Background Low dose computed tomography (LDCT) for lung cancer screening is widely employed in China as a result of increasing cancer screening awareness. Although some pulmonary lesions detected by LDCT are cancerous, most of the pulmonary nodules are benign. It is important to make effective preoperative differentiation of pulmonary lesions and to obviate the need for surgery in some patients with benign disease. Methods From January 1, 2017 to December 31, 2018, patients in our institution with surgical pathology confirmed benign pulmonary lesions in which malignancy could not be excluded in preoperative assessment were enrolled in this study. Retrospective analysis of clinical data was conducted. Results 297 cases were collected in this study. Prevalence of benign disease in patients underwent resection for focal pulmonary lesions is 9.8% in our institution. In 197 patients (66.3%), pulmonary lesions were detected by LDCT screening. A total of 323 assessable pulmonary lesions were detected by chest CT. The average diameter of pulmonary lesions was (17.9±12.1) mm, and 91.0% of which were greater than or equal to 8 mm. Solid nodules accounted for 65.6% of these lesions. Imaging characteristics suggesting malignancy were common, including spicule sign (71/323, 22.0%), lobulation (94/323, 29.1%), pleural indentation (81/323, 25.1%), vascular convergence sign (130/323, 40.2%) and vacuole sign (23/323, 7.1%). 292 patients (98.3%) underwent video-assisted thoracoscopic surgery (VATS). Pulmonary wedge resection was performed in 232 cases (78.1%), segmental resection in 13 cases (4.4%) and lobotomy in 51 cases (17.2%). Surgical complications occurred in 4 patients (1.3%). The most frequent findings on surgical pathology analysis were: infectious lesions in 98 cases (33.0%), inflammatory nodules in 96 cases (32.3%), and hamartoma in 64 cases (21.5%). Conclusions Solid nodules accounted for most of these benign pulmonary lesions in which malignancy could not be excluded preoperatively, and imaging characteristics suggesting malignancy were common. VATS is an important biopsy method to identify etiology and pathology for lesions. The most frequent benign pulmonary diseases that are suspected to be malignant and underwent surgical resection are: infectious lesions, inflammatory nodules and hamartoma.
The utility of circulating tumor cells (CTCs) as prognostic biomarkers in non-small cell lung cancer (NSCLC) is inconclusive due to the limitations of current CTC detection methods. Using a novel high-efficiency detection method, we determined the ability of CTCs to predict survival and chemotherapeutic responses in NSCLC. In 127 patients with advanced NSCLC, CTCs were counted and analyzed at baseline and during follow-up. Median overall survival (OS) and progression-free survival (PFS) were longer in patients with baseline CTC counts <8 CTCs/3.2 mL (20.0 vs. 10.4 months [P = 0.009] and 7.2 vs. 5.5 months [P < 0.001], respectively). Patients with post-treatment increases in the CTC count had poorer OS and PFS than those without increases (12.0 vs. 13.3 months [P = 0.028] and 5.2 vs. 6.4 months [P = 0.022], respectively). There was no association between the baseline CTC count and chemotherapeutic response (P = 0.734). However, the rate of progressive disease in patients with and without post-treatment increases in the CTC count were 15.6% and 2.4% (P = 0.042), respectively. The baseline CTC count and the change in the CTC count during treatment were both valuable prognostic indicators for NSCLC.
Intradural extramedullary spinal cord metastases in lung cancer is rare, and it leads to severe neurological damage. The aim of this study is to identify the clinical features of intradural extramedullary spinal cord metastases in primary lung cancer patients.The 8 cases of lung cancer with intradural extramedullary metastases, who were hospitalized in Peking Union Medical College Hospital (PUMCH) during May 2013 to May 2016, were enrolled in the retrospective study. Medical charts of the 8 patients were reviewed systematically.Intradural extramedullary spinal cord metastases was diagnosed in 7 cases with non-small cell lung cancer (NSCLC) and 1 case with small cell lung cancer (SCLC). Cauda equina syndrome was the most common clinical manifestation. Malignant cells in cerebrospinal fluid were positive in all the 5 cases (100%) who underwent lumbar puncture. Contrast-enhanced magnetic resonance imaging (MRI) of spine manifested as diffuse abnormal enhancement of pial lining of spinal cordin 3 cases, intradural extramedullary nodules in 4 cases, and both of them in 1 case. Neurological symptoms were improved or stable in 4 cases who underwent targeted therapy and/or radiotherapy. The median overall survival was 5.8 months.Intradural extramedullary spinal cord metastases can be diagnosed with caution according to its neurological symptoms and contrast-enhanced MRI presentation.Targeted therapy and/or radiotherapy may be effective for symptoms control.背景与目的 肺癌硬膜下脊髓外转移罕见，可导致严重的神经损害，本研究旨在阐明其临床特征。方法 2013年5月-2016年5月，北京协和医院8例确诊硬膜下脊髓外转移肺癌患者纳入该研究，系统回顾分析临床资料。结果 7例非小细胞肺癌及1例小细胞肺癌合并硬膜下脊髓外转移。马尾综合征是最常见的临床表现。行腰椎穿刺的5例（100%）患者脑脊液找到肿瘤细胞。脊髓增强核磁（magnetic resonance imaging, MRI）发现，3例软脊膜弥漫线样增强，4例硬膜下脊髓外多发结节，1例具有上述两种表现。4例接受靶向治疗和/或放疗患者神经系统症状改善或稳定。中位生存时间是5.8个月。结论 硬膜下脊髓外转移需依靠神经系统症状及增强MRI影像学检查诊断。靶向治疗和/或放疗可能有效。.
This study compared the accuracy of predicting transarterial chemoembolization (TACE) outcomes for hepatocellular carcinoma (HCC) patients in the four different classifiers, and comprehensive models were constructed to improve predictive performance.The subjects recruited for this study were HCC patients who had received TACE treatment from April 2016 to June 2021. All participants underwent enhanced MRI scans before and after intervention, and pertinent clinical information was collected. Registry data for the 144 patients were randomly assigned to training and test datasets. The robustness of the trained models was verified by another independent external validation set of 28 HCC patients. The following classifiers were employed in the radiomics experiment: machine learning classifiers k-nearest neighbor (KNN), support vector machine (SVM), the least absolute shrinkage and selection operator (Lasso), and deep learning classifier deep neural network (DNN).DNN and Lasso models were comparable in the training set, while DNN performed better in the test set and the external validation set. The CD model (Clinical & DNN merged model) achieved an AUC of 0.974 (95% CI: 0.951-0.998) in the training set, superior to other models whose AUCs varied from 0.637 to 0.943 (p < 0.05). The CD model generalized well on the test set (AUC = 0.831) and external validation set (AUC = 0.735).DNN model performs better than other classifiers in predicting TACE response. Integrating with clinically significant factors, the CD model may be valuable in pre-treatment counseling of HCC patients who may benefit the most from TACE intervention.
Immunotherapy has dramatically revolutionized the therapeutic landscape for patients with cancer. Although immune checkpoint inhibitors are now accepted as effective anticancer therapies, they introduce a novel class of toxicity, termed immune-related adverse events, which can lead to the temporary or permanent discontinuation of immunotherapy and life-threatening tumor progression. Therefore, the effective prevention and treatment of immune-related adverse events is a clinical imperative to maximize the utility of immunotherapies. Immune-related adverse events are related to the intestinal microbiota, baseline gut microbiota composition is an important determinant of immune checkpoint inhibitor-related colitis, and antibiotics exacerbate these undesirable side-effects. Supplementation with specific probiotics reduces immune checkpoint inhibitor-related colitis in mice, and fecal microbiota transplantation has now been shown to effectively treat refractory immune checkpoint inhibitor-related colitis in the clinic. Hence, modifying the microbiota holds great promise for preventing and treating immune-related adverse events. Microbiomes and their metabolites play important roles in the potential underlying mechanisms through interactions with both innate and adaptive immune cells. Here we review the gut microbiota and immune regulation; the changes occurring in the microbiota during immune checkpoint inhibitor therapy; the relationship between the microbiota and immune-related adverse events, antibiotics, probiotics/prebiotics, and fecal microbiota transplantation in immune checkpoint inhibitor-related colitis; and the protective mechanisms mediated by the microbiome and metabolites in immune-related adverse events.
Peripheral blood-based biomarkers (PBB) predicting response, survival and immune-related adverse events (irAEs) in patients with advanced non-small cell lung cancer (NSCLC) treated with immune checkpoint inhibitors (ICIs) are still a matter of debate. Thus, we investigated the associations between PBB, the efficacy of ICIs and the incidence of irAEs.Patients with advanced NSCLC, who had been treated at Peking Union Medical College Hospital and received ICIs or chemoimmunotherapy from January 2015 to December 2020, were retrospectively identified. PBBs results were retrieved from medical records. Associations with overall response rate, survival, and incidence of irAEs were assessed using Kruskal-Wallis, Kaplan-Meier analysis, Pearson's chi-squared and Student's t-tests as required. Cox proportional hazards and logistic regression models were used to determine independent risk factors. Analyses were performed on the whole population (n=103), patients receiving ICIs only (n=32), and patients receiving chemoimmunotherapy (n=71). Changes in pretreatment and on-treatment PBB were also analyzed.Among 103 patients, 38 (36.9%) developed irAEs. Pretreatment absolute lymphocyte count (ALC) was related to an increased risk of irAEs in the whole population [odds ratio (OR), 2.165; 95% confidence interval (CI): 1.040 to 4.509, P=0.039] and patients receiving ICIs only (OR, 6.461; 95% CI: 1.067 to 39.112; P=0.042). A low prognostic nutritional index (PNI ≤45) was associated with worse progression-free survival (PFS) and overall survival (OS) in the whole population, in patients receiving ICIs only, and in patients receiving chemoimmunotherapy. High pretreatment interleukin (IL)-6 was associated with both worse PFS and OS in the whole population (IL-6 >13.80 pg/mL), in patients receiving ICIs only (IL-6 >11.30 pg/mL), and in patients receiving chemoimmunotherapy (IL-6 >11.85 pg/mL). Increase of IL-6 during treatment was associated with inferior OS in the whole population (P<0.001).Pretreatment ALC has the potential to predict irAEs in patients with advanced NSCLC treated with ICIs. Additionally, a low level of pretreatment PNI and high level of IL-6 may be associated with shorter survival.
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