Accuracy of endoscopic ultrasound-guided needle aspiration specimens for molecular diagnosis of non-small-cell lung carcinoma

BACKGROUND Endoscopic ultrasonography-guided fine-needle aspiration(EUS-FNA)and endobronchial ultrasound-guided transbronchial needle aspiration(EBUS-TBNA)are highly sensitive for diagnosing and staging lung cancer.In recent years,targeted therapy has shown great significance in the treatment of non-small cell lung carcinoma(NSCLC).Using these minimally invasive techniques to obtain specimens for molecular testing will provide patients with a more convenient diagnostic approach.AIM To evaluate the feasibility and accuracy of tissue samples obtained using EUSFNA and EBUS-TBNA for molecular diagnosis of NSCLC.METHODS A total of 83 patients with NSCLC underwent molecular testing using tissues obtained from EUS-FNA or EBUS-TBNA at the Tianjin Medical University Cancer Hospital from January 2017 to June 2019.All enrolled patients underwent chest computed tomography or positron emission tomography/computed tomography prior to puncture.We detected abnormal expression of EGFR,KRAS,MET,HER2,ROS1 and anaplastic lymphoma kinase protein.Two patients failed to complete molecular testing due to insufficient tumor tissue.The clinical features,puncture records,molecular testing results and targeted treatment in the remaining 81 patients were summarized.RESULTS In a total of 99 tissue samples obtained from 83 patients,molecular testing was successfully completed in 93 samples with a sample adequacy ratio of 93.9%(93/99).Biopsy samples from two patients failed to provide test results due to insufficient tumor tissue.In the remaining 81 patients,62 cases(76.5%)were found to have adenocarcinoma,11 cases(13.6%)had squamous cell carcinoma,3 cases(3.7%)had adenosquamous carcinoma and 5 cases(6.2%)had NSCLC-not otherwise specified.The results of molecular testing showed EGFR mutations in 21 cases(25.9%),KRAS mutations in 9 cases(11.1%),ROS-1 rearrangement in 1 case(1.2%)and anaplastic lymphoma kinase-positive in 5 cases(6.2%).Twentyfour patients with positive results received targeted therapy.The total effectiveness rate of targeted therapy was 66.7%(16/24),and the disease control rate was 83.3%(20/24).CONCLUSION Tissue samples obtained by EUS-FNA or EBUS-TBNA are feasible for the molecular diagnosis of NSCLC and can provide reliable evidence for clinical diagnosis and treatment.

Relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma

Objective:To study the relevance of EGFR gene mutation with pathological features and prognosis in patients with non-small-cell lung carcinoma.Methods:A total of 297 patients from July 2009 to May 2013 were chosen as objects.EGFR gene mutation were detected with fluorescence quantitative PCR.Relevance of EGFR gene mutation with clinical and pathological features was analyzed,and the prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was compared.Results:In 297 patients.136(45.79%) showed EGFR gene mutation.EGFR gene mutation had no significant relevance with age.gender,smoking history,family history of cancer and clinical stage(P>0.05);there was significant relevance between EGFR gene mutation and blood type,pathologic types,differentiation and diameter of cancer(P<0.05).The difference between prognosis of EGFR- mutant-patients and that of EGFR- wide type-patients was statistical significance(P<0.05).Conclusions:EGFR gene mutation has significant relevance with pathological features,the prognosis of EGFRmutant-paticnts is better than that of EGFR- wide type-patients.

Inhibitory Effect of MiR-449b on Cancer Cell Growth and Invasion through LGR4 in Non-Small-Cell Lung Carcinoma

Non-small-cell lung carcinoma （NSCLC） is one of the most frequently diagnosed malignancies worldwide. Previous studies have shown that microRNA-449b （miR-449b） functions as a tumor suppressor in many cancers. However, the role of miR- 449b in NSCLC is still unknown. In the present study, miR-449b was significantly down- regulated in NSCLC samples and cell lines. Bioinformatics analysis revealed that 3＇-UTR region of leucine rich repeat containing G protein-coupled receptor 4 （LGR4） mRNA had putative complementary sequences to miR-449b, which was further confirmed by the luciferase assay. Western blotting showed that restoration of miR-449b in NSCLC cells decreased the expression of LGR4. Interestingly, over-expression of miR-449b inhibited growth and invasion of NSCLC cells in vitro. Furthermore, ectopic expression of LGR4 reversed miR-449b-suppressed proliferation and invasion of NSCLC cells. Therefore, the data of the present study demonstrate that miR-449b inhibits tumor cell growth and invasion by targeting LGR4 in NSCLC.

Clinical Observation on Treatment of NonParvicellular Carcinoma of the Lung with Jin Fu Kang Oral Liquid

Jin Fu Kang Oral Liquid ([symbol: see text]), made of traditional Chinese drugs for supplementing qi and nourishing yin, was developed according to the common symptoms in lung carcinoma with deficiency of both qi and yin. Of the 96 cases in the Jin Fu Kang group, 1 case got complete remission (CR) after treatment, 8 cases partial remission (PR), 52 cases no change (NC), PR + NC covering 63.5%. Of the 52 cases in the group of Jin Fu Kang plus chemotherapy, 11 cases got PR after treatment, 26 cases NC, PR + NC covering 71.2%. Of the 25 cases in the chemotherapy group, 4 cases got PR after treatment, 11 cases NC, PR + NC covering 60.0%. The results show that the therapeutic effectiveness in the Jin Fu Kang group and the group of Jin Fu Kang plus chemotherapy was better than that in the chemotherapy group. The one-year survival rate and the two-year survival rate after treatment in the Jin Fu Kang group were 67.3% and 67.3% respectively; 66.7% and 66.7% in the group of Jin Fu Kang plus chemotherapy; and 40.3% and 0.0% in the chemotherapy group. The improvement of clinical symptoms, increase of body weight and improvement of health situation (KPS marks) after treatment in both the Jin Fu Kang group and the group of Jin Fu Kang plus chemotherapy were better than that in the chemotherapy group. Some indicators of immunology and hemogram after treatment were greatly improved in the Jin Fu Kang group, worse in the chemotherapy group, but no obvious improvement in the group of Jin Fu Kang plus chemotherapy.

Pembrolizumab-emerging treatment of pulmonary sarcomatoid carcinoma: A case report

BACKGROUND Few studies have addressed the efficacy of pembrolizumab in pulmonary sarcomatoid carcinoma(PSC),a rare,previously rapidly fatal subtype of nonsmall-cell lung cancer.CASE SUMMARY We report the case of a 69-year-old man presented with respiratory distress caused by a large left upper lung lobe mass diagnosed as PSC with programmed death-ligand 1 expressed on more than 50 percent of tumor cells.The patient was started on pembrolizumab and,after 5 cycles,there was a more than 80 percent decrease in the size of the tumor mass.Further decrease was seen at the end of 10 cycles.The patient has been tolerating pembrolizumab well,with no limiting side-effects.Fourteen months after first coming into the hospital,he remains asymptomatic.CONCLUSION Pembrolizumab appears as a viable emerging treatment for PSC.

Advances in adjuvant systemic therapy for non-small-cell lung cancer

Non-small-cell lung cancer remains a leading cause of death around the world. For most cases, the only chance of cure comes from resection for localised disease, however relapse rates remain high following surgery. Data has emerged over recent years regarding the utility of adjuvant chemotherapy for improving disease-free and overall survival of patients following curative resection. This paper reviews the clinical trials that have been conducted in this area along with the studies integrating radiation therapy in the adjuvant setting. The role of prognostic gene signatures are reviewed as well as ongoing clinical trials including those incorporating biological or targeted therapies.

Pang Fuwan Uses Yao Medicine to Observe the Therapeutic Effects on the Physical and Mental Symptoms of Patients with Advanced Non-Small Cell Lung Cancer

Objective: Investigate the efficacy and safety of Yao Medicine in the treatment of advanced non-small-cell lung carcinoma, and explore the best therapeutic measure for clinical benefit. Methods: From July 2020 to July 2022, 84 patients with advanced non-small-cell lung carcinoma were selected and randomly divided into the Observation Group and control group, and the control group was treated with routine Western medicine, with 42 cases in each group. The activity of daily living (ADL) was assessed before and after treatment, meanwhile, the self-rating depression scale (SDS) and self-rating anxiety SAS (SAS) were used to assess the improvement of a bad mood, and quality of life SF-36 was used to assess the quality of life, to judge the efficacy and safety. Results: The effective rate of observation group was 91.67%. The effective rate of the control group was 76.19%. The effective rate of the observation group was significantly higher than that of the control group (P 0.05). There were no significant differences in the scores of SDS, SAS and quality of life between the two groups before treatment (P > 0.05), and after treatment, the scores of SDS, SAS and quality of life in the two groups were compared with those in the control group (P > 0.05), the scores of VAS, SDS and SAS decreased significantly, while ESCV, angle of straight leg elevation, ADL, physiological score, emotional score, social score and health status score increased significantly, the difference was statistically significant (P 0.05). Conclusion: Yao Medicine can improve the psychosomatic symptoms of patients with advanced non-small-cell lung carcinoma better, with better efficacy and higher safety.

Unresectable stage Ⅲ non-small-cell lung cancer: Have we made any progress?

Lung cancer is responsible for the most cancer deaths worldwide with an incidence that is still rising. One third of patients have unresectable stage ⅢA or stage ⅢB disease. The standard of care for locally advanceddisease in patients with good performance status consists of combined modality therapy in particular concurrent chemoradiotherapy. But despite a lot of efforts done in the past, local control and survival of patients with unresectable stage Ⅲ non-small-cell lung cancer(NSCLC) remains poor. Improving outcomes for patients with unresectable stage Ⅲ NSCLC has therefore been an area of ongoing research. Research has focused on improving systemic therapy, improving radiation therapy or adding a maintenance therapy to consolidate the initial therapy. Also implementation of newer targeted therapies and immunotherapy has been investigated as well as the option of prophylactic cranial irradiation. This article reviews the latest literature on improving local control and preventing distant metastases. It seems that we have reached a plateau with conventional chemotherapy. Radiotherapy dose escalation did not improve outcome although increasing radiation dose-intensity with new radiotherapy techniques and the use of newer agents, e.g., immunotherapy might be promising. In the future well-designed clinical trials are necessary to prove those promising results.

Differentially Expressed Genes with Diagnostic and Prognostic Value for Non-small-cell Lung Cancer

Background Lung cancer is the most common cancer worldwide and remains the leading cause of cancer-related mortality.A method that can be used for the early detection and diagnosis of non-small-cell lung cancer(NSCLC)is urgently needed.Materials and Methods We identified differentially expressed genes based on RNA sequencing data for NSCLC from The Cancer Genome Atlas(TCGA)database.Then,we conducted receiver operating characteristic(ROC)curve and survival analyses to determine which genes had diagnostic and/or prognostic value.Results A total of 24991 genes were included in the TCGA database,and a differential gene expression analysis was conducted for 971 NSCLC and 108 normal samples.There were 1709 differentially expressed genes identified using three methods.It was noted that 29 of the 1709 genes were enriched in the“Transcriptional misregulation in cancer”pathway,such as HOXA11,HOXA10,HMGA2,MMP3,and MMP9.Based on the ROC curve and survival analyses,27 of the 1709 differentially expressed genes were with exact diagnostic and prognostic value for NSCLC,such as SLC2A1,LGR4,EMP2,CLDN5,PRC1,ANLN,GAPDH.GAPDH took the center position in the protein-protein interaction(PPI)network.Conclusion Twenty-seven differentially expressed genes with diagnostic and prognostic value were identified that can serve as potential biomarkers for NSCLC.

Apoptosis of Lewis Lung Carcinoma Cells Induced by Microwave via p53 and Proapoptotic Proteins In vivo

Background： Microwave therapy is a minimal invasive procedure and has been employed in clinical practice for the treatment of various types of cancers. However, its therapeutic application in non-small-cell lung cancer and the underlying mechanism remains to be investigated. This study aimed to investigate its effect on Lewis lung carcinoma （LLC） tumor in vivo. Methods： Fifty LLC tumor-bearing C57BL/6 mice were adopted to assess the effect of microwave radiation on the growth and apoptosis of LLC tumor in vivo. These mice were randomly assigned to 10 groups with 5 mice in each group. Five groups were treated by single pulse microwave at different doses for different time, and the other five groups were radiated by multiple-pulse treatment of a single dose. Apoptosis of cancer cells was determined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Western blotting was applied to detect the expression of proteins. Results： Single pulse of microwave radiation for 5 min had little effect on the mice. Only 15-min microwave radiation at 30 mW/cm2 significantly increased the mice body temperature （2.20 ± 0.82）℃ as compared with the other groups （0.78 ± 0.29 ℃, 1.24 ± 0.52 ℃, 0.78 ± 0.42 ℃, respectively）, but it did not affect the apoptosis of LLC tumor cells significantly. Continous microwave radiation exposure, single dose microwave radiation once per day for up to seven days, inhibited cell division and induced apoptosis of LLC tumor cells in a dose- and duration-dependent manner. It upregulated the protein levels of p53, Caspase 3, Bax and downregulated Bcl-2 protein. Conclusions： Multiple exposures of LLC-bearing mice to microwave radiation effectively induced tumor cell apoptosis at least partly by upregulating proapoptotic proteins and downregulating antiapoptotic proteins. Continuous radiation at low microwave intensity Ibr a short time per day is promising in treating non-small-cell lung cancer.

Lung squamous cell carcinoma combined with tuberculous pleurisy

A58-year old male patient was admitted to our .hospital with repeated coughing, expectoration withblood in the sputum for more than 10 months, bilateral wrists and ankles with pain and afternoon low fever, chest tightness and shortness of breath in the latest one month. The patient had a history of joint pain for more than 3 years without special treatment. He had a smoking history for more than 30 years with 10 cigarettes a day. He had no family tumor history. Physical examination： T 38.5℃, P 100/min, R 22/min, blood pressure （BP） 107/77 mmHg; the double upper fingers visible clubbing, bilateral supraclavicular lymph node not feelable, left inferior pulmonary respiratory sounds disappeared, and wet and dry sounds not heard.

Advancements in next-generation sequencing for diagnosis and treatment of non-small-cell lung cancer

In recent years, lung cancer has been the most commonly diagnosed cancer globally; 1.6 million people died of lung cancer in 2012 globally, making lung cancer the leading cause of cancer-related deaths.1,2 Lung cancer can be mainly histologically classified into two types: non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC), ac-counting for approximately 85% and 15% of cases, respectively.3 NSCLC can be further classified as squamous cell carcinoma, adenocarcinoma, and large-cell lung carcinoma, among which lung adenocarci-noma is the most common primary malignant tumor. Unfortunately, most NSCLC cases are diagnosed at a late stage when the survival rate is low; the 5-year survival rate is approximately 16%.

The Therapeutic Effects of the Radiotherapy Plus TCM Treatment Observed in Senile Non-Parvicellular Lung Cancer Patients at the Late Stage

47 senile non-parvicellular lung cancer patients at stage Ⅲ or Ⅳ were randomly divided into a treatment group (26 cases) treated by radiotherapy plus traditional Chinese medicine (TCM) and a control group (21 cases) treated only by radiotherapy for observation of the therapeutic effects.The patients in the treatment group orally took Chinese medicine during and after the radiotherapy.There was no obvious difference in short-term therapeutic effects between the two groups,but the long-term curative effects in the treatment group was obviously superior to that in the control group (P<0.05 or P<0.01).Conclusion:radiotherapy plus TCM can prolong the survival period for senile non-parvicellular lung cancer patients.

Molecular Mechanisms Contributing to Resistance to Tyrosine Kinase-Targeted Therapy for Non-Small Cell Lung Cancer

One of the most important pathways in non-small cell lung cancer(NSCLC) is the epidermal growth factor receptor(EGFR) pathway. This pathway affects several crucial processes in tumor development and progression,including tumor cell proliferation,apoptosis regulation,angiogenesis,and metastatic invasion.Targeting EGFR is currently being intensely explored.We are witnessing the development of a number of potential molecular-inhibiting treatments for application in clinical oncology.In the last decade,the tyrosine kinase(TK) domain of the EGFR was identified in NSCLC patients,and it has responded very well with a dramatic clinical improvement to TK inhibitors such are gefitinib and erlotinib.Unfortunately,there were primary and/or secondary resistance to these treatments,as shown by clinical trials.Subsequent molecular biology studies provided some explanations for the drug resistance phenomenon.The molecular mechanisms of resistance need to be clarified.An in-depth understanding of these targeted-therapy resistance may help us explore new strategies for overcoming or reversing the resistance to these inhibitors for the future of NSCLC treatment.

Further understanding of an uncommon disease of combined small cell lung cancer： clinical features and prognostic factors of 114 cases

Objective： Combined small cell lung cancer （C-SCLC） is an uncommon subgroup of small cell lung cancer （SCLC） and few clinical data can be referred. Our study is to investigate the clinical features and prognostic factors of C-SCLC, as well as the role of multimodality treatment.Methods： Between January 2004 and December 2012, patients with histologically diagnosed C-SCLC were retrospectively analyzed. The survivals were evaluated with the Kaplan-Meier method. Univariate and multivariate analyses were used to evaluate potential prognostic factors.Results： One hundred and fourteen patients were enrolled, with a median age of 59 （range： 20-79） years old. The most common combined component was squamous cell carcinoma （52.6%）. Among these patients, the disease was stage I, II, III and IV in 9.6%, 19.3%, 46.5% and 24.6% of the patients, respectively. Eighty patients （70.2%） received at least two of the three modalities containing chemotherapy, radiotherapy and surgery. The median follow-up was 32.5 months. The median time of overall survival （OS） was 26.2 months. On univariate analysis, smoking （P=0.029）, Karnofsky performance score （KPS） 〈80 （P=0.000）, advanced TNM stage （P=0.000）, no surgery （P=0.010）, positive resection margin （P=0.000）, positive lymph nodes ≥4 （P=0.000）, positive lymph node ratio 〉10% （P=0.000） and non-multimodality treatment （P=0.004） were associated with poor OS. Multivariate analysis confirmed that smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio 〉 10% were poor prognostic features. Conclusions： C-SCLC has a relatively early stage and good prognosis, which may due to the underestimated diagnosis in non-surgical patients. Multimodality therapy is recommended, especially for limited disease. Smoking, advanced TNM stage, positive resection margin and positive lymph nodes ratio 〉10% are poor prognostic factors.

肺癌合并肺结核的诊断和临床治疗现状

肺癌和肺结核是严重危害全球健康的两大呼吸系统疾病,严重危害着人类健康,造成全球每年各约160万例死亡患者。特别是在发展中国家,两种疾病均存在较高的发病率。已有流行病学研究证据表明,肺结核增加了肺癌的患病风险。肺结核与肺癌的临床症状极为相似,两病共存及相互影响给疾病的诊治带来困难,也给患者带来巨大负担。笔者对肺癌合并肺结核的发生机制、诊断和治疗相关方面进行综述。

Value of COX-2 and HER-2 in Judging Condition and Prognosis in Non-Small Cell Lung Cancer Patients

OBJECTIVE To investigate the expressions of cyclooxygenase 2 （COX-2） and human epidermal growth factor receptor-2 （HER-2） in non-small cell lung cancer （NSCLC） and their clinical significance in identifying the progression and prognosis of the NSCLC patients. METHODS Immunohistochemical indirect method was used to detect the expressions of the COX-2 and HER-2 protein in 54 NSCLC specimens, 16 paraneoplastic specimens, and 10 normal tissue specimens. RESULTS The positive rates of COX-2 and HER-2 protein expressions were respectively 75.9% and 40.7% in the NSCLC specimens, 25% and 12.5% in the paraneoplastic specimens, and 0 in the normal tissue. The COX-2 protein expression in lung cancer （LC） was not only related to the smoking habit of the patients and histological grades of LC, but also to the TNM stages, and lymphatic metastasis （P 〈 0.05）. HER-2 protein expression closely correlated to the pathologic types, histological grades, TNM stages, and lymphatic metastasis （P 〈 0.05）. The result of univariate analysis showed that all the histological grades, TNM stages, lymphatic metastasis, and expressions of COX-2/HER-2 correlated to the prognosis of NSCLC patients （mean of P value 〈 0.01）. The multivariate survival analysis indicated that there were signi.cant di.erences in comparison of the survival time between the COX-2 （＋＋/＋＋＋） /HER-2 （＋＋/＋＋＋） and the COX-2 （-/＋）/HER-2 （-/＋） groups （P〈 0.001）, suggesting the COX-2/HER-2 was a negative prognostic factor. CONCLUSION COX-2 and HER-2 are valuable in identifying the progression of NSCLC and predicting the prognosis of NSCLC patients. COX-2 and HER-2 are useful for judging the NSCLC patient＇s condition, and are of great value to the decision of NSCLC prognosis.

原发性肺淋巴上皮癌7例临床病理学分析

目的探讨原发性肺淋巴上皮癌的临床病理特点。方法回顾性分析海南医学院第一附属医院2016-06—2022-10期间诊断的病例7例,分析其临床特征,组织学形态,免疫表型及分子检测结果。结果男性患者1例,女性6例,患者年龄33~63岁(平均49岁,中位年龄50岁),2例为肺门型,4例为周围型肿块。镜下所见,所有病例肿瘤细胞呈巢状或弥漫散在排列,胞质淡染或嗜酸,细胞核圆或椭圆形,染色质较细呈空泡状,部分肿瘤细胞呈合胞体样,有较显著的嗜酸性核仁,癌巢内及癌巢之间有多少不等的淋巴细胞及浆细胞浸润。免疫组化检测显示所有肿瘤细胞均表达panCK+,5例CK5/6+、p40+and p63(70%),不表达CK7、TTF-1、NapsinA,Ki-67增殖指数介于20%~80%,原位杂交分子检测显示所有病例EBER均为阳性。结论原发性肺淋巴上皮癌好发于中年人群,病理形态上与多种肿瘤具有重叠的表现,易于误诊,EBER检测有利于提高本病的诊断率。

Role of positron emission tomography-computed tomography in non-small cell lung cancer

Lung cancer is the leading cause of cancer-related mortality worldwide. Non-small cell carcinoma and small cell carcinoma are the main histological subtypes and constitutes around 85% and 15% of all lung cancer respectively. Multimodality treatment plays a key role in the successful management of lung cancer depending upon the histological subtype, stage of disease, and performance status. Imaging modalities play an important role in the diagnosis and accurate staging of the disease, in assessing the response to neoadjuvant therapy, and in the follow-up of the patients. Last decade has witnessed voluminous upsurge in the use of positron emission tomography-computed tomography(PET-CT); role of PET-CT has widened exponentially in the management of lung cancer. The present article reviews the role of 18-fluoro-deoxyglucose PET-CT in the management of non small cell lung cancer with emphasis on staging of the disease and the assessment of response to neoadjuvant therapy based on available literature.

双重癌:左肺腺癌合并甲状腺内胸腺癌1例

多原发癌(MPC)又名重复癌,是指同一机体内同时或先后发生的两种或两种以上不相关的原发性恶性肿瘤。随着现代医学进步,多原发癌并不罕见,所有肿瘤患者的多原发恶性肿瘤(MPM)发病率约为0.73%~5.20%,这种广泛的差异与不同医院的医生和诊断工具不同有关。肺癌死亡率最高,由于低剂量肺癌筛查及人们健康意识的提高,大量早期肺癌被筛查出来,随着治疗方式的改进,如分子靶向治疗,使肺癌预后取得了大量进步,因此患者存活的时间足够长,可以发展为随后的原发肿瘤,但肺癌合并甲状腺内胸腺癌(ITTC)实属罕见。