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.

Small cell lung carcinoma metastatic to the stomach: Commonly overlooked, limited treatment options

Small cell lung carcinoma metastatic to the stomach,whether synchronous or metachronous,is a rare phenomenon accounting for<0.5%of lung cancers.Hence it can be overlooked by clinicians resulting in delayed diagnosis.This manuscript comments on Yang et al’s article which reported 3 such cases.The main diagnostic features are based on routine morphology comprised of small cells with hyperchromatic nuclei,scant cytoplasm,brisk mitoses and necrosis.This can be supplemented by immunohistochemistry demonstrating positivity for cytokeratin,thyroid transcription factor-1 and neuroendocrine markers as well as a high Ki-67 labelling index.Imaging modalities such as positron emission tomography/contrast computed tomography help to confirm lung origin and rule out the possibility of extra-pulmonary small cell carcinoma.The predominant mechanism of spread is most likely hematogeneous.Prognosis is generally poor since this represents stage 4 disease but survival can be improved by chemo/ra-diotherapy and palliative surgery in select cases.Though outcomes have not changed much in the last several decades,the recent Food and Drug Adminis-tration approval of immune checkpoint inhibitors was a significant milestone as was the delineation of small cell lung carcinoma molecular subtypes.Liquid biopsies are increasingly being used for biomarker studies in clinical trials to assess treatment response and prognosis.

Combined gastroscopic and laparoscopic resection of gastric metastatic adenosquamous carcinoma from lung: A case report

BACKGROUND Primary lung cancer is the leading cause of cancer-related death worldwide.Common metastatic sites include the brain,liver,bones,and adrenal glands.However,gastric metastases from lung cancer are rare.This case may be the first report of a combined gastroscopic and laparoscopic resection for gastric metasta-tic adenosquamous carcinoma(ASC).CASE SUMMARY We report a case of gastric metastasis from lung cancer.The patient was a 61-year-old Han Chinese female who first attended our hospital complaining of a per-sistent cough,leading to the diagnosis of advanced-stage lung adenocarcinoma.After more than four years of chemotherapy,the patient began to experience epi-gastric pain.Endoscopy was performed,and pathological examination of biopsy specimens confirmed that the gastric lesion was a metastasis from lung cancer.The lesion was successfully resected by combined gastroscopy and laparoscopy.Histopathological examination of the resected gastric specimen revealed ASC.CONCLUSION Gastric metastases from lung cancer are rare.Endoscopy,histological and immunohistochemical staining are useful for diagnosing metastatic lesions.Surgical management may provide extended survival in appropriately selected patients.

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.

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.

Therapy for non-small-cell lung cancer patients with brain metastasis

Brain metastasis is a major cause of poor prognosis and high mortality for non-small cell lung cancer patients. The prognosis of non-small-cell lung cancer(NSCLC) patients with brain metastasis is generally poor and more effective treatment is required to improve their prognosis. Whole-brain radiotherapy, surgery, stereotactic radiosurgery, chemotherapy and targeted therapy are the main treatment for brain metastasis. This review focuses on the five therapeutic strategy and in particular, on targeted therapy.

In Surgical Treatment of Non-Small-Cell Lung Cancer a Minimum Number of Resected Mediastinal Lymph Nodes Is Mandatory for Accurate Staging

Objective: Increased numbers of removed lymph nodes (LN) are resulting in more accurate staging of the patient (Will-Rogers-Phenomenon). This study evaluates dependence of lymph node sample size to 1) Will-Rogers-Phenomenom, 2) influence of sample size on overall survival and in?terms of 3) morbidity and mortality. Methods: 131 patients after pulmonary resection were?retrospectively analysed concerning surgery, number of removed lymph nodes, stage, complications and survival. Patients were stratified according to the median number of lymph nodes in two groups (A <12 lymph nodes and B ≥12 lymph nodes). Results: 5% of the patients had only local lymphadenectomy and in 14% a systematic lymphadenectomy was performed. 17% of the patients showed skip metastasis. Lymph node positivity was correlated to the number of removed lymph nodes (p = 0.003). The approximated median survival for UICC (Union internationale contre le cancer) stage I was 511, stage II 521 and stage III 290 days. Subgroup analysis of survival data showed in group A an approximated median survival at stage I of 495 days, at II 537 days and at III 451.5 days. Group B showed at stage I 675 days, at II 521 days and at III 221 days. There was no difference in complications and mortality. Conclusion: A too low sample size leads to understaging due to skip metastasis. Obligatory mediastinal lymph node sampling would decrease the risk of understaging due to skip metastasis and does not increase morbidity or complications. Lymph node sampling is not inferior concerning morbidity and survival in our patient collective. This study cannot recommend a minimum number of LN to be resected. The evaluated limit of 12 LN proves to be suitable as a guideline.

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.

ADJUVANT CHEMOTHERAPY FOLLOWING RADICAL SURGERYFOR NON-SMALL CELL LUNG CANCER:A RANDOMIZED STUDY

Objective: To evaluate the efficacy of adjuvant chemotherapy after radical surgery for non-small cell lung cancer (NSCLC). Methods: Seventy patients with NSCLC (stage I–III) undergone radical surgery were randomized into two groups: 35 patients received adjuvant chemotherapy with cyclophosphamide (CTX) 300 mg/m2, vincristine (VCR) 1.4% mg/m2, adriamycin (ADM) 50 mg/m2, lomustine (CCNU) 50 mg/m2 dl, cisplatin (DDP) 20 mg/m2, d1–5, for 4 cycles, and followed by oral Ftorafur (FT-207) 600–900 mg/d for 1 year (adjuvant chemotherapy group). The other 35 patients received surgical treatment only (surgery group). Results: The overall 5-year survival rate was 48.6% in the adjuvant chemotherapy group, and 31.4% in the surgery group, respectively. The difference between the two groups was not statistically significant (P>0.05). The 5-year survival rate of patients in stage III was 44.0% and 20.8% received surgery with and without adjuvant chemotherapy, respectively. The difference between the two groups was statistically significant (P<0.025). The 5-year survival rate of patients in stage I–II in the two groups was 60.0% and 54.5%, respectively (P>0.75). Conclusion: Postoperative adjuvant chemotherapy in NSCLC can improve survival, for those patients in stage III, it suggests significantly 5-year survival rate in the adjuvant chemotherapy group was higher than that in the surgery alone group.

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.

Partial removal of the pulmonary artery in video-assisted thoracic surgery for non-small cell lung cancer

Lobectomy with partial removal of the pulmonary artery in video-assisted thoracic surgery （VATS） currently remains a challenge for thoracic surgeons. We were interested in introducing pulmonary vessel blocking techniques in open thoracic surgery into video-assisted thoracic surgery （VATS） procedures. In this study, we reported a surgical technique simultaneously blocking the pulmonary artery and the pulmonary vein for partial removal of the pulmonary artery under VATS. Seven patients with non-small-cell lung cancer （NSCLC） received lobectomy with partial removal of the pulmonary artery using the technique between December 2007 and March 2012. Briefly, rather than using a small clamp on the distal pulmonary artery to the area of invading cancer, we replaced a vascular clamp with a ribbon and Hem-o-lock clip to block the preserved pulmonary veins so as to prevent back bleeding and yield a better view for surgeons. The mean occlusion time of the pulmonary artery and pulmonary veins were 44.0±10.0 and 41.3±9.7 minutes, respectively. The mean repair time of the pulmonary artery was 25.3±13.7 minutes. No complications occurred. No patients showed abnormal blood flow through the reconstructed vessel. There were no local recurrences on the pulmonary artery. In conclusion, the technique for blocking the pulmonary artery and veins is feasible and safe in VATS and reduces the risk of abrupt intraoperative bleeding and the chance of converting to open thoracotomy, and extends the indications of VATS lobectomy.

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.

A Prospective Randomized Study of Adjuvant Chemotherapy in Completely Resected Stage III-N2 Non Small Cell Lung Cancer

To evaluate the effect of postoperative adjuvant chemotherapy on survival after complete resection of stage III-N2 non-small-cell lung cancer. Methods： From Jan. 1999 to Dec. 2003, one-hundred and fifty patients, who were diagnosed as stage III-N2 non-small cell lung cancer after operation, were randomly devided into chemotherapy group and control group. The former received four cycles of chemotherapy with NVB （25 mg/m^2, D1, D5）/paclitaxel （175 mg/m^2, D1） and Carboplatin （AUC=5, D1）. Results： In chemotherapy group, 75.8% （68/79） of patients had finished the 4 cycles of chemotherapy and no one died of toxic effects of chemotherapy. Twenty-five percent of the patients had grade 3-4 neutropenia and 2% had febrile neutropenia. The median survival for the entire 150 patients was 879 d, with 1-year survival rate of 81%, 2-year survival rate of 59% and 3-year survival rate of 43%. There was no significant difference in median survival between chemotherapy and control group （897 d vs 821 d, P=0.0527）, but there was significant difference in the 1-year and 2-year overall survival （94.71%, 76.28% vs 512 d, P=0.122）, but there was significant difference in the 2-year survival rate between two groups with brain metastases （66.7% vs 37.6% P〈0.05）. The median survival after brain metastasis appeared was 190 days. Conclusion： Postoperative adjuvant chemotherapy does not significantly improve median survival among patients with completely resected stage II-N2 non-small-cell lung cancer, but significantly improves the 1-year and 2-year overall survival. It neither decreases the incidence of brain metastasis but put off the time of brain metastasis.

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.

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.