Large Cell Carcinoma Research Articles

Clinical profiles and trend analysis of newly diagnosed lung cancer in a tertiary care hospital of East China during 2011-2015.

More than one-third of lung cancer worldwide occurring in China. However, the clinical profiles of lung cancer patients in the mainland of China are rarely reported and largely unknown. The objective of this study is to analyze the characteristics and time trends of newly diagnosed lung cancer cases during the past 5 years in East China. The data came from an academic tertiary care hospital of East China. Patients who were newly diagnosed as lung cancer from 2011 to 2015 were enrolled. All new cases got pathological supports by lung biopsy or surgery. Tumor staging was performed according to the seventh edition of the tumor node metastasis (TNM) classification of malignant tumors. The patients' disease information was collected from the database of the hospital information system (HIS). From 2011 to 2015, aggregately 5,779 patients, including 3,719 males and 2,060 females, were diagnosed as lung cancer. The major histologic subtypes of lung cancer were adenocarcinoma (ADC, 60.0%), squamous cell carcinoma (SCC, 25.6%), small cell lung cancer (SCLC, 8.5%), large cell carcinoma (0.6%), adenosquamous carcinoma (1%), other non-small cell carcinoma (1.6%) and unclassified or rare carcinoma (2.8%). ADC proportion of female was much higher than that of male. A higher proportion of advanced stage (stage IIIB, IV) of lung cancer existed in patients who were admitted to hospital due to respiratory or cancer related symptoms (RCRS) than those without RCRS. Smoking rate in male patients reached 80.2%, while it was only 2.7% in females. EGFR mutation existed in 66% of female and 37% of male patients with ADC. This study demonstrates the clinicopathologic characteristics of lung cancer patients from East China, including histologic composition, staging proportion, smoking prevalence and gene mutation status. During the past 5 years, the proportion of ADC has increased gradually whereas SCC decreased.

TRIM59 is a novel potential prognostic biomarker in patients with non-small cell lung cancer: A research based on bioinformatics analysis.

Lung cancer is the leading cause of cancer-associated mortality worldwide and its prognosis is poor. Few effective biomarkers for non-small cell lung cancer (NSCLC) have been translated into the clinical practice aiming to assist in the treatment plan design and prognosis evaluation. The aim of the present study was to identify novel potential prognostic biomarkers for NSCLC. Tripartite motif 59 (TRIM59) was identified from a microarray dataset of matched-samples and was verified as an aberrantly upregulated gene in NSCLC tissue. The expression level of TRIM59 in NSCLC subtypes was observed to be significantly increased in large cell lung carcinoma and squamous cell carcinoma as compared with that in adenocarcinoma. Its expression correlated with several clinicopathological features, including gender, smoking habits, and unfavorable tumor node and pathological stages. Notably, TRIM59 demonstrated a negative correlation with survival time and its overexpression indicated a poor prognosis in NSCLC. Furthermore, univariate and multivariate Cox's regression analyses indicated that TRIM59 was an independent prognostic factor in tumor tissue as compared with age, gender, tumor stage, node stage, and metastasis. Gene set enrichment analysis and protein-protein interaction network construction revealed that TRIM59 was associated with oncogenic mammalian target of rapamycin (MTOR) and eukaryotic initiation factor 4E (EIF4E) signaling through ubiquitin C binding. In conclusion, it was revealed that TRIM59 is a novel prognostic biomarker modulating oncogenic MTOR and EIF4E signaling pathways in NSCLC. These findings provided a novel insight into the clinical application of TRIM59. Therefore, TRIM59 may serve as an independent predictor for prognosis and a potential therapeutic target for NSCLC.

Analysis of gastrointestinal metastasis of primary lung cancer: Clinical characteristics and prognosis.

The prevalence of gastrointestinal metastasis of lung cancer is low. The aim of the present study was to analyze the frequency and clinical characteristics of metastases to the gastrointestinal tract by retrospectively assessing the clinical records of 2,066 patients with lung cancer. A total of 7 patients (0.33%) were diagnosed with gastrointestinal metastasis, including 4 patients with adenocarcinoma, 1 patient with large cell carcinoma and 2 patients with pleomorphic carcinoma. Furthermore, 3 of the patients presented with small bowel metastases, 2 with gastric metastases, 1 with large bowel metastasis and 1 with metastasis of the appendix. The mean time between the diagnosis of the lung tumors and the identification of gastrointestinal metastasis was 13.5 months (range, 3-49 months). The mean time between the identification of the gastrointestinal metastasis and mortality was 100.6 days (range, 21-145 days). In conclusion, the prognosis of patients with recurrence in distant organs, including the gastrointestinal tract, may be worse than patients with recurrence in distant organs, excluding the gastrointestinal tract, particularly those with symptomatic gastrointestinal metastasis. Therefore, the presence of clinical gastrointestinal metastasis may be life threatening; comprehensive evaluations are required to detect and monitor gastrointestinal metastasis during follow-up.

Serotype-Specific Killing of Large Cell Carcinoma Cells by Reovirus.

Reovirus is under development as a therapeutic for numerous types of cancer. In contrast to other oncolytic viruses, the safety and efficacy of reovirus have not been improved through genetic manipulation. Here, we tested the oncolytic capacity of recombinant strains (rs) of prototype reovirus laboratory strains T1L and T3D (rsT1L and rsT3D, respectively) in a panel of non-small cell lung cancer (NSCLC) cell lines. We found that rsT1L was markedly more cytolytic than rsT3D in the large cell carcinoma cell lines tested, whereas killing of adenocarcinoma cell lines was comparable between rsT1L and rsT3D. Importantly, non-recombinant T1L and T3D phenocopied the kinetics and magnitude of cell death induced by recombinant strains. We identified gene segments L2, L3, and M1 as viral determinants of strain-specific differences cell killing of the large cell carcinoma cell lines. Together, these results indicate that recombinant reoviruses recapitulate the cell killing properties of non-recombinant, tissue culture-passaged strains. These studies provide a baseline for the use of reverse genetics with the specific objective of engineering more effective reovirus oncolytics. This work raises the possibility that type 1 reoviruses may have the capacity to serve as more effective oncolytics than type 3 reoviruses in some tumor types.

Occupational exposure to diesel motor exhaust and risk of lung cancer by histological subtype: a population-based case\u2013control study in Swedish men

We investigated occupational exposure to diesel motor exhaust (DME) and the risk of lung cancer by histological subtype among men, using elemental carbon (EC) as a marker of DME exposure. 993 cases and 2359 controls frequency-matched on age and year of study inclusion were analyzed by unconditional logistic regression in this Swedish case–control study. Work and smoking histories were collected by a questionnaire and telephone interviews. DME was assessed by a job-exposure matrix. We adjusted for age, year of study inclusion, smoking, occupational exposure to asbestos and combustion products (other than motor exhaust), residential exposure to radon and exposure to air pollution from road traffic. The OR for lung cancer for ever vs. never exposure to DME was 1.15 (95% CI 0.94–1.41). The risk was higher for squamous and large cell, anaplastic or mixed cell carcinoma than for alveolar cell cancer, adenocarcinoma and small cell carcinoma. The OR in the highest quartile of exposure duration (≥34 years) vs. never exposed was 1.66 (95% CI 1.08–2.56; p for trend over all quartiles: 0.027) for lung cancer overall, 1.73 (95% CI 1.00–3.00; p: 0.040) for squamous cell carcinoma and 2.89 (95% CI 1.37–6.11; p: 0.005) for the group of undifferentiated, large cell, anaplastic and mixed cell carcinomas. We found no convincing association between exposure intensity and lung cancer risk. Long-term DME exposure was associated with an increased risk of lung cancer, particularly to squamous cell carcinoma and the group of undifferentiated, large cell, anaplastic or mixed carcinomas.

Small suitability of the DLEC1, MLH1 and TUSC4 mRNA expression analysis as potential prognostic or differentiating markers for NSCLC patients in the Polish population.

According to the latest data, lung cancer is one of the most common cancer worldwide, men contributing nearly 21.2% and women 8.6% of all diagnosed cancers. Late detection of tumour drastically reduces the chance for a cure. Thus, it is important to search for candidate biomarkers for screening of early stage nonsmall cell lung carcinoma (NSCLC). Tumour suppressor genes, DLEC1, TUSC4 and MLH1, localized on 3p21 are recognized to play a role in NSCLC carcinogenesis. The aim of this study was to assess the relationship between the DLEC1, TUSC4 and MLH1 mRNA expression, and clinical features of NSCLC patients, tobacco addiction, and tumour histopathological characteristics. The DLEC1, TUSC4 and MLH1 expression was analysed in lung tumour tissue samples obtained from 69 patients diagnosed with NSCLC: squamous cell carcinoma (n = 34), adenocarcinoma (n = 24), large cell carcinoma (n = 5), carcinoma adenosquamosum (n = 5). A decreased gene expression (RQ < 0.7) was observed for DLEC1 in 60.9% of tumour samples, for MLH1 in 50.7% and for TUSC4 in 26% of NSCLC samples. DLEC1 was decreased in more aggressive subtypes: large cell carcinoma and adenocarcinoma-squamous cell carcinoma. The simultaneous downregulation of two of the studied genes, DLEC1 andMLH1,was observed in 30.4% of NSCLCsamples, highlighting the importance of these two genes in lung carcinogenesis. We found no correlation between the DLEC1, TUSC4 and MLH1 gene expression and NSCLC patient characteristics (gender, age and smoking) or cancer histopathology. No significant differences in the gene expression among NSCLC subtypes indicate the weakness of DLEC1, TUSC4 and MLH1 expression analysis as potential differentiating markers of NSCLC subtypes in the Polish population.

Clinical efficacy evaluation of tyrosine kinase inhibitors for non-adenocarcinoma lung cancer patients harboring EGFR-sensitizing mutations.

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) as a standard therapy have been used in EGFR-mutated adenocarcinoma of non-small-cell lung cancer (NSCLC) patients in recent years. But in current randomized prospective clinical trials, due to few cases of non-adenocarcinoma patients having been found, the efficacy of TKIs for EGFR-mutated non-adenocarcinoma and the relationship with clinicopathological characteristics remained debatable. The results of retrospective studies showed that the frequency of EGFR mutation was significantly associated with nationality, gender, smoking history, and histology type. Being female, never-smoker and adenocarcinoma had a higher mutation rate. Furthermore, the EGFR mutation rate and efficacies of TKIs in adenocarcinoma were higher than those in non-adenocarcinoma. And in non-adenocarcinoma, the EGFR mutation rate and efficacies of TKIs in adenosquamous cell carcinoma were higher than those in squamous cell carcinoma or in large-cell lung carcinoma. In conclusion, it may be necessary to conduct a large sample prospective study to understand the clinicopathological characteristics of non-adenocarcinomas and to evaluate the efficacy of EGFR TKI and/or chemotherapy for EGFR-mutated non-adenocarcinoma NSCLC. So we searched relevant articles between the year 2010 and 2016 through the major indexed literature database PubMed by searching the keywords such as EGFR mutation, Tyrosine kinase inhibitors, and Non-adenocarcinoma.

NUCLEAR LOCALIZATION OF CRABP1 IN NEUROENDOCRINE LUNG TUMORS IS ASSOCIATED WITH THE DEGREE OF TUMOR MALIGNANCY

Bronchopulmonary neuroendocrine tumors (NETs) refer to malignant epithelial neoplasms of neuroendocrine origin, which form highly heterogeneous group with respect to biological behavior and clinical manifestations. Three main categories of different grades of malignancy are distinguished in the diagnosis of lung NETs: typical carcinoids (TK), atypical carcinoids (AK) and the most aggressive low-differentiated tumors including small-cell and large-cell neuroendocrine lung carcinomas. These groups differ in terms of disease prognosis and therapeutic approaches, but the criteria currently used do not always allow clear boundaries between different histological variants. The search for additional diagnostic parameters and individual prognosis markers is currently actual for the grading and optimal classification of NETs. For the first time we studied the expression of Retinoic Acid Binding Protein-1 (CRABP1) in different variants of lung NETs. IHC analysis of 43 samples of lung NETs with various degrees of differentiation and grades revealed the statistically significant correlation between nuclear localization of CRABP1 and proliferation index «Ki-67» and tumor grade. The results pointed on the involvement of CRABP1 in the pathogenesis of lung NETs and indicated the need for further investigation of the relationship of the nuclear CRABP1 with clinical parameters and patient survival to determine whether this protein can be used as a marker for differential diagnosis and/or disease prognosis.

Basal cell carcinoma: 10-year experience with electrochemotherapy

BackgroundElectrochemotherapy (ECT), by combining manageable cytotoxic agents with short electric pulses, represents an effective palliative skin-directed therapy. The accumulated evidence indicates that ECT stands out as a safe and well-tolerated alternative treatment for patients with multiple or large basal cell carcinoma (BCC), who are not suitable for conventional treatments. However, long-term data and shared indications are lacking.MethodsIn this observational study, we retrospectively analyzed 84 prospectively collected patients with multiple, recurrent or locally advanced BCC who were not candidate for standard therapies and received bleomycin-based ECT according to the European Standard Operative Procedures of ECT, from 2006 to 2016.ResultsDisease extent was local, locally advanced and metastatic in 40 (48%), 41 (49%) and 3 (3%), respectively. Forty-four (52%) individuals had multiple BCCs. Grade 3 skin toxicity after ECT was observed in 6% of cases. Clearance rate was 50% (95% CI 39–61%). Primary presentation (p = 0.004), tumor size <3 cm (p < 0.001), well-defined borders (p = 0.021), absence of tumor ulceration (p = 0.001), non-aggressive BCC histology (p = 0.046) and age ≤69 years were associated with higher complete response rate. In patients with local BCC, the clearance rate was 72.5 and 85% after one or two ECT cycles, respectively. In the laBCC group, 32 patients (78%) achieved an objective response. Five-year recurrence rate for local and laBCC was 20 and 38%, respectively (p ≤ 0.001).ConclusionsOne or two ECT cycles with bleomycin may be a valuable palliative treatment in well-selected patients with multiple BCCs and favorable tumor features. Validation of predictive factors will be imperative to match patients with optimal ECT treatment modalities. Management of laBCC with ECT warrants further investigation.Trial registration ISRCTN14633165 Registered 24 March 2017 (retrospectively registered)

Causes of death in long-term lung cancer survivors: a SEER database analysis

Background: Long-term (>5 years) lung cancer survivors represent a small but distinct subgroup of lung cancer patients and information about the causes of death of this subgroup is scarce.Methods: The Surveillance, Epidemiology and End Results (SEER) database (1988–2008) was utilized to determine the causes of death of long-term survivors of lung cancer. Survival analysis was conducted using Kaplan–Meier analysis and multivariate analysis was conducted using a Cox proportional hazard model. Clinicopathological characteristics and survival outcomes were assessed for the whole cohort.Results: A total of 78,701 lung cancer patients with >5 years survival were identified. This cohort included 54,488 patients surviving 5–10 years and 24,213 patients surviving >10 years. Among patients surviving 5–10 years, 21.8% were dead because of primary lung cancer, 10.2% were dead because of other cancers, 6.8% were dead because of cardiac disease and 5.3% were dead because of non-malignant pulmonary disease. Among patients surviving >10 years, 12% were dead because of primary lung cancer, 6% were dead because of other cancers, 6.9% were dead because of cardiac disease and 5.6% were dead because of non-malignant pulmonary disease. On multivariate analysis, factors associated with longer cardiac-disease-specific survival in multivariate analysis include younger age at diagnosis (p < .0001), white race (vs. African American race) (p = .005), female gender (p < .0001), right-sided disease (p = .003), adenocarcinoma (vs. large cell or small cell carcinoma), histology and receiving local treatment by surgery rather than radiotherapy (p < .0001).Conclusion: The probability of death from primary lung cancer is still significant among other causes of death even 20 years after diagnosis of lung cancer. Moreover, cardiac as well as non-malignant pulmonary causes contribute a considerable proportion of deaths in long-term lung cancer survivors.

Multiregion gene-expression profiling to reveal heterogeneity in molecular subtypes and immunotherapy response signatures in lung cancer.

e20077 Background: Intra-tumor heterogeneity (ITH) may be present in all molecular levels. Genomic ITH at the exome level has been reported in many cancer types, but comprehensive gene expression ITH has not been well studied. Methods: We collected 35 samples from 10 NSCLC patients (3 or 4 regions/tumor) including lung adenocarcinoma (n = 6), squamous cell carcinoma (n = 2), large cell carcinoma (n = 1) and pleomorphic carcinoma (n = 1). Using Affymetrix Gene 1.0 ST arrays, we generated the gene expression data for each sample. Diverse gene expression signatures associated with clinical outcomes were tested for ITH. Results: Inter-tumor heterogeneity was generally higher than intra-tumor heterogeneity, but some tumors showed a substantial level of ITH. The analysis of various clinically relevant gene expression signatures including molecular subtype, EMT and immunotherapy response signatures also revealed heterogeneity between different regions of the same tumor. The gene expression ITH we observed was associated with heterogeneous tumor microenvironments represented by stromal and immune cells infiltrated. Conclusions: Our data suggest that RNA-based prognostic or predictive molecular tests should be carefully conducted in consideration of the gene expression ITH.

Response to salvage chemotherapy following exposure to immune checkpoint inhibitors in patients with non-small cell lung cancer.

9084 Background: Immune checkpoint inhibitors are active for patients with stage IV NSCLC who have progressed following platinum-based chemotherapy. We evaluated responses to chemotherapy in patients who had progressed on a checkpoint inhibitor. Methods: Eligible patients were adults with NSCLC who received salvage chemotherapy following PD-1/PD-L1 inhibitors (cases) versus no PD-1/PD-L1 inhibitors (controls). CT-imaging was done within 4 weeks of initiation of salvage chemotherapy and every 6 weeks thereafter. Revised RECIST guidelines were used to define response. Clinical and imaging data were abstracted from review of electronic medical records. Multivariate logistic regression analysis was used to calculate probability of response. Results: Three-hundred and fifty patients’ charts were reviewed and 82 patients met eligibility criteria. Among evaluable patients, 46 were males. Sixty-seven patients were cases versus 15 controls. Fifty-six patients received nivolumab, 7 pembrolizumab and 4 atezolizumab. Sixty-three (77%) had adenocarcinoma, 18 (22%) squamous cell carcinoma and 1 (1%) large cell carcinoma. The mean number of chemotherapy regimens prior to salvage chemotherapy was 2.37 (95% C.I. 2.10-2.64)) in cases versus 1.93 (95% C.I: 1.32-2.54) in controls. Salvage drugs included docetaxel (62%), pemetrexed (20%), gemcitabine (12%), paclitaxel (6%). Eighteen (27%) cases had partial response to chemotherapy versus 1(7%) controls. Fifteen (22%) cases had progressive disease versus 6 (40%) controls. Thirty-four (51%) cases had stable disease versus 8 (53%) controls. The odd ratio for achieving a partial response was 0.30 (95% CI: 0.18 to 0.50, P = 0.000). In multiple logistic regression model, age, gender, number of prior chemotherapy regimens, tumor histology, smoking status, different salvage chemotherapy regimens were not associated with the likelihood of achieving a partial response. Conclusions: The odds of achieving a partial response to salvage chemotherapy were more than 3 times higher inpatients with prior exposure to PD-1/PD-L1 inhibitors. Ongoing investigations include the duration of response as well as evaluation of toxicity.

The real-world experience with nivolumab in previously treated patients with advanced non small cell lung cancer (NSCLC): A Galician Lung Cancer Group clinical practice.

e20564 Background: Nivolumab, was the first checkpoint inhibitor to show a survival benefit in previously treated patients with advanced NSCLC in two randomized trials (CheckMate 017 and 057). Experience in routine clinical practice may differ from that seen in a controlled clinical trial. This is an observational study that represents the real-world experience. Methods: Elegibility criteria included, histologically confirmed NSCLC stage IIIB vs IV, evaluable disease and at least one prior therapy. Patients received nivolumab 3 mg/kg IV (60 min) every 2 weeks until progressive disease or unacceptable toxicity. The aim of the study was to report the efficacy and safety profile of Nivolumab in pretreated patients with advanced NSCLC of our everyday clinical practice. The exploratory assessments include response rate (RR), progression-free survival (PFS), overall survival (OS) and treatment related adverse events (AEs). Results: From August 2015 to January 2017, with a median follow time of 18 months, 188 patients were enrolled from 9 different centers. Patients demographics were: median age 62 years, 44 female and 144 male; 17 never smoker and 171 former or current smoker; 105 adenocarcinoma, 7 large-cell carcinoma, 66 squamous, 3 adenosquamous and 7 NSCLC; 61 stage IIIB and 129 stage IV; 42 with central nervous system metastasis; and 70 received 2 or more prior therapy lines. Among 156 patients evaluated, 1,3% had CR, 28,2% PR, 29,7% SD and 40,8% PD. At the time of database lock, the median of PFS was 2.9 IC 95% (2,3-3.4) and OS was 12,8 IC 95% (9,2-16,4). The evaluation of PFS and OS by baseline characteristics doesn´t revealed statistical significance. Grade 1-2 treatment related adverse events (AEs) occurred in 58% of the patients: asthenia (22%), rash (14%), diarrhea (8%), anorexia (7%), endocrine (6%) and neumonitis (1,5%). Grade 3-4 AEs occurred in 5 patients; (3) diarrhea and (2) neumonitis and there were 3 treatment-related deaths. Conclusions: This study represents the real-word experience with nivolumab and the results are consistent with those previously reported in the CheckMate 017 and 057 trials.

Development of LC-QTOF-MS method for human lung tissue fingerprinting. A preliminary application to nonsmall cell lung cancer.

The major histologic subtypes of non-small cell lung cancer (NSCLC) include adenocarcinoma (ADC), squamous cell lung carcinoma (SCC), and large-cell carcinoma (LCC). Clinical trials of targeted agents and newer chemotherapy agents yielded differences in outcomes according to histologic subgroups providing a rationale for histology-based treatment in NSCLC. Currently, NSCLC subtyping is performed based on histopathological examinations and immunohistochemistry. However available methods leave about 10% of NSCLC cases as not otherwise specified. The purpose of this study was development of an LC-QTOF-MS method for human lung tissue metabolic fingerprinting that could discriminate NSCLC histological subtypes and propose biomarkers candidates that could support proper NSCLC diagnosis. Metabolites were extracted with acetonitrile or methanol/ethanol and different chromatographic conditions were tested. In the final method 10 mg of lung tissue was homogenized with 50% methanol and metabolites were extracted with acetonitrile. Metabolites were separated on C8-RP and HILIC columns. About 3500 and 2000 of metabolic features (in both ion modes) were detected with good repeatability (CV<20%) by RP and HILIC methods, respectively. Lung tumor and control tissue samples obtained from NSCLC patients were analyzed with developed methodology. Acylcarnitines, fatty acids, phospholipids, and amino acids were found more abundant in tumor as compared to control tissue. Acylcarnitines, lysophospholipids, creatinine, creatine, and alanine were identified as potential targets enabling classification of NSCLC subtypes.

Clinicopathologic features and genetic profile of the redefined large cell lung carcinoma

Objective: To investigate the clinicopathologic features and genetic profile of large cell lung carcinoma (LCC) redefined by new classification. Methods: Basing on 2015 WHO classification criteria in redefining large cell lung carcinoma, the expression of specific markers (TTF1, Napsin A, p40, CK5/6, CK, vimentin and ZEB1) was detected by immunohistochemistry and D-PAS staining in 303 surgically-removed lung specimens previously diagnosed as large cell lung carcinoma. The clinicopathologic and genetic characteristics (including EGFR, KRAS, BRAF, ALK and ROS1 gene mutation) were analyzed. Results: Based on the new definition of LCC, 116 cases (116/303, 38.3%) of LCC formerly diagnosed were reclassified as solid adenocarcinoma, 49 cases (49/303, 16.2%) as squamous cell carcinoma, 6 cases (6/303, 2.0%) as adenosquamous carcinoma, 22 cases (22/303, 7.3%) as spindle cell carcinoma and only 110 cases (110/303, 36.3%) as large cell carcinoma. Redefined LCCs were characterized as middle-age (range 40-80), male (102/110, 92.7%) and smoking patients (64/110, 58.2%) with intermediate-advanced stage. Among 110 cases, 9 cases with EGFR mutation and 10 cases with KRAS mutation and 1 case with ALK fusion were found. No BRAF and ROS1 alterations were identified. Conclusions: According to the new classification, LCCs formerly diagnosed are mostly reclassified as adenocarcinoma and non-keratinizing squamous cell carcinoma. The newly defined LCC may significantly benefit from clinical therapy.

Evaluation of erlotinib for the treatment of patients with non-small cell lung cancer with epidermal growth factor receptor wild type

Erlotinib is one of the treatment choices for patients with advanced non-small cell lung cancer (NSCLC), regardless of the epidermal growth factor receptor (EGFR) mutation status. However, its efficacy for the treatment of patients with NSCLC with EGFR wild type or who are beyond the usage of gefitinib remains controversial. The present study therefore retrospectively assessed the efficacy of erlotinib in patients with wild type EGFR who had previously undergone gefitinib therapy. A total of 222 patients with NSCLC who received chemotherapeutic treatment with erlotinib between July 2007 and February 2013 were evaluated. The background variables, response rates, progression-free survival (PFS) and overall survival rates were retrospectively analyzed. The male/female ratio of patients was 103/119, and patients had a median age of 63 years (range, 33-95 years). A total of 10 of the 222 patients had clinical stages IIIB/IV, 191 had adenocarcinoma, 5 had large cell carcinoma, 10 had squamous cell carcinoma and 6 had NSCLC of a variety not otherwise specified. The EGFR mutation was positive, wild type or unknown in 95, 52 and 75 patients, respectively. In the 52 patients with EGFR wild type, there were 3 partial responders, 25 with stable disease and 24 with progressive disease, for a response rate of 6% [95% confidence interval (CI), 1.3-15%]. The median PFS of EGFR wild type and positive were 1.1 months (95% CI, 1.04-1.16 months) and 5.42 months (95% CI, 5.43-5.68 months), respectively. The results of the study demonstrated that erlotinib is not sufficiently effective for patients with NSCLC who possess the EGFR wild type status.

Synergistic Effects of Omeprazole and Metformin on Glycemic Control in Type 2 Diabetic Patients. A Randomized Clinical Study

Background: Lung cancer is one of the most common malignancies worldwide. Cigarette smoking is considered as the major risk factor for bronchogenic carcinoma. The four common types namely – squamous cell; small cell; adeno and large cell carcinomas account for more than 90% cases of Bronchogenic carcinoma. Initially it is detected by plain chest radiography but it is considered as an insensitive. Computed Tomography can detect early stage disease 6-10 times more frequently than X-rays. Objective: To determine diagnostic accuracy of Contrast Enhanced Computed Tomography in detecting Bronchogenic Carcinoma taking histopathology as Gold Standard. Methods: Total 157 patients presented with pulmonary nodule or suspicious lesion on X-Ray and had history of haemoptysis, weight loss, cough and chest pain for more than two months were included. CT was performed with I/V contrast. Axial images were taken with patients lying supine. Images were analyzed. The same radiologist assessed the patient included in the study. All patients then underwent biopsy and samples were sent for histopathology. Sensitivity, specificity, and accuracy of computed tomography were calculated using histopathology as gold standard. Results: There were 101 male and 56 female patients. The mean age was 59.77±7.97 years. On CT Scan 89 patients were diagnosed with bronchogenic carcinoma. On histopathology, 90 patients were diagnosed with bronchogenic carcinoma. The sensitivity of CT Scan was 90.0%, specificity was 88.0% and diagnostic accuracy was 89.1%. Conclusion: CT scan is a sensitive imaging modality in diagnosing malignancy in pulmonary lesions

A selected reaction monitoring mass spectrometric assessment of biomarker candidates diagnosing large-cell neuroendocrine lung carcinoma by the scaling method using endogenous references

Selected reaction monitoring mass spectrometry (SRM-MS) -based semi-quantitation was performed to assess the validity of 46 selected candidate proteins for specifically diagnosing large-cell neuroendocrine lung carcinoma (LCNEC) and differentiating it from other lung cancer subtypes. The scaling method was applied in this study using specific SRM peak areas (AUCs) derived from the endogenous reference protein that normalizes all SRM AUCs obtained for the candidate proteins. In a screening verification study, we found that seven out of the 46 candidate proteins were statistically significant for the LCNEC phenotype, including 4F2hc cell surface antigen heavy chain (4F2hc/CD98) (p-ANOVA ≤ 0.0012), retinal dehydrogenase 1 (p-ANOVA ≤ 0.0029), apolipoprotein A-I (p-ANOVA ≤ 0.0004), β-enolase (p-ANOVA ≤ 0.0043), creatine kinase B-type (p-ANOVA ≤ 0.0070), and galectin-3-binding protein (p-ANOVA = 0.0080), and phosphatidylethanolamine-binding protein 1 (p-ANOVA ≤ 0.0012). In addition, we also identified candidate proteins specific to the small-cell lung carcinoma (SCLC) subtype. These candidates include brain acid soluble protein 1 (p-ANOVA < 0.0001) and γ-enolase (p-ANOVA ≤ 0.0013). This new relative quantitation-based approach utilizing the scaling method can be applied to assess hundreds of protein candidates obtained from discovery proteomic studies as a first step of the verification phase in biomarker development processes.

Efficacy and tolerability of nanoparticle albumin-bound paclitaxel in combination with carboplatin as a late-phase chemotherapy for recurrent and advanced non-small-cell lung cancer: A multi-center study of the Fukushima lung cancer association group of surgeons.

The present retrospective multi-center study aimed to evaluate the efficacy and feasibility of nanoparticle albumin-bound (nab)-paclitaxel plus carboplatin as a second or late-phase chemotherapy in patients with non-small cell lung cancer (NSCLC). A total of 25 patients with recurrent or advanced NSCLC who had received previous chemotherapy were treated with nab-paclitaxel (70-100 mg/m2, intravenously) on days 1, 8 and 15 every 28 days with a carboplatin area under the concentration-time curve of 4-6 on day 1. The overall response rate, disease control rate, progression-free survival (PFS), overall survival (OS) and toxicities were statistically evaluated. Of the 25 patients, there were 9 cases of recurrent disease following surgery, 16 cases of advanced disease, 13 cases of adenocarcinoma, 11 cases of squamous cell carcinoma and 1 case of large cell carcinoma. A total of 13 patients received second-line chemotherapy and 12 received fourth-line or later chemotherapy. One patient exhibited a complete response, 7 had a partial response, 10 exhibited stable disease and 7 had progressive disease. The overall response rate was 32.0% and the disease control rate was 72.0%. The median PFS and median OS following nab-paclitaxel treatment were 4.0 and 14.0 months, respectively. Frequent treatment-associated adverse events were myelosuppression, peripheral neuropathy, gastrointestinal symptoms and baldness, the majority of which were grade 1-2. Grade 3-4 neutropenia, thrombocytopenia and anemia occurred in 7 (28.0%), 3 (12.0%) and 2 (8.0%) patients, respectively. No patients experienced grade 3-4 sensory neuropathy and no grade 5 adverse effects were observed. Nab-paclitaxel plus carboplatin as second-phase or later chemotherapy provided a small but significant survival benefit for patients with recurrent or advanced NSCLC, with tolerable adverse effects. To the best of our knowledge, the results of the present study demonstrated for the first time that nab-paclitaxel plus carboplatin is a promising and feasible late-phase chemotherapeutic agent for NSCLC.

Cell blocks histopathology versus FNA cytology in diagnosis of primary malignant lung mass: A comparative study

Background and objective: Fine needle aspiration cytology with cell block preparation is widely used for preoperative confirmation of solitary lung mass and classification of the histologic types. This study aimed to highlight the importance of cell-block preparation in the diagnosis of primary malignant lung lesion by comparing cytomorphological preservation on paired cell block and conventional fine needle aspiration samples. Methods: During January 2012 to October 2015, a total of 100 cases with solitary lung mass were included, either visited Rizgary Teaching Hospital or Walfare private hospital. All the patients had undergone fine needle aspiration and cell block preparation under a CT-guide. Results: The samples were evaluated by the fine needle aspirations and cell blocks preparations from primary lung lesion under a CT-guide. 74% were male, and the majority of them were in the sixth and seventh decade. Squamous cell carcinoma was the most common histologic type consisting 42% of the studied cases, followed by adenocarconima (31%), small cell carcinoma (19%) and the remaining 8% were large cell carcinomas. In the assessment of agreement of cellularity between the two methods of sample preparation, cell block served better than fine needle aspiration (P = 0.715). However, this difference was statistically non-significant. A significant relation was found for morphology which was preserved in fine needle aspiration samples better than that in cell block samples (P <0.05). In contrast, all cell block samples displayed a statistically highly significant architectural preservation compared to fine needle aspiration samples (P <0.001). The sensitivity and specificity of the present study were 98.46%, 99.2% respectively. Conclusion: Direct fine needle aspiration smears and cell blocks complement each other, and our results indicate that both are needed in the diagnostic work-up of patients with a primary malignant lung mass.