBs) and interlobular septa (ILS). After comparing these CT findings among the three groups using the χ2test, multiple logistic regression analyses (infectious vs noninfectious diseases, DILI vs non-DILI, and PIUM vs non-PIUM) were performed to detect useful indicators for differentiation. RESULTS: Significant differences were detected in many HRCT findings by the χ2 test. The results from the multiple logistic regression analyses identified several indicators: nodules without a perilymphatic distribution [p = 0.012, odds ratio (95% confidence interval): 4.464 (1.355-11.904)], nodules with a tree-in-bud pattern [p = 0.011, 8.364 (1.637-42.741)], and the absence of ILS thickening[p = 0.003, 3.621 (1.565-8.381)] for infectious diseases, the presence of ILS thickening [p = 0.001, 7.166 (2.343-21.915)] for DILI, and nodules with a perilymphatic distribution [p = 0.011, 4.256 (1.397-12.961)] and lymph node enlargement (p = 0.008, 3.420 (1.385-8.441)] for PIUM. CONCLUSION: ILS thickening, nodules with a perilymphatic distribution, tree-in-bud pattern, and lymph node enlargement could be useful indicators for differentiating among infectious diseases, DILI, and PIUM in patients with hematological malignancies.

High-resolution CT findings of pulmonary infections in patients with hematologic malignancy: comparison between patients with or without hematopoietic stem cell transplantation.

PURPOSE: To evaluate the high-resolution CT (HRCT) findings of pulmonary infections in patients with hematologic malignancy and compare them between patients with or without hematopoietic stem cell transplantation (HSCT). MATERIALS AND METHODS: A total of 128 patients with hematologic malignancy and pulmonary infection were included in this study. The diagnoses of the patients consisted of bacterial pneumonia (37 non-HSCT cases and 14 HSCT cases), pneumocystis pneumonia (PCP) (29 non-HSCT cases and 11 HSCT cases), and fungal infection other than PCP (20 non-HSCT cases and 17 HSCT cases). Two chest radiologists retrospectively evaluated the HRCT criteria and compared them using chi-squared tests and a multiple logistic regression analysis. RESULTS: According to the multiple logistic regression analysis, nodules were an indicator in HSCT patients with PCP (p = 0.025; odds ratio, 5.8; 95% confidence interval, 1.2-26.6). The centrilobular distribution of nodules was the most frequent (n = 4, 36%) in HSCT patients with PCP. A mosaic pattern was an indicator of PCP in both HSCT and non-HSCT patients. There were no significant differences in other infections. CONCLUSION: The mosaic pattern could be an indicator of PCP in both HSCT and non-HSCT patients. Nodules with centrilobular distribution might be relatively frequent HRCT findings of PCP in HSCT patients.

Correlation between pleural tags on CT and visceral pleural invasion of peripheral lung cancer that does not appear touching the pleural surface.

OBJECTIVES: To evaluate the association between a sign and visceral pleural invasion (VPI) of peripheral non-small-cell lung cancer (NSCLC) that does not appear touching the pleural surface. METHODS: A total of 221 consecutive patients with NSCLC that did not appear touching the pleural surface, ≤ 3 cm in solid tumor diameter, and was surgically resected between January 2009 and December 2015 were included. We focused on the flat distortion of the tumor caused by an arch-shaped linear tag between the tumor and the pleura on CT and named it a bridge tag sign. We evaluated the associations between the clinicopathological features of the tumor, including the bridge tag sign, and VPI. We also evaluated the associations between histopathological findings and the bridge tag sign. The utility of the bridge tag sign in the diagnosis of VPI was statistically assessed. RESULTS: The bridge tag sign was observed in 48 (20.8%) patients. VPI was positive in 9 (4.1%) patients; among these, the bridge tag sign was positive in 8 patients. In multivariate analysis, a bridge tag sign was significantly associated with VPI. The bridge tag sign was associated with longer contact length of the pleura with the tumor and trapezoid type pleural retraction. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the bridge tag sign in the diagnosis of VPI were 88.9%, 83.5%, 83.7%, 18.6%, and 99.4%, respectively. CONCLUSIONS: A bridge tag sign on CT might improve the accuracy of the prediction of VPI. KEY POINTS: • We present the bridge tag sign which is defined as a flat distortion of an NSCLC tumor by an arch-shaped linear tag between the tumor and chest wall or interlobar fissure. • The bridge tag sign was an independent predictive factor for visceral pleural invasion. • The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of the bridge tag sign in the diagnosis of visceral pleural invasion were 88.9%, 83.5%, 83.7%, 18.6%, and 99.4%, respectively.

Medication persistence rates and predictive factors for discontinuation of antifibrotic agents in patients with idiopathic pulmonary fibrosis: a real-world observational study.

BACKGROUND: In patients with idiopathic pulmonary fibrosis (IPF), continuing treatment with antifibrotic agents is crucial to decrease the reduction of forced vital capacity and mortality rate. However, predictive factors for the discontinuation of antifibrotic agents are unknown. This study aims to investigate the clinical characteristics and predictive factors for the discontinuation of antifibrotic agents in patients with IPF. METHODS: This was a double-center retrospective study that enrolled patients with IPF treated with pirfenidone or nintedanib between 2009 and 2017. We compared clinical parameters between the medication-continuing group and the discontinued group. The predictive factors were determined using Cox proportional hazards analyses. RESULTS: A total of 66 subjects were included: 43 received pirfenidone and 23 received nintedanib. At 1 year, 23 of 66 patients had discontinued due to adverse events (n = 12), disease progression (n = 9), or death (n = 2). The characteristics of the discontinuation group were poor performance status (PS) and delay from diagnosis to treatment. In the receiver operating characteristic (ROC) analysis associated with the discontinuation of antifibrotic agents, PS was the highest area under the ROC curve (AUC) value (cut-off value, 2; AUC, 0.83; specificity, 63%; sensitivity, 87%). This finding was consistent even when analyzing, except for examples of death and adjusting for the type of antifibrotic agent. The treatment persistence rate by PS was PS 0-1 = 90%, PS 2 = 65%, and PS 3 = 19%. Analysis of the relationship between PS and administration period of antifibrotic agents revealed that delays from diagnosis to treatment led to worsening of dyspnea, a decline in lung function, and deterioration of PS. CONCLUSIONS: PS may be informative for predicting discontinuation of medication. Our data reinforced the importance of early initiation of antifibrotic treatment, and we suggest PS should be used as a guide for starting antifibrotic agents in everyday practice. The reviews of this paper are available via the supplementary material section.

Air bronchogram in pleomorphic carcinoma of the lung is associated with favorable prognosis.

BACKGROUND: Pleomorphic carcinoma (PC) of the lung is a rare histological type of lung carcinoma. The association between computed tomography (CT) findings and histology with outcome remains unclear. We examined the relationships between CT features and histopathologic findings, and evaluated the impact of CT features and other clinicopathologic factors on survival. METHODS: Thirty-five consecutive patients with PC of the lung who underwent surgery between October 2010 and December 2015 were enrolled in this study. The 35 tumors were classified with or without air bronchogram in the tumors, and with or without intratumoral ground glass opacity (GGO) on CT. RESULTS: Air bronchogram and GGO were detected in 12 (34.3%) and 5 (14.3%) tumors, respectively. Multivariate analysis revealed that air bronchogram was significantly associated with the presence of adenocarcinoma components with lepidic growth patterns (P = 0.005), and predominance of adenocarcinomas (P = 0.026). GGO was significantly associated with the presence of adenocarcinoma component with lepidic growth pattern (P = 0.010). Air bronchogram was an independent favorable prognostic factor for overall survival, whereas GGO did not have a significant effect on survival. CONCLUSION: Air bronchogram observed in PCs of the lung is strongly related with histological components of the tumor and favorable outcome.

The impact of coexisting lung diseases on outcomes in patients with pathological Stage I non-small-cell lung cancer.

OBJECTIVES: Cigarette smoking is a well-known cause of interstitial lung disease (ILD), pulmonary emphysema and lung cancer. Coexisting pulmonary disease can affect prognosis in patients with lung cancer. The aim of this study was to determine the influence of pulmonary disease on outcomes in patients with a smoking history who had undergone surgery for pathological Stage I non-small-cell lung cancer. METHODS: Medical records of 257 patients with a smoking history who underwent surgery for pathological Stage I non-small-cell lung cancer between June 2009 and December 2014 were reviewed. Coexisting ILDs were evaluated using high-resolution computed tomography. The degree of pulmonary emphysema was determined using image analysis software according to the Goddard classification. The impact of clinicopathological factors on outcome was evaluated. RESULTS: Among the 257 patients, ILDs were detected via high-resolution computed tomography in 60 (23.3%) patients; of these, usual interstitial pneumonia (UIP) patterns and non-UIP patterns were seen in 25 (9.7%) and 35 (13.6%) patients, respectively. The degree of pulmonary emphysema was classified as none, mild and moderate and included 50 (19.5%), 162 (63.0%) and 45 (17.5%) patients, respectively. The 5-year overall survival, cancer-specific survival and relapse-free survival were 80.7%, 88.0% and 74.9%, respectively, during a median follow-up period of 50.5 months. In multivariate analysis, the presence of a UIP pattern was shown to be an independent risk factor for poor outcome. CONCLUSIONS: The presence of a UIP-pattern ILD on high-resolution computed tomography images was shown to be a risk factor for poor outcome in patients with a smoking history who had undergone surgery for pathological Stage I non-small-cell lung cancer.

Survival from an Acute Exacerbation of Idiopathic Pulmonary Fibrosis with or without Direct Hemoperfusion with a Polymyxin B-immobilized Fiber Column: A Retrospective Analysis.

Objective Acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF) are fatal episodes of acute respiratory worsening of unknown etiology. Previous studies on acute respiratory distress syndrome have shown that direct hemoperfusion with a polymyxin B-immobilized fiber column (PMX-DHP) can have a beneficial effect on the respiratory status. This retrospective study investigated the prognosis and survival outcome of patients with AE-IPF who underwent PMX-DHP. Methods We examined the records of 50 patients with AE-IPF treated in our hospital. All patients received corticosteroid pulse therapy. We compared the disease outcome between 27 patients who underwent PMX-DHP (PMX group) and 23 patients who did not (non-PMX group). The independent predictors of survival were determined using Cox proportional hazards analyses. Results A multivariate analysis of all patients revealed that PMX-DHP therapy was a significant predictor of survival (HR=0.442, 95% CI 0.223-0.873; p=0.019). The 12-month survival rate was significantly higher in the PMX group than in the non-PMX group (41.7% vs. 9.8%; p=0.040). According to a subanalysis of the PMX group, the time from AE-IPF onset to PMX-DHP was a significant predictor of survival (HR=1.080, 95% CI 1.001-1.166; p=0.049). Conclusion PMX-DHP improved the prognosis of AE-IPF. The time from AE-IPF onset to PMX-DHP may therefore be informative for predicting the patient outcome.

Enhanced sialylation of a human chimeric IgG1 variant produced in human and rodent cell lines.

Glycosylation of the IgG-Fc is essential for optimal binding and activation of Fcγ receptors and the C1q component of complement. However, it has been reported that the effector functions are down-regulated when the Fc glycans terminate in sialic acid residues and that sialylated IgG mediates anti-inflammatory effects of intravenous immunoglobulin (IVIG). Although recombinant IgG is hypo-sialylated, Fc sialylation is shown to be markedly increased when a mouse/human chimeric IgG3 Phe243Ala (F243A) variant is expressed in Chinese hamster ovary (CHO)-K1 cells. Here we investigate whether sialylation is increased in IgG1 F243A when expressed in CHO-K1, mouse myeloma J558L and human embryonic kidney (HEK) 293. Although the sialylation level was 2-5% for IgG1 wild type (WT), it was increased to 31%, 10% and 33% for the variant from CHO-K1, J558L and HEK293 cells, respectively. Interestingly, an increased addition of bisecting GlcNAc and α(1-3)-galactose residues to the Fc glycan was observed for HEK293-derived and J558L-derived IgG1 F243A, respectively. Fucosylation of HEK293-derived IgG1 F243A was maintained despite increased bisecting GlcNAc content. Although sialic acid and bisecting GlcNAc residues are reported to have an opposing effect on antibody-dependent cellular cytotoxicity (ADCC), IgG1 F243A showed 7 times lower ADCC activities than IgG1 WT, irrespective of bisecting GlcNAc residue. Thus, highly sialylated, human cell-derived IgG1 F243A with lowered ADCC activity may be of interest for the development of therapeutic antibodies with anti-inflammatory properties as an alternative to IVIG.

HRCT findings of small cell lung cancer measuring 30 mm or less located in the peripheral lung.

PURPOSE: To evaluate the high-resolution CT (HRCT) features of peripherally located small cell lung cancer (SCLC). MATERIALS AND METHODS: We retrospectively reviewed the HRCT findings of 33 patients with peripherally located SCLC measuring 30 mm or less. The shape and marginal and internal characteristics of the nodules were evaluated. We also assessed the differences in these HRCT findings associated with the differences in the stages of disease. In 10 surgically treated cases, the HRCT-pathological correlations were evaluated. RESULTS: The findings of a well-defined margin (97.0 %), lobulation (78.8 %), thickening of the bronchovascular bundle (BVB) (57.6 %) and inhomogeneous enhancement (64.0 %) were common. A vermiform/branching and polygonal shape were observed in 33.3 and 21.2 % of cases, respectively. Air bronchograms (15.2 %) and marginal ground-glass opacity (GGO) (3.0 %) were less common findings. The vermiform/branching shape and thickening of the BVB were more frequently observed in non-stage I than in stage I tumors. The pathologic findings showed expansive tumor growth along the lymphatics and minimal necrosis between the tumor nests. CONCLUSION: A non-round shape and thickening of the BVB were common, while marginal GGO and air bronchogram were less common in small-sized, peripherally located SCLC. Furthermore, the vermiform/branching shape and thickening of the BVB suggested relatively advanced disease.

Immediate and late outcomes of bronchial and systemic artery embolization for palliative treatment of patients with nonsmall-cell lung cancer having hemoptysis.

BACKGROUND: Hemoptysis in patients with advanced lung cancer can be a life threatening. OBJECTIVES: To evaluate immediate outcomes and late outcomes of bronchial artery embolization (BAE) for palliative treatment in patients with advanced nonsmall-cell lung cancer (NSCLC) having hemoptysis. METHODS: The BAE was performed in 28 patients with NSCLC. Hemoptysis was defined as follows: massive bleeding greater than 300 mL within 24 hours (n = 8), moderate bleeding of 100 to 300 mL within 24 hours (n =12), and slight bleeding less than100 mL within 24 hours (n = 8). RESULTS: Success rate was 96%. Immediate clinical success within 24 hours after BAE was achieved in 22 of the 27 patients who underwent embolization. CONCLUSIONS: The BAE with gelatin sponge particles can provide good management of hemoptysis as a palliative treatment in patients with advanced NSCLC.

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

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

Long term follow-up for small pure ground-glass nodules: implications of determining an optimum follow-up period and high-resolution CT findings to predict the growth of nodules.

PURPOSE: To identify the optimum follow-up period for pure ground-glass nodules (GGN) measuring less than 15 mm in diameter, and to evaluate whether the initial HRCT findings can be used as predictors for the progression of pure GGN. MATERIALS AND METHODS: A total of 150 pure GGNs present in 111 patients were evaluated. The series of HRCT images for each GGN at the time of the initial detection, 2 years after detection, and at the final follow-up were evaluated. The HRCT findings of GGN were compared between the "increasing nodule" and "non-increasing nodule" groups. RESULTS: Most (87.3%) pure GGN did not increase whereas some nodules (12.7%) eventually increased after long-term follow-up (mean 66.0 ± 25.0 months). Six (31.6%) out of the 19 increasing nodules were regarded as stable at the 2 year follow-up examination. Some morphological findings on initial HRCT, including a size greater than 10 mm (p = 0.001), lobulated margins (p = 0.015), and a bubble-like appearance (p = 0.002), were significantly associated with the growth of pure GGNs. CONCLUSION: More than 2 years of follow-up are necessary to detect the growth of pure GGNs. Some characteristic findings indicated a high likelihood of future growth of the GGN.

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

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

Streptomycin alleviates irinotecan-induced delayed-onset diarrhea in rats by a mechanism other than inhibition of ß-glucuronidase activity in intestinal lumen.

Irinotecan hydrochloride (CPT-11) is a useful drug for cancer chemotherapy but sometimes induces severe diarrhea clinically. CPT-11 is mainly activated to SN-38 by carboxylesterase (CES) and then detoxified to SN-38 glucuronide (SN-38G) by UDP-glucuronosyltransferase (UGT) in the liver. SN-38G is excreted via bile and de-conjugated to SN-38 by ß-glucuronidase (ß-GLU) in the intestinal content. In order to clarify the alleviative effect of antibiotics on CPT-11-induced diarrhea, we examined whether penicillin G and streptomycin (SM) alleviate CPT-11-induced delayed-onset diarrhea using three diarrheal models, i.e., Wistar rats with repeated dosing of CPT-11 (60 mg/kg/day i.v. for 4 consecutive days) and Wistar and Gunn rats with a single dosing of CPT-11 (200 and 20 mg/kg i.v., respectively). Gunn rats have an inherited deficiency of UGT1A and cannot conjugate SN-38 to SN-38G. Therefore, onset of CPT-11-induced diarrhea in Gunn rats is not affected by ß-GLU activity. SM alleviated diarrhea in all three diarrheal models. The alleviation of diarrhea by SM in Gunn rats indicated that the effect of SM occurred by a mechanism other than the inhibition of ß-GLU activity. SM decreased CPT-11 and/or SN-38 concentrations in intestinal tissues and alleviated epithelial damage from the ileum to colon. SM did not inhibit ß-GLU activity in the cecal content. SM also inhibited the intestinal absorption of CPT-11 and decreased CES activity and increased UGT activity in the intestinal epithelium. These findings indicated that SM decreased the exposure of CPT-11 and SN-38 to the intestinal epithelium by inhibiting the absorption of CPT-11 from the intestinal lumen and the change of CES and UGT activities in the intestinal epithelium and alleviated delayed-onset diarrhea.

Differential diagnosis between (18)F-FDG-avid metastatic lymph nodes in non-small cell lung cancer and benign nodes on dual-time point PET/CT scan.

OBJECTIVE: To clarify the difference of (18)F-FDG uptake kinetics between FDG-avid metastatic lymph nodes (LNs) in patients with non-small-cell lung cancer (NSCLC) and FDG-avid benign LNs associated with various etiologies on dual-time point PET/CT scan, and to determine the optimal parameter for differentiation. METHODS: The subjects were 134 FDG-avid metastatic LNs in 67 patients with NSCLC and 62 FDG-avid benign LNs in 61 patients with various lung disorders including NSCLC. PET/CT scan was performed at 2 time points (at 60 min and at 120 min) after intravenous injection of 4.4 MBq/kg (18)F-FDG. The maximum standardized uptake value (SUVmax) on early and delayed scans and the percent change of SUVmax (%DeltaSUVmax) were measured at each FDG-avid LN. The optimal parameter for differentiation was determined by the receiver-operating characteristic analysis. RESULTS: Delayed SUVmax was increased compared with early SUVmax in 114 (85.0%) FDG-avid metastatic LNs and 42 (67.7%) FDG-avid benign LNs, with significant higher delayed SUVmax than early values (7.0 +/- 5.0 vs. 5.9 +/- 3.4; P < 0.0001, and 3.0 +/- 1.3 vs. 2.8 +/- 1.0; P < 0.05, respectively). Early and delayed SUVmax and %DeltaSUVmax in metastatic LNs were significantly higher than those in benign LNs (P < 0.0001). The optimal parameter for the differentiation was the combined use of early SUVmax > 3.0 or delayed SUVmax > 4.0, yielding sensitivity of 88.8%, specificity of 80.6%, accuracy of 86.2%, negative predictive value of 76.9%, and positive predictive value of 90.6%. It provided better results than the use of early SUVmax > 3.0 alone (P = 0.019) or the optimal parameter for %DeltaSUVmax (>5%) (P = 0.012). However, 12 (19.3%) benign LNs were indistinguishable from metastatic LNs. CONCLUSIONS: Although dual-time point PET/CT scan enhances the difference of FDG uptake between FDG-avid metastatic and benign LNs and improves the differentiation when compared with a single scan, biopsy procedure may be still required for accurate assessment of LN status in patients with NSCLC and possible etiologies showing intensive FDG uptake in benign LNs.

Dual-time point 18F-FDG PET/CT scan for differentiation between 18F-FDG-avid non-small cell lung cancer and benign lesions.

OBJECTIVE: The aim of this study is to clarify the difference of F-18 FDG uptake kinetics between FDG-avid non-small-cell lung cancer (NSCLC) and benign lesions associated with various etiologies on dual-time point PET/CT scan, and to determine the optimal parameter for differentiation. MATERIALS AND METHODS: The materials were 76 FDG-avid solitary NSCLC in 76 patients and 57 FDG-avid solitary benign lesions associated with various etiologies in 61 patients. FDG PET/CT scan was performed at 60 and 120 min after intravenous injection of 4.4 MBq/kg F-18 FDG. The maximum standardized uptake value (SUVmax) on early and delayed scans and the percent change of SUVmax (%DeltaSUVmax) between the two time points were measured. The optimal differential parameter was determined by receiver-operating characteristic curve analysis and evaluation of diagnostic accuracy. RESULTS: The mean +/- SD of early SUV max, delayed SUVmax and %DeltaSUVmax were 8.3 +/- 5.2, and 10.2 +/- 6.5, and 21.9% +/- 18.9 in FDG-avid NSCLC, and 3.8 +/- 3.2, 4.0 +/- 3.7, and 11.3% +/- 26.0 in FDG-avid benign lesions, respectively. Delayed SUVmax in NSCLC was significantly higher than early SUVmax (P < 0.0001); while not different in benign lesions. Percent change of SUVmax in NSCLC was also significantly higher than that in benign lesions (P < 0.01). The optimal parameter for the differentiation was delayed SUVmax > 5.5 and yielded sensitivity of 77.6%, specificity of 80.7% and accuracy of 78.9%, which provided better differentiation than the use of %DeltaSUVmax or the traditional parameter of early SUVmax > 2.5. However, 11 (19.2%) benign lesions were indistinguishable from NSCLC. CONCLUSION: Although delayed PET/CT scan enhances the difference of FDG uptake between FDG-avid NSCLC and benign lesions, and the use of delayed SUVmax > 5.5 appears to improve the differentiation of these hypermetabolic lesions compared with an early scan, careful interpretation and management for correct differentiation are still required.