Diagnosis Of Lung Adenocarcinoma Research Articles

P52-9 Hard diagnosis and treatment in a patient with HER-2 and TTF-1 positive adenocarcinoma

TTF-1 immunoreactivity in breast cancer has been reported to be rare. We experienced the patients with TTF-1 and HER2(+) adenocarcinoma in both pulmonary and breast lesions. Herein, we reported the case in which the treatment strategy of HER2(+) breast cancer was successful after the failure of the chemotherapy for advanced lung adenocarcinoma. A 60-year-old woman visited our institute with cough and shortness of breath. Inflammatory change of left breast with ipsilateral left axillary and supra-clavicular lymphadenopathies was observed by physical examinations. CT revealed a tumor in the left lung, bilateral pleural effusion and skin thickening in the breast. Histological analysis of the left supra-clavicular lymph node led to the diagnosis of lung adenocarcinoma (CK7 +, TTF-1 +, EGFR wt, no ALK and ROS1 rearrangement, PD-L1 TPS <1%, HER2 IHC 3+, ER -, PR -, mammaglobin-), which was also confirmed in the skin biopsy of left breast. The tumor was classified as clinical T4N3M1, stage IV. She received 4 cycles of CBDCA, pemetrexed and pembrolizumab. Partial response was achieved, but she experienced progressive disease due to cancerous pericarditis after 2 cycles of a maintenance therapy. The second line chemotherapy of docetaxel and ramucirumab was performed immediately. After 2 cycles, new lesions appeared in right mammary gland and left parotid gland. The histological diagnosis in a core needle biopsy of the right breast lesion was as same as in the left supra-clavicular lymph node. Because a possibility of TTF-1 positive breast cancer as a primary tumor could not be denied, we adopted the chemotherapy of trastuzumab, pertuzumab and paclitaxel according to the treatment strategy of HER2 (+) breast cancer. Partial response was obtained after 2 cycles and continued for 8 months. The tumor agnostic approach is important not only for drug development but also for daily clinical practice in the field of medical oncology.

Deep Learning-Based Stage-Wise Risk Stratification for Early Lung Adenocarcinoma in CT Images: A Multi-Center Study.

Simple SummaryPrediction of the malignancy and invasiveness of ground glass nodules (GGNs) from computed tomography images is a crucial task for radiologists in risk stratification of early-stage lung adenocarcinoma. In order to solve this challenge, a two-stage deep neural network (DNN) was developed based on the images collected from four centers. A multi-reader multi-case observer study was conducted to evaluate the model capability. The performance of our model was comparable or even more accurate than that of senior radiologists, with average area under the curve values of 0.76 and 0.95 for two tasks, respectively. Findings suggest (1) a positive trend between the diagnostic performance and radiologist’s experience, (2) DNN yielded equivalent or even higher performance in comparison with senior radiologists, and (3) low image resolution reduced the model performance in predicting the risks of GGNs.This study aims to develop a deep neural network (DNN)-based two-stage risk stratification model for early lung adenocarcinomas in CT images, and investigate the performance compared with practicing radiologists. A total of 2393 GGNs were retrospectively collected from 2105 patients in four centers. All the pathologic results of GGNs were obtained from surgically resected specimens. A two-stage deep neural network was developed based on the 3D residual network and atrous convolution module to diagnose benign and malignant GGNs (Task1) and classify between invasive adenocarcinoma (IA) and non-IA for these malignant GGNs (Task2). A multi-reader multi-case observer study with six board-certified radiologists’ (average experience 11 years, range 2–28 years) participation was conducted to evaluate the model capability. DNN yielded area under the receiver operating characteristic curve (AUC) values of 0.76 ± 0.03 (95% confidence interval (CI): (0.69, 0.82)) and 0.96 ± 0.02 (95% CI: (0.92, 0.98)) for Task1 and Task2, which were equivalent to or higher than radiologists in the senior group with average AUC values of 0.76 and 0.95, respectively (p > 0.05). With the CT image slice thickness increasing from 1.15 mm ± 0.36 to 1.73 mm ± 0.64, DNN performance decreased 0.08 and 0.22 for the two tasks. The results demonstrated (1) a positive trend between the diagnostic performance and radiologist’s experience, (2) the DNN yielded equivalent or even higher performance in comparison with senior radiologists, and (3) low image resolution decreased model performance in predicting the risks of GGNs. Once tested prospectively in clinical practice, the DNN could have the potential to assist doctors in precision diagnosis and treatment of early lung adenocarcinoma.

Dissecting the multi-omics atlas of the exosomes released by human lung adenocarcinoma stem-like cells

Lung adenocarcinoma is heterogeneous and hierarchically organized, with a subpopulation of stem-like cells (CSCs) that reside at the apex of the hierarchy, in which exosomes act as important mediators by transporting specific molecules among different cell populations. Although there have been numerous studies on tumor exosomes, the constituents and functional properties of CSC-derived exosomes are still poorly characterized. Here we present a detail transcriptome and proteome atlas of the exosomes released by human lung adenocarcinoma stem-like cells (LSLCs). The transcriptome analysis indicates the specific patterns of exosomal constituents, including the fragmentation of transcripts and the low-level presence of circular RNAs, and identifies multiple exosomal-enriched mRNAs and lncRNAs. Integrative analysis of transcriptome and proteome data reveals the diverse functions of exosomal-enriched RNAs and proteins, many of which are associated with tumorigenesis. Importantly, several LSLC markers we identified are highly expressed in LSLC-derived exosomes and associate with poor survival, which may serve as promising liquid biopsy biomarkers for lung adenocarcinoma diagnosis. Our study provides a resource for the future elucidation of the functions of tumor-derived exosomes and their regulatory mechanisms in mediating lung cancer development.

MTHFD2 promotes tumorigenesis and metastasis in lung adenocarcinoma by regulating AKT/GSK-3β/β-catenin signalling.

Recent studies have demonstrated that one‐carbon metabolism plays a significant role in cancer development. Methylenetetrahydrofolate dehydrogenase 2 (MTHFD2), a mitochondrial enzyme of one‐carbon metabolism, has been reported to be dysregulated in many cancers. However, the specific role and mechanism of MTHFD2 in lung adenocarcinoma (LUAD) still remains unclear. In this study, we evaluated the clinicopathological and prognostic values of MTHFD2 in LUAD patients. We conducted a series of functional experiments in vivo and in vitro to explore novel mechanism of MTHFD2 in LUAD. The results showed that MTHFD2 was significantly up‐regulated in LUAD tissues and predicted poor prognosis of LUAD patients. Knockdown of MTHFD2 dramatically inhibited cell proliferation and migration by blocking the cell cycle and inducing the epithelial‐mesenchymal transition (EMT). In addition, MTHFD2 knockdown suppressed LUAD growth and metastasis in cell‐derived xenografts. Mechanically, we found that MTHFD2 promoted LUAD cell growth and metastasis via AKT/GSK‐3β/β‐catenin signalling. Finally, we identified miR‐30a‐3p as a novel regulator of MTHFD2 in LUAD. Collectively, MTHFD2 plays an oncogenic role in LUAD progression and is a promising target for LUAD diagnosis and therapy.

Association between CNVs of BMI-related gene and survival status of LUAD and LUSC patients.

e20524 Background: In recent decades, many GWAS studies help to discover the gene related to BMI or obesity. FTO, BDNF, LEPR, MC4R, SH2B1, GNPDA2, INSIG2, KCTD15, LEP, MTCH2, NEGR1, NPC1, PCSK1, POMC, TMEM18 and UCP2 are 16 genes showing most significant association with BMI. Those genes impact BMI by either alternating sex hormone metabolism, influencing insulin and insulin-like growth factor, or mediating inflammatory and adipokines. Those pathways impact cancer cells also. Here we report the association between copy number variables (CNV) of those genes and outcome of lung adenocarcinoma (LUAD) and lung squamous cell cancer (LUSC). Methods: 522 individuals in LUAD dataset of TCGA and 504 individuals in LUSC dataset of TCGA are included in this study. CNVs of each gene are main predictors, the survival time is the main outcome in the study, and gender, tumor stage, smoking status are chosen to adjust model. Multivariable Cox models are generated for LUAD patients and LUSC patients respectively. To control false discovery rate (FDR), Benjamini-Hochberg procedure is employed. Results: For LUAD patients, tumor stages impact survival status significantly, but age, gender and smoking status don’t impact survival time significantly. At the same time, CNV of TMEM18 has hazard ratio of 0.0353 (95% CI: 0.0032, 0.3910), which means the gain of genetic materials on the position of TMEM18 gene will protect patients to die after diagnosis of LUAD, and the effect is extremely large. The p-value of 0.006 is less than 0.00625, which is derived with Benjamini-Hochberg procedure with false discovery rate of 0.1. For LUSC patients, only serious tumor stages, tumor stage III and tumor stage IV, impact survival status significantly, and old age will cause patients die earlier significantly. Neither gender nor smoking status don’t impact survival status significantly. When adjusting age, gender, smoking status, and tumor stage, gain of genetic materials on the position of NEGR1 gene does increase the risk of death significantly, and the hazard ratio of CNV of NEGR1 is 9.920 (95% CI: 1.237, 79.552). The p-value of 0.031 is large than 0.00625, which is derived with Benjamini-Hochberg procedure with fase discovery rate of 0.1. Conclusion: Copy number variable of TMEM18 gene impact outcome of LUAD patients significantly. The gain of TMEM18 genetic materials protects patients to die, meanwhile the loss of TMEM18 genetic materials cause patients to have shorter overall survival time. TMEM18 affect the central nervous system to imbalance energy metabolism in previous murine models, and here we found TMEM18 has significant impact on survival status of LUAD patients, so the transmembrane protein gene TMEM18 may be a key factor to outcome of LUAD.

Application of TTF1 immunohistochemistry combined with elastic fiber double staining in the diagnosis of lung adenocarcinoma

Application of TTF1 immunohistochemistry combined with elastic fiber double staining in the diagnosis of lung adenocarcinoma

The application of cytokeratin 7 and elastic fiber double staining with automation platform in the diagnosis of lung adenocarcinoma

为更好地显示肺腺癌中弹力纤维的变化及其与肿瘤细胞的关系，应用全自动免疫组织化学和全自动特殊染色平台对30例肺腺癌组织细胞进行角蛋白（CK）7和弹力纤维双重染色，结果显示在双染切片中CK7免疫组织化学的特异度和灵敏度与单独染色基本没有差异，两者相结合除可以特异性显示胸膜受侵的情况，还观察到多数厚壁血管弹力纤维的增生和血管壁的重构，以及更多CK7和弹力纤维单独染色难以观察到的肿瘤细胞早期浸润血管壁的现象。.

Lung metastasis induced chronic compartment syndrome of the lower leg

&lt;p class="abstract"&gt;Compartment syndrome occurs when the pressure within a defined compartmental space increases above a critical pressure threshold. Lung cancer is one of the world's most frequently diagnosed cancer whose metastases are rare cause of compartment syndrome. We present a 50 year old male patient who was admitted to our emergency department due to painful left lower leg, swelling and paresthesia of the medial side of the foot that lasted about 2 months back. The diagnosis of metastatic lung adenocarcinoma was set 9 months earlier. Physical examination revealed an ill-defined, tense, and tender swelling left calf and X-ray images confirmed periosteal reaction on all four cortices of both bones without osteolytic lesions. After an adequate laboratory analyses and preoperative preparation, debridement with biopsy and fasciotomy was performed. Histopathological evaluation showed necrotic tumor tissue that morphologically and immunohistochemically corresponds to lung cancer. We performed an above knee amputation and the next day, the patient was discharged home, due to his personal request.&lt;/p&gt;

Identifying and Validating Potential Biomarkers of Early Stage Lung Adenocarcinoma Diagnosis and Prognosis

BackgroundLung adenocarcinoma (LUAD) is the most common pathological type of lung cancer. At present, most patients with LUAD are diagnosed at an advanced stage, and the prognosis of advanced LUAD is poor. Hence, we aimed to identify novel biomarkers for the diagnosis and treatment of early stage LUAD and to explore their predictive value.MethodsThe microarray datasets GSE63459, GSE27262, and GSE33532 were searched, and the differentially expressed genes (DEGs) were obtained using GEO2R. The DEGs were subjected to gene ontology (GO) and pathway enrichment analyses using METASCAPE. A protein–protein interaction (PPI) network was plotted with STRING and visualized by Cytoscape. Module analysis of the PPI network was performed using MCODE. Overall survival (OS) analysis and analysis of the mRNA expression levels of genes identified by MCODE were performed with UALCAN. Western blot analysis of hub genes in LUAD patients, MTS assays, and clonogenic assays were performed to test the effects of the hub genes on cell proliferation in vitro.ResultsA total of 341 DEGs were obtained, which were mainly enriched in terms related to blood vessel development, growth factor binding, and extracellular matrix organization. A PPI network consisting of 300 nodes and 1140 edges was constructed, and a significant module including 15 genes was identified. Elevated expression of ASPM, CCNB2, CDCA5, PRC1, KIAA0101, and UBE2T was associated with poor OS in LUAD patients. In the protein level, the hub gene was overexpressed in LUAD patients. In vitro experiments showed that knockdown of the hub genes in the LUAD cell lines could promote cell proliferation.ConclusionsDEGs are potential biomarkers for early stage lung adenocarcinoma and could have utility for the diagnosis and predicting treatment efficacy.

Germline mutations and age at onset of lung adenocarcinoma.

To identify additional at-risk groups for lung cancer screening, which targets persons with a long history of smoking and thereby misses younger or nonsmoking cases, the authors evaluated germline pathogenic variants (PVs) in patients with lung adenocarcinoma for an association with an accelerated onset. The authors assembled a retrospective cohort (1999-2018) of oncogenetic clinic patients with lung adenocarcinoma. Eligibility required a family history of cancer, data on smoking, and a germline biospecimen to screen via a multigene panel. Germline PVs (TP53/EGFR, BRCA2, other Fanconi anemia [FA] pathway genes, and non-FA DNA repair genes) were interrogated for associations with the age at diagnosis via an accelerated failure time model. Subjects (n = 187; age, 28-89 years; female, 72.7%; Hispanic, 11.8%) included smokers (minimum of 5 pack-years; n = 65) and nonsmokers (lighter ever smokers [n = 18] and never smokers [n = 104]). Overall, 26.7% of the subjects carried 1 to 2 germline PVs: TP53 (n = 5), EGFR (n = 2), BRCA2 (n = 6), another FA gene (n = 11), or another DNA repair gene (n = 28). After adjustment for smoking, sex, and ethnicity, the diagnosis of lung adenocarcinoma was accelerated 12.2 years (95% confidence interval [CI], 2.5-20.6 years) by BRCA2 PVs, 9.0 years (95% CI, 0.5-16.5 years) by TP53/EGFR PVs, and 6.1 years (95% CI, -1.0 to 12.6 years) by PVs in other FA genes. PVs in other DNA repair genes showed no association. Germline associations did not vary by smoking. Among lung adenocarcinoma cases, germline PVs (TP53, EGFR, BRCA2, and possibly other FA genes) may be associated with an earlier onset. With further study, the criteria for lung cancer screening may need to include carriers of high-risk PVs, and findings could influence precision therapy and reduce lung cancer mortality by earlier stage diagnosis.

The Diagnostic and Prognostic Roles of Combined Expression of Novel Biomarkers in Lung Adenocarcinoma and Lung Squamous Cell Carcinoma: An Immunohistochemical Study.

Background & Objective:Diagnosis and discrimination of lung adenocarcinoma (LUAD) from lung squamous cell carcinoma (LUSC) is critical to select the appropriate treatment regimen as recently targeted therapies require accurate subtyping of nonsmall-cell lung carcinoma (NSCLCs). There are currently several biomarkers that could be used for differentiation between LUAD and LUSC, but they have less sensitivity, specificity, and clinical applicability. The aim of this study was to assess the diagnostic and prognostic values of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin tissue expression in the tissues retrieved from LUAD and LUSC patients using immunohistochemistry.Methods:The current study was performed on the samples retrieved from sixty primary lung masses that were diagnosed as LUAD and LUSC. Immunohistochemistry was performed by using a panel of CLCA2, SPATS2, and ST6GALNAC1. We assessed the diagnostic roles of the studied markers in the discrimination between LUAD and LUSC and their prognostic values. Results:SPATS2 and CLCA2 were expressed higher in LUSC than LUAD. ST6GALNAC1 and Adipophilin showed higher expression in LUAD than LUSC (P<0.001). The sensitivity and specificity of CLCA2, SPATS2, ST6GALNAC1 and Adipophilin in adequate subtyping and reaching the accurate diagnosis was 100%. We found only significant difference in survival rate between the patients with negative and positive CLCA2 expression (P=0.038 and P=0.019, respectively). Conclusion:The combination of biomarkers of CLCA2, SPATS2, ST6GALNAC1, and Adipophilin may lead to an appropriate subtyping of lung cancer and reaching accurate diagnosis with the highest sensitivity and specificity.

Lung adenocarcinoma concomitant with xeroderma pigmentosum: a case report

BackgroundXeroderma pigmentosum is a rare, autosomal-recessive photosensitive dermatosis. Patients with xeroderma pigmentosum have an impaired ability to repair deoxyribonucleic acid damage caused by ultraviolet rays, resulting in skin cancer. Patients with xeroderma pigmentosum are more susceptible to some cancers. We herein report a case of xeroderma pigmentosum accompanied by lung cancer.Case presentationThe patient was a Japanese woman in her 70s with a family history of consanguineous marriage. Her medical history included squamous cell carcinoma and basal cell carcinoma, in addition to xeroderma pigmentosum. She presented with dry skin with small, pigmented spots, which were particularly focused around the areas exposed to sunlight. Chest computed tomography was conducted to assess for any evidence of metastatic skin carcinoma, and revealed a tumor in the left upper subpleural lobe of the lung. Consequently, she was referred to our department. Finally, we diagnosed lung adenocarcinoma (pT2aN0M1b: stage IVA). She had an epidermal growth factor receptor (EGFR) mutation (p.L858R). Treatment with an epidermal growth factor receptor tyrosine kinase inhibitor (gefitinib) was initiated, and the tumor gradually regressed. No side effects were observed. However, she later died from aspiration pneumonia.ConclusionsAlthough xeroderma pigmentosum is rare, a history of consanguineous marriage should be verified. Because of the severe side effects of cisplatin and radiotherapy in xeroderma pigmentosum patients, the risks and benefits of treatment should be considered thoroughly.

Targeted Luminescent Probes for Precise Upconversion/NIR II Luminescence Diagnosis of Lung Adenocarcinoma.

In this research, the antibody of the searched hub genes has been proposed to combine with a rare-earth composite for an upconversion luminescence (UCL) and downconversion (DCL) NIR-II imaging strategy for the diagnosis of lung adenocarcinoma (LUAD). Weighted gene co-expression network analysis is used to search the most relevant hub genes, and the required top genes that contribute to tumorigenesis (negative: CLEC3B, MFAP4, PECAM1, and FHL1; positive: CCNB2, CDCA5, HMMR, and TOP2A) are identified and validated by survival analysis and transcriptional and translational results. Meanwhile, fluorescence imaging probes (NaYF4:Yb,Er,Eu@NaYF4:Nd, denoted as NYF:Eu NPs) with multimodal optical imaging properties of downconversion and upconversion luminescence in the visible region and luminescence in the near infrared II region are designed with various uniform sizes and enhanced penetration and sensitivity. Finally, when the NYF:Eu NP probe is combined with antibodies of these chosen positive hub genes (such as, TOP2A and CCNB2), the in vitro and in vivo animal experiments (flow cytometry, cell counting kit-8 assay using A549 cells, and in vivo immunohistochemistry IHC microscopy images of LUAD from patient cases) indicate that the designed nanoprobes can be excellently used as a targeted optical probe for future accurate diagnosis and surgery navigation of LUAD in contrast with other cancer cells and normal cells. This strategy of antibodies combined with optical probes provides a dual-modal luminescence imaging method for precise medicine.

48-Year-Old Woman With Dyspnea and Chest Pain

48-Year-Old Woman With Dyspnea and Chest Pain

Pulmonary Mucinous Adenocarcinoma

Mucinous adenocarcinoma is a rare malignant tumor of the lung, which is accompanied by extremely scarce and nonspecific symptoms. This leads to an increase in the timing of its recognition, especially in young women. Given the poor prognosis of the pathlogy, the problem of its early diagnosis with histological and immuno-histochemical studies is extremely urgent. The presented clinical case demonstrates the possibilities of computed tomography with intravenous contrast enhancement in a young woman for the diagnosis of mucinous lung adenocarcinoma.

Computer-aided diagnosis of ground glass pulmonary nodule by fusing deep learning and radiomics features

Objectives. This study aims to develop a computer-aided diagnosis (CADx) scheme to classify between benign and malignant ground glass nodules (GGNs), and fuse deep leaning and radiomics imaging features to improve the classification performance. Methods. We first retrospectively collected 513 surgery histopathology confirmed GGNs from two centers. Among these GGNs, 100 were benign and 413 were malignant. All malignant tumors were stage I lung adenocarcinoma. To segment GGNs, we applied a deep convolutional neural network and residual architecture to train and build a 3D U-Net. Then, based on the pre-trained U-Net, we used a transfer learning approach to build a deep neural network (DNN) to classify between benign and malignant GGNs. With the GGN segmentation results generated by 3D U-Net, we also developed a CT radiomics model by adopting a series of image processing techniques, i.e. radiomics feature extraction, feature selection, synthetic minority over-sampling technique, and support vector machine classifier training/testing, etc. Finally, we applied an information fusion method to fuse the prediction scores generated by DNN based CADx model and CT-radiomics based model. To evaluate the proposed model performance, we conducted a comparison experiment by testing on an independent testing dataset. Results. Comparing with DNN model and radiomics model, our fusion model yielded a significant higher area under a receiver operating characteristic curve (AUC) value of 0.73 ± 0.06 (P < 0.01). The fusion model generated an accuracy of 75.6%, F1 score of 84.6%, weighted average F1 score of 70.3%, and Matthews correlation coefficient of 43.6%, which were higher than the DNN model and radiomics model individually. Conclusions. Our experimental results demonstrated that (1) applying a CADx scheme was feasible to diagnosis of early-stage lung adenocarcinoma, (2) deep image features and radiomics features provided complementary information in classifying benign and malignant GGNs, and (3) it was an effective way to build DNN model with limited dataset by using transfer learning. Thus, to build a robust image analysis based CADx model, one can combine different types of image features to decode the imaging phenotypes of GGN.

FP02.09 Effects of Chinese Reimbursement Policy on Molecular Diagnosis and Therapy of NSCLC from the Northern Part of Henan Province

Gefitinib (Irisa) have significantly prolonged the overall survival of advanced non-small cell lung cancer (NSCLC) patients with the EGFR sensitivity mutations positive (EGFR+). Our hospital, the first affiliated hospital of Xinxiang Medical University, is the largest provincial Grade 3A hospital in northern part of Henan Province, most of the patients come from rural areas, and the incomes of the patients and their family members are too low to afford the expensive antitumor costs. Therefore, the expensive costs prevent the timely and sufficient treatment with gefitinib in patients with positive EGFR+ in our hospital. Fortunately, on September 2016, gefitinib was included in health care policy of Henan Province, thus the expenses were reduced significantly. The purpose of this study was to investigate the influence of China's reimbursement policy on molecular diagnosis and treatment of advanced lung adenocarcinoma (LUAD) in our hospital. Here, the data of the LUAD from February 2015 to August 2016, as well as from September 2016 to March 2018 of our hospital were collected. The chi-square test is used to analysis: (1)the detection rate of EGFR gene mutations (EGFR-M) before and after reimbursement. (2)the detection rate of EGFR-M in the department of oncology before and after reimbursement respectively. (3) the detection rate of EGFR-M in the department of non-oncology before and after reimbursement respectively. (4)the application of EGFR-TKIs(including gefitinib and icotinib) in patients with EGFR+ before & after reimbursement. In this study, 315 cases and 405 cases were collected befor and after Semptember 2016 respectively: (1)The detection rate of EGFR-M was increased from 13.65% to 44.55% after reimbursement (P≤0.01) (Fig1A). (2)In the department of oncology, the detection rate of EGFR-M was elevated from 20.53% to 58.94% after reimbursement (P≤0.01). (3) In the department of non-oncology, the detection rate was also increased from 3.20% to 35% after reimbursement (P≤0.01). (4) The detection rate of EGFR-M was higher in the department of oncology than that of non-oncology department both before and after reimbursement (P≤0.01) (Fig1B & C). (5) After reimbursement, the application of EGFR-TKIs on patients with EGFR+ was increased prominently. There are only 21.74%(5/23) patients received treatment of EGFR-TKIs before September 2016, while most of patients with positive EGFR-sensitive mutations (72.55%, 74/102) were treated by EGFR-TKIs after September 2016(Fig1D) (P≤0.01). Chinese reimbursement policy can affect the molecular analysis and therapy of NSCLC from the northern part of Henan province significantly.

Feasibility of intraoperative diagnosis of lung adenocarcinoma in situ to avoid excessive resection.

BackgroundLimited lung resection is generally believed to be available for lung adenocarcinoma in situ (AIS). At our institute, intraoperative hematoxylin-eosin staining of frozen-section slides is routinely performed for evaluating tumor invasiveness after partial resection to avoid excessive lung resection. This study aimed to evaluate the feasibility and usefulness of intraoperative frozen-section diagnosis of AIS.MethodsWe retrospectively reviewed 143 patients with 151 AISs diagnosed by intraoperative frozen sections between 2012 and 2019 at our institute. All patients underwent limited resection because of the result of intraoperative frozen-section diagnosis.ResultsThe total concordance rate between the diagnoses of AIS by intraoperative frozen sections and postoperative paraffin-embedded sections was 82.7% for 151 nodules. Although 21 minimally invasive adenocarcinomas (MIA) and 5 invasive adenocarcinomas were diagnosed as AIS intraoperatively, no patient had tumor recurrence after resection. Among 125 pathologically proven cases of AIS postoperatively, there were 67 (53.6%) radiologically invasive tumors including ground-glass nodules (GGNs) with part-solid component or pure-solid nodules.ConclusionsThis intraoperative evaluation of frozen-section slides will help surgeons avoid excessive lung resection for AIS that was radiologically diagnosed as invasive adenocarcinoma. Intraoperative frozen-section diagnosis will provide to be clinically useful and lead to less invasive surgical treatment for lung nodules.

Comparison of real-life data from patients with NGS panel negative and KRAS mutation positive metastatic lung adenocarcinoma

To evaluate clinical and demographic characteristics and the results of cytotoxic treatments of KRASG12C, KRASother, and next-generation sequencing (NGS) panel negative patients. NGS data of 1264 patients with non-small cell lung cancer were retrospectively evaluated. Among these patients, the mutation distributions of 1081 patients with metastatic lung adenocarcinoma were analyzed. A total of 150 patients with negative NGS panel or mutant KRAS followed up in our clinic were included. Clinical features, overall survival, first-line chemotherapy responses, and progression-free survival of NGS panel negative, KRASG12C, and KRASother groups were compared. In 1081 patients who underwent NGS from tumor tissue with the diagnosis of metastatic lung adenocarcinoma, 296 (27%) NGS panel negative and 276 (26%) KRAS mutant patients were detected. Among these patients, 150 patients whose data were available were 71 (47.3%) NGS panel negative, 54 (36%) KRASother, and 25 (16.7%) KRASG12C. Clinical features, brain metastasis, and first-line chemotherapy response were similar among groups. Bone metastases were detected more often in the NGS panel negative group (p = 0.03). The median follow-up was 8.4 months. Overall, 107 deaths had occurred at the time of analysis. There was no difference in overall survival (p = 0.56) or progression-free survival (p = 0.71) among NGS panel negative, KRASother, and KRASG12C patients. There is no difference in overall survival, first-line chemotherapy response, or progression-free survival among patients with NGS panel negative, KRASG12C, or KRASother metastatic lung adenocarcinoma. Bone metastases were observed more frequently in the NGS panel negative group.

Transesophageal endoscopic ultrasound fine needle aspiration of vertebral body osteolytic tumors - a novel diagnostic approach. Case series.

Vertebral lesions, either primary or more frequently metastasis, are difficult targets for percutaneous guided biopsies and surgical biopsies and are associated with greater risks of complications. We investigated the feasibility of endoscopic ultrasound (EUS) fine needle aspiration (FNA) biopsy in the assessment of vertebral osteolytic tumors as an alternative to CT guided biopsy which is the technique currently used. Four patients with osteolytic tumors of the vertebral bodies identified by imaging methods (CT or MRI) - 3 patients, and one with a tumor detected primarily during EUS procedure were included in order to evaluate the feasibility of the procedure. The lesions were located either at the dorsal or lumbar vertebrae. In all cases we performed EUS FNA of the osteolytic vertebral body lesions with 22G needles using the transesophageal or transgastric approach. In all cases EUS FNA provided enough tissue for an accurate histopathological report, with no procedural complication. We diagnosed lung adenocarcinoma, hepatocarcinoma and a pancreatic adenocarcinoma vertebral metastasis and one case of lymphoma. EUS FNA is a valuable technique which should be considered in selected cases, when a "traditional approach" is not applicable or associated with a higher risk. Treatment guidelines are based on the histology of the tumor, histopathological examination being nowadays mandatory. Therefore, we propose for selected cases a feasible technique, with significantly lower procedural risks, as an alternative for open surgical biopsies or computed tomography guided biopsies.