Bioresorbable Scaffolds: Current Evidence and Ongoing Clinical Trials

Bioresorbable scaffolds (BRS) represent a novel approach in coronary stent technology. In contrast to the metallic stents, they provide transient scaffolding, thereby safeguarding early vessel patency and acute gain. Subsequently a process of "decomposition" occurs, that results in the complete absorption of the scaffold. This reduces the risk of late complications, allowing the vessel to maintain its integrity and physiological function. This unique ability has attracted interest and nowadays several BRS are available. The aim of this review article is to describe the advances in the field, present the evidence from the preclinical and clinical evaluation of these devices, and provide an overview of the ongoing clinical trials that were designed to examine the effectiveness of BRS in the clinical setting.     

Pulmonary Toxicities of Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials

Gefitinib is a selective tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) used to treat adults with EGFR mutation-positive non-small-cell lung cancer (NSCLC). Clinical benefits of gefitinib administration in NSCLC patients have been observed in clinical practice, but the extent of the pulmonary toxicity of gefitinib in patients with advanced NSCLC remains unclear.The aim of this systematic review was to evaluate the overall incidence and risk of gefitinib-related pulmonary toxicity in advanced NSCLC patients.Relevant trials were identified from the databases of Pubmed, Embase, Cochrane Library, and the clinicaltrials.gov of the U.S. National Institutes of Health. The outcomes included the overall incidence, odds ratios (ORs), and 95% confidence intervals (CIs). Fixed-effects models were used in the statistical analyses according to the heterogeneity of the included studies.According to the data from the included trials, the overall incidence of high-grade hemoptysis, pneumonia, pneumonitis, and interstitial lung disease (ILD) was 0.49% (95% CI: 0.24%–0.99%), 2.33% (95% CI: 1.47%–3.66%), 2.24% (95% CI: 1.34%–3.72%), and 1.43% (95% CI: 0.98%–2.09%), respectively. The pooled ORs of high-grade hemoptysis, pneumonia, pneumonitis, and ILD were 1.73 (95% CI: 0.46–6.52; P = 0.42), 0.99 (95% CI: 0.66–1.49; P = 0.95), 4.70 (95% CI: 1.48–14.95; P = 0.0087), and 2.64 (95% CI: 1.22–5.69; P = 0.01), respectively.Gefitinib was associated with a significantly increased risk of high-grade/fatal ILD and pneumonitis compared with the controls, whereas the risk of other high-grade pulmonary events (pneumonia and hemoptysis) was not significant. Careful surveillance of gefitinib-related pulmonary toxicity is critical for the safe use of this drug.     

对肺癌患者检测血清肿瘤标志物的临床价值和意义

目的:分析血清肿瘤标志物的检测对肺癌临床诊断的价值及意义.方法:选取112例肺癌患者作为研究组,另选取104例肺良性疾病患者作为对照组,两组患者均给予化学发光法进行癌胚抗原(CEA)、糖类抗原19-9 (CA19-9)、糖类抗原125 (CA125)、糖类抗原15-3 (CA15-3)、细胞角蛋白19片段(Cyfra21-1)、血清神经元特异性烯醇化酶(NSE)、恶性肿瘤生长因子(TSGF)7种血清肿瘤标志物的检测.结果:研究组的7种血清肿瘤标志物水平与对照组相比,有统计学意义(P＜0.05);鳞癌患者的Cyfra21-1阳性率显著高于腺癌患者,且CEA、CA125、CA15-3阳性率显著低于腺癌患者,有统计学意义(P＜0.05);非小细胞肺癌(NSCLC)患者CA19-9、CAl25、CA15-3的阳性率显著高于小细胞肺癌(SCLC)患者,有统计学意义(P＜0.05); NSCLC患者的NSE阳性率显著低于SCLC患者,有统计学意义(P＜0.05);7种血清肿瘤标志物联合检测的灵敏度为91.07％、特异度为86.54％、准确度为88.89％,均显著高于任意单项检测,有统计学意义(P＜0.05).结论:对肺癌患者进行多种血清肿瘤标志物联合检测,能有效提高肺癌诊断的灵敏度、特异度及准确度,有利于为临床肺癌的鉴别与诊断提供更多的依据,从而减少临床误诊、漏诊等情况的发生.     

Clinical Outcome of Stage III Non-small-cell Lung Cancer Patients After Definitive Radiotherapy

Primarily combined radiotherapy and chemotherapy are used to treat unresectable non-small-cell lung cancer; however, the results are not satisfactory. In this study treatment results were retrospectively analyzed and the prognostic factors related to survival were identified. From March 1999 to January 2004, 102 patients with stage IIIA/IIIB non-small-cell lung cancer received definitive radiotherapy with or without chemotherapy. Radiotherapy involved a daily dose of 1.8–2.0 Gy five times a week; 60 Gy was set as the total dose. Maximal chemotherapy was given to patients with normal kidney, liver, and bone marrow functions. The 5-year overall survival rate was 22.2%; the median survival was 18 months. The median follow-up of surviving patients was 53 months. The complete or partial response rate was 85%. At the time of the last follow-up, 21 patients were alive and 81 patients had died, including 5 patients who had died due to radiation pneumonitis. There were significant differences in survival and in the fatal radiation pneumonitis rate between patients with superior lobe lesions and those with middle or inferior lobe lesions. Patients whose primary tumor is located in the superior lobe appear to have a better clinical outcome.     

Clusterin Immunoexpression and its Clinical Significance in Patients with Non-Small Cell Lung Cancer

Clusterin is an enigmatic glycoprotein with a nearly ubiquitous tissue distribution. It plays important roles in various pathophysiological processes, including tissue remodeling, reproduction, lipid transport, complement regulation, and apoptosis. Clusterin appears to have two main isoforms that result from alternative splicing. The secreted and nuclear forms of clusterin have been reported to play different roles in human malignancies. The purpose of this study was to examine clusterin immunoexpression and its clinical significance in a group of Chinese patients with non-small cell lung cancer (NSCLC). Tissue samples from the primary tumors of 121 patients with completely resected NSCLC were obtained. Clusterin protein expression was evaluated by immunohistochemical staining with an antibody against all clusterin isoforms. Staining patterns were observed and graded based on intensity and density and were correlated with clinical and pathological data. Both cytoplasmic and nuclear clusterin immunostaining patterns were observed. Clusterin staining was observed only in the cytoplasm in 70 patients (57.9%), only in the nucleus in 27 patients (22.3%), and in both the cytoplasm and nucleus in 16 patients (13.2%). A significant association was observed between positive cytoplasmic clusterin expression and histologic type as indicated by adenocarcinomas that were more likely to have clusterin staining only in the cytoplasm. Clusterin immunostaining was neither associated with recurrence-free survival (RFS) nor overall survival of patients by univariate or multivariate analysis. For patients undergoing chemotherapy, those with only cytoplasmic clusterin staining had worse survival than other patients. In conclusion, both cytoplasmic and nuclear immunostaining patterns of clusterin were detected in the tumors of patients with NSCLC. Adenocarcinomas were more likely to have only cytoplasmic staining. The immunoexpression of clusterin was not associated with prognosis, and cytoplasm-only immunostaining of clusterin was inversely correlated with chemosensitivity in this group of patients.     

TP和GP方案治疗晚期非小细胞肺癌的临床观察

目的观察TP方案和GP方案对晚期非小细胞肺癌（NSCLC）的疗效和毒副反应。方法分析43例晚期接受化疗的NSCLC患者资料,其中Ⅲ期NSCLC患者27例,占62.8%,Ⅳ期NSCLC患者16例,占37.2%。总结接受的TP组和GP组至少接受2个周期以上。结果 TP和GP总的有效率分别为40.9%和38.1%。不良反应均在可耐受的范围。结论 TP和GP方案均对晚期NSCLS有效且安全,可作为晚期初治NSCLC的一线化疗方案。     

Therapeutic Interventions for Frail Elderly Patients: Part II. Ongoing and Unpublished Randomized Trials

There is increasing momentum to measure frailty in clinical practice given its proven value as a predictor of outcomes, particularly in elderly patients with cardiovascular disease. The number of randomized clinical trials targeting frail older adults has been modest to date. Therefore, we systematically searched the ClinicalTrials.gov registry in order to review the frailty intervention trials that had been actively initiated or completed but not yet published. The interventions studied were exercise training in 2 trials, nutritional supplementation in 3 trials, combined exercise plus nutritional supplementation in 5 trials, pharmaceutical agents in 5 trials, multi-dimensional programs in 2 trials, and home-based services in 3 trials. Their respective study designs, populations, interventions, and planned outcomes are presented in this article.     

Recent Clinical Trials in Atrial Fibrillation in Hypertensive Patients

Atrial Fibrillation (AF) is the most common clinically significant sustained cardiac arrhythmia, and Hypertension (HTN) is the most common cardiovascular disorder. AF is a major risk factor for strokes whether it is symptomatic or silent. Recent publications have shed light on the role of antihypertensive regiments in prevention of AF, while others have provided data on the efficacy and safety of novel antiarrhythmic drugs such as dronedarone and vernakalant. The older CHADS(2) score and its more refined modern counterparts are well validated to determine stroke risk and guide antithrombotic therapy, but haemorrhagic risk has to be respected as well, and scores such as HAS-BLED should be widely used. Novel classes of anticoagulants that overcome many of the drawbacks of warfarin have been introduced with promising results and pose new questions that need to be answered in the near future.     

Homeless Patients with Lung Cancer in Metropolitan Tokyo

Background Homeless persons are those who carry out their activities of daily living in city parks and other facilities. Little is known about homeless patients with lung cancer in Japan. Therefore, we characterized the clinical features and outcomes of homeless people in metropolitan Tokyo. Methods Between January 2014 and August 2018, 2,068 homeless patients were admitted to the homeless patient care unit at Tokyo Saiseikai Central Hospital. Of these, 13 patients were treated for primary lung cancer. We retrospectively analyzed the patients'' clinical characteristics, including their age, gender, treatment, and outcome, obtained from the hospital''s electronic medical records. Results A total of 13 patients were treated for lung cancer. The median age was 66.2 (range, 51-77) years old. Twelve patients (92.3%) were smokers. All of the patients were men and had advanced lung cancer. Of these, four patients had adenocarcinoma, four had squamous carcinoma, and four had other histologies. Ten patients received chemotherapy, and 3 received chemoradiotherapy (carboplatin, n=8; cisplatin, n=2, immune check point inhibitor, n=2; other, n=1). Of the patients on first-line treatment, 58% discontinued treatment, with 71% doing so willfully. The median overall survival was 7.5 (1-44) months. During the study, nine patients died in the hospital, and four were lost to follow up. Conclusion It is difficult for homeless patients to continue chemotherapy, and they often quit therapy willfully. Therefore, it is necessary to develop an education and health insurance support system to ensure treatment continuity in a good social environment.     

Predicting Survival in Potentially Curable Lung Cancer Patients

Lung cancer is the most common cause of cancer death with unchanged mortality for 50 years. Only localized nonsmall-cell lung cancer (NSCLC) is curable. In these patients it is essential to accurately predict survival to help identify those that will benefit from treatment and those at risk of relapse. Despite needing this clinical information, prospective data are lacking. We therefore prospectively identified prognostic factors in patients with potentially curable lung cancer. Over 2 years, 110 consecutive patients with confirmed localized NSCLC (stages 1–3A) were recruited from a single tertiary center. Prognostic factors investigated included age, gender, body mass index (BMI), performance status, comorbidity, disease stage, quality of life, and respiratory physiology. Patients were followed up for 3-5 years and mortality recorded. The data were analyzed using survival analysis methods. Twenty-eight patients died within 1 year, 15 patients died within 2 years, and 11 patients died within 3 years postsurgery. Kaplan-Meier survival estimates show a survival rate of 51% at 3 years. Factors significantly (p < 0.05) associated with poor overall survival were age at assessment, diabetes, serum albumin, peak VO₂ max, shuttle walk distance, and predicted postoperative transfer factor. In multiple-variable survival models, the strongest predictors of survival overall were diabetes and shuttle walk distance. The results show that potentially curable lung cancer patients should not be discriminated against with respect to weight and smoking history. Careful attention is required when managing patients with diabetes. Respiratory physiologic measurements were of limited value in predicting long-term survival after lung cancer surgery.     

Considerations for Endpoint Selection When Designing HIV Clinical Trials

Selecting the primary endpoint is one of the most important decisions in designing clinical trials. Many HIV trials are powered for surrogate markers, often virologic suppression. Among 49 recently published Phase 3 or higher randomized HIV trials only 14% were powered for clinical outcomes such as the progression to AIDS, death, or serious non-AIDS diseases. We provide two examples where interventions modified the targeted surrogate markers but failed to provide clinical benefit. We review the use of surrogate and clinical endpoints, discuss the composition of clinical endpoints, and the need for endpoint verification. In HIV-infected individuals with CD4 cell counts above 200 cells/mm³ serious non-AIDS conditions such as cardiovascular, renal, hepatic diseases and cancer contribute substantially to morbidity and mortality. In this population clinical endpoint trials should be powered for non-AIDS morbidity along with AIDS.     

Status and Perspectives of Clinical Modes in Surgical Patients With Lung Cancer: A Retrospective Study

To investigate the association between the clinical characteristics and clinical modes of surgically treated lung cancer patients, we conducted a retrospective study with 1097 lung cancer patients receiving pulmonary resection between 2012 and 2013.A physical examination or screening (PES) group (n = 267) and a symptomatic (SY) group (n = 830) were established depending on the new clinical mode (sequence of physical examination, early detection and sequential medical treatment) and the conventional mode (hospitalization due to occurrence of relevant symptoms), respectively.A higher proportion of patients referred to our unit directly form a junior medical unit is found in PES group (43.8%, 117/267 vs 13.6%, 113/830) (P < 0.001) and 37.5% (100/267) patients in PES group spent <1 months from detection or first medical visit to diagnosis compared with 15.4% (128/830) patient in SY group (P < 0.001). A significantly higher proportion of PES patients versus SY patients received video-assisted thoracoscopic surgery (VATS) resection (67.8%, 183/267 vs 42.6%, 352/830; P < 0.001). A significantly higher proportion of PES patients versus SY patients chose sublobar resection (16.9%, 45/267 vs 7.6%, 63/830; P < 0.001). A significantly higher proportion of PES patients versus SY patients are at stage 0 or I (64.4%, 172/267 vs 40.7%, 338/830; P < 0.000). The postoperative incidence rate of complications in 30 days is significantly higher in SY group than in PES group (34.9% vs 27.3%; P = 0.022).Helping to early diagnosis and surgical treatment, early tumor detection via PES may contribute to significantly higher proportions of early-stage lung cancer, use of VATS pulmonary resection, and sublobectomy as well as lower complication rate.