Survival Benefit and Genetic Profile of Pemetrexed as Initial Chemotherapy in Selected Chinese Patients With Advanced Lung Adenocarcinoma.

Objective: This study investigated survival in selected Chinese patients with advanced lung adenocarcinoma who received initial chemotherapy with pemetrexed. We also explored the relationship between genetic biomarkers and pemetrexed efficacy. Methods: We retrospectively collected patients (n = 1,047) enrolled in the Chinese Patient Assistance Program from multiple centers who received pemetrexed alone or combined with platinum as initial chemotherapy and continued pemetrexed maintenance therapy for advanced lung adenocarcinoma from November 2014 to June 2017. The outcomes were duration of treatment (DOT) and overall survival (OS). Clinical features were analyzed for their influence on the treatment effect and prognosis. Next-generation sequencing (NGS) was performed to identify genetic biomarkers associated with the efficacy of pemetrexed. Results: The median DOT was 9.1 months (95% CI: 8.5-9.8), and the median OS was 26.2 months (95% CI: 24.2-28.1). OS was positively correlated with DOT (r = 0.403, P < 0.001). Multivariable analysis showed that smoking status and Eastern Cooperative Oncology Group (ECOG) performance status (PS) were independently associated with DOT; smoking status, ECOG PS, targeted therapy, and EGFR/ALK/ROS1 status were independently associated with OS. NGS in 22 patients with available samples showed genes with high mutation rates were: TP53 (54.5%), EGFR (50.0%), MYC (18.2%), and PIK3CA (13.6%). When grouped based on progression-free survival (PFS) reported in the PARAMOUNT study, the DOT > 6.9 months set was associated with PIK3CA, ALK, BRINP3, CDKN2A, CSMD3, EPHA3, KRAS, and RB1 mutations, while ERBB2 mutation was observed only in the DOT ≤ 6.9 months set. Conclusion: This study shows that initial chemotherapy with pemetrexed is an effective regimen for advanced lung adenocarcinoma in selected Chinese patients. There is no specific genetic profile predicting the benefit of pemetrexed found by NGS. Biomarkers predicting the efficacy of pemetrexed need further exploration.

EGFR mutations in early-stage and advanced-stage lung adenocarcinoma: Analysis based on large-scale data from China.

BACKGROUND: EGFR-tyrosine kinase inhibitors play an important role in the treatment of advanced non-small cell lung cancer (NSCLC). EGFR mutations in advanced NSCLC occur in approximately 35% of Asian patients and 60% of patients with adenocarcinoma. However, the frequency and type of EGFR mutations in early-stage lung adenocarcinoma remain unclear. METHODS: We retrospectively collected data on patients diagnosed with lung adenocarcinoma tested for EGFR mutation. Early stage was defined as pathological stage IA-IIIA after radical lung cancer surgery, and advanced stage was defined as clinical stage IIIB without the opportunity for curative treatment or stage IV according to the American Joint Committee on Cancer Staging Manual, 7th edition. RESULTS: A total of 1699 patients were enrolled in this study from May 2014 to May 2016; 750 were assigned to the early-stage and 949 to the advanced-stage group. Baseline characteristics of the two groups were balanced, except that there were more smokers in the advanced-stage group (P < 0.001). The total EGFR mutation rate in the early-stage group was similar to that in the advanced-stage group (53.6% vs. 51.4%, respectively; P = 0.379). There was no significant difference in EGFR mutation type between the two groups. In subgroup analysis of smoking history, there was no difference in EGFR mutation frequency or type between the early-stage and advanced-stage groups. CONCLUSION: Early-stage and advanced-stage groups exhibited the same EGFR mutation frequencies and types.

Liquid biopsy in non-small cell lung cancer: a key role in the future of personalized medicine?

INTRODUCTION: Liquid biopsies, especially the analysis of circulating tumor DNA (ctDNA), as a novel and non-invasive method for the diagnosis and monitoring of non-small cell lung cancer (NSCLC) have already been implemented in clinical settings. The majority of ctDNA is released from apoptotic or necrotic tumor cells, thus reflecting the genetic profile of a tumor. Numerous studies have reported a high concordance in mutation profiles derived from liquid biopsy and tissue biopsy, especially in driver genes. Liquid biopsy could overcome the clonal heterogeneity of tumour biopsy, as it provides a single snapshot of a tumour tissue. Moreover, non-invasiveness is the biggest advantage for liquid biopsy, and the procedure can be repeatedly performed during the treatment for the purpose of monitoring. Therefore, ctDNA could act as a potential complementary method for tissue biopsies in diagnosis, prognostic, treatment response and resistance. Areas covered: This review summarizes the recent advancements in liquid biopsy with a focus on NSCLC, including its applications and technologies associated with assessing ctDNA. The authors conclude the review by discussing the challenges associated with liquid biopsy. Expert commentary: The analysis of ctDNA represents a promising method for liquid biopsy, which will be a novel and potentially complementary method in diagnosis, treatment and prognostic in NSCLC at all stages.

Diagnosis of Vein of Galen aneurysmal malformation using fetal MRI.

PURPOSE: To present three fetal vein of Galen aneurysmal malformations (VGAMs), which were diagnosed through magnetic resonance imaging (MRI), and highlight these cardiovascular findings. MATERIALS AND METHODS: We retrospectively reviewed three fetuses with VGAM at 31, 32, and 33 weeks of gestation. Feeding arteries and draining veins were observed by MRI. Secondary changes in the brain and high-output heart failure caused by high blood flow in the lesion were evaluated. Two fetuses were born, and neonatal MRI was performed. One fetus was terminated. RESULTS: A characteristic dilated structure in the midline of the brain presented in each fetus. The arteriovenous fistula led to anatomical brain changes such as in the hydrocephalus, dilated feeding vessels (one or more), jugular vein, and/or superior vena cava. Substantial brachiocephalic vessel dilation was observed in two fetuses. Following parturition, one baby had neonatal asphyxia and sinus thrombosis, and MRI revealed hypoxic-ischemic encephalopathy. Cardiomegaly was detected in all three cases. CONCLUSION: With a large field of view, fetal MRI can observe brain VGAM, as well as the heart and affected large vessels. It can determine hydrocephalus, ischemia, intracranial hemorrhage, and sinus thrombosis. Providing such information on the infant's entire body can aid clinicians in determining the most appropriate treatment. LEVEL OF EVIDENCE: 4 J. Magn. Reson. Imaging 2017;46:1535-1539.

[Prognostic determinants of adrenocortical carcinoma in adults].

OBJECTIVE: To investigate the clinical features and prognostic determinants of adrenocortical carcinoma (ACC) in adult patients. METHODS: All adult patients (aged > or =18 years old) who were admitted to West China Hospital, Sichuan University from 1st Jan., 2000 to 31st Jan., 2013 with a pathologically diagnosed ACC were included in this study. Data about the demographics, clinical characteristics, laboratory examinations and outcomes of those patients were extracted and analyzed. RESULTS: A total of 52 cases were identified, with a median follow-up of 26 months (3-159 months). The patients had a median survival time of 29 months (1-156 months), with a 1-year, 3-year; and 5-year survival rate of 71.0%, 47.0%, and 42.7%, respectively. In the univariate analysis, aged >45 years old at diagnosis (P = 0.017), advanced stage (III-IV stage, P<0.001), incomplete resection (P = 0.011), symptomatic (P = 0.017), hypoalbuminemia (P = 0.003), and elevated lactate dehydrogenase (LDH) (P = 0.017) were associated with poor prognosis of ACC. The multivariate analysis confirmed that hypoalbuminemia Chazard ratio (HR) = 5.306; 95% confidence interval (95% CI: 1.975, 14.258; P = 0.001), female (HR = 4.020; 95% CI: 1.610, 10.038; P = 0.003), advanced stage (HR = 7.405; 95% CI: 2.561, 21.410; P < 0.001), and older age (HR = 4.628; 95% CI: 1.791, 11.959; P = 0.002) were predictors of poor prognosis of ACC. CONCLUSION: Hypoalbuminemia, female, older age, and advanced stage are independent risk factors associated with poor prognosis of ACC.in adult patients.

[Study of glycated albumin cut-off point in diabetes mellitus and impaired glucose regulation].

OBJECTIVE: To investigate the cut-off point of glycated albumin (GA) in the detection of diabetes mellitus (DM) and impaired glucose regulation (IGR). METHODS: This study was conducted in 20-84 years-old adults who had risk factors of diabetes but no previously diagnosed diabetes. There were finally 392 individuals included and received the measurement of GA and HbA1c. Receiver operating characteristic curve (ROC) was plotted to determine the performance of GA. RESULTS: (1) Based on the diabetes diagnosis criteria of WHO (1999), the subjects were divided into DM group (n = 131), IGR group (n = 126), and normal glucose tolerance (NGT) group (n = 135). The GA level in the three groups tended to increase (P < 0.05). (2) Spearman correlation analysis demonstrated that GA was positively correlated with glycated haemoglobin A1c (HbA1c) (r = 0.942 1, P < 0.05), fasting plasma glucose (FPG) (r = 0.856 6, P < 0.05) and 2 h post-load plasma glucose (2-hPG) (r = 0.813 7, P < 0.05). (3) The mean levels of serum GA/HbA1c were 2.58 +/- 0.37, 2.44 +/- 0.37 and 2.17 +/- 0.25 for DM, IGR and NGT respectively. (4) The optimal cut-off points for detecting diabetes were 16.6% in GA [area under the carve (AUC) = 0.888], producing the sensitivity of 71.8% and the specificity of 87.4%. CONCLUSION: GA as a single screening test shows adequate to detect newly diagnosed DM, and the optimal GA cut-off point was 16.6% in this study.

[Preliminary study on the expression of cystatin C in primary liver cancer].

OBJECTIVE: To preliminarily investigate the expression of cysteine proteinase inhibitors C (cystatin C) in primary hepatic carcinoma. METHODS: Hepatic tissue samples and peripheral blood samples were collected from 41 cases of primary hepatic carcinoma, 24 cases of cirrhosis and 40 cases of normal control. To primary hepatic carcinoma, three kinds of hepatic tissue samples were harvested, including carcinoma tissue, adjacent non-tumor tissue, and distant normal tissue. The expression levels of cystatin C in hepatic samples and blood samples were measured by immunohistochemistry method and latex enhanced immune turbidimetric method respectively, and the differences of cystatin C expressions were compared in primary hepatic cancer, cirrhosis, and normal control. Furthermore, the relationships of cystatin C expression with tumor size, intrahepatic metastasis, serum AFP level were studied with correlation analysis. RESULTS: The expression of cystatin C was positive, in primary hepatic carcinoma. Part of adjacent non-tumor tissue, and distant normal tissue and cirrhosis tissues had some degree of cyctatin C expression. Wilcoxon test showed that the differences of cyctatin C expression in different hepatic tissues were statistics significance (P < 0.01). The proportion of positive cell, staining intensity, and the product of these two was: carcinoma tissues > adjacent non-tumor tissues> cirrhosis tissues > distant normal tissue. Compared with normal control, primary hepatic carcinoma and cirrhosis both had higher serum cystatin C level (P < 0.001), but there was no difference between hepatic carcinoma and cirrhosis (P = 0.769). The correlation analysis showed that the level of serum cystatin C was not related to serum AFP, tumor size, or intrahepatic metastasis. CONCLUSION: The expression of cystatin C in primary hepatic carcinoma is higher than that of adjacent non-tumor tissue, distant normal tissue, and cirrohsis tissue. The serum cystatin C level of primary hepatic carcinoma is higher than that of normal control.

[Construction of recombinant lentiviral vector of Tie2-RNAi and its influence on malignant melanoma cells in vitro].

OBJECTIVE: To construct lentivector carrying Tie2-Small interfering RNA (SiRNA), so as to study its influence on malignant melanoma cells. METHODS: Recombinant plasmid pSilencer 1.0-U6-Tie2-siRNA and plasmid pNL-EGFP were digested with XbaI, ligated a target lentiviral transfer plasmid of pNL-EGFP-U6-Tie2-I or pNL-EGFP-U6-Tie2-II, and then the electrophoresis clones was sequenced. Plasmids of pNL-EGFP-U6-Tie2-I and pNL-EGFP-U6-Tie2-II were constructed and combined with pVSVG and pHelper, respectively, to constitute lentiviral vector system of three plasmids. The Lentiviral vector system was transfected into 293T cell to produce pNL-EGFP-U6-Tie2- I and pNL-EGFP-U6-Tie2-II lentivirus. Then the supernatant was collected to determine the titer. Malignant melanoma cells were infected by both lentiviruses and identified by Realtime RT-PCR to assess inhibitory efficiency. RESULTS: The recombinant lentiviral vectors of Tie2-RNAi were constructed successfully which were analyzed with restriction enzyme digestion and identified by sequencing. And the titer of lentiviral vector was 8.8 x 10(3)/ml, which was determined by 293T cell. The results of Realtime RT-PCR demonstrated that the lentiviral vectors of Tie2-RNAi could infect malignant melanoma cells and inhibit the expression of Tie2 genes in malignant melanoma cells (P<0.01). There was no significant difference in the expression level (P>0.05) between the two lentiviral vectors of Tie2-RNAi. CONCLUSIONS: Lentivector carrying Tie2-SiRNA can be constructed successfully and inhibit the expression of Tie2 gene in vitro significantly. The study will supply the theory basis for the further research on the inhibition of tumor growth in vivo.

[Nonalcoholic steatohepatitis: a clinicopathological analysis of liver biopsy in 32 cases].

OBJECTIVE: To investigate the clinicopathological features of nonalcoholic steatohepatitis (NASH) and elucidate its diagnosis and differential diagnosis. METHODS: Liver biopsy tissues and clinical data of 32 patients with NASH were collected and the clinicopathological findings by HE and Masson staining were evaluated for NASH grading. RESULTS: Ballooning degeneration of the liver cells and fibrosis around hepatic sinusoid was scarce in mild NASH cases and increased in moderate to severe cases. Steatotic and inflammatory cells in the liver lobes decrease in liver cirrhosis related to seatohepatitis. CONCLUSION: Ballooning degeneration of the liver cells and fibrosis around the hepatic sinusoid have important value in differential diagnosis of mild from moderate to severe NASH, and correct histological grading benefits clinical intervention and prognostic evaluation of NASH.