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Gut dysbiosis caused by antibiotics impairs response to immune checkpoint blockade (ICB). Gut microbiota is becoming an attractive therapeutic target for cancer. The Clostridium butyricum MIYAIRI 588 strain is a probiotic therapy used to improve symptoms related to antibiotic-induced dysbiosis in Japan. We hypothesized that probiotic Clostridium butyricum therapy (CBT) may affect the therapeutic efficacy of ICBs. We retrospectively evaluated 118 patients with advanced non–small cell lung cancer treated with ICBs at Kumamoto University Hospital (Kumamoto-shi, Kumamoto, Japan). Survival analysis comparing patients given CBT before and/or after ICB was conducted using univariate analyses and Cox proportional hazards regression models using propensity score. Propensity score analyses confirmed that probiotic CBT significantly prolonged progression-free survival (PFS) and overall survival (OS). Probiotic CBT significantly associated with longer PFS and OS even in patients who received antibiotic therapy. This study suggests that probiotic CBT may have a positive impact on therapeutic efficacy of ICB in patients with cancer. See articles by Hakozaki et al., p. 1243, and Peng et al., p. 1251

We examined whether fluorine-18 2-fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) performed before chemotherapy could predict the onset of acute exacerbation of interstitial lung disease (AE-ILD) in patients with lung cancer and ILD treated with chemotherapy. Thirty-three patients with lung cancer and ILD who underwent 18F-FDG PET/CT and were treated with chemotherapy at Kumamoto University Hospital between April 2006 and March 2018 were retrospectively analyzed. The maximum standardized uptake value (SUVmax) of interstitial lesions was measured to quantify the background ILD activity. A prediction model of AE-ILD was developed using logistic regression analyses for the SUVmax, and receiver operating characteristic (ROC) curve analyses were conducted. Among the 33 patients, 7 experienced AE-ILD. The SUVmax of contralateral interstitial lesions was significantly higher in patients with vs. without AE-ILD (median SUVmax: 2.220 vs. 1.795, P = 0.025). Univariable logistic regression analyses showed that the SUVmax of contralateral interstitial lesions trended towards being significantly associated with the onset of AE-ILD [odds ratio: 8.683, 95% confidence interval (CI) 0.88–85.83, P = 0.064]. The area under the ROC curve of the SUVmax for predicting AE-ILD was 0.780 (95% CI 0.579–0.982, P = 0.025). The optimal cut-off value for SUVmax was 2.005, with sensitivity and specificity values of 0.857 and 0.769, respectively. The SUVmax of contralateral interstitial lesions in 18F-FDG PET/CT images might be useful for predicting the onset of AE-ILD in patients with lung cancer and ILD treated with chemotherapy.

Lung cancer patients have a high risk of cerebral infarction, but the clinical significance of cerebral infarction in advanced non-small cell lung cancer (NSCLC) remains unclear. This study aimed to comprehensively investigate the incidence, prognostic impact, and risk factors of cerebral infarction in patients with NSCLC.We retrospectively examined 710 consecutive patients with advanced or post-operative recurrent NSCLC treated between January 2010 and July 2020 at Kumamoto University Hospital. Cerebral infarction was diagnosed according to the detection of high-intensity lesions on diffusion-weighted magnetic resonance imaging regardless of the presence of neurological symptoms during the entire course from 3 months before NSCLC diagnosis. The prognostic impact and risk factors of cerebral infarction were evaluated based on propensity score matching (PSM) and multivariate logistic regression analysis.Cerebral infarction occurred in 36 patients (5%). Of them, 21 (58%) and 15 (42%) patients developed asymptomatic and symptomatic cerebral infarction, respectively. PSM analysis for survival showed that cerebral infarction was an independent prognostic factor (hazards ratio: 2.45, 95% confidence interval (CI): 1.24-4.85, P = 0.010). On multivariate logistic regression analysis, D-dimer (odds ratio [OR]: 1.09, 95% CI 1.05-1.14, P 0.001) and C-reactive protein (OR: 1.10, 95% CI 1.01-1.19, P = 0.023) levels were independent risk factors.Cerebral infarction occurred in 5% of NSCLC patients, and asymptomatic cerebral infarction was more frequent. Cerebral infarction was a negative prognostic factor and was associated with hyper-coagulation and inflammation. The high frequency of asymptomatic cerebral infarction and its risk in NSCLC patients with these conditions should be recognized.

BACKGROUND/AIM The impact of interstitial lung disease (ILD) on the clinical outcome of patients with small-cell lung cancer (SCLC) is not fully understood. The aim of this study was to investigate the impact of ILD on treatment and survival outcomes of SCLC patients. PATIENTS AND METHODS A retrospective analysis was performed on the clinical outcomes of SCLC patients, treated with chemotherapy, with or without ILD ([ILD group (n=16) and non-ILD group (n=51)]. RESULTS Median PFS and OS were significantly shorter in the ILD group than in the non-ILD group (median PFS, 184 vs. 290 days, p=0.008; median OS, 236 vs. 691 days, p

Objectives With the aim of searching for novel oncofetal tumor biomarkers of lung adenocarcinoma other than carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP), we developed a strategy involving monoclonal antibodies generated from embryonic tissue of miniature swine. Materials and methods Using immunohistochemistry, we selected suitable hybridoma clones that were reactive against swine fetal lung but not adult lung using tissue microarray loading of human normal lung, lung cancer, and fetal and adult swine tissues. Results The selected clones included several that were uniquely reactive against both swine fetal lung and human lung adenocarcinoma, and protein microarray revealed that the antigen they recognized was "drebrin" ( DBN1 ). We then examined the association between the pattern of drebrin expression and the clinicopathological characteristics of lung adenocarcinoma using surgically resected samples of human lung adenocarcinoma. Two hundred formalin-fixed and paraffin-embedded tumor samples were immunostained for drebrin using clone B246, one of the clones that were reactive against drebrin. The cases were divided into those with strong (n=85) and weak (n=115) drebrin expression. In terms of disease-free survival, cases showing strong drebrin expression had a significantly poorer prognosis than those with weak drebrin expression (p=0.033). Conclusion The present findings indicate that "drebrin" is a unique oncofetal protein that can be applied as a new biomarker of lung adenocarcinoma.

Backgrounds Adenocarcinoma in situ (AIS) of the lung has an extremely favorable prognosis. However, early but invasive adenocarcinoma (eIA) sometimes has a fatal outcome. We had previously compared the expression profiles of AIS with those of eIA showing lymph node metastasis or a fatal outcome, and found that stratifin (SFN, 14-3-3 sigma) was a differentially expressed gene related to cell proliferation. Here, we performed an in vivo study to clarify the role of SFN in initiation and progression of lung adenocarcinoma. Findings Suppression of SFN expression in A549 (a human lung adenocarcinoma cell line) by siSFN significantly reduced cell proliferation activity and the S-phase subpopulation. In vivo, tumor development or metastasis to the lung was reduced in shSFN-transfected A549 cells. Moreover, we generated SFN-transgenic mice (Tg-SPC-SFN+/−) showing lung-specific expression of human SFN under the control of a tissue-specific enhancer, the SPC promoter. We found that Tg-SPC-SFN+/− mice developed lung tumors at a significantly higher rate than control mice after administration of chemical carcinogen, NNK. Interestingly, several Tg-SPC-SFN+/− mice developed tumors without NNK. These tumor cells showed high hSFN expression. Conclusion These results suggest that SFN facilitates lung tumor development and progression. SFN appears to be a novel oncogene with potential as a therapeutic target. Electronic supplementary material The online version of this article (doi:10.1186/s12943-015-0414-1) contains supplementary material, which is available to authorized users.

Vascular invasion (VI) has been accepted as a universally important prognostic factor for patients with lung carcinoma. However, the clinical significance of VI in each of the histological subtypes has been unclear. The aim of the present study was to investigate differences in the clinicopathological implications of VI between adenocarcinoma and squamous cell carcinoma.A total of 336 patients were evaluated, of whom 81 were diagnosed as having peripheral-type squamous cell carcinoma, and 255 as having adenocarcinoma.Among the 336 patients, the five-year survival rates for those who were VI-positive and VI-negative were 38.4% and 76.3%, respectively, the difference being significant (p0.0001). Multivariate analysis identified VI as an independent prognostic factor (hazard ratio: 1.86). Although the difference in cancer-free survival between VI-positive and -negative patients was statistically significant for adenocarcinoma (p0.0001), it was not significant for squamous cell carcinoma (p=0.086). For adenocarcinoma, the difference between the survival curves for VI-positive and -negative patients was significant for the subtypes with a predominant lepidic (p0.0001), papillary (p=0.0026), and acinar (p=0.0060) component, whereas that for the predominantly solid subtype was not significant (p=0.58). Squamous cell carcinomas were then divided into two groups on the basis of the diameter of vessels that had been invaded by the cancer cells: large-vessel invasion (LVI; 1000 μm or more) and small-vessel invasion (SVI; less than 1000 μm). Although there was no difference in the survival curves between the LVI and SVI groups, the LVI group showed a significantly higher incidence of cavity formation and distant metastasis.We conclude that VI is a useful prognostic indicator in lung carcinoma, although the clinical implications of VI differ between adenocarcinoma and squamous cell carcinoma.