Crucial involvement of the CCL3-CCR5 axis-mediated fibroblast accumulation in colitis-associated carcinogenesis in mice

Patients with inflammatory bowel diseases often develop colon carcinoma. Combined treatment of azoxymethane (AOM) and dextran sulfate sodium (DSS) recapitulates colitis-associated cancer in mice. AOM/DSS-induced tumor formation was reduced in CCL3- or its specific receptor, CCR5-deficient mice despite the presence of a massive infiltration of inflammatory cells. However, AOM/DSS-induced type I collagen-positive fibroblast accumulation in the colon was reduced in CCL3- or CCR5-deficient mice. This was associated with depressed expression of heparin-binding epidermal growth factor-like growth factor (HB-EGF), which is expressed mainly by fibroblasts. Moreover in vitro, CCL3 induced fibroblasts to proliferate and to enhance HB-EGF expression. Furthermore, CCR5 blockade reduced tumor formation together with reduced fibroblast accumulation and HB-EGF expression, even when administered after the development of multiple colon tumors. Thus, CCL3-CCR5-mediated fibroblast accumulation may be required, in addition to leukocyte infiltration, to induce full-blown colitis-associated carcinogenesis. Our studies shed light on a therapeutic potential of CCR5 antagonist for patients with colitis-associated cancer. What\u27s new? Inflammation of the bowel can lead to cancer, in some cases. By learning how one leads to the other, researchers hope to find a way to stave off this progression. Previously, it\u27s been observed that these cancers have a lot of chemokine CCL3 hanging around. In this paper, the authors replicated these colitis-induced cancers in mice and investigated what CCL3 was doing. They learned that CCL3 and its receptor, CCR5, gather up cancer-associated fibroblasts, which promote transformation and tumor growth. Leukocyte infiltration wasn\u27t enough, they found; without CCL3 and CCL5 bringing in fibroblasts, the tumor development slowed. © 2014 UICC

Susceptibility to oxygen desaturation during bronchoscopy in elderly patients with pulmonary fibrosis

Background: Fiber-optic flexible bronchoscopy (FFB) is a frequently performed procedure for the diagnosis and treatment of pulmonary disorders. However, hypoxemia occasionally occurs during FFB. Objectives: We attempted to examine the causes of arterial oxygen desaturation during FFB. Methods: We studied 336 patients who underwent FFB without intervention between June 1, 2001 and September 30, 2002. Arterial oxygen saturation (SpO2) was continuously monitored using oximetry with a recording system. We analyzed the relationship between a reduction in SpO2 during FFB and various clinical parameters or background lung diseases. Results: Of the 336 patients, 73 (22%) had an episode of oxygen desaturation (SpO2 <90% over 10 s). Of patients over 80 years old, 55% had an episode of oxygen desaturation, which was significantly higher than 27% observed in the patients of 80 and less than 80 years old (p < 0.05). Patients with pulmonary fibrosis had a higher risk of desaturation (55%) compared to patients with other complications or patients without any complication (p < 0.05). Multivariable analysis revealed that both age and pulmonary fibrosis were independent predictors of oxygen desaturation. However, the majority of the patients (94%) did not require routine oxygen supplementation. Conclusion: Although FFB is safe and does not require oxygen supplementation in most cases, age over 80 years and pulmonary fibrosis are high risk factors for significant oxygen desaturation during FFB. Copyright © 2006 S. Karger AG, Base

EBUS-GS and VBN for GGO lesions

Background: Endobronchial ultrasonography with guide sheath (EBUS-GS) could be useful for diagnosing ground-glass opacity (GGO) predominant-type lesions in the peripheral lung. Furthermore, several studies have reported that transbronchial biopsy using EBUS-GS and virtual bronchoscopic navigation (VBN) was safe and effective for diagnosing small peripheral lung lesions. Our objectives were to diagnose solitary peripheral GGO predominant-type lesions by transbronchial biopsy using EBUS-GS and VBN under radiographic fluoroscopic guidance, and to evaluate the clinical factors associated with diagnostic yield. Methods: The medical records of 169 patients with GGO predominant-type lesions who underwent transbronchial biopsy using EBUS-GS and VBN under radiographic fluoroscopic guidance were retrospectively reviewed. Results: Endobronchial ultrasonography images could be obtained for 156 (92%) of 169 GGO predominant-type lesions, and 116 (69%) were successfully diagnosed by this method (20 of 31 pure GGO lesions [65%]; 96 of 138 mixed GGO predominant-type lesions [70%]). The mean size of diagnosed lesions was significantly larger than that of nondiagnosed lesions (22 mm versus 18 mm, p < 0.01). Regarding diagnostic yield based on computed tomography sign, cases with presence of a bronchus leading directly to a lesion had significantly higher diagnostic yield than the other lesions (p < 0.01). Conclusions: The addition of VBN to EBUS-GS could be useful in clinical practice for diagnosing GGO predominant-type lesions in the peripheral lung

Combining transbronchial biopsy using endobronchial ultrasonography with a guide sheath and positron emission tomography for the diagnosis of small peripheral pulmonary lesions

To evaluate the combination of transbronchial biopsy (TBB) using endobronchial ultrasonography with a guide sheath (EBUS-GS) and positron emission tomography with fluorodeoxyglucose (FDG-PET) for the diagnosis of small peripheral pulmonary lesions (PPLs) 20 mm and ≤30 mm and for malignant lesions. Combination of TBB using EBUS-GS and FDG-PET is useful for the diagnosis of small PPLs

Impact of histamine type-2 receptor antagonists on the anticancer efficacy of gefitinib in patients with non-small cell lung cancer

Purpose Gefitinib is one of the standard treatments for non-small cell lung cancer (NSCLC) with epidermal growth factor receptor mutations. It has been reported that acid suppressants (AS) decrease the anti-tumor effect of gefitinib by reducing its solubility. AS is sometimes necessary in cancer patients; however, previous reports have not shown the most compatible AS with gefitinib administration in cancer patients. This study was conducted to determine if histamine type 2 receptor antagonists (H2RAs) can affect the anti-tumor efficacy of gefitinib. Methods Eighty-seven patients with NSCLC who were administered gefitinib were retrospectively investigated. Patients who were co-administered H2RA were compared with non-AS control patients. H2RA was administered once a day at about 3-5 or 8-12 h after gefitinib intake. The primary endpoint of this study was progression-free survival (PFS), and secondary endpoints were overall survival (OS), overall response rate (ORR), and adverse effects. Results Median PFS in H2RA group and control group was 8.0 months and 9.0 months, respectively, with no significant difference (p = 0.82). The incidence of liver dysfunction was significantly less in patients administered H2RA, whereas there were no differences between the two groups with regard to skin toxicity and diarrhea. Multivariate analysis suggested that H2RA co-administration is not a risk factor for worse PFS and OS (hazard ratio of 0.95, 0.86; 95% confidence interval of 0.60-1.48, 0.52-1.43;p = 0.82 and 0.60, respectively). Conclusion This study demonstrated that concomitant administration of H2RA with gefitinib does not affect the efficacy of gefitinib

Stereotactic body radiotherapy using gated radiotherapy with real-time tumor-tracking for stage I non-small cell lung cancer

Background: To clarify the clinical outcomes of two dose schedule of stereotactic body radiotherapy (SBRT) for stage I non-small cell lung cancer (NSCLC) using a real-time tumor-tracking radiation therapy (RTRT) system in single institution. Methods: Using a superposition algorithm, we administered 48 Gy in 4 fractions at the isocenter in 2005-2006 and 40 Gy in 4 fractions to the 95% volume of PTV in 2007-2010 with a treatment period of 4 to 7 days. Target volume margins were fixed irrespective of the tumor amplitude. Results: In total, 109 patients (79 T1N0M0 and 30 T2N0M0). With a median follow-up period of 25 months (range, 4 to 72 months), the 5-year local control rate (LC) was 78% and the 5-year overall survival rate (OS) was 64%. Grade 2, 3, 4, and 5 radiation pneumonitis (RP) was experienced by 15 (13.8%), 3 (2.8%), 0, and 0 patients, respectively. The mean lung dose (MLD) and the volume of lung receiving 20 Gy (V20) were significantly higher in patients with RP Grade 2/3 than in those with RP Grade 0/1 (MLD p = 0.002, V20 p = 0.003). There was no correlation between larger maximum amplitude of marker movement and larger PTV (r = 0.137), MLD (r = 0.046), or V20 (r = 0.158). Conclusions: SBRT using the RTRT system achieved LC and OS comparable to other SBRT studies with very low incidence of RP, which was consistent with the small MLD and V20 irrespective of tumor amplitude. For stage I NSCLC, SBRT using RTRT was suggested to be reliable and effective, especially for patients with large amplitude of tumor movement