Severe bronchoconstriction due to sarcoid-like reaction to lung cancer.

Chest radiography in a 59-year-old woman with recurrent pneumonia showed infiltrates in her left upper lung field. Fiberoptic bronchoscopy and chest computed tomography revealed severe constriction in the upper bronchus and a nodule in the left upper lobe. After lobectomy, adenocarcinoma was confirmed, with multiple non-caseating granulomas in the lung parenchyma and lymph nodes. Bronchial constriction was thought to be due to a sarcoid-like reaction secondary to lung cancer, leading to granuloma formation.

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.

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.

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.

Serotonin and melatonin, neurohormones for homeostasis, as novel inhibitors of infections by the intracellular parasite chlamydia.

OBJECTIVES: Chlamydiae are obligate intracellular bacteria, causing a variety of diseases, i.e. pneumonia, sexually transmitted disease, conjunctivitis and zoonosis. Tryptophan depletion by interferon-gamma (IFN-gamma) is the most important host defence system against chlamydial infection. Thus chlamydial tryptophan metabolism is thought to play key roles for IFN-gamma resistance, persistent infection and host/tissue tropisms. We tested tryptophan derivatives for activity against chlamydia-infected cells. METHODS: Rates of chlamydial infection and sizes of the inclusions were evaluated by in vitro infection using three Chlamydiaceae species, Chlamydia trachomatis, Chlamydophila pneumoniae and Chlamydophila felis, which show significant divergence of tryptophan synthesis genes and different susceptibilities to IFN-gamma. RESULTS: Melatonin and serotonin, which are recognized as neural hormones for maintenance of organism homeostasis, reduced chlamydial infection but not other bacterial growth tested here. Unlike IFN-gamma, melatonin limited infection of all three chlamydiae and the effects were not recovered by tryptophan supplementation. Melatonin treatment only of host cells could diminish infection and the infection reduction was neutralized by a pertussis toxin, an inhibitor of G proteins. Ligands of melatonin and serotonin receptors also hampered infection. CONCLUSIONS: Inhibition mechanisms of chlamydial infection by melatonin and serotonin appear to be different from those of IFN-gamma and involve specific G-protein-coupled receptors. Melatonin is deemed to inhibit early progression of the chlamydial development cycle, such as establishment of intracellular infection and/or conversion from elementary body to reticulate body. Utilization of melatonin, serotonin or their derivatives may be advantageous for harmless prevention of chlamydial infection.